Showing papers by "Benjamin Richard published in 2013"

New prospects in the roles of the C-terminal domains of VEGF-A and their cooperation for ligand binding, cellular signaling and vessels formation.

Abstract: VEGF-A is a crucial growth factor for blood vessel homeostasis and pathological angiogenesis. Due to alternative splicing of its pre-mRNA, VEGF-A is produced under several isoforms characterized by the combination of their C-terminal domains, which determines their respective structure, availability and affinity for co-receptors. As controversies still exist about the specific roles of these exon-encoded domains, we systematically compared the properties of eight natural and artificial variants containing the domains encoded by exons 1–4 and various combinations of the domains encoded by exons 5, 7 and 8a or 8b. All the variants (VEGF111a, VEGF111b, VEGF121a, VEGF121b, VEGF155a, VEGF155b, VEGF165a, VEGF165b) have a similar affinity for VEGF-R2, as determined by Surface plasmon resonance analyses. They strongly differ however in terms of binding to neuropilin-1 and heparin/heparan sulfate proteoglycans. Data indicate that the 6 amino acids encoded by exon 8a must be present and cooperate with those of exons 5 or 7 for efficient binding, which was confirmed in cell culture models. We further showed that VEGF165b has inhibitory effects in vitro, as previously reported, but that the shortest VEGF variant possessing also the 6 amino acids encoded by exon 8b (VEGF111b) is remarkably proangiogenic, demonstrating the critical importance of domain interactions for defining the VEGF properties. The number, size and localization of newly formed blood vessels in a model of tumour angiogenesis strongly depend also on the C-terminal domain composition, suggesting that association of several VEGF isoforms may be more efficient for treating ischemic diseases than the use of any single variant.

Current knowledge on plant/canopy architectural traits that reduce the expression and development of epidemics

Abstract: To reduce the use of pesticides, innovative studies have been developed to introduce the plant as the centre of the crop protection system. The aim of this paper is to explain how architectural traits of plants and canopies induce a more or less severe epidemic and how they may be modified in order to reduce disease development. In particular, it focuses on three key questions: i) which processes linked to epidemics can be influenced by architecture ii) how can architecture be characterized relative to these modes of action, and iii) how can these effects be explored and exploited? The roles of plant/canopy architecture on inoculum interception, on epidemic development via the microclimate and on tissue receptivity are discussed. In addition, the concepts of disease avoidance, canopy porosity and an ideotype unfavourable for disease development are described. This paper shows that many advances have already been made, but progress is still required in four main fields: microclimatology, mathematical modelling of plants, molecular genetics and ideotype conception.

Smad2-Dependent Protease Nexin-1 Overexpression Differentiates Chronic Aneurysms From Acute Dissections of Human Ascending Aorta

Abstract: Objective— Tissue activation of proteolysis is involved in acute intramural rupture (dissections, acute ascending aortic dissection) and in progressive dilation (aneurysms, thoracic aneurysm of the ascending aorta) of human ascending aorta. The translational aim of this study was to characterize the regulation of antiproteolytic serpin expression in normal, aneurysmal, and dissecting aorta. Approach and Results— We explored expression of protease nexin-1 (PN-1) and plasminogen activator inhibitor-1 and their regulation by the Smad2 signaling pathway in human tissue and cultured vascular smooth muscle cells (VSMCs) of aneurysms (thoracic aneurysm of the ascending aorta; n=46) and acute dissections (acute ascending aortic dissection; n=10) of the ascending aorta compared with healthy aortas (n=10). Both PN-1 and plasminogen activator inhibitor-1 mRNA and proteins were overexpressed in medial tissue extracts and primary VSMC cultures from thoracic aneurysm of the ascending aorta compared with acute ascending aortic dissection and controls. Transforming growth factor-β induced increased PN-1 expression in control but not in aneurysmal VSMCs. PN-1 and plasminogen activator inhibitor-1 overexpression by aneurysmal VSMCs was associated with increased Smad2 binding on their promoters and, functionally, resulted in VSMC self-protection from plasmin-induced detachment and death. This phenomenon was restricted to aneurysms and not observed in acute dissections. Conclusions— These results demonstrate that epigenetically regulated PN-1 overexpression promotes development of an antiproteolytic VSMC phenotype and might favor progressive aneurysmal dilation, whereas absence of this counter-regulation in dissections would lead to acute wall rupture.

