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41.
42.
Shan Xiao Lin Wei Zongqin Hong Li Rao Yanliang Ren Jian Wan Lingling Feng 《Bioorganic & medicinal chemistry》2019,27(5):805-812
By using a new Fragment-Based Virtual Screen strategy, two series of novel FBA-II inhibitors (thiourea derivatives) were de novo discovered based on the active site of fructose-1, 6-bisphosphate aldolase from Cyanobacterial (CyFBA). In comparison, most of the N-(2-benzoylhydrazine-1-carbonothioyl) benzamide derivatives (L14~L22) exhibit higher CyFBA-II inhibitory activities compared to N-(phenylcarbamothioyl) benzamide derivatives (L1~L13). Especially, compound L14 not only shows higher CyFBA-II activity (Ki?=?0.65?μM), but also exhibits most potent in vivo activity against Synechocystis sp. PCC 6803 (EC50?=?0.09?ppm), higher (7-fold) than that of our previous inhibitor (EC50?=?0.6?ppm). The binding modes of compound L14 and CyFBA-II were further elucidated by jointly using DOX computational protocol, MM-PBSA and site-directed mutagenesis assays. The positive results suggest that strategy adopted in this study was promising to rapidly discovery the potent inhibitors with novel scaffolds. The satisfactory algicide activities suggest that the thiourea derivatives is very likely to be a promising lead for the development of novel specific algicides to solve Cyanobacterial harmful algal blooms (CHABs). 相似文献
43.
运用虚拟现实暴露疗法治疗飞行恐惧症的研究述评 总被引:2,自引:0,他引:2
虚拟现实暴露疗法是治疗飞行恐惧症的新方法。与传统的暴露疗法相比,虚拟现实暴露疗法集合了实体暴露疗法和想象暴露疗法的优点。避免了二者的不足,具有灵活、高效、安全、可重复和易于操控的特点。研究者们利用数据头盔、双通道立体声耳机、追踪设备、感应器等设备给飞行恐惧症患者呈现实时的计算机动画、双通道立体声和触觉刺激,使之沉浸在虚拟的飞行情景中,从而激发出患者的恐惧情绪。在虚拟现实暴露治疗的过程中,治疗师根据患者的情况使之逐步暴露在不同等级的刺激性情景中,经反复练习逐渐耐受并适应这些情景,最终克服不合理的恐惧。近10年的大量研究表明:虚拟现实暴露疗法能有效地治愈飞行恐惧症,在临床上具有良好的应用前景。今后的研究将进一步比较虚拟现实暴露疗法与其他治疗方法的疗效,并开发出成本更低、临场感更好的虚拟现实设备以扩展虚拟现实暴露疗法在飞行恐惧症治疗中的应用。 相似文献
44.
The prediction of the complex structure of a small ligand with a protein, the so-called protein–ligand docking problem, is
a central part of the rational drug design process. For this purpose, we introduce the docking algorithm PLANTS (Protein–Ligand
ANT System), which is based on ant colony optimization, one of the most successful swarm intelligence techniques. We study
the effectiveness of PLANTS for several parameter settings and present a direct comparison of PLANTS’s performance to a state-of-the-art
program called GOLD, which is based on a genetic algorithm and frequently used in the pharmaceutical industry for this task.
Last but not least, we also show that PLANTS can make effective use of protein flexibility giving example results on cross-docking and virtual screening experiments for protein kinase A.
This article is based on a paper that won the best paper award at ANTS 2006, the 5th International Workshop on Ant Colony
Optimization and Swarm Intelligence held in Brussels, Belgium, 2006. This article includes new types of experiments and also
the possibility of considering flexibility of protein side-chains. 相似文献
45.
Panagiota Koskinioti Erica Ras Antonios A. Augustinos George Tsiamis Leo W. Beukeboom Carlos Caceres Kostas Bourtzis 《Entomologia Experimentalis et Applicata》2019,167(3):197-208
The olive fruit fly, Bactrocera oleae (Rossi) (Diptera: Tephritidae), is the major insect pest of olive orchards (Olea europaea L.), causing extensive damages on cultivated olive crops worldwide. Due to its economic importance, it has been the target species for a variety of population control approaches including the sterile insect technique (SIT). However, the inefficiency of the current mass‐rearing techniques impedes the successful application of area‐wide integrated pest management programs with an SIT component. It has been shown that insect mass rearing and quality of sterile insects can be improved by the manipulation of the insect gut microbiota and probiotic applications. In order to exploit the gut bacteria, it is important to investigate the structure of the gut microbial community. In the current study, we characterized the gut bacterial profile of two wild olive fruit fly populations introduced in laboratory conditions using next generation sequencing of two regions of the 16S rRNA gene. We compared the microbiota profiles regarding the geographic origin of the samples. Additionally, we investigated potential changes in the gut bacteria community before and after the first exposure of the wild adult flies to artificial adult diet with and without antibiotics. Various genera – such as Erwinia, Providencia, Enterobacter, and Klebsiella – were detected for the first time in B. oleae. The most dominant species was Candidatus Erwinia dacicola Capuzzo et al. and it was not affected by the antibiotics in the artificial adult diet used in the first generation of laboratory rearing. Geographic origin affected the overall structure of the gut community of the olive fruit fly, but antibiotic treatment in the first generation did not significantly alter the gut microbiota community. 相似文献
46.
