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991.
Adamczyk M Chen YY Gebler JC Johnson DD Mattingly PG Moore JA Reddy RE Wu J Yu Z 《Steroids》2000,65(6):295-303
A series of chemiluminescent 17beta-estradiol probes were synthesized. Relative equilibrium dissociation constants (K(D)) for the interaction of an anti-E(2) Fab fragment for the probes in solution were evaluated using a single E(2)-analog biosensor surface on a BIAcore surface plasmon resonance instrument. The results show the antibody fragment binds all chemiluminescent conjugates tested with high affinity showing only minor preferences for site of substitution (C6 versus C7), stereochemistry (alpha versus beta), or linker moiety. 相似文献
992.
By testing the sensitivity of Escherichia coli OmpF porin to various natural and synthetic polyamines of different lengths, charge and other molecular characteristics, we were able to identify the molecular properties required for compounds to act as inhibitors of OmpF in the nanomolar range. Inhibitors require at least two amine groups to be effective. For diamines, the optimum length of the hydrocarbon spacer was found to be of eight to ten methylene groups. Triamine molecules based on a 12-carbon motif were found to be more effective that spermidine, an eight-carbon trivalent derivative. But differences in inhibition efficiencies were also found for trivalent compounds depending on the relative position of the internal secondary amine group with respect to the terminal groups. Finally, quaternary ammonium derivatives had no effect, suggesting that the nature of the terminal amine is important for the interaction. From these observations, we deduce that inhibition efficiency in the nanomolar range requires a 12-carbon chain triamine with terminal primary amine groups and replacement of the eighth methylene by a secondary amine. The need for this type of molecular architecture suggests that inhibition is governed by interactions between specific amine groups and protein residues, and that this is not simply due to the accumulation of charges into the pore. Together with previous observations from site-directed mutagenesis studies and inspection of the crystal structure of OmpF, these results allowed us to propose three residues (D113, D121 and Y294) as putative sites of interaction between the channel and spermine. Alanine substitution at each of these three residues resulted in a loss of inhibition by spermine, while mutations of only D113 and D121 affected inhibition by spermidine. Based on these observations, we suggest a model for the molecular determinants involved in the porin-polyamine interaction. 相似文献
993.
The co-incubation of morin hydrate with either doxorubicin or mitomycin C could minimize the toxicity of these anti-tumor drugs on cardiovascular cells, such as red blood cells, human umbilical vein endothelial cells (ECV304) and primary mouse cardiomyocytes, whereas morin hydrate did not lower the cytotoxicity of the drugs on human hepatocellular carcinoma cells (HepG2). Morin hydrate may not exert its antioxidant effect by enhancing the antioxidant enzymatic activity because it did not cause any induction on the mRNA levels of manganese superoxide dismutase expression in ECV304 cells and HepG2 cells. 相似文献
994.
According to a previous study, alcohol concentration influences the enantiomeric ratio and initial rate of Candida cylindracea lipase-catalyzed enantioselective esterification of racemic 2-(6-methoxy-2-naphthyl) propionic acid in microaqueous isooctane in a similar manner. Such an influence might be attributed to the different water partitioning coefficients. In this work, we performed enzymatic resolutions in controlled water activity atmospheres, thereby separating the influence of alcohol concentrations from the effect of water partitioning. Despite this constant water activity condition, a similar dependence of enantiospecificity and initial rate on the concentration of acyl acceptor (n-butanol) was also found. This finding suggests that the alcohol concentration influences enzyme performance, but not because it strips water from the enzyme. The unexpected observations imply that an undetermined factor must be considered when the enzymatic resolution is performed in nonconventional media. 相似文献
995.
