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91.
92.
Cross-adaptation and molecular modeling study of receptor mechanisms common to four taste stimuli in humans 总被引:2,自引:2,他引:0
Psychophysical cross-adaptation experiments were performed with two
carbohydrates, sucrose (SUC) and fructose (FRU), and two sweeteners,
acesulfame-K (MOD) and dulcin (DUL). Seven subjects were asked to match
concentrations that elicited the same intensity as a sucrose reference (30
g/l). Cross-adaptation levels were calculated as the ratio of isointense
concentrations measured for a given stimulus before and under adaptation.
On average, cross-adaptation between SUC and FRU is low and apparently
reciprocal. By contrast, cross-adaptation between SUC and MOD is clearly
non-reciprocal: SUC adapts MOD significantly (24%, P < 0.005), but MOD
fails to adapt SUC (2%, P < 0.79). Significant and reciprocal
cross-enhancement is observed between DUL and MOD (approximately -20%, P
< 0.03), and also between SUC and DUL (approximately -15%, P < 0.08).
In parallel, molecular modeling of the four tastants was performed in order
to look for the 12 common binding motifs that were isolated on 14 other
tastants in a previous study. SUC and FRU each display 10 out of the 12
binding motifs, whereas DUL and MOD only display four and five distinct
motifs respectively and do not have any motif in common. Experimental
cross-adaptation levels seem to correlate well with the number of motifs
that molecules have in common. FRU and SUC share a majority of binding
motifs and correlatively show mutual cross-adaptation. Four motifs of MOD
are found among the 10 motifs of SUC, which may explain why SUC
cross-adapts MOD but not vice versa. By contrast, DUL and MOD do not share
any motif and do not cross- adapt. The various molecular mechanisms that
may be responsible for cross-adaptation and/or cross-enhancement are
discussed in light of our results.
相似文献
93.
Blonder J Conrads TP Yu LR Terunuma A Janini GM Issaq HJ Vogel JC Veenstra TD 《Proteomics》2004,4(1):31-45
A simple and rapid method for characterizing hydrophobic integral membrane proteins and its utility for membrane proteomics using microcapillary liquid chromatography coupled on-line with tandem mass spectrometry (microLC-MS/MS) is described. The present technique does not rely on the use of detergents, strong organic acids or cyanogen bromide-mediated proteolysis. A buffered solution of 60% methanol was used to extract, solubilize, and tryptically digest proteins within a preparation of Halobacterium (H.) halobium purple membranes. Analysis of the digested purple membrane proteins by microLC-MS/MS resulted in the identification of all the predicted tryptic peptides of bacteriorhodopsin, including those that are known to be post-translationally modified. In addition, 40 proteins from the purple membrane preparation were also identified, of which 80% are predicted to contain between 1 and 16 transmembrane domains. To evaluate the general applicability of the method, the same extraction, solubilization, and digestion conditions were applied to a plasma membrane fraction prepared from human epidermal sheets. A total of 117 proteins was identified in a single microLC-MS/MS analysis, of which 55% are known to be integral or associated with the plasma membrane. Due to its simplicity, efficiency, and absence of MS interfering compounds, this technique can be used for the characterization of other integral membrane proteins and may be concomitantly applied for the analysis of membrane protein complexes or large-scale proteomic studies of different membrane samples. 相似文献
94.
Background
A new sequence independent bioinformatics approach allowing genome-wide search for proteins with similar three dimensional structures has been developed. By utilizing the numerical output of the sequence threading it establishes putative non-obvious structural similarities between proteins. When applied to the testing set of proteins with known three dimensional structures the developed approach was able to recognize structurally similar proteins with high accuracy.Results
The method has been developed to identify pathogenic proteins with low sequence identity and high structural similarity to host analogues. Such protein structure relationships would be hypothesized to arise through convergent evolution or through ancient horizontal gene transfer events, now undetectable using current sequence alignment techniques. The pathogen proteins, which could mimic or interfere with host activities, would represent candidate virulence factors.The developed approach utilizes the numerical outputs from the sequence-structure threading. It identifies the potential structural similarity between a pair of proteins by correlating the threading scores of the corresponding two primary sequences against the library of the standard folds. This approach allowed up to 64% sensitivity and 99.9% specificity in distinguishing protein pairs with high structural similarity.Conclusion
Preliminary results obtained by comparison of the genomes of Homo sapiens and several strains of Chlamydia trachomatis have demonstrated the potential usefulness of the method in the identification of bacterial proteins with known or potential roles in virulence.95.
