Global Correlation and Non-Correlation of Topography with Color and Reflectance on Pluto

Science.gov (United States)

Schenk, Paul M.; Beyer, Ross A.; Moore, Jeffrey M.; Young, Leslie; Ennico, Kimberly; Olkin, Catherine; Weaver, Harold A.; Stern, S. Alan; New Horizons Geology and Geophysics Team

2017-10-01

A key objective of the New Horizons mission at Pluto in July 2015 was completion of global maps of surface brightness and color patterns (covering 78% of surface) and topography (covering ~42%) of Pluto and its large moon Charon. The first calibrated and registered versions of these maps have now been completed for posting in the PDS this fall (with a peer-reviewed report on these products to be submitted). Rich in detail, investigation into the roles of local topography and insolation are ongoing (e.g., Lewis et al., 2017). Here we focus on the data sets and links between elevation and global color and brightness patterns and the global mapping revealed by them. In the “north,” yellowish deposits correlate with non-depressed portions of an eroded polar topographic dome ~600 km wide & 2-3 km high (e.g., Young et al., 2017). The broad dark band along the equator forming Cthulhu Macula to the west of Sputnik Planitia is topographically indistinguishable from the vast smooth lightly cratered plains to the north, indicating that latitude is the primary control, not topography. The curious lack of dark material along the equatorial band east of Sputnik Planitia may be partly due to topography of Eastern Tombaugh Regio, which is ~500 m above eroded plains the north and Cthulhu Macula itself. To the south of Cthulhu Macula, plains are slightly brighter, which correlates with a modest rise in topography of Macula, however, an abrupt increase in reflectance correlates with the edge of elevated plateau that rises 2-3 km above the plains. The areas with the strongest signature in the CH4-band are associated with bladed terrain, the highest standing geologic unit in absolute elevation. Similar colored amoeboid-shaped units are evident along the equator in the low-resolution mapping areas, indicating their probable occurrence elsewhere. Thus, while many of Pluto’s major color and albedo features correlate well with topography and are thus controlled by it, some

Global unitary fixing and matrix-valued correlations in matrix models

International Nuclear Information System (INIS)

Adler, Stephen L.; Horwitz, Lawrence P.

2003-01-01

We consider the partition function for a matrix model with a global unitary invariant energy function. We show that the averages over the partition function of global unitary invariant trace polynomials of the matrix variables are the same when calculated with any choice of a global unitary fixing, while averages of such polynomials without a trace define matrix-valued correlation functions, that depend on the choice of unitary fixing. The unitary fixing is formulated within the standard Faddeev-Popov framework, in which the squared Vandermonde determinant emerges as a factor of the complete Faddeev-Popov determinant. We give the ghost representation for the FP determinant, and the corresponding BRST invariance of the unitary-fixed partition function. The formalism is relevant for deriving Ward identities obeyed by matrix-valued correlation functions

Gene Expression Correlation for Cancer Diagnosis: A Pilot Study

Directory of Open Access Journals (Sweden)

Binbing Ling

2014-01-01

Full Text Available Poor prognosis for late-stage, high-grade, and recurrent cancers has been motivating cancer researchers to search for more efficient biomarkers to identify the onset of cancer. Recent advances in constructing and dynamically analyzing biomolecular networks for different types of cancer have provided a promising novel strategy to detect tumorigenesis and metastasis. The observation of different biomolecular networks associated with normal and cancerous states led us to hypothesize that correlations for gene expressions could serve as valid indicators of early cancer development. In this pilot study, we tested our hypothesis by examining whether the mRNA expressions of three randomly selected cancer-related genes PIK3C3, PIM3, and PTEN were correlated during cancer progression and the correlation coefficients could be used for cancer diagnosis. Strong correlations (0.68≤r≤1.0 were observed between PIK3C3 and PIM3 in breast cancer, between PIK3C3 and PTEN in breast and ovary cancers, and between PIM3 and PTEN in breast, kidney, liver, and thyroid cancers during disease progression, implicating that the correlations for cancer network gene expressions could serve as a supplement to current clinical biomarkers, such as cancer antigens, for early cancer diagnosis.

Correlation and network topologies in global and local stock indices

Science.gov (United States)

Nobi, Ashadun; Lee, Sungmin; Kim, Doo Hwan; Lee, Jae Woo

2014-07-01

We examined how the correlation and network structure of the global indices and local Korean indices have changed during years 2000-2012. The average correlations of the global indices increased with time, while the local indices showed a decreasing trend except for drastic changes during the crises. A significant change in the network topologies was observed due to the financial crises in both markets. The Jaccard similarities identified the change in the market state due to a crisis in both markets. The dynamic change of the Jaccard index can be used as an indicator of systemic risk or precursors of the crisis.

Gene set analysis using variance component tests.

Science.gov (United States)

Huang, Yen-Tsung; Lin, Xihong

2013-06-28

Gene set analyses have become increasingly important in genomic research, as many complex diseases are contributed jointly by alterations of numerous genes. Genes often coordinate together as a functional repertoire, e.g., a biological pathway/network and are highly correlated. However, most of the existing gene set analysis methods do not fully account for the correlation among the genes. Here we propose to tackle this important feature of a gene set to improve statistical power in gene set analyses. We propose to model the effects of an independent variable, e.g., exposure/biological status (yes/no), on multiple gene expression values in a gene set using a multivariate linear regression model, where the correlation among the genes is explicitly modeled using a working covariance matrix. We develop TEGS (Test for the Effect of a Gene Set), a variance component test for the gene set effects by assuming a common distribution for regression coefficients in multivariate linear regression models, and calculate the p-values using permutation and a scaled chi-square approximation. We show using simulations that type I error is protected under different choices of working covariance matrices and power is improved as the working covariance approaches the true covariance. The global test is a special case of TEGS when correlation among genes in a gene set is ignored. Using both simulation data and a published diabetes dataset, we show that our test outperforms the commonly used approaches, the global test and gene set enrichment analysis (GSEA). We develop a gene set analyses method (TEGS) under the multivariate regression framework, which directly models the interdependence of the expression values in a gene set using a working covariance. TEGS outperforms two widely used methods, GSEA and global test in both simulation and a diabetes microarray data.

Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling

Directory of Open Access Journals (Sweden)

Enrique J. Cobos

2018-01-01

Full Text Available Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia in a model of partial nerve injury, and this temporal divergence was associated with major differences in global gene expression in innervating dorsal root ganglia. Transcripts whose expression change correlates with the onset of cold allodynia were nociceptor related, whereas those correlating with tactile hypersensitivity were immune cell centric. Ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity, whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain incorporates reactive processes of sensory neurons and immune cells, each leading to distinct forms of hypersensitivity, potentially allowing drug development targeted to each pain type.

Correlations in the population structure of music, genes and language

Science.gov (United States)

Brown, Steven; Savage, Patrick E.; Ko, Albert Min-Shan; Stoneking, Mark; Ko, Ying-Chin; Loo, Jun-Hun; Trejaut, Jean A.

2014-01-01

We present, to our knowledge, the first quantitative evidence that music and genes may have coevolved by demonstrating significant correlations between traditional group-level folk songs and mitochondrial DNA variation among nine indigenous populations of Taiwan. These correlations were of comparable magnitude to those between language and genes for the same populations, although music and language were not significantly correlated with one another. An examination of population structure for genetics showed stronger parallels to music than to language. Overall, the results suggest that music might have a sufficient time-depth to retrace ancient population movements and, additionally, that it might be capturing different aspects of population history than language. Music may therefore have the potential to serve as a novel marker of human migrations to complement genes, language and other markers. PMID:24225453

Global gene expression analysis of the zoonotic parasite Trichinella spiralis revealed novel genes in host parasite interaction.

Directory of Open Access Journals (Sweden)

Xiaolei Liu

Full Text Available BACKGROUND: Trichinellosis is a typical food-borne zoonotic disease which is epidemic worldwide and the nematode Trichinella spiralis is the main pathogen. The life cycle of T. spiralis contains three developmental stages, i.e. adult worms, new borne larva (new borne L1 larva and muscular larva (infective L1 larva. Stage-specific gene expression in the parasites has been investigated with various immunological and cDNA cloning approaches, whereas the genome-wide transcriptome and expression features of the parasite have been largely unknown. The availability of the genome sequence information of T. spiralis has made it possible to deeply dissect parasite biology in association with global gene expression and pathogenesis. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, we analyzed the global gene expression patterns in the three developmental stages of T. spiralis using digital gene expression (DGE analysis. Almost 15 million sequence tags were generated with the Illumina RNA-seq technology, producing expression data for more than 9,000 genes, covering 65% of the genome. The transcriptome analysis revealed thousands of differentially expressed genes within the genome, and importantly, a panel of genes encoding functional proteins associated with parasite invasion and immuno-modulation were identified. More than 45% of the genes were found to be transcribed from both strands, indicating the importance of RNA-mediated gene regulation in the development of the parasite. Further, based on gene ontological analysis, over 3000 genes were functionally categorized and biological pathways in the three life cycle stage were elucidated. CONCLUSIONS AND SIGNIFICANCE: The global transcriptome of T. spiralis in three developmental stages has been profiled, and most gene activity in the genome was found to be developmentally regulated. Many metabolic and biological pathways have been revealed. The findings of the differential expression of several protein

Integrated global digital image correlation for interface delamination characterization

KAUST Repository

Hoefnagels, Johan P.M.; Blaysat, Benoî t; Lubineau, Gilles; Geers, Marc G D

2013-01-01

, but require accurate interface models to capture (irreversible) crack initiation and propagation behavior observed in experiments. Therefore, an Integrated Global Digital Image Correlation (I-GDIC) strategy is developed for accurate determination of mechanical

Local and global responses in complex gene regulation networks

Science.gov (United States)

Tsuchiya, Masa; Selvarajoo, Kumar; Piras, Vincent; Tomita, Masaru; Giuliani, Alessandro

2009-04-01

An exacerbated sensitivity to apparently minor stimuli and a general resilience of the entire system stay together side-by-side in biological systems. This apparent paradox can be explained by the consideration of biological systems as very strongly interconnected network systems. Some nodes of these networks, thanks to their peculiar location in the network architecture, are responsible for the sensitivity aspects, while the large degree of interconnection is at the basis of the resilience properties of the system. One relevant feature of the high degree of connectivity of gene regulation networks is the emergence of collective ordered phenomena influencing the entire genome and not only a specific portion of transcripts. The great majority of existing gene regulation models give the impression of purely local ‘hard-wired’ mechanisms disregarding the emergence of global ordered behavior encompassing thousands of genes while the general, genome wide, aspects are less known. Here we address, on a data analysis perspective, the discrimination between local and global scale regulations, this goal was achieved by means of the examination of two biological systems: innate immune response in macrophages and oscillating growth dynamics in yeast. Our aim was to reconcile the ‘hard-wired’ local view of gene regulation with a global continuous and scalable one borrowed from statistical physics. This reconciliation is based on the network paradigm in which the local ‘hard-wired’ activities correspond to the activation of specific crucial nodes in the regulation network, while the scalable continuous responses can be equated to the collective oscillations of the network after a perturbation.

Correlation and network topologies in global and local stock indices

DEFF Research Database (Denmark)

Nobi, A.; Lee, S.; Kim, D. H.

2014-01-01

the crises. A significant change in the network topologies was observed due to the financial crises in both markets. The Jaccard similarities identified the change in the market state due to a crisis in both markets. The dynamic change of the Jaccard index can be used as an indicator of systemic risk......We examined how the correlation and network structure of the global indices and local Korean indices have changed during years 2000-2012. The average correlations of the global indices increased with time, while the local indices showed a decreasing trend except for drastic changes during...... or precursors of the crisis. (C) 2014 Elsevier B.V. All rights reserved....

Childhood temperament: passive gene-environment correlation, gene-environment interaction, and the hidden importance of the family environment.

Science.gov (United States)

Lemery-Chalfant, Kathryn; Kao, Karen; Swann, Gregory; Goldsmith, H Hill

2013-02-01

Biological parents pass on genotypes to their children, as well as provide home environments that correlate with their genotypes; thus, the association between the home environment and children's temperament can be genetically (i.e., passive gene-environment correlation) or environmentally mediated. Furthermore, family environments may suppress or facilitate the heritability of children's temperament (i.e., gene-environment interaction). The sample comprised 807 twin pairs (mean age = 7.93 years) from the longitudinal Wisconsin Twin Project. Important passive gene-environment correlations emerged, such that home environments were less chaotic for children with high effortful control, and this association was genetically mediated. Children with high extraversion/surgency experienced more chaotic home environments, and this correlation was also genetically mediated. In addition, heritability of children's temperament was moderated by home environments, such that effortful control and extraversion/surgency were more heritable in chaotic homes, and negative affectivity was more heritable under crowded or unsafe home conditions. Modeling multiple types of gene-environment interplay uncovered the complex role of genetic factors and the hidden importance of the family environment for children's temperament and development more generally.

Global impact of mature biofilm lifestyle on Escherichia coli K-12 gene expression

DEFF Research Database (Denmark)

Beloin, C.; Valle, J.; Latour-Lambert, P.

2004-01-01

The formation of biofilm results in a major lifestyle switch that is thought to affect the expression of multiple genes and operons. We used DNA arrays to study the global effect of biofilm formation on gene expression in mature Escherichia coli K-12 biofilm. We show that, when biofilm is compared...... that 20 of these genes are required for the formation of mature biofilm. This group includes 11 genes of previously unknown function. These results constitute a comprehensive analysis of the global transcriptional response triggered in mature E. coli biofilms and provide insights into its physiological...

Global analysis of epigenetic regulation of gene expression in response to drought stress in Sorghum.

Energy Technology Data Exchange (ETDEWEB)

Reddy, Anireddy [Colorado State Univ., Fort Collins, CO (United States); Ben-Hur, Asa [Colorado State Univ., Fort Collins, CO (United States)

2017-11-22

Abiotic stresses including drought are major limiting factors of crop yields and cause significant crop losses. Acquisition of stress tolerance to abiotic stresses requires coordinated regulation of a multitude of biochemical and physiological changes, and most of these changes depend on alterations in gene expression. The goal of this work is to perform global analysis of differential regulation of gene expression and alternative splicing, and their relationship with chromatin landscape in drought sensitive and tolerant cultivars. our Iso-Seq study revealed transcriptome-wide full-length isoforms at an unprecedented scale with over 11000 novel splice isoforms. Additionally, we uncovered alternative polyadenylation sites of ~11000 expressed genes and many novel genes. Overall, Iso-Seq results greatly enhanced sorghum gene annotations that are not only useful in analyzing all our RNA-seq, ChIP-seq and ATAC-seq data but also serve as a great resource to the plant biology community. Our studies identified differentially expressed genes and splicing events that are correlated with the drought-resistant phenotype. An association between alternative splicing and chromatin accessibility was also revealed. Several computational tools developed here (TAPIS and iDiffIR) have been made freely available to the research community in analyzing alternative splicing and differential alternative splicing.

Correlation between the methylation of APC gene promoter and colon cancer.

Science.gov (United States)

Li, Bing-Qiang; Liu, Peng-Peng; Zhang, Cai-Hua

2017-08-01

The present study was planned to explore the correlation between the methylation of APC (adenomatous polyposis coli) and colon carcinogenesis. Colon cancer tissues and tumor-adjacent normal tissues of 60 colon cancer patients (who received surgical operation in our hospital from January 2012 to December 2014) were collected. SW1116 cells in human colon cancer tissues were selected for culturing. 5-aza-2c-deoxycytidine (5-aza-dC) was utilized as an inhibitor of the methylation for APC gene. Methylation specific PCR (MSP) was utilized for detection of APC methylation in SW1116 cells. The MTT and Transwell assays were performed to detect the effect of the methylation of APC gene on the proliferation and invasive abilities of SW1116 cells. The correlation between the methylation of APC gene and pathological parameters of colon cancer patients was analyzed. MSP results revealed that 41 cases (68.33%) showed methylation of APC gene in colon cancer tissues. No methylation of APC gene was found in tumor-adjacent normal tissues. 5-aza-dC was able to inhibit the methylation of APC gene in SW1116 cells. APC gene methylation was correlated with tumor size, differentiation degree, lymph node metastasis and Dukes staging. In conclusion, the levels of the methylation of APC in colon cancer tissues and SW1116 cells are relatively high. The methylation of APC promoted the proliferation and invasion abilities of SW1116 cells. Furthermore, methylation is correlated with a variety of clinicopathological features of colon cancer patients.

Global Regulatory Differences for Gene- and Cell-Based Therapies

DEFF Research Database (Denmark)

Coppens, Delphi G M; De Bruin, Marie L; Leufkens, Hubert G M

2017-01-01

Gene- and cell-based therapies (GCTs) offer potential new treatment options for unmet medical needs. However, the use of conventional regulatory requirements for medicinal products to approve GCTs may impede patient access and therapeutic innovation. Furthermore, requirements differ between...... jurisdictions, complicating the global regulatory landscape. We provide a comparative overview of regulatory requirements for GCT approval in five jurisdictions and hypothesize on the consequences of the observed global differences on patient access and therapeutic innovation....

Identification of a new gene regulatory circuit involving B cell receptor activated signaling using a combined analysis of experimental, clinical and global gene expression data

Science.gov (United States)

Schrader, Alexandra; Meyer, Katharina; Walther, Neele; Stolz, Ailine; Feist, Maren; Hand, Elisabeth; von Bonin, Frederike; Evers, Maurits; Kohler, Christian; Shirneshan, Katayoon; Vockerodt, Martina; Klapper, Wolfram; Szczepanowski, Monika; Murray, Paul G.; Bastians, Holger; Trümper, Lorenz; Spang, Rainer; Kube, Dieter

2016-01-01

To discover new regulatory pathways in B lymphoma cells, we performed a combined analysis of experimental, clinical and global gene expression data. We identified a specific cluster of genes that was coherently expressed in primary lymphoma samples and suppressed by activation of the B cell receptor (BCR) through αIgM treatment of lymphoma cells in vitro. This gene cluster, which we called BCR.1, includes numerous cell cycle regulators. A reduced expression of BCR.1 genes after BCR activation was observed in different cell lines and also in CD10+ germinal center B cells. We found that BCR activation led to a delayed entry to and progression of mitosis and defects in metaphase. Cytogenetic changes were detected upon long-term αIgM treatment. Furthermore, an inverse correlation of BCR.1 genes with c-Myc co-regulated genes in distinct groups of lymphoma patients was observed. Finally, we showed that the BCR.1 index discriminates activated B cell-like and germinal centre B cell-like diffuse large B cell lymphoma supporting the functional relevance of this new regulatory circuit and the power of guided clustering for biomarker discovery. PMID:27166259

Autism and increased paternal age related changes in global levels of gene expression regulation.

Directory of Open Access Journals (Sweden)

Mark D Alter

2011-02-01

Full Text Available A causal role of mutations in multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations in global levels of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for changes in the overall distribution of gene expression levels. For instance, in mice, variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in variance might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on RNA from peripheral blood lymphocytes (PBL of children with autism (n = 82 and controls (n = 64. Variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance. A decrease in the variance in the distribution of gene expression levels in PBL was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Global regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other

Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 (Kir4.1).

Science.gov (United States)

Nwaobi, Sinifunanya E; Olsen, Michelle L

2015-09-26

DNA methylation serves to regulate gene expression through the covalent attachment of a methyl group onto the C5 position of a cytosine in a cytosine-guanine dinucleotide. While DNA methylation provides long-lasting and stable changes in gene expression, patterns and levels of DNA methylation are also subject to change based on a variety of signals and stimuli. As such, DNA methylation functions as a powerful and dynamic regulator of gene expression. The study of neuroepigenetics has revealed a variety of physiological and pathological states that are associated with both global and gene-specific changes in DNA methylation. Specifically, striking correlations between changes in gene expression and DNA methylation exist in neuropsychiatric and neurodegenerative disorders, during synaptic plasticity, and following CNS injury. However, as the field of neuroepigenetics continues to expand its understanding of the role of DNA methylation in CNS physiology, delineating causal relationships in regards to changes in gene expression and DNA methylation are essential. Moreover, in regards to the larger field of neuroscience, the presence of vast region and cell-specific differences requires techniques that address these variances when studying the transcriptome, proteome, and epigenome. Here we describe FACS sorting of cortical astrocytes that allows for subsequent examination of a both RNA transcription and DNA methylation. Furthermore, we detail a technique to examine DNA methylation, methylation sensitive high resolution melt analysis (MS-HRMA) as well as a luciferase promoter assay. Through the use of these combined techniques one is able to not only explore correlative changes between DNA methylation and gene expression, but also directly assess if changes in the DNA methylation status of a given gene region are sufficient to affect transcriptional activity.

Global correlation imaging of magnetic total field gradients

International Nuclear Information System (INIS)

Guo, Lianghui; Meng, Xiaohong; Shi, Lei

2012-01-01

Firstly we introduce the correlation imaging approach for the x-, y- and z-gradients of a magnetic total field anomaly for deriving the distribution of equivalent magnetic sources of the subsurface. In this approach, the subsurface space is divided into a regular grid, and then a correlation coefficient function is computed at each grid node, based on the cross-correlation between the x-gradient (or y-gradient or z-gradient) of the observed magnetic total field anomaly and the x-gradient (or y-gradient or z-gradient) of the theoretical magnetic total field anomaly due to a magnetic dipole. The resultant correlation coefficient is used to describe the probability of a magnetic dipole occurring at the node. We then define a global correlation coefficient function for comprehensively delineating the probability of an occurrence of a magnetic dipole, which takes, at each node, the maximum positive value of the corresponding correlation coefficient function of the three gradients. We finally test the approach both on synthetic data and real data from a metallic deposit area in the middle-lower reaches of the Yangtze River, China. (paper)

Cross-species comparison of biological themes and underlying genes on a global gene expression scale in a mouse model of colorectal liver metastasis and in clinical specimens

Directory of Open Access Journals (Sweden)

Schirmacher Peter

2008-09-01

Full Text Available Abstract Background Invasion-related genes over-expressed by tumor cells as well as by reacting host cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models. Results This study examined the suitability of a murine model (CT26/Balb/C of colorectal liver metastasis to represent clinical liver metastasis specimens using a global gene expression approach. Cross-species similarity was examined between pure liver, liver invasion, tumor invasion and pure tumor compartments through overlap of up-regulated genes and gene ontology (GO-based biological themes on the level of single GO-terms and of condensed GO-term families. Three out of four GO-term families were conserved in a compartment-specific way between the species: secondary metabolism (liver, invasion (invasion front, and immune response (invasion front and liver. Among the individual GO-terms over-represented in the invasion compartments in both species were "extracellular matrix", "cell motility", "cell adhesion" and "antigen presentation" indicating that typical invasion related processes are operating in both species. This was reflected on the single gene level as well, as cross-species overlap of potential target genes over-expressed in the combined invasion front compartments reached up to 36.5%. Generally, histopathology and gene expression correlated well as the highest single gene overlap was found to be 44% in syn-compartmental comparisons (liver versus liver whereas cross-compartmental overlaps were much lower (e.g. liver versus tumor: 9.7%. However, single gene overlap was surprisingly high in some cross-compartmental comparisons (e.g. human liver invasion compartment and murine tumor invasion compartment: 9.0% despite little histolopathologic similarity indicating that invasion relevant genes are not necessarily confined to histologically defined compartments. Conclusion In summary, cross

BRAIN NETWORKS. Correlated gene expression supports synchronous activity in brain networks.

Science.gov (United States)

Richiardi, Jonas; Altmann, Andre; Milazzo, Anna-Clare; Chang, Catie; Chakravarty, M Mallar; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Lemaître, Hervé; Mann, Karl F; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomáš; Pausova, Zdenka; Rietschel, Marcella; Robbins, Trevor W; Smolka, Michael N; Spanagel, Rainer; Ströhle, Andreas; Schumann, Gunter; Hawrylycz, Mike; Poline, Jean-Baptiste; Greicius, Michael D

2015-06-12

During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function. Copyright © 2015, American Association for the Advancement of Science.

Global similarity and local divergence in human and mouse gene co-expression networks

Directory of Open Access Journals (Sweden)

Koonin Eugene V

2006-09-01

Full Text Available Abstract Background A genome-wide comparative analysis of human and mouse gene expression patterns was performed in order to evaluate the evolutionary divergence of mammalian gene expression. Tissue-specific expression profiles were analyzed for 9,105 human-mouse orthologous gene pairs across 28 tissues. Expression profiles were resolved into species-specific coexpression networks, and the topological properties of the networks were compared between species. Results At the global level, the topological properties of the human and mouse gene coexpression networks are, essentially, identical. For instance, both networks have topologies with small-world and scale-free properties as well as closely similar average node degrees, clustering coefficients, and path lengths. However, the human and mouse coexpression networks are highly divergent at the local level: only a small fraction ( Conclusion The dissonance between global versus local network divergence suggests that the interspecies similarity of the global network properties is of limited biological significance, at best, and that the biologically relevant aspects of the architectures of gene coexpression are specific and particular, rather than universal. Nevertheless, there is substantial evolutionary conservation of the local network structure which is compatible with the notion that gene coexpression networks are subject to purifying selection.

The impact of endurance exercise on global and AMPK gene-specific DNA methylation

Energy Technology Data Exchange (ETDEWEB)

King-Himmelreich, Tanya S.; Schramm, Stefanie; Wolters, Miriam C.; Schmetzer, Julia; Möser, Christine V.; Knothe, Claudia [pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590, Frankfurt am Main (Germany); Resch, Eduard [Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Project Group for Translational Medicine & Pharmacology (TMP), 60596, Frankfurt/Main (Germany); Peil, Johannes [Sports Clinic, Bad Nauheim, MCI GmbH, In der Aue 30-32, 61231, Bad Nauheim (Germany); Geisslinger, Gerd [pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590, Frankfurt am Main (Germany); Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Project Group for Translational Medicine & Pharmacology (TMP), 60596, Frankfurt/Main (Germany); Niederberger, Ellen, E-mail: e.niederberger@em.uni-frankfurt.de [pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590, Frankfurt am Main (Germany)

2016-05-27

Alterations in gene expression as a consequence of physical exercise are frequently described. The mechanism of these regulations might depend on epigenetic changes in global or gene-specific DNA methylation levels. The AMP-activated protein kinase (AMPK) plays a key role in maintenance of energy homeostasis and is activated by increases in the AMP/ATP ratio as occurring in skeletal muscles after sporting activity. To analyze whether exercise has an impact on the methylation status of the AMPK promoter, we determined the AMPK methylation status in human blood samples from patients before and after sporting activity in the context of rehabilitation as well as in skeletal muscles of trained and untrained mice. Further, we examined long interspersed nuclear element 1 (LINE-1) as indicator of global DNA methylation changes. Our results revealed that light sporting activity in mice and humans does not alter global DNA methylation but has an effect on methylation of specific CpG sites in the AMPKα2 gene. These regulations were associated with a reduced AMPKα2 mRNA and protein expression in muscle tissue, pointing at a contribution of the methylation status to AMPK expression. Taken together, these results suggest that exercise influences AMPKα2 gene methylation in human blood and eminently in the skeletal muscle of mice and therefore might repress AMPKα2 gene expression. -- Highlights: •AMPK gene methylation increases after moderate endurance exercise in humans and mice. •AMPKα mRNA and protein decrease after moderate endurance exercise in mice. •Global DNA methylation is not affected under the same conditions.

The impact of endurance exercise on global and AMPK gene-specific DNA methylation

International Nuclear Information System (INIS)

King-Himmelreich, Tanya S.; Schramm, Stefanie; Wolters, Miriam C.; Schmetzer, Julia; Möser, Christine V.; Knothe, Claudia; Resch, Eduard; Peil, Johannes; Geisslinger, Gerd; Niederberger, Ellen

2016-01-01

Alterations in gene expression as a consequence of physical exercise are frequently described. The mechanism of these regulations might depend on epigenetic changes in global or gene-specific DNA methylation levels. The AMP-activated protein kinase (AMPK) plays a key role in maintenance of energy homeostasis and is activated by increases in the AMP/ATP ratio as occurring in skeletal muscles after sporting activity. To analyze whether exercise has an impact on the methylation status of the AMPK promoter, we determined the AMPK methylation status in human blood samples from patients before and after sporting activity in the context of rehabilitation as well as in skeletal muscles of trained and untrained mice. Further, we examined long interspersed nuclear element 1 (LINE-1) as indicator of global DNA methylation changes. Our results revealed that light sporting activity in mice and humans does not alter global DNA methylation but has an effect on methylation of specific CpG sites in the AMPKα2 gene. These regulations were associated with a reduced AMPKα2 mRNA and protein expression in muscle tissue, pointing at a contribution of the methylation status to AMPK expression. Taken together, these results suggest that exercise influences AMPKα2 gene methylation in human blood and eminently in the skeletal muscle of mice and therefore might repress AMPKα2 gene expression. -- Highlights: •AMPK gene methylation increases after moderate endurance exercise in humans and mice. •AMPKα mRNA and protein decrease after moderate endurance exercise in mice. •Global DNA methylation is not affected under the same conditions.

bc-GenExMiner 3.0: new mining module computes breast cancer gene expression correlation analyses.

Science.gov (United States)

Jézéquel, Pascal; Frénel, Jean-Sébastien; Campion, Loïc; Guérin-Charbonnel, Catherine; Gouraud, Wilfried; Ricolleau, Gabriel; Campone, Mario

2013-01-01

We recently developed a user-friendly web-based application called bc-GenExMiner (http://bcgenex.centregauducheau.fr), which offered the possibility to evaluate prognostic informativity of genes in breast cancer by means of a 'prognostic module'. In this study, we develop a new module called 'correlation module', which includes three kinds of gene expression correlation analyses. The first one computes correlation coefficient between 2 or more (up to 10) chosen genes. The second one produces two lists of genes that are most correlated (positively and negatively) to a 'tested' gene. A gene ontology (GO) mining function is also proposed to explore GO 'biological process', 'molecular function' and 'cellular component' terms enrichment for the output lists of most correlated genes. The third one explores gene expression correlation between the 15 telomeric and 15 centromeric genes surrounding a 'tested' gene. These correlation analyses can be performed in different groups of patients: all patients (without any subtyping), in molecular subtypes (basal-like, HER2+, luminal A and luminal B) and according to oestrogen receptor status. Validation tests based on published data showed that these automatized analyses lead to results consistent with studies' conclusions. In brief, this new module has been developed to help basic researchers explore molecular mechanisms of breast cancer. DATABASE URL: http://bcgenex.centregauducheau.fr

Differential and correlation analyses of microarray gene expression data in the CEPH Utah families

DEFF Research Database (Denmark)

Tan, Qihua; Zhao, Jinghua; Li, Shuxia

2008-01-01

-regulated genes identifies cell-cell signaling as an important functional category implicated in human aging. Sex-dependent gene expression is characterized by genes that may escape X-inactivation and, most interestingly, such a pattern is not affected by the aging process. Analysis on sibship correlation on gene...... expression revealed a large number of significant genes suggesting the importance of a genetic mechanism in regulating transcriptional activities. In addition, we observe an interesting pattern of sibship correlation on gene expression that increases exponentially with the mean of gene expression reflecting...

StereoGene: rapid estimation of genome-wide correlation of continuous or interval feature data.

Science.gov (United States)

Stavrovskaya, Elena D; Niranjan, Tejasvi; Fertig, Elana J; Wheelan, Sarah J; Favorov, Alexander V; Mironov, Andrey A

2017-10-15

Genomics features with similar genome-wide distributions are generally hypothesized to be functionally related, for example, colocalization of histones and transcription start sites indicate chromatin regulation of transcription factor activity. Therefore, statistical algorithms to perform spatial, genome-wide correlation among genomic features are required. Here, we propose a method, StereoGene, that rapidly estimates genome-wide correlation among pairs of genomic features. These features may represent high-throughput data mapped to reference genome or sets of genomic annotations in that reference genome. StereoGene enables correlation of continuous data directly, avoiding the data binarization and subsequent data loss. Correlations are computed among neighboring genomic positions using kernel correlation. Representing the correlation as a function of the genome position, StereoGene outputs the local correlation track as part of the analysis. StereoGene also accounts for confounders such as input DNA by partial correlation. We apply our method to numerous comparisons of ChIP-Seq datasets from the Human Epigenome Atlas and FANTOM CAGE to demonstrate its wide applicability. We observe the changes in the correlation between epigenomic features across developmental trajectories of several tissue types consistent with known biology and find a novel spatial correlation of CAGE clusters with donor splice sites and with poly(A) sites. These analyses provide examples for the broad applicability of StereoGene for regulatory genomics. The StereoGene C ++ source code, program documentation, Galaxy integration scripts and examples are available from the project homepage http://stereogene.bioinf.fbb.msu.ru/. favorov@sensi.org. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Multitarget Effects of Danqi Pill on Global Gene Expression Changes in Myocardial Ischemia

Directory of Open Access Journals (Sweden)

Qiyan Wang

2018-01-01

Full Text Available Danqi pill (DQP is a widely prescribed traditional Chinese medicine (TCM in the treatment of cardiovascular diseases. The objective of this study is to systematically characterize altered gene expression pattern induced by myocardial ischemia (MI in a rat model and to investigate the effects of DQP on global gene expression. Global mRNA expression was measured. Differentially expressed genes among the sham group, model group, and DQP group were analyzed. The gene ontology enrichment analysis and pathway analysis of differentially expressed genes were carried out. We quantified 10,813 genes. Compared with the sham group, expressions of 339 genes were upregulated and 177 genes were downregulated in the model group. The upregulated genes were enriched in extracellular matrix organization, response to wounding, and defense response pathways. Downregulated genes were enriched in fatty acid metabolism, pyruvate metabolism, PPAR signaling pathways, and so forth. This indicated that energy metabolic disorders occurred in rats with MI. In the DQP group, expressions of genes in the altered pathways were regulated back towards normal levels. DQP reversed expression of 313 of the 516 differentially expressed genes in the model group. This study provides insight into the multitarget mechanism of TCM in the treatment of complex diseases.

Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease.

Directory of Open Access Journals (Sweden)

Peter R Sinnaeve

Full Text Available Systemic and local inflammation plays a prominent role in the pathogenesis of atherosclerotic coronary artery disease, but the relationship of whole blood gene expression changes with coronary disease remains unclear. We have investigated whether gene expression patterns in peripheral blood correlate with the severity of coronary disease and whether these patterns correlate with the extent of atherosclerosis in the vascular wall. Patients were selected according to their coronary artery disease index (CADi, a validated angiographical measure of the extent of coronary atherosclerosis that correlates with outcome. RNA was extracted from blood of 120 patients with at least a stenosis greater than 50% (CADi > or = 23 and from 121 controls without evidence of coronary stenosis (CADi = 0. 160 individual genes were found to correlate with CADi (rho > 0.2, P<0.003. Prominent differential expression was observed especially in genes involved in cell growth, apoptosis and inflammation. Using these 160 genes, a partial least squares multivariate regression model resulted in a highly predictive model (r(2 = 0.776, P<0.0001. The expression pattern of these 160 genes in aortic tissue also predicted the severity of atherosclerosis in human aortas, showing that peripheral blood gene expression associated with coronary atherosclerosis mirrors gene expression changes in atherosclerotic arteries. In conclusion, the simultaneous expression pattern of 160 genes in whole blood correlates with the severity of coronary artery disease and mirrors expression changes in the atherosclerotic vascular wall.

Global analysis of genes involved in freshwater adaptation in threespine sticklebacks (Gasterosteus aculeatus).

Science.gov (United States)

DeFaveri, Jacquelin; Shikano, Takahito; Shimada, Yukinori; Goto, Akira; Merilä, Juha

2011-06-01

Examples of parallel evolution of phenotypic traits have been repeatedly demonstrated in threespine sticklebacks (Gasterosteus aculeatus) across their global distribution. Using these as a model, we performed a targeted genome scan--focusing on physiologically important genes potentially related to freshwater adaptation--to identify genetic signatures of parallel physiological evolution on a global scale. To this end, 50 microsatellite loci, including 26 loci within or close to (directional selection were detected in 24 loci, including 17 physiologically important genes, in at least one location. Although no loci showed consistent signatures of selection in all divergent population pairs, several outliers were common in multiple locations. In particular, seven physiologically important genes, as well as reference ectodysplasin gene (EDA), showed signatures of selection in three or more locations. Hence, although these results give some evidence for consistent parallel molecular evolution in response to freshwater colonization, they suggest that different evolutionary pathways may underlie physiological adaptation to freshwater habitats within the global distribution of the threespine stickleback. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Global regulation of gene expression by the MafR protein of Enterococcus faecalis

Directory of Open Access Journals (Sweden)

Sofía eRuiz-Cruz

2016-01-01

Full Text Available Enterococcus faecalis is a natural inhabitant of the human gastrointestinal tract. However, as an opportunistic pathogen, it is able to colonize other host niches and cause life-threatening infections. Its adaptation to new environments involves global changes in gene expression. The EF3013 gene (here named mafR of E. faecalis strain V583 encodes a protein (MafR, 482 residues that has sequence similarity to global response regulators of the Mga/AtxA family. The enterococcal OG1RF genome also encodes the MafR protein (gene OG1RF_12293. In this work, we have identified the promoter of the mafR gene using several in vivo approaches. Moreover, we show that MafR influences positively the transcription of many genes on a genome-wide scale. The most significant target genes encode components of PTS-type membrane transporters, components of ABC-type membrane transporters, and proteins involved in the metabolism of carbon sources. Some of these genes were previously reported to be up-regulated during the growth of E. faecalis in blood and/or in human urine. Furthermore, we show that a mafR deletion mutant strain induces a significant lower degree of inflammation in the peritoneal cavity of mice, suggesting that enterococcal cells deficient in MafR are less virulent. Our work indicates that MafR is a global transcriptional regulator. It might facilitate the adaptation of E. faecalis to particular host niches and, therefore, contribute to its potential virulence.

Correlating Information Contents of Gene Ontology Terms to Infer Semantic Similarity of Gene Products

Directory of Open Access Journals (Sweden)

Mingxin Gan

2014-01-01

Full Text Available Successful applications of the gene ontology to the inference of functional relationships between gene products in recent years have raised the need for computational methods to automatically calculate semantic similarity between gene products based on semantic similarity of gene ontology terms. Nevertheless, existing methods, though having been widely used in a variety of applications, may significantly overestimate semantic similarity between genes that are actually not functionally related, thereby yielding misleading results in applications. To overcome this limitation, we propose to represent a gene product as a vector that is composed of information contents of gene ontology terms annotated for the gene product, and we suggest calculating similarity between two gene products as the relatedness of their corresponding vectors using three measures: Pearson’s correlation coefficient, cosine similarity, and the Jaccard index. We focus on the biological process domain of the gene ontology and annotations of yeast proteins to study the effectiveness of the proposed measures. Results show that semantic similarity scores calculated using the proposed measures are more consistent with known biological knowledge than those derived using a list of existing methods, suggesting the effectiveness of our method in characterizing functional relationships between gene products.

