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141.
Yakov A. Tsepilov So-Youn Shin Nicole Soranzo Tim D. Spector Cornelia Prehn Jerzy Adamski Gabi Kastenmüller Rui Wang-Sattler Konstantin Strauch Christian Gieger Yurii S. Aulchenko Janina S. Ried 《Genetics》2015,200(3):707-718
Genome-wide association studies (GWAS) are widely applied to analyze the genetic effects on phenotypes. With the availability of high-throughput technologies for metabolite measurements, GWAS successfully identified loci that affect metabolite concentrations and underlying pathways. In most GWAS, the effect of each SNP on the phenotype is assumed to be additive. Other genetic models such as recessive, dominant, or overdominant were considered only by very few studies. In contrast to this, there are theories that emphasize the relevance of nonadditive effects as a consequence of physiologic mechanisms. This might be especially important for metabolites because these intermediate phenotypes are closer to the underlying pathways than other traits or diseases. In this study we analyzed systematically nonadditive effects on a large panel of serum metabolites and all possible ratios (22,801 total) in a population-based study [Cooperative Health Research in the Region of Augsburg (KORA) F4, N = 1,785]. We applied four different 1-degree-of-freedom (1-df) tests corresponding to an additive, dominant, recessive, and overdominant trait model as well as a genotypic model with two degree-of-freedom (2-df) that allows a more general consideration of genetic effects. Twenty-three loci were found to be genome-wide significantly associated (Bonferroni corrected P ≤ 2.19 × 10−12) with at least one metabolite or ratio. For five of them, we show the evidence of nonadditive effects. We replicated 17 loci, including 3 loci with nonadditive effects, in an independent study (TwinsUK, N = 846). In conclusion, we found that most genetic effects on metabolite concentrations and ratios were indeed additive, which verifies the practice of using the additive model for analyzing SNP effects on metabolites. 相似文献
142.
Lekka M Gil D Dąbroś W Jaczewska J Kulik AJ Lekki J Stachura Z Stachura J Laidler P 《Journal of molecular recognition : JMR》2011,24(5):833-842
The expression of N‐cadherin, characteristic of various cancers, very often leads to changes in the cells' adhesive properties. Thus, we sought to find out if N‐cadherin expressed in various, but cancer‐related cells, differs in its functional properties that could contribute to variations in cells' phenotypes. In our work, measurements of an unbinding force of a single N‐cadherin molecule, probed with the same antibody both on a surface of living non‐malignant (HCV29) and malignant cells (T24) of bladder cancer, were carried out with the use of an atomic force microscopy. The results show the enhanced N‐cadherin level in T24 malignant cells (8.7% vs. 3.6% obtained for non‐malignant one), confirmed by the Western blot and the immunohistochemical staining. The effect was accompanied by changes in unbinding properties of an individual N‐cadherin molecule. Lower unbinding force values (26.1 ± 7.1 pN) in non‐malignant cells reveal less stable N‐cadherin complexes, as compared to malignant cells (61.7 ± 14.6 pN). This suggests the cancer‐related changes in a structure of the binding site of the antibody, located at the extracellular domain of N‐cadherin. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
143.
144.
Cancer cells have several specific metabolic features, which have been explored for targeted therapies. Agents that promote apoptosis in tumors are currently considered as a powerful tool for cancer therapeutics. The present study aimed to design a fast, reliable and robust system for metabolite measurements in cells lines to observe impact of apoptosis on the metabolome. For that purpose the NBS (newborn screen) mass spectrometry-based metabolomics assay was adapted for cell culture approach. In HEK 293 and in cancer cell lines HepG2, PC3, and MCF7 we searched for metabolic biomarkers of apoptosis differing from that of necrosis. Already nontreated cell lines revealed distinct concentrations of metabolites. Several metabolites indicative for apoptotic processes in cell culture including aspartate, glutamate, methionine, alanine, glycine, propionyl carnitine (C3-carnitine), and malonyl carnitine (C3DC-carnitine) were observed. In some cell lines metabolite changes were visible as early as 4?h after apoptosis induction and preceeding the detection by caspase 3/7 assay. We demonstrated for the first time that the metabolomic signatures might be used in the tests of efficacy of agents causing apoptosis in cell culture. These signatures could be obtained in fast high-throughput screening. 相似文献
145.
Mikołajczyk MM Zaleśny R Czyżnikowska Z Toman P Leszczynski J Bartkowiak W 《Journal of molecular modeling》2011,17(9):2143-2149
An assessment of several widely used exchange--correlation potentials in computing charge-transfer integrals is performed.
In particular, we employ the recently proposed Coulomb-attenuated model which was proven by other authors to improve upon
conventional functionals in the case of charge-transfer excitations. For further validation, two distinct approaches to compute
the property in question are compared for a phthalocyanine dimer. 相似文献
146.
147.
Błaszczyk L Popiel D Chełkowski J Koczyk G Samuels GJ Sobieralski K Siwulski M 《Journal of applied genetics》2011,52(2):233-243
In the present study, we reinvestigate the diversity of Trichoderma in Poland utilizing a combination of morphological and molecular/phylogenetic methods. A total of 170 isolates were collected
from six different substrata at 49 sites in Poland. These were divided among 14 taxa as follows: 110 of 170 Trichoderma isolates were identified to the species level by the analysis of their ITS1, ITS2 rDNA sequences as: T. harzianum (43 isolates), T. aggressivum (35), T. citrinoviride (11), T. hamatum (9), T. virens (6), T. longibrachiatum (4), T. polysporum (1), and T. tomentosum (1); 60 isolates belonging to the Viride clade were identified based on a fragment of the translation-elongation factor 1-alpha
(tef1) gene as: T. atroviride (20 isolates), T. gamsii (2), T. koningii (17), T. viridescens (13), T. viride (7), and T. koningiopsis (1). Identifications were made using the BLAST interface in TrichOKEY and TrichoBLAST (). The most diverse substrata were soil (nine species per 22 isolates) and decaying wood (nine species per 75 isolates). The
most abundant species (25%) isolated from all substrata was T. harzianum. 相似文献
148.
149.
Epigenetic contribution to stress adaptation in plants 总被引:5,自引:0,他引:5
Plant epigenetics has recently gained unprecedented interest, not only as a subject of basic research but also as a possible new source of beneficial traits for plant breeding. We discuss here mechanisms of epigenetic regulation that should be considered when undertaking the latter. Since these mechanisms are responsible for the formation of heritable epigenetic gene variants (epialleles) and also regulate transposons mobility, both aspects could be exploited to broaden plant phenotypic and genetic variation, which could improve long-term plant adaptation to environmental challenges and, thus, increase productivity. 相似文献
150.
Next generation sequencing provides rapid access to the genome of Puccinia striiformis f. sp. tritici, the causal agent of wheat stripe rust 总被引:2,自引:0,他引:2
Cantu D Govindarajulu M Kozik A Wang M Chen X Kojima KK Jurka J Michelmore RW Dubcovsky J 《PloS one》2011,6(8):e24230