Control of bacterial virulence through the peptide signature of the habitat

To optimize fitness, pathogens selectively activate their virulence program upon host entry. Here, we report that the facultative intracellular bacterium Listeria monocytogenes exploits exogenous oligopeptides, a ubiquitous organic N source, to sense the environment and control the activity of its virulence transcriptional activator, PrfA. Using a genetic screen in adsorbent- treated ( PrfA-inducing) medium, we found that PrfA is functionally regulated by the balance between activating and inhibitory nutritional peptides scavenged via the Opp transport system. Activating peptides provide essential cysteine precursor for the PrfA-inducing cofactor glutathione ( GSH). Non-cysteine-containing peptides cause promiscuous PrfA inhibition. Biophysical and co-crystallization studies reveal that peptides inhibit PrfA through steric blockade of the GSH binding site, a regulation mechanism directly linking bacterial virulence and metabolism. L. monocytogenes mutant analysis in macrophages and our functional data support a model in which changes in the balance of antagonistic Oppimported oligopeptides promote PrfA induction intra-cellularly and PrfA repression outside the host

Mise en place d'une base de données régionale et pluridisciplinaire sur le cancer de prostate (étude de faisabilité)

Nous avons mis en place une base de données régionale pluridisciplinaire sur la prise en charge du cancer de prostate. Le cancer de prostate est le premier cancer de l'homme en incidence. L'intérêt d'une base est de répondre à un manque d'informations précises sur les caractéristiques détaillées des patients et de leur cancer. Les objectifs sont de fédérer les intervenants de la prise en charge du cancer de prostate? D'obtenir une photographie évolutive des patients traités, de participer à l'évaluation des pratiques professionnelles, et de permettre des travaux de recherche clinique. L'intérêt personnel des participants est de pouvoir consulter leurs propres données et éventuellement de les comparer aux statistiques générales de la base. Création de la base les items reprennent tous les éléments indispensables à la prise en charge des patients atteints de cancer de prostate. La création de l'outil informatique, réalisé par une société d'experts en solutions multimédia, satisfait à des obligations de protection des données et de lisibilité facilitant la saisie de nombreuses informations. Mise en place de la base Les données sont saisies par du personnel extérieur aux services médicaux pour ne pas modifier le fonctionnement médical quotidien, facteur majeur d'adhésion au projet. Le lancement de la base se fait dans un nombre restreint de centres pendant la première année, permettant d'évaluer la faisabilité logistique, informatique et économique. Cette phase-pilote est soutenue financièrement par l'industrie pharmaceutique. Aspects juridiques une base de données est régie par les Lois n78-17 du 6 janvier 1978 et n2002-303 du 4 mars 2002. Ceci impose une reconnaissance par la CNIL, une anonymisation des données et le respect du secret médical. L'objectif est une pérennisation régionale et une éventuelle diffusion national de la base, dépendant essentiellement des contraintes économiques. Les difficultés à la mise en place d'une base sont d'ordre logistique, avec la saisie des informations ; juridique, avec la Loi Informatique et liberté et la Loi relative aux Droits des Malades ; et économiques pour assurer sa pérennisation et sa diffusion.ST ETIENNE-BU Médecine (422182102) / SudocSudocFranceF

New insights on the formation of nuclear star clusters

Nuclear Clusters (NCs) are common stellar systems in the centres of galaxies. Yet, the physical mechanisms involved in their formation are still debated. Using a parsec-resolution hydrodynamical simulation of a dwarf galaxy, we propose an updated formation scenario for NCs. In this 'wet migration scenario', a massive star cluster forms in the gas-rich disc, keeping a gas reservoir, and growing further while it migrates to the centre via a combination of interactions with other substructures and dynamical friction. A wet merger with another dense cluster and its own gas reservoir can occur, although this is not a pre-requisite for the actual formation of the NC. The merging process does significantly alter the properties of the NC (mass, morphology, star formation history), also quenching the on-going local star formation activity, thus leading to interesting observational diagnostics for the physical origin of NCs. A population of lower mass clusters co-exist during the simulation, but these are either destroyed via tidal forces, or have high angular momentum preventing them to interact with the NC and contribute to its growth. The proposed updated scenario emphasises the role of gas reservoirs associated with the densest star clusters formed in a gas-rich low-mass galaxy.Comment: MNRAS accepte

Observation des forêts en 3D. Utilisation de données Lidar pour l'estimation de la ressource forestière et d'indicateurs de biodiversité

