Montpellier, France
Montpellier, France

The University of Montpellier was a French university in Montpellier Hérault, in Languedoc-Roussillon region in south-east France. Its present-day university legacy has been renamed and is currently known as the University of Montpellier 1, Montpellier 2 University and Paul Valéry University, Montpellier III until 2015 when l'université de Montpellier was created a second time. Moreover, the prestigious and famous secondary high-school Lycée Joffre is also a direct heir from the outstanding Montpellier University system. Wikipedia.

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Vib Vzw, Ghent University, French National Center for Scientific Research, Montpellier University, Montpellier University Hospital Center and University of Osnabrück | Date: 2016-09-28

This disclosure relates to a modified -helical bundle cytokine, with reduced activity via an -helical bundle cytokine receptor, wherein the -helical bundle cytokine is specifically delivered to target cells. Preferably, the -helical bundle cytokine is a mutant, more preferably it is a mutant interferon, with low affinity to the interferon receptor, wherein the mutant interferon is specifically delivered to target cells. The targeting is realized by fusion of the modified -helical bundle cytokine to a targeting moiety, preferably an antibody. This disclosure relates further to the use of such targeted modified -helical bundle cytokine to treat diseases. A preferred embodiment is the use of a targeted mutant interferon, to treat diseases, preferably viral diseases and tumors.

French Institute of Health, Medical Research and Montpellier University | Date: 2016-11-21

The present invention relates to a method for selecting a competent oocyte or a competent embryo by determining the expression level of specific microRNA species in a body fluid or in cumulus cells.

French Institute of Health, Medical Research, Montpellier University and University Dauvergne | Date: 2015-04-24

The present invention relates to a compound of formula (I) wherein: i is 0 or 1; j is 0 or 1; k is 0 or 1; R_(1 )and R_(2 )are in particular H, (C_(1)-C_(12))alkyl, or a group of formula C(O)R; R is a, linear or branched, alkyl radical, comprising at least 19 carbon atoms; R_(3 )is H and k=0 when j=1; or, when j=0, R_(3 )is C(O)R or -L-C(O)R; L, U and L are linkers; wherein, when j=0, at least one of the groups R_(1); R_(2 )and R_(3 )comprises a radical R.

Idenix Pharmaceuticals, University of Cagliari, French National Center for Scientific Research and Montpellier University | Date: 2016-12-14

2 and/or 3 prodrugs of 1, 2, 3 or 4-branchednucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions.

French Institute of Health, Medical Research, Montpellier University, Assistance Publique Hopitaux De Paris, University Paris Est Creteil and University of Angers | Date: 2016-10-17

The present invention relates to methods and pharmaceutical compositions for cardioprotection of subjects who experienced a myocardial infarction. In particular, the present invention relates to a ligand of the sonic hedgehog signaling pathway for use in the cardioprotection of a subject who experienced a myocardial infarction.

French National Center for Scientific Research, Montpellier University and Toulouse 1 University Capitole | Date: 2015-01-22

The invention relates to a method for the in vitro diagnosis of prostate cancer in a patient, characterised in that it comprises a step of measuring the expression level of the gene of the cation-independent mannose-6-phosphate receptor (CI-M6PR) in a sample of prostate tissue of the patient, the determination of overexpression of said CI-M6PR gene indicating the presence of prostate cancer in said patient.

It comprises new systematic procedures for filtering synchronization data (raw data: tap times and sound/musical beat reference times) in order to obtain accurate and reliable measures of synchronization accuracy and variability (or consistency). The procedures detailed are used to provide reliable synchronization data that can be used to compute measures of synchronization accuracy and variability based on linear statistics or circular statistics. These procedures are particularly appropriate for analyzing synchronization performance in individuals with rhythmic disorders.

Fellous S.,Montpellier University | Duncan A.B.,Montpellier University | Quillery E.,Montpellier University | Vale P.F.,CNRS Center of Evolutionary and Functional Ecology | Kaltz O.,Montpellier University
Ecology Letters | Year: 2012

Epidemiology in host meta-populations depends on parasite ability to disperse between, establish and persist in distinct sub-populations of hosts. We studied the genetic factors determining the short-term establishment, and long-term maintenance, of pathogens introduced by infected hosts (i.e. carriers) into recipient populations. We used experimental populations of the freshwater ciliate Paramecium caudatum and its bacterial parasite Holospora undulata. Parasite short-term spread (approximately one horizontal transmission cycle) was affected mainly by carrier genotype, and its interactions with parasite and recipient genotypes. By contrast, parasite longer term spread (2-3 horizontal transmission cycles) was mostly determined by parasite isolate. Importantly, measures of parasite short-term success (reproductive number, R) were not good predictors for longer term prevalence, probably because of the specific interactions between host and parasite genotypes. Analogous to variation in vectorial capacity and super-spreader occurrence, two crucial components of epidemiology, we show that carrier genotype can also affect disease spread within meta-populations. © 2012 Blackwell Publishing Ltd/CNRS.

Raevel V.,CNRS Center of Evolutionary and Functional Ecology | Violle C.,CNRS Center of Evolutionary and Functional Ecology | Munoz F.,Montpellier University
Oikos | Year: 2012

Successions are a central issue of ecological theory. They are governed by changes in community assembly processes that can be tracked by species' traits. While single-trait-based approaches have been mostly promoted to address community assembly, ecological strategies actually encompass tradeoffs between multiple traits that are relevant to succession theory. We analyzed plant ecological strategies along a 140-year-long succession primary succession of 52 vertical outcrop communities after roadwork. We performed a RLQ analysis to relate six functional traits, associated with resource acquisition, competition, colonization ability and phenology, to the age of the outcrops. We found the prominence of two main axes of specialization, one related to resource acquisition and the other to reproduction and regeneration. We further examined the community-level variation in ecological strategies to assess the abiotic and biotic drivers of community assembly. Using trait-based statistics of functional richness, regularity and divergence, we found that different processes drove the variation in ecological strategies along the axes of specialization. In late succession, functional convergence was detected for the traits related to resource acquisition as a signature of habitat filtering, while the coexistence of contrasted strategies was found for the traits related to reproduction and regeneration as a result of spatial micro-heterogeneity. We observed a lack of niche differentiation along the succession, revealing a weak importance of biotic interactions for the regulation of community assembly in the outcrops. Overall, we highlight a prominent role of habitat filtering and spatial micro-heterogeneity in driving the primary succession governed by water and nutrient limitation. © 2012 The Authors. Oikos © 2012 Nordic Society Oikos.

Besnard E.,Functional Genomics Institute | Besnard E.,Gladstone | Babled A.,Functional Genomics Institute | Lapasset L.,Functional Genomics Institute | And 6 more authors.
Nature Structural and Molecular Biology | Year: 2012

DNA replication is highly regulated, ensuring faithful inheritance of genetic information through each cell cycle. In metazoans, this process is initiated at many thousands of DNA replication origins whose cell type-specific distribution and usage are poorly understood. We exhaustively mapped the genome-wide location of replication origins in human cells using deep sequencing of short nascent strands and identified ten times more origin positions than we expected; most of these positions were conserved in four different human cell lines. Furthermore, we identified a consensus G-quadruplex-forming DNA motif that can predict the position of DNA replication origins in human cells, accounting for their distribution, usage efficiency and timing. Finally, we discovered a cell type-specific reprogrammable signature of cell identity that was revealed by specific efficiencies of conserved origin positions and not by the selection of cell type-specific subsets of origins. © 2012 Nature America, Inc. All rights reserved.

Bonhomme V.,French Institute of Pondicherry | Picq S.,University of Québec | Gaucherel C.,Montpellier University | Claude J.,French Institute of Pondicherry
Journal of Statistical Software | Year: 2014

We introduce here Momocs, a package intended to ease and popularize modern mor-phometrics with R, and particularly outline analysis, which aims to extract quantitative variables from shapes. It mostly hinges on the functions published in the book entitled Modern Morphometrics Using R by Claude (2008). From outline extraction from raw data to multivariate analysis, Momocs provides an integrated and convenient toolkit to students and researchers who are, or may become, interested in describing the shape and its variation. The methods implemented so far in Momocs are introduced through a simplistic case study that aims to test if two sets of bottles have different shapes.

Violle C.,Montpellier University | Reich P.B.,University of Minnesota | Reich P.B.,University of Western Sydney | Pacala S.W.,Princeton University | And 4 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Understanding, modeling, and predicting the impact of global change on ecosystem functioning across biogeographical gradients can benefit from enhanced capacity to represent biota as a continuous distribution of traits. However, this is a challenge for the field of biogeography historically grounded on the species concept. Here we focus on the newly emergent field of functional biogeography: the study of the geographic distribution of trait diversity across organizational levels. We show how functional biogeography bridges species-based biogeography and earth science to provide ideas and tools to help explain gradients in multifaceted diversity (including species, functional, and phylogenetic diversities), predict ecosystem functioning and services worldwide, and infuse regional and global conservation programs with a functional basis. Although much recent progress has been made possible because of the rising of multiple data streams, new developments in ecoinformatics, and new methodological advances, future directions should provide a theoretical and comprehensive framework for the scaling of biotic interactions across trophic levels and its ecological implications.

Duputie A.,CNRS Center of Evolutionary and Functional Ecology | Duputie A.,University of Texas at Austin | Massol F.,University of Texas at Austin | Massol F.,IRSTEA | And 3 more authors.
Ecology Letters | Year: 2012

Species may be able to respond to changing environments by a combination of adaptation and migration. We study how adaptation affects range shifts when it involves multiple quantitative traits evolving in response to local selection pressures and gene flow. All traits develop clines shifting in space, some of which may be in a direction opposite to univariate predictions, and the species tracks its environmental optimum with a constant lag. We provide analytical expressions for the local density and average trait values. A species can sustain faster environmental shifts, develop a wider range and greater local adaptation when spatial environmental variation is low (generating low migration load) and multitrait adaptive potential is high. These conditions are favoured when nonlinear (stabilising) selection is weak in the phenotypic direction of the change in optimum, and genetic variation is high in the phenotypic direction of the selection gradient. © 2012 Blackwell Publishing Ltd/CNRS.

Chiari Y.,Montpellier University | Cahais V.,Montpellier University | Galtier N.,Montpellier University | Delsuc F.,Montpellier University
BMC Biology | Year: 2012

Background: The morphological peculiarities of turtles have, for a long time, impeded their accurate placement in the phylogeny of amniotes. Molecular data used to address this major evolutionary question have so far been limited to a handful of markers and/or taxa. These studies have supported conflicting topologies, positioning turtles as either the sister group to all other reptiles, to lepidosaurs (tuatara, lizards and snakes), to archosaurs (birds and crocodiles), or to crocodilians. Genome-scale data have been shown to be useful in resolving other debated phylogenies, but no such adequate dataset is yet available for amniotes.Results: In this study, we used next-generation sequencing to obtain seven new transcriptomes from the blood, liver, or jaws of four turtles, a caiman, a lizard, and a lungfish. We used a phylogenomic dataset based on 248 nuclear genes (187,026 nucleotide sites) for 16 vertebrate taxa to resolve the origins of turtles. Maximum likelihood and Bayesian concatenation analyses and species tree approaches performed under the most realistic models of the nucleotide and amino acid substitution processes unambiguously support turtles as a sister group to birds and crocodiles. The use of more simplistic models of nucleotide substitution for both concatenation and species tree reconstruction methods leads to the artefactual grouping of turtles and crocodiles, most likely because of substitution saturation at third codon positions. Relaxed molecular clock methods estimate the divergence between turtles and archosaurs around 255 million years ago. The most recent common ancestor of living turtles, corresponding to the split between Pleurodira and Cryptodira, is estimated to have occurred around 157 million years ago, in the Upper Jurassic period. This is a more recent estimate than previously reported, and questions the interpretation of controversial Lower Jurassic fossils as being part of the extant turtles radiation.Conclusions: These results provide a phylogenetic framework and timescale with which to interpret the evolution of the peculiar morphological, developmental, and molecular features of turtles within the amniotes. © 2012 Chiari et al; licensee BioMed Central Ltd.

Guillot G.,Technical University of Denmark | Guillot G.,CNRS Biometry and Evolutionary Biology Laboratory | Renaud S.,CNRS Biometry and Evolutionary Biology Laboratory | Ledevin R.,University of Zürich | And 2 more authors.
Systematic Biology | Year: 2012

Recognition of evolutionary units (species, populations) requires integrating several kinds of data, such as genetic or phenotypic markers or spatial information in order to get a comprehensive view concerning the differentiation of the units. We propose a statistical model with a double original advantage: (i) it incorporates information about the spatial distribution of the samples, with the aim to increase inference power and to relate more explicitly observed patterns to geography and (ii) it allows one to analyze genetic and phenotypic data within a unified model and inference framework, thus opening the way to robust comparisons between markers and possibly combined analyses. We show from simulated data as well as real data that our method estimates parameters accurately and is an improvement over alternative approaches in many situations. The power of this method is exemplified using an intricate case of inter- and intraspecies differentiation based on an original data set of georeferenced genetic and morphometric markers obtained on Myodes voles from Sweden. A computer program is made available as an extension of the R package Geneland. © 2012 The Author(s).

Martin G.,Montpellier University | Martin G.,IRD Montpellier | Gandon S.,CNRS Center of Evolutionary and Functional Ecology
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2010

The lethal mutagenesis hypothesis states that within-host populations of pathogens can be driven to extinction when the load of deleterious mutations is artificially increased with a mutagen, and becomes too high for the population to be maintained. Although chemical mutagens have been shown to lead to important reductions in viral titres for a wide variety of RNA viruses, the theoretical underpinnings of this process are still not clearly established. A few recent models sought to describe lethal mutagenesis but they often relied on restrictive assumptions. We extend this earlier work in two novel directions. First, we derive the dynamics of the genetic load in a multivariate Gaussian fitness landscape akin to classical quantitative genetics models. This fitness landscape yields a continuous distribution of mutation effects on fitness, ranging from deleterious to beneficial (i.e. compensatory) mutations. We also include an additional class of lethal mutations. Second, we couple this evolutionary model with an epidemiological model accounting for the within-host dynamics of the pathogen. We derive the epidemiological and evolutionary equilibrium of the system. At this equilibrium, the density of the pathogen is expected to decrease linearly with the genomic mutation rate U. We also provide a simple expression for the critical mutation rate leading to extinction. Stochastic simulations show that these predictions are accurate for a broad range of parameter values. As they depend on a small set of measurable epidemiological and evolutionary parameters, we used available information on several viruses to make quantitative and testable predictions on critical mutation rates. In the light of this model, we discuss the feasibility of lethal mutagenesis as an efficient therapeutic strategy. © 2010 The Royal Society.

Maurel C.,Montpellier University | Simonneau T.,French National Institute for Agricultural Research | Sutka M.,Montpellier University | Sutka M.,University of Buenos Aires
Journal of Experimental Botany | Year: 2010

Roots are the primary sites of water uptake by plants. Roots also sense most of the physico-chemical parameters of the soil, perceive signals from the shoots, and adjust their growth and water transport properties accordingly. The present opinion paper discusses the significance of the variable water transport capacity (hydraulic conductance) of roots during development and in response to environmental stimuli. It is shown that root hydraulics determines water uptake intensities but also water potential gradients within the plant. It is indicated how the dynamics of root hydraulics contributes to many integrated plant nutritional and growth functions. For instance, the heterogeneity of soil water and nutrient availability and the heterogeneity of root hydraulic properties feed each other and play critical roles in root transport functions. Another important aspect is the integration of root hydraulics within the mutual interactions of roots and shoots, for co-ordinated growth and water-saving responses to drought. © 2010 The Author(s).

Plantard G.,CNRS PROMES | Janin T.,CNRS PROMES | Janin T.,Societe Resolution Espace Entreprises Mediterranee | Goetz V.,CNRS PROMES | Brosillon S.,Montpellier University
Applied Catalysis B: Environmental | Year: 2012

In the field of advanced oxidization processes based on solar radiation, heterogeneous solar catalysis involves exciting a photocatalyst with UV rays and one of the major problem encountered is optimizing the use of the sunlight. Catalysts in suspension develop the best ability to degrade polluting molecules. In this study, two TiO 2 catalysts in suspension which develop the best ability to degrade polluting molecules, with a granulometric ratio of 1000, have been investigated. All the experiments were performed under natural sunlight in a photoreactor consisting of three identical but independent reactors. A simple kinetic model of degradation is purposed for the media each in its optimal configuration, considering the irradiation, the catalyst and pollutant concentrations. First of all, we show that the kinetics of degradation decline as a function of the quantity of photons used and that the two catalysts (with a granulometric ratio of 1000), achieved similar performances when they were used in their optimal configurations. Secondly, the logarithm of the concentration of pyrimethanil decreased linearly as a function of the combination QUVCTiO2m. This indicates the direct dependence of the quantity degraded on the quantity of UV energy effectively available for the photocatalytic reaction. © 2011 Elsevier B.V.

Deabate S.,Montpellier University | Gebel G.,CEA Grenoble | Huguet P.,Montpellier University | Morin A.,CEA Grenoble | Pourcelly G.,Montpellier University
Energy and Environmental Science | Year: 2012

Proton exchange membrane fuel cells have been recognized as a promising zero-emission power source for portable, mobile and stationary applications. The information of water content distribution in the different components of the cell during operation, particularly the proton conducting membrane, is a critical issue for the validation of mass transfer models, the definition of optimized operating conditions and the development of efficient systems with innovative designs for efficient water management. In order to fully understand the way a fuel cell performs, water transport and distribution have to be investigated in situ and operando. In this review, we critically examine the state-of-the-art of operando diagnostics sensitive to the membrane water content, particularly those techniques able (in principle) to give insights into water transport occurring along both the in- and through-plane directions. Particular attention is devoted to experimental results obtained across the membrane thickness i.e. to the determination of water concentration profiles originating from the water activity and electrical gradients occurring through the working fuel cell. Different operando techniques have been developed for this purpose, from the early 1990s up to the last few years: internal resistance measurements, magnetic resonance and neutron imaging, neutron and X-ray scattering, confocal μ-Raman spectroscopy. These techniques can be roughly separated as either direct (i.e. the water amount can be directly derived from the detected signal, avoiding sometimes arbitrary assumptions during data processing) but intrusive (i.e. they require significant modification of the fuel cell, compared to the current design and materials) or indirect but with a significantly lower intrusiveness. It appears that operando measurements of the membrane water distribution allow a unique picture of how the internal part of the fuel cell works, thus certainly contributing to the development of more effective cell designs and materials in the near future. Nevertheless, improvement in the fundamental understanding of the actual fuel cell requires further efforts to increase spatial and, more particularly, temporal resolution of current operando techniques. Also, the comparison of limitations arising from the basic principles of the different operando approaches suggests that ultimate progress will arise from the combination of complementary techniques for simultaneous measurements. © 2012 The Royal Society of Chemistry.

Demoly P.,Montpellier University | Hagedoorn P.,University of Groningen | De Boer A.H.,University of Groningen | Frijlink H.W.,University of Groningen
Respiratory Medicine | Year: 2014

Background Although understanding of the scientific basis of aerosol therapy with dry powder inhalers (DPIs) has increased, some misconceptions still persist. These include the beliefs that high resistance inhalers are unsuitable for some patients, that extra fine (<1.0 μm) particles improve peripheral lung deposition and that inhalers with flow rate-independent fine particle fractions (FPFs) produce a more consistent delivered dose to the lungs. Objectives This article aims to clarify the complex inter-relationships between inhaler design and resistance, inspiratory flow rate (IFR), FPF, lung deposition and clinical outcomes, as a better understanding may result in a better choice of DPI for individual patients. Methods The various factors that determine the delivery of drug particles into the lungs are reviewed. These include aerodynamic particle size distribution, the inspiratory manoeuvre, airway geometry and the three basic principles that determine the site and extent of deposition: inertial impaction, sedimentation and diffusion. DPIs are classed as either dependent or independent of inspiratory flow rate and vary in their internal resistance to inspiration. The effects of these characteristics on drug deposition in the airways are described using data from studies directly comparing currently available inhaler devices. Results Clinical experience shows that most patients can use a high resistance DPI effectively, even during exacerbations. Particles in the aerodynamic size range from 1.5-5 μm are shown to be optimal, as particles <1.0 μm are very likely to be exhaled again while those >5 μm may impact on the oropharynx. For DPIs with a constant FPF at all flow rates, less of the delivered dose reaches the central and peripheral lung when the flow rate increases, risking under-dosing of the required medication. In contrast, flow rate-dependent inhalers increase their FPF output at higher flow rates, which compensates for the greater impaction on the upper airways as flow rate increases. Conclusions The technical characteristics of different inhalers and the delivery and deposition of the fine particle dose to the lungs may be important additional considerations to help the physician to select the most appropriate device for the individual patient to optimise their treatment. © 2014 Published by Elsevier Ltd.

Muyle A.,Montpellier University | Serres-Giardi L.,Montpellier University | Ressayre A.,French National Institute for Agricultural Research | Escobar J.,Montpellier University | Glemin S.,Montpellier University
Molecular Biology and Evolution | Year: 2011

Base composition varies among and within eukaryote genomes. Although mutational bias and selection have initially been invoked, more recently GC-biased gene conversion (gBGC) has been proposed to play a central role in shaping nucleotide landscapes, especially in yeast, mammals, and birds. gBGC is a kind of meiotic drive in favor of G and C alleles, associated with recombination. Previous studies have also suggested that gBGC could be at work in grass genomes. However, these studies were carried on third codon positions that can undergo selection on codon usage. As most preferred codons end in G or C in grasses, gBGC and selection can be confounded. Here we investigated further the forces that might drive GC content evolution in the rice genus using both coding and noncoding sequences. We found that recombination rates correlate positively with equilibrium GC content and that selfing species (Oryza sativa and O. glaberrima) have significantly lower equilibrium GC content compared with more outcrossing species. As recombination is less efficient in selfing species, these results suggest that recombination drives GC content. We also detected a positive relationship between expression levels and GC content in third codon positions, suggesting that selection favors codons ending with G or C bases. However, the correlation between GC content and recombination cannot be explained by selection on codon usage alone as it was also observed in noncoding positions. Finally, analyses of polymorphism data ruled out the hypothesis that genomic variation in GC content is due to mutational processes. Our results suggest that both gBGC and selection on codon usage affect GC content in the Oryza genus and likely in other grass species. © 2011 The Author.

Borgel J.,Montpellier University | Guibert S.,Montpellier University | Li Y.,Montpellier University | Li Y.,Kyushu University | And 5 more authors.
Nature Genetics | Year: 2010

DNA methylation is extensively reprogrammed during the early phases of mammalian development, yet genomic targets of this process are largely unknown. We optimized methylated DNA immunoprecipitation for low numbers of cells and profiled DNA methylation during early development of the mouse embryonic lineage in vivo. We observed a major epigenetic switch during implantation at the transition from the blastocyst to the postimplantation epiblast. During this period, DNA methylation is primarily targeted to repress the germline expression program. DNA methylation in the epiblast is also targeted to promoters of lineage-specific genes such as hematopoietic genes, which are subsequently demethylated during terminal differentiation. De novo methylation during early embryogenesis is catalyzed by Dnmt3b, and absence of DNA methylation leads to ectopic gene activation in the embryo. Finally, we identify nonimprinted genes that inherit promoter DNA methylation from parental gametes, suggesting that escape of post-fertilization DNA methylation reprogramming is prevalent in the mouse genome. © 2010 Nature America, Inc. All rights reserved.

Brauer V.S.,University of Amsterdam | Brauer V.S.,University of Groningen | Brauer V.S.,Montpellier University | Stomp M.,University of Amsterdam | Huisman J.,University of Amsterdam
American Naturalist | Year: 2012

Resource competition theory predicts that the outcome of competition for two nutrients depends on the ratio at which these nutrients are supplied. Yet there is considerable debate whether nutrient ratios or absolute nutrient loads determine the species composition of phytoplankton and plant communities. Here we extend the classical resource competition model for two nutrients by including light as additional resource. Our results suggest the nutrientload hypothesis, which predicts that nutrient ratios determine the species composition in oligotrophic environments, whereas nutrient loads are decisive in eutrophic environments. The underlying mechanism is that nutrient enrichment shifts the species interactions from competition for nutrients to competition for light, which favors the dominance of superior light competitors overshadowing all other species. Intermediate nutrient loads can generate high biodiversity through a fine-grained patchwork of two-species and three-species coexistence equilibria. Depending on the species traits, however, competition for nutrients and light may also produce multiple alternative stable states, suppressing the predictability of the species composition. The nutrient-load hypothesis offers a solution for several discrepancies between classical resource competition theory and field observations, explains why eutrophication often leads to diversity loss, and provides a simple conceptual framework for patterns of biodiversity and community structure observed in nature. © 2012 by The University of Chicago.

Mouquet N.,Montpellier University | Gravel D.,University of Quebec at Rimouski | Massol F.,IRSTEA | Massol F.,CNRS Center of Evolutionary and Functional Ecology | Calcagno V.,CNRS Sophia Agrobiotech Institute
Ecology Letters | Year: 2013

Keystone species are defined as having disproportionate importance in their community. This concept has proved useful and is now often used in conservation ecology. Here, we introduce the concept of keystone communities (and ecosystems) within metacommunities (and metaecosystems). We define keystone and burden communities as communities with impacts disproportionately large (positive or negative respectively) relative to their weight in the metacommunity. We show how a simple metric, based on the effects of single-community removals, can characterise communities along a 'keystoneness' axis. We illustrate the usefulness of this approach with examples from two different theoretical models. We further distinguish environmental heterogeneity from species trait heterogeneity as determinants of keystoneness. We suggest that the concept of keystone communities/ecosystems will be highly beneficial, not only as a fundamental step towards understanding species interactions in a spatial context, but also as a tool for the management of disturbed landscapes. © 2012 Blackwell Publishing Ltd/CNRS.

Chiriac A.M.,Allergy Unit | Demoly P.,Allergy Unit | Demoly P.,Montpellier University
Current Opinion in Allergy and Clinical Immunology | Year: 2013

PURPOSE OF REVIEW: The multiple drug hypersensitivity syndrome (MDH) is a distinct clinical entity, different from cross-reactivity and flare-up reactions. Following its initial description in 1989 by Sullivan et al., several authors have addressed the issues surrounding this peculiar form of drug hypersensitivity. Whether this syndrome is single or can be further classified in several entities is still a matter of debate. RECENT FINDINGS: Case reports, case series or studies involving large populations on MDH are few. The use of this term in the literature is heterogeneous, and the definitions variable. Given the major advances in the study of drug hypersensitivities in general, and ongoing research regarding severe cutaneous adverse reactions in particular, careful study of the subgroup of patients with demonstrated immunological basis of MDH has enabled the generation of possible pathogenetic hypotheses. Together with the studies (despite their limitations) to estimate the prevalence of this syndrome in adult and paediatric patients these emerging data need confirmation through larger studies with well defined populations. SUMMARY: Bringing together the experience of groups involved in the field of drug allergy should help to move knowledge regarding this peculiar form of drug hypersensitivity forward. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Hubert N.,Montpellier University | Calcagno V.,CNRS Sophia Agrobiotech Institute | Etienne R.S.,University of Groningen | Mouquet N.,Montpellier University
Ecology Letters | Year: 2015

The emergence of new frameworks combining evolutionary and ecological dynamics in communities opens new perspectives on the study of speciation. By acknowledging the relative contribution of local and regional dynamics in shaping the complexity of ecological communities, metacommunity theory sheds a new light on the mechanisms underlying the emergence of species. Three integrative frameworks have been proposed, involving neutral dynamics, niche theory, and life history trade-offs respectively. Here, we review these frameworks of metacommunity theory to emphasise that: (1) studies on speciation and community ecology have converged towards similar general principles by acknowledging the central role of dispersal in metacommunities dynamics, (2) considering the conditions of emergence and maintenance of new species in communities has given rise to new models of speciation embedded in the metacommunity theory, (3) studies of diversification have shifted from relating phylogenetic patterns to landscapes spatial and ecological characteristics towards integrative approaches that explicitly consider speciation in a mechanistic ecological framework. We highlight several challenges, in particular the need for a better integration of the eco-evolutionary consequences of dispersal and the need to increase our understanding on the relative rates of evolutionary and ecological changes in communities. © 2015 John Wiley & Sons Ltd/CNRS.

Rivero A.,IRD Montpellier | Vezilier J.,IRD Montpellier | Weill M.,Montpellier University | Read A.F.,Pennsylvania State University | And 2 more authors.
PLoS Pathogens | Year: 2010

Many of the most dangerous human diseases are transmitted by insect vectors. After decades of repeated insecticide use, all of these vector species have demonstrated the capacity to evolve resistance to insecticides. Insecticide resistance is generally considered to undermine control of vector-transmitted diseases because it increases the number of vectors that survive the insecticide treatment. Disease control failure, however, need not follow from vector control failure. Here, we review evidence that insecticide resistance may have an impact on the quality of vectors and, specifically, on three key determinants of parasite transmission: vector longevity, competence, and behaviour. We argue that, in some instances, insecticide resistance is likely to result in a decrease in vector longevity, a decrease in infectiousness, or in a change in behaviour, all of which will reduce the vectorial capacity of the insect. If this effect is sufficiently large, the impact of insecticide resistance on disease management may not be as detrimental as previously thought. In other instances, however, insecticide resistance may have the opposite effect, increasing the insect's vectorial capacity, which may lead to a dramatic increase in the transmission of the disease and even to a higher prevalence than in the absence of insecticides. Either way-and there may be no simple generality-the consequence of the evolution of insecticide resistance for disease ecology deserves additional attention. © 2010 Rivero et al.

Tonkin M.L.,University of Victoria | Crawford J.,University of Victoria | Lebrun M.L.,Montpellier University | Boulanger M.J.,University of Victoria
Protein Science | Year: 2013

Host cell invasion by the obligate intracellular apicomplexan parasites, including Plasmodium (malaria) and Toxoplasma (toxoplasmosis), requires a step-wise mechanism unique among known host-pathogen interactions. A key step is the formation of the moving junction (MJ) complex, a circumferential constriction between the apical tip of the parasite and the host cell membrane that traverses in a posterior direction to enclose the parasite in a protective vacuole essential for intracellular survival. The leading model of MJ assembly proposes that Rhoptry Neck Protein 2 (RON2) is secreted into the host cell and integrated into the membrane where it serves as the receptor for apical membrane antigen 1 (AMA1) on the parasite surface. We have previously demonstrated that the AMA1-RON2 interaction is an effective target for inhibiting apicomplexan invasion. To better understand the AMA1-dependant molecular recognition events that promote invasion, including the significant AMA1-RON2 interaction, we present the structural characterization of AMA1 from the apicomplexan parasites Babesia divergens (BdAMA1) and Neospora caninum (NcAMA1) by X-ray crystallography. These studies offer intriguing structural insight into the RON2-binding surface groove in the AMA1 apical domain, which shows clear evidence for receptor-ligand co-evolution, and the hyper variability of the membrane proximal domain, which in Plasmodium is responsible for direct binding to erythrocytes. By incorporating the structural analysis of BdAMA1 and NcAMA1 with existing AMA1 structures and complexes we were able to define conserved pockets in the AMA1 apical groove that could be targeted for the design of broadly reactive therapeutics. © 2012 The Protein Society.

Guibert S.,Montpellier University | Guibert S.,CNRS Biotechnology and Cell Signaling Laboratory | Forne T.,Montpellier University | Weber M.,Montpellier University | Weber M.,CNRS Biotechnology and Cell Signaling Laboratory
Genome Research | Year: 2012

Epigenetic reprogramming, characterized by loss of cytosine methylation and histone modifications, occurs during mammalian development in primordial germ cells (PGCs), yet the targets and kinetics of this process are poorly characterized. Here we provide a map of cytosine methylation on a large portion of the genome in developing male and female PGCs isolated from mouse embryos. We show that DNA methylation erasure is global and affects genes of various biological functions. We also reveal complex kinetics of demethylation that are initiated at most genes in early PGC precursors around embryonic day 8.0-9.0. In addition, besides intracisternal A-particles (IAPs), we identify rare LTRERV1 retroelements and single-copy sequences that resist global methylation erasure in PGCs as well as in preimplantation embryos. Our data provide important insights into the targets and dynamics of DNA methylation reprogramming in mammalian germ cells. © 2012 by Cold Spring Harbor Laboratory Press.

Thomasse S.,Montpellier University
Journal of Combinatorial Theory. Series B | Year: 2012

We prove a general result concerning cyclic orderings of the elements of a matroid. For each matroid M, weight function ω:E(M)→N, and positive integer D, the following are equivalent. (1) For all A⊆E(M), we have ∑ a∈Aω(a)≤D{dot operator}r(A). (2) There is a map φ that assigns to each element e of E(M) a set φ(e) of ω(e) cyclically consecutive elements in the cycle (1, 2, . . ., D) so that each set {e|i∈φ(e)}, for i=1, . . ., D, is independent.As a first corollary we obtain the following. For each matroid M such that |E(M)| and r(M) are coprime, the following are equivalent. (1). For all non-empty A⊆E(M), we have |A|/r(A) ≤|E(M)|/r(M)(2). There is a cyclic permutation of E(M) in which all sets of r(M) cyclically consecutive elements are bases of M. A second corollary is that the circular arboricity of a matroid is equal to its fractional arboricity.These results generalise classical results of Edmonds, Nash-Williams and Tutte on covering and packing matroids by bases and graphs by spanning trees. © 2011 Elsevier Inc.

Kocer A.,Biomade Technology Foundation | Kocer A.,University of Groningen | Tauk L.,Montpellier University | Dejardin P.,Montpellier University
Biosensors and Bioelectronics | Year: 2012

The use of nanopores of well controlled geometry for sensing molecules in solution is reviewed. Focus is concentrated especially on synthetic track-etch pores in polymer foils and on biological nanopores, i.e. ion channels. After a brief section about multipore sensors, specific attention is provided to works relative to a single nanopore sensor. The different strategies to combine the robustness of supports with the high selectivity of the biological channels are reviewed. The scope ranges from keeping the membrane natural environment of biological channels in supported and suspended bilayer membranes, to considering completely abiotic designed nanopores created through synthetic materials. The α-hemolysine channel and the mechanosensitive channel of large conductance with their modifications are especially considered in the first strategy, the conical functionalized nanopores created in polymer foils in the second one. The different attempts of reading macromolecules are also discussed. A third hybrid strategy, which was not extensively explored, consists in the inclusion of a biological structure into a well-designed nanopore through the support, as recently with gramicidin. © 2012 Elsevier B.V.

Maerten F.,IGEOSS France | Maerten F.,Montpellier University
Engineering Analysis with Boundary Elements | Year: 2010

We present the hierarchical matrix (H -matrix) technique combined with the adaptive cross-approximation (ACA) applied to a three-dimensional (3D) elastostatic problem using the boundary element method (BEM). This is used in structural geology and geomechanics for the evaluation of the deformation and perturbed stress field associated with surfaces of displacement discontinuity. Such optimization significantly reduces (i) the time and memory needed for the resolution of the system of equations, but more importantly (ii) the time needed for the post-processing at observation points where the deformation and the perturbed stress field are evaluated. Specifically, it is shown that the H -matrix structure used with the ACA, clearly captures the kernel smoothness during the post-processing stage according to the field point positions, and optimizes the computation accordingly. Combined with the parallelization on multi-core processors, this technique allows intensive computations to be done on personal desktop and laptop computers. Numerical simulations are presented, showing the advantages of such optimizations compared to the standard method. © 2009 Elsevier Ltd. All rights reserved.

Monnier L.,Montpellier University | Colette C.,Montpellier University | Dejager S.,Hospital Pitie Salpetriere | Owens D.,University of Swansea
Diabetes Care | Year: 2013

Objective-To assess the magnitude of the dawn phenomenon and its impact on the total glucose exposure in type 2 diabetes. Research design and methods-A total of 248 noninsulin-treated persons with type 2 diabetes who underwent continuous glucose monitoring were divided into three groups selected by treatments: diet alone (n = 53); insulin sensitizers alone (n = 82); and insulin secretagogues alone or incombination with insulin sensitizers (n = 113). The dawn phenomenon (∂ glucose, mg/dL) was quantified by its absolute increment from nocturnal nadir to prebreakfast value. The participants were secondarily divided into two paired subsets after they had been separated by the presence/absence of a dawn phenomenon based on a threshold of 20mg/dL andmatched for glucose nadir. The impact of the dawn phenomenon was assessed on HbA 1c and 24-h mean glucose. Results-The median of ∂ glucose (interquartile range) was 16.0 (0-31.5 mg/dL) in the 248 subjects, and no differences were observed across groups selected by HbA1c or treatments. In the overall population, the mean impacts on HbA1c and 24-h mean glucose were 4.3 ± 1.3 mmol/mol (0.39 ± 0.12%) and 12.4 ± 2.4 mg/dL, respectively. The mean impact on 24-h mean glucose was not statistically different between those on diet alone (16.7 ± 5.9 mg/dL) compared with the two subsets treated with oral hypoglycemic agents (11.2 ± 5.3 and 8.5 ± 7.5 mg/dL). Conclusions-The impact of the dawn phenomenon on overall glycemic control in type 2 diabetes, as depicted by the HbA1c level, was;0.4% and not eliminated by any of the currently available armamentarium of oral antidiabetes agents. © 2013 by the American Diabetes Association.

Thomann M.,CNRS Center of Evolutionary and Functional Ecology | Imbert E.,Montpellier University | Devaux C.,Montpellier University | Cheptou P.-O.,CNRS Center of Evolutionary and Functional Ecology
Trends in Plant Science | Year: 2013

There is now compelling evidence of a reduction of pollinator richness and density at a global scale. In this opinion article, we argue that such pollinator decline intensifies pollen limitation and reduces plant reproductive success, threatening natural populations of extinction. We use genetic architecture and selection experiments on floral traits and evaluate the potential for plant reproductive strategies to adapt rapidly to new pollination environments. We propose that plant reproductive strategies could adapt to the current pollinator decline by decreasing or increasing their reliance to pollinators, for example, increasing autonomous selfing or reinforcing interactions with pollinators. We further discuss if and how adaptation of plant reproductive strategies can buffer the demographic consequences of pollinator decline, and possibly rescue plant populations from extinction. © 2013 Elsevier Ltd.

Gil-Robles S.,Hospital Quiron | Duffau H.,Montpellier University
Neurosurgical Focus | Year: 2010

Object. Recent surgical studies have demonstrated that the extent of resection is significantly correlated with median survival in WHO Grade II gliomas. Consequently, thanks to advances in intraoperative functional mapping, the authors questioned whether it is actually necessary to leave a "security" margin around eloquent structures. Methods. The authors first reviewed the classic literature, especially that based on epilepsy surgery and functional neuroimaging techniques, which led them to propose the rule of a security margin. Second, they detailed new developments in the field of intrasurgical electrical mapping, especially with regard to subcortical stimulation of the projection and long-distance association pathways. On the basis of these advances, the removal of gliomas according to functional boundaries has recently been suggested, with no margin around eloquent structures. Results. Comparative results showed that the rate of permanent deficit was similar with or without a security margin, that is, < 2%. However, a higher rate of transient neurological worsening in the immediate postsurgical period was associated with the absence of a margin, with recovery following adapted rehabilitation. On the other hand, the extent of resection was in essence improved with no margin. Conclusions. This no-margin technique, based on the subpial dissection, and the repetition of both cortical and subcortical stimulation to preserve eloquent cortex as well as the white matter tracts (U-fibers, projection pathways, and long-distance connectivity) allow optimization of the extent of resection while preserving the quality of life (despite transitory impairment) thanks to mechanisms of brain plasticity.

Chollet S.,CNRS Center of Evolutionary and Functional Ecology | Chollet S.,Montpellier University | Martin J.-L.,CNRS Center of Evolutionary and Functional Ecology
Diversity and Distributions | Year: 2013

Aim: We evaluate the possible link between increasing deer populations and declines in woodland birds. Location: North American continent. Methods: We used a group of 73 forest bird species that had been tested for their sensitivity to the impact of overabundant deer on forest understory. We used Breeding Bird Survey data to assess population trends for these 73 songbird species between 1966 and 2009, a period of marked continent-wide increases in white-tailed (Odocoileus virginianus) and mule or black-tailed (Odocoileus hemionus) deer. Results: We show a continent-wide link between increase in deer populations and declines in forest-songbird species-dependent on understory for nesting and/or foraging. Main conclusions: Increasing deer populations may actually play an important and underestimated role in the decline of North American songbirds. © 2012 Blackwell Publishing Ltd.

Costa P.,Montpellier University
Drugs | Year: 2012

The global burden of erectile dysfunction (ED) is increasing. It is estimated that 819 of men in Europe have ED and that by 2025 the prevalence of ED worldwide will reach 322 million. The gold standard therapy for ED is an oral phosphodiesterase type 5 (PDE5) inhibitor, but they are not suitable for everyone; approximately 25 of patients do not respond to this therapy and it is contraindicated in others, e.g. those with vascular disease. When PDE5 inhibitors are not suitable, available options include intraurethral and intracavernosal alprostadila synthetic vasodilator chemically identical to the naturally occurring prostaglandin E1 indicated for the treatment of ED. Intraurethral alprostadil is delivered by the Medicated System for Erection (MUSE). a single-use pellet containing alprostadil suspended in polyethylene glycol administered using an applicator. It is recommended that intraurethral alprostadil be initiated at a dose of 500μg, as it has a higher efficacy than the 250μg dose, with minimal differences with regard to adverse events. Data from key clinical studies of intraurethral alprostadil show that it has a fast onset of effect and a good safety profile, with no occurrences of priapism, fibrosis (as seen with intracavernosal injection) or the typical systemic effects observed with oral ED pharmacological treatments. Intraurethral alprostadil has been associated with high patient preference, acceptance rates and quality of life versus intracavernosal injection due to its ease of administration. Evidence has shown that combination treatment with sildenafil may be a possible efficient alternative when single oral or local treatment has failed. Intraurethral alprostadil can be administered in all patients irrespective of ED origin and should be the first option in patients with ED for whom therapy with PDE5 inhibitors has failed or is contraindicated. Adis © 2012 Springer International Publishing AG. All rights reserved.

Bierne N.,Montpellier University | Gagnaire P.-G.,French National Center for Scientific Research | David P.,CNRS Center of Evolutionary and Functional Ecology
Current Zoology | Year: 2013

When incompletely isolated taxa coexist in a patchy environment (e.g. mosaic hybrid zones, host-race complexes), patterns of variation may differ between selected traits/genes and neutral markers. While the genetic structure of selected traits/loci tends to coincide with habitat variables (producing Genetic-Environment Association or GEA), genetic differentiation at neutral loci unlinked to any selected locus rather depends on geographic connectivity at a large scale (e.g. Isolation-By-Distance or IBD), although these loci often display GEA at a small scale. This discrepancy has been repeatedly taken as evidence for parallel primary divergence driven by local adaptation. We argue that this interpretation needs to be addressed more thoroughly by considering the alternative hypothesis that speciation was initiated in allopatry and secondary introgression has subsequently erased the signal of past differentiation at neutral loci. We present a model of neutral introgression after secondary contact in a mosaic hybrid zone, which describes how GEAs dissipate with time and how neutral variation self-organizes according to the environmental and geographic structures. We show that although neutral loci can be affected by environmental selectionthey are often more affected by history and connectivity: the neutral structure retains the initial geographic separation more than it correlates with the environment during the colonization and introgression phases, and then converges to a migration-drift balance, the most frequent outcome of which is GEA at a local scale but IBD at a large scale. This is the exact pattern usually attributed to parallel ecological speciation. Introgression is heterogeneous in space and depends on the landscape structure (e.g. it is faster in small patches, which are more impacted by immigration). Furthermore, there is no directionality in the association and it is possible to observe reversed GEAs between distant regions. We argue that the history of differentiation should ideally be reconstructed with selected loci or neutral loci linked to them, not neutral ones, and review some case studies for which the hypothesis of a long co-existence of co-adapted genetic backgrounds might have been refuted too hastily. © 2013 Current Zoology.

