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141.
Analysis of protein interactions on protein arrays by a wavelength interrogation-based surface plasmon resonance biosensor 总被引:1,自引:0,他引:1
We have investigated whether surface plasmon resonance (SPR) sensors based on the wavelength interrogation are able to analyze protein interactions on protein arrays. The spectral SPR sensor was self-constructed and its detection limit, expressed as the minimal refractive index variation, was calculated to be 6.6x10(-5) with the signal fluctuation of 1.0x10(-5). The protein array surface was modified by a mixed thiol monolayer to immobilize proteins. Protein arrays were analyzed by the line-scanning mode of the SPR sensor, which scanned every 100 microm along the central line of array spots and the scanned results were presented by color spectra from blue to red. Glutathione S-transferase (GST)-rac1 caused a concentration-dependent increase of SPR wavelength shift on protein arrays. The surface structure of the protein arrays was analyzed by atomic force microscopy. Specific interactions of antigens with antibodies were analyzed on the protein arrays by using three antibodies and eight proteins. These results suggest that the wavelength interrogation-based SPR sensor can be used as the biosensor for the high-throughput analysis of protein interactions on protein arrays. 相似文献
142.
Sonic hedgehog--regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system 总被引:29,自引:0,他引:29
Lu QR Yuk D Alberta JA Zhu Z Pawlitzky I Chan J McMahon AP Stiles CD Rowitch DH 《Neuron》2000,25(2):317-329
During development, basic helix-loop-helix (bHLH) proteins regulate formation of neurons from multipotent progenitor cells. However, bHLH factors linked to gliogenesis have not been described. We have isolated a pair of oligodendrocyte lineage genes (Olg-1 and Olg-2) that encode bHLH proteins and are tightly associated with development of oligodendrocytes in the vertebrate central nervous system (CNS). Ectopic expression of Olg-1 in rat cortical progenitor cell cultures promotes formation of oligodendrocyte precursors. In developing mouse embryos, Olg gene expression overlaps but precedes the earliest known markers of the oligodendrocyte lineage. Olg genes are expressed at the telencephalon-diencephalon border and adjacent to the floor plate, a source of the secreted signaling molecule Sonic hedgehog (Shh). Gain- and loss-of-function analyses in transgenic mice demonstrate that Shh is both necessary and sufficient for Olg gene expression in vivo. 相似文献
143.
Bordetella bronchiseptica chronically infects a wide range of mammals, and resides primarily in the nasal cavity of the infected host. Multiple virulence factors of Bordetella species have been studied in the context of lower respiratory tract infections, but relatively less is known about the bacterial life cycle in the nasal cavity. Evidences were discovered for Bvg intermediate (Bvg(i)) phase expression in vivo and that the major adhesin filamentous hemagglutinin plays a major role in the colonization of B. bronchiseptica in the unciliated olfactory epithelia of the nasal cavity. 相似文献
144.
Yiwen Liu Robert Carmer Gaonan Zhang Prahatha Venkatraman Skye Ashton Brown Chi-Pui Pang Mingzhi Zhang Ping Ma Yuk Fai Leung 《PloS one》2015,10(10)
Zebrafish larvae display rich locomotor behaviour upon external stimulation. The movement can be simultaneously tracked from many larvae arranged in multi-well plates. The resulting time-series locomotor data have been used to reveal new insights into neurobiology and pharmacology. However, the data are of large scale, and the corresponding locomotor behavior is affected by multiple factors. These issues pose a statistical challenge for comparing larval activities. To address this gap, this study has analyzed a visually-driven locomotor behaviour named the visual motor response (VMR) by the Hotelling’s T-squared test. This test is congruent with comparing locomotor profiles from a time period. Different wild-type (WT) strains were compared using the test, which shows that they responded differently to light change at different developmental stages. The performance of this test was evaluated by a power analysis, which shows that the test was sensitive for detecting differences between experimental groups with sample numbers that were commonly used in various studies. In addition, this study investigated the effects of various factors that might affect the VMR by multivariate analysis of variance (MANOVA). The results indicate that the larval activity was generally affected by stage, light stimulus, their interaction, and location in the plate. Nonetheless, different factors affected larval activity differently over time, as indicated by a dynamical analysis of the activity at each second. Intriguingly, this analysis also shows that biological and technical repeats had negligible effect on larval activity. This finding is consistent with that from the Hotelling’s T-squared test, and suggests that experimental repeats can be combined to enhance statistical power. Together, these investigations have established a statistical framework for analyzing VMR data, a framework that should be generally applicable to other locomotor data with similar structure. 相似文献
145.
