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1.
We have examined the effects of the local anesthetic tetracaine on the orientational and dynamic properties of glycolipid model membranes. We elected to study the interactions of tetracaine with the pure glycolipid 1,2-di-O-tetradecyl-3-O-(beta-D-glucopyranosyl)-sn-glycerol (beta-DTGL) and a mixture of beta-DTGL (20 mol%) in dimyristoylphosphatidylcholine (DMPC) by deuterium NMR (2H-NMR) spectroscopy. 2H-NMR spectra of beta-DTGL have been measured as a function of temperature in the presence of both the charged (pH 5.5) and uncharged forms (pH 9.5) of tetracaine. The results indicate that the anesthetic induces the formation of non-lamellar phases. Specifically, the incorporation of uncharged tetracaine results in the formation of a hexagonal phase which is stable from 52 to 60 degrees C. At lower pH, the spectrum at 52 degrees C is very reminescent of that of the beta-glucolipid alone in a bilayer environment, while as the temperature is elevated to 60 degrees C, a transition from a spectrum indicative of axial symmetry to one due to nearly isotropic motion or symmetry occurs, which may result from the formation of a cubic phase. Although it leads to an alteration in the phase behavior, the presence of tetracaine does not induce large changes in the headgroup orientation of beta-DTGL. In contrast to the pure glycolipid situation, the interaction of tetracaine with beta-DTGL (20 mol%) in DMPC does not trigger the formation of non-lamellar phases, but leads to a slight reduction in molecular ordering. The presence of the charged form of the local anesthetic near the aqueous interface of the bilayer appears to induce a small change in the conformation about the C2-C3 bond of the glycerol backbone of beta-DTGL in the mixed lipid system. Thus, the major influence of the local anesthetic on glycolipids is a change in the stability of the lamellar phase, facilitating conversion to phases with hexagonal or isotropic environments for the lipid molecules. 相似文献
2.
PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells 总被引:94,自引:0,他引:94
A phosphatidylinositol (PI) kinase activity associated with certain protein tyrosine kinases important in cell proliferation phosphorylates the 3' hydroxyl position of PI to produce phosphatidylinositol-3-phosphate (PI-3-P). Here we report that, in addition to PI-3' kinase activity, anti-phosphotyrosine (alpha-P-tyr) immunoprecipitates from platelet-derived growth factor (PDGF)-stimulated smooth muscle cells (SMC) contain lipid kinase activities that utilize the substrates phosphatidylinositol-4-phosphate (PI-4-P) and phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2). These activities are absent in alpha-P-tyr immunoprecipitates from quiescent SMC. The product of PI-4-P phosphorylation appears to be phosphatidylinositol-3,4-bisphosphate (PI-3,4-P2), a lipid not previously reported. The product of PI-4,5-P2 phosphorylation is phosphatidylinositol-trisphosphate (PIP3). PI-3-P was detected in quiescent SMC and increased only slightly in response to PDGF. PIP3 and the putative PI-3,4-P2 appeared only after the addition of mitogen. Both the temporal production of these novel phospholipids after PDGF stimulation and the observation of the enzymatic activities that produce them in alpha-P-tyr immunoprecipitates suggest that these phospholipids are excellent candidates for mediators of the PDGF mitogenic response. 相似文献
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Several recent papers indicate that the blood concentration of inhibin B measured by the dimeric assay is a marker of human spermatogenesis. The aim of the present study was to validate the dimeric assay in our hospital. For this purpose, we studied a population of 106 patients attending our infertility clinic. We found that serum inhibin B levels were positively correlated with the level of sperm production as reflected by the sperm concentration and negatively correlated with serum FSH levels. Serum inhibin B concentrations were found to be superior to FSH levels for discriminating between subgroups of patients with different levels of sperm production. For example, the differences in the inhibin B levels in severe oligozoospermia (< 5×106 