Fanin N.,CNRS Center of Evolutionary and Functional Ecology | Fanin N.,Montpellier University | Fromin N.,CNRS Center of Evolutionary and Functional Ecology | Buatois B.,CNRS Center of Evolutionary and Functional Ecology | Hattenschwiler S.,CNRS Center of Evolutionary and Functional Ecology
Ecology Letters | Year: 2013

Stoichiometric homeostasis of heterotrophs is a common, but not always well-examined premise in ecological stoichiometry. We experimentally evaluated the relationship between substrate (plant litter) and consumer (microorganisms) stoichiometry for a tropical terrestrial decomposer system. Variation in microbial C : P and N : P ratios tracked that of the soluble litter fraction, but not that of bulk leaf litter material. Microbial N and P were not isometrically related, suggesting higher rates of P than N sequestration in microbial biomass. Shifts in microbial stoichiometry were related to changes in microbial community structure. Our results indicate that P in dissolved form is a major driver of terrestrial microbial stoichiometry, similar to aquatic environments. The demonstrated relative plasticity in microbial C : P and N : P and the critical role of P have important implications for theoretical modelling and contribute to a process-based understanding of stoichiometric relationships and the flow of elements across trophic levels in decomposer systems. © 2013 John Wiley & Sons Ltd/CNRS.

Locatelli F.,Alessandro Manzoni Hospital | Canaud B.,Montpellier University
Nephrology Dialysis Transplantation | Year: 2012

The need to improve haemodialysis (HD) therapies and to reduce cardiovascular and all-cause mortality frequently encountered by dialysis patients has been recognized and addressed for many years. A number of approaches, including increasing the frequency versus duration of treatment, have been proposed and debated in terms of their clinical efficacy and economic feasibility. Future prescription of dialysis to an expanding end-stage chronic kidney disease (CKD-5D) population needs a re-evaluation of existing practices while maintaining the emphasis on patient well-being both in the short and in the long term. Efficient cleansing of the blood of all relevant uraemic toxins, including fluid and salt overload, remains the fundamental objective of all dialysis therapies. Simultaneously, metabolic disorders (e.g. anaemia, mineral bone disease, oxidative stress) that accompany renal failure need to be corrected also as part of the delivery of dialysis therapy itself. Usage of high-flux membranes that enable small and large uraemic toxins to be eliminated from the blood is the first prerequisite towards the aforementioned goals. Application of convective therapies [(online-haemodiafiltration (OL-HDF)] further enhances the detoxification effects of high-flux haemodialysis (HF-HD). However, despite an extended clinical experience with both HF-HD and OL-HDF spanning more than two decades, a more widespread prescription of convective treatment modalities awaits more conclusive evidence from large-scale prospective randomized controlled trials. In this review, we present a European perspective on the need to implement optimal dialysis and to improve it by adopting high convective therapies and to discuss whether inertia to implement these practice patterns may deprive patients of significantly improved well-being and survival. © The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Cota I.,University of Seville | Blanc-Potard A.B.,Montpellier University | Casadesus J.,University of Seville
PLoS ONE | Year: 2012

STM2209 and STM2208 are contiguous loci annotated as putative protein-coding genes in the chromosome of Salmonella enterica. Lack of homologs in related Enterobacteria and low G+C content suggest that S. enterica may have acquired STM2209-STM2208 by horizontal transfer. STM2209 and STM2208 are co-transcribed from a promoter upstream STM2209, and their products are inner (cytoplasmic) membrane proteins. Analysis with the bacterial adenylate cyclase two-hybrid system suggests that STM2209 and STM2208 may interact. Expression of STM2209-STM2208 is subjected to phase variation in wild type Salmonella enterica serovar Typhimurium. Switching frequencies in LB medium are 6.1×10-5 (OFF→ON) and 3.7×10-2 (ON→OFF) per cell and generation. Lack of DNA adenine methylation locks STM2209-STM2208 in the ON state, and lack of the LysR-type factor OxyR locks STM2209-STM2208 in the OFF state. OxyR-dependent activation of STM2209-STM2208 expression is independent of the oxidation state of OxyR. Salmonella cultures locked in the ON state show alteration of O-antigen length in the lipopolysaccharide, reduced absorption of bacteriophage P22, impaired resistance to serum, and reduced proliferation in macrophages. Phenotypic heterogeneity generated by STM2209-STM2208 phase variation may thus provide defense against phages. In turn, formation of a subpopulation unable to proliferate in macrophages may restrain Salmonella spread in animal organs, potentially contributing to successful infection. © 2012 Cota et al.

Nielsen-LeRoux C.,French National Institute for Agricultural Research | Gaudriault S.,French National Institute for Agricultural Research | Gaudriault S.,Montpellier University | Ramarao N.,French National Institute for Agricultural Research | And 3 more authors.
Current Opinion in Microbiology | Year: 2012

Insects are the largest group of animals on earth. Like mammals, virus, fungi, bacteria and parasites infect them. Several tissue barriers and defense mechanisms are common for vertebrates and invertebrates. Therefore some insects, notably the fly Drosophila and the caterpillar Galleria mellonella, have been used as models to study host-pathogen interactions for several insect and mammal pathogens. They are excellent tools to identify pathogen determinants and host tissue cell responses. We focus here on the comparison of effectors used by two different groups of bacterial insect pathogens to accomplish the infection process in their lepidopteran larval host: Bacillus thuringiensis and the nematode-associated bacteria, Photorhabdus and Xenorhabdus. The comparison reveals similarities in function and expression profiles for some genes, which suggest that such factors are conserved during evolution in order to attack the tissue encountered during the infection process. © 2012 Elsevier Ltd.

Morales L.F.G.,German Research Center for Geosciences | Mainprice D.,Montpellier University | Boudier F.,Montpellier University
Tectonophysics | Year: 2013

To better understand the microstructural evolution of a "serpentinized" mantle rock and the influence of various hydrous phases on the seismic properties of the mantle wedge, we have conducted the detailed microstructural analyses of a sample of tremolite-chlorite-antigorite schist collected from the Moses Rock dike (central part of the Colorado Plateau). We performed differential effective media (DEM) modelling to study the effect of three hydrous phases forming two-phase aggregates with olivine, considering the crystallographic preferred orientation (CPO) of each phase and the shape ratio of the hydrous phases. We have demonstrated that in a partially serpentinized peridotite, the olivine CPO characteristic of [100](010) dislocation glide is still preserved, and the high-temperature asthenospheric flow is preserved with a foliation normal to that of antigorite schist. The transformation of olivine into antigorite occurs predominantly (~ 75%) by the relationship (100)ol || (001)atg with [001]ol || [010]atg, with the (010)ol || (001)atg and [001]ol || [010]atg relationship observed in areas of weak antigorite CPO. Chlorite results from the phase transformation of olivine in a relatively static environment, as shown by the correlation between the olivine-chlorite CPOs with (100)ol || (100)ch, (010)ol || (001)ch and (001)ol || (010)ch. The fluid percolation that caused the localized metasomatism and partial hydration of the mantle occurred possibly along trans-lithospheric shear zones. The presence of chlorite induces the most important drop on the P-wave velocities and may help to explain some local low velocities in the fore-arc mantle wedges, but is unlikely to be of global importance due to its very high Vp/Vs ratio. ~ 1.9. On the other hand, antigorite is the only phase that causes important modification on the propagation directions of P and S-waves, and the only phase to explain the polarization of the fastest shear waves parallel to the subduction trench. © 2013 Elsevier B.V.

Kosoy M.,Centers for Disease Control and Prevention | Khlyap L.,RAS Severtsov Institute of Ecology | Cosson J.-F.,French National Institute for Agricultural Research | Morand S.,Montpellier University
Vector-Borne and Zoonotic Diseases | Year: 2015

From the perspective of ecology of zoonotic pathogens, the role of the Old World rats of the genus Rattus is exceptional. The review analyzes specific characteristics of rats that contribute to their important role in hosting pathogens, such as host-pathogen relations and rates of rat-borne infections, taxonomy, ecology, and essential factors. Specifically the review addresses recent taxonomic revisions within the genus Rattus that resulted from applications of new genetic tools in understanding relationships between the Old World rats and the infectious agents that they carry. Among the numerous species within the genus Rattus, only three species - the Norway rat (R. norvegicus), the black or roof rat (R. rattus), and the Asian black rat (R. tanezumi) - have colonized urban ecosystems globally for a historically long period of time. The fourth invasive species, R. exulans, is limited to tropical Asia-Pacific areas. One of the points highlighted in this review is the necessity to discriminate the roles played by rats as pathogen reservoirs within the land of their original diversification and in regions where only one or few rat species were introduced during the recent human history. © 2015, Mary Ann Liebert, Inc.

Broseus J.,University of Lorraine | Park J.-H.,University of Burgundy | Carillo S.,University of Nimes | Carillo S.,Montpellier University | And 3 more authors.
Blood | Year: 2014

Calreticulin (CALR) mutations have been reported in Janus kinase 2 (JAK2)- and myeloproliferative leukemia (MPL )-negative essential thrombocythemia and primary myelofibrosis. In contrast, no CALR mutations have ever been reported in the context of polycythemia vera (PV). Here, we describe 2 JAK2V617F-JAK2exon12-negative PV patients who presented with a CALR mutation in peripheral granulocytes at the time of diagnosis. In both cases, the CALR mutation was a 52-bp deletion. Single burst-forming units-erythroid (BFU-E) from 1 patient were grown in vitro and genotyped: the same CALR del 52-bp mutation was noted in 31 of the 37 colonies examined; 30 of 31 BFU-E were heterozygous for CALR del 52 bp, and 1 of 31 BFU-E was homozygous for CALR del 52 bp. In summary, although unknown mutations leading to PV cannot be ruled out, our results suggest that CALR mutations can be associated with JAK2-negative PV. © 2014 by The American Society of Hematology.

Roland A.,Interloire | Roland A.,Montpellier University | Schneider R.,French National Institute for Agricultural Research | Razungles A.,Montpellier University | Cavelier F.,French National Center for Scientific Research
Chemical Reviews | Year: 2011

Varietal thiols, especially 4-mercapto-4-methylpentan-2-one (4MMP, 1), 3-mercaptohexyl acetate (3MHA, 2), and 3-mercaptohexan-1-ol (3MH, 3), have been identified as key molecules of young wines elaborated with many varieties. These compounds belong to the class of varietal aromas because they result from the cleavage of odorless precursors present in grapes or musts by yeast during alcoholic fermentation. The presence of varietal thiols in wine results from many factors affecting the precursor concentrations. This occurs at all levels in grapes, in their extracts, in their release during fermentation, and in their conservation at a convenient level until the wine is consumed. The presence of precursors in grapes depends on several viticultural factors, such as nitrogen and water nutrition, vine management, and maturity. After alcoholic fermentation, when thiols have been released, all of the technology employed must be focused against oxidation.

Devillier P.,CNRS Laboratory for Molecular and Pharmacological Mechanisms of Bronchial Obstruction | Devillier P.,Foch Hospital | Dreyfus J.-F.,Foch Hospital | Demoly P.,Montpellier University | And 2 more authors.
BMC Medicine | Year: 2014

Background: The capacity of sublingual allergen immunotherapy (SLIT) to provide effective symptom relief in pollen-induced seasonal allergic rhinitis is often questioned, despite evidence of clinical efficacy from meta-analyses and well-powered, double-blind, placebo-controlled randomized clinical trials. In the absence of direct, head-to-head, comparative trials of SLIT and symptomatic medication, only indirect comparisons are possible.Methods: We performed a meta-analysis of classes of products (second-generation H1-antihistamines, nasal corticosteroids and grass pollen SLIT tablet formulations) and single products (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor antagonist montelukast) for the treatment of seasonal allergic rhinitis in adults, adolescents and/or children. We searched the literature for large (n >100 in the smallest treatment arm) double-blind, placebo-controlled randomized clinical trials. For each drug or drug class, we performed a meta-analysis of the effect on symptom scores. For each selected trial, we calculated the relative clinical impact (according to a previously published method) on the basis of the reported post-treatment or season-long nasal or total symptom scores: 100 × (scorePlacebo - scoreActive)/scorePlacebo.Results: Twenty-eight publications on symptomatic medication trials and ten on SLIT trials met our selection criteria (total number of patients: n = 21,223). The Hedges' g values from the meta-analyses confirmed the presence of a treatment effect for all drug classes. In an indirect comparison, the weighted mean (range) relative clinical impacts were -29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, -17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and -6.5% (-3% to -10%) for montelukast.Conclusions: In an indirect comparison, grass pollen SLIT tablets had a greater mean relative clinical impact than second-generation antihistamines and montelukast and much the same mean relative clinical impact as nasal corticosteroids. This result was obtained despite the presence of methodological factors that mask the clinical efficacy of SLIT for the treatment of seasonal allergic rhinitis. © 2014 Devillier et al.; licensee BioMed Central Ltd.

Owens D.R.,University of Swansea | Monnier L.,Montpellier University | Bolli G.B.,University of Perugia
Diabetes and Metabolism | Year: 2013

Metabolic consequences of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are the result of enhanced glucose-stimulated insulin secretion, inhibition of glucagon release, delayed gastric emptying and increased satiety. These attributes make GLP-1 agonists a treatment option in type 2 diabetes mellitus (T2DM). To optimise treatment choice, a detailed understanding of the effects of GLP-1 RAs on glucose homeostasis in individuals with T2DM is necessary. Although the various GLP-1 RAs share the same basic mechanisms of action, differences in pharmacokinetic/pharmacodynamic characteristics translate into differential effects on parameters of glycaemia. Head-to-head comparisons between long-acting non-prandial (liraglutide once daily and exenatide once weekly) and shorter-acting prandial (exenatide twice daily and lixisenatide once daily prandial) GLP-1 RAs confirm their differential effects on fasting plasma glucose (FPG) and post-prandial glucose (PPG). Liraglutide once daily and exenatide once weekly demonstrate greater reductions in FPG but lesser impacts on PPG excursions plasma than exenatide twice daily. Prandial GLP-1 RAs have a profound effect on post-prandial glycaemia, mediated by delaying gastric emptying, which is not subject to the tachyphylaxis occurring due to the sustained elevated plasma GLP-1 concentrations after treatment with long-acting GLP-1 RAs. Lixisenatide once-daily prandial, in contrast to liraglutide, strongly suppresses post-prandial glucagon secretion, further contributing to the more pronounced PPG-lowering effect found with lixisenatide. Evidence suggests that the GLP-1 RAs that predominantly target the prandial glucose excursions, such as exenatide twice daily and lixisenatide once-daily prandial, are therefore best used as combination therapy with basal insulin and will form an important new treatment option for individuals with T2DM. © 2013.

Jousselin E.,French National Institute for Agricultural Research | Coeur D'Acier A.,French National Institute for Agricultural Research | Vanlerberghe-Masutti F.,French National Institute for Agricultural Research | Duron O.,Montpellier University
Molecular Ecology | Year: 2013

Endosymbiotic bacteria are important drivers of insect evolutionary ecology, acting both as partners that contribute to host adaptation and as subtle parasites that manipulate host reproduction. Among them, the genus Arsenophonus is emerging as one of the most widespread lineages. Its biology is, however, entirely unknown in most cases, and it is therefore unclear how infections spread through insect populations. Here we examine the incidence and evolutionary history of Arsenophonus in aphid populations from 86 species, characterizing the processes that shape their diversity. We identify aphids as harbouring an important diversity of Arsenophonus strains. Present in 7% of the sampled species, incidence was especially high in the Aphis genus with more than 31% of the infected species. Phylogenetic investigations revealed that these Arseno-phonus strains do not cluster within an aphid-specific clade but rather exhibit distinct evolutionary origins showing that they undergo repeated horizontal transfers (HT) between distantly related host species. Their diversity pattern strongly suggests that ecological interactions, such as plant mediation and parasitism, are major drivers for Arsenophonus dispersal, dictating global incidence across insect communities. Notably, plants hosting aphids may be important ecological arenas for global exchange of Arsenophonus, serving as reservoirs for HT. © 2012 Blackwell Publishing Ltd.

Bershtein M.A.,Independent University of Moscow | Fateev V.A.,Montpellier University | Litvinov A.V.,Rutgers University
Nuclear Physics B | Year: 2011

In this paper we consider parafermionic Liouville field theory. We study integral representations of three-point correlation functions and develop a method allowing us to compute them exactly. In particular, we evaluate the generalization of Selberg integral obtained by insertion of parafermionic polynomial. Our result is justified by different approach based on dual representation of parafermionic Liouville field theory described by three-exponential model. © 2011 Elsevier B.V.

Berngruber T.W.,CNRS Center of Evolutionary and Functional Ecology | Froissart R.,Montpellier SupAgro | Froissart R.,Montpellier University | Choisy M.,Montpellier University | And 2 more authors.
PLoS Pathogens | Year: 2013

Theory predicts that selection for pathogen virulence and horizontal transmission is highest at the onset of an epidemic but decreases thereafter, as the epidemic depletes the pool of susceptible hosts. We tested this prediction by tracking the competition between the latent bacteriophage λ and its virulent mutant λcI857 throughout experimental epidemics taking place in continuous cultures of Escherichia coli. As expected, the virulent λcI857 is strongly favored in the early stage of the epidemic, but loses competition with the latent virus as prevalence increases. We show that the observed transient selection for virulence and horizontal transmission can be fully explained within the framework of evolutionary epidemiology theory. This experimental validation of our predictions is a key step towards a predictive theory for the evolution of virulence in emerging infectious diseases. © 2013 Berngruber et al.

Emery P.,University of Leeds | Hammoudeh M.,Hamad Medical | FitzGerald O.,St Vincents University Hospital | Combe B.,Montpellier University | And 7 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND: We assessed the effects of reduction and withdrawal of treatment in patients with rheumatoid arthritis who had a remission while receiving etanercept-plus-methotrexate therapy. METHODS: Patients with early active disease who had not previously received methotrexate or biologic therapy received 50 mg of etanercept plus methotrexate weekly for 52 weeks (open-label phase). We then randomly assigned patients who had qualifying responses at weeks 39 and 52 to receive 25 mg of etanercept plus methotrexate (combination-therapy group), methotrexate alone, or placebo for 39 weeks (double-blind phase). Patients who had qualifying responses at week 39 of the double-blind phase had all treatment withdrawn at that time and were followed to week 65 (treatment-withdrawal phase). The primary end point was the proportion of patients with sustained remission in the double-blind phase. RESULTS: Of 306 patients enrolled, 193 underwent randomization in the double-blind phase; 131 qualified for the treatment-withdrawal phase. More patients in the combination-therapy group than in the methotrexate-alone group or the placebo group met the criterion for the primary end point (40 of 63 [63%] vs. 26 of 65 [40%] and 15 of 65 [23%], respectively; P=0.009 for combination therapy vs. methotrexate alone; P<0.001 for combination therapy vs. placebo). At 65 weeks, 28 patients (44%) who had received combination therapy, 19 (29%) who had received methotrexate alone, and 15 (23%) who had received placebo were in remission (P=0.10 for combination therapy vs. methotrexate alone; P=0.02 for combination therapy vs. placebo; P=0.55 for methotrexate alone vs. placebo). No significant between-group differences were observed in radiographic progression of disease. Serious adverse events were reported in 3 patients (5%) in the combination-therapy group, 2 (3%) in the methotrexate-alone group, and 2 (3%) in the placebo group. CONCLUSIONS: In patients with early rheumatoid arthritis who had a remission while receiving full-dose etanercept-plus-methotrexate therapy, continuing combination therapy at a reduced dose resulted in better disease control than switching to methotrexate alone or placebo, but no significant difference was observed in radiographic progression. Copyright © 2014 Massachusetts Medical Society.

Morquette P.,University of Montréal | Verdier D.,University of Montréal | Kadala A.,University of Montréal | Fethiere J.,University of Montréal | And 4 more authors.
Nature Neuroscience | Year: 2015

Communication between neurons rests on their capacity to change their firing pattern to encode different messages. For several vital functions, such as respiration and mastication, neurons need to generate a rhythmic firing pattern. Here we show in the rat trigeminal sensori-motor circuit for mastication that this ability depends on regulation of the extracellular Ca 2+ concentration ([Ca 2+ ] e) by astrocytes. In this circuit, astrocytes respond to sensory stimuli that induce neuronal rhythmic activity, and their blockade with a Ca 2+ chelator prevents neurons from generating a rhythmic bursting pattern. This ability is restored by adding S100β, an astrocytic Ca 2+ -binding protein, to the extracellular space, while application of an anti-S100β antibody prevents generation of rhythmic activity. These results indicate that astrocytes regulate a fundamental neuronal property: the capacity to change firing pattern. These findings may have broad implications for many other neural networks whose functions depend on the generation of rhythmic activity. © 2015 Nature America, Inc.

Middleton A.M.,The Interdisciplinary Center | Farcot E.,Montpellier University | Owen M.R.,University of Nottingham | Vernoux T.,French National Institute for Agricultural Research
Plant Cell | Year: 2012

We now have unprecedented capability to generate large data sets on the myriad genes and molecular players that regulate plant development. Networks of interactions between systems components can be derived from that data in various ways and can be used to develop mathematical models of various degrees of sophistication. Here, we discuss why, in many cases, it is productive to focus on small networks. We provide a brief and accessible introduction to relevant mathematical and computational approaches to model regulatory networks and discuss examples of small network models that have helped generate new insights into plant biology (where small is beautiful), such as in circadian rhythms, hormone signaling, and tissue patterning. We conclude by outlining some of the key technical and modeling challenges for the future. © 2012 American Society of Plant Biologists. All rights reserved.

Owens D.R.,University of Swansea | Matfin G.,International Diabetes Center | Monnier L.,Montpellier University
Diabetes/Metabolism Research and Reviews | Year: 2014

Insulin remains the most effective and consistent means of controlling blood glucose levels in diabetes. Since 1946, neutral protamine Hagedorn (NPH) has been the predominant basal insulin in clinical use. However, absorption is variable due to the need for resuspension and the time-action profile (peak activity 4-6h after subcutaneous administration) confers an increased propensity for between-meal and nocturnal hypoglycaemia. In the 1980s, recombinant DNA technology enabled modifications to the insulin molecule resulting in the soluble long-acting insulin analogues, glargine and detemir. Both exhibit a lower risk of hypoglycaemia compared with neutral protamine Hagedorn due to improved time-action profiles and reduced day-to-day glucose variability. Glargine is indicated for administration once daily and detemir once or twice daily. Degludec is the latest prolonged-acting insulin which forms long subcutaneous multi-hexamers that delay absorption. Recent phase III trials in type 1 and type 2 diabetes show that degludec was non-inferior to comparators (predominantly glargine) with a minimal although inconsistent reduction in overall hypoglycaemia and a small absolute difference in nocturnal hypoglycaemia. Newer developmental agents include LY2605541 and glargine U300. LY2605541 comprises insulin lispro combined with polyethylene glycol, thereby increasing its hydrodynamic size and retarding absorption from the subcutaneous tissue. Glargine U300 is a new formulation of glargine resulting in a flatter and more prolonged time-action profile than its predecessor. This article reviews recent advances in basal insulin analogues, including a critical appraisal of the degludec trials. © 2013 John Wiley & Sons, Ltd.

Glemin S.,Montpellier University | Clement Y.,Montpellier University | Clement Y.,Montpellier SupAgro | David J.,Montpellier SupAgro | Ressayre A.,French National Institute for Agricultural Research
Trends in Genetics | Year: 2014

In angiosperms (as in other species), GC content varies along and between genes, within a genome, and between genomes of different species, but the reason for this distribution is still an open question. Grass genomes are particularly intriguing because they exhibit a strong bimodal distribution of genic GC content and a sharp 5'-3' decreasing GC content gradient along most genes. Here, we propose a unifying model to explain the main patterns of GC content variation at the gene and genome scale. We argue that GC content patterns could be mainly determined by the interactions between gene structure, recombination patterns, and GC-biased gene conversion. Recent studies on fine-scale recombination maps in angiosperms support this hypothesis and previous results also fit this model. We propose that our model could be used as a null hypothesis to search for additional forces that affect GC content in angiosperms. © 2014 Elsevier Ltd.

Zele F.,IRD Montpellier | Zele F.,Montpellier University | Zele F.,CNRS Center of Evolutionary and Functional Ecology
Proceedings. Biological sciences / The Royal Society | Year: 2014

Current views about the impact of Wolbachia on Plasmodium infections are almost entirely based on data regarding artificially transfected mosquitoes. This work has shown that Wolbachia reduces the intensity of Plasmodium infections in mosquitoes, raising the exciting possibility of using Wolbachia to control or limit the spread of malaria. Whether natural Wolbachia infections have the same parasite-inhibiting properties is not yet clear. Wolbachia-mosquito combinations with a long evolutionary history are, however, key for understanding what may happen with Wolbachia-transfected mosquitoes after several generations of coevolution. We investigate this issue using an entirely natural mosquito-Wolbachia-Plasmodium combination. In contrast to most previous studies, which have been centred on the quantification of the midgut stages of Plasmodium, we obtain a measurement of parasitaemia that relates directly to transmission by following infections to the salivary gland stages. We show that Wolbachia increases the susceptibility of Culex pipiens mosquitoes to Plasmodium relictum, significantly increasing the prevalence of salivary gland stage infections. This effect is independent of the density of Wolbachia in the mosquito. These results suggest that naturally Wolbachia-infected mosquitoes may, in fact, be better vectors of malaria than Wolbachia-free ones.

Ferrara A.,University of Milan | Nikolov A.,Open University Milton Keynes | Scharffe F.,Montpellier University
International Journal on Semantic Web and Information Systems | Year: 2011

By specifying that published datasets must link to other existing datasets, the 4th linked data principle ensures a Web of data and not just a set of unconnected data islands. The authors propose in this paper the term data linking to name the problem of finding equivalent resources on the Web of linked data. In order to perform data linking, many techniques were developed, finding their roots in statistics, database, natural language processing and graph theory. The authors begin this paper by providing background information and terminological clarifications related to data linking. Then a comprehensive survey over the various techniques available for data linking is provided. These techniques are classified along the three criteria of granularity, type of evidence, and source of the evidence. Finally, the authors survey eleven recent tools performing data linking and we classify them according to the surveyed techniques. © 2011 IGI Global.

Agency: Cordis | Branch: H2020 | Program: SGA-RIA | Phase: FETFLAGSHIP | Award Amount: 89.00M | Year: 2016

This project is the second in the series of EC-financed parts of the Graphene Flagship. The Graphene Flagship is a 10 year research and innovation endeavour with a total project cost of 1,000,000,000 euros, funded jointly by the European Commission and member states and associated countries. The first part of the Flagship was a 30-month Collaborative Project, Coordination and Support Action (CP-CSA) under the 7th framework program (2013-2016), while this and the following parts are implemented as Core Projects under the Horizon 2020 framework. The mission of the Graphene Flagship is to take graphene and related layered materials from a state of raw potential to a point where they can revolutionise multiple industries. This will bring a new dimension to future technology a faster, thinner, stronger, flexible, and broadband revolution. Our program will put Europe firmly at the heart of the process, with a manifold return on the EU investment, both in terms of technological innovation and economic growth. To realise this vision, we have brought together a larger European consortium with about 150 partners in 23 countries. The partners represent academia, research institutes and industries, which work closely together in 15 technical work packages and five supporting work packages covering the entire value chain from materials to components and systems. As time progresses, the centre of gravity of the Flagship moves towards applications, which is reflected in the increasing importance of the higher - system - levels of the value chain. In this first core project the main focus is on components and initial system level tasks. The first core project is divided into 4 divisions, which in turn comprise 3 to 5 work packages on related topics. A fifth, external division acts as a link to the parts of the Flagship that are funded by the member states and associated countries, or by other funding sources. This creates a collaborative framework for the entire Flagship.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.2.1-7 | Award Amount: 10.33M | Year: 2009

Mitochondrial dysfunction is a major hallmark of various neurodegenerative disorders including Alzheimers disease, Parkinsons disease, Huntingtons diseases or Amyotrophic Lateral Sclerosis (ALS). However linking mitochondrial dysfunction to the pathogenesis of some of these diseases still needs to be elucidated. Furthermore, in pathologies where this link is already established, the question remains whether specific targets or mechanisms involved in mitochondrial dysfunction will be amenable to therapeutic intervention. MitoTarget is an ambitious project aimed at providing solid data to better understand and exploit the circumstantial evidence linking mitochondrial dysfunction with neuronal dysfunction culminating in neurodegenerative disease. A 36 months translational research program will bring together a unique partnership between basic scientists, a seasoned team of clinical investigators and a SME that has identified a first-in-class compound, TRO19622, that targets mitochondria and has powerful neuroprotective and neuroregenerative activities. In parallel, and orchestrated by the SME that is the coordinator of the project, MitoTarget will bring together a more comprehensive insight into the mechanisms leading to mitochondrial impairments and establish their clinical relevance in a severe orphan neurodegenerative disease, ALS. If successful, it is expected that from this proof of principle a new class of therapeutic agents targeting the underlying mitochondrial dysfunction in neurons or their supporting cells will emerge. Results of the project have the potential to create a new paradigm for the drug discovery for neurodegenerative diseases.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.3.1-1 | Award Amount: 7.75M | Year: 2014

Transition to adulthood is the period of onset of most of the serious mental disorders that disable or kill in adult life. Current service configuration of distinct Child and Adolescent Mental Health (CAMHS) and Adult Mental Health (AMHS) Services is considered the weakest link where the care pathway should be most robust. Transition-related discontinuity of care is a major socioeconomic and societal challenge for the EU. The MILESTONE project is an EU-wide study determining care gaps in current services across diverse healthcare systems and robustly evaluating an innovative transitional care model. In ten high-quality work packages we will map current services and transitional policies across EU; develop and validate transition-specific outcomes measures; conduct a longitudinal cohort study of transition process and outcomes across eight EU countries; develop and test, in a cluster-randomised trial, the clinical and cost-effectiveness of an innovative transitional care model; create clinical, organisational, policy and ethics guidelines for improving care and outcomes for transition age youth; and develop and implement training packages for clinicians across EU. The project will provide robust evidence for the most cost-effective way to meet the as-yet-unmet need of young people who fall through the CAMHS-AMHS divide; facilitate the development of integrated models of care and function; improve health care outcomes and system efficiencies; and ensure take-up of best practice. The project has active and intensive participation of young people, carers, advocacy groups and key stakeholders and involves two SMEs, Concentris and HealthTracker. Findings from the project will transform mental health care in EU for young people. Our results will assist policy makers in making informed and evidence-based decisions for improving health systems, enhancing patient outcomes, quality of life, service satisfaction, and improving health status at individual and population levels.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.4.2-3 | Award Amount: 3.75M | Year: 2010

The emergence of suicidality in patients receiving drug treatment is of concern because of the overall burden and the possible link with completed suicide. The lack of uniform requirements for defining, detecting and recording suicidality and the presence of disease related confounders create major problems. It is possible that Medication-Related Suicidality (MRS) differs from Psychopathology-Related Suicidality (PRS) in terms of phenomenology, clinical expression and time course, and may vary between children and adults. Unlike PRS, the time-course of MRS may be associated with possible differences in drug pharmacokinetics; abrupt onset; absence of suicidality prior to start of medication; and emergence of suicidality related co-morbidities after treatment. This proposal will focus on developing a web-based comprehensive methodology for the assessment and monitoring of suicidality and its mediators in children and adolescents using the HealthTrackerTM (a paediatric web-based health outcome monitoring system), with the aim of developing a Suicidality Assessment and Monitoring Module, a Bio-psycho-social Mediators of Suicidality Assessment Module, and a Suicidality-Related Psychiatric and Physical Illness Module. The information obtained will be used to computer-generate classification of suicidality using the Classification of Suicide-Related Thoughts and Behaviour (Silverman et al, 2007) and the Columbia Classification Algorithm of Suicidal Assessment (C-CASA) (Posner et al, 2007). The existing Medication Characteristics Module will be expanded to allow documentation of pharmacological characteristics of medication, to explore whether they mediate MRS. The methodology will then be tested in 3 paediatric observational trials (risperidone in conduct disorder; fluoxetine in depression, and montelukast in bronchial asthma) and standardized, which can be used pharmacovigilance and in epidemiological, observational, and registration trials.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 3.82M | Year: 2012

Parasites exact a devastating toll on health and economic productivity, infecting man and also domestic livestock. Drugs used to combat parasitic diseases are deficient in many ways and new, better drugs are needed to establish sustainable means to combat diseases caused by protozoan parasites that include malaria, trypanosomiasis and leishmaniasis in man, and coccidiosis among others in animals. This ITN will train a new generation of European scientists in the requisites of preclinical drug discovery, combining academic excellence in innovation with industrial rigor and thus providing training from an industrial and academic perspective. The programme works on the premise that parasite metabolism offers a multitude of potential targets that can be exploited for drug design. Advances in genomics, transcriptomics, metabolomics and protein chemistry, alongside computational systems biology are integral to the activities of the network. The programme is populated with projects at all levels of the preclinical drug discovery cascade to ensure ESRs and ERs are exposed to requirements and aspects of every step of this process. Therefore aspects of drug design, medicinal chemistry and small molecule screening will also be central to the programme. ESRs will perform research in two different laboratories providing them with multidisciplinary intersectoral training that we consider essential for the development of a highly skilled, knowledgeable new generation of researchers capable of innovation and application of research in a research area of global importance to human health..

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: WASTE-7-2015 | Award Amount: 7.82M | Year: 2016

NoAW : No Agro-Waste. Innovative approaches to turn agricultural waste into ecological and economic assets. Driven by a near zero-waste society requirement, the goal of NoAW project is to generate innovative efficient approaches to convert growing agricultural waste issues into eco-efficient bio-based products opportunities with direct benefits for both environment, economy and EU consumer. To achieve this goal, the NoAW concept relies on developing holistic life cycle thinking able to support environmentally responsible R&D innovations on agro-waste conversion at different TRLs, in the light of regional and seasonal specificities, not forgetting risks emerging from circular management of agro-wastes (e.g. contaminants accumulation). By involving all agriculture chain stakeholders in a territorial perspective, the project will: (1) develop innovative eco-design and hybrid assessment tools of circular agro-waste management strategies and address related gap of knowledge and data via extensive exchange through the Knowledge exchange Stakeholders Platform, (2) develop breakthrough knowledge on agro-waste molecular complexity and heterogeneity in order to upgrade the most widespread mature conversion technology (anaerobic digestion) and to synergistically eco-design robust cascading processes to fully convert agro-waste into a set of high added value bio-energy, bio-fertilizers and bio-chemicals and building blocks, able to substitute a significant range of non-renewable equivalents, with favourable air, water and soil impacts and (3) get insights of the complexity of potentially new, cross-sectors, business clusters in order to fast track NoAW strategies toward the field and develop new business concepts and stakeholders platform for cross-chain valorisation of agro-waste on a territorial and seasonal basis.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: ENV.2007. | Award Amount: 5.60M | Year: 2009

The implementation of the WFD in catchments with temporary rivers presents a significant challenge for watershed managers. The MIRAGE project will, for the first time, comprehensively investigate the applicability of specific management options under the characteristic flush and drought conditions of temporary streams. Through investigations in seven basins, MIRAGE will provide a framework for managing the many Mediterranean water bodies dominated by temporary waters. MIRAGE will deploy a multi-scale approach to improve understanding of temporary river responses to hydrologic, biogeochemical and sediment transport events. The principal research and project objectives of MIRAGE are to (1) provide an applicable and transferable set of reference conditions for temporary streams, specifically linking terrestrial and aquatic ecology; (2) determine effects of dry periods on accumulation and transformation of nutrients, sediments and hazardous substances on land and in river channels, at selected sites with test catchments. (3) specify and test measures to support achieving good ecological and water quality status including the integration of up- and downstream management. This will be done initially for the two mirror basins Candelaro (Italy) and Evrotas (Greece) in close cooperation with local water management organisations; (4) support the implementation of the WFD and the development of strategies for integrated water resources management for Mediterranean river basins, generalising from the Mirror Basins on the basis of modern ecohydrology concepts, in the context of characterising runoff regimes and flood responses on a regional basis. Five other Mediterranean catchments, including one in Morocco, will be used as the primary focus for this work; The transfer of experience and the establishment of common guidelines is then seen as a significant support for WFD implementation across the region.

Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.89M | Year: 2017

Reliability and radiation damage issues have a long and important history in the domain of satellites and space missions. Qualification standards were established and expertise was built up in space agencies (ESA), supporting institutes and organizations (CNES, DLR, etc.) as well as universities and specialized companies. During recent years, radiation concerns are gaining attention also in aviation, automotive, medical and other industrial sectors due to the growing ubiquity and complexity of electronic systems and their increased radiation sensitivity owing to technology scaling. This raises the demand for dedicated design and qualification guidelines, as well as associated technical expertise. Addressing open questions linked to respective qualification requirements, the proposed training network RADiation and Reliability Challenges for Electronics used in Space, Aviation, Ground and Accelerators (RADSAGA) will for the first time bring together industry, universities, laboratories and test-facilities in order to innovate and train young scientists and engineers in all aspects related to electronics exposed to radiation. The expertise of the space and avionics sectors will be complemented with new and unique test facilities, design and qualification methodologies of the accelerator sector, promising for other application areas. Driven by the industrial needs, the students will be trained by established specialists in all required skills, and acquire expertise through innovative scientific projects, allowing to: (i) push the scientific frontier in design, testing and qualification of complex electronic systems for mixed field radiation environments (ii) establish related courses to train future engineers/physicists; and (iii) issue design and test guidelines to support industry in the field, protecting European competitiveness when radiation effects become as important as thermal or mechanical constraints for the aviation, automotive and other industrial sectors.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.4-2 | Award Amount: 3.88M | Year: 2012

Disorders of sex development (DSD) are a conglomerate of rare diseases with an estimated incidence of 1: 4500. The causes of DSD are mainly disorders with gonadal dysgenesis, decreased androgen synthesis or function in XY males or disorders with elevated androgen production in XX females. Decision on sex of rearing is difficult in some cases as the prenatal androgen imbalances result in ambiguous genitalia at birth and furthermore they are likely to influence psychosexual development. Genital constructive surgery is needed in most cases. Lifelong cortisone replacement is needed in DSD due to defects of cortisone synthesis. Sex hormone substitution is indicated in many cases of DSD in puberty and adult life. Decision of sex of rearing, genital surgery and hormone therapies have a life-long impact on the affected individuals, which become evident mainly after puberty. In many cases psychological counselling is advised. Interpretation of previous outcome studies of DSD is hampered by small patient numbers and conglomerates of diagnoses and therapies. The study DSD-Life investigates and compares the long-term outcome of different off-label treatments in adequate numbers of adolescents and adults with different known genetic entities of DSD to develop evidence base guidelines for treatment of DSD for which no dedicated treatment is currently approved. To reach this aim, the influences and interrelations of sex assignment, genital surgery, hormone therapy, metabolism, fertility, psychological intervention but also cultural influences and patients and parents views on psychosocial adaption, health related quality of life and psychological well-being and will be investigated. The long-term impact of the study will be improvement of care and subsequently higher quality of life with better integration and participation of individuals with DSD in the society.

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-1.4-1;HEALTH-2009-1.4-3 | Award Amount: 12.08M | Year: 2010

Osteoarthritis (OA) is a degenerative joint disease for which no efficient therapy is available. The ADIPOA consortium has previously shown that intraarticular injections of stromal cells prevents OA in two different models, but the mechanisms of this chondroprotective effect remains unknown, and the activation of cartilage derived endogenous stem cells is suspected. The participants have experience on cell therapy, logistic and production facilities for adipose derived stromal cells (ASC) and clinical studies focusing on cartilage repair. They have shown that stromal cells have anti-inflammatory and antiapoptosis effets, prevent cells from senescence and protect endogenous cells from oxidative stress. ASC are well described, and the procedure to expand the ASC in GMP clinical grade by one of us has been approved by regulatory authorities. This has prompted us to propose an original and innovative regenerative medicine approach for OA in a four years programme organised around 6 workpackages : WP 1 ASC biology, cell processing & optimization for chondral protection WP 2 In vivo validation of chondroprotective effect of ASC WP 3 Safety, Security & regulatory issues WP 4 Clinical trial endogenous ASC injected intraarticular in OA WP 5 Management and Coordination WP 6 Training and Education ADIPOA project will then lead to the optimisation and standardisation of production procedures. In vivo validation and optimisation shall lead to a phase 1 clinical trial and the design and initiation of a phase 2 controlled study in OA. The ADIPOA Consortium comprises 10 academic and 2 sme participants and gathers researchers and clinicians with expertise in clinical research, chondrocytes and adipose stem cell biology and regenerative medicine. The Sme participation will ensure the dissemination of the project results. The critical mass achieved by the ADIPOA Consortium should enable clinical applications in OA.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: ISIB-06-2015 | Award Amount: 6.21M | Year: 2016

CELBICON aims at the development, from TRL3 to TRL5, of new CO2-to-chemicals technologies, conjugating at once small-scale for an effective decentralized market penetration, high efficiency/yield, low cost, robustness, moderate operating temperatures and low maintenance costs. In line with the reference Topic text, these technologies will bridge cost-effective CO2 capture and purification from the atmosphere through sorbents (with efficient heat integration of the CO2 desorption step with the subsequent process stages), with electrochemical conversion of CO2 (via PEM electrolysis concepts, promoting CO2 reduction at their cathode in combination with a fruitful oxidation carried out simultaneously at the anode), followed by bioreactors carrying out the fermentation of the CO2-reduction intermediates (syngas, C1 water-soluble molecules) to form valuable products (bioplastics like Poly-Hydroxy-Alkanoates - PHA -, isoprene, lactic acid, methane, etc.) as well as effective routes for their recovery from the process outlet streams. A distinctive feature of the CELBICON approach is the innovative interplay and advances of key technologies brought in by partners (high-tech SMEs & companies, research centres) to achieve unprecedented yield and efficiency results along the following two processing lines: i) High pressure process line tailored to the production of a PHA bioplastic and pressurized methane via intermediate electrochemical generation of pressurized syngas followed by specific fermentation steps; ii) Low pressure processing line focused on the production of value-added chemicals by fermentation of CO2-reduction water-soluble C1 intermediates. Over a 42 months project duration, the two process lines described will undergo a thorough component development R&D programme so as to be able to assemble three optimised TRL5 integrated test-rigs (one per TP) to prove the achievement of all the quantified techno-economical targets.

French National Center for Scientific Research, National Graduate School of Chemistry, Montpellier and Montpellier University | Date: 2013-07-08

The invention concerns a mono- or polyfunctional polysilylated organosilane compound, and the method for preparing same.

