Oxydation de phospholipides polyinsaturés dans des systèmes membranaires biomimétiques (effets de molécules amphiphiles et d'enzymes antioxydantes)

Le stress oxydant résulte de l'altération par des radicaux libres de nombreuses cibles cellulaires. De nombreuses maladies ainsi que les phénomènes liés au vieillissement découlent de ces attaques radicalaires. Afin de mieux cerner les processus physiopathologiques liés au stress oxydant, nous nous sommes intéressés à l'oxydation lipidique des membranes dans un système membranaire biomimétique : les monocouches de Langmuir. Les études ont porté sur l'oxydation d'un phospholipide polyinsaturé, la 1,2-dilinoléoyl-sn-glycéro-3-phosphocholine (DLiPC). L'oxydation de la DLiPC, réalisée par exposition à un rayonnement UV à 254 nm, se traduit par une diminution de l'aire moléculaire. Après irradiation, les isothermes de compression et le module d'élasticité de surface révèlent l'apparition de nouvelles espèces moléculaires à l'interface air-eau. Grâce à ce système d'analyse, nous avons testé les propriétés d'agents anti-oxydants naturels (plasmalogène et cholestérol) et d'antioxydants synthétiques (dérivés de l' -phényl-N-tert-butylnitrone). En déterminant le temps de latence, précédent la diminution d'aire moléculaire, ainsi que l'amplitude de cette diminution, l'effet protecteur de ces molécules a pu être quantifié. Nous avons ensuite comparé les propriétés interfaciales des deux enzymes impliquées dans le stress oxydant : les peroxydases à glutathion (GPx) de type 1 et 4. Les différences de comportement observées pour les deux GPx indiquent une affinité différente selon la nature du phospholipide insaturé à l'interface air-eau pour la GPx-4 ce qui n'est pas le cas pour la GPx-1. Nous avons également caractérisé les propriétés interfaciales des adduits de Michaël qui résultent de la modification de phospholipides par des produits d'oxydation.LYON1-BU.Sciences (692662101) / SudocSudocFranceF

PBN derived amphiphilic spin-traps. II/Study of their antioxidant properties in biomimetic membranes.

International audienceThe work reported herein deals with the evaluation of the antioxidant properties of bitailed amphiphilic ␣-phenyl-N-tert-butylnitrone derivatives (BPBNs) towards oxidation of an unsaturated lipid, the 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLoPC). Oxidation was induced either by UV light irradiation or radical initiators, i.e. the water soluble AAPH and the Fenton reaction, and the antioxidant evaluation was carried out using two biomimetic systems, namely Langmuir monolayers and large unilamellar vesicles. Measurement of the molecular area and the membrane fluidity of pure nitrone monolayers before and after UV-irradiation demonstrated the better stability and antioxidant properties of B 17 PBN, the derivative with two C 17 H 35 alkyl chains, compared to its analogue B 11 PBN with two C 11 H 23 alkyl chains. At only 5% molar ratio of nitrone in mixed DLoPC/nitrone monolayers, a complete inhibition of the molecular area decrease was observed for B 17 PBN whereas B 11 PBN showed lower protection. The oxidation of mixed DLoPC/nitrones large unilamellar vesicles in the presence of free radicals arising from AAPH decomposition or Fenton reaction was assessed by measuring lipid conjugated dienes and thiobarbituric acid reactive substances on the whole series of nitrone, i.e. C 11-, C 13-, C 15-and C 17-based compounds. Compared to the saturated 1,2-dimyristoyl-sn-glycero-3-phosphocholine, all bitailed amphiphilic nitrones were able to decrease conjugated dienes and TBARS in both oxidative paradigms, demonstrating therefore antioxidant property. The inhibition of phospholipids oxidation was increased when increasing the concentration of nitrone with the two B 11 PBN and B 13 PBN derivatives exhibiting higher potency. This study underlines the importance in the choice of a model membrane system when evaluating the potency of antioxidants against lipid oxidation

Plasmalogens protect unsaturated lipids against UV-induced oxidation in monolayer

AbstractOxidative stress results from the attack by free radicals of several cellular targets (proteins, DNA and lipids). The cell equilibrium is a direct consequence of the pro-/antioxidant balance. In order to understand the physiological processes involved in oxidative stress, we followed oxidation of unsaturated lipids using a biomimetic system: Langmuir monolayers. The oxidation mode chosen was UV-irradiation and the lipid model was a polyunsaturated phospholipid: 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC). The monomolecular film technique was used to measure membrane rheology before and after UV-irradiation. We showed that the UV-irradiation of a DLPC monomolecular film led to a molecular area and surface elasticity modulus decrease that attests to the apparition of new molecular species at the air–water interface. The antioxidant effect of a synthetic plasmalogen (1-O-(1′-(Z)-hexadecenyl)-2-O-oleoyl-sn-glycero-3-phosphocholine or PPLMOPE) was tested on the oxidation of DLPC. Indeed, for about 25% mol PPLMOPE in mixed DLPC/PPLMOPE monolayers, a complete inhibition of the molecular area and the surface elasticity modulus decreases was observed in our experimental conditions. Lower PPLMOPE quantities delayed but did not prevent the DLPC oxidation in mixed monolayers

