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排序方式: 共有283条查询结果,搜索用时 187 毫秒
41.
Garrett B. Goh Benjamin S. Hulbert Huiqing Zhou Charles L. Brooks III 《Proteins》2014,82(7):1319-1331
pH is a ubiquitous regulator of biological activity, including protein‐folding, protein‐protein interactions, and enzymatic activity. Existing constant pH molecular dynamics (CPHMD) models that were developed to address questions related to the pH‐dependent properties of proteins are largely based on implicit solvent models. However, implicit solvent models are known to underestimate the desolvation energy of buried charged residues, increasing the error associated with predictions that involve internal ionizable residue that are important in processes like hydrogen transport and electron transfer. Furthermore, discrete water and ions cannot be modeled in implicit solvent, which are important in systems like membrane proteins and ion channels. We report on an explicit solvent constant pH molecular dynamics framework based on multi‐site λ‐dynamics (CPHMDMSλD). In the CPHMDMSλD framework, we performed seamless alchemical transitions between protonation and tautomeric states using multi‐site λ‐dynamics, and designed novel biasing potentials to ensure that the physical end‐states are predominantly sampled. We show that explicit solvent CPHMDMSλD simulations model realistic pH‐dependent properties of proteins such as the Hen‐Egg White Lysozyme (HEWL), binding domain of 2‐oxoglutarate dehydrogenase (BBL) and N‐terminal domain of ribosomal protein L9 (NTL9), and the pKa predictions are in excellent agreement with experimental values, with a RMSE ranging from 0.72 to 0.84 pKa units. With the recent development of the explicit solvent CPHMDMSλD framework for nucleic acids, accurate modeling of pH‐dependent properties of both major class of biomolecules—proteins and nucleic acids is now possible. Proteins 2014; 82:1319–1331. © 2013 Wiley Periodicals, Inc. 相似文献
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Summary A factorial field experiment was designed to test the effects of small mammals and above- and below-ground invertebrates on plant species richness and composition in native tallgrass prairie at Konza Prairie Research Natural Area, northeast Kansas. Over a 4-year period, Microtus ochrogaster densities were maintained by live-trapping in fenced plots, and invertebrate levels were reduced using the pesticides carbaryl for above-ground invertebrates and an organophosphate (isofenphos) for belowground invertebrates. ANOVA according to a split-plot design of plant species biomass data harvested in 1984 and 1986 revealed few significant effects of either small mammal densities or pesticide application. Of 54 species harvested from both sample dates, only 10 were significantly affected by either treatment. Analysis of species richness according to 8 life-form classes provided a clearer pattern of response than did biomass either by species or life-form class. For example, numbers of C4 grasses were reduced by increasing small mammal densities, whereas numbers of C4 annual forbs were lowest when above-ground herbivory was reduced. While consumers have been shown to have strong effects on successional communities, the few significant results observed in this study suggests that the manipulated levels of small mammals and insects had few effects on a mature tallgrass prairie.Deceased May, 1986 相似文献
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45.
Fernando A. Salinas Kian H. Wee Hulbert K. B. Silver 《Cancer immunology, immunotherapy : CII》1995,12(1):11-19
Summary We have investigated the membrane-binding properties of fetal liver cells (FLC) and developed an assay to quantitate circulating immune complexes (CIC) based on complement (C) receptor binding on FLC. Both binding and blocking studies identified FLC membrane receptors for IgG-Fc, C, and antifetal antibodies (FL-Ab), but not IgG F(ab)2. Fc binding of IgG or aggregated human IgG (AHG) was relatively weak, with an association constant of 1.5×107 l/mol. In contrast, there was a six- to seven-fold increase in binding of AHG by C receptors, with an association constant of 108 l/mol. A simple and sensitive procedure for detecting CIC in the sera of patients with various disease states has been developed by the use of C receptors on FLC. Reference to an AHG standard curve permits quantitation of CIC in micrograms of AHG equivalent per milliliter of serum. Clinical evaluation in patients with active collagen vascular disease and in cancer patients confirmed the reliability, specificity of binding, and sensitivity of the FLC method. Although there was overall agreement with the Raji cell method for CIC detection, FLC-RIA quantiation of CIC was found to be more sensitive than the Raji cell assay. Other discrepancies could be explained by differing sensitivity to CIC size.Preliminary results were presented at the Seventieth Annual Meeting of the American Association for Cancer Research, May 1979 [40] 相似文献
46.
Disease Lesion Mimicry Caused by Mutations in the Rust Resistance Gene rp1 总被引:2,自引:0,他引:2 下载免费PDF全文
The rp1 locus of maize controls race-specific resistance to the common rust fungus Puccinia sorghi. Four mutant or recombinant Rp1 alleles (rp1-NC3, Rp1-D21, Rp1-MD19, and Rp1-Kr1N) were identified. They condition necrotic phenotypes in the absence of the rust pathogen. These Rp1 lesion mimics fall into three different phenotypic classes: (1) The rp1-NC3 and Rp1-D21 alleles require rust infection or other biotic stimulus to initiate necrotic lesions. These alleles react strongly to all maize rust biotypes tested and also to nonhost rusts. (2) The Rp1-MD19 allele, which has a similar phenotype, also requires a biotic stimulus to initiate lesions. However, Rp1-MD19 shows the race specificity of the Rp1-D gene. (3) The Rp1-Kr1N allele specifies a diffuse necrotic phenotype in the absence of any biotic stimulus and a race-specific reaction when inoculated with maize rust. 相似文献
47.
