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81.
Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia, with drug resistance to 2 μM staurosporine established within 30 min of hypoxia. Annexin-V/Sytox Green apoptosis assays over 9 h showed 78.0% viability, compared to 84.5% viability in control cells (normoxic cells with no staurosporine). Normoxic cells exposed to the same staurosporine concentration had a viability of 48.6% after 9 h. Hypoxia adaptation was rapid and reversible, with Hypoxic cells treated with 20% oxygen for 30 min responding to staurosporine with 51.6% viability after drug treatment for 9 h. Induction of apoptosis through the receptor-mediated pathway, which bypasses anti-apoptosis mechanisms induced by hypoxia, resulted in 39.4 ± 7% cell viability. The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target.  相似文献   
82.
Noncovalent protein–ligand and protein–protein complexes are readily detected using electrospray ionization mass spectrometry (ESI MS). Furthermore, recent reports have demonstrated that careful use of electron capture dissociation (ECD) fragmentation allows covalent backbone bonds of protein complexes to be dissociated without disruption of noncovalent protein–ligand interactions. In this way the site of protein–ligand interfaces can be identified. To date, protein–ligand complexes, which have proven tractable to this technique, have been mediated by ionic electrostatic interactions, i.e., ion pair interactions or salt bridging. Here we extend this methodology by applying ECD to study a protein–peptide complex that contains no electrostatics interactions. We analyzed the complex between the 21 kDa p53-inhibitor protein anterior gradient-2 and its hexapeptide binding ligand (PTTIYY). ECD fragmentation of the 1:1 complex occurs with retention of protein–peptide binding and analysis of the resulting fragments allows the binding interface to be localized to a C-terminal region between residues 109 and 175. These finding are supported by a solution-phase competition assay, which implicates the region between residues 108 and 122 within AGR2 as the PTTIYY binding interface. Our study expands previous findings by demonstrating that top-down ECD mass spectrometry can be used to determine directly the sites of peptide–protein interfaces. This highlights the growing potential of using ECD and related top-down fragmentation techniques for interrogation of protein–protein interfaces.  相似文献   
83.
In quantitative on-line/in-line monitoring of chemical and bio-chemical processes using spectroscopic instruments, multivariate calibration models are indispensable for the extraction of chemical information from complex spectroscopic measurements. The development of reliable multivariate calibration models is generally time-consuming and costly. Therefore, once a reliable multivariate calibration model is established, it is expected to be used for an extended period. However, any change in the instrumental response or variations in the measurement conditions can render a multivariate calibration model invalid. In this contribution, a new method, spectral space transformation (SST), has been developed to maintain the predictive abilities of multivariate calibration models when the spectrometer or measurement conditions are altered. SST tries to eliminate the spectral differences induced by the changes in instruments or measurement conditions through the transformation between two spectral spaces spanned by the corresponding spectra of a subset of standardization samples measured on two instruments or under two sets of experimental conditions. The performance of the method has been tested on two data sets comprising NIR and MIR spectra. The experimental results show that SST can achieve satisfactory analyte predictions from spectroscopic measurements subject to spectrometer/probe alteration, when only a few standardization samples are used. Compared with the existing popular methods designed for the same purpose, i.e. global PLS, univariate slope and bias correction (SBC) and piecewise direct standardization (PDS), SST has the advantages of implementation simplicity, wider applicability and better performance in terms of predictive accuracy.  相似文献   
84.
The complexing ability of derivatives of azobenzene (I) is well known (I) and responsible for the production of a wide variety of dyestuffs and analytical chemicals. While the azo group generally participates in the coordination, the determination of the degree of its interaction is complicated by other functional groups which are also coordinated with the transition metal. In a previous publication (2), we reported the preparation of the silver and palladium complexes of benzo[c]cinnoline (II) and proposed that these results might be used to explain the electron donor properties of azobenzene. We are now reporting the preparation of some additional complexes with ligands containing the azo group.  相似文献   
85.
