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排序方式: 共有209条查询结果,搜索用时 15 毫秒
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Radi M Brullo C Crespan E Tintori C Musumeci F Biava M Schenone S Dreassi E Zamperini C Maga G Pagano D Angelucci A Bologna M Botta M 《Bioorganic & medicinal chemistry letters》2011,21(19):5928-5933
Neuroblastoma (NB) represents the most common extracranial paediatric solid tumor for which no specific FDA-approved treatment is currently available. The tyrosine kinase c-Src has been reported to play an important role in the differentiation, cell-adhesion and survival of NB cells. Starting from dual Src/Abl inhibitors previously found active in NB cell lines (1-3), small modification of the original structures almost abolished the Abl activity with a contemporary improvement of affinity and specificity for c-Src. Among the synthesized compounds, the most potent c-Src inhibitor (10a) showed a very interesting antiproliferative activity in SH-SY5Y cells with an IC(50) of 80 nM and a favourable ADME profile. A 3D SAR analysis was also attempted and may guide the design of more potent c-Src inhibitors as potential agents for NB treatment. 相似文献
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Amoroso A Concia L Maggio C Raynaud C Bergounioux C Crespan E Cella R Maga G 《The Plant cell》2011,23(2):806-822
The oxidized base 7,8-oxoguanine (8-oxo-G) is the most common DNA lesion generated by reactive oxygen species. This lesion is highly mutagenic due to the frequent misincorporation of A opposite 8-oxo-G during DNA replication. In mammalian cells, the DNA polymerase (pol) family X enzyme DNA pol λ catalyzes the correct incorporation of C opposite 8-oxo-G, together with the auxiliary factor proliferating cell nuclear antigen (PCNA). Here, we show that Arabidopsis thaliana DNA pol λ, the only member of the X family in plants, is as efficient in performing error-free translesion synthesis past 8-oxo-G as its mammalian homolog. Arabidopsis, in contrast with animal cells, possesses two genes for PCNA. Using in vitro and in vivo approaches, we observed that PCNA2, but not PCNA1, physically interacts with DNA pol λ, enhancing its fidelity and efficiency in translesion synthesis. The levels of DNA pol λ in transgenic plantlets characterized by overexpression or silencing of Arabidopsis POLL correlate with the ability of cell extracts to perform error-free translesion synthesis. The important role of DNA pol λ is corroborated by the observation that the promoter of POLL is activated by UV and that both overexpressing and silenced plants show altered growth phenotypes. 相似文献
165.
Vissers LE Cox TC Maga AM Short KM Wiradjaja F Janssen IM Jehee F Bertola D Liu J Yagnik G Sekiguchi K Kiyozumi D van Bokhoven H Marcelis C Cunningham ML Anderson PJ Boyadjiev SA Passos-Bueno MR Veltman JA Smyth I Buckley MF Roscioli T 《PLoS genetics》2011,7(9):e1002278
The premature fusion of the paired frontal bones results in metopic craniosynostosis (MC) and gives rise to the clinical phenotype of trigonocephaly. Deletions of chromosome 9p22.3 are well described as a cause of MC with variably penetrant midface hypoplasia. In order to identify the gene responsible for the trigonocephaly component of the 9p22.3 syndrome, a cohort of 109 patients were assessed by high-resolution arrays and MLPA for copy number variations (CNVs) involving 9p22. Five CNVs involving FREM1, all of which were de novo variants, were identified by array-based analyses. The remaining 104 patients with MC were then subjected to targeted FREM1 gene re-sequencing, which identified 3 further mutant alleles, one of which was de novo. Consistent with a pathogenic role, mouse Frem1 mRNA and protein expression was demonstrated in the metopic suture as well as in the pericranium and dura mater. Micro-computed tomography based analyses of the mouse posterior frontal (PF) suture, the human metopic suture equivalent, revealed advanced fusion in all mice homozygous for either of two different Frem1 mutant alleles, while heterozygotes exhibited variably penetrant PF suture anomalies. Gene dosage-related penetrance of midfacial hypoplasia was also evident in the Frem1 mutants. These data suggest that CNVs and mutations involving FREM1 can be identified in a significant percentage of people with MC with or without midface hypoplasia. Furthermore, we present Frem1 mutant mice as the first bona fide mouse model of human metopic craniosynostosis and a new model for midfacial hypoplasia. 相似文献
166.
