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排序方式: 共有184条查询结果,搜索用时 31 毫秒
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Myers RA Casals F Gauthier J Hamdan FF Keebler J Boyko AR Bustamante CD Piton AM Spiegelman D Henrion E Zilversmit M Hussin J Quinlan J Yang Y Lafrenière RG Griffing AR Stone EA Rouleau GA Awadalla P 《PLoS genetics》2011,7(2):e1001318
Deep resequencing of functional regions in human genomes is key to identifying potentially causal rare variants for complex disorders. Here, we present the results from a large-sample resequencing (n = 285 patients) study of candidate genes coupled with population genetics and statistical methods to identify rare variants associated with Autism Spectrum Disorder and Schizophrenia. Three genes, MAP1A, GRIN2B, and CACNA1F, were consistently identified by different methods as having significant excess of rare missense mutations in either one or both disease cohorts. In a broader context, we also found that the overall site frequency spectrum of variation in these cases is best explained by population models of both selection and complex demography rather than neutral models or models accounting for complex demography alone. Mutations in the three disease-associated genes explained much of the difference in the overall site frequency spectrum among the cases versus controls. This study demonstrates that genes associated with complex disorders can be mapped using resequencing and analytical methods with sample sizes far smaller than those required by genome-wide association studies. Additionally, our findings support the hypothesis that rare mutations account for a proportion of the phenotypic variance of these complex disorders. 相似文献
93.
Samuel Mondy Aurore Lenglet Amelie Beury‐Cirou Celestin Libanga Pascal Ratet Denis Faure Yves Dessaux 《Molecular ecology》2014,23(19):4846-4861
To investigate how exudation shapes root‐associated bacterial populations, transgenic Arabidopsis thaliana plants that exuded the xenotopic compound octopine at low and high rates were grown in a nonsterile soil. Enumerations of both cultivable and octopine‐degrading bacteria demonstrated that the ratios of octopine degraders increased along with octopine concentration. An artificial exudation system was also set up in which octopine was brought at four ratios. The density of octopine‐degrading bacteria directly correlated with the input of octopine. Bacterial diversity was analysed by rrs amplicon pyrosequencing. Ensifer and Pseudomonas were significantly more frequently detected in soil amended with artificial exudates. However, the density of Pseudomonas increased as a response to carbon supplementation while that of Ensifer only correlated with octopine concentrations possibly in relation to two opposed colonization strategies of rhizosphere bacteria, that is, copiotrophy and oligotrophy. 相似文献
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Background
Increasing efforts and financial resources are being invested in early cancer detection research. Blood assays detecting tumor biomarkers promise noninvasive and financially reasonable screening for early cancer with high potential of positive impact on patients'' survival and quality of life. For novel tumor biomarkers, the actual tumor detection limits are usually unknown and there have been no studies exploring the tumor burden detection limits of blood tumor biomarkers using mathematical models. Therefore, the purpose of this study was to develop a mathematical model relating blood biomarker levels to tumor burden.Methods and Findings
Using a linear one-compartment model, the steady state between tumor biomarker secretion into and removal out of the intravascular space was calculated. Two conditions were assumed: (1) the compartment (plasma) is well-mixed and kinetically homogenous; (2) the tumor biomarker consists of a protein that is secreted by tumor cells into the extracellular fluid compartment, and a certain percentage of the secreted protein enters the intravascular space at a continuous rate. The model was applied to two pathophysiologic conditions: tumor biomarker is secreted (1) exclusively by the tumor cells or (2) by both tumor cells and healthy normal cells. To test the model, a sensitivity analysis was performed assuming variable conditions of the model parameters. The model parameters were primed on the basis of literature data for two established and well-studied tumor biomarkers (CA125 and prostate-specific antigen [PSA]). Assuming biomarker secretion by tumor cells only and 10% of the secreted tumor biomarker reaching the plasma, the calculated minimally detectable tumor sizes ranged between 0.11 mm3 and 3,610.14 mm3 for CA125 and between 0.21 mm3 and 131.51 mm3 for PSA. When biomarker secretion by healthy cells and tumor cells was assumed, the calculated tumor sizes leading to positive test results ranged between 116.7 mm3 and 1.52 × 106 mm3 for CA125 and between 27 mm3 and 3.45 × 105 mm3 for PSA. One of the limitations of the study is the absence of quantitative data available in the literature on the secreted tumor biomarker amount per cancer cell in intact whole body animal tumor models or in cancer patients. Additionally, the fraction of secreted tumor biomarkers actually reaching the plasma is unknown. Therefore, we used data from published cell culture experiments to estimate tumor cell biomarker secretion rates and assumed a wide range of secretion rates to account for their potential changes due to field effects of the tumor environment.Conclusions
This study introduced a linear one-compartment mathematical model that allows estimation of minimal detectable tumor sizes based on blood tumor biomarker assays. Assuming physiological data on CA125 and PSA from the literature, the model predicted detection limits of tumors that were in qualitative agreement with the actual clinical performance of both biomarkers. The model may be helpful in future estimation of minimal detectable tumor sizes for novel proteomic biomarker assays if sufficient physiologic data for the biomarker are available. The model may address the potential and limitations of tumor biomarkers, help prioritize biomarkers, and guide investments into early cancer detection research efforts. 相似文献96.