Non-intrusive global/local analysis for the study of fine cracking

Abstract: SUMMARY The description of damaged zones in large scale structures can nowadays be assessed by means of a finite element approach using an appropriate damage model. Nevertheless, a fine description of cracking (crack pattern, crack length, crack opening, crack tortuosity) is of primary importance to satisfy new requirements in design codes, especially when dealing with structure durability. In this paper, a computational strategy to quantify cracking at structural case is proposed. A continuous damage model is used to perform a full resolution at the global scale. Then, a reanalysis (implemented as a post-treatment) of the damaged zones is performed at the local scale with a discrete element model. A non-intrusive and decoupled numerical scheme allows for a two-scale analysis using each mechanical model (continuous as well as discrete) within its more efficient level. 2D and 3D test cases will be treated to illustrate the non-intrusive global/local analysis. Copyright © 2013 John Wiley & Sons, Ltd.

Effect of pea canopy architecture on microclimate and consequences on ascochyta blight infection under field conditions

Abstract: In order to investigate the impact of pea canopy architecture and development on microclimate and infection by Mycosphaerella pinodes, two field experiments were conducted in 2009 and 2010 at Le Rheu (France) to obtain canopies contrasted in height, closure dynamic, leaf area index (LAI) and leaf area density (LAD). Three pea cultivars (Athos, Antares, Gregor) were sown at two (80 and 40 seeds/m2 in 2009) and three densities (80, 40 and 30 seeds/m2 in 2010) and microclimatic sensors were located inside the canopy (at the bottom and in the middle) and outside. Two main sources of wetness were identified: rainfall and dew. During rainfall periods, average daily leaf wetness duration (LWD) was about 15 h, and 3 to 10 h longer inside than outside the canopies. LWD was positively correlated with LAI until canopy closure during these periods. During dry periods when dew was the only source of leaf wetness, average daily LWD was short, decreasing as the canopy developed. Shorter LWDs were observed at the base than at the mid-level of the canopies and longer LWDs were observed outside the canopy and inside the less dense canopies irrespective of the cultivar. LWD was negatively correlated with canopy height and LAI during these periods. Slow wind speeds were recorded inside the canopies (less than 0.5 km/h) and no significant canopy effect was observed on air temperature. An infection model was developed and showed that only rainfall periods which induced long LWDs inside the canopy, were favourable to M. pinodes infection under our climatic conditions and suggested a more favourable microclimate inside dense canopies.

PROJET 'ARCHIDEMIO'. Modéliser les interactions entre développement de la plante, architecture du couvert et épidémies de maladies fongiques aériennes, pour une gestion durable des cultures

Abstract: Dans le projet ANR « Archidemio » (2009 – 2012, appel d’offre SYSTERRA), nous avons explore si les caracteristiques de la plante et du couvert vegetal (architecture, developpement, niveaux de resistance) pouvaient etre des determinants majeurs du developpement epidemique des maladies aeriennes, et de leur maitrise dans des strategies integrees de phytoprotection. Le projet etait structure en trois grands volets : 1) La construction d’un modele generique couplant le developpement de la plante et le developpement epidemique de maladies aeriennes fongiques, 2) L’acquisition de connaissances sur 4 pathosystemes (vigne/oidium, igname/anthracnose, pois/ascochytose, pomme de terre/mildiou) en fonction de leur caracteristiques (sensibilite au micro-climat et a la plante), et des leviers potentiels activables cote plante (genetique, conduite de la culture), 3) L’elaboration de scenarii de gestion au niveau de la plante (architecture / genotype - ideotypes varietaux) et/ou de la culture (densite, taille, tuteurage).

Toward a physically-motivated damping model

Abstract: The way of modeling the damping phenomenon in nonlinear time history analyses is still an opened question and remains a motivating challenge in the scientific community. The well-known approach lies in considering nonphysical viscous forces that are proportional to the velocity field. A damping matrix must be defined and its identification is not based on physical considerations. This study aims at exploring the possibility of identifying a local constitutive model in order to account for damping in a natural way. To reach this objective, an experimental campaign based on reinforced concrete beams subjected to reverse threepoint bending tests have been performed in order to identify in an accurate way the hysteretic scheme used to take into account the hysteretic phenomenon. A specific hysteretic scheme is identified as relevant in terms of energy dissipation. Numerical free vibration tests are then carried out in order to demonstrate that the use of a viscous damping can be avoided if the local constitutive concrete model accounting for hysteretic phenomenon is accurately identified. Finally, as perspectives of this work, a method to develop a simplified physically motivated damping model is exposed and discussed.