Role of protein kinase C and epidermal growth factor receptor signalling in growth stimulation by neurotensin in colon carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Neurotensin has been found to promote colon carcinogenesis in rats and mice, and proliferation of human colon carcinoma cell lines, but the mechanisms involved are not clear. We have examined signalling pathways activated by neurotensin in colorectal and pancreatic carcinoma cells.</p> <p>Methods</p> <p>Colon carcinoma cell lines HCT116 and HT29 and pancreatic adenocarcinoma cell line Panc-1 were cultured and stimulated with neurotensin or epidermal growth factor (EGF). DNA synthesis was determined by incorporation of radiolabelled thymidine into DNA. Levels and phosphorylation of proteins in signalling pathways were assessed by Western blotting.</p> <p>Results</p> <p>Neurotensin stimulated the phosphorylation of both extracellular signal-regulated kinase (ERK) and Akt in all three cell lines, but apparently did so through different pathways. In Panc-1 cells, neurotensin-induced phosphorylation of ERK, but not Akt, was dependent on protein kinase C (PKC), whereas an inhibitor of the β-isoform of phosphoinositide 3-kinase (PI3K), TGX221, abolished neurotensin-induced Akt phosphorylation in these cells, and there was no evidence of EGF receptor (EGFR) transactivation. In HT29 cells, in contrast, the EGFR tyrosine kinase inhibitor gefitinib blocked neurotensin-stimulated phosphorylation of both ERK and Akt, indicating transactivation of EGFR, independently of PKC. In HCT116 cells, neurotensin induced both a PKC-dependent phosphorylation of ERK and a metalloproteinase-mediated transactivation of EGFR that was associated with a gefitinib-sensitive phosphorylation of the downstream adaptor protein Shc. The activation of Akt was also inhibited by gefitinib, but only partly, suggesting a mechanism in addition to EGFR transactivation. Inhibition of PKC blocked neurotensin-induced DNA synthesis in HCT116 cells.</p> <p>Conclusions</p> <p>While acting predominantly through PKC in Panc-1 cells and via EGFR transactivation in HT29 cells, neurotensin used both these pathways in HCT116 cells. In these cells, neurotensin-induced activation of ERK and stimulation of DNA synthesis was PKC-dependent, whereas activation of the PI3K/Akt pathway was mediated by stimulation of metalloproteinases and subsequent transactivation of the EGFR. Thus, the data show that the signalling mechanisms mediating the effects of neurotensin involve multiple pathways and are cell-dependent.</p

The GenTree Platform: growth traits and tree-level environmental data in 12 European forest tree species

Background: Progress in the field of evolutionary forest ecology has been hampered by the huge challenge of phenotyping trees across their ranges in their natural environments, and the limitation in high-resolution environmental information. Findings: The GenTree Platform contains phenotypic and environmental data from 4,959 trees from 12 ecologically and economically important European forest tree species: Abies alba Mill. (silver fir), Betula pendula Roth. (silver birch), Fagus sylvatica L. (European beech), Picea abies (L.) H. Karst (Norway spruce), Pinus cembra L. (Swiss stone pine), Pinus halepensis Mill. (Aleppo pine), Pinus nigra Arnold (European black pine), Pinus pinaster Aiton (maritime pine), Pinus sylvestris L. (Scots pine), Populus nigra L. (European black poplar), Taxus baccata L. (English yew), and Quercus petraea (Matt.) Liebl. (sessile oak). Phenotypic (height, diameter at breast height, crown size, bark thickness, biomass, straightness, forking, branch angle, fructification), regeneration, environmental in situ measurements (soil depth, vegetation cover, competition indices), and environmental modeling data extracted by using bilinear interpolation accounting for surrounding conditions of each tree (precipitation, temperature, insolation, drought indices) were obtained from trees in 194 sites covering the species’ geographic ranges and reflecting local environmental gradients. Conclusion: The GenTree Platform is a new resource for investigating ecological and evolutionary processes in forest trees. The coherent phenotyping and environmental characterization across 12 species in their European ranges allow for a wide range of analyses from forest ecologists, conservationists, and macro-ecologists. Also, the data here presented can be linked to the GenTree Dendroecological collection, the GenTree Leaf Trait collection, and the GenTree Genomic collection presented elsewhere, which together build the largest evolutionary forest ecology data collection available