Plymoth A Löfdahl CG Ekberg-Jansson A Dahlbäck M Lindberg H Fehniger TE Marko-Varga G 《Proteomics》2003,3(6):962-972
Respiratory diseases are an important health problem throughout the world. Whether caused by industrial pollutants, infections, smoking, cancer or metabolic diseases, damage to the lungs and airways often lead to morbidity or death. Bronchoalveolar lavage (BAL) obtained by fiber-optic bronchoscopy is a biofluid mirroring the expression of normally secreted pulmonary proteins and the products of activated cells and destructive processes. The characterization of the proteome within this compartment provides an opportunity to establish temporal and prognostic indicators of airway disease. The objective of this study was to develop methods of analysis of BAL samples, which achieved the highest level of annotation of the expression map of this proteome. We have optimized the process of sample preparation after investigating a variety of techniques including dialysis, ultramembrane filtration, precipitation and gel filtration. We have further studied methods to remove albumin from BAL in order to unmask proteins hidden on two-dimensional gels. In a pilot application of the method, BAL protein profiles obtained from healthy nonsmokers and smokers at risk for developing chronic obstructive pulmonary disease showed distinct differences. 相似文献
97.
1. As species are often considered discrete natural units, interspecific sexual interactions are often disregarded as potential factors determining community composition. Nevertheless reproductive interference, ranging from signal jamming to hybridization, can have significant costs for species sharing similar signal channels. 2. We combined laboratory and field experiments to test whether the coexistence of two congeneric ground-hopper species with overlapping ranges might be influenced by sexual interactions. 3. In the laboratory experiment the number of conspecific copulations of Tetrix ceperoi decreased substantially in the presence of Tetrix subulata. Males of T. ceperoi performed more mating attempts with heterospecific females, whereas females of T. subulata rejected these heterospecific approaches more often than those of conspecifics. Although no heterospecific matings occurred in the laboratory, the reproductive success of T. ceperoi was reduced substantially in field experiments. Negative effects on T. subulata were found only at high densities. 4. Our results suggest that reproductive interference could have similar consequences as competition, such as demographic displacement of one species ('sexual exclusion'). As reproductive interference should be selected against, it may also drive the evolution of signals (reproductive character displacement) or promote habitat, spatial or temporal segregation. 相似文献
98.
Using software‐modified smartphones to validate self‐reported mobile phone use in young people: A pilot study
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99.
Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence
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Roberto Ferrari Amelie Montel‐Hagen Ben Van Handel Marc A Kerényi Rajkumar Sasidharan Liudmilla Rubbi Yuko Fujiwara Matteo Pellegrini Stuart H Orkin Siavash K Kurdistani Hanna KA Mikkola 《The EMBO journal》2015,34(6):759-777
Scl/Tal1 confers hemogenic competence and prevents ectopic cardiomyogenesis in embryonic endothelium by unknown mechanisms. We discovered that Scl binds to hematopoietic and cardiac enhancers that become epigenetically primed in multipotent cardiovascular mesoderm, to regulate the divergence of hematopoietic and cardiac lineages. Scl does not act as a pioneer factor but rather exploits a pre‐established epigenetic landscape. As the blood lineage emerges, Scl binding and active epigenetic modifications are sustained in hematopoietic enhancers, whereas cardiac enhancers are decommissioned by removal of active epigenetic marks. Our data suggest that, rather than recruiting corepressors to enhancers, Scl prevents ectopic cardiogenesis by occupying enhancers that cardiac factors, such as Gata4 and Hand1, use for gene activation. Although hematopoietic Gata factors bind with Scl to both activated and repressed genes, they are dispensable for cardiac repression, but necessary for activating genes that enable hematopoietic stem/progenitor cell development. These results suggest that a unique subset of enhancers in lineage‐specific genes that are accessible for regulators of opposing fates during the time of the fate decision provide a platform where the divergence of mutually exclusive fates is orchestrated. 相似文献
100.
Mai H. Oushy Rebecca Palacios Alan E. C. Holden Amelie G. Ramirez Kipling J. Gallion Mary A. O’Connell 《PloS one》2015,10(9)