排序方式: 共有61条查询结果,搜索用时 515 毫秒
51.
Abramovich C Shen WF Pineault N Imren S Montpetit B Largman C Humphries RK 《The Journal of biological chemistry》2000,275(34):26172-26177
PBX1 is a homeodomain protein that functions in complexes with other homeodomain-containing proteins to regulate gene expression during developmental and/or differentiation processes. A yeast two-hybrid screen of a fetal liver-hematopoietic cDNA library using PBX1a as bait led to the discovery of a novel non-homeodomain-containing protein that interacts with PBX1 as well as PBX2 and PBX3. RNA analysis revealed it to be expressed in CD34(+) hematopoietic cell populations enriched in primitive progenitors, as is PBX1; search of the expressed sequence tag data base indicated that it is also expressed in other early embryonic as well as adult tissues. The full-length cDNA encodes a 731-amino acid protein that has no significant homology to known proteins. This protein that we have termed hematopoietic PBX-interacting protein (HPIP) is mainly localized in the cytosol and in small amounts in the nucleus. The region of PBX that interacts with HPIP includes both the homeodomain and immediate N-terminal flanking sequences. Strikingly, electrophoretic mobility shift assays revealed that HPIP inhibits the ability of PBX-HOX heterodimers to bind to target sequences. Moreover, HPIP strongly inhibits the transactivation activity of E2A-PBX. Together these findings suggest that HPIP is a new regulator of PBX function. 相似文献
52.
More than 99.9 % of the sequence is identical when comparing the DNA from two individuals. The remaining 0.1 % is responsible, along with other factors such as the environment, for the risk level of developing complex diseases (such as asthma, diabetes or cancer) or for the different pharmacological response to drugs. Despite the incredible advances in genomics in the past few years, identifying the variants involved remains difficult because of the prodigious amount of information to process. The recent completion of the Haplotype Map of the human genome has raised great hopes in the field as it is expected to help reduce the complexity of association studies and thus accelerate the discovery of genes associated with complex diseases. This review details the rationale behind the HapMap project, gives a summary of the results and also describes potential applications of the Haplotype Map. 相似文献
53.
Yohan Bossé François Bacot Alexandre Montpetit Johan Rung Hui-Qi Qu James C. Engert Constantin Polychronakos Thomas J. Hudson Philippe Froguel Robert Sladek Martin Desrosiers 《Human genetics》2009,125(3):305-318
The success of genome-wide association studies (GWAS) to identify risk loci of complex diseases is now well-established. One
persistent major hurdle is the cost of those studies, which make them beyond the reach of most research groups. Performing
GWAS on pools of DNA samples may be an effective strategy to reduce the costs of these studies. In this study, we performed
pooling-based GWAS with more than 550,000 SNPs in two case-control cohorts consisting of patients with Type II diabetes (T2DM)
and with chronic rhinosinusitis (CRS). In the T2DM study, the results of the pooling experiment were compared to individual
genotypes obtained from a previously published GWAS. TCF7L2 and HHEX SNPs associated with T2DM by the traditional GWAS were
among the top ranked SNPs in the pooling experiment. This dataset was also used to refine the best strategy to correctly identify
SNPs that will remain significant based on individual genotyping. In the CRS study, the top hits from the pooling-based GWAS
located within ten kilobases of known genes were validated by individual genotyping of 1,536 SNPs. Forty-one percent (598
out of the 1,457 SNPs that passed quality control) were associated with CRS at a nominal P value of 0.05, confirming the potential of pooling-based GWAS to identify SNPs that differ in allele frequencies between
two groups of subjects. Overall, our results demonstrate that a pooling experiment on high-density genotyping arrays can accurately
determine the minor allelic frequency as compared to individual genotyping and produce a list of top ranked SNPs that captures
genuine allelic differences between a group of cases and controls. The low cost associated with a pooling-based GWAS clearly
justifies its use in screening for genetic determinants of complex diseases.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
54.
William G. Simpson Benjamen M. Kennedy Kenneth G. Ostrand 《Environmental Biology of Fishes》2009,86(4):473-482
We compared the diet of hatchery-reared steelhead produced from an integrated hatchery program as emigrating spring smolts
and non-migrating hatchery residuals to their sympatric wild counterparts. Our results suggest that there is a potential for
hatchery fish to affect wild steelhead populations due to dietary overlap and subyearling salmonid predation; however, relative
ecological risk did not increase as steelhead delayed or forwent emigration. Predation by hatchery smolts was related to release
timing, but not experience with native fish. Diet composition appears to be more strongly affected by seasonal and yearly
differences in prey abundance and presence rather than differences in rearing environments. Hatchery and wild steelhead showed
small but important foraging differences. Hatchery smolts did not consume as many salmonids as wild fish and hatchery residuals
showed relatively stronger surface oriented feeding behavior than wild parr. Because most hatchery smolts emigrated shortly
after release and the overall number of residuals in the study creek was low, we speculate that in this case there is low
dietary and predatory-based risk of hatchery steelhead in Abernathy Creek negatively impacting wild salmonids. 相似文献
55.