A major goal of proteomics is to develop methods that enable the systematic characterization of every protein within the cell or particular subcellular proteome using a single analytical platform. Although the equivalent has already been achieved in genomics, reaching this goal in proteomics represents a much greater challenge due to the wide dynamic range of protein expression, numerous post-translational modifications and remarkable physicochemical heterogeneity of proteins. A major analytical challenge has involved developing more effective means for proteome-scale investigations of membrane proteins, whose solubility differs drastically from that of cytoplasmic proteins. Fortunately, rapid progress has increased the ability to characterize this critically important class of proteins on a scale analogous to that of aqueous soluble proteins. 相似文献
96.
Efficient estimation of the prevalence of multiple rare traits 总被引:1,自引:0,他引:1
97.
Background
Genomic imprinting is an epigenetic mechanism that can lead to differential gene expression depending on the parent-of-origin of a received allele. While most studies on imprinting address its underlying molecular mechanisms or attempt at discovering genomic regions that might be subject to imprinting, few have focused on the amount of phenotypic variation contributed by such epigenetic process. In this report, we give a brief review of a one-locus imprinting model in a quantitative genetics framework, and provide a decomposition of the genetic variance according to this model. Analytical deductions from the proposed imprinting model indicated a non-negligible contribution of imprinting to genetic variation of complex traits. Also, we performed a whole-genome scan analysis on mouse body mass index (BMI) aiming at revealing potential consequences when existing imprinting effects are ignored in genetic analysis.Results
10,021 SNP markers were used to perform a whole-genome single marker regression on mouse BMI using an additive and an imprinting model. Markers significant for imprinting indicated that BMI is subject to imprinting. Marked variance changed from 1.218 ×10−4 to 1.842 ×10−4 when imprinting was considered in the analysis, implying that one third of marked variance would be lost if existing imprinting effects were not accounted for. When both marker and pedigree information were used, estimated heritability increased from 0.176 to 0.195 when imprinting was considered.Conclusions
When a complex trait is subject to imprinting, using an additive model that ignores this phenomenon may result in an underestimate of additive variability, potentially leading to wrong inferences about the underlying genetic architecture of that trait. This could be a possible factor explaining part of the missing heritability commonly observed in genome-wide association studies (GWAS). 相似文献98.
Shane Deegan Svetlana Saveljeva Susan E Logue Karolina Pakos-Zebrucka Sanjeev Gupta Peter Vandenabeele Mathieu JM Bertrand Afshin Samali 《Autophagy》2014,10(11):1921-1936
Endoplasmic reticulum (ER) stress-induced cell death is normally associated with activation of the mitochondrial apoptotic pathway, which is characterized by CYCS (cytochrome c, somatic) release, apoptosome formation, and caspase activation, resulting in cell death. In this study, we demonstrate that under conditions of ER stress cells devoid of CASP9/caspase-9 or BAX and BAK1, and therefore defective in the mitochondrial apoptotic pathway, still undergo a delayed form of cell death associated with the activation of caspases, therefore revealing the existence of an alternative stress-induced caspase activation pathway. We identified CASP8/caspase-8 as the apical protease in this caspase cascade, and found that knockdown of either of the key autophagic genes, ATG5 or ATG7, impacted on CASP8 activation and cell death induction, highlighting the crucial role of autophagy in the activation of this novel ER stress-induced death pathway. In line with this, we identified a protein complex composed of ATG5, FADD, and pro-CASP8 whose assembly coincides with caspase activation and cell death induction. Together, our results reveal the toxic potential of autophagy in cells undergoing ER stress that are defective in the mitochondrial apoptotic pathway, and suggest a model in which the autophagosome functions as a platform facilitating pro-CASP8 activation. Chemoresistance, a common problem in the treatment of cancer, is frequently caused by the downregulation of key mitochondrial death effector proteins. Alternate stress-induced apoptotic pathways, such as the one described here, may become of particular relevance for tackling the problem of chemoresistance in cancer cells. 相似文献
99.
JM Mcnulty 《Biotechnic & histochemistry》2013,88(5-6):191-196
Zirconyl hematoxylin stains acidic mucins darkly and specifically using a solution of 100 mg hematoxylin, 5 ml ethanol, 5 ml 0.5% sodium iodate, 400 mg zirconyl chloride octahydrate, and 30 ml 25% aqueous glycerol. The stain is especially advantageous for studying goblet cells and Paget cells. 相似文献
100.
Roland F Hoffmann Sina Zarrintan Simone M Brandenburg Arjan Kol Harold G de Bruin Shabnam Jafari Freark Dijk Dharamdajal Kalicharan Marco Kelders Harry R Gosker Nick HT ten Hacken Johannes J van der Want Antoon JM van Oosterhout Irene H Heijink 《Respiratory research》2013,14(1):97