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51.
Lorthiois E Bernardelli P Vergne F Oliveira C Mafroud AK Proust E Heuze L Moreau F Idrissi M Tertre A Bertin B Coupe M Wrigglesworth R Descours A Soulard P Berna P 《Bioorganic & medicinal chemistry letters》2004,14(18):4623-4626
The synthesis and SAR studies of spiroquinazolinones as novel PDE7 inhibitors are discussed. The best compounds from the series displayed nanomolar inhibitory affinity and were selective versus other PDE isoenzymes. 相似文献
52.
Berkane N Carlier P Verstraete L Mathieu E Heim N Uzan S 《Birth defects research. Part A, Clinical and molecular teratology》2004,70(8):547-549
BACKGROUND: Published cases suggest that the use of angiotensin II receptor antagonists is fetotoxic during the third trimester, but not in early pregnancy. CASE: We report a case in which the adverse fetal effect of angiotensin II receptor antagonist treatment was reversed. A woman with chronic hypertension was treated with valsartan until gestation week (GW) 20, when a complete anhydramnios was observed. Six days after interruption of the treatment, amniotic fluid reappeared. It reached a normal level at GW 23.5. The plasmatic creatinine level and the renal ultrasound examination were within normal limits at the six-month follow-up. CONCLUSIONS: Whereas angiotensin-II-receptor antagonist generates a severe renal toxicity, this case suggests that, at least in the first half of pregnancy, these effects can be reversed. 相似文献
53.
Comparison of the epidemiology, drug resistance mechanisms, and virulence of Candida dubliniensis and Candida albicans 总被引:1,自引:0,他引:1
Sullivan DJ Moran GP Pinjon E Al-Mosaid A Stokes C Vaughan C Coleman DC 《FEMS yeast research》2004,4(4-5):369-376
Candida dubliniensis is a pathogenic yeast species that was first identified as a distinct taxon in 1995. Epidemiological studies have shown that C. dubliniensis is prevalent throughout the world and that it is primarily associated with oral carriage and oropharyngeal infections in human immunodeficiency virus (HIV)-infected and acquired immune deficiency syndrome (AIDS) patients. However, unlike Candida albicans, C. dubliniensis is rarely found in the oral microflora of normal healthy individuals and is responsible for as few as 2% of cases of candidemia (compared to approximately 65% for C. albicans). The vast majority of C. dubliniensis isolates identified to date are susceptible to all of the commonly used antifungal agents, however, reduced susceptibility to azole drugs has been observed in clinical isolates and can be readily induced in vitro. The primary mechanism of fluconazole resistance in C. dubliniensis has been shown to be overexpression of the major facilitator efflux pump Mdr1p. It has also been observed that a large number of C. dubliniensis strains express a non-functional truncated form of Cdr1p, and it has been demonstrated that this protein does not play a significant role in fluconazole resistance in the majority of strains examined to date. Data from a limited number of infection models reflect findings from epidemiological studies and suggest that C. dubliniensis is less pathogenic than C. albicans. The reasons for the reduced virulence of C. dubliniensis are not clear as it has been shown that the two species express a similar range of virulence factors. However, although C. dubliniensis produces hyphae, it appears that the conditions and dynamics of induction may differ from those in C. albicans. In addition, C. dubliniensis is less tolerant of environmental stresses such as elevated temperature and NaCl and H(2)O(2) concentration, suggesting that C. albicans may have a competitive advantage when colonising and causing infection in the human body. It is our hypothesis that a genomic comparison between these two closely-related species will help to identify virulence factors responsible for the far greater virulence of C. albicans and possibly identify factors that are specifically implicated in either superficial or systemic candidal infections. 相似文献
54.
Marchand C Le Maréchal P Meyer Y Miginiac-Maslow M Issakidis-Bourguet E Decottignies P 《Proteomics》2004,4(9):2696-2706
Proteomics was used to search for putative thioredoxin (TRX) targets in leaves of the model plant, Arabidopsis thaliana. About forty different proteins have been found to be reduced by TRX, after TRX itself has been specifically reduced by its NADPH-dependent reductase. Twenty-one of the identified proteins were already known or recently proposed to be TRX-dependent and nineteen of the proteins were new potential targets. The identified proteins are involved in a wide variety of processes, including the Calvin cycle, metabolism, photosynthesis, folding, defense against oxidative stress and amino acid synthesis. Two proteins from the glycine cleavage complex were also identified as putative TRX targets, and a new role can be postulated in leaves for TRX in defense against herbivores and/or pathogens. 相似文献
55.
Three monosomic lines (MSLs) and three nullisomic lines (NSLs) of the homeologous group 1 and one euploid line of the bread wheat Triticum aestivum cultivar Courtot were used in a proteomic approach to investigate the effects of zero, one or two doses of chromosomes 1A, 1B and 1D on the amount of endosperm proteins. Polypeptides whose amounts changed significantly between each aneuploid line and the euploid line were identified using image analyses of two-dimensional gel electrophoresis patterns resulting from specific endosperm protein extractions. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry and electrospray ionization tandem mass spectrometry were also used for protein identification. Removing one chromosome or a chromosome pair allowed varying responses to be observed for the remaining endosperm protein genes. Compensation phenomena for the high molecular weight glutenin subunits (HMW-GS) were detected only in the MSLs. Subunits Bx7, By8 and Dy12 were the only HMW-GS overexpressed (from 152-737%) when chromosomes 1A or 1B or 1D were at hemizygous state. Thirteen new protein spots were detected only in the NSL1D, and seven were identified as HMW-GS analogs. These seven new spots may result from the expression of inactive genes. The HMW-GS were of significantly higher volume in MSLs, whereas the low molecular weight glutenin subunits and the gamma-gliadins were of lower volume in aneuploid lines. Most of the down-regulated proteins in the MSLs were storage proteins encoded at loci located on another chromosome pair. Complex regulations between chromosomes and loci of the homeologous groups 1 and 6 in bread wheat are discussed. 相似文献
56.
