An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome.

Human tuberculosis disease (TB), caused by Mycobacterium tuberculosis (Mtb), is a complex disease, with a spectrum of outcomes. Genomic, transcriptomic and methylation studies have revealed differences between Mtb lineages, likely to impact on transmission, virulence and drug resistance. However, so far no studies have integrated sequence-based genomic, transcriptomic and methylation characterisation across a common set of samples, which is critical to understand how DNA sequence and methylation affect RNA expression and, ultimately, Mtb pathogenesis. Here we perform such an integrated analysis across 22 M. tuberculosis clinical isolates, representing ancient (lineage 1) and modern (lineages 2 and 4) strains. The results confirm the presence of lineage-specific differential gene expression, linked to specific SNP-based expression quantitative trait loci: with 10 eQTLs involving SNPs in promoter regions or transcriptional start sites; and 12 involving potential functional impairment of transcriptional regulators. Methylation status was also found to have a role in transcription, with evidence of differential expression in 50 genes across lineage 4 samples. Lack of methylation was associated with three novel variants in mamA, likely to cause loss of function of this enzyme. Overall, our work shows the relationship of DNA sequence and methylation to RNA expression, and differences between ancient and modern lineages. Further studies are needed to verify the functional consequences of the identified mechanisms of gene expression regulation

Gla-rich protein function as an anti-inflammatory agent in monocytes/macrophages: implications for calcification-related chronic inflammatory diseases

Calcification-related chronic inflammatory diseases are multifactorial pathological processes, involving a complex interplay between inflammation and calcification events in a positive feed-back loop driving disease progression. Gla-rich protein (GRP) is a vitamin K dependent protein (VKDP) shown to function as a calcification inhibitor in cardiovascular and articular tissues, and proposed as an anti-inflammatory agent in chondrocytes and synoviocytes, acting as a new crosstalk factor between these two interconnected events in osteoarthritis. However, a possible function of GRP in the immune system has never been studied. Here we focused our investigation in the involvement of GRP in the cell inflammatory response mechanisms, using a combination of freshly isolated human leucocytes and undifferentiated/differentiated THP-1 cell line. Our results demonstrate that VKDPs such as GRP and matrix gla protein (MGP) are synthesized and gamma-carboxylated in the majority of human immune system cells either involved in innate or adaptive immune responses. Stimulation of THP-1 monocytes/macrophages with LPS or hydroxyapatite (HA) up-regulated GRP expression, and treatments with GRP or GRP-coated basic calcium phosphate crystals resulted in the down-regulation of mediators of inflammation and inflammatory cytokines, independently of the protein gamma-carboxylation status. Moreover, overexpression of GRP in THP-1 cells rescued the inflammation induced by LPS and HA, by down-regulation of the proinflammatory cytokines TNF alpha, IL-1 beta and NFkB. Interestingly, GRP was detected at protein and mRNA levels in extracellular vesicles released by macrophages, which may act as vehicles for extracellular trafficking and release. Our data indicate GRP as an endogenous mediator of inflammatory responses acting as an anti-inflammatory agent in monocytes/macrophages. We propose that in a context of chronic inflammation and calcification-related pathologies, GRP might act as a novel molecular mediator linking inflammation and calcification events, with potential therapeutic application.Portuguese Science and Technology Foundation (FCT) [PTDC/SAU-ORG/117266/2010, PTDC/BIM-MEC/1168/2012, UID/Multi/ 04326/2013]; FCT fellowships [SFRH/BPD/70277/2010, SFRH/BD/111824/2015

Pois et féverole d’hiver : une meilleure caractérisation du risque de gel

National audienc

Pipeline Transportation of Heavy Oils, a Strategic, Economic and Technological Challenge

Because of very large reserves mainly located in Venezuela and Canada, heavy crude oils represent a significant energy supply. This article gives an overview of the geographical distribution of their resources and lists the recent projects of production. These projects have to face technological challenges in all phases of operation: reservoir, transportation and refining. The paper focuses on transportation, describing the different methods (heating, dilution, oil-in-water emulsion, upgrading and core annular flow). In order to improve them or develop new ones, a structural and rheological study was undertaken to appraise the origin of the high viscosity and counteract its effect