Dysregulated Pathway Identification of Alzheimer's Disease Based on Internal Correlation Analysis of Genes and Pathways.

Science.gov (United States)

Kong, Wei; Mou, Xiaoyang; Di, Benteng; Deng, Jin; Zhong, Ruxing; Wang, Shuaiqun

2017-11-20

Dysregulated pathway identification is an important task which can gain insight into the underlying biological processes of disease. Current pathway-identification methods focus on a set of co-expression genes and single pathways and ignore the correlation between genes and pathways. The method proposed in this study, takes into account the internal correlations not only between genes but also pathways to identifying dysregulated pathways related to Alzheimer's disease (AD), the most common form of dementia. In order to find the significantly differential genes for AD, mutual information (MI) is used to measure interdependencies between genes other than expression valves. Then, by integrating the topology information from KEGG, the significant pathways involved in the feature genes are identified. Next, the distance correlation (DC) is applied to measure the pairwise pathway crosstalks since DC has the advantage of detecting nonlinear correlations when compared to Pearson correlation. Finally, the pathway pairs with significantly different correlations between normal and AD samples are known as dysregulated pathways. The molecular biology analysis demonstrated that many dysregulated pathways related to AD pathogenesis have been discovered successfully by the internal correlation detection. Furthermore, the insights of the dysregulated pathways in the development and deterioration of AD will help to find new effective target genes and provide important theoretical guidance for drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Time-varying correlations in global real estate markets: A multivariate GARCH with spatial effects approach

Science.gov (United States)

Gu, Huaying; Liu, Zhixue; Weng, Yingliang

2017-04-01

The present study applies the multivariate generalized autoregressive conditional heteroscedasticity (MGARCH) with spatial effects approach for the analysis of the time-varying conditional correlations and contagion effects among global real estate markets. A distinguishing feature of the proposed model is that it can simultaneously capture the spatial interactions and the dynamic conditional correlations compared with the traditional MGARCH models. Results reveal that the estimated dynamic conditional correlations have exhibited significant increases during the global financial crisis from 2007 to 2009, thereby suggesting contagion effects among global real estate markets. The analysis further indicates that the returns of the regional real estate markets that are in close geographic and economic proximities exhibit strong co-movement. In addition, evidence of significantly positive leverage effects in global real estate markets is also determined. The findings have significant implications on global portfolio diversification opportunities and risk management practices.

Gene-Environment Correlation Underlying the Association between Parental Negativity and Adolescent Externalizing Problems

Science.gov (United States)

Marceau, Kristine; Horwitz, Briana N.; Narusyte, Jurgita; Ganiban, Jody M.; Spotts, Erica L.; Reiss, David; Neiderhiser, Jenae M.

2013-01-01

Studies of adolescent or parent-based twins suggest that gene-environment correlation (rGE) is an important mechanism underlying parent-adolescent relationships. However, information on how parents' and children's genes and environments influence correlated parent "and" child behaviors is needed to distinguish types of rGE. The present…

A global evolutionary and metabolic analysis of human obesity gene risk variants.

Science.gov (United States)

Castillo, Joseph J; Hazlett, Zachary S; Orlando, Robert A; Garver, William S

2017-09-05

It is generally accepted that the selection of gene variants during human evolution optimized energy metabolism that now interacts with our obesogenic environment to increase the prevalence of obesity. The purpose of this study was to perform a global evolutionary and metabolic analysis of human obesity gene risk variants (110 human obesity genes with 127 nearest gene risk variants) identified using genome-wide association studies (GWAS) to enhance our knowledge of early and late genotypes. As a result of determining the mean frequency of these obesity gene risk variants in 13 available populations from around the world our results provide evidence for the early selection of ancestral risk variants (defined as selection before migration from Africa) and late selection of derived risk variants (defined as selection after migration from Africa). Our results also provide novel information for association of these obesity genes or encoded proteins with diverse metabolic pathways and other human diseases. The overall results indicate a significant differential evolutionary pattern for the selection of obesity gene ancestral and derived risk variants proposed to optimize energy metabolism in varying global environments and complex association with metabolic pathways and other human diseases. These results are consistent with obesity genes that encode proteins possessing a fundamental role in maintaining energy metabolism and survival during the course of human evolution. Copyright © 2017. Published by Elsevier B.V.

Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

KAUST Repository

Horiuchi, Youko

2015-12-23

Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis-eQTLs. Expression

Application of multi-source waveform inversion to marine streamer data using the global correlation norm

KAUST Repository

Choi, Yun Seok

2012-05-02

Conventional multi-source waveform inversion using an objective function based on the least-square misfit cannot be applied to marine streamer acquisition data because of inconsistent acquisition geometries between observed and modelled data. To apply the multi-source waveform inversion to marine streamer data, we use the global correlation between observed and modelled data as an alternative objective function. The new residual seismogram derived from the global correlation norm attenuates modelled data not supported by the configuration of observed data and thus, can be applied to multi-source waveform inversion of marine streamer data. We also show that the global correlation norm is theoretically the same as the least-square norm of the normalized wavefield. To efficiently calculate the gradient, our method employs a back-propagation algorithm similar to reverse-time migration based on the adjoint-state of the wave equation. In numerical examples, the multi-source waveform inversion using the global correlation norm results in better inversion results for marine streamer acquisition data than the conventional approach. © 2012 European Association of Geoscientists & Engineers.

A mechanistic explanation of popularity: genes, rule breaking, and evocative gene-environment correlations.

Science.gov (United States)

Burt, Alexandra

2009-04-01

Previous work has suggested that the serotonergic system plays a key role in "popularity" or likeability. A polymorphism within the 5HT-sub(2A) serotonin receptor gene (-G1438A) has also been associated with popularity, suggesting that genes may predispose individuals to particular social experiences. However, because genes cannot code directly for others' reactions, any legitimate association should be mediated via the individual's behavior (i.e., genes-->behaviors-->social consequences), a phenomenon referred to as an evocative gene-environment correlation (rGE). The current study aimed to identify one such mediating behavior. The author focused on rule breaking given its prior links to both the serotonergic system and to increased popularity during adolescence. Two samples of previously unacquainted late-adolescent boys completed a peer-based interaction paradigm designed to assess their popularity. Analyses revealed that rule breaking partially mediated the genetic effect on popularity, thereby furthering our understanding of the biological mechanisms that underlie popularity. Moreover, the present results represent the first meaningfully explicated evidence that genes predispose individuals not only to particular behaviors but also to the social consequences of those behaviors. (c) 2009 APA, all rights reserved.

Canonical correlation analysis for gene-based pleiotropy discovery.

Directory of Open Access Journals (Sweden)

Jose A Seoane

2014-10-01

Full Text Available Genome-wide association studies have identified a wealth of genetic variants involved in complex traits and multifactorial diseases. There is now considerable interest in testing variants for association with multiple phenotypes (pleiotropy and for testing multiple variants for association with a single phenotype (gene-based association tests. Such approaches can increase statistical power by combining evidence for association over multiple phenotypes or genetic variants respectively. Canonical Correlation Analysis (CCA measures the correlation between two sets of multidimensional variables, and thus offers the potential to combine these two approaches. To apply CCA, we must restrict the number of attributes relative to the number of samples. Hence we consider modules of genetic variation that can comprise a gene, a pathway or another biologically relevant grouping, and/or a set of phenotypes. In order to do this, we use an attribute selection strategy based on a binary genetic algorithm. Applied to a UK-based prospective cohort study of 4286 women (the British Women's Heart and Health Study, we find improved statistical power in the detection of previously reported genetic associations, and identify a number of novel pleiotropic associations between genetic variants and phenotypes. New discoveries include gene-based association of NSF with triglyceride levels and several genes (ACSM3, ERI2, IL18RAP, IL23RAP and NRG1 with left ventricular hypertrophy phenotypes. In multiple-phenotype analyses we find association of NRG1 with left ventricular hypertrophy phenotypes, fibrinogen and urea and pleiotropic relationships of F7 and F10 with Factor VII, Factor IX and cholesterol levels.

Roles of genes and Alu repeats in nonlinear correlations of HUMHBB DNA sequence

International Nuclear Information System (INIS)

Xiao Yi; Huang Yanzhao

2004-01-01

DNA sequences of different species and different portion of the DNA of the same species may have completely different correlation properties, but the origin of these correlations is still not very clear and is currently being investigated, especially in different particular cases. We report here a study of the DNA sequence of human beta globin region (HUMHBB) which has strong linear and nonlinear correlations. We studied the roles of two of the typical elements of DNA sequence, genes and Alu repeats, in the nonlinear correlations of HUMHBB. We find that there exist strong nonlinear correlations between the exons or introns in different genes and between the Alu repeats. They may be one of the major sources of the nonlinear correlations in HUMBHB

Global and system-specific resting-state fMRI fluctuations are uncorrelated: principal component analysis reveals anti-correlated networks.

Science.gov (United States)

Carbonell, Felix; Bellec, Pierre; Shmuel, Amir

2011-01-01

The influence of the global average signal (GAS) on functional-magnetic resonance imaging (fMRI)-based resting-state functional connectivity is a matter of ongoing debate. The global average fluctuations increase the correlation between functional systems beyond the correlation that reflects their specific functional connectivity. Hence, removal of the GAS is a common practice for facilitating the observation of network-specific functional connectivity. This strategy relies on the implicit assumption of a linear-additive model according to which global fluctuations, irrespective of their origin, and network-specific fluctuations are super-positioned. However, removal of the GAS introduces spurious negative correlations between functional systems, bringing into question the validity of previous findings of negative correlations between fluctuations in the default-mode and the task-positive networks. Here we present an alternative method for estimating global fluctuations, immune to the complications associated with the GAS. Principal components analysis was applied to resting-state fMRI time-series. A global-signal effect estimator was defined as the principal component (PC) that correlated best with the GAS. The mean correlation coefficient between our proposed PC-based global effect estimator and the GAS was 0.97±0.05, demonstrating that our estimator successfully approximated the GAS. In 66 out of 68 runs, the PC that showed the highest correlation with the GAS was the first PC. Since PCs are orthogonal, our method provides an estimator of the global fluctuations, which is uncorrelated to the remaining, network-specific fluctuations. Moreover, unlike the regression of the GAS, the regression of the PC-based global effect estimator does not introduce spurious anti-correlations beyond the decrease in seed-based correlation values allowed by the assumed additive model. After regressing this PC-based estimator out of the original time-series, we observed robust anti-correlations

Modelling the correlation between the activities of adjacent genes in drosophila

NARCIS (Netherlands)

Thygesen, Helene H.; Zwinderman, Aeilko H.

2005-01-01

Background: Correlation between the expression levels of genes which are located close to each other on the genome has been found in various organisms, including yeast, drosophila and humans. Since such a correlation could be explained by several biochemical, evolutionary, genetic and technological

Anti-correlated networks, global signal regression, and the effects of caffeine in resting-state functional MRI.

Science.gov (United States)

Wong, Chi Wah; Olafsson, Valur; Tal, Omer; Liu, Thomas T

2012-10-15

Resting-state functional connectivity magnetic resonance imaging is proving to be an essential tool for the characterization of functional networks in the brain. Two of the major networks that have been identified are the default mode network (DMN) and the task positive network (TPN). Although prior work indicates that these two networks are anti-correlated, the findings are controversial because the anti-correlations are often found only after the application of a pre-processing step, known as global signal regression, that can produce artifactual anti-correlations. In this paper, we show that, for subjects studied in an eyes-closed rest state, caffeine can significantly enhance the detection of anti-correlations between the DMN and TPN without the need for global signal regression. In line with these findings, we find that caffeine also leads to widespread decreases in connectivity and global signal amplitude. Using a recently introduced geometric model of global signal effects, we demonstrate that these decreases are consistent with the removal of an additive global signal confound. In contrast to the effects observed in the eyes-closed rest state, caffeine did not lead to significant changes in global functional connectivity in the eyes-open rest state. Copyright © 2012 Elsevier Inc. All rights reserved.

Global gene transcriptome analysis in vaccinated cattle revealed a dominant role of IL-22 for protection against bovine tuberculosis.

Directory of Open Access Journals (Sweden)

Sabin Bhuju

2012-12-01

Full Text Available Bovine tuberculosis (bTB is a chronic disease of cattle caused by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex group of bacteria. Vaccination of cattle might offer a long-term solution for controlling the disease and priority has been given to the development of a cattle vaccine against bTB. Identification of biomarkers in tuberculosis research remains elusive and the goal is to identify host correlates of protection. We hypothesized that by studying global gene expression we could identify in vitro predictors of protection that could help to facilitate vaccine development. Calves were vaccinated with BCG or with a heterologous BCG prime adenovirally vectored subunit boosting protocol. Protective efficacy was determined after M. bovis challenge. RNA was prepared from PPD-stimulated PBMC prepared from vaccinated-protected, vaccinated-unprotected and unvaccinated control cattle prior to M. bovis challenge and global gene expression determined by RNA-seq. 668 genes were differentially expressed in vaccinated-protected cattle compared with vaccinated-unprotected and unvaccinated control cattle. Cytokine-cytokine receptor interaction was the most significant pathway related to this dataset with IL-22 expression identified as the dominant surrogate of protection besides INF-γ. Finally, the expression of these candidate genes identified by RNA-seq was evaluated by RT-qPCR in an independent set of PBMC samples from BCG vaccinated and unvaccinated calves. This experiment confirmed the importance of IL-22 as predictor of vaccine efficacy.

Improved correlation of monthly mean daily and hourly diffuse radiation with the corresponding global radiation for Indian stations

International Nuclear Information System (INIS)

Garg, H.P.; Garg, S.N.

1985-12-01

Several existing correlations between radiation monthly mean ratios of global to extraterrestrial and diffuse to global were tried for four Indian stations and found inadequate. New correlations were established for these stations and it was shown that these correlations are highly climate dependent. Classical equation of Liu and Jordon was tried to find hourly diffuse and global radiation from daily sums of diffuse and global radiation respectively. It was suitably modified to suit the Indian data. Equations developed by Collares-Pereira and Rabl have shown excellent agreement with the observed values

Integrated global digital image correlation for interface delamination characterization

KAUST Repository

Hoefnagels, Johan P.M.

2013-07-23

Interfacial delamination is a key reliability challenge in composites and micro-electronic systems due to (high-density) integration of dissimilar materials. Predictive finite element models are used to minimize delamination failures during design, but require accurate interface models to capture (irreversible) crack initiation and propagation behavior observed in experiments. Therefore, an Integrated Global Digital Image Correlation (I-GDIC) strategy is developed for accurate determination of mechanical interface behavior from in-situ delamination experiments. Recently, a novel miniature delamination setup was presented that enables in-situ microscopic characterization of interface delamination while sensitively measuring global load-displacement curves for all mode mixities. Nevertheless, extraction of detailed mechanical interface behavior from measured images is challenging, because deformations are tiny and measurement noise large. Therefore, an advanced I-GDIC methodology is developed which correlates the image patterns by only deforming the images using kinematically-admissible \\'eigenmodes\\' that correspond to the few parameters controlling the interface tractions in an analytic description of the crack tip deformation field, thereby greatly enhancing accuracy and robustness. This method is validated on virtual delamination experiments, simulated using a recently developed self-adaptive cohesive zone (CZ) finite element framework. © The Society for Experimental Mechanics, Inc. 2014.

Characterization of Timed Changes in Hepatic Copper Concentrations, Methionine Metabolism, Gene Expression, and Global DNA Methylation in the Jackson Toxic Milk Mouse Model of Wilson Disease

Directory of Open Access Journals (Sweden)

Anh Le

2014-05-01

Full Text Available Background: Wilson disease (WD is characterized by hepatic copper accumulation with progressive liver damage to cirrhosis. This study aimed to characterize the toxic milk mouse from The Jackson Laboratory (Bar Harbor, ME, USA (tx-j mouse model of WD according to changes over time in hepatic copper concentrations, methionine metabolism, global DNA methylation, and gene expression from gestational day 17 (fetal to adulthood (28 weeks. Methods: Included liver histology and relevant biochemical analyses including hepatic copper quantification, S-adenosylmethionine (SAM and S-adenosylhomocysteine (SAH liver levels, qPCR for transcript levels of genes relevant to methionine metabolism and liver damage, and DNA dot blot for global DNA methylation. Results: Hepatic copper was lower in tx-j fetuses but higher in weanling (three weeks and adult tx-j mice compared to controls. S-adenosylhomocysteinase transcript levels were significantly lower at all time points, except at three weeks, correlating negatively with copper levels and with consequent changes in the SAM:SAH methylation ratio and global DNA methylation. Conclusion: Compared to controls, methionine metabolism including S-adenosylhomocysteinase gene expression is persistently different in the tx-j mice with consequent alterations in global DNA methylation in more advanced stages of liver disease. The inhibitory effect of copper accumulation on S-adenosylhomocysteinase expression is associated with progressively abnormal methionine metabolism and decreased methylation capacity and DNA global methylation.

Defining global neuroendocrine gene expression patterns associated with reproductive seasonality in fish.

Directory of Open Access Journals (Sweden)

Dapeng Zhang

Full Text Available BACKGROUND: Many vertebrates, including the goldfish, exhibit seasonal reproductive rhythms, which are a result of interactions between external environmental stimuli and internal endocrine systems in the hypothalamo-pituitary-gonadal axis. While it is long believed that differential expression of neuroendocrine genes contributes to establishing seasonal reproductive rhythms, no systems-level investigation has yet been conducted. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, by analyzing multiple female goldfish brain microarray datasets, we have characterized global gene expression patterns for a seasonal cycle. A core set of genes (873 genes in the hypothalamus were identified to be differentially expressed between May, August and December, which correspond to physiologically distinct stages that are sexually mature (prespawning, sexual regression, and early gonadal redevelopment, respectively. Expression changes of these genes are also shared by another brain region, the telencephalon, as revealed by multivariate analysis. More importantly, by examining one dataset obtained from fish in October who were kept under long-daylength photoperiod (16 h typical of the springtime breeding season (May, we observed that the expression of identified genes appears regulated by photoperiod, a major factor controlling vertebrate reproductive cyclicity. Gene ontology analysis revealed that hormone genes and genes functionally involved in G-protein coupled receptor signaling pathway and transmission of nerve impulses are significantly enriched in an expression pattern, whose transition is located between prespawning and sexually regressed stages. The existence of seasonal expression patterns was verified for several genes including isotocin, ependymin II, GABA(A gamma2 receptor, calmodulin, and aromatase b by independent samplings of goldfish brains from six seasonal time points and real-time PCR assays. CONCLUSIONS/SIGNIFICANCE: Using both

Global patterns of diversity and selection in human tyrosinase gene.

Science.gov (United States)

Hudjashov, Georgi; Villems, Richard; Kivisild, Toomas

2013-01-01

Global variation in skin pigmentation is one of the most striking examples of environmental adaptation in humans. More than two hundred loci have been identified as candidate genes in model organisms and a few tens of these have been found to be significantly associated with human skin pigmentation in genome-wide association studies. However, the evolutionary history of different pigmentation genes is rather complex: some loci have been subjected to strong positive selection, while others evolved under the relaxation of functional constraints in low UV environment. Here we report the results of a global study of the human tyrosinase gene, which is one of the key enzymes in melanin production, to assess the role of its variation in the evolution of skin pigmentation differences among human populations. We observe a higher rate of non-synonymous polymorphisms in the European sample consistent with the relaxation of selective constraints. A similar pattern was previously observed in the MC1R gene and concurs with UV radiation-driven model of skin color evolution by which mutations leading to lower melanin levels and decreased photoprotection are subject to purifying selection at low latitudes while being tolerated or even favored at higher latitudes because they facilitate UV-dependent vitamin D production. Our coalescent date estimates suggest that the non-synonymous variants, which are frequent in Europe and North Africa, are recent and have emerged after the separation of East and West Eurasian populations.

Correlations between in situ denitrification activity and nir-gene abundances in pristine and impacted prairie streams

International Nuclear Information System (INIS)

Graham, David W.; Trippett, Clare; Dodds, Walter K.; O'Brien, Jonathan M.; Banner, Eric B.K.; Head, Ian M.; Smith, Marilyn S.; Yang, Richard K.; Knapp, Charles W.

2010-01-01

Denitrification is a process that reduces nitrogen levels in headwaters and other streams. We compared nirS and nirK abundances with the absolute rate of denitrification, the longitudinal coefficient of denitrification (i.e., K den , which represents optimal denitrification rates at given environmental conditions), and water quality in seven prairie streams to determine if nir-gene abundances explain denitrification activity. Previous work showed that absolute rates of denitrification correlate with nitrate levels; however, no correlation has been found for denitrification efficiency, which we hypothesise might be related to gene abundances. Water-column nitrate and soluble-reactive phosphorus levels significantly correlated with absolute rates of denitrification, but nir-gene abundances did not. However, nirS and nirK abundances significantly correlated with K den , as well as phosphorus, although no correlation was found between K den and nitrate. These data confirm that absolute denitrification rates are controlled by nitrate load, but intrinsic denitrification efficiency is linked to nirS and nirK gene abundances. - Denitrification efficiency best correlated to nirS and nirK gene abundances.

Sparse canonical correlation analysis for identifying, connecting and completing gene-expression networks

NARCIS (Netherlands)

Waaijenborg, S.; Zwinderman, A.H.

2009-01-01

ABSTRACT: BACKGROUND: We generalized penalized canonical correlation analysis for analyzing microarray gene-expression measurements for checking completeness of known metabolic pathways and identifying candidate genes for incorporation in the pathway. We used Wold's method for calculation of the

Measuring capital market efficiency: Global and local correlations structure

Czech Academy of Sciences Publication Activity Database

Krištoufek, Ladislav; Vošvrda, Miloslav

2013-01-01

Roč. 392, č. 1 (2013), s. 184-193 ISSN 0378-4371 R&D Projects: GA ČR(CZ) GBP402/12/G097 Institutional support: RVO:67985556 Keywords : Capital market efficiency * Fractal dimension * Long-range dependence * Short-range dependence Subject RIV: AH - Economics Impact factor: 1.722, year: 2013 http://library.utia.cas.cz/separaty/2012/E/kristoufek-measuring capital market efficiency global and local correlations structure.pdf

Gene expression of circulating tumour cells and its correlation with tumour stage in breast cancer patients

Directory of Open Access Journals (Sweden)

Bölke E

2009-09-01

Full Text Available Abstract Background Breast cancer (BC represents one of the leading causes of cancer related deaths worldwide. New tools for diagnostic staging and therapeutic monitoring are needed to improve individualized therapies and improve clinical outcome. The analyses of circulating tumour cells may provide important prognostic information in the clinical setting. Materials and methods Circulating tumour cells (CTC of 63 BC patients were isolated from peripheral blood (PB through immunomagnetic separation. Subsequently, RT-PCR or mPCR for the genes ga733.2, muc-1, c-erbB2, mgb-1, spdef and c-erbB2 were performed. Subsequently, expression data were correlated with the tumour stages. Fourteen healthy individuals served as controls. Results Significant correlations with tumour stages were found in single gene analyses of ga733.2, muc-1 and in multi-gene analyses of ga733.2/muc-1/mgb1/spdef. Furthermore, a significant correlation of Ca 15-3 and all studied genes was also observed. Conclusion Herein, we demonstrated a positive correlation of a gene signature consisting of ga733.2, muc-1, mgb1 and spdef and advanced stages of BC. Moreover, all studied genes and gene patterns revealed a significant correlation with Ca 15-3 positive cases.

HD CAG-correlated gene expression changes support a simple dominant gain of function

Science.gov (United States)

Jacobsen, Jessie C.; Gregory, Gillian C.; Woda, Juliana M.; Thompson, Morgan N.; Coser, Kathryn R.; Murthy, Vidya; Kohane, Isaac S.; Gusella, James F.; Seong, Ihn Sik; MacDonald, Marcy E.; Shioda, Toshi; Lee, Jong-Min

2011-01-01

Huntington's disease is initiated by the expression of a CAG repeat-encoded polyglutamine region in full-length huntingtin, with dominant effects that vary continuously with CAG size. The mechanism could involve a simple gain of function or a more complex gain of function coupled to a loss of function (e.g. dominant negative-graded loss of function). To distinguish these alternatives, we compared genome-wide gene expression changes correlated with CAG size across an allelic series of heterozygous CAG knock-in mouse embryonic stem (ES) cell lines (HdhQ20/7, HdhQ50/7, HdhQ91/7, HdhQ111/7), to genes differentially expressed between Hdhex4/5/ex4/5 huntingtin null and wild-type (HdhQ7/7) parental ES cells. The set of 73 genes whose expression varied continuously with CAG length had minimal overlap with the 754-member huntingtin-null gene set but the two were not completely unconnected. Rather, the 172 CAG length-correlated pathways and 238 huntingtin-null significant pathways clustered into 13 shared categories at the network level. A closer examination of the energy metabolism and the lipid/sterol/lipoprotein metabolism categories revealed that CAG length-correlated genes and huntingtin-null-altered genes either were different members of the same pathways or were in unique, but interconnected pathways. Thus, varying the polyglutamine size in full-length huntingtin produced gene expression changes that were distinct from, but related to, the effects of lack of huntingtin. These findings support a simple gain-of-function mechanism acting through a property of the full-length huntingtin protein and point to CAG-correlative approaches to discover its effects. Moreover, for therapeutic strategies based on huntingtin suppression, our data highlight processes that may be more sensitive to the disease trigger than to decreased huntingtin levels. PMID:21536587

Feature Genes Selection Using Supervised Locally Linear Embedding and Correlation Coefficient for Microarray Classification.

Science.gov (United States)

Xu, Jiucheng; Mu, Huiyu; Wang, Yun; Huang, Fangzhou

2018-01-01

The selection of feature genes with high recognition ability from the gene expression profiles has gained great significance in biology. However, most of the existing methods have a high time complexity and poor classification performance. Motivated by this, an effective feature selection method, called supervised locally linear embedding and Spearman's rank correlation coefficient (SLLE-SC 2 ), is proposed which is based on the concept of locally linear embedding and correlation coefficient algorithms. Supervised locally linear embedding takes into account class label information and improves the classification performance. Furthermore, Spearman's rank correlation coefficient is used to remove the coexpression genes. The experiment results obtained on four public tumor microarray datasets illustrate that our method is valid and feasible.

Altered global gene expression profiles in human gastrointestinal epithelial Caco2 cells exposed to nanosilver

Directory of Open Access Journals (Sweden)

Saura C. Sahu

Full Text Available Extensive consumer exposure to food- and cosmetics-related consumer products containing nanosilver is of public safety concern. Therefore, there is a need for suitable in vitro models and sensitive predictive rapid screening methods to assess their toxicity. Toxicogenomic profile showing subtle changes in gene expressions following nanosilver exposure is a sensitive toxicological endpoint for this purpose. We evaluated the Caco2 cells and global gene expression profiles as tools for predictive rapid toxicity screening of nanosilver. We evaluated and compared the gene expression profiles of Caco-2 cells exposed to 20 nm and 50 nm nanosilver at a concentration 2.5 μg/ml. The global gene expression analysis of Caco2 cells exposed to 20 nm nanosilver showed that a total of 93 genes were altered at 4 h exposure, out of which 90 genes were up-regulated and 3 genes were down-regulated. The 24 h exposure of 20 nm silver altered 15 genes in Caco2 cells, out of which 14 were up-regulated and one was down-regulated. The most pronounced changes in gene expression were detected at 4 h. The greater size (50 nm nanosilver at 4 h exposure altered more genes by more different pathways than the smaller (20 nm one. Metallothioneins and heat shock proteins were highly up-regulated as a result of exposure to both the nanosilvers. The cellular pathways affected by the nanosilver exposure is likely to lead to increased toxicity. The results of our study presented here suggest that the toxicogenomic characterization of Caco2 cells is a valuable in vitro tool for assessing toxicity of nanomaterials such as nanosilver. Keywords: Nanosilver, Silver nanoparticles, Nanoparticles, Toxicogenomics, DNA microarray, Global gene expression profiles, Caco2 cells

Cross-correlation Doppler global velocimetry (CC-DGV)

Science.gov (United States)

Cadel, Daniel R.; Lowe, K. Todd

2015-08-01

A flow velocimetry method, cross-correlation Doppler global velocimetry (CC-DGV), is presented as a robust, simplified, and high dynamic range implementation of the Doppler global/planar Doppler velocimetry technique. A sweep of several gigahertz of the vapor absorption spectrum is used for each velocity sample, with signals acquired from both Doppler-shifted scattered light within the flow and a non-Doppler shifted reference beam. Cross-correlation of these signals yields the Doppler shift between them, averaged over the duration of the scan. With presently available equipment, velocities from 0 ms-1 to over 3000 ms-1 can notionally be measured simultaneously, making the technique ideal for high speed flows. The processing routine is shown to be robust against large changes in the vapor pressure of the iodine cell, benefiting performance of the system in facilities where ambient conditions cannot be easily regulated. Validation of the system was performed with measurements of a model wind turbine blade boundary layer made in a 1.83 m by 1.83 m subsonic wind tunnel for which laser Doppler velocimetry (LDV) measurements were acquired alongside the CC-DGV results. CC-DGV uncertainties of ±1.30 ms-1, ±0.64 ms-1, and ±1.11 ms-1 were determined for the orthogonal stream-wise, transverse-horizontal, and transverse-vertical velocity components, and root-mean-square deviations of 2.77 ms-1 and 1.34 ms-1 from the LDV validation results were observed for Reynolds numbers of 1.5 million and 2 million, respectively. Volumetric mean velocity measurements are also presented for a supersonic jet, with velocity uncertainties of ±4.48 ms-1, ±16.93 ms-1, and ±0.50 ms-1 for the orthogonal components, and self-validation done by collapsing the data with a physical scaling.

Correlations of gene expression with ratings of inattention and hyperactivity/impulsivity in tourette syndrome: a pilot study

Directory of Open Access Journals (Sweden)

Tian Yingfang

2012-10-01

Full Text Available Abstract Background Inattentiveness, impulsivity and hyperactivity are the primary behaviors associated with attention-deficit hyperactivity disorder (ADHD. Previous studies showed that peripheral blood gene expression signatures can mirror central nervous system disease. Tourette syndrome (TS is associated with inattention (IA and hyperactivity/impulsivity (HI symptoms over 50% of the time. This study determined if gene expression in blood correlated significantly with IA and/or HI rating scale scores in participants with TS. Methods RNA was isolated from the blood of 21 participants with TS, and gene expression measured on Affymetrix human U133 Plus 2.0 arrays. To identify the genes that correlated with Conners’ Parents Ratings of IA and HI ratings of symptoms, an analysis of covariance (ANCOVA was performed, controlling for age, gender and batch. Results There were 1201 gene probesets that correlated with IA scales, 1625 that correlated with HI scales, and 262 that correlated with both IA and HI scale scores (Prp|>0.4. Immune, catecholamine and other neurotransmitter pathways were associated with IA and HI behaviors. A number of the identified genes (n=27 have previously been reported in ADHD genetic studies. Many more genes correlated with either IA or HI scales alone compared to those that correlated with both IA and HI scales. Conclusions These findings support the concept that the pathophysiology of ADHD and/or its subtypes in TS may involve the interaction of multiple genes. These preliminary data also suggest gene expression may be useful for studying IA and HI symptoms that relate to ADHD in TS and perhaps non-TS participants. These results will need to be confirmed in future studies.

Effect of spatially correlated noise on stochastic synchronization in globally coupled FitzHugh-Nagumo neuron systems

Directory of Open Access Journals (Sweden)

Yange Shao

2014-01-01

Full Text Available The phenomenon of stochastic synchronization in globally coupled FitzHugh-Nagumo (FHN neuron system subjected to spatially correlated Gaussian noise is investigated based on dynamical mean-field approximation (DMA and direct simulation (DS. Results from DMA are in good quantitative or qualitative agreement with those from DS for weak noise intensity and larger system size. Whether the consisting single FHN neuron is staying at the resting state, subthreshold oscillatory regime, or the spiking state, our investigation shows that the synchronization ratio of the globally coupled system becomes higher as the noise correlation coefficient increases, and thus we conclude that spatial correlation has an active effect on stochastic synchronization, and the neurons can achieve complete synchronization in the sense of statistics when the noise correlation coefficient tends to one. Our investigation also discloses that the noise spatial correlation plays the same beneficial role as the global coupling strength in enhancing stochastic synchronization in the ensemble. The result might be useful in understanding the information coding mechanism in neural systems.

Environmental dissemination of antibiotic resistance genes and correlation to anthropogenic contamination with antibiotics

Science.gov (United States)

Berglund, Björn

2015-01-01

Antibiotic resistance is a growing problem which threatens modern healthcare globally. Resistance has traditionally been viewed as a clinical problem, but recently non-clinical environments have been highlighted as an important factor in the dissemination of antibiotic resistance genes (ARGs). Horizontal gene transfer (HGT) events are likely to be common in aquatic environments; integrons in particular are well suited for mediating environmental dissemination of ARGs. A growing body of evidence suggests that ARGs are ubiquitous in natural environments. Particularly, elevated levels of ARGs and integrons in aquatic environments are correlated to proximity to anthropogenic activities. The source of this increase is likely to be routine discharge of antibiotics and resistance genes, for example, via wastewater or run-off from livestock facilities and agriculture. While very high levels of antibiotic contamination are likely to select for resistant bacteria directly, the role of sub-inhibitory concentrations of antibiotics in environmental antibiotic resistance dissemination remains unclear. In vitro studies have shown that low levels of antibiotics can select for resistant mutants and also facilitate HGT, indicating the need for caution. Overall, it is becoming increasingly clear that the environment plays an important role in dissemination of antibiotic resistance; further studies are needed to elucidate key aspects of this process. Importantly, the levels of environmental antibiotic contamination at which resistant bacteria are selected for and HGT is facilitated at should be determined. This would enable better risk analyses and facilitate measures for preventing dissemination and development of antibiotic resistance in the environment. PMID:26356096

Global Analysis of miRNA Gene Clusters and Gene Families Reveals Dynamic and Coordinated Expression

Directory of Open Access Journals (Sweden)

Li Guo

2014-01-01

Full Text Available To further understand the potential expression relationships of miRNAs in miRNA gene clusters and gene families, a global analysis was performed in 4 paired tumor (breast cancer and adjacent normal tissue samples using deep sequencing datasets. The compositions of miRNA gene clusters and families are not random, and clustered and homologous miRNAs may have close relationships with overlapped miRNA species. Members in the miRNA group always had various expression levels, and even some showed larger expression divergence. Despite the dynamic expression as well as individual difference, these miRNAs always indicated consistent or similar deregulation patterns. The consistent deregulation expression may contribute to dynamic and coordinated interaction between different miRNAs in regulatory network. Further, we found that those clustered or homologous miRNAs that were also identified as sense and antisense miRNAs showed larger expression divergence. miRNA gene clusters and families indicated important biological roles, and the specific distribution and expression further enrich and ensure the flexible and robust regulatory network.

Genetic analysis of rust resistance genes in global wheat cultivars: an overview

International Nuclear Information System (INIS)

Aktar-Uz-Zaman, Md; Tuhina-Khatun, Mst; Hanafi, Mohamed Musa; Sahebi, Mahbod

2017-01-01

Rust is the most devastating fungal disease in wheat. Three rust diseases, namely, leaf or brown rust caused by Puccinia triticina Eriks, stem or black rust caused by Puccinia graminis f. sp. tritici West, and stripe or yellow rust caused by Puccinia striiformis f. Tritici Eriks, are the most economically significant and common diseases among global wheat cultivars. Growing cultivars resistant to rust is the most sustainable, cost-effective and environmentally friendly approach for controlling rust diseases. To date, more than 187 rust resistance genes (80 leaf rust, 58 stem rust and 49 stripe rust) have been derived from diverse wheat or durum wheat cultivars and the related wild species using different molecular methods. This review provides a detailed discussion of the different aspects of rust resistance genes, their primitive sources, their distribution in global wheat cultivars and the importance of durable resistant varieties for controlling rust diseases. This information will serve as a foundation for plant breeders and geneticists to develop durable rust-resistant wheat varieties through marker-assisted breeding or gene pyramiding

Challenges for modeling global gene regulatory networks during development: insights from Drosophila.

Science.gov (United States)

Wilczynski, Bartek; Furlong, Eileen E M

2010-04-15

Development is regulated by dynamic patterns of gene expression, which are orchestrated through the action of complex gene regulatory networks (GRNs). Substantial progress has been made in modeling transcriptional regulation in recent years, including qualitative "coarse-grain" models operating at the gene level to very "fine-grain" quantitative models operating at the biophysical "transcription factor-DNA level". Recent advances in genome-wide studies have revealed an enormous increase in the size and complexity or GRNs. Even relatively simple developmental processes can involve hundreds of regulatory molecules, with extensive interconnectivity and cooperative regulation. This leads to an explosion in the number of regulatory functions, effectively impeding Boolean-based qualitative modeling approaches. At the same time, the lack of information on the biophysical properties for the majority of transcription factors within a global network restricts quantitative approaches. In this review, we explore the current challenges in moving from modeling medium scale well-characterized networks to more poorly characterized global networks. We suggest to integrate coarse- and find-grain approaches to model gene regulatory networks in cis. We focus on two very well-studied examples from Drosophila, which likely represent typical developmental regulatory modules across metazoans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Methods for simultaneously identifying coherent local clusters with smooth global patterns in gene expression profiles

Directory of Open Access Journals (Sweden)

Lee Yun-Shien

2008-03-01

Full Text Available Abstract Background The hierarchical clustering tree (HCT with a dendrogram 1 and the singular value decomposition (SVD with a dimension-reduced representative map 2 are popular methods for two-way sorting the gene-by-array matrix map employed in gene expression profiling. While HCT dendrograms tend to optimize local coherent clustering patterns, SVD leading eigenvectors usually identify better global grouping and transitional structures. Results This study proposes a flipping mechanism for a conventional agglomerative HCT using a rank-two ellipse (R2E, an improved SVD algorithm for sorting purpose seriation by Chen 3 as an external reference. While HCTs always produce permutations with good local behaviour, the rank-two ellipse seriation gives the best global grouping patterns and smooth transitional trends. The resulting algorithm automatically integrates the desirable properties of each method so that users have access to a clustering and visualization environment for gene expression profiles that preserves coherent local clusters and identifies global grouping trends. Conclusion We demonstrate, through four examples, that the proposed method not only possesses better numerical and statistical properties, it also provides more meaningful biomedical insights than other sorting algorithms. We suggest that sorted proximity matrices for genes and arrays, in addition to the gene-by-array expression matrix, can greatly aid in the search for comprehensive understanding of gene expression structures. Software for the proposed methods can be obtained at http://gap.stat.sinica.edu.tw/Software/GAP.