Butyrylcholinesterase (BChE) is recently considered as a new target for the treatment of Alzheimer’s disease (AD). There is an increasing interest in the development of BChE inhibitors. In the present study, a set of pharmacophore models for BChE was developed and validated. Based on the models, virtual screening was performed on five compound collections, from which seventeen potential hits were retained for biological investigation. In total, eight of these seventeen potential hits showed selective BChE inhibitory activity. Moreover, four compounds displayed IC50 values in sub-micromolar range on eqBChE and three displayed IC50 values < 2 μM on huBChE. The diverse scaffolds of the active compounds provided good starting point further development of selective BChE inhibitors. As far as we concerned, here we disclose the first selective pharmacophore model targeting BChE. The high rate of the model in the identification of active hits indicates it is a valuable tool for the development of selective BChE inhibitors, which may benefit the treatment of AD. 相似文献
47.
Stefano Mammola 《Ecography》2019,42(7):1331-1351
The use of semi‐isolated habitats such as oceanic islands, lakes and mountain summits as model systems has played a crucial role in the development of evolutionary and ecological theory. Soon after the discovery of life in caves, different pioneering authors similarly recognized the great potential of these peculiar habitats as biological model systems. In their 1969 paper in Science, ‘The cave environment’, Poulson and White discussed how caves can be used as natural laboratories in which to study the underlying principles governing the dynamics of more complex environments. Together with other seminal syntheses published at the time, this work contributed to establishing the conceptual foundation for expanding the scope and relevance of cave‐based studies. Fifty years after, the aim of this review is to show why and how caves and other subterranean habitats can be used as eco‐evolutionary laboratories. Recent advances and directions in different areas are provided, encompassing community ecology, trophic‐webs and ecological networks, conservation biology, macroecology and climate change biology. Special emphasis is given to discuss how caves are only part of the extended network of fissures and cracks that permeate most substrates and, thus, their ecological role as habitat islands is critically discussed. Numerous studies have quantified the relative contribution of abiotic, biotic and historical factors in driving species distributions and community turnovers in space and time, from local to regional scales. Conversely, knowledge of macroecological patterns of subterranean organisms at a global scale remains largely elusive, due to major geographical and taxonomical biases. Also, knowledge regarding subterranean trophic webs and the effect of anthropogenic climate change on deep subterranean ecosystems is still limited. In these research fields, the extensive use of novel molecular and statistical tools may hold promise for quickly producing relevant information not accessible hitherto. 相似文献
48.
A colony of Amblyomma neumanni was started with engorged females collected from cattle in the province of Salta (24° 51S, 65° 33W), Argentina. The larvae and nymphs were fed on rabbits and the adults on calves. The non-parasitic stages were maintained in darkness at 27 ± 1°C and 83–86% RH. The life cycle (pre-feeding period not tested) had a mean duration of 205.7 days. The mean time (days) for the different phases of the cycle were as follows: feeding of females 8.8, pre-oviposition 23.8, oviposition 41.4, minimum egg incubation 76.1, feeding of larvae 8.5, pre-moult to nymphs 16.4, feeding of nymphs 7.9 and pre-moult to adults 22.8. The mean recovery rates of larvae, nymphs and females were 83.8, 85.6 and 89.3%, respectively. The nymphs moulting to females were heavier (8.1 ± 2.34 mg) than those moulting to males (6.0 ± 2.34 mg; p < 0.01), but their range of engorgement weight showed overlap (2.3–16.2 versus 2.2–12.8 mg, respectively). Two gynandromorphs were detected between the nymphs. A comparison of biological parameters of A. neumanni with other American Amblyomma species from mammals is presented. © Rapid Science Ltd. 1998 相似文献
49.
Oh M Im I Lee YJ Kim YH Yoon JH Park HG Higashiyama S Kim YC Park WJ 《Bioorganic & medicinal chemistry letters》2004,14(24):6071-6074
We describe a series of potent and selective inhibitors of ADAM12 that were discovered using computational screening of a focused virtual library. The initial structure-based virtual screening selected 64 compounds from a 3D database of 67,062 molecules. Being evaluated by a cell-based ADAM12 activity assay, compounds 5, 11, 14, 16 were further identified as the potent and selective inhibitors of ADAM12 with low nanomolar IC50 values. The mechanism underlying the potency and selectivity of a representative compound, 5, was investigated through molecular docking studies. 相似文献
50.
Gainer A 《Trends in genetics : TIG》2002,18(12):651-653
What makes for a good lab? Obviously the principle investigator and members of the team are important. So too, of course, are the correct services and environmental conditions. But there is another aspect, less quantifiable but of great importance. It's the ability of a laboratory to maximize the possibilities for scientific interaction. Having spent many years as an architect designing laboratories, here I give my views on designing successfully for interaction. 相似文献