Nanotechnology in biodevices

Nanotechnology is the creation and utilization of materials, devices, and systems through the control of matter on the nanometer. The technology has been applied to biodevices such as bioelectronics and biochips to improve their performances. Nanoparticles, such as gold (Au) nanoparticles, are the most widely used of the various other nanotechnologies for manipulation at the nanoscale as well as nanobiosensors. The immobilization of biomolecules is playing an increasingly important role in the development of biodevices with high performance. Nanopatterning technology, which is able to increase the density of chip arrays, offers several advantages, including cost lowering, simultaneous multicomponent detection, and the efficiency increase of biochemical reactions. A microfluidic system incorporated with control of nanoliter of fluids is also one of the main applications of nanotechnologies. This can be widely utilized in the various fields because it can reduce detection time due to tiny amounts of fluids, increase signal-to-noise ratio by nanoparticles in channel, and detect multi-targets simultaneously in one chamber. This article reviews nanotechnologies such as the application of nanoparticles for the detection of biomolecules, the immobilization of biomolecules at nanoscale, nanopatterning technologies, and the microfluidic system for molecular diagnosis.     

FGF15 Activates Hippo Signaling to Suppress Bile Acid Metabolism and Liver Tumorigenesis

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HSP27 regulates IL-1 stimulated IKK activation through interacting with TRAF6 and affecting its ubiquitination

Heat shock protein 27 (HSP27) is an ubiquitiously expressed protein, which has been mediated in various biological functions. Here, we present a novel mechanism utilized by HSP27 in regulating IL-1beta induced NF-small ka, CyrillicB activation. Both over-expression and RNAi experiments indicate that HSP27 physically interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6) and promotes TRAF6 ubiquitination. Over-expressed HSP27 augments IL-1beta induced TRAF6 ubiquitination and Ismall ka, CyrillicB kinase (IKK) activation. On the other hand, IL-1beta stimulation reduces endogenous HSP27/TRAF6 association, but inhibiting HSP27 phosphorylation by using SB202190, an inhibitor of p38, and MAPKAPK2 RNAi increases HSP27/TRAF6 association and thereby enhances TRAF6 ubiquitination, IKK phosphorylation as well as NF-small ka, CyrillicB activation. Furthermore, co-transfection study shows that HSP27 S78/82A, two phosphorylated serine site deficient mutants, but not wild-type HSP27 (HSP27 WT) and HSP27 S15A mutant increases TRAF6 ubiquitination and thereby mediates IL-1beta triggered IKK phosphorylation. Taken together, our data indicate that HSP27 regulates IL-1beta triggered NF-small ka, CyrillicB activation via a feedback loop which includes the interaction between HSP27 phosphorylation and ability of HSP27 to bind with TRAF6. The findings of this study reveal a novel mechanism by which HSP27 controls cytokine stimulation.     

Synthesis and characterization of a novel spring-like organotin complex containing guest benzene molecules

A novel spring-like organotin complex [(Ph₃Sn)(C₇H₅ClNO₂)]_n·3C₆H₆ (1), has been synthesized by treatment of 6-chloro-3-pyridineacetic acid bis(triphenyltin)oxide on the condition of reflux. The complex was characterized by elemental analysis, FT-IR, NMR (¹H, ¹³C and ¹¹⁹Sn) spectroscopy, and X-ray crystallography diffraction analysis. The structure analyses reveals that complex 1 is an 1D infinite chain linked by intermolecular Sn-O bonds, in which the guest benzene molecules are established in the cavity of this helical chain; all the tin atoms of complex 1 are five-coordinated.     

Dephosphorylation-dependent Inhibitory Activity of Juxtanodin on Filamentous Actin Disassembly

In the vertebrate central nervous system, maturation of oligodendrocytes is accompanied by a dramatic transformation of cell morphology. Juxtanodin (JN) is an actin cytoskeleton-related oligodendroglial protein that promotes arborization of cultured oligodendrocytes. We performed in vitro and in culture experiments to further elucidate the biochemical effects, molecular interactions, and activity regulation of JN. Pulldown and co-sedimentation assays confirmed JN binding to filamentous but not globular β-actin largely through a C-terminal domain of 14 amino acid residues. JN had much lower affinity to F-α-actin than to F-β-actin. Bundling and actin polymerization assays revealed no JN influence on F-β-actin cross-linking or G-β-actin polymerization. Sedimentation assay, however, demonstrated that JN slowed the rate of F-β-actin disassembly induced by dilution with F-actin depolymerization buffer. JN-S278E mutant, a mimic of phosphorylated JN at serine 278, exhibited a much diminished affinity/stabilizing effect on F-β-actin. Immunoblotting revealed both phosphorylated and dephosphorylated native JN of the brain, with the former migrating slightly slower than the latter and becoming undetectable when brain lysate was subjected to in vitro dephosphorylation prior to being loaded for electrophoresis. In cultured OLN-93 cells, overexpression of JN promoted the formation of actin fibers and inhibited F-actin disassembly induced by latrunculin A. S278E phosphomimetic mutation resulted in loss of JN activity in cultured cells, whereas S278A, T258A, and T258E dephospho-/phosphomimetic mutations did not. These findings establish JN as an actin cytoskeleton-stabilizing protein that may play active roles in oligodendroglial differentiation and myelin formation. Specific phosphorylation of JN might serve as an important mechanism regulating JN functions.     