[Correlation of angiotensin-converting enzyme 2 gene polymorphism with antihypertensive effects of benazepril].

Science.gov (United States)

Chen, Qing; Tang, Xun; Yu, Can-qing; Chen, Da-fang; Tian, Jun; Cao, Yang; Fan, Wen-yi; Cao, Wei-hua; Zhan, Si-yan; Lv, Jun; Guo, Xiao-xia; Li, Li-ming; Hu, Yong-hua

2010-06-18

To explore the correlation of rs2106809 from angiotensin-converting enzyme 2 gene with antihypertensive effects of benazepril, as well as its interactions with polymorphisms of angiotensinogen(AGT) and angiotensin II type 1 receptor(AGTR1) gene. Correlation between rs2106809 and blood pressure reduction was estimated based on a field trail with 1 831 hypertensive patients using benazepril for 2 weeks. Generalized multifactor dimensionality reduction (GMDR) was used to explore the interactions of rs2106809 and 8 single nucleotide polymorphisms (SNPs) of AGTR1 gene and 3 SNPs of AGT gene. rs2106809 was found to be associated with reduction in systolic blood pressure and pulse pressure in women, as well as pulse pressure reduction in men. T allele carriers presented more blood pressure reduction (1.4, 1.3 and 0.9 mmHg/T allele respectively). Gene-gene interactions involving rs2106809 were found in systolic blood pressure reduction of men, and the response to benazepril of non-sensitive genotypes carriers was 8.2 (95% confidence interval: 6.6-9.7) mmHg, lower than that of sensitive genotypes carriers. rs2106809 might act as an independent influencing factor or component of gene-gene interaction in blood pressure reducing effects of benazepril.

Supplementary Material for: Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

KAUST Repository

Horiuchi, Youko; Harushima, Yoshiaki; Fujisawa, Hironori; Mochizuki, Takako; Fujita, Masahiro; Ohyanagi, Hajime; Kurata, Nori

2015-01-01

Abstract Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis

Neighboring Genes Show Correlated Evolution in Gene Expression

Science.gov (United States)

Ghanbarian, Avazeh T.; Hurst, Laurence D.

2015-01-01

When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543

Monocyte activation in HIV/HCV coinfection correlates with cognitive impairment.

Directory of Open Access Journals (Sweden)

Hans Rempel

Full Text Available Coinfection with human immunodeficiency virus (HIV and hepatitis C virus (HCV challenges the immune system with two viruses that elicit distinct immune responses. Chronic immune activation is a hallmark of HIV infection and an accurate indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART effectively prolongs life and significantly improves immune function. HIV/HCV coinfected individuals have peripheral immune activation despite effective ART control of HIV viral load. Here we examined freshly isolated CD14 monocytes for gene expression using high-density cDNA microarrays and analyzed T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV and HIV, and HIV-suppressed coinfected subjects. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological performance, which were summarized as a global deficit score (GDS. Monocyte gene expression analysis in HIV-suppressed coinfected subjects identified 43 genes that were elevated greater than 2.5 fold. Correlative analysis of subjects' GDS and gene expression found eight genes with significance after adjusting for multiple comparisons. Correlative expression of six genes was confirmed by qPCR, five of which were categorized as type 1 IFN response genes. Global deficit scores were not related to plasma lipopolysaccharide levels. In the T cell compartment, coinfection significantly increased expression of activation markers CD38 and HLADR on both CD4 and CD8 T cells but did not correlate with GDS. These findings indicate that coinfection is associated with a type 1 IFN monocyte activation profile which was further found to correlate with cognitive impairment, even in subjects with controlled HIV infection. HIV-suppressed coinfected subjects with controlled HIV viral load experiencing immune activation could benefit significantly from successful anti-HCV therapy and may be

The population genomics of begomoviruses: global scale population structure and gene flow

Directory of Open Access Journals (Sweden)

Prasanna HC

2010-09-01

Full Text Available Abstract Background The rapidly growing availability of diverse full genome sequences from across the world is increasing the feasibility of studying the large-scale population processes that underly observable pattern of virus diversity. In particular, characterizing the genetic structure of virus populations could potentially reveal much about how factors such as geographical distributions, host ranges and gene flow between populations combine to produce the discontinuous patterns of genetic diversity that we perceive as distinct virus species. Among the richest and most diverse full genome datasets that are available is that for the dicotyledonous plant infecting genus, Begomovirus, in the Family Geminiviridae. The begomoviruses all share the same whitefly vector, are highly recombinogenic and are distributed throughout tropical and subtropical regions where they seriously threaten the food security of the world's poorest people. Results We focus here on using a model-based population genetic approach to identify the genetically distinct sub-populations within the global begomovirus meta-population. We demonstrate the existence of at least seven major sub-populations that can further be sub-divided into as many as thirty four significantly differentiated and genetically cohesive minor sub-populations. Using the population structure framework revealed in the present study, we further explored the extent of gene flow and recombination between genetic populations. Conclusions Although geographical barriers are apparently the most significant underlying cause of the seven major population sub-divisions, within the framework of these sub-divisions, we explore patterns of gene flow to reveal that both host range differences and genetic barriers to recombination have probably been major contributors to the minor population sub-divisions that we have identified. We believe that the global Begomovirus population structure revealed here could

Correlation of SHOX2 Gene Amplification and DNA Methylation in Lung Cancer Tumors

International Nuclear Information System (INIS)

Schneider, Katja U; Liebenberg, Volker; Kneip, Christoph; Seegebarth, Anke; Erdogan, Fikret; Rappold, Gudrun; Schmidt, Bernd; Dietrich, Dimo; Fleischhacker, Michael; Leschber, Gunda; Merk, Johannes; Schäper, Frank; Stapert, Henk R; Vossenaar, Erik R; Weickmann, Sabine

2011-01-01

DNA methylation in the SHOX2 locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with SHOX2 gene expression and/or copy number alterations. An amplification of the SHOX2 gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples. SHOX2 expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect SHOX2 DNA methylation levels. SHOX2 expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH. A hypermethylation of the SHOX2 locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p < 0.0001), while the expression of the SHOX2 gene showed no difference. Frequent gene amplification correlated with hypermethylation of the SHOX2 gene locus. This concerted effect qualifies SHOX2 DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples

A review of gene-environment correlations and their implications for autism: a conceptual model.

Science.gov (United States)

Meek, Shantel E; Lemery-Chalfant, Kathryn; Jahromi, Laudan B; Valiente, Carlos

2013-07-01

A conceptual model is proposed that explains how gene-environment correlations and the multiplier effect function in the context of social development in individuals with autism. The review discusses the current state of autism genetic research, including its challenges, such as the genetic and phenotypic heterogeneity of the disorder, and its limitations, such as the lack of interdisciplinary work between geneticists and social scientists. We discuss literature on gene-environment correlations in the context of social development and draw implications for individuals with autism. The review expands upon genes, behaviors, types of environmental exposure, and exogenous variables relevant to social development in individuals on the autism spectrum, and explains these factors in the context of the conceptual model to provide a more in-depth understanding of how the effects of certain genetic variants can be multiplied by the environment to cause largely phenotypic individual differences. Using the knowledge gathered from gene-environment correlations and the multiplier effect, we outline novel intervention directions and implications. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

Science.gov (United States)

Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

2014-01-01

The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

Global identification of bursicon-regulated genes in Drosophila melanogaster

Directory of Open Access Journals (Sweden)

Beerntsen Brenda

2008-09-01

Full Text Available Abstract Background Bursicon is a heterodimer neuropeptide responsible for regulating cuticle sclerotization and wing expansion in several insect species. Recent studies indicate that the action of bursicon is mediated by a specific G protein-coupled receptor DLGR2 and the cAMP/PKA signaling pathway. However, little is known regarding the genes that are regulated by bursicon. The identification of bursicon-regulated genes is the focus of this investigation. Results We used DNA microarray analysis to identify bursicon-regulated genes in neck-ligated flies (Drosophila melanogaster that received recombinant bursicon (r-bursicon. Fifty four genes were found to be regulated by bursicon 1 h post r-bursicon injection, 52 being up-regulated and 2 down-regulated while 33 genes were influenced by r-bursicon 3 h post-injection (24 up-regulated and 9 down-regulated genes. Analysis of these genes by inference from the fly database http://flybase.bio.indiana.edu revealed that these genes encode proteins with diverse functions, including cell signaling, gene transcription, DNA/RNA binding, ion trafficking, proteolysis-peptidolysis, metabolism, cytoskeleton formation, immune response and cell-adhesion. Twenty eight genes randomly selected from the microarray-identified list were verified by real time PCR (qPCR which supported the microarray data. Temporal response studies of 13 identified and verified genes by qPCR revealed that the temporal expression patterns of these genes are consistent with the microarray data. Conclusion Using r-bursicon, we identified 87 genes that are regulated by bursicon, 30 of which have no previously known function. Most importantly, all genes randomly selected from the microarray-identified list were verified by real time PCR. Temporal analysis of 13 verified genes revealed that the expression of these genes was indeed induced by bursicon and correlated well with the cuticle sclerotization process. The composite data suggest that

The Children's Global Assessment Scale (CGAS) and Global Assessment of Psychosocial Disability (GAPD) in clinical practice--substance and reliability as judged by intraclass correlations

DEFF Research Database (Denmark)

Dyrborg, J; Larsen, F W; Nielsen, S

2000-01-01

Studies on the inter-rater reliability on the Children's Global Assessment Scale (CGAS) and the Global Assessment of Psychosocial Disability (GAPD) involving different subgroups of 145 outpatients from 4 to 16 years of age showed fair to substantial intraclass correlations of 0.59 to 0.90. Raters...

Gene expression profiling--Opening the black box of plant ecosystem responses to global change

Energy Technology Data Exchange (ETDEWEB)

Leakey, A.D.B.; Ainsworth, E.A.; Bernard, S.M.; Markelz, R.J.C.; Ort, D.R.; Placella, S.A.P.; Rogers, A.; Smith, M.D.; Sudderth, E.A.; Weston, D.J.; Wullschleger, S.D.; Yuan, S.

2009-11-01

The use of genomic techniques to address ecological questions is emerging as the field of genomic ecology. Experimentation under environmentally realistic conditions to investigate the molecular response of plants to meaningful changes in growth conditions and ecological interactions is the defining feature of genomic ecology. Since the impact of global change factors on plant performance are mediated by direct effects at the molecular, biochemical and physiological scales, gene expression analysis promises important advances in understanding factors that have previously been consigned to the 'black box' of unknown mechanism. Various tools and approaches are available for assessing gene expression in model and non-model species as part of global change biology studies. Each approach has its own unique advantages and constraints. A first generation of genomic ecology studies in managed ecosystems and mesocosms have provided a testbed for the approach and have begun to reveal how the experimental design and data analysis of gene expression studies can be tailored for use in an ecological context.

Observations of geographically correlated orbit errors for TOPEX/Poseidon using the global positioning system

Science.gov (United States)

Christensen, E. J.; Haines, B. J.; Mccoll, K. C.; Nerem, R. S.

1994-01-01

We have compared Global Positioning System (GPS)-based dynamic and reduced-dynamic TOPEX/Poseidon orbits over three 10-day repeat cycles of the ground-track. The results suggest that the prelaunch joint gravity model (JGM-1) introduces geographically correlated errors (GCEs) which have a strong meridional dependence. The global distribution and magnitude of these GCEs are consistent with a prelaunch covariance analysis, with estimated and predicted global rms error statistics of 2.3 and 2.4 cm rms, respectively. Repeating the analysis with the post-launch joint gravity model (JGM-2) suggests that a portion of the meridional dependence observed in JGM-1 still remains, with global rms error of 1.2 cm.

Genomic Deletions Correlate with Underexpression of Novel Candidate Genes at Six Loci in Pediatric Pilocytic Astrocytoma

Directory of Open Access Journals (Sweden)

Nicola Potter

2008-08-01

Full Text Available The molecular pathogenesis of pediatric pilocytic astrocytoma (PA is not well defined. Previous cytogenetic and molecular studies have not identified nonrandom genetic aberrations. To correlate differential gene expression and genomic copy number aberrations (CNAs in PA, we have used Affymetrix GeneChip HG_U133A to generate gene expression profiles of 19 pediatric patients and the SpectralChip 2600 to investigate CNAs in 11 of these tumors. Hierarchical clustering according to expression profile similarity grouped tumors and controls separately. We identified 1844 genes that showed significant differential expression between tumor and normal controls, with a large number clearly influencing phosphatidylinositol and mitogen-activated protein kinase signaling in PA. Most CNAs identified in this study were single-clone alterations. However, a small region of loss involving up to seven adjacent clones at 7q11.23 was observed in seven tumors and correlated with the underexpression of BCL7B. Loss of four individual clones was also associated with reduced gene expression including SH3GL2 at 9p21.2-p23, BCL7A (which shares 90% sequence homology with BCL7B at 12q24.33, DRD1IP at 10q26.3, and TUBG2 and CNTNAP1 at 17q21.31. Moreover, the down-regulation of FOXG1B at 14q12 correlated with loss within the gene promoter region in most tumors. This is the first study to correlate differential gene expression with CNAs in PA.

Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution.

Science.gov (United States)

Tagliazucchi, Enzo; Roseman, Leor; Kaelen, Mendel; Orban, Csaba; Muthukumaraswamy, Suresh D; Murphy, Kevin; Laufs, Helmut; Leech, Robert; McGonigle, John; Crossley, Nicolas; Bullmore, Edward; Williams, Tim; Bolstridge, Mark; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin

2016-04-25

Lysergic acid diethylamide (LSD) is a non-selective serotonin-receptor agonist that was first synthesized in 1938 and identified as (potently) psychoactive in 1943. Psychedelics have been used by indigenous cultures for millennia [1]; however, because of LSD's unique potency and the timing of its discovery (coinciding with a period of major discovery in psychopharmacology), it is generally regarded as the quintessential contemporary psychedelic [2]. LSD has profound modulatory effects on consciousness and was used extensively in psychological research and psychiatric practice in the 1950s and 1960s [3]. In spite of this, however, there have been no modern human imaging studies of its acute effects on the brain. Here we studied the effects of LSD on intrinsic functional connectivity within the human brain using fMRI. High-level association cortices (partially overlapping with the default-mode, salience, and frontoparietal attention networks) and the thalamus showed increased global connectivity under the drug. The cortical areas showing increased global connectivity overlapped significantly with a map of serotonin 2A (5-HT2A) receptor densities (the key site of action of psychedelic drugs [4]). LSD also increased global integration by inflating the level of communication between normally distinct brain networks. The increase in global connectivity observed under LSD correlated with subjective reports of "ego dissolution." The present results provide the first evidence that LSD selectively expands global connectivity in the brain, compromising the brain's modular and "rich-club" organization and, simultaneously, the perceptual boundaries between the self and the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Haloperidol induces pharmacoepigenetic response by modulating miRNA expression, global DNA methylation and expression profiles of methylation maintenance genes and genes involved in neurotransmission in neuronal cells.

Science.gov (United States)

Swathy, Babu; Banerjee, Moinak

2017-01-01

Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects. SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated. Methylation at global level is maintained by methylation maintenance machinery and certain miRNAs. Therefore, the expression of methylation maintenance genes and their putative miRNA expression profiles were assessed. These global methylation alterations could result in gene expression changes. Therefore genes expressions for neurotransmitter receptors, regulators, ion channels and transporters were determined. Subsequently, we were also keen to identify a strong candidate miRNA based on biological and in-silico approach which can reflect on the pharmacoepigenetic trait of haloperidol and can also target the altered neuroscience panel of genes used in the study. Haloperidol induced increase in global DNA methylation which was found to be associated with corresponding increase in expression of various epigenetic modifiers that include DNMT1, DNMT3A, DNMT3B and MBD2. The expression of miR-29b that is known to putatively regulate the global methylation by modulating the expression of epigenetic modifiers was observed to be down regulated by haloperidol. In addition to miR-29b, miR-22 was also found to be downregulated by haloperidol treatment. Both these miRNA are known to putatively target several genes associated with various epigenetic modifiers, pharmacogenes and neurotransmission. Interestingly some of these putative target genes involved in neurotransmission

Haloperidol induces pharmacoepigenetic response by modulating miRNA expression, global DNA methylation and expression profiles of methylation maintenance genes and genes involved in neurotransmission in neuronal cells.

Directory of Open Access Journals (Sweden)

Babu Swathy

Full Text Available Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects.SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated. Methylation at global level is maintained by methylation maintenance machinery and certain miRNAs. Therefore, the expression of methylation maintenance genes and their putative miRNA expression profiles were assessed. These global methylation alterations could result in gene expression changes. Therefore genes expressions for neurotransmitter receptors, regulators, ion channels and transporters were determined. Subsequently, we were also keen to identify a strong candidate miRNA based on biological and in-silico approach which can reflect on the pharmacoepigenetic trait of haloperidol and can also target the altered neuroscience panel of genes used in the study.Haloperidol induced increase in global DNA methylation which was found to be associated with corresponding increase in expression of various epigenetic modifiers that include DNMT1, DNMT3A, DNMT3B and MBD2. The expression of miR-29b that is known to putatively regulate the global methylation by modulating the expression of epigenetic modifiers was observed to be down regulated by haloperidol. In addition to miR-29b, miR-22 was also found to be downregulated by haloperidol treatment. Both these miRNA are known to putatively target several genes associated with various epigenetic modifiers, pharmacogenes and neurotransmission. Interestingly some of these putative target genes involved in

Correlation of Dynamic PET and Gene Array Data in Patients with Gastrointestinal Stromal Tumors

Directory of Open Access Journals (Sweden)

Ludwig G. Strauss

2012-01-01

Full Text Available Introduction. The results obtained with dynamic PET (dPET were compared to gene expression data obtained in patients with gastrointestinal stromal tumors (GIST. The primary aim was to assess the association of the dPET results and gene expression data. Material and Methods. dPET was performed following the injection of F-18-fluorodeoxyglucose (FDG in 22 patients with GIST. All patients were examined prior to surgery for staging purpose. Compartment and noncompartment models were used for the quantitative evaluation of the dPET examinations. Gene array data were based on tumor specimen obtained by surgery after the PET examinations. Results. The data analysis revealed significant correlations for the dPET parameters and the expression of zinc finger genes (znf43, znf85, znf91, znf189. Furthermore, the transport of FDG (k1 was associated with VEGF-A. The cell cycle gene cyclin-dependent kinase inhibitor 1C was correlated with the maximum tracer uptake (SUVmax in the tumors. Conclusions. The data demonstrate a dependency of the tracer kinetics on genes associated with prognosis in GIST. Furthermore, angiogenesis and cell proliferation have an impact on the tracer uptake.

Over-expression of Eph and ephrin genes in advanced ovarian cancer: ephrin gene expression correlates with shortened survival

Directory of Open Access Journals (Sweden)

Lincoln Douglas

2006-06-01

Full Text Available Abstract Background Increased expression of Eph receptor tyrosine kinases and their ephrin ligands has been implicated in tumor progression in a number of malignancies. This report describes aberrant expression of these genes in ovarian cancer, the commonest cause of death amongst gynaecological malignancies. Methods Eph and ephrin expression was determined using quantitative real time RT-PCR. Correlation of gene expression was measured using Spearman's rho statistic. Survival was analysed using log-rank analysis and (was visualised by Kaplan-Meier survival curves. Results Greater than 10 fold over-expression of EphA1 and a more modest over-expression of EphA2 were observed in partially overlapping subsets of tumors. Over-expression of EphA1 strongly correlated (r = 0.801; p Conclusion These data imply that increased levels of ephrins A1 and A5 in the presence of high expression of Ephs A1 and A2 lead to a more aggressive tumor phenotype. The known functions of Eph/ephrin signalling in cell de-adhesion and movement may explain the observed correlation of ephrin expression with poor prognosis.

Suppression of prolactin gene expression in GH cells correlates with site-specific DNA methylation.

Science.gov (United States)

Zhang, Z X; Kumar, V; Rivera, R T; Pasion, S G; Chisholm, J; Biswas, D K

1989-10-01

Prolactin- (PRL) producing and nonproducing subclones of the GH line of (rat) pituitary tumor cells have been compared to elucidate the regulatory mechanisms of PRL gene expression. Particular emphasis was placed on delineating the molecular basis of the suppressed state of the PRL gene in the prolactin-nonproducing (PRL-) GH subclone (GH(1)2C1). We examined six methylatable cytosine residues (5, -CCGG- and 1, -GCGC-) within the 30-kb region of the PRL gene in these subclones. This analysis revealed that -CCGG-sequences of the transcribed region, and specifically, one in the fourth exon of the PRL gene, were heavily methylated in the PRL-, GH(1)2C1 cells. Furthermore, the inhibition of PRL gene expression in GH(1)2C1 was reversed by short-term treatment of the cells with a sublethal concentration of azacytidine (AzaC), an inhibitor of DNA methylation. The reversion of PRL gene expression by AzaC was correlated with the concurrent demethylation of the same -CCGG- sequences in the transcribed region of PRL gene. An inverse correlation between PRL gene expression and the level of methylation of the internal -C- residues in the specific -CCGG-sequence of the transcribed region of the PRL gene was demonstrated. The DNase I sensitivity of these regions of the PRL gene in PRL+, PRL-, and AzaC-treated cells was also consistent with an inverse relationship between methylation state, a higher order of structural modification, and gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation between Gene Expression and Osteoarthritis Progression in Human.

Science.gov (United States)

Zhong, Leilei; Huang, Xiaobin; Karperien, Marcel; Post, Janine N

2016-07-14

Osteoarthritis (OA) is a multifactorial disease characterized by gradual degradation of joint cartilage. This study aimed to quantify major pathogenetic factors during OA progression in human cartilage. Cartilage specimens were isolated from OA patients and scored 0-5 according to the Osteoarthritis Research Society International (OARSI) guidelines. Protein and gene expressions were measured by immunohistochemistry and qPCR, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used to detect apoptotic cells. Cartilage degeneration in OA is a gradual progress accompanied with gradual loss of collagen type II and a gradual decrease in mRNA expression of SOX9, ACAN and COL2A1. Expression of WNT antagonists DKK1 and FRZB was lost, while hypertrophic markers (RUNX2, COL10A1 and IHH) increased during OA progression. Moreover, DKK1 and FRZB negatively correlated with OA grading, while RUNX2 and IHH showed a significantly positive correlation with OA grading. The number of apoptotic cells was increased with the severity of OA. Taken together, our results suggested that genetic profiling of the gene expression could be used as markers for staging OA at the molecular level. This helps to understand the molecular pathology of OA and may lead to the development of therapies based on OA stage.

Correlation between NFATC1 gene polymorphisms and congenital heart disease in children.

Science.gov (United States)

Li, C-L; Niu, L; Fu, M-Y; Tian, J; Wang, Q-W; An, X-J

2017-08-01

To analyze the links between NFATC1 gene polymorphism and congenital heart disease in children. In the present study, we selected 85 children patients with congenital heart disease who were hospitalized from February 2013 to February 2015 as research subjects (observation group), and 92 healthy subjects as control group. Restriction fragment length polymorphism (RFLP) was used for analysis of NFATC1 gene in samples from each group. The distribution of NFATC1 genotype and allele between the observation group (children with congenital heart disease) and the control group showed no significant difference (p >0.05), but AA, GG genotypes, and allele frequency between pathological samples of children with congenital heart disease and the control group displayed significant difference (p congenital heart disease in observation group also showed a difference, i.e., homozygote (AA, GG) ratio in children with severe congenital heart disease is relatively high. There is a correlation between NFATC1 genes and the incidence of congenital heart disease in children, and a correlation between different genotypes and allele frequency and the incidence of the disease.

Genetic and non-genetic influences during pregnancy on infant global and site specific DNA methylation: role for folate gene variants and vitamin B12.

Directory of Open Access Journals (Sweden)

Jill A McKay

Full Text Available Inter-individual variation in patterns of DNA methylation at birth can be explained by the influence of environmental, genetic and stochastic factors. This study investigates the genetic and non-genetic determinants of variation in DNA methylation in human infants. Given its central role in provision of methyl groups for DNA methylation, this study focuses on aspects of folate metabolism. Global (LUMA and gene specific (IGF2, ZNT5, IGFBP3 DNA methylation were quantified in 430 infants by Pyrosequencing®. Seven polymorphisms in 6 genes (MTHFR, MTRR, FOLH1, CβS, RFC1, SHMT involved in folate absorption and metabolism were analysed in DNA from both infants and mothers. Red blood cell folate and serum vitamin B(12 concentrations were measured as indices of vitamin status. Relationships between DNA methylation patterns and several covariates viz. sex, gestation length, maternal and infant red cell folate, maternal and infant serum vitamin B(12, maternal age, smoking and genotype were tested. Length of gestation correlated positively with IGF2 methylation (rho = 0.11, p = 0.032 and inversely with ZNT5 methylation (rho = -0.13, p = 0.017. Methylation of the IGFBP3 locus correlated inversely with infant vitamin B(12 concentration (rho = -0.16, p = 0.007, whilst global DNA methylation correlated inversely with maternal vitamin B(12 concentrations (rho = 0.18, p = 0.044. Analysis of common genetic variants in folate pathway genes highlighted several associations including infant MTRR 66G>A genotype with DNA methylation (χ(2 = 8.82, p = 0.003 and maternal MTHFR 677C>T genotype with IGF2 methylation (χ(2 = 2.77, p = 0.006. These data support the hypothesis that both environmental and genetic factors involved in one-carbon metabolism influence DNA methylation in infants. Specifically, the findings highlight the importance of vitamin B(12 status, infant MTRR genotype and maternal MTHFR genotype, all of which may influence the supply of methyl groups for

Ploidy-dependent changes in the epigenome of symbiotic cells correlate with specific patterns of gene expression

KAUST Repository

Nagymihály, Marianna

2017-04-13

The formation of symbiotic nodule cells in Medicago truncatula is driven by successive endoreduplication cycles and transcriptional reprogramming in different temporal waves including the activation of more than 600 cysteine-rich NCR genes expressed only in nodules. We show here that the transcriptional waves correlate with growing ploidy levels and have investigated how the epigenome changes during endoreduplication cycles. Differential DNA methylation was found in only a small subset of symbiotic nodule-specific genes, including more than half of the NCR genes, whereas in most genes DNA methylation was unaffected by the ploidy levels and was independent of the genes\\' active or repressed state. On the other hand, expression of nodule-specific genes correlated with ploidy-dependent opening of the chromatin as well as, in a subset of tested genes, with reduced H3K27me3 levels combined with enhanced H3K9ac levels. Our results suggest that endoreduplication-dependent epigenetic changes contribute to transcriptional reprogramming in the differentiation of symbiotic cells.

Shared control of gene expression in bacteria by transcription factors and global physiology of the cell.

NARCIS (Netherlands)

Berthoumieux, S.; Jong, H. de; Baptist, G.; Pinel, C.; Ranquet, C.; Ropers, D.; Geiselmann, J.

2013-01-01

Gene expression is controlled by the joint effect of (i) the global physiological state of the cell, in particular the activity of the gene expression machinery, and (ii) DNA-binding transcription factors and other specific regulators. We present a model-based approach to distinguish between these

Nitrogenase gene amplicons from global marine surface waters are dominated by genes of non-cyanobacteria.

Directory of Open Access Journals (Sweden)

Hanna Farnelid

Full Text Available Cyanobacteria are thought to be the main N(2-fixing organisms (diazotrophs in marine pelagic waters, but recent molecular analyses indicate that non-cyanobacterial diazotrophs are also present and active. Existing data are, however, restricted geographically and by limited sequencing depths. Our analysis of 79,090 nitrogenase (nifH PCR amplicons encoding 7,468 unique proteins from surface samples (ten DNA samples and two RNA samples collected at ten marine locations world-wide provides the first in-depth survey of a functional bacterial gene and yield insights into the composition and diversity of the nifH gene pool in marine waters. Great divergence in nifH composition was observed between sites. Cyanobacteria-like genes were most frequent among amplicons from the warmest waters, but overall the data set was dominated by nifH sequences most closely related to non-cyanobacteria. Clusters related to Alpha-, Beta-, Gamma-, and Delta-Proteobacteria were most common and showed distinct geographic distributions. Sequences related to anaerobic bacteria (nifH Cluster III were generally rare, but preponderant in cold waters, especially in the Arctic. Although the two transcript samples were dominated by unicellular cyanobacteria, 42% of the identified non-cyanobacterial nifH clusters from the corresponding DNA samples were also detected in cDNA. The study indicates that non-cyanobacteria account for a substantial part of the nifH gene pool in marine surface waters and that these genes are at least occasionally expressed. The contribution of non-cyanobacterial diazotrophs to the global N(2 fixation budget cannot be inferred from sequence data alone, but the prevalence of non-cyanobacterial nifH genes and transcripts suggest that these bacteria are ecologically significant.

Inferring nonlinear gene regulatory networks from gene expression data based on distance correlation.

Directory of Open Access Journals (Sweden)

Xiaobo Guo

Full Text Available Nonlinear dependence is general in regulation mechanism of gene regulatory networks (GRNs. It is vital to properly measure or test nonlinear dependence from real data for reconstructing GRNs and understanding the complex regulatory mechanisms within the cellular system. A recently developed measurement called the distance correlation (DC has been shown powerful and computationally effective in nonlinear dependence for many situations. In this work, we incorporate the DC into inferring GRNs from the gene expression data without any underling distribution assumptions. We propose three DC-based GRNs inference algorithms: CLR-DC, MRNET-DC and REL-DC, and then compare them with the mutual information (MI-based algorithms by analyzing two simulated data: benchmark GRNs from the DREAM challenge and GRNs generated by SynTReN network generator, and an experimentally determined SOS DNA repair network in Escherichia coli. According to both the receiver operator characteristic (ROC curve and the precision-recall (PR curve, our proposed algorithms significantly outperform the MI-based algorithms in GRNs inference.

A powerful nonparametric method for detecting differentially co-expressed genes: distance correlation screening and edge-count test.

Science.gov (United States)

Zhang, Qingyang

2018-05-16

Differential co-expression analysis, as a complement of differential expression analysis, offers significant insights into the changes in molecular mechanism of different phenotypes. A prevailing approach to detecting differentially co-expressed genes is to compare Pearson's correlation coefficients in two phenotypes. However, due to the limitations of Pearson's correlation measure, this approach lacks the power to detect nonlinear changes in gene co-expression which is common in gene regulatory networks. In this work, a new nonparametric procedure is proposed to search differentially co-expressed gene pairs in different phenotypes from large-scale data. Our computational pipeline consisted of two main steps, a screening step and a testing step. The screening step is to reduce the search space by filtering out all the independent gene pairs using distance correlation measure. In the testing step, we compare the gene co-expression patterns in different phenotypes by a recently developed edge-count test. Both steps are distribution-free and targeting nonlinear relations. We illustrate the promise of the new approach by analyzing the Cancer Genome Atlas data and the METABRIC data for breast cancer subtypes. Compared with some existing methods, the new method is more powerful in detecting nonlinear type of differential co-expressions. The distance correlation screening can greatly improve computational efficiency, facilitating its application to large data sets.

Gene and transcript abundances of bacterial type III secretion systems from the rumen microbiome are correlated with methane yield in sheep.

Science.gov (United States)

Kamke, Janine; Soni, Priya; Li, Yang; Ganesh, Siva; Kelly, William J; Leahy, Sinead C; Shi, Weibing; Froula, Jeff; Rubin, Edward M; Attwood, Graeme T

2017-08-08

Ruminants are important contributors to global methane emissions via microbial fermentation in their reticulo-rumens. This study is part of a larger program, characterising the rumen microbiomes of sheep which vary naturally in methane yield (g CH 4 /kg DM/day) and aims to define differences in microbial communities, and in gene and transcript abundances that can explain the animal methane phenotype. Rumen microbiome metagenomic and metatranscriptomic data were analysed by Gene Set Enrichment, sparse partial least squares regression and the Wilcoxon Rank Sum test to estimate correlations between specific KEGG bacterial pathways/genes and high methane yield in sheep. KEGG genes enriched in high methane yield sheep were reassembled from raw reads and existing contigs and analysed by MEGAN to predict their phylogenetic origin. Protein coding sequences from Succinivibrio dextrinosolvens strains were analysed using Effective DB to predict bacterial type III secreted proteins. The effect of S. dextrinosolvens strain H5 growth on methane formation by rumen methanogens was explored using co-cultures. Detailed analysis of the rumen microbiomes of high methane yield sheep shows that gene and transcript abundances of bacterial type III secretion system genes are positively correlated with methane yield in sheep. Most of the bacterial type III secretion system genes could not be assigned to a particular bacterial group, but several genes were affiliated with the genus Succinivibrio, and searches of bacterial genome sequences found that strains of S. dextrinosolvens were part of a small group of rumen bacteria that encode this type of secretion system. In co-culture experiments, S. dextrinosolvens strain H5 showed a growth-enhancing effect on a methanogen belonging to the order Methanomassiliicoccales, and inhibition of a representative of the Methanobrevibacter gottschalkii clade. This is the first report of bacterial type III secretion system genes being associated with high

Correlation between leptin receptor gene polymorphism and type 2 diabetes in Chinese population: a meta-analysis

Directory of Open Access Journals (Sweden)

Miao HE

2015-11-01

Full Text Available Objective　To evaluate the correlation between leptin receptor gene (LEPR polymorphism and type 2 diabetes (T2DM in Chinese population. Methods　The literature concerning the correlation between LEPR polymorphism and T2DM in Chinese population were searched from Chinese databases (CNKI, VIP, WanFang, CBM with "leptin receptor gene" and "type 2 diabetes" as keywords, and from English databases (PubMed, Web of Knowledge, EBSCO with "leptin receptor gene", "LEPR", "OBR", "OB-R", "type 2 diabetes" and "T2DM" as keywords. The relevant articles were searched up to September 20, 2014. Then, meta-analysis was performed using RevMan 5.1 and Stata 11.0 software. The Newcastle-Ottawa Scale was applied to assess methodological quality of included articles from 3 aspects, namely, selection of participants, comparability and outcome assessment. Results　Seventeen case-control studies involving 12 533 cases of T2DM and 3348 controls were included in Meta-analysis. A significant correlation was found between rs1137100 polymorphism in LEPR gene and T2DM (for recessive genetic model: OR=0.67, 95%CI 0.52-0.88, P=0.00; for allele contrast genetic model: OR=1.46, 95%CI 1.15-1.85, P=0.00. A strong correlation was also found between rs1137101 polymorphism and T2DM (for additive genetic model: OR=1.54, 95%CI 1.20-1.98, P=0.00; for allele contrast genetic model: OR=1.15, 95%CI 1.01-1.30, P=0.00. In addition, rs1805096 polymorphism was closely correlated with T2DM (for dominant genetic model: OR=1.32, 95%CI 1.07-1.62, P=0.00; for recessive genetic model: OR=1.30, 95%CI 1.09-1.54, P=0.00; for allele contrast genetic model: OR=0.67, 95%CI 0.59-0.75, P=0.00. Conclusions　There is a significant correlation between rs1137100, rs1805096 of LEPR gene and T2DM in Chinese population under allele contrast genetic model as well as in recessive genetic model. Rs1137101 of LEPR gene is closely correlated with T2DM in Chinese population under additive genetic model. For dominant

Correlation Dimension Estimates of Global and Local Temperature Data.

Science.gov (United States)

Wang, Qiang

1995-11-01

The author has attempted to detect the presence of low-dimensional deterministic chaos in temperature data by estimating the correlation dimension with the Hill estimate that has been recently developed by Mikosch and Wang. There is no convincing evidence of low dimensionality with either global dataset (Southern Hemisphere monthly average temperatures from 1858 to 1984) or local temperature dataset (daily minimums at Auckland, New Zealand). Any apparent reduction in the dimension estimates appears to be due large1y, if not entirely, to effects of statistical bias, but neither is it a purely random stochastic process. The dimension of the climatic attractor may be significantly larger than 10.

Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1.

Directory of Open Access Journals (Sweden)

Christopher Terranova

Full Text Available Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development.

Correlation between the GP78 Gene Polymorphism and Coronary Atherosclerotic Heart Disease

Directory of Open Access Journals (Sweden)

Long Wang

2018-01-01

Full Text Available Objective: To study the correlation between the GP78 gene polymorphism and blood fat, blood glucose, blood pressure and coronary atherosclerotic heart disease. Methods: A total of 72 patients with coronary atherosclerotic heart disease were selected as the observation group, and 68 healthy participants were selected as the control group. The gp78 gene polymorphism of both groups was studied via polymerase chain reaction-restriction fragment length polymorphism (RFLP. At the same time, the multiple expression quantities of the GP78 gene in the tissues of both groups were tested via fluorogenic quantitative PCR, enzyme-linked immunosorbent assay (ELISA and Western-blotting assay. Furthermore, the blood fat, blood glucose and blood pressure of subjects in both groups were tested. Results: The percentages of the gp78 gene polymorphisms of Arg/Arg, Arg/Gly and Gly/Gly at the 145 locus of the study subjects in the observation group were 12.3%, 43.2% and 44.5%, respectively, while those in the control group were 74.3%, 11.2% and 14.5%, respectively, and there were significant differences between both groups. Based on the test results of the blood fat, blood glucose and blood pressure of the objects in the observation group and control group, significant differences were found between the two groups (P<0.05. Conclusion: There was a significant correlation between the 145 locus of the gp89 gene and coronary atherosclerotic heart disease, indexes of blood fat, blood glucose and blood pressure. Keywords: blood fat, blood glucose, blood pressure, coronary sclerosis, heart disease

Correlation between Gene Expression and Osteoarthritis Progression in Human

Directory of Open Access Journals (Sweden)

Leilei Zhong

2016-07-01

Full Text Available Osteoarthritis (OA is a multifactorial disease characterized by gradual degradation of joint cartilage. This study aimed to quantify major pathogenetic factors during OA progression in human cartilage. Cartilage specimens were isolated from OA patients and scored 0–5 according to the Osteoarthritis Research Society International (OARSI guidelines. Protein and gene expressions were measured by immunohistochemistry and qPCR, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assays were used to detect apoptotic cells. Cartilage degeneration in OA is a gradual progress accompanied with gradual loss of collagen type II and a gradual decrease in mRNA expression of SOX9, ACAN and COL2A1. Expression of WNT antagonists DKK1 and FRZB was lost, while hypertrophic markers (RUNX2, COL10A1 and IHH increased during OA progression. Moreover, DKK1 and FRZB negatively correlated with OA grading, while RUNX2 and IHH showed a significantly positive correlation with OA grading. The number of apoptotic cells was increased with the severity of OA. Taken together, our results suggested that genetic profiling of the gene expression could be used as markers for staging OA at the molecular level. This helps to understand the molecular pathology of OA and may lead to the development of therapies based on OA stage.

