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31.
Kristina M. Mahan Joseph T. Penrod Kou-San Ju Natascia Al Kass Watumesa A. Tan Richard Truong Juanito V. Parales Rebecca E. Parales 《Applied and environmental microbiology》2015,81(1):309-319
Acidovorax sp. strain JS42 uses 2-nitrotoluene as a sole source of carbon and energy. The first enzyme of the degradation pathway, 2-nitrotoluene 2,3-dioxygenase, adds both atoms of molecular oxygen to 2-nitrotoluene, forming nitrite and 3-methylcatechol. All three mononitrotoluene isomers serve as substrates for 2-nitrotoluene dioxygenase, but strain JS42 is unable to grow on 3- or 4-nitrotoluene. Using both long- and short-term selections, we obtained spontaneous mutants of strain JS42 that grew on 3-nitrotoluene. All of the strains obtained by short-term selection had mutations in the gene encoding the α subunit of 2-nitrotoluene dioxygenase that changed isoleucine 204 at the active site to valine. Those strains obtained by long-term selections had mutations that changed the same residue to valine, alanine, or threonine or changed the alanine at position 405, which is just outside the active site, to glycine. All of these changes altered the regiospecificity of the enzymes with 3-nitrotoluene such that 4-methylcatechol was the primary product rather than 3-methylcatechol. Kinetic analyses indicated that the evolved enzymes had enhanced affinities for 3-nitrotoluene and were more catalytically efficient with 3-nitrotoluene than the wild-type enzyme. In contrast, the corresponding amino acid substitutions in the closely related enzyme nitrobenzene 1,2-dioxygenase were detrimental to enzyme activity. When cloned genes encoding the evolved dioxygenases were introduced into a JS42 mutant lacking a functional dioxygenase, the strains acquired the ability to grow on 3-nitrotoluene but with significantly longer doubling times than the evolved strains, suggesting that additional beneficial mutations occurred elsewhere in the genome. 相似文献
32.
Andrew Yates Cliburn Chan Jessica Strid Simon Moon Robin Callard Andrew JT George Jaroslav Stark 《BMC bioinformatics》2007,8(1):196
Background
Quantifying cell division and death is central to many studies in the biological sciences. The fluorescent dye CFSE allows the tracking of cell division in vitro and in vivo and provides a rich source of information with which to test models of cell kinetics. Cell division and death have a stochastic component at the single-cell level, and the probabilities of these occurring in any given time interval may also undergo systematic variation at a population level. This gives rise to heterogeneity in proliferating cell populations. Branching processes provide a natural means of describing this behaviour. 相似文献33.
Jennifer E Totonchy Lisa Clepper Kevin G Phillips Owen JT McCarty Ashlee V Moses 《Cell Adhesion & Migration》2014,8(2):165-176
The homeostatic function of endothelial cells (EC) is critical for a number of physiological processes including vascular integrity, immunity, and wound healing. Indeed, vascular abnormalities resulting from EC dysfunction contribute to the development and spread of malignancies. The alternative SDF-1/CXCL12 receptor CXCR7 is frequently and specifically highly expressed in tumor-associated vessels. In this study, we investigate whether CXCR7 contributes to vascular dysfunction by specifically examining the effect of CXCR7 expression on EC barrier function and motility. We demonstrate that CXCR7 expression in EC results in redistribution of CD31/PECAM-1 and loss of contact inhibition. Moreover, CXCR7+ EC are deficient in barrier formation. We show that CXCR7-mediated motility has no influence on angiogenesis but contributes to another motile process, the invasion of CXCR7+ EC into ligand-rich niches. These results identify CXCR7 as a novel manipulator of EC barrier function via alteration of PECAM-1 homophilic junctions. As such, aberrant expression of CXCR7 in the vasculature has the potential to disrupt vascular homeostasis and could contribute to vascular dysfunction in cancer systems. 相似文献
34.
35.
Roel GW Verhaak Frank JT Staal Peter JM Valk Bob Lowenberg Marcel JT Reinders Dick de Ridder 《BMC bioinformatics》2006,7(1):105-15
Background
Intensity values measured by Affymetrix microarrays have to be both normalized, to be able to compare different microarrays by removing non-biological variation, and summarized, generating the final probe set expression values. Various pre-processing techniques, such as dChip, GCRMA, RMA and MAS have been developed for this purpose. This study assesses the effect of applying different pre-processing methods on the results of analyses of large Affymetrix datasets. By focusing on practical applications of microarray-based research, this study provides insight into the relevance of pre-processing procedures to biology-oriented researchers. 相似文献36.
Hoover BR Reed MN Su J Penrod RD Kotilinek LA Grant MK Pitstick R Carlson GA Lanier LM Yuan LL Ashe KH Liao D 《Neuron》2010,68(6):1067-1081
The microtubule-associated protein tau accumulates in Alzheimer's and other fatal dementias, which manifest when forebrain neurons die. Recent advances in understanding these disorders indicate that brain dysfunction precedes neurodegeneration, but the role of tau is unclear. Here, we show that early tau-related deficits develop not from the loss of synapses or neurons, but rather as a result of synaptic abnormalities caused by the accumulation of hyperphosphorylated tau within intact dendritic spines, where it disrupts synaptic function by impairing glutamate receptor trafficking or synaptic anchoring. Mutagenesis of 14 disease-associated serine and threonine amino acid residues to create pseudohyperphosphorylated tau caused tau mislocalization while creation of phosphorylation-deficient tau blocked the mistargeting of tau to dendritic spines. Thus, tau phosphorylation plays a critical role in mediating tau mislocalization and subsequent synaptic impairment. These data establish that the locus of early synaptic malfunction caused by tau resides in dendritic spines. 相似文献
37.