Chronic toxicity of rare-earth elements on human beings 总被引:3,自引:0,他引:3
Zhang H Feng J Zhu W Liu C Xu S Shao P Wu D Yang W Gu J 《Biological trace element research》2000,73(1):1-17
Blood analyses for rare-earth element (REE)-high background regions in South Jiangxi show that the population averages of
many of the biochemical indices deviate markedly from normal values in the normal region. These deviations are thought to
be caused by prolonged intake of REE through food chains in view of that the toxicity of other harmful metals such as Pb and
Cd can be neglected because of their insignificant amounts in the environment. In comparison with the normal region, blood
biochemical indices abnormal in the REE-high regions are manifested as low total serum protein (TSP), albumin, β-globulin,
glutamic pyruvic transitanase, serium triglycerides, and immunoglobulin, but high cholesterol. These deviations may be related
to the REE concentration and composition of food chains, and are sex dependent. Certain blood indices (such as TSP) of different
age groups in the LREE-high region indicate that the influence of REE on males is a one-way irreversible process, whereas
females show a strong ability of restoration. 相似文献
996.
A putative tertiary structure model of the dog's olfactory receptor (olfd canfa) is established in this study. By using a target odorous compound (trimethylamine), it is possible to locate the most plausible binding sites between the receptor model structure and the target odorous molecules through computer docking simulations. The two short oligo-peptide sequences (orp61 and orp188) for trimethylamine sensing were identified, synthesized, purified and coated onto the surface of the separate piezoelectric gold electrodes. These two peptides show a high binding capability for trimethylamine. To further enhance the sensitivity of the polypeptides towards the target compound, the polarity and the degree of docking were changed by a site-specific modification technique. The orp61 sequence was modified by substituting two amino acids in the binding pocket resulting in 33% increase in sensitivity towards trimethylamine and reduced noises from other non-target chemicals. The techniques used in the present study offer a unique approach for synthesizing peptides in mimicking binding domain of olfactory receptors. The approach can be easily applied to further development of recognized molecules for gas sensing, especially for use in 'electronic noses'. 相似文献
997.
998.
Integrin and Cadherin Synergy Regulates Contact Inhibition of Migration and Motile Activity 总被引:16,自引:2,他引:14 下载免费PDF全文
Anna Huttenlocher Margot Lakonishok Melissa Kinder Stanley Wu Tho Truong Karen A. Knudsen Alan F. Horwitz 《The Journal of cell biology》1998,141(2):515-526
Integrin receptors play a central role in cell migration through their roles as adhesive receptors for both other cells and extracellular matrix components. In this study, we demonstrate that integrin and cadherin receptors coordinately regulate contact-mediated inhibition of cell migration. In addition to promoting proliferation (Sastry, S., M. Lakonishok, D. Thomas, J. Muschler, and A. Horwitz. 1996. J. Cell Biol. 133:169–184), ectopic expression of the α5 integrin in cultures of primary quail myoblasts promotes a striking contact-mediated inhibition of cell migration. Myoblasts ectopically expressing α5 integrin (α5 myoblasts) move normally when not in contact, but upon contact, they show inhibition of migration and motile activity (i.e., extension and retraction of membrane protrusions). As a consequence, these cells tend to grow in aggregates and do not migrate to close a wound. This phenotype is also seen with ectopic expression of β1 integrin, paxillin, or activated FAK (CD2 FAK) and therefore appears to result from enhanced integrin-mediated signaling. The contact inhibition observed in the α5 myoblasts is mediated by N-cadherin, whose expression is upregulated more than fivefold. Perturbation studies using low calcium conditions, antibody inhibition, and ectopic expression of wild-type and mutant N-cadherins all implicate N-cadherin in the contact inhibition of migration. Ectopic expression of N-cadherin also produces cells that show inhibited migration upon contact; however, they do not show suppressed motile activity, suggesting that integrins and cadherins coordinately regulate motile activity. These observations have potential importance to normal and pathologic processes during embryonic development and tumor metastasis. 相似文献
999.
The outer hair cell (OHC) from the mammalian organ of Corti possesses a bell-shaped voltage-dependent capacitance function.
The nonlinear capacitance reflects the activity of membrane bound voltage sensors associated with membrane motors that control
OHC length. We have studied the effects of the lipophilic ions, tetraphenylborate (TPB−) and tetraphenylphosphonium (TPP+), on nonlinear capacitance and motility of isolated guinea-pig OHCs. Effects on supporting cells were also investigated.
