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991.
Pruitt JR Batt DG Wacker DA Bostrom LL Booker SK McLaughlin E Houghton GC Varnes JG Christ DD Covington M Das AM Davies P Graden D Kariv I Orlovsky Y Stowell NC Vaddi KG Wadman EA Welch PK Yeleswaram S Solomon KA Newton RC Decicco CP Carter PH Ko SS 《Bioorganic & medicinal chemistry letters》2007,17(11):2992-2997
DPC168, a benzylpiperidine-substituted aryl urea CCR3 antagonist evaluated in clinical trials, was a relatively potent inhibitor of the 2D6 isoform of cytochrome P-450 (CYP2D6). Replacement of the cyclohexyl central ring with saturated heterocycles provided potent CCR3 antagonists with improved selectivity against CYP2D6. The favorable preclinical profile of DPC168 was maintained in an acetylpiperidine derivative, BMS-570520. 相似文献
992.
Lagu B Lebedev R Pio B Yang M Pelton PD 《Bioorganic & medicinal chemistry letters》2007,17(12):3491-3496
A number of RXR modulators with novel structural features were synthesized and screened in the functional assays. The synthesis and the structure-activity relationship within the series of compounds will be presented. Some in vivo data generated in the models for dyslipidemia and diabetes will also be presented. 相似文献
993.
994.
Lagu B Pio B Lebedev R Yang M Pelton PD 《Bioorganic & medicinal chemistry letters》2007,17(12):3497-3503
A number of RXR agonists were synthesized and screened in functional assays. The synthesis and the structure-activity relationship (SAR) within the series of compounds will be presented. Some in vivo data in rodent models for dyslipidemia and diabetes will also be presented. 相似文献
995.
It is well established that sea turtles return to natal rookeries to mate and lay their eggs, and that individual females are faithful to particular nesting sites within the rookery. Less certain is whether females are precisely returning to their natal beach. Attempts to demonstrate such precise natal philopatry with genetic data have had mixed success. Here we focused on the green turtles of three nesting sites in the Ascension Island rookery, separated by 5-15 km. Our approach differed from previous work in two key areas. First, we used male microsatellite data (five loci) reconstructed from samples collected from their offspring (N = 17) in addition to data for samples taken directly from females (N = 139). Second, we employed assignment methods in addition to the more traditional F-statistics. No significant genetic structure could be demonstrated with F(ST). However, when average assignment probabilities of females were examined, those for nesting populations in which they were sampled were indeed significantly higher than their probabilities for other populations (Mann-Whitney U-test: P < 0.001). Further evidence was provided by a significant result for the mAI(C) test (P < 0.001), supporting greater natal philopatry for females compared with males. The results suggest that female natal site fidelity was not sufficient for significant genetic differentiation among the nesting populations within the rookery, but detectable with assignment tests. 相似文献
996.
目的:采用基因表达谱分析方法,探讨小麦耐铝的分子机理。方法:利用抑制消减杂交(SSH)技术,以小麦的铝敏感品种Chisholm及其耐铝近等基因系Chisholm-T(其耐铝性来自小麦品种Atlas66)的根尖为材料,构建了2个铝胁迫后的SSHcDNA文库,共含有1628个表达序列标签(EST),利用这些EST制作了小麦根系的cDNA基因芯片。以cDNA基因芯片为平台,在铝胁迫后6h、1d、3d和7d,分别比较Chisholm和Chisholm-T之间的基因表达谱差异。结果:在各个时间点,耐铝和不耐铝小麦材料之间约有5%的EST表现出差异表达。对所有差异表达的EST进行测序分析,序列数据经Pipe-Online2.0进行毗连序列群(contig)拼接,发现只有8.3%的重复序列。结论:SSH是一种非常有效的差减和均一化的建库方法。对有功能注释的差异表达基因进行功能分类分析,表明这些基因参与了植物体内的电子传递、信号传导、植物保护和次生物质的代谢活动。 相似文献
997.