Nucleotide sequence analysis of the lemur beta-globin gene family: evidence for major rate fluctuations in globin polypeptide evolution 总被引:1,自引:0,他引:1
Lemur beta-related globin genes have been isolated and sequenced. Orthology
of prosimian and human epsilon-, gamma-, and beta-related globin genes was
established by dot-matrix analysis. All of these lemur globin genes
potentially encode functional beta-related globin polypeptides, though
precisely when the gamma-globin gene is expressed remains unknown. The
organization of the 18-kb brown lemur beta-globin gene cluster (5'
epsilon-gamma-[psi eta-delta]-beta 3') is consistent with its evolution by
contraction via unequal crossing-over from the putative ancestral mammalian
beta-globin gene cluster (5' epsilon-gamma- eta-delta-beta 3'). The dwarf
lemur nonadult globin genes are arranged as in the brown lemur. Similar
levels of synonymous (silent) nucleotide substitutions and noncoding DNA
sequence differences have accumulated between species in all of these
genes, suggesting a uniform rate of noncoding DNA divergence throughout
primate beta-globin gene clusters. These differences are comparable with
those observed in the nonfunctional psi eta pseudogene and have therefore
accumulated at the presumably maximal neutral rate. In contrast,
nonsynonymous (replacement) nucleotide substitutions show a significant
heterogeneity in distribution for both the same gene in different lineages
and different genes in the same lineage. These major fluctuations in
replacement but not silent substitution rates cannot be attributed to
changes in mutation rate, suggesting that changes in the rate of globin
polypeptide evolution in primates is not governed solely by variable
mutation rates.
相似文献
48.
Man S. F.; Hulbert W. C.; Mok K.; Ryan T.; Thomson A. B. 《Journal of applied physiology》1986,60(2):416-426
The bioelectric and barrier properties of the tracheal epithelium in nose-breathing dogs and in dogs that had been exposed for 75 min to compressed air or to two high concentrations of SO2 were measured and compared. We also studied tissues that had been treated with chloroform. Based on a model of restrictive diffusion we demonstrated heteropores (6 and 250 A) in the control tissues. Bioelectric changes due to 100-ppm SO2 were minimal. After exposure to 500 ppm SO2, adverse changes in the bioelectric properties were focal; they were marked in 8 out of 12 animals but were less striking in the other 4. Nonelectrolyte permeability increased with an increase in SO2 concentrations. Small pores were still present in the tissues severely affected by SO2 but they were absent in chloroform-treated tissues. Scanning electron microscopy of tissues from animals exposed to 500 ppm SO2 showed that in the same dog tissue appearance varied from normal to one of repair (normal bioelectric properties) or one of marked exfoliation of ciliated cells (abnormal bioelectric measurements). 相似文献
49.
S F Man W Hulbert D S Park A B Thomson J C Hogg 《Journal of applied physiology (Bethesda, Md. : 1985)》1984,57(5):1338-1346
The symmetry of osmotic conductivity of the canine tracheal epithelial cells was examined in vitro. When an osmotic load of 100 mosM sucrose was added to the serosal bathing solution, no change in the transepithelial potential difference was observed in 15 tissue preparations. In contrast, when the same osmotic load was added to the mucosal bathing solution, there was a rapid decrease in the transepithelial potential difference of 3.9 +/- 0.5 mV (n = 23); ouabain (10(-4) M) eliminated this change. Tissues that had been exposed to the osmotic load added to either the mucosal or serosal side were compared with the control using light and electron microscopy. When the osmotic load was added to the mucosal fluid, there was no change in the nuclear-to-cytoplasmic area ratio of the cell types examined. However, when the same osmotic load was added to the serosal fluid, a marked increase in the nuclear-to-cytoplasmic area ratio of the ciliated cells was observed. This finding indicated cell shrinkage. Dilution potentials measured by substituting NaCl with mannitol also showed asymmetry. The morphological features are probably caused by differences in the osmotic conductivity (Lp) of the basolateral and apical cell membranes, with the Lp of the apical membrane being less than that of the basolateral membrane. The basis for osmotically induced potentials remained undetermined. 相似文献
50.
Genetic Analysis of the Fungus, Bremia Lactucae, Using Restriction Fragment Length Polymorphisms 总被引:4,自引:2,他引:2 下载免费PDF全文
S. H. Hulbert T. W. Ilott E. J. Legg S. E. Lincoln E. S. Lander R. W. Michelmore 《Genetics》1988,120(4):947-958
Restriction fragment length polymorphisms (RFLPs) were developed as genetic markers for Bremia lactucae, the biotrophic Oomycete fungus which causes lettuce downy mildew. By using 55 genomic and cDNA probes, a total of 61 RFLP loci were identified among three heterothallic isolates of B. lactucae. Of these 61 RFLP loci, 53 were heterozygous in at least one of the three strains and thus were informative for linkage analysis in at least one of two F1 crosses that were performed. Analysis of the cosegregation of these 53 RFLPs, eight avirulence loci and the mating type locus allowed the construction of a preliminary genetic linkage map consisting of 13 small linkage groups. Based on the extent of linkage detected among probes, the genome of B. lactucae can be estimated to be approximately 2000 cM. Linkage was detected between a RFLP locus and an avirulence gene, providing a potential starting point for chromosome walking to clone an avirulence gene. The high frequency of DNA polymorphism in naturally occurring isolates and the proper Mendelian segregation of loci detected by low copy number probes indicates that it will be possible to construct a detailed genetic map of B. lactucae using RFLPs as markers. The method of analysis employed here should be applicable to many other outbreeding, heterozygous species for which defined inbred lines are not available. 相似文献