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91.
The cytoplasm-to-vacuole targeting (Cvt) pathway of Saccharomyces cerevisiae delivers aminopeptidase I (Ape1) from the cytosol to the vacuole, bypassing the normal secretory route. The Cvt pathway, although well-studied, was known only in S. cerevisiae. We demonstrate its existence in the methylotrophic yeast, Pichia pastoris, where it also delivers P. pastoris Ape1 (PpApe1) to the vacuole. Most proteins known to be required for the Cvt pathway in S. cerevisiae were, to the extent we found orthologs, also required in P. pastoris. The P. pastoris Cvt pathway differs, however, from that in S. cerevisiae, in that new proteins, such as PpAtg28 and PpAtg26, are involved. The discovery of a Cvt pathway in P. pastoris makes it an excellent model system for the dissection of autophagy-related pathways in a single organism and for the discovery of new Cvt pathway components. 相似文献
92.
For reliable protein identification and quantitation, it is important to minimize the variability associated with two-dimensional electrophoresis (2-DE) analysis. Since experimental factors contribute largely to the variability observed in 2-DE, most studies have focused on reducing this variability with modest concern to the variability associated with post-experimental analyses. Although often ignored, software analyses of 2-DE gel images present a considerable source of variability in the analysis of proteins. In particular, cropping of gel images prior to quantitative 2-DE analysis has been shown to contribute a significant amount of variability in image analysis. To address this problem, we propose a simple, reliable, and objective method of cropping 2-DE gel images to consequently minimize the variability in 2-DE analysis. 相似文献
93.
94.
Antonetta B.C. Buskermolen Hamsini Suresh Siamak S. Shishvan Andrea Vigliotti Antonio DeSimone Nicholas A. Kurniawan Carlijn V.C. Bouten Vikram S. Deshpande 《Biophysical journal》2019,116(10):1994-2008
Contact guidance—the widely known phenomenon of cell alignment induced by anisotropic environmental features—is an essential step in the organization of adherent cells, but the mechanisms by which cells achieve this orientational ordering remain unclear. Here, we seeded myofibroblasts on substrates micropatterned with stripes of fibronectin and observed that contact guidance emerges at stripe widths much greater than the cell size. To understand the origins of this surprising observation, we combined morphometric analysis of cells and their subcellular components with a, to our knowledge, novel statistical framework for modeling nonthermal fluctuations of living cells. This modeling framework is shown to predict not only the trends but also the statistical variability of a wide range of biological observables, including cell (and nucleus) shapes, sizes, and orientations, as well as stress-fiber arrangements within the cells with remarkable fidelity with a single set of cell parameters. By comparing observations and theory, we identified two regimes of contact guidance: 1) guidance on stripe widths smaller than the cell size (w ≤ 160 μm), which is accompanied by biochemical changes within the cells, including increasing stress-fiber polarization and cell elongation; and 2) entropic guidance on larger stripe widths, which is governed by fluctuations in the cell morphology. Overall, our findings suggest an entropy-mediated mechanism for contact guidance associated with the tendency of cells to maximize their morphological entropy through shape fluctuations. 相似文献
95.
Uzay Gormus Alka Chaubey Suresh Shenoy Yong Wee Wong Lee Yin Chan Bao Ping Choo Liza Oraha Anna Gousseva Fredrik Persson Lawrence Prensky Ephrem Chin Madhuri Hegde 《Current issues in molecular biology》2021,43(2):958
Background: Rolling-circle replication (RCR) is a novel technology that has not been applied to cell-free DNA (cfDNA) testing until recently. Given the cost and simplicity advantages of this technology compared to other platforms currently used in cfDNA analysis, an assessment of RCR in clinical laboratories was performed. Here, we present the first validation study from clinical laboratories utilizing RCR technology. Methods: 831 samples from spontaneously pregnant women carrying a singleton fetus, and 25 synthetic samples, were analyzed for the fetal risk of trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13), by three laboratories on three continents. All the screen-positive pregnancies were provided post-test genetic counseling and confirmatory diagnostic invasive testing (e.g., amniocentesis). The screen-negative pregnancies were routinely evaluated at birth for fetal aneuploidies, using newborn examinations, and any suspected aneuploidies would have been offered diagnostic testing or confirmed with karyotyping. Results: The study found rolling-circle replication to be a highly viable technology for the clinical assessment of fetal aneuploidies, with 100% sensitivity for T21 (95% CI: 82.35–100.00%); 100.00% sensitivity for T18 (71.51–100.00%); and 100.00% sensitivity for T13 analyses (66.37–100.00%). The specificities were >99% for each trisomy (99.7% (99.01–99.97%) for T21; 99.5% (98.62–99.85%) for T18; 99.7% (99.03–99.97%) for T13), along with a first-pass no-call rate of 0.93%. Conclusions: The study showed that using a rolling-circle replication-based cfDNA system for the evaluation of the common aneuploidies would provide greater accuracy and clinical utility compared to conventional biochemical screening, and it would provide comparable results to other reported cfDNA methodologies. 相似文献
96.
