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91.
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
92.
Comparative evolutionary analysis of rDNA ITS regions in Drosophila 总被引:17,自引:2,他引:15
Schlotterer C; Hauser MT; von Haeseler A; Tautz D 《Molecular biology and evolution》1994,11(3):513-522
The internal transcribed spacer (ITS) of the ribosomal DNA is generally
considered to be under low functional constraint, and it is therefore often
treated as a typical nonfunctional spacer sequence. We have analyzed the
ITS regions of five species from the Drosophila melanogaster subgroup, two
Drosophila species from outside this group (D. pseudoobscura and D.
virilis), as well as from the more distantly related dipteran fly Musca
domestica. The sequence comparisons show a distinctive
conservation/divergence pattern, indicating that some regions are more
conserved than others. Moreover, secondary-structure calculations indicate
several conserved structural elements within the ITS regions. On the other
hand, a statistical test that allows us to estimate the fraction of sites
that are not under selective constraint suggests that more than half of the
spacer is apparently free to diverge and evolves with a rate that is close
to the neutral rate of sequence evolution in Drosophila. The ITS sequences
can be used to derive a molecular phylogeny for the species under study. We
find that the ITS tree is largely in line with the so-far-known phylogeny
of this group of species, with one difference. The species most distant
within the D. melanogaster subgroup is D. yakuba, rather than D. orena, as
is normally assumed.
相似文献
93.
94.
Phospholipase C-mediated hydrolysis of phosphatidylcholine is activated by muscarinic agonists. 总被引:3,自引:0,他引:3
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M T Diaz-Meco P Larrodera M Lopez-Barahona M E Cornet P G Barreno J Moscat 《The Biochemical journal》1989,263(1):115-120
The phospholipase C-catalysed breakdown of inositol-containing phospholipids is an important source of diacylglycerol in cells stimulated by several agonists. However, recent experimental evidence suggests that major phospholipids such as phosphatidylcholine may also be substrates of the phosphodiesteratic hydrolysis activated by hormones, growth factors and oncogene products. We show here that stimulation of muscarinic agonists activates the release of phosphocholine, which, along with diacylglycerol, is a metabolic product of phospholipase C-mediated hydrolysis of phosphatidylcholine. Fluoroaluminates mimic this muscarinic effect, strongly suggesting that carbachol-activated release of phosphocholine may be mediated by a guanine-nucleotide-binding protein. Evidence for this was obtained from experiments using permeabilized cells in which non-hydrolysable analogues of GTP activated phosphocholine release synergistically with carbachol. 相似文献
95.
96.
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
97.
98.
Signal specificity of multifunctional enzymes is achieved through protein-protein interactions involving specific domains on scaffold proteins. p62 (also known as sequestosome 1) is such a scaffold protein that possesses PB1 and UBA domains, and the TRAF6 binding sequence. Proteins recruited to these domains enable p62 to integrate kinase-activated and ubiquitin-mediated signaling pathways. The biological function of p62 has been studied in diverse systems and processes such as osteoclastogenesis, inflammation, differentiation, neurotrophin biology and obesity. The availability of mice in which p62 has been genetically inactivated is providing new insight into the mechanism and function of p62 at a whole-organism level. 相似文献
99.
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100.
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