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41.
High nucleotide sequence variation in a region of low recombination in Drosophila simulans is consistent with the background selection model 总被引:2,自引:0,他引:2
We surveyed nucleotide sequence variation at glucose dehydrogenase (Gld),
in a region of low recombination on chromosome 3R, from a population sample
of Drosophila simulans. The levels of nucleotide variation were
surprisingly high. There was no departure from the expectation of a neutral
model for the level of polymorphism, indicating no evidence of a selective
sweep in this region. There was a significant deficiency of singleton
polymorphisms according to the Fu and Li test, although Tajima and Hudson,
Kreitman, and Aguade (HKA) tests do not provide evidence of a significant
elevation of variation due to balancing selection. Genetic map data for the
D. simulans third chromosome were used to calculate expected values of pi
for Gld under a current model of background selection, varying the values
for the parameter sh (selection coefficient against deleterious mutations).
We show that the recombinational landscape of D. simulans is sufficiently
different from that of D. melanogaster that we expect higher variation
under the background selection model, even when effective population sizes
are assumed to be equal. The data for Gld were tested against the
predictions using computer simulations of the distribution of the number of
segregating sites conditioned on pi. Background selection alone can explain
our observations as long as sh is larger than 0.005 and species-level
effective population size is assumed to be several- fold larger than in D.
melanogaster. Alternatively, the deleterious mutation rate may be smaller
in D. simulans, or balancing selection may be acting nearby, thereby
reducing the effect of background selection.
相似文献
42.
Molecular evolution of chloroplast DNA sequences 总被引:13,自引:1,他引:12
Comparative data on the evolution of chloroplast genes are reviewed. The
chloroplast genome has maintained a similar structural organization over
most plant taxa so far examined. Comparisons of nucleotide sequence
divergence among chloroplast genes reveals marked similarity across the
plant kingdom and beyond to the cyanobacteria (blue-green algae). Estimates
of rates of nucleotide substitution indicate a synonymous rate of 1.1 x
10(-9) substitutions per site per year. Noncoding regions also appear to be
constrained in their evolution, although addition/deletion events are
common. There have also been evolutionary changes in the distribution of
introns in chloroplast encoded genes. Relative to mammalian mitochondrial
DNA, the chloroplast genome evolves at a conservative rate.
相似文献
43.
44.
Norimah AK H. C. Koo Hamid Jan JM Mohd Nasir MT S. Y. Tan Mahendran Appukutty Nurliyana AR Frank Thielecke Sinead Hopkins M. K. Ong C. Ning E. S. Tee 《PloS one》2015,10(10)
Background
Diets rich in whole grain are associated with several health benefits. Little is known however, about whole grain consumption patterns in Malaysia. The aim of this study was to assess whole grain intakes and dietary source in Malaysian children and adolescents.Methods
This analysis is from the MyBreakfast study, a national cross sectional study investigating eating habits among primary and secondary school children throughout Malaysia, conducted in 2013. Children (n = 5,165) and adolescents (n = 2,947) who completed two days of dietary assessment using a food record or recall respectively were included. The whole grain content of foods was estimated mainly through the use of quantitative ingredient declarations on food labels. All wholegrain foods were considered irrespective of the amount of whole grain they contained.Results
Overall, only 25% of children and 19% of adolescents were wholegrain consumers. Mean daily intakes in the total sample were 2.3g/d (SD 5.8g/d) in children and 1.7g/d (SD 4.7g/d) in adolescents and in the consumer’s only sample, mean intakes reached 9.1g/d (SD 8.6) and 9.2g/d (SD 7.1g/d) respectively. Wheat was the main grain source of whole grain while ready to eat breakfast cereals and hot cereals were the main food contributors. Less than 3% of the children and adolescents reached the US quantitative whole grain recommendation of 48g/day.Conclusion
Whole grain is consumed by only a minority of Malaysian children and adolescents and even among consumers, intakes are well below recommendations. Efforts are needed to firstly understand the barriers to whole grain consumption among Malaysian children in order to design effective health promotion initiatives to promote an increase in whole grain consumption. 相似文献45.
Fernando M Botelho Jake K Nikota Carla MT Bauer Mathieu C Morissette Yoichiro Iwakura Roland Kolbeck Donna Finch Alison A Humbles Martin R St?mpfli 《Respiratory research》2012,13(1):81
Background
Evidence suggests that dendritic cells accumulate in the lungs of COPD patients and correlate with disease severity. We investigated the importance of IL-1R1 and its ligands IL-1α and β to dendritic cell accumulation and maturation in response to cigarette smoke exposure.Methods
Mice were exposed to cigarette smoke using a whole body smoke exposure system. IL-1R1-, TLR4-, and IL-1α-deficient mice, as well as anti-IL-1α and anti-IL-1β blocking antibodies were used to study the importance of IL-1R1 and TLR4 to dendritic cell accumulation and activation.Results
Acute and chronic cigarette smoke exposure led to increased frequency of lung dendritic cells. Accumulation and activation of dendritic cells was IL-1R1/IL-1α dependent, but TLR4- and IL-1β-independent. Corroborating the cellular data, expression of CCL20, a potent dendritic cells chemoattractant, was IL-1R1/IL-1α-dependent. Studies using IL-1R1 bone marrow-chimeric mice revealed the importance of IL-1R1 signaling on lung structural cells for CCL20 expression. Consistent with the importance of dendritic cells in T cell activation, we observed decreased CD4+ and CD8+ T cell activation in cigarette smoke-exposed IL-1R1-deficient mice.Conclusion
Our findings convey the importance of IL-1R1/IL-1α to the recruitment and activation of dendritic cells in response to cigarette smoke exposure. 相似文献46.
