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41.
E. Flückiger U. Briner B. Clark A. Closse A. Enz P. Gull A. Hofmann R. Markstein L. Tolcsvai H. R. Wagner 《Cellular and molecular life sciences : CMLS》1988,44(5):431-436
Summary The profile of action in animals of CQP 201-403, a novel 8-amino-ergoline, is in most aspects that of a very potent dopaminomimetic, both as a prolactin secretion inhibitor, and at the levels of the CNS and the cardiovascular system. Qualitatively CQP 201-403 differs slightly from bromocriptine and apomorphine in its effects on the CNS (no influence on serotonin metabolism in the rat cortex; induction of masculine mounting behavior in rats) and the cardiovascular system of the dog (reflex tachycardia in response to a blood-pressure fall). In man the new compound proved to be highly active in lowering prolactin serum levels and to be more potent than bromocriptine (Parlodel®).In memory of Dr Annemarie Closse, who died 14 June 1987. 相似文献
42.
The prediction of a protein's tertiary structure is still a considerable problem because the huge amount of possible conformational space1 makes it computationally difficult. With regard to side-chain modelling, a solution has been attempted by the grouping of side-chain conformations into representative sets of rotamers2??. Nonetheless, an exhaustive combinatorial search is still limited to carefully indentified packing units?? containing a limited number of residues. For larger systems other strategies had to be developed, such as the Monte Carlo Procedure?? and the genetic algorithm and clustering approach?. Here we present a theorem, referred to as the 'dead-end elimination' theorem, which imposes a suitable condition to identify rotamers that cannot be members of the global minimum energy conformation. Application of this theorem effectively controls the computational explosion of the rotamer combinatorial problem, thereby allowing the determination of the global minimum energy conformation of a large collection of side chains. 相似文献
43.
Definition of a consensus binding site for p53. 总被引:35,自引:0,他引:35
Recent experiments have suggested that p53 action may be mediated through its interaction with DNA. We have now identified 18 human genomic clones that bind to p53 in vitro. Precise mapping of the binding sequences within these clones revealed a consensus binding site with a striking internal symmetry, consisting of two copies of the 10 base pair motif 5'-PuPuPuC(A/T)(T/A)GPyPyPy-3' separated by 0-13 base pairs. One copy of the motif was insufficient for binding, and subtle alterations of the motif, even when present in multiple copies, resulted in loss of affinity for p53. Mutants of p53, representing each of the four "hot spots" frequently altered in human cancers, failed to bind to the consensus dimer. These results define the DNA sequence elements with which p53 interacts in vitro and which may be important for p53 action in vivo. 相似文献
44.
A E Davis K Aulak R B Parad H P Stecklein E Eldering C E Hack J Kramer R C Strunk J Bissler F S Rosen 《Nature genetics》1992,1(5):354-358
Heterozygosity for a mutant dysfunctional C1 inhibitor protein, a member of the serine proteinase inhibitor (serpin) superfamily, results in type II hereditary angioneurotic oedema. We identified a "hinge" region mutation in C1 inhibitor with a Val to Glu replacement at P14 Val-432. Recombinant C1 inhibitors P10 Ala-->Thr and P14Val-->Glu did not form stable complexes with fluid phase C1s or kallikrein. The P14 Val-->Glu mutant, however, was cleaved to a 96K form by C1s, while the P10 Ala-->Thr mutant was not. The recombinant P10 mutant also did not complex with C1s, kallikrein or beta-factor Xlla-Sepharose. The two mutations, therefore, result in dysfunction by different mechanisms: in one (P14 Val-->Glu), the inhibitor is converted to a substrate, while in the other (P10 Ala-->Thr), interaction with target protease is blocked. 相似文献
45.