Calderon M.A.,Imperial College London | Cox L.,Nova Southeastern University | Casale T.B.,Creighton University | Moingeon P.,Stallergenes SA | Demoly P.,Montpellier University
Journal of Allergy and Clinical Immunology | Year: 2012

In allergen immunotherapy there is debate as to whether polysensitized patients are best treated with many allergens simultaneously (chosen according to the sensitization profile, a predominantly North American approach) or a single allergen (chosen according to the most clinically problematic allergy, a predominantly European approach). In patients seeking treatment for moderate-to-severe respiratory allergies, polysensitization is more prevalent (range, 50% to 80%) than monosensitization in both the United States and Europe. Safe, effective, single-allergen preparations will most likely have been tested in polysensitized patients. In robust, large-scale clinical trials of grass pollen sublingual tablets, polysensitized patients benefited at least as much from allergen immunotherapy as monosensitized patients. A recent review of multiallergen immunotherapy concluded that simultaneous delivery of multiple unrelated allergens can be clinically effective but that there was a need for additional investigation of therapy with more than 2 allergen extracts (particularly in sublingual allergen immunotherapy). More work is also required to determine whether single-allergen and multiallergen immunotherapy protocols elicit distinct immune responses in monosensitized and polysensitized patients. Sublingual and subcutaneous multiallergen immunotherapy in polysensitized patients requires more supporting data to validate its efficacy in practice. © 2012 American Academy of Allergy, Asthma & Immunology.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2011.9.13 | Award Amount: 14.27M | Year: 2011

There is a continued need for higher compute performance: scientific grand challenges, engineering, geophysics, bioinformatics, etc. However, energy is increasingly becoming one of the most expensive resources and the dominant cost item for running a large supercomputing facility. In fact the total energy cost of a few years of operation can almost equal the cost of the hardware infrastructure. Energy efficiency is already a primary concern for the design of any computer system and it is unanimously recognized that Exascale systems will be strongly constrained by power.\n\nThe analysis of the performance of HPC systems since 1993 shows exponential improvements at the rate of one order of magnitude every 3 years: One petaflops was achieved in 2008, one exaflops is expected in 2020. Based on a 20 MW power budget, this requires an efficiency of 50 GFLOPS/Watt. However, the current leader in energy efficiency achieves only 1.7 GFLOPS / Watt. Thus, a 30x improvement is required.\n\nIn this project, we believe that HPC systems developed from todays energy-efficient solutions used in embedded and mobile devices are the most likely to succeed. As of today, the CPUs of these devices are mostly designed by ARM. However, ARM processors have not been designed for HPC, and ARM chips have never been used in HPC systems before, leading to a number of significant challenges.\n\nThe Mont-Blanc project has three objectives:\n- To develop a fully functional energy-efficient HPC prototype using low-power commercially available embedded technology\n- To design a next-generation HPC system together with a range of embedded technologies in order to overcome the limitations identified in the prototype system\n- To develop a portfolio of exascale applications to be run on this new generation of HPC systems.\n\nThis will produce a new type of computer architecture capable of setting future global HPC standards that will provide Exascale performance using 15 to 30 times less energy.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2013.12.1 | Award Amount: 11.49M | Year: 2013

The Mont-Blanc project aims to develop a European Exascale approach leveraging on commodity power-efficient embedded technologies. The project has developed a HPC system software stack on ARM, and will deploy the first integrated ARM-based HPC prototype by 2014, and is also working on a set of 11 scientific applications to be ported and tuned to the prototype system.\n\nThe rapid progress of Mont-Blanc towards defining a scalable power efficient Exascale platform has revealed a number of challenges and opportunities to broaden the scope of investigations and developments. Particularly, the growing interest of the HPC community in accessing the Mont-Blanc platform calls for increased efforts to setup a production-ready environment.\n\nThe Mont-Blanc 2 proposal has 4 objectives:\n1. To complement the effort on the Mont-Blanc system software stack, with emphasis on programmer tools (debugger, performance analysis), system resiliency (from applications to architecture support), and ARM 64-bit support\n2. To produce a first definition of the Mont-Blanc Exascale architecture, exploring different alternatives for the compute node (from low-power mobile sockets to special-purpose high-end ARM chips), and its implications on the rest of the system\n3. To track the evolution of ARM-based systems, deploying small cluster systems to test new processors that were not available for the original Mont-Blanc prototype (both mobile processors and ARM server chips)\n4. To provide continued support for the Mont-Blanc consortium, namely operations of the Mont-Blanc prototype, and hands-on support for our application developers\n\nMont-Blanc 2 contributes to the development of extreme scale energy-efficient platforms, with potential for Exascale computing, addressing the challenges of massive parallelism, heterogeneous computing, and resiliency. Mont-Blanc 2 has great potential to create new market opportunities for successful EU technology, by placing embedded architectures in servers and HPC.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.2.2-2 | Award Amount: 3.88M | Year: 2012

The increasing number of elderly people will have a major impact on the prevalence of age-related diseases, which will pose major challenges to keep health systems in Europe sustainable. Current knowledge is insufficient to identify the transition of normal brain ageing into Alzheimer`s Disease (AD)-like brain damage. Elucidation of the genes and pathways contributing to the earliest stages of AD pathology and associated neurodegeneration should be instrumental to allow intervention when the condition is still reversible. The aim of the DEVELAGE project is to characterise shared molecular pathways between early developmental processes in the brain and brain ageing. Our concept is based on the hypothesis that disorders of neural development contribute to age-related neurodegeneration, that developmentally essential proteins might have a role in neurodegeneration, and that neurodegeneration-related proteins and genes are important during the development of the brain. The DEVELAGE approach is unique in that it is brain tissue-based, derived from neuropathological diagnosis with detailed molecular analysis of the spectrum of developmental and ageing changes in the very same brain samples used for a comprehensive array of investigations in humans as well as in experimental models at genetic, epigenetic, transcription and protein levels. DEVELAGE contributes to the understanding of biological variation by examining relevant number of cases with different phases of ageing and neurodegeneration as well as developing brains with or without developmental disorders. Pathways examined in humans will be validated in animal models, including a non-human primate, and vice versa. The combination of human samples and animal models susceptible to experimental manipulation will promote the translation of clinically relevant data into experimentally testable predictions and promotes the exploitation of therapeutically relevant targets to reverse or halt disease progresssion.

Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: SiS.2013.2.2.1-1 | Award Amount: 2.90M | Year: 2014

The overall aim of the EC call is building up a scientifically literate society, which enables its citizens to participate in the research and innovation process as part of Responsible Research and Innovation (RRI). This calls for democratic citizenship education, in which two educational approaches, often presented independently in schools, are integrated, viz. Inquiry-Based Science Education (IBSE) and Socio-Scientific Issues-Based Learning (SSI). We call this integrated approach Socio-Scientific Inquiry-Based Learning (SSIBL). The aim of the project is to collect and share existing best practices across Europe and develop learning tools, materials and in/pre-service training courses for science teachers based on the SSIBL approach. This educational methodology promotes democratic citizenship through the integration of social issues and related scientific knowledge. Our aim is to empower and facilitate science teachers and teacher educators, by in-service and pre-service professional development courses, based on reshaped best practices available among the partners. These shared selected best practices will be reflected on from an RRI perspective and improved by an international community of learners who incorporate RRI in their teaching and learning processes. The project will establish a multidisciplinary team and facilitate networking activities among teachers, teacher educators and educational researchers of 18 institutions in 11 countries. In addition, the project will build on recently developed IBSE insights and foster implementation of IBSE in educational practice.

Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.91M | Year: 2016

The SUBITOP ETN is a framework for training and career development of young researchers in Geodynamics, Geophysics, Geology and Geomorphology. It has a scientific focus on the dynamics of continental margins where tectonic plates are recycled through subduction. Subduction processes have shaped and govern many aspects of the topography of Europe, and other continents, and they determine the patterns and intensity of geological hazards such as earthquakes, volcanic activity and landsliding. The Training Network will imbue 15 young scientists with the ability to address the links between the geological processes within subduction zones and the processes that impact the Earths surface above, using a comprehensive range of modelling and observation techniques and exploiting the full diversity of active and ancient subduction systems within Europe. SUBITOP fuses research and training at ten leading centres of the Earth Sciences in Europe and forges partnerships with 15 companies for its fellows, with participants in eight countries. It will train Early Stage Researchers (ESR) through a structured programme of cross-disciplinary, collaborative research, and integrated skills and outreach activities. This experience-based training is centred on PhD projects, covering a spectrum of topics from the deep mechanics of subduction zones to the erosion of their uplifted topography. Together the projects probe the functioning of the subduction system in its entirety, and they are welded together by shared techniques, study sites and data sets. Through their projects, the ESRs will acquire skills in modelling and observation of coupled processes in complex geological systems. SUBITOP will also impart essential communication, outreach and career management skills, and first-hand experience of the private sector through project-specific secondments and co-supervision by industry partners, and embed its ESRs in the active TOPO-Europe research community.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2007.3.6 | Award Amount: 4.76M | Year: 2008

Amputation of a limb is a surgical intervention used as a last resort to remove irreparably damaged, diseased, or congenitally malformed limbs where retention of the limb is a threat to the well-being of the individual. The procedure traumatically alters the body image, but often leaves sensations that refer to the missing body part, the phantom limb. In 50-80% of cases, these sensations are painful and currently, there are no effective treatment modalities. Given sufficient control over a large number of nerve fibers, a neural interface may be able to artificially evoke sensations of touch, or counteract the phantom limb pain. The application of Micro/nano technologies with functional electrical micro stimulation can not only pave the road towards a treatment, but also also provide amputees a means to sense virtual environments directly. The ultimate aim of this project is to develop this novel Human Machine Interface (HMI). A novel microfabricated neural interface, the Thin-film Intrafascicular Multichannel Electrode array, and implantable multichannel stimulator system will form the key core technological developments in the project. The work is structured in 10 work packages in three phases. The technological development phase will model, design, manufacture and characterize the multi-channel electrode (TIME) and design, manufacture and test an implantable, multi-channel stimulator. In vivo characterization phase will evaluate the TIME electrodes for biocompatibility, stability and chronic safety in animals and develop a psychophysical test platform for system integration. Finally, pre-clinical evaluation will test the system in short-term implants in amputee subjects. The work will provide direct contribution to the next-generation smart systems in the ICT-2007.3.6 Nano/Micro priority, strengthen Europes leading position in advanced electronic systems/biomedical applications, and improve the quality of life for amputees with phantom limb pain

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: KBBE-2007-1-2-09 | Award Amount: 4.41M | Year: 2008

SELFDOTT proposes to implement knowledge already obtained on the artificial control of reproduction of the Atlantic bluefin tuna (BFT), Thunnus thynnus, to obtain viable eggs, and study embryonic and larval development for the production of fry (juveniles). At the same time, suitable and environmentally performing feeds for the growout of BFT will be developed, thus reducing or eliminating the practice of raw fish importation and feeding by the fattening industry. Wild juvenile and mature BFT will be reared in captivity at two sites in the Mediterranean, and will be used to study puberty, gametogenesis, and the influence of diet on reproductive maturation and gamete quality. Mature fish will be induced to spawn using hormone implants and the eggs will be collected using devices designed specifically for cages. To establish the knowledge-base for controlled development of BFT larvae, the mesocosm and artificial larval rearing methods will be employed. The ontogenesis of essential biological functions will be studied, including environmental perception, digestion, immunity and behaviour. A protocol for the commercial-scale larval rearing of BFT will be recommended at the end of the project. Whole body and stomach composition of wild fish will be analyzed and serve as a guide to formulate nutritionally complete artificial feeds for BFT. Juveniles will be captured from the wild, adapted to captive conditions and used to carry out weaning and feeding experiments, using moist and dry pelleted diets. The environmental impact of the formulated feeds will be examined and compared to existing raw-fish practises. SELFDOTT will produce the basic knowledge necessary for the development of a self-sustained aquaculture industry for the BFT in the Mediterranean, thus enhancing the competitiveness of the EU aquaculture industry, while at the same time reducing the pressure on the wild BFT stocks and ensuring the conservation and recovery of this magnificent fish.

Agency: Cordis | Branch: H2020 | Program: IA | Phase: ICT-28-2015 | Award Amount: 4.30M | Year: 2016

Drug hypersensitivity to antibiotics, mainly Beta-lactams (BLCs) affects more than 2.5 million European citizens. Moreover, preventable adverse drug reactions are estimated in additional hospitalization costs of 1750-4500 /patient. Currently, the allergy diagnosis is mainly based on the information given by invasive, single, and risky in vivo assays. In daily practice, few in vitro diagnostic methods are available and only used at the tertiary health services. These tests also lack of sensitivity (>0.35 kUA/L) and selectivity (<98%), resulting in an inaccurate diagnosis, analyze few drugs allergens (5), are time consuming (60-180 min), and expensive (30 /allergen). COBIOPHAD aims the development of an innovative in vitro diagnostic (IVD) device for diagnosis of IgE-mediated drug allergies by building an integrated biophotonic system based on compact disc technology. For that, key enabling technologies will be integrated in order to achieve high sensitive (<0.1 kUA/L), selective (>98%), multiplexed (10 BLCs), rapid (30 min), and low-cost (2.4 /allergen) drug allergy test. The solution involves an advanced approach to the diagnosis and management of drug allergy with the aim to ameliorate patient safety. The consortium comprises multidisciplinary knowledge on optics, electronics, advanced materials, biotechnology, smart microstructures, microfluidics, surface/organic chemistry, allergy, manufacturing systems, and telecom networking. Also, the key industrial actors, present in the consortium, will contribute to the manufacturing and placing the product on the IVD market.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-5 | Award Amount: 8.03M | Year: 2013

Amputation of a limb may result from trauma or surgical intervention. The amputation traumatically alters the body image, but often leaves sensations that refer to the missing body part. In 50-80% amputees, neuropathic pain develops, also called phantom limb pain (PLP). Both peripheral and central nervous system factors have been implicated as determinants of PLP. Also, PLP may be triggered by physical (changes in the weather) and psychological factors (emotional stress). Recent evidence suggests that PLP may be intricately related to neuroplastic changes in the cortex, and that these changes may modulated by providing sensory input to the stump or amputation zone. However, the understanding of why PLP occurs is still poor, the basic research results have not been tested on a large scale in the clinic, and there are no fully effective, long-term treatments readily available on the market. We aim to challenge the status-quo of PLP therapy by offering technological solutions that will invasively or non-invasively induce natural, meaningful sensations to the amputee to restore the neuroplastic changes in the cortex and thereby control and alleviate PLP. We will assess the effect of cortical neuroplastic, psychological and cognitive components of pain and integrate the knowledge into clinical guidelines. The proposed work directly targets the HEALTH.2013.2.2.1-5 topic. The consortium will build solutions based on existing technologies emerging from previous EU funded research which are presently only available in experimental settings. We believe that implementation of proposed work will be the cornerstone needed to exploit, validate and translate the basic research results into clinical applications and provide long-term, patient-specific solutions to a large group of patients suffering from PLP. The work will assist to improve the quality of life for amputees suffering from phantom limb pain and is of high socio-economic relevance to the EU.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: PEOPLE-2007-1-1-ITN | Award Amount: 2.98M | Year: 2008

Malaria exacts a devastating social and economic cost across the globe. Europe is at the forefront of the battle against this disease. It contains many of the leading malaria research groups, most of which are members of at least one of two consortia; BioMalPar, a Network of Excellence focused on basic research into the biology and pathology of malaria; and AntiMal, an integrated project aiming to develop a portfolio of new antimalarial drugs, urgently needed to meet the problems of drug-resistant malaria. To sustain the competitiveness of European malaria research into the future, there is a need to integrate these initiatives by the establishment of a broad-based training programme that emphasises the path from fundamental research to translation into disease control strategies. To address this need, it is proposed to establish an international training programme called InterMalTraining which will train a cohort of early stage researchers (ESR) to PhD level by means of collaborative malaria research projects. Each project will be jointly supervised by two principal investigators from separate partner institutions and usually different countries, affording a multicultural and multidisciplinary element to the training. Through this and additional broad-based, intensive training provided by experts from both the malaria research community and the industrial sector, it is intended to create a new generation of mobile, highly skilled young scientists who will be well acquainted with each other and with the leading malaria groups in Europe and beyond, enhancing their prospects for a career in their chosen area and suiting them to be future leaders in research institutions and industry. The cross-disciplinary nature of the training will have the breadth to ensure that it is applicable across and beyond the field of infectious diseases, allowing mobility of the young scientists into these areas and forging future links across the life sciences and into industry.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ENERGY.2013.2.4.1 | Award Amount: 13.30M | Year: 2013

The IMAGE project will develop a reliable science based exploration and assessment method to IMAGE geothermal reservoirs using an interdisciplinary approach based on three general pillars: 1 Understanding the processes and properties that control the spatial distribution of critical exploration parameters at European to local scales. The focus will be on prediction of temperatures, in-situ stresses, fracture permeability and hazards which can be deduced from field analogues, public datasets, predictive models and remote constraints. It provides rock property catalogues for 2 and 3. 2 Improving well-established exploration techniques for imaging and detection beyond the current state of the art and testing of novel geological, geophysical and geochemical methods to provide reliable information on critical subsurface exploration parameters. Methods include a) geophysical techniques such as ambient seismic noise correlation and magnetotellurics with improved noise filtering, b) fibre-optic down-hole logging tools to assess subsurface structure, temperature and physical rock properties, and c) the development of new tracers and geothermometers. 3 Demonstration of the added value of an integrated and multidisciplinary approach for site characterization and well-siting, based on conceptual advances, improved models/parameters and exploration techniques developed in 1 and 2. Further, it provides recommendations for a standardized European protocol for resource assessment and supporting models. The IMAGE consortium comprises the leading European geothermal research institutes and industry partners who will perform testing and validation of the new methods at existing geothermal sites owned by the industry partners, both in high temperature magmatic, including supercritical, and in basement/deep sedimentary systems. Application of the methods as part of exploration in newly developed fields will provide direct transfer from the research to the demonstration stage.

The I-MOVE\ Consortium includes European Union (EU) Public Health Institutes, SME and Universities. It aims at measuring and comparing the effectiveness (VE) and impact (VI) of influenza and Pneumococcal vaccines and vaccination strategies a in the elderly population in Europe. The goal is to develop a sustainable platform of primary care practices, hospitals and laboratory networks that share validated methods to evaluate post marketing vaccine performances. The objectives are to identify, pilot test, and disseminate in EU the best study designs to measure, on a real time basis, VE (direct effect) and the VI of vaccination programmes (indirect and overall effect) against laboratory confirmed cases of influenza (types/subtypes) and pneumococcal disease (serotypes), and clinical outcomes. Cost effectiveness analysis will be conducted. Results will allow to understand factors affecting specific VE, the duration of protection of influenza and pneumococcal vaccines, the interaction between vaccines, the role of repeated vaccinations, the occurrence of serotype replacement (pneumococcus); identify vaccine types and brands with low VE; guide the decision of the WHO committees on vaccine strain selection (influenza); provide robust benefit indicators (VE and VI) and cost benefit and effectiveness results; guide vaccination strategies (schedules, doses, boosters). This EU member state collaboration will respond to questions that require studies based on large sample sizes and sharing of expertise that cannot be achieved by one country alone. It will allow the best methods to be used and results to benefit to all EU countries whatever their current public health achievements. Results will be shared with international partners.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.3-1 | Award Amount: 7.19M | Year: 2013

MAILPAN (MAcroencapsulation of PANcreatic Islets) is a prototype of bioartificial pancreas usable in the human designed to treat type 1 diabetic patients. The prototype was developed along different stages since 1996 and led to the creation of the SME called Defymed in 2011. Next step is now to bring the prototype to the pre-clinical and clinical phases necessary to the ensuing commercialization of MAILPAN whose ultimate goal is to improve the life of at least 20 million persons in the world while providing positive effects on healthcare management and expenses, the environment and the competitiveness of the biomaterials industry. In order to reach this goal, CeeD and Defymed gathered a consortium made of seven partners from academia, clinical/public health research sector and industry/SMEs from three different European countries Belgium, France and UK. The expertise gathered include encapsulation techniques, islet isolation, cell engineering, islet transplantation, islet preconditioning, surgical implantation, and medium formulation; items that are complementary and necessary to the implementation of the present project proposal. The project proposal of a 36-month duration intends to bring the most modern and up to date improvements that the bioartificial pancreas still needs and can receive such as to enhance cells survival inside the device by formulating a new adapted cell culture medium, to further lower the rejection risk by studying the biocompatibility and anti-inflammatory mechanisms, to test the prototype in primates, and to validate its further use in humans. Safety, bio-compatibility and interoperability of MAILPAN device combined to the islets/pseudo-islets, will be assessed, in respect to the applied regulatory directives.

Agency: Cordis | Branch: FP7 | Program: JTI-CP-FCH | Phase: SP1-JTI-FCH.2012.1.5 | Award Amount: 4.68M | Year: 2013

Project CATAPULT proposes to develop a radically new concept for automotive PEM fuel cell catalysts based on novel structures wherein platinum is deposited as an extremely thin layer ( <3 nm) on corrosion resistant supports of various morphologies, including particulate, nanofibrous and nanotubular, as well as nano-hierarchical combinations of these. In this approach, platinum is deposited using atomic layer deposition as thin, contiguous and conformal films that allow development of extended platinum or platinum alloy surfaces. Non-PGM catalysts will be developed via the tailored synthesis of metal-organic frameworks for their use either sacrificially to generate the C/N support for non-PGM species, or directly as a non-PGM catalyst. Hybrid ultra-low Pt/non-PGM catalysts and catalyst layers will also be investigated as a further novel approach. Increased fundamental understanding from supporting theoretical modelling will provide guidance to the strategies developed experimentally and to the down-selection of the new corrosion-resistant supports and their supported catalyst designs. Down-selected catalysts will be integrated into novel electrode designs and into MEAs incorporating state of the art membranes best adapted for automotive power trains, and evaluated according to protocols reproducing the stresses encountered in a drive cycle. The candidate MEA best satisfying performance and stability targets will be scaled-up for further assessment at large MEA and short stack levels. Techno-economic assessment will consider the scale up processability, and the impact of MEA performance and durability on stack costs. The well-balanced partnership, comprising two large industries (including an automotive OEM), two SMEs, two research organisations and two universities, will ensure close cooperation between industrial and institute partners, know-how, experience, research leadership, complementarity and industrial relevance.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2011.9.1 | Award Amount: 2.38M | Year: 2012

In industry, society and science advanced software is used for solving planning, scheduling and resource allocation problems, collectively known as constraint satisfaction or optimization problems. At the same time, one continuously gathers vast amounts of data about these problems. This project starts from the observation that current software typically does not exploit such data to update schedules, resources and plans. It aims at developing a new approach in which gathered data is analysed systematically in order to dynamically revise and adapt constraints and optimization criteria. Ultimately, this could create a new ICT paradigm, called Inductive Constraint Programming, that bridges the gap between the areas of data mining and machine learning on the one hand, and constraint programming on the other hand. If successful, this would change the face of data mining as well as constraint programming technology. It would not only allow one to use data mining techniques in constraint programming to improve the formulation and solution of constraint satisfaction problems, but also to employ declarative constraint programming principles in data mining and machine learning.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-3 | Award Amount: 5.84M | Year: 2014

Conduct Disorder (CD) is the key paediatric disorder characterized by severe aggression. It is heterogeneous, and our understanding of the neurobiology to subtype aggression is limited. MATRICS is a multidisciplinary consortium of academic partners and SMEs that focuses on the subtyping of aggression both within CD and of the broader cross-disorder trait of aggression. MATRICS will test the hypothesis that reactive and instrumental aggression result from aberrant autonomic reactivity coupled to the differential impairment of three basic neural functions: 1) regulation of control mechanisms of aggression, 2) emotional value rating of others, and 3) empathy and moral decision making. MATRICS will employ the same psychological tasks assessing 1), 2) and 3) in animal aggression models and human CD samples concurrent with the assessment of neural, neurochemical, (epi)-genetic and autonomic nervous system markers. These data will be integrated with matching expression profiling from neurons derived from CD IPSCs. MATRICS also examines how environmental risks, whether or not they interact with genetic factors, are translated in epigenetic and neural changes. MATRICS will data-mine existing large integrated imaging-genetics cohorts (NeuroIMAGE; IMAGEN) and prospective cohorts (TRAILS; ALSPAC) with follow-up into adulthood and the (epi)genetic profiling of the PERS CD cohort, and collect a large new CD cohort and controls for collection of MRI, (epi)-genetic, biochemical and environmental measures. Bayesian machine learning tools will integrate multi-source and multi-level data, and generate predictive algorithms of persistent aggression into adulthood. MATRICS will identify new potentially druggable targets, develop novel animal models and conduct pilot medication and neuro/biofeedback studies in high-risk and CD patients. MATRICS builds on existing fruitful EU collaborations which maximises feasibility and successful output.

Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.95M | Year: 2015

Photonics, nanotechnology, advanced materials, and advanced manufacturing technologies have been identified as key enabling technologies (KETs) for the EU. Today the photonics global market alone is around 300 billion and Europe has established a strong position with a total share of 20%, directly employing about 290,000 people. However, the shortage of sufficient skilled labour and entrepreneurs capable of handling the highly multi-disciplinary nature of KETs remains a major problem in the EU. Tailoring of semiconductors at the nanoscale is an important enabling technology for a wide range of photonics and electronics applications in diverse areas. In the training network proposed here, a cohort of 15 early stage researchers will be trained in the full range of skills required for a career in photonics, including materials growth, device fabrication, characterisation, design, theory, and commercialisation. A carefully-chosen, well-balanced consortium of 8 academic partners, 2 full industry partners and 7 associated partners are well placed to provide the training in these skills, with European and worldwide reputations as leaders in each field. These skills will be developed within four burgeoning research areas; Semiconductor Metamaterials & Plasmonics, Dilute Nitride semiconductor nanostructures, Hydrogenated Semiconductors and Metamorphic structures. The outcomes of this enabling fundamental research are well focused to deliver advances in sources for secure communications, sensitive detectors for security applications, more efficient solar cells for energy generation, LEDs and sensors for environmental gas and bio-sensing. Each researcher will experience both academic and commercial environments thanks to the strong industrial involvement, resulting in multi-skilled, industry-focused graduates. PROMIS therefore directly addresses the need for additional skilled photonics professionals, as identified by the European Technology Platform, Photonics21.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-15-2014 | Award Amount: 6.00M | Year: 2015

Osteoarthritis (OA) is an incurable disease that has evaded pharmacological interference, biologic therapy or surgical intervention to prevent disease progression. Currently, OA is designated the 11th highest contributor (of 291 diseases) of global disability. In the absence of effective treatment options, cellular therapies using mesenchymal stem/stromal cells (MSCs) have emerged as potential candidates to overcome this clinical short-coming. Autologous adipose-derived mesenchymal stromal cells (ASCs) are attractive for cellular therapy given the abundance of tissue, high frequency of MSCs and minimally invasive harvest procedure. The EU consortium ADIPOA has shown in a first in man 2-centre Phase I safety study that intraarticular injection of a single dose of autologous ASCs to the knee (18 patients, 12 month follow-up) was well-tolerated, had no adverse effects, and resulted in an improvement in pain score and functional outcome. ADIPOA2 will deliver a large-scale clinical trial in regenerative medicine for OA. The purpose of the project is to design and implement a phase IIb study to assess the safety and efficacy of autologous (patient-derived) ACSs in the treatment of advanced OA of the knee. The cells will be prepared from samples of adipose tissue harvested from patients by lipoaspiration. ADIPOA2 will comprise a multi-centre, randomized clinical trial comparing culture-expanded, autologous adult ASCs in subjects with knee OA with another widely used therapeutic approach for knee degeneration (injection of Hyaluronan). There are two large elements of the study: (1) the production of consistent batches of high-quality autologous ASCs under GMP-compliant conditions and (2) delivery of these cell doses to patients in a trial which will meet all national and European regulatory and ethical standards and which will have sufficient statistical power to provide an unambiguous and definitive assessment of safety and efficacy.

Clement Y.,Montpellier SupAgro | Clement Y.,Montpellier University | Arndt P.F.,Max Planck Institute for Molecular Genetics
Molecular Biology and Evolution | Year: 2013

Meiotic recombination is known to influence GC-content evolution in large regions of mammalian genomes by favoring the fixation of G and C alleles and increasing the rate of A/T to G/C substitutions. This process is known as GC-biased gene conversion (gBGC). Until recently, genome-wide measures of fine-scale recombination activity were unavailable in mice. Additionally, comparative studies focusing on mouse were limited as the closest organism with its genome fully sequenced was rat. Here, we make use of the recent mapping of double strand breaks (DSBs), the first step of meiotic recombination, in the mouse genome and of the sequencing of mouse closely related subspecies to analyze the fine-scale evolutionary signature of meiotic recombination on GC-content evolution in recombination hotspots, short regions that undergo extreme rates of recombination. We measure substitution rates around DSB hotspots and observe that gBGC is affecting a very short region (∼1 kbp) in length around these hotspots. Furthermore, we can infer that the locations of hotspots evolved rapidly during mouse evolution. © 2013 The Author.

Peeters M.,Montpellier University | Aghokeng A.F.,Virology Laboratory IMPM IRD | Delaporte E.,Montpellier University
Clinical Microbiology and Infection | Year: 2010

The tremendous diversity of human immunodeficiency virus (HIV)-1 strains circulating worldwide has an important impact on almost all aspects of the management of this infection, from the identification of infected persons, through treatment efficacy and monitoring, and prevention strategies such as vaccine design. The areas where HIV-1 genetic diversity is highest are those where the majority of patients in need of treatment and biological monitoring live. With increased access to treatment in these areas, it is expected that the demand for monitoring tools such as viral load assays and resistance tests will also increase, and their reliability will be critical. Regular updates of these assays during the last two decades have aimed at improving their performances in different ways that include their reliability with different HIV-1 strains. We here review to what extent HIV-1 genetic diversity still limits or not the use of currently available viral load and resistance tests. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.

Ghareeb F.,Riyadh Military Hospital | Duffau H.,Montpellier University
Journal of Neurosurgery | Year: 2012

Object. Beyond its oncological benefit, surgery could improve seizure control in paralimbic frontotemporoinsular or temporoinsular WHO Grade II gliomas generating intractable seizures. However, no studies have examined the impact of hippocampal resection on chronic epilepsy when the hippocampus is not invaded by Grade II gliomas. Here, the authors compared the epileptological outcomes and return to work in 2 groups of patients who underwent surgery with or without hippocampectomy for paralimbic Grade II gliomas eliciting intractable epilepsy despite no tumoral involvement of the hippocampus. Methods. Surgery was performed in 15 consecutive patients who were unable to work (median Karnofsky Performance Scale [KPS] Score 70) because of refractory epilepsy due to paralimbic Grade II gliomas that were not invading the hippocampus. In Group A (8 patients), the hippocampus was preserved. In Group B (7 patients), glioma removal was associated with hippocampectomy. Results. No patient died or suffered a permanent deficit after surgery. Postoperatively, in Group A, no patients were seizure free (4 patients were in Engel Class II and 4 were in Class III). In Group B, all 7 patients were seizure free (Class I) (p = 0.02). Only 62.5% of patients returned to work in Group A, whereas all patients are working full time in Group B. The postsurgical median KPS score was 85 in Group A, that is, not significantly improved in comparison with the preoperative score, while the postsurgical median KPS was 95 in Group B, that is, significantly improved in comparison with the preoperative score (p = 0.03). Conclusions. The authors' data support, for the first time, the significant impact of hippocampectomy in patients with intractable epilepsy generated by a paralimbic Grade II glioma, even if it does not invade the hippocampus. Hippocampal resection allowed seizure control in all patients, with an improvement in KPS scores, since all patients resumed their social and professional activities. Thus, the authors suggest performing a resection of the nontumoral hippocampus in addition to resection of the tumor in patients with refractory epilepsy due to paralimbic Grade II gliomas.

Wolf J.B.,University of Bath | Oakey R.J.,King's College London | Feil R.,Montpellier University
Heredity | Year: 2014

Diverse mechanisms contribute to the evolution of reproductive barriers, a process that is critical in speciation. Amongst these are alterations in gene products and in gene dosage that affect development and reproductive success in hybrid offspring. Because of its strict parent-of-origin dependence, genomic imprinting is thought to contribute to the aberrant phenotypes observed in interspecies hybrids in mammals and flowering plants, when the abnormalities depend on the directionality of the cross. In different groups of mammals, hybrid incompatibility has indeed been linked to loss of imprinting. Aberrant expression levels have been reported as well, including imprinted genes involved in development and growth. Recent studies in humans emphasize that genetic diversity within a species can readily perturb imprinted gene expression and phenotype as well. Despite novel insights into the underlying mechanisms, the full extent of imprinted gene perturbation still remains to be determined in the different hybrid systems. Here we review imprinted gene expression in intra- and interspecies hybrids and examine the evolutionary scenarios under which imprinting could contribute to hybrid incompatibilities. We discuss effects on development and reproduction and possible evolutionary implications. © 2014 Macmillan Publishers Limited All rights reserved.

Neri I.,CNRS Charles Coulomb Laboratory | Kern N.,CNRS Charles Coulomb Laboratory | Parmeggiani A.,Montpellier University | Parmeggiani A.,French National Center for Scientific Research
Physical Review Letters | Year: 2011

We study the totally asymmetric simple exclusion process (TASEP) on complex networks, as a paradigmatic model for transport subject to excluded volume interactions. Building on TASEP phenomenology on a single segment and borrowing ideas from random networks we investigate the effect of connectivity on transport. In particular, we argue that the presence of disorder in the topology of vertices crucially modifies the transport features of a network: irregular networks involve homogeneous segments and have a bimodal distribution of edge densities, whereas regular networks are dominated by shocks leading to a unimodal density distribution. The proposed numerical approach of solving for mean-field transport on networks provides a general framework for studying TASEP on large networks, and is expected to generalize to other transport processes. © 2011 American Physical Society.

Chabab M.,Cadi Ayyad University | Peyranere M.C.,Montpellier University | Rahili L.,Cadi Ayyad University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

Using the most recent results of CMS and ATLAS, we study the Higgs decays to γγ and Zγ in the scenario where the two CP-even Higgs predicted by the type II seesaw model (Higgs triplet models) are close to mass degenerate with a mass near 125 GeV. We analyze the effects of the Higgs potential parameters constrained by the full set of perturbative unitarity, boundedness from below as well as from precision electroweak measurements on these decay modes. Our analysis demonstrates that the observed excess in the diphoton Higgs decay channel can be interpreted in our scenario within a delineated region controlled by λ1 and λ4 coupling. We also find a deviation in the Higgs decay to Zγ with respect to the Standard Model prediction and the largest enhancement is found for a ratio RZγ of the order 1.6. Furthermore we show that consistency with current ATLAS data on the diphoton decay channel favors a light doubly charged Higgs with mass in the range 92-180 GeV. Finally, we find that the γγ and Zγ Higgs decay modes are generally correlated and the magnitude of correlation is sensitive to the sign of the λ1 parameter. © 2014 American Physical Society.

Mackay A.,University of Wollongong | Stewart B.A.,University of Michigan | Chase B.M.,Montpellier University | Chase B.M.,University of Bergen
Journal of Human Evolution | Year: 2014

The later Pleistocene archaeological record of southernmost Africa encompasses several Middle Stone Age industries and the transition to the Later Stone Age. Through this period various signs of complex human behaviour appear episodically, including elaborate lithic technologies, osseous technologies, ornaments, motifs and abstract designs. Here we explore the regional archaeological record using different components of lithic technological systems to track the transmission of cultural information and the extent of population interaction within and between different climatic regions. The data suggest a complex set of coalescent and fragmented relationships between populations in different climate regions through the late Pleistocene, with maximum interaction (coalescence) during MIS 4 and MIS 2, and fragmentation during MIS 5 and MIS 3. Coalescent phases correlate with increases in the frequency of ornaments and other forms of symbolic expression, leading us to suggest that population interaction was a significant driver in their appearance. © 2014 Elsevier Ltd.

Renaud S.,CNRS Biometry and Evolutionary Biology Laboratory | Alibert P.,University of Burgundy | Auffray J.-C.,Montpellier University
BMC Evolutionary Biology | Year: 2012

Abstract. Background: Hybridization is often seen as a process dampening phenotypic differences accumulated between diverging evolutionary units. For a complex trait comprising several relatively independent modules, hybridization may however simply generate new phenotypes, by combining into a new mosaic modules inherited from each parental groups and parts intermediate with respect to the parental groups. We tested this hypothesis by studying mandible size and shape in a set of first and second generation hybrids resulting from inbred wild-derived laboratory strains documenting two subspecies of house mice, Musmusculus domesticus and Musmusculus musculus. Phenotypic variation of the mandible was divided into nested partitions of developmental, evolutionary and functional modules. Results: The size and shape of the modules were differently influenced by hybridization. Some modules seemed to be the result of typical additive effects with hybrids intermediate between parents, some displayed a pattern expected in the case of monogenic dominance, whereas in other modules, hybrids were transgressive. The result is interpreted as the production of novel mandible morphologies. Beyond this modularity, modules in functional interaction tended to display significant covariations. Conclusions: Modularity emerges as a source of novel morphological variation by its simple potential to combine different parts of the parental phenotypes into a novel offspring mosaic of modules. This effect is partly counterbalanced by bone remodeling insuring an integration of the mosaic mandible into a functional ensemble, adding a non-genetic component to the production of transgressive phenotypes in hybrids. © 2012 Renaud et al.; licensee BioMed Central Ltd.

Feil R.,Montpellier University | Fraga M.F.,CSIC - National Center for Biotechnology | Fraga M.F.,University of Oviedo
Nature Reviews Genetics | Year: 2012

Epigenetic phenomena in animals and plants are mediated by DNA methylation and stable chromatin modifications. There has been considerable interest in whether environmental factors modulate the establishment and maintenance of epigenetic modifications, and could thereby influence gene expression and phenotype. Chemical pollutants, dietary components, temperature changes and other external stresses can indeed have long-lasting effects on development, metabolism and health, sometimes even in subsequent generations. Although the underlying mechanisms remain largely unknown, particularly in humans, mechanistic insights are emerging from experimental model systems. These have implications for structuring future research and understanding disease and development. © 2012 Macmillan Publishers Limited. All rights reserved.

Ellwanger U.,University Paris - Sud | Hugonie C.,Montpellier University
Advances in High Energy Physics | Year: 2012

We study the NMSSM with universal Susy breaking terms (besides the Higgs sector) at the GUT scale. Within this constrained parameter space, it is not difficult to find a Higgs boson with a mass of about 125 GeV and an enhanced cross-section in the diphoton channel. An additional lighter Higgs boson with reduced couplings and a mass ≲ 123 GeV is potentially observable at the LHC. The NMSSM-specific Yukawa couplings λ and κ are relatively large and tan β is small, such that λ, κ, and the top Yukawa coupling are of (1) at the GUT scale. The lightest stop can be as light as 105 GeV, and the fine-tuning is modest. WMAP constraints can be satisfied by a dominantly Higgsino-like LSP with substantial bino, wino, and singlino admixtures and a mass of 6090 GeV, which would potentially be detectable by XENON100. © 2012 Ulrich Ellwanger and Cyril Hugonie.

Oukacine F.,Montpellier University | Morel A.,BASF | Cottet H.,Montpellier University
Langmuir | Year: 2011

Poly(styrene-co-acrylic acid) (St/AA) and poly(styrene-co-methacrylic acid) (St/MA) nanolatexes with different acid contents were prepared by emulsion copolymerization and were analyzed by capillary electrophoresis (CE) and by laser doppler velocimetry (LDV). Due to the intrinsic differences in the methodologies, CE (separative technique) and LDV (zetametry, nonseparative technique) lead to very different electrophoretic mobility distributions. Beyond these differences, the variation of the electrophoretic mobility is a complex and nonlinear function of the hydrodynamic radius, the ionic strength, and the zeta potential. To gain better insight on the influence of the ionic strength and the acid content on the electrophoretic behavior of the nanolatexes, the electrophoretic mobility data were changed into surface charge densities using the O'Brien, White, and Ohshima modeling. This approach leads to the conclusion that the surface charge density is mainly controlled at high ionic strength (∼50 mM) by the adsorption of anionic surfactants coming from the sample. On the contrary, at low ionic strength, and/or in the presence of neutral surfactant in the electrolyte, the acid content was the main parameter controlling the surface charge density of the nanolatexes. © 2011 American Chemical Society.

Guinot G.,Natural History Museum | Adnet S.,Montpellier University | Cavin L.,Natural History Museum | Cappetta H.,Montpellier University
Nature Communications | Year: 2013

Cladodontomorph sharks are Palaeozoic stem chondrichthyans thought to go extinct at the end-Permian mass extinction. This extinction preceded the diversification of euselachians, including modern sharks. Here we describe an outer-platform cladodontomorph shark tooth assemblage from the Early Cretaceous of southern France, increasing the fossil record of this group by circa 120 million years. Identification of this material rests on new histological observations and morphological evidence. Our finding shows that this lineage survived mass extinctions most likely by habitat contraction, using deep-sea refuge environments during catastrophic events. The recorded gap in the cladodontomorph lineage represents the longest gap in the fossil record for an extinct marine vertebrate group. This discovery demonstrates that the deep-sea marine diversity, poorly known during most of the fish evolutionary history, contains essential data for a complete understanding of the long-term evolution of marine fish paleobiodiversity. © 2013 Macmillan Publishers Limited. All rights reserved.

Ellwanger U.,University Paris - Sud | Hugonie C.,Montpellier University | Teixeira A.M.,University Paris - Sud | Teixeira A.M.,University of Lisbon
Physics Reports | Year: 2010

We review the theoretical and phenomenological aspects of the Next-to-Minimal Supersymmetric Standard Model: the Higgs sector including radiative corrections and the 2-loop β-functions for all parameters of the general NMSSM; the tadpole and domain wall problems, baryogenesis; NMSSM phenomenology at colliders, B physics and dark matter; specific scenarios as the constrained NMSSM, gauge mediated supersymmetry breaking, U(1)'-extensions, CP and R-parity violation. © 2010 Elsevier B.V.

Cairns A.B.,University of Oxford | Catafesta J.,Charles Gerhardt Institute | Catafesta J.,CNRS Charles Coulomb Laboratory | Levelut C.,CNRS Charles Coulomb Laboratory | And 7 more authors.
Nature Materials | Year: 2013

The counterintuitive phenomenon of negative linear compressibility (NLC) is a highly desirable but rare property exploitable in the development of artificial muscles, actuators and next-generation pressure sensors. In all cases, material performance is directly related to the magnitude of intrinsic NLC response. Here we show the molecular framework material zinc(II) dicyanoaurate(I), Zn[Au(CN) 2 ] 2, exhibits the most extreme and persistent NLC behaviour yet reported: under increasing hydrostatic pressure its crystal structure expands in one direction at a rate that is an order of magnitude greater than both the typical contraction observed for common engineering materials and also the anomalous expansion in established NLC candidates. This extreme behaviour arises from the honeycomb-like structure of Zn[Au(CN) 2 ] 2 coupling volume reduction to uniaxial expansion, and helical Au...Au 'aurophilic' interactions accommodating abnormally large linear strains by functioning as supramolecular springs. © 2013 Macmillan Publishers Limited. All rights reserved.

Neri I.,CNRS Charles Coulomb Laboratory | Kern N.,CNRS Charles Coulomb Laboratory | Parmeggiani A.,CNRS Charles Coulomb Laboratory | Parmeggiani A.,Montpellier University | Parmeggiani A.,French National Center for Scientific Research
Physical Review Letters | Year: 2013

We introduce the totally asymmetric simple exclusion process with Langmuir kinetics on a network as a microscopic model for active motor protein transport on the cytoskeleton, immersed in the diffusive cytoplasm. We discuss how the interplay between active transport along a network and infinite diffusion in a bulk reservoir leads to a heterogeneous matter distribution on various scales: we find three regimes for steady state transport, corresponding to the scale of the network, of individual segments, or local to sites. At low exchange rates strong density heterogeneities develop between different segments in the network. In this regime one has to consider the topological complexity of the whole network to describe transport. In contrast, at moderate exchange rates the transport through the network decouples, and the physics is determined by single segments and the local topology. At last, for very high exchange rates the homogeneous Langmuir process dominates the stationary state. We introduce effective rate diagrams for the network to identify these different regimes. Based on this method we develop an intuitive but generic picture of how the stationary state of excluded volume processes on complex networks can be understood in terms of the single-segment phase diagram. © 2013 American Physical Society.

