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31.
An important issue in the phylogenetic analysis of nucleotide sequence data using the maximum likelihood (ML) method is the
underlying evolutionary model employed. We consider the problem of simultaneously estimating the tree topology and the parameters
in the underlying substitution model and of obtaining estimates of the standard errors of these parameter estimates. Given
a fixed tree topology and corresponding set of branch lengths, the ML estimates of standard evolutionary model parameters
are asymptotically efficient, in the sense that their joint distribution is asymptotically normal with the variance–covariance
matrix given by the inverse of the Fisher information matrix. We propose a new estimate of this conditional variance based
on estimation of the expected information using a Monte Carlo sampling (MCS) method. Simulations are used to compare this
conditional variance estimate to the standard technique of using the observed information under a variety of experimental
conditions. In the case in which one wishes to estimate simultaneously the tree and parameters, we provide a bootstrapping
approach that can be used in conjunction with the MCS method to estimate the unconditional standard error. The methods developed
are applied to a real data set consisting of 30 papillomavirus sequences. This overall method is easily incorporated into
standard bootstrapping procedures to allow for proper variance estimation. 相似文献
32.
33.
Eukaryotic aminoacyl-tRNA synthetases have dispensable extensions appended at the amino- or carboxyl-terminus as compared to their bacterial counterparts. While a synthetic peptide corresponding to the basic amino-terminal extension in yeast Asp-tRNA synthetase binds to DNA, the extension in the intact protein evidently binds to tRNA and enhances the tRNA specificity of Asp-tRNA synthetase. On the other hand, the amino-terminal extension in human Asp-tRNA synthetase, both within the intact protein and as a synthetic peptide, binds to tRNA. Here, the tRNA binding of a synthetic peptide, hKRS(Arg(25)-Glu(42)), corresponding to the amino-terminal extension of human Lys-tRNA synthetase (hKRS) was analyzed. This basic peptide bound to tRNA(Phe) and the apparent-binding constant increased with increasing concentrations of Mg(2+). The hKRS peptide also bound to DNA and polyphosphate; however, the apparent DNA-binding constants decreased at increasing concentrations of Mg(2+). The ability of the hKRS peptide to adopt alpha-helical conformation was demonstrated by NMR and circular dichroism. A Lys-rich peptide derived from the elongation factor 1alpha was also examined and bound to DNA but not to tRNA. 相似文献
34.
SetB was identified as a high-copy suppressor of the partition defect of a mutation in parC, encoding one of the subunits of topoisomerase IV. Deletion of this integral inner membrane protein causes a delay in chromosome segregation, whereas its overproduction causes nucleoid disintegration and stretching, leading to a cell division defect. setB deletion mutants also exhibit a synthetic phenotype when combined with mutations that delete the C-terminal motor domain of the septal ring protein FtsK. SetB localizes in the cell as a helix and interacts with MreB, the bacterial actin homologue, which also forms a helix. These observations suggest that there may be a link between chromosome segregation and cellular infrastructure. 相似文献
35.
36.
Kumar S Kalsi J Ravirajan CT Rahman A Athwal D Latchman DS Isenberg DA Pearl LH 《The Journal of biological chemistry》2000,275(45):35129-35136
The Fabs of three human autoantibodies (B3/33H11, anti-DNA; UK4, anti-phospholipid) and six related hybrids have been cloned, expressed in Escherichia coli, and purified to homogeneity. SDS-polyacrylamide gel electrophoresis and Western blot analysis of the recombinant Fab demonstrated the purified Fab to be of correct size and in assembled form. Protein expression levels of up to 5-9 mg per liter of culture were achievable. A sensitive and reliable comparative anti-DNA enzyme-linked immunosorbent assay, involving a defined biotinylated 35-mer oligonucleotide in its single- or double-stranded form, is also described. Crithidia assay and anti-DNA or anti-cardiolipin antibody enzyme-linked immunosorbent assay analyses demonstrated convincing binding of the recombinant Fab proteins to DNA/cardiolipin, confirming the expression of functional molecule. The comparative DNA/cardiolipin binding analyses of the nine Fabs revealed that the anti-DNA (light, B3/33H11) or anti-cardiolipin (heavy, UK4) activity lies predominantly on one of the two chains. However, a compatible partner chain is necessary for optimum antigen binding activity of the antibody. 相似文献
37.
