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121.
122.
Edwards A Elwyn G Stott N 《BMJ (Clinical research ed.)》1999,318(7183):603; author reply 603-603; author reply 604
123.
Purified renal globotriaosyl ceramide (Gb3)/cholesterol mixtures sonicated heated in a Triton-containing buffer placed below a discontinuous sucrose gradient form glycosphingolipid (GSL)-containing dense lipid structures at the 30/5% sucrose interface after centrifugation. Inclusion of fluorescein-labeled verotoxin 1 B subunit (FITC-VT1 B) within the most dense sucrose layer results in the fluorescent labeling of this Gb3-containing raft structure. Alternatively inclusion of I-labeled VT1 fractionation allows quantitation of binding. FITC-VT1 B effectively competes for I-VT1/Gb3 raft binding. This assay will allow the definition of the optimal raft composition for VT1 (or any other ligand) binding. The effect of several potential cellular raft components are reported. Increased cholesterol content increased VT1 binding. Addition of phosphatidylethanolamine had minimal effect while phosphatidylserine was inhibitory. Although inclusion of sphingomyelin increased the Gb3 content of the "raft" reduced VT1 binding was seen. Inclusion of other glycolipids can also be inhibitory. The addition of globotetraosyl ceramide had no effect; however addition of sulfogalactosyl ceramide but not sulfogalactoglycerolipid inhibited VT1/Gb3 raft binding. These results suggest that certain GSLs can disfavor the formation of the appropriate 'raft' structure for ligand binding that this is dependent on both their carbohydrate lipid structure. Such "deceptor" GSLs may provide an as yet unappreciated mechanism for the regulation of cellular GSL receptor activity. This model is an effective tool to approach the dynamics ligand-binding specificity of GSL/cholesterol-containing lipid microdomains. 相似文献
124.
Increased attention to spatial context increases both place field stability and spatial memory 总被引:2,自引:0,他引:2
The hippocampal formation is critical for the acquisition and consolidation of memories. When recorded in freely moving animals, hippocampal pyramidal neurons fire in a location-specific manner: they are "place" cells, comprising a hippocampal representation of the animal's environment. To explore the relationship between place cells and spatial memory, we recorded from mice in several behavioral contexts. We found that long-term stability of place cell firing fields correlates with the degree of attentional demands and that successful spatial task performance was associated with stable place fields. Furthermore, conditions that maximize place field stability greatly increase orientation to novel cues. This suggests that storage and retrieval of place cells is modulated by a top-down cognitive process resembling attention and that place cells are neural correlates of spatial memory. We propose a model whereby attention provides the requisite neuromodulatation to switch short-term homosynaptic plasticity to long-term heterosynaptic plasticity, and we implicate dopamine in this process. 相似文献
125.
Zeyl C 《FEMS microbiology letters》2004,240(2):187-192
Variation in the prominence of haploidy and diploidy is a striking feature of eukaryote life cycles that has not been explained from an evolutionary point of view. the ease with which ploidy and other variables of population genetics may be manipulated in yeast make Saccharomyces cerevisiae an excellent subject for experiments on the fitness effects of ploidy. Several hypotheses have been advanced to explain the emphasis on diploidy in plants and animals, and yeast experiments have been particularly informative for a few. Evidence suggests that diploids may enjoy an immediate advantage over haploids in masking harmful mutations, avoiding the fitness cost such mutations impose on haploids. A convincing longer-term advantage for diploidy has proven elusive, and different evolutionary explanations for the origin and for the subsequent maintenance of diploidy may be required. 相似文献
126.
Populations of European hare (Lepus europaeus) are in decline in Europe, and populations in Australia remain at low densities. Populations are sensitive to size of the breeding stock, which is influenced by fertility in the females. From 1996 to 1999, a total of 272 adult female hares from three Australian populations were dissected and their reproductive systems examined for abnormalities. Cystic endometrial hyperplasia was relatively common and often accompanied by hydrosalpinx. Extrauterine fetuses, neoplasms, pseudopregnancies, and resorptions also were found. However, although pseudopregnancies and resorptions were found in young adults (<12 mo) as well as older hares, conditions possibly causing infertility were almost always in older hares with prevalences up to 46.2%. Only hares with access to known sources of estrogens exhibited pathologic conditions, but sympatric European rabbits (Oryctolagus cuniculus) did not, which is consistent with known difference in responses between the corpora lutea of the two species to exogenous estrogen. Infertility at such a high prevalence could compound and extend the impact of years of low juvenile survival on recruitment. 相似文献
127.
the JigCell model builder and run manager 总被引:2,自引:0,他引:2
Vass M Allen N Shaffer CA Ramakrishnan N Watson LT Tyson JJ 《Bioinformatics (Oxford, England)》2004,20(18):3680-3681
SUMMARY: We describe the JigCell Model Builder (JCMB), a tool for creating biochemical reaction network models. JCMB is designed for ease of use and its interface uses the standard spreadsheet metaphor. The JigCell Run Manager (JCRM) is a tool for organizing the large collections of simulation runs typically required by reaction network modeling activities. AVAILABILITY: JCMB and JCRM are part of the JigCell suite available at http://jigcell.biol.vt.edu. 相似文献
128.
