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T. W. Stone 《Cellular and molecular life sciences : CMLS》1974,30(7):827-829
Résumé On a construit des modèles moléculaires de plusieurs phénothiazines et du LSD, et observé que la structure des phénothiazines peut se superposer à celle du LSD. Cette observation explique peut-être pourquoi les phénothiazines manifestent un antagonisme envers les alkaloïdes d'ergot. La similarité de ces structures est la plus exacte pour les phénothiazines qui combattent le plus efficacement les psychoses. 相似文献
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T. W. Stone 《Cellular and molecular life sciences : CMLS》1976,32(5):581-583
Summary Applied by microiontophoresis, 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) antagonized excitation by glutamic acid but not by acetylcholine of neurones in the rat cuneate nucleus. HA-966 blocked the short latency excitation of cuneate neurones following stimulation of the pyramidal tract on 28 of 40 cells (70%). Thus, glutamate or a related amino-acid may be the neurotransmitter released by pyramidal tract neurones.Acknowledgment. I wish to thank Dr.J. C. Watkins for the gift of a sample of HA-966. 相似文献
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Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease 总被引:24,自引:0,他引:24
Rioux JD Daly MJ Silverberg MS Lindblad K Steinhart H Cohen Z Delmonte T Kocher K Miller K Guschwan S Kulbokas EJ O'Leary S Winchester E Dewar K Green T Stone V Chow C Cohen A Langelier D Lapointe G Gaudet D Faith J Branco N Bull SB McLeod RS Griffiths AM Bitton A Greenberg GR Lander ES Siminovitch KA Hudson TJ 《Nature genetics》2001,29(2):223-228
Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10(-4)). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P< 2 x 10(-7)) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence-each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general. 相似文献
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At low doses, theophylline blocks the neuronal depressant effects of 5'-AMP, but not cyclic AMP. Higher doses (100 mg/kg) block cyclic AMP responses and reduce the effects of noradrenaline and GABA. It is concluded that cyclic AMP does not depress neurones via the adenosine receptor. 相似文献
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Wooding S Bufe B Grassi C Howard MT Stone AC Vazquez M Dunn DM Meyerhof W Weiss RB Bamshad MJ 《Nature》2006,440(7086):930-934
It was reported over 65 years ago that chimpanzees, like humans, vary in taste sensitivity to the bitter compound phenylthiocarbamide (PTC). This was suggested to be the result of a shared balanced polymorphism, defining the first, and now classic, example of the effects of balancing selection in great apes. In humans, variable PTC sensitivity is largely controlled by the segregation of two common alleles at the TAS2R38 locus, which encode receptor variants with different ligand affinities. Here we show that PTC taste sensitivity in chimpanzees is also controlled by two common alleles of TAS2R38; however, neither of these alleles is shared with humans. Instead, a mutation of the initiation codon results in the use of an alternative downstream start codon and production of a truncated receptor variant that fails to respond to PTC in vitro. Association testing of PTC sensitivity in a cohort of captive chimpanzees confirmed that chimpanzee TAS2R38 genotype accurately predicts taster status in vivo. Therefore, although Fisher et al.'s observations were accurate, their explanation was wrong. Humans and chimpanzees share variable taste sensitivity to bitter compounds mediated by PTC receptor variants, but the molecular basis of this variation has arisen twice, independently, in the two species. 相似文献
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Regulatory peptides in the eye 总被引:5,自引:0,他引:5