Calderon M.A.,Imperial College London | Linneberg A.,Glostrup University Hospital | Linneberg A.,Copenhagen University | Kleine-Tebbe J.,Allergy and Asthma Center Westend Outpatient Clinic Hanf | And 4 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

The house dust mite (HDM) is a major perennial allergen source and a significant cause of allergic rhinitis and allergic asthma. However, awareness of the condition remains generally low. This review assesses the links between exposure to HDM, development of the allergic response, and pathologic consequences in patients with respiratory allergic diseases. We investigate the epidemiology of HDM allergy to explore the interaction between mites and human subjects at the population, individual, and molecular levels. Core and recent publications were identified by using "house dust mite" as a key search term to evaluate the current knowledge of HDM epidemiology and pathophysiology. Prevalence data for HDM allergen sensitization vary from 65 to 130 million persons in the general population worldwide to as many as 50% among asthmatic patients. Heterogeneity of populations, terminology, and end points in the literature confound estimates, indicating the need for greater standardization in epidemiologic research. Exposure to allergens depends on multiple ecological strata, including climate and mite microhabitats within the domestic environment, with the latter providing opportunity for intervention measures to reduce allergen load. Inhaled mite aeroallergens are unusually virulent: they are able to activate both the adaptive and innate immune responses, potentially offering new avenues for intervention. The role of HDM allergens is crucial in the development of allergic rhinitis and asthma, but the translation of silent sensitization into symptomatic disease is still incompletely understood. Improved understanding of HDMs, their allergens, and their microhabitats will enable development of more effective outcomes for patients with HDM allergy. © 2014 The Authors.

Ellwanger U.,University Paris - Sud | Ellwanger U.,University of Southampton | Hugonie C.,Montpellier University
Journal of High Energy Physics | Year: 2016

Abstract: The excess of events in the diphoton final state near 750 GeV observed by ATLAS and CMS can be explained within the NMSSM near the R-symmetry limit. Both scalars beyond the Standard Model Higgs boson have masses near 750 GeV, mix strongly, and share sizeable production cross sections in association with b-quarks as well as branching fractions into a pair of very light pseudoscalars. Pseudoscalars with a mass of ∼ 210 MeV decay into collimated diphotons, whereas pseudoscalars with a mass of ∼ 500–550 MeV can decay either into collimated diphotons or into three π0 resulting in collimated photon jets. Various such scenarios are discussed; the dominant constraints on the latter scenario originate from bounds on radiative Y decays, but they allow for a signal cross section up to 6.7 fb times the acceptance for collimated multiphotons to pass as a single photon. © 2016, The Author(s).

Prantzos N.,CNRS Paris Institute of Astrophysics | Boehm C.,LAPP | Bykov A.M.,RAS Ioffe Physical - Technical Institute | Diehl R.,Max Planck Institute for Extraterrestrial Physics | And 8 more authors.
Reviews of Modern Physics | Year: 2011

The first γ-ray line originating from outside the Solar System that was ever detected is the 511 keV emission from positron annihilation in the Galaxy. Despite 30 years of intense theoretical and observational investigation, the main sources of positrons have not been identified up to now. Observations in the 1990s with OSSE/CGRO (Oriented Scintillation Spectrometer Experiment on GRO satellite/Compton Gamma Ray Observatory) showed that the emission is strongly concentrated toward the Galactic bulge. In the 2000s, the spectrometer SPI aboard the European Space Agency's (ESA) International Gamma Ray Astrophysics Laboratory (INTEGRAL) allowed scientists to measure that emission across the entire Galaxy, revealing that the bulge-to-disk luminosity ratio is larger than observed at any other wavelength. This mapping prompted a number of novel explanations, including rather "exotic" ones (e.g., dark matter annihilation). However, conventional astrophysical sources, such as type Ia supernovae, microquasars, or x-ray binaries, are still plausible candidates for a large fraction of the observed total 511 keV emission of the bulge. A closer study of the subject reveals new layers of complexity, since positrons may propagate far away from their production sites, making it difficult to infer the underlying source distribution from the observed map of 511 keV emission. However, in contrast to the rather well-understood propagation of high-energy (>GeV) particles of Galactic cosmic rays, understanding the propagation of low-energy (∼MeV) positrons in the turbulent, magnetized interstellar medium still remains a formidable challenge. The spectral and imaging properties of the observed 511 keV emission are reviewed and candidate positron sources and models of positron propagation in the Galaxy are critically discussed. © 2011 American Physical Society.

Schucht P.,University of Bern | Ghareeb F.,Riyadh Military Hospital | Duffau H.,Montpellier University | Duffau H.,French Institute of Health and Medical Research
Journal of Neurosurgery | Year: 2013

Object. A main concern with regard to surgery for low-grade glioma (LGG, WHO Grade II) is maintenance of the patient's functional integrity. This concern is particularly relevant for gliomas in the central region, where damage can have grave repercussions. The authors evaluated postsurgical outcomes with regard to neurological deficits, seizures, and quality of life. Methods. Outcomes were compared for 33 patients with central LGG (central cohort) and a control cohort of 31 patients with frontal LGG (frontal cohort), all of whom had had medically intractable seizures before undergoing surgery with mapping while awake. All surgeries were performed in the period from February 2007 through April 2010 at the same institution. Results. For the central cohort, the median extent of resection was 92% (range 80%-97%), and for the frontal cohort, the median extent of resection was 93% (range 83%-98%; p = 1.0). Although the rate of mild neurological deficits was similar for both groups, seizure freedom (Engel Class I) was achieved for only 4 (12.1%) of 33 patients in the central cohort compared with 26 (83.9%) of 31 patients in the frontal cohort (p < 0.0001). The rate of return to work was lower for patients in the central cohort (4 [12.1%] of 33) than for the patients in the frontal cohort (28 [90.3%] of 31; p < 0.0001). Conclusions. Resection of central LGG is feasible and safe when appropriate intraoperative mapping is used. However, seizure control for these patients remains poor, a finding that contrasts markedly with seizure control for patients in the frontal cohort and with that reported in the literature. For patients with central LGG, poor seizure control ultimately determines quality of life because most will not be able to return to work. © AANS, 2013.

Luu D.-T.,Montpellier University | Martiniare A.,Oxford Brookes University | Sorieul M.,Montpellier University | Sorieul M.,University of Warwick | And 2 more authors.
Plant Journal | Year: 2012

The constitutive cycling of plant plasma membrane (PM) proteins is an essential component of their function and regulation under resting or stress conditions. Transgenic Arabidopsis plants that express GFP fusions with AtPIP1;2 and AtPIP2;1, two prototypic PM aquaporins, were used to develop a fluorescence recovery after photobleaching (FRAP) approach. This technique was used to discriminate between PM and endosomal pools of the aquaporin constructs, and to estimate their cycling between intracellular compartments and the cell surface. The membrane trafficking inhibitors tyrphostin A23, naphthalene-1-acetic acid and brefeldin A blocked the latter process. By contrast, a salt treatment (100 mm NaCl for 30 min) markedly enhanced the cycling of the aquaporin constructs and modified their pharmacological inhibition profile. Two distinct models for PM aquaporin cycling in resting or salt-stressed root cells are discussed. © 2011 Blackwell Publishing Ltd.

Campbell I.A.,Montpellier University | Lundow P.H.,KTH Royal Institute of Technology
Physical Review B - Condensed Matter and Materials Physics | Year: 2011

It is often assumed that for treating numerical (or experimental) data on continuous transitions the formal analysis derived from the renormalization- group theory can only be applied over a narrow temperature range, the "critical region"; outside this region correction terms proliferate rendering attempts to apply the formalism hopeless. This pessimistic conclusion follows largely from a choice of scaling variables and scaling expressions, which is traditional but very inefficient for data covering wide temperature ranges. An alternative "extended scaling" approach can be made where the choice of scaling variables and scaling expressions is rationalized in the light of well established high-temperature series expansion developments. We present the extended scaling approach in detail, and outline the numerical technique used to study the three-dimensional (3D) Ising model. After a discussion of the exact expressions for the historic 1D Ising spin chain model as an illustration, an exhaustive analysis of high quality numerical data on the canonical simple cubic lattice 3D Ising model is given. It is shown that in both models, with appropriate scaling variables and scaling expressions (in which leading correction terms are taken into account where necessary), critical behavior extends from Tc up to infinite temperature. © 2011 American Physical Society.

Callan-Jones A.,CNRS Charles Coulomb Laboratory | Callan-Jones A.,Montpellier University | Bassereau P.,University Pierre and Marie Curie
Current Opinion in Solid State and Materials Science | Year: 2013

Cellular transport requires that membranes have the ability to recruit specific lipids and proteins to particular positions and at specific times. Here, we review recent work showing that lipids and proteins can be redistributed by spatially varying membrane curvature, without necessarily the need for biochemical targeting signals. We present here an emerging understanding of the various mechanisms by which membrane curvature can sort lipids and proteins, providing the experimental methods in addition to the supporting theoretical concepts. © 2013 Elsevier Ltd. All rights reserved.

Mariette X.,University Paris - Sud | Gottenberg J.-E.,University of Strasbourg | Ravaud P.,French Institute of Health and Medical Research | Combe B.,Montpellier University
Rheumatology | Year: 2011

Objectives. Clinical registries have shown their effectiveness in capturing the long-term benefit of drugs in routine care. In France, two types of registry have been established to analyse the safety and efficacy of biological agents. Methods. The Research Axed on Tolerance of Biotherapies (RATIO) registry was designed to prospectively collect all cases of lymphoma and opportunistic infections occurring in patients receiving anti-TNF blockers for any indication. We also examined the results from nationwide prospective cohorts in order to investigate the safety and efficacy of rituximab (RTX), abatacept (ABA) and tocilizumab in RA and other autoimmune diseases. Results. Analysis of the RATIO registry demonstrated an increased risk of Legionella pneumophila infection in patients receiving anti-TNF therapy, a higher risk of tuberculosis [odds ratio (OR) (95% CI): 13.3 (2.6, 69.0) and 17.1 (3.6, 80.6) for infliximab and adalimumab vs etanercept, respectively], opportunistic infections and incidence of lymphoma, with mAb than with soluble-receptor anti-TNF. The characteristics of RA patients in RTX and ABA registries showed that some patients did not receive previous TNF blockers [20% in autoimmunity and RTX (AIR) and 13% in Orencia and RA (ORA)] and one-third of them were treated without concomitant DMARDs. Patients receiving RTX showed an increased proportion of severe infections (5.0/100 patient-years). Lung and cardiac comorbidities, extra-articular involvement and low immunoglobulin G before RTX were predictive factors of severe infections. In addition, the AIR registry suggested the effectiveness of RTX in patients with SLE. Conclusion. The establishment of biological registries in rheumatic diseases, in France, with their different methods, has already provided additional data to controlled trials, mainly on the risk of severe infections and lymphoma. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Said Hassane F.,Montpellier University | Saleh A.F.,Medical Research Council | Abes R.,Montpellier University | Gait M.J.,Medical Research Council | Lebleu B.,Montpellier University
Cellular and Molecular Life Sciences | Year: 2010

Crossing biological barriers represents a major limitation for clinical applications of biomolecules such as nucleic acids, peptides or proteins. Cell penetrating peptides (CPP), also named protein transduction domains, comprise short and usually basic amino acids-rich peptides originating from proteins able to cross biological barriers, such as the viral Tat protein, or are rationally designed. They have emerged as a new class of non-viral vectors allowing the delivery of various biomolecules across biological barriers from low molecular weight drugs to nanosized particles. Encouraging data with CPP-conjugated oligonucleotides have been obtained both in vitro and in vivo in animal models of diseases such as Duchenne muscular dystrophy. Whether CPP-cargo conjugates enter cells by direct translocation across the plasma membrane or by endocytosis remains controversial. In many instances, however, endosomal escape appears as a major limitation of this new delivery strategy.

Frigerio M.,CNRS Charles Coulomb Laboratory | Villanova Del Moral A.,Montpellier University
Journal of High Energy Physics | Year: 2013

Present data prefer a large but non-maximal 2 - 3 mixing in the lepton sector. We argue that this value, in connection with sinθ 13 ≃ 0.15, is the generic outcome of minimal flavour structures. We present a few different incarnations of this statement, in terms of lepton mass matrices depending on a small number of parameters, that can be justified by discrete flavour symmetries. We also propose a general procedure to study the correlation between θ 23, the absolute scale and ordering of the neutrino masses, and the leptonic CP-violating phases. © 2013 SISSA.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: FETPROACT-01-2016 | Award Amount: 7.98M | Year: 2017

A novel concept for a photo-electro-catalytic (PEC) cell able to directly convert water and CO2 into fuels and chemicals (CO2 reduction) and oxygen (water oxidation) using exclusively solar energy will be designed, built, validated, and optimized. The cell will be constructed from cheap multifunction photo-electrodes able to transform sun irradiation into an electrochemical potential difference (expected efficiency > 12%); ultra-thin layers and nanoparticles of metal or metal oxide catalysts for both half-cell reactions (expected efficiency > 90%); and stateof- the-art membrane technology for gas/liquid/products separation to match a theoretical target solar to fuels efficiency above 10%. All parts will be assembled to maximize performance in pH > 7 solution and moderate temperatures (50-80 C) as to take advantage of the high stability and favorable kinetics of constituent materials in these conditions. Achieving this goal we will improve the state-of-the-art of all components for the sake of cell integration: 1) Surface sciences: metal and metal oxide catalysts (crystals or nanostructures grown on metals or silicon) will be characterized for water oxidation and CO2 reduction through atomically resolved experiments (scanning probe microscopy) and spatially-averaged surface techniques including surface analysis before, after and in operando electrochemical reactions. Activity and performance will be correlated to composition, thickness, structure and support as to determine the optimum parameters for device integration. 2) Photoelectrodes: This unique surface knowledge will be transferred to the processing of catalytic nanostructures deposited on semiconductors through different methods to match the surface chemistry results through viable up-scaling processes. Multiple thermodynamic and kinetic techniques will be used to characterize and optimize the performance of the interfaces with spectroscopy and photo-electrochemistry tools to identify best matching between light absorbers and chemical catalysts along optimum working conditions (pH, temperature, pressure). 3) Modeling: Materials, catalysts and processes will be modeled with computational methods as a pivotal tool to understand and to bring photo-catalytic-electrodes to their theoretical limits in terms of performance. The selected optimum materials and environmental conditions as defined from these parallel studies will be integrated into a PEC cell prototype. This design will include ion exchange membranes and gas diffusion electrodes for product separation. Performance will be validated in real working conditions under sun irradiation to assess the technological and industrial relevance of our A-LEAF cell.

Agency: Cordis | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2015 | Award Amount: 1.06M | Year: 2016

MAKERS will bring together leaders from business, academia and policy to study issues related to the drivers and dynamics of sustaining the competitiveness of EU manufacturing sectors. The projects innovative research, training and mobility activities will address key concerns related to the historic opportunity for the EU to lead a manufacturing renaissance that not only upgrades existing manufacturing competences but, more importantly, develops new technological capabilities across EU regions to support regional industrial resilience for more distributed and sustainable socio-economic growth and prosperity. MAKERS will create a multi-stakeholder platform to discuss the current understanding of issues related to manufacturing renaissance, including (1) the role of small, medium and large manufacturing firms and local production systems plugged into local-global value chains; (2) what are the drivers and processes for innovation, technological capabilities and technology transfer from research intuitions to firms; (3) trends in reshoring and nearshoring and the potentials for re-industrialisation and shorter value chains; (4) the impact of the socio-economic-environmental sustainability agenda on EU competitiveness; (5) skills requirements and training; and finally (6) how policy can ensure the competitiveness of EU manufacturing sectors for more distributed and sustainable socio-economic growth and prosperity. MAKERS training programme comprises: 1) annual summer schools that will cover the breadth of the issues above and address methodological requirements; 2) work package-specific Business/Academia/Policy (BAP) workshops; 3) dissemination activities within the network in conjunction with mobility, such as presentations at faculty seminar series, and doctoral level guest lectures; 4) dissemination activities at events outside the network, such as presentations at international conferences, policy fora and multi-media engagement.

Agency: Cordis | Branch: FP7 | Program: CP-FP-SICA | Phase: HEALTH.2011.2.4.3-4 | Award Amount: 4.32M | Year: 2012

MEDIGENE project will study genetic and environmental (G x E) determinants of the metabolic syndrome (MetS) in recent immigrants in Europe by a novel approach integrating ancestry of Mediterranean populations in epidemiology, locus refining and Genome Wide Association Studies (GWAS). West Mediterranean shores are place of pre-historical termini of population expansion from Southern Europe and North Africa. Archaeogenetic studies in Europe indicated that Y chromosome and mitochondrial DNA patterns or Ancestry Informative Markers (AIMs) revealed a close relationship between genetic and geographic distances able to locate an individual DNA within few hundred kilometers. The project will use this information in mapping the genetic basis of insulin resistance, cardiovascular and metabolic complications in immigrants (Albanians, Romanians, Turkish, Tunisians, Algerians and Morocco) in host countries France, Spain, Italy and Greece. Ancestry markers and studies on ancient DNA from Roman historical migration in Catalonia will help to give a better picture of the genetic landscape of Europe and North Africa. Genes for MetS will be studied in existing samples from host and home countries by GWAS, locus refining by next-generation sequencing and haplotype mapping. Informative filtered SNPs will be then used in epidemiology and novel DNA samples to reveal G x E interactions and specificities of the pathogenesis of MetS. Genetic findings will be replicated in home countries (Anatolia and North Africa) in the goal to develop markers ethnic specific and significant at a clinical scale. Major impact is expected from dissemination of our findings to prevent the occurrence of MetS and obesity in children and adolescents or in descendants of modern immigration, understanding variability clinical manifestations of MetS in the context of malnutrition and from the novel approach of GWAS strategies by ameliorating the association signal and bursting R&D activities of SMEs.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: KBBE-2007-1-2-13 | Award Amount: 4.70M | Year: 2008

A particular attention has been paid worldwide on longline fisheries as they catch considerable amount of by-catch (seabirds, turtles, sharks, etc.). Seabird and turtles by-catch mitigation methods have now been established in many fisheries worldwide, but similar efforts must be put to reduce by-catch of sharks. In the same ecosystems, another issue attracts the attention of international tuna commissions: the use of drifting fish aggregating devices (FADs). These FADs are responsible for major catches of juvenile tuna and non target pelagic species (sharks). Finally, the effects of thousands of FADs released regularly in the tropical oceans are unknown, and must be studied to estimate if they impact the biology of pelagic species. The European open ocean tropical and Mediterranean pelagic fishery (Spain, France, Portugal, Italy, Greece) is one of the main sources of catch, income and employment for the European fishery, with interactions with many developing countries. The main objective of the project is to develop measures to mitigate adverse impacts of fisheries targeting large pelagic fish in the open ocean: purse seiners using FADs and longliners. Two main categories of mitigation measures will be studied: spatial management issues (e.g. closure areas) and technical solutions to reduce by-catch in these fisheries. The main concept of MADE is to follow a multi-disciplinary and comparative approach, combining biological and technological studies with economical analyses in different sites (Indian and Atlantic oceans, Mediterranean Sea), with a particular effort to closely associate fishers from the beginning of this research. High-tech technology and novel approaches will be employed (electronic tagging, in situ and in vitro experiments, etc.), and a particular effort will be devoted to disseminate results to fishers, tuna commissions, EU DG Fisheries, and scientists.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2013.3.4 | Award Amount: 3.87M | Year: 2013

Advanced multi-functional computing systems realized in forthcoming manufacturing technologies hold the promise of a significant increase in device integration density complemented by an increase in system performance and functionality. However, a dramatic reduction in single device quality and reliability is also expected.\nCLERECO research project recognizes early accurate reliability evaluation as one of the most important and challenging tasks throughout the design cycle of computing systems across all domains. In order to continue harvesting the performance and functionality offerings of technology scaling, we need to dramatically improve current methodologies to evaluate the reliability of the system.\nOn one hand, we need accurate methodologies that reduce the performance and energy tax paid to guarantee correct operation of systems. The rising energy costs needed to compensate for increasing unpredictability are rapidly becoming unacceptable in todays environment where energy consumption is often the limiting factor on integrated circuit performance. On the other hand, early budgeting for reliability has the potential to save significant design effort and resources and has a profound impact on the TTM of a product.\nCLERECO addresses early reliability evaluation with a cross-layer approach across different computing disciplines, across computing system layers and across computing market segments to address reliability for the emerging computing continuum. CLERECO methodology will consider low-level information such as raw failure rates as well as the entire set of hardware and software components of the system that eventually determine the reliability delivered to the end users.\nThe CLERECO project methodology for early reliability evaluation will be comprehensively assessed and validated in advanced designs from different applications provided by the industrial partners for the full stack of hardware and software layers.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2010-ITN | Award Amount: 3.06M | Year: 2011

The FUNEA vision is to develop an integrated and multidisciplinary research and training programme in the field of inorganic nitrides for energy applications. In terms of fundamental research, the FUNEA aims to advance the state-of-the-art knowledge and understanding of inorganic nitrides and mixed nitride-anion systems by achieving the ability to synthesise, manipulate, characterize, understand and model binary and ternary nitrides and oxonitrides with functional properties. By this a breakthrough in the nitride chemistry will be achieved steering in a new era for materials with advanced functionality and exceptional levels of performance. In terms of technological applications, the FUNEA focuses on the energetic applications of novel nitride-based materials with this addressing the main needs of the 21st century. To meet this vision, eight European academic research groups with complementary expertise in the synthesis, processing and characterization of materials and five industrial partners, each of whom have made a commitment to study these new functional nitrides, have decided to create a network of scientific cooperation with the following goals: (i) to create an interdisciplinary approach to the synthesis, processing and characterization of novel nitrides for energy applications, (ii) to train high-quality young researchers, experienced in the interdisciplinary science of the nitrides. These young professionals will lead the field forward and onward to its bright future in the European science and technology. Specifically, FUNEA aims to train 11 ESRs and 2 ERs with an overall target of 40% women researchers, and (iii) to establish a European network of scientists in academic institutes and industry in the field of inorganic nitrides, that will continue to grow and enhance European competitiveness over the next years.

Agency: Cordis | Branch: FP7 | Program: BSG-SME | Phase: SME-1 | Award Amount: 1.37M | Year: 2010

The consortium behind AGROBIOFILM project a group of European SME suppliers and users of agricultural plastics wishes to address a major market opportunity through the development and performance demonstration of mulch films that would be able to fulfill the three main following requirements: to be more environmentally friendly (i.e; biodegradable in soil without containing a high content in fossil carbon); to be compliant with common farming methods; and to match or improve crops performance as expected in the case of conventional plastic films and other biodegradable mulch films available in the market. Specifically, the consortium wants to enhance mulch films based on biodegradable raw materials, which will be customized to specific crops and regions, with a possible positive effect on crop yield and quality, pests and/or disease control, soil preparation and fertilization. The goal of this project is to use a very recent Mater-Bi formulation characterized by a higher content in renewable feedstocks as compared to the other biodegradable mulch films currently used, the Novamonts Mater-Bi CF04P grade (which is not widely widespread), in order to produce, through a be-spoke optimization of processing conditions, customized and enhanced biodegradable mulch films (BMF) that should be more competitive and more sustainable, at both the technical and the economic point-of-view. These new mulches will be tested on four selected crops (muskmelon, bell-pepper, grapevine, strawberry open field and strawberry in greenhouse) known to require different specific expectations in terms of mulching lifetime. A full life cycle analysis is therefore fundamental in order to measure the economic viability of this new product AGROBIOFILM will significantly promote the uptake of highly productive and environmentally friendly farming practices among end-users, who are currently facing a number of competitive challenges threatening the economic stability of the sector. The project will also increase the competitiveness of the participating SME manufacturers by providing them with a state-of-the-art platform to develop competitive biodegradable mulch films, and therefore widening the applicability of their biodegradable products to new markets. Agrobiofilm project runs from 01 April 2010 to 28 March 2013, but the effective duration of the project is 30 months.

Honeywell, Montpellier University and French National Center for Scientific Research | Date: 2015-12-16

A polymeric molecule having the formula: X[C(A)_(2)C(B)(B)]_(n)-Q[CYC(Z)(Z)] or [C(A)_(2)=C(B)]_(n)-Q[C(Y)(Y)C(Z)(Z)]X, wherein A is either H or F; B and B are either H, F, or Cl, and are not necessarily the same; X and X are Br, Cl or I (and are not necessarily the same); Y and Y are F, Br, Cl or I (and are not necessarily the same); and wherein Z and Z are F, Br, Cl or I (and are not necessarily the same); Q is optional and is either oxygen (O) or sulfur (S); and n is at least 1.

French National Center for Scientific Research, ESPCI ParisTech, Montpellier University, University of Paris 13 and University Paris - Sud | Date: 2014-02-25

The use of compounds of formula (1) as defined in the description, for reducing or preventing the onset of metastases in a patient suffering from cancer. Pharmaceutical compositions for using in human or veterinary medicine, including at least one compound of formula (1) are also described.

ZENTARIS GmbH, French National Center for Scientific Research and Montpellier University | Date: 2010-09-13

The present invention provides novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors according to formula (I) that are useful in the treatment or prophylaxis of physiological and/or pathophysiological conditions in mammals, preferably humans, that are mediated by GHS receptors. The present invention further provides GHS receptor antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular growth retardation, cachexia, short-, medium- and/or long term regulation of energy balance; short-, medium- and/or long term regulation (stimulation and/or inhibition) of food intake; adipogenesis, adiposity and/or obesity; body weight gain and/or reduction; diabetes, diabetes type I, diabetes type II, tumor cell proliferation; inflammation, inflammatory effects, gastric postoperative ileus, postoperative ileus and/or gastrectomy (ghrelin replacement therapy).

Vassallo R.,University of Savoy | Ritz J.-F.,Montpellier University | Carretier S.,Toulouse 1 University Capitole
Geomorphology | Year: 2011

The dating of alluvial landforms by cosmogenic nuclides requires distinguishing the pre-deposition inheritance from the post-deposition history of the clasts in the studied marker. Moreover, estimating catchment-scale erosion rates from the concentrations of cosmogenic nuclides in active alluvia requires a good knowledge of the local/regional relationships between rock exhumation and transport through space and time. This is still poorly known for timescales of tens of thousand years. In order to document the evolution of clast exhumation and transport rates through time, we analyze in situ 10Be concentrations in boulders and cobbles from hillslopes to outlet of an arid mountainous catchment located in Gobi-Altay, Mongolia, strongly affected by global climatic changes during the Pleistocene-Holocene period. Samples were collected on bedrock, abandoned alluvial deposits, active colluvia and alluvia. Our results show a large 10Be scattering in the active river bed, consistent with a low and discontinuous catchment erosion rate dominated by mass wasting and fluvial incision. On the contrary, pre-exposure signal within abandoned terraces is much more homogeneous, consistent with climatic pulses responsible of strong erosional events on hillslopes and rapid fluvial transport. These results show that exhumation/transport processes at the catchment scale vary in style and intensity through time as a consequence of climatic oscillations. The occurrence of abrupt climatic changes during short periods of time recorded by 10Be concentrations in abandoned alluvia raise questions about the temporal applicability of catchment erosion rates derived from cosmogenic nuclide concentrations measured in sediments of active rivers. On the other hand, strong and short erosion events limit and homogenize the pre-exposure 10Be signal in associated deposits like debris-flows, making them particularly suitable markers for dating in active tectonic and paleoclimatic studies. © 2011 Elsevier B.V.

Djamour Y.,P.A. College | Vernant P.,Montpellier University | Nankali H.R.,National Cartographic Center | Tavakoli F.,National Cartographic Center
Earth and Planetary Science Letters | Year: 2011

A network of continuous GPS stations has been installed in NW Iran since 2005 to complement the survey GPS network already existing in the region. We present the 1999-2009 GPS-derived velocity field for this region based on the continuous and survey-mode observations. The results confirm a right lateral slip of 7 ± 1. mm/yr for the North Tabriz fault, in agreement with previous studies. This rate is consistent with earthquakes of magnitude 7-7.3 and recurrence times of 250-300. yr. The higher spatial coverage of the new network shows that deformation is localized in the vicinity of the Chalderan, south Gailatu-Siah Cheshmeh-Khoy fault and the North Tabriz fault. However the eastern end of the North Tabriz fault appears to cross Mount Bozgush rather than following its southern foothills. This new velocity field does not indicate the 8. mm/yr of NNE-SSW extension suggested earlier for the region, but rather shows lower extension of 1-2 ± 1. mm/yr across the eastern segment of the North Tabriz fault and the Talesh. To the west, the Chalderan and the western North Tabriz fault segment act like pure strike slip faults without significant extension or compression. The denser network in the Rudbar earthquake region (Ms 7.3, 1992) shows no significant motion across the fault, suggesting that the recurrence time of earthquakes like the Rudbar event must be very long. The lack of substantial compressive strain and the sharp azimuth change of the velocity vectors in the transition zone from Arabia to Lesser Caucasus motion imply that processes other than "extrusion", possibly related to old subduction or delamination, contribute to active deformation. © 2011 Elsevier B.V.

Le S.Q.,Montpellier University | Le S.Q.,Wellcome Trust Sanger Institute | Gascuel O.,Montpellier University
Systematic Biology | Year: 2010

Amino acid substitution models are essential to most methods to infer phylogenies from protein data. These models represent the ways in which proteins evolve and substitutions accumulate along the course of time. It is widely accepted that the substitution processes vary depending on the structural configuration of the protein residues. However, this information is very rarely used in phylogenetic studies, though the 3-dimensional structure of dozens of thousands of proteins has been elucidated. Here, we reinvestigate the question in order to fill this gap. We use an improved estimation methodology and a very large database comprising 1471 nonredundant globular protein alignments with structural annotations to estimate new amino acid substitution models accounting for the secondary structure and solvent accessibility of the residues. These models incorporate a confidence coefficient that is estimated from the data and reflects the reliability and usefulness of structural annotations in the analyzed sequences. Our results with 300 independent test alignments show an impressive likelihood gain compared with standard models such as JTT or WAG. Moreover, the use of these models induces significant topological changes in the inferred trees, which should be of primary interest to phylogeneticists. Our data, models, and software are available for download from phyml-structure/.

Luquot L.,Montpellier University | Andreani M.,University Claude Bernard Lyon 1 | Gouze P.,Montpellier University | Camps P.,Montpellier University
Chemical Geology | Year: 2012

Underground CO 2 sequestration is highly recommended as an effective means of significantly decreasing CO 2 concentration in the atmosphere. Mineral storage is the more secure technology, but requires the presence of high concentration of divalent cations in the pore-fluid. Results from CO 2 percolation experiments through chlorite/zeolite-rich sandstone samples from the Pretty Hill Formation (Otway Basin, Australia) are presented. The dissolution of the laumontite (7wt.%) and chamosite (7wt.%) are the potential sources of calcium, iron and magnesium required for carbonate precipitation. The percolation experiment was setup to reproduce, at laboratory scale, the in situ temperature and pressure conditions (T=95°C and P=10MPa). The fluid injected at constant flow rate is a rock-equilibrated brine subsequently enriched in CO 2 up to partial pressure of 6MPa.We observe feldspars, laumontite and chamosite dissolution, kaolinite and silica precipitation and a noticeable sink of CO 2 in the sample which is attributed to the precipitation of both amorphous carbon due to the reduction of CO 2 and Fe-rich carbonate. Permeability decreases of about one order of magnitude due to the localization of the kaolinite precipitation in the main flow paths, while porosity increases.The high reactivity of this sandstone makes this reservoir a valuable target for CO 2 mineralization, but the associated permeability decrease may limit the injection rate and the spreading of the CO 2 in the reservoir. © 2011 Elsevier B.V.

Jimenez-Moreno G.,University of Granada | Fauquette S.,Montpellier University | Suc J.-P.,University Claude Bernard Lyon 1
Review of Palaeobotany and Palynology | Year: 2010

Pollen analysis of Miocene and Pliocene sediments from the Iberian Peninsula shows a progressive reduction in plant diversity through time caused by the disappearance of thermophilous and high-water requirement plants. In addition, an increase in warm-temperate (mesothermic), seasonal-adapted "Mediterranean" taxa, high-elevation conifers and herbs (mainly Artemisia) occurred during the Middle and Late Miocene and Pliocene. This has mainly been interpreted as a response of the vegetation to global and regional processes, including climate cooling related to the development of the East Antarctic Ice Sheet and then the onset of the Arctic Ice Sheet, uplift of regional mountains related to the Alpine uplift and the progressive movement of Eurasia towards northern latitudes as a result of the northwards subduction of Africa. The development of steppe-like vegetation in southern Iberia is ancient and probably started during the Oligocene. The onset of a contrasted seasonality in temperature during the Mid-Pliocene superimposed on the pre-existing seasonality in precipitation, the annual length of which increased southward. The Mediterranean climatic rhythm (summer drought) began about 3.4. Ma and caused the individualization of modern Mediterranean ecosystems. Quaternary-type Mediterranean climatic fluctuations started at 2.6. Ma (Gelasian) resulting in repeated steppe vs. forest alternations. A latitudinal climatic gradient between the southern and the northern parts of the Iberian Peninsula existed since the Middle Miocene. © 2009 Elsevier B.V.

Ducros A.,Montpellier University | Wolff V.,University of Strasbourg
Headache | Year: 2016

During the last 10 years, reversible cerebral vasoconstriction syndrome (RCVS) has emerged as the most frequent cause of thunderclap headache (TCH) in patients without aneurysmal subarachnoid hemorrhage, and as the most frequent cause of recurrent TCHs. The typical TCHs of RCVS are multiple, recurring over a few days to weeks, excruciating, short-lived, and brought up by exertion, sexual activities, emotion, Valsalva maneuvers, or bathing, among other triggers. All these triggers induce sympathetic activation. In a minority of cases with RCVS, TCH heralds stroke and rarely death. Early diagnosis of RCVS in patients who present with isolated headache enables proper management and might reduce the risk of eventual stroke. This review describes the characteristics, triggers, diagnosis, and management of TCH in RCVS. One aim is to underline that the TCH pattern of RCVS is so typical that it enables, according to the 2013 revision of the International Classification of Headache Disorders, the diagnosis of "probable RCVS" in patients with such a headache pattern, normal cerebral angiography, and no other cause. Another objective is to discuss the role of physical and emotional stress in RCVS and in other related conditions involving similar triggers. © 2016 American Headache Society.

Al-Zein A.,Montpellier University | Al-Zein A.,Charles Gerhardt Institute | Hlinka J.,ASCR Institute of Physics Prague | Rouquette J.,Charles Gerhardt Institute | Hehlen B.,Montpellier University
Physical Review Letters | Year: 2010

Hyper-Raman scattering experiments suggest that a splitting of the lowest F1u-symmetry mode of PbMg1/3Nb2/3O3 crystal occurs in a wide temperature range around its Burns temperature Td≈630K. The upper-frequency component, earlier investigated by inelastic neutron scattering experiments above Td, appears to be underdamped even hundred of degrees below Td. The lower-frequency component, known below Td from far-IR spectroscopy, actually becomes underdamped above Td. This suggests that the lower-frequency mode is the "primary" polar soft mode of PbMg1/3Nb2/3O3, responsible for the Curie-Weiss behavior of its dielectric permittivity above Td. © 2010 The American Physical Society.

Desbrosses G.J.,Montpellier University | Stougaard J.,University of Aarhus
Cell Host and Microbe | Year: 2011

Legume plants have an exceptional capacity for association with microorganisms, ranging from largely nonspecific to very specific interactions. Legume-rhizobial symbiosis results in major developmental and metabolic changes for both the microorganism and host, while providing the plant with fixed nitrogen. A complex signal exchange leads to the selective rhizobial colonization of plant cells within nodules, new organs that develop on the roots of host plants. Although the nodulation mechanism is highly specific, it involves the same subset of plant phytohormones, namely auxin, cytokinin, and ethylene, which are required for root development. In addition, nodulation triggered by the rhizobia affects the development of the host root system, indicating that the microorganism can alter host developmental pathways. Nodulation by rhizobia is a prime example of how microorganisms and plants have coevolved and exemplifies how microbial colonization may affect plant developmental pathways. © 2011 Elsevier Inc.

Renaud S.,University Claude Bernard Lyon 1 | Auffray J.-C.,Montpellier University
Journal of Zoological Systematics and Evolutionary Research | Year: 2010

Morphometric methods allow the quantification of directions of phenotypic changes and their statistical comparison in a morphometric space. We applied this approach to investigate several candidate factors to explain changes in mandible shape occurring in house mice (Mus musculus domesticus, Mammalia, Rodentia) in Corsica and a nearby islet. The role of niche widening and of the concomitant change in diet was evaluated by comparing the micro-evolutionary insular change to the macro-evolutionary difference between omnivorous and herbivorous rodents. Phenotypic plasticity, which may contribute to rapid insular evolution, was assessed by breeding laboratory mice on hard versus soft food. The related change in mandible shape was compared with differences between continental and insular populations. The role of allometry was evaluated by assessing shape change related to size within the continental population and comparing this direction of change with differences on islands. Finally, evolution may be facilitated along the direction of the greatest phenotypic variance. This hypothesis was tested by computing in wild populations vectors corresponding to this direction and by comparing these vectors with those corresponding to estimates of shape changes related to plasticity, micro- and macro-evolutionary processes. In Corsica, the congruence in directions of macro- and micro-evolutionary phenotypic vectors (Corsican/continental mice versus omnivorous/herbivorous rodents) supports the hypothesis of adaptation in mandible shape evolution. By contrast, on the islet, phenotypic divergence follows directions of plastic response to food consistency as well as within-population allometry. Thus, results suggest differences in the relative importance of processes which may influence rodent mandibular shape depending on the size of the islands they colonized. Faster evolution and plasticity may be more evident in small and often ephemeral populations living on small islands, whereas micro-evolutionary processes may have enough time and genetic variability to progressively 'align' with macro-evolutionary trends in large populations from big islands. © 2009 Blackwell Verlag GmbH.

Barthes J.,Montpellier University | Godelle B.,Montpellier University | Raymond M.,CNRS Montpellier Institute of Evolutionary Sciences
Evolution and Human Behavior | Year: 2013

Male homosexual preference (MHP) challenges evolutionary thinking because the preference for male-male relationships is heritable, implies a fertility cost (lower offspring number), and is relatively frequent in some societies (2%-6% in Western countries) for a costly trait. Proximate explanations include the hypothesis of a "sexually antagonistic factor" in which a trait that increases fertility in females also promotes the emergence of MHP. Because no animal species is known to display consistent MHP in the wild (only transient and contextual homosexual behavior has been described), additional human-specific features must contribute to the maintenance of MHP in human populations. We built a theoretical model that revealed that, in a stratified society, a relatively high frequency of MHP could be maintained as a result of the social ascension of females signaling high fertility (hypergyny). Additional computer simulations confirmed that this result applies to populations with various numbers of classes, conditions of demographic regulation, and mating systems. The prediction that MHP is more prevalent in stratified societies was significantly supported in a sample of 48 societies for which the presence or absence of MHP has been anthropologically documented. More generally, any traits associated with up-migration are likely to be selected for in a stratified society and will be maintained by frequency dependence even if they induce a pleiotropic cost, such as MHP. These results offer a new perspective for understanding seemingly paradoxical traits in human populations. © 2013 Elsevier Inc.

Mouillot D.,Montpellier University | Villeger S.,CNRS Biological Evolution and Diversity Laboratory | Scherer-Lorenzen M.,Albert Ludwigs University of Freiburg | Mason N.W.H.,Landcare Research
PLoS ONE | Year: 2011

The accelerating rate of change in biodiversity patterns, mediated by ever increasing human pressures and global warming, demands a better understanding of the relationship between the structure of biological communities and ecosystem functioning (BEF). Recent investigations suggest that the functional structure of communities, i.e. the composition and diversity of functional traits, is the main driver of ecological processes. However, the predictive power of BEF research is still low, the integration of all components of functional community structure as predictors is still lacking, and the multifunctionality of ecosystems (i.e. rates of multiple processes) must be considered. Here, using a multiple-processes framework from grassland biodiversity experiments, we show that functional identity of species and functional divergence among species, rather than species diversity per se, together promote the level of ecosystem multifunctionality with a predictive power of 80%. Our results suggest that primary productivity and decomposition rates, two key ecosystem processes upon which the global carbon cycle depends, are primarily sustained by specialist species, i.e. those that hold specialized combinations of traits and perform particular functions. Contrary to studies focusing on single ecosystem functions and considering species richness as the sole measure of biodiversity, we found a linear and non-saturating effect of the functional structure of communities on ecosystem multifunctionality. Thus, sustaining multiple ecological processes would require focusing on trait dominance and on the degree of community specialization, even in species-rich assemblages. © 2011 Mouillot et al.

Le S.Q.,Montpellier University | Le S.Q.,Wellcome Trust Sanger Institute | Dang C.C.,Vietnam National University, Hanoi | Gascuel O.,Montpellier University
Molecular Biology and Evolution | Year: 2012

Most protein substitution models use a single amino acid replacement matrix summarizing the biochemical properties of amino acids. However, site evolution is highly heterogeneous and depends on many factors that influence the substitution patterns. In this paper, we investigate the use of different substitution matrices for different site evolutionary rates. Indeed, the variability of evolutionary rates corresponds to one of the most apparent heterogeneity factors among sites, and there is no reason to assume that the substitution patterns remain identical regardless of the evolutionary rate. We first introduce LG4M, which is composed of four matrices, each corresponding to one discrete gamma rate category (of four). These matrices differ in their amino acid equilibrium distributions and in their exchangeabilities, contrary to the standard gamma model where only the global rate differs from one category to another. Next, we present LG4X, which also uses four different matrices, but leaves aside the gamma distribution and follows a distribution-free scheme for the site rates. All these matrices are estimated from a very large alignment database, and our two models are tested using a large sample of independent alignments. Detailed analysis of resulting matrices and models shows the complexity of amino acid substitutions and the advantage of flexible models such as LG4M and LG4X. Both significantly outperform single-matrix models, providing gains of dozens to hundreds of log-likelihood units for most data sets. LG4X obtains substantial gains compared with LG4M, thanks to its distribution-free scheme for site rates. Since LG4M and LG4X display such advantages but require the same memory space and have comparable running times to standard models, we believe that LG4M and LG4X are relevant alternatives to single replacement matrices. Our models, data, and software are available from http://www.atgc- © 2012 The Author.

Girard C.,Montpellier University | Renaud S.,University Claude Bernard Lyon 1
PLoS ONE | Year: 2012

Early periods in Earth's history have seen a progressive increase in complexity of the ecosystems, but also dramatic crises decimating the biosphere. Such patterns are usually considered as large-scale changes among supra-specific groups, including morphological novelties, radiation, and extinctions. Nevertheless, in the same time, each species evolved by the way of micro-evolutionary processes, extended over millions of years into the evolution of lineages. How these two evolutionary scales interacted is a challenging issue because this requires bridging a gap between scales of observation and processes. The present study aims at transferring a typical macro-evolutionary approach, namely disparity analysis, to the study of fine-scale evolutionary variations in order to decipher what processes actually drove the dynamics of diversity at a micro-evolutionary level. The Late Frasnian to Late Famennian period was selected because it is punctuated by two major macro-evolutionary crises, as well as a progressive diversification of marine ecosystem. Disparity was estimated through this period on conodonts, tooth-like fossil remains of small eel-like predators that were part of the nektonic fauna. The study was focused on the emblematic genus of the period, Palmatolepis. Strikingly, both crises affected an already impoverished Palmatolepis disparity, increasing risks of random extinction. The major disparity signal rather emerged as a cycle of increase and decrease in disparity during the inter-crises period. The diversification shortly followed the first crisis and might correspond to an opportunistic occupation of empty ecological niche. The subsequent oriented shrinking in the morphospace occupation suggests that the ecological space available to Palmatolepis decreased through time, due to a combination of factors: deteriorating climate, expansion of competitors and predators. Disparity changes of Palmatolepis thus reflect changes in the structure of the ecological space itself, which was prone to evolve during this ancient period where modern ecosystems were progressively shaped. © 2012 Girard, Renaud.

