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121.
Ma Jiachi Liang Wanqing Qiang Yaosheng Li Lei Du Jun Pan Chengwu Chen Bangling Zhang Chensong Chen Yuzhong Wang Qingkang 《Cell communication and signaling : CCS》2021,19(1):1-12
Wnt signaling plays key roles in cellular and physiological processes, including cell proliferation, differentiation and migration during development and tissue homeostasis in adults. This pathway can be defined as Wnt/β-catenin-dependent or β-catenin-independent or “non-canonical”, both signaling are involved in neurite and synapse development/maintenance. Porcupine (PORCN), an acylase that o-acylates Wnt ligands, a major modification in secretion and interaction with its receptors. We use Wnt-C59, a specific PORCN inhibitor, to block the secretion of endogenous Wnts in embryonic hippocampal neurons (DIV 4). Under these conditions, the activity of exogenous Wnt ligands on the complexity of the dendritic tree and axonal polarity were evaluated Cultured primary embryonic hippocampal neurons obtained from Sprague–Dawley rat fetuses (E18), were cultured until day in vitro (DIV) 4 (according to Banker´s protocol) and treated with Wnt-C59 for 24 h, Wnt ligands were added to the cultures on DIV 3 for 24 h. Dendritic arbors and neurites were analysis by fluorescence microscopy. Transfection with Lipofectamine 2000 on DIV 2 of plasmid expressing eGFP and KIF5-Cherry was carried out to evaluate neuronal polarity. Immunostaining was performed with MAP1B and Tau protein. Immunoblot analysis was carried out with Wnt3a, β-catenin and GSK-3β (p-Ser9). Quantitative analysis of dendrite morphology was carried out with ImageJ (NIH) software with Neuron J Plugin. We report, here, that Wnt-C59 treatment changed the morphology of the dendritic arbors and neurites of embryonic hippocampal neurons, with decreases β-catenin and Wnt3a and an apparent increase in GSK-3β (p-Ser9) levels. No effect was observed on axonal polarity. In sister cultures, addition of exogenous Wnt3a, 5a and 7a ligands rescued the changes in neuronal morphology. Wnt3a restored the length of neurites to near that of the control, but Wnt7a increased the neurite length beyond that of the control. Wnt5a also restored the length of neurites relative to Wnt concentrations. Results indicated that Wnt ligands, added exogenously, restored dendritic arbor complexity in embryonic hippocampal neurons, previously treated with a high affinity specific Porcupine inhibitor. We proposed that PORCN is an emerging molecular target of interest in the search for preclinical options to study and treat Wnt-related diseases. 相似文献
122.
The Protein Journal - Myo9a is an actin-based molecular motor with a RhoGAP domain in its C-terminal tail. It plays a role in a variety of biological processes, such as in regulating the immune... 相似文献
123.
Li Zhenzi Liu Pan Yuan Yanan Liang Xiaoxiao Lei Jun Zhu Xiaobin Zhang Zuoqi Cai Lin 《Biomechanics and modeling in mechanobiology》2021,20(5):2013-2030
Biomechanics and Modeling in Mechanobiology - Osteoporosis (OP), a skeletal disease making bone mechanically deteriorate and easily fracture, is a global public health issue due to its high... 相似文献
124.
海拔变化会引起气压、温度、降水、土壤湿度和风速等环境因子发生急剧变化, 植物功能性状-海拔的相互关系对于预测全球变化背景下山地植物的适应方式具有重要意义。该研究在青海湖流域海拔3 400-4 200 m范围内布设了5个样地(海拔间隔约200 m), 通过植物群落调查, 测定植物功能性状和土壤理化性质, 结合气象数据, 探讨了海拔对青海湖流域群落水平植物功能性状的影响。结果如下: (1)群落加权平均植株高度(H)、叶片干物质含量(LDMC)、叶片碳氮比(C:N)和叶片氮磷比(N:P)随海拔升高显著降低, 比根表面积(SRA)随海拔升高波动下降, 比叶面积(SLA)、叶片氮含量(LNC)和叶片磷含量(LPC)随海拔升高显著升高, 叶片碳含量(LCC)、比根长(SRL)和根组织密度(RTD)随海拔未发生显著变化。(2)所有性状的变异来源以物种组成变化为主, N:P和LPC的种内性状变异与物种组成变化呈现正的协变效应, 其余性状为负的协变效应。(3)降水和0- 10 cm土层土壤养分含量对SLA变化的解释率较高, 温度和10-20 cm土层土壤养分含量对其余性状随海拔变化的解释率较高。以上结果表明青海湖流域植物群落主要通过物种更替来适应随海拔升高而剧烈变化的环境, 且各群落中的非优势种倾向于占据与优势种相反的性状空间来提高资源利用率, 随海拔变化的热量和深层土壤养分含量是群落水平植物功能性状变化的主要影响因子。 相似文献
125.
