细胞外基质刚度调控压电型机械敏感离子通道组件1对神经干细胞分化的影响

目的 本研究旨在探讨细胞外基质刚度变化对神经干细胞（neural stem cells,NSCs）分化的影响及其作用机制。方法 本研究基于成功构建脊髓损伤大鼠模型,并制备不同刚度（0.7 kPa、40 kPa）的聚丙烯酰胺凝胶基底,将大鼠原代NSCs于不同刚度基底上培养。压电型机械敏感离子通道组件1（piezo type mechanosensitive ion channel component 1,Piezo1）shRNA质粒转染NSCs细胞。免疫荧光染色检测神经元标志物双皮质醇（doublecortion,DCX）和星形胶质细胞标志物胶质纤维酸性蛋白（glial fibrillary acidic protein,GFAP）阳性细胞百分比。免疫组织化学及蛋白质免疫印迹（Western blot）法检测损伤组织及NSCs细胞中Piezo1蛋白的表达水平。结果 与0.7 kPa基质刚度组相比,40 kPa基质刚度组中DCX阳性细胞数增加,而GFAP阳性细胞数减少,Piezo1蛋白表达量上升。脊髓损伤大鼠损伤组织Piezo1蛋白表达显著高于空白对照（sham）组。40 kPa基质刚度条件下沉默Piezo1后,DCX阳性细胞数减少,而GFAP阳性细胞数增加,差异具有统计学意义（P<0.05）。机制研究发现,沉默Piezo1导致IV型胶原及纤连蛋白表达下降。重组纤连蛋白逆转了Piezo1 shRNA对NSCs分化的影响,即DCX阳性细胞数增加,而GFAP阳性细胞数减少。结论 综上可见,硬基底刚度通过促进Piezo1蛋白表达,上调IV型胶原及纤连蛋白表达,从而调控NSCs细胞分化。本研究为基于生物材料治疗脊髓损伤提供了新的视角。     

节律性听觉刺激下的神经振荡同步化及其应用

大脑的感觉、情绪、认知等功能与其神经振荡模式有密切的联系。通过施加节律性刺激可以调控大脑的神经振荡模式,进而影响个体感受、情绪状态和认知功能等。与近年来常见的非侵入性电刺激和磁刺激相比,同样依赖于外部刺激输入的节律性感觉刺激具有成本低、易操作等优点,被认为是一种极具潜力的神经调控手段。本文以节律性听觉刺激为例,系统综述了不同类型的节律性听觉刺激如何影响大脑的神经振荡模式,进而影响相关状态和功能;并通过总结外部节律性听觉刺激对个体感知觉、情绪与认知功能的影响,讨论其生理机制和应用前景。     

具有节点偏置的高阶神经网络模型

在汪涛文献基础上提出了一个具有节点偏置的高阶神经网络模型、给出了模型的哈密顿量和学习算法,证明了学习算法的收敛性,该模型能对每一神经元自动引入一个节点偏置使得网络能够存储所有学习图样包括相关图样,其存储容量远高于Hebb—rule—like学习算法下的高阶神经网络模型.对由30个神经元组成的二阶神经网络进行了计算机仿真,结果证实了上述结论.此外,对初始突触强度对学习效果的影响和不同存储图样数目下的平均吸引半径进行了仿真计算并分析了所得结果.新模型的特点使其具有良好的应用前景     

采用Reichardt运动检测器和Boltzmann Machine神经网络的运动计算

建立了一个探讨灵长类视皮层从Ｖ１区到ＭＴ区的运动信息加工原理的计算模型,这个过程的突出特征是视觉运动信息经过了从局部检测进步到整体感知。模型的第一层由用于抽提运动模式的局部速度以及结构性质的Ｒｅｉｃｈａｒｄｔ运动检测器组成,进一步的加工是通过Ｂｏｌｔｚｍａｎｎ Ｍａｃｈｉｎｅ神经网络来实现的。这种网络的学习算法具有局部更新的显著性质,在学习阶段,网络不断地修改联结权重以形成对于记录在网络的显单元上     

国家公园类型划分与空间识别——以云南省为例

国家公园是我国推进生态文明建设的重大制度创新,如何科学地对国家公园进行类型划分及空间识别,是国家公园布局和建设中的基础性工作,既有必要性也有紧迫性。本研究以中国国情为基础,参考国际经验,将国家公园划分为荒野导向型、生态优先型、游憩导向型与遗产导向型,构建了一个比较完整的国家公园分类体系。并以自然和人文多样化程度较高的云南为案例,以“双评价”为基础建立了一套指标体系和区划规则,利用人工神经网络建立土地利用演化学习算法,利用融入自适应惯性机制的元胞自动机展开时空模拟,对云南全域进行高分辨率不同类型国家公园的空间辨识,并通过收缩-膨胀原理对识别区域进行比较、修正和优化,进而提出未来云南国家公园布局的综合方案。结果表明: 云南省国家公园主要集中在三江地区与横断山区、滇西以及西南部地区,这3类地区可作为未来国家公园区划与分类保护的重点。本研究所建立的国家公园类型划分和空间识别的一般性可推广的研究范式和工作流程可作为全国应用的参考。     