Sanyal U.,Indian Institute of Science | Demirci U.B.,University Claude Bernard Lyon 1 | Demirci U.B.,Montpellier University | Jagirdar B.R.,Indian Institute of Science | Miele P.,Montpellier University
ChemSusChem | Year: 2011

In today's era of energy crisis and global warming, hydrogen has been projected as a sustainable alternative to depleting CO 2-emitting fossil fuels. However, its deployment as an energy source is impeded by many issues, one of the most important being storage. Chemical hydrogen storage materials, in particular B-N compounds such as ammonia borane, with a potential storage capacity of 19.6 wt % H 2 and 0.145 kg H 2 L -1, have been intensively studied from the standpoint of addressing the storage issues. Ammonia borane undergoes dehydrogenation through hydrolysis at room temperature in the presence of a catalyst, but its practical implementation is hindered by several problems affecting all of the chemical compounds in the reaction scheme, including ammonia borane, water, borate byproducts, and hydrogen. In this Minireview, we exhaustively survey the state of the art, discuss the fundamental problems, and, where applicable, propose solutions with the prospect of technological applications. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Philippon M.,VU University Amsterdam | Brun J.-P.,University of Rennes 1 | Gueydan F.,Montpellier University
Tectonophysics | Year: 2012

The Cycladic Blueschist Unit (CBU) represents the northern passive margin of the Adria continental block and ophiolites that are the remnants of the Pindos Ocean, which were affected by high pressure-low temperature metamorphism in the blueschist and eclogite facies during the Eocene. Prior to the Lutetian, the ophiolitic and margin units were thrust towards the SW inside a NE-dipping subduction zone. Two subsequent exhumation stages are characterized by top-to-the-NE senses of shear: i) from mantle depths to lower crustal levels, before 37. Ma, which was accommodated by an extensional inversion of the Vardar suture zone, and ii) from deep crustal levels to the near-surface, between 30 and 20. Ma, which was accommodated by the North Cycladic Detachment. It is during this late stage of ductile exhumation that the central Cyclades Core Complex was exhumed. Segmentation of the CBU by normal faults started at 12. Ma, as recorded by the low temperature thermochronometers, and was coeval with block rotation and folding with NS-trending axes, which were predominantly controlled by the Myrthes-Ikaria strike-slip fault in the centre of the Cyclades. A map restoration of the CBU geometry, prior to segmentation, has been carried out using available structural and paleomagnetic data. The restoration shows that, following the CBU exhumation from mantle depths to crustal levels, a single core complex was exhumed along a single NE dipping detachment. © 2011 Elsevier B.V.

Rico A.,University Claude Bernard Lyon 1 | Strauss O.,Montpellier University
International Journal of Approximate Reasoning | Year: 2010

In most sensor measure based applications, the raw sensor signal has to be processed by an appropriate filter to increase the signal-to-noise ratio or simply to recover the signal to be measured. In both cases, the filter output is obtained by convoluting the sensor signal with a supposedly known appropriate impulse response. However, in many real life situations, this impulse response cannot be precisely specified. The filtered value can thus be considered as biased by this arbitrary choice of one impulse response among all possible impulse responses considered in this specific context. In this paper, we propose a new approach to perform filtering that aims at computing an interval valued signal containing all outputs of filtering processes involving a coherent family of conventional linear filters. This approach is based on a very straightforward extension of the expectation operator involving appropriate concave capacities. © 2010 Elsevier Inc. All rights reserved.

Arribas J.R.,Hospital La Paz | Pialoux G.,University Pierre and Marie Curie | Gathe J.,Baylor College of Medicine | Di Perri G.,University of Turin | And 6 more authors.
The Lancet Infectious Diseases | Year: 2014

Background: Patients with HIV on antiretroviral therapy might benefit from regimen simplification to reduce pill burden and dosing frequency. We aimed to assess the safety and efficacy of simplifying the treatment regimen for adults with virologically suppressed HIV infection from a ritonavir-boosted protease inhibitor and emtricitabine plus tenofovir disoproxil fumarate (tenofovir) regimen to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir. Methods: STRATEGY-PI is a 96 week, international, multicentre, randomised, open-label, phase 3b trial in which HIV-infected adults with a plasma HIV-1 RNA viral load of less than 50 copies per mL for at least 6 months who were taking a ritonavir-boosted protease inhibitor with emtricitabine plus tenofovir were randomly assigned (2:1) either to switch to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir or to continue on their existing regimen. Key eligibility criteria included no history of virological failure, no resistance to emtricitabine and tenofovir, and creatinine clearance of 70 mL/min or higher. Neither participants nor investigators were masked to group allocation. The primary endpoint was the proportion of participants with a viral load of less than 50 copies per mL at week 48, based on a US Food and Drug Administration snapshot algorithm for the modified intention-to-treat population, which excluded major protocol violations (prohibited resistance or not receiving a protease inhibitor at baseline). We prespecified non-inferiority with a 12% margin; if non-inferiority was established, superiority was tested as per a prespecified sequential testing procedure. This trial is registered at, number NCT01475838. Findings: Between Dec 12, 2011, and Dec 20, 2012, 433 participants were randomly assigned and received at least one dose of study drug. Of these participants, 293 were assigned to switch to the simplified regimen (switch group) and 140 to remain on their existing regimen (no-switch group); after exclusions, 290 and 139 participants, respectively, were analysed in the modified intention-to-treat population. At week 48, 272 (93·8%) of 290 participants in the switch group maintained a viral load of less than 50 copies per mL, compared with 121 (87·1%) of 139 in the no-switch group (difference 6·7%, 95% CI 0·4-13·7; p=0·025). The statistical superiority of the simplified regimen was mainly caused by a higher proportion of participants in the no-switch group than in the switch group discontinuing treatment for non-virological reasons; virological failure was rare in both groups (two [1%] of 290 vs two [1%] of 139). We did not detect any treatment-emergent resistance in either group. Adverse events leading to discontinuation were rare in both groups (six [2%] of 293 vs four [3%] of 140). Switching to the simplified regimen was associated with a small, non-progressive increase from baseline in serum creatinine concentration. Nausea was more common in the switch group than in the no-switch group, but rates of diarrhoea and bloating decreased compared with baseline from week 4 to week 48 in the switch group, whereas there were generally no changes for these symptoms in the no-switch group. Interpretation: Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir might be a useful regimen simplification option for virologically supressed adults with HIV taking a multitablet ritonavir-boosted protease inhibitor regimen. Funding: Gilead Sciences. © 2014 Elsevier Ltd.

Schneider M.,MPI of Biophysical Chemistry | Will C.L.,MPI of Biophysical Chemistry | Anokhina M.,MPI of Biophysical Chemistry | Tazi J.,Montpellier University | And 2 more authors.
Molecular Cell | Year: 2010

The first step in splicing of pre-mRNAs with long introns is exon definition, where U1 and U2 snRNPs bind at opposite ends of an exon. After exon definition, these snRNPs must form a complex across the upstream intron to allow splicing catalysis. Exon definition and conversion of cross-exon to cross-intron spliceosomal complexes are poorly understood. Here we demonstrate that, in addition to U1 and U2 snRNPs, cross-exon complexes contain U4, U5, and U6 (which form the tri-snRNP). Tri-snRNP docking involves the formation of U2/U6 helix II. This interaction is stabilized by a 5′ splice site (SS)-containing oligonucleotide, which can bind the tri-snRNP and convert the cross-exon complex into a cross-intron, B-like complex. Our data suggest that the switch from cross-exon to cross-intron complexes can occur directly when an exon-bound tri-snRNP interacts with an upstream 5′SS, without prior formation of a cross-intron A complex, revealing an alternative spliceosome assembly pathway. © 2010 Elsevier Inc. All rights reserved.

Maimoun L.,Service dHormonologie | Sultan C.,Service dHormonologie | Sultan C.,Montpellier University
Metabolism: Clinical and Experimental | Year: 2011

Physical exercise is recommended to improve bone mass in growing children and decrease bone loss in elderly men and women. However, the specific mechanisms by which exercise influences bone metabolism are still not thoroughly understood. The effect of physical activity on the skeleton is generally evaluated by dual-energy x-ray absorptiometry, which measures bone mineral density. However, a relatively long period is needed to detect even a minor variation in bone mineral density with this technique, limiting its usefulness. Bone biochemical markers that reflect the cellular activities of bone formation and resorption are thus also useful tools, both to monitor the acute effects of exercise on bone remodeling and to investigate the mechanisms of exercise-induced changes in bone mass. This article describes the effects of physical activity on bone remodeling in various types of population. The comparison of sedentary individuals and athletes with many years of high-volume sports practice, for example, has clarified some of the long-term effects of exercise. Moreover, the acute variation in bone cell activities after brief exercise or a training program is here examined. The interpretation of results is difficult, however, because of the many parameters, such as age, that are involved. The various populations are therefore categorized to reflect the biological factors implicated in the modulation of bone marker response during exercise. © 2011 Elsevier Inc. All rights reserved.

Antonelli P.,Gran Sasso Science Institute | Carles R.,Montpellier University | Silva J.D.,University of Lisbon
Communications in Mathematical Physics | Year: 2014

We consider the nonlinear Schrödinger equation under a partial quadratic confinement. We show that the global dispersion corresponding to the direction(s) with no potential is enough to prove global in time Strichartz estimates, from which we infer the existence of wave operators, thanks to suitable vector-fields. Conversely, given an initial Cauchy datum, the solution is global in time and asymptotically free, provided that confinement affects one spatial direction only. This stems from anisotropic Morawetz estimates, involving a marginal of the position density. © 2014, Springer-Verlag Berlin Heidelberg.

Dutheil J.Y.,University of Aarhus | Dutheil J.Y.,Montpellier University | Jossinet F.,University of Strasbourg | Westhof E.,University of Strasbourg
Molecular Biology and Evolution | Year: 2010

It has long been accepted that the structural constraints stemming from the 3D structure of ribosomal RNA (rRNA) lead to coevolution through compensating mutations between interacting sites. State-of-the-art methods for detecting coevolving sites, however, while reaching high levels of specificity and sensitivity for Watson-Crick (WC) pairs of the helices defining the secondary structure, only scarcely reveal tertiary interactions occurring at the level of the 3D structure. In order to understand the relative failure of coevolutionary methods to detect such interactions, we analyze 2,682 interacting sites derived from high-resolution structures, which include a comprehensive data set of rRNA sequences from Archaea and Bacteria. We report a striking difference in the amount of coevolution between WC and non-WC pairs. In order to understand this pattern, we derive fitness landscapes from the geometry of base pairing interactions and construct neutral networks of substitutions for each type of interaction. These networks show that coevolution is a property of WC pairs because, unlike non-WC pairs, their landscapes exhibit fitness valleys, a single mutation in a WC pair resulting in a fitness drop. Second, we used the inferred neutral networks to estimate the level of constraint acting on each type of base pair and show that it correlates negatively with the observed rate of substitutions for all non-WC pairs. WC pairs appear as outliers, fixing more substitutions than expected according to their level of constraint. We here propose that the rate of substitution in WC pairs is due to coevolution resulting from constraints acting at intermediate levels of organization, namely the one of the helical stem with its forming WC pairs. In agreement with this hypothesis, we report a significant excess of intrahelical, inter-WC pairs coevolution compared with interhelices pairs. Altogether, these results show that detailed biochemical knowledge is required and has to be incorporated into evolutionary reasoning in order to understand the fine patterns of variation at the molecular level. They also demonstrate that coevolutionary analysis provides almost exclusively 2D information and only little 3D signal. © The Author 2010. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.

Bitume E.V.,Earth and Life Institute | Bitume E.V.,Montpellier University | Bonte D.,Ghent University | Ronce O.,Montpellier University | And 4 more authors.
Ecology Letters | Year: 2013

Although dispersal distance plays a major role in determining whether organisms will reach new habitats, empirical data on the environmental factors that affect dispersal distance are lacking. Population density and kin competition are two factors theorised to increase dispersal distance. Using the two-spotted spider mite as a model species, we altered these two environmental conditions and measured the mean dispersal distance of individuals, as well as other attributes of the dispersal kernel. We find that both density and relatedness in the release patch increase dispersal distance. Relatedness, but not density, changes the shape of the dispersal kernel towards a more skewed and leptokurtic shape including a longer 'fat-tail'. This is the first experimental demonstration that kin competition can shape the whole distribution of dispersal distances in a population, and thus affect the geographical spread of dispersal phenotypes. © 2013 Blackwell Publishing Ltd/CNRS.

Andreev S.V.,Montpellier University | Varlamov A.A.,CNR Institute of Neuroscience | Kavokin A.V.,University of Southampton | Kavokin A.V.,Saint Petersburg State University
Physical Review Letters | Year: 2014

We address, theoretically, the puzzling similarity observed in the thermodynamic behavior of independent clouds of cold dipolar excitons in coupled semiconductor quantum wells. We argue that the condensation of self-trapped exciton gas starts at the same critical temperature in all traps due to the specific scaling rule. As a consequence of the reduced dimensionality of the system, the scaling parameters appear to be insensitive to disorder. © 2014 American Physical Society.

Renaud S.,University Claude Bernard Lyon 1 | Pantalacci S.,CNRS Lyon Institute of Functional Genomics | Auffray J.-C.,Montpellier University
PLoS ONE | Year: 2011

Variation within a population is a key feature in evolution, because it can increase or impede response to selection, depending on whether or not the intrapopulational variance is correlated to the change under selection. Hence, main directions of genetic variance have been proposed to constitute "lines of least resistance to evolution" along which evolution would be facilitated. Yet, the screening of selection occurs at the phenotypic level, and the phenotypic variance is not only the product of the underlying genetic variance, but also of developmental processes. It is thus a key issue for interpreting short and long term evolutionary patterns to identify whether main directions of phenotypic variance indeed constitute direction of facilitated evolution, and whether this is favored by developmental processes preferably generating certain phenotypes. We tackled these questions by a morphometric quantification of the directions of variance, compared to the direction of evolution of the first upper and lower molars of wild continental and insular house mice. The main phenotypic variance indeed appeared as channeling evolution between populations. The upper molar emerged as highly evolvable, because a strong allometric component contributed to its variance. This allometric relationship drove a repeated but independent evolution of a peculiar upper molar shape whenever size increased. This repeated evolution, together with knowledge about the molar development, suggest that the main direction of phenotypic variance correspond here to a "line of least developmental resistance" along which evolution between population is channeled. © 2011 Renaud et al.

Carillon J.,Montpellier University | Rouanet J.-M.,Montpellier University | Cristol J.-P.,Montpellier University | Brion R.,Center CAPIO BAYARD
Pharmaceutical Research | Year: 2013

Oxidative stress, involved in many diseases, is defined as an impaired balance between reactive oxygen species (ROS) production and antioxidant defences. Antioxidant enzymes such as superoxide dismutase (SOD) play a key role in diminishing oxidative stress. Thus, the removal of ROS by exogenous SODs could be an effective preventive strategy against various diseases. The poor bioavailability of exogenous SODs has been criticized. However, improvements in SOD formulation may overcome this limitation and boost interest in its therapeutic properties. Here, we provide a review of animal and human studies about SODs supplementation in order to evaluate their therapeutic value. Protective effects have been observed against irradiation, carcinogenesis, apoptosis and neurodegeneration. SODs administration has also been reported to alleviate inflammatory, infectious, respiratory, metabolic and cardiovascular diseases and genitourinary and fertility disorders, raising the question of its mechanism of action in these diverse situations. Some authors have shown an increase in endogenous antioxidant enzymes after exogenous SODs administration. The induction of endogenous antioxidant defence and, consequently, a decrease in oxidative stress, could explain all the effects observed. Further investigations need to be carried out to test the hypothesis that SODs supplementation acts by inducing an endogenous antioxidant defence. © 2013 Springer Science+Business Media New York.

Duran A.,Montpellier University | Liang Q.,Newcastle University | Marche F.,Montpellier University
Journal of Computational Physics | Year: 2013

We consider in this work a finite volume numerical approximation of weak solutions of the shallow water equations with varying topography, on unstructured meshes. Relying on an alternative formulation of the shallow water equations that involves the free surface as a conservative variable, instead of the water height, we introduce a simple discretization of the bed slope source term, together with some suitable conservative variables reconstructions. The resulting scheme is automatically consistent and well-balanced, for any given consistent numerical flux for the homogeneous system. We obtain a very simple formulation, which do not need to be modified when second order accuracy MUSCL reconstructions are adopted. Additionally, the positivity of the water height is preserved under a relevant stability condition, as soon as the numerical flux for the associated homogeneous system does. Numerical assessments, involving dry areas and complex geometry are performed. © 2012 Elsevier Inc.

Moeller A.H.,Yale University | Peeters M.,Montpellier University | Ndjango J.-B.,University of Kisangani | Li Y.,University of Pennsylvania | And 2 more authors.
Genome Research | Year: 2013

The gut microbial communities within great apes have been shown to reflect the phylogenetic history of their hosts, indicating codiversification between great apes and their gut microbiota over evolutionary timescales. But because the great apes examined to date represent geographically isolated populations whose diets derive from different sources, it is unclear whether this pattern of codiversification has resulted from a long history of coadaptation between microbes and hosts (heritable factors) or from the ecological and geographic separation among host species (environmental factors). To evaluate the relative influences of heritable and environmental factors on the evolution of the great ape gut microbiota, we assayed the gut communities of sympatric and allopatric populations of chimpanzees, bonobos, and gorillas residing throughout equatorial Africa. Comparisons of these populations revealed that the gut communities of different host species can always be distinguished from one another but that the gut communities of sympatric chimpanzees and gorillas have converged in terms of community composition, sharing on average 53% more bacterial phylotypes than the gut communities of allopatric hosts. Host environment, independent of host genetics and evolutionary history, shaped the distribution of bacterial phylotypes across the Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria, the four most common phyla of gut bacteria. Moreover, the specific patterns of phylotype sharing among hosts suggest that chimpanzees living in sympatry with gorillas have acquired bacteria from gorillas. These results indicate that geographic isolation between host species has promoted the evolutionary differentiation of great ape gut bacterial communities. © 2013, Published by Cold Spring Harbor Laboratory Press.

Kelsey G.,Babraham Institute | Kelsey G.,University of Cambridge | Feil R.,Montpellier University
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2013

Fundamental to genomic imprinting in mammals is the acquisition of epigenetic marks that differ in male and female gametes at 'imprinting control regions' (ICRs). These marks mediate the allelic expression of imprinted genes in the offspring. Much has been learnt about the nature of imprint marks, the times during gametogenesis at which they are laid down and some of the factors responsible especially for DNA methylation. Recent work has revealed that transcription and histone modifications are critically involved in DNA methylation acquisition, and these findings allow us to propose rational models for methylation establishment. A completely novel perspective on gametic DNA methylation has emerged from epigenomic profiling. Far more differentially methylated loci have been identified in gametes than known imprinted genes, which leads us to revise the notion that methylation of ICRs is a specifically targeted process. Instead, it seems to obey default processes in germ cells, giving rise to distinct patterns of DNA methylation in sperm and oocytes. This new insight, together with the identification of proteins that preserve DNA methylation after fertilization, emphasizes the key role played by mechanisms that selectively retain differential methylation at imprinted loci during early development. Addressing these mechanisms will be essential to understanding the specificity and evolution of genomic imprinting. © 2012 The Author(s) Published by the Royal Society. All rights reserved.

French National Center for Scientific Research, Montpellier University and University Claude Bernard Lyon 1 | Date: 2013-04-04

The present invention relates to a modified oligonucleotide having two or more thiol functions, which can be immobilized on a gold surface or on a grafted surface, in particular a surface comprising at least one carbon-carbon double bond or carbon-carbon triple bond or haloacetamide functions, preferably maleimide or acrylamide functions. The invention also relates to a method for detecting a nucleic acid in a biological sample comprising a step of detecting hybridization between a modified oligonucleotide and a target nucleic acid amplified from the biological sample. The invention relates more particularly to a method for detecting, genotyping or sequencing a pathogenic organism, preferably a virus.

Institute Polytechnique Of Grenoble, Montpellier University and French National Center for Scientific Research | Date: 2014-06-20

The invention relates to processes for coating a surface with a crosslinked polyelectrolytes multilayer film incorporating a protein, preferably a growth factor type protein. The invention also relates to crosslinked polyelectrolytes multilayer films obtained by this process, and a coated surface obtained therefrom.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2013.3.4 | Award Amount: 4.03M | Year: 2013

Computing devices with multiple processing cores are now the norm. Most smartphones, tablets, game consoles, and of course personal computers and servers, can process software tasks in true parallel fashion. This trend will keep on going, and the number of cores per device will grow to dozens and hundreds, which will enable us to run more complex applications, and more of them at the same time. However, balancing the load imposed by the multiple applications over dozens or hundreds of cores is not trivial. For example, a system with 20 application tasks and 2 cores can have 380 distinct allocations of tasks to cores, but simply by increasing the number of cores to 4, the number of possible allocations becomes 116280. Going further, the number of possible allocations of a system with 25 tasks and 25 cores is larger than the number of stars in the observable universe!\nDreamClouds mission is to develop novel load balancing mechanisms that can be applied during runtime in a wide range of manycore systems, allowing for a fine-tuning of the trade-off between performance guarantees and system efficiency according to the application needs. Such mechanisms will be organised in distinct types of cloud-like system software infrastructure that will manage the workload on different kinds of systems. Embedded Clouds will be used in systems with time-critical behaviour (such as the flight control in an aircraft), allowing for restricted load balancing and privileging strict performance guarantees. Micro Clouds will rely on novel extensions to operating systems and virtual machines, allowing for dynamic migration of threads or full virtual machines from one core to another. Finally, High Performance Clouds will balance highly dynamic workloads, aiming for full utilisation of the underlying platform but at the same time providing performance guarantees to selected applications. A number of techniques will be explored as the underlying allocation heuristics, including bio-inspired and market-inspired techniques and control-theoretic closed loop mechanisms.\nThe project includes case studies in three different domains automotive, digital video streaming and scientific computing aiming to validate the three types of cloud infrastructure developed within the project. The aim is to deliver a well-tested library of reference implementations of load balancing mechanisms that can be applied to domains with similar workloads and requirements (e.g. aerospace, gaming). Through the dissemination activities industrial project partners like Bosch, and industry standardisation efforts of The Open Group with over 400 members, the reference implementations will facilitate the adoption of the new load balancing technologies by different industries, which will finally be able to deliver products based on more efficient and predictable manycore devices. These advances will result in lower costs and increased reliability of manycore devices for consumers.

FUNENTECH intends to reinforce technology transfer of Ultra High Pressure Homogenising (UHPH) processing to SME of liquid-food and cosmetic sectors. The Consortium is constituted by five SME and four RTD partners: Stansted Fluid Power Ltd (UHPH equipment); Nectina S.A. (vegetable milks); NAHO Cosmetics (innovative cosmetics); ABbiotics (biotechnology); Universitat Autnoma de Barcelona (UAB), Universit Montpellier II (UMII) and Federal Centre for Nutrition and Food (FRCNF), and commits to exploit and disseminate the knowledge generated taking into account intellectual property rights agreed. The RTD institutions gather proved experience in the application of non-thermal technologies, food safety, chemistry, technology, nutrition and toxicology. The main objectives are: to study the (techno-) and biological functionality of UHPH-processed foods and cosmetics to design functional foods of high safety and nutritional values, and to target specific industrial adaptation of the prototypes for food and cosmetic production in two years time. It is also aimed at providing valid information to policy regulatory bodies and consumers. It is expected to obtain novel products with improved functional characteristics (better stability during storage; longer shelf-life; reduced immunoreactivity; containing nano and micro transport-delivery systems of bioactive-compounds; excellent organoleptic characteristics) that build up national and trans-regional new markets niches for the SMEs involved.

Vib Vzw, Ghent University, French National Center for Scientific Research, Montpellier University, Montpellier University Hospital Center and University of Osnabrück | Date: 2013-01-17

This disclosure relates to a modified -helical bundle cytokine, with reduced activity via an -helical bundle cytokine receptor, wherein the -helical bundle cytokine is specifically delivered to target cells. Preferably, the -helical bundle cytokine is a mutant, more preferably it is a mutant interferon, with low affinity to the interferon receptor, wherein the mutant interferon is specifically delivered to target cells. The targeting is realized by fusion of the modified -helical bundle cytokine to a targeting moiety, preferably an antibody. This disclosure relates further to the use of such targeted modified -helical bundle cytokine to treat diseases. A preferred embodiment is the use of a targeted mutant interferon, to treat diseases, preferably viral diseases and tumors.

Hansen M.M.,University of Aarhus | Olivieri I.,Montpellier University | Waller D.M.,University of Wisconsin - Madison | Nielsen E.E.,Technical University of Denmark
Molecular Ecology | Year: 2012

Widespread environmental changes including climate change, selective harvesting and landscape alterations now greatly affect selection regimes for most organisms. How animals and plants can adapt to these altered environments via contemporary evolution is thus of strong interest. We discuss how to use genetic monitoring to study adaptive responses via repeated analysis of the same populations over time, distinguishing between phenotypic and molecular genetics approaches. After describing monitoring designs, we develop explicit criteria for demonstrating adaptive responses, which include testing for selection and establishing clear links between genetic and environmental change. We then review a few exemplary studies that explore adaptive responses to climate change in Drosophila, selective responses to hunting and fishing, and contemporary evolution in Daphnia using resurrected resting eggs. We further review a broader set of 44 studies to assess how well they meet the proposed criteria, and conclude that only 23% fulfill all criteria. Approximately half (43%) of these studies failed to rule out the alternative hypothesis of replacement by a different, better-adapted population. Likewise, 34% of the studies based on phenotypic variation did not test for selection as opposed to drift. These shortcomings can be addressed via improved experimental designs and statistical testing. We foresee monitoring of adaptive responses as a future valuable tool in conservation biology, for identifying populations unable to evolve at sufficiently high rates and for identifying possible donor populations for genetic rescue. Technological advances will further augment the realization of this potential, especially next-generation sequencing technologies that allow for monitoring at the level of whole genomes. © 2012 Blackwell Publishing Ltd.

Agency: Cordis | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2013-IRSES | Award Amount: 921.50K | Year: 2014

At the doorstep of Europe, the NW African plate boundary system is paradoxically the least understood segment of the Earth global plate system. This largely reflects the intrinsic complexity of the present-day plate boundary, characterized by a diffuse geometry and several lithospheric domains accommodating the relative motion between Eurasia and Africa. Despite long stand collaborations, research in the area is highly fragmented due to the lack of a sustainable multilateral transfer of knowledge between EU & Maghreb researchers. Further advances in our understanding of the structure and dynamics of this key area, along with advances the societal issues related to geohazards and georesources, entails the combined analysis of surface evolution with knowledge on deep structures and mantle dynamics. This scientific challenge requires to greatly improving the transfer of knowledge and networking of research staff from EU and the key MPC Maghreb partners involved in multidisciplinary studies in the fields of Geodynamics, Geohazards and Applied Geology. MEDYNA is aimed at filling this gap fostering the transfer of knowledge through a 4 year programme of research staff exchange as an essential step forward to lay the foundations for a sustainable collaboration network on Integrated Earth Science studies between EU-Maghreb researchers working in NW Africa. MEDYNA it is an ambitious exchange scheme on Integrated Earth Sciences that will involve the exchange of over 100 ESR/ERS (489 months) between 4 Mediterranean EU institutions from Spain, France and Portugal, and 17 MPC institutions from Morocco, Algeria and Tunisia. MEDYNA will reinforce networks for long-term, joint research projects and high-level training of researchers between EU and Maghreb staff and will sparks synergies to become a sustainable and key initiative for widening ERA towards MPCs in the field of Integrated Earth Sciences.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.1-3 | Award Amount: 7.82M | Year: 2013

Long-term side-effects of radiotherapy impact on the quality-of-life (QoL) of cancer survivors. These side-effects could be reduced if predicted in advance. Previous work identified clinical and biological predictors but a major, coordinated approach is needed to validate them so they can be used clinically. The EU has ~17.8 million people living with a prior diagnosis of cancer of whom ~7 million received radiotherapy. In the long-term, potentially 20% of those suffering with mild to severe side-effects (~1.4 million) might benefit from alleviation of symptoms, with resulting reductions in the cost of care in the EU. REQUITE aims to develop validated clinical models and incorporate biomarkers to identify before treatment cancer patients at risk of side-effects and use the models to design interventional trials aimed at reducing side-effects and improving QoL in cancer survivors who underwent radiotherapy. REQUITE will: 1. carry out a multi-centre, longitudinal, observational study to collect standardised data and samples in breast, prostate and lung cancer patients; 2. validate biomarkers with published evidence of predictive value; 3. replicate published clinical models and incorporate replicated biomarkers to create validated predictive algorithms; 4. use the prospectively validated models and biomarkers to design interventional trial protocols aiming to reduce side-effects and improve QoL in high-risk patients. REQUITE builds on collaborations with a proven history of data sharing, enlarged to a consortium with expertise in patient recruitment, knowledge management, biomarker testing and predictive model development. SME involvement for biomarker assays will facilitate future clinical implementation and commercial exploitation. The outcome of this project will be validated predictive models for three common cancers and trial protocols using the models to investigate interventions aimed at reducing long-term side-effects and improving the QoL of cancer survivors.

Institute Polytechnique Of Grenoble, French National Center for Scientific Research and Montpellier University | Date: 2010-01-15

The invention relates to processes for coating a surface with a crosslinked polyelectrolytes multilayer film incorporating a protein, preferably a growth factor type protein. The invention also relates to crosslinked polyelectrolytes multilayer films obtained by this process, and a coated surface obtained therefrom.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: NMP-2008-2.4-2 | Award Amount: 4.68M | Year: 2010

The objective is to develop radically innovative electrical insulating tapes and process to improve the energy conversion efficiency of electrotechnical systems. It mainly addresses the electric power generation issue. Today, the energy conversion efficiency of generators is restricted by (i) thermal as well as (ii) electrical strength limitations due to the electrical insulator tapes themselves. The concepts of these multifunctional tapes are far behind the electrical insulating state of the art. The project aims to develop a new process chain leading to a drastic improvement of insulating tape structure homogeneity. The todays limitations of tape come from its heterogeneous multilayer structure bringing together very different materials like glass fibre fabric, mica flakes and polymers. Enabling this homogenisation requires higher performance materials, which will be obtained by adjunct of inorganic nanofillers according to two proposed development routes: nanodielectrics polymer or inorganic polymers (sol-gel). This will lead to a more robust process chain with a better productivity (\50%) and an insulating tape with enhanced performances like a higher field strength (\40%), a better thermal conduction (\60%). At the end, a much thinner tape (-30%) enabling the design of more compact generators is expected. This project can strongly impact the energy production field. For instance at the European scale, a \0.2% gain in generator conversion efficiency could save the equivalent of one nuclear power plant of 1000 MW (1.5 billions ), or nearly 10 fossil fuel power plants and related reduction in CO2 emission. It will also affect other very large markets like the industrial motor field using similar insulation tapes. The consortium of ANASTASIA project is equally composed of industrials and research laboratories, namely two manufacturers (tape and power generator), two generator end-users, four academic laboratories and the CEA research institute as coordinator.

French National Center for Scientific Research, Hospices Civils De Lyon, Ecole Normale Superieure de Lyon, University Claude Bernard Lyon 1 and Montpellier University | Date: 2014-09-29

The subject matter of the present invention is compounds which have a 6-aminopurine backbone corresponding to formula (I): in which R_(1), R_(2), R_(3), X, Y and Z are as defined in any one of claims 1 to 5, and Ar is a biphenyl or a naphthyl which may be substituted with R_(3), for use in the treatment of cancer.

French National Center for Scientific Research, Montpellier University and University of Rennes 1 | Date: 2010-12-07

The invention relates to compounds of formula (I)

National Polytechnic Institute of Toulouse, Montpellier University and University of Toulouse II – Le Mirail | Date: 2011-06-24

The invention relates to a static converter connected between an electrical voltage source (4) and an electrical load (6), said converter including a main static conversion arm (16) comprising an output electronic switching cell and a backup conversion arm (18) having identical structures. The static converter includes a pair of fuses (70, 72) connected on either side of the main arm (16), and a switching circuit (26) comprising a connection element (80) connecting the backup arm (18) to the connection points between the fuses and the input terminals of the main arm, such that, when a fault occurs on one of the switching cells forming the main arm (16), a stable conductive link is established between the two fuses (70, 72), the main arm (16) is isolated by the two fuses (70, 72), and the backup arm (18) is spontaneously connected to the output of the main arm (18) via the conductive line and replaces the main arm.

Girindus Ag, French National Center for Scientific Research and Montpellier University | Date: 2011-05-25

A solution phase synthesis method for preparing an oligonucleotide, wherein at least some of the reagents are solid supported. The method suitable for large- scale synthesis comprises coupling a protected compound with a nucleotide derivative having a protection group in the presence of a solid supported activator to give an elongated oligonucleotide with a P(III)-internucleotide bond; optionally processing the elongated oligonucleotide by capping by reaction with a solid supported capping agent and/or by oxidizing or sulfurizing by reaction of the oligonucleotide with a solid supported oxidizing or sulfurization reagent; and removing the protection group. The coupling may include reacting a 3-protected compound of formula: with a nucleotide derivative having a 5-protection group, or reacting a 5-protected compound of formula with a nucleotide derivative having a 3-protection group.

The World Health Organisation (WHO) has included low back pain in its list of twelve priority diseases. Notably, Degenerative disc disease (DDD) presents a large, unmet medical need which results in a disabling loss of mechanical function. Today, no efficient therapy is available. Chronic cases often receive surgery, which may lead to biomechanical problems and accelerated degeneration of adjacent segments. Our consortium partners have developed and studied stem cell-based, regenerative therapies with encouraging results in phase 1 and 2a trials. Patients exhibited rapid and progressive improvement of functional and pain indexes by 50% within 6 months and by 65% to 78% after 1 year with no side effects. In addition, MRI T2 relaxation measurements demonstrated a significant improvement. To develop the worlds first rigorously proven, effective treatment of DDD, RESPINE aims to assess, via a multicentre, randomized, controlled, phase 2b clinical trial including 112 patients with DDD, the efficacy of an allogenic intervertebral mesenchymal stem cell (MSC)-based therapy. This innovative therapy aims to rapidly (within 3 months) and sustainably (at least 24 months) reduce pain and disability. In addition, the consortium aims to provide new knowledge on immune response & safety associated with allogeneic BM-MSC intradiscal injection. This simple procedure would be cost-effective, minimally invasive, and standardised. The transfer to the clinic will be prepared at a cost below 10k thanks to the strategy of production of allogenic cells, automation & EU standardisation. At the end of the RESPINE trial, we aim to propose a broadly available and clinically applicable treatment for DDD, marketed by European SMEs.

Soustelle V.,Montpellier University | Tommasi A.,Montpellier University | Demouchy S.,Montpellier University | Ionov D.A.,Jean Monnet University
Journal of Petrology | Year: 2010

The mantle above a subducting slab is the site of complex interactions between deformation, partial melting, fluid migration and magma transport. To constrain these interactions and their effects on olivine deformation, we analyze microstructures, crystal preferred orientations, and water contents of peridotite xenoliths entrained by andesites of the Avacha volcano, southern Kamchatka arc. These xenoliths are refractory spinel harzburgites that have coarse-grained microstructures with widely spaced subgrain boundaries and sinuous grain boundaries in olivine, consistent with deformation by dislocation creep under low deviatoric stress (≤13 MPa) and with a significant contribution from diffusional processes. Analysis of crystal preferred orientations (CPO) indicates dominant activation of high-temperature, low-stress {0kl}[100] slip systems in olivine and of(100)[001] in orthopyroxene. In most samples, coarse opx crystals, elongated parallel to the lineation, enclose small olivine grains in crystallographic continuity with neighbouring crystals, indicating crystallization of orthopyroxene at the expense of olivine as a result of reactive percolation of Si-rich fluids coeval with the high-temperature deformation. Secondary crystallization of interstitial orthopyroxene led locally to development of opx-rich lenses parallel to the foliation, characterized by a decrease in olivine grain size and dispersion of the olivine CPO without changing the dominant slip systems. Half of the samples also show acicular orthopyroxene aggregates with which is associated a fine-grained matrix composed of rounded strain-free olivine, orthopyroxene, spinel, and rare amphibole crystals. This matrix occurs pervasively along grain boundaries or forms millimeter-scale irregular lenses and anastomosing veinlets that crosscut the coarse crystals and their ductile deformation structures. Both acicular orthopyroxene and the fine-grained matrix are interpreted as resulting from reactive transport of H. 2O-rich fluids under static conditions, probably in the lithospheric mantle. Infrared analyses show that olivine contains 1-8·6 ppm by weight of water. These low water contents are similar to those observed in spinel peridotites from other subduction zones and probably record both the low solubility of water in olivine at low pressure and dehydration during exhumation of the xenoliths. Water contents in orthopyroxene are highly variable (25-506 ppm H. 2O), probably recording spatially heterogeneous interaction with fluids or melts and compositional disequilibrium in the studied samples. Change in the dominant percolation mechanism from porous flow to fracturing suggests cooling, consistent with the low temperatures estimated from pyroxene thermometry (≤ 800-900°C). The Avacha xenoliths therefore record pervasive deformation of a region of the mantle under asthenospheric conditions, followed by its accretion to the base of the lithosphere, probably as a result of cooling of the mantle wedge. Percolation of Si-rich fluids or hydrous melts is recorded at all stages; this probably enhanced diffusion and lowered deviatoric stresses during ductile deformation, but did not change the dominant slip direction in olivine from [100] to [001]. © The Author 2010. Published by Oxford University Press.

Avadi A.,IRD Montpellier | Avadi A.,Montpellier University | Vazquez-Rowe I.,CRP Henri Tudor | Freon P.,IRD Montpellier
Journal of Cleaner Production | Year: 2014

The Peruvian anchoveta fishery is currently targeted by a large fleet featuring a wide range of vessel sizes (segments), with highly variable capacities. In addition, the landings of the industrial fleet are used exclusively by the reduction industry, while those performed by small- and medium-scale vessels are destined mainly for direct human consumption. Despite these differences, the entire fleet is made up of purse seiners that perform similar operations when at sea. Therefore, the main aim of this study is to identify the differences in eco-efficiency between the different fleet segments in order to delve into the potential environmental improvements that could be attained through operational benchmarking. To this end, the combined use of Life Cycle Assessment (LCA) and Data Envelopment Analysis (DEA) was applied to the Peruvian anchoveta fleet. More specifically, a modified 5-step LCA + DEA method, whose particularities are broadly discussed throughout the study, was computed to obtain the desired operational benchmarks and, thereafter, estimate the target environmental gains. Results led to an average efficiency score of 86% throughout the segments, with a total of eight fleet segments out of 13 (62%) operating inefficiently. Nevertheless, no clear pattern was identified through the segments, although certain correlations with stock abundance, fuel use intensity, overcapacity and climatic conditions are discussed. Reduction in material inputs based on operational benchmarks translated into environmental gains that ranged from 26% to 53% for inefficient segments. Finally, it is expected that the findings in this study may aid stakeholders and policy makers when revising fuel use optimisation and overcapacity management strategies. © 2014 Elsevier Ltd. All rights reserved.

Fellous S.,Cornell University | Fellous S.,Montpellier University | Lazzaro B.P.,Cornell University
Molecular Ecology | Year: 2011

Almost all studies of the immune system of animals with metamorphosis have focused on either larval or on adult immunity, implicitly assuming that these traits are either perfectly correlated or evolutionarily independent. In this study, we use 80 crosses among 21 Drosophila melanogaster lines to investigate the degree and constancy of genetic correlation in immune system activity between larvae and adults. The constitutive transcription of Diptericin, a gene encoding a defensive antimicrobial peptide, was controlled by the same genetic factors in larvae and adults, with variation in expression determined exclusively by nonadditive genetic effects. This contrasted with another peptide-encoding gene, Drosomycin, in which larval transcription was highly variable and determined by additive effects but adult transcription genetically invariant. We found no evidence for a fitness cost to the transcription of these genes in our study. The shared genetic control of larval and adult Diptericin transcription stands in contrast to predictions of the adaptive decoupling hypothesis, which states that distinct life-stages should permit the independent evolution of larval and adult phenotypes. Importantly, genetic correlations between larval and adult immunities imply that parasite pressure on one life-stage can drive the evolution of immunity (and resistance) in the other life-stage. © 2011 Blackwell Publishing Ltd.

Debrie J.,University Paris Est Creteil | Lavaud-Letilleul V.,Montpellier University | Parola F.,Parthenope University of Naples
Journal of Transport Geography | Year: 2013

The evolution of public-private relationships has driven many economic sectors to undergo de-centralisation and de-regulation. Throughout these transformations, an appreciation of governance is key to understanding the process. In recent years, seaports have undergone dramatic changes in governance as reported in academic and policy literature. The World Bank, for example, outlined a well-known taxonomy of major governance models. However, this literature does not capture of the specificities of local environments, or " embed" the changes in specific institutional and economic contexts. This paper analyses embeddedness in ports and their associated governance structures. We analyse and discuss (i) the complexity and the heterogeneity of the institutional framework, (ii) the multi-layered decisional chain, (iii) the geo-economic dimension, and (iv) the socio-cultural environment of reformed ports. The paper takes a dynamic view of port reform trajectories. We illustrate the theoretical discussion with a comparison of ports in France and Italy. We show the effects of local forces in shaping national port reform schemes, and we examine the relationship between global trends and embeddedness. © 2012 Elsevier Ltd.

Guilhaumon F.,Montpellier University | Mouillot D.,Montpellier University | Gimenez O.,Center dEcologie Fonctionnelle et Evolutive
Ecography | Year: 2010

The species-area relationship (SAR) is one of the most fundamental tools in ecology. After almost a century of quantitative ecology, however, the quest for a "best SAR model" still remains elusive, with a substantial uncertainty about the best fitting SAR model frequently being observed. Recent research has required that this uncertainty be addressed, and a multimodel SAR framework has been devised. Here we introduce the mmSAR R-package, which is a flexible and scalable implementation of the multimodel SAR framework for species-area datasets, and provide some examples of its use. This R-package provides functions for fitting SAR models, performing model selection, and the build up of multimodel SARs. © 2010 The Authors. Journal compilation © 2010 Ecography.

Zamponi G.W.,University of Calgary | Lory P.,Montpellier University | Perez-Reyes E.,University of Virginia
Pflugers Archiv European Journal of Physiology | Year: 2010

It is well established that idiopathic generalized epilepsies (IGEs) show a polygenic origin and may arise from dysfunction of various types of voltage-and ligandgated ion channels. There is an increasing body of literature implicating both high-and low-voltage-activated (HVA and LVA) calcium channels and their ancillary subunits in IGEs. Cav2.1 (P/Q-type) calcium channels control synaptic transmission at presynaptic nerve terminals, and mutations in the gene encoding the Cav2.1 α1 subunit (CACNA1A) have been linked to absence seizures in both humans and rodents. Similarly, mutations and loss of function mutations in ancillary HVA calcium channel subunits known to coassemble with Cav2.1 result in IGE phenotypes in mice. It is important to note that in all these mouse models with mutations in HVA subunits, there is a compensatory increase in thalamic LVA currents which likely leads to the seizure phenotype. In fact, gain-of-function mutations have been identified in Cav3.2 (an LVA or T-type calcium channel encoded by the CACNA1H gene) in patients with congenital forms of IGEs, consistent with increased excitability of neurons as a result of enhanced T-type channel function. In this paper, we provide a broad overview of the roles of voltage-gated calcium channels, their mutations, and how they might contribute to the river that terminates in epilepsy. © Springer-Verlag 2009.

