Analyse de données et modèle pour l'étude de la chromatine, des G-quadruplexes et de la réparation de l'ADN

Les cassures double brin de l'ADN (DSB) sont des lésions délétères qui peuvent survenir sur le génome suite à une exposition à des agents génotoxiques, mais aussi de façon endogène, parmi lesquelles la formation de structures secondaires de l'ADN, telles que les G-quadruplexes (G4). Des méthodes computationnelles antérieures ont été développées pour prédire les G4 en fonction de motifs spécifiques, mais des approches récentes, basées sur le séquençage à haut débit ont permis d'identifier les G4 à l'échelle du génome. J'ai développé un nouveau modèle de Deep Learning pour prédire les régions G4 actives en utilisant les séquences d'ADN et l'accessibilité de la chromatine. En utilisant ce modèle, nous avons identifié de nouveaux motifs prédicteurs, y compris des facteurs de transcription connus qui pourraient réguler directement ou indirectement l'activité des G4. Nous avons également cartographié des milliers de régions G4 actives qui peuvent être utilisées dans le traitement du cancer pour identifier des cibles potentielles de médicaments récents à base de ligand-G4. De plus, une fois induites sur le génome, les DSB déclenchent des modifications locales de la chromatine, comme la phosphorylation du variant d'histone H2AX (gammaH2AX) par la kinase ATM, pour former des foyers de réparation à l'échelle du mégabase. Comment ces domaines sont formés pour permettre la signalisation rapide des DSB, et comment ces changements locaux de la chromatine sont gérés par la cellule n'est pas encore bien connu. Nous avons découvert que le recrutement des composants de réparation et la phosphorylation de H2AX sont régis par des domaines topologiques associatifs (TAD) préexistants. De plus, nous avons mis en évidence un processus d'extrusion de boucle unidirectionnel médié par le complexe de cohésine des deux côtés des DSB, ce qui permet la formation de foyers de réparation par ATM. Nous avons également découvert qu'à grande échelle, les DSB peuvent former un nouveau compartiment "D" de chromatine, composé de domaines de chromatine décorés par gH2AX, mais aussi de gènes de la réponse aux dommages à l'ADN (DDR), suggérant un rôle du regroupement des DSB dans l'activation de la DDR.DNA Double-strand breaks (DSBs) are harmful lesions that can occur on the genome fol­lowing exposure to genotoxic agents but also due to endogenous causes, among which the formation of DNA secondary structures, such as G-quadruplexes (G4). Previous methods were developed to com­putationaly predict G4s based on specific motifs, and recent Next Generation Sequencing approaches identified G4 distribution genome-wide. I developed a novel Deep learning model to predict active G4 regions using the DNA sequences and chromatin accessibility. Using this model, we found new motifs predictors including known transcription factors that could regulate directly or indirectly G4s activity. We also mapped thousand of active G4s regions that can be used in cancer therapy to identify potential targets of recent G4-ligand drugs. Moreover, once induced on the genome, DSBs trigger local chromatin modifications including the phos­phorylation of the H2AX histone variant (gamma H2AX) by the ATM kinase, to form megabase-sized repair foci. How these domains are formed to enable rapid signaling of DSBs, and how these local chromatin changes are handled by the cell is still unclear. We found, that the recruitment of repair components and the phosphorylation of H2AX is governed by pre-existing Topologically Associating Domain (TADs). Moreover we discovered that an unidirectional loop-extrusion process mediated by the cohesin complex takes place on both side of the DSBs, which allow repair foci formation by ATM. We also found, at a global scale, that DSBs can form a novel "D" chromatin compartment, composed of gH2AX-decorated chromatin domains, but also of DNA damage responsive genes, suggesting a role of DSB clustering in activating the DNA Damage Response

