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91.
ABSTRACT

Inhibitors of monoamine oxidase (MAO)-B have been used for many years in the therapy of Parkinson’s disease (PD). Owing to the safety concerns of the currently used agents, the discovery of novel scaffolds is of considerable interest. MAO-B inhibitory potential of rutin, a flavonoid derived from natural sources, has been established in experimental findings. Hence, the current study seeks to examine the interactions between rutin and crystal structure of human MAO-B enzyme. Molecular docking calculations, as well as molecular dynamics simulations, were employed to investigate the binding mode and the stability of the rutin/MAO-B complex. Energies of highest occupied/lowest unoccupied molecular orbitals were computed through DFT studies and used to calculate electron affinity, hardness, chemical potential, electronegativity, and electrophilicity index in order to investigate the capability of these parameters to influence the ligand–receptor interactions. It was found that rutin traverses both the entrance cavity and the substrate cavity, forcing the Ile-199 ‘gate’ to rotate into its open conformation. It results in the fusion of the two cavities of the MAO-B binding site and directly leads to better binding interactions. Results of the current study can be used for lead modification and development of novel drugs for the treatment of PD.  相似文献   
92.
The use of a Monte–Carlo formalism in a centrifugal gas process separation simulation provides an efficient predictor of dew-pointing as a function of the imposed radial pressure gradient. Previously, this was done by simply calculating radial pressure and then resorting to a separate equation of state routine for evaluating whether condensation will occur or not. In our model, we incorporate the potential energy associated with rotation of a gas element into the simulation along with molecular interaction terms. This enables us to predict when sufficient nucleation has occurred that condensed material forms—an important limit for stable operation of a gas centrifuge.  相似文献   
93.
Djungarian hamsters (Phodopus sungorus) exhibit pronounced winter acclimatization with changes in body mass, gonads, fur, and thermogenic capacity induced by decreasing daylength. To determine whether the annual activity pattern reflects the crucial role of the photoperiod for the hamsters' seasonality, animals with and without access to a running wheel (RW) were exposed to natural lighting conditions (~52°N) and ambient temperatures. Registration of locomotion in hamsters with a RW revealed a clear activity pattern closely related to dusk and dawn throughout the year. In contrast, animals without RW access showed a less stable phase relationship between the activity and the day‐night cycle in autumn and winter. During these seasons, the activity phase either exceeded the dark phase or even became indistinguishable from the rest phase. This correlated not only with increased locomotion during the light phase but also over the whole 24 h period, especially in autumn. In RW hamsters, a similar but attenuated trend was found that possibly reflects foraging due to increased food hoarding before winter. The more stable correlation between activity time and night length in RW hamsters might be explained by a suppressing effect of light on wheel‐running behavior (negative masking) and/or a stabilizing effect of running exercise on rhythmicity. In a further experiment, the phase‐reference points lights‐off and lights‐on within artificial light‐dark (LD) cycles were compared to sunset and sunrise in an intermediate ratio of light and dark and in long days. With respect to the defined phase‐reference points of the zeitgeber, the phase relation between activity and the LD cycle was similar in natural and corresponding artificial lighting conditions, and dependent on the LD ratio.  相似文献   
94.
Radioresistance is a major cause of decreasing the efficiency of radiotherapy for non-small cell lung cancer (NSCLC). To understand the radioresistance mechanisms in NSCLC, we focused on the radiation-induced Notch-1 signaling pathway involved in critical cell fate decisions by modulating cell proliferation. In this study, we investigated the use of Notch-1-regulating flavonoid compounds as novel therapeutic drugs to regulate radiosensitivity in NSCLC cells, NCI-H1299 and NCI-H460, with different levels of radioresistance. Rhamnetin and cirsiliol were selected as candidate Notch-1-regulating radiosensitizers based on the results of assay screening for activity and pharmacological properties. Treatment with rhamnetin or cirsiliol reduced the proliferation of NSCLC cells through the suppression of radiation-induced Notch-1 expression. Indeed, rhamnetin and cirsiliol increased the expression of tumor-suppressive microRNA, miR-34a, in a p53-dependent manner, leading to inhibition of Notch-1 expression. Consequently, reduced Notch-1 expression promoted apoptosis through significant down-regulation of the nuclear factor-κB pathway, resulting in a radiosensitizing effect on NSCLC cells. Irradiation-induced epithelial-mesenchymal transition was also notably attenuated in the presence of rhamnetin and cirsiliol. Moreover, an in vivo xenograft mouse model confirmed the radiosensitizing and epithelial-mesenchymal transition inhibition effects of rhamnetin and cirsiliol we observed in vitro. In these mice, tumor volume was significantly reduced by combinational treatment with irradiation and rhamnetin or cirsiliol compared with irradiation alone. Taken together, our findings provided evidence that rhamnetin and cirsiliol can act as promising radiosensitizers that enhance the radiotherapeutic efficacy by inhibiting radiation-induced Notch-1 signaling associated with radioresistance possibly via miR-34a-mediated pathways.  相似文献   
95.
Metabolic profiling and structural elucidation of novel secondary metabolites obtained from derived deletion strains of the filamentous fungus Penicillium chrysogenum were used to reassign various previously ascribed synthetase genes of the roquefortine/meleagrin pathway to their corresponding products. Next to the structural characterization of roquefortine F and neoxaline, which are for the first time reported for P. chrysogenum, we identified the novel metabolite roquefortine L, including its degradation products, harboring remarkable chemical structures. Their biosynthesis is discussed, questioning the exclusive role of glandicoline A as key intermediate in the pathway. The results reveal that further enzymes of this pathway are rather unspecific and catalyze more than one reaction, leading to excessive branching in the pathway with meleagrin and neoxaline as end products of two branches.  相似文献   
96.