1-Thio-beta-D-galactofuranosides: synthesis and evaluation as beta-D- galactofuranosidase inhibitors
Marino C; Marino K; Miletti L; Manso Alves MJ; Colli W; de Lederkremer RM 《Glycobiology》1998,8(9):901-904
Beta-D-galactofuranosidase is a good chemotherapeutic target for the design
of inhibitors, since beta-D-galactofuranose is a constituent of important
parasite glycoconjugates but is not present in the host mammals. With this
aim, we have synthesized for the first time alkyl, benzyl and aryl
1-thio-beta-D-galactofuranosides by condensation of
penta-O-benzoyl-alpha,beta-D-galactofuranose with the corresponding thiols,
in the presence of SnCl4as catalyst. The complete chemical and
spectroscopical characterization of these compounds showed that the
reaction was stereoselective. Debenzoylation with sodium methoxide afforded
the beta-S-galactofuranosides in high yield. The thioglycosides were tested
as inhibitors of the beta-D- galactofuranosidase of Penicillium fellutanum,
using for the first time 4-nitrophenyl-beta-D-galactofuranoside as
chromogenic substrate. The 4- aminophenyl-1-thio-beta-D-galactofuranoside,
obtained by catalytic hydrogenation of the nitrophenyl derivative, was the
best inhibitor being then an adequate ligand for the preparation of an
affinity phase aimed at the isolation of beta-d-galactofuranosidases from
different sources. Also the inhibitory activity of d-galactono-1, 4-lactone
was shown.
相似文献
38.
Rebecca Vicente-Steijn Roderick W. C. Scherptong Boudewijn P. T. Kruithof Sjoerd N. Duim Marie Jose T. H. Goumans Lambertus J. Wisse Bin Zhou William T. Pu Robert E. Poelmann Martin J. Schalij Michelle D. Tallquist Adriana C. Gittenberger-de Groot Monique RM Jongbloed 《PloS one》2015,10(9)
Background
Morphological and functional differences of the right and left ventricle are apparent in the adult human heart. A differential contribution of cardiac fibroblasts and smooth muscle cells (populations of epicardium-derived cells) to each ventricle may account for part of the morphological-functional disparity. Here we studied the relation between epicardial derivatives and the development of compact ventricular myocardium.Results
Wildtype and Wt1CreERT2/+ reporter mice were used to study WT-1 expressing cells, and Tcf21lacZ/+ reporter mice and PDGFRα-/-;Tcf21LacZ/+ mice to study the formation of the cardiac fibroblast population. After covering the heart, intramyocardial WT-1+ cells were first observed at the inner curvature, the right ventricular postero-lateral wall and left ventricular apical wall. Later, WT-1+ cells were present in the walls of both ventricles, but significantly more pronounced in the left ventricle. Tcf21-LacZ + cells followed the same distribution pattern as WT-1+ cells but at later stages, indicating a timing difference between these cell populations. Within the right ventricle, WT-1+ and Tcf21-lacZ+ cell distribution was more pronounced in the posterior inlet part. A gradual increase in myocardial wall thickness was observed early in the left ventricle and at later stages in the right ventricle. PDGFRα-/-;Tcf21LacZ/+ mice showed deficient epicardium, diminished number of Tcf21-LacZ + cells and reduced ventricular compaction.Conclusions
During normal heart development, spatio-temporal differences in contribution of WT-1 and Tcf21-LacZ + cells to right versus left ventricular myocardium occur parallel to myocardial thickening. These findings may relate to lateralized differences in ventricular (patho)morphology in humans. 相似文献39.
We propose a model based approach to use multiple gene trees to estimate the species tree. The coalescent process requires
that gene divergences occur earlier than species divergences when there is any polymorphism in the ancestral species. Under
this scenario, speciation times are restricted to be smaller than the corresponding gene split times. The maximum tree (MT)
is the tree with the largest possible speciation times in the space of species trees restricted by available gene trees. If
all populations have the same population size, the MT is the maximum likelihood estimate of the species tree. It can be shown
the MT is a consistent estimator of the species tree even when the MT is built upon the estimates of the true gene trees if
the gene tree estimates are statistically consistent. The MT converges in probability to the true species tree at an exponential
rate. 相似文献
40.
S.A. Bauer K.E. Leslie D.L. Pearl J. Fournier P.V. Turner 《Journal of medical primatology》2010,39(6):408-416
Background Captive cynomolgus macaques are prone to obesity, increasing their risk for developing hyperglycemia and type 2 diabetes mellitus (T2DM). Social rank may be a contributing risk factor predisposing macaques to adverse health events. Methods Using retrospective health records from 259 animals, a matched case–control study was conducted to assess risk factors for developing hyperglycemia in group‐housed, adult females aged 10 or older. Univariable exact and conditional logistic regression models were used to analyze the data. Result The odds of developing hyperglycemia were significantly greater in animals with more frequent counts of injury. Similarly, subordinate animals had higher odds of developing hyperglycemia than affiliates. Conclusions Subordinate social status may increase the risk of hyperglycemia in mature female cynomolgus macaques. Opportunities for subordinates to alter feeding strategies are reduced in captivity. This may be associated with increased social stress around feeding, and for animals housed long‐term could predispose them to obesity and hyperglycemia. 相似文献