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排序方式: 共有182条查询结果,搜索用时 31 毫秒
51.
52.
McBriar MD Guzik H Shapiro S Xu R Paruchova J Clader JW O'neill K Hawes B Sorota S Margulis M Tucker K Weston DJ Cox K 《Bioorganic & medicinal chemistry letters》2006,16(16):4262-4265
Herein, we report the discovery of an effective strategy to modulate liabilities related to affinity of previously disclosed bicyclohexane MCHR-1 antagonists for the hERG channel. This paper describes one of several strategies incorporated to limit hERG binding via modifications of a terminal aryl group in an otherwise promising bicyclohexyl urea series. 相似文献
53.
Xu R Li S Paruchova J McBriar MD Guzik H Palani A Clader JW Cox K Greenlee WJ Hawes BE Kowalski TJ O'Neill K Spar BD Weig B Weston DJ 《Bioorganic & medicinal chemistry》2006,14(10):3285-3299
Melanin concentrating hormone (MCH) receptor antagonists have been proposed as potential treatments of obesity. MCH receptor antagonists with a biphenylamine subunit have been reported previously at Schering-Plough. Herein, we report the discovery of bicyclo[4.1.0]heptanes as replacements for the middle phenyl ring of the biphenylamine moiety in order to eliminate its potential mutagenic liability. Structure-activity relationships in this series were found to be very similar to those of the original biphenylamine series, suggesting that the two series have similar binding modes. 相似文献
54.
Jaroslava Ovesna Kamila Strymplova Stastna Katerina Vaculova Jarmila Milotova 《Biologia》2010,65(1):75-80
The allelic status at bmy1, which encodes the enzyme β-amylase 1 in the barley grain, has an important influence over a cultivar’s malting quality. Changes in the malting process
have been responsible for the need to improve the thermostability of this enzyme. We have compared a published bmy1 haplotyping assay based on TDI-FRET (template-directed dye-terminator incorporation fluorescence resonance energy transfer)
with a SNaPshot protocol by jointly analysing a set of 21 cultivars of known haplotype. The two methods gave the same result,
but the SNaPshot assay was easier to interpret. The SNaPshot assay was therefore used to haplotype the Czech malting barley
core collection with respect to bmy1. The old Czech cultivar Kasticky was the only entry identified as carrying the high thermostability haplotype, with the remainder
carrying either the intermediate or the low thermostability haplotypes. Older materials were the most variable in terms of
bmy1 haplotype, but the majority carried the intermediate type. Most of the descendants of cv. Diamant carried the low thermostability
haplotype. The most recently released cultivars recommended for the brewing of Czech beer tend to carry the intermediate allele. 相似文献
55.
Probing the Role of the Internal Disulfide Bond in Regulating Conformational Dynamics in Neuroglobin
Luisana Astudillo Valérie Derrien Pierre Sebban Jaroslava Miksovska 《Biophysical journal》2010,99(2):L16-L18
In this report, we demonstrate that the internal disulfide bridge in human neuroglobin modulates structural changes associated with ligand photo-dissociation from the heme active site. This is evident from time-resolved photothermal studies of CO photo-dissociation, which reveal a 13.4± 0.9 mL mol−1 volume expansion upon ligand photo-release from human neuroglobin, whereas the CO dissociation from rat neuroglobin leads to a significantly smaller volume change (ΔV = 4.6 ± 0.3 mL mol−1). Reduction of the internal disulfide bond in human neuroglobin leads to conformational changes (reflected by ΔV) nearly identical to those observed for rat Ngb. Our data favor the hypothesis that the disulfide bond between Cys46 and Cys55 modulates the functioning of human neuroglobin. 相似文献
56.
Denisa Petrackova Jaroslav Vecer Jaroslava Svobodova Petr Herman 《The Journal of membrane biology》2010,233(1-3):73-83
We characterized physical and chemical properties of cell-membrane fragments from Bacillus subtilis 168 (trpC2) grown at pH 5.0, 7.0 and 8.5. Effects of long-term bacterial adaptation reflected in growth rates and in changes of the membrane lipid composition were correlated with lipid order and dynamics using time-resolved fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene. We demonstrate that the pH adaptation results in a modification of a fatty acid content of cellular membranes that significantly influences both the lipid-chain order and dynamics. For cultivation at acidic conditions, the lipid order increases and membrane dynamics decreases compared to pH 7.0. This results in rigid and ordered membranes. Cultivation at pH 8.5 causes slight membrane disordering. Instant pH changes induce qualitatively similar but smaller effects. Proton flux measurements performed on intact cells adapted to both pH 5.0 and 8.5 revealed lower cell-membrane permeability compared to bacteria cultivated at pH optimum. Our results indicate that both acidic and alkalic pH stress represent a permanent challenge for B. subtilis to keep a functional membrane state. The documented adaptation-induced adjustments of membrane properties could be an important part of mechanisms maintaining an optimal intracellular pH at a wide range of extracellular proton concentrations. 相似文献
57.