During the G1/S transition, p21 proteolysis is mediated by Skp2; however, p21 reaccumulates in G2 and is degraded again in prometaphase. How p21 degradation is controlled in mitosis remains unexplored. We found that Cdc20 (an activator of the ubiquitin ligase APC/C) binds p21 in cultured cells and identified a D box motif in p21 necessary for APC/C(Cdc20)-mediated ubiquitylation of p21. Overexpression of Cdc20 or Skp2 destabilized wild-type p21; however, only Skp2, but not Cdc20, was able to destabilize a p21(D box) mutant. Silencing of Cdc20 induced an accumulation of p21, increased the fraction of p21 bound to Cdk1, and inhibited Cdk1 activity in p21(+/+) prometaphase cells, but not in p21(-/-) cells. Thus, in prometaphase Cdc20 positively regulates Cdk1 by mediating the degradation of p21. We propose that the APC/C(Cdc20)-mediated degradation of p21 contributes to the full activation of Cdk1 necessary for mitotic events and prevents mitotic slippage during spindle checkpoint activation. 相似文献
998.
López-Martínez R Hernández-Hernández F Millán-Chiu BE Manzano-Gayosso P Méndez-Tovar LJ 《Revista iberoamericana de micología》2007,24(4):283-288
We present a study on the control and elimination of the fungi affecting the mummies specifically at the museum "El Carmen", in San Angel, Mexico City. Twelve analysed mummies presented an important deterioration attributed to colonizing fungi. The degree of fungal contamination and the efficacy of imazalil were evaluated. Two samplings were performed in order to isolate and identify the fungal genera, one for control and the other after the treatment. Isolation was done by the carpet-square technique and identification was performed by morphological features. Each sampling gave a total of 100 samples as follows: 17 from the air, 23 from the walls and 60 from the mummies. Samples were cultured on Sabouraud dextrose agar. From the first sampling a total of 649 colonies corresponding to 24 genera were obtained being the most frequent Penicillium, Cladophialophora and Aspergillus. From the second sampling, after the imazalil treatment, which was applied by means of lit candles containing the antifungal drug, 57 colonies were recovered, representing a 91.2% fungal reduction; 18 genera were eliminated. In spite of resistance showed by many Penicillium strains, the imazalil is an alternative drug for the control of fungal colonization on these studied materials. 相似文献
999.
Daniel Krewski Victoria Hogan Michelle C. Turner Patricia L. Zeman Ian McDowell Nancy Edwards 《人类与生态风险评估》2007,13(6):1288-1312
The traditional medical model of health and health policy development has focused on individuals and the role of medical care in preventing and treating disease and injury. Recent attention to health inequities and social determinants of health has raised the profile of population heath and evidence-based strategies for improving the health of whole populations. At the same time, risk science has emerged as an important new discipline for the assessment and management of risks to health. This article reviews historical developments in the fields of risk management and population health and proposes a joint population health risk management framework that integrates the key elements of both fields. Applying this integrated approach to managing population health risks will facilitate the development of evidence-based health policy. It will encourage a more systematic and comprehensive evaluation of population health issues and promote the use of a broader suite of interventions to reduce health risks and enhance population health status. 相似文献
1000.
Cheng AC Coleman RG Smyth KT Cao Q Soulard P Caffrey DR Salzberg AC Huang ES 《Nature biotechnology》2007,25(1):71-75
Lead generation is a major hurdle in small-molecule drug discovery, with an estimated 60% of projects failing from lack of lead matter or difficulty in optimizing leads for drug-like properties. It would be valuable to identify these less-druggable targets before incurring substantial expenditure and effort. Here we show that a model-based approach using basic biophysical principles yields good prediction of druggability based solely on the crystal structure of the target binding site. We quantitatively estimate the maximal affinity achievable by a drug-like molecule, and we show that these calculated values correlate with drug discovery outcomes. We experimentally test two predictions using high-throughput screening of a diverse compound collection. The collective results highlight the utility of our approach as well as strategies for tackling difficult targets. 相似文献