Yuk Lung Wong Ingmar Lautenschl?ger Heike Dombrowsky Karina Zitta Berthold Bein Thorsten Krause Torsten Goldmann Inez Frerichs Markus Steinfath Norbert Weiler Martin Albrecht 《PloS one》2015,10(3)
BackgroundThe application of hydroxyethyl starch (HES) for volume resuscitation is controversially discussed and clinical studies have suggested adverse effects of HES substitution, leading to increased patient mortality. Although, the intestine is of high clinical relevance and plays a crucial role in sepsis and inflammation, information about the effects of HES on intestinal function and barrier integrity is very scarce. We therefore evaluated the effects of clinically relevant concentrations of HES on intestinal function and barrier integrity employing an isolated perfused model of the mouse small intestine.MethodsAn isolated perfused model of the mouse small intestine was established and intestines were vascularly perfused with a modified Krebs-Henseleit buffer containing 3% Albumin (N=7) or 3% HES (130/0.4; N=7). Intestinal metabolic function (galactose uptake, lactate-to-pyruvate ratio), edema formation (wet-to-dry weight ratio), morphology (histological and electron microscopical analysis), fluid shifts within the vascular, lymphatic and luminal compartments, as well as endothelial and epithelial barrier permeability (FITC-dextran translocation) were evaluated in both groups.ResultsCompared to the Albumin group, HES perfusion did not significantly change the wet-to-dry weight ratio and lactate-to-pyruvate ratio. However, perfusing the small intestine with 3% HES resulted in a significant loss of vascular fluid (p<0.01), an increased fluid accumulation in the intestinal lumen (p<0.001), an enhanced translocation of FITC-dextran from the vascular to the luminal compartment (p<0.001) and a significantly impaired intestinal galactose uptake (p<0.001). Morphologically, these findings were associated with an aggregation of intracellular vacuoles within the intestinal epithelial cells and enlarged intercellular spaces.ConclusionA vascular perfusion with 3% HES impairs the endothelial and epithelial barrier integrity as well as metabolic function of the small intestine. 相似文献
146.
A series of inhibitors for anti-apoptotic Bcl-2 proteins based on BHI-1 were synthesized and their binding interactions with Bcl-2, Bcl-X(L), and Bcl-w were evaluated. It was found that modification of BHI-1 resulted in varied binding profiles among Bcl-2, Bcl-X(L), and Bcl-w, and a set of inhibitors with varied selectivity to Bcl-2, Bcl-X(L), and Bcl-w proteins have been identified. Molecular modeling of the interaction of the BHI-1 based analogues with the anti-apoptotic Bcl-2 proteins suggested that the binding site for the BHI-1 based inhibitor was the least conserved section among Bcl-2, Bcl-X(L), and Bcl-w: targeting the non-conserved section may account for the observed selectivity of the BHI-1 based inhibitors among the anti-apoptotic Bcl-2 proteins. The validity of the model was supported by a strong correlation between the model-calculated binding energy and the experimental binding affinity. In summary, our studies suggest that most of the reported inhibitors for anti-apoptotic Bcl-2 proteins are nonselective and BHI-1 is a promising template to distinguish among Bcl-2, Bcl-X(L), and Bcl-w by targeting the non-conserved domain among the anti-apoptotic Bcl-2 proteins. Molecular-modeling-aided rational development of BHI-1 based selective inhibitor for anti-apoptotic Bcl-2 proteins is underway. 相似文献
147.
148.