Comparison of Subset-Based Local and Finite Element-Based Global Digital Image Correlation

KAUST Repository

Pan, Bing; Wang, B.; Lubineau, Gilles; Moussawi, Ali

2015-01-01

Digital image correlation (DIC) techniques require an image matching algorithm to register the same physical points represented in different images. Subset-based local DIC and finite element-based (FE-based) global DIC are the two primary image matching methods that have been extensively investigated and regularly used in the field of experimental mechanics. Due to its straightforward implementation and high efficiency, subset-based local DIC has been used in almost all commercial DIC packages. However, it is argued by some researchers that FE-based global DIC offers better accuracy because of the enforced continuity between element nodes. We propose a detailed performance comparison between these different DIC algorithms both in terms of measurement accuracy and computational efficiency. Then, by measuring displacements of the same calculation points using the same calculation algorithms (e.g., correlation criterion, initial guess estimation, subpixel interpolation, optimization algorithm and convergence conditions) and identical calculation parameters (e.g., subset or element size), the performances of subset-based local DIC and two FE-based global DIC approaches are carefully compared in terms of measurement error and computational efficiency using both numerical tests and real experiments. A detailed examination of the experimental results reveals that, when subset (element) size is not very small and the local deformation within a subset (element) can be well approximated by the shape function used, standard subset-based local DIC approach not only provides better results in measured displacements, but also demonstrates much higher computation efficiency. However, several special merits of FE-based global DIC approaches are indicated.

Comparison of Subset-Based Local and Finite Element-Based Global Digital Image Correlation

KAUST Repository

Pan, Bing

2015-02-12

Digital image correlation (DIC) techniques require an image matching algorithm to register the same physical points represented in different images. Subset-based local DIC and finite element-based (FE-based) global DIC are the two primary image matching methods that have been extensively investigated and regularly used in the field of experimental mechanics. Due to its straightforward implementation and high efficiency, subset-based local DIC has been used in almost all commercial DIC packages. However, it is argued by some researchers that FE-based global DIC offers better accuracy because of the enforced continuity between element nodes. We propose a detailed performance comparison between these different DIC algorithms both in terms of measurement accuracy and computational efficiency. Then, by measuring displacements of the same calculation points using the same calculation algorithms (e.g., correlation criterion, initial guess estimation, subpixel interpolation, optimization algorithm and convergence conditions) and identical calculation parameters (e.g., subset or element size), the performances of subset-based local DIC and two FE-based global DIC approaches are carefully compared in terms of measurement error and computational efficiency using both numerical tests and real experiments. A detailed examination of the experimental results reveals that, when subset (element) size is not very small and the local deformation within a subset (element) can be well approximated by the shape function used, standard subset-based local DIC approach not only provides better results in measured displacements, but also demonstrates much higher computation efficiency. However, several special merits of FE-based global DIC approaches are indicated.

Succinate production positively correlates with the affinity of the global transcription factor Cra for its effector FBP in Escherichia coli.

Science.gov (United States)

Wei, Li-Na; Zhu, Li-Wen; Tang, Ya-Jie

2016-01-01

Effector binding is important for transcription factors, affecting both the pattern and function of transcriptional regulation to alter cell phenotype. Our previous work suggested that the affinity of the global transcription factor catabolite repressor/activator (Cra) for its effector fructose-1,6-bisphosphate (FBP) may contribute to succinate biosynthesis. To support this hypothesis, single-point and three-point mutations were proposed through the semi-rational design of Cra to improve its affinity for FBP. For the first time, a positive correlation between succinate production and the affinity of Cra for FBP was revealed in Escherichia coli . Using the best-fit regression function, a cubic equation was used to examine and describe the relationship between succinate production and the affinity of Cra for FBP, demonstrating a significant positive correlation between the two factors (coefficient of determination R 2  = 0.894, P  = 0.000 Cra and DNA showed that Cra bound to the promoter regions of pck and aceB to activate the corresponding genes. Normally, Cra-regulated operons under positive control are deactivated in the presence of FBP. Therefore, theoretically, the enhanced affinity of Cra for FBP will inhibit the activation of pck and aceB . However, the activation of genes involved in CO 2 fixation and the glyoxylate pathway was further improved by the Cra mutant, ultimately contributing to succinate biosynthesis. Enhanced binding of Cra to FBP or active site mutations may eliminate the repressive effect caused by FBP, thus leading to increased activation of genes associated with succinate biosynthesis in the Cra mutant. This work demonstrates an important transcriptional regulation strategy in the metabolic engineering of succinate production and provides useful information for better understanding of the regulatory mechanisms of transcription factors.

Does the correlation between solar cycle lengths and Northern Hemisphere land temperatures rule out any significant global warming from greenhouse gases?

DEFF Research Database (Denmark)

Laut, Peter; Gundermann, Jesper

1998-01-01

Since the discovery of a striking correlation between solar cycle lengths and Northern Hemisphere land temperatures there have been widespread speculations as to whether these findings would rule out any significant contributions to global warming from the enhanced concentrations of greenhouse...... gases. The present analysis shows that a similar degree of correlation is obtained when testing the solar data against a couple of fictitious temperature series representing different global warming trends. Therefore, the correlation cannot be used to estimate the magnitude of a possible contribution...... to global warming from human activities, nor to rule out a sizable contribution from that source....

Global changes in Staphylococcus aureus gene expression during human prosthetic joint infection

DEFF Research Database (Denmark)

Xu, Yijuan; Nielsen, Per Halkjær; Nielsen, Jeppe Lund

2016-01-01

and Environmental Engineering, Aalborg University, Denmark 2: Danish Technological Institute, Aarhus, Denmark Aim: ”The aim of this study was to gain insight into the in vivo expression of virulence and metabolic genes of Staphylococcus aureus in a prosthetic joint infection in a human subject” Method: ”Deep RNA......Global changes in Staphylococcus aureus gene expression during human prosthetic joint infection Xu, Yijuan1; Nielsen, Per H.1; Nielsen, Jeppe L.1; Thomsen, Trine R. 1,2; Nielsen, Kåre L.1 and the PRIS study group 1: Center for Microbial Communities, Department of Biotechnology, Chemistry...... involved overexpression of various enzymes related to cell-wall synthesis and multidrug efflux pumps. Interestingly, these efflux pumps are only known to be related to fluoroquinolone resistance. Many of the genes encoding virulence factors were upregulated, including toxins and superantigen-like proteins...

Global gene expression in cotton (Gossypium hirsutum L. leaves to waterlogging stress.

Directory of Open Access Journals (Sweden)

Yanjun Zhang

Full Text Available Cotton is sensitive to waterlogging stress, which usually results in stunted growth and yield loss. To date, the molecular mechanisms underlying the responses to waterlogging in cotton remain elusive. Cotton was grown in a rain-shelter and subjected to 0 (control-, 10-, 15- and 20-d waterlogging at flowering stage. The fourth-leaves on the main-stem from the top were sampled and immediately frozen in liquid nitrogen for physiological measurement. Global gene transcription in the leaves of 15-d waterlogged plants was analyzed by RNA-Seq. Seven hundred and ninety four genes were up-regulated and 1018 genes were down-regulated in waterlogged cotton leaves compared with non-waterlogged control. The differentially expressed genes were mainly related to photosynthesis, nitrogen metabolism, starch and sucrose metabolism, glycolysis and plant hormone signal transduction. KEGG (Kyoto Encyclopedia of Genes and Genomes analysis indicated that most genes related to flavonoid biosynthesis, oxidative phosphorylation, amino acid metabolism and biosynthesis as well as circadian rhythm pathways were differently expressed. Waterlogging increased the expression of anaerobic fermentation related genes, such as alcohol dehydrogenase (ADH, but decreased the leaf chlorophyll concentration and photosynthesis by down-regulating the expression of photosynthesis related genes. Many genes related to plant hormones and transcription factors were differently expressed under waterlogging stress. Most of the ethylene related genes and ethylene-responsive factor-type transcription factors were up-regulated under water-logging stress, suggesting that ethylene may play key roles in the survival of cotton under waterlogging stress.

Global gene expression profile progression in Gaucher disease mouse models

Directory of Open Access Journals (Sweden)

Zhang Wujuan

2011-01-01

Full Text Available Abstract Background Gaucher disease is caused by defective glucocerebrosidase activity and the consequent accumulation of glucosylceramide. The pathogenic pathways resulting from lipid laden macrophages (Gaucher cells in visceral organs and their abnormal functions are obscure. Results To elucidate this pathogenic pathway, developmental global gene expression analyses were conducted in distinct Gba1 point-mutated mice (V394L/V394L and D409 V/null. About 0.9 to 3% of genes had altered expression patterns (≥ ± 1.8 fold change, representing several categories, but particularly macrophage activation and immune response genes. Time course analyses (12 to 28 wk of INFγ-regulated pro-inflammatory (13 and IL-4-regulated anti-inflammatory (11 cytokine/mediator networks showed tissue differential profiles in the lung and liver of the Gba1 mutant mice, implying that the lipid-storage macrophages were not functionally inert. The time course alterations of the INFγ and IL-4 pathways were similar, but varied in degree in these tissues and with the Gba1 mutation. Conclusions Biochemical and pathological analyses demonstrated direct relationships between the degree of tissue glucosylceramides and the gene expression profile alterations. These analyses implicate IFNγ-regulated pro-inflammatory and IL-4-regulated anti-inflammatory networks in differential disease progression with implications for understanding the Gaucher disease course and pathophysiology.

[Correlation analysis of G870A CCND1 gene polymorphism with digestive system tumors].

Science.gov (United States)

Yang, Shu-Min; Shi, Ya-Lin

2016-11-20

To study the correlation of G870A CCND1 gene polymorphism and digestive system tumors. From August 2010 to August 2014, 164 digestive system cancer patients (including 82 patients with gastric cancer and 82 with colorectal cancer) and 82 healthy subjects (control group) were examined with PCR-restriction fragment length polymorphism (PCR-RFLP). The distribution of CCND1 gene G870A frequency in the 3 groups and its association with tumor staging and grading were analyzed. The frequencies of the GG, GA and AA genotypes in G870A CCND1 gene loci in patients with gastric cancer and colorectal cancer differed significantly from those in the control group (Pdigestive system tumors (Pdigestive system cancer risk than the GG genotype (Pdigestive system tumors. The allele A is associated with an increased risk of digestive system tumors and correlated with the tumor differentiation and staging of the tumor.

Impact of elevated plasma serotonin on global gene expression of murine megakaryocytes.

Directory of Open Access Journals (Sweden)

Charles P Mercado

Full Text Available Serotonin (5-HT is a biogenic amine that also acts as a mitogen and a developmental signal early in rodent embryogenesis. Genetic and pharmacological disruption of 5-HT signaling causes various diseases and disorders via mediating central nervous system, cardiovascular system, and serious abnormalities on a growing embryo. Today, neither the effective modulators on 5-HT signaling pathways nor the genes affected by 5-HT signal are well known yet.In an attempt to identify the genes altered by 5-HT signaling pathways, we analyzed the global gene expression via the Illumina array platform using the mouse WG-6 v2.0 Expression BeadChip containing 45,281 probe sets representing 30,854 genes in megakaryocytes isolated from mice infused with 5-HT or saline. We identified 723 differentially expressed genes of which 706 were induced and 17 were repressed by elevated plasma 5-HT.Hierarchical gene clustering analysis was utilized to represent relations between groups and clusters. Using gene ontology mining tools and canonical pathway analyses, we identified multiple biological pathways that are regulated by 5-HT: (i cytoskeletal remodeling, (ii G-protein signaling, (iii vesicular transport, and (iv apoptosis and survival. Our data encompass the first extensive genome-wide based profiling in the progenitors of platelets in response to 5-HT elevation in vivo.

Genes located in a chromosomal inversion are correlated with territorial song in white-throated sparrows.

Science.gov (United States)

Zinzow-Kramer, W M; Horton, B M; McKee, C D; Michaud, J M; Tharp, G K; Thomas, J W; Tuttle, E M; Yi, S; Maney, D L

2015-11-01

The genome of the white-throated sparrow (Zonotrichia albicollis) contains an inversion polymorphism on chromosome 2 that is linked to predictable variation in a suite of phenotypic traits including plumage color, aggression and parental behavior. Differences in gene expression between the two color morphs, which represent the two common inversion genotypes (ZAL2/ZAL2 and ZAL2/ZAL2(m) ), may therefore advance our understanding of the molecular underpinnings of these phenotypes. To identify genes that are differentially expressed between the two morphs and correlated with behavior, we quantified gene expression and terrirorial aggression, including song, in a population of free-living white-throated sparrows. We analyzed gene expression in two brain regions, the medial amygdala (MeA) and hypothalamus. Both regions are part of a 'social behavior network', which is rich in steroid hormone receptors and previously linked with territorial behavior. Using weighted gene co-expression network analyses, we identified modules of genes that were correlated with both morph and singing behavior. The majority of these genes were located within the inversion, showing the profound effect of the inversion on the expression of genes captured by the rearrangement. These modules were enriched with genes related to retinoic acid signaling and basic cellular functioning. In the MeA, the most prominent pathways were those related to steroid hormone receptor activity. Within these pathways, the only gene encoding such a receptor was ESR1 (estrogen receptor 1), a gene previously shown to predict song rate in this species. The set of candidate genes we identified may mediate the effects of a chromosomal inversion on territorial behavior. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Correlation measure to detect time series distances, whence economy globalization

Science.gov (United States)

Miśkiewicz, Janusz; Ausloos, Marcel

2008-11-01

An instantaneous time series distance is defined through the equal time correlation coefficient. The idea is applied to the Gross Domestic Product (GDP) yearly increments of 21 rich countries between 1950 and 2005 in order to test the process of economic globalisation. Some data discussion is first presented to decide what (EKS, GK, or derived) GDP series should be studied. Distances are then calculated from the correlation coefficient values between pairs of series. The role of time averaging of the distances over finite size windows is discussed. Three network structures are next constructed based on the hierarchy of distances. It is shown that the mean distance between the most developed countries on several networks actually decreases in time, -which we consider as a proof of globalization. An empirical law is found for the evolution after 1990, similar to that found in flux creep. The optimal observation time window size is found ≃15 years.

The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma.

Directory of Open Access Journals (Sweden)

Fumiharu Ohka

Full Text Available Gliomas are the most frequently occurring primary brain tumor in the central nervous system of adults. Glioblastoma multiformes (GBMs, WHO grade 4 have a dismal prognosis despite the use of the alkylating agent, temozolomide (TMZ, and even low grade gliomas (LGGs, WHO grade 2 eventually transform to malignant secondary GBMs. Although GBM patients benefit from promoter hypermethylation of the O(6-methylguanine-DNA methyltransferase (MGMT that is the main determinant of resistance to TMZ, recent studies suggested that MGMT promoter methylation is of prognostic as well as predictive significance for the efficacy of TMZ. Glioma-CpG island methylator phenotype (G-CIMP in the global genome was shown to be a significant predictor of improved survival in patients with GBM. Collectively, we hypothesized that MGMT promoter methylation might reflect global DNA methylation. Additionally in LGGs, the significance of MGMT promoter methylation is still undetermined. In the current study, we aimed to determine the correlation between clinical, genetic, and epigenetic profiles including LINE-1 and different cancer-related genes and the clinical outcome in newly diagnosed 57 LGG and 54 GBM patients. Here, we demonstrated that (1 IDH1/2 mutation is closely correlated with MGMT promoter methylation and 1p/19q codeletion in LGGs, (2 LINE-1 methylation levels in primary and secondary GBMs are lower than those in LGGs and normal brain tissues, (3 LINE-1 methylation is proportional to MGMT promoter methylation in gliomas, and (4 higher LINE-1 methylation is a favorable prognostic factor in primary GBMs, even compared to MGMT promoter methylation. As a global DNA methylation marker, LINE-1 may be a promising marker in gliomas.

Promoter Analysis Reveals Globally Differential Regulation of Human Long Non-Coding RNA and Protein-Coding Genes

KAUST Repository

Alam, Tanvir

2014-10-02

Transcriptional regulation of protein-coding genes is increasingly well-understood on a global scale, yet no comparable information exists for long non-coding RNA (lncRNA) genes, which were recently recognized to be as numerous as protein-coding genes in mammalian genomes. We performed a genome-wide comparative analysis of the promoters of human lncRNA and protein-coding genes, finding global differences in specific genetic and epigenetic features relevant to transcriptional regulation. These two groups of genes are hence subject to separate transcriptional regulatory programs, including distinct transcription factor (TF) proteins that significantly favor lncRNA, rather than coding-gene, promoters. We report a specific signature of promoter-proximal transcriptional regulation of lncRNA genes, including several distinct transcription factor binding sites (TFBS). Experimental DNase I hypersensitive site profiles are consistent with active configurations of these lncRNA TFBS sets in diverse human cell types. TFBS ChIP-seq datasets confirm the binding events that we predicted using computational approaches for a subset of factors. For several TFs known to be directly regulated by lncRNAs, we find that their putative TFBSs are enriched at lncRNA promoters, suggesting that the TFs and the lncRNAs may participate in a bidirectional feedback loop regulatory network. Accordingly, cells may be able to modulate lncRNA expression levels independently of mRNA levels via distinct regulatory pathways. Our results also raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed lncRNA genes is warranted in the future.

The global relationship between chromatin physical topology, fractal structure, and gene expression

DEFF Research Database (Denmark)

Almassalha, Luay M; Tiwari, A; Ruhoff, P T

2017-01-01

in an empty space, but in a highly complex, interrelated, and dense nanoenvironment that profoundly influences chemical interactions. We explored the relationship between the physical nanoenvironment of chromatin and gene transcription in vitro. We analytically show that changes in the fractal dimension, D...... show that the increased heterogeneity of physical structure of chromatin due to increase in fractal dimension correlates with increased heterogeneity of gene networks. These findings indicate that the higher order folding of chromatin topology may act as a molecular-pathway independent code regulating...

Gene activation by UV light, fungal elicitor or fungal infection in Petroselinum crispum is correlated with repression of cell cycle-related genes

International Nuclear Information System (INIS)

Logemann, E.; Wu ShengCheng; Schröder, J.; Schmelzer, E.; Somssich, I.E.; Hahlbrock, K.

1995-01-01

The effects of UV light or fungal elicitors on plant cells have so far been studied mostly with respect to defense-related gene activation. Here, an inverse correlation of these stimulatory effects with the activities of several cell cycle-related genes is demonstrated. Concomitant with the induction of flavonoid biosynthetic enzymes in UV-irradiated cell suspension cultures of parsley (Petroselinum crispum), total histone synthesis declined to about half the initial rate. A subclass of the histone H3 gene family was selected to demonstrate the close correlation of its expression with cell division, both in intact plants and cultured cells. Using RNA-blot and run-on transcription assays, it was shown that one arbitrarily selected subclass of each of the histone H2A, H2B, H3 and H4 gene families and of the genes encoding a p34cdc2 protein kinase and a mitotic cyclin were transcriptionally repressed in UV-irradiated as well as fungal elicitor-treated parsley cells. The timing and extent of repression differed between the two stimuli; the response to light was more transient and smaller in magnitude. These differential responses to light and elicitor were inversely correlated with the induction of phenylalanine ammonia-lyase, a key enzyme of phenylpropanoid metabolism. Essentially the same result was obtained with a defined oligopeptide elicitor, indicating that the same signaling pathway is responsible for defense-related gene activation and cell cycle-related gene repression. A temporary (UV light) or long-lasting (fungal elicitor) cessation of cell culture growth is most likely due to an arrest of cell division which may be a prerequisite for full commitment of the cells to transcriptional activation of full commitment of the cells to transcriptional activation of pathways involved in UV protection or pathogen defense. This conclusion is corroborated by the observation that the histone H3 mRNA level greatly declined around fungal infection sites in young parsley

Rate variation in parasitic plants: correlated and uncorrelated patterns among plastid genes of different function

Directory of Open Access Journals (Sweden)

dePamphilis Claude W

2005-02-01

Full Text Available Abstract Background The analysis of synonymous and nonsynonymous rates of DNA change can help in the choice among competing explanations for rate variation, such as differences in constraint, mutation rate, or the strength of genetic drift. Nonphotosynthetic plants of the Orobanchaceae have increased rates of DNA change. In this study 38 taxa of Orobanchaceae and relatives were used and 3 plastid genes were sequenced for each taxon. Results Phylogenetic reconstructions of relative rates of sequence evolution for three plastid genes (rbcL, matK and rps2 show significant rate heterogeneity among lineages and among genes. Many of the non-photosynthetic plants have increases in both synonymous and nonsynonymous rates, indicating that both (1 selection is relaxed, and (2 there has been a change in the rate at which mutations are entering the population in these species. However, rate increases are not always immediate upon loss of photosynthesis. Overall there is a poor correlation of synonymous and nonsynonymous rates. There is, however, a strong correlation of synonymous rates across the 3 genes studied and the lineage-speccific pattern for each gene is strikingly similar. This indicates that the causes of synonymous rate variation are affecting the whole plastid genome in a similar way. There is a weaker correlation across genes for nonsynonymous rates. Here the picture is more complex, as could be expected if there are many causes of variation, differing from taxon to taxon and gene to gene. Conclusions The distinctive pattern of rate increases in Orobanchaceae has at least two causes. It is clear that there is a relaxation of constraint in many (though not all non-photosynthetic lineages. However, there is also some force affecting synonymous sites as well. At this point, it is not possible to tell whether it is generation time, speciation rate, mutation rate, DNA repair efficiency or some combination of these factors.

Heritability of growth traits and correlation with hepatic gene expression among hybrid striped bass exhibiting extremes in performance

Science.gov (United States)

We set out to better understand the genetic basis behind growth variation in hybrid striped bass (HSB) by determining whether gene expression changes could be detected between the largest and smallest HSB in a population using a global gene expression approach by RNA sequencing of liver. Fingerling...

Global sensitivity analysis of a dynamic model for gene expression in Drosophila embryos

Science.gov (United States)

McCarthy, Gregory D.; Drewell, Robert A.

2015-01-01

It is well known that gene regulation is a tightly controlled process in early organismal development. However, the roles of key processes involved in this regulation, such as transcription and translation, are less well understood, and mathematical modeling approaches in this field are still in their infancy. In recent studies, biologists have taken precise measurements of protein and mRNA abundance to determine the relative contributions of key factors involved in regulating protein levels in mammalian cells. We now approach this question from a mathematical modeling perspective. In this study, we use a simple dynamic mathematical model that incorporates terms representing transcription, translation, mRNA and protein decay, and diffusion in an early Drosophila embryo. We perform global sensitivity analyses on this model using various different initial conditions and spatial and temporal outputs. Our results indicate that transcription and translation are often the key parameters to determine protein abundance. This observation is in close agreement with the experimental results from mammalian cells for various initial conditions at particular time points, suggesting that a simple dynamic model can capture the qualitative behavior of a gene. Additionally, we find that parameter sensitivites are temporally dynamic, illustrating the importance of conducting a thorough global sensitivity analysis across multiple time points when analyzing mathematical models of gene regulation. PMID:26157608

Global gene expression response to telomerase in bovine adrenocortical cells

International Nuclear Information System (INIS)

Perrault, Steven D.; Hornsby, Peter J.; Betts, Dean H.

2005-01-01

The infinite proliferative capability of most immortalized cells is dependent upon the presence of the enzyme telomerase and its ability to maintain telomere length and structure. However, telomerase may be involved in a greater system than telomere length regulation, as recent evidence has shown it capable of increasing wound healing in vivo, and improving cellular proliferation rate and survival from apoptosis in vitro. Here, we describe the global gene expression response to ectopic telomerase expression in an in vitro bovine adrenocortical cell model. Telomerase-immortalized cells showed an increased ability for proliferation and survival in minimal essential medium above cells transgenic for GFP. cDNA microarray analyses revealed an altered cell state indicative of increased adrenocortical cell proliferation regulated by the IGF2 pathway and alterations in members of the TGF-B family. As well, we identified alterations in genes associated with development and wound healing that support a model that high telomerase expression induces a highly adaptable, progenitor-like state

Distinct differences in global gene expression profiles in non-implanted blastocysts and blastocysts resulting in live birth

DEFF Research Database (Denmark)

Kirkegaard, Kirstine Kjær; Fredsted, Palle Villesen; Jensen, Jacob Malte

2015-01-01

Results from animal models points towards the existence of a gene expression profile that is distinguishably different in viable embryos compared with non-viable embryos. Knowledge of human embryo transcripts is however limited, in particular with regard to how gene expression is related...... to clinical outcome. The purpose of the present study was therefore to determine the global gene expression profiles of human blastocysts. Next Generation Sequencing was used to identify genes that were differentially expressed in non-implanted embryos and embryos resulting in live birth. Three trophectoderm...

Correlating Mediterranean shallow water deposits with global Oligocene–Miocene stratigraphy and oceanic events☆

Science.gov (United States)

Reuter, Markus; Piller, Werner E.; Brandano, Marco; Harzhauser, Mathias

2013-01-01

Shallow-marine sediment records have the strong potential to display sensitive environmental changes in sedimentary geometries and skeletal content. However, the time resolution of most neritic carbonate records is not high enough to be compared with climatic events as recorded in the deep-sea sediment archives. In order to resolve the paleoceanographic and paleoclimatic changes during the Oligocene–Miocene transition in the Mediterranean shallow water carbonate systems with the best possible time resolution, we re-evaluated the Decontra section on the Maiella Platform (central Apennines, Italy), which acts as a reference for the correlation of Oligocene–Miocene shallow water deposits in the Mediterranean region. The 120-m-thick late Oligocene–late Miocene carbonate succession is composed of larger foraminiferal, bryozoan and corallinacean limestones interlayered with distinct planktonic foraminiferal carbonates representing a mostly outer neritic setting. Integrated multi-proxy and facies analyses indicate that CaCO3 and total organic carbon contents as well as gamma-ray display only local to regional processes on the carbonate platform and are not suited for stratigraphic correlation on a wider scale. In contrast, new biostratigraphic data correlate the Decontra stable carbon isotope record to the global deep-sea carbon isotope record. This links relative sea level fluctuations, which are reflected by facies and magnetic susceptibility changes, to third-order eustatic cycles. The new integrated bio-, chemo-, and sequence stratigraphic framework enables a more precise timing of environmental changes within the studied time interval and identifies Decontra as an important locality for correlating not only shallow and deep water sediments of the Mediterranean region but also on a global scale. PMID:25844021

Correlating Mediterranean shallow water deposits with global Oligocene-Miocene stratigraphy and oceanic events.

Science.gov (United States)

Reuter, Markus; Piller, Werner E; Brandano, Marco; Harzhauser, Mathias

2013-12-01

Shallow-marine sediment records have the strong potential to display sensitive environmental changes in sedimentary geometries and skeletal content. However, the time resolution of most neritic carbonate records is not high enough to be compared with climatic events as recorded in the deep-sea sediment archives. In order to resolve the paleoceanographic and paleoclimatic changes during the Oligocene-Miocene transition in the Mediterranean shallow water carbonate systems with the best possible time resolution, we re-evaluated the Decontra section on the Maiella Platform (central Apennines, Italy), which acts as a reference for the correlation of Oligocene-Miocene shallow water deposits in the Mediterranean region. The 120-m-thick late Oligocene-late Miocene carbonate succession is composed of larger foraminiferal, bryozoan and corallinacean limestones interlayered with distinct planktonic foraminiferal carbonates representing a mostly outer neritic setting. Integrated multi-proxy and facies analyses indicate that CaCO 3 and total organic carbon contents as well as gamma-ray display only local to regional processes on the carbonate platform and are not suited for stratigraphic correlation on a wider scale. In contrast, new biostratigraphic data correlate the Decontra stable carbon isotope record to the global deep-sea carbon isotope record. This links relative sea level fluctuations, which are reflected by facies and magnetic susceptibility changes, to third-order eustatic cycles. The new integrated bio-, chemo-, and sequence stratigraphic framework enables a more precise timing of environmental changes within the studied time interval and identifies Decontra as an important locality for correlating not only shallow and deep water sediments of the Mediterranean region but also on a global scale.

Orientation, distance, regulation and function of neighbouring genes

Directory of Open Access Journals (Sweden)

Gherman Adrian

2009-01-01

Full Text Available Abstract The sequencing of the human genome has allowed us to observe globally and in detail the arrangement of genes along the chromosomes. There are multiple lines of evidence that this arrangement is not random, both in terms of intergenic distances and orientation of neighbouring genes. We have undertaken a systematic evaluation of the spatial distribution and orientation of known genes across the human genome. We used genome-level information, including phylogenetic conservation, single nucleotide polymorphism density and correlation of gene expression to assess the importance of this distribution. In addition to confirming and extending known properties of the genome, such as the significance of gene deserts and the importance of 'head to head' orientation of gene pairs in proximity, we provide significant new observations that include a smaller average size for intervals separating the 3' ends of neighbouring genes, a correlation of gene expression across tissues for genes as far as 100 kilobases apart and signatures of increasing positive selection with decreasing interval size surprisingly relaxing for intervals smaller than ~500 base pairs. Further, we provide extensive graphical representations of the genome-wide data to allow for observations and comparisons beyond what we address.

Global ozone–CO correlations from OMI and AIRS: constraints on tropospheric ozone sources

Directory of Open Access Journals (Sweden)

P. S. Kim

2013-09-01

Full Text Available We present a global data set of free tropospheric ozone–CO correlations with 2° × 2.5° spatial resolution from the Ozone Monitoring Instrument (OMI and Atmospheric Infrared Sounder (AIRS satellite instruments for each season of 2008. OMI and AIRS have near-daily global coverage of ozone and CO respectively and observe coincident scenes with similar vertical sensitivities. The resulting ozone–CO correlations are highly statistically significant (positive or negative in most regions of the world, and are less noisy than previous satellite-based studies that used sparser data. Comparison with ozone–CO correlations and regression slopes (dO3/dCO from MOZAIC (Measurements of OZone, water vapour, carbon monoxide and nitrogen oxides by in-service AIrbus airCraft aircraft profiles shows good general agreement. We interpret the observed ozone–CO correlations with the GEOS (Goddard Earth Observing System-Chem chemical transport model to infer constraints on ozone sources. Driving GEOS-Chem with different meteorological fields generally shows consistent ozone–CO correlation patterns, except in some tropical regions where the correlations are strongly sensitive to model transport error associated with deep convection. GEOS-Chem reproduces the general structure of the observed ozone–CO correlations and regression slopes, although there are some large regional discrepancies. We examine the model sensitivity of dO3/dCO to different ozone sources (combustion, biosphere, stratosphere, and lightning NOx by correlating the ozone change from that source to CO from the standard simulation. The model reproduces the observed positive dO3/dCO in the extratropical Northern Hemisphere in spring–summer, driven by combustion sources. Stratospheric influence there is also associated with a positive dO3/dCO because of the interweaving of stratospheric downwelling with continental outflow. The well-known ozone maximum over the tropical South Atlantic is

Thanatophoric dysplasia. Correlation among bone X-ray morphometry, histopathology, and gene analysis

International Nuclear Information System (INIS)

Pazzaglia, Ugo E.; Donzelli, Carla M.; Izzi, Claudia; Baldi, Maurizia; Di Gaetano, Giuseppe; Bondioni, MariaPia

2014-01-01

Documentation through X-ray morphometry and histology of the steady phenotype expressed by FGFR3 gene mutation and interpolation of mechanical factors on spine and long bones dysmorphism. Long bones and spine of eight thanatophoric dysplasia and three age-matched controls without skeletal dysplasia were studied after pregnancy termination between the 18th and the 22nd week with X-ray morphometry, histology, and molecular analysis. Statistical analysis with comparison between TD cases and controls and intraobserver/interobserver variation were applied to X-ray morphometric data. Generalized shortening of long bones was observed in TD. A variable distribution of axial deformities was correlated with chondrocyte proliferation inhibition, defective seriate cell columns organization, and final formation of the primary metaphyseal trabeculae. The periosteal longitudinal growth was not equally inhibited, so that decoupling with the cartilage growth pattern produced the typical lateral spurs around the metaphyseal growth plates. In spine, platyspondyly was due to a reduced height of the vertebral body anterior ossification center, while its enlargement in the transversal plane was not restricted. The peculiar radiographic and histopathological features of TD bones support the hypothesis of interpolation of mechanical factors with FGFR3 gene mutations. The correlated observations of X-ray morphometry, histopathology, and gene analysis prompted the following diagnostic workup for TD: (1) prenatal sonography suspicion of skeletal dysplasia; (2) post-mortem X-ray morphometry for provisional diagnosis; (3) confirmation by genetic tests (hot-spot exons 7, 10, 15, and 19 analysis with 80-90 % sensibility); (4) in negative cases if histopathology confirms TD diagnosis, research of rare mutations through sequential analysis of FGFR3 gene. (orig.)

Thanatophoric dysplasia. Correlation among bone X-ray morphometry, histopathology, and gene analysis

Energy Technology Data Exchange (ETDEWEB)

Pazzaglia, Ugo E. [University of Brescia, Orthopaedic Clinic, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Brescia (Italy); Donzelli, Carla M. [Spedali Civili di Brescia, Morbid Anatomy Department, Brescia (Italy); Izzi, Claudia [University of Brescia, Prenatal Diagnosis Unit, Department of Obstetrics and Gynaecology, Brescia (Italy); Baldi, Maurizia [Hospital Galliera, Human Genetic Laboratory, Genova (Italy); Di Gaetano, Giuseppe; Bondioni, MariaPia [University of Brescia, Paediatric Radiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Brescia (Italy)

2014-09-15

Documentation through X-ray morphometry and histology of the steady phenotype expressed by FGFR3 gene mutation and interpolation of mechanical factors on spine and long bones dysmorphism. Long bones and spine of eight thanatophoric dysplasia and three age-matched controls without skeletal dysplasia were studied after pregnancy termination between the 18th and the 22nd week with X-ray morphometry, histology, and molecular analysis. Statistical analysis with comparison between TD cases and controls and intraobserver/interobserver variation were applied to X-ray morphometric data. Generalized shortening of long bones was observed in TD. A variable distribution of axial deformities was correlated with chondrocyte proliferation inhibition, defective seriate cell columns organization, and final formation of the primary metaphyseal trabeculae. The periosteal longitudinal growth was not equally inhibited, so that decoupling with the cartilage growth pattern produced the typical lateral spurs around the metaphyseal growth plates. In spine, platyspondyly was due to a reduced height of the vertebral body anterior ossification center, while its enlargement in the transversal plane was not restricted. The peculiar radiographic and histopathological features of TD bones support the hypothesis of interpolation of mechanical factors with FGFR3 gene mutations. The correlated observations of X-ray morphometry, histopathology, and gene analysis prompted the following diagnostic workup for TD: (1) prenatal sonography suspicion of skeletal dysplasia; (2) post-mortem X-ray morphometry for provisional diagnosis; (3) confirmation by genetic tests (hot-spot exons 7, 10, 15, and 19 analysis with 80-90 % sensibility); (4) in negative cases if histopathology confirms TD diagnosis, research of rare mutations through sequential analysis of FGFR3 gene. (orig.)

Intergenic DNA sequences from the human X chromosome reveal high rates of global gene flow

Directory of Open Access Journals (Sweden)

Wall Jeffrey D

2008-11-01

Full Text Available Abstract Background Despite intensive efforts devoted to collecting human polymorphism data, little is known about the role of gene flow in the ancestry of human populations. This is partly because most analyses have applied one of two simple models of population structure, the island model or the splitting model, which make unrealistic biological assumptions. Results Here, we analyze 98-kb of DNA sequence from 20 independently evolving intergenic regions on the X chromosome in a sample of 90 humans from six globally diverse populations. We employ an isolation-with-migration (IM model, which assumes that populations split and subsequently exchange migrants, to independently estimate effective population sizes and migration rates. While the maximum effective size of modern humans is estimated at ~10,000, individual populations vary substantially in size, with African populations tending to be larger (2,300–9,000 than non-African populations (300–3,300. We estimate mean rates of bidirectional gene flow at 4.8 × 10-4/generation. Bidirectional migration rates are ~5-fold higher among non-African populations (1.5 × 10-3 than among African populations (2.7 × 10-4. Interestingly, because effective sizes and migration rates are inversely related in African and non-African populations, population migration rates are similar within Africa and Eurasia (e.g., global mean Nm = 2.4. Conclusion We conclude that gene flow has played an important role in structuring global human populations and that migration rates should be incorporated as critical parameters in models of human demography.

Global Gene-Expression Analysis to Identify Differentially Expressed Genes Critical for the Heat Stress Response in Brassica rapa.

Directory of Open Access Journals (Sweden)

Xiangshu Dong

Full Text Available Genome-wide dissection of the heat stress response (HSR is necessary to overcome problems in crop production caused by global warming. To identify HSR genes, we profiled gene expression in two Chinese cabbage inbred lines with different thermotolerances, Chiifu and Kenshin. Many genes exhibited >2-fold changes in expression upon exposure to 0.5- 4 h at 45°C (high temperature, HT: 5.2% (2,142 genes in Chiifu and 3.7% (1,535 genes in Kenshin. The most enriched GO (Gene Ontology items included 'response to heat', 'response to reactive oxygen species (ROS', 'response to temperature stimulus', 'response to abiotic stimulus', and 'MAPKKK cascade'. In both lines, the genes most highly induced by HT encoded small heat shock proteins (Hsps and heat shock factor (Hsf-like proteins such as HsfB2A (Bra029292, whereas high-molecular weight Hsps were constitutively expressed. Other upstream HSR components were also up-regulated: ROS-scavenging genes like glutathione peroxidase 2 (BrGPX2, Bra022853, protein kinases, and phosphatases. Among heat stress (HS marker genes in Arabidopsis, only exportin 1A (XPO1A (Bra008580, Bra006382 can be applied to B. rapa for basal thermotolerance (BT and short-term acquired thermotolerance (SAT gene. CYP707A3 (Bra025083, Bra021965, which is involved in the dehydration response in Arabidopsis, was associated with membrane leakage in both lines following HS. Although many transcription factors (TF genes, including DREB2A (Bra005852, were involved in HS tolerance in both lines, Bra024224 (MYB41 and Bra021735 (a bZIP/AIR1 [Anthocyanin-Impaired-Response-1] were specific to Kenshin. Several candidate TFs involved in thermotolerance were confirmed as HSR genes by real-time PCR, and these assignments were further supported by promoter analysis. Although some of our findings are similar to those obtained using other plant species, clear differences in Brassica rapa reveal a distinct HSR in this species. Our data could also provide a

Divergence and gene flow in the globally distributed blue-winged ducks

Science.gov (United States)

Nelson, Joel; Wilson, Robert E.; McCracken, Kevin G.; Cumming, Graeme; Joseph, Leo; Guay, Patrick-Jean; Peters, Jeffrey

2017-01-01

The ability to disperse over long distances can result in a high propensity for colonizing new geographic regions, including uninhabited continents, and lead to lineage diversification via allopatric speciation. However, high vagility can also result in gene flow between otherwise allopatric populations, and in some cases, parapatric or divergence-with-gene-flow models might be more applicable to widely distributed lineages. Here, we use five nuclear introns and the mitochondrial control region along with Bayesian models of isolation with migration to examine divergence, gene flow, and phylogenetic relationships within a cosmopolitan lineage comprising six species, the blue-winged ducks (genus Anas), which inhabit all continents except Antarctica. We found two primary sub-lineages, the globally-distributed shoveler group and the New World blue-winged/cinnamon teal group. The blue-winged/cinnamon sub-lineage is composed of sister taxa from North America and South America, and taxa with parapatric distributions are characterized by low to moderate levels of gene flow. In contrast, our data support strict allopatry for most comparisons within the shovelers. However, we found evidence of gene flow from the migratory, Holarctic northern shoveler (A. clypeata) and the more sedentary, African Cape shoveler (A. smithii) into the Australasian shoveler (A. rhynchotis), although we could not reject strict allopatry. Given the diverse mechanisms of speciation within this complex, the shovelers and blue-winged/cinnamon teals can serve as an effective model system for examining how the genome diverges under different evolutionary processes and how genetic variation is partitioned among highly dispersive taxa.

