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991.
Haixia Ge Yan Zhang Zhuo Yang Kun Qiang Chao Chen Laiyu Sun Ming Chen Jian Zhang 《Bioorganic & medicinal chemistry》2019,27(10):2100-2111
Dopamine D1/D2 receptors are important targets for drug discovery in the treatment of central nervous system diseases. To discover new and potential D1/D2 ligands, 17 derivatives of tetrahydroprotoberberine (THPB) with various substituents were prepared by chemical synthesis or microbial transformation using Streptomyces griseus ATCC 13273. Their functional activities on D1 and D2 receptors were determined by cAMP assay and calcium flux assay. Seven compounds showed high activity on D1/D2 receptor with low IC50 values less than 1?µM. Especially, top compound 5 showed strong antagonistic activity on both D1 and D2 receptor with an IC50 of 0.391 and 0.0757?µM, respectively. Five compounds displayed selective antagonistic activity on D1 and D2 receptor. The SAR studies revealed that (1) the hydroxyl group at C-9 position plays an important role in keeping a good activity and small or fewer substituents on ring D of THPBs may also stimulate their effects, (2) the absence of substituents at C-9 position tends to be more selective for D2 receptor, and (3) hydroxyl substitution at C-2 position and the substitution at C-9 position may facilitate the conversion of D1 receptor from antagonist to agonist. Molecular docking simulations found that Asp 103/Asp 114, Ser 107/Cys 118, and Trp 285/ Trp 386 of D1/ D2 receptors are the key residues, which have strong interactions with the active D1/D2 compounds and may influence their functional profiles. 相似文献
992.
Mammalian Genome - Increasing evidence shows that miRNAs play pivotal roles in cardiovascular diseases, including heart failure (HF). The aim of this study was to investigate the role of miR-129-5p... 相似文献
993.
994.
995.
Britt Paulsen Kim Alex Fredriksen Dirk Petersen Louis Maes An Matheeussen Ali-Oddin Naemi Anne Aamdal Scheie Roger Simm Rui Ma Baojie Wan Scott Franzblau Lise-Lotte Gundersen 《Bioorganic & medicinal chemistry》2019,27(4):620-629
(+)-N6-Hydroxyagelasine D, the enantiomer of the proposed structure of (?)-ageloxime D, as well as N6-hydroxyagelasine analogs were synthesized by selective N-7 alkylation of N6-[tert-butyl(dimethyl)silyloxy]-9-methyl-9H-purin-6-amine in order to install the terpenoid side chain, followed by fluoride mediated removal of the TBDMS-protecting group. N6-Hydroxyagelasine D and the analog carrying a geranylgeranyl side chain displayed profound antimicrobial activities against several pathogenic bacteria and protozoa and inhibited bacterial biofilm formation. However these compounds were also toxic towards mammalian fibroblast cells (MRC-5). The spectral data of N6-hydroxyagelasine D did not match those reported for ageloxime D before. Hence, a revised structure of ageloxime D was proposed. Basic hydrolysis of agelasine D gave (+)-N-[4-amino-6-(methylamino)pyrimidin-5-yl]-N-copalylformamide, a compound with spectral data in full agreement with those reported for (?)-ageloxime D. 相似文献
996.
Maria Dornelas Nicholas J. Gotelli Hideyasu Shimadzu Faye Moyes Anne E. Magurran Brian J. McGill 《Ecology letters》2019,22(5):847-854
Scientists disagree about the nature of biodiversity change. While there is evidence for widespread declines from population surveys, assemblage surveys reveal a mix of declines and increases. These conflicting conclusions may be caused by the use of different metrics: assemblage metrics may average out drastic changes in individual populations. Alternatively, differences may arise from data sources: populations monitored individually, versus whole‐assemblage monitoring. To test these hypotheses, we estimated population change metrics using assemblage data. For a set of 23 241 populations, 16 009 species, in 158 assemblages, we detected significantly accelerating extinction and colonisation rates, with both rates being approximately balanced. Most populations (85%) did not show significant trends in abundance, and those that did were balanced between winners (8%) and losers (7%). Thus, population metrics estimated with assemblage data are commensurate with assemblage metrics and reveal sustained and increasing species turnover. 相似文献
997.