Between but not within species variation in the distribution of fitness effects

New mutations provide the raw material for evolution and adaptation. The distribution of fitness effects (DFE) describes the spectrum of effects of new mutations that can occur along a genome, and is therefore of vital interest in evolutionary biology. Recent work has uncovered striking similarities in the DFE between closely related species, prompting us to ask whether there is variation in the DFE among populations of the same species, or among species with different degrees of divergence, i.e., whether there is variation in the DFE at different levels of evolution. Using exome capture data from six tree species sampled across Europe we characterised the DFE for multiple species, and for each species, multiple populations, and investigated the factors potentially influencing the DFE, such as demography, population divergence and genetic background. We find statistical support for there being variation in the DFE at the species level, even among relatively closely related species. However, we find very little difference at the population level, suggesting that differences in the DFE are primarily driven by deep features of species biology, and that evolutionarily recent events, such as demographic changes and local adaptation, have little impact

Impact of CGNS on CFD Workflow

CFD tools are an integral part of industrial and research processes, for which the amount of data is increasing at a high rate. These data are used in a multi-disciplinary fluid dynamics environment, including structural, thermal, chemical or even electrical topics. We show that the data specification is an important challenge that must be tackled to achieve an efficient workflow for use in this environment. We compare the process with other software techniques, such as network or database type, where past experiences showed how difficult it was to bridge the gap between completely general specifications and dedicated specific applications. We show two aspects of the use of CFD General Notation System (CGNS) that impact CFD workflow: as a data specification framework and as a data storage means. Then, we give examples of projects involving CFD workflows where the use of the CGNS standard leads to a useful method either for data specification, exchange, or storage

Faut-il mettre en isolement tous les patients qui bénéficient d’une recherche de tuberculose pulmonaire dans les services de médecine interne ?

National audienceIntroduction La tuberculose est une pathologie fréquente et grave dont le mode de transmission et la contagiosité facilitent sa transmission intrahospitalière. La recherche d’une tuberculose est une situation fréquente dans un service de médecine interne mais réalisée le plus souvent dans le but d’éliminer le diagnostic. Malgré tout, la prévention des cas secondaires passe par des mesures d’isolement respiratoire contraignantes et peu adaptées à certains services. L’objectif de cette étude était donc de faire le point dans un service de médecine interne sur les modalités d’isolement des patients chez qui une tuberculose est recherchée, ainsi que de tester des scores décisionnels afin d’optimiser la mise en place des mesures d’isolement. Patients et méthodes Il s’agit d’une étude observationnelle rétrospective réalisée dans un service de médecine interne. Les patients ayant bénéficié d’une recherche de tuberculose du 1e avril 2010 au 31 mars 2015 ont été recensés grâce au service de bactériologie et seuls les patients ayant au moins 1 prélèvement positif ont été inclus. Après analyse de la cohorte et des modalités d’isolement à partir des dossiers médicaux, 2 scores décisionnels d’isolement ont été testés sur la population : (i) le score de Tattevin et al. obtenu en pondérant les facteurs prédictifs de tuberculose identifiés en analyse multivariée ; (ii) le score de Wisnievki et al. établi à partir d’une population à faible prévalence de tuberculose. Résultats Vingt-quatre patients ont été inclus soit une incidence de 2 %. Les deux tiers des patients étaient atteints d’une tuberculose pulmonaire et un quart avait une forme extrapulmonaire associée. Les principaux facteurs de risque retrouvés étaient l’antécédent de tuberculose et un contage. La majorité des patients était symptomatique au moment du diagnostic (87,5 %, n = 21), avec prédominance d’altération de l’état général, de fièvre et de signes respiratoires dans 74 % des cas (n = 18). La totalité des patients a bénéficié d’une imagerie thoracique, retrouvant des signes de tuberculose dans plus de 70 % des cas. Tous les patients ont eu une recherche bactériologique de tuberculose pulmonaire. Le délai moyen de réalisation des prélèvements par rapport à l’entrée est de 5 jours. Seuls 70 % ont bénéficié d’au moins 3 prélèvements conformément aux recommandations. Plus de la moitié des prélèvements (58,3 %, n = 14) étaient négatifs à l’examen direct. Seuls 15 patients ont été isolés et parmi les 6 patients non isolés (3 données manquantes), tous ont eu un résultat d’examen direct négatif. Parmi les patients bacillifères, 30 % (n = 3) ont été isolés dès l’entrée. Le délai moyen d’isolement était de 1,8 jours Le taux d’isolement chez les patients ayant un résultat d’examen direct positif était de 100 %. Il n’a été diagnostiqué aucun cas de tuberculose secondaire parmi le personnel soignant. Le score de Tattevin et al. a une sensibilité de 54 % sur cette population alors que l’application du score de Wisnieski et al. permettrait l’isolement de 92 % des patients. Conclusion Cette étude met donc en évidence (i) la faible incidence de la tuberculose dans les services de médecine interne ; (ii) les difficultés de mise en œuvre des mesures d’isolement respiratoire recommandées ; (iii) la fréquence des résultats d’examen direct négatifs, confirmant donc la faible sensibilité de cet examen ; (iv) l’absence de transmission nosocomiale malgré les défauts d’isolement. La validation de scores décisionnels adaptés aux populations à faible prévalence est donc nécessaire pour identifier rapidement les patients nécessitant un isolement et la généralisation de méthodes diagnostiques rapides pourrait être utile pour lever au plus vite les isolements par excès et donc minimiser leur impact et leurs contraintes logistique