Crude Oil Emulsion Properties and Their Application to Heavy Oil Transportation

Many advances have been made in the field of emulsions in recent years. Emulsion behavior is largely controlled by the properties of the adsorbed layers that stabilize the oil-water surfaces. The knowledge of surface tension alone is not sufficient to understand emulsion properties, and surface rheology plays an important role in a variety of dynamic processes. The complexity of petroleum emulsions comes from the oil composition in terms of surface-active molecules contained in the crude, such as low molecular weight fatty acids, naphthenic acids and asphaltenes. These molecules can interact and reorganize at oil/water interfaces. The pronounced nonlinear behavior of surface rheology for asphaltene layers might explain differences in behavior between surfactant and asphaltene emulsions. These effects are very important in the case of heavy oils because this type of crude contains a large amount of asphaltene and surface-active compounds. This article reviews different petroleum emulsion properties and the transport of high viscosity hydrocarbon as a crude oil in water emulsion

Heavy Oil Dilution

Heavy crude oils cannot be transported by pipeline without a prior reduction of their viscosity. This is commonly obtained by blending the oil with light hydrocarbons. In that case, the resulting viscosity of the mixture depends only on the dilution rate, on the respective viscosities and densities of the oil, and of the diluent. The addition of a polar solvent to a solution of asphaltenes in toluene acts on the colloidal structure of the asphaltenes. The relative viscosity of the solution decreases. Small-angle X-ray scattering (SAXS) measurements show that the radius of gyration of the aggregates of asphaltenes decreases too. In the same way, by mixing hydrocarbons and solvents owning polar functional groups in their molecule, it is shown that the efficiency of the dilution of heavy crude oils is enhanced. Hansen's theory can be used to screen the solvent efficiency. At constant dilution rate, the higher the polarity parameter or the hydrogen bonding parameter of the solvent, the greater the relative viscosity reduction of the diluted crude oil. Nevertheless, solvent owning high hydrogen bonding are generally more viscous than hydrocarbons. The influence of their interactions with the asphaltenes is hidden when the results are expressed in absolute viscosity. Only polar solvents giving few hydrogen bonding give a significant reduction of the viscosity of the diluted crude oil

Mechanical Degradation Onset of Polyethylene Oxide Used as a Hydrosoluble Model Polymer for Enhanced Oil Recovery

Résumé — Seuil de dégradation mécanique de solutions de polymères utilisés en récupération assistée des hydrocarbures — Les polymères hydrosolubles comme les polyacrylamides peuvent être utilisés en récupération assistée des hydrocarbures (Enhanced Oil Recovery (EOR)) par injection de polymère. Cette technique vise à augmenter la production de brut en le poussant du réservoir vers un puits producteur à l’aide d’une solution de polymère suffisamment visqueuse. Les polymères utilisés à cet effet ont des masses moléculaires supérieures à 106 g/mol, ce qui les rend sensibles à la dégradation. En raison des débits élevés utilisés lors de leur injection, mais aussi en raison des taux d’élongation élevés rencontrés dans le réservoir, les polymères peuvent se rompre et perdre leurs propriétés viscosifiantes. Dans la littérature, il a été clairement montré, pour des solutions diluées en régime laminaire, que la dégradation des macromolécules n’était initiée qu’au-delà d’un taux d’élongation critique noté ε · c, et que ce taux d’élongation était une fonction puissance de la masse moléculaire du polymère: ε · c ≈ Mw –k. La présente étude expérimentale de la dégradation mécanique a été menée sur des solutions d’oxydes de polyéthylène pour comprendre la dégradation mécanique non seulement en écoulement laminaire ou turbulent, mais aussi en régime dilué et semi-dilué, ainsi qu’en bon ou mauvais solvant. Il a été mis en évidence que la dégradation mécanique affecte principalement les longue

Le réchauffement climatique diminue-t-il le risque de dégâts par le gel pour les cultures de climat tempéré ?

