Impairing flow-mediated endothelial remodeling reduces extravasation of tumor cells

Tumor progression and metastatic dissemination are driven by cell-intrinsic and biomechanical cues that favor the growth of life-threatening secondary tumors. We recently identified pro-metastatic vascular regions with blood flow profiles that are permissive for the arrest of circulating tumor cells. We have further established that such flow profiles also control endothelial remodeling, which favors extravasation of arrested CTCs. Yet, how shear forces control endothelial remodeling is unknown. In the present work, we aimed at dissecting the cellular and molecular mechanisms driving blood flow-dependent endothelial remodeling. Transcriptomic analysis of endothelial cells revealed that blood flow enhanced VEGFR signaling, among others. Using a combination of in vitro microfluidics and intravital imaging in zebrafish embryos, we now demonstrate that the early flow-driven endothelial response can be prevented upon specific inhibition of VEGFR tyrosine kinase and subsequent signaling. Inhibitory targeting of VEGFRs reduced endothelial remodeling and subsequent metastatic extravasation. These results confirm the importance of VEGFR-dependent endothelial remodeling as a driving force of CTC extravasation and metastatic dissemination. Furthermore, the present work suggests that therapies targeting endothelial remodeling might be a relevant clinical strategy in order to impede metastatic progression.</p

Geography, Plants, and Growing Systems Shape the Genetic Structure of Tunisian Botrytis cinerea Populations

BGPI : équipe 5International audienceBotrytis cinerea, considered for a long time as a generalist fungal pathogen of a multitude of plants, was recently shown to exhibit significant population structure in France according to the host, suggesting sympatric specialization. Recent models also showed that adaptation to new hosts may facilitate the process of sympatric speciation in fungal plant pathogens. The present work aimed at investigating if host plants, combined with geographic origin and growing systems, shape the diversity and structure of Tunisian populations of B. cinerea. We genotyped 153 isolates with 9 microsatellites. In all the investigated populations, the fungus reproduced mainly sexually. Gene flow was significantly reduced between greenhouses and open fields from strawberry but not from grapevine. Populations from tomatoes, sampled under greenhouses only, exhibited a low genotypic diversity. The effects of plant and geography from open fields were investigated on a sample of 74 isolates. Six populations were inferred, mainly structured according to a geographic barrier corresponding to the Grande Dorsale Mountain. However, this effect could not be separated from the host plant origin of isolates. The analysis of 63 isolates recovered from strawberries and faba beans in the Cap Bon and Centre regions did not reveal any significant effect of plant on pathogen population differentiation

Low diversity and fast evolution in the population of Puccinia triticina causing durum wheat leaf rust in France from 1999 to 2009, as revealed by an adapted differential set

No internationally agreed differential set is available for characterization of virulences in populations of Puccinia triticinacausing wheat leaf rust on durum wheat. In a first step, 73 potentially differential host genotypes were tested with 96 durumleaf rust isolates collected in France. A differential set, adapted to the local epidemiological context and useful for comparisonwith international studies was selected, including French commercial cultivars, Thatcher lines with Lr genes, and internationalcultivars. In the second step, a sample of 310 isolates collected in France from 1999 to 2009 was characterized onthis set. Diversity was very low, as only five pathotypes were distinguished. Genotyping of a subset of 76 isolates accordingto 20 SSR markers confirmed this low diversity, with 73 isolates belonging to a single dominant genotype. Population wasstrongly shaped by cultivars, and the findings explain the successive breakdown of resistance sources deployed in Frenchdurum wheat cultivars. The gene Lr14a, suggested to be an efficient source of resistance in several European and Americancountries, was overcome by pathotypes frequent in France since 2000. Postulation of resistance genes in the commercial cultivarsled to a proposed simplified version of the differential set. This study, providing new information about leaf rust resistancegenes present in the French durum wheat germplasm, highlights the need to diversify sources of resistance toP. triticina in this germplasm. The results are also discussed in terms of relatedness and intercontinental migration of P. triticinaon durum wheat

Etude morpho-sédimentaire du plateau rocheux de la Méloine (Finistère nord). Recueil des données acoustiques, sédimentaires et d’observations acquises pendant les missions GEOMELOINE et NEOMELEC’H en 2014

Etude morpho-sédimentaire du plateau rocheux de la Méloine (Finistère nord). Recueil des données acoustiques, sédimentaires et d’observations acquises pendant les missions GEOMELOINE et NEOMELEC’H en 201

Improving the assembly of Botrytis cinerea genome using a genetic map and a BAC ends sequences library

Session 5 : Bio-Informatics and Comparative Genomics : P5.1absen

Etude morpho-sédimentaire du plateau rocheux de la Méloine (Finistère nord). Méthodologie appliquée aux traitements des données et résultats sur la distribution des roches dans l’archipel

Etude morpho-sédimentaire du plateau rocheux de la Méloine (Finistère nord) Méthodologie appliquée aux traitements des données et résultats sur la distribution des roches dans l’archipel

Botrytis pseudocinerea, a new cryptic species causing grey mould in French vineyards in symatry with Botrytis cinerea

International audienc

Development of SNP markers to detect natural selection in a fungal genome.

absen

Sugar accumulation and malic degradation uncoupled by temperature in microwine berries

UMR AGAP - équipe DAAV (Diversité, adaptation et amélioration de la vigne)Global warming has already become a critical problem for wine quality in many viticulture regions. However the developmental and molecular mechanisms involved in the response of the grapevine fruit to temperature remain still very elusive. Field experimentation introduces biases in abiotic stress studies on perennial plants such as the grapevine, due to fluctuating uncontrolled conditions. In addition, un-synchronized berry ripening is a major issue that needs to be addressed in abiotic stress studies to reduce experimental noise. In the present study, several long-term temperature treatments were conducted under precisely controlled conditions, using the microvine (DRCF-mutant) as a model. Fruit development and physiology, and the transcriptome adaptation to heat were monitored both at single berry and population levels. Monitoring of the sugar and organic acid content of single berries illustrates that berry heterogeneity within post-véraison clusters spans from plateau herbacé to early maturity, as usually observed on average clusters sequentially sampled along this developmental period. Temperature studies showed an advanced green berry development at higher temperature followed by faster malic acid breakdown during ripening. For the first time in grapevine, we observed a uncoupling of sugar and malic-acid metabolism at the inception of ripening under low temperature. RNA-seq analyses yielded a total of 10 787 temperature-modulated transcripts supporting a range of physiological functions related to primary metabolism. This work, which is the first abiotic stress study on fleshy fruits using RNA-seq for transcriptomic analysis, provides new clues on the mechanisms underlying the metabolic changes caused by temperature during berry developmen