Gene regulatory networks in lactation: identification of global principles using bioinformatics

Directory of Open Access Journals (Sweden)

Pollard Katherine S

2007-11-01

Full Text Available Abstract Background The molecular events underlying mammary development during pregnancy, lactation, and involution are incompletely understood. Results Mammary gland microarray data, cellular localization data, protein-protein interactions, and literature-mined genes were integrated and analyzed using statistics, principal component analysis, gene ontology analysis, pathway analysis, and network analysis to identify global biological principles that govern molecular events during pregnancy, lactation, and involution. Conclusion Several key principles were derived: (1 nearly a third of the transcriptome fluctuates to build, run, and disassemble the lactation apparatus; (2 genes encoding the secretory machinery are transcribed prior to lactation; (3 the diversity of the endogenous portion of the milk proteome is derived from fewer than 100 transcripts; (4 while some genes are differentially transcribed near the onset of lactation, the lactation switch is primarily post-transcriptionally mediated; (5 the secretion of materials during lactation occurs not by up-regulation of novel genomic functions, but by widespread transcriptional suppression of functions such as protein degradation and cell-environment communication; (6 the involution switch is primarily transcriptionally mediated; and (7 during early involution, the transcriptional state is partially reverted to the pre-lactation state. A new hypothesis for secretory diminution is suggested – milk production gradually declines because the secretory machinery is not transcriptionally replenished. A comprehensive network of protein interactions during lactation is assembled and new regulatory gene targets are identified. Less than one fifth of the transcriptionally regulated nodes in this lactation network have been previously explored in the context of lactation. Implications for future research in mammary and cancer biology are discussed.

Selective decline of neurotrophin and neurotrophin receptor genes within CA1 pyramidal neurons and hippocampus proper: Correlation with cognitive performance and neuropathology in mild cognitive impairment and Alzheimer's disease.

Science.gov (United States)

Ginsberg, Stephen D; Malek-Ahmadi, Michael H; Alldred, Melissa J; Che, Shaoli; Elarova, Irina; Chen, Yinghua; Jeanneteau, Freddy; Kranz, Thorsten M; Chao, Moses V; Counts, Scott E; Mufson, Elliott J

2017-09-09

Hippocampal CA1 pyramidal neurons, a major component of the medial temporal lobe memory circuit, are selectively vulnerable during the progression of Alzheimer's disease (AD). The cellular mechanism(s) underlying degeneration of these neurons and the relationship to cognitive performance remains largely undefined. Here, we profiled neurotrophin and neurotrophin receptor gene expression within microdissected CA1 neurons along with regional hippocampal dissections from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), or AD using laser capture microdissection (LCM), custom-designed microarray analysis, and qPCR of CA1 subregional dissections. Gene expression levels were correlated with cognitive test scores and AD neuropathology criteria. We found a significant downregulation of several neurotrophin genes (e.g., Gdnf, Ngfb, and Ntf4) in CA1 pyramidal neurons in MCI compared to NCI and AD subjects. In addition, the neurotrophin receptor transcripts TrkB and TrkC were decreased in MCI and AD compared to NCI. Regional hippocampal dissections also revealed select neurotrophic gene dysfunction providing evidence for vulnerability within the hippocampus proper during the progression of dementia. Downregulation of several neurotrophins of the NGF family and cognate neurotrophin receptor (TrkA, TrkB, and TrkC) genes correlated with antemortem cognitive measures including the Mini-Mental State Exam (MMSE), a composite global cognitive score (GCS), and Episodic, Semantic, and Working Memory, Perceptual Speed, and Visuospatial domains. Significant correlations were found between select neurotrophic expression downregulation and neuritic plaques (NPs) and neurofibrillary tangles (NFTs), but not diffuse plaques (DPs). These data suggest that dysfunction of neurotrophin signaling complexes have profound negative sequelae within vulnerable hippocampal cell types, which play a role in mnemonic and executive dysfunction

Measurement of indicator genes using global complementary DNA (cDNA) amplification, by polyadenylic acid reverse transcriptase polymerase chain reaction (poly A RT-PCR): A feasibility study using paired samples from tissue and ductal juice in patients undergoing pancreatoduodenectomy.

Science.gov (United States)

Sanyal, Sudip; Siriwardena, Ajith K; Byers, Richard

2018-06-01

The aim of this study is to compare gene expression profiles in RNA isolated from pancreatic ductal juice with the RNA expression profiles of the same genes from matched intra-operative tissue samples from pancreatic tumours. Intra-operative sampling of pancreatic juice and collection of matched tissue samples was undertaken in patients undergoing pancreatoduodenectomy for clinically suspected pancreatic cancer and a precursor lesion, main-duct intraductal papillary mucinous neoplasm. RNA was isolated and Poly A PCR was used to globally amplify the RNA. Real-time polymerase chain reaction (RT-PCR) was used to measure expression levels of 17 genes selected from microarray studies. Spearman's rank correlation test was used to examine the relationship of gene expression between pancreatic juice and tissue. The study was approved by Regional Ethics Committee. Mesothelin (MSLN) showed significant correlation (p cDNA using poly A PCR is technically feasible. Application of the technique to non-invasively obtained pancreatic juice during endoscopic assessment of tumours and the use of gene arrays of cancer indicator genes are the next steps in development of this technique. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Expression of the BRCA1 gene in a breast tumor: Correlation with the effect of neoadjuvant chemotherapy

Science.gov (United States)

Tsyganov, M. M.; Ibragimova, M. K.; Deryusheva, I. V.; Slonimskaya, E. M.; Litviakov, N. V.

2017-09-01

Most current research is limited by only germinal mutations of the BRCA1 gene (more often 5382insC) and the number of studies, which characterize various somatic alterations of the BRCA1 gene in a tumor, namely the expression of this gene and its correlation with the efficiency of chemotherapy, which is scarce. Taking into account the data on the connection between the genetic mutation of BRCA1 with the high efficiency of the platinum medication one may suggest that the expression of the BRCA1 gene is also associated with the high sensitivity of the tumor to the platinum medication. Aim: to evaluate the correlation between the expression of the BRCA1 gene in a breast tumor with the neoadjuvant chemotherapy (NACT) efficiency. The research included 86 patients with BC. We evaluated the expression of BRCA1 in the tumor material before and after NACT. We established that objective response to NACT is connected with a high level of BRCA1 in the general group of patients (p = 0.01) and in case of docetaxel monotherapy (p < 0.05).

Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects.

Directory of Open Access Journals (Sweden)

Tiziano Pramparo

2011-03-01

Full Text Available Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. LIS1 is part of a protein complex including NDEL1 and 14-3-3ε that regulates dynein motor function and microtubule dynamics, while DCX stabilizes microtubules and cooperates with LIS1 during neuronal migration and neurogenesis. Targeted gene mutations of Lis1, Dcx, Ywhae (coding for 14-3-3ε, and Ndel1 lead to neuronal migration defects in mouse and provide models of human lissencephaly, as well as aid the study of related neuro-developmental diseases. Here we investigated the developing brain of these four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations. Consistent with the overall successful development of the mutant brains, unsupervised clustering and co-expression analysis suggested that cell cycle and synaptogenesis genes are similarly expressed and co-regulated in WT and mutant brains in a time-dependent fashion. By contrast, focused co-expression analysis in the Lis1 and Ndel1 mutants uncovered substantial differences in the correlation among pathways. Differential expression analysis revealed that cell cycle, cell adhesion, and cytoskeleton organization pathways are commonly altered in all mutants, while synaptogenesis, cell morphology, and inflammation/immune response are specifically altered in one or more mutants. We found several commonly dysregulated genes located within pathogenic deletion/duplication regions, which represent novel candidates of human mental retardation and neurocognitive disabilities. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can

Average correlation clustering algorithm (ACCA) for grouping of co-regulated genes with similar pattern of variation in their expression values.

Science.gov (United States)

Bhattacharya, Anindya; De, Rajat K

2010-08-01

Distance based clustering algorithms can group genes that show similar expression values under multiple experimental conditions. They are unable to identify a group of genes that have similar pattern of variation in their expression values. Previously we developed an algorithm called divisive correlation clustering algorithm (DCCA) to tackle this situation, which is based on the concept of correlation clustering. But this algorithm may also fail for certain cases. In order to overcome these situations, we propose a new clustering algorithm, called average correlation clustering algorithm (ACCA), which is able to produce better clustering solution than that produced by some others. ACCA is able to find groups of genes having more common transcription factors and similar pattern of variation in their expression values. Moreover, ACCA is more efficient than DCCA with respect to the time of execution. Like DCCA, we use the concept of correlation clustering concept introduced by Bansal et al. ACCA uses the correlation matrix in such a way that all genes in a cluster have the highest average correlation values with the genes in that cluster. We have applied ACCA and some well-known conventional methods including DCCA to two artificial and nine gene expression datasets, and compared the performance of the algorithms. The clustering results of ACCA are found to be more significantly relevant to the biological annotations than those of the other methods. Analysis of the results show the superiority of ACCA over some others in determining a group of genes having more common transcription factors and with similar pattern of variation in their expression profiles. Availability of the software: The software has been developed using C and Visual Basic languages, and can be executed on the Microsoft Windows platforms. The software may be downloaded as a zip file from http://www.isical.ac.in/~rajat. Then it needs to be installed. Two word files (included in the zip file) need to

Directed partial correlation: inferring large-scale gene regulatory network through induced topology disruptions.

Directory of Open Access Journals (Sweden)

Yinyin Yuan

Full Text Available Inferring regulatory relationships among many genes based on their temporal variation in transcript abundance has been a popular research topic. Due to the nature of microarray experiments, classical tools for time series analysis lose power since the number of variables far exceeds the number of the samples. In this paper, we describe some of the existing multivariate inference techniques that are applicable to hundreds of variables and show the potential challenges for small-sample, large-scale data. We propose a directed partial correlation (DPC method as an efficient and effective solution to regulatory network inference using these data. Specifically for genomic data, the proposed method is designed to deal with large-scale datasets. It combines the efficiency of partial correlation for setting up network topology by testing conditional independence, and the concept of Granger causality to assess topology change with induced interruptions. The idea is that when a transcription factor is induced artificially within a gene network, the disruption of the network by the induction signifies a genes role in transcriptional regulation. The benchmarking results using GeneNetWeaver, the simulator for the DREAM challenges, provide strong evidence of the outstanding performance of the proposed DPC method. When applied to real biological data, the inferred starch metabolism network in Arabidopsis reveals many biologically meaningful network modules worthy of further investigation. These results collectively suggest DPC is a versatile tool for genomics research. The R package DPC is available for download (http://code.google.com/p/dpcnet/.

Correlating single nucleotide polymorphisms in the myostatin gene with performance traits in rabbit

Directory of Open Access Journals (Sweden)

E.M. Abdel-Kafy

2016-09-01

Full Text Available The Myostatin (MSTN, or Growth and Differentiation Factor 8 (GDF8, gene has been implicated in the double muscling phenomenon, in which a series of mutations render the gene inactive and unable to properly regulate muscle fibre deposition. Single nucleotide polymorphisms (SNPs in the MSTN gene have been correlated to production traits, making it a candidate target gene to enhance livestock and fowl productivity. This study aimed to assess any association of three SNPs in the rabbit MSTN gene (c.713T>A in exon 2, c.747+34C>T in intron 2, and c.*194A>G in 3’-untranslated region and their combinations, with carcass, production and reproductive traits. The investigated traits included individual body weight, daily body weight gain, carcass traits and reproductive traits. The 3 SNPs were screened using PCR-restriction fragment length polymorphism (RFLP-based analysis and the effects of the different SNP genotypes and their combinations were estimated in a rabbit population. Additionally, additive and dominance effects were estimated for significant traits. The results found no significant association between the c.713 T>A SNP and all the examined traits. Allele T at the c.747+34C>T SNP was only significantly associated (PG, allele G was significantly associated (PG SNP also had positive effects on most carcass traits. The estimated additive genetic effect for the c.*194A>G SNP was significant (PA and c.747+34C>T, GG at the c.*194A>G SNP correlated with highest values in body weight and daily weight gain. In conclusion, the ‘G’ allele at the c.*194A>G SNP had positive effects on growth and carcass traits and so could be used as a favourable allele in planning rabbit selection. Further population-wide studies are necessary to test the association of the c.*194A>G SNP with carcass traits. We also recommend evaluation of the potential effects of the c.*194A>G SNP on MSTN gene expression.

GSMA: Gene Set Matrix Analysis, An Automated Method for Rapid Hypothesis Testing of Gene Expression Data

Directory of Open Access Journals (Sweden)

Chris Cheadle

2007-01-01

Full Text Available Background: Microarray technology has become highly valuable for identifying complex global changes in gene expression patterns. The assignment of functional information to these complex patterns remains a challenging task in effectively interpreting data and correlating results from across experiments, projects and laboratories. Methods which allow the rapid and robust evaluation of multiple functional hypotheses increase the power of individual researchers to data mine gene expression data more efficiently.Results: We have developed (gene set matrix analysis GSMA as a useful method for the rapid testing of group-wise up- or downregulation of gene expression simultaneously for multiple lists of genes (gene sets against entire distributions of gene expression changes (datasets for single or multiple experiments. The utility of GSMA lies in its flexibility to rapidly poll gene sets related by known biological function or as designated solely by the end-user against large numbers of datasets simultaneously.Conclusions: GSMA provides a simple and straightforward method for hypothesis testing in which genes are tested by groups across multiple datasets for patterns of expression enrichment.

Alteration of gene expression profile in Niemann-Pick type C mice correlates with tissue damage and oxidative stress.

Directory of Open Access Journals (Sweden)

Mary C Vázquez

Full Text Available BACKGROUND: Niemann-Pick type C disease (NPC is a neurovisceral lipid storage disorder mainly characterized by unesterified cholesterol accumulation in lysosomal/late endosomal compartments, although there is also an important storage for several other kind of lipids. The main tissues affected by the disease are the liver and the cerebellum. Oxidative stress has been described in various NPC cells and tissues, such as liver and cerebellum. Although considerable alterations occur in the liver, the pathological mechanisms involved in hepatocyte damage and death have not been clearly defined. Here, we assessed hepatic tissue integrity, biochemical and oxidative stress parameters of wild-type control (Npc1(+/+; WT and homozygous-mutant (Npc1(-/-; NPC mice. In addition, the mRNA abundance of genes encoding proteins associated with oxidative stress, copper metabolism, fibrosis, inflammation and cholesterol metabolism were analyzed in livers and cerebella of WT and NPC mice. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed various oxidative stress parameters in the liver and hepatic and cerebellum gene expression in 7-week-old NPC1-deficient mice compared with control animals. We found signs of inflammation and fibrosis in NPC livers upon histological examination. These signs were correlated with increased levels of carbonylated proteins, diminished total glutathione content and significantly increased total copper levels in liver tissue. Finally, we analyzed liver and cerebellum gene expression patterns by qPCR and microarray assays. We found a correlation between fibrotic tissue and differential expression of hepatic as well as cerebellar genes associated with oxidative stress, fibrosis and inflammation in NPC mice. CONCLUSIONS/SIGNIFICANCE: In NPC mice, liver disease is characterized by an increase in fibrosis and in markers associated with oxidative stress. NPC is also correlated with altered gene expression, mainly of genes involved in oxidative stress

Gene-specific correlation of RNA and protein levels in human cells and tissues

DEFF Research Database (Denmark)

Edfors, Fredrik; Danielsson, Frida; Hallström, Björn M.

2016-01-01

An important issue for molecular biology is to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. Here, we have developed a targeted proteomics approach for a set of human non-secreted proteins based on parallel reaction monitoring...... to measure, at steady-state conditions, absolute protein copy numbers across human tissues and cell lines and compared these levels with the corresponding mRNA levels using transcriptomics. The study shows that the transcript and protein levels do not correlate well unless a gene-specific RNA-to-protein (RTP...

Comparison of subset-based local and FE-based global digital image correlation: Theoretical error analysis and validation

KAUST Repository

Pan, B.; Wang, Bo; Lubineau, Gilles

2016-01-01

Subset-based local and finite-element-based (FE-based) global digital image correlation (DIC) approaches are the two primary image matching algorithms widely used for full-field displacement mapping. Very recently, the performances

Genes for hereditary sensory and autonomic neuropathies: a genotype–phenotype correlation

Science.gov (United States)

Rotthier, Annelies; Baets, Jonathan; Vriendt, Els De; Jacobs, An; Auer-Grumbach, Michaela; Lévy, Nicolas; Bonello-Palot, Nathalie; Kilic, Sara Sebnem; Weis, Joachim; Nascimento, Andrés; Swinkels, Marielle; Kruyt, Moyo C.; Jordanova, Albena; De Jonghe, Peter

2009-01-01

Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven genes: two genes for autosomal dominant (SPTLC1 and RAB7) and five genes for autosomal recessive forms of HSAN (WNK1/HSN2, NTRK1, NGFB, CCT5 and IKBKAP). We performed a systematic mutation screening of the coding sequences of six of these genes on a cohort of 100 familial and isolated patients diagnosed with HSAN. In addition, we screened the functional candidate gene NGFR (p75/NTR) encoding the nerve growth factor receptor. We identified disease-causing mutations in SPTLC1, RAB7, WNK1/HSN2 and NTRK1 in 19 patients, of which three mutations have not previously been reported. The phenotypes associated with mutations in NTRK1 and WNK1/HSN2 typically consisted of congenital insensitivity to pain and anhidrosis, and early-onset ulcero-mutilating sensory neuropathy, respectively. RAB7 mutations were only found in patients with a Charcot-Marie-Tooth type 2B (CMT2B) phenotype, an axonal sensory-motor neuropathy with pronounced ulcero-mutilations. In SPTLC1, we detected a novel mutation (S331F) corresponding to a previously unknown severe and early-onset HSAN phenotype. No mutations were found in NGFB, CCT5 and NGFR. Overall disease-associated mutations were found in 19% of the studied patient group, suggesting that additional genes are associated with HSAN. Our genotype–phenotype correlation study broadens the spectrum of HSAN and provides additional insights for molecular and clinical diagnosis. PMID:19651702

[Correlation of gene expression related to amount of ginseng saponin in 15 tissues and 6 kinds of ginseng saponin biosynthesis].

Science.gov (United States)

Wang, Kang-yu; Zhang, Mei-ping; Li, Chuang; Jiang, Shi-cui; Yin, Rui; Sun, Chun-yu; Wang, Yi

2015-08-01

Fifteen tissues of 4-year-old fruit repining stage Jilin ginseng were chosen as materials, six kinds of monomer saponins (ginsenosides Rg1, Re, Rb1, Rc, Rb2 and Rd) content in 15 tissues was measured by HPLC and vanillin-sulfuric acid method. The relative expression of FPS, SQS, SQE, OSC, β-AS and P450 genes in 15 tissues was analyzed by real-time PCR. The correlations between ginseng saponin content in 15 tissues of Jilin ginseng and biosynthetic pathway -related genes were obtained. The results showed that was a synergistic increase and decrease trend of positive linear correlation among six kinds of monomer saponin content, and there was a significantly (P saponin content and total saponins content. Monomer saponin content and 6 kinds of enzyme gene correlation were different. Biosynthesis of ginseng total saponins and monomer saponin were regulated by six kinds of participation ginsenoside biosynthesis enzyme genes, the expression of these six kinds of genes in different tissues of ginseng showed collaborative increase and decrease trend, and regulated biosynthesis of ginseng ginsenoside by group coordinative manner.

A comparison of the Angstrom-type correlations and the estimation of monthly average daily global irradiation

International Nuclear Information System (INIS)

Jain, S.; Jain, P.C.

1985-12-01

Linear regression analysis of the monthly average daily global irradiation and the sunshine duration data of 8 Zambian locations has been performed using the least square technique. Good correlation (r>0.95) is obtained in all the cases showing that the Angstrom equation is valid for Zambian locations. The values of the correlation parameters thus obtained show substantial unsystematic scatter. The analysis was repeated after incorporating the effects of (i) multiple reflections of radiation between the ground and the atmosphere, and (ii) not burning of the sunshine recorder chart, into the Angstrom equation. The surface albedo measurements at Lusaka were used. The scatter in the correlation parameters was investigated by graphical representation, by regression analysis of the data of the individual stations as well as the combined data of the 8 stations. The results show that the incorporation of none of the two effects reduces the scatter significantly. A single linear equation obtained from the regression analysis of the combined data of the 8 stations is found to be appropriate for estimating the global irradiation over Zambian locations with reasonable accuracy from the sunshine duration data. (author)

Global occurrence of archaeal amoA genes in terrestrial hot springs.

Science.gov (United States)

Zhang, Chuanlun L; Ye, Qi; Huang, Zhiyong; Li, Wenjun; Chen, Jinquan; Song, Zhaoqi; Zhao, Weidong; Bagwell, Christopher; Inskeep, William P; Ross, Christian; Gao, Lei; Wiegel, Juergen; Romanek, Christopher S; Shock, Everett L; Hedlund, Brian P

2008-10-01

transcribed in situ in one spring and the transcripts were closely related to the amoA genes amplified from the same spring. Our study demonstrates the global occurrence of putative archaeal amoA genes in a wide variety of terrestrial hot springs and suggests that geography may play an important role in selecting different assemblages of AOA.

Global Occurrence of Archaeal amoA Genes in Terrestrial Hot Springs▿

Science.gov (United States)

Zhang, Chuanlun L.; Ye, Qi; Huang, Zhiyong; Li, WenJun; Chen, Jinquan; Song, Zhaoqi; Zhao, Weidong; Bagwell, Christopher; Inskeep, William P.; Ross, Christian; Gao, Lei; Wiegel, Juergen; Romanek, Christopher S.; Shock, Everett L.; Hedlund, Brian P.

2008-01-01

transcribed in situ in one spring and the transcripts were closely related to the amoA genes amplified from the same spring. Our study demonstrates the global occurrence of putative archaeal amoA genes in a wide variety of terrestrial hot springs and suggests that geography may play an important role in selecting different assemblages of AOA. PMID:18676703

Long-Term Improvement of Neurological Signs and Metabolic Dysfunction in a Mouse Model of Krabbe's Disease after Global Gene Therapy.

Science.gov (United States)

Marshall, Michael S; Issa, Yazan; Jakubauskas, Benas; Stoskute, Monika; Elackattu, Vince; Marshall, Jeffrey N; Bogue, Wil; Nguyen, Duc; Hauck, Zane; Rue, Emily; Karumuthil-Melethil, Subha; Zaric, Violeta; Bosland, Maarten; van Breemen, Richard B; Givogri, Maria I; Gray, Steven J; Crocker, Stephen J; Bongarzone, Ernesto R

2018-03-07

We report a global adeno-associated virus (AAV)9-based gene therapy protocol to deliver therapeutic galactosylceramidase (GALC), a lysosomal enzyme that is deficient in Krabbe's disease. When globally administered via intrathecal, intracranial, and intravenous injections to newborn mice affected with GALC deficiency (twitcher mice), this approach largely surpassed prior published benchmarks of survival and metabolic correction, showing long-term protection of demyelination, neuroinflammation, and motor function. Bone marrow transplantation, performed in this protocol without immunosuppressive preconditioning, added minimal benefits to the AAV9 gene therapy. Contrasting with other proposed pre-clinical therapies, these results demonstrate that achieving nearly complete correction of GALC's metabolic deficiencies across the entire nervous system via gene therapy can have a significant improvement to behavioral deficits, pathophysiological changes, and survival. These results are an important consideration for determining the safest and most effective manner for adapting gene therapy to treat this leukodystrophy in the clinic. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

CEBPG transcription factor correlates with antioxidant and DNA repair genes in normal bronchial epithelial cells but not in individuals with bronchogenic carcinoma

International Nuclear Information System (INIS)

Mullins, D'Anna N; Crawford, Erin L; Khuder, Sadik A; Hernandez, Dawn-Alita; Yoon, Youngsook; Willey, James C

2005-01-01

Cigarette smoking is the primary cause of bronchogenic carcinoma (BC), yet only 10–15% of heavy smokers develop BC and it is likely that this variation in risk is, in part, genetically determined. We previously reported a set of antioxidant genes for which transcript abundance was lower in normal bronchial epithelial cells (NBEC) of BC individuals compared to non-BC individuals. In unpublished studies of the same NBEC samples, transcript abundance values for several DNA repair genes were correlated with these antioxidant genes. From these data, we hypothesized that antioxidant and DNA repair genes are co-regulated by one or more transcription factors and that inter-individual variation in expression and/or function of one or more of these transcription factors is responsible for inter-individual variation in risk for BC. The putative transcription factor recognition sites common to six of the antioxidant genes were identified through in silico DNA sequence analysis. The transcript abundance values of these transcription factors (n = 6) and an expanded group of antioxidant and DNA repair genes (n = 16) were measured simultaneously by quantitative PCR in NBEC of 24 non-BC and 25 BC individuals. CEBPG transcription factor was significantly (p < 0.01) correlated with eight of the antioxidant or DNA repair genes in non-BC individuals but not in BC individuals. In BC individuals the correlation with CEBPG was significantly (p < 0.01) lower than that of non-BC individuals for four of the genes (XRCC1, ERCC5, GSTP1, and SOD1) and the difference was nearly significant for GPX1. The only other transcription factor correlated with any of these five target genes in non-BC individuals was E2F1. E2F1 was correlated with GSTP1 among non-BC individuals, but in contrast to CEBPG, there was no significant difference in this correlation in non-BC individuals compared to BC individuals. We conclude that CEBPG is the transcription factor primarily responsible for regulating

Correlation between endometriosis combined with infertility and STAT3 gene polymorphisms

Directory of Open Access Journals (Sweden)

Juan Hu

2016-05-01

Full Text Available Objective: To investigate the correlation between STAT3 gene polymorphisms and endometriosis complicated with infertility. Methods: A total of 35 patients with endometriosis complicated with infertility and 35 cases of healthy volunteer from October 2014 to October 2015 in our hospital were selected as research objects. STAT3 gene polymorphisms of all objects were detected by PCR-RFLP method. Results: Polymorphic sites of STAT3 gene rs2293152 were expressed as three genotypes, namely, CC, GC, and GG. There were 18 cases, 10 cases and 7 cases of type CC, GC and GG in the observation group, accounted for 51.43%, 28.57% and 20.00%, respectively. There were 29 cases, 3 cases and 3 cases of type CC, GC and GG in the control group, accounted for 82.86%, 8.57% and 8.57%. There was a statistically difference` between the two groups. The frequency of C and G allele in the observation group and the control group were 65.71%, 34.29% and 87.14%, 12.86%, respectively. There were statistically significant differences between two groups. In addition, compared with the CC genotype, genotype G might increase the risk of the disease. Conclusions: The susceptibility of endometriosis complicated with infertility may be associated with STAT3 gene polymorphism and women who carried the G allele may have an increased the risk of the disease.

Expression of alcoholism-relevant genes in the liver are differently correlated to different parts of the brain.

Science.gov (United States)

Wang, Lishi; Huang, Yue; Jiao, Yan; Chen, Hong; Cao, Yanhong; Bennett, Beth; Wang, Yongjun; Gu, Weikuan

2013-01-01

The purpose of this study is to investigate whether expression profiles of alcoholism-relevant genes in different parts of the brain are correlated differently with those in the liver. Four experiments were conducted. First, we used gene expression profiles from five parts of the brain (striatum, prefrontal cortex, nucleus accumbens, hippocampus, and cerebellum) and from liver in a population of recombinant inbred mouse strains to examine the expression association of 10 alcoholism-relevant genes. Second, we conducted the same association analysis between brain structures and the lung. Third, using five randomly selected, nonalcoholism-relevant genes, we conducted the association analysis between brain and liver. Finally, we compared the expression of 10 alcoholism-relevant genes in hippocampus and cerebellum between an alcohol preference strain and a wild-type control. We observed a difference in correlation patterns in expression levels of 10 alcoholism-relevant genes between different parts of the brain with those of liver. We then examined the association of gene expression between alcohol dehydrogenases (Adh1, Adh2, Adh5, and Adh7) and different parts of the brain. The results were similar to those of the 10 genes. Then, we found that the association of those genes between brain structures and lung was different from that of liver. Next, we found that the association patterns of five alcoholism-nonrelevant genes were different from those of 10 alcoholism-relevant genes. Finally, we found that the expression level of 10 alcohol-relevant genes is influenced more in hippocampus than in cerebellum in the alcohol preference strain. Our results show that the expression of alcoholism-relevant genes in liver is differently associated with the expression of genes in different parts of the brain. Because different structural changes in different parts of the brain in alcoholism have been reported, it is important to investigate whether those structural differences in

Global study of quadrupole correlation effects

International Nuclear Information System (INIS)

Bender, M.; Bertsch, G.F.; Heenen, P.-H.

2006-01-01

We discuss the systematics of ground-state quadrupole correlations of binding energies and mean-square charge radii for all even-even nuclei, from 16 O up to the superheavies, for which data are available. To that aim we calculate their correlated J=0 ground state by means of the angular-momentum and particle-number projected generator coordinate method, using the axial mass quadrupole moment as the generator coordinate and self-consistent mean-field states restricted only by axial, parity, and time-reversal symmetries. The calculation is performed within the framework of a nonrelativistic self-consistent mean-field model by use of the same Skyrme interaction SLy4 and to a density-dependent pairing force to generate the mean-field configurations and to mix them. These are the main conclusions of our study: (i) The quadrupole correlation energy varies between a few 100 keV and about 5.5 MeV. It is affected by shell closures, but varies only slightly with mass and asymmetry. (ii) Projection on angular momentum J=0 provides the major part of the energy gain of up to about 4 MeV; all nuclei in the study, including doubly magic ones, gain energy by deformation. (iii) The mixing of projected states with different intrinsic axial deformations adds a few 100 keV up to 1.5 MeV to the correlation energy. (iv) Typically nuclei below mass A≤60 have a larger correlation energy than static deformation energy whereas the heavier deformed nuclei have larger static deformation energy than correlation energy. (v) Inclusion of the quadrupole correlation energy improves the description of mass systematics, particularly around shell closures, and of differential quantities, namely two-nucleon separation energies and two-nucleon gaps. The correlation energy provides an explanation of 'mutually enhanced magicity'. (vi) The correlation energy tends to decrease the shell effect on binding energies around magic numbers, but the magnitude of the suppression is not large enough to explain

Global sequence diversity of the lactate dehydrogenase gene in Plasmodium falciparum.

Science.gov (United States)

Simpalipan, Phumin; Pattaradilokrat, Sittiporn; Harnyuttanakorn, Pongchai

2018-01-09

Antigen-detecting rapid diagnostic tests (RDTs) have been recommended by the World Health Organization for use in remote areas to improve malaria case management. Lactate dehydrogenase (LDH) of Plasmodium falciparum is one of the main parasite antigens employed by various commercial RDTs. It has been hypothesized that the poor detection of LDH-based RDTs is attributed in part to the sequence diversity of the gene. To test this, the present study aimed to investigate the genetic diversity of the P. falciparum ldh gene in Thailand and to construct the map of LDH sequence diversity in P. falciparum populations worldwide. The ldh gene was sequenced for 50 P. falciparum isolates in Thailand and compared with hundreds of sequences from P. falciparum populations worldwide. Several indices of molecular variation were calculated, including the proportion of polymorphic sites, the average nucleotide diversity index (π), and the haplotype diversity index (H). Tests of positive selection and neutrality tests were performed to determine signatures of natural selection on the gene. Mean genetic distance within and between species of Plasmodium ldh was analysed to infer evolutionary relationships. Nucleotide sequences of P. falciparum ldh could be classified into 9 alleles, encoding 5 isoforms of LDH. L1a was the most common allelic type and was distributed in P. falciparum populations worldwide. Plasmodium falciparum ldh sequences were highly conserved, with haplotype and nucleotide diversity values of 0.203 and 0.0004, respectively. The extremely low genetic diversity was maintained by purifying selection, likely due to functional constraints. Phylogenetic analysis inferred the close genetic relationship of P. falciparum to malaria parasites of great apes, rather than to other human malaria parasites. This study revealed the global genetic variation of the ldh gene in P. falciparum, providing knowledge for improving detection of LDH-based RDTs and supporting the candidacy of

In Vitro Global Gene Expression Analyses Support the Ethnopharmacological Use of Achyranthes aspera

Directory of Open Access Journals (Sweden)

Pochi R. Subbarayan

2013-01-01

Full Text Available Achyranthes aspera (family Amaranthaceae is known for its anticancer properties. We have systematically validated the in vitro and in vivo anticancer properties of this plant. However, we do not know its mode of action. Global gene expression analyses may help decipher its mode of action. In the absence of identified active molecules, we believe this is the best approach to discover the mode of action of natural products with known medicinal properties. We exposed human pancreatic cancer cell line MiaPaCa-2 (CRL-1420 to 34 μg/mL of LE for 24, 48, and 72 hours. Gene expression analyses were performed using whole human genome microarrays (Agilent Technologies, USA. In our analyses, 82 (54/28 genes passed the quality control parameter, set at FDR ≤ 0.01 and FC of ≥±2. LE predominantly affected pathways of immune response, metabolism, development, gene expression regulation, cell adhesion, cystic fibrosis transmembrane conductance regulation (CFTR, and chemotaxis (MetaCore tool (Thomson Reuters, NY. Disease biomarker enrichment analysis identified LE regulated genes involved in Vasculitis—inflammation of blood vessels. Arthritis and pancreatitis are two of many etiologies for vasculitis. The outcome of disease network analysis supports the medicinal use of A. aspera, viz, to stop bleeding, as a cure for pancreatic cancer, as an antiarthritic medication, and so forth.

Role of SeqA and Dam in Escherichia coli gene expression: A global/microarray analysis

DEFF Research Database (Denmark)

Løbner-Olesen, Anders; Marinus, M.G.; Hansen, Flemming G.

2003-01-01

High-density oligonucleotide arrays were used to monitor global transcription patterns in Escherichia coli with various levels of Dam and SeqA proteins. Cells lacking Dam methyltransferase showed a modest increase in transcription of the genes belonging to the SOS regulon. Bacteria devoid...... of the SeqA protein, which preferentially binds hemimethylated DNA, were found to have a transcriptional profile almost identical to WT bacteria overexpressing Dam methyltransferase. The latter two strains differed from WT in two ways. First, the origin proximal genes were transcribed with increased...... frequency due to increased gene dosage. Second, chromosomal domains of high transcriptional activity alternate with regions of low activity, and our results indicate that the activity in each domain is modulated in the same way by SeqA deficiency or Dam overproduction. We suggest that the methylation status...

Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

DEFF Research Database (Denmark)

Basse, Astrid L.; Dixen, Karen; Yadav, Rachita

2015-01-01

abundance and down-regulation of gene expression related to mitochondrial function and oxidative phosphorylation. Global gene expression profiling demonstrated that the time points grouped into three phases: a brown adipose phase, a transition phase and a white adipose phase. Between the brown adipose...

Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines

Energy Technology Data Exchange (ETDEWEB)

Solmi, Rossella [Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Via Belmeloro 8, 40126 Bologna (Italy); Montroni, Isacco [Dipartimento Emergenza/Urgenza, Chirurgia Generale e dei Trapianti, Università di Bologna, Bologna (Italy); Mattei, Gabriella [Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Via Belmeloro 8, 40126 Bologna (Italy); Taffurelli, Mario [Dipartimento Emergenza/Urgenza, Chirurgia Generale e dei Trapianti, Università di Bologna, Bologna (Italy); Santini, Donatella [Dipartimento di Patologia, Università di Bologna, Bologna (Italy); Pezzetti, Furio [Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Via Belmeloro 8, 40126 Bologna (Italy); Ruggeri, Alessandro [Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell' Apparato Locomotore, Università di Bologna, Bologna (Italy); Castellani, Gastone [Centro Interdipartimentale L. Galvani, Università di Bologna, Bologna (Italy); DIMORFIPA, Università di Bologna, Bologna (Italy); Guidotti, Lia [Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Via Belmeloro 8, 40126 Bologna (Italy); Coppola, Domenico [H. Lee Moffit Cancer Center and Research Institute, University of South Florida, Tampa, FL (United States); Strippoli, Pierluigi; Lauriola, Mattia [Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Via Belmeloro 8, 40126 Bologna (Italy); Francesconi, Mirko [Centro Interdipartimentale L. Galvani, Università di Bologna, Bologna (Italy); DIMORFIPA, Università di Bologna, Bologna (Italy); Martini, Désirée [Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell' Apparato Locomotore, Università di Bologna, Bologna (Italy); Voltattorni, Manuela [Laboratori di Biotecnologie, Via Beverara 123, Bologna (Italy); Ceccarelli, Claudio [Dipartimento di Patologia, Università di Bologna, Bologna (Italy); Ugolini, Giampaolo; Rosati, Giancarlo; Zanotti, Simone [Dipartimento Emergenza/Urgenza, Chirurgia Generale e dei Trapianti, Università di Bologna, Bologna (Italy)

2008-08-08

EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and in combination with EGF. Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression and scanning electron microscopy (SEM) evidenced the ultrastructural morphology. Gene expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40 K array A. Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this level of cell cycle distribution after treatment, suggesting a predominantly differentiated state. Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the 2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment. In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes appeared to be less stimulated than for single drug cases. This is the first study to have systematically investigated the effect of cetuximab or gefitinib, alone and in combination

Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines

Directory of Open Access Journals (Sweden)

Pezzetti Furio

2008-08-01

Full Text Available Abstract Background EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and in combination with EGF. Methods Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression and scanning electron microscopy (SEM evidenced the ultrastructural morphology. Gene expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40 K array A. Results Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this level of cell cycle distribution after treatment, suggesting a predominantly differentiated state. Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important reduction of the microvilli (which also lose their erect position in Caco-2, possibly invalidating microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the 2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment. In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes appeared to be less stimulated than for single drug cases. Conclusion This is the first study to have systematically investigated

Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines

International Nuclear Information System (INIS)

Solmi, Rossella; Montroni, Isacco; Mattei, Gabriella; Taffurelli, Mario; Santini, Donatella; Pezzetti, Furio; Ruggeri, Alessandro; Castellani, Gastone; Guidotti, Lia; Coppola, Domenico; Strippoli, Pierluigi; Lauriola, Mattia; Francesconi, Mirko; Martini, Désirée; Voltattorni, Manuela; Ceccarelli, Claudio; Ugolini, Giampaolo; Rosati, Giancarlo; Zanotti, Simone

2008-01-01

EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and in combination with EGF. Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression and scanning electron microscopy (SEM) evidenced the ultrastructural morphology. Gene expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40 K array A. Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this level of cell cycle distribution after treatment, suggesting a predominantly differentiated state. Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the 2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment. In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes appeared to be less stimulated than for single drug cases. This is the first study to have systematically investigated the effect of cetuximab or gefitinib, alone and in combination

Different Temporal Effects of Ebola Virus VP35 and VP24 Proteins on Global Gene Expression in Human Dendritic Cells.