Monocarbonyl Analogs of Curcumin with Potential to Treat Colorectal Cancer

Curcumin has a plethora of biological properties, making this compound potentially effective in the treatment of several diseases, including cancer. However, curcumin clinical use is compromised by its poor pharmacokinetics, being crucial to find novel analogs with better pharmacokinetic and pharmacological properties. Here, we aimed to evaluate the stability, bioavailability and pharmacokinetic profiles of monocarbonyl analogs of curcumin. A small library of monocarbonyl analogs of curcumin 1a–q was synthesized. Lipophilicity and stability in physiological conditions were both assessed by HPLC-UV, while two different methods assessed the electrophilic character of each compound monitored by NMR and by UV-spectroscopy. The potential therapeutic effect of the analogs 1a–q was evaluated in human colon carcinoma cells and toxicity in immortalized hepatocytes. Our results showed that the curcumin analog 1e is a promising agent against colorectal cancer, with improved stability and efficacy/safety profile.     

Antiproliferative Potential of Olneya tesota PF2 Lectin in Human Acute Monocytic Leukemia Cells

Acute monocytic leukemia is a type of myeloid leukemia that develops in monocytes. The current clinical therapies for leukemia are unsatisfactory due to their side effects and nonspecificity toward target cells. Some lectins display antitumor activity and may specifically recognize cancer cells by binding to carbohydrate structures on their surface. Therefore, this study evaluated the response of the human monocytic leukemia cell lines THP-1 to the Olneya tesota PF2 lectin. The induction of apoptosis and reactive oxygen species production in PF2-treated cells was evaluated by flow cytometry, and the lectin-THP-1 cell interaction and mitochondrial membrane potential were evaluated by confocal fluorescence microscopy. PF2 genotoxicity was evaluated by DNA fragmentation analysis via gel electrophoresis. The results showed that PF2 binds to THP-1 cells, triggers apoptosis and DNA degradation, changes the mitochondrial membrane potential, and increases reactive oxygen species levels in PF2-treated THP-1 cells. These results suggest the potential use of PF2 for developing alternative anticancer treatments with enhanced specificity.     

Sesquiterpenoids from the Resina Commiphora Promoting the Apoptotic Activity of PC-3 Prostate Cancer Cells

Four new germacrane-type sesquiterpenes commiphoranes M1-M4 ( 1 - 4 ) together with eighteen sesquiterpenes were isolated from the Resina Commiphora. The structures and relative configurations of new substances were determined by using spectroscopic methods. Biological activity investigation revealed that nine compounds including 7 , 9 , 14 , 16 , (+)- 17 , (−)- 17 , 18 , 19 , and 20 could induce the apoptosis of prostate cancer originated PC-3 cells, through classic apoptosis signaling pathway, even using flow cytometry showed that the compound (+)- 17 caused apoptosis of PC-3 cells more than 40 %, suggesting their potential therapeutic application in the development of novel drugs against prostate cancer.     

Changing synaptic specificities in the nervous system of Caenorhabditis elegans: Differentiation of the DD motoneurons

During postembryonic development, the DD motoneurons in the nematode Caenorhabditis elegans completely reorganize their pattern of synapses. Ablation of a pair of embryonic precursors results in the absence of this entire class of motoneurons. In their absence animals exhibit two developmentally distinct locomotory defects. The transition period from one defect to the other is correlated with the synaptic reorganization of the DD mns. Mutations in a gene (unc-123) have been isolated that exhibit locomotory defects similar to those of the ablated adult animals. Genetic and cellular analyses of one of these alleles suggest that the unc-123 gene product may be involved in the reestablishment of functional synapses in these neurons. © 1993 John Wiley & Sons, Inc.     

Neuronal specificity and its development in the Drosophila wing disc and its derivatives

The imaginal wing disc of flies gives rise to the adult wing blade and dorsal thorax (notum). A great deal has been learned in recent years about the process of neurogenesis in this disc; a number of genes that play crucial roles in the formation of sensory mother cells and in the differentiation of the sensory organs have been identified and their roles defined. Given this extensive background of developmental genetics, it has seemed profitable to summarize what is known about the end-products of neural development, the adult sensory organs. Discussed are their physiological function and role in behavior, the pathways followed by their axons in the CNS, and both genes and epigenetic processes that might play some role in the later stages of neural development and in adult function. The highly individual characteristics of certain of the sensory organs is emphasized, both in the context of their adult roles and as a challenge for future studies in developmental genetics. © 1993 John Wiley & Sons, Inc.