Gounaris G.J.,Aristotle University of Thessaloniki | Renard F.M.,Montpellier University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Studying e-e+→W-W+ at the one-loop electroweak order, we derive very accurate and simple expressions for the four helicity conserving amplitudes which dominate this process at high energies. The calculations are done in both the standard model and minimal supersymmetric standard model frameworks. Such expressions, called supersimple, nicely emphasize the dynamical contents of each framework. Numerical illustrations are presented, which show the accuracy of this description, and how it can be used for identifying possible additional new physics contributions, like, e.g., anomalous gauge couplings or a new Z ′ vector boson exchange. The procedure is useful even if only the standard model is visible at the future linear collider energies. © 2013 American Physical Society.

Gounaris G.J.,Aristotle University of Thessaloniki | Renard F.M.,Montpellier University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We study the process e-e+→γH, where H represents HSM, h0, or H0. This process occurs at the one loop level in the standard model or in the minimal supersymmetric standard model (MSSM). We establish supersimple (sim) high energy expressions for all helicity amplitudes of this process, and we identify their level of accuracy for describing the various polarized and unpolarized observables, and for distinguishing SM from MSSM or another beyond the standard model. We pay special attention to transverse e± polarization and azimuthal dependencies induced by the imaginary parts of the amplitudes, which are relatively important in this process. © 2015 American Physical Society.

Demoly P.,Montpellier University | Annunziata K.,Kantar Health | Gubba E.,Post Synaptic Ltd | Adamek L.,Glaxosmithkline
European Respiratory Review | Year: 2012

Although the main goal of asthma management guidelines is to achieve and maintain clinical control, reported levels of not well-controlled asthma remain high. The aim of this analysis was to compare the levels of asthma control and the associated impact on patients' health status in Europe in 2006, 2008 and 2010. An additional outcome was the comparison of the burden of asthma with diabetes. Data were obtained from the cross-sectional, self-reported, European National Health and Wellness Surveys conducted in France, Germany, Italy, Spain and the UK. Asthma control (Asthma Control Test TM; QualityMetric, Inc., Lincoln, RI, USA) and health status (Short Form (SF)-12 health survey and the Work Productivity Loss and Activity Impairment questionnaire) were assessed. In 2010, the proportion of treated asthma patients assessed as having not well-controlled asthma was 53.5%, compared with 56.6% and 55.0% in 2008 and 2006, respectively. A significant reduction in not well-controlled asthma was observed in Germany between 2006 (72.3%) and 2010 (62.5%; p50.005). Fluctuations in control levels were observed in other countries. For all surveys, having at least well-controlled asthma was associated with a significantly lower number of healthcare contacts in the previous 6 months, better mean¡SD SF-12 scores for the physical (data for 2010: not well controlled 39.9¡11.38, at least well-controlled 48.0¡9.89; p,0.001) and mental (data for 2010: not well-controlled 40.6¡10.95, at least well-controlled 45.0¡10.91; p,0.001) components, and significantly less impact on Work Productivity Loss and Activity Impairment. Asthma and diabetes were associated with a similar overall negative impact on health status. A substantial proportion of asthmatics remain not well-controlled across five European countries, resulting in a significant impact on health resources and patients' health status. The overall burden of asthma appears to be similar to that of diabetes. © ERS 2012.

Sutin A.R.,Florida State University | Stephan Y.,Montpellier University | Luchetti M.,University of Bologna | Terracciano A.,Florida State University
Obesity | Year: 2014

Objective Perceived weight discrimination has been linked to health outcomes, including risk of obesity. Less is known about how discrimination is associated with intermediate physiological markers of health, such as systemic inflammation. This research examined the association between weight discrimination and C-reactive protein (CRP) and whether it varied by participants' body mass index (BMI). Methods Cross-sectional design using data from the Health and Retirement Study. Among participants who were overweight or obese (N-=-7,394), regression analysis was used to test for an association between weight discrimination and CRP and whether this association was moderated by BMI. Similar associations among seven other attributions for discrimination were tested. Results The association between weight discrimination and CRP varied as a function of BMI: At BMI between the thresholds for overweight and obesity (BMI ∼25-30), weight discrimination was associated with higher circulating levels of CRP; there was no association between weight discrimination and CRP as BMI approached Class 3 obesity (BMI ∼40). A similar pattern emerged for discrimination based on a physical disability, but not for the other attributions for discrimination (e.g., race, age). Conclusions Weight discrimination is associated with higher circulating CRP, an association that is moderated by BMI. © 2014 The Obesity Society.

Mookherjee M.,Cornell University | Mainprice D.,Montpellier University
Geophysical Research Letters | Year: 2014

Using first principle simulations we calculated the elasticity of chlorite. At a density ρ~ 2.60 g cm-3, the elastic constant tensor reveals significant elastic anisotropy: VP ~27%, VS1 ~56%, and VS2 ~43%. The shear anisotropy is exceptionally large for chlorite and enhances upon compression. Upon compression, the shear elastic constant component C44 and C55 decreases, whereas C66 shear component stiffens. The softening in C44 and C55 is reflected in shear modulus, G, and the shear wave velocity, VS. Our results on elastic anisotropy at conditions relevant to the mantle wedge indicates that a 10-20 km layer of hydrated peridotite with serpentine and chlorite could account for the observed shear polarization anisotropy and associated large delay times of 1-2 s observed in some subduction zone settings. In addition, chlorite could also explain the low VP/VS ratios that have been observed in recent high-resolution seismological studies. Key Points First report of high pressure elasticity of chlorite Unusual shear wave anisotropy for chlorite Shear elastic anisotropy explains seismological observations in subduction zones ©2014. American Geophysical Union. All Rights Reserved.

Trap P.,University of Franche Comte | Faure M.,CNRS Earth Sciences Institute of Orléans | Lin W.,CAS Institute of Geology and Geophysics | Le Breton N.,CNRS Earth Sciences Institute of Orléans | Monie P.,Montpellier University
Precambrian Research | Year: 2012

In this contribution we present a reconstruction of the overall lithotectonic architecture, from inner zones to external ones, of the Paleoproterozoic Trans-North China Orogen, within the North China Craton. Moreover, forward thermobarometrical modelling on a kyanite-bearing gneiss yields a reliable prograde P-T-t-D path. In addition, 40Ar/39Ar dating on rocks from distinct litho-tectonic units helps us to distinguish several tectono-metamorphic events during the orogenic development. Considering these results, we propose a geodynamic model involving three cratonic blocks, namely the Western, Fuping and Eastern Blocks, separated by two oceans, the Lüliang and Taihang Oceans. The opening of oceanic basins occurred around 2.2-2.3Ga. After the westward subductions of oceanic lithosphere, the Trans-North China Orogen was built up through a polyphase tectonic evolution within the period 1900-1800Ma. The first event (D1) corresponded to the emplacement of lower and upper nappes herein called the Orthogneiss-and-Volcanite Unit (OVU) and the Low-Grade-and-Mafic Unit (LGMU), respectively. The syn-metamorphic D1 deformation (1880±10Ma) is characterized by a NW-SE stretching and mineral lineation with a top-to-the SE sense of shear. During ongoing compression of the thickening orogenic crust, a second deformation event D2 (1850±10Ma) was responsible for (1) syn-anatectic lateral flow and exhumation of the orogenic root and (2) folding of the middle and upper parts of the orogenic wedge that consequently acquired a fan-type geometry. The late D3 (1830±10Ma) and D4 (1810±10Ma) events are related to late-orogenic normal and strike-slip shearing, respectively. In our present state of knowledge, the Paleoproterozoic Trans-North China Orogen might be regarded as the assemblage of two continent-continent collisional belts, both of which are characterized by nappe stacking accommodated by top-to-the E/SE ductile shearing. Continental subduction, crustal thickening, partial melting of overthickened crust, exhumation of HP rocks and deposition of syn-orogenic detrital basins are typical features of modern collisional-type orogens. © 2011 Elsevier B.V..

Stephan Y.,Montpellier University | Sutin A.R.,Florida State University | Terracciano A.,Florida State University
Brain, Behavior, and Immunity | Year: 2015

Subjective age, or how young or old individuals experience themselves to be, is related to a range of health-related outcomes in old age, including mortality risk. Little is known, however, about its association with markers of systemic inflammation. Using data from the Health and Retirement Study (HRS), the present study examined the relation between subjective age and C-reactive protein (CRP). Participants were 4120 older adults from the 2008 wave of the HRS who provided measures of subjective age, CRP, demographic variables, Body Mass Index (BMI), depression, smoking, physical activity and disease burden. Regression analyses revealed that a younger subjective age was related to lower CRP, controlling for demographic factors. This association was reduced by half but remained significant when health and behavioral covariates were adjusted for, suggesting that BMI, physical activity and disease burden may partially account for lower inflammation in individuals with a younger subjective age. Furthermore, a logistic regression revealed that feeling younger than one's age was associated with reduced risk of exceeding the clinical threshold of CRP, controlling for covariates. The present study provides the first evidence of an association between subjective age and systemic inflammation among older adults. It suggests that individuals' ratings of their subjective age may help identify individuals at greater risk for immune dysfunction related to morbidity and mortality. © 2014 Elsevier Inc.

Albuquerque R.M.,University of Sao Paulo | Narison S.,Montpellier University | Nielsen M.,University of Sao Paulo
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2010

We extract directly (for the first time) the charmed (C = 1) and bottom (B = - 1) heavy-baryons (spin 1/2 and 3/2) mass-splittings due to SU (3) breaking using double ratios of QCD spectral sum rules (QSSR) in full QCD, which are less sensitive to the exact value and definition of the heavy quark mass, to the perturbative radiative corrections and to the QCD continuum contributions than the simple ratios commonly used for determining the heavy baryon masses. Noticing that most of the mass-splittings are mainly controlled by the ratio κ ≡ 〈 over(s, ̄) s 〉 / 〈 over(d, ̄) d 〉 of the condensate, we extract this ratio, by allowing 1σ deviation from the observed masses of the Ξ c, b and of the Ω c. We obtain: κ = 0.74 (3), which improves the existing estimates: κ = 0.70 (10) from light hadrons. Using this value, we deduce M Ωb = 6078.5 (27.4) MeV which agrees with the recent CDF data but disagrees by 2.4σ with the one from D0. Predictions of the Ξ Q ′ and of the spectra of spin 3/2 baryons containing one or two strange quark are given in Table 2. Predictions of the hyperfine splittings Ω Q * - Ω Q and Ξ Q * - Ξ Q are also given in Table 3. Starting for a general choice of the interpolating currents for the spin 1/2 baryons, our analysis favours the optimal value of the mixing angle b ≃ (- 1 / 5 - 0) found from light and non-strange heavy baryons. © 2010 Elsevier B.V. All rights reserved.

Di Pietro D.A.,Montpellier University | Ern A.,University Paris Est Creteil
Computer Methods in Applied Mechanics and Engineering | Year: 2015

We devise an arbitrary-order locking-free method for linear elasticity. The method relies on a pure-displacement (primal) formulation and leads to a symmetric, positive definite system matrix with compact stencil. The degrees of freedom are vector-valued polynomials of arbitrary order k≥1 on the mesh faces, so that in three space dimensions, the lowest-order scheme only requires 9 degrees of freedom per mesh face. The method can be deployed on general polyhedral meshes. The key idea is to reconstruct the symmetric gradient and divergence inside each mesh cell in terms of the degrees of freedom by solving inexpensive local problems. The discrete problem is assembled cell-wise using these operators and a high-order stabilization bilinear form. Locking-free error estimates are derived for the energy norm and for the L2-norm of the displacement, with optimal convergence rates of order (k+1) and (k+2), respectively, for smooth solutions on general meshes. The theoretical results are confirmed numerically, and the CPU cost is evaluated on both standard and polygonal meshes. © 2014 Elsevier B.V.

Albuquerque R.M.,University of Sao Paulo | Albuquerque R.M.,Montpellier University | Narison S.,Montpellier University
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2010

We consider (for the first time) the ratios of doubly heavy baryon masses (spin 3/2 over spin 1/2 and SU(3) mass-splittings) using double ratios of sum rules (DRSR), which are more accurate than the usual simple ratios often used in the literature for getting the hadron masses. In general, our results agree and compete in precision with potential model predictions. In our approach, the αs corrections induced by the anomalous dimensions of the correlators are the main sources of the ΞQQ*-ΞQQ mass-splittings, which seem to indicate a 1/MQ behaviour and can only allow the electromagnetic decay ΞQQ*→ΞQQ+γ but not to ΞQQ+Π. Our results also show that the SU(3) mass-splittings are (almost) independent of the spin of the baryons and behave approximately like 1/MQ, which could be understood from the QCD expressions of the corresponding two-point correlator. Our results can improved by including radiative corrections to the SU(3) breaking terms and can be tested, in the near future, at Tevatron and LHCb. © 2010.

Gounaris G.J.,Aristotle University of Thessaloniki | Renard F.M.,Montpellier University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

According to supersimplicity in MSSM, a renormalization scheme (SRS) may be defined for any high-energy 2-to-2 process, to the 1loop EW order; where the helicity conserving (HC) amplitudes, are expressed as a linear combination of just three universal logarithm-involving forms. All other helicity amplitudes vanish asymptotically. Including to these SRS amplitudes the corresponding counterterms, the supersimple expressions for the high-energy HC amplitudes, renormalized on-shell, are obtained. Previously, this property was noted for a large number of processes that do not involve Yukawa interactions or renormalization group corrections. Here we extend this to e -e +→tt̄, which does involve large Yukawa and renormalization group contributions. We show that the resulting supersimple expressions may provide an accurate description, even at energies comparable to the SUSY scale. Such descriptions clearly identify the origin of the important SUSY effects, and they may be used for quickly constraining physics contributions, beyond MSSM. © 2012 American Physical Society.

Renard E.,Montpellier University | Cobelli C.,University of Padua | Kovatchev B.P.,University of Virginia
Diabetes Research and Clinical Practice | Year: 2013

Insulin delivery in a closed-loop mode has been a dream for many patients with insulin-treated diabetes since bedside artificial pancreas (AP) systems were developed in the 1970s. Beside safe near-normal glucose levels, the goal of AP is to alleviate patients' burden and fear of continual adjustment of insulin delivery needed to cope with daily activities and events. Portable pumps using subcutaneous (SC) insulin infusion and 'needle-type' enzymatic sensors allowing continuous glucose monitoring (CGM) in the interstitial SC fluid are typically used in the current AP prototypes. Model predictive control algorithms which take into account the delays inherent with SC insulin infusion and glucose sensing have shown improved glucose control in hospital setting. Currently, pilot trials are performed in home-like conditions to assess the technical feasibility, safety and efficacy of glucose control, and patients' ability to manage AP. Recently developed wearable smart phone-based platforms connect wirelessly to the insulin pump and the CGM, run control algorithms, provide online information to/from the patient, and allow remote monitoring reaching a new frontier - first outpatient experiments. The future holds expansion of home trials supporting the approval of systems which could revolutionize diabetes treatment and make easier the daily life of patients with diabetes. © 2013 Elsevier Ireland Ltd.

Ruda R.,University of Turin | Bello L.,University of Milan | Duffau H.,Montpellier University | Soffietti R.,University of Turin
Neuro-Oncology | Year: 2012

Seizures represent a common symptom in low-grade gliomas; when uncontrolled, they significantly contribute to patient morbidity and negatively impact quality of life. Tumor location and histology influence the risk for epilepsy. The pathogenesis of tumor-related epilepsy is multifactorial and may differ among tumor histologies (glioneuronal tumors vs diffuse grade II gliomas). Gross total resection is the strongest predictor of seizure freedom in addition to clinical factors, such as preoperative seizure duration, type, and control with antiepileptic drugs (AEDs). Epilepsy surgery may improve seizure control. Radiotherapy and chemotherapy with alkylating agents (procarbazine CCNU vincristine, temozolomide) are effective in reducing the frequency of seizures in patients with pharmacoresistant epilepsy. Newer AEDs (levetiracetam, topiramate, lacosamide) seem to be better tolerated than the old AEDs (phenobarbital, phenytoin, carbamazepine), but there is lack of evidence regarding their superiority in terms of efficacy. © 2012 The Author(s). Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved.

Leizorovicz A.,University of Lyon | Becker F.,University of Geneva | Buchmuller A.,Jean Monnet University | Quere I.,Montpellier University | And 2 more authors.
Blood | Year: 2013

The clinical relevance of symptomatic extension of spontaneous, acute, symptomatic, lower-limb superficial-vein thrombosis (SVT) is debated. We performed a post hoc analysis of a double-blind trial comparing fondaparinux with placebo. The main study outcome was SVT extension by day 77, whether to ≤3 cmor >3 cm from the sapheno-femoral junction (SFJ). All events were objectively confirmed and validated by an adjudication committee. With placebo (n 5 1500), symptomatic SVT extension to ≤3cmor >3 cmfrom the SFJ occurred in 54 (3.6%) and 56 (3.7%) patients, respectively, inducing comparable medical resource consumption (eg, anticoagulant drugs and SFJ ligation); subsequent deep-vein thrombosis or pulmonary embolism occurred in 9.3% (5/54) and 8.9% (5/56) of patients, respectively. Fondaparinux was associated with lower incidences of SVT extension to ≤3 cm(0.3%; 5/1502; P <.001) and >3 cm (0.8%; 12/1502; P <.001) from the SFJ and reduced relateduse ofmedical resources; no subsequent deep-vein thrombosis or pulmonary embolism was observed in fondaparinux patients. Thus, symptomatic extensions are common SVT complications and, whether or not reaching the SFJ, are associated with a significant risk of venous thromboembolic complications and medical resource consumption, all reduced by fondaparinux. © 2013 by The American Society of Hematology.

Blanquart F.,Center dEcologie Fonctionnelle et Evolutive | Kaltz O.,Montpellier University | Nuismer S.L.,University of Idaho | Gandon S.,Center dEcologie Fonctionnelle et Evolutive
Ecology Letters | Year: 2013

Patterns of local adaptation are expected to emerge when selection is spatially heterogeneous and sufficiently strong relative to the action of other evolutionary forces. The observation of local adaptation thus provides important insight into evolutionary processes and the adaptive divergence of populations. The detection of local adaptation, however, suffers from several conceptual, statistical and methodological issues. Here, we provide practical recommendations regarding (1) the definition of local adaptation, (2) the analysis of transplant experiments and (3) the optimisation of the experimental design of local adaptation studies. Together, these recommendations provide a unified approach for measuring local adaptation and understanding the adaptive divergence of populations in a wide range of biological systems. © 2013 John Wiley & Sons Ltd/CNRS.

Carles R.,Montpellier University | Danchin R.,University Paris Est Creteil | Saut J.-C.,French National Center for Scientific Research
Nonlinearity | Year: 2012

This paper surveys various aspects of the hydrodynamic formulation of the nonlinear Schrödinger equation obtained via the Madelung transform in connection to models of quantum hydrodynamics and to compressible fluids of the Korteweg type. © 2012 IOP Publishing Ltd & London Mathematical Society.

Gutierrez F.,University of Zaragoza | Parise M.,National Research Council Italy | De Waele J.,University of Bologna | Jourde H.,Montpellier University
Earth-Science Reviews | Year: 2014

Karst environments are characterized by distinctive landforms related to dissolution and a dominant subsurface drainage. The direct connection between the surface and the underlying high permeability aquifers makes karst aquifers extremely vulnerable to pollution. A high percentage of the world population depends on these water resources. Moreover, karst terrains, frequently underlain by cavernous carbonate and/or evaporite rocks, may be affected by severe ground instability problems. Impacts and hazards associated with karst are rapidly increasing as development expands upon these areas without proper planning taking into account the peculiarities of these environments. This has led to an escalation of karst-related environmental and engineering problems such as sinkholes, floods involving highly transmissive aquifers, and landslides developed on rocks weakened by karstification. The environmental fragility of karst settings, together with their endemic hazardous processes, have received an increasing attention from the scientific community in the last decades. Concurrently, the interest of planners and decision-makers on a safe and sustainable management of karst lands is also growing. This work reviews the main natural and human-induced hazards characteristic of karst environments, with specific focus on sinkholes, floods and slope movements, and summarizes the main outcomes reached by karst scientists regarding the assessment of environmental impacts and their mitigation. © 2014 Elsevier B.V.

Demoly P.,Montpellier University | Emminger W.,Allergy Outpatient Clinic | Rehm D.,ALK | Backer V.,Copenhagen University | And 2 more authors.
Journal of Allergy and Clinical Immunology | Year: 2016

Background The SQ HDM SLIT-tablet (ALK) has been developed for treatment of house dust mite (HDM)-induced respiratory allergic disease. Objective This trial investigated the efficacy and safety of the SQ HDM SLIT-tablet in adults with moderate-to-severe HDM-induced allergic rhinitis (AR). Methods The trial was a randomized, double-blind, placebo-controlled phase III trial conducted in 12 European countries including 992 adults with moderate-to-severe HDM-induced AR despite treatment with pharmacotherapy. Subjects were randomized 1:1:1 to 1 year of daily treatment with placebo, 6 SQ-HDM, or 12 SQ-HDM. The primary end point was the total combined rhinitis score (ie, the sum of rhinitis symptom and medication scores) during the efficacy assessment period (approximately the last 8 weeks of the treatment period). Key secondary end points were rhinitis symptoms, medication scores, quality of life, and the combined rhinoconjunctivitis score. Results Analysis of the primary end point (observed data) demonstrated absolute reductions in total combined rhinitis score of 1.18 (P =.002) and 1.22 (P =.001) compared with placebo for 6 SQ-HDM and 12 SQ-HDM, respectively. The statistically significant treatment effect was evident from 14 weeks of treatment onward. For all key secondary end points, efficacy was confirmed for 12 SQ-HDM, with statistically significant reductions of rhinitis symptoms and medication scores, improved quality of life, and a reduced combined rhinoconjunctivitis score in the efficacy assessment period compared with placebo. The treatment was well tolerated. Conclusion The trial confirmed the efficacy and favorable safety profile of both 6 SQ-HDM and 12 SQ-HDM in adults with HDM-induced AR. The treatment effect was present from 14 weeks of treatment onward. © 2015 The Authors.

Narison S.,French National Center for Scientific Research | Narison S.,Montpellier University | Navarra F.S.,University of Sao Paulo | Nielsen M.,University of Sao Paulo
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

We have studied some possible four-quark and molecule configurations of the X(3872) using double ratios of sum rules, which are more accurate than the usual simple ratios often used in the literature to obtain hadron masses. We found that the different structures (3̄-3 and 6̄-6 tetraquarks and D-D(*) molecule) lead to the same prediction for the mass (within the accuracy of the method), indicating that the alone prediction of the X mass may not be sufficient to reveal its nature. In doing these analyses, we also find that (within our approximation) the use of the MS̄ running m ̄c(mc2), rather than the on-shell mass, is more appropriate to obtain the J/ψ and X meson masses. Using vertex sum rules to roughly estimate the X(3872) hadronic and radiative widths, we found that the available experimental data does not exclude a λ-J/ψ-like molecule current.© 2011 American Physical Society.

Rastinejad F.,Sanford Burnham Institute for Medical Research | Ollendorff V.,Montpellier University | Polikarpov I.,University of Sao Paulo
Trends in Biochemical Sciences | Year: 2015

The crystal structures of three nuclear receptor (NR) complexes have emerged to reveal their multidomain architectures on DNA. These pictures provide unprecedented views of interfacial couplings between the DNA-binding domains (DBDs) and ligand-binding domains (LBDs). The detailed pictures contrast with previous interpretations of low-resolution electron microscopy (EM) and small angle X-ray scattering (SAXS) data, which had suggested a common architecture with noninteracting DBDs and LBDs. Revisiting both historical and recent interpretations of NR architecture, we invoke new principles underlying higher-order quaternary organization and the allosteric transmission of signals between domains. We also discuss how NR architectures are being probed in living cells to understand dimerization and DNA-binding events in real time. © 2014 Elsevier Ltd.

Fellous S.,Cornell University | Fellous S.,Montpellier University | Lazzaro B.P.,Cornell University
Molecular Ecology | Year: 2010

The potential effect of larval condition on adult immunity in holometabolous insects is rarely considered. We show here that larval food composition can impact adult immunity independent from effects on general condition of the animal. Rather, our data indicate a plastic allocation of resources to immunity in high-protein environments. Specifically, we found that increasing the nutritional yeast (protein) available to larval Drosophila melanogaster increased the adult's constitutive transcription of two genes encoding defensive antimicrobial peptides. Adult dry weight was not significantly affected by larval food composition, while adult fat content decreased when larval yeast increased. Larval immune activity was unaffected by alterations of larval diet, indicating a lack of covariation in this trait across life-stages. We conclude that the nutritional environment of insect larvae can affect adult immunity by influencing plastic allocation of resources. These influences are less predictable than constraints linked to general condition would be. © 2010 Blackwell Publishing Ltd.

Carles R.,Montpellier University | Fermanian-Kammerer C.,University Paris Est Creteil
Communications in Mathematical Physics | Year: 2011

We consider the propagation of wave packets for the nonlinear Schrödinger equation, in the semi-classical limit. We establish the existence of a critical size for the initial data, in terms of the Planck constant: if the initial data are too small, the nonlinearity is negligible up to the Ehrenfest time. If the initial data have the critical size, then at leading order the wave function propagates like a coherent state whose envelope is given by a nonlinear equation, up to a time of the same order as the Ehrenfest time. We also prove a nonlinear superposition principle for these nonlinear wave packets. © 2010 Springer-Verlag.

Sutin A.R.,Florida State University | Stephan Y.,Montpellier University | Carretta H.,Florida State University | Terracciano A.,Florida State University
American Journal of Geriatric Psychiatry | Year: 2015

Objective To examine whether perceived discrimination based on multiple personal characteristics is associated with physical, emotional, and cognitive health concurrently, prospectively, and with change in health over time among older adults. Design Longitudinal. Setting Health and Retirement Study (HRS). Participants Participants (N = 7,622) who completed the Leave-Behind Questionnaire as part of the 2006 HRS assessment (mean age 67 years); participants (N = 6,450) completed the same health measures again in 2010. Measurements Participants rated their everyday experience with discrimination and attributed those experiences to eight personal characteristics: race, ancestry, sex, age, weight, physical disability, appearance, and sexual orientation. At both the 2006 and 2010 assessments, participants completed measures of physical health (subjective health, disease burden), emotional health (life satisfaction, loneliness), and cognitive health (memory, mental status). Results Discrimination based on age, weight, physical disability, and appearance was associated with poor subjective health, greater disease burden, lower life satisfaction, and greater loneliness at both assessments and with declines in health across the four years. Discrimination based on race, ancestry, sex, and sexual orientation was associated with greater loneliness at both time points, but not with change over time. Discrimination was mostly unrelated to cognitive health. Conclusions The detrimental effect of discrimination on physical and emotional health is not limited to young adulthood but continues to contribute to health and well-being in old age. These effects were driven primarily by discrimination based on personal characteristics that change over time (e.g., age, weight) rather than discrimination based on more stable characteristics (e.g., race, sex). © 2015 American Association for Geriatric Psychiatry.

French Institute of Health, Medical Research, Institute Regional Du Cancer Of Montpellier Val Daurelle, Montpellier University and Oribase Pharma | Date: 2012-06-22

The present invention relates to anti-Axl antibodies and uses thereof in diagnostic and therapeutic methods. More particularly, the present invention relates to a monoclonal antibody having specificity for Axl comprising an heavy chain variable region comprising SEQ ID NO:2 in the H-CDR1 region, SEQ ID NO:3 in the H-CDR2 region and SEQ ID NO:4 in the H-CDR3 region; and a light chain variable region comprising SEQ ID NO: 6 in the L-CDR1 region, SEQ ID NO:7 in the L-CDR2 region and SEQ ID NO:8 in the L-CDR3 region. Said monoclonal antibody binds to the extracellular domain of Axl via, SEQ ID NO:9 and SEQ ID NO: 10.

Tohoku University, Montpellier University and French National Center for Scientific Research | Date: 2010-12-03

The purpose of the present invention is to improve the efficiency of conversion between terahertz electromagnetic wave energy and direct current energy via plasma waves in a terahertz electromagnetic wave conversion device with a field effect transistor structure. This invention has an HEMT structure having a substrate, an electron transit layer, an electron supply layer, a source and a drain, and includes a first and second group of gates. The gate length of each finger of the first group of gates is narrower than the gate length of each finger of the second group of gates, and each finger of each group of gates is disposed between the source and the drain on the same cycle. A first and second distance from each finger of the first group of gates to two fingers of the second group of gates adjacent to each finger are unequal lengths.

Oribase Pharma, Institute Regional Du Cancer Of Montpellier Val D Aurelle, French Institute of Health, Medical Research and Montpellier University | Date: 2012-06-22

The present invention relates to anti-Axl antibodies and uses thereof in diagnostic and therapeutic methods. More particularly, the present invention relates to a monoclonal antibody having specificity for Axl comprising an heavy chain variable region comprising SEQ ID NO:2 in the H-CDR1 region, SEQ ID NO:3 in the H-CDR2 region and SEQ ID NO:4 in the H-CDR3 region; and a light chain variable region comprising SEQ ID NO: 6 in the L-CDR1 region, SEQ ID NO:7 in the L-CDR2 region and SEQ ID NO:8 in the L-CDR3 region. Said monoclonal antibody binds to the extracellular domain of Axl via, SEQ ID NO:9, SEQ ID NO: 10 and SEQ ID NO: 11.

Diamandis E.P.,University of Toronto | Diamandis E.P.,Mount Sinai Hospital | Goodglick L.,University of California at Los Angeles | Planque C.,Montpellier University | Thornquist M.D.,Fred Hutchinson Cancer Research Center
Clinical Cancer Research | Year: 2011

Purpose: Our objective was to validate the performance of three new candidate lung cancer biomarkers, pentraxin-3 (PTX3), human kallikrein 11 (KLK11), and progranulin. Experimental Design: We analyzed by commercial ELISA, and with a blinded protocol, 422 samples from 203 patients with lung carcinoma, 180 individuals with high risk for lung cancer (heavy smokers), and 43 individuals with cancers other than lung. All samples were obtained from the Early Detection Research Network (Reference set A). Results: We found that progranulin and KLK11 were not informative lung cancer biomarkers, with areas under the receiver operating characteristic curve (AUC; ROC), close to 0.50. However, PTX3 was an informative lung cancer biomarker, with considerable ability to separate lung cancer patients from highrisk controls. At 90% and 80% specificity, the sensitivities versus the high-risk control group were 37% and 48%, respectively. The discriminatory ability of PTX3 was about the same with all major subtypes and histotypes of lung cancer. The AUC of the ROC curves increased according to the disease stage, from 0.64 (stage I) to 0.72 (stage IV). Conclusion: PTX3, but not KLK11 or progranulin, is a new serum biomarker for lung carcinoma. Its diagnostic sensitivity and specificity is similar to other clinically used lung cancer biomarkers. More studies are needed to establish if PTX3 has clinical utility for lung cancer diagnosis and management. Clin Cancer © 2011 American Association for Cancer Research.

Fateev V.A.,Montpellier University | Litvinov A.V.,Rutgers University
Journal of High Energy Physics | Year: 2010

In these notes we consider relation between conformal blocks and the Nekrasov partition function of certain N = 2 SYM theories proposed recently by Alday, Gaiotto and Tachikawa. We concentrate on N = 2* theory, which is the simplest example of AGT relation. © SISSA 2010.

Burks A.W.,University of North Carolina at Chapel Hill | Calderon M.A.,Imperial College London | Casale T.,Creighton University | Cox L.,Nova Southeastern University | And 4 more authors.
Journal of Allergy and Clinical Immunology | Year: 2013

Allergy immunotherapy (AIT) is an effective treatment for allergic asthma and rhinitis, as well as venom-induced anaphylaxis. In addition to reducing symptoms, AIT can change the course of allergic disease and induce allergen-specific immune tolerance. In current clinical practice immunotherapy is delivered either subcutaneously or sublingually; some allergens, such as grass pollen, can be delivered through either route, whereas others, such as venoms, are only delivered subcutaneously. Both subcutaneous and sublingual immunotherapy appear to have a duration of efficacy of up to 12 years, and both can prevent the development of asthma and new allergen sensitivities. In spite of the advances with AIT, safer and more effective AIT strategies are needed, especially for patients with asthma, atopic dermatitis, or food allergy. Novel approaches to improve AIT include use of adjuvants or recombinant allergens and alternate routes of administration. As part of the PRACTALL initiatives, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology nominated an expert team to develop a comprehensive consensus report on the mechanisms of AIT and its use in clinical practice, as well as unmet needs and ongoing developments in AIT. This resulting report is endorsed by both academies. © 2012 American Academy of Allergy, Asthma & Immunology.

Devictor V.,Montpellier University | Mouillot D.,Montpellier University | Meynard C.,Montpellier University | Jiguet F.,CNRS Science Conservation Center | And 2 more authors.
Ecology Letters | Year: 2010

Functional and phylogenetic diversity are increasingly quantified in various fields of ecology and conservation biology. The need to maintain diversity turnover among sites, so-called beta-diversity, has also been raised in theoretical and applied ecology. In this study, we propose the first comprehensive framework for the large-scale mapping of taxonomic, phylogenetic and functional diversity and of their respective turnover. Using high-resolution data on the spatial distribution and abundance of birds at a country scale, we disentangled areas of mismatches and congruencies between biodiversity components. We further revealed unequal representation of each component in protected areas: functional diversity was significantly under-represented whereas taxonomic diversity was significantly over-represented in protected areas. Our results challenge the use of any one diversity component as a surrogate for other components and stress the need to adopt an integrative approach to biodiversity conservation. © 2010 Blackwell Publishing Ltd/CNRS.

Royer C.,Montpellier University | Winter R.,TU Dortmund
Current Opinion in Colloid and Interface Science | Year: 2011

Pressure effects on proteins stem from volumetric differences between their conformational states. These differences implicate rigid structure-based solvent excluded void volumes, although hydration and thermal expansivity differences between states may also play a role. Defining quantitatively the contributions of hydration and solvent excluded voids to protein volumetric properties and thermal expansivities remains a major challenge. Experimental information concerning thermal expansivity can be gained from pressure perturbation calorimetric studies (PPC). We review here recent results from PPC that suggest that while hydration plays a significant role in the volumetric properties of unfolded states of proteins, the volumetric properties of folded states are defined by structural and energetic properties of the folded chain. © 2011 Elsevier Ltd.

Whitfield A.K.,South African Institute For Aquatic Biodiversity | Panfili J.,IRD Montpellier | Durand J.-D.,Montpellier University
Reviews in Fish Biology and Fisheries | Year: 2012

This study reviews published information on Mugil cephalus from around the world, with recent genetic studies indicating that the flathead mullet may indeed be a species complex. Disciplines that are covered range from the taxonomy, genetics and systematics, through a variety of biological and ecological attributes, to biomarker and fisheries studies. The eurytopic nature of M. cephalus is emphasized, with the migratory life history covering a succession of very different aquatic environments (e. g. rivers, estuaries, coastal lakes/lagoons, marine littoral, open ocean), each of which is occupied for varying lengths of time, depending on the population characteristics within a region and the life-history stage of the species. Interpretation of these movements over time has been greatly enhanced by the use of otolith micro-chemistry which has enabled scientists to map out the different habitats occupied by individual fish at the different life stages. The range of physico-chemical attributes within these environments necessitates a wide tolerance to differing conditions, especially with regard to salinity, turbidity, dissolved oxygen and temperature, all of which are discussed in this review. The importance of M. cephalus to the ecological functioning of coastal systems is emphasized, as well as the pivotal role that this species fulfills in fisheries in some parts of the world. The parasites range from internal trematode and cestode infestations, to external branchyuran and copepod parasites, which use M. cephalus as either an intermediate or final host. The value of the flathead mullet as a biomarker for the monitoring of the health of coastal habitats is discussed, as well as its potential as an indicator or sentinel species for certain ecosystems. © 2012 Springer Science+Business Media B.V.

Briant L.,Montpellier University | Despres P.,Institute Pasteur Paris | Choumet V.,Institute Pasteur Paris | Misse D.,IRD Montpellier
Virology | Year: 2014

Due to climate change and the propagation of competent arthropods worldwide, arboviruses have become pathogens of major medical importance. Early transmission to vertebrates is initiated by skin puncture and deposition of virus together with arthropod saliva in the epidermis and dermis. Saliva components have the capacity to modulate skin cell responses by enhancing and/or counteracting initial replication and establishment of systemic viral infection. Here, we review the nature of the cells targeted by arboviruses at the skin level and discuss the type of cellular responses elicited by these pathogens in light of the immunomodulatory properties of arthropod vector-derived salivary factors injected at the inoculation site. Understanding cutaneous arbovirus-host interactions may provide new clues for the design of future therapeutics. © 2014 .

Poisot T.,Montpellier University | Bever J.D.,Indiana University Bloomington | Nemri A.,CSIRO | Thrall P.H.,CSIRO | Hochberg M.E.,Montpellier University
Ecology Letters | Year: 2011

Ecological specialisation concerns all species and underlies many major ecological and evolutionary patterns. Yet its status as a unifying concept is not always appreciated because of its similarity to concepts of the niche, the many levels of biological phenomena to which it applies, and the complexity of the mechanisms influencing it. The evolution of specialisation requires the coupling of constraints on adaptive evolution with covariation of genotype and environmental performance. This covariation itself depends upon organismal properties such as dispersal behaviour and life history and complexity in the environment stemming from factors such as species interactions and spatio-temporal heterogeneity in resources. Here, we develop a view on specialisation that integrates across the range of biological phenomena with the goal of developing a more predictive conceptual framework that specifically accounts for the importance of biotic complexity and coevolutionary events. © 2011 Blackwell Publishing Ltd/CNRS.

Georgess D.,CNRS Lyon Institute of Functional Genomics | Machuca-Gayet I.,CNRS Lyon Institute of Functional Genomics | Blangy A.,Montpellier University | Jurdic P.,CNRS Lyon Institute of Functional Genomics
Cell Adhesion and Migration | Year: 2014

Osteoclasts are the cells responsible for physiological bone resorption. A specific organization of their most prominent cytoskeletal structures, podosomes, is crucial for the degradation of mineralized bone matrix. Each podosome is constituted of an F-actin-enriched central core surrounded by a loose F-actin network, called the podosome cloud. In addition to intrinsic actin dynamics, podosomes are defined by their adhesion to the extracellular matrix, mainly via core-linking CD44 and cloud-linking integrins. These properties allow podosomes to collectively evolve into different patterns implicated in migration and bone resorption. Indeed, to resorb bone, osteoclasts polarize, actively secrete protons, and proteases into the resorption pit where these molecules are confined by a podosome-containing sealing zone. Here, we review recent advancements on podosome structure and regulatory pathways in osteoclasts. We also discuss the distinct functions of different podosome patterns during the lifespan of a single osteoclast. © 2014 Landes Bioscience.

Charmantier G.,Montpellier University | Anger K.,Alfred Wegener Institute for Polar and Marine Research
Journal of Experimental Marine Biology and Ecology | Year: 2011

Ontogenetic changes in osmoregulation were compared between two geographically separate populations of a South American shrimp, Macrobrachium amazonicum, originating from the Amazon delta (A) and the Pantanal (P), respectively. Population A lives in coastal rivers and estuaries in northern Brazil, whereas population P may be considered as land-locked, spending its entire life cycle in inland freshwater (FW) habitats in southwestern Brazil. All life-history stages of population A tolerated brackish and seawater (SW) conditions, being hyper-osmoregulators at salinities <. 17, iso-osmotic at ca. 17, and hypo-regulators at higher concentrations. The capabilities to survive and osmoregulate in FW were in this population expressed already at hatching (zoea I), but not any longer in the subsequent larval stages (II-IX), which showed complete mortality during an experimental 24. h exposure to fully limnic conditions. FW tolerance re-appeared only in the juvenile and adult life-history stages. Similarly, the ability to hyper-regulate at salinities 1-5 was strong in the zoea I, weaker in the subsequent larval stages, and increasing again after metamorphosis. The function of hypo-regulation in concentrated media including SW was present throughout ontogeny, particularly in late larval and early juvenile stages. These ontogenetic patterns of osmoregulation and FW tolerance are congruent with a diadromous life cycle, which includes larval release in FW and a subsequent downstream transport of the salt-dependent early larvae towards estuarine or coastal marine waters, where development to metamorphosis is possible. The FW-tolerant juveniles can later migrate upstream, recruiting to riverine populations. In the land-locked population P, all life-history stages tolerated FW and brackish conditions up to salinity 25, but mortality was high in SW (100% in adults). All postembryonic stages of this population were hyper-osmoregulators at salinities <. 17, with a strong osmoregulatory capacity in FW. Unlike in population A, all stages were osmoconformers at higher salinities, lacking the function of hypo-regulation. In summary, our results show in two hydrologically and genetically isolated shrimp populations close relationships between differential patterns of ontogenetic change in osmoregulatory functions, salinity tolerance, and the ecology of successive life-history stages. In all postembryonic stages of the hololimnetic Pantanal population, the acquisition of an increased ability to hyper-osmoregulate in FW and, in particular, the complete loss of the ability to hypo-osmoregulate at high salt concentrations represent striking differences to the diadromous population from the Amazon estuary. These differences reflect different life styles and reproductive strategies, suggesting an at least incipient phylogenetic separation. © 2010 Elsevier B.V.

Derakhshan S.,Iran University of Science and Technology | Mohammadi B.,Montpellier University | Nourbakhsh A.,University of Tehran
Computers and Fluids | Year: 2010

In the present work, a centrifugal pump impeller's blades shape was redesigned to reach a higher efficiency in turbine mode using two different optimization algorithms: one is a local method as incomplete sensitivities-gradient based optimization algorithm coupled by 3D Navier-Stokes flow solver, and another is a global method as Genetic algorithms and artificial neural network coupled by 3D Navier-Stokes flow solver. New impeller was manufactured and tested in the test rig. Comparison of the local optimization method results with the global optimization method results showed that the gradient based method has detected the global optimum point. Experimental results confirmed the numerical efficiency improvement in all measured points. This study illustrated that the developed gradient based optimization method is efficient for 3D radial turbomachinery blade optimization. © 2010 Elsevier Ltd.

Calderon M.A.,Imperial College London | Casale T.B.,Creighton University | Nelson H.S.,National Jewish Health | Demoly P.,Montpellier University
Journal of Allergy and Clinical Immunology | Year: 2013

Background: According to meta-analyses and reviews, subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are beneficial in patients with allergic rhinitis (AR) and allergic asthma (AA) induced by house dust mites (HDMs). However, the reported effect sizes have varied greatly from one study to another. Objective: We sought to perform an evidence-based medicine assessment of commercially available SCIT and SLIT formulations in patients with HDM-induced AA and HDM-induced AR. Methods: We searched for double-blind, placebo-controlled randomized clinical trials and analyzed study designs, doses, regimens, patient-reported outcomes, safety reporting, and compliance. Results: Forty-four studies met our inclusion criteria. Some studies tested both SLIT and SCIT or scored both AA and AR outcomes; therefore we reviewed 35 treatment arms in patients with AA (20 for SCIT and 15 for SLIT) and 23 treatment arms in patients with AR (7 for SCIT and 16 for SLIT). The treatment duration ranged from 6 weeks to 3 years. For SCIT, the dose of Der p 1 major allergen (when reported) ranged from 7 to 30 μg for maintenance doses and 60 to 420 μg for cumulative doses. For SLIT, the doses of Der p 1 (when reported) were 0.8 to 70 μg for maintenance doses and 60 to 23,695 μg for cumulative doses. Safety data were often absent or poorly reported. A statistically significant active versus placebo symptom score was observed more frequently for SCIT than for SLIT. Conclusion: There is no consensus on basic treatment parameters (eg, dose and duration) in HDM SCIT and SLIT. There is an urgent need for rigorous, long-term, double-blind, placebo-controlled randomized clinical trials with an efficacy criterion that reflects the particular features of HDM-induced allergic disease. © 2013 American Academy of Allergy, Asthma & Immunology.

