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901.
Vishakha Karnawat 《Journal of biomolecular structure & dynamics》2016,34(3):640-652
Deaza analogues of nucleobases are potential drugs against infectious diseases caused by parasites. A caveat is that apart from binding their target parasite enzymes, they also bind and inhibit enzymes of the host. In order to design derivatives of deaza analogues which specifically bind target enzymes, knowledge of their molecular structure, protonation state, and predominant tautomers at physiological conditions is essential. We have employed resonance Raman spectroscopy at an excitation wavelength of 260 nm, to decipher solution structure of 9-deazaguanine (9DAG) and 9-deazahypoxanthine (9DAH). These are analogues of guanine and hypoxanthine, respectively, and have been exploited to study static complexes of nucleobase binding enzymes. Such enzymes are known to perturb pKa of their ligands, and thus, we also determined solution structures of these analogues at two, acidic and alkaline, pH. Structure of each possible protonation state and tautomer was computed using density functional theoretical calculations. Species at various pHs were identified based on isotopic shifts in experimental wavenumbers and by comparing these shifts with corresponding computed isotopic shifts. Our results show that at physiological pH, N1 of pyrimidine ring in 9DAG and 9DAH bears a proton. At lower pH, N3 is place of protonation, and at higher pH, deprotonation occurs at N1 position. The proton at N7 of purine ring remains intact even at pH 12.5. We have further compared these results with naturally occurring nucleotides. Our results identify key vibrational modes which can report on hydrogen bonding interactions, protonation and deprotonation in purine rings upon binding to the active site of enzymes. 相似文献
902.
Although population density is believed to be an important factor influencing evolutionary processes, surprisingly few studies have documented the existence or nature of density-dependent selection. We quantified the effects of density on directional selection on seed mass (the mass of a sown seed) and emergence time in the greenhouse and field for the annual plant Plantago wrightiana. In the greenhouse, we quantified selection on seed mass and emergence time at each of five planting densities (1 m–2 to 10,000 m–2) using the relationship between final plant mass and each trait at each density. We observed no significant selection on either seed mass or emergence time when plants were grown alone. At all higher densities, there was significant selection favoring early emergence and large seed mass, but there were no significant differences among the selection gradients determined at densities greater than individually grown plants. In the field, we detected no relationship between the magnitude of selection for early emergence and density. Our results suggest that selection on seed mass and time of emergence is density dependent, but the relationship between density and the magnitude of directional selection on these traits is not continuously increasing. Over broad ranges of density in the greenhouse and in the field, there was no detectable relationship between density and the magnitude of directional selection. 相似文献
903.
904.
The present investigation assesses a number of explanations for the patterns of variability in dental dimensions. Coefficients of variation were calculated for mesiodistal and buccolingual diameters in a sample of 105 Papio ursinus crania (52 male, 53 female). Variability profiles consisting of arrays of values of coefficients of variation were evaluated by means of Friedman's two-way analysis of variance and Kendall's coefficient of concordance. Although molar teeth were found to be the most dimensionally stable, our results failed to support either the morphogenetic field theory or the occlusal complexity hypothesis. The data presented here are generally supportive of Pengilly's phenotypic complexity theory. However, speciesspecific clustering patterns found in our regressions of dimensional variability on mean tooth size suggest that differences in variability levels might be related to differences in selective pressures. 相似文献
905.
906.
Jian-Hong Chen Lei-Li Wang Lin Tao Bin Qi Yong Wang Yu-Jie Guo Liu Miao 《Journal of cellular and molecular medicine》2021,25(22):10736-10746
The present study aimed to explore the potential hub genes and pathways of ischaemic cardiomyopathy (ICM) and to investigate the possible associated mechanisms. Two microarray data sets ( GSE5406 and GSE57338 ) were downloaded from the Gene Expression Omnibus (GEO) database. The limma package was used to analyse the differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology (DO) and Gene Ontology (GO) annotation analyses were performed. A protein-protein interaction (PPI) network was set up using Cytoscape software. Significant modules and hub genes were identified by the Molecular Complex Detection (MCODE) app. Then, further functional validation of hub genes in other microarrays and survival analysis were performed to judge the prognosis. A total of 1065 genes were matched, with an adjusted p < 0.05, and 17 were upregulated and 25 were downregulated with|log2 (fold change)|≥1.2. After removing the lengthy entries, GO identified 12 items, and 8 pathways were enriched at adjusted p < 0.05 (false discovery rate, FDR set at <0.05). Three modules with a score >8 after MCODE analysis and MYH6 were ultimately identified. When validated in GSE23561 , MYH6 expression was lower in patients with CAD than in healthy controls (p < 0.05). GSE60993 data suggested that MYH6 expression was also lower in AMI patients (p < 0.05). In the GSE59867 data set, MYH6 expression was lower in CAD patients than in AMI patients and lower in heart failure (HF) patients than in non-HF patients. However, there was no difference at different periods within half a year, and HF was increased when MYH6 expression was low (p < 0.05–0.01). We performed an integrated analysis and validation and found that MYH6 expression was closely related to ICM and HF. However, whether this marker can be used as a predictor in blood samples needs further experimental verification. 相似文献
907.