Mamadou Amadou Diallo Alix Sausset Audrey Gnahoui‐David Adeline Ribeiro E Silva Aurlien Brionne Yves Le Vern Franoise I. Bussire Julie Tottey Sonia Lacroix‐Lamand Fabrice Laurent Anne Silvestre 《Cellular microbiology》2019,21(7)
Coccidia are obligate intracellular protozoan parasites responsible for human and veterinary diseases. Eimeria tenella, the aetiologic agent of caecal coccidiosis, is a major pathogen of chickens. In Toxoplasma gondii, some kinases from the rhoptry compartment (ROP) are key virulence factors. ROP kinases hijack and modulate many cellular functions and pathways, allowing T. gondii survival and development. E. tenella's kinome comprises 28 putative members of the ROP kinase family; most of them are predicted, as pseudokinases and their functions have never been characterised. One of the predicted kinase, EtROP1, was identified in the rhoptry proteome of E. tenella sporozoites. Here, we demonstrated that EtROP1 is active, and the N‐terminal extension is necessary for its catalytic kinase activity. Ectopic expression of EtROP1 followed by co‐immunoprecipitation identified cellular p53 as EtROP1 partner. Further characterisation confirmed the interaction and the phosphorylation of p53 by EtROP1. E. tenella infection or overexpression of EtROP1 resulted both in inhibition of host cell apoptosis and G0/G1 cell cycle arrest. This work functionally described the first ROP kinase from E. tenella and its noncanonical structure. Our study provides the first mechanistic insight into host cell apoptosis inhibition by E. tenella. EtROP1 appears as a new candidate for coccidiosis control. 相似文献
998.
极端耐盐碱菌株的筛选及其菌肥对盐碱条件下小麦生长和土壤环境的影响 总被引:2,自引:0,他引:2
为获得具有盐碱地改良应用潜力的耐盐碱菌株,将采集于东营盐碱地的土样稀释涂布于pH 9、盐浓度100 g·L-1的Gibbson改良培养基上,共获得18株细菌.通过提高盐浓度、pH值,最终获得在pH 12、盐浓度20%的条件下仍然可以生长的极端耐盐碱菌株N14.对N14进行形态学、生理生化特征和16S rDNA序列分析鉴定,结果表明:菌株N14为马氏芽孢杆菌.盆栽试验结果表明,与盐碱土(CK)相比,N14菌肥可以显著提高小麦的生物量,株高、鲜重、干重分别提高了21.8%、57.9%、41.7%;显著增加小麦叶绿素a、叶绿素b、叶绿素总量,增长率分别为36.4%、20.0%、31.7%;显著提高盐碱土壤中的蔗糖酶、脲酶和碱性磷酸酶的活性,增长率分别为23.2%、68.8%、106.5%;显著提高小麦根系的超氧化物歧化酶、过氧化物酶和过氧化氢酶的活性,增长率分别为109.6%、17.8%、50%;显著减少小麦根系丙二醛的含量,减少率为39.8%.本研究为极端耐盐碱菌的应用提供了一条新思路,为盐碱地的改良提供了一条新途径. 相似文献
999.
为探明猕猴桃溃疡病在四川的适生性,选用MaxEnt模型,基于分布信息和环境变量,对该病在四川潜在分布区进行预测,分析主要环境变量对其分布的影响,并利用受试者工作特征曲线对模拟准确度进行评价.结果表明: 10次重复模拟的曲线下面积平均值为0.914,预测结果准确.猕猴桃溃疡病在四川的高适生区主要位于成都市、德阳市、绵阳市、广元市、巴中市、达州市和雅安市,中适生区在四川21地市州均有分布.刀切法筛选出影响猕猴桃溃疡病潜在分布的主要环境变量及其指标为:最冷月最低气温(-6.8~7.5 ℃)、最暖季度平均气温(15.6~32.3 ℃)、最干季度平均气温(-0.8~21 ℃)、年降水量(709~950.9 mm)和气温季节性变化标准差(4.7~9.6 ℃).本研究对制定猕猴桃溃疡病早期监测、预警及控制措施意义重大. 相似文献
1000.
于2015年4月(春季)、2015年6月(夏季)、2015年10月(秋季)、2016年1月(冬季),在海南东寨港红树林保护区潮间带进行多次采样,分选小型底栖动物,并测定沉积物中有机质和叶绿素a含量,分析不同季节东寨港红树林小型底栖动物丰度与有机质、Chla的相关性。研究结果,沉积物中小型底栖动物主要包括自由生活线虫、桡足类、涡虫、多毛类、寡毛类,线虫为优势类群;有机质含量为25.22%—93.41%,平均值为46.6%; Chla含量为0.188—6.303μg/g,平均值为1.731μg/g。相关性分析显示,春季小型底栖动物的丰度和Chla含量呈显著正相关(Pearson's r=0.684; P0.05),夏季小型底栖动物的丰度与有机质含量呈显著负相关(Pearson's r=-0.518; P0.05)。 相似文献