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151.
Network analysis of temporal functionalities of the gut induced by perturbations in new-born piglets
Nirupama Benis Dirkjan Schokker Maria Suarez-Diez Vitor AP Martins dos Santos Hauke Smidt Mari A Smits 《BMC genomics》2015,16(1)
Background
Evidence is accumulating that perturbation of early life microbial colonization of the gut induces long-lasting adverse health effects in individuals. Understanding the mechanisms behind these effects will facilitate modulation of intestinal health. The objective of this study was to identify biological processes involved in these long lasting effects and the (molecular) factors that regulate them. We used an antibiotic and the same antibiotic in combination with stress on piglets as an early life perturbation. Then we used host gene expression data from the gut (jejunum) tissue and community-scale analysis of gut microbiota from the same location of the gut, at three different time-points to gauge the reaction to the perturbation. We analysed the data by a new combination of existing tools. First, we analysed the data in two dimensions, treatment and time, with quadratic regression analysis. Then we applied network-based data integration approaches to find correlations between host gene expression and the resident microbial species.Results
The use of a new combination of data analysis tools allowed us to identify significant long-lasting differences in jejunal gene expression patterns resulting from the early life perturbations. In addition, we were able to identify potential key gene regulators (hubs) for these long-lasting effects. Furthermore, data integration also showed that there are a handful of bacterial groups that were associated with temporal changes in gene expression.Conclusion
The applied systems-biology approach allowed us to take the first steps in unravelling biological processes involved in long lasting effects in the gut due to early life perturbations. The observed data are consistent with the hypothesis that these long lasting effects are due to differences in the programming of the gut immune system as induced by the temporary early life changes in the composition and/or diversity of microbiota in the gut.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1733-8) contains supplementary material, which is available to authorized users. 相似文献152.
153.
McCard Monica South Josie Cuthbert Ross N. Dickey James W. E. McCard Nathan Dick Jaimie T. A. 《Biological invasions》2021,23(6):2019-2032
Biological Invasions - Biodiversity is declining on a global scale and the spread of invasive alien species (IAS) is a major driver, particularly through predatory impacts. Thus, effective means of... 相似文献
154.
Ross N. Cuthbert Tatenda Dalu Ryan J. Wasserman Arnaud Sentis Olaf L. F. Weyl P. William Froneman Amanda Callaghan Jaimie T. A. Dick 《Ecology and evolution》2021,11(11):6504
Predation is a critical ecological process that directly and indirectly mediates population stabilities, as well as ecosystem structure and function. The strength of interactions between predators and prey may be mediated by multiple density dependences concerning numbers of predators and prey. In temporary wetland ecosystems in particular, fluctuating water volumes may alter predation rates through differing search space and prey encounter rates. Using a functional response approach, we examined the influence of predator and prey densities on interaction strengths of the temporary pond specialist copepod Lovenula raynerae preying on cladoceran prey, Daphnia pulex, under contrasting water volumes. Further, using a population dynamic modeling approach, we quantified multiple predator effects across differences in prey density and water volume. Predators exhibited type II functional responses under both water volumes, with significant antagonistic multiple predator effects (i.e., antagonisms) exhibited overall. The strengths of antagonistic interactions were, however, enhanced under reduced water volumes and at intermediate prey densities. These findings indicate important biotic and abiotic contexts that mediate predator–prey dynamics, whereby multiple predator effects are contingent on both prey density and search area characteristics. In particular, reduced search areas (i.e., water volumes) under intermediate prey densities could enhance antagonisms by heightening predator–predator interference effects. 相似文献
155.
Coughlan Neil E. Bradbeer Stephanie J. Cuthbert Ross N. Cunningham Eoghan M. Crane Kate Potts Stephen Caffrey Joe M. Lucy Frances E. Dunn Alison M. Davis Eithne Renals Trevor Quinn Claire Dick Jaimie T. A. 《Wetlands Ecology and Management》2020,28(2):285-295
Wetlands Ecology and Management - Biosecurity protocols designed to prevent further spread of invasive alien species have become a key component of invader management strategies. Yet, the... 相似文献
156.
Flávia C Rodrigues-Lisoni Paulo PeitlJr Alessandra Vidotto Giovana M Polachini José V Maniglia Juliana Carmona-Raphe Bianca R Cunha Tiago Henrique Caique F Souza Rodrigo AP Teixeira Erica E Fukuyama Pedro MichaluartJr Marcos B de Carvalho Sonia M Oliani Head Neck Genome Project GENCAPO Eloiza H Tajara 《BMC medical genomics》2010,3(1):14
Background
The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression.Methods
The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells.Results
We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR.Conclusions
A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.157.
Background
Affymetrix High Density Oligonuclotide Arrays (HDONA) simultaneously measure expression of thousands of genes using millions of probes. We use correlations between measurements for the same gene across 6685 human tissue samples from NCBI's GEO database to indicated the quality of individual HG-U133A probes. Low correlation indicates a poor probe. 相似文献158.