Science.gov (United States)

Ilinykh, Philipp A; Lubaki, Ndongala M; Widen, Steven G; Renn, Lynnsey A; Theisen, Terence C; Rabin, Ronald L; Wood, Thomas G; Bukreyev, Alexander

2015-08-01

Ebola virus (EBOV) causes a severe hemorrhagic fever with a deficient immune response, lymphopenia, and lymphocyte apoptosis. Dendritic cells (DC), which trigger the adaptive response, do not mature despite EBOV infection. We recently demonstrated that DC maturation is unblocked by disabling the innate response antagonizing domains (IRADs) in EBOV VP35 and VP24 by the mutations R312A and K142A, respectively. Here we analyzed the effects of VP35 and VP24 with the IRADs disabled on global gene expression in human DC. Human monocyte-derived DC were infected by wild-type (wt) EBOV or EBOVs carrying the mutation in VP35 (EBOV/VP35m), VP24 (EBOV/VP24m), or both (EBOV/VP35m/VP24m). Global gene expression at 8 and 24 h was analyzed by deep sequencing, and the expression of interferon (IFN) subtypes up to 5 days postinfection was analyzed by quantitative reverse transcription-PCR (qRT-PCR). wt EBOV induced a weak global gene expression response, including markers of DC maturation, cytokines, chemokines, chemokine receptors, and multiple IFNs. The VP35 mutation unblocked the expression, resulting in a dramatic increase in expression of these transcripts at 8 and 24 h. Surprisingly, DC infected with EBOV/VP24m expressed lower levels of many of these transcripts at 8 h after infection, compared to wt EBOV. In contrast, at 24 h, expression of the transcripts increased in DC infected with any of the three mutants, compared to wt EBOV. Moreover, sets of genes affected by the two mutations only partially overlapped. Pathway analysis demonstrated that the VP35 mutation unblocked pathways involved in antigen processing and presentation and IFN signaling. These data suggest that EBOV IRADs have profound effects on the host adaptive immune response through massive transcriptional downregulation of DC. This study shows that infection of DC with EBOV, but not its mutant forms with the VP35 IRAD and/or VP24 IRAD disabled, causes a global block in expression of host genes. The temporal

Comparative gene expression between two yeast species

Directory of Open Access Journals (Sweden)

Guan Yuanfang

2013-01-01

Full Text Available Abstract Background Comparative genomics brings insight into sequence evolution, but even more may be learned by coupling sequence analyses with experimental tests of gene function and regulation. However, the reliability of such comparisons is often limited by biased sampling of expression conditions and incomplete knowledge of gene functions across species. To address these challenges, we previously systematically generated expression profiles in Saccharomyces bayanus to maximize functional coverage as compared to an existing Saccharomyces cerevisiae data repository. Results In this paper, we take advantage of these two data repositories to compare patterns of ortholog expression in a wide variety of conditions. First, we developed a scalable metric for expression divergence that enabled us to detect a significant correlation between sequence and expression conservation on the global level, which previous smaller-scale expression studies failed to detect. Despite this global conservation trend, between-species gene expression neighborhoods were less well-conserved than within-species comparisons across different environmental perturbations, and approximately 4% of orthologs exhibited a significant change in co-expression partners. Furthermore, our analysis of matched perturbations collected in both species (such as diauxic shift and cell cycle synchrony demonstrated that approximately a quarter of orthologs exhibit condition-specific expression pattern differences. Conclusions Taken together, these analyses provide a global view of gene expression patterns between two species, both in terms of the conditions and timing of a gene's expression as well as co-expression partners. Our results provide testable hypotheses that will direct future experiments to determine how these changes may be specified in the genome.

Improving sensitivity of linear regression-based cell type-specific differential expression deconvolution with per-gene vs. global significance threshold.

Science.gov (United States)

Glass, Edmund R; Dozmorov, Mikhail G

2016-10-06

The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from blood samples suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. Combined with cell counts, heterogeneous gene expression may provide deeper insights into the gene expression differences on the cell type-specific level. Published computational methods use linear regression to estimate cell type-specific differential expression, and a global cutoff to judge significance, such as False Discovery Rate (FDR). Yet, they do not consider many artifacts hidden in high-dimensional gene expression data that may negatively affect linear regression. In this paper we quantify the parameter space affecting the performance of linear regression (sensitivity of cell type-specific differential expression detection) on a per-gene basis. We evaluated the effect of sample sizes, cell type-specific proportion variability, and mean squared error on sensitivity of cell type-specific differential expression detection using linear regression. Each parameter affected variability of cell type-specific expression estimates and, subsequently, the sensitivity of differential expression detection. We provide the R package, LRCDE, which performs linear regression-based cell type-specific differential expression (deconvolution) detection on a gene-by-gene basis. Accounting for variability around cell type-specific gene expression estimates, it computes per-gene t-statistics of differential detection, p-values, t-statistic-based sensitivity, group-specific mean squared error, and several gene-specific diagnostic metrics. The sensitivity of linear regression-based cell type-specific differential expression detection differed for each gene as a function of mean squared error, per group sample sizes, and variability of the proportions

Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira

Science.gov (United States)

Adhikarla, Haritha; Wunder, Elsio A.; Mechaly, Ariel E.; Mehta, Sameet; Wang, Zheng; Santos, Luciane; Bisht, Vimla; Diggle, Peter; Murray, Gerald; Adler, Ben; Lopez, Francesc; Townsend, Jeffrey P.; Groisman, Eduardo; Picardeau, Mathieu; Buschiazzo, Alejandro; Ko, Albert I.

2018-01-01

Leptospirosis is an emerging zoonotic disease with more than 1 million cases annually. Currently there is lack of evidence for signaling pathways involved during the infection process of Leptospira. In our comprehensive genomic analysis of 20 Leptospira spp. we identified seven pathogen-specific Two-Component System (TCS) proteins. Disruption of two these TCS genes in pathogenic Leptospira strain resulted in loss-of-virulence in a hamster model of leptospirosis. Corresponding genes lvrA and lvrB (leptospira virulence regulator) are juxtaposed in an operon and are predicted to encode a hybrid histidine kinase and a hybrid response regulator, respectively. Transcriptome analysis of lvr mutant strains with disruption of one (lvrB) or both genes (lvrA/B) revealed global transcriptional regulation of 850 differentially expressed genes. Phosphotransfer assays demonstrated that LvrA phosphorylates LvrB and predicted further signaling downstream to one or more DNA-binding response regulators, suggesting that it is a branched pathway. Phylogenetic analyses indicated that lvrA and lvrB evolved independently within different ecological lineages in Leptospira via gene duplication. This study uncovers a novel-signaling pathway that regulates virulence in pathogenic Leptospira (Lvr), providing a framework to understand the molecular bases of regulation in this life-threatening bacterium. PMID:29600195

AAV-PHP.B-Mediated Global-Scale Expression in the Mouse Nervous System Enables GBA1 Gene Therapy for Wide Protection from Synucleinopathy.

Science.gov (United States)

Morabito, Giuseppe; Giannelli, Serena G; Ordazzo, Gabriele; Bido, Simone; Castoldi, Valerio; Indrigo, Marzia; Cabassi, Tommaso; Cattaneo, Stefano; Luoni, Mirko; Cancellieri, Cinzia; Sessa, Alessandro; Bacigaluppi, Marco; Taverna, Stefano; Leocani, Letizia; Lanciego, José L; Broccoli, Vania

2017-12-06

The lack of technology for direct global-scale targeting of the adult mouse nervous system has hindered research on brain processing and dysfunctions. Currently, gene transfer is normally achieved by intraparenchymal viral injections, but these injections target a restricted brain area. Herein, we demonstrated that intravenous delivery of adeno-associated virus (AAV)-PHP.B viral particles permeated and diffused throughout the neural parenchyma, targeting both the central and the peripheral nervous system in a global pattern. We then established multiple procedures of viral transduction to control gene expression or inactivate gene function exclusively in the adult nervous system and assessed the underlying behavioral effects. Building on these results, we established an effective gene therapy strategy to counteract the widespread accumulation of α-synuclein deposits throughout the forebrain in a mouse model of synucleinopathy. Transduction of A53T-SCNA transgenic mice with AAV-PHP.B-GBA1 restored physiological levels of the enzyme, reduced α-synuclein pathology, and produced significant behavioral recovery. Finally, we provided evidence that AAV-PHP.B brain penetration does not lead to evident dysfunctions in blood-brain barrier integrity or permeability. Altogether, the AAV-PHP.B viral platform enables non-invasive, widespread, and long-lasting global neural expression of therapeutic genes, such as GBA1, providing an invaluable approach to treat neurodegenerative diseases with diffuse brain pathology such as synucleinopathies. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Deletion and down-regulation of HRH4 gene in gastric carcinomas: a potential correlation with tumor progression.

Directory of Open Access Journals (Sweden)

Chao Zhang

Full Text Available BACKGROUND: Histamine is an established growth factor for gastrointestinal malignancies. The effect of histamine is largely determined locally by the histamine receptor expression pattern. Histamine receptor H4 (HRH4, the newest member of the histamine receptor family, is positively expressed on the epithelium of the gastrointestinal tract, and its function remains to be elucidated. Previously, we reported the decreased expression of HRH4 in colorectal cancers and revealed its correlation with tumor proliferation. In the current study, we aimed to investigate the abnormalities of HRH4 gene in gastric carcinomas (GCs. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed H4R expression in collected GC samples by quantitative PCR, Western blot analysis, and immunostaining. Our results showed that the protein and mRNA levels of HRH4 were reduced in some GC samples, especially in advanced GC samples. Copy number decrease of HRH4 gene was observed (17.6%, 23 out of 131, which was closely correlated with the attenuated expression of H4R. In vitro studies, using gastric cancer cell lines, showed that the alteration of HRH4 expression on gastric cancer cells influences tumor growth upon exposure to histamine. CONCLUSIONS/SIGNIFICANCE: We show for the first time that deletion of HRH4 gene is present in GC cases and is closely correlated with attenuated gene expression. Down-regulation of HRH4 in gastric carcinomas plays a role in histamine-mediated growth control of GC cells.

Satellite observations of tropospheric ammonia and carbon monoxide: Global distributions, regional correlations and comparisons to model simulations

Science.gov (United States)

Ammonia (NH3) and carbon monoxide (CO) are primary pollutants emitted to the Earth's atmosphere from common as well as distinct sources associated with anthropogenic and natural activities. The seasonal and global distributions and correlations of NH3 and CO from the Tropospheric...

Rift Valley fever virus NSS gene expression correlates with a defect in nuclear mRNA export.

Science.gov (United States)

Copeland, Anna Maria; Van Deusen, Nicole M; Schmaljohn, Connie S

2015-12-01

We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NSS gene, but not the N, GN or NSM genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NSS, confirming that expression of NSS is likely responsible for this phenomenon. Published by Elsevier Inc.

Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells

International Nuclear Information System (INIS)

Zacapala-Gómez, Ana Elvira; Del Moral-Hernández, Oscar; Villegas-Sepúlveda, Nicolás; Hidalgo-Miranda, Alfredo; Romero-Córdoba, Sandra Lorena

2016-01-01

We analyzed the effects of the expression of HPV 16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350, E-G350), and the E-Prototype in global gene expression profiles in an in vitro model. E6 gene was cloned into an expression vector fused to GFP and was transfected in C33-A cells. Affymetrix GeneChip Human Transcriptome Array 2.0 platform was used to analyze the expression of over 245,000 coding transcripts. We found that HPV16 E6 variants altered the expression of 387 different genes in comparison with E-Prototype. The altered genes are involved in cellular processes related to the development of cervical carcinoma, such as adhesion, angiogenesis, apoptosis, differentiation, cell cycle, proliferation, transcription and protein translation. Our results show that polymorphic changes in HPV16 E6 natural variants are sufficient to alter the overall gene expression profile in C33-A cells, explaining in part the observed differences in oncogenic potential of HPV16 variants. - Highlights: • Amino acid changes in HPV16 E6 variants modulate the transciption of specific genes. • This is the first comparison of global gene expression profile of HPV 16 E6 variants. • Each HPV 16 E6 variant appears to have its own molecular signature.

Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells

Energy Technology Data Exchange (ETDEWEB)

Zacapala-Gómez, Ana Elvira, E-mail: zak_ana@yahoo.com.mx [Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Gro., México (Mexico); Del Moral-Hernández, Oscar, E-mail: odelmoralh@gmail.com [Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Gro., México (Mexico); Villegas-Sepúlveda, Nicolás, E-mail: nvillega@cinvestav.mx [Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D.F., México (Mexico); Hidalgo-Miranda, Alfredo, E-mail: ahidalgo@inmegen.gob.mx [Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), México, D.F., México (Mexico); Romero-Córdoba, Sandra Lorena, E-mail: sromero_cordoba@hotmail.com [Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), México, D.F., México (Mexico); and others

2016-01-15

We analyzed the effects of the expression of HPV 16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350, E-G350), and the E-Prototype in global gene expression profiles in an in vitro model. E6 gene was cloned into an expression vector fused to GFP and was transfected in C33-A cells. Affymetrix GeneChip Human Transcriptome Array 2.0 platform was used to analyze the expression of over 245,000 coding transcripts. We found that HPV16 E6 variants altered the expression of 387 different genes in comparison with E-Prototype. The altered genes are involved in cellular processes related to the development of cervical carcinoma, such as adhesion, angiogenesis, apoptosis, differentiation, cell cycle, proliferation, transcription and protein translation. Our results show that polymorphic changes in HPV16 E6 natural variants are sufficient to alter the overall gene expression profile in C33-A cells, explaining in part the observed differences in oncogenic potential of HPV16 variants. - Highlights: • Amino acid changes in HPV16 E6 variants modulate the transciption of specific genes. • This is the first comparison of global gene expression profile of HPV 16 E6 variants. • Each HPV 16 E6 variant appears to have its own molecular signature.

Global fluctuations of cerebral blood flow indicate a global brain network independent of systemic factors.

Science.gov (United States)

Zhao, Li; Alsop, David C; Detre, John A; Dai, Weiying

2017-01-01

Global synchronization across specialized brain networks is a common feature of network models and in-vivo electrical measurements. Although the imaging of specialized brain networks with blood oxygenation sensitive resting state functional magnetic resonance imaging (rsfMRI) has enabled detailed study of regional networks, the study of globally correlated fluctuations with rsfMRI is confounded by spurious contributions to the global signal from systemic physiologic factors and other noise sources. Here we use an alternative rsfMRI method, arterial spin labeled perfusion MRI, to characterize global correlations and their relationship to correlations and anti-correlations between regional networks. Global fluctuations that cannot be explained by systemic factors dominate the fluctuations in cerebral blood flow. Power spectra of these fluctuations are band limited to below 0.05 Hz, similar to prior measurements of regional network fluctuations in the brain. Removal of these global fluctuations prior to measurement of regional networks reduces all regional network fluctuation amplitudes to below the global fluctuation amplitude and changes the strength and sign of inter network correlations. Our findings support large amplitude, globally synchronized activity across networks that require a reassessment of regional network amplitude and correlation measures.

Correlations during the day of diffuse solar radiation to the global solar radiation in Vigo (Spain); Correlaciones minutarias, horarias y diarias de la radiacion solar difusa a la radiacion solar global en Vigo

Energy Technology Data Exchange (ETDEWEB)

Vazquez, M.; Santos, J.

2004-07-01

In the Solar Energy Lab of the University of Vigo a weather station has been in operation since October 2001. Two Kipp and Zonen pyranometers, one of them with a shade ring, have been measuring global and diffuse solar radiation. From these data of the years 2002 and 2003, the diffuse-to-global minute, hourly and daily correlations are obtained and shown in graphs. These correlations are also plotted together with other correlations referred in the literature for comparison. The graphs show the effect of the clear-cloudy behaviour of the solar radiation for short periods of time, effect that is not seen for larger periods of time as daily periods. (Author)

Global gene expression profiling displays a network of dysregulated genes in non-atherosclerotic arterial tissue from patients with type 2 diabetes

Directory of Open Access Journals (Sweden)

Skov Vibe

2012-02-01

Full Text Available Abstract Background Generalized arterial alterations, such as endothelial dysfunction, medial matrix accumulations, and calcifications are associated with type 2 diabetes (T2D. These changes may render the vessel wall more susceptible to injury; however, the molecular characteristics of such diffuse pre-atherosclerotic changes in diabetes are only superficially known. Methods To identify the molecular alterations of the generalized arterial disease in T2D, DNA microarrays were applied to examine gene expression changes in normal-appearing, non-atherosclerotic arterial tissue from 10 diabetic and 11 age-matched non-diabetic men scheduled for a coronary by-pass operation. Gene expression changes were integrated with GO-Elite, GSEA, and Cytoscape to identify significant biological pathways and networks. Results Global pathway analysis revealed differential expression of gene-sets representing matrix metabolism, triglyceride synthesis, inflammation, insulin signaling, and apoptosis. The network analysis showed a significant cluster of dysregulated genes coding for both intra- and extra-cellular proteins associated with vascular cell functions together with genes related to insulin signaling and matrix remodeling. Conclusions Our results identify pathways and networks involved in the diffuse vasculopathy present in non-atherosclerotic arterial tissue in patients with T2D and confirmed previously observed mRNA-alterations. These abnormalities may play a role for the arterial response to injury and putatively for the accelerated atherogenesis among patients with diabetes.

Global gene expression profiling of individual human oocytes and embryos demonstrates heterogeneity in early development.

Directory of Open Access Journals (Sweden)

Lisa Shaw

Full Text Available Early development in humans is characterised by low and variable embryonic viability, reflected in low fecundity and high rates of miscarriage, relative to other mammals. Data from assisted reproduction programmes provides additional evidence that this is largely mediated at the level of embryonic competence and is highly heterogeneous among embryos. Understanding the basis of this heterogeneity has important implications in a number of areas including: the regulation of early human development, disorders of pregnancy, assisted reproduction programmes, the long term health of children which may be programmed in early development, and the molecular basis of pluripotency in human stem cell populations. We have therefore investigated global gene expression profiles using polyAPCR amplification and microarray technology applied to individual human oocytes and 4-cell and blastocyst stage embryos. In order to explore the basis of any variability in detail, each developmental stage is replicated in triplicate. Our data show that although transcript profiles are highly stage-specific, within each stage they are relatively variable. We describe expression of a number of gene families and pathways including apoptosis, cell cycle and amino acid metabolism, which are variably expressed and may be reflective of embryonic developmental competence. Overall, our data suggest that heterogeneity in human embryo developmental competence is reflected in global transcript profiles, and that the vast majority of existing human embryo gene expression data based on pooled oocytes and embryos need to be reinterpreted.

Global regulator SoxR is a negative regulator of efflux pump gene expression and affects antibiotic resistance and fitness in Acinetobacter baumannii.

Science.gov (United States)

Li, Henan; Wang, Qi; Wang, Ruobing; Zhang, Yawei; Wang, Xiaojuan; Wang, Hui

2017-06-01

SoxR is a global regulator contributing to multidrug resistance in Enterobacteriaceae. However, the contribution of SoxR to antibiotic resistance and fitness in Acinetobacter baumannii has not yet been studied. Comparisons of molecular characteristics were performed between 32 multidrug-resistant A. baumannii isolates and 11 susceptible isolates. A soxR overexpression mutant was constructed, and its resistance phenotype was analyzed. The impact of SoxR on efflux pump gene expression was measured at the transcription level. The effect of SoxR on the growth and fitness of A. baumannii was analyzed using a growth rate assay and an in vitro competition assay. The frequency of the Gly39Ser mutation in soxR was higher in multidrug-resistant A. baumannii, whereas the soxS gene was absent in all strains analyzed. SoxR overexpression led to increased susceptibility to chloramphenicol (4-fold), tetracycline (2-fold), tigecycline (2-fold), ciprofloxacin (2-fold), amikacin (2-fold), and trimethoprim (2-fold), but it did not influence imipenem susceptibility. Decreased expression of abeS (3.8-fold), abeM (1.3-fold), adeJ (2.4-fold), and adeG (2.5-fold) were correlated with soxR overexpression (P baumannii.

Global Analysis of WRKY Genes and Their Response to Dehydration and Salt Stress in Soybean.

Science.gov (United States)

Song, Hui; Wang, Pengfei; Hou, Lei; Zhao, Shuzhen; Zhao, Chuanzhi; Xia, Han; Li, Pengcheng; Zhang, Ye; Bian, Xiaotong; Wang, Xingjun

2016-01-01

WRKY proteins are plant specific transcription factors involved in various developmental and physiological processes, especially in biotic and abiotic stress resistance. Although previous studies suggested that WRKY proteins in soybean (Glycine max var. Williams 82) involved in both abiotic and biotic stress responses, the global information of WRKY proteins in the latest version of soybean genome (Wm82.a2v1) and their response to dehydration and salt stress have not been reported. In this study, we identified 176 GmWRKY proteins from soybean Wm82.a2v1 genome. These proteins could be classified into three groups, namely group I (32 proteins), group II (120 proteins), and group III (24 proteins). Our results showed that most GmWRKY genes were located on Chromosome 6, while chromosome 11, 12, and 20 contained the least number of this gene family. More GmWRKY genes were distributed on the ends of chromosomes to compare with other regions. The cis-acting elements analysis suggested that GmWRKY genes were transcriptionally regulated upon dehydration and salt stress. RNA-seq data analysis indicated that three GmWRKY genes responded negatively to dehydration, and 12 genes positively responded to salt stress at 1, 6, and 12 h, respectively. We confirmed by qRT-PCR that the expression of GmWRKY47 and GmWRKY 58 genes was decreased upon dehydration, and the expression of GmWRKY92, 144 and 165 genes was increased under salt treatment.

DNA methylation differences at growth related genes correlate with birth weight: a molecular signature linked to developmental origins of adult disease?

Directory of Open Access Journals (Sweden)

Turan Nahid

2012-04-01

Full Text Available Abstract Background Infant birth weight is a complex quantitative trait associated with both neonatal and long-term health outcomes. Numerous studies have been published in which candidate genes (IGF1, IGF2, IGF2R, IGF binding proteins, PHLDA2 and PLAGL1 have been associated with birth weight, but these studies are difficult to reproduce in man and large cohort studies are needed due to the large inter individual variance in transcription levels. Also, very little of the trait variance is explained. We decided to identify additional candidates without regard for what is known about the genes. We hypothesize that DNA methylation differences between individuals can serve as markers of gene "expression potential" at growth related genes throughout development and that these differences may correlate with birth weight better than single time point measures of gene expression. Methods We performed DNA methylation and transcript profiling on cord blood and placenta from newborns. We then used novel computational approaches to identify genes correlated with birth weight. Results We identified 23 genes whose methylation levels explain 70-87% of the variance in birth weight. Six of these (ANGPT4, APOE, CDK2, GRB10, OSBPL5 and REG1B are associated with growth phenotypes in human or mouse models. Gene expression profiling explained a much smaller fraction of variance in birth weight than did DNA methylation. We further show that two genes, the transcriptional repressor MSX1 and the growth factor receptor adaptor protein GRB10, are correlated with transcriptional control of at least seven genes reported to be involved in fetal or placental growth, suggesting that we have identified important networks in growth control. GRB10 methylation is also correlated with genes involved in reactive oxygen species signaling, stress signaling and oxygen sensing and more recent data implicate GRB10 in insulin signaling. Conclusions Single time point measurements of gene

Big Data solution for CTBT monitoring: CEA-IDC joint global cross correlation project

Science.gov (United States)

Bobrov, Dmitry; Bell, Randy; Brachet, Nicolas; Gaillard, Pierre; Kitov, Ivan; Rozhkov, Mikhail

2014-05-01

Waveform cross-correlation when applied to historical datasets of seismic records provides dramatic improvements in detection, location, and magnitude estimation of natural and manmade seismic events. With correlation techniques, the amplitude threshold of signal detection can be reduced globally by a factor of 2 to 3 relative to currently standard beamforming and STA/LTA detector. The gain in sensitivity corresponds to a body wave magnitude reduction by 0.3 to 0.4 units and doubles the number of events meeting high quality requirements (e.g. detected by three and more seismic stations of the International Monitoring System (IMS). This gain is crucial for seismic monitoring under the Comprehensive Nuclear-Test-Ban Treaty. The International Data Centre (IDC) dataset includes more than 450,000 seismic events, tens of millions of raw detections and continuous seismic data from the primary IMS stations since 2000. This high-quality dataset is a natural candidate for an extensive cross correlation study and the basis of further enhancements in monitoring capabilities. Without this historical dataset recorded by the permanent IMS Seismic Network any improvements would not be feasible. However, due to the mismatch between the volume of data and the performance of the standard Information Technology infrastructure, it becomes impossible to process all the data within tolerable elapsed time. To tackle this problem known as "BigData", the CEA/DASE is part of the French project "DataScale". One objective is to reanalyze 10 years of waveform data from the IMS network with the cross-correlation technique thanks to a dedicated High Performance Computer (HPC) infrastructure operated by the Centre de Calcul Recherche et Technologie (CCRT) at the CEA of Bruyères-le-Châtel. Within 2 years we are planning to enhance detection and phase association algorithms (also using machine learning and automatic classification) and process about 30 terabytes of data provided by the IDC to

Link-based quantitative methods to identify differentially coexpressed genes and gene Pairs

Directory of Open Access Journals (Sweden)

Ye Zhi-Qiang

2011-08-01

Full Text Available Abstract Background Differential coexpression analysis (DCEA is increasingly used for investigating the global transcriptional mechanisms underlying phenotypic changes. Current DCEA methods mostly adopt a gene connectivity-based strategy to estimate differential coexpression, which is characterized by comparing the numbers of gene neighbors in different coexpression networks. Although it simplifies the calculation, this strategy mixes up the identities of different coexpression neighbors of a gene, and fails to differentiate significant differential coexpression changes from those trivial ones. Especially, the correlation-reversal is easily missed although it probably indicates remarkable biological significance. Results We developed two link-based quantitative methods, DCp and DCe, to identify differentially coexpressed genes and gene pairs (links. Bearing the uniqueness of exploiting the quantitative coexpression change of each gene pair in the coexpression networks, both methods proved to be superior to currently popular methods in simulation studies. Re-mining of a publicly available type 2 diabetes (T2D expression dataset from the perspective of differential coexpression analysis led to additional discoveries than those from differential expression analysis. Conclusions This work pointed out the critical weakness of current popular DCEA methods, and proposed two link-based DCEA algorithms that will make contribution to the development of DCEA and help extend it to a broader spectrum.

Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

KAUST Repository

Horiuchi, Youko; Harushima, Yoshiaki; Fujisawa, Hironori; Mochizuki, Takako; Fujita, Masahiro; Ohyanagi, Hajime; Kurata, Nori

2015-01-01

Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue

Correlation of mRNA and protein levels: Cell type-specific gene expression of cluster designation antigens in the prostate

Directory of Open Access Journals (Sweden)

Deutsch Eric W

2008-05-01

Full Text Available Abstract Background: Expression levels of mRNA and protein by cell types exhibit a range of correlations for different genes. In this study, we compared levels of mRNA abundance for several cluster designation (CD genes determined by gene arrays using magnetic sorted and laser-capture microdissected human prostate cells with levels of expression of the respective CD proteins determined by immunohistochemical staining in the major cell types of the prostate – basal epithelial, luminal epithelial, stromal fibromuscular, and endothelial – and for prostate precursor/stem cells and prostate carcinoma cells. Immunohistochemical stains of prostate tissues from more than 50 patients were scored for informative CD antigen expression and compared with cell-type specific transcriptomes. Results: Concordance between gene and protein expression findings based on 'present' vs. 'absent' calls ranged from 46 to 68%. Correlation of expression levels was poor to moderate (Pearson correlations ranged from 0 to 0.63. Divergence between the two data types was most frequently seen for genes whose array signals exceeded background (> 50 but lacked immunoreactivity by immunostaining. This could be due to multiple factors, e.g. low levels of protein expression, technological sensitivities, sample processing, probe set definition or anatomical origin of tissue and actual biological differences between transcript and protein abundance. Conclusion: Agreement between these two very different methodologies has great implications for their respective use in both molecular studies and clinical trials employing molecular biomarkers.

Early warning model based on correlated networks in global crude oil markets

Science.gov (United States)

Yu, Jia-Wei; Xie, Wen-Jie; Jiang, Zhi-Qiang

2018-01-01

Applying network tools on predicting and warning the systemic risks provides a novel avenue to manage risks in financial markets. Here, we construct a series of global crude oil correlated networks based on the historical 57 oil prices covering a period from 1993 to 2012. Two systemic risk indicators are constructed based on the density and modularity of correlated networks. The local maximums of the risk indicators are found to have the ability to predict the trends of oil prices. In our sample periods, the indicator based on the network density sends five signals and the indicator based on the modularity index sends four signals. The four signals sent by both indicators are able to warn the drop of future oil prices and the signal only sent by the network density is followed by a huge rise of oil prices. Our results deepen the application of network measures on building early warning models of systemic risks and can be applied to predict the trends of future prices in financial markets.

The responses of a forest model to serial correlations of global warming

International Nuclear Information System (INIS)

Cohen, Y.; Pastor, J.

1991-01-01

Predictions of CO 2 -inducing changes to climate have focused on equilibrial responses of the global climate system to different levels of trace-gas forcings. The authors forced a forest ecosystem model with linear changes in temperature and precipitation and varied the degree of serial correlation around mean values. The ecosystem model considers the establishment and growth of individual trees in a 1/12 haplot and their responses to degree days, soil water deficits, soil nitrogen availability, and light. A recent formal analysis indicates that the model output is more sensitive to changes in means and variances of temperature, as opposed to precipitation. Of particular interest to the current paper is the assumption that the probability of mortality increases from about 10% to 30% upon two consecutive years of slow growth due to stress. Thus, year-to-year serial correlations could potentially increase mortality compared with random variation between years. Using this model, Pastor and Post (1988) showed that the forests of the boreal-northern hardwood transition zone in the Lake Superior region are particularly sensitive to climate warming

Developmental changes of BOLD signal correlations with global human EEG power and synchronization during working memory.

Directory of Open Access Journals (Sweden)

Lars Michels

Full Text Available In humans, theta band (5-7 Hz power typically increases when performing cognitively demanding working memory (WM tasks, and simultaneous EEG-fMRI recordings have revealed an inverse relationship between theta power and the BOLD (blood oxygen level dependent signal in the default mode network during WM. However, synchronization also plays a fundamental role in cognitive processing, and the level of theta and higher frequency band synchronization is modulated during WM. Yet, little is known about the link between BOLD, EEG power, and EEG synchronization during WM, and how these measures develop with human brain maturation or relate to behavioral changes. We examined EEG-BOLD signal correlations from 18 young adults and 15 school-aged children for age-dependent effects during a load-modulated Sternberg WM task. Frontal load (in-dependent EEG theta power was significantly enhanced in children compared to adults, while adults showed stronger fMRI load effects. Children demonstrated a stronger negative correlation between global theta power and the BOLD signal in the default mode network relative to adults. Therefore, we conclude that theta power mediates the suppression of a task-irrelevant network. We further conclude that children suppress this network even more than adults, probably from an increased level of task-preparedness to compensate for not fully mature cognitive functions, reflected in lower response accuracy and increased reaction time. In contrast to power, correlations between instantaneous theta global field synchronization and the BOLD signal were exclusively positive in both age groups but only significant in adults in the frontal-parietal and posterior cingulate cortices. Furthermore, theta synchronization was weaker in children and was--in contrast to EEG power--positively correlated with response accuracy in both age groups. In summary we conclude that theta EEG-BOLD signal correlations differ between spectral power and

Diazotroph-Bacterial Community Structure of Root Nodules Account for Two-Fold Differences in Plant Growth: Consequences for Global Biogeochemical Cycles

Science.gov (United States)

Williams, M. A.

2016-12-01

The bacterial communities that inhabit and function as mutualists in the nodules of soybean, a major worldwide crop, are a fundamental determinant of plant growth and global nitrogen and carbon cycles. Unfertilized soybean can derive up to 90% of its nitrogen through bacterial-driven diazotrophy. It was the goal of the research in this study to assess whether different bacterial taxa (e.g. Bradyrhizobia spp.) differ in their soybean growth supportive role, which could then feedback to alter global biogeochemical cycling. Using 16S rRNA and NifH genes, nodule bacterial communities were shown to vary across 9 different cultivars of soybean, and that the variation between cultivars were highly correlated to plant yield (97 to 188 bu/Ha) and nitrogen. The relative abundances of gene sequences associated with the closest taxonomic match (NCBI), indicated that several taxa were (r= 0.76) negatively (e.g. Bradyrhizobium sp Ec3.3) or (r= 0.84) positively (e.g. Bradyrhizobium elkanii WSM 2783) correlated with plant yield. Other non-Rhizobiaceae taxa, such as Rhodopseudomonas spp. were also prevalent and correlated with plant yield. Soybeans and other leguminous crops will become increasingly important part of world food production, soil fertility and global biogeochemical cycles with rising population and food demand. The study demonstrates the importance of plant-microbial feedbacks driving plant growth but also ramifications for global cycling of nitrogen and carbon.

Presence of activating KRAS mutations correlates significantly with expression of tumour suppressor genes DCN and TPM1 in colorectal cancer

Directory of Open Access Journals (Sweden)

Rems Miran

2009-08-01

Full Text Available Abstract Background Despite identification of the major genes and pathways involved in the development of colorectal cancer (CRC, it has become obvious that several steps in these pathways might be bypassed by other as yet unknown genetic events that lead towards CRC. Therefore we wanted to improve our understanding of the genetic mechanisms of CRC development. Methods We used microarrays to identify novel genes involved in the development of CRC. Real time PCR was used for mRNA expression as well as to search for chromosomal abnormalities within candidate genes. The correlation between the expression obtained by real time PCR and the presence of the KRAS mutation was investigated. Results We detected significant previously undescribed underexpression in CRC for genes SLC26A3, TPM1 and DCN, with a suggested tumour suppressor role. We also describe the correlation between TPM1 and DCN expression and the presence of KRAS mutations in CRC. When searching for chromosomal abnormalities, we found deletion of the TPM1 gene in one case of CRC, but no deletions of DCN and SLC26A3 were found. Conclusion Our study provides further evidence of decreased mRNA expression of three important tumour suppressor genes in cases of CRC, thus implicating them in the development of this type of cancer. Moreover, we found underexpression of the TPM1 gene in a case of CRCs without KRAS mutations, showing that TPM1 might serve as an alternative path of development of CRC. This downregulation could in some cases be mediated by deletion of the TPM1 gene. On the other hand, the correlation of DCN underexpression with the presence of KRAS mutations suggests that DCN expression is affected by the presence of activating KRAS mutations, lowering the amount of the important tumour suppressor protein decorin.

Gene expression analysis to identify molecular correlates of pre- and post-conditioning derived neuroprotection.

Science.gov (United States)

Prasad, Shiv S; Russell, Marsha; Nowakowska, Margeryta; Williams, Andrew; Yauk, Carole

2012-06-01

Mild ischaemic exposures before or after severe injurious ischaemia that elicit neuroprotective responses are referred to as preconditioning and post-conditioning. The corresponding molecular mechanisms of neuroprotection are not completely understood. Identification of the genes and associated pathways of corresponding neuroprotection would provide insight into neuronal survival, potential therapeutic approaches and assessments of therapies for stroke. The objectives of this study were to use global gene expression approach to infer the molecular mechanisms in pre- and post-conditioning-derived neuroprotection in cortical neurons following oxygen and glucose deprivation (OGD) in vitro and then to apply these findings to predict corresponding functional pathways. To this end, microarray analysis was applied to rat cortical neurons with or without the pre- and post-conditioning treatments at 3-h post-reperfusion, and differentially expressed transcripts were subjected to statistical, hierarchical clustering and pathway analyses. The expression patterns of 3,431 genes altered under all conditions of ischaemia (with and without pre- or post-conditioning). We identified 1,595 genes that were commonly regulated within both the pre- and post-conditioning treatments. Cluster analysis revealed that transcription profiles clustered tightly within controls, non-conditioned OGD and neuroprotected groups. Two clusters defining neuroprotective conditions associated with up- and downregulated genes were evident. The five most upregulated genes within the neuroprotective clusters were Tagln, Nes, Ptrf, Vim and Adamts9, and the five most downregulated genes were Slc7a3, Bex1, Brunol4, Nrxn3 and Cpne4. Pathway analysis revealed that the intracellular and second messenger signalling pathways in addition to cell death were predominantly associated with downregulated pre- and post-conditioning associated genes, suggesting that modulation of cell death and signal transduction pathways

Correlating gene expression with deformities caused by aryl hydrocarbon receptor agonists in zebrafish (Danio rerio)

Energy Technology Data Exchange (ETDEWEB)

Bugiak, B.; Weber, L. [Saskatchewan Univ., Saskatoon, SK (Canada)

2009-07-01

Exposure to aryl hydrocarbon receptor (AhR) agonists in fish causes lethal disturbances in fish development, but the effects of acute AhR agonist exposure on the cardiovascular system and deformities remain unclear. This study addressed this issue by performing a series of experiments on zebrafish (Danio rerio). The authors hypothesized that genes needed for cardiovascular regulation (PTGS) would exhibit a stronger link to deformities than detoxification enzymes (CYPs). Zebrafish eggs were exposed aqueously until 4 days post-fertilization (dpf) to the AhR agonists benzo(a)pyrene (BaP) or 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD) alone and in combination with the putative AhR antagonists resveratrol or alpha-naphthoflavone (ANF). Gene expression was measured using real-time, reverse transcriptase PCR in zebrafish at 5 and 10 dpf. Although the mortalities did not differ considerably among groups at 10 dpf, the deformities increased significantly after BaP-ANF at 5 dpf and after BaP at 10 dpf, but not after TCDD treatment. CYP and PTGS isozymes exhibited small, but statistically significant changes at 5 dpf. By 10 dpf, the expression returned to control values. In general, CYP1A and PTGS-1 expression at 5 dpf were positively correlated with deformities, while all other genes were negatively correlated with deformities. It was concluded that changes in CYP1A, CYP1C2, and PTGS-1 gene expression at 5 dpf are associated with developmental deformities, but additional work is needed to determine which has the most important mechanistic link.