Hanghoj K.,Lamont Doherty Earth Observatory | Kelemen P.B.,Lamont Doherty Earth Observatory | Hassler D.,Statoil | Godard M.,Montpellier University
Journal of Petrology | Year: 2010

The Oman ophiolite consists of several massifs cropping out along a 500 km long band trending NW-SE along the coast of Oman; it is one of the best exposed sections of oceanic crust and mantle in the world. There is a gradient in igneous processes and composition in the ophiolite, with the northern massifs recording a polygenetic igneous history involving an increasingly important subduction component, whereas the southern massifs were formed primarily via a mid-ocean ridge basalt (MORB)-like, single-stage process at a submarine spreading ridge. In this study we use geochemical data from Wadi Tayin, which is one of the southern massifs of the Oman ophiolite, to constrain the composition and genesis of oceanic crust and upper mantle. The Wadi Tayin harzburgites are residues of partial melting that are as depleted as the most depleted mid-ocean ridge peridotites. They have low middle- to heavy rare earth element ratios, most probably reflecting melting close to and beyond the exhaustion of clinopyroxene. Like many abyssal peridotites, the Wadi Tayin samples show enrichment in highly incompatible elements, giving rise to U-shaped MORB-normalized trace element patterns. We favor the idea that this is caused by enrichment of highly incompatible elements along grain boundaries in peridotite, which may be the result of near-equilibrium partitioning between grain boundaries and grain interiors, rather than disequilibrium processes. Equilibrium partitioning between crystals and grain boundaries during melting and melt extraction is also our preferred explanation for ubiquitous high Pb contents relative to Ce and La in our samples as well as in most abyssal peridotites. The Wadi Tayin samples record substantial variability in terms of osmium isotopic composition and platinum group element (PGE) concentrations. The more radiogenic nature of the dunites and impregnated peridotites compared with the residual harzburgites may be due to relatively high . 187Os/. 188Os in melt transported through the dunites. The presence of residual peridotites with whole-rock osmium isotopic compositions less radiogenic than MORB may be explained by melting of a veined (upwelling) mantle forming mixed melts in which much of the Os derives from veins with high Re/Os in a matrix of previously depleted peridotite. An important result of this study is that the shallowest samples are refertilized (i.e. anomalously enriched in incompatible elements), and record relatively high metamorphic closure temperatures. These observations suggest that migrating melt underwent crystallization during rapid cooling in the uppermost mantle during and immediately after ridge magmatism. A variety of geothermometers all yield the result that the stratigraphically highest harzburgites equilibrated at higher temperature than the deeper ones. The systematic decrease in closure temperature with increasing depth below the Moho transition zone probably reflects systematic variation in cooling rate as a function of depth in the mantle section. We hypothesize that the refertilization and higher closure temperatures recorded by the uppermost mantle samples are linked. More rapid cooling led to higher closure temperatures, and to partial crystallization of migrating melts in the shallowest part of the mantle section, yielding slightly elevated abundances of elements such as Ca and Na, and incompatible trace elements. © The Author 2010. Published by Oxford University Press.

Dauvilliers Y.,Montpellier University | Siegel J.M.,University College Los Angeles | Lopez R.,Montpellier University | Torontali Z.A.,University of Toronto | Peever J.H.,University of Toronto
Nature Reviews Neurology | Year: 2014

Cataplexy is the pathognomonic symptom of narcolepsy, and is the sudden uncontrollable onset of skeletal muscle paralysis or weakness during wakefulness. Cataplexy is incapacitating because it leaves the individual awake but temporarily either fully or partially paralyzed. Occurring spontaneously, cataplexy is typically triggered by strong positive emotions such as laughter and is often underdiagnosed owing to a variable disease course in terms of age of onset, presenting symptoms, triggers, frequency and intensity of attacks. This disorder occurs almost exclusively in patients with depletion of hypothalamic orexin neurons. One pathogenetic mechanism that has been hypothesized for cataplexy is the activation, during wakefulness, of brainstem circuitry that normally induces muscle tone suppression in rapid eye movement sleep. Muscle weakness during cataplexy is caused by decreased excitation of noradrenergic neurons and increased inhibition of skeletal motor neurons by 3-aminobutyric acid-releasing or glycinergic neurons. The amygdala and medial prefrontal cortex contain neural pathways through which positive emotions probably trigger cataplectic attacks. Despite major advances in understanding disease mechanisms in cataplexy, therapeutic management is largely symptomatic, with antidepressants and 3-hydroxybutyrate being the most effective treatments. This Review describes the clinical and pathophysiological aspects of cataplexy, and outlines optimal therapeutic management strategies. © 2014 Macmillan Publishers Limited.

Rugarabamu G.,University of Geneva | Marq J.-B.,University of Geneva | Guerin A.,Montpellier University | Lebrun M.,Montpellier University | Soldati-Favre D.,University of Geneva
Molecular Microbiology | Year: 2015

Host cell entry by the Apicomplexa is associated with the sequential secretion of invasion factors from specialized apical organelles. Secretion of micronemal proteins (MICs) complexes by Toxoplasma gondii facilitates parasite gliding motility, host cell attachment and entry, as well as egress from infected cells. The shedding of MICs during these steps is mediated by micronemal protein proteases MPP1, MPP2 and MPP3. The constitutive activity of MPP1 leads to the cleavage of transmembrane MICs and is linked to the surface rhomboid protease 4 (ROM4) and possibly to rhomboid protease 5 (ROM5). To determine their importance and respective contribution to MPP1 activity, in this study ROM4 and ROM5 genes were abrogated using Cre-recombinase and CRISPR-Cas9 nuclease, respectively, and shown to be dispensable for parasite survival. Parasites lacking ROM4 predominantly engage in twirling motility and exhibit enhanced attachment and impaired invasion, whereas intracellular growth and egress is not affected. The substrates MIC2 and MIC6 are not cleaved in rom4-ko parasites, in contrast, intramembrane cleavage of AMA1 is reduced but not completely abolished. Shedding of MICs and invasion are not altered in the absence of ROM5; however, this protease responsible for the residual cleavage of AMA1 is able to cleave other AMA family members and exhibits a detectable contribution to invasion in the absence of ROM4. © 2015 John Wiley & Sons Ltd.

Mueller C.,University of Geneva | Klages N.,University of Geneva | Jacot D.,University of Geneva | Santos J.M.,University of Geneva | And 4 more authors.
Cell Host and Microbe | Year: 2013

Members of the phylum Apicomplexa actively enter host cells by a process involving the discharge of the apically localized microneme and rhoptry organelles. To unravel the processes involved in rhoptry organelle biogenesis, we focused on the Toxoplasma gondii armadillo repeats only protein (TgARO), a conserved acylated protein homogenously anchored to the rhoptry membrane. Conditional disruption of TgARO results in the random cytosolic dispersion of rhoptries and a severe defect in T. gondii invasion, with no effects on intracellular growth or host cell egress. Importantly, rhoptry displacement upon ARO depletion can be functionally complemented with wild-type TgARO but not an acylation mutant. TgARO interacts with myosin F, and inhibition of actin polymerization or myosin function also results in rhoptry dispersal, indicating that the apical positioning of rhoptries is an actomyosin-based process. Thus, TgARO mediates the apical localization of rhoptries, which is specifically required for host cell invasion. © 2013 Elsevier Inc.

Xu J.,Northeastern University | Gattacceca F.,Northeastern University | Gattacceca F.,Montpellier University | Amiji M.,Northeastern University
Molecular Pharmaceutics | Year: 2013

The objective of this study was to evaluate qualitative and quantitative biodistribution of epidermal growth factor receptor (EGFR)-targeted thiolated type B gelatin nanoparticles in vivo in subcutaneous human pancreatic adenocarcinoma (Panc-1) bearing female SCID Beige mice. EGFR-targeted nanoparticles showed preferential and sustained accumulation in the tumor mass, especially at early time points. Higher blood concentrations and higher tumor accumulations were observed with PEG-modified and EGFR-targeted nanoparticles during the study (AUClast: 17.38 and 19.56%ID/mL·h in blood, 187 and 322%ID/g·h in tumor for PEG-modified and EGFR-targeted nanoparticles, respectively), as compared to control, unmodified particles (AUClast: 10.71%ID/mL·h in blood and 138%ID/g·h in tumor). EGFR-targeted nanoparticles displayed almost twice tumor targeting efficiency than either PEG-modified or the unmodified nanoparticles, highlighting the efficacy of the active targeting strategy. In conclusion, this study shows that EGFR-targeted and PEG-modified nanoparticles were suitable vehicles for specific systemic delivery in subcutaneous Panc-1 tumor xenograft models. © 2013 American Chemical Society.

Killen S.S.,University of Glasgow | Marras S.,CNR Institute for Coastal Marine Environment | Metcalfe N.B.,University of Glasgow | McKenzie D.J.,Montpellier University | Domenici P.,CNR Institute for Coastal Marine Environment
Trends in Ecology and Evolution | Year: 2013

Although correlations have frequently been observed between specific physiological and behavioural traits across a range of animal taxa, the nature of these associations has been shown to vary. Here we argue that a major source of this inconsistency is the influence of environmental stressors, which seem capable of revealing, masking, or modulating covariation in physiological and behavioural traits. These effects appear to be mediated by changes in the observed variation of traits and differential sensitivity to stressors among phenotypes. Considering that wild animals routinely face a range of biotic and abiotic stressors, increased knowledge of these effects is imperative for understanding the causal mechanisms of a range of ecological phenomena and evolutionary responses to stressors associated with environmental change. © 2013.

Thuiller W.,CNRS Alpine Ecology Laboratory | Munkemuller T.,CNRS Alpine Ecology Laboratory | Lavergne S.,CNRS Alpine Ecology Laboratory | Mouillot D.,IRD Montpellier | And 4 more authors.
Ecology Letters | Year: 2013

The demand for projections of the future distribution of biodiversity has triggered an upsurge in modelling at the crossroads between ecology and evolution. Despite the enthusiasm around these so-called biodiversity models, most approaches are still criticised for not integrating key processes known to shape species ranges and community structure. Developing an integrative modelling framework for biodiversity distribution promises to improve the reliability of predictions and to give a better understanding of the eco-evolutionary dynamics of species and communities under changing environments. In this article, we briefly review some eco-evolutionary processes and interplays among them, which are essential to provide reliable projections of species distributions and community structure. We identify gaps in theory, quantitative knowledge and data availability hampering the development of an integrated modelling framework. We argue that model development relying on a strong theoretical foundation is essential to inspire new models, manage complexity and maintain tractability. We support our argument with an example of a novel integrated model for species distribution modelling, derived from metapopulation theory, which accounts for abiotic constraints, dispersal, biotic interactions and evolution under changing environmental conditions. We hope such a perspective will motivate exciting and novel research, and challenge others to improve on our proposed approach. © 2013 John Wiley & Sons Ltd/CNRS.

Avadi A.,Montpellier University | Freon P.,IRD Montpellier
Fisheries Research | Year: 2013

This review aims to synthesise and discuss current literature applying the Life Cycle Assessment (LCA) framework for the environmental assessment of fisheries. The review introduces and illustrates the LCA framework, and highlights energy use by fishing vessels, among other key factors determining environmental impacts of fisheries operations. Moreover, the review concludes with recommendations on future developments of LCA in the fisheries and seafood sectors.We reviewed 16 studies on LCA applied to fisheries, with perspectives from a few additional publications on closely related topics. The main Aspects considered in the ad hoc comparison of studies include: scope and system boundaries, functional units, allocation strategies for co-products, conventional and fishery-specific impact categories used, fuel use, impact assessment methods, level of detail in inventories, normalisation of results and sensitivity analyses.A number of patterns and singularities were detected. Fishery-specific impact categories, despite not being standardised, and fuel use in fishing operations were identified as the main contributors to environmental impacts. Energy efficiency was found to be strongly related to the fishing gear used. Several studies discussed the impacts of antifouling substances and metals use. The need for standardisation of fisheries LCA research is justified and ideas on how to do so and what elements to standardise (fisheries-specific impact categories, inventory details, normalisation references, etc.) are discussed. Finally, fisheries LCA constitute a useful research field when studying the sustainability of seafood and fisheries-based agrifood, and it should likewise contribute to an ecosystem approach to fisheries. © 2013 Elsevier B.V.

Graham N.A.J.,James Cook University | Jennings S.,Center for Environment | Jennings S.,University of East Anglia | MacNeil M.A.,James Cook University | And 5 more authors.
Nature | Year: 2015

Climate-induced coral bleaching is among the greatest current threats to coral reefs, causing widespread loss of live coral cover. Conditions under which reefs bounce back from bleaching events or shift from coral to algal dominance are unknown, making it difficult to predict and plan for differing reef responses under climate change. Here we document and predict long-term reef responses to a major climate-induced coral bleaching event that caused unprecedented region-wide mortality of Indo-Pacific corals. Following loss of >90% live coral cover, 12 of 21 reefs recovered towards pre-disturbance live coral states, while nine reefs underwent regime shifts to fleshy macroalgae. Functional diversity of associated reef fish communities shifted substantially following bleaching, returning towards pre-disturbance structure on recovering reefs, while becoming progressively altered on regime shifting reefs. We identified threshold values for a range of factors that accurately predicted ecosystem response to the bleaching event. Recovery was favoured when reefs were structurally complex and in deeper water, when density of juvenile corals and herbivorous fishes was relatively high and when nutrient loads were low. Whether reefs were inside no-take marine reserves had no bearing on ecosystem trajectory. Although conditions governing regime shift or recovery dynamics were diverse, pre-disturbance quantification of simple factors such as structural complexity and water depth accurately predicted ecosystem trajectories. These findings foreshadow the likely divergent but predictable outcomes for reef ecosystems in response to climate change, thus guiding improved management and adaptation. © 2015 Macmillan Publishers Limited. All rights reserved.

Galanaud J.-P.,Montpellier University | Laroche J.-P.,Montpellier University | Righini M.,University of Geneva
Journal of Thrombosis and Haemostasis | Year: 2013

Deep vein thrombosis (DVT) is a common disease. However, unlike that of varicose veins, which have been depicted since antiquity in art and literature, its description was more recent in the history of medicine. The first well-documented case of DVT was reported during the Middle Ages: in 1271, Raoul developed a unilateral edema in the ankle, which then extended to the leg. The number of reported DVT cases steadily increased thereafter, particularly in pregnant and postpartum women. During the first half of the 20th century, well before the discovery of anticoagulants, many therapeutic approaches were used, and arose from the pathologic hypotheses that prevailed at their time. Despite the development of anticoagulants, and the fact that they were thought to dramatically decrease DVT mortality, numerous complementary treatments have also been developed during the last 50 years: they include vena cava clips and surgical thrombectomy, and are intended to decrease mortality or to prevent late complications. Most of these treatments have now been abandoned, or even forgotten. In this review, we recall also the discovery and the use of vitamin K antagonists and heparin, which have constituted the mainstay of treatment for decades. We also bring some perspective to historical aspects of this disease and its treatment, notably regarding elastic compression and early mobilization, but also abandoned and complementary treatments. In these times of change regarding DVT treatment, mainly marked by the arrival of new oral anticoagulants, efforts of physicians through the ages to treat this common disease provide a beautiful example of the history of knowledge. © 2013 International Society on Thrombosis and Haemostasis.

Different seafood products based on Peruvian anchoveta (Engraulis ringens) fisheries and freshwater aquaculture of trout (Oncorhynchus mykiss), tilapia (Oreochromis spp.) and black pacu (Colossoma macropomum), contribute at different scales to the socio-economic development, environmental degradation and nutrition of the Peruvian population. Various indicators have been used in the literature to assess the performance of these industries regarding different aspects of sustainability, notably their socio-economic performance. In this study, a novel set of indicators is proposed to evaluate the sustainability performance of these industries in Peru, based on life cycle assessment (LCA) and nutritional profiling, as well as on energy and socio-economic assessment approaches. The emphasis is put on the potential of different products to contribute to improving the nutrition of the Peruvian population in an energy-efficient, environmentally friendly and socio-economically sound way. The set of indicators includes biotic resource use (BRU), cumulative energy demand (CED), energy return on investment (EROI), production costs, gross profit generation, added value, and nutritional profile in terms of vitamins, minerals and essential fatty acids; as well as a number of life cycle impact assessment indicators commonly used in seafood studies, and some recently proposed indicators of resource status (measuring the impacts of fish biomass removal at the species and ecosystem levels). Results suggest that more energy-intensive/highly processed products (cured and canned anchoveta products) represent a higher burden, in terms of environmental impact, than less energy-intensive products (salted and frozen anchoveta products, semi-intensive aquaculture products). This result is confirmed when comparing all products regarding their industrial-to-nutritional energy ratio. Regarding the other attributes analysed, the scoring shows that salted and frozen anchoveta products generate fewer jobs and lower gross profit than canned and cured, while aquaculture products maximise them. Overall, it was concluded that less energy-intensive industries (anchoveta freezing and salting) are the least environmentally impacting but also the least economically interesting products, yet delivering higher nutritional value. Aquaculture products maximise gross profit and job creation, with lower energy efficiency and nutritional values. The proposed set of sustainability indicators fulfilled its goal in providing a multi-criteria assessment of anchoveta direct human consumption and freshwater aquaculture products. As often the case, there is no ideal product and the best trade-off must be sought when making decision regarding fisheries and seafood policy. No threshold for performance of the different indicators is offered, because the goal of the comparison is to contrast the relative performance among products, not of products against reference values. © 2014 Elsevier Ltd. All rights reserved.

Calderon M.A.,Imperial College London | Casale T.B.,Creighton University | Nelson H.S.,National Jewish Health | Demoly P.,Montpellier University
Journal of Allergy and Clinical Immunology | Year: 2013

Background According to meta-analyses and reviews, subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are beneficial in patients with allergic rhinitis (AR) and allergic asthma (AA) induced by house dust mites (HDMs). However, the reported effect sizes have varied greatly from one study to another. Objective We sought to perform an evidence-based medicine assessment of commercially available SCIT and SLIT formulations in patients with HDM-induced AA and HDM-induced AR. Methods We searched for double-blind, placebo-controlled randomized clinical trials and analyzed study designs, doses, regimens, patient-reported outcomes, safety reporting, and compliance. Results Forty-four studies met our inclusion criteria. Some studies tested both SLIT and SCIT or scored both AA and AR outcomes; therefore we reviewed 35 treatment arms in patients with AA (20 for SCIT and 15 for SLIT) and 23 treatment arms in patients with AR (7 for SCIT and 16 for SLIT). The treatment duration ranged from 6 weeks to 3 years. For SCIT, the dose of Der p 1 major allergen (when reported) ranged from 7 to 30 μg for maintenance doses and 60 to 420 μg for cumulative doses. For SLIT, the doses of Der p 1 (when reported) were 0.8 to 70 μg for maintenance doses and 60 to 23,695 μg for cumulative doses. Safety data were often absent or poorly reported. A statistically significant active versus placebo symptom score was observed more frequently for SCIT than for SLIT. Conclusion There is no consensus on basic treatment parameters (eg, dose and duration) in HDM SCIT and SLIT. There is an urgent need for rigorous, long-term, double-blind, placebo-controlled randomized clinical trials with an efficacy criterion that reflects the particular features of HDM-induced allergic disease. © 2013 American Academy of Allergy, Asthma & Immunology.

Quemener D.,Montpellier University | Deratani A.,Montpellier University | Lecommandoux S.,CNRS Organic Polymer Chemistry Laboratory
Topics in Current Chemistry | Year: 2012

Block copolymers (BCs) are well-known building blocks for the creation of a large variety of nanostructured materials or objects through a dynamic assembly stage which can be either autonomous or guided by an external force. Today's nanotechnologies require sharp control of the overall architecture from the nanoscale to the macroscale. BCs enable this dynamic assembly through all the scales, from few aggregated polymer chains to large bulk polymer materials. Since the discovery of controlled methods to polymerize monomers with different functionalities, a broad diversity of BCs exists, giving rise to many different nanoobjects and nanostructured materials. This chapter will explore the potentialities of block copolymer chains to be assembled through dynamic interactions either in solution or in bulk. © 2011 Springer-Verlag Berlin Heidelberg.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2007.3.5 | Award Amount: 3.35M | Year: 2008

The SensHy proposal focuses on novel photonic gas sensors for the detection of hydrocarbons. Hydrocarbons can be detected most sensitively in the 3.0 to 3.6 m wavelength range. Two particular challenging applications with significant market potential are investigated within the project. Unfortunately there are no application grade semiconductor lasers in this wavelength range yet: On the short-wavelength side of this range interband lasers are available (RT cw operation for emission up to about 3.0 m), while intraband quantum cascade lasers were demonstrated on the long-wavelength side (RT cw operation for emission above about 3.8 m). An additional complication for applications in gas detection is given by the maximum available tuning range for suitable mono mode laser diodes, which is currently limited to a few nanometers. Concepts for an increased tuning range have so far been predominantly investigated at wavelengths around 1.55 m for telecom applications. The aim of the SensHy proposal is to overcome these limitations and to achieve the following goals:\n\n- realize GaSb based laser material enabling RT cw operation in the wavelength range from 3.0 to 3.6 m\n- develop multi-section DFB/DBR Lasers with increased electrical tuning capability\n- demonstrate highly sensitive hydrocarbon detection making use of widely tuneable lasers and novel digital-signal-processing schemes to identify various gas constituents within a multi-component hydrocarbon gas mixture\n\nIn order to reach these goals significant challenges have to be overcome in various fields ranging from epitaxial semiconductor growth via laser design and processing to mid infrared sensor development of the project. For this the consortium comprises renowned research groups, academic and industrial partners including SMEs from across Europe with a range of complementary competencies covering all aspects from semiconductor material and characterization to photonic components and sensor systems.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2009.8.4 | Award Amount: 12.43M | Year: 2010

VERE aims to carry out research on the fusion of the human body with virtual or physical surrogates. By fuse we mean that human participants would operate under the illusion that the virtual body is their own, or that they are actually in the physical space of the real world in a robotic body that they perceive as their own. As well as providing a radical extension of traditional virtual reality through the notion of virtual body ownership, VERE would pioneer remote body ownership, that is where the participant stays in a reclining and immobile position but operates a virtual or physical remote body via a brain and body computer interface (BBCI). This BBCI uses real-time EEG and other physiological data to infer participant intentions, and exploits machine learning to drive the virtual or robotic body. Two exemplary applications would be developed during the research: one in the context of gender-based domestic violence and the other to give physically impaired people such as tetraplegics the ability to operate again in the physical world through their surrogate. Both applications will be with domain professionals. There would be up to two further applications during the course of the project, managed by external groups who would submit proposals to the VERE consortium to exploit the technology for other unforeseen applications. The proposal is organised as eight scientific workpackages underpinned by one on the science of body ownership led by a team of cognitive neuroscientists. The work is informed by consideration of its ethical implications, and provides a testing ground for experiments in neuroethics. Moreover the work clearly has implications for the notion of self and consciousness, and one WP will be devoted to these issues. The proposal has been formed by a highly interdisciplinary group. It also draws on earlier FET projects IMMERSENCE and PRESENCCIA but opens the door to a radically new form of human-computer confluence with beneficial applications.

The proposals overall aim is to improve cervical cancer prevention programs for HIVinfected women in Africa, by evaluating the effectiveness and cost-effectiveness of alternative screening strategies, and by developing algorithms leading to earlier detection and management of cervical cancer in these high-risk populations. The proposals hypotheses are that: i) the use of simplified point of care diagnostic tests to detect high-risk (HR) HPV DNA , never before evaluated in Africa, alone or combination with other tests in various triage strategies has the potential to improve the coverage of cervical cancer screening in high-risk populations, and that it will prove a cost-effective cervical cancer prevention intervention in the long term; and ii) immune restoration and control of HIV replication through highly active antiretroviral therapy (HAART) or HAART initiation improves clearance of HPV infection among high-risk (HR)-HPV infected women, therefore slowing the development or progression of cervical precursor lesions. These findings may suggest that varying strategies or frequencies of screening may be required for women on HAART or not. The study will enroll 1200 HIV positive women (half on HAART or about to start HAART; and half with high CD4 count>350) in Burkina Faso and South Africa in a cross-sectional evaluation of cervical cancer screening strategies, from which about 1100 HIV-infected women without CIN2\ will be followed at one year to detect incident CIN2\ and persistence, incidence and clearance of HR HPV. A costing and modelling studies will determine the cost-effectiveness of triage strategies targeting HIV\ women.

Deinove, Montpellier University and French National Center for Scientific Research | Date: 2010-05-12

The present invention relates to novel stress-resistant bacteria and the uses thereof. More specifically, the invention relates to isolated stress-resistant bacteria having advantageous properties for the production of organic acids or alcohols in various culture conditions. The invention also relates to methods of producing organic acids or alcohols using said bacteria, particularly from biomass.

Umicore AG, Saft, Montpellier University and French National Center for Scientific Research | Date: 2010-02-10

The invention relates to active material for the negative electrode of secondary rechargeable lithium batteries, wherein the active material is based on doped or undoped carbon-bearing lithium titanium ramsdellite oxide with general formula Li_(2)Ti_(3)O_(7 )or Li_(2.28)Ti_(3.43)O_(8). The active material comprises a carbon substituted ramsdellite phase having a general formula Li_(24c)C_(c)Ti_(3)O_(7), with 0.1

Jacot D.,University of Geneva | Daher W.,University of Geneva | Daher W.,Montpellier University | Soldati-Favre D.,University of Geneva
EMBO Journal | Year: 2013

Members of the Apicomplexa phylum possess an organelle surrounded by four membranes, originating from the secondary endosymbiosis of a red alga. This so-called apicoplast hosts essential metabolic pathways. We report here that apicoplast inheritance is an actin-based process. Concordantly, parasites depleted in either profilin or actin depolymerizing factor, or parasites overexpressing the FH2 domain of formin 2, result in loss of the apicoplast. The class XXII myosin F (MyoF) is conserved across the phylum and localizes in the vicinity of the Toxoplasma gondii apicoplast during division. Conditional knockdown of TgMyoF severely affects apicoplast turnover, leading to parasite death. This recapitulates the phenotype observed upon perturbation of actin dynamics that led to the accumulation of the apicoplast and secretory organelles in enlarged residual bodies. To further dissect the mode of action of this motor, we conditionally stabilized the tail of MyoF, which forms an inactive heterodimer with endogenous TgMyoF. This dominant negative mutant reveals a central role of this motor in the positioning of the two centrosomes prior to daughter cell formation and in apicoplast segregation.

Deinove, French National Center for Scientific Research and Montpellier University | Date: 2015-10-16

The present invention relates to composition and methods of producing bioenergy. More specifically, the invention relates to the use of bacterium of the genus Deinococcus and/or related genera for the modification of biomass or biomass derivatives with a view to producing bioenergy products and metabolites.

Agency: Cordis | Branch: H2020 | Program: IA | Phase: ICT-25-2016-2017 | Award Amount: 4.30M | Year: 2017

The recent trends of mass customization of products and lean approaches impacts production by a drastic reduction of production lot sizes. However, traditional automation and robotics fail to be competitive in such a context since all individual product variant would require a complete automation project. In addition, keeping up with the introduction of robots outside of the traditional sectors require to automate much more complex manual tasks, where again traditional robotics automation fails to provide a good ratio of cost vs robustness, mainly due to the rigidity of existing production equipment in terms of programming and tools. The overall objective of the project is to provide a bridge for transferring, demonstrating and validating the latest R&D results in robotics towards different industrial environments proving their applicability and effectiveness. More specifically, VERSATILE will apply dual arm robots in executing complex tasks that are traditionally assigned to humans due to their manipulation requirements. By providing the tools to quickly setup, program and operate innovative robotic systems the end user will have robotic cells flexible enough to automatically adapt to the high number of products variants. In this context the project will focus on advancing the TRL level of the latest developments in the areas of: - Perception for Operation in semi-structured environment - Easy Programming framework to improve the re-configurability/ programmability of the robotic systems - Mobile dual-arm robotics manipulation capabilities - Open frameworks for the Plug and Produce based coordination of these resources This will be investigated in three industry driven use cases including both static and mobile dual arm robots. The project will focus on three main applications: - Automotive: assembly of vehicle dashboards at PSA - Aerospace: assembly of aircraft wing parts at AIRBUS - Consumer goods: handling and packaging of shaver handles at BIC

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2013.5.1 | Award Amount: 3.83M | Year: 2013

There is a tight link between the rhythm of external information (e.g., auditory) and movement. It can be seen when we spontaneously or deliberately move on the beat of music (e.g., in dance), or when we enjoy performing physical and sport activities (e.g., running or cycling) together with music. This propensity to match movement to rhythm is natural, develops very precociously, and is likely hard-wired in humans, as shown by cognitive sciences and neurosciences. In this proposal, we exploit this compelling link between music and movement for boosting individual performance and enhancing health and wellness. This goal will be achieved by creating an intelligent technological architecture - BeatHealth. Our architecture will deliver embodied, flexible, and efficient rhythmical stimulation adapted to the individuals skills with the goal of enhancing or recovering features of movement performance (i.e., kinematics and physiological performance). This endeavour is highly multidisciplinary. It involves (i) fundamental research aimed at improving information parameters, for maximizing the beneficial effects of rhythmic stimulation on movement kinematics and physiology, (ii) technological development to achieve state-of-the-art system reliability, flexibility, and portability of the BeatHealth architecture, and (iii) the creation of a new IT service in the form of a network-based application for collecting on the fly kinematic data and sharing them with online with others (e.g., medical doctors, family, coach, etc). The beneficial effects of BeatHealth will be evaluated in patients with movement disorders (i.e., Parkinsons disease), and in healthy citizens of various ages with moderate physical activity.

Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: NMP-2008-2.6-3 | Award Amount: 684.05K | Year: 2009

Membranes are nano-/micro-porous multifunctional materials the main property of which is permselectivity regarding to different ionic and molecular species. This property results in a great number of applications in processes of aqueous and gaseous mixture separation. The small material and energy consumption and high eco-efficiency of separation by membranes determine strategic role of membrane processes as technologies making a bridge between industry and environment. The main objective of the proposal is to make a step towards reaching an effective integration of research activities, training, equipment sharing, and thus answer the needs for a coordinated membrane science and technology R&D in Europe and Russia oriented primarily at development of eco-efficient methods in industry. This objective replies to one of most important priorities of FP7: Elaboration of concepts aimed at sustainable development, and societal innovation. This objective will be attained by rapprochement of two membrane networks: Network of Excellence NanoMemPro in Europe and Russian Membrane Network being in the way of formation. The project foresees the organisation of two meetings of 25 representatives of European institutions belonging to NanoMemPro and of the equivalent number of Russian and NIS scientists. The basis for a European-Russian Membrane Science and Innovation Technology Platform will be founded as well. As a result of the project, a well structured programme/concept of scientific collaboration and diverse actions (in the field of researches, training, equipment sharing, person mobility, technological innovation) for the next several years will be elaborated. The proposed project should prepare grounds for further larger and amplified actions between European and Russian membrane networks following the axe of environmental protection, in the framework of FP7 and other international and regional programmes.

Guindon S.,Montpellier University | Guindon S.,University of Auckland | Dufayard J.-F.,Montpellier University | Lefort V.,Montpellier University | And 6 more authors.
Systematic Biology | Year: 2010

PhyML is a phylogeny software based on the maximum-likelihood principle. Early PhyML versions used a fast algorithm performing nearest neighbor interchanges to improve a reasonable starting tree topology. Since the original publication (Guindon S., Gascuel O. 2003. A simple, fast and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst. Biol. 52:696-704), PhyML has been widely used (>2500 citations in ISI Web of Science) because of its simplicity and a fair compromise between accuracy and speed. In the meantime, research around PhyML has continued, and this article describes the new algorithms and methods implemented in the program. First, we introduce a new algorithm to search the tree space with user-defined intensity using subtree pruning and regrafting topological moves. The parsimony criterion is used here to filter out the least promising topology modifications with respect to the likelihood function. The analysis of a large collection of real nucleotide and amino acid data sets of various sizes demonstrates the good performance of this method. Second, we describe a new test to assess the support of the data for internal branches of a phylogeny. This approach extends the recently proposed approximate likelihood-ratio test and relies on a nonparametric, Shimodaira-Hasegawa-like procedure. A detailed analysis of real alignments sheds light on the links between this new approach and the more classical nonparametric bootstrap method. Overall, our tests show that the last version (3.0) of PhyML is fast, accurate, stable, and ready to use. A Web server and binary files are available from

Beier K.T.,Howard Hughes Medical Institute | Beier K.T.,Stanford University | Steinberg E.E.,Stanford University | Deloach K.E.,Howard Hughes Medical Institute | And 8 more authors.
Cell | Year: 2015

Dopamine (DA) neurons in the midbrain ventral tegmental area (VTA) integrate complex inputs to encode multiple signals that influence motivated behaviors via diverse projections. Here, we combine axon-initiated viral transduction with rabies-mediated trans-synaptic tracing and Cre-based cell-type-specific targeting to systematically map input-output relationships of VTA-DA neurons. We found that VTA-DA (and VTA-GABA) neurons receive excitatory, inhibitory, and modulatory input from diverse sources. VTA-DA neurons projecting to different forebrain regions exhibit specific biases in their input selection. VTA-DA neurons projecting to lateral and medial nucleus accumbens innervate largely non-overlapping striatal targets, with the latter also sending extensive extra-striatal axon collaterals. Using electrophysiology and behavior, we validated new circuits identified in our tracing studies, including a previously unappreciated top-down reinforcing circuit from anterior cortex to lateral nucleus accumbens via VTA-DA neurons. This study highlights the utility of our viral-genetic tracing strategies to elucidate the complex neural substrates that underlie motivated behaviors. © 2015 Elsevier Inc.

Suc J.-P.,University Pierre and Marie Curie | Fauquette S.,Montpellier University
Palaeogeography, Palaeoclimatology, Palaeoecology | Year: 2012

Northern Hemisphere vegetation is generally zoned as a consequence of latitudinal and altitudinal gradients. Temperature reconstruction from three successive pollen floral assemblages (of Tortonian, Messinian and Zanclean age) from the eastern Pyrenees has been used to estimate the altitudinal evolution of the uplifted Cerdanya Basin and its surrounding massifs. A new method has been developed for the uplifted basins, which completes that already applied to pollen floras from coastal marine deposits close to mountains. In contrast to previous hypotheses, it seems that the eastern Pyrenees occurred at a lower altitude in the Late Miocene before continuous uplift began 10. Ma ago. The rate of this uplift ranged between 0.06 and 0.12. mm/yr. © 2012 Elsevier B.V.

Bjordal M.,University of Nice Sophia Antipolis | Bjordal M.,French National Center for Scientific Research | Bjordal M.,French Institute of Health and Medical Research | Arquier N.,University of Nice Sophia Antipolis | And 7 more authors.
Cell | Year: 2014

The brain is the central organizer of food intake, matching the quality and quantity of the food sources with organismal needs. To ensure appropriate amino acid balance, many species reject a diet lacking one or several essential amino acids (EAAs) and seek out a better food source. Here, we show that, in Drosophila larvae, this behavior relies on innate sensing of amino acids in dopaminergic (DA) neurons of the brain. We demonstrate that the amino acid sensor GCN2 acts upstream of GABA signaling in DA neurons to promote avoidance of the EAA-deficient diet. Using real-time calcium imaging in larval brains, we show that amino acid imbalance induces a rapid and reversible activation of three DA neurons that are necessary and sufficient for food rejection. Taken together, these data identify a central amino-acid-sensing mechanism operating in specific DA neurons and controlling food intake. © 2014 Elsevier Inc.

Ferre S.,U.S. National Institutes of Health | Casado V.,University of Barcelona | Casado V.,Research Center Biomedica en Red sobre Enfermedades Neurodegenerativas | Devi L.A.,Mount Sinai School of Medicine | And 9 more authors.
Pharmacological Reviews | Year: 2014

Most evidence indicates that, as for family C G protein-coupled receptors (GPCRs), family A GPCRs form homo- and heteromers. Homodimers seem to be a predominant species, with potential dynamic formation of higher-order oligomers, particularly tetramers. Although monomeric GPCRs can activate G proteins, the pentameric structure constituted by one GPCR homodimer and one heterotrimeric G protein may provide a main functional unit, and oligomeric entities can be viewed as multiples of dimers. It still needs to be resolved if GPCR heteromers are preferentially heterodimers or if they are mostly constituted by heteromers of homodimers. Allosteric mechanisms determine a multiplicity of possible unique pharmacological properties of GPCR homomers and heteromers. Some general mechanisms seemto apply, particularly at the level of ligand-binding properties. In the frame of the dimer-cooperativity model, the two-state dimer model provides the most practical method to analyze ligand-GPCR interactions when considering receptor homomers. In addition to ligand-binding properties, unique properties for each GPCR oligomer emerge in relation to different intrinsic efficacy of ligands for different signaling pathways (functional selectivity). This gives a rationale for the use of GPCR oligomers, and particularly heteromers, as novel targets for drug development. Herein, we review the functional and pharmacological properties of GPCR oligomers and provide some guidelines for the application of discrete direct screening and highthroughput screening approaches to the discovery of receptor-heteromer selective compounds.

Ibrahim A.,Montpellier University | Allison S.A.,Georgia State University | Cottet H.,Montpellier University
Analytical Chemistry | Year: 2012

The effective mobility (μep) is the main parameter characterizing the electrophoretic behavior of a given solute. It is well-known that μep is a decreasing function of the ionic strength for all solutes. Nevertheless, the decrease depends strongly on the nature of the solute (small ions, polyelectrolyte, nanoparticles). Different electrophoretic models from the literature can describe this ionic strength dependence. However, the complexity of the ionic strength dependence with the solute characteristics and the variety of analytical expressions of the different existing models make the phenomenological ionic strength dependence difficult to comprehend. In this work, the ionic strength dependence of the effective mobility was systematically investigated on a set of different solutes [small mono- and multicharged ions, polyelectrolytes, and organic/inorganic (nano)particles]. The phenomenological decrease of electrophoretic mobility with ionic strength was experimentally described by calculating the relative electrophoretic mobility decrease per ionic strength decade (S) in the range of 0.005-0.1 M ionic strength. Interestingly, the "slope plot" displaying S as a function of the solute electrophoretic mobility at 5 mM ionic strength allows for defining different zones that are characteristic of the solute nature. This new representative approach should greatly help experimentalists to better understand the ionic strength dependence of analyte and may contribute to the characterization of unknown analytes via their ionic strength dependence of electrophoretic mobility. © 2012 American Chemical Society.

Malavieille J.,Montpellier University | Malavieille J.,French National Center for Scientific Research | Malavieille J.,International Laboratory LIA
GSA Today | Year: 2010

Interaction between surface and tectonic processes plays a key role in the structural evolution, kinematics, and exhumation of rocks in orogenic wedges. The deformation patterns observed in analog models show that strain partitioning has a strong impact on the vertical component of displacement of tectonic units, which in return favors erosion in domains of important uplift. Partitioning is controlled by tectonic processes and by climate-dependent surface processes, including erosion and sedimentation. The effects of partitioning include localization of deformed domains, exhumation above areas of deep underplating, and steady-state maintenance of wedges for long time periods. Simple models illustrate well how the morphostructural evolution of mountain belts is determined by these complex interactions.

Courbet A.,French National Center for Scientific Research | Endy D.,Stanford University | Renard E.,Montpellier University | Molina F.,French National Center for Scientific Research | Bonnet J.,Montpellier University
Science Translational Medicine | Year: 2015

Whole-cell biosensors have several advantages for the detection of biological substances and have proven to be useful analytical tools. However, several hurdles have limited whole-cell biosensor application in the clinic, primarily their unreliable operation in complex media and low signal-to-noise ratio. We report that bacterial biosensors with genetically encoded digital amplifying genetic switches can detect clinically relevant biomarkers in human urine and serum. These bactosensors perform signal digitization and amplification, multiplexed signal processing with the use of Boolean logic gates, and data storage. In addition, we provide a framework with which to quantify wholecell biosensor robustness in clinical samples together with a method for easily reprogramming the sensor module for distinct medical detection agendas. Last, we demonstrate that bactosensors can be used to detect pathological glycosuria in urine from diabetic patients. These next-generation whole-cell biosensors with improved computing and amplification capacity could meet clinical requirements and should enable new approaches for medical diagnosis. © 2015, American Association for the Advancement of Science. All rights reserved.

Girardot M.,Montpellier University | Cavaille J.,University Paul Sabatier | Cavaille J.,French National Center for Scientific Research | Feil R.,Montpellier University
Epigenetics | Year: 2012

More than a hundred protein-coding genes are controlled by genomic imprinting in humans. These atypical genes are organized in chromosomal domains, each of which is controlled by a differentially methylated 'imprinting control region' (ICR). How ICRs mediate the parental allele-specific expression of close-by genes is now becoming understood. At several imprinted domains, this epigenetic mechanism involves the action of long non-coding RNAs. It is less well appreciated that imprinted gene domains also transcribe hundreds of microRNA and small nucleolar RNA genes and that these represent the densest clusters of small RNA genes in mammalian genomes. The evolutionary reasons for this remarkable enrichment of small regulatory RNAs at imprinted domains remain unclear. However, recent studies show that imprinted small RNAs modulate specific functions in development and metabolism and also are frequently perturbed in cancer. Here, we review our current understanding of imprinted small RNAs in the human genome and discuss how perturbation of their expression contributes to disease. © 2012 Landes Bioscience.

Hoareau T.B.,University of Pretoria | Boissin E.,University of Pretoria | Berrebi P.,Montpellier University
Molecular Phylogenetics and Evolution | Year: 2012

Compared to endemics, widespread species are of particular interest to retrace recent evolutionary history. These species have a large population size which provides a clearer genetic signature of past events. Moreover, their wide geographic range increases the potential occurrence of evolutionary events (expansion, divergence, etc.). Here, we used several coalescent-based methods to disentangle the evolutionary history of a widespread amphidromous goby (Sicyopterus lagocephalus), in the light of sea-level variations during the Pleistocene. Using 75 samples recovered from three biogeographic regions (Western Indian Ocean, Melanesia and Polynesia), we analysed a portion of the cytochrome b gene and confirmed three major haplogroups, each specific to a region. Furthermore, we found that: (1) the Melanesian haplogroup was the oldest while the two peripheral regions hosted daughter haplogroups; (2) two centrifugal colonisation events occurred from Melanesia to the periphery, each synchronised with periods of strong paleo-ENSO episodes; (3) the demographic contraction-expansion events were linked to Pleistocene sea-level changes; (4) Melanesia and Polynesia acted as efficient refuges during the Last Glacial Maximum. These results highlight the importance of studying widespread species to better understand the role of climate changes and paleo-oceanography on the evolution of biodiversity. © 2011 Elsevier Inc.

Poli J.,French National Center for Scientific Research | Tsaponina O.,Umeå University | Crabbe L.,French National Center for Scientific Research | Crabbe L.,Salk Institute for Biological Studies | And 5 more authors.
EMBO Journal | Year: 2012

Intracellular deoxyribonucleoside triphosphate (dNTP) pools must be tightly regulated to preserve genome integrity. Indeed, alterations in dNTP pools are associated with increased mutagenesis, genomic instability and tumourigenesis. However, the mechanisms by which altered or imbalanced dNTP pools affect DNA synthesis remain poorly understood. Here, we show that changes in intracellular dNTP levels affect replication dynamics in budding yeast in different ways. Upregulation of the activity of ribonucleotide reductase (RNR) increases elongation, indicating that dNTP pools are limiting for normal DNA replication. In contrast, inhibition of RNR activity with hydroxyurea (HU) induces a sharp transition to a slow-replication mode within minutes after S-phase entry. Upregulation of RNR activity delays this transition and modulates both fork speed and origin usage under replication stress. Interestingly, we also observed that chromosomal instability (CIN) mutants have increased dNTP pools and show enhanced DNA synthesis in the presence of HU. Since upregulation of RNR promotes fork progression in the presence of DNA lesions, we propose that CIN mutants adapt to chronic replication stress by upregulating dNTP pools. © 2012 European Molecular Biology Organization | All Rights Reserved.