Zhiting Chen Hongyan Liu Chongyang Xu Xiuchen Wu Boyi Liang Jing Cao Deliang Chen 《Ecology and evolution》2021,11(12):7335
Climate sensitivity of vegetation has long been explored using statistical or process‐based models. However, great uncertainties still remain due to the methodologies’ deficiency in capturing the complex interactions between climate and vegetation. Here, we developed global gridded climate–vegetation models based on long short‐term memory (LSTM) network, which is a powerful deep‐learning algorithm for long‐time series modeling, to achieve accurate vegetation monitoring and investigate the complex relationship between climate and vegetation. We selected the normalized difference vegetation index (NDVI) that represents vegetation greenness as model outputs. The climate data (monthly temperature and precipitation) were used as inputs. We trained the networks with data from 1982 to 2003, and the data from 2004 to 2015 were used to validate the models. Error analysis and sensitivity analysis were performed to assess the model errors and investigate the sensitivity of global vegetation to climate change. Results show that models based on deep learning are very effective in simulating and predicting the vegetation greenness dynamics. For models training, the root mean square error (RMSE) is <0.01. Model validation also assure the accuracy of our models. Furthermore, sensitivity analysis of models revealed a spatial pattern of global vegetation to climate, which provides us a new way to investigate the climate sensitivity of vegetation. Our study suggests that it is a good way to integrate deep‐learning method to monitor the vegetation change under global change. In the future, we can explore more complex climatic and ecological systems with deep learning and coupling with certain physical process to better understand the nature. 相似文献
126.
127.
Jian Liu Yu Wen Lina Gao Liang Gao Fengjun He Jingxian Zhou 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):72-84
Abstract Fibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragment-based virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC50 = 15.0?nM) and modest anti-proliferative activity (IC50 = 785.8?nM). Through two rounds of optimisation, the indazole derivative 9?u stood out as the most potent FGFR1 inhibitors with the best enzyme inhibitory activity (IC50 = 3.3?nM) and cellular activity (IC50 = 468.2?nM). Moreover, 9?u also exhibited good kinase selectivity. In addition, molecular docking study was performed to investigate the binding mode between target compounds and FGFR1. 相似文献
128.
Jing-Wei Liang Ming-Yang Wang Shan Wang Shi-Long Li Wan-Qiu Li 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):235-244
Abstract Cyclin-dependent kinase 2 (CDK2) is the family of Ser/Thr protein kinases that has emerged as a highly selective with low toxic cancer therapy target. A multistage virtual screening method combined by SVM, protein-ligand interaction fingerprints (PLIF) pharmacophore and docking was utilised for screening the CDK2 inhibitors. The evaluation of the validation set indicated that this method can be used to screen large chemical databases because it has a high hit-rate and enrichment factor (80.1% and 332.83 respectively). Six compounds were screened out from NCI, Enamine and Pubchem database. After molecular dynamics and binding free energy calculation, two compounds had great potential as novel CDK2 inhibitors and they also showed selective inhibition against CDK2 in the kinase activity assay. 相似文献
129.
A rapid and sensitive flow‐injection chemiluminescence (FI–CL) method is described for the determination of diazepam based on its reaction with N‐bromosuccinimide (NBS) in alkaline medium in the presence of dichlorofluorescein (DCF) as an effective energy‐transfer agent. Under optimum conditions, the proposed method allowed the measurement of diazepam over the range of 2.0 × 10?6 to 2.0 × 10?4 mol/L with a detection limit of 5.0 × 10?7 mol/L. The relative standard deviation for 11 parallel measurements of 2.0 × 10?5 mol/L diazepam was 2.1%. The method was applied satisfactorily for the determination of diazepam in pharmaceutical preparations, and the results agree well with those obtained by spectrophotometry. The use of the proposed system for the determination of diazepam in urine and plasma samples was also tested. The possible mechanism of the chemiluminescence reaction is discussed briefly. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
130.
Fahui Liu Xinying Zhang Xiaoyan Liu Xueping Chen Xia Liang Chiquan He 《Soil & Sediment Contamination》2013,22(8):1013-1027
This study assessed the potential abilities of Scirpus triqueter for phytoremediation of soils contaminated with Pb-PAHs, amended with environment-friendly surfactant alkyl polyglucoside (APG). The effects of APG on the removal of PAHs from soil and the plant uptake and translocation of Pb were tested with plant growth and soil enzymatic activities. Experiments demonstrated that APG has an ability to facilitate PAH degradation and Pb uptake in the plant body at appropriate concentrations (20–40mg L?1). The highest PAH removal rate was observed in 30 mg L?1 APG treatment, and the highest accumulation of Pb was detected as 40 mg L?1 APG. Experiments documented the effects of APG on plant growth, soil enzymatic activity, bioaccumulation and translocation of Pb in Scirpus triqueter. Results indicated that the addition of appropriate APG enhanced PAH removal rate and increased plant uptake and translocation of Pb. 相似文献