Lee YJ Choi IS Park MH Lee YM Song JK Kim YH Kim KH Hwang DY Jeong JH Yun YP Oh KW Jung JK Han SB Hong JT 《Free radical biology & medicine》2011,50(1):66-77
Presenilin 2 (PS2) mutation increases Aβ generation and neuronal cell death in the brains of Alzheimer disease (AD) patients. In a previous study, we showed that increased oxidative damage and activation of extracellular signal-regulated kinase (ERK) were associated with Aβ generation and neuronal cell death in neuronal cells expressing mutant PS2. In this study, we show that oral treatment with 4-O-methylhonokiol, a novel compound isolated from Magnolia officinalis, for 3 months (1.0mg/kg) prevented PS2 mutation-induced memory impairment and neuronal cell death accompanied by a reduction in Aβ(1-42) accumulation. We also found that 4-O-methylhonokiol inhibited PS2 mutation-induced activation of ERK and β-secretase, and oxidative protein and lipid damage, but recovered glutathione levels in the cortex and hippocampus of PS2 mutant mice. Additionally, 4-O-methylhonokiol prevented PS2 mutation-induced activation of astrocytes as well as production of TNF-α, IL-1β, reactive oxygen species (ROS), and nitric oxide (NO) in neurons. Generation of TNF-α, IL-1β, ROS, and NO and ERK activation in cultured astrocytes treated with lipopolysaccharide (1μg/ml) were also prevented by 4-O-methylhonokiol in a dose-dependent manner. These results suggest that the improving effects of 4-O-methylhonokiol on memory function may be associated with a suppression of the activation of ERK and astrocytes as well as a reduction in oxidative damage. Thus, 4-O-methylhonokiol may be useful in the prevention and treatment of AD. 相似文献
149.
Yan Wang Marcus J. Curtis-Long Heung Joo Yuk Dae Wook Kim Xue Fei Tan Ki Hun Park 《Bioorganic & medicinal chemistry》2013,21(21):6398-6404
Bacterial neuraminidase (NA) is one of the key enzymes involved in pathogenesis of inflammation during infection. The organic extract of the roots of Flemingia philippinensis showed high bacterial NA inhibitory activity with an IC50 of around 5 μg/mL. Activity-guided separation of the methanol extract yielded nine prenylated isoflavones together with the novel species isoflavone (2) which was given the name flemingsin. Isolated prenylated isoflavones (1–9) were evaluated for NA inhibition and their IC50 values were determined to range between 0.30 and 56.8 μM. The most potent inhibitor 4 (IC50 = 300 nM, Ki = 130 nM) features a catechol motif in the B-ring and a furan in the A-ring. Structure–activity analysis also showed a 4-hydroxyl group within the B-ring was essential for NA inhibitory activity, because isoflavone (9) having protected 4-hydroxyl group was much less potent than its hydroxylated counterpart. All neuraminidase compounds screened were found to be reversible noncompetitive inhibitors. Furthermore, the most active NA inhibitors (1–9) were proven to be present in the native roots in high quantities by HPLC and LC-DAD-ESI/MS. 相似文献
150.
Skinner JA Pilione MR Shen H Harvill ET Yuk MH 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(7):4647-4652
Chronic bacterial infection reflects a balance between the host immune response and bacterial factors that promote colonization and immune evasion. Bordetella bronchiseptica uses a type III secretion system (TTSS) to persist in the lower respiratory tract of mice. We hypothesize that colonization is facilitated by bacteria-driven modulation of dendritic cells (DCs), which leads to an immunosuppressive adaptive host response. Migration of DCs to the draining lymph nodes of the respiratory tract was significantly increased in mice infected with wild-type B. bronchiseptica compared with mice infected with TTSS mutant bacteria. Reduced colonization by TTSS-deficient bacteria was evident by 7 days after infection, whereas colonization by wild-type bacteria remained high. This decrease in colonization correlated with peak IFN-gamma production by restimulated splenocytes from infected animals. Wild-type bacteria also elicited peak IFN-gamma production on day 7, but the quantity was significantly lower than that elicited by TTSS mutant bacteria. Additionally, wild-type bacteria elicited higher levels of the immunosuppressive cytokine IL-10 compared with the TTSS mutant bacteria. B. bronchiseptica colonization in IL-10(-/-) mice was significantly reduced compared with infections in wild-type mice. These findings suggest that B. bronchiseptica use the TTSS to rapidly drive respiratory DCs to secondary lymphoid tissues where these APCs stimulate an immunosuppressive response characterized by increased IL-10 and decreased IFN-gamma production that favors bacterial persistence. 相似文献