Activation of neuromedin U type 1 receptor inhibits L-type Ca2+ channel currents via phosphatidylinositol 3-kinase-dependent protein kinase C epsilon pathway in mouse hippocampal neurons

Neuromedin U (NMU) plays very important roles in the central nervous system. However, to date, any role of NMU in hippocampal neurons and the relevant mechanisms still remain unknown. In the present study, we report that NMU selectively inhibits L-type high-voltage-gated Ca²⁺ channels (HVGCC) in mouse hippocampal neurons, in which NMU type 1 receptor (NMUR1), but not NMUR2, is endogenously expressed. In wild type mice, NMU (0.1 μM) reversibly inhibited HVGCC barium currents (I_Ba) by ～ 28%, while in NMUR1^?/? mice NMU had no significant effects. Intracellular infusion of GDP-β-S or a selective antibody raised against the G_oα, as well as pretreatment of the neurons with pertussis toxin, blocked the inhibitory effects of NMU, indicating the involvement of G_o-protein. This NMUR1-mediated effect did not display the characteristics of a direct interaction between G-protein βγ subunit (G_βγ) and L-type HVGCC, but was abolished by dialyzing cells with QEHA peptide or an antibody to the G_β. The classical and novel protein kinase C (PKC) antagonist calphostin C, as well as phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, abolished NMU responses, whereas the classical PKC antagonist Gö6976 had no such effects. Cells dialyzed with a PKC epsilon isoform (PKCε) specific inhibitor peptide, GAVSLLPT, abolished NMU responses. In contrast, in cells dialyzed with an inactive PKCε control scramble peptide, LSGTLPAV, no significant effects were observed. In summary, these results suggest that NMU inhibits L-type HVGCC via activation of NMUR1 and downstream G_βγ, PI3K, and a novel PKCε signaling pathway.     

心肌梗塞后大鼠左心室舒张性能和顺应性的动态改变

心室的舒张性能和顺应性是心脏功能的两个重要方面。为了查明心肌梗塞后这两个特性的演变规律,我们在离体条件下观察了大鼠心脏舒张性能和顺应性在左冠状动脉结扎后2秒到21天之间的动态过程。实验表明,结扎冠状动脉后,左室舒张性能指标有明显改变(T值延长,-dp/dtmax降低),在恢复期未见明显改善;左室顺应性的变化有明显的时相性,表现为先有一过性增高,之后明显降低,继而回升到接近对照水平,到恢复期则明显增高。     

钝叶水丝梨化学成分研究

自钝叶水丝梨(Sycopsis tutckerii Hemsl)树皮中得到二十一个化合物。经鉴定为豆甾烷-6α-羟基-3β-月桂酸酯(Ia);豆甾烷-6α-羟基3β-肉豆蔻酸酯(Ib);豆甾烷-6α-羟基-3β-棕榈酸酯(Ic);及其它两个豆甾烷-6α-羟基-3β-脂肪酸酯(Id、Ie,其酸部分结构待定);乙酰白桦脂酸甲酯(Ⅱa);乙酰白桦脂酸(Ⅱb);白桦脂酸甲酯(Ⅱc);白桦酯酸(Ⅱb);乙酰齐墩果酸(Ⅲa);齐墩果酸(Ⅲb);β-谷甾醇(Ⅳa);β-谷甾醇-β-D-葡萄糖甙(Ⅳb);3-O-甲基-鞣花酸-4'-α-L-鼠李糖甙(Ya);3-O-甲基鞣花酸(Vb);3,4-二-O-甲基鞣花酸(Vc);鞣花酸(Vd);(?)-茶儿茶素(Ⅵ);没食子酸(Ⅷa);原儿茶酸(Ⅷd);焦性没食子酚(Ⅶc)。其中Ia-Ie是一组尚未单离的新化合物。上述化令物,除( )-茶儿茶素外,均系首次从水丝梨属植物中发现。