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Celine Scornavacca Vincent Berry Vincent Lefort Emmanuel JP Douzery Vincent Ranwez 《BMC bioinformatics》2008,9(1):413
Background
Supertree methods combine phylogenies with overlapping sets of taxa into a larger one. Topological conflicts frequently arise among source trees for methodological or biological reasons, such as long branch attraction, lateral gene transfers, gene duplication/loss or deep gene coalescence. When topological conflicts occur among source trees, liberal methods infer supertrees containing the most frequent alternative, while veto methods infer supertrees not contradicting any source tree, i.e. discard all conflicting resolutions. When the source trees host a significant number of topological conflicts or have a small taxon overlap, supertree methods of both kinds can propose poorly resolved, hence uninformative, supertrees. 相似文献22.
Helen Baines Margaret O Nwagwu Graham R Hastie Roman A Wiles Terry M Mayhew Francis JP Ebling 《Reproductive biology and endocrinology : RB&E》2008,6(1):4
Background
The hypogonadal (hpg) mouse is widely used as an animal model with which to investigate the endocrine regulation of spermatogenesis. Chronic treatment of these GnRH-deficient mice with estradiol is known to induce testicular maturation and restore qualitatively normal spermatogenesis. The aim of the current studies was to investigate whether these effects of estradiol are direct effects in the testis, or indirect actions via paradoxical stimulation of FSH secretion from the pituitary gland. 相似文献23.
J Klein J Gonzalez J Duchene L Esposito JP Pradère E Neau C Delage D Calise A Ahluwalia P Carayon JB Pesquero M Bader JP Schanstra JL Bascands 《FASEB journal》2009,23(1):134-142
Renal fibrosis is the common histological feature of advanced glomerular and tubulointerstitial disease leading to end-stage renal disease (ESRD). However, specific antifibrotic therapies to slow down the evolution to ESRD are still absent. Because persistent inflammation is a key event in the development of fibrosis, we hypothesized that the proinflammatory kinin B1 receptor (B1R) could be such a new target. Here we show that, in the unilateral ureteral obstruction model of renal fibrosis, the B1R is overexpressed and that delayed treatment with an orally active nonpeptide B1R antagonist blocks macrophage infiltration, leading to a reversal of the level of renal fibrosis. In vivo bone marrow transplantation studies as well as in vitro studies on renal cells show that part of this antifibrotic mechanism of B1R blockade involves a direct effect on resident renal cells by inhibiting chemokine CCL2 and CCL7 expression. These findings suggest that blocking the B1R is a promising antifibrotic therapy. 相似文献
24.
Effect of single mutations in the OGG1 gene found in human tumors on the substrate specificity of the Ogg1 protein 总被引:2,自引:2,他引:2 下载免费PDF全文
We have investigated the effect of single amino acid substitutions of conserved arginines on the catalytic activities of the human Ogg1 protein (α-hOgg1-Ser326) (wild-type α-hOgg1). Mutant forms of hOgg1 with mutations Arg46→Gln (α-hOgg1-Gln46) and Arg154→His (α-hOgg1-His154) have previously been identified in human tumors. The mutant proteins α-hOgg1-Gln46 and α-hOgg1-His154 were expressed in Escherichia coli and purified to homogeneity. The substrate specificities of these proteins and wild-type α-hOgg1 were investigated using γ-irradiated DNA and the technique of gas chromatography/isotope-dilution mass spectrometry. All three enzymes excised 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) and 8-hydroxyguanine (8-OH-Gua) from γ-irradiated DNA containing a multiplicity of base lesions. Michaelis–Menten kinetics of excision were measured. Significant differences between excision kinetics of these three enzymes were observed. Excision of FapyGua and 8-OH-Gua by wild-type α-hOgg1 was greater than that by α-hOgg1-Gln46 and α-hOgg1-His154. The latter mutant protein was less active than the former. The diminished activity of the mutant proteins was more pronounced for 8-OH-Gua than for FapyGua. Cleavage assays were also performed using 32P-labeled 34mer oligonucleotide duplexes containing a single 8-OH-Gua paired to each of the four DNA bases. The results obtained with the oligonucleotide containing the 8-OH-Gua/Cyt pair were in good agreement with those observed with γ-irradiated DNA. Wild-type α-hOgg1 and its mutants repaired the three mismatches less efficiently than the 8-OH-Gua/Cyt pair. The substitution of Arg154, in addition to diminishing the activity on 8-OH-Gua, relaxes the selectivity found in the wild-type α-hOgg1 for the base opposite 8-OH-Gua. Taken together the results show that the mutant forms α-hOgg1-Gln46 and α-hOgg1-His154 found in human tumors are defective in their catalytic capacities. 相似文献
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On association in a copula with time transformations 总被引:2,自引:0,他引:2
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