Turck N Richert S Gendry P Stutzmann J Kedinger M Leize E Simon-Assmann P Van Dorsselaer A Launay JF 《Proteomics》2004,4(1):93-105
Self-renewing tissues such as the intestine contain progenitor proliferating cells which subsequently differentiate. Cell proliferation and differentiation involve gene regulation processes which take place in the nucleus. A human intestinal epithelial cell line model (Caco2/TC7) which reproduces these dynamic processes has been used to perform proteomic studies on nuclear proteins. Nuclei from Caco2/TC7 cells at proliferative and differentiated stages were purified by subcellular fractionation. After two-dimensional gel electrophoresis separation and ruthenium staining, 400 protein spots were detected by image analysis. Eighty-five spots corresponding to 60 different proteins were identified by matrix-assisted laser desorption/ionization mass spectrometry in nuclei from proliferative cells. Comparison of nuclear proteomes from proliferative or differentiated cells by differential display resulted in the identification of differentially expressed proteins such as nucleolin, hnRNP A2/B1 and hnRNP A1. By using Western blot analysis, we found that the expression and number of specific isoforms of these nuclear proteins decreased in differentiated cells. Immunocytochemistry experiments also showed that in proliferative cells nucleolin was distributed in nucleoli-like bodies. In contrast, hnRNPs A2/B1 and A1 were dispersed throughout the nucleus. This study of the nuclear proteome from intestinal epithelial cells represents the first step towards the establishment of a protein database which will be a valuable resource in future studies on the differential expression of nuclear proteins in response to physiological, pharmacological and pathological modulations. 相似文献
57.
Large-scale exploration of growth inhibition caused by overexpression of genomic fragments in Saccharomyces cerevisiae
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Boyer J Badis G Fairhead C Talla E Hantraye F Fabre E Fischer G Hennequin C Koszul R Lafontaine I Ozier-Kalogeropoulos O Ricchetti M Richard GF Thierry A Dujon B 《Genome biology》2004,5(9):R72-19
We have screened the genome of Saccharomyces cerevisiae for fragments that confer a growth-retardation phenotype when overexpressed in a multicopy plasmid with a tetracycline-regulatable (Tet-off) promoter. We selected 714 such fragments with a mean size of 700 base-pairs out of around 84,000 clones tested. These include 493 in-frame open reading frame fragments corresponding to 454 distinct genes (of which 91 are of unknown function), and 162 out-of-frame, antisense and intergenic genomic fragments, representing the largest collection of toxic inserts published so far in yeast. 相似文献
58.
Picard M Duval-Terrié C Dé E Champeil P 《Protein science : a publication of the Protein Society》2004,13(11):3056-3058
Amphipathic polymers derived from polysaccharides, namely hydrophobically modified pullulans, were previously suggested to be useful as polymeric substitutes of ordinary surfactants for efficient and structure-conserving solubilization of membrane proteins, and one such polymer, 18C(10), was optimized for solubilization of proteins derived from bacterial outer membranes (Duval-Terrie et al. 2003). We asked whether a similar ability to solubilize proteins could also be demonstrated in eukaryotic membranes, namely sarcoplasmic reticulum (SR) fragments, the major protein of which is SERCA1a, an integral membrane protein with Ca(2+)-dependent ATPase and Ca(2+)-pumping activity. We found that 18C(10)-mediated solubilization of these SR membranes did not occur. Simultaneously, however, we found that low amounts of this hydrophobically modified pullulan were very efficient at preventing long-term aggregation of these SR membranes. This presumably occurred because the negatively charged polymer coated the membranous vesicles with a hydrophilic corona (a property shared by many other amphipathic polymers), and thus minimized their flocculation. Reminiscent of the old Arabic gum, which stabilizes Indian ink by coating charcoal particles, the newly designed amphipathic polymers might therefore unintentionally prove useful also for stabilization of membrane suspensions. 相似文献
59.
Influence of food availability on demography and local population dynamics in a long-lived seabird 总被引:2,自引:0,他引:2
Oro D Cam E Pradel R Martínez-Abraín A 《Proceedings. Biological sciences / The Royal Society》2004,271(1537):387-396
Few studies have addressed the effects of food availability as a proximate factor affecting local adult survival in long-lived organisms and their consequences at local population dynamics. We used capture-recapture analysis of resightings of 10 birth cohorts of ringed Audouin's gulls, Larus audouinii, to estimate adult survival and dispersal (both emigration and immigration). For the first time, permanent emigration (the transient effect in capture-recapture analysis) was modelled for the whole population and not only for the newly marked birds. Gulls exploit to a large extent fishes discarded from trawlers, and a trawling moratorium established since 1991 has decreased food supply for the colony. This was used as a natural experiment of food availability to assess its effects on adult survival and emigration. These and other demographic parameters were used in a projection modelling to assess the probabilities of extinction of the colony under two scenarios of lower and higher food availability. Food availability (together with the age of individuals) influenced emigration probabilities, but not adult survival, which was estimated at 0.91 (s.e. = 0.02). When food was in shorter supply during the chick-rearing period, emigration was very high (ca. 65%) for younger breeders, although this rate decreased sharply with age. Probabilities of extinction were very high when food availability was low, and when environmental stochasticity was introduced, and only stochastic immigration from the outside seemed to prevent extinction. The results highlight the importance of dispersal processes in the population dynamics of long-lived organisms. 相似文献
60.