Tunable Surface-Enhanced Raman Spectroscopy via Plasmonic Coupling Between Nanodot-Arrayed Ag Film and Ag Nanocube

Herein, a flexible surface-enhanced Raman spectroscopy (SERS) substrate composed of nanodot-arrayed Ag film and Ag nanocubes was fabricated through a simple method. The large-area nanodot-arrayed Ag film was produced at low cost and high reproducibility. The experimental results show that the coupled structure produces a much stronger SERS signal than the Ag nanocube alone and the isolated nanodot-arrayed Ag film. Furthermore, the coupling effect is sensitive to geometrical parameter of the period of the dot-array. Numerical simulations are performed to verify the electric field enhancement of the composite SERS substrate and support the experimental results.     

Shikonin Kills Glioma Cells through Necroptosis Mediated by RIP-1

Background and Purpose

Shikonin was reported to induce necroptosis in leukemia cells, but apoptosis in glioma cell lines. Thus, it is needed to clarify whether shikonin could cause necroptosis in glioma cells and investigate its underlying mechanisms.

Methods

Shikonin and rat C6 glioma cell line and Human U87 glioma cell line were used in this study. The cellular viability was assayed by MTT. Flow cytometry with annexin V-FITC and PI double staining was used to analyze cellular death modes. Morphological alterations in C6 glioma cells treated with shikoinin were evaluated by electronic transmission microscopy and fluorescence microscopy with Hoechst 33342 and PI double staining. The level of reactive oxygen species was assessed by using redox-sensitive dye DCFH-DA. The expressional level of necroptosis associated protein RIP-1 was analyzed by western blotting.

Results

Shikonin induced cell death in C6 and U87 glioma cells in a dose and time dependent manner. The cell death in C6 and U87 glioma cells could be inhibited by necroptosis inhibitor necrotatin-1, not by pan-caspase inhibitor z-VAD-fmk. Shikonin treated C6 glioma cells presented electron-lucent cytoplasm, loss of plasma membrane integrity and intact nuclear membrane in morphology. The increased ROS level caused by shikonin was attenuated by necrostatin-1 and blocking ROS by anti-oxidant NAC rescued shikonin-induced cell death in both C6 and U87 glioma cells. Moreover, the expressional level of RIP-1 was up-regulated by shikonin in a dose and time dependent manner as well, but NAC suppressed RIP-1 expression.

Conclusions

We demonstrated that the cell death caused by shikonin in C6 and U87 glioma cells was mainly via necroptosis. Moreover, not only RIP-1 pathway, but also oxidative stress participated in the activation of shikonin induced necroptosis.     

北京溪泥甲科二新种及一新亚种（鞘翅目：泥甲总科）

本文记述溪泥甲科２新种──北京溪泥甲Ｓｔｅｎｅｌｍｉｓｂｅｉｊｉｎｇａｎａ,ｓｐ．ｎｏｖ．,杨氏溪泥甲Ｓｔｅｎｅｌｍｉｓｙａｎｇｉ,ｓｐ．ｎｏｖ．及１新亚种──无毛缢溪泥甲Ｌｅｐｔｅｌｍｉｓｇｒａｃｉｌｉｓｉｍｐｕｂｉｓ,ｓｓｐ．ｎｏｖ．。模式标本存北京农业大学昆虫标本馆。     

捕食者对空心莲子草叶甲种群的生物胁迫

广食性捕食者广泛捕食植食性昆虫,常被用于有害生物的生物防治,也因此影响植食性昆虫对杂草的生物效果。空心莲子草叶甲(Agasicles hygrophila)(鞘翅目:叶甲科Chrysomelidae)作为入侵恶性杂草空心莲子草(Alternanthera philoxeroides)(苋科:莲子草属Alternanthera)的专性天敌,从美国的弗罗里达州引入中国,在释放地防治空心莲子草取得了较好的防治效果。虽然空心莲子草叶甲在引入地均已建立田间种群并有一定程度的自然扩散,但丰富的食物资源,并未使空心莲子草叶甲的自然种群数量变得繁荣,因此其未能有效抑制空心莲子草的扩散蔓延。在野外调查时发现空心莲子草生境中存在大量广食性捕食者。这些广食性捕食者是抑制空心莲子草叶甲种群数量扩张的生物胁迫因子吗?为此,选择捕食性昆虫龟纹瓢虫(Propylaea japonica)(鞘翅目:瓢虫科Coccinellidae)、蜘蛛类捕食者拟水狼蛛(Pirata subpiraticus)(蜘蛛目:狼蛛科Lycosidae)与斜纹猫蛛(Oxyopes sertatus)(蜘蛛目:猫蛛科Oxyopidae)为捕食者,分别以空心莲子草叶甲各虫态为猎物,构建简单的捕食者-猎物系统,在室内检测了上述3种捕食者对空心莲子草叶甲各虫态在不同密度下的日捕食量,以期了解捕食者对空心莲子草叶甲的捕食作用,客观评估空心莲子草叶甲的生物防治效能。研究结果表明:捕食者龟纹瓢虫、斜纹猫蛛与拟水狼蛛均捕食空心莲子草叶甲的卵粒及1龄、2龄幼虫,斜纹猫蛛与拟水狼蛛捕食3龄幼虫,捕食者的捕食量均随着猎物密度的升高而增加,寻找效应降低。三者均不捕食成虫。除拟水狼蛛对3龄幼虫的捕食用Holling II模型拟合不呈显著相关关系外,其余捕食反应均拟合Holling II模型并显著相关。通过拟合方程得出捕食者对空心莲子草叶甲卵粒的理论日最大捕食量为:斜纹猫蛛10.9粒,拟水狼蛛为6.2粒,龟纹瓢虫为5.6粒;对1龄幼虫的理论日最大捕食量为:斜纹猫蛛为17.1头;拟水狼蛛为35.8头,龟纹瓢虫为10.4头;对2龄幼虫的理论日最大捕食量为:斜纹猫蛛为6.6头,拟水狼蛛为11.2头,龟纹瓢虫为2.9头;对3龄幼虫的理论日最大捕食量为:斜纹猫蛛捕食12.3头,拟水狼蛛为1.1头。研究结果证实了捕食者可通过捕食作用降低空心莲子草叶甲种群密度,削弱空心莲子草叶甲对空心莲子草的控害效能,是空心莲子草叶甲种群存活的生物胁迫因子。建议在提高空心莲子草叶甲田间种群数量,达到对空心莲子有效的持续控制效果方面开展进一步研究。     