Mallari JP Choy CJ Hu Y Martinez AR Hosaka M Toriyabe Y Maung J Blecha JE Pavkovic SF Berkman CE 《Bioorganic & medicinal chemistry》2004,12(22):6011-6020
A series of alkyl and aryl phosphonyl, thiophosphonyl, and dithiophosphonyl derivatives of (S)- and (R)-glutamic acid were prepared and examined for inhibitory potency against glutamate carboxypeptidase (carboxypeptidase G). The acquisition of the phosphonamidodithioic acids and the individual phosphonamidothioic acid diastereomers was achieved through a common phosphonamidothiolate precursor, which also allowed for the chromatographic resolution of the chiral phosphorus center of the phosphonamidothioic acids. The most potent inhibitor of the series was the n-butylphosphonamidate derivative of the natural isomer of glutamic acid. Although each diastereomeric pair of three phosphonamidothionates exhibited stereoselective inhibition consistent with the configuration of the chiral phosphorus center, this effect was generally not remarkable. More important, was the effect of carbon stereochemistry upon glutamate carboxypeptidase inhibition as exemplified by a limited series of enantiomeric pairs of phosphonamidate and phosphonamidodithionate derivatives of glutamic acid. The phosphonamidate analogs derived from the unnatural stereoisomer of glutamic acid were devoid of inhibitory potency in contrast to their enantiomers. Surprisingly, the phosphonamidodithionates derived from the unnatural stereoisomer of glutamic acid demonstrated greater inhibitory potency than their naturally-derived antipodes. 相似文献
129.
Kim IJ Ullrich T Janetka JW Furness MS Jacobson AE Rothman RB Dersch CM Flippen-Anderson JL George C Rice KC 《Bioorganic & medicinal chemistry》2003,11(22):4761-4768
We have explored the synthesis of compounds that have good affinity for both mu- and delta-opioid receptors from the (alphaR,2S,5S) class of diaryldimethylpiperazines. These non-selective compounds were related to opioids that have been found to interact selectively with mu- or delta-opioid receptors as agonists or antagonists. In our initial survey, we found two compounds, (+)-4-[(alphaR)-alpha-(4-allyl-(2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenyl)methyl]-N-ethyl-N-phenylbenzamide (14) and its N-H relative, (-)-4-[(alphaR)-alpha-(2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenyl)methyl]-N-ethyl-N-phenylbenzamide (15), that interacted with delta-receptors with good affinity, and, as we hoped, with much higher affinity at mu-receptors than SNC80. The relative configuration of the benzylic position in (+)-4-[(alphaR)-alpha-(4-allyl-(2S,5S)-dimethyl-1-piperazinyl)-(3-methoxyphenyl)methyl]-benzyl alcohol (10) was determined by X-ray crystallographic analysis of a crystal that was an unresolved twin. The absolute stereochemistry of that benzylic stereogenic center was unequivocally derived by the X-ray crystallographic analysis from the two other centers of asymmetry in the molecule that were known. Those were established from the synthesis via a dipeptide cyclo-L-Ala-L-Ala in which the absolute stereochemistry was established. 相似文献
130.
Absorption and retinol equivalence of beta-carotene in humans is influenced by dietary vitamin A intake 总被引:1,自引:0,他引:1
Lemke SL Dueker SR Follett JR Lin Y Carkeet C Buchholz BA Vogel JS Clifford AJ 《Journal of lipid research》2003,44(8):1591-1600
The effect of vitamin A supplements on metabolic behavior of an oral tracer dose of [14C]beta-carotene was investigated in a longitudinal test-retest design in two adults. For the test, each subject ingested 1 nmol of [14C]beta-carotene (100 nCi) in an emulsified olive oil-banana drink. Total urine and stool were collected for up to 30 days; concentration-time patterns of [14C]beta-carotene, [14C]retinyl esters, and [14C]retinol were determined for 46 days. On Day 53, the subjects were placed on a daily vitamin A supplement (10000 IU/day), and a second dose of [14C]beta-carotene (retest) was given on Day 74. All 14C determinations were made using accelerator mass spectrometry. In both subjects, the vitamin A supplementation was associated with three main effects: 1). increased apparent absorption: test versus retest values rose from 57% to 74% (Subject 1) and from 52% to 75% (Subject 2); 2). an approximately 10-fold reduction in urinary excretion; and 3). a lower ratio of labeled retinyl ester/beta-carotene concentrations in the absorptive phase. The molar vitamin A value of the dose for the test was 0.62 mol (Subject 1) and 0.54 mol (Subject 2) vitamin A to 1 mol beta-carotene. Respective values for the retest were 0.85 and 0.74. These results show that while less cleavage of beta-carotene occurred due to vitamin A supplementation, higher absorption resulted in larger molar vitamin A values. 相似文献