Sensorless force/position control of a single-acting actuator applied to compliant object interaction

International audienceThis paper deals with a sensorless control approach of a lightweight electric actuator. Force and motion control are necessary to perform manipulation tasks with object interaction of different stiffnesses. The controller must ensure stability in a wide range of rigidity, particularly in soft contact cases. The approach proposed here is based on a force/position control scheme. First, a nonlinear position controller is performed through a linear parameter-varying state feedback. A state observer is added to estimate unmeasurable variables coming from an absence of terminal sensors. Subsequently, an output feedback force control is determined using an H∞ framework. The controller is experimentally applied on a single-acting actuator to demonstrate the efficiency of this approach dedicated to compliant object interaction

Combining least-squares and gradient-based algorithms for the identification of a co-current flow heat exchanger

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Combining least-squares and gradient-based algorithms for the identification of a co-current flow heat exchanger

<p>Because of the high-dimensional nature of partial differential equations (PDEs), identifying accurate models of processes, the behaviour of which is governed by PDEs, is a challenging problem which still deserves a lot of attention. We address the problem of identifying a grey-box model of a heat exchanger by combining equation-error and output-error-based algorithms. First, in order to estimate rough but reliable values of the sought physical parameters characterising the heat exchanger behaviour, we use the interesting properties of the reinitialised partial moments (RPMs) developed initially for ordinary differential equations to deal with the problem of inaccessible partial derivatives of the PDE. Such an adaptation of the RPM features to PDEs leads to a direct continuous-time system identification problem for which convex least-squares solutions can be found. Second, thanks to a description of the heat exchanger dynamics with a 2D linear time-invariant Roesser model, the aforementioned rough estimates are used as reliable initial guesses for the nonlinear optimisation of a standard non-convex cost function introduced to estimate the state-space matrices of the Roesser model we want to identify. The efficiency of this two-step approach in terms of physical parameter estimation is validated through the simulation of a co-current flow heat exchanger.</p

Végétation tricuspidienne au cours d’une maladie de Still, une manifestation non infectieuse rare de lésion intracardiaque [Intra-cardiac manifestation during adult-onset Still's disease's, a tricuspid vegetation as a rare expression of systemic disease]

National audienc