International audienceAméliorer la connaissance et la description fidèle des écosystèmes forestiers est un prérequis indispensable pour parvenir à relever le défi de la gestion durable des forêts. L’organisation spatiale de la végétation joue un rôle fondamental dans le fonctionnement de ces écosystèmes. L’utilisation d’un système Lidar en milieu forestier permet de caractériser la structure en 3D de la végétation, ainsi que la topographie du terrain sous le couvert. L’objectif de cette intervention est de présenter des méthodes développées à l’Irstea et à l’Université de Sherbrooke pour analyser les données Lidar et en déduire des indicateurs de structure ou des paramètres biophysiques au niveau des arbres ou à l’échelle des peuplements. Ces approches nous permettent d’évaluer la ressource forestière en termes de volume de bois, de biomasse et de densité (e.g. surface terrière, profil vertical de végétation ou taux de couvert) sur des peuplements de complexité variable. Les capacités du Lidar sont aussi évaluées pour l’étude du lien entre la structure de la végétation forestière et la biodiversité, afin d’identifier des pratiques sylvicoles favorables à la biodiversité. Des systèmes Lidar terrestre et aérien sont utilisés et leur complémentarité est évaluée pour des études limitées aux massifs forestiers ou à l’échelle d’une région. Des projets de Lidars spatiaux sont aussi à l’étude en France dans le but de caractériser la ressource forestière à l’échelle mondiale et de permettre d’améliorer la quantification des stocks et flux de carbone des écosystèmes forestiers. Ces informations sont nécessaires aux modèles utilisés pour prédire l’évolution du climat à moyen et long terme et renforcer le rôle des forêts dans la régulation de ce changement global

The dual effect of abscisic acid on stomatal conductance

International audienceThe classical view that the drought-related hormone abscisic acid (ABA) simply acts at the guard cell level to induce stomatal closure is questioned by discrepancies in stomatal response to ABA between isolated epidermis and intact plants. We tested the hypothesis that ABA mediates an additional effect in planta by changing hydraulic regulation in the leaf upstream the stomata. By gravimetry, porometry to water vapour and argon, and psychrometry, we investigated the effect of exogenous ABA on transpiration, stomatal conductance and leaf hydraulic conductance of mutants described as ABAinsensitive in epidermal peels. We show that stomatal transpiration of ABA-insensitive mutants does respond to ABA in folio. We then demonstrate that ABA decreases stomatal conductance by downregulating leaf hydraulic conductance in both the wild-type Col-0 and the ABA-insensitive ost2. We propose that ABA promotes stomatal closure both via its biochemical effect on guard cells and via an indirect hydraulic effect through a decrease in leaf water permeability, triggered within vascular tissues by distinct signalling components. Variability in sensitivity of leaf hydraulic conductance to ABA among species could provide a physiological basis to the isohydric or anisohydric behaviour

The dual effect of abscisic acid on stomata

International audienceThe classical view that the drought-related hormone ABA simply acts locally at the guard cell level to induce stomatal closure is questioned by differences between isolated epidermis and intact leaves in stomatal response to several stimuli. We tested the hypothesis that ABA mediates, in addition to a local effect, a remote effect in planta by changing hydraulic regulation in the leaf upstream of the stomata. By gravimetry, porometry to water vapour and argon, and psychrometry, we investigated the effect of exogenous ABA on transpiration, stomatal conductance and leaf hydraulic conductance of mutants described as ABA-insensitive at the guard cell level. We show that foliar transpiration of several ABA-insensitive mutants decreases in response to ABA. We demonstrate that ABA decreases stomatal conductance and down-regulates leaf hydraulic conductance in both the wildtype Col-0 and the ABA-insensitive mutant ost2-2. We propose that ABA promotes stomatal closure in a dual way via its already known biochemical effect on guard cells and a novel, indirect hydraulic effect through a decrease in water permeability within leaf vascular tissues. Variability in sensitivity of leaf hydraulic conductance to ABA among species could provide a physiological basis to the isohydric or anisohydric behaviour

Comparaison de méthodes d'estimation de paramètres forestiers par télédétection, Lidar inclus. Cas d'étude sur les Vosges

International audienceCette étude compare différentes méthodes pour l'estimation de paramètres forestiers à partir de données de télédétection, incluant le lidar, sur une vaste zone situées dans les Vosges haut-rhinoises

An investigation into lidar scan angle impacts on stand attribute predictions in different forest environments

