287 research outputs found
Metabolism of apolipoproteins AI and AII in subjects carrying similar apoAI mutations, apoAI Milano and apoAI Paris
No full textApoAI Milano (AI(M)) and apoAI Paris (AI(P)) are mutant forms of apoAI in which cysteine is substituted for arginine at residues 173 and 151 respectively leading to the formation of homodimers and heterodimers with apoAII. Heterozygous subjects with these mutants are characterized by low levels of plasma HDL cholesterol and apoAI. The present study analyzed the metabolism of the different complexes of apoAI in three subjects, two AI(M) and one AI(P), using a primed-constant infusion of trideuterated leucine. In AI(M) carriers, the mutant form was almost equally distributed in AI(M) dimer, AI(M):AII heterodimer and the monomer, whereas, in the AI(P) subject, the mutant apoAI was essentially in the apoAI(P):AII complex. Normal apoAI was low in the AI(M) subjects (20 and 16 mg/dl) but very low in the AI(P) subject (0.3 mg/dl). In the AI(M) subjects, the low levels of apoAI were due to a rapid catabolism with a normal synthetic rate. However, the apoAI kinetics were heterogeneous with a rapid catabolism of the AI(M):AII complex (FCR of 0.430 and 0.401 day-1) and the AI(M) monomer (FCR of 0.570 and 0.406 day-1) whereas the AI(M) dimer was catabolized slowly (FCR of 0.114 and 0.118 day-1). In contrast, AI(P) was catabolized relatively slowly with a FCR of 0.263, 0.182 and 0.258 day-1 for AI(P) homodimer, apoAI(P):AII heterodimer and AI(P) monomer. In the three subjects, normal apoAI was catabolized quickly, with an FCR of 0.805 and 0.601 day-1 in AI(M) carriers and 0.526 day-1 in the AI(P) carrier. Therefore, the low level of apoAI in the AI(P) carrier is caused by a low production rate of apoAI, particularly of normal apoAI. In conclusion, apoAI is kinetically heterogeneous in AI(M) and in AI(P) subjects. Moreover, the two mutations lead to significant differences in the kinetic behavior of mutant apoAI depending on its inclusion in its complexes. Copyright (C) 2000 Elsevier Science Ireland Ltd
PPARalpha inhibits vascular smooth muscle cell proliferation underlying intimal hyperplasia by inducing the tumor suppressor gene p16INK4a
No full textVascular SMC proliferation is a crucial event in occlusive cardiovascular diseases. PPAR alpha is a nuclear receptor controlling lipid metabolism and inflammation, but its role in the regulation of SMC growth remains to be established. Here, we show that PPARa. controls SMC cell-cycle progression at the G(1)/S transition by targeting the cyclin-dependent kinase inhibitor and tumor suppressor p16(INK4a) (p16), resulting in an inhibition of retinoblastoma protein phosphorylation. PPARa activates p16 gene transcription by both binding to a canonical PPAR-response element and interacting with the transcription factor Sp1 at specific proximal Sp1-binding sites of the p16 promoter. In a carotid arterial-injury mouse model, p16 deficiency results in an enhanced SMC proliferation underlying intimal hyperplasia.. Moreover, PPAR alpha activation inhibits SMC growth in vivo, and this effect requires p 16 expression. These results identify an unexpected role for p16 in SMC cell-cycle control and demonstrate that PPARa. inhibits SMC proliferation through p16. Thus, the PPAR alpha/p16 pathway may be a potential pharmacological target for the prevention of cardiovascular occlusive complications of atherosclerosis
Magnetic properties of self-assembled FeRh nanomagnets