The CMS Statistical Analysis and Combination Tool: COMBINE

International audienceThis paper describes the COMBINE software package used for statistical analyses by the CMS Collaboration. The package, originally designed to perform searches for a Higgs boson and the combined analysis of those searches, has evolved to become the statistical analysis tool presently used in the majority of measurements and searches performed by the CMS Collaboration. It is not specific to the CMS experiment, and this paper is intended to serve as a reference for users outside of the CMS Collaboration, providing an outline of the most salient features and capabilities. Readers are provided with the possibility to run COMBINE and reproduce examples provided in this paper using a publicly available container image. Since the package is constantly evolving to meet the demands of ever-increasing data sets and analysis sophistication, this paper cannot cover all details of COMBINE. However, the online documentation referenced within this paper provides an up-to-date and complete user guide

Dark sector searches with the CMS experiment

Astrophysical observations provide compelling evidence for gravitationally interacting dark matter in the universe that cannot be explained by the standard model of particle physics. The extraordinary amount of data from the CERN LHC presents a unique opportunity to shed light on the nature of dark matter at unprecedented collision energies. This Report comprehensively reviews the most recent searches with the CMS experiment for particles and interactions belonging to a dark sector and for dark-sector mediators. Models with invisible massive particles are probed by searches for signatures of missing transverse momentum recoiling against visible standard model particles. Searches for mediators are also conducted via fully visible final states. The results of these searches are compared with those obtained from direct-detection experiments. Searches for alternative scenarios predicting more complex dark sectors with multiple new particles and new forces are also presented. Many of these models include long-lived particles, which could manifest themselves with striking unconventional signatures with relatively small amounts of background. Searches for such particles are discussed and their impact on dark-sector scenarios is evaluated. Many results and interpretations have been newly obtained for this Report.Astrophysical observations provide compelling evidence for gravitationally interacting dark matter in the universe that cannot be explained by the standard model of particle physics. The extraordinary amount of data from the CERN LHC presents a unique opportunity to shed light on the nature of dark matter at unprecedented collision energies. This Report comprehensively reviews the most recent searches with the CMS experiment for particles and interactions belonging to a dark sector and for dark-sector mediators. Models with invisible massive particles are probed by searches for signatures of missing transverse momentum recoiling against visible standard model particles. Searches for mediators are also conducted via fully visible final states. The results of these searches are compared with those obtained from direct-detection experiments. Searches for alternative scenarios predicting more complex dark sectors with multiple new particles and new forces are also presented. Many of these models include long-lived particles, which could manifest themselves with striking unconventional signatures with relatively small amounts of background. Searches for such particles are discussed and their impact on dark-sector scenarios is evaluated. Many results and interpretations have been newly obtained for this Report

Search for long-lived heavy neutrinos in the decays of B mesons produced in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search for long-lived heavy neutrinos (N) in the decays of \PB mesons produced in proton-proton collisions at $\sqrt{s}$ = 13 TeV is presented. The data sample corresponds to an integrated luminosity of 41.6 fb$^{-1}$ collected in 2018 by the CMS experiment at the CERN LHC, using a dedicated data stream that enhances the number of recorded events containing B mesons. The search probes heavy neutrinos with masses in the range 1 $\lt$$m_\mathrm{N}$$\lt$ 3 GeV and decay lengths in the range 10$^{-2}$$\lt$$c\tau$$\lt$ 10$^{4}$ mm, where $\tau_\mathrm{N}$ is the N proper mean lifetime. Signal events are defined by the signature B $\to$$\ell_\mathrm{B}$NX; N $\to$$\ell^{\pm} \pi^{\mp}$, where the leptons $\ell_\mathrm{B}$ and $\ell$ can be either a muon or an electron, provided that at least one of them is a muon. The hadronic recoil system, X, is treated inclusively and is not reconstructed. No significant excess of events over the standard model background is observed in any of the $\ell^{\pm}\pi^{\mp}$ invariant mass distributions. Limits at 95% confidence level on the sum of the squares of the mixing amplitudes between heavy and light neutrinos, $\vert V_\mathrm{N}\vert^2$, and on $c\tau$ are obtained in different mixing scenarios for both Majorana and Dirac-like N particles. The most stringent upper limit $\vert V_\mathrm{N}\vert^2$ $\lt$ 2.0$\times$10$^{-5}$ is obtained at $m_\mathrm{N}$ = 1.95 GeV for the Majorana case where N mixes exclusively with muon neutrinos. The limits on $\vert V_\mathrm{N}\vert^2$ for masses 1 $\lt$ $m_\mathrm{N}$ $\lt$ 1.7 GeV are the most stringent from a collider experiment to date

Search for flavor-changing neutral current interactions of the top quark mediated by a Higgs boson in proton-proton collisions at 13 TeV

International audienceA search for flavor-changing neutral current interactions of the top quark (t) and the Higgs boson (H) is presented. The search is based on proton-proton collision data collected in 2016-2018 at a center-of-mass energy of 13 TeV with the CMS detector at the LHC, and corresponding to an integrated luminosity of 138 fb$^{-1}$. Events containing a pair of leptons with the same-sign electric charge and at least one jet are considered. The results are used to constrain the branching fraction ($\mathcal{B}$) of the top quark decaying to a Higgs boson and an up (u) or charm (c) quark. No significant excess above the estimated background was found. The observed (expected) upper limits at 95% confidence level are found to be 0.072% (0.059%) for $\mathcal{B}$(t $\to$ Hu) and 0.043% (0.062%) for $\mathcal{B}$(t $\to$ Hc). These results are combined with two other searches performed by the CMS Collaboration for flavor-changing neutral current interactions of top quarks and Higgs bosons in final states with a pair of photons or of bottom quarks. The resulting observed (expected) upper limits at 95% confidence level are 0.019% (0.027%) for $\mathcal{B}$(t $\to$ Hu) and 0.037% (0.035%) for $\mathcal{B}$(t $\to$ Hc). These results constitute the most stringent limits on these branching fractions to date