TPB− produced an increase in the peak capacitance (Cm
pk
) and shifted the voltage at peak capacitance (V
pkCm
) to hyperpolarized levels. Washout reversed the effects. Perfusion of 0.4 μm TPB− caused an average increase in Cm
pk
of 16.3 pF and V
pkCm
shift of 13.6 mV. TPP+, on the other hand, only shifted V
pkCm
in the positive direction, with no change in Cm
pk
. The contributions from native OHC and TPB−-induced capacitance were dissected by a double Boltzmann fitting paradigm, and by blocking native OHC capacitance. While
mechanical response studies indicate little effect of TPB− on the motility of OHCs which were in normal condition or treated with salicylate or gadolinium, the voltage at maximum mechanical
gain (V
δ
Lmax
) was shifted in correspondence with native V
pkCm
, and both changed in a concentration-dependent manner. Both TPB−-induced changes in Cm
pk
and V
pkCm
were affected by voltage prepulses and intracellular turgor pressure. TPB− induced a voltage-dependent capacitance in supporting cells whose characteristics were similar to those of the OHC, but no
indication of mechanical responses was noted. Our results indicate that OHC mechanical responses are not simply related to
quantity of nonspecific nonlinear charge moved within the membrane, but to the effects of motility voltage-sensor charge movement
functionally coupled to a mechanical effector.
Received: 14 May 1998/Revised: 24 August 1998 相似文献
1000.
Characterization of tissue tolerance to iron by molecular markers in different lines of rice 总被引:4,自引:0,他引:4
Wu P. Hu B. Liao C.Y. Zhu J.M. Wu Y.R. Senadhira D. Paterson A.H. 《Plant and Soil》1998,203(2):217-226
Ferrous iron (Fe2+) toxicity is a major disorder in rice prod uction on acid, flooded soils. Rice ( Oryza sativa L.) genotypes differ widely in tolerance to Fe2+ toxicity, which makes it possible to bre ed more tolerant rice varieties. Tissue tolerance to higher iron concentrations in plants has been considered to be important to Fe2+ tolerance in ri ce. Segregation for leaf bronzing and growth reduction due to Fe2+ to xicity was observed in a doubled haploid (DH) population with 135 lines derived from a Fe2+ tolerant japonica variety, Azucena, and a sensitive indic a variety, IR64 in a solution culture with Fe2+ stress condition at a Fe2+concentration of 250 mg L-1 at pH 4.5. To better understand the mechanism of tissue tolerance, Leaf Bronzing Index (LBI), total iron concentration in shoot tissue and the enzymes of ascorbate peroxidase (AP), dehydroascorbate reductase (DR) and glutathione reductase (GR), and concentrations of ascorbate (AS) and dehydroascorbate (DHA), which are involved in the ascorbate-specific H2O2-scavenging system, were determined for the population under Fe2+ stress. A non-normal distribution of LBI was found. About 38 lines showed no bronzing, while the lines with non-zero LBI values ranged from 0.05 to 0.85 and showed a normal distribution. The other parameters measured showed normal distribution. The total iron concentrations in the 38 tolerant lines ranged from 1.76 mg Fe g-1 to 4.12 mg Fe g-1 and was in a similar range as in the non-tolerant genotype (2.04 – 4.55 mg Fe g-1). No significant differences in the activities of the enzymes were found between the parents under normal culture, but remarkably higher Fe2+ induced enzyme activities were observed in the tolerant parent. AS was similar between the parents under both normal and Fe2+ stress, but its concentration was sharply decreased under Fe2+ stress. DHA was much lower in the tolerant parent than in the sensitive parent under Fe2+ stress. Single locus analysis and interval mapping analysis based on 175 molecular markers revealed that the interval flanked by RG345 and RZ19 on chromosome one was an important location of gene(s) for Fe2+ tolerance. The ascorbate-specific system for scavenging Fe2+-mediated oxygen free radicals may be an important mechanism for tissue Fe2+ tolerance. A gene locus with relative small effect on root ability to exclude Fe2+ was also detected. 相似文献