7 pagesInternational audienceLes réponses d'une culture d'hiver à l'augmentation des températures sont très complexes et variées. Dans uncontexte de réchauffement, certains travaux pointent une augmentation paradoxale des dégâts du gel pour la végétation desclimats froids et tempérés. Ces résultats nécessitent d'être précisés et élargis afin de documenter cette évolution pour lescultures d'hiver. Cinq séries complètes de températures quotidiennes (maximales et minimales) ont été analysées etalimentent un modèle de dégât du gel paramétré et validé pour le pois d'hiver (semis en automne). Ce modèle prend encompte l'acclimatation des plantes au froid (ou endurcissement), tout en permettant de changer la date de semis. Ladémarche a consisté à 1) caractériser la nature (amplitude, robustesse) du réchauffement, ce qui a permis l'identification dedeux périodes (avant et après une rupture en 1987/1988) ; 2) simuler pour les mois d'octobre à mars les dégâts du gel enfaisant varier la date de semis et les caractéristiques variétales de résistance-seuil au gel et de vitesse d’endurcissement ;3) de quantifier l’évolution du risque par une modélisation simultanée de l'occurrence et de l'intensité des événements gélifs.Une augmentation moyenne de 1.1°C des températures annuelles est observée entre les deux périodes. Ce réchauffemententraîne paradoxalement une augmentation du nombre annuel moyen de jours de dégât de gel : de 3,5 à 4,5. Cette évolutionest très sensible aux critères de résistance-seuil et de vitesse d'endurcissement. À l'opposé, l'intensité du risque décroîtfortement de -14 à -6 degrés-cumulés avec une moindre sensibilité aux critères variétaux. Ces résultats suggèrent de nuancerl'effet paradoxal d'augmentation des dégâts par le gel avec le réchauffement climatique. Ils questionnent quant à l'évolutionpossible du risque en fonction des scénarios de changement climatique et des critères variétaux

Regional projection of winter frost risk on a legume crop due to warming in a temperate climate

International audiencePea (Pisum sativum L.) is an important annual legume crop grown in temperate regions for its high seed nitrogenconcentration and environmental benefits. In the recent climate warming, a subtle evolution of the winter cropfrost risk was observed: a paradoxical increase of frost stress events and a frost stress intensity decrease (Castel etal. 2017). Such results are questioning the future winter frost risk for peas. We assessed the winter frost damageevolution along 2006 to 2100 in Burgundy-Franche-Comté (a French region - western part of Europe). The approachis based on the combination of i) a dynamical downscaled climate data of two RCP trajectories (4.5 and 8.5) (Boulardet al. 2016) and ii) a winter frost stress model calibrated and validated for pea (using varieties with different frostresistance levels and acclimation rates) (Lecomte et al. 2003; Castel et al. 2017). Our results show that frost risk willnot disappear with warming climate (Fig. 1). Compared to the historical period (1980-2005), the frost risk for the peavariety with a frost resistance level of -13°C will increase along the near future period (2020-2050) for RCP 8.5: withan increase of both the median and the spread of the cumulative frost degree days (Fig. 1B). With a highest warmingalong the far future period (2070-2100) for RCP 8.5, the results show a significant decrease of the cumulative frostdegree days compared to the near future and the historical periods, but the frost risk will persist (Fig. 1B). It suggeststhat frost risk will significantly increase for an extended winter warming below + 2°C, while it will decrease whenthis threshold will be overpassed (Fig. 1). The figure 2 depicts the evolution of the two components of the froststress with warming: intensity and number of the frost stress events. The increase of the cumulative frost degreedays in the near future period (2020-2050) for RCP 8.5 is determined by the increase of frost stress events intensity(Fig. 2A). By contrast the number of frost stress events slightly decrease during this period (Fig. 2B). This resultdiffers from the past evolution of these components with the observed warming from 1961 to 2018 (Castel et al.2019) and suggests a change in the winter frost risk structure. For the end of the century (period 2070-2100) andfor the RCP 8.5, both intensity and number of the frost stress events will decrease (Fig. 2). Finally the projectionsshow a contrasted geography of the frost risk evolution. This geographic trend depends on the frost resistance leveland acclimation rate of the pea variety. Our results seem to confirm subtle evolutions of winter climate warmingdynamics revealed by the change in the pea crop frost risk structure. Moreover, this work provides leads for breedingand crop management techniques strategies for winter pea adaptation to climate change to avoid the detrimentaleffects of frost while taking advantage of the potential of this crop