DNA-protein cross-links are generated by both endogenous and exogenous DNA damaging agents, as intermediates during normal DNA metabolism, and during abortive base excision repair. Cross-links are relatively common lesions that are lethal when they block progression of DNA polymerases. DNA-protein cross-links may be broadly categorized into four groups by the DNA and protein chemistries near the cross-link and by the source of the cross-link: DNA-protein cross-links may be found (1) in nicked DNA at the 3' end of one strand (topo I), (2) in nicked DNA at the 5' end of one strand (pol beta), (3) at the 5' ends of both strands adjacent to nicks in close proximity (topo II; Spo 11), and (4) in one strand of duplex DNA (UV irradiation; bifunctional carcinogens and chemotherapeutic agents). Repair mechanisms are reasonably well-defined for groups 1 and 3, and suggested for groups 2 and 4. Our work is focused on the recognition and removal of DNA-protein cross-links in duplex DNA (group 4). 相似文献
38.
Effects of nucleotide sequence alignment on phylogeny estimation: a case study of 18S rDNAs of apicomplexa 总被引:13,自引:5,他引:8
The reconstruction of phylogenetic history is predicated on being able to
accurately establish hypotheses of character homology, which involves
sequence alignment for studies based on molecular sequence data. In an
empirical study investigating nucleotide sequence alignment, we inferred
phylogenetic trees for 43 species of the Apicomplexa and 3 of Dinozoa based
on complete small-subunit rDNA sequences, using six different
multiple-alignment procedures: manual alignment based on the secondary
structure of the 18S rRNA molecule, and automated similarity-based
alignment algorithms using the PileUp, ClustalW, TreeAlign, MALIGN, and SAM
computer programs. Trees were constructed using neighboring-joining,
weighted-parsimony, and maximum- likelihood methods. All of the multiple
sequence alignment procedures yielded the same basic structure for the
estimate of the phylogenetic relationship among the taxa, which presumably
represents the underlying phylogenetic signal. However, the placement of
many of the taxa was sensitive to the alignment procedure used; and the
different alignments produced trees that were on average more dissimilar
from each other than did the different tree-building methods used. The
multiple alignments from the different procedures varied greatly in length,
but aligned sequence length was not a good predictor of the similarity of
the resulting phylogenetic trees. We also systematically varied the gap
weights (the relative cost of inserting a new gap into a sequence or
extending an already-existing gap) for the ClustalW program, and this
produced alignments that were at least as different from each other as
those produced by the different alignment algorithms. Furthermore, there
was no combination of gap weights that produced the same tree as that from
the structure alignment, in spite of the fact that many of the alignments
were similar in length to the structure alignment. We also investigated the
phylogenetic information content of the helical and nonhelical regions of
the rDNA, and conclude that the helical regions are the most informative.
We therefore conclude that many of the literature disagreements concerning
the phylogeny of the Apicomplexa are probably based on differences in
sequence alignment strategies rather than differences in data or
tree-building methods.
相似文献
39.
Cross-hybridizing snake satellite, Drosophila, and mouse DNA sequences may have arisen independently 总被引:2,自引:0,他引:2
Previous reports have interpreted hybridization between snake satellite DNA
and DNA clones from a variety of distant taxonomic groups as evidence for
evolutionary conservation, which implies common ancestry (homology) and/or
convergence (analogy) to produce the cross- hybridizing sequences. We have
isolated 11 clones from a genomic library of Drosophila melanogaster, using
a cloned 2.5-kb snake satellite probe of known nucleotide sequence. We have
also analysed published sequence data from snakes, mice, and Drosophila.
These data show that (1) all of the cross-hybridization between the snake,
fly, and mouse clones can be accounted for by the presence of either of two
tandem repeats, [GATA]n and [GACA]n and (2) these tandem repeats are
organized differently among the different species. We find no evidence that
these sequences are homologous apart from the existence of the simple
repeat itself, although their divergence from a common ancestral sequence
cannot be ruled out. The sequences contain a variety of homogeneous
clusters of tandem repeats of CATA, GA, TA, and CA, as well as GATA and
GACA. We suggest that these motifs may have arisen by a self-accelerating
process involving slipped-strand mispairing of DNA. Homogeneity of the
clusters might simply be the result of a rate of accumulation of tandem
repeats that exceeds that of other mutations.
相似文献
40.
Structural comparison of fibroblast growth factor-specific heparan sulfates derived from a growing or differentiating neuroepithelial cell line 总被引:3,自引:1,他引:2
Brickman YG; Nurcombe V; Ford MD; Gallagher JT; Bartlett PF; Turnbull JE 《Glycobiology》1998,8(5):463-471
Heparan sulfate (HS) glycosaminoglycans are essential modulators of
fibroblast growth factor (FGF) activity both in vivo and in vitro, and
appear to act by cross-linking particular forms of FGF to appropriate FGF
receptors. We have recently isolated and characterized two separate HS
pools derived from immortalized embryonic day 10 mouse neuroepithelial 2.3D
cells: one from cells in log growth phase, which greatly potentiates the
activity of FGF-2, and the other from cells undergoing contact-inhibition
and differentiation, which preferentially activates FGF-1. These two pools
of HS have very similar functional activities to those species isolated
from primary neuroepithelial cells at corresponding stages of active
proliferation or differentiation. We present here a structural comparison
between these cell line HS species to establish the nature of the changes
that occur in the biosynthesis of HS. A combination of chemical and
enzymatic cleavage, low pressure chromatography and strong anion-exchange
HPLC were used to generate full chain models of each species. Overall, the
HS pools synthesized in the dividing cell line pools possessed less complex
sulfation than those derived from more differentiated, growth arrested
cells.
相似文献