Dead-end ultrafiltration concentration and IMS/ATP-bioluminescence detection of Escherichia coli O157:H7 in recreational water and produce wash 总被引:1,自引:0,他引:1
Hunter DM Leskinen SD Magaña S Schlemmer SM Lim DV 《Journal of microbiological methods》2011,87(3):338-342
The purpose of this study was to develop a detection method for viable E. coli O157:H7 in fresh produce and recreational water. The method was evaluated using eight samples of produce wash and recreational water with or without spiked E. coli O157:H7 at ≤ 102 CFU·ml− 1 and concentrated using dead-end ultrafiltration (DEUF) to produce primary and secondary retentates. Fifty-four matrix replicates of undiluted secondary retentates or dilutions (1:2 or 1:10 in buffer) were evaluated using an IMS/ATP bioluminescence assay (IMS/ATP). Combining primary and secondary DEUF yielded a 2-4 log10 increase in E. coli O157:H7 concentrations in spiked samples and resulted in signal-to-noise ratios 2-219 fold higher than controls, depending on the sample type. DEUF increased the concentration of E. coli O157:H7 to within the detectable limits of IMS/ATP. The combined assay provided detection of viable E. coli O157:H7 in produce and recreational water. Accurate detection of microbial pathogens using DEUF and IMS/ATP could reduce disease outbreaks from contaminated water sources and food products. 相似文献
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Background
Stand-alone nutritional set-ups are useful tools to grow plants at defined nutrient availabilities and to measure nutrient uptake rates continuously, in particular that for nitrate. Their use is essential when the measurements are meant to cover long time periods. These complex systems have, however, important drawbacks, including poor long-term reliability and low precision at high nitrate concentration. This explains why the information dealing with diel dynamics of nitrate uptake rate is scarce and concerns mainly young plants grown at low nitrate concentration.Scope
The novel system detailed in this paper has been developed to allow versatile use in growth rooms, greenhouses or open fields at nitrate concentrations ranging from a few micro- to several millimoles per litres. The system controls, at set frequencies, the solution nitrate concentration, pH and volumes. Nitrate concentration is measured by spectral deconvolution of UV spectra. The main advantages of the set-up are its low maintenance (weekly basis), an ability to diagnose interference or erroneous analyses and high precision of nitrate concentration measurements (0·025 % at 3 mm). The paper details the precision of diurnal nitrate uptake rate measurements, which reveals sensitivity to solution volume at low nitrate concentration, whereas at high concentration, it is mostly sensitive to the precision of volume estimates.Conclusions
This novel set-up allows us to measure and characterize the dynamics of plant nitrate nutrition at high temporal resolution (minutes to hours) over long-term experiments (up to 1 year). It is reliable and also offers a novel method to regulate up to seven N treatments by adjusting the daily uptake of test plants relative to controls, in variable environments such as open fields and glasshouses. 相似文献170.
Manfroni G Meschini F Barreca ML Leyssen P Samuele A Iraci N Sabatini S Massari S Maga G Neyts J Cecchetti V 《Bioorganic & medicinal chemistry》2012,20(2):866-876
Hepatitis C virus (HCV) infection has been recognized as the major cause of liver failure that can lead to hepatocellular carcinoma. Among all the HCV proteins, NS5B polymerase represents a leading target for drug discovery strategies. Herein, we describe our initial research efforts towards the identification of new chemotypes as allosteric NS5B inhibitors. In particular, the design, synthesis, in vitro anti-NS5B and in cellulo anti-HCV evaluation of a series of 1-oxo-1H-pyrido[2,1-b][1,3]benzothiazole-4-carboxylate derivatives are reported. Some of the newly synthesized compounds showed an IC(50) ranging from 11 to 23 μM, and molecular modeling and biochemical studies suggested that the thumb domain could be the target site for this new class of NS5B inhibitors. 相似文献