Amyloid β-peptide (Aβ) pathology is an invariant feature of Alzheimer disease, preceding any detectable clinical symptoms by more than a decade. To this end, we seek to identify agents that can reduce Aβ levels in the brain via novel mechanisms. We found that (20S)-Rg3, a triterpene natural compound known as ginsenoside, reduced Aβ levels in cultured primary neurons and in the brains of a mouse model of Alzheimer disease. The (20S)-Rg3 treatment induced a decrease in the association of presenilin 1 (PS1) fragments with lipid rafts where catalytic components of the γ-secretase complex are enriched. The Aβ-lowering activity of (20S)-Rg3 directly correlated with increased activity of phosphatidylinositol 4-kinase IIα (PI4KIIα), a lipid kinase that mediates the rate-limiting step in phosphatidylinositol 4,5-bisphosphate synthesis. PI4KIIα overexpression recapitulated the effects of (20S)-Rg3, whereas reduced expression of PI4KIIα abolished the Aβ-reducing activity of (20S)-Rg3 in neurons. Our results substantiate an important role for PI4KIIα and phosphoinositide modulation in γ-secretase activity and Aβ biogenesis.  相似文献   
97.
This paper describes a prey–predator type fishery model with prey dispersal in a two-patch environment, one of which is a free fishing zone and other is a protected zone. The existence of possible steady states, along with their local stability, is discussed. A geometric approach is used to derive the sufficient conditions for global stability of the system at the positive equilibrium. Relative size of the reserve is considered as control in order to study optimal sustainable yield policy. Subsequently, the optimal system is derived and then solved numerically using an iterative method with Runge–Kutta fourth-order scheme. Numerical simulations are carried out to illustrate the importance of marine reserve in fisheries management. It is noted that the marine protected area enables us to protect and restore multi-species ecosystem. The results illustrate that dynamics of the system is extremely interesting if simultaneous effects of a regulatory mechanism like marine reserve is coupled with harvesting effort. It is observed that the migration of the resource, from protected area to unprotected area and vice versa, is playing an important role towards the standing stock assessment in both the areas which ultimately control the harvesting efficiency and enhance the fishing stock up to some extent.  相似文献   
98.
阐明水鸟栖息地利用与环境因子的关系有助于制定针对性的水鸟保护对策。本研究在2012~2013年冬季对崇明东滩鸟类栖息地优化区内越冬水鸟的种类、数量以及6种环境因子(植被面积比例、裸地面积比例、水深、地形变异、栖息地结构多样性和干扰)进行调查,以了解水鸟对人工湿地的栖息地利用及其影响因子。野外调查共记录到水鸟24种9 018只,其中优势种为斑嘴鸭(Anas poecilorhyncha)和绿头鸭(A.platyrhynchos);栖息地优化区内水鸟休息的个体数量占总数量的79.2%,这表明优化区是大多数水鸟的休息地,而小(Tachybaptus ruficollis)、白骨顶(Fulica atra)、黑水鸡(Gallinula chloropus)、白琵鹭(Platalea leucorodia)和黑脸琵鹭(P.minor)的觅食个体数量超过60%,说明优化区也为这些鸟类提供了觅食地。逐步回归分析表明,裸地面积比例是影响越冬水鸟种类分布的最主要因子;尽管游禽在地形变异较大、植被面积比例较低的区域数量较多,但在休息时游禽更偏好于裸地面积比例较高的区域,而涉禽休息时偏好于地形变异较大的区域。为增加栖息地优化区内的水鸟多样性,建议在优化区内种植水鸟可食的沉水植物以增加水鸟的食物资源,同时增加裸地面积比例和地形变异程度,更好地为水鸟提供栖息地。  相似文献   
99.
贵州梵净山自然保护区土壤甲螨群落的季节动态   总被引:1,自引:0,他引:1  
2001年7月至2002年4月在不同的季节,对梵净山自然保护区属级水平上土壤甲螨结构的季节变化进行了调查.结果显示,土壤甲螨多度的四季变化为春季>冬季>秋季>夏季.土壤甲螨多样性的四季变化为秋季>夏季>冬季>春季.不同的季节土壤甲螨群落组成不同,但小奥甲螨属、小盾珠甲螨属、木单翼甲螨属3个属在每个季节均为绝对优势属.土壤甲螨主要分布在表层,但从夏季到冬季,土壤甲螨从表层向深层迁徙.  相似文献   
100.
Eleven compounds were identified as estrogen receptor modulators from an in-house natural product database (NPD) by structure-based virtual screening for ERα and ERβ. Among them, 3 compounds were confirmed as ER agonists and 8 compounds were confirmed as ER antagonists by yeast two-hybrid (Y2H) assay, with EC50 values ranging from several micromolar to 100 micromolar. In this study, a novel series of cycloartane triterpenoids isolated from Schisandra glaucescens Diels was found to have ER antagonistic effect, the most potent antagonist of which exhibited activity with EC50 value of 2.55 and 4.68 μM for ERα and ERβ, respectively. Moreover, the types of modulation and subtype selectivity were also investigated through molecular docking simulation.  相似文献   
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