sperm/ml) compared to non-obstructive azoospermia were more pronounced than the differences in FSH (p=0.0002 vs p=0.007, respectively). Overall, the results obtained in the present study were similar to those reported in other studies based on the same assay. Serum inhibin B levels in patients with non obstructive azoospermia were ten times lower than in patients with normal sperm concentrations. From a practical point of view, the measurement of serum inhibin B opens up new possibilities for the diagnosis and prognosis of many testicular disorders. Firstly, serum inhibin B determination should be performed whenever reproductive hormones are prescribed. In the particular case of azoospermia, serum inhibin B concentrations appear to be particularly useful to distinguish between obstructive and non-obstructive situations. Finally, according to a recent publication, a serum inhibin B cut-off value (> 40 pg/mL) could predict the success of testicular sperm extraction in patients with non-obstructive azoospermia. Serum inhibin B could therefore represent a unique non-invasive marker of focal hypospermatogenesis in men with non-obstructive azoospermia, who are candidates for intracytoplasmic sperm injection (ICSI) and a useful early marker to monitor possible recovery of spermatogenesis after chemotherapy or radiotherapy. 相似文献
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Amaria Darmellah Amel Rayah Rodolphe Auger Marie-Hélène Cuif Magali Prigent Monique Arpin Andres Alcover Cécile Delarasse Jean M. Kanellopoulos 《The Journal of biological chemistry》2012,287(41):34583-34595
The amyloid precursor protein (APP) can be cleaved by α-secretases in neural cells to produce the soluble APP ectodomain (sAPPα), which is neuroprotective. We have shown previously that activation of the purinergic P2X7 receptor (P2X7R) triggers sAPPα shedding from neural cells. Here, we demonstrate that the activation of ezrin, radixin, and moesin (ERM) proteins is required for the P2X7R-dependent proteolytic processing of APP leading to sAPPα release. Indeed, the down-regulation of ERM by siRNA blocked the P2X7R-dependent shedding of sAPPα. We also show that P2X7R stimulation triggered the phosphorylation of ERM. Thus, ezrin translocates to the plasma membrane to interact with P2X7R. Using specific pharmacological inhibitors, we established the order in which several enzymes trigger the P2X7R-dependent release of sAPPα. Thus, a Rho kinase and the MAPK modules ERK1/2 and JNK act upstream of ERM, whereas a PI3K activity is triggered downstream. For the first time, this work identifies ERM as major partners in the regulated non-amyloidogenic processing of APP. 相似文献
7.
Turbelin Anna J. Diagne Christophe Hudgins Emma J. Moodley Desika Kourantidou Melina Novoa Ana Haubrock Philip J. Bernery Camille Gozlan Rodolphe E. Francis Robert A. Courchamp Franck 《Biological invasions》2022,24(7):2061-2079
Biological Invasions - Introduction pathways play a pivotal role in the success of Invasive Alien Species (IAS)—the subset of alien species that have a negative environmental and/or... 相似文献
8.
Brazier Thomas Cherif Emira Martin Jean-François Gilles André Blanchet Simon Zhao Yahui Combe Marine McCairns R. J. Scott Gozlan Rodolphe E. 《Biological invasions》2022,24(8):2399-2420
Biological Invasions - Insufficient data on the origins of the first introduced propagule and the initial stages of invasion complicate the reconstruction of a species’ invasion history.... 相似文献
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Christine Jacomet Clotilde Allavena Fleur Peyrol Bruno Pereira Laurence Morand Joubert Haleh Bagheri Laurent Cotte Rodolphe Garaffo Laurent Gerbaud Pierre Dellamonica 《PloS one》2015,10(2)
BackgroundIn the interest of cost effectiveness, switching antiretroviral brand name medications to generics is recommended in France since 2013. The study objective was to evaluate the perception of generics per se and antiretroviral generics in HIV-infected patients and their hospital physiciansConclusionsAcceptability of antiretroviral generics in this French population was mostly dictated by the patient’s and physician’s knowledge and use of generics overall. It should be improved with an efficient information of both patients and physicians. 相似文献