In 1986, Brown and Clemmons (Proc. natl Acad. Sci. USA83 (1986) 3321) showed that platelets contain a substance, platelet-derived growth inhibitor (PDGI), that inhibits in vitro endothelial cell replication. Although platelets are rich in transforming grwoth factor (TGF-), PDGI was considered not to be related to TGF-, on the basis of its reported properties (extraction from platelets at neutral pH, binding to heparin-Sepharose). However, we purified PDGI to near homogeneity and showed that on the basis of HPLC retention behavior, in vitro growth inhibitory activities with several cell types, receptor binding, and immunoneutralization of growth inhibitory activity with specific anti-TGF- type 1 antibodies, PDGI is most probably identical with TGF- type 1. 相似文献
46.
R. Wiesendanger B. Martinoni T. Boller D. Arigoni 《Cellular and molecular life sciences : CMLS》1986,42(2):207-209
Summary Under the action of the appropriate synthase from ripe tomatoes a 11 mixture of (3S, 4R)-[3,4-2H2] and (3R, 4S)-[3,4-2H2]-(2S)-adenosylmethionine is transformed into a 11 mixture of the two meso forms of [2H2]-1-aminocyclopropanecarboxylic acid, a result which proves the operation of an inversion mechanism and which is consistent with direct nucleophilic displacement of the leaving group in the substrate. 相似文献
47.
Summary During molt-induced atrophy of the pectoralis muscle of the Giant Canada Goose (Branta canadensis maxima), the zinc content of the muscle was significantly reduced (p0.0139), though the concentration of zinc per unit weight of muscle appeared higher (p0.0232). Zinc lost from the muscle during molt could be utilized for growth of the new flight feathers.Acknowledgments. Funds for this study were obtained from an operating grant awarded to J. C. G. by the Natural Sciences and Engineering Research Council of Canada. 相似文献
48.
Evolution of the atmosphere and oceans 总被引:1,自引:0,他引:1
The residence times of most constituents of the atmosphere and oceans are small fractions of the age of the Earth and, in general, their rate of output has been nearly equal to their rate of input. We are disturbing a number of these dynamic equilibria quite severely. The mineralogy of marine evaporites rules out drastic changes in the composition of sea water during the last 900 Myr. The chemistry of soils formed more than 1,000 Myr ago suggests that the atmosphere then contained significantly more CO2 and less O2 than at present. Hydrogen peroxide may well have been the principal oxidant and formaldehyde the main reductant in rain water between 3,000 and 1,000 Myr ago. Major changes in atmospheric chemistry since that time are almost certainly related to the evolution of the biosphere. 相似文献
49.
Secular variation in carbon isotope ratios from Upper Proterozoic successions of Svalbard and East Greenland 总被引:12,自引:0,他引:12
Analyses of stratigraphically continuous suites of samples from Upper Proterozoic sedimentary successions of East Greenland, Spitsbergen and Nordaustlandet (Svalbard) provide an approximation to the secular variation in carbon isotope ratios during a geologically and biologically important period of change from around 900 million years ago to the beginning of the Cambrian period. Late Riphean carbonates and organic material show a stratigraphically useful pattern of enrichment in 13C relative to Phanerozoic or earlier Proterozoic samples. Isotopic compositions of isolated samples from other localities are consistent with a worldwide extended interval of enhanced organic burial and consequent net survival of oxidized material, probably O2, just before the initial radiation of metazoans. 相似文献
50.
Summary Human whole blood was irradiated with 2.5 Gy of 220 kVp X-rays and stored before culture with 9.7 M BrdU and 19.4 or 38.7 M BrdU for 0, 24, 48 and 72 h. The frequency of dicentrics and ring chromosomes was determined in cells staining as first division (M1) metaphases with the fluorescence plus Giemsa technique. Storage had no influence on the observed aberration yields in 44 h cultures containing 9.7 M BrdU. In 66 h cultures at 19.4 M BrdU the observed yields after 2 and 3 days' storage were significantly lower as compared to cultures from fresh blood. No storage effect was revealed in 66 h cultures containing 38.7 M BrdU. In cases where cytogenetic radiation dosimetry has to be carried out using blood samples which have been in transit for 2–3 days, the findings are of relevance for a correct determination of the chromosome damage in M1 cells. 相似文献