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21.
Nazaré M Matter H Klingler O Al-Obeidi F Schreuder H Zoller G Czech J Lorenz M Dudda A Peyman A Nestler HP Urmann M Bauer A Laux V Wehner V Will DW 《Bioorganic & medicinal chemistry letters》2004,14(11):2801-2805
A series of novel, highly potent, achiral factor Xa inhibitors based on a benzoic acid scaffold and containing a chlorophenethyl moiety directed towards the protease S1 pocket is described. A number of structural features, such as the requirements of the P1, P4 and ester-binding pocket ligands were explored with respect to inhibition of factor Xa. Compound 46 was found to be the most potent compound in a series of antithrombotic secondary assays. 相似文献
22.
Nazaré M Essrich M Will DW Matter H Ritter K Urmann M Bauer A Schreuder H Dudda A Czech J Lorenz M Laux V Wehner V 《Bioorganic & medicinal chemistry letters》2004,14(16):4191-4195
A series of novel, highly potent 2-carboxyindole-based factor Xa inhibitors is described. Structural requirements for neutral ligands, which bind in the S1 pocket of factor Xa were investigated with the 2-carboxyindole scaffold. This privileged fragment assembly approach yielded a set of equipotent, selective inhibitors with structurally diverse neutral P1 substituents. 相似文献
23.
An efficiently expressed rDNA plasmid was used to quantitatively analyze the effect of base changes in modified positions associated with the peptidyl transferase center of the 25S rRNA from the yeast Schizosaccharomyces pombe. The results show that, unlike normal RNA and relative to a less conserved modified position outside the center, these mutant RNAs are highly unstable and rapidly degraded with little or no effect on cell growth. These results provide direct evidence that the positions of modification can be critical sites for nuclease attack. Taken together with previous genetic analyses of rRNA modification, they raise the possibility that rRNA modification may act, at least in part, as a quality control mechanism to help ensure that only functional RNA is incorporated into active ribosomes. 相似文献
24.
In Schizosaccharomyces pombe, interdependency in rRNA processing is mediated by a large protein complex (RAC) which contains independent binding sites for each of the transcribed spacers. The RAC complex exhibits no nuclease activity but dramatically alters the efficiency and specificity of the Pac1 nuclease, leading to the complete removal of the 3' ETS. Furthermore, the affinity of RAC protein for mutant 3' ETS correlates closely with in vivo effects on rRNA processing, and changes which disrupt RAC protein binding also inhibit Pac1 nuclease cleavage at the 3' end of the 25S rRNA sequence. The observations indicate that, in the presence of the RAC protein/3' ETS complex, cleavage by the RNase III-like homolog is not restricted to the known intermediate sites but also is directed at the 3' end of the 25S rRNA. 相似文献
25.
Z Brzezińska K Nazar H Kaciuba-U?ci?ko I Falecka-Wieczorek E Wójcik-Zió?kowska 《Journal of physiology and pharmacology》1998,49(4):591-595
The aim of this study was to find out whether creatine (Cr) feeding affects total creatine (TCr), phosphocreatine (PCr), adenine nucleotide contents and beta-hydroxy-acyl-CoA-dehydrogenase (HAD) activity in myocardium as compared to red skeletal muscle. Ten adult Wistar rats received Cr (2.5% of diet weight) for 7 days. In Cr fed rats, PCr was increased (by approx. 20%) in cardiac and in soleus muscles with ATP elevated in myocardium and TCr and free Cr in soleus. In both muscles, Cr feeding enhanced HAD activity. It is concluded, that dietary Cr does increase cardiac muscle high energy phosphate reserves and its oxidative potential. 相似文献
26.
27.
Ungvari Z Orosz Z Rivera A Labinskyy N Xiangmin Z Olson S Podlutsky A Csiszar A 《American journal of physiology. Heart and circulatory physiology》2007,292(5):H2417-H2424
Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. However, the mechanisms by which resveratrol exerts its vasculoprotective effects are not completely understood. Because oxidative stress and endothelial cell injury play a critical role in vascular aging and atherogenesis, we evaluated whether resveratrol inhibits oxidative stress-induced endothelial apoptosis. We found that oxidized LDL and TNF-alpha elicited significant increases in caspase-3/7 activity in endothelial cells and cultured rat aortas, which were prevented by resveratrol pretreatment (10(-6)-10(-4) mol/l). The protective effect of resveratrol was attenuated by inhibition of glutathione peroxidase and heme oxygenase-1, suggesting a role for antioxidant systems in the antiapoptotic action of resveratrol. Indeed, resveratrol treatment protected cultured aortic segments and/or endothelial cells against increases in intracellular H(2)O(2) levels and H(2)O(2)-mediated apoptotic cell death induced by oxidative stressors (exogenous H(2)O(2), paraquat, and UV light). Resveratrol treatment also attenuated UV-induced DNA damage (comet assay). Resveratrol treatment upregulated the expression of glutathione peroxidase, catalase, and heme oxygenase-1 in cultured arteries, whereas it had no significant effect on the expression of SOD isoforms. Resveratrol also effectively scavenged H(2)O(2) in vitro. Thus resveratrol seems to increase vascular oxidative stress resistance by scavenging H(2)O(2) and preventing oxidative stress-induced endothelial cell death. We propose that the antioxidant and antiapoptotic effects of resveratrol, together with its previously described anti-inflammatory actions, are responsible, at least in part, for its cardioprotective effects. 相似文献
28.
García-Cruz D Zafra de la Rosa GF Sánchez-Corona J Nazará Z López-Cardona MG García-Ortiz JE Corona-Rivera JR Cantú JM 《Genetic counseling (Geneva, Switzerland)》2007,18(1):85-97
We describe two unrelated patients and the mother of one of them showing clinical and radiological features as those previously described in the spondyloepiphyseal dysplasia-brachydactyly and distinctive speech (SED-BDS, also named Fantasy Island syndrome or Tattoo dysplasia) clinically characterized by short stature with acral shortness, distinctive face, mild blepharophimosis, upslanted palpebral fissures, abundant eyebrows and eyelashes, thick and abundant hair and coarse voice; and radiologically by brachymetacarpalia, brachymetatarsalia and brachyphalangia of all fingers and toes, short and broad long bones with normal morphology and small pelvis. The clinical and radiological features present in mother and son suggest a probable autosomal dominant mode of inheritance and variable expressivity. 相似文献
29.
Evaluation of blood pressure in feline night monkeys (Aotus azarae infulatus) under different restraint protocols
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30.
Jefferson José da Silva Santos Tereza Magalh?es José Valter Joaquim Silva Junior Andréa Nazaré Monteiro Rangel da Silva Marli Tenório Cordeiro Laura Helena Vega Gonzales Gil 《Memórias do Instituto Oswaldo Cruz》2015,110(5):677-683
Full-length dengue virus (DENV) cDNA clones are an invaluable tool for many studies,
including those on the development of attenuated or chimeric vaccines and on
host-virus interactions. Furthermore, the importance of low passage DENV infectious
clones should be highlighted, as these may harbour critical and unique
strain-specific viral components from field-circulating isolates. The successful
construction of a functional Brazilian low passage DENV serotype 2 full-length clone
through homologous recombination reported here supports the use of a strategy that
has been shown to be highly useful by our group for the development of flavivirus
infectious clones and replicons. 相似文献