International audienceAs studies have underlined the sensitivity of lidar metrics to scan angles, the objective of this study was twofold. Firstly, we further investigated the influence of lidar scan angle on the ABA predictions of stand attributes of riparian (29 field plots), broadleaf (42 field plots), coniferous (31 field plots) and mixed (45 field plots) forest types in France. Secondly, we evaluated the potential of voxelisation approaches to normalise scan angle effects in lidar metrics and mitigate scan angle effects in ABA models. To achieve these objectives, we first selected a model based on four lidar metrics with different sensitivities to lidar scan angle, i.e. mean and variance of canopy height values, gap-fraction, and coefficient of variation of plant area density (PAD) profile. For each plot, we considered the point cloud scanned from one flight line independently and characterised each resulting point cloud by the mean scan angle (MSA) and classified them into one of three classes: A (0° <=MSA < 10°), B (10°<=MSA < 20°) or C (20°<=MSA < 30°). An experimental setup involving nine scenarios was conceived to study the impact of the number of flight lines (scenarios fl1, fl2 and fl3) and predominant scan angle (scenarios A, B or C) or combination of scan angle directions (scenarios A and B, or A and C, or B and C), on area-based approach (ABA) models. We built ABA models for the same forest plots for 5000 resampled datasets in each scenario to predict three forest attributes, i.e., stem and total volume (Vst and Vtot) and basal area (BA). Three goodness-of-fit criteria were computed for each model (coefficient of determination (R2), relative root mean square error (rRMSE) and mean percentage error (MPE). We compared the distributions of the goodness-of-fit criteria between scenarios to assess the behaviour of the predictive models when: 1) the number of flight lines (i.e., scan angles) increases (fl1, fl2 or fl3); 2) lidar datasets comprise specific scan angle (A, B or C) or combination of scan angles (AB, AC or BC); 3) voxelisation is used to compute Pf and CVPAD. The results show that models built with point clouds scanned from multiple flight lines were more robust, with a lower standard deviation of their goodness-of-fit criteria. On average, across all forest types, compared to fl1, the standard deviations of R2 distributions were lower for fl2 and fl3 by 42 % and 77 %, respectively. We also observed that a dataset with a predominantly nadir configuration (i.e., scenario A) did not always result in better predictions (mean R2 higher by 0.08, 0.07, 0.04 for scenario B for broadleaf, coniferous and mixed, respectively). For a set of calibration plots, the resulting forest attribute models depend on the acquisition geometry over the plots, as observed in this study, which could result in unreliable wall-to-wall predictions. The risk is particularly high in acquisitions with low overlapping rates, with many areas covered by only one flight line. Using voxel-based Pf and CVPAD together with the mean and variance of heights helped to mitigate the impacts of changes in scan angles by a) increasing the means of the distributions, thereby improving the accuracy of predictions, or b) reducing the standard deviations, thereby increasing prediction precision, or c) both of the above

Oral Vinorelbine and Cisplatin with Concurrent Radiotherapy After Induction Chemotherapy with Cisplatin and Docetaxel for Patients with Locally Advanced Non-small Cell Lung Cancer: The GFPC 05-03 Study

Introduction:The aim of this multicenter phase II trial was to evaluate the combination of oral vinorelbine and cisplatin with radiotherapy (RT) after cisplatin-docetaxel induction chemotherapy (CT) in patients with locally advanced non-small cell lung cancer (NSCLC).Patients and Methods:Patients with previously untreated, inoperable, histologically or cytologically confirmed stage IIIA or IIIB NSCLC, with performance status ≤1 and weight loss ≤10% received two cycles of induction CT with cisplatin (75 mg/m2) and docetaxel (75 mg/m2) every 3 weeks. Patients with a tumor response or stabilization continued to receive cisplatin (80 mg/m2) and oral vinorelbine (40 mg/m2) on days 1 and 8 for two cycles, with concomitant thoracic RT (2 Gy/d, 5 d/wk, and total dose 66 Gy).Results:Fifty-six patients were enrolled. All patients (n = 38) who received CT-RT were assessable for the tumor response. There were no complete responses. In the intent-to-treat analysis, the response rates were 32.1% after induction CT and 41.1% after CT-RT. The median progression-free and overall survival times were 9.2 months (95% confidence interval: 7–14) and 20.8 months (95% confidence interval: 13.7–24.1), respectively. Adverse effects of RT-CT were grades 3 to 4 neutropenia (four patients) and grade 3 esophageal toxicity (one patient). No treatment-related deaths occurred.Conclusion:The oral vinorelbine-cisplatin combination with concurrent RT is feasible and has a favorable risk-benefit ratio in stage IIIA/IIIB NSCLC