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排序方式: 共有226条查询结果,搜索用时 31 毫秒
41.
Structure-activity analysis of the effects of lysophosphatidic acid on platelet aggregation. 总被引:34,自引:0,他引:34
G Gueguen B Gaigé J M Grévy P Rogalle J Bellan M Wilson A Klaébé F Pont M F Simon H Chap 《Biochemistry》1999,38(26):8440-8450
Lysophosphatidic acid (1-acyl-sn-glycero-3-phosphate or LPA) is a phospholipid mediator displaying numerous and widespread biological activities and thought to act via G-protein-coupled receptors. Here we have studied the effects on human platelets of a number of LPA analogues, including two enantiomers of both N-palmitoyl-(L)-serine-3-phosphate ((L) and (D)NAPS for N-acyl-phosphoserine) and 2-(R)-N-palmitoyl-norleucinol-1-phosphate ((R) and (S)PNPA), cyclic analogues of 1-acyl-sn-glycero-3-phosphate (cPA) and of 1-O-hexadecyl-sn-glycero-3-phosphate (cAGP), sphingosine-1-phosphate (SPP), as well as two palmitoyl derivatives of dioxazaphosphocanes bearing either a P-H or a P-OH bond (DOXP-H and DOXP-OH, respectively). Nine of these compounds induced platelet aggregation with the following order of potency: SPP < cAGP < DOXP-OH < (L)NAPS = (D)NAPS < (R)PNPA = (S)PNPA < LPA < AGP, EC50 varying between 9.8 nM and 8.3 microM. Two of these compounds (SPP and cAGP) appeared as weak agonists inducing platelet aggregation to only 33% and 41%, respectively, of the maximal response attained with LPA and other analogues. In cross-desensitization experiments, all of these compounds specifically inhibited LPA-induced aggregation, suggesting that they were all acting on the same receptor(s). In contrast, cPA and DOXP-H did not trigger platelet aggregation but instead specifically inhibited the effects of LPA in a concentration-dependent manner. The inhibitory action of cPA did not vary with the acyl chain length or the presence of a double bond and did not involve an increase in cAMP. These data thus confirm the lack of stereospecificity of platelet LPA receptor(s). In addition, since the order of potency of some analogues is different from that described in other cells, our results suggest that platelets contain (a) pharmacologically distinct receptor(s) whose molecular identity still remains to be established. Finally, this unique series of compounds might be used for further characterization of other endogenous or recombinant LPA receptors. 相似文献
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A comparative study of various procedures for tryptophanyl peptide bond cleavage by BNPS-skatole [2-(2-nitrophenyl)-3-methyl-3-bromoindolenine] was carried out on native and on reduced and alkylated bovine β-lactoglobulin (BLG). The reaction yield and the composition of the derived products were studied in acetic acid, trifluoroacetic acid (TFA), and ethanol/TFA. For BNPS-skatole removal, extraction by water or ethyl ether was compared with dialysis and gel filtration. The three expected peptides (1–19, 20–61, 62–162) and incomplete cleaved fragments (1–61, 20–162) were separated and characterized by electrophoresis, reverse-phase high-performance liquid chromatography, and mass spectrometry. The highest hydrolysis yield (67.4%) occurred with native BLG cleaved in 88% acetic acid at 47°C for 60 min. Subsequent water extraction and gel filtration led to total recovery of the material, but reagent elimination was only quantitative after gel filtration. Cleavage specificity was ensured by mass spectrometry and the amino acid composition of peptides 1–19 and 62–162. The chemical side reactions identified are discussed. 相似文献
44.
Cédric Morio Mark J. Lake Nils Gueguen Guillaume Rao Laurent Baly 《Journal of biomechanics》2009,42(13):2081-2088
There are evidences to suggest that wearing footwear constrains the natural barefoot motion during locomotion. Unlike prior studies that deduced foot motions from shoe sole displacement parameters, the aim of this study was to examine the effect of footwear motion on forefoot to rearfoot relative motion during walking and running. The use of a multi-segment foot model allowed accurate both shoe sole and foot motions (barefoot and shod) to be quantified. Two pairs of identical sandals with different midsole hardness were used. Ten healthy male subjects walked and ran in each of the shod condition.The results showed that for barefoot locomotion there was more eversion of the forefoot and it occurred faster than for shod locomotion. In this later condition, the range of eversion was reduced by 20% and the rate of eversion in late stance by 60% in comparison to the barefoot condition. The sole constrained both the torsional (eversion/inversion) and adduction range of motion of the foot. Interestingly, during the push-off phase of barefoot locomotion the rate and direction of forefoot torsion varied between individuals. However, most subjects displayed a forefoot inversion direction of motion while shod. Therefore, this experiment showed that the shoes not only restricted the natural motion of the barefoot but also appeared to impose a specific foot motion pattern on individuals during the push-off phase. These findings have implications for the matching of footwear design characteristics to individual natural foot function. 相似文献
45.