Rungroj N Devonald MA Cuthbert AW Reimann F Akkarapatumwong V Yenchitsomanus PT Bennett WM Karet FE 《The Journal of biological chemistry》2004,279(14):13833-13838
Mutations in SLC4A1, encoding the chloride-bicarbonate exchanger AE1, cause distal renal tubular acidosis (dRTA), a disease of defective urinary acidification by the distal nephron. In this study we report a novel missense mutation, G609R, causing dominant dRTA in affected members of a large Caucasian pedigree who all exhibited metabolic acidosis with alkaline urine, prominent nephrocalcinosis, and progressive renal impairment. To investigate the potential disease mechanism, the consequent effects of this mutation were determined. We first assessed anion transport function of G609R by expression in Xenopus oocytes. Western blotting and immunofluorescence demonstrated that the mutant protein was expressed at the oocyte cell surface. Measuring chloride and bicarbonate fluxes revealed normal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-inhibitable anion exchange, suggesting that loss-of-function of kAE1 cannot explain the severe disease phenotype in this kindred. We next expressed epitope-tagged wild-type or mutant kAE1 in Madin-Darby canine kidney cells. In monolayers grown to polarity, mutant kAE1 was detected subapically and at the apical membrane, as well as at the basolateral membrane, in contrast to the normal basolateral appearance of wild-type kAE1. These findings suggest that the seventh transmembrane domain that contains Gly-609 plays an important role in targeting kAE1 to the correct cell surface compartment. They confirm that dominant dRTA is associated with non-polarized trafficking of the protein, with no significant effect on anion transport function in vitro, which remains an unusual mechanism of human disease. 相似文献
159.
Genetic evidence for interaction of the 5q31 cytokine locus and the CARD15 gene in Crohn disease 总被引:7,自引:0,他引:7
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Mirza MM Fisher SA King K Cuthbert AP Hampe J Sanderson J Mansfield J Donaldson P Macpherson AJ Forbes A Schreiber S Lewis CM Mathew CG 《American journal of human genetics》2003,72(4):1018-1022
A common haplotype spanning 250 kb in the cytokine gene cluster on chromosome 5q31 has recently been reported to be strongly associated with Crohn disease (CD) in Canadian families. We have replicated this finding by both the transmission-disequilibrium test (TDT) (P=.016) and in a case-control association study (P=.008) in a large European cohort of patients with CD, although the increase in disease risk was small (odds ratio 1.49 for homozygotes, 95% CI 1.11-2.0). No association was detected in families or individuals with ulcerative colitis (UC). Stratification of offspring with CD in the TDT sample by mutation status in the CD susceptibility gene CARD15 showed that the association with the 5q31 risk haplotype was present only in offspring with at least one of the known CARD15 disease susceptibility alleles (P=.044). The 5q31 risk haplotype frequency was 53.1% in unrelated individuals with CD who had one or two CARD15 mutations versus 43.7% in control subjects (P=.0001) but was not significantly elevated in individuals with CD who had no CARD15 mutations (45.4%, P=.41). Kaplan-Meier survival analysis of age at disease onset showed a significantly earlier onset in homozygotes for the 5q31 risk haplotype (P=.0019). These findings suggest that genetic variants at the 5q31 (IBD5) locus may hasten the onset of Crohn disease and cooperate with CARD15 in disease causation. 相似文献
160.
A novel syndrome affecting multiple mitochondrial functions, located by microcell-mediated transfer to chromosome 2p14-2p13 总被引:3,自引:0,他引:3
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Seyda A Newbold RF Hudson TJ Verner A MacKay N Winter S Feigenbaum A Malaney S Gonzalez-Halphen D Cuthbert AP Robinson BH 《American journal of human genetics》2001,68(2):386-396
We have studied cultured skin fibroblasts from three siblings and one unrelated individual, all of whom had fatal mitochondrial disease manifesting soon after birth. After incubation with 1 mM glucose, these four cell strains exhibited lactate/pyruvate ratios that were six times greater than those of controls. On further analysis, enzymatic activities of the pyruvate dehydrogenase complex, the 2-oxoglutarate dehydrogenase complex, NADH cytochrome c reductase, succinate dehydrogenase, and succinate cytochrome c reductase were severely deficient. In two of the siblings the enzymatic activity of cytochrome oxidase was mildly decreased (by approximately 50%). Metabolite analysis performed on urine samples taken from these patients revealed high levels of glycine, leucine, valine, and isoleucine, indicating abnormalities of both the glycine-cleavage system and branched-chain alpha-ketoacid dehydrogenase. In contrast, the activities of fibroblast pyruvate carboxylase, mitochondrial aconitase, and citrate synthase were normal. Immunoblot analysis of selected complex III subunits (core 1, cyt c(1), and iron-sulfur protein) and of the pyruvate dehydrogenase complex subunits revealed no visible changes in the levels of all examined proteins, decreasing the possibility that an import and/or assembly factor is involved. To elucidate the underlying molecular defect, analysis of microcell-mediated chromosome-fusion was performed between the present study's fibroblasts (recipients) and a panel of A9 mouse:human hybrids (donors) developed by Cuthbert et al. (1995). Complementation was observed between the recipient cells from both families and the mouse:human hybrid clone carrying human chromosome 2. These results indicate that the underlying defect in our patients is under the control of a nuclear gene, the locus of which is on chromosome 2. A 5-cM interval has been identified as potentially containing the critical region for the unknown gene. This interval maps to region 2p14-2p13. 相似文献