Balancing the immune response in the brain: IL-10 and its regulation

Background: The inflammatory response is critical to fight insults, such as pathogen invasion or tissue damage, but if not resolved often becomes detrimental to the host. A growing body of evidence places non-resolved inflammation at the core of various pathologies, from cancer to neurodegenerative diseases. It is therefore not surprising that the immune system has evolved several regulatory mechanisms to achieve maximum protection in the absence of pathology. Main body: The production of the anti-inflammatory cytokine interleukin (IL)-10 is one of the most important mechanisms evolved by many immune cells to counteract damage driven by excessive inflammation. Innate immune cells of the central nervous system, notably microglia, are no exception and produce IL-10 downstream of pattern recognition receptors activation. However, whereas the molecular mechanisms regulating IL-10 expression by innate and acquired immune cells of the periphery have been extensively addressed, our knowledge on the modulation of IL-10 expression by central nervous cells is much scattered. This review addresses the current understanding on the molecular mechanisms regulating IL-10 expression by innate immune cells of the brain and the implications of IL-10 modulation in neurodegenerative disorders. Conclusion: The regulation of IL-10 production by central nervous cells remains a challenging field. Answering the many remaining outstanding questions will contribute to the design of targeted approaches aiming at controlling deleterious inflammation in the brain.We acknowledge the Portuguese Foundation for Science and Technology (FCT) for providing a PhD grant to DLS (SFRH/BD/88081/2012) and a post-doctoral fellowship to SR (SFRH/BPD/72710/2010). DS, AGC and SR were funded by FEDER through the Competitiveness Factors Operational Programme (COMPETE) and National Funds through FCT under the scope of the project POCI-01-0145-FEDER007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The MS lab was financed by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT in the framework of the project “Institute for Research and Innovation in Health Sciences ” (POCI-01-0145-FEDER-007274). MS is a FCT Associate Investigator. The funding body had no role in the design of the study and collection, analysis, and interpretation of the data and in writing the manuscript

Loading rate effect on lateral force measurements on nanostructured Ti and TiN thin films

International audienceTribological properties of titanium and titanium nitride nanostructured thin films as well as of silicon substrate have been studied. We report onthe effect of lateral tip displacement direction and normal force loading mode on lateral force measurements. On hard coatings such as titaniumnitride thin films, we show that the tip's scratch direction has almost no effect on lateral force measurements. A completely different behaviour hasbeen observed on titanium films. In this last case, the measured lateral force is very dependent on the scratch direction.Concerning the effect of normal force loading mode, we will show how the loading rate, rather than the sliding speed, is a very importantparameter in the case of a ramping normal load. For this purpose we have performed two sets of six scratches, for each sample. Scratch length wasfixed to 10 μm in all cases.In the first set, the scratch length and duration were kept constant. In the second one, the scratch duration was tuned in order to achieve aconstant value of the normal loading rate dFzdt. In this last case, the experimental data leads to a unique curve. This means that during nanoscratchmeasurements, normal tip displacement is controlled by the normal force loading rate. Consequently, lateral displacement speed dxdtmust be tunedin order to obtain the required value of dFzdt. This behaviour seems to be universal and not related to material hardness and Young modulus.© 2005 Elsevier B.V. All rights reserved

Propriétés tribologiques de films minces nanostructurés

International audienceTribological properties of nanostructured thin films. In order todetermine the tribological properties of nanostructured thin layers of titanium andtitanium nitride with thicknesses of 300 nm, we have studied the influence of Berkovichtip’s lateral displacement orientation and normal loading rate on friction properties.For the hardest films (titanium nitride), we have showed that tip direction scratch doesnot have any effect on tribological properties. A completely different behavior isobserved for titanium. For this last case, the measured lateral force is smaller whenthe scratch test is carried out following forward tip direction. Concerning dynamicseffect on scratch measurements, we have established scaling laws for normaldisplacement versus normal force. We have showed that the relevant parameter forscratch measurements is the loading rate , deduced from these scaling laws. Thus,during scratch tests, the lateral displacement speed must be adapted to the maximumvalue of the applied normal load.Afin de déterminer les propriétés tribologiques de couches mincesnanostructurées de nitrure de titane et de titane de 300 nm d’épaisseur, nous avonsétudié l’influence du sens de déplacement latéral d’une pointe Berkovich et du tauxde chargement normal sur le comportement en frottement. Pour les films les plus durs(nitrure de titane), nous avons montré que le sens de déplacement latéral de la pointen’a aucun effet sur les propriétés tribologiques. Un comportement complètementdifférent est observé pour les films les moins durs (titane). Dans ce dernier cas, laforce latérale mesurée est plus faible lorsque le scratch test est effectué vers l’avantde la pointe. En ce qui concerne l’effet de la dynamique sur les mesures de scratch,nous avons établi des lois d’échelle pour le déplacement normal en fonction de la forcenormale. Nous avons montré que le paramètre pertinent pour les mesures est le tauxde chargement , déduit des lois d’échelle. Ainsi, durant les essais de rayures, lavitesse de déplacement latéral doit être adaptée à la valeur maximale de l’effort normalappliqué