No full textMagnetické nanočástice a nanostrukturované materiály jsou velkým příslibem v mnoha oblastech, včetně biomedicíny, sanace životního prostředí nebo získávání energie. Proto neustále roste zájem o výzkum jejich jedinečných vlastností a vývoj uskutečnitelných výrobních postupů. Tato práce se zabývá metodou samouspořádávání, spočívající v povrchové precipitaci tenkých vrstev, za účelem výroby epitaxních polí nanoostrůvků ze slitiny FeRh na různých monokrystalických substrátech. Při tomto výrobním postupu zůstává zachována metamagnetická fázová přeměna nanoostrůvků. Morfologie a magnetické vlastnosti samouspořádaných nanomagnetů z FeRh jsou charakterizovány kombinací experimentálních technik a modelování, přičemž bylo zjištěno, že jejich rovnovážné tvary a magnetické uspořádání jsou navzájem propojeny. Kromě toho je navržena cesta pro získání volných nanočástic, která by mohla potenciálně umožnit využití metamagnetických nanostruktur v buněčných kulturách a biomedicíně obecně. Za tímto účelem jsou nanoostrůvky FeRh uvolňovány ze substrátu chemickým leptáním. Chování nanočástic a jejich reakce na teplotu a magnetické pole jsou studovány v kapalném prostředí. Metamagnetické vlastnosti separovaných nanočástic jsou charakterizovány pomocí vibrační magnetometrie
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No full textStructural Model of Ligand-G Protein-coupled Receptor (GPCR) Complex Based on Experimental Double Mutant Cycle Data
No full textInternational audienceThe snake toxin MT7 is a potent and specific allosteric modulator of the human M1 muscarinic receptor (hM1). We previously characterized by mutagenesis experiments the functional determinants of the MT7-hM1 receptor interaction (FruchartGaillard, C., Mourier, G., Marquer, C., Stura, E., Birdsall, N. J.,and Servent, D. (2008) Mol. Pharmacol. 74, 1554–1563) and more recently collected evidence indicating that MT7 may bind to a dimeric form of hM1 (Marquer, C., Fruchart-Gaillard, C., Mourier, G., Grandjean, O., Girard, E., le Maire, M., Brown, S., and Servent, D. (2010) Biol. Cell 102, 409– 420). To structurally characterize the MT7-hM1 complex, we adopted a strategy combining double mutant cycle experiments and molecular modeling calculations. First, thirty-three ligand-receptor proximities were identified from the analysis of sixty-one double mutant binding affinities. Several toxin residues that are more than 25 A˚ apart still contact the same residues on the receptor. As a consequence, attempts to satisfy all the restraints by docking the toxin onto a single receptor failed. The toxin was then positioned onto two receptors during five independent flexible docking simulations. The different possible ligand and receptor extracellular loop conformations were described by performing simulations in explicit solvent. All the docking calculations converged to the same conformation of the MT7-hM1 dimer complex, satisfying the experimental restraints and in which (i) the toxin interacts with the extracellular side of the receptor, (ii) the tips of MT7 loops II and III contact one hM1 protomer, whereas the tip of loop I binds to the other protomer, and (iii) the hM1dimeric interface involves the transmembrane helices TM6 and TM7. These results structurally support the high affinity and selectivity of the MT7-hM1 interaction and highlight the atypical mode of interaction of this allosteric ligand on its G proteincoupled receptor target
Calculation Of The Giant Magnetocaloric Effect In The Mnfep 0.45as0.55 Compound
No full textWe report the theoretical investigations on the giant magnetocaloric compound MnFeP0.45As0.55. The magnetic state equation used takes into account the magnetoelastic effect that leads the magnetic system to order under first order paramagnetic-ferromagnetic phase transition. The model parameters were determined from the magnetization data adjustment and used to calculate the magnetocaloric thermodynamic quantities. The theoretical calculations are compared with the available experimental data.709944101-094410-5Yu, B.F., Gao, Q., Zhang, B., Mang, X.Z., Chen, Z., (2003) Int. J. Refrig., 26, p. 622Gschneidner Jr., K.A., Pecharsky, V.K., (1997) Rare Earths: Science, Technology and Application III, , edited by R. C. Bautista, C. O. Bounds, T. W. Ellis, and B. T. Kilbourn The Minerals, Metals & Materials Society, WarendaleBrown, G.V., (1976) J. Appl. Phys., 47, p. 3673Pecharsky, V.K., Gschneidner Jr., K.A., (1997) Phys. Rev. Lett., 78, p. 4494Tegus, O., Brück, E., Buschow, K.H.J., De Boer, F.R., (2002) Nature, 415, p. 150. , LondonMorellon, L., Algarabel, P.A., Ibarra, M.R., Blasco, J., García-Landa, B., Arnold, Z., Albertini, F., (1998) Phys. Rev. B, 58, pp. R14721Rodbell, D.S., (1961) Phys. Rev. Lett., 7, p. 1Bean, C.P., Rodbell, D.S., (1961) Phys. Rev., 126, p. 104Bacmann, M., Soubeyroux, J.