This study shows the feasibility of using density gradient centrifugation in the “A” zonal rotor for large-scale purification of Toxoplasma gondii tachyzoites from the host cells of mouse peritoneal exudate. Ficoll and Dextran 40 were used as gradients. Using Ficoll gradient, up to 70% of the toxoplasms were recovered by pooling purified fractions with the peak fractions giving recoveries around 38%. In the experiment using dextran gradients Toxoplasma recovery was of 41%, but the band of host cells was not so sharply formed. 相似文献
908.
Wen-Ge Han 《Inorganica chimica acta》2008,361(4):973-986
Mössbauer isomer shift parameters have been obtained for both density functional theory (DFT) OPBE and OLYP functionals by linear regressions between the measured isomer shifts and calculated electron densities at Fe nuclei for a number of Fe2+,2.5+ and Fe2.5+,3+,3.5+,4+ complexes grouped separately. The calculated isomer shifts and quadrupole splittings on the sample Fe complexes from OPBE and OLYP functionals are similar to those of PW91 calculations [J. Comput. Chem. 27 (2006) 1292], however the fit parameters from the linear regressions differ between PW91 and OPBE, OLYP. Four models for the active site structure of intermediate Q of the hydroxylase component of soluble methane monooxygenase (MMOH) have been studied, using three DFT functionals OPBE, OLYP, and PW91, incorporated with broken-symmetry methodology and the conductor-like screening (COSMO) solvation model. The calculated properties, including optimized geometries, electronic energies, pKa’s, Fe net spin populations, and Mössbauer isomer shifts and quadrupole splittings, have been reported and compared with available experimental values. The high-spin antiferromagnetically (AF) coupled Fe4+ sites are correctly predicted by OPBE and OLYP methods for all active site models. PW91 potential overestimates the Fe-ligand covalencies for some of the models because of spin crossover. Our calculations and data analysis support the structure (our current model II shown in Fig. 8) proposed by Friesner and Lippard’s group [J. Am. Chem. Soc. 123 (2001) 3836-3837], which contains an Fe4+(μ-O)2Fe4+ center, one axial water which also H-bonds to both side chains of Glu243 and Glu114, and one bidentate carboxylate group from the side chain of Glu144, which is likely to represent the active site of MMOH-Q. A new model structure (model IV shown in Fig. 9), which has a terminal hydroxo and a protonated His147 which is dissociated from a nearby Fe, is more asymmetric in its Fe(μ-O)2Fe diamond core, and is another very good candidate for intermediate Q. 相似文献
909.
The long preservation and recovery of functional (contractile) properties in cultured aortic smooth muscle cells, even after replating or deep-frozen storage and the measurement of their responses are now technically settled issues. We could thus study extensively the responses of single cultured cells from rat thoracic aorta. Responses were elicited by the addition of KCl 40 mmol/L without or with a calcium blocker PN 200-100 (10–6 mol/L); angiostein II (10–11–10–6 mol/L) without or with antagonist (losartan 10–5 mol/L); or serotonin (10–9–10–4 mol/L) without or with antagonist (naftidrofuryl 10–5 mol/L). Results thus obtained enabled us to propose a new hypothesis for the interpretation of the contractile responses of an elastic vascular smooth muscle. The different maximal effects of different agonists result mainly from the different proportions of cells they can mobilize; the agonist concentration-contraction relationship is mainly due to the increase of the proportion of cells involved up to a maximal value typical of the agonist used. An antagonist primarily reduce the proportion of cells an agonist can mobilize. Some of the consequences of this hypothesis are briefly outlined. 相似文献
910.