A simple and efficient feedback control strategy for wastewater denitrification

Due to severe mathematical modeling and calibration difficulties open-loop feedforward control is mainly employed today for wastewater denitrification, which is a key ecological issue. In order to improve the resulting poor performances a new model-free control setting and its corresponding "intelligent" controller are introduced. The pitfall of regulating two output variables via a single input variable is overcome by introducing also an open-loop knowledge-based control deduced from the plant behavior. Several convincing computer simulations are presented and discussed.Comment: IFAC 2017 World Congress, Toulouse, Franc

Hydrocarbons and heavy metals in the different sewer deposits in the ‘Le Marais’ catchment (Paris, France): stocks, distributions and origins

International audienceThe knowledge of the pollution stored in combined sewers is of prime importance in terms of management of wet weather flow pollution since sewer deposits play a significant role as source of pollution in combined sewer overflows. This work, which focused on the hydrocarbon (aliphatic and aromatic hydrocarbons) and metallic (Fe, Zn, Pb, Cu and Cd) pollution fixed to the different kinds of sewer deposits (gross bed sediment wGBSx, organic layer wOLx and biofilm), was performed in order to provide a complete overview of the contaminant storage in the ‘Le Marais’ combined sewer (Central Paris, France).Firstly , our results have shown that, for all kinds of pollutants, a major part was stored in the GBS (87 to 98%), a lesser part in the OL (2 to 13%) and an insignificant part in the biofilm (< 1%). These results demonstrated that the potential contribution of biofilm to wet weather pollution was negligible compared to the OL one. Secondly, the investigation of hydrocarbon fingerprints in each deposit has provided relevant information about contamination origins: (1) aliphatic hydrocarbon distributions were indicative of petroleum input in the GBS and reflected a mixture of biogenic and petroleum inputs in the OL and biofilm, (2) aromatic hydrocarbon distributions suggested an important pyrolytic contamination in all the deposits.Finally , the study of pollutant fingerprints in the different deposits and in the suspended solids going through the collector has shown that: (1) the suspended solids were the major component of OL and biofilm while urban runoff seemed to be the main transport mechanism introducing pollutants in the GBS and (2) the residence times in sewer of OL and biofilm were quite short compared to those for GBS.

La biofiltration des eaux résiduaires urbaines : retour d’expérience du SIAAP

Depuis plus de 15 ans, la Direction de la Recherche et du Développement du Syndicat Interdépartemental pour l’Assainissement de l’Agglomération Parisienne (SIAAP) étudie le procédé de biofiltration des eaux résiduaires urbaines. Les différents travaux de recherche et développement, menés à l’échelle industrielle et semi-industrielle (stations d’épuration/ prototypes/pilotes) ont permis au SIAAP d’acquérir une réelle expérience sur ce procédé de traitement. L’objectif de cet article de synthèse est d’extraire de ces 15 années de travail des informations clés sur les performances et les limites des biofiltres (charges éliminées et influence des conditions d’exploitation sur l’élimination de la pollution) ainsi que sur les mécanismes de colonisation et d’encrassement des massifs filtrants.For more than 15 years, the interdepartmental association for sewage disposal in Paris conurbation (SIAAP) research center has studied wastewater treatment by biofiltration. Such studies, carried out at industrial and semi-industrial scales (wastewater treatment plants/pilot and prototype units), have allowed SIAAP to expand its knowledge of this wastewater treatment technology. This paper aims to review the available information on the performance and limits of these immersed biological systems (purification performances and effects of the operating conditions on the pollution abatement efficiencies) and about the mechanisms of colonization of filter media by bacteria populations

The preparation of magnetic iron oxide nanoparticles in microreactors

The preparation of magnetic iron oxide nanoparticles within microreactors is reported. The proportion of γ-Fe2O3 and Fe 3O4 in the sample was determined, an important parameter for reproducibility in applications. © 2013 Akadémiai Kiadó

Alkylphenolic compounds and bisphenol A contamination within a heavily urbanized area: case study of Paris.