ABC转运蛋白及其在合成生物学中的应用

ABC转运蛋白(ATP-binding cassette transporter,ABC transporter)作为一种超大膜转运蛋白家族,在大多数生物体中发挥着重要作用。文中从结构特征、转运机制以及生理功能等方面论述了ABC转运蛋白的研究进展,进而着重综述了近些年来ABC转运蛋白在合成生物学领域中的应用,并为今后进一步的研究提出了展望,希望为扩展其应用提供指导。     

Human serum and glucocorticoid-inducible kinase-like kinase (SGKL) phosphorylates glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9 through direct interaction

Serum and glucocorticoid-inducible kinase-like kinase (SGKL) has been identified as a new integrator that decodes lipid signals produced by the activation of phosphoinositide 3-kinase (PI3K). SGKL is activated via its lipid-binding domain (phox homology domain) in response to PI3K signaling. However, downstream targets of SGKL as well as the role of SGKL as a mediator in PI3K signaling in human tissues remain to be established. In this study, we identified human glycogen synthase kinase 3 beta (GSK-3beta) as a specific interacting partner with SGKL in a yeast two-hybrid screening of human brain cDNA library. The association between these two proteins is confirmed independently in human embryonic kidney (HEK293) cells by co-immunoprecipitation. Furthermore, the kinase activity of wild-type SGKL was required for the in vitro phosphorylation of a GSK-3 crosstide fusion protein at serine-21/9 as demonstrated with a Phospho-GSK-3alpha/beta (Ser21/9) specific antibody. The present results provide strong evidences that SGKL could utilize GSK-3beta as a direct downstream target by phosphorylating GSK-3beta at serine-9.     

Identification of Novel Piperazinylquinoxaline Derivatives as Potent Phosphoinositide 3-Kinase (PI3K) Inhibitors

Background

Development of small-molecule inhibitors targeting phosphoinositide 3-kinase (PI3K) has been an appealing strategy for the treatment of various types of cancers.

Methodology/Principal Finding

Our approach was to perform structural modification and optimization based on previously identified morpholinoquinoxaline derivative WR1 and piperidinylquinoxaline derivative WR23 with a total of forty-five novel piperazinylquinoxaline derivatives synthesized. Most target compounds showed low micromolar to nanomolar antiproliferative potency against five human cancer cell lines using MTT method. Selected compounds showed potent PI3Kα inhibitory activity in a competitive fluorescent polarization assay, such as compound 22 (IC₅₀ 40 nM) and 41 (IC₅₀: 24 nM), which induced apoptosis in PC3 cells. Molecular docking analysis was performed to explore possible binding modes between target compounds and PI3K.

Conclusions/Significance

The identified novel piperazinylquinoxaline derivatives that showed potent PI3Kα inhibitory activity and cellular antiproliferative potency may be promising agents for potential applications in cancer treatment.     

A computational analysis framework for molecular cell dynamics: case-study of exocytosis

One difficulty in conducting biologically meaningful dynamic analysis at the systems biology level is that in vivo system regulation is complex. Meanwhile, many kinetic rates are unknown, making global system analysis intractable in practice. In this article, we demonstrate a computational pipeline to help solve this problem, using the exocytotic process as an example. Exocytosis is an essential process in all eukaryotic cells that allows communication in cells through vesicles that contain a wide range of intracellular molecules. During this process a set of proteins called SNAREs acts as an engine in this vesicle-membrane fusion, by forming four-helical bundle complex between (membrane) target-specific and vesicle-specific SNAREs. As expected, the regulatory network for exocytosis is very complex. Based on the current understanding of the protein-protein interaction network related to exocytosis, we mathematically formulated the whole system, by the ordinary differential equations (ODE). We then applied a mathematical approach (called inverse problem) to estimating the kinetic parameters in the fundamental subsystem (without regulation) from limited in vitro experimental data, which fit well with the reports by the conventional assay. These estimates allowed us to conduct an efficient stability analysis under a specified parameter space for the exocytotic process with or without regulation. Finally, we discuss the potential of this approach to explain experimental observations and to make testable hypotheses for further experimentation.     

新疆察布查尔锡伯族体质特征调查

本文调查了新疆察布查尔锡伯族居民220人(男130人、女90人),年龄从20岁到78岁。观察22项,测量65项。调查结果表明,锡伯族居民具有典型的黄种人东亚人种的特征。如头圆宽且高,胡须少,眼裂狭窄、上眼睑褶皱多达睫毛处。耳大、鼻梁较直、鼻高中等,指距长、骨盆宽等。这些特征用等差级数法比较,与达斡尔族、华北地区汉族、蒙古族较接近,与苗族、黎族较远。