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排序方式: 共有186条查询结果,搜索用时 15 毫秒
51.
Bolen DW 《Methods (San Diego, Calif.)》2004,34(3):312-322
Protein solubility and stability are issues of consideration in attempts to crystallize proteins. These two properties of proteins are also at issue in the cells of organisms that have adapted to water stress conditions that could ordinarily denature or inactivate some proteins. Most organisms that have adapted to environmental stresses have done so by production and accumulation of certain small organic molecules, known as osmolytes, that arose by natural selection and have the ability to stabilize intracellular proteins against the environmental stress. Here, concepts developed to understand the special properties of the naturally occurring osmolytes in effecting protein stability and solubility, and the principles that have come from studies of these compounds have been presented. Along with excluded volume and preferential interaction parameters, identification of the osmophobic effect and the attenuation of this effect by favorable interactions of solute with side-chains appear to contribute to the full set of effects protecting osmolytes have on protein stability and solubility. With these concepts in mind and the fact that urea interacts favorably with the peptide backbone we note that: (1) osmolyte-induced effects on protein stability ranging from denaturation to forcing proteins to fold can be achieved experimentally and the underlying principles understood at near molecular-level detail, and (2) osmolyte-mediated solubility effects ranging from protein precipitation to protein solubilization are predictable based on these principles. These effects are contrasted and compared with effects of 2-methyl-2,4-pentanediol and polyethylene glycol on proteins, and how the principles found for the naturally occurring osmolytes can be applied to these two commonly used protein crystallizing agents. 相似文献
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Lipoteichoic acid (LTA) isolated from Staphylococcus aureus was found to exert a synergistic effect with calf serum to enhance DNA synthesis and growth of mouse embryo fibroblasts. LTA alone had no effect on DNA synthesis or cell multiplication. Mild base hydrolysis of LTA, which separates the molecule into its hydrophilic and hydrophobic moieties, completely destroyed its biological activity in this regard. Results are presented which suggest that LTA may enhance serum-induced DNA synthesis through interaction with cell surface components. The data indicate that LTA may prove to be a useful tool with which to probe cell membrane parameters involved in the regulation of cell proliferation. 相似文献
55.
HeLa S-3 and KB cells were grown in a LKB Batch Microcalorimeter under a variety of nutrient medium conditions amd mixing intervals. These conditions produced rather large apparent endothermic and exothermic responses on mixing that could be correlated with the presence of suspended cells (unattached) as well as cells attached to the glass calorimeter vessel. Cells capable of being resuspended upon mixing of the calorimeter vessel produces first an endothermic followed by an exothermic signal while attached cells produced only an apparent endothermic response. The exothermic response is believed to be associated with increased metabolic heat on suspending the cells followed by partial suppression of the steady state metabolic heat on cell settling. Rates of cell settling correlated well with the rate of decay of the exothermic signal. The rapid appearance of endothermicity on mixing suggests it is associated with rapid events such as binding of nutrients to cell surfaces. The response in the endothermic direction on mixing is discussed in terms of the disruption of mechanisms which tend to exclude nutrients from the surface of the cell. 相似文献
56.
Gur Yaari Christopher R. Bolen Juilee Thakar Steven H. Kleinstein 《Nucleic acids research》2013,41(18):e170
Enrichment analysis of gene sets is a popular approach that provides a functional interpretation of genome-wide expression data. Existing tests are affected by inter-gene correlations, resulting in a high Type I error. The most widely used test, Gene Set Enrichment Analysis, relies on computationally intensive permutations of sample labels to generate a null distribution that preserves gene–gene correlations. A more recent approach, CAMERA, attempts to correct for these correlations by estimating a variance inflation factor directly from the data. Although these methods generate P-values for detecting gene set activity, they are unable to produce confidence intervals or allow for post hoc comparisons. We have developed a new computational framework for Quantitative Set Analysis of Gene Expression (QuSAGE). QuSAGE accounts for inter-gene correlations, improves the estimation of the variance inflation factor and, rather than evaluating the deviation from a null hypothesis with a P-value, it quantifies gene-set activity with a complete probability density function. From this probability density function, P-values and confidence intervals can be extracted and post hoc analysis can be carried out while maintaining statistical traceability. Compared with Gene Set Enrichment Analysis and CAMERA, QuSAGE exhibits better sensitivity and specificity on real data profiling the response to interferon therapy (in chronic Hepatitis C virus patients) and Influenza A virus infection. QuSAGE is available as an R package, which includes the core functions for the method as well as functions to plot and visualize the results. 相似文献
57.
Mixed osmolytes: the degree to which one osmolyte affects the protein stabilizing ability of another
Mixtures of organic osmolytes occur in cells of many organisms, raising the question of whether their actions on protein stability are independent or synergistic. To investigate this question it is desirable to develop a system that permits evaluation of the effect of one osmolyte on the efficacy of another to either force-fold or denature a protein. A means of evaluating the efficacy of an osmolyte is provided by its m-value, an experimental quantity that measures the ability of the osmolyte to force a protein to unfold or fold. An experimental system is presented that enables evaluations of the m-values of osmolytes in the presence and absence of a second osmolyte. The experimental system involves use of a marginally stable protein in 10 mM buffer (pH 7, 200 mM salt, and 34 degrees C) that is at the midpoint of its native to denatured transition. These conditions enable determination of m-values for protecting and denaturing osmolytes in the presence and absence of a second osmolyte, permitting assessment of the extent to which the two osmolytes affect each other's efficacy. The two osmolytes investigated in this work are the denaturing osmolyte, urea, and the protecting osmolyte, sarcosine. Results show unequivocally that neither osmolyte alters the efficacy of the other in forcing the protein to fold or unfold-the osmolytes act independently on the protein despite their combined concentrations being in the multi-molar range. These osmolytes avoid altering one another's efficacy at these high concentrations because the number of osmolyte interaction sites on the protein is large and the binding constants are quite small. Consequently, the site occupancies are low enough in number that the two osmolytes neither compete nor cooperate in interacting with the protein. 相似文献
58.
Y Deng J Zhao D Sakurai KM Kaufman JC Edberg RP Kimberly DL Kamen GS Gilkeson CO Jacob RH Scofield CD Langefeld JA Kelly ME Alarcón-Riquelme BIOLUPUS GENLES Networks JB Harley TJ Vyse BI Freedman PM Gaffney KM Sivils JA James TB Niewold RM Cantor W Chen BH Hahn EE Brown PROFILE BP Tsao 《Arthritis research & therapy》2012,14(Z3):A5
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Vidushi S Patel Steven JB Cooper Janine E Deakin Bob Fulton Tina Graves Wesley C Warren Richard K Wilson Jennifer AM Graves 《BMC biology》2008,6(1):34