International audienceThis study evaluates the influence of a heavily urbanized area (Paris Metropolitan area), on receiving water contamination by both bisphenol A (BPA) and alkylphenol ethoxylate (APE) biodegradation product. The study began by investigating concentrations within urban sources. In addition to the more commonly studied wastewater treatment plant effluent, wet weather urban sources (including combined sewer overflows, urban runoff, and total atmospheric fallout) were considered. The initial results highlight a significant contamination of all urban sources (from a few nanograms per liter in atmospheric fallout to several micrograms per liter in the other sources) with clearly distinguishable distribution patterns. Secondly, concentration changes along the Seine River from upstream of the Paris Metropolitan area to downstream were investigated. While the concentrations of BPA and nonylphenoxy acetic acid (NP(1)EC) increase substantially due to urban sources, the 4-nonylphenol concentrations remain homogeneous along the Seine. These results suggest a broad dissemination of 4-nonylphenol at the scale of the Seine River basin. Moreover, the relationship between pollutant concentrations and Seine River flow was assessed both upstream and downstream of the Paris conurbation. Consequently, a sharp decrease in dissolved NP(1)EC concentrations relative to Seine River flow underscores the influence of single-point urban pollution on Seine River contamination. Conversely, dissolved 4-nonylphenol concentrations serve to reinforce the hypothesis of its widespread presence at the Seine River basin scale

Priority pollutants in urban stormwater: Part 2 - Case of combined sewers

Postprint de l'article : Priority pollutants in urban stormwater in urban stormwater - Case of combined sewers. J. Gasperi, S. Zgheib, M. Cladière, V. Rocher, R. Moilleron, G. Chebbo. Water research, special issue on urban stormwater 2011International audienceThis study has evaluated the quality of combined sewer overflows (CSO) in an urban watershed, such as Paris, by providing accurate data on the occurrence of priority pollutants (PPs) and additional substances, as well as on the significance of their concentrations in comparison with wastewater and stormwater. Of the 88 substances monitored, 49 PPs were detected, with most of these also being frequently encountered in wastewater and stormwater, thus confirming their ubiquity in urban settings. For the majority of organic substances, concentrations range between 0.01 and 1 µg.l-1, while metals tend to display concentrations above 10 µg.l-1. Despite this ubiquity, CSO, wastewater and stormwater feature a number of differences in both their concentration ranges and pollutant patterns. For most hydrophobic organic pollutants and some particulate-bound metals, CSOs exhibit higher concentrations than those found in stormwater and wastewater, due to the contribution of in-sewer deposit erosion. For pesticides and Zn, CSOs have shown concentrations close to those of stormwater, suggesting runoff as the major contributor, while wastewater appears to be the main source of volatile organic compounds. Surprisingly, similar concentration ranges have been found for DEHP and tributyltin compounds in CSOs, wastewater and stormwater. The last section of this article identifies substances for which CSO discharges might constitute a major risk of exceeding Environmental Quality Standards in receiving waters and moreover indicates a significant risk for PAHs, tributyltin compounds and chloroalkanes. The data generated during this survey can subsequently be used to identify PPs of potential significance that merit further investigation

Silicon diimide gel as an efficient stationary phase in thin layer chromatography for acid-sensitive organic compounds

We report the use of mesoporous silicon diimide gel as a basic stationary phase in thin layer chromatography for the characterisation and purification of acid-sensitive compounds. The gel is prepared by a simple sol-gel process and exhibits a large specific surface area, almost monodisperse pores and basic properties due to free-hanging amine groups

Production of topological defects at the end of inflation

Hybrid inflation within supersymmetric grand unified theories, as well as inflation through brane collisions within braneworld cosmological models, lead to the formation of one-dimensional defects. Observational data, mainly from the cosmic microwave background temperature anisotropies but also from the gravitational wave background, impose constraints on the free parameters of the models. I review these inflationary models and discuss the constraints from the currently available data.Comment: 9 pages, Invited talk in the Conference "Challenges in Particle Astrophysics" -- 6th Rencontres du Vietnam, Hanoi (Vietnam) 6-12 Aug. 200