Fine needle aspiration biopsy of mixed medullary-follicular thyroid carcinoma. A report of two cases
BACKGROUND: Mixed differentiated thyroid carcinomas are rare tumors, difficult to recognize on fine needle aspiration biopsy (FNAB). Most cases are diagnosed only after histologic investigation. CASES: The cases entailed two cytologic samples and a thyroidectomy specimen. Two FNAB thyroidectomy specimens from a 60-year-old man presenting with a solitary thyroid nodule (case 1) were investigated. Both cytologic samples were referred as atypical, with a mixture of features indicating a proliferating follicular lesion but also containing some characteristics of medullary carcinoma. The serum calcitonin level was borderline. Surgery was recommended because of a suspicion of malignancy. The diagnosis of mixed medullary follicular carcinoma was established after a complex histologic investigation. The tumor was encapsulated, with partly microfollicular architecture. Immunohistochemistry was positive for both calcitonin and thyreoglobulin. Electron microscopy from the formol-paraffin block found neurosecretory granules in many cells. The patient was well one year after the operation. One FNAB and thyroidectomy specimen from a 47-year-old woman with long-treated lymphoplasmocellular thyroiditis (case 2) was investigated. The tumor in case 2 was diagnosed on FNAB as medullary carcinoma. Only after histologic and immunohistochemical investigation was mixed differentiation proven. CONCLUSION: Mixed differentiated thyroid tumors are a diagnostic challenge on fine needle aspiration. Irrespective of their rarity, they can be suspected if combined features are present. FNAB recognition of the medullary component in both cases was of crucial importance. Nevertheless, definitive diagnosis remains a histologic problem due to the necessity for topographic information. 相似文献
58.
Zoltán Dömény Daniela Smogrovicová Peter Gemeiner Ernest Sturdík Jaroslava Pátková Anna Malovíková 《Biotechnology letters》1998,20(11):1041-1045
An immobilised yeast, two-stage reactor system was applied to laboratory fermentations of wort. The first stage, the primary fermentation process was carried out in an up-flow gas-lift bioreactor, and in the second stage, fermentation was processed in column reactors consisting of eight packed-beds filled with both yeasts entrapped in three different polysaccharide hydrogels (calcium alginate, calcium pectate, sodium carrageenan) and with free yeast in parallel. The residence time for the two-stage immobilised system varied from 74 to 108 h. © Rapid Science Ltd. 1998 相似文献
59.
In order to test the proposition that hypoxia leads to a change in the concentration ratio of reduced (GSH) and oxidized (GSSG) glutathione in the brain, enzymatic, fluorometric assays were worked out for measuring GSH and GSSG. In lightly anaesthetized and immobilized rats. GSH concentrations in the cerebral cortex and the cerebellum were close to 2 μmol.g-1 while a slightly lower concentration (approx 1.4μmol.g-1) was found in the brain stem. In order to avoid artefactual oxidation of GSH during sample preparation for GSSG determination the tissue was extracted with trichloroacetic acid, following alkylation of SH groups with N-ethylmaleimide. With these precautions GSSG concentrations were approx 0.7% of the corresponding GSH concentrations. However. the results indicated that the true GSSG concentrations may be even lower. During hypoxia there was neither a decrease in GSH nor an increase in GSSG concentrations in cortical tissue or cisternal CSF. 相似文献
60.
Here, we report the volume and enthalpy changes accompanying CO photodissociation from the mixed valence form of cytochrome bo3 oxidase from Escherichia coli. The results of photoacoustic calorimetry indicate two kinetic phases with distinct volume and enthalpy changes accompanying CO photodissociation from heme o3 and its transfer to CuB. The first phase occurring on a timescale of <50 ns is characterized by a volume decrease of -1.3+/-0.3 mL mol-1 and enthalpy change of 32+/-1.6 kcal mol-1. Subsequently, a volume increase of 2.9 mL mol-1 with an enthalpy change of -5.3+/-2.5 kcal mol-1 is observed with the lifetime of approximately 250 ns (this phase has not been detected in previous optical studies). These volume and enthalpy changes differ from the volume and enthalpy changes observed for CO dissociation from fully reduced cytochrome bo3 oxidase indicating that the heme o3/CuB active site dynamics are affected by the redox state of heme b. 相似文献