Urine mercury levels correlate with DNA methylation of imprinting gene H19 in the sperm of reproductive-aged men.

Directory of Open Access Journals (Sweden)

Zhaoxu Lu

Full Text Available Mercury (Hg is a well-recognized environmental pollutant known by its toxicity of development and neurotoxicity, which results in adverse health outcomes. However, the mechanisms underlying the teratogenic effects of Hg are not well understood. Imprinting genes are emerging regulators for fetal development subjecting to environmental pollutants impacts. In this study, we examined the association between preconceptional Hg exposure and the alteration of DNA methylation of imprinting genes H19, Meg3, and Peg3 in human sperm DNA.A total of 616 men, aged from 22 to 59, were recruited from Reproductive Medicine Clinic of Maternal and Child Care Service Center and the Urologic Surgery Clinic of Shanxi Academy of Medical Sciences during April 2015 and March 2016. Demographic information was collected through questionnaires. Urine was collected and urinary Hg concentrations were measured using a fully-automatic double-channel hydride generation atomic fluorescence spectrometer. Methylation of imprinting genes H19, Meg3 and Peg3 of sperm DNA from 242 participants were examined by bisulfite pyrosequencing. Spearman's rank and multivariate regression analysis were used for correlation analysis between sperm DNA methylation status of imprinting genes and urinary Hg levels.The median concentration of Hg for 616 participants was 9.14μg/l (IQR: 5.56-12.52 μg/l; ranging 0.16-71.35μg/l. A total of 42.7% of the participants are beyond normal level for non-occupational exposure according to the criterion of Hg poisoning (≥10 μg/L. Spearman's rank analysis indicated a negative correlation between urinary Hg concentrations and average DNA methylation levels of imprinted genes H19 (rs = -0.346, p <0.05, but there was no such a correlation for Peg3 and Meg3. Further, we analyzed the correlation between methylation level at individual CpG site of H19 and urinary Hg level. The results showed a negative correlation between urinary Hg concentrations and three out of

Global earthquake catalogs and long-range correlation of seismic activity (Invited)

Science.gov (United States)

Ogata, Y.

2009-12-01

In view of the long-term seismic activity in the world, homogeneity of a global catalog is indispensable. Lately, Engdahl and Villaseñor (2002) compiled a global earthquake catalog of magnitude (M)7.0 or larger during the last century (1900-1999). This catalog is based on the various existing catalogs such as Abe catalog (Abe, 1981, 1984; Abe and Noguchi, 1983a, b) for the world seismicity (1894-1980), its modified catalogs by Perez and Scholz (1984) and by Pacheco and Sykes (1992), and also the Harvard University catalog since 1975. However, the original surface wave magnitudes of Abe catalog were systematically changed by Perez and Scholz (1984) and Pacheco and Sykes (1992). They suspected inhomogeneity of the Abe catalog and claimed that the two seeming changes in the occurrence rate around 1922 and 1948 resulted from magnitude shifts for some instrumental-related reasons. They used a statistical test assuming that such a series of large earthquakes in the world should behave as the stationary Poisson process (uniform occurrences). It is obvious that their claim strongly depends on their a priori assumption of an independent or short-range dependence of earthquake occurrence. We question this assumption from the viewpoint of long-range dependence of seismicity. We make some statistical analyses of the spectrum, dispersion-time diagrams and R/S for estimating and testing of the long-range correlations. We also attempt to show the possibility that the apparent rate change in the global seismicity can be simulated by a certain long-range correlated process. Further, if we divide the globe into the two regions of high and low latitudes, for example, we have different shapes of the cumulative curves to each other, and the above mentioned apparent change-points disappear from the both regions. This suggests that the Abe catalog shows the genuine seismic activity rather than the artifact of the suspected magnitude shifts that should appear in any wide enough regions

Boys' serotonin transporter genotype affects maternal behavior through self-control: a case of evocative gene-environment correlation.

Science.gov (United States)

Pener-Tessler, Roni; Avinun, Reut; Uzefovsky, Florina; Edelman, Shany; Ebstein, Richard P; Knafo, Ariel

2013-02-01

Self-control, involving processes such as delaying gratification, concentrating, planning, following instructions, and adapting emotions and behavior to situational requirements and social norms, may have a profound impact on children's adjustment. The importance of self-control suggests that parents are likely to modify their parenting based on children's ability for self-control. We study the effect of children's self-control, a trait partially molded by genetics, on their mothers' parenting, a process of evocative gene-environment correlation. Israeli 3.5-year-old twins (N = 320) participated in a lab session in which their mothers' parenting was observed. DNA was available from most children (N = 228). Mothers described children's self-control in a questionnaire. Boys were lower in self-control and received less positive parenting from their mothers, in comparison with girls. For boys, and not for girls, the serotonin transporter linked polymorphic region gene predicted mothers' levels of positive parenting, an effect mediated by boys' self-control. The implications of this evocative gene-environment correlation and the observed sex differences are discussed.

Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure

Energy Technology Data Exchange (ETDEWEB)

Ozden, Sibel, E-mail: stopuz@istanbul.edu.tr [Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul (Turkey); Turgut Kara, Neslihan [Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Istanbul (Turkey); Sezerman, Osman Ugur [Department of Biostatistics and Medical Informatics, Acibadem University, Istanbul (Turkey); Durasi, İlknur Melis [Biological Sciences and Bioengineering, Faculty of Engineering and Natural Sciences, Sabancı University, Istanbul (Turkey); Chen, Tao [Department of Toxicology, School of Public Health, Soochow University, Suzhou (China); Demirel, Goksun; Alpertunga, Buket [Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul (Turkey); Chipman, J. Kevin [School of Biosciences, The University of Birmingham, Birmingham (United Kingdom); Mally, Angela [Department of Toxicology, University of Würzburg, Würzburg (Germany)

2015-12-01

Altered expression of tumor suppressor genes and oncogenes, which is regulated in part at the level of DNA methylation, is an important event involved in non-genotoxic carcinogenesis. This may serve as a marker for early detection of non-genotoxic carcinogens. Therefore, we evaluated the effects of non-genotoxic hepatocarcinogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hexachlorobenzene (HCB), methapyrilene (MPY) and male rat kidney carcinogens, d-limonene, p-dichlorobenzene (DCB), chloroform and ochratoxin A (OTA) on global and CpG island promoter methylation in their respective target tissues in rats. No significant dose-related effects on global DNA hypomethylation were observed in tissues of rats compared to vehicle controls using LC–MS/MS in response to short-term non-genotoxic carcinogen exposure. Initial experiments investigating gene-specific methylation using methylation-specific PCR and bisulfite sequencing, revealed partial methylation of p16 in the liver of rats treated with HCB and TCDD. However, no treatment related effects on the methylation status of Cx32, e-cadherin, VHL, c-myc, Igfbp2, and p15 were observed. We therefore applied genome-wide DNA methylation analysis using methylated DNA immunoprecipitation combined with microarrays to identify alterations in gene-specific methylation. Under the conditions of our study, some genes were differentially methylated in response to MPY and TCDD, whereas d-limonene, DCB and chloroform did not induce any methylation changes. 90-day OTA treatment revealed enrichment of several categories of genes important in protein kinase activity and mTOR cell signaling process which are related to OTA nephrocarcinogenicity. - Highlights: • Studied non-genotoxic carcinogens caused no change on global DNA hypomethylation. • d-Limonene, DCB and chloroform did not show any genome-wide methylation changes. • Some genes were differentially methylated in response to MPY, TCDD and OTA. • Protein kinase activity

Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure

International Nuclear Information System (INIS)

Ozden, Sibel; Turgut Kara, Neslihan; Sezerman, Osman Ugur; Durasi, İlknur Melis; Chen, Tao; Demirel, Goksun; Alpertunga, Buket; Chipman, J. Kevin; Mally, Angela

2015-01-01

Altered expression of tumor suppressor genes and oncogenes, which is regulated in part at the level of DNA methylation, is an important event involved in non-genotoxic carcinogenesis. This may serve as a marker for early detection of non-genotoxic carcinogens. Therefore, we evaluated the effects of non-genotoxic hepatocarcinogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hexachlorobenzene (HCB), methapyrilene (MPY) and male rat kidney carcinogens, d-limonene, p-dichlorobenzene (DCB), chloroform and ochratoxin A (OTA) on global and CpG island promoter methylation in their respective target tissues in rats. No significant dose-related effects on global DNA hypomethylation were observed in tissues of rats compared to vehicle controls using LC–MS/MS in response to short-term non-genotoxic carcinogen exposure. Initial experiments investigating gene-specific methylation using methylation-specific PCR and bisulfite sequencing, revealed partial methylation of p16 in the liver of rats treated with HCB and TCDD. However, no treatment related effects on the methylation status of Cx32, e-cadherin, VHL, c-myc, Igfbp2, and p15 were observed. We therefore applied genome-wide DNA methylation analysis using methylated DNA immunoprecipitation combined with microarrays to identify alterations in gene-specific methylation. Under the conditions of our study, some genes were differentially methylated in response to MPY and TCDD, whereas d-limonene, DCB and chloroform did not induce any methylation changes. 90-day OTA treatment revealed enrichment of several categories of genes important in protein kinase activity and mTOR cell signaling process which are related to OTA nephrocarcinogenicity. - Highlights: • Studied non-genotoxic carcinogens caused no change on global DNA hypomethylation. • d-Limonene, DCB and chloroform did not show any genome-wide methylation changes. • Some genes were differentially methylated in response to MPY, TCDD and OTA. • Protein kinase activity

Correlation between Group B Streptococcal Genotypes, Their Antimicrobial Resistance Profiles, and Virulence Genes among Pregnant Women in Lebanon

Directory of Open Access Journals (Sweden)

Antoine Hannoun

2009-01-01

Full Text Available The antimicrobial susceptibility profiles of 76 Streptococcus agalactiae (Group B Streptococci [GBS] isolates from vaginal specimens of pregnant women near term were correlated to their genotypes generated by Random Amplified Polymorphic DNA analysis and their virulence factors encoding genes cylE, lmb, scpB, rib, and bca by PCR. Based on the distribution of the susceptibility patterns, six profiles were generated. RAPD analysis detected 7 clusters of genotypes. The cylE gene was present in 99% of the isolates, the lmb in 96%, scpB in 94.7%, rib in 33%, and bca in 56.5% of isolates. The isolates demonstrated a significant correlation between antimicrobial resistance and genotype clusters denoting the distribution of particular clones with different antimicrobial resistance profiles, entailing the practice of caution in therapeutic options. All virulence factors encoding genes were detected in all seven genotypic clusters with rib and bca not coexisting in the same genome.

Global analysis of gene expression profiles in developing physic nut (Jatropha curcas L.) seeds.

Science.gov (United States)

Jiang, Huawu; Wu, Pingzhi; Zhang, Sheng; Song, Chi; Chen, Yaping; Li, Meiru; Jia, Yongxia; Fang, Xiaohua; Chen, Fan; Wu, Guojiang

2012-01-01

Physic nut (Jatropha curcas L.) is an oilseed plant species with high potential utility as a biofuel. Furthermore, following recent sequencing of its genome and the availability of expressed sequence tag (EST) libraries, it is a valuable model plant for studying carbon assimilation in endosperms of oilseed plants. There have been several transcriptomic analyses of developing physic nut seeds using ESTs, but they have provided limited information on the accumulation of stored resources in the seeds. We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of developing physic nut seeds 14, 19, 25, 29, 35, 41, and 45 days after pollination (DAP). The acquired profiles reveal the key genes, and their expression timeframes, involved in major metabolic processes including: carbon flow, starch metabolism, and synthesis of storage lipids and proteins in the developing seeds. The main period of storage reserves synthesis in the seeds appears to be 29-41 DAP, and the fatty acid composition of the developing seeds is consistent with relative expression levels of different isoforms of acyl-ACP thioesterase and fatty acid desaturase genes. Several transcription factor genes whose expression coincides with storage reserve deposition correspond to those known to regulate the process in Arabidopsis. The results will facilitate searches for genes that influence de novo lipid synthesis, accumulation and their regulatory networks in developing physic nut seeds, and other oil seeds. Thus, they will be helpful in attempts to modify these plants for efficient biofuel production.

Global transgenerational gene expression dynamics in two newly synthesized allohexaploid wheat (Triticum aestivum lines

Directory of Open Access Journals (Sweden)

Qi Bao

2012-01-01

terms. Nonetheless, those genes showing non-additive expression exhibited a significant enrichment for vesicle-function. Conclusions Our results show that two patterns of global alteration in gene expression are conditioned by allohexaploidization in wheat, that is, parental dominance expression and non-additive expression. Both altered patterns of gene expression but not the identity of the genes involved are likely to play functional roles in stabilization and establishment of the newly formed allohexaploid plants, and hence, relevant to speciation and evolution of T. aestivum.

Bi-directional gene set enrichment and canonical correlation analysis identify key diet-sensitive pathways and biomarkers of metabolic syndrome

Directory of Open Access Journals (Sweden)

Gaora Peadar Ó

2010-10-01

Full Text Available Abstract Background Currently, a number of bioinformatics methods are available to generate appropriate lists of genes from a microarray experiment. While these lists represent an accurate primary analysis of the data, fewer options exist to contextualise those lists. The development and validation of such methods is crucial to the wider application of microarray technology in the clinical setting. Two key challenges in clinical bioinformatics involve appropriate statistical modelling of dynamic transcriptomic changes, and extraction of clinically relevant meaning from very large datasets. Results Here, we apply an approach to gene set enrichment analysis that allows for detection of bi-directional enrichment within a gene set. Furthermore, we apply canonical correlation analysis and Fisher's exact test, using plasma marker data with known clinical relevance to aid identification of the most important gene and pathway changes in our transcriptomic dataset. After a 28-day dietary intervention with high-CLA beef, a range of plasma markers indicated a marked improvement in the metabolic health of genetically obese mice. Tissue transcriptomic profiles indicated that the effects were most dramatic in liver (1270 genes significantly changed; p Conclusion Bi-directional gene set enrichment analysis more accurately reflects dynamic regulatory behaviour in biochemical pathways, and as such highlighted biologically relevant changes that were not detected using a traditional approach. In such cases where transcriptomic response to treatment is exceptionally large, canonical correlation analysis in conjunction with Fisher's exact test highlights the subset of pathways showing strongest correlation with the clinical markers of interest. In this case, we have identified selenoamino acid metabolism and steroid biosynthesis as key pathways mediating the observed relationship between metabolic health and high-CLA beef. These results indicate that this type of

Axin gene methylation status correlates with radiosensitivity of lung cancer cells

International Nuclear Information System (INIS)

Yang, Lian-He; Stoecker, Maggie; Wang, Endi; Xu, Ke; Wang, En-Hua; Han, Yang; Li, Guang; Xu, Hong-Tao; Jiang, Gui-Yang; Miao, Yuan; Zhang, Xiu-Peng; Zhao, Huan-Yu; Xu, Zheng-Fan

2013-01-01

We previously reported that Axin1 (Axin) is down-regulated in many cases of lung cancer, and X-ray irradiation increased Axin expression and inhibited lung cancer cells. The mechanisms, however, were not clear. Four lung cancer cell lines were used to detect the methylation status of Axin with or without X-ray treatment. Real-time PCR was used to quantify the expression of Axin, and western blot analysis was applied to measure protein levels of Axin, β-catenin, Cyclin D1, MMP-7, DNMTS, MeCP2 and acetylated histones. Flow cytometric analysis, colony formation assay, transwell assay and xenograft growth experiment were used to study the biological behavior of the cells with hypermethylated or unmethylated Axin gene after X-ray treatment. Hypermethylated Axin gene was detected in 2 of 4 cell lines, and it correlated inversely with Axin expression. X-ray treatment significantly up-regulated Axin expression in H446 and H157 cells, which possess intrinsic hypermethylation of the Axin gene (P<0.01), but did not show up-regulation in LTE and H460 cells, which have unmethylated Axin gene. 2Gy X-ray significantly reduced colony formation (from 71% to 10.5%) in H157 cells, while the reduction was lower in LTE cells (from 71% to 20%). After X-ray irradiation, xenograft growth was significantly decreased in H157 cells (from 1.15 g to 0.28 g) in comparison with LTE cells (from 1.06 g to 0.65 g). Significantly decreased cell invasiveness and increased apoptosis were also observed in H157 cells treated with X-ray irradiation (P<0.01). Down-regulation of DNMTs and MeCP2 and up-regulation of acetylated histones could be detected in lung cancer cells. X-ray-induced inhibition of lung cancer cells may be mediated by enhanced expression of Axin via genomic DNA demethylation and histone acetylation. Lung cancer cells with a different methylation status of the Axin gene showed different radiosensitivity, suggesting that the methylation status of the Axin gene may be one important factor

Antibiotic Resistance Genes and Correlations with Microbial Community and Metal Resistance Genes in Full-Scale Biogas Reactors As Revealed by Metagenomic Analysis

DEFF Research Database (Denmark)

Luo, Gang; Li, Bing; Li, Li-Guan

2017-01-01

resistance genes (MRGs). The total abundance of ARGs in all the samples varied from 7 × 10-3 to 1.08 × 10-1 copy of ARG/copy of 16S-rRNA gene, and the samples obtained from thermophilic biogas reactors had a lower total abundance of ARGs, indicating the superiority of thermophilic anaerobic digestion......Digested residues from biogas plants are often used as biofertilizers for agricultural crops cultivation. The antibiotic resistance genes (ARGs) in digested residues pose a high risk to public health due to their potential spread to the disease-causing microorganisms and thus reduce...... the susceptibility of disease-causing microorganisms to antibiotics in medical treatment. A high-throughput sequencing (HTS)-based metagenomic approach was used in the present study to investigate the variations of ARGs in full-scale biogas reactors and the correlations of ARGs with microbial communities and metal...

The genetics of music accomplishment: evidence for gene-environment correlation and interaction.

Science.gov (United States)

Hambrick, David Z; Tucker-Drob, Elliot M

2015-02-01

Theories of skilled performance that emphasize training history, such as K. Anders Ericsson and colleagues' deliberate-practice theory, have received a great deal of recent attention in both the scientific literature and the popular press. Twin studies, however, have demonstrated evidence for moderate-to-strong genetic influences on skilled performance. Focusing on musical accomplishment in a sample of over 800 pairs of twins, we found evidence for gene-environment correlation, in the form of a genetic effect on music practice. However, only about one quarter of the genetic effect on music accomplishment was explained by this genetic effect on music practice, suggesting that genetically influenced factors other than practice contribute to individual differences in music accomplishment. We also found evidence for gene-environment interaction, such that genetic effects on music accomplishment were most pronounced among those engaging in music practice, suggesting that genetic potentials for skilled performance are most fully expressed and fostered by practice.

Global loss of bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism.

Directory of Open Access Journals (Sweden)

David John Kennaway

Full Text Available The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood. Here we investigated adipocyte function and the metabolic status of mice with a global loss of the core clock gene Bmal1 fed either a normal or a high fat diet (22% by weight. Bmal1 null mice aged 2 months were killed across 24 hours and plasma adiponectin and leptin, and adipose tissue expression of Adipoq, Lep, Retn and Nampt mRNA measured. Glucose, insulin and pyruvate tolerance tests were conducted and the expression of liver glycolytic and gluconeogenic enzyme mRNA determined. Bmal1 null mice displayed a pattern of increased plasma adiponectin and plasma leptin concentrations on both control and high fat diets. Bmal1 null male and female mice displayed increased adiposity (1.8 fold and 2.3 fold respectively on the normal diet, but the high fat diet did not exaggerate these differences. Despite normal glucose and insulin tolerance, Bmal1 null mice had increased production of glucose from pyruvate, implying increased liver gluconeogenesis. The Bmal1 null mice had arrhythmic clock gene expression in epigonadal fat and liver, and loss of rhythmic transcription of a range of metabolic genes. Furthermore, the expression of epigonadal fat Adipoq, Retn, Nampt, AdipoR1 and AdipoR2 and liver Pfkfb3 mRNA were down-regulated. These results show for the first time that global loss of Bmal1, and the consequent arrhythmicity, results in compensatory changes in adipokines involved in the cellular control of glucose metabolism.

Global gene expression in Escherichia coli biofilms

DEFF Research Database (Denmark)

Schembri, Mark; Kjærgaard, K.; Klemm, Per

2003-01-01

It is now apparent that microorganisms undergo significant changes during the transition from planktonic to biofilm growth. These changes result in phenotypic adaptations that allow the formation of highly organized and structured sessile communities, which possess enhanced resistance to antimicr......It is now apparent that microorganisms undergo significant changes during the transition from planktonic to biofilm growth. These changes result in phenotypic adaptations that allow the formation of highly organized and structured sessile communities, which possess enhanced resistance...... the transition to biofilm growth, and these included genes expressed under oxygen-limiting conditions, genes encoding (putative) transport proteins, putative oxidoreductases and genes associated with enhanced heavy metal resistance. Of particular interest was the observation that many of the genes altered...... in expression have no current defined function. These genes, as well as those induced by stresses relevant to biofilm growth such as oxygen and nutrient limitation, may be important factors that trigger enhanced resistance mechanisms of sessile communities to antibiotics and hydrodynamic shear forces....

Global Indicators Analysis and Consultancy Experience Insights into Correlation between Entrepreneurial Activities and Business Environment

Directory of Open Access Journals (Sweden)

Jovan Krivokapić

2015-02-01

Full Text Available Many researches and practical experiences clearly indicate the existence of a strong relationship between entrepreneurial activities and the business environment in which these activities are initiated. Although this topic has been quite ignored until the late twentieth century, a lot of studies and consulting practice have contributed to the fact that there are now a number of theories concerning mentioned correlation. These theories aim to offer a model that would provide better utilization of the possibilities from the business environment which could be very important for the development from both macroeconomic and microeconomic aspects. An increasing number of articles on this topic says enough about its importance, and numerous researches by many reputable globally recognized institutions go in favor of this claim. There are many indicators that observe the economic situation in a country or a region from different aspects, so the analyses of these indicators make it possible to determine the specific relationships between entrepreneurial activities and the local and the global business environment. Given the complexity of these relations, the impact cannot be observed partially, without taking into consideration other important factors, but more detailed analyses, however, result in some useful conclusions, which in the proper context can have a positive impact on many economic factors. It is very important to emphasize the fact that the correlation between the business environment and entrepreneurial activities is bidirectional, since this influence is mutual, so that changes in one of these factors can and usually cause some modifications in the other. Frequent series of such iterations actually lead to changes in the business environment, while entrepreneurial activity changes its shape and affects the economy of a country or a region, which is of particular importance for its competitiveness in the era of globalization.

A Decade of Global mRNA and miRNA Profiling of HPV-Positive Cell Lines and Clinical Specimens

DEFF Research Database (Denmark)

Kaczkowski, Bogumil; Morevati, Marya; Rossing, Maria

2012-01-01

For more than a decade, global gene expression profiling has been extensively used to elucidate the biology of human papillomaviruses (HPV) and their role in cervical- and head-and-neck cancers. Since 2008, the expression profiling of miRNAs has been reported in multiple HPV studies. Two major...... as the fragmented miRNA-mRNA target correlation evidence. Furthermore, we propose an approach for future research to include more comprehensive miRNA-mRNA target correlation analysis and to apply systems biology/gene networks methodology....... strategies have been employed in the gene and miRNA profiling studies: In the first approach, HPV positive tumors were compared to normal tissues or to HPV negative tumors. The second strategy relied on analysis of cell cultures transfected with single HPV oncogenes or with HPV genomes compared...

Retinal phenotype-genotype correlation of pediatric patients expressing mutations in the Norrie disease gene.

Science.gov (United States)

Wu, Wei-Chi; Drenser, Kimberly; Trese, Michael; Capone, Antonio; Dailey, Wendy

2007-02-01

To correlate the ophthalmic findings of patients with pediatric vitreoretinopathies with mutations occurring in the Norrie disease gene (NDP). One hundred nine subjects with diverse pediatric vitreoretinopathies and 54 control subjects were enrolled in the study. Diagnoses were based on retinal findings at each patient's first examination. Samples of DNA from each patient underwent polymerase chain reaction amplification and direct sequencing of the NDP gene. Eleven male patients expressing mutations in the NDP gene were identified in the test group, whereas the controls demonstrated wild-type NDP. All patients diagnosed as having Norrie disease had mutations in the NDP gene. Four of the patients with Norrie disease had mutations involving a cysteine residue in the cysteine-knot motif. Four patients diagnosed as having familial exudative vitreoretinopathy were found to have noncysteine mutations. One patient with retinopathy of prematurity had a 14-base deletion in the 5' untranslated region (exon 1), and 1 patient with bilateral persistent fetal vasculature syndrome expressed a noncysteine mutation in the second exon. Mutations disrupting the cysteine-knot motif corresponded to severe retinal dysgenesis, whereas patients with noncysteine mutations had varying degrees of avascular peripheral retina, extraretinal vasculature, and subretinal exudate. Patients exhibiting severe retinal dysgenesis should be suspected of carrying a mutation that disrupts the cysteine-knot motif in the NDP gene.

Global analysis of gene expression profiles in developing physic nut (Jatropha curcas L. seeds.

Directory of Open Access Journals (Sweden)

Huawu Jiang

Full Text Available BACKGROUND: Physic nut (Jatropha curcas L. is an oilseed plant species with high potential utility as a biofuel. Furthermore, following recent sequencing of its genome and the availability of expressed sequence tag (EST libraries, it is a valuable model plant for studying carbon assimilation in endosperms of oilseed plants. There have been several transcriptomic analyses of developing physic nut seeds using ESTs, but they have provided limited information on the accumulation of stored resources in the seeds. METHODOLOGY/PRINCIPAL FINDINGS: We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of developing physic nut seeds 14, 19, 25, 29, 35, 41, and 45 days after pollination (DAP. The acquired profiles reveal the key genes, and their expression timeframes, involved in major metabolic processes including: carbon flow, starch metabolism, and synthesis of storage lipids and proteins in the developing seeds. The main period of storage reserves synthesis in the seeds appears to be 29-41 DAP, and the fatty acid composition of the developing seeds is consistent with relative expression levels of different isoforms of acyl-ACP thioesterase and fatty acid desaturase genes. Several transcription factor genes whose expression coincides with storage reserve deposition correspond to those known to regulate the process in Arabidopsis. CONCLUSIONS/SIGNIFICANCE: The results will facilitate searches for genes that influence de novo lipid synthesis, accumulation and their regulatory networks in developing physic nut seeds, and other oil seeds. Thus, they will be helpful in attempts to modify these plants for efficient biofuel production.

FTO gene variant modulates the neural correlates of visual food perception.

Science.gov (United States)

Kühn, Anne B; Feis, Delia-Lisa; Schilbach, Leonhard; Kracht, Lutz; Hess, Martin E; Mauer, Jan; Brüning, Jens C; Tittgemeyer, Marc

2016-03-01

Variations in the fat mass and obesity associated (FTO) gene are currently the strongest known genetic factor predisposing humans to non-monogenic obesity. Recent experiments have linked these variants to a broad spectrum of behavioural alterations, including food choice and substance abuse. Yet, the underlying neurobiological mechanisms by which these genetic variations influence body weight remain elusive. Here, we explore the brain structural substrate of the obesity-predisposing rs9939609 T/A variant of the FTO gene in non-obese subjects by means of multivariate classification and use fMRI to investigate genotype-specific differences in neural food-cue reactivity by analysing correlates of a visual food perception task. Our findings demonstrate that MRI-derived measures of morphology along middle and posterior fusiform gyrus (FFG) are highly predictive for FTO at-risk allele carriers, who also show enhanced neural responses elicited by food cues in the same posterior FFG area. In brief, these findings provide first-time evidence for FTO-specific differences in both brain structure and function already in non-obese individuals, thereby contributing to a mechanistic understanding of why FTO is a predisposing factor for obesity. Copyright © 2015 Elsevier Inc. All rights reserved.

Correlation of gene expression and protein production rate - a system wide study

Directory of Open Access Journals (Sweden)

Arvas Mikko

2011-12-01

Full Text Available Abstract Background Growth rate is a major determinant of intracellular function. However its effects can only be properly dissected with technically demanding chemostat cultivations in which it can be controlled. Recent work on Saccharomyces cerevisiae chemostat cultivations provided the first analysis on genome wide effects of growth rate. In this work we study the filamentous fungus Trichoderma reesei (Hypocrea jecorina that is an industrial protein production host known for its exceptional protein secretion capability. Interestingly, it exhibits a low growth rate protein production phenotype. Results We have used transcriptomics and proteomics to study the effect of growth rate and cell density on protein production in chemostat cultivations of T. reesei. Use of chemostat allowed control of growth rate and exact estimation of the extracellular specific protein production rate (SPPR. We find that major biosynthetic activities are all negatively correlated with SPPR. We also find that expression of many genes of secreted proteins and secondary metabolism, as well as various lineage specific, mostly unknown genes are positively correlated with SPPR. Finally, we enumerate possible regulators and regulatory mechanisms, arising from the data, for this response. Conclusions Based on these results it appears that in low growth rate protein production energy is very efficiently used primarly for protein production. Also, we propose that flux through early glycolysis or the TCA cycle is a more fundamental determining factor than growth rate for low growth rate protein production and we propose a novel eukaryotic response to this i.e. the lineage specific response (LSR.

Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

DEFF Research Database (Denmark)

Basse, Astrid L.; Dixen, Karen; Yadav, Rachita

2015-01-01

. Conclusions: Using global gene expression profiling of the postnatal BAT to WAT transformation in sheep, we provide novel insight into adipose tissue plasticity in a large mammal, including identification of novel transcriptional components linked to adipose tissue remodeling. Moreover, our data set provides...... NR1H3, MYC, KLF4, ESR1, RELA and BCL6, which were linked to the overall changes in gene expression during the adipose tissue remodeling. Finally, the perirenal adipose tissue expressed both brown and brite/beige adipocyte marker genes at birth, the expression of which changed substantially over time...

Femoral anteversion is correlated with acetabular version and coverage in Asian women with anterior and global deficient subgroups of hip dysplasia: a CT study

International Nuclear Information System (INIS)

Akiyama, Mio; Nakashima, Yasuharu; Fujii, Masanori; Sato, Taishi; Yamamoto, Takuaki; Mawatari, Taro; Motomura, Goro; Matsuda, Shuichi; Iwamoto, Yukihide

2012-01-01

Morphological correlation between the acetabulum and femur at the hip joint is still controversial. We tested the hypothesis that femoral anteversion correlates with acetabular version and coverage in patients with developmental dysplasia of the hip (DDH). Using pelvic computed tomography (CT) images of 79 hips in 49 Asian women with DDH and 49 normal hips, we measured femoral anteversion, the axial and vertical acetabular version and the acetabular sector angle (ASA) to demarcate femoral head coverage. Depending on the location of the acetabular bone defect, dysplastic hips were divided into three subgroups: the anterior, global and posterior deficiency groups. We performed a comparative analysis between dysplastic and normal hips using the Wilcoxon rank sum test, and a relative analysis between femoral anteversion and acetabular measurements in dysplastic hips using Pearson's correlation coefficient. The amount of femoral anteversion in dysplastic hips was greater and more variable than in normal hips (p < 0.0001, p = 0.0277 respectively). Femoral anteversion in dysplastic hips correlated significantly with acetabular anteversion in the groups with anterior and global deficiency subgroups (p < 0.05, r = 0.2990, p < 0.05, r = 0.451 respectively), but not with the posterior deficiency subgroup. Femoral anteversion also correlated with vertical acetabular version. When acetabular coverage was examined, significant correlations were noted between femoral anteversion and anterior and superior coverage, but not with posterior coverage. These correlations were not observed in normal hips. Our results showed significantly greater and more variable femoral anteversion in DDH, and a significant correlation between femoral anteversion and acetabular version and coverage in DDH with anterior and global acetabular bone deficiency. (orig.)

Femoral anteversion is correlated with acetabular version and coverage in Asian women with anterior and global deficient subgroups of hip dysplasia: a CT study

Energy Technology Data Exchange (ETDEWEB)

Akiyama, Mio; Nakashima, Yasuharu; Fujii, Masanori; Sato, Taishi; Yamamoto, Takuaki; Mawatari, Taro; Motomura, Goro; Matsuda, Shuichi; Iwamoto, Yukihide [Kyushu University, Department of Orthopaedic Surgery, Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka (Japan)

2012-11-15

Morphological correlation between the acetabulum and femur at the hip joint is still controversial. We tested the hypothesis that femoral anteversion correlates with acetabular version and coverage in patients with developmental dysplasia of the hip (DDH). Using pelvic computed tomography (CT) images of 79 hips in 49 Asian women with DDH and 49 normal hips, we measured femoral anteversion, the axial and vertical acetabular version and the acetabular sector angle (ASA) to demarcate femoral head coverage. Depending on the location of the acetabular bone defect, dysplastic hips were divided into three subgroups: the anterior, global and posterior deficiency groups. We performed a comparative analysis between dysplastic and normal hips using the Wilcoxon rank sum test, and a relative analysis between femoral anteversion and acetabular measurements in dysplastic hips using Pearson's correlation coefficient. The amount of femoral anteversion in dysplastic hips was greater and more variable than in normal hips (p < 0.0001, p = 0.0277 respectively). Femoral anteversion in dysplastic hips correlated significantly with acetabular anteversion in the groups with anterior and global deficiency subgroups (p < 0.05, r = 0.2990, p < 0.05, r = 0.451 respectively), but not with the posterior deficiency subgroup. Femoral anteversion also correlated with vertical acetabular version. When acetabular coverage was examined, significant correlations were noted between femoral anteversion and anterior and superior coverage, but not with posterior coverage. These correlations were not observed in normal hips. Our results showed significantly greater and more variable femoral anteversion in DDH, and a significant correlation between femoral anteversion and acetabular version and coverage in DDH with anterior and global acetabular bone deficiency. (orig.)

Global Gene Expression Profiling of Human Genome Following Exposure to Sarin and Soman

International Nuclear Information System (INIS)

Gopalakrishnakone, P.; Pachiappan, A.; Srinivasan, K. N.; Loke, W. K.; Lee, F. K.

2007-01-01

Toxicogenomics merges genomics with toxicology is a rapidly expanding field on the assumption that the transcriptional responses of cells to different toxic exposure are sufficiently distinct robust and reproducible to discriminate toxin from different families/classes which can be called as 'fingerprints' or 'Atlases'. In this study chemical weapons sarin was studied in a time and dose dependent manner after exposure to human neuroblastoma cell line. (Sarin or GB) exerts its effect through inhibition of acetylcholinesterase activity and induction of delayed neurotoxicity in a dose [EC 50 50 ppm, (around 372.4 μM)] and time-dependent manner. The effect and/or the mechanism of single or repeated exposures to GB, however, are less clear and yet to be explored at cellular level. The present study aims to scrutinize, the global gene expression profile following sarin toxicity in neuronal cells using Affymetrix-GeneChips. A tim-course study on the effect of a single (3 or 24h) or repeated (24 or 48h) doses of sarin (5ppm) on SHSY5Y cells was carried out. Using GeneSpring (PCA) analysis, 550 genes whose expression was significantly (p less than 0.01) altered by at least 2.5-fold, were selected. The results indicate that the low-level single dose exposure do not always parallel acute toxicity, but can cause a reversible down-regulation of genes and a range of anti-cholinesterase effects. In contrast, repeated doses produced persistent irreversible down-regulation of genes related to neurodegenerative mechanism at 48h. Real-time PCR and western blot analysis confirmed the reduced expression of presenilin 1 (TMP21), 2 and dopa.decarboxylase (DDC) mRNA and proteins. Besides providing an in vitro experimental model for studies on the neuropathophysiology and brain cells this investigation indicate possible mechanisms by which sarin could mediate neuro-degeneration. A comparison will be made with similar study with soman. (author)

Global cognitive impairment should be taken into account in SPECT-neuropsychology correlations: the example of verbal memory in very mild Alzheimer's disease

International Nuclear Information System (INIS)

Rodriguez, G.; Brugnolo, A.; Girtler, N.; Nobili, F.; Morbelli, S.; Piccardo, A.; Calvini, P.; Dougall, N.J.; Ebmeier, K.P.; Baron, J.C.

2005-01-01

To examine the impact of severity of global cognitive impairment on SPECT-neuropsychology correlations, we correlated a verbal memory test with brain perfusion in patients with very mild Alzheimer's disease (AD), taking into account the Mini-Mental State Examination (MMSE) score as an index of global cognitive impairment. Twenty-nine outpatients (mean age 78.2±5.5 years) affected by very mild, probable AD underwent brain SPECT with 99m Tc-ethylcysteinate dimer and a word list learning test. SPM99 was used for voxel-based correlation analysis after normalisation to mean cerebellar counts (height threshold: p<0.01). In a first analysis, only age and years of education were inserted as nuisance covariates, while in a second analysis the MMSE score was inserted as well. In the first analysis, two clusters of significant correlation were found in both hemispheres, mainly including regions of the right hemisphere, such as the inferior parietal lobule, the middle temporal gyrus and the posterior cingulate. Significant correlation in the left hemisphere was observed in the lingual lobule, the parietal precuneus and the posterior cingulate. After taking into consideration the MMSE, the largest cluster of correlation was found in the left hemisphere, including the parietal gyrus angularis, the posterior cingulate and the middle temporal gyrus. (orig.)

Global gene expression in muscle from fasted/refed trout reveals up-regulation of genes promoting myofibre hypertrophy but not myofibre production.

