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61.
L. Manzo R. Passoni A. D. Segre F. Bertè A. Crema 《Cellular and molecular life sciences : CMLS》1976,32(10):1318-1320
Summary Oxine-5-sulphonic acid inhibits the metabolism of aminopyrine in the rat liver in vitro. The characteristics of this inhibition vary according to whether the oxidativeN-demethylation of the substrate is determined by the formation of the metabolite 4-aminoantipyrine or by the production of formaldehyde. 相似文献
62.
J Fèvre 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1975,281(24):2009-2012
Foetal and maternal blood samples are taken on the sow at the end of pregnancy. No variations in maternal cortisol are found, but plasma cortisol levels in the foetus, which are relatively constant between days 70 and 100 of pregnancy (10 to 20 ng/ml), increase suddenly at the end of pregnancy reaching a mean of 210 ng/ml at birth. This high increase of foetal corticosteroids at birth, similar to that found in other species (ewe, goat, etc.), probably plays a role in the mechanisms releasing parturition. It also permits us to understand the action of ACTH which induces premature birth when given to the pig foetus in the last days of pregnancy. 相似文献
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Entangled polymer solutions and melts exhibit elastic, solid-like resistance to quick deformations and a viscous, fluid-like response to slow deformations. This viscoelastic behaviour reflects the dynamics of individual polymer chains driven by brownian motion: since individual chains can only move in a snake-like fashion through the mesh of surrounding polymer molecules, their diffusive transport, described by reptation, is so slow that the relaxation of suddenly imposed stress is delayed. Entangled polymer solutions and melts therefore elastically resist deforming motions that occur faster than the stress relaxation time. Here we show that the protein myosin II permits active control over the viscoelastic behaviour of actin filament solutions. We find that when each actin filament in a polymerized actin solution interacts with at least one myosin minifilament, the stress relaxation time of the polymer solution is significantly shortened. We attribute this effect to myosin's action as a 'molecular motor', which allows it to interact with randomly oriented actin filaments and push them through the solution, thus enhancing longitudinal filament motion. By superseding reptation with sliding motion, the molecular motors thus overcome a fundamental principle of complex fluids: that only depolymerization makes an entangled, isotropic polymer solution fluid for quick deformations. 相似文献
65.
Dinosaurian growth rates and bird origins 总被引:7,自引:0,他引:7
Dinosaurs, like other tetrapods, grew more quickly just after hatching than later in life. However, they did not grow like most other non-avian reptiles, which grow slowly and gradually through life. Rather, microscopic analyses of the long-bone tissues show that dinosaurs grew to their adult size relatively quickly, much as large birds and mammals do today. The first birds reduced their adult body size by shortening the phase of rapid growth common to their larger theropod dinosaur relatives. These changes in timing were primarily related not to physiological differences but to differences in growth strategy. 相似文献
66.
Vanhove M Zakhem M Devreese B Franceschini N Anne C Bebrone C Amicosante G Rossolini GM Van Beeumen J Frère JM Galleni M 《Cellular and molecular life sciences : CMLS》2003,60(11):2501-2509
The CphA metallo--lactamase produced by Aeromonas hydrophila exhibits two zinc-binding sites. Maximum activity is obtained upon binding of one zinc ion, whereas binding of the second zinc ion results in a drastic decrease in the hydrolytic activity. In this study, we analyzed the role of Asn116 and Cys221, two residues of the active site. These residues were replaced by site-directed mutagenesis and the different mutants were characterized. The C221S and C221A mutants were seriously impaired in their ability to bind the first, catalytic zinc ion and were nearly completely inactive, indicating a major role for Cys221 in the binding of the catalytic metal ion. By contrast, the binding of the second zinc ion was only slightly affected, at least for the C221S mutant. Mutation of Asn116 did not lead to a drastic decrease in the hydrolytic activity, indicating that this residue does not play a key role in the catalytic mechanism. However, the substitution of Asn116 by a Cys or His residue resulted in an approximately fivefold increase in the affinity for the second, inhibitory zinc ion. Together, these data suggested that the first zinc ion is located in the binding site involving the Cys221 and that the second zinc ion binds in the binding site involving Asn116 and, presumably, His118 and His196.Received 3 March 2003; received after revision 4 August 2003; accepted 25 August 2003 相似文献
67.
Lamarre D Anderson PC Bailey M Beaulieu P Bolger G Bonneau P Bös M Cameron DR Cartier M Cordingley MG Faucher AM Goudreau N Kawai SH Kukolj G Lagacé L LaPlante SR Narjes H Poupart MA Rancourt J Sentjens RE St George R Simoneau B Steinmann G Thibeault D Tsantrizos YS Weldon SM Yong CL Llinàs-Brunet M 《Nature》2003,426(6963):186-189
Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at risk of developing significant morbidity and mortality. Current interferon-based therapies are suboptimal especially in patients infected with HCV genotype 1, and they are poorly tolerated, highlighting the unmet medical need for new therapeutics. The HCV-encoded NS3 protease is essential for viral replication and has long been considered an attractive target for therapeutic intervention in HCV-infected patients. Here we identify a class of specific and potent NS3 protease inhibitors and report the evaluation of BILN 2061, a small molecule inhibitor biologically available through oral ingestion and the first of its class in human trials. Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 protease inhibitor. Our results further illustrate the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics. 相似文献
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