Implication de TAK1 dans la modulation des réponses du neutrophile humain au fMLP et au GM-CSF

Les neutrophiles sont d'une grande importance dans la première ligne de défense de l'organisme contre les pathogènes. Ils participent activement par leurs actions antimicrobiennes, comme la phagocytose et la relâche de granules, mais influencent également la réponse immunitaire par les différentes cytokines et chimiokines qu'ils produisent. L'étude des différentes fonctions du neutrophile a permis d'établir les étapes clés de la signalisation intracellulaire qui mène à ces différentes fonctions. De plus, les études dé signalisation, dans différents organismes, ont placé TAK1, une MAP3K, à l'avant-plan dans l'activation des sentiers MAP kinase et des facteurs de transcription NF-kB. Nos efforts pour élucider les sentiers métaboliques du neutrophile nous ont fait nous pencher sur le rôle que TAK1 pouvait y jouer. Nous avons donc découvert que TAK1 était la kinase d'importance dans le contrôle des fonctions du neutrophile avec le LPS et le TNF[alpha], deux stimuli activateurs de NF-kB. Dans cette étude, nous nous sommes penchés sur le rôle de TAK1 chez le neutrophile avec des stimuli dont les réponses cellulaires ne passent pas par l'activation de NF-kB. C'est dans cette perspective que nous avons utilisé un chimioattractant, le fMLP, et un facteur de croissance, le GM-CSF. Ce sont deux stimuli physiologiques fréquemment retrouvés aux sites inflammatoires. Le fMLP et le GM-CSF activent rapidement TAK1 et celle-ci se retrouve en amont de la voie MEK/ERK, mais pas des voies p38 MAPK et PI3K/AKT. L'inhibition de TAK1 diminue l'expression et la sécrétion d'IL-8 et d'IL-1RA. L'inhibition de MEK/ERK et de PI3K/AKT a le même effet. De plus, l'inhibition de TAK1 empêche l'effet antiapoptotique du GM-CSF ainsi que diminue la production de leucotriènes par le fMLP. En conclusion, les travaux présentés montrent que TAK1 est une MAP3K essentielle dans les réponses fonctionnelles du neutrophile au fMLP et au GM-CSF. Cette découverte ouvre la porte à de nouvelles cibles thérapeutiques, particulièrement dans le cas de maladies chroniques impliquant le GM-CSF

Feed drive modelling for the simulation of tool path tracking in multi-axis High Speed Machining

International audienceWithin the context of High Speed Machining, it is essential to manage the trajectory generation to achieve both high surface quality and high productivity. As feed drives are one part of the set Machine tool - Numerical Controller, it is necessary to improve their performances to optimize feed drive dynamics during trajectory follow up. Hence, this paper deals with the modelling of the feed drive in the case of multi axis machining. This model can be used for the simulation of axis dynamics and tool-path tracking to tune parameters and optimize new frameworks of command strategies. A procedure of identification based on modern NC capabilities is presented and applied to industrial HSM centres. Efficiency of this modelling is assessed by experimental verifications on various representative trajectories. After implementing a Generalized Predictive Control, reliable simulations are performed thanks to the model. These simulations can then be used to tune parameters of this new framework according to the tool-path geometry

Dynamics of small unilamellar vesicles

This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in J. Chem. Phys. 148, 104901 (2018) and may be found at https://doi.org/10.1063/1.5009424.In this paper, we investigate the dynamics of small unilamellar vesicles with the aid of neutron spin-echo spectroscopy. The purpose of this investigation is twofold. On the one hand, we investigate the influence of solubilised cosurfactant on the dynamics of the vesicle’s surfactant bilayer. On the other hand, the small unilamellar vesicles used here have a size between larger vesicles, with dynamics being well described by the Zilman-Granek model and smaller microemulsion droplets which can be described by the Milner-Safran model. Therefore, we want to elucidate the question, which model is more suitable for the description of the membrane dynamics of small vesicles, where the finite curvature of the bilayer is felt by the contained amphiphilic molecules. This question is of substantial relevance for our understanding of membranes and how their dynamics is affected by curvature, a problem that is also of key importance in a number of biological questions. Our results indicate the even down to vesicle radii of 20 nm the Zilman-Granek model appears to be the more suitable one.BMBF, 05K13KT1, Probenumgebung und paralle Charakterisierung bei hochpräzisen Neutronen Spin-Echo (NSE) Messungen an komplexen Systemen der weichen Materi

A small-angle neutron scattering environment for in-situ observation of chemical processes

A new sample environment for the observation of ongoing chemical reactions is introduced for small-angle neutron scattering (SANS) experiments which enables structural changes to be followed continuously across a wide Q-range in response to changes in the chemical environment. The approach is demonstrated and validated by performing single and multiple potentiometric titrations on an aqueous anionic surfactant solution (oligo-oxyethylene alkylether carboxylic acid in D2O) with addition times varying from 1s to 2h. It is shown that the continuous flow set-up offers considerable advantages over classical ‘static’ measurements with regards to sample throughput, compositional precision and the ability to observe fast structural transitions. Finally, the capabilities and ongoing optimisation of the sample environment are discussed with reference to potential applications in the fields of biology, colloidal systems and complex soft matter.DFG, 325093850, Open Access Publizieren 2017 - 2018 / Technische Universität Berli