S. F. Perry C. J. Montpetit A. E. Julio K. Moore 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1999,169(4-5):335-343
The effect of long-term (7 day) anaemia on catecholamine release was examined in rainbow trout (Oncorhynchus mykiss) in vivo during acute exposure to hypoxia and in situ using a perfused post-cardinal vein preparation. The first goal was
to distinguish among reductions in blood O2 partial pressure, O2 concentration and haemoglobin percentage saturation as potential stimuli for, or correlates of, catecholamine secretion during
hypoxia. The second goal was to elucidate the role of these factors in promoting enhanced chromaffin cell responsiveness in
trout subjected to chronic hypoxia (Montpetit and Perry 1998). Anaemic fish (haematocrit lowered from 28.4±2.4% to 11.9±1.6%)
displayed a marked reduction in haemoglobin-O2 binding affinity [P
50 (P
aO2 at 50% Hb-O2 saturation) was increased from 14.7 mm Hg to 24.3 mm Hg]. Upon exposure to hypoxia, the anaemic fish released catecholamines
into their circulation at higher values of arterial O2 partial pressure (∼52 mm Hg versus ∼18 mm Hg) and haemoglobin O2 saturation (<70% versus <55%) than did control fish. In addition, anaemic fish achieved significantly greater circulating
levels of total catecholamines (noradrenaline plus adrenaline) during acute hypoxia (294.8±67.3 versus 107.0±35.6 nmol l−1). These results do not support the view that catecholamine release is triggered by a reduction in haemoglobin O2 saturation or arterial PO2, per se. Nor are they consistent with the idea that catecholamine release occurs at a threshold value of arterial PO2 corresponding to a critical reduction in blood O2 concentration. The effects of the non-selective cholinergic receptor carbachol on catecholamine secretion from chromaffin
tissue were assessed using perfused posterior cardinal vein preparations derived from control or anaemic fish. For adrenaline
secretion, there was no statistically significant change in the ED50 (dose eliciting 50% response). For noradrenaline secretion however, preparations originating from anaemic fish displayed
an enhanced responsiveness to carbachol as indicated by a significant 4.5-fold reduction in the carbachol ED50 value from 2.53 × 10−6 mol kg−1 to 5.67 × 10−7 mol kg−1. These results demonstrate that anaemia-induced hypoxaemia, in the absence of any lowering of PO2, is able to modulate the responsiveness of chromaffin cells to cholinergic stimulation.
Accepted: 21 April 1999 相似文献
56.
Rearrangements of the short arm of chromosome 12 are frequently observed in hematological malignancies and in certain solid
neoplasias. Loss of heterozygosity studies identified a small genetic interval on chromosome 12p12.3 that is frequently deleted
in childhood acute lymphoblastic leukemia (ALL). Two genes, ETV6 and CDKN1B, are located within this interval although evidence has accumulated that an as yet unidentified tumor suppressor gene is
closely linked. Here we report the physical mapping of the G-protein coupled receptor 19 (GPR19) at approximately 40 kb from CDKN1B. The delineation of the gene order tel-ETV6-CDKN1B-GPR19-cen excluded GPR19 from the region commonly deleted in childhood ALL, but it could still be the target of genetic alterations found in other
cancers.
Electronic Publication 相似文献
57.
Zi Chen Benjamen A. Filas Victor D. Varner Larry A. Taber 《Birth defects research. Part C, Embryo today : reviews》2012,96(2):132-152
In the developing embryo, tissues differentiate, deform, and move in an orchestrated manner to generate various biological shapes driven by the complex interplay between genetic, epigenetic, and environmental factors. Mechanics plays a key role in regulating and controlling morphogenesis, and quantitative models help us understand how various mechanical forces combine to shape the embryo. Models allow for the quantitative, unbiased testing of physical mechanisms, and when used appropriately, can motivate new experimentaldirections. This knowledge benefits biomedical researchers who aim to prevent and treat congenital malformations, as well as engineers working to create replacement tissues in the laboratory. In this review, we first give an overview of fundamental mechanical theories for morphogenesis, and then focus on models for specific processes, including pattern formation, gastrulation, neurulation, organogenesis, and wound healing. The role of mechanical feedback in development is also discussed. Finally, some perspectives aregiven on the emerging challenges in morphomechanics and mechanobiology. Birth Defects Research (Part C) 96:132–152, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
58.
The acetylcholine-activated channel of vertebrate skeletal muscle, as manifested in cultured, developing cells, is able to adopt more than one conductance state. This paper briefly reviews the evidence for such multiple conductance channels and presents results showing that the amplitude of subconductance states does not depend on agonist size and (or) valence. This seems to rule out the possibility that subconductances occur during partial occlusion of the channel (by agonist molecules) and supports the idea that subconductances represent discrete, allosterically activated channel conformations. 相似文献
59.
C E Morris M R Montpetit W J Sigurdson K Iwasa 《Canadian journal of physiology and pharmacology》1989,67(2):152-158
Curare action on nicotinic acetylcholine receptors has a number of facets, of which the best known is competitive antagonism. Here we describe the weak agonist action of 10(-5) M curare on the murine skeletal muscle cell line, G8. Although curare induces no depolarization in G8 cells, single-channel recordings reveal short-lived curare-induced currents. A feature of these brief events is the multiplicity of conductance levels (of the four levels with conductances of 48, 37, 14, and 6 pS, none had a lifetime greater than 1.5 ms). Most well-resolved events (about 17% of which are to a subconductance) last less than 0.5 ms, with activation occurring predominantly as isolated events rather than in bursts. Agonism is not, however, a high probability action for curare: calculations based on the frequency of events at half-saturating conditions suggest that curare-induced channel openings occur during less than 1% of acetylcholine receptor-curare binding episodes. The outcome is (a) an agonist action too feeble to perturb the membrane voltage and (b) a powerful competitive antagonist action. 相似文献
60.