Keerthi T.R. Suresh P.V. Sabu A. Rajeevkumar S. Chandrasekaran M. 《World journal of microbiology & biotechnology》1999,15(6):751-752
Beauveria sp. BTMF S10 isolated from marine sediment produced extracellular L-glutaminase. Maximal L-glutaminase yield (46.9U/ml) was obtained in a medium supplemented with 1% (w/v) yeast extract and sorbitol, 9% (w/v) sodium chloride and 0.2% (w/v) methionine, initial pH 9.0 and at 27 °C after 108h. This enzyme was inducible and growth-associated. 相似文献
97.
Estrogen has a profound impact on human physiology and affects numerous genes. The classical estrogen reaction is mediated by its receptors (ERs), which bind to the estrogen response elements (EREs) in target gene's promoter region. Due to tedious and expensive experiments, a limited number of human genes are functionally well characterized. It is still unclear how many and which human genes respond to estrogen treatment. We propose a simple, economic, yet effective computational method to predict a subclass of estrogen responsive genes. Our method relies on the similarity of ERE frames across different promoters in the human genome. Matching ERE frames of a test set of 60 known estrogen responsive genes to the collection of over 18,000 human promoters, we obtained 604 candidate genes. Evaluating our result by comparison with the published microarray data and literature, we found that more than half (53.6%, 324/604) of predicted candidate genes are responsive to estrogen. We believe this method can significantly reduce the number of testing potential estrogen target genes and provide functional clues for annotating part of genes that lack functional information. 相似文献
98.
The simulations in this paper show that exposure measurement error affects the parameter estimates of the biologically motivated two-stage clonal expansion (TSCE) model. For both Berkson and classical error models, we show that likelihood-based techniques of correction work reliably. For classical errors, the distribution of true exposures needs to be known or estimated in addition to the distribution of recorded exposures conditional on true exposures. Usually the exposure uncertainty biases the model parameters toward the null and underestimates the precision. But when several parameters are allowed to be dependent on exposure, e.g. initiation and promotion, then their relative importance is also influenced, and more complicated effects of exposure uncertainty can occur. The application part of this paper shows for two different types of Berkson errors that a recent analysis of the data for the Colorado plateau miners with the TSCE model is not changed substantially when correcting for such errors. Specifically, the conjectured promoting action of radon remains as the dominant radiation effect for explaining these data. The estimated promoting action of radon increases by a factor of up to 1.2 for the largest assumed exposure uncertainties. 相似文献
99.
Suresh Babu K Tiwari AK Srinivas PV Ali AZ China Raju B Rao JM 《Bioorganic & medicinal chemistry letters》2004,14(14):3841-3845
The methanolic extract of rhizome of Himalayan rhubarb Rheum emodi displayed mild yeast as well as mammalian intestinal alpha-glucosidase inhibitory activity. However, further fractionation of active extract led to the isolation of several potent molecules in excellent yields, displaying varying degrees of inhibition on two test models of alpha-glucosidase. Rhapontigenin, desoxyrhapontigenin, chrysophanol-8-O-beta-d-glucopyranoside, torachrysone-8-O-beta-d-glucopyranoside displayed potent yeast alpha-glucosidase inhibition. However chrysophanol-8-O-beta-d-glucopyranoside, desoxyrhaponticin and torachrysone-8-O-beta-d-glucopyranoside displayed potent to moderate mammalian alpha-glucosidase inhibitory activity. Other compounds displayed mild activity on both the tests. Except desoxyrhapontigenin and rhapontigenin that increased Vmax, other compounds including crude extract decreased the Vmax significantly (p<0.02) in yeast alpha-glucosidase test. Further kinetic analysis on mammalian alpha-glucosidase inhibition showed that chrysophanol-8-O-beta-d-glucopyranoside, desoxyrhaponticin and torachrysone-8-O-beta-d-glucopyranoside may be classified as mixed-noncompetitive inhibitors. However, desoxyrhapontigenin and rhapontigenin may be classified as modulators of enzyme activity. Presence and position of glycoside moiety in compounds appear important for better inhibition of mammalian alpha-glucosidase. This is the first report assigning particularly, mammalian intestinal alpha-glucosidase inhibitory activity to these compounds. Chrysophanol-8-O-beta-d-glucopyranoside, desoxyrhaponticin, desoxyrhapontigenin and rhapontigenin have been isolated in substantial yields from R. emodi for the first time. Therefore, these compounds may have value in the treatment and prevention of hyperglycemia associated diabetes mellitus. 相似文献
100.
Koltun DO Marquart TA Shenk KD Elzein E Li Y Nguyen M Kerwar S Zeng D Chu N Soohoo D Hao J Maydanik VY Lustig DA Ng KJ Fraser H Zablocki JA 《Bioorganic & medicinal chemistry letters》2004,14(2):549-552
New inhibitors of palmitoylCoA oxidation were synthesized based on a structurally novel lead, CVT-3501 (1). Investigation of structure-activity relationships was conducted with respect to potency of inhibition of cardiac mitochondrial palmitoylCoA oxidation and metabolic stability. Potent and metabolically stable analogues 33, 42, and 43 were evaluated in vitro for cytochrome P450 inhibition and potentially adverse electrophysiological effects. Compound 33 was also found to have favorable pharmacokinetic properties in rat. 相似文献