-L., Barrett, R., Fruchart, D., Zach, R., Niziol, S., Fruchart, R., (1983) J. Magn. Magn. Mater., 134, p. 59Brück, E., Tegus, O., Li, X.W., Deboer, F.R., Buschow, K.H.J., (2003) Physica B, 327, p. 431Tegus, O., Brück, E., Zhang, L., Dagula, Buschow, K.H.J., De Boer, F.R., (2002) Physica B, 319, p. 174Zach, R., Guillot, M., Tobola, J., (1998) J. Appl. Phys., 83, p. 7237Tegus, O., (2003) Novel Materials for Magnetic Refrigeration, , PhD thesis, Van der Waals-Zeeman Instituut, Universiteit van Amsterdam, Printer Partners Ipskamp B. V., ISBN: 9057761076, OctoberVon Ranke, P.J., Grangeia, D.F., Caldas, A., De Oliveira, N.A., (2003) J. Appl. Phys., 93, p. 4055Wada, H., Tanabe, Y., (2001) Appl. Phys. Lett., 79, p. 3302Wada, H., Morikawa, T., Taniguchi, K., Shibata, T., Yamada, Y., Akishige, Y., (2003) Physica B, 328, p. 11
Computation of topological phase diagram of disordered Pb1-xSnxTe using the kernel polynomial method
No full textWe present an algorithm to determine topological invariants of inhomogeneous systems, such as alloys, disordered crystals, or amorphous systems. Based on the kernel polynomial method, our algorithm allows us to study samples with more than 107 degrees of freedom. Our method enables the study of large complex compounds, where disorder is inherent to the system. We use it to analyze Pb1-xSnxTe and tighten the critical concentration for the phase transition. Moreover, we obtain the topological phase diagram for related alloys in the family of three-dimensional mirror Chern insulators.QRD/Kouwenhoven LabQN/Akhmerov Grou
Influence of the materials magnetic state on the accurate determination of the magnetocaloric effect
No full textIn this paper, we report a detailed study of the magnetocaloric effect (MCE) in different first order magnetic transition (FOMT) materials with different situation of the magnetic state (magnetic order). For this purpose, R-Co2, MnAs based compounds were considered in this study. The MCE is discussed in terms of Maxwell relation (MR) and Clausius-Clapeyron (C-C) equation. The deviation observed between both methods is discussed and analyzed. On the other hand, practically all the reported data of the MCE in the literature are associated to the applied external magnetic field and have not been corrected taking into account the demagnetization effect related to the materials shape. The obtained results demonstrate that this phenomenon can alter drastically the MCE values by cancelling out a large part of the external field, resulting in spurious values of the measured MCE. The effect of the demagnetization field on the magnetocaloric performances is also the subject of this paper
Antioxidant Quercetin 3-O-Glycosylated Plant Flavonols Contribute to Transthyretin Stabilization
No full textPlants are rich in secondary metabolites, which are often useful as a relevant source of nutraceuticals. Quercetin (QUE) is a flavonol aglycone able to bind Transthyretin (TTR), a plasma protein that under pathological conditions can lose its native structure leading to fibrils formation and amyloid diseases onset. Here, the dual nature of five quercetin 3-O-glycosylated flavonol derivatives, isolated from different plant species, such as possible binders of TTR and antioxidants, was investigated. The crystal structure of 3-O-β-D-galactopyranoside in complex with TTR was solved, suggesting that not only quercetin but also its metabolites can contribute to stabilizing the TTR tetramer
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