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排序方式: 共有89条查询结果,搜索用时 187 毫秒
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Detecting non-neutral heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence 总被引:11,自引:4,他引:7
Natural selection, in the form of balancing selection or selective sweeps,
can result in a decoupling of the amounts of molecular polymorphism and
divergence. Thus natural selection can cause some areas of DNA sequence to
have greater silent polymorphism, relative to divergence between species,
than other areas. It would be useful to have a statistical test for
heterogeneity in the polymorphism to divergence ratio across a region of
DNA sequence, one that could identify heterogeneity greater than that
expected from the neutral processes of mutation, drift, and recombination.
The only currently available test requires that a region be arbitrarily
divided into sections that are compared with each other, and the
subjectivity of this division could be problematic. Here a test is proposed
in which runs of polymorphic and fixed sites are counted, where a "run" is
a set of one or more sites of one type preceded and followed by the other
type. The number of runs is smaller than otherwise expected if
polymorphisms are clumped together. By simulating neutral evolution and
comparing the observed number of runs to the simulations, a statistical
test is possible which does not require any a priori decisions about
subdivision.
相似文献
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Ivana Šagud Nikolina Maček Hrvat Ana Grgičević Tena Čadež Josipa Hodak Milena Dragojević 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):460-467
Abstract The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are primary targets in attenuating the symptoms of neurodegenerative diseases. Their inhibition results in elevated concentrations of the neurotransmitter acetylcholine which supports communication among nerve cells. It was previously shown for trans-4/5-arylethenyloxazole compounds to have moderate AChE and BChE inhibitory properties. A preliminary docking study showed that elongating oxazole molecules and adding a new NH group could make them more prone to bind to the active site of both enzymes. Therefore, new trans-amino-4-/5-arylethenyl-oxazoles were designed and synthesised by the Buchwald-Hartwig amination of a previously synthesised trans-chloro-arylethenyloxazole derivative. Additionally, naphthoxazole benzylamine photoproducts were obtained by efficient photochemical electrocyclization reaction. Novel compounds were tested as inhibitors of both AChE and BChE. All of the compounds exhibited binding preference for BChE over AChE, especially for trans-amino-4-/5-arylethenyl-oxazole derivatives which inhibited BChE potently (IC50 in µM range) and AChE poorly (IC50?100?µM). Therefore, due to the selectivity of all of the tested compounds for binding to BChE, these compounds could be applied for further development of cholinesterase selective inhibitors.
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Series of oxazole benzylamines were designed and synthesised
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The tested compounds showed binding selectivity for BChE
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Naphthoxazoles were more potent AChE inhibitors
7.
Janine JH Oosterhof G Jolanda Elving Ietse Stokroos Arie van nieuw Amerongen Henny C van der Mei Henk J Busscher 《Biofouling》2013,29(6):347-353
The integrity of biofilms on voice prostheses used to rehabilitate speech in laryngectomized patients causes unwanted increases in airflow resistance, impeding speech. Biofilm integrity is ensured by extracellular polymeric substances (EPS). This study aimed to determine whether synthetic salivary peptides or mucolytics, including N-acetylcysteine and ascorbic acid, influence the integrity of voice prosthetic biofilms. Biofilms were grown on voice prostheses in an artificial throat model and exposed to synthetic salivary peptides, mucolytics and two different antiseptics (chlorhexidine and Triclosan). Synthetic salivary peptides did not reduce the air flow resistance of voice prostheses after biofilm formation. Although both chlorhexidine and Triclosan reduced microbial numbers on the prostheses, only the Triclosan-containing positive control reduced the air flow resistance. Unlike ascorbic acid, the mucolytic N-acetylcysteine removed most EPS from the biofilms and induced a decrease in air flow resistance. 相似文献
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Lilach Moyal Nataly Feldbaum Neta Goldfeiz Ada Rephaeli Abraham Nudelman Michal Weitman Nataly Tarasenko Batia Gorovitz Leah Maron Shiran Yehezkel Iris Amitay-Laish Ido Lubin Emmilia Hodak 《PloS one》2016,11(1)
The 2 histone deacetylase inhibitors (HDACIs) approved for the treatment of cutaneous T-cell lymphoma (CTCL) including mycosis fungoides/sezary syndrome (MF/SS), suberoylanilide hydroxamic acid (SAHA) and romidepsin, are associated with low rates of overall response and high rates of adverse effects. Data regarding combination treatments with HDACIs is sparse. Butyroyloxymethyl diethylphosphate (AN-7) is a novel HDACI, which was found to have selective anticancer activity in several cell lines and animal models. The aim of this study was to compare the anticancer effects of AN-7 and SAHA, either alone or combined with doxorubicin, on MF/SS cell lines and peripheral blood lymphocytes (PBL) from patients with Sezary syndrome (SPBL). MyLa cells, Hut78 cells, SPBL, and PBL from healthy normal individuals (NPBL) were exposed to the test drugs, and the findings were analyzed by a viability assay, an apoptosis assay, and Western blot. AN-7 was more selectively toxic to MyLa cells, Hut78 cells, and SPBL (relative to NPBL) than SAHA and also acted more rapidly. Both drugs induced apoptosis in MF/SS cell lines, SAHA had a greater effect on MyLa cell line, while AN-7 induced greater apoptosis in SPBL; both caused an accumulation of acetylated histone H3, but AN-7 was associated with earlier kinetics; and both caused a downregulation of the HDAC1 protein in MF/SS cell lines. AN-7 acted synergistically with doxorubicin in both MF/SS cell lines and SPBL, and antagonistically with doxorubicin in NPBL. By contrast, SAHA acted antagonistically with doxorubicin on MF/SS cell lines, SPBL, and NPBL, leaving <50% viable cells. In conclusion, AN-7 holds promise as a therapeutic agent in MF/SS and has several advantages over SAHA. Our data provide a rationale for combining AN-7, but not SAHA, with doxorubicin to induce the cell death in MF/SS. 相似文献
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Improved tests for heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence 总被引:15,自引:9,他引:6
The neutral theory of molecular evolution predicts that the ratio of
polymorphisms to fixed differences should be fairly uniform across a region
of DNA sequence. Significant heterogeneity in this ratio can indicate the
effects of balancing selection, selective sweeps, mildly deleterious
mutations, or background selection. Comparing an observed heterogeneity
statistic with simulations of the heterogeneity resulting from random
phylogenetic and sampling variation provides a test of the statistical
significance of the observed pattern. When simulated data sets containing
heterogeneity in the polymorphism-to-divergence ratio are examined,
different statistics are most powerful for detecting different patterns of
heterogeneity. The number of runs is most powerful for detecting patterns
containing several peaks of polymorphism; the Kolmogorov-Smirnov statistic
is most powerful for detecting patterns in which one end of the gene has
high polymorphism and the other end has low polymorphism; and a newly
developed statistic, the mean sliding G statistic, is most powerful for
detecting patterns containing one or two peaks of polymorphism with reduced
polymorphism on either side. Nine out of 27 genes from the Drosophila
melanogaster subgroup exhibit heterogeneity that is significant under at
least one of these three tests, with five of the nine remaining significant
after a correction for multiple comparisons, suggesting that detectable
evidence for the effects of some kind of selection is fairly common.
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