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排序方式: 共有182条查询结果,搜索用时 15 毫秒
21.
Ferrero DM Wacker D Roque MA Baldwin MW Stevens RC Liberles SD 《ACS chemical biology》2012,7(7):1184-1189
Trace amine-associated receptors (TAARs) are vertebrate olfactory receptors. However, ligand recognition properties of TAARs remain poorly understood, as most are "orphan receptors" without known agonists. Here, we identify the first ligands for many rodent TAARs and classify these receptors into two subfamilies based on the phylogeny and binding preference for primary or tertiary amines. Some mouse and rat orthologs have similar response profiles, although independent Taar7 gene expansions led to highly related receptors with altered ligand specificities. Using chimeric TAAR7 receptors, we identified an odor contact site in transmembrane helix III that functions as a selectivity filter. Homology models based on the β(2) adrenergic receptor structure indicate spatial proximity of this site to the ligand. Gain-of-function mutations at this site created olfactory receptors with radically altered odor recognition properties. These studies provide new TAAR ligands, valuable tools for studying receptor function, and general insights into the molecular pharmacology of G protein-coupled receptors. 相似文献
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Marseille-Tremblay C Ethier-Chiasson M Forest JC Giguère Y Masse A Mounier C Lafond J 《Molecular reproduction and development》2008,75(6):1054-1062
Maternal hypercholesterolemia (HC) during pregnancy and gestational diabetes mellitus (GDM) are associated with disturbance of fetal development which may also modify key features of placental functions. In this study, we evaluated the impact of maternal hypercholesterolemia on placental cholesterol and lipid metabolism in 59 women classified in two groups according to the median concentration of plasma total cholesterol (6.42 mM). The impact of GDM was also evaluated on the metabolism of placentas obtained from 7 insulin-treated GDM and 7 non-GDM women. We showed that high maternal circulating cholesterol is associated with a significant increase in the LDL-cholesterol, ApoB-100 and triglyceride concentrations in the maternal blood. However the level of cholesterol in the venous cord blood and placenta remains unchanged in response to modification in maternal cholesterol profile. The levels of Fatty acid synthase (FAS) and SREBP-2 expressions in placenta are significantly increased in the HC group while expression of both sterol regulatory element-binding proteins-1 (SREBP-1) and HMG-CoA reductase (HMGR) are not modified. GDM is not associated with modification in the maternal lipid profile but it increases the concentration of inflammatory cytokines (IL-1beta and TNF-alpha) in placenta which correlates with a dramatic induction of FAS expression without affecting the expression of mature SREBPs proteins. In conclusion, our study suggests that in placenta, expressions of key proteins involved in de novo lipid synthesis are affected by changes in maternal metabolism (HC and GDM) that may subsequently affect fetal development. 相似文献
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We developed and tested a method to produce DNA standards and controls for quantitative PCR by designing and performing partial hybridization of long oligonucleotides before double stranded DNA fragments were synthesized and subsequently amplified by conventional PCR. This approach does not require any natural DNA template. Applications include the production of standards, which cannot be easily produced from DNA extracted from bacteria or plants. 相似文献
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Marsault E Hoveyda HR Gagnon R Peterson ML Vézina M Saint-Louis C Landry A Pinault JF Ouellet L Beauchemin S Beaubien S Mathieu A Benakli K Wang Z Brassard M Lonergan D Bilodeau F Ramaseshan M Fortin N Lan R Li S Galaud F Plourde V Champagne M Doucet A Bhérer P Gauthier M Olsen G Villeneuve G Bhat S Foucher L Fortin D Peng X Bernard S Drouin A Déziel R Berthiaume G Dory YL Fraser GL Deslongchamps P 《Bioorganic & medicinal chemistry letters》2008,18(16):4731-4735
A new method for solid phase parallel synthesis of chemically and conformationally diverse macrocyclic peptidomimetics is reported. A key feature of the method is access to broad chemical and conformational diversity. Synthesis and mechanistic studies on the macrocyclization step are reported. 相似文献
25.
A B John A Ramlal H Jackson G H Maude A W Sharma G R Serjeant 《BMJ (Clinical research ed.)》1984,288(6430):1567-1570
The efficacy of prophylactic penicillin and of 14 valent pneumococcal vaccine in preventing pneumococcal infection in homozygous sickle cell (SS) disease was investigated in 242 children aged 6 months to 3 years at entry. In the first five years of the trial there were 11 pneumococcal infections in the pneumococcal vaccine treated group, 10 by serotypes present in the vaccine. Type 23 accounted for five of these, and there was evidence of higher infection rates in those given the vaccine before age 1. No pneumococcal isolations occurred in the penicillin group while receiving penicillin, although four isolations occurred within one year of stopping penicillin. Probably the most effective prophylaxis against pneumococcal infection requires penicillin beyond the age of 3. The age at which pneumococcal vaccine should be given must await further data on antibody response and clinical efficacy in these patients. 相似文献
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Mapping protein interactions of sodium channel NaV1.7 using epitope‐tagged gene‐targeted mice 下载免费PDF全文
Honglei Huang Martina Pyrski Queensta Millet Stéphane Lolignier Toru Morohashi Samuel J Gossage Maude Jay John E Linley Georgios Baskozos Benedikt M Kessler James J Cox Annette C Dolphin Frank Zufall John N Wood Jing Zhao 《The EMBO journal》2018,37(3):427-445
The voltage‐gated sodium channel NaV1.7 plays a critical role in pain pathways. We generated an epitope‐tagged NaV1.7 mouse that showed normal pain behaviours to identify channel‐interacting proteins. Analysis of NaV1.7 complexes affinity‐purified under native conditions by mass spectrometry revealed 267 proteins associated with Nav1.7 in vivo. The sodium channel β3 (Scn3b), rather than the β1 subunit, complexes with Nav1.7, and we demonstrate an interaction between collapsing‐response mediator protein (Crmp2) and Nav1.7, through which the analgesic drug lacosamide regulates Nav1.7 current density. Novel NaV1.7 protein interactors including membrane‐trafficking protein synaptotagmin‐2 (Syt2), L‐type amino acid transporter 1 (Lat1) and transmembrane P24‐trafficking protein 10 (Tmed10) together with Scn3b and Crmp2 were validated by co‐immunoprecipitation (Co‐IP) from sensory neuron extract. Nav1.7, known to regulate opioid receptor efficacy, interacts with the G protein‐regulated inducer of neurite outgrowth (Gprin1), an opioid receptor‐binding protein, demonstrating a physical and functional link between Nav1.7 and opioid signalling. Further information on physiological interactions provided with this normal epitope‐tagged mouse should provide useful insights into the many functions now associated with the NaV1.7 channel. 相似文献
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Phospholipids of bovine outer segments 总被引:6,自引:0,他引:6