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The structure-based design of a mutant form of the thromboxane A(2) prostanoid receptor (TP) was instrumental in characterizing the structural determinants of the hetero-dimerization process of this G protein coupled receptor (GPCR). The results suggest that the hetero-dimeric complexes between the TPα and β isoforms are characterized by contacts between hydrophobic residues in helix 1 from both monomers. Functional characterization confirms that TPα-TPβ hetero-dimerization serves to regulate TPα function through agonist-induced internalization, with important implications in cardiovascular homeostasis. The integrated approach employed in this study can be adopted to gain structural and functional insights into the dimerization/oligomerization process of all GPCRs for which the structural model of the monomer can be achieved at reasonable atomic resolution.  相似文献   
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Riassunto Gli autori riescono ad ottenere la sopravvivenza in cultura di gangli cefalici larvali diDrosophila melanogaster per oltre un mese, con mitosi duranfe la 2a e 3a settimana, mentre le ghiandole della linfa si mantengono vive solo per 10–13 giorni.  相似文献   
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Riassunto Gli autori analizzano il comportamento in cultura di gangli cefalici larvali di Drosofile appartenenti a 3 ceppi inbred, confrontandolo con quello dei 2 genotipi eterozigoti da questi ottenuti. Gli eterozigoti sembrano utilizzare meglio certe sostanze nutritizie del terreno, ed inoltre uno di essi rivela col suo comportamento in cultura, analizzato sotto diversi aspetti, la dominanza di un ceppo parentale, l'altro invece una interazione tra i genotipi parentali.  相似文献   
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The effect of alpha-mercaptopropinyl-glycine on the in vitro proliferative response of healthy subjects' lymphocytes was studied. Low doses of the drug enhanced spontaneous lymphocyte blastigenesis but had no effect on the PHA-induced blastic response. With increasing concentrations of alpha-mercaptopropionyl-glycine inhibition of 3H-thymidine incorporation was found in unstimulated as well as in PHA stimulated lymphocytes.  相似文献   
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讨论了Microsoft C语言中调用MASM 5.0汇编语言程序的方法,并针对一些易出现的问题,如程序接口部分的要求,C语言与汇编程序间参数的传递,寄存器的使用等,提出了解决办法.  相似文献   
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In class A GPCRs the E/DRY motif is critical for receptor activation and function. According to experimental and computational data, R3.50 forms a double salt bridge with the adjacent E/D3.49 and E/D6.30 in helix 6, constraining the receptor in an inactive state. The disruption of this network of interactions facilitates conformational transitions that generate a signal or constitutive activity. Here we demonstrate that non-conservative substitution of either E129(3.49) or E240(6.30) of thromboxane prostanoid receptor (TP) resulted in mutants characterized by agonist-induced more efficient signaling properties, regardless of the G protein coupling. Results of computational modeling suggested a more effective interaction between Gq and the agonist-bound forms of the TP mutants, compared to the wild type. Yet, none of the mutants examined revealed any increase in basal activity, precluding their classification as constitutively active mutants. Here, we propose that these alternative active conformations might be identified as superactive mutants or SAM.  相似文献   
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Riassunto Sono stati coltivati in identica condizione gangli nervosi e ghiandole della linfa di diversi ceppi diDrosophila, differenti genotipicamente. Si sono notate diverse peculiarità di comportamento che — sebbene in parte forse artefatti — denotano l'esistenza di differenze fra il fenotipo, che risulta così analizzato a livello cellulare. Il metodo sembra adatto a ulteriori analisi del fenotipo, in rapporto a genotipi diversi.

This investigation was supported financially by the Rockefeller Foundation N.Y.  相似文献   
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