µ-Calpain Conversion of Antiapoptotic Bfl-1 (BCL2A1) into a Prodeath Factor Reveals Two Distinct alpha-Helices Inducing Mitochondria-Mediated Apoptosis

Anti-apoptotic Bfl-1 and pro-apoptotic Bax, two members of the Bcl-2 family sharing a similar structural fold, are classically viewed as antagonist regulators of apoptosis. However, both proteins were reported to be death inducers following cleavage by the cysteine protease µ-calpain. Here we demonstrate that calpain-mediated cleavage of full-length Bfl-1 induces the release of C-terminal membrane active α-helices that are responsible for its conversion into a pro-apoptotic factor. A careful comparison of the different membrane-active regions present in the Bfl-1 truncated fragments with homologous domains of Bax show that helix α5, but not α6, of Bfl-1 induces cell death and cytochrome c release from purified mitochondria through a Bax/Bak-dependent mechanism. In contrast, both helices α5 and α6 of Bax permeabilize mitochondria regardless of the presence of Bax or Bak. Moreover, we provide evidence that the α9 helix of Bfl-1 promotes cytochrome c release and apoptosis through a unique membrane-destabilizing action whereas Bax-α9 does not display such activities. Hence, despite a common 3D-structure, C-terminal toxic domains present on Bfl-1 and Bax function in a dissimilar manner to permeabilize mitochondria and induce apoptosis. These findings provide insights for designing therapeutic approaches that could exploit the cleavage of endogenous Bcl-2 family proteins or the use of Bfl-1/Bax-derived peptides to promote tumor cell clearance

Carbon nanoparticles from local biomass for tribological applications First results

International audienceFriction and wear phenomena are the main causes of the decrease in performances and durability of mechanical systems. Manufacturing techniques for metal parts must meet the growing economic demands of the market, such as improved material durability, reduced maintenance costs and energy consumption. The use of tribology is essential and constitutes an important economic issue. Pure lubricating bases (mineral or synthetic oil) cannot provide all protective functions, so that additives are added to improve their reducing properties of friction and wear. New lubrication strategies use dispersed colloidal particles in lubricants. The approach is to supply the sliding contact with solid particles, which can instantly form the tribological film. My thesis project focuses on the synthesis of new friction reducer additives from local biomass, in order to produce ecofriendly lubricants. These new carbon phases are obtained using the spray-pyrolysis technique [1] with sugarcane from local biomass. It consists in nebulizing a solution of saccharose in the form of micro-droplets, transported to a tubular oven heated at temperatures ranging from 800°C to 1000°C. The first results have permitted to see the effects of the different synthesis conditions, i.e. oven temperature, catalyst concentration and carrier gas pressure, using scanning electron microscopy to observe the spherical shape and the porosity of the particles. This part will concern the tribological properties of our particles, measured with a sphere/plan contact tribometer. The effect of an annealing process on these particles will also be studied

FROM SUGARCANE TO CARBON NANOSPHERES FOR TRIBOLOGICAL APPLICATIONS

International audienceFriction and wear phenomena are the main causes of the decrease in performances and durability of mechanical systems. The use of tribology, defined as the science that studies the phenomena of friction, wear and lubrication, is essential and constitutes an important economic issue. It is the role of lubrication to minimize friction and protect surfaces from wear. The strategy used to reduce these phenomena is to introduce a lubricant between the sliding surfaces. This lubricant can be solid, liquid or gaseous, and must prevent direct contact between surfaces, with specific properties such as friction reduction, anti-oxidizing or antiwear action. Pure lubricating bases (mineral or synthetic oil) cannot provide all protective functions, so that additives are added to improve their reducing properties of friction and wear. New lubrication strategies use dispersed nanoparticles in lubricants. The approach is to supply the sliding contact with solid particles, which can instantly form a protected low shearing tribological film. This work focuses on the synthesis of new friction reducer additives from local biomass, in order to produce ecofriendly lubricants. These new carbon phases are obtained using the spray-pyrolysis technique [1] with sugarcane from local biomass. It consists in nebulizing a solution of saccharose in the form of micro-droplets, transported to a tubular oven heated at temperatures ranging from 800°C to 1000°C, in order to obtain carbon nanospheres. The first results have permitted to evidence the effects of synthesis conditions (oven temperature, catalyst concentration and carrier gas pressure), on the nanoparticles morphology, using scanning electron microscopy. Raman spectroscopy gives us information about the graphitization degree of the carbon phase .The effect of an annealing process on these particles is studied in order to improve the nanospheres tribological propertie

From sugarcane to carbon nanospheres for tribological applications

International audienc

Utilisation des (nano)carbones pour la mise au point de nouvelles générations de lubrifiants.

International audienc

PReS-FINAL-2173: Protein kinase C delta deficiency is a new cause of monogenic SLE

International audienceObjectives Our objective was to identify the cause of an autosomalrecessive form of SLE in an inbred family with threeaffected siblings.MethodsWe investigated three siblings and used next generationsequencing to identify mutations in the disease-associatedgene. We performed extensive biochemical, immunologi-cal and functional assays to assess the impact of the identi-fied mutations on B cell biology.ResultsGenetic mapping and targeted exome sequencing lead tothe identification of a homozygous mutation in PRKCD,encoding protein kinase C delta (PKCδ). Mutation ofPRKCD resulted in reduced expression and activity ofencoded protein PKCδ.Inmouse,PKCδplays a crucialrole in the deletion of autoreactive B cells. As for micedeficient in PKCδ, we demonstrated that B cells display aresistance to calcium-dependent apoptosis and a higherproliferation rate associated with an increase of immatureB cells in affected patients, and a developmental shifttoward an immature phenotype of naïve B cells. Conclusion Our findings indicate that PKCδis crucial in regulating B cell tolerance and preventing self-reactivity in humans