Analysis of the accumulation of radiation damage in selected crystals

International audienceDamage accumulation in SiC and MgAl2O4 was interpreted in the framework of the multi step damage accumulation (MSDA) model. The concept is based on the assumption that damage build-ups occur in several stages, each step being triggered by the destabilization of the current structural organization of the material. The analysis of the damaging process may thus be regarded as an identification of the current structure at each subsequent step of the damage build-up and of the forces leading to the destabilization of current structure. The analysis of mechanical properties provides a useful tool for this purpose by allowing the recognition of the mechanisms of phase transformations and helping to clarify the detailed structures of irradiated materials. (C) 2008 Elsevier B.V. All rights reserved

Déformation inélastique induite par nanoindentation cyclique de verres métalliques à base de Zirconium

International audienceInelastic deformation induced by cyclic nanoindentation in Zr-basedbulk metallic glasses. Monotonic and cyclic nanoindentation tests were carried out onZr50Cu40Al10 bulk metallic glass (BMG) at loading rates ranging from 250 to 2500 μN/s andat ambient temperature. We found that cyclic loadings induced a mechanical softeningwhich appears to be dependent on the number of cycles and the loading rates. The effectof loading rates was compared with the same nanoindentation tests on specimens of Zrbasedmetallic glass coated with CrN and TiN films. The inelastic deformation on Zr-basedmetallic glass was studied by analysing the remnant indent morphology using atomic forcemicroscopy. A free-volume mechanism was proposed for interpreting these observationsquantitatively.Des essais de nanoindentation instrumenté pour des chargements monotoneset cycliques sur deux verres métalliques massifs (VMM) à base Zirconium ont été réalisésà température ambiante et avec une vitesse de chargement qui varie de 250 à 2500 μN/s.Nous avons trouvé que les chargements cycliques induisent un adoucissement qui sembleêtre dépendant du nombre de cycles et du taux de chargement. L’effet de la vitesse de chargementa été comparé avec des essais effectués sur des échantillons du verre métallique àbase Zirconium revêtus par des films de TiN et de CrN. La déformation inélastique dans leverre métallique à base Zirconium a été étudiée en analysant par microscopie à force atomiqueles empreintes résultantes des essais de nanoindentation. Le mécanisme de volumelibre est proposé pour l’interprétation quantitative de ces observations

Nanomechanical measurements of irradiated layers: Methodology, possibilities and pitfalls

International audienceIon irradiation is frequently used to tailor functional properties of materials or to simulate the effects caused by ionizing radiations. In both cases the evolution of the mechanical properties of materials upon irradiation is of crucial importance. However, reliable and quantitative determination of the mechanical properties of irradiated materials is a rather complicated task. In this paper a discussion of the methodology used for nanomechanical measurements of irradiated layers is presented with a special emphasis on the description of possible experimental errors. The possibilities offered by nanornechanical studies for the interpretation of structural transformations in irradiated materials are also discussed. The study has been performed on irradiated Sic and MgAl(2)O(4) crystals. (C) 2009 Elsevier Ltd. All rights reserved

Mechanical properties of irradiated spinel ceramic

International audienceThe effects of grain size on the nanomechanical properties of Ar-irradiated magnesium-aluminate spinels was studied. Spinel single crystals and ceramics of different grain size varying from similar to 1 mu m up to few tens of micrometers were used in the experiments. The measurements were performed in both grain centers and grain boundaries and point to rapidly disappearing differences between bulk and boundaries in irradiated ceramics. The stress-induced hardening has been observed as well. This last effect depends on the grain size of the irradiated material and may serve as an indicator of the stress evolution in the irradiated samples. (c) 2010 Elsevier B.V. All rights reserved

Templated polycondensation of aminopropyltrimethoxysilane on DNA

International audienceThe polycondensation of a silane derivative such asaminopropyltrimethoxysilane (ATMS) in the presence of DNA was investigated in an organicsolvent for the first time. Here, NMR observation showed that the hydrolysis step of ATMSbefore polycondensation was faster when the reaction was carried out in presence of doublestranded DNA (146 bp) in chloroform. In order to test the specificity of this enhancementeffect, the influence of the different components of DNA on ATMS hydrolysis and/orpolycondensation was then investigated using different bases, nucleosides and nucleotides.The results showed that the kinetics of ATMS hydrolysis was affected by the typeofnucleotide units used, the faster hydrolysis reaction rate being observed with moleculescontaining adenosine group, and that in the absence of water the amino group ofdeoxyadenosine units can react with ATMS methoxy groups

Nanohardness and brittleness of irradiated spinel ceramics

International audienceThe influence of the size of crystalline regions on mechanical properties of irradiated oxides has been studied using magnesium aluminate spinel MgAl2O4. The samples characterized by different dimensions of crystalline domains, from sintered ceramics with grains of few micrometers in size up to single crystals, were used in the experiments. The samples were irradiated at room temperature with 320 keV Ar2+ ions up to fluences reaching 5 × 1016 cm−2. Nanomechanical properties were measured by using a nanoindentation technique and the resistance to crack formation by measurement of the total crack lengths made by Vickers indenter. The results revealed: correlation of nanohardness with accumulated damage, radiation-induced hardness increase in grain-boundary region and significant improvement of material resistance to crack formation

Micromechanical Properties of Nanometer-Thick Layers of Implanted Alumina

International audienc