Dauvilliers Y.,Montpellier University | Bassetti C.,University of Bern | Lammers G.J.,Leiden University | Arnulf I.,Sleep Disorder Unit | And 7 more authors.
The Lancet Neurology | Year: 2013

Background: Narcolepsy is characterised by excessive daytime sleepiness (EDS) and cataplexy. Histamine neurons are crucial to maintain wakefulness. We assessed the safety and efficacy of pitolisant (previously called BF2.649), a selective histamine H3 receptor inverse agonist that activates these neurons, in patients with narcolepsy. Methods: For this double-blind, randomised, parallel-group controlled trial, we recruited patients with narcolepsy from 32 sleep disorder centres in five European countries. Patients were eligible if they were aged 18 years or older, had not taken psychostimulants for at least 14 days, and had EDS (defined as an Epworth Sleepiness Scale [ESS] score of at least 14). Using a computer-generated randomisation sequence, we randomly allocated patients to receive pitolisant, modafinil, or placebo (1:1:1). Treatment lasted 8 weeks: 3 weeks of flexible dosing according to investigator's judgment (10 mg, 20 mg, or 40 mg a day of pitolisant; 100 mg, 200 mg or 400 mg a day of modafinil) followed by 5 weeks of stable dosing. Patients took four tablets a day in a double-dummy design to ensure masking. For the primary analysis, assessed in the intention-to-treat population, we assessed the superiority of pitolisant versus placebo, and the non-inferiority of pitolisant versus modafinil. This trial is registered with, number NCT01067222. Findings: Between May 26, 2009, and June 30, 2010, we screened 110 patients, 95 of whom were eligible and randomly assigned to treatment: 30 to placebo, 32 to pitolisant, and 33 to modafinil. Over the 8-week treatment period, mean ESS score reductions were -3·4 (SD 4·2) in the placebo group, -5·8 (6·2) in the pitolisant group, and -6·9 (6·2) in the modafinil group. Our primary analysis of between-group differences in mean ESS score at endpoint (adjusted for baseline) showed pitolisant to be superior to placebo (difference -3·0, 95% CI -5·6 to -0·4; p=0·024), but not non-inferior to modafinil (difference 0·12, 95% CI -2·5 to 2·7; p=0·250). We recorded 22 adverse events with pitolisant, 26 with modafinil, and ten with placebo. Six severe adverse events were treatment-related: one with pitolisant (abdominal discomfort) and five with modafinil (abdominal pain, abnormal behaviour, amphetamine-like withdrawal symptoms, lymphoadenopathy, and inner ear disorders). Interpretation: Pitolisant at doses up to 40 mg was efficacious on EDS compared with placebo and well tolerated compared with modafinil. If these findings are substantiated in further studies, pitolisant could offer a new treatment option for patients with narcolepsy. Funding: Bioprojet, France. © 2013 Elsevier Ltd.

Alexandrov S.,Montpellier University | Persson D.,ETH Zurich | Pioline B.,University Pierre and Marie Curie
Journal of High Energy Physics | Year: 2011

We investigate quantum corrections to the hypermultiplet moduli space M in Calabi-Yau compactifications of type II string theories, with particular emphasis on instanton effects from Euclidean NS5-branes. Based on the consistency of D-and NS5-instanton corrections, we determine the topology of the hypermultiplet moduli space at fixed string coupling, as previewed in [1]. On the type IIB side, we compute corrections from (p, k)-fivebrane instantons to the metric on M (specifically, the correction to the complex contact structure on its twistor space Z) by applying S-duality to the D-instanton sum. For fixed fivebrane charge k, the corrections can be written as a non-Gaussian theta series, whose summand for k = 1 reduces to the topological A-model amplitude. By mirror symmetry, instanton corrections induced from the chiral type IIA NS5-brane are similarly governed by the wave function of the topological B-model. In the course of this investigation we clarify charge quantization for coherent sheaves and find hitherto unnoticed corrections to the Heisenberg, monodromy and S-duality actions on M, as well as to the mirror map for Ramond-Ramond fields and D-brane charges. © SISSA 2011.

Bantignies F.,French National Center for Scientific Research | Roure V.,French National Center for Scientific Research | Comet I.,French National Center for Scientific Research | Leblanc B.,French National Center for Scientific Research | And 5 more authors.
Cell | Year: 2011

In Drosophila melanogaster, Hox genes are organized in an anterior and a posterior cluster, called Antennapedia complex and bithorax complex, located on the same chromosome arm and separated by 10 Mb of DNA. Both clusters are repressed by Polycomb group (PcG) proteins. Here, we show that genes of the two Hox complexes can interact within nuclear PcG bodies in tissues where they are corepressed. This colocalization increases during development and depends on PcG proteins. Hox gene contacts are conserved in the distantly related Drosophila virilis species and they are part of a large gene interaction network that includes other PcG target genes. Importantly, mutations on one of the loci weaken silencing of genes in the other locus, resulting in the exacerbation of homeotic phenotypes in sensitized genetic backgrounds. Thus, the three-dimensional organization of Polycomb target genes in the cell nucleus stabilizes the maintenance of epigenetic gene silencing. © 2011 Elsevier Inc.

Corbeau P.,Nimes University Hospital Center | Corbeau P.,French National Center for Scientific Research | Corbeau P.,Montpellier University | Reynes J.,Montpellier University | Reynes J.,Montpellier University Hospital Center
Blood | Year: 2011

Although highly active antiretroviral therapy has enabled constant progress in reducing HIV-1 replication, in some patients who are "aviremic" during treatment, the problem of insufficient immune restoration remains, and this exposes them to the risk of immune deficiency-associated pathologies. Various mechanisms may combine and account for this impaired immunologic response to treatment. A first possible mechanism is immune activation, which may be because of residual HIV production, microbial translocation, co-infections, immuno-senescence, or lymphopenia per se. A second mechanism is ongoing HIV replication. Finally, deficient thymus output, sex, and genetic polymorphism influencing apoptosis may impair immune reconstitution. In this review we will discuss the tools at our disposal to identify the various mechanisms at work in a given patient and the specific therapeutic strategies we could propose based on this etiologic diagnosis. © 2011 by The American Society of Hematology.

Caracas R.,French National Center for Scientific Research | Mainprice D.,Montpellier University | Thomas C.,University of Munster
Geophysical Research Letters | Year: 2010

We determine the elasticity of FeSiO3 perovskite for various spin configurations using density-functional theory calculations. The elastic moduli and the bulk seismic wave velocities are weakly affected by the spin transition. However we show that the intrinsic differences in seismic anisotropy between the high-spin and low-spin phases of Fe-bearing perovskite coupled with lattice preferred orientation that can develop due and during the convection may lead to distinct seismic signatures between the top and the bottom of the lower mantle. These signatures should be detectable in observations and they need to be taken into account in tomographic studies of the Earth's lower mantle. © 2010 by the American Geophysical Union.

Thery-Parisot I.,French National Center for Scientific Research | Chabal L.,Montpellier University | Chrzavzez J.,French National Center for Scientific Research
Palaeogeography, Palaeoclimatology, Palaeoecology | Year: 2010

A discussion on the representativeness of charcoal from archaeological contexts and their potential for palaeoecological reconstruction is presented. The charcoal deposits studied are the result of human activities and natural processes, difficult to separate on the basis of their effects only. This is why "taphonomy" should not be limited to the study of charcoal, after the extinction of fire. As a result our questioning has been widened to include the entire succession of processes, from past vegetation to the anthracological diagram. We propose a review of the taphonomic processes affecting anthracological assemblages in archaeological contexts, from wood gathering to the analysis of charcoal results. Human practices appear clearly as the first filter determining or conditioning the assemblage. The combustion process can induce a double filter by limiting the taxonomic information and by falsifying the initial quantity of burned wood. Post-depositional agents represent a third level of filters between the vegetation and the anthracological assemblage. Finally, sampling and quantification methods can also induce a distortion of the assemblage. The aim of this paper is to present the state of the discipline today, the problems already solved, and the questions that remain to be studied. © 2009 Elsevier B.V. All rights reserved.

Abkarian M.,French National Center for Scientific Research | Massiera G.,French National Center for Scientific Research | Berry L.,Montpellier University | Roques M.,French National Center for Scientific Research | And 2 more authors.
Blood | Year: 2011

The culminating step of the intraerythrocytic development of Plasmodium falciparum, the causative agent of malaria, is the spectacular release of multiple invasive merozoites on rupture of the infected erythrocyte membrane. This work reports for the first time that the whole process, taking place in time scales as short as 400 milliseconds, is the result of an elastic instability of the infected erythrocyte membrane. Using high-speed differential interference contrast (DIC) video microscopy and epifluorescence, we demonstrate that the release occurs in 3 main steps after osmotic swelling of the infected erythrocyte: a pore opens in ∼100 milliseconds, ejecting 1-2 merozoites, an outward curling of the erythrocyte membrane is then observed, ending with a fast eversion of the infected erythrocyte membrane, pushing the parasites forward. It is noteworthy that this last step shows slight differences when infected erythrocytes are adhering. We rationalize our observations by considering that during the parasite development, the infected erythrocyte membrane acquires a spontaneous curvature and we present a subsequent model describing the dynamics of the curling rim. Our results show that sequential erythrocyte membrane curling and eversion is necessary for the parasite efficient angular dispersion and might be biologically essential for fast and numerous invasions of new erythrocytes. © 2011 by The American Society of Hematology.

Anisimova M.,ETH Zurich | Anisimova M.,Swiss Institute of Bioinformatics | Anisimova M.,Montpellier University | Gil M.,ETH Zurich | And 5 more authors.
Systematic Biology | Year: 2011

Phylogenetic inference and evaluating support for inferred relationships is at the core of many studies testing evolutionary hypotheses. Despite the popularity of nonparametric bootstrap frequencies and Bayesian posterior probabilities, the interpretation of these measures of tree branch support remains a source of discussion. Furthermore, both methods are computationally expensive and become prohibitive for large data sets. Recent fast approximate likelihood-based measures of branch supports (approximate likelihood ratio test [aLRT] and Shimodaira-Hasegawa [SH]-aLRT) provide a compelling alternative to these slower conventional methods, offering not only speed advantages but also excellent levels of accuracy and power. Here we propose an additional method: a Bayesian-like transformation of aLRT (aBayes). Considering both probabilistic and frequentist frameworks, we compare the performance of the three fast likelihood-based methods with the standard bootstrap (SBS), the Bayesian approach, and the recently introduced rapid bootstrap. Our simulations and real data analyses show that with moderate model violations, all tests are sufficiently accurate, but aLRT and aBayes offer the highest statistical power and are very fast. With severe model violations aLRT, aBayes and Bayesian posteriors can produce elevated false-positive rates. With data sets for which such violation can be detected, we recommend using SH-aLRT, the nonparametric version of aLRT based on a procedure similar to the Shimodaira-Hasegawa tree selection. In general, the SBS seems to be excessively conservative and is much slower than our approximate likelihood-based methods. © 2011 The Author(s).

Shih Y.-J.,Chung Yuan Christian University | Shih Y.-J.,Montpellier University | Chang Y.,Chung Yuan Christian University | Deratani A.,Montpellier University | Quemener D.,Montpellier University
Biomacromolecules | Year: 2012

"Schizophrenic" diblock copolymers containing nonionic and zwitterionic blocks were prepared with well-controlled molecular weights via atom-transfer radical polymerization (ATRP). In this work, we report a systematic study of how morphological changes of poly(N-isopropylacrylamide)- block-poly(sulfobetaine methacrylate) (PNIPAAm-b-PSBMA) copolymers affect hemocompatibility in human blood solution. The "schizophrenic" behavior of PNIPAAm-b-PSBMA was observed by 1H NMR, dynamic light scattering (DLS), and turbidity measurement with double morphological transition, exhibiting both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) in aqueous solution. Below the UCST of PSBMA block, micelles were obtained with a core of insoluble PSBMA association and a shell of soluble PNIPAAm, whereas the opposite micelle structure was observed above the LCST of PNIPAAm block. In between the UCST and LCST, unimers with both soluble blocks were detected. Hydrodynamic size of prepared polymers and copolymers is determined to illustrate the correlations between intermolecular nonionic/zwitterionic associations and blood compatibility of PNIPAAm, PNIPAAm-b-PSBMA, and PSBMA suspension in human blood. Human fibrinogen adsorption onto the PNIPAAm-b-PSBMA copolymers from single-protein solutions was measured by DLS to determine the nonfouling stability of copolymer suspension. The new nonfouling nature of PNIPAAm-b-PSBMA copolymers was demonstrated to show extremely high anticoagulant activity and antihemolytic activity in human blood over a wide range of explored temperatures from 4 to 40 °C. The temperature-independent blood compatibility of nonionic/zwitterionic block copolymer along with their schizophrenic phase behavior in aqueous solution suggests their potential in blood-contacting applications. © 2012 American Chemical Society.

Bierne N.,Montpellier University | Bierne N.,French National Center for Scientific Research | Roze D.,University Pierre and Marie Curie | Roze D.,French National Center for Scientific Research | Welch J.J.,University of Cambridge
Molecular Ecology | Year: 2013

It is now common for population geneticists to estimate FST for a large number of loci across the genome, before testing for selected loci as being outliers to the FST distribution. One surprising result of such FST scans is the often high proportion (>1% and sometimes >10%) of outliers detected, and this is often interpreted as evidence for pervasive local adaptation. In this issue of Molecular Ecolog, Fourcade et al. () observe that a particularly high rate of FST outliers has often been found in river organisms, such as fishes or damselflies, despite there being no obvious reason why selection should affect a larger proportion of the genomes of these organisms. Using computer simulations, Fourcade et al. () show that the strong correlation in co-ancestry produced in long one-dimensional landscapes (such as rivers, valleys, peninsulas, oceanic ridges or coastlines) greatly increases the neutral variance in FST, especially when the landscape is further reticulated into fractal networks. As a consequence, outlier tests have a high rate of false positives, unless this correlation can be taken into account. Fourcade et al.'s study highlights an extreme case of the general problem, first noticed by Robertson (,b) and Nei & Maruyama (), that correlated co-ancestry inflates the neutral variance in FST when compared to its expectation under an island model of population structure. Similar warnings about the validity of outlier tests have appeared regularly since then but have not been widely cited in the recent genomics literature. We further emphasize that FST outliers can arise in many different ways and that outlier tests are not designed for situations where the genetic architecture of local adaptation involves many loci. © 2013 Blackwell Publishing Ltd.

Roux C.,Montpellier University | Roux C.,French National Center for Scientific Research | Tsagkogeorga G.,Montpellier University | Tsagkogeorga G.,Queen Mary, University of London | And 3 more authors.
Molecular Biology and Evolution | Year: 2013

Inferring a realistic demographic model from genetic data is an important challenge to gain insights into the historical events during the speciation process and to detect molecular signatures of selection along genomes. Recent advances in divergence population genetics have reported that speciation in face of gene flow occurred more frequently than theoretically expected, but the approaches used did not account for genome-wide heterogeneity (GWH) in introgression rates. Here, we investigate the impact of GWH on the inference of divergence with gene flow between two cryptic species of the marine model Ciona intestinalis by analyzing polymorphism and divergence patterns in 852 protein-coding sequence loci. These morphologically similar entities are highly diverged molecular-wise, but evidence of hybridization has been reported in both laboratory and field studies. We compare various speciation models and test for GWH under the approximate Bayesian computation framework. Our results demonstrate the presence of significant extents of gene flow resulting from a recent secondary contact after >3 My of divergence in isolation. The inferred rates of introgression are relatively low, highly variable across loci and mostly unidirectional, which is consistent with the idea that numerous genetic incompatibilities have accumulated over time throughout the genomes of these highly diverged species. A genomic map of the level of gene flow identified two hotspots of introgression, that is, large genome regions of unidirectional introgression. This study clarifies the history and degree of isolation of two cryptic and partially sympatric model species and provides a methodological framework to investigate GWH at various stages of speciation process. © 2013 The Author.

Gueydan F.,Montpellier University | Precigout J.,CNRS Institute of Earth Sciences | Montesi L.G.J.,University of Maryland University College
Tectonophysics | Year: 2014

Much debate exists concerning the strength distribution of the continental lithosphere, how it controls lithosphere-scale strain localization and hence enables plate tectonics. No rheological model proposed to date is comprehensive enough to describe both the weakness of plate boundary and rigid-like behaviour of plate interiors. Here we show that the duality of strength of the lithosphere corresponds to different stages of microstructural evolution. Geological constraints on lithospheric strength and large strain numerical experiments reveal that the development of layers containing weak minerals and the onset of grain boundary sliding upon grain size reduction in olivine cause strain localisation and reduce strength in the crust and subcontinental mantle, respectively. The positive feedback between weakening and strain localization leads to the progressive development of weak plate boundaries while plate interiors remain strong. © 2014 Elsevier B.V.

Callan-Jones A.,Montpellier University | Sorre B.,University Pierre and Marie Curie | Sorre B.,Rockefeller University | Bassereau P.,University Pierre and Marie Curie
Cold Spring Harbor Perspectives in Biology | Year: 2011

It has often been suggested that the high curvature of transport intermediates in cells may be a sufficient means to segregate different lipid populations based on the relative energy costs of forming bent membranes. In this review, we present in vitro experiments that highlight the essential physics of lipid sorting at thermal equilibrium: It is driven by a trade-off between bending energy, mixing entropy, and interactions between species. We collect evidence that lipid sorting depends strongly on lipid-lipid and protein-lipid interactions, and hence on the underlying composition of the membrane and on the presence of bound proteins. © 2011 Cold Spring Harbor Laboratory Press.

Gosset C.C.,Montpellier University | Gosset C.C.,French National Center for Scientific Research | Bierne N.,Montpellier University | Bierne N.,French National Center for Scientific Research
Journal of Evolutionary Biology | Year: 2013

Scanning genomes for loci with high levels of population differentiation has become a standard of population genetics. FST outlier loci are most often interpreted as signatures of local selection, but outliers might arise for many other reasons too often left unexplored. Here, we tried to identify further the history and genetic basis underlying strong differentiation at FST outlier loci in a marine mussel. A genome scan of genetic differentiation has been conducted between Atlantic and Mediterranean populations of Mytilus galloprovincialis. The differentiation was low overall (FST = 0.03), but seven loci (2%) were strong FST outliers. We then analysed DNA sequence polymorphism at two outlier loci. The genetic structure proved to be the consequence of differential introgression of alleles from the sister-hybridizing species Mytilus edulis. Surprisingly, the Mediterranean population was the most introgressed at these two loci, although the contact zone between the two species is nowadays localized along the Atlantic coasts of France and the British Isles. A historical contact between M. edulis and Mediterranean M. galloprovincialis should have happened during glacial periods. It proved difficult to disentangle two hypotheses: (i) introgression was adaptive, implying edulis alleles have been favoured in Mediterranean populations, or (ii) the genetic architecture of the barrier to edulis gene flow is different between the two M. galloprovincialis backgrounds. Five of the seven outliers between M. galloprovincialis populations were also outliers between M. edulis and Atlantic M. galloprovincialis, which would support the latter hypothesis. Differential introgression across semi-permeable barriers to gene flow is a neglected scenario to interpret outlying loci that may prove more widespread than anticipated. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

Benkirane M.,French National Center for Scientific Research | Sardet C.,Montpellier University | Coux O.,Montpellier University
Biochemical Society Transactions | Year: 2010

The critical tumour suppressor p53 plays a major role in response to DNA damage and, more generally, to genotoxic stress. The regulation of its expression and functions is under very tight controls, and involves, in particular, an extremely complex set of post-translational modifications, thanks to a variety of 'modifiers', including ubiquitylation E3s and acetyltransferases, that fine-tune the stability and activity of the protein. Work of the last few years has revealed that, in addition to targeting p53, these modifiers also modify each other, forming an intricate network of regulatory molecules and events that must be taken into account to understand p53 regulation. We propose that this network allows a metastable equilibrium that confers both sensitivity and robustness on the p53 pathway, two properties that allow the pathway to respectively answer to a variety of stimuli and return to its initial stage when the stimuli disappear. © The Authors Journal compilation.

Dulic V.,Institute Of Genetique Moleculaire | Dulic V.,French National Center for Scientific Research | Dulic V.,Montpellier University
Methods in Molecular Biology | Year: 2013

The senescence program is activated in response to diverse stress stimuli potentially compromising genetic stability and leads to an irreversible cell cycle arrest. The mTOR pathway plays a crucial role in the regulation of cell metabolism and cellular growth. The goal of this chapter is to present evidence linking these two processes, which have one common regulator-the tumor suppressor p53. While the role of mTOR in senescence is still controversial, recent papers have shed new light onto this issue. This review, far from being exhaustive given the complexity of the field, will hopefully stimulate further research in this domain, whose relevance for ageing is becoming increasingly documented. © Springer Science+Business Media New York 2013.

Dombry C.,University of Poitiers | Eyi-Minko F.,University of Poitiers | Ribatet M.,Montpellier University
Biometrika | Year: 2013

Since many environmental processes are spatial in extent, a single extreme event may affect several locations, and the spatial dependence must be taken into account in an appropriate way. This paper proposes a framework for conditional simulation of max-stable processes and gives closed forms for the regular conditional distributions of Brown-Resnick and Schlather processes. We test the method on simulated data and present applications to extreme rainfall around Zurich and extreme temperatures in Switzerland. The proposed framework provides accurate conditional simulations and can handle problems of realistic size. © 2012 Biometrika Trust.

Winter C.,University of Vienna | Bouvier T.,Montpellier University | Weinbauer M.G.,University Pierre and Marie Curie | Thingstad T.F.,University of Bergen
Microbiology and Molecular Biology Reviews | Year: 2010

A trade-off between strategies maximizing growth and minimizing losses appears to be a fundamental property of evolving biological entities existing in environments with limited resources. In the special case of unicellular planktonic organisms, the theoretical framework describing the trade-offs between competition and defense specialists is known as the "killing the winner" hypothesis (KtW). KtW describes how the availability of resources and the actions of predators (e.g., heterotrophic flagellates) and parasites (e.g., viruses) determine the composition and biogeochemical impact of such organisms. We extend KtW conceptually by introducing size- or shape-selective grazing of protozoans on prokaryotes into an idealized food web composed of prokaryotes, lytic viruses infecting prokaryotes, and protozoans. This results in a hierarchy analogous to a Russian doll, where KtW principles are at work on a lower level due to selective viral infection and on an upper level due to size- or shape-selective grazing by protozoans. Additionally, we critically discuss predictions and limitations of KtW in light of the recent literature, with particular focus on typically neglected aspects of KtW. Many aspects of KtW have been corroborated by in situ and experimental studies of isolates and natural communities. However, a thorough test of KtW is still hampered by current methodological limitations. In particular, the quantification of nutrient uptake rates of the competing prokaryotic populations and virus population-specific adsorption and decay rates appears to be the most daunting challenge for the years to come. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Scambelluri M.,University of Genoa | Pettke T.,University of Bern | Rampone E.,University of Genoa | Godard M.,Montpellier University | Reusser E.,ETH Zurich
Journal of Petrology | Year: 2014

At Cima di Gagnone, garnet peridotite and chlorite harzburgite lenses within pelitic schists and gneisses correspond to eclogite-facies breakdown products of hydrated peridotites and are suitable for studying dehydration of serpentinized mantle.Thermobarometry and pseudosection modelling yield peak temperatures of 750-850°C and pressures <3 GPa.The minimum temperature recorded by the garnet peridotite corresponds to the maximum conditions experienced by the chlorite harzburgite, suggesting that these rocks recrystallized cofacially at ̃800°C. Alternatively, they might have decoupled during subduction, as achieved in tectonically active plate interface boundaries. The major and rare earth element (REE) variability of the peridotites was mostly acquired during pre-subduction mantle evolution as a result of partial melting and reactive melt flow.The ultramafic suite is also characterized by fluid-mobile element enrichments (B, Pb, As, Sb, Cs, Li, U, Be), which confirm derivation from variably serpentinized protoliths. Similarity in the U, Pb, B, Li and Sr contents of the Gagnone peridotites to present-day oceanic serpentinites suggests that these elements were partly taken up during initial serpentinization by seawater-derived fluids. Positive Be, As and Sb anomalies suggest involvement of fluids equilibrated with crustal (metasedimentary) reservoirs during subsequent subduction metamorphism and peridotite entrainment in (meta)sediments. Fluid-mobile element enrichment characterizes all peak eclogitic minerals, implying that multiple hydration events and element influx pre-dated the eclogite-facies dehydration. Peak anhydrous minerals retain B, Li, As and Sb concentrations exceeding primitive mantle values and may introduce geochemical anomalies into the Earth's mantle.The relatively low contents of large ion lithophile elements and light REE in the Gagnone peridotites with respect to much higher enrichments shown by metasomatized garnet peridotite pods hosted in migmatites (Ulten Zone, Eastern Alps) suggest that the crustal rocks at Gagnone did not experience partial melting. The Gagnone garnet peridotite, despite showing evidence for chlorite dehydration, retains significant amounts of fluid-mobile elements documenting that no partial melting occurred upon chlorite breakdown.We propose that the Gagnone ultramafic rocks represent a prime example of multi-stage peridotite hydration and subsequent dehydration in a plate interface setting. © The Author 2014. Published by Oxford University Press. All rights reserved.

Juge F.,French National Center for Scientific Research | Fernando C.,Montpellier University | Fic W.,Montpellier University | Tazi J.,French National Center for Scientific Research
PLoS Genetics | Year: 2010

DNA- and RNA-processing pathways are integrated and interconnected in the eukaryotic nucleus to allow efficient gene expression and to maintain genomic stability. The recruitment of DNA Topoisomerase I (Topo I), an enzyme controlling DNA supercoiling and acting as a specific kinase for the SR-protein family of splicing factors, to highly transcribed loci represents a mechanism by which transcription and processing can be coordinated and genomic instability avoided. Here we show that Drosophila Topo I associates with and phosphorylates the SR protein B52. Surprisingly, expression of a high-affinity binding site for B52 in transgenic flies restricted localization, not only of B52, but also of Topo I to this single transcription site, whereas B52 RNAi knockdown induced mis-localization of Topo I in the nucleolus. Impaired delivery of Topo I to a heat shock gene caused retention of the mRNA at its site of transcription and delayed gene deactivation after heat shock. Our data show that B52 delivers Topo I to RNA polymerase II-active chromatin loci and provide the first evidence that DNA topology and mRNA release can be coordinated to control gene expression. © 2010 Juge et al.

Lorand J.-P.,CNRS Nantes Laboratory of Planetology and Geodynamics | Luguet A.,University of Bonn | Alard O.,Montpellier University
Lithos | Year: 2013

The platinum-group element (PGE) systematics of continental mantle peridotites show large variability, reflecting petrogenetic processing of the upper mantle during partial melting and melt/fluid percolation inside the lithosphere. By removing Pd-Cu-Ni rich sulfides, partial melting events that have stabilized the sub-continental mantle lithosphere fractionated PPGEs (Palladium-group PGE; Pt, Pd) relative to IPGEs (Iridium-group PGE; Os, Ir, Ru, Rh). Residual base-metal sulfides (BMS) survive as enclosed IPGE-enriched Monosulfide Solid Solutions (Mss), which otherwise decompose into Ru-Os-Ir-rich refractory platinum-group minerals (PGMs) once the partial melts become S-undersaturated. The small-scale heterogeneous distribution of these microphases may cause extreme nugget effects, as seen in the huge variations in absolute PGE concentrations documented in cratonic peridotites. Magmas fluxing through the lithospheric mantle may change the initial PGE budgets inherited from the melting events, resulting in the great diversity of PGE systematics seen in peridotites from the sub-continental lithosphere. For instance, melt-rock reactions at increasing melt/rock ratios operate as open-system melting processes removing residual BMS/PGMs. Highly percolated peridotites are characterized by extreme PGE depletion, coupled with PGE patterns and Os-isotope compositions that gradually evolve toward that of the percolating melt. Reactions at decreasing melt-rock ratios (usually referred to as «mantle metasomatism») precipitate PPGE-enriched BMS that yield suprachondritic Pd/Ir and occasionally affect Pt/Ir and Rh/Ir ratios as well. Moreover, volatile-rich, small volume melts fractionate Os relative to Ir and S relative to Se, thereby producing rocks with supra-chondritic Os/Ir and S/Se coupled with supra-chondritic Pd/Ir and Pt/Ir. Major magmatic inputs at the lithosphere-asthenosphere boundary may rejuvenate the PGE systematics of the depleted mantle. Integrated studies of «refertilized» peridotites with worldwide provenance provide evidence for mixing between old PGM-rich harzburgitic protoliths and newly-precipitated BMS. Long-lived PGMs carry the Os-isotope compositions of ancient melt-depletion events into seemingly undepleted fertile lherzolites. Another diagnostic feature of major refertilization processes is the increasing modal abundance of Pt-Pd-Te-Bi or Pt-As-S microphases. Due to regional-scale refertilization processes, sizeable (>. 100. km) domains of the upper lithospheric mantle are now significantly enriched in Pd, Au, Cu, Se, and other incompatible chalcophile elements that are of considerable importance in PGE-ore forming events. © 2012 Elsevier B.V.

Deschamps F.,Montpellier University | Godard M.,Montpellier University | Guillot S.,French National Center for Scientific Research | Hattori K.,University of Ottawa
Lithos | Year: 2013

Over the last decades, numerous studies have emphasized the role of serpentinites in the subduction zone geodynamics. Their presence and role in subduction environments are recognized through geophysical, geochemical and field observations of modern and ancient subduction zones and large amounts of geochemical database of serpentinites have been created. Here, we present a review of the geochemistry of serpentinites, based on the compilation of ~. 900 geochemical data of abyssal, mantle wedge and exhumed serpentinites after subduction. The aim was to better understand the geochemical evolution of these rocks during their subduction as well as their impact in the global geochemical cycle.When studying serpentinites, it is essential to determine their protoliths and their geological history before serpentinization. The geochemical data of serpentinites shows little mobility of compatible and rare earth elements (REE) at the scale of hand-specimen during their serpentinization. Thus, REE abundance can be used to identify the protolith for serpentinites, as well as magmatic processes such as melt/rock interactions before serpentinization. In the case of subducted serpentinites, the interpretation of trace element data is difficult due to the enrichments of light REE, independent of the nature of the protolith. We propose that enrichments are probably not related to serpentinization itself, but mostly due to (. sedimentary-derived) fluid/rock interactions within the subduction channel after the serpentinization. It is also possible that the enrichment reflects the geochemical signature of the mantle protolith itself which could derive from the less refractory continental lithosphere exhumed at the ocean-continent transition.Additionally, during the last ten years, numerous analyses have been carried out, notably using in situ approaches, to better constrain the behavior of fluid-mobile elements (FME; e.g. B, Li, Cl, As, Sb, U, Th, Sr) incorporated in serpentine phases. The abundance of these elements provides information related to the fluid/rock interactions during serpentinization and the behavior of FME, from their incorporation to their gradual release during subduction. Serpentinites are considered as a reservoir of the FME in subduction zones and their role, notably on arc magma composition, is underestimated presently in the global geochemical cycle. © 2013 Elsevier B.V.

Ibrahim A.,Montpellier University | Ohshima H.,Tokyo University of Science | Allison S.A.,Georgia State University | Cottet H.,Montpellier University
Journal of Chromatography A | Year: 2012

In this paper, a systematic and comparative study related to the effective charge determination of three kinds of solutes (small ions, polyelectrolytes and nanoparticles) was performed. Four approaches were compared regarding their conditions of validity and their advantages/disadvantages. Three of them allow the effective charge determination from the electrophoretic mobility and the hydrodynamic radius of the solutes using electrophoretic mobility modelings based on Nernst-Einstein (NE), O'Brien-White-Ohshima (OWO) and Yoon and Kim (YK) equations. Electrophoretic mobility and hydrodynamic radius were determined by capillary electrophoresis and Taylor dispersion analysis, respectively, using the same instrumentation in similar conditions, on a large set of samples. A fourth experimental approach based on the sensitivity of detection in indirect UV detection mode (IUV) was compared to the previously mentioned methods. OWO and YK modelings are well adapted for the effective charge determination of small ions and nanoparticles, while IUV is the only method adapted for polyelectrolytes. © 2012 Elsevier B.V.

Del Gado E.,ETH Zurich | Kob W.,Montpellier University
Soft Matter | Year: 2010

By means of molecular dynamics simulations, we study the structure and the dynamics of a microscopic model for colloidal gels at low volume fractions. The presence of directional interactions leads to the formation of a persistent interconnected network at temperatures where phase separation does not occur. We find that large scale spatial correlations strongly depend on the volume fraction and characterize the formation of the persistent network. We observe a pre-peak in the static structure factor and relate it to the network structure. The slow dynamics at gelation is characterized by the coexistence of fast collective motion of the mobile parts of the network structure (chains) with large scale rearrangements producing stretched exponential relaxations. We show that, once the network is sufficiently persistent, it induces slow, cooperative processes related to the network nodes. We suggest that this peculiar glassy dynamics is a hallmark of the physics of colloidal gels at low volume fractions. © 2010 The Royal Society of Chemistry.

Filippi-Codaccioni O.,University Pierre and Marie Curie | Devictor V.,Montpellier University | Bas Y.,University Pierre and Marie Curie | Julliard R.,University Pierre and Marie Curie
Biological Conservation | Year: 2010

In order to face the large and worrying biodiversity decline in agricultural landscapes, important policy instruments like agri-environmental schemes (AES) have been implemented. Studies that have examined the ecological effects of AES are now numerous and generally use indicators of biodiversity such as species richness and diversity as well as species abundance. Yet, it has been shown that simple metrics such as species richness or abundance may give misleading messages about biodiversity status and fate. Moreover, those indicators cannot detect another important source of biodiversity loss, biotic homogenisation. In this context, taking into account to a wider extent ecological difference among species would be more relevant, as well as focusing on the species specialisation which is known to be linked to higher species vulnerability. A bibliographic review investigating the criteria generally used to assess the success of AES showed that 55% of studies used species richness and/or abundance exclusively without any consideration of specialisation or other ecological traits in their evaluation of AES effectiveness. Based on data from the French breeding bird survey and studies at regional scale in France on farmland birds, we show that: (i) species richness and specialisation are generally negatively correlated in agricultural areas, (ii) habitat heterogeneity does not benefit specialist species, and (iii) monitoring of species diversity should be coupled with the monitoring of specialist species to improve conservation strategies in farming systems. Overall, this study emphasizes the need to account for both community richness and composition when assessing AES or similar conservation planning. © 2010 Elsevier Ltd.

Alexandrov S.,Montpellier University | Persson D.,ETH Zurich | Pioline B.,University Pierre and Marie Curie
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

By analyzing qualitative aspects of NS5-brane instanton corrections, we determine the topology of the hypermultiplet moduli space MH in Calabi-Yau compactifications of type II string theories at fixed value of the dilaton and of the Calabi-Yau metric. Specifically, we show that for fivebrane instanton couplings to be well-defined, translations along the intermediate Jacobian must induce nontrivial shifts of the Neveu-Schwarz axion which had thus far been overlooked. As a result, the Neveu-Schwarz axion parametrizes the fiber of a circle bundle, isomorphic to the one in which the fivebrane partition function is valued. In a companion paper, we go beyond the present analysis and take steps towards a quantitative description of fivebrane instanton corrections, using a combination of mirror symmetry, S-duality, topological string theory and twistor techniques. © 2011 American Physical Society.

Crabbe L.,French National Center for Scientific Research | Crabbe L.,Salk Institute for Biological Studies | Thomas A.,French National Center for Scientific Research | Pantesco V.,Montpellier University | And 3 more authors.
Nature Structural and Molecular Biology | Year: 2010

Maintenance of genome integrity relies on surveillance mechanisms that detect and signal arrested replication forks. Although evidence from budding yeast indicates that the DNA replication checkpoint (DRC) is primarily activated by single-stranded DNA (ssDNA), studies in higher eukaryotes have implicated primer ends in this process. To identify factors that signal primed ssDNA in Saccharomyces cerevisiae, we have screened a collection of checkpoint mutants for their ability to activate the DRC, using the repression of late origins as readout for checkpoint activity. This quantitative analysis reveals that neither RFC Rad24 and the 9-1-1 clamp nor the alternative clamp loader RFC Elg1 is required to signal paused forks. In contrast, we found that RFC Ctf18 is essential for the Mrc1-dependent activation of Rad53 and for the maintenance of paused forks. These data identify RFC Ctf18 as a key DRC mediator, potentially bridging Mrc1 and primed ssDNA to signal paused forks. © 2010 Nature America, Inc. All rights reserved.

Blanchard J.M.,French National Center for Scientific Research | Blanchard J.M.,Montpellier University
Oncogene | Year: 2014

Whether it is nobler in the mind to suffer the slings and arrows of outrageous proliferation, or to take arms against stroma, and favor metastasis. This pastiche of Hamlet's famous monologue illustrates recent reports on the paradoxical functions of well-established proliferation markers such as c-Myc or cyclin A2 that have revealed their ambiguous roles in the control of proliferation and metastasis. On the one hand, overexpression of c-Myc, while stimulating local proliferation, inhibits invasiveness of cancer cells, whereas on the other, downregulation of cyclin A2 leads to increased motility of transformed cells. © 2014 American Heart Association, Inc.

Bockaert J.,French National Center for Scientific Research | Bockaert J.,French Institute of Health and Medical Research | Bockaert J.,Montpellier University | Marin P.,French National Center for Scientific Research | And 2 more authors.
Physiological Reviews | Year: 2015

TOR (target of rapamycin) and its mammalian ortholog mTOR have been discovered in an effort to understand the mechanisms of action of the immunosuppressant drug rapamycin extracted from a bacterium of the Easter Island (Rapa Nui) soil. mTOR is a serine/threonine kinase found in two functionally distinct complexes, mTORC1 and mTORC2, which are differentially regulated by a great number of nutrients such as glucose and amino acids, energy (oxygen and ATP/AMP content), growth factors, hormones, and neurotransmitters. mTOR controls many basic cellular functions such as protein synthesis, energy metabolism, cell size, lipid metabolism, autophagy, mitochondria, and lysosome biogenesis. In addition, mTOR-controlled signaling pathways regulate many integrated physiological functions of the nervous system including neuronal development, synaptic plasticity, memory storage, and cognition. Thus it is not surprising that deregulation of mTOR signaling is associated with many neurological and psychiatric disorders. Preclinical and preliminary clinical studies indicate that inhibition of mTORC1 can be beneficial for some pathological conditions such as epilepsy, cognitive impairment, and brain tumors, whereas stimulation of mTORC1 (direct or indirect) can be beneficial for other pathologies such as depression or axonal growth and regeneration. © 2015 the American Physiological Society.

Lesne A.,University Pierre and Marie Curie | Lesne A.,Montpellier University | Riposo J.,University Pierre and Marie Curie | Roger P.,University Pierre and Marie Curie | And 2 more authors.
Nature Methods | Year: 2014

A computational challenge raised by chromosome conformation capture (3C) experiments is to reconstruct spatial distances and three-dimensional genome structures from observed contacts between genomic loci. We propose a two-step algorithm, ShRec3D, and assess its accuracy using both in silico data and human genome-wide 3C (Hi-C) data. This algorithm avoids convergence issues, accommodates sparse and noisy contact maps, and is orders of magnitude faster than existing methods. © 2014 Nature America, Inc.

Societe Splicos, Montpellier University, Institute Curie and French National Center for Scientific Research | Date: 2010-06-14

The present invention relates to compound (I) wherein: means a pyridazine, a pyrimidine or a pyrazine group, R independently represent a hydrogen atom, a halogen atom or a group chosen among a CN group, a hydroxyl group, a COOR_(1 )group, a (C_(1)-C_(3))fluoroalkyl group, a (C_(1)-C_(3))fluoroalkoxy group, a NO2 group, a NRiR2 group, a (C_(1)-C_(4))alkoxy group, a phenoxy group and a (C_(1)-C_(3))alkyl group, said alkyl being optionally mono-substituted by a hydroxyl group, n is 1, 2 or 3, n is 1 or 2, R is a hydrogen atom, a halogen atom or a group chosen among a (Ci-C3)alkyl group, a hydroxyl group, a COOR_(1 )group, a NO2 group, a NR_(1)R_(2 )group, a morpholinyl or a morpholino group, a N-methylpiperazinyl group, a (Ci-C3)fluoroalkyl group, a (C_(1)-C_(4))alkoxy group and a CN group, Z is N or C, Y is N or C, X is N or C, W is N or C, T is N or C, U is N or C, for use as an agent for preventing, inhibiting or treating pathological or nonpathological conditions linked with premature aging. Some of said compounds are new and also form part of the invention.

French National Center for Scientific Research, Institute Regional Du Cancer Of Montpellier and Montpellier University | Date: 2013-02-26

The present invention relates to an association of poly (N-acryloyl glycinamide) with at least one active principle and/or at least one product which is visible in medical imaging, in a physiologically acceptable aqueous medium.

Societe Splicos, Montpellier University, Institute Curie and French National Center for Scientific Research | Date: 2010-06-14

The present invention relates to compound (I) wherein: means a pyridazine, a pyrimidine or a pyrazine group, R independently represent a hydrogen atom, a halogen atom or a group chosen among a CN group, a hydroxyl group, a COOR_(1 )group, a (C_(1)-C_(3))fluoroalkyl group, a (C_(1)-C_(3))fluoroalkoxy group, a NO_(2 )group, a NR_(1)R_(2 )group, a (C_(1)-C_(4))alkoxy group, a phenoxy group and a (C_(1)-C_(3))alkyl group, said alkyl being optionally mono-substituted by a hydroxyl group, n is 1, 2 or 3, n is 1 or 2, R is a hydrogen atom, a halogen atom or a group chosen among a (C_(1)-C_(3))alkyl group, a hydroxyl group, a COOR_(1 )group, a NO_(2 )group, a NR_(1)R_(2 )group, a morpholinyl or a morpholino group, a N-methylpiperazinyl group, a (C_(1)-C_(3))fluoroalkyl group, a (C1-C4)alkoxy group and a CN group, Z is N or C, Y is N or C, X is N or C, W is N or C, T is N or C, U is N or C, for use as an agent for preventing, inhibiting or treating cancer. Some of said compounds are new and also form part of the invention.

French National Center for Scientific Research, Montpellier SupAgro and Montpellier University | Date: 2010-11-19

A method for preparing a formaldehyde-free phenolic plastic resin, includes a step of preparing a hardener via careful oxidation of a polyol and a step of reacting the hardener with phenolic compounds.

French National Center for Scientific Research and Montpellier University | Date: 2013-09-06

The present invention provides a method for determining all the molecular causes of Inherited Neuromuscular Disorders comprising determining a number of copy number variation(s), and/or determining a number of point mutation(s) on a physiological sample comprising a genome of a subject.

French National Center for Scientific Research, Montpellier University and Institute Curie | Date: 2013-11-04

The present invention relates to a compound of one of the formulas I to XXI; a pharmaceutical composition comprising at least one such compound; and the use of at least one such compound in preparing a drug to treat, in a subject, a genetic disease resulting from at least one splicing anomaly.

Montpellier University and French National Center for Scientific Research | Date: 2012-06-14