Self-assembly mechanism of pH-responsive glycolipids : micelles, fibers, vesicles, and bilayers

A set of four structurally related glycolipids are described: two of them have one glucose unit connected to either stearic or oleic acid, and two other ones have a diglucose headgroup (sophorose) similarly connected to either stearic or oleic acid. The self-assembly properties of these compounds, poorly known, are important to know due to their use in various fields of application from cleaning to cosmetics to medical. At basic pH, they all form mainly small micellar aggregates. At acidic pH, the oleic and stearic derivatives of the monoglucose form, respectively, vesicles and bilayer, while the same derivatives of the sophorose headgroup form micelles and twisted ribbons. We use pH-resolved in situ small angle X-ray scattering (SAXS) under synchrotron radiation to characterize the pH-dependent mechanism of evolution from micelles to the more complex aggregates at acidic pH. By pointing out the importance of the COO-/COOH ratio, the melting temperature, T-m, of the lipid moieties, hydration of the glycosidic headgroup, the packing parameter, membrane rigidity, and edge stabilization, we are now able to draw a precise picture of the full self-assembly mechanism. This work is a didactical illustration of the complexity of the self-assembly process of a stimuli-responsive amphiphile during which many concomitant parameters play a key role at different stages of the process

Faunal and Archaeological Remains as Evidence of Climate Change in Freezing Caverns, Yukon Territory, Canada

Animal and plant remains, some associated with prehistoric artifacts, were collected in freezing caverns (glacières) of northern Yukon Territory. Radiocarbon dates show that the oldest remains are Middle Wisconsinan ca. 38 000 BP). The absence of material of Late Wisconsinan age likely indicates that the caves were infilled by ice during this cold period. Climate warming and ice melting during the Holocene allowed animals and prehistoric hunters to regularly visit these caves. Ice plugs were evidently smaller during the early Holocene than they are now.Des restes d'animaux et de plantes, parfois associés à des vestiges préhistoriques, ont été récoltés dans des glacières du nord du Territoire du Yukon. Leur âge radiocarbone indique que les plus anciens vestiges datent du Wisconsinien moyen (v. 38 000 BP). L'absence de matériel contemporain du Wisconsinien supérieur semble indiquer que pendant cette période froide les cavernes étaient comblées par de la glace. Au cours de l'Holocène, le réchauffement du climat et la fonte subséquente des glaces ont permis aux animaux et aux chasseurs préhistoriques de visiter les cavernes sur une base régulière. Les bouchons de glace étaient de toute évidence moins développés au début de l'Holocène qu'ils ne le sont aujourd'hui

Comparison of small‑angle neutron and X‑ray scattering for studying cortical bone nanostructure

In this study, we present a combined small-angle neutron and X-ray scattering (SANS and SAXS) study of the nanoscale structure of cortical bone specimens from three different species. The variation of the scattering cross section of elements across the periodic table is very different for neutrons and X-rays. For X-rays, it is proportional to the electron density while for neutrons it varies irregularly with the atomic number. Hence, combining the two techniques on the same specimens allows for a more detailed interpretation of the scattering patterns as compared to a single-contrast experiment. The current study was performed on bovine, porcine and ovine specimens, obtained in two perpendicular directions with respect to the main axis of the bone (longitudinal and radial) in order to maximise the understanding of the nanostructural organisation. The specimens were also imaged with high resolution micro-computed tomography (micro-CT), yielding tissue mineral density and microstructural orientation as reference. We show that the SANS and SAXS patterns from the same specimen are effectively identical, suggesting that these bone specimens can be approximated as a two-component composite material. Hence, the observed small-angle scattering results mainly from the mineral-collagen contrast, apart from minor features associated with the internal collagen structure

Formation and structure of slightly anionically charged nanoemulsions obtained by the phase inversion concentration (PIC) method

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.While nanoemulsions (10–200 nm) are not thermodynamically stable systems they can exhibit quite long term stability. In this paper oil/surfactant mixtures, containing diethylhexyl carbonate/phenoxyethanol/parabens as oil and polyglyceryl-4 laurate/dilauryl citrate as surfactant, form nanoemulsions simply by dilution with water, i.e. by means of the phase inversion concentration (PIC) method. In order to study this highly interesting phenomenon an investigation at constant oil-to-surfactant (O/S) ratio was done by means of viscosity, conductivity, and UV/Vis-transmittance measurements. This phase study as a function of the dilution by water shows that at an intermediate water content a two-phase system of bicontinuous structure is formed, which exhibits a very pronounced viscosity and conductivity maximum shortly before the homogeneous nanoemulsion phase is reached. In the same region SANS shows a high degree of ordering of this bicontinuous structure. SANS and cryo-TEM investigations of the nanoemulsion regime show an increasing average size with dilution and, more interestingly, the presence of two populations with different average particle sizes around 10–15 nm and 25–40 nm. The relative proportion of each population depends on the amount of added water, leading to an average growth of the particle size with increasing dilution