The fulleride dianions C(60)(2-) and C(70)(2-) were generated by deprotonation of the corresponding hydrogenated fullerenes, 1,2-C(60)H(2) and 1,2-C(70)H(2). These anions were prepared in the presence of a variety of alkylating agents, and mono- or dialkylated products were obtained. Alkylation was not successful with sulfonate ester alkylating agents. Deprotonation of monoalkylated compounds, followed by second alkylation with a different alkylating agent, produced heterodialkylated compounds. The monoalkyated material was invariably the 1,2-isomers, while the dialkylated materials were generally 1,4-isomers, although some 1,2-isomer was observed in the C(70) context. The major product from alkylation of C(70)(2-) was the 7,23-isomer 13a, a structure where the alkylation took place near the equator of the fullerene cage, rather than at the more strained carbons near the poles.  相似文献   
86.
Variations in natural abundance of carbon (C) and nitrogen (N) stable isotopes are widely used as tools for many aspects of scientific research. By examining variations in the ratios of heavy to light stable isotopes, information can be obtained as to what physical, chemical and biological processes may be occurring. The spatial heterogeneity of soil δ15N‐ and δ13C‐values across a range of scales and under different land use have been described by a number of researchers and the natural abundances of the C and N stable isotopes in soils have been found to be correlated with many factors including hydrology, topography, land use, vegetation cover and climate. In this study the Latin square sampling +1 (LSS+1) sampling method was compared with a simple grid sampling approach for δ13C and δ15N measurement at the field scale. A set of 144 samples was collected and analysed for δ15N and δ13C from a 12 × 12 grid (in a 1 ha improved grassland field in south‐west England). The dimension of each cell of the grid was approximately 11 × 6 m. The 12 × 12 grid was divided into four 6 × 6 grids and the LSS+1 sampling technique was applied to these and the main 12 × 12 grid for a comparison of sample means and variation. The LSS+1 means from the 12 × 12 grid and the four 6 × 6 grids compared well with the overall grid mean because of the low variation within the field. The LSS+1 strategy (13 samples) generated representative samples from the 12 × 12 grid, and hence would be an acceptable method for sampling similar plots for the measurement of mean isotopic composition. Copyright © 2010 John Wiley & Sons, Ltd.  相似文献   
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89.

Background  

Minichromosome maintenance proteins (Mcm) 2, 3, 4, 5, 6 and 7 are related by sequence and form a variety of complexes that unwind DNA, including Mcm4/6/7. A Mcm4/6/7 trimer forms one half of the Mcm2-7 hexameric ring and can be thought of as the catalytic core of Mcm2-7, the replicative helicase in eukaryotic cells. Oligomeric analysis of Mcm4/6/7 suggests that it forms a hexamer containing two Mcm4/6/7 trimers, however, under certain conditions trimeric Mcm4/6/7 has also been observed. The functional significance of the different Mcm4/6/7 oligomeric states has not been assessed. The results of such an assessment would have implications for studies of both Mcm4/6/7 and Mcm2-7.  相似文献   
90.
We report boronate-caged guanidine-lipid 1 that activates liposomes for cellular delivery only upon uncaging of this compound by reactive oxygen species (ROS) to produce cationic lipid products. These liposomes are designed to mimic the exceptional cell delivery properties of cell-penetrating peptides (CPPs), while the inclusion of the boronate cage is designed to enhance selectivity such that cell entry will only be activated in the presence of ROS. Boronate uncaging by hydrogen peroxide was verified by mass spectrometry and zeta potential (ZP) measurements. A microplate-based fluorescence assay was developed to study the ROS-mediated vesicle interactions between 1 -liposomes and anionic membranes, which were further elucidated via dynamic light scattering (DLS) analysis. Cellular delivery studies utilizing fluorescence microscopy demonstrated significant enhancements in cellular delivery only when 1 -liposomes were incubated with hydrogen peroxide. Our results showcase that lipid 1 exhibits strong potential as an ROS-responsive liposomal platform for targeted drug delivery applications.  相似文献   
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