47.
The influence of several metabolic inhibitors and pharmacologic agents on macrophage deformation (induced by fluid shear stress) was examined in relationship to changes in ATP content and phagocytosis of latex beads. Two relatively specific inhibitors of glycolysis (iodoacetate [IA], and sodium fluoride [NaF]) and a sulfhydryl-binding agent (N-ethylmaleimide [NEM] markedly inhibited phagocytosis and reduced cell deformability. A microtubule-disrupting agent (vinblastine) and a highly specific inhibitor of glycolysis (2-deoxyglucose) markedly inhibited phagocytosis without influencing cell deformability. An organomercurial sulfhydryl binding agent p-chloromercuribenzene (PCMBS) and a microfilament-disrupting agent (cytochalasin B) inhibited phagocytosis and increased cell deformability. The effects of these agents on phagocytosis and cell deformability bore no consistent relationship to alterations in cellular content of ATP. The observation that 2-deoxyglucose, the most specific inhibitor of glycolysis examined, reduced ATP content to levels far lower (15 percent of control values) than those achieved by any other agent examined and inhibited phagocytosis without altering cell deformability, suggests that alterations in cell deformability induced by NaF, IA, NEM, PCMBS, and cytochalasin B are not due to inhibition of glycolysis per se, but instead result from direct or indirect effects of these agents on cell constituents, possibly contractile proteins, which are determinants of cell deformability. The finding that cytochalasin B, NEM, PCMBS, and IA interfere with phagocytosis and alter cell deformability, together with evidence that these agents interact with isolated actin and myosin, suggests that contractile proteins are important both in phagocytosis and as determinants of cell deformability. The observation that vinblastine, colchicines, and heavy water (D(2)O) did not alter cell deformability, even though vinblastine caused formation of intracellular crystals of microtubular protein, indicates that microtubules are not major determinants of cell deformability. The observations that beads adhered normally to surfaces of cytochalasin B- and of PCMBS-treated cells and that shear-stress induced deformation was increased whereas phagocytosis was markedly inhibited, suggest that deformation of cells around beads associated with ingestion depends on some form of cellular (contractile?) activity, whereas deformation of cells by fluid shear stress is a passive phenomenon. 相似文献
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Ruoqi Peng Sriram Sridhar Gaurav Tyagi Jonathan E. Phillips Rosario Garrido Paul Harris Lisa Burns Lorena Renteria John Woods Leena Chen John Allard Palanikumar Ravindran Hans Bitter Zhenmin Liang Cory M. Hogaboam Chris Kitson David C. Budd Jay S. Fine Carla MT. Bauer Christopher S. Stevenson 《PloS one》2013,8(4)
The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show for the first time that genes differentially expressed during the fibrotic phase of the single challenge bleomycin model were significantly enriched in the expression profiles of IPF patients. The genes that contributed most to the enrichment were largely involved in mitosis, growth factor, and matrix signaling. Interestingly, these same mitotic processes were increased in the expression profiles of fibroblasts isolated from rapidly progressing, but not slowly progressing, IPF patients relative to control subjects. The data also indicated that TGFβ was not the sole mediator responsible for the changes observed in this model since the ALK-5 inhibitor SB525334 effectively attenuated some but not all of the fibrosis associated with this model. Although some would suggest that repetitive bleomycin injuries may more effectively model IPF-like changes, our data do not support this conclusion. Together, these data highlight that a single bleomycin instillation effectively replicates several of the specific pathogenic molecular changes associated with IPF, and may be best used as a model for patients with active disease. 相似文献
50.
Functional normalization of 450k methylation array data improves replication in large cancer studies
Jean-Philippe Fortin Aurélie Labbe Mathieu Lemire Brent W Zanke Thomas J Hudson Elana J Fertig Celia MT Greenwood Kasper D Hansen 《Genome biology》2014,15(11)
We propose an extension to quantile normalization that removes unwanted technical variation using control probes. We adapt our algorithm, functional normalization, to the Illumina 450k methylation array and address the open problem of normalizing methylation data with global epigenetic changes, such as human cancers. Using data sets from The Cancer Genome Atlas and a large case–control study, we show that our algorithm outperforms all existing normalization methods with respect to replication of results between experiments, and yields robust results even in the presence of batch effects. Functional normalization can be applied to any microarray platform, provided suitable control probes are available.