Jérémy Dufourt Cynthia Dennis Antoine Boivin Nathalie Gueguen Emmanuelle Théron Coline Goriaux Pierre Pouchin Stéphane Ronsseray Emilie Brasset Chantal Vaury 《Nucleic acids research》2014,42(4):2512-2524
During Drosophila oogenesis, transposable element (TE) repression involves the Piwi-interacting RNA (piRNA) pathway which ensures genome integrity for the next generation. We developed a transgenic model to study repression of the Idefix retrotransposon in the germline. Using a candidate gene KD-approach, we identified differences in the spatio-temporal requirements of the piRNA pathway components for piRNA-mediated silencing. Some of them (Aub, Vasa, Spn-E) are necessary in very early stages of oogenesis within the germarium and appear to be less important for efficient TE silencing thereafter. Others (Piwi, Ago3, Mael) are required at all stages of oogenesis. Moreover, during early oogenesis, in the dividing cysts within the germarium, Idefix anti-sense transgenes escape host control, and this is associated with very low piwi expression. Silencing of P-element-based transgenes is also strongly weakened in these cysts. This region, termed the ‘Piwiless pocket’ or Pilp, may ensure that new TE insertions occur and are transmitted to the next generation, thereby contributing to genome dynamics. In contrast, piRNA-mediated silencing is strong in germline stem cells in which TE mobilization is tightly repressed ensuring the continued production of viable germline cysts. 相似文献
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47.
D Taruscio C Morciano P Laricchiuta P Mincarone F Palazzo CG Leo S Sabina R Guarino J Auld T Sejersen D Gavhed K Ritchie M Hilton-Boon J Manson PG Kanavos D Tordrup V Tzouma Y Le Cam J Senecat G Filippini S Minozzi C Del Giovane H Schünemann JJ Meerpohl B Prediger L Schell R Stefanov G Iskrov T Miteva-Katrandzhieva P Serrano-Aguilar L Perestelo-Perez MM Trujillo-Martín J Pérez-Ramos A Rivero-Santana A Brand H van Kranen K Bushby A Atalaia J Ramet L Siderius M Posada I Abaitua-Borda V Alonso Ferreira M Hens-Pérez FJ Manzanares 《Orphanet journal of rare diseases》2014,9(Z1):O14
48.
Micelle‐enhanced spectrofluorimetric method for determination of sitagliptin and identification of potential alkaline degradation products using LC‐MS
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A novel, quick, simple and highly sensitive spectrofluorimetric method was developed and validated for the determination of sitagliptin (SG) in its pharmaceutical formulations. The proposed method is based on investigation of the fluorescence spectral behavior of sitagliptin in an SDS micellar system. In an aqueous solution of phosphate buffer pH 4.0, the fluorescence intensity of SG in the presence of SDS was greatly enhanced, by 200%, i.e. twofold enhancement. The fluorescence intensity of SG was measured at 300 nm after excitation at 270 nm. The method showed good linearity in the range 0.03–10.0 µg/mL with a good correlation coefficient (r = 0.9998). The limits of detection and quantitation values were 5.31 and 16.1 ng/mL, respectively. The proposed method was successfully applied to the analysis of SG in its single and co‐formulated commercial tablets; the results were in good agreement with those obtained using a reference method. Application of the proposed method was extended to stability studies of SG after exposure to different forced degradation conditions according to the ICH guidelines, such as acidic, alkaline, thermal, photo‐ and oxidative stress. The chemical structure of certain potential degradation products (DPs) were investigated using LC‐MS. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
49.
Gruber Véronique Berna Patrick P. Arnaud Thierry Bournat Philippe Clément Christèle Mison Dominique Olagnier Béatrice Philippe Laurence Theisen Manfred Baudino Sylvie Bénicourt Claude Cudrey Claire Bloës Carole Duchateau Nathalie Dufour Sylvie Gueguen Catherine Jacquet Séverine Ollivo Catherine Poncetta Christine Zorn Nathalie Ludevid Dolores Van Dorsselaer Alain Verger Robert Doherty Annette Mérot Bertrand Danzin Charles 《Molecular breeding : new strategies in plant improvement》2001,7(4):329-340
A recombinant dog gastric lipase with therapeutic potential for the treatment of exocrine pancreatic insufficiency was expressed in transgenic tobacco plants. We targeted the protein using two different signal sequences for either vacuolar retention or secretion. In both cases, an active glycosylated recombinant protein was obtained. The recombinant enzymes and the native enzyme displayed similar properties including acid resistance and acidic optimum pH. The proteolytic maturation and the specific activity of the recombinant proteins, however, were found to be dependent on subcellular compartmentalization. Expression levels of recombinant dog gastric lipase were about 5% and 7% of acid extractable plant proteins for vacuolar retention and secretion respectively. This expression system already has allowed the production of tens of grams of purified lipase through open-field culture of transgenic tobacco plants. 相似文献
50.
Sok‐Keng Tong Karen Mouriec Ming‐Wei Kuo Elisabeth Pellegrini Marie‐Madeleine Gueguen François Brion Olivier Kah Bon‐chu Chung 《Genesis (New York, N.Y. : 2000)》2009,47(2):67-73
Aromatase is an enzyme that catalyzes the synthesis of estrogen in gonads and brain. Teleost fish express aromatase (AroB) strongly in the brain facilitating its detailed examination. To understand the function of AroB in the brain, we generated transgenic zebrafish that expresses green fluorescent protein (GFP) driven by the brain aromatase cyp19a1b promoter. GFP was found in the radial glial cells of transgenic larvae and adult fish that overlap with AroB immunoreactivity in the correct temporal and spatial pattern. GFP was also coexpressed with radial cell marker BLBP, but was not in neurons. In addition, GFP expression in the radial glial cells was stimulated by estrogen, same as endogenous AroB expression. Thus, this transgenic line faithfully mimics the regulation of AroB expression in radial glial cells. It provides a powerful tool to further characterize progenitor radial cells in adult and developing fish and to evaluate estrogenic activities of xenoestrogens and phytoestrogens. genesis 47:67–73, 2009. © 2008 Wiley‐Liss, Inc. 相似文献