Science.gov (United States)

Rescan, Pierre-Yves; Le Cam, Aurelie; Rallière, Cécile; Montfort, Jérôme

2017-06-07

Compensatory growth is a phase of rapid growth, greater than the growth rate of control animals, that occurs after a period of growth-stunting conditions. Fish show a capacity for compensatory growth after alleviation of dietary restriction, but the underlying cellular mechanisms are unknown. To learn more about the contribution of genes regulating hypertrophy (an increase in muscle fibre size) and hyperplasia (the generation of new muscle fibres) in the compensatory muscle growth response in fish, we used high-density microarray analysis to investigate the global gene expression in muscle of trout during a fasting-refeeding schedule and in muscle of control-fed trout displaying normal growth. The compensatory muscle growth signature, as defined by genes up-regulated in muscles of refed trout compared with control-fed trout, showed enrichment in functional categories related to protein biosynthesis and maturation, such as RNA processing, ribonucleoprotein complex biogenesis, ribosome biogenesis, translation and protein folding. This signature was also enriched in chromatin-remodelling factors of the protein arginine N-methyl transferase family. Unexpectedly, functional categories related to cell division and DNA replication were not inferred from the molecular signature of compensatory muscle growth, and this signature contained virtually none of the genes previously reported to be up-regulated in hyperplastic growth zones of the late trout embryo myotome and to potentially be involved in production of new myofibres, notably genes encoding myogenic regulatory factors, transmembrane receptors essential for myoblast fusion or myofibrillar proteins predominant in nascent myofibres. Genes promoting myofibre growth, but not myofibre formation, were up-regulated in muscles of refed trout compared with continually fed trout. This suggests that a compensatory muscle growth response, resulting from the stimulation of hypertrophy but not the stimulation of hyperplasia

Predicting survival in patients with metastatic kidney cancer by gene-expression profiling in the primary tumor.

Science.gov (United States)

Vasselli, James R; Shih, Joanna H; Iyengar, Shuba R; Maranchie, Jodi; Riss, Joseph; Worrell, Robert; Torres-Cabala, Carlos; Tabios, Ray; Mariotti, Andra; Stearman, Robert; Merino, Maria; Walther, McClellan M; Simon, Richard; Klausner, Richard D; Linehan, W Marston

2003-06-10

To identify potential molecular determinants of tumor biology and possible clinical outcomes, global gene-expression patterns were analyzed in the primary tumors of patients with metastatic renal cell cancer by using cDNA microarrays. We used grossly dissected tumor masses that included tumor, blood vessels, connective tissue, and infiltrating immune cells to obtain a gene-expression "profile" from each primary tumor. Two patterns of gene expression were found within this uniformly staged patient population, which correlated with a significant difference in overall survival between the two patient groups. Subsets of genes most significantly associated with survival were defined, and vascular cell adhesion molecule-1 (VCAM-1) was the gene most predictive for survival. Therefore, despite the complex biological nature of metastatic cancer, basic clinical behavior as defined by survival may be determined by the gene-expression patterns expressed within the compilation of primary gross tumor cells. We conclude that survival in patients with metastatic renal cell cancer can be correlated with the expression of various genes based solely on the expression profile in the primary kidney tumor.

Global gene expression in larval zebrafish (Danio rerio) exposed to selective serotonin reuptake inhibitors (fluoxetine and sertraline) reveals unique expression profiles and potential biomarkers of exposure

International Nuclear Information System (INIS)

Park, June-Woo; Heah, Tze Ping; Gouffon, Julia S.; Henry, Theodore B.; Sayler, Gary S.

2012-01-01

Larval zebrafish (Danio rerio) were exposed (96 h) to selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline and changes in transcriptomes analyzed by Affymetrix GeneChip ® Zebrafish Array were evaluated to enhance understanding of biochemical pathways and differences between these SSRIs. The number of genes differentially expressed after fluoxetine exposure was 288 at 25 μg/L and 131 at 250 μg/L; and after sertraline exposure was 33 at 25 μg/L and 52 at 250 μg/L. Same five genes were differentially regulated in both SSRIs indicating shared molecular pathways. Among these, the gene coding for FK506 binding protein 5, annotated to stress response regulation, was highly down-regulated in all treatments (results confirmed by qRT-PCR). Gene ontology analysis indicated at the gene expression level that regulation of stress response and cholinesterase activities were influenced by these SSRIs, and suggested that changes in transcription of these genes could be used as biomarkers of SSRI exposure. - Highlights: ► Exposure of zebrafish to selective serotonin reuptake inhibitors (SSRIs). ► Fluoxetine and sertraline generate different global gene expression profiles. ► Genes linked to stress response and acetylcholine esterase affected by both SSRIs. - Global gene expression profiles in zebrafish exposed to selective serotonin reuptake inhibitors.

Correlation Between qacE and qacE∆1 Efflux Pump Genes, Antibiotic and Disinfectant Resistant Among Clinical Isolates of E.coli.

Science.gov (United States)

Shafaati, Maryam; Boroumand, Mohammadali; Nowroozi, Jamileh; Amiri, Pouya; Kazemian, Hossein

2016-01-01

Antiseptics and disinfectants have been used widely in hospitals and other health care settings to control the growth of microorganisms. However, some disinfectant resistant strains were reported. The objectives of our study were to evaluate correlation between the efflux pump genes, drugs and disinfectant resistant among clinical isolates of E.coli. A total of 102 of E. coli strains were isolated from urine sample of hospitalized patients. The antibiotic susceptibility was carried out by disc diffusion method. Didecyl di-methyl ammonium chloride (DDDMAC) was used as Quaternary ammonium compound (QAC) disinfectant which was used in Heart Center Hospital. PCR reaction was carried out for detection of qacE and qac∆E efflux pump genes. Almost all the strains had higher resistance to ampicillin, ciproflaxacin, cotrimaxazole and cephalothin. Totally 49% (n: 50) of strains were produced ESBL. Almost all the strains have MIC value between 0.00195 to 0.0078 mg/l for DDDMAC. Correlation between presence of qacE and qac∆E genes and antibiotic resistance was perceived. Presence of qacE and qac∆E genes among strains that have high disinfectant MIC value were 96.9% and 93.7% respectively. In addition, 98% of ESBL producing strains harbored qacE gene and 94% of ESBL producing strains harbored qac∆E gene. Our study indicated that there was a strong correlation between presence of qacE and qac∆E genes with resistance to some antibiotics and growth in media which contain high concentration of disinfectant. In conclusion, other mechanisms also play important role in resistant to antimicrobial agents but the role of efflux pumps in resistant to antimicrobial agents should not be neglected. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Correlations among obesity-associated gene polymorphisms, body composition, and physical activity in patients with type 2 diabetes mellitus

Directory of Open Access Journals (Sweden)

Sanae Saitoh

2015-01-01

Full Text Available Context: Various studies have focused on the correlation between β2-adrenergic receptor (β2AR, the β3-adrenergic receptor (β3AR, and the uncoupling protein 1 (UCP1 polymorphisms and obesity in patients with type 2 diabetes mellitus (T2DM. Aims: We examined the correlation between these polymorphisms and body composition variables and between body composition and lifestyle variables in Japanese T2DM patients. Materials and Methods: Of the 48, T2DM outpatients in Kanagawa prefecture recruited for participation, 32 (6 men and 26 women met the study criteria and were enrolled. Obesity-related gene polymorphisms were identified in 3 genes β3AR, UCP1, and β2AR using the SMart amplification process. Body composition variables were measured using a body composition analyzer. Data regarding food and nutrient consumption, family history, and lifestyle factors were collected via administration of questionnaires. Results: Because significant differences in body composition variables were found between men and women, statistical analysis was performed with data from the 25 female subjects only. On the basis of results of genetic testing, the subjects were divided into genotype groups for two-group and three-group comparison. The β3AR, UCP1, and β2AR polymorphisms and body composition significantly correlated with the percentage of subcutaneous fat in both arms as compared with the wild type or hetero groups with β3AR polymorphisms. However, physical activity correlated with several body composition variables. Conclusions: These results suggest that obesity in T2DM patients is not the result of presence of an obesity-related gene polymorphism but rather the absence of daily physical activity.

Global gene expression profiling in PAI-1 knockout murine heart and kidney: molecular basis of cardiac-selective fibrosis.

Directory of Open Access Journals (Sweden)

Asish K Ghosh

Full Text Available Fibrosis is defined as an abnormal matrix remodeling due to excessive synthesis and accumulation of extracellular matrix proteins in tissues during wound healing or in response to chemical, mechanical and immunological stresses. At present, there is no effective therapy for organ fibrosis. Previous studies demonstrated that aged plasminogen activator inhibitor-1 (PAI-1 knockout mice develop spontaneously cardiac-selective fibrosis without affecting any other organs. We hypothesized that differential expressions of profibrotic and antifibrotic genes in PAI-1 knockout hearts and unaffected organs lead to cardiac selective fibrosis. In order to address this prediction, we have used a genome-wide gene expression profiling of transcripts derived from aged PAI-1 knockout hearts and kidneys. The variations of global gene expression profiling were compared within four groups: wildtype heart vs. knockout heart; wildtype kidney vs. knockout kidney; knockout heart vs. knockout kidney and wildtype heart vs. wildtype kidney. Analysis of illumina-based microarray data revealed that several genes involved in different biological processes such as immune system processing, response to stress, cytokine signaling, cell proliferation, adhesion, migration, matrix organization and transcriptional regulation were affected in hearts and kidneys by the absence of PAI-1, a potent inhibitor of urokinase and tissue-type plasminogen activator. Importantly, the expressions of a number of genes, involved in profibrotic pathways including Ankrd1, Pi16, Egr1, Scx, Timp1, Timp2, Klf6, Loxl1 and Klotho, were deregulated in PAI-1 knockout hearts compared to wildtype hearts and PAI-1 knockout kidneys. While the levels of Ankrd1, Pi16 and Timp1 proteins were elevated during EndMT, the level of Timp4 protein was decreased. To our knowledge, this is the first comprehensive report on the influence of PAI-1 on global gene expression profiling in the heart and kidney and its implication

Global O3-CO correlations in a chemistry and transport model during July-August: evaluation with TES satellite observations and sensitivity to input meteorological data and emissions

Science.gov (United States)

Choi, Hyun-Deok; Liu, Hongyu; Crawford, James H.; Considine, David B.; Allen, Dale J.; Duncan, Bryan N.; Horowitz, Larry W.; Rodriguez, Jose M.; Strahan, Susan E.; Zhang, Lin; Liu, Xiong; Damon, Megan R.; Steenrod, Stephen D.

2017-07-01

We examine the capability of the Global Modeling Initiative (GMI) chemistry and transport model to reproduce global mid-tropospheric (618 hPa) ozone-carbon monoxide (O3-CO) correlations determined by the measurements from the Tropospheric Emission Spectrometer (TES) aboard NASA's Aura satellite during boreal summer (July-August). The model is driven by three meteorological data sets (finite-volume General Circulation Model (fvGCM) with sea surface temperature for 1995, Goddard Earth Observing System Data Assimilation System Version 4 (GEOS-4 DAS) for 2005, and Modern-Era Retrospective Analysis for Research and Applications (MERRA) for 2005), allowing us to examine the sensitivity of model O3-CO correlations to input meteorological data. Model simulations of radionuclide tracers (222Rn, 210Pb, and 7Be) are used to illustrate the differences in transport-related processes among the meteorological data sets. Simulated O3 values are evaluated with climatological profiles from ozonesonde measurements and satellite tropospheric O3 columns. Despite the fact that the three simulations show significantly different global and regional distributions of O3 and CO concentrations, they show similar patterns of O3-CO correlations on a global scale. All model simulations sampled along the TES orbit track capture the observed positive O3-CO correlations in the Northern Hemisphere midlatitude continental outflow and the Southern Hemisphere subtropics. While all simulations show strong negative correlations over the Tibetan Plateau, northern Africa, the subtropical eastern North Pacific, and the Caribbean, TES O3 and CO concentrations at 618 hPa only show weak negative correlations over much narrower areas (i.e., the Tibetan Plateau and northern Africa). Discrepancies in regional O3-CO correlation patterns in the three simulations may be attributed to differences in convective transport, stratospheric influence, and subsidence, among other processes. To understand how various

No evidential correlation between veterinary antibiotic degradation ability and resistance genes in microorganisms during the biodegradation of doxycycline.

Science.gov (United States)

Wen, Xin; Wang, Yan; Zou, Yongde; Ma, Baohua; Wu, Yinbao

2018-01-01

Biodegradation of antibiotic residues in the environment by microorganisms may lead to the generation of antibiotic resistance genes (ARGs), which are of great concern to human health. The aim of this study was to determine whether there is a relationship between the ability to degrade antibiotic doxycycline (DOX) and the development of resistance genes in microorganisms. We isolated and identified ten bacterial strains from a vegetable field that had received long-term manure application as fertilizer and were capable of surviving in a series of DOX concentrations (25, 50, 80, and 100mg/L). Our results showed no evidential correlation between DOX degradation ability and the development of resistance genes among the isolated microorganisms that had high DOX degradation capability (P > 0.05). This was based on the fact that Escherichia sp. and Candida sp. were the most efficient bacterial strains to degrade DOX (92.52% and 91.63%, respectively), but their tetracycline resistance genes showed a relatively low risk of antibiotic resistance in a 7-day experiment. Moreover, the tetM of the ribosomal protection protein genes carried by these two preponderant bacteria was five-fold higher than that carried by other isolates (P genes of three isolates, except for Escherichia sp. and Candida sp., showed remarkable negative correlations (P < 0.05), mainly because tetG markedly increased during the DOX degradation process. Our results concluded that the biodegradation of antibiotic residues may not necessarily lead to the development of ARGs in the environment. In addition, the two bacteria that we isolated, namely, Escherichia sp. and Candida sp., are potential candidates for the engineering of environmentally friendly bacteria. Copyright © 2017 Elsevier Inc. All rights reserved.

A new measure for gene expression biclustering based on non-parametric correlation.

Science.gov (United States)

Flores, Jose L; Inza, Iñaki; Larrañaga, Pedro; Calvo, Borja

2013-12-01

One of the emerging techniques for performing the analysis of the DNA microarray data known as biclustering is the search of subsets of genes and conditions which are coherently expressed. These subgroups provide clues about the main biological processes. Until now, different approaches to this problem have been proposed. Most of them use the mean squared residue as quality measure but relevant and interesting patterns can not be detected such as shifting, or scaling patterns. Furthermore, recent papers show that there exist new coherence patterns involved in different kinds of cancer and tumors such as inverse relationships between genes which can not be captured. The proposed measure is called Spearman's biclustering measure (SBM) which performs an estimation of the quality of a bicluster based on the non-linear correlation among genes and conditions simultaneously. The search of biclusters is performed by using a evolutionary technique called estimation of distribution algorithms which uses the SBM measure as fitness function. This approach has been examined from different points of view by using artificial and real microarrays. The assessment process has involved the use of quality indexes, a set of bicluster patterns of reference including new patterns and a set of statistical tests. It has been also examined the performance using real microarrays and comparing to different algorithmic approaches such as Bimax, CC, OPSM, Plaid and xMotifs. SBM shows several advantages such as the ability to recognize more complex coherence patterns such as shifting, scaling and inversion and the capability to selectively marginalize genes and conditions depending on the statistical significance. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

New inter-correlated genes targeted by diatom-derived polyunsaturated aldehydes in the sea urchin Paracentrotus lividus.

Science.gov (United States)

Ruocco, Nadia; Maria Fedele, Anna; Costantini, Susan; Romano, Giovanna; Ianora, Adrianna; Costantini, Maria

2017-08-01

The marine environment is continually subjected to the action of stressors (including natural toxins), which represent a constant danger for benthic communities. In the present work using network analysis we identified ten genes on the basis of associated functions (FOXA, FoxG, GFI-1, nodal, JNK, OneCut/Hnf6, TAK1, tcf4, TCF7, VEGF) in the sea urchin Paracentrotus lividus, having key roles in different processes, such as embryonic development and asymmetry, cell fate specification, cell differentiation and morphogenesis, and skeletogenesis. These genes are correlated with three HUB genes, Foxo, Jun and HIF1A. Real Time qPCR revealed that during sea urchin embryonic development the expression levels of these genes were modulated by three diatom-derived polyunsaturated aldehydes (PUAs), decadienal, heptadienal and octadienal. Our findings show how changes in gene expression levels may be used as an early indicator of stressful conditions in the marine environment. The identification of key genes and the molecular pathways in which they are involved represents a fundamental tool in understanding how marine organisms try to afford protection against toxicants, to avoid deleterious consequences and irreversible damages. The genes identified in this work as targets for PUAs can be considered as possible biomarkers to detect exposure to different environmental pollutants. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Global map of physical interactions among differentially expressed genes in multiple sclerosis relapses and remissions.

Science.gov (United States)

Tuller, Tamir; Atar, Shimshi; Ruppin, Eytan; Gurevich, Michael; Achiron, Anat

2011-09-15

Multiple sclerosis (MS) is a central nervous system autoimmune inflammatory T-cell-mediated disease with a relapsing-remitting course in the majority of patients. In this study, we performed a high-resolution systems biology analysis of gene expression and physical interactions in MS relapse and remission. To this end, we integrated 164 large-scale measurements of gene expression in peripheral blood mononuclear cells of MS patients in relapse or remission and healthy subjects, with large-scale information about the physical interactions between these genes obtained from public databases. These data were analyzed with a variety of computational methods. We find that there is a clear and significant global network-level signal that is related to the changes in gene expression of MS patients in comparison to healthy subjects. However, despite the clear differences in the clinical symptoms of MS patients in relapse versus remission, the network level signal is weaker when comparing patients in these two stages of the disease. This result suggests that most of the genes have relatively similar expression levels in the two stages of the disease. In accordance with previous studies, we found that the pathways related to regulation of cell death, chemotaxis and inflammatory response are differentially expressed in the disease in comparison to healthy subjects, while pathways related to cell adhesion, cell migration and cell-cell signaling are activated in relapse in comparison to remission. However, the current study includes a detailed report of the exact set of genes involved in these pathways and the interactions between them. For example, we found that the genes TP53 and IL1 are 'network-hub' that interacts with many of the differentially expressed genes in MS patients versus healthy subjects, and the epidermal growth factor receptor is a 'network-hub' in the case of MS patients with relapse versus remission. The statistical approaches employed in this study enabled us

Transcript levels of several epigenome regulatory genes in bovine somatic donor cells are not correlated with their cloning efficiency.

Science.gov (United States)

Zhou, Wenli; Sadeghieh, Sanaz; Abruzzese, Ronald; Uppada, Subhadra; Meredith, Justin; Ohlrichs, Charletta; Broek, Diane; Polejaeva, Irina

2009-09-01

Among many factors that potentially affect somatic cell nuclear transfer (SCNT) embryo development is the donor cell itself. Cloning potentials of somatic donor cells vary greatly, possibly because the cells have different capacities to be reprogrammed by ooplasma. It is therefore intriguing to identify factors that regulate the reprogrammability of somatic donor cells. Gene expression analysis is a widely used tool to investigate underlying mechanisms of various phenotypes. In this study, we conducted a retrospective analysis investigating whether donor cell lines with distinct cloning efficiencies express different levels of genes involved in epigenetic reprogramming including histone deacetylase-1 (HDAC1), -2 (HDAC2); DNA methyltransferase-1 (DNMT1), -3a (DNMT3a),-3b (DNMT3b), and the bovine homolog of yeast sucrose nonfermenting-2 (SNF2L), a SWI/SNF family of ATPases. Cell samples from 12 bovine donor cell lines were collected at the time of nuclear transfer experiments and expression levels of the genes were measured using quantitative polymerase chain reaction (PCR). Our results show that there are no significant differences in expression levels of these genes between donor cell lines of high and low cloning efficiency defined as live calving rates, although inverse correlations are observed between in vitro embryo developmental rates and expression levels of HDAC2 and SNF2L. We also show that selection of stable reference genes is important for relative quantification, and different batches of cells can have different gene expression patterns. In summary, we demonstrate that expression levels of these epigenome regulatory genes in bovine donor cells are not correlated with cloning potential. The experimental design and data analysis method reported here can be applied to study any genes expressed in donor cells.

Liver steatosis correlates with iron overload but not with HFE gene mutations in chronic hepatitis C.

Science.gov (United States)

Sikorska, Katarzyna; Stalke, Piotr; Romanowski, Tomasz; Rzepko, Robert; Bielawski, Krzysztof Piotr

2013-08-01

Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non-alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients. A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients. Liver function tests, serum markers of iron metabolism, cholesterol and triglycerides were assayed. The inflammatory activity, fibrosis, iron deposits and steatosis stages were assessed in liver specimens. HFE gene polymorphisms were investigated by PCR-RFLP. Liver steatosis was associated with obesity and diabetes mellitus. This disease was confirmed in 76/174 (44%) CHC patients, most of whom were infected with genotype 1. The average grade of steatosis was higher in NAFLD patients. CHC patients had significantly higher iron concentrations and transferrin saturations than NAFLD patients. Compared with CHC patients, HH patients had higher values of serum iron parameters and more intensive hepatocyte iron deposits without differences in the prevalence and intensity of liver steatosis. In the CHC group, lipids accumulation in hepatocytes was significantly associated with the presence of serum markers of iron overload. No correlation between the HFE gene polymorphism and liver steatosis in CHC patients was found. Liver steatosis was diagnosed in nearly half of CHC patients, most of whom were infected with genotype 1. The intensity of steatosis was lower in CHC patients than that in NAFLD patients because of a less frequent diagnosis of metabolic syndrome. Only in CHC patients were biochemical markers of iron accumulation positively correlated with liver steatosis; these findings were independent of HFE gene mutations.

Altered Autophagy-Associated Genes Expression in T Cells of Oral Lichen Planus Correlated with Clinical Features

Directory of Open Access Journals (Sweden)

Ya-Qin Tan

2016-01-01

Full Text Available Oral lichen planus (OLP is a T cell-mediated inflammatory autoimmune disease. Autophagy has emerged as a fundamental trafficking event in mediating T cell response, which plays crucial roles in innate and adaptive immunity. The present study mainly investigated the mRNA expression of autophagy-associated genes in peripheral blood T cells of OLP patients and evaluated correlations between their expression and the clinical features of OLP. Five differentially expressed autophagy-associated genes were identified by autophagy array. Quantitative real-time RT-PCR results confirmed that IGF1 expression in the peripheral blood T cells of OLP patients was significantly higher than that in controls, especially in female and middle-aged (30–50 years old OLP patients. In addition, ATG9B mRNA levels were significantly lower in nonerosive OLP patients. However, no significant differences were found in the expression of HGS, ESR1, and SNCA between OLP patients and controls. Taken together, dysregulation of T cell autophagy may be involved in immune response of OLP and may be correlated with clinical patterns.

Gene-environment correlations in the cross-generational transmission of parenting: Grandparenting moderates the effect of child 5-HTTLPR genotype on mothers' parenting.

Science.gov (United States)

Kopala-Sibley, Daniel C; Hayden, Elizabeth P; Singh, Shiva M; Sheikh, Haroon I; Kryski, Katie R; Klein, Daniel N

2017-11-01

Evidence suggests that parenting is associated cross-generationally and that children's genes may elicit specific parenting styles (evocative gene-environment correlation). This study examined whether the effect of children's genotype, specifically 5-HTTLPR, on mothers' parenting behaviors was moderated by her own parenting experiences from her mother. Two independent samples of three-year-olds (N = 476 and 405) were genotyped for the serotonin transporter gene, and observational measures of parenting were collected. Mothers completed measures of the parenting they received as children. The child having a short allele on 5-HTTLPR was associated with more maternal hostility (sample 1 and 2) and with less maternal support (sample 1), but only if the mother reported lower quality grandmothers' parenting (abuse and indifference in Sample 1 and lower levels of grandmother care in Sample 2). Results support the possibility of a moderated evocative gene-environment correlation.

Gene-environment correlations in the cross-generational transmission of parenting: Grandparenting moderates the effect of child 5-HTTLPR genotype on mothers’ parenting

Science.gov (United States)

Kopala-Sibley, Daniel C.; Hayden, Elizabeth P.; Singh, Shiva M.; Sheikh, Haroon I.; Kryski, Katie R.; Klein, Daniel N.

2017-01-01

Evidence suggests that parenting is associated cross-generationally and that children’s genes may elicit specific parenting styles (evocative gene-environment correlation). This study examined whether the effect of children’s genotype, specifically 5-HTTLPR, on mothers’ parenting behaviors was moderated by her own parenting experiences from her mother. Two independent samples of three-year-olds (N = 476 and 405) were genotyped for the serotonin transporter gene, and observational measures of parenting were collected. Mothers completed measures of the parenting they received as children. The child having a short allele on 5-HTTLPR was associated with more maternal hostility (sample 1 and 2) and with less maternal support (sample 1), but only if the mother reported lower quality grandmothers’ parenting (abuse and indifference in Sample 1 and lower levels of grandmother care in Sample 2). Results support the possibility of a moderated evocative gene-environment correlation. PMID:29628626

Correlation of gene expression and contaminat concentrations in wild largescale suckers: a field-based study

Science.gov (United States)

Christiansen, Helena E.; Mehinto, Alvine C.; Yu, Fahong; Perry, Russell W.; Denslow, Nancy D.; Maule, Alec G.; Mesa, Matthew G.

2014-01-01

Toxic compounds such as organochlorine pesticides (OCs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ether flame retardants (PBDEs) have been detected in fish, birds, and aquatic mammals that live in the Columbia River or use food resources from within the river. We developed a custom microarray for largescale suckers (Catostomus macrocheilus) and used it to investigate the molecular effects of contaminant exposure on wild fish in the Columbia River. Using Significance Analysis of Microarrays (SAM) we identified 72 probes representing 69 unique genes with expression patterns that correlated with hepatic tissue levels of OCs, PCBs, or PBDEs. These genes were involved in many biological processes previously shown to respond to contaminant exposure, including drug and lipid metabolism, apoptosis, cellular transport, oxidative stress, and cellular chaperone function. The relation between gene expression and contaminant concentration suggests that these genes may respond to environmental contaminant exposure and are promising candidates for further field and laboratory studies to develop biomarkers for monitoring exposure of wild fish to contaminant mixtures found in the Columbia River Basin. The array developed in this study could also be a useful tool for studies involving endangered sucker species and other sucker species used in contaminant research.

Parents' global rating of mental health correlates with SF-36 scores and health services satisfaction.

Science.gov (United States)

Mah, Jean K; Tough, Suzanne; Fung, Thomas; Douglas-England, Kathleen; Verhoef, Marja

2006-10-01

Patient satisfaction surveys are often used to measure quality of care. However, patient satisfaction may not be a reliable indicator of service quality because satisfaction can be influenced by clients' characteristics such as their health status. Parents of children attending a pediatric neurology clinic completed the Short Form Health Survey (SF-36) and global ratings of their physical and mental health. They also completed the Client Satisfaction Questionnaire (CSQ), the Measure of Processes of Care (MPOC), and the Family-Centered Care Survey (FCCS). 104 parents completed the survey. The correlation between the global rating of physical or mental health and their corresponding SF-36 scores was high. The majority (88%) of parents were satisfied, with a median CSQ score of 28 (IQR, 24 to 31) and a FCCS score of 4.7 (IQR, 4.2 to 4.9). Logistic regression identified parents' mental health as a significant predictor of client satisfaction (OR, 1.07; 95% CI, 1.01 to 1.14). Given the positive association between parents' mental health and satisfaction with care, it is important to consider mental status as a covariate in interpreting satisfaction surveys. Parents' global rating of mental health appears to be a reasonable indicator of their SF-36 mental scores.

Differential retention of metabolic genes following whole-genome duplication.

Science.gov (United States)

Gout, Jean-François; Duret, Laurent; Kahn, Daniel

2009-05-01

Classical studies in Metabolic Control Theory have shown that metabolic fluxes usually exhibit little sensitivity to changes in individual enzyme activity, yet remain sensitive to global changes of all enzymes in a pathway. Therefore, little selective pressure is expected on the dosage or expression of individual metabolic genes, yet entire pathways should still be constrained. However, a direct estimate of this selective pressure had not been evaluated. Whole-genome duplications (WGDs) offer a good opportunity to address this question by analyzing the fates of metabolic genes during the massive gene losses that follow. Here, we take advantage of the successive rounds of WGD that occurred in the Paramecium lineage. We show that metabolic genes exhibit different gene retention patterns than nonmetabolic genes. Contrary to what was expected for individual genes, metabolic genes appeared more retained than other genes after the recent WGD, which was best explained by selection for gene expression operating on entire pathways. Metabolic genes also tend to be less retained when present at high copy number before WGD, contrary to other genes that show a positive correlation between gene retention and preduplication copy number. This is rationalized on the basis of the classical concave relationship relating metabolic fluxes with enzyme expression.

Global analysis of gene expression profiles in physic nut (Jatropha curcas L.) seedlings exposed to salt stress.

Science.gov (United States)

Zhang, Lin; Zhang, Chao; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

2014-01-01

Salt stress interferes with plant growth and production. Plants have evolved a series of molecular and morphological adaptations to cope with this abiotic stress, and overexpression of salt response genes reportedly enhances the productivity of various crops. However, little is known about the salt responsive genes in the energy plant physic nut (Jatropha curcas L.). Thus, excavate salt responsive genes in this plant are informative in uncovering the molecular mechanisms for the salt response in physic nut. We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of physic nut plants (roots and leaves) 2 hours, 2 days and 7 days after the onset of salt stress. A total of 1,504 and 1,115 genes were significantly up and down-regulated in roots and leaves, respectively, under salt stress condition. Gene ontology (GO) analysis of physiological process revealed that, in the physic nut, many "biological processes" were affected by salt stress, particular those categories belong to "metabolic process", such as "primary metabolism process", "cellular metabolism process" and "macromolecule metabolism process". The gene expression profiles indicated that the associated genes were responsible for ABA and ethylene signaling, osmotic regulation, the reactive oxygen species scavenging system and the cell structure in physic nut. The major regulated genes detected in this transcriptomic data were related to trehalose synthesis and cell wall structure modification in roots, while related to raffinose synthesis and reactive oxygen scavenger in leaves. The current study shows a comprehensive gene expression profile of physic nut under salt stress. The differential expression genes detected in this study allows the underling the salt responsive mechanism in physic nut with the aim of improving its salt resistance in the future.

Field Strain Measurement on the Fiber Scale in Carbon Fiber Reinforced Polymers Using Global Finite-Element Based Digital Image Correlation

KAUST Repository

Tao, Ran

2015-01-01

is aimed to accurately measure the displacement and strain fields at the fiber-matrix scale in a cross-ply composite. First, the theories of both local subset-based digital image correlation (DIC) and global finite-element based DIC are outlined. Second, in

Integrated analysis of gene expression, CpG island methylation, and gene copy number in breast cancer cells by deep sequencing.

Directory of Open Access Journals (Sweden)

Zhifu Sun

Full Text Available We used deep sequencing technology to profile the transcriptome, gene copy number, and CpG island methylation status simultaneously in eight commonly used breast cell lines to develop a model for how these genomic features are integrated in estrogen receptor positive (ER+ and negative breast cancer. Total mRNA sequence, gene copy number, and genomic CpG island methylation were carried out using the Illumina Genome Analyzer. Sequences were mapped to the human genome to obtain digitized gene expression data, DNA copy number in reference to the non-tumor cell line (MCF10A, and methylation status of 21,570 CpG islands to identify differentially expressed genes that were correlated with methylation or copy number changes. These were evaluated in a dataset from 129 primary breast tumors. Gene expression in cell lines was dominated by ER-associated genes. ER+ and ER- cell lines formed two distinct, stable clusters, and 1,873 genes were differentially expressed in the two groups. Part of chromosome 8 was deleted in all ER- cells and part of chromosome 17 amplified in all ER+ cells. These loci encoded 30 genes that were overexpressed in ER+ cells; 9 of these genes were overexpressed in ER+ tumors. We identified 149 differentially expressed genes that exhibited differential methylation of one or more CpG islands within 5 kb of the 5' end of the gene and for which mRNA abundance was inversely correlated with CpG island methylation status. In primary tumors we identified 84 genes that appear to be robust components of the methylation signature that we identified in ER+ cell lines. Our analyses reveal a global pattern of differential CpG island methylation that contributes to the transcriptome landscape of ER+ and ER- breast cancer cells and tumors. The role of gene amplification/deletion appears to more modest, although several potentially significant genes appear to be regulated by copy number aberrations.

Identification and characterization of single nucleotide polymorphisms in 6 growth-correlated genes in porcine by denaturing high performance liquid chromatography.

Science.gov (United States)

Liu, Dewu; Zhang, Yushan; Du, Yinjun; Yang, Guanfu; Zhang, Xiquan

2007-06-01

The growth-correlated genes that are part of the neuroendocrine growth axis play crucial roles in the regulation of growth and development of pig. The identification of genetic polymorphisms in these genes will enable the scientist to evaluate the biological relevance of such polymorphisms and to gain a better understanding of quantitative traits like growth. In the present study, seven pairs of primers were designed to obtain unknown sequences of growth-correlated genes, and other 25 pairs of primers were designed to identify single nucleotide polymorphisms (SNP) using the denaturing high-performance liquid chromatography (DHPLC) technology in four pig breeds (Duroc, Landrace, Lantang and Wuzhishan), significantly differing in growth and development characteristics. A total of 101 polymorphisms were discovered in 10,707 base pairs (bp) from six genes of the ghrelin (GHRL), leptin (LEP), insulin-like growth factor II (IGF-II), insulin-like growth factor binding protein 2 (IGFBP-2), insulin-like growth factor binding protein 3 (IGFBP-3), and somatostatin (SS). The observed average distances between the SNP in the 5'UTR, coding regions, introns and 3'UTR were 134, 521, 81 and 92 bp, respectively. Four SNPs were found in the coding regions of IGF-II, IGFBP-2 and LEP, respectively. Two synonymous mutations were obtained in IGF-II and LEP genes respectively, and two non-synonymous were found in IGFBP-2 and LEP genes, respectively. Seven other mutations were also observed. Thirty-two PCR-RFLP markers were found among 101 polymorphisms of the six genes. The SNP discovered in this study would provide suitable markers for association studies of candidate genes with growth related traits in pig.

Mutations in TET2 and DNMT3A genes are associated with changes in global and gene-specific methylation in acute myeloid leukemia.

Science.gov (United States)

Ponciano-Gómez, Alberto; Martínez-Tovar, Adolfo; Vela-Ojeda, Jorge; Olarte-Carrillo, Irma; Centeno-Cruz, Federico; Garrido, Efraín

2017-10-01

Acute myeloid leukemia is characterized by its high biological and clinical heterogeneity, which represents an important barrier for a precise disease classification and accurate therapy. While epigenetic aberrations play a pivotal role in acute myeloid leukemia pathophysiology, molecular signatures such as change in the DNA methylation patterns and genetic mutations in enzymes needed to the methylation process can also be helpful for classifying acute myeloid leukemia. Our study aims to unveil the relevance of DNMT3A and TET2 genes in global and specific methylation patterns in acute myeloid leukemia. Peripheral blood samples from 110 untreated patients with acute myeloid leukemia and 15 healthy control individuals were collected. Global 5-methylcytosine and 5-hydroxymethylcytosine in genomic DNA from peripheral blood leukocytes were measured by using the MethylFlashTM Quantification kits. DNMT3A and TET2 expression levels were evaluated by real-time quantitative polymerase chain reaction. The R882A hotspot of DNMT3A and exons 6-10 of TET2 were amplified by polymerase chain reaction and sequenced using the Sanger method. Methylation patterns of 16 gene promoters were evaluated by pyrosequencing after treating DNA with sodium bisulfite, and their transcriptional products were measured by real-time quantitative polymerase chain reaction.Here, we demonstrate altered levels of 5-methylcytosine and 5-hydroxymethylcytosine and highly variable transcript levels of DNMT3A and TET2 in peripheral blood leukocytes from acute myeloid leukemia patients. We found a mutation prevalence of 2.7% for DNMT3A and 11.8% for TET2 in the Mexican population with this disease. The average overall survival of acute myeloid leukemia patients with DNMT3A mutations was only 4 months. In addition, we showed that mutations in DNMT3A and TET2 may cause irregular DNA methylation patterns and transcriptional expression levels in 16 genes known to be involved in acute myeloid leukemia pathogenesis

Morphological correlates of genital HPV infection: Viral replication, transcription and gene expression

International Nuclear Information System (INIS)

Crum, C.P.; Friedman, D.; Nuovo, G.; Silverstein, S.J.

1987-01-01

Current studies indicate a strong correlation between specific morphological changes and the presence of certain HPV strains in precancerous squamous epithelium of the cervix, vulva and vagina. HPV type 16 is the most commonly detected HPV type in cervical lesions in our experience, and 85% of these lesions exhibit some morphological features associated with aneuploid epithelium (CIN). However, over 50% of these lesions containing HPV 16 DNA exhibit, in addition, foci of epithelium indistinguishable from condyloma, although in our experience, only one HPV type(16) is detected in the majority of these lesions. DNA-DNA in situ hybridization analysis of these lesions containing HPV 16 DNA has demonstrated nucleic acids in areas resembling both condyloma and CIN, with the greatest concentration in mature cells containing cytoplasmic maturation. Ten percent of lesions containing HPV 16 produce detectable capsid antigens, and we have confirmed the presence of these antigens in the same areas which hybridize in-situ for HPV DNA. Recent studies using biotin and S-35 labeled RNa probes constructed in GEM-1 vectors indicate that early HPV genes are expressed primarily in the upper (more mature) regions of the neoplastic epithelium. Thus maturation appears to exert a positive influence on a variety of HPV functions in neoplastic epithelium, including DNA replication, early and late gene expression. It is possible that patterns of gene expression may vary between lesions associated with different HPV types or different morphologies. This possibility is being explored

Global O3–CO correlations in a chemistry and transport model during July–August: evaluation with TES satellite observations and sensitivity to input meteorological data and emissions

Directory of Open Access Journals (Sweden)

H.-D. Choi

2017-07-01

Full Text Available We examine the capability of the Global Modeling Initiative (GMI chemistry and transport model to reproduce global mid-tropospheric (618 hPa ozone–carbon monoxide (O3–CO correlations determined by the measurements from the Tropospheric Emission Spectrometer (TES aboard NASA's Aura satellite during boreal summer (July–August. The model is driven by three meteorological data sets (finite-volume General Circulation Model (fvGCM with sea surface temperature for 1995, Goddard Earth Observing System Data Assimilation System Version 4 (GEOS-4 DAS for 2005, and Modern-Era Retrospective Analysis for Research and Applications (MERRA for 2005, allowing us to examine the sensitivity of model O3–CO correlations to input meteorological data. Model simulations of radionuclide tracers (222Rn, 210Pb, and 7Be are used to illustrate the differences in transport-related processes among the meteorological data sets. Simulated O3 values are evaluated with climatological profiles from ozonesonde measurements and satellite tropospheric O3 columns. Despite the fact that the three simulations show significantly different global and regional distributions of O3 and CO concentrations, they show similar patterns of O3–CO correlations on a global scale. All model simulations sampled along the TES orbit track capture the observed positive O3–CO correlations in the Northern Hemisphere midlatitude continental outflow and the Southern Hemisphere subtropics. While all simulations show strong negative correlations over the Tibetan Plateau, northern Africa, the subtropical eastern North Pacific, and the Caribbean, TES O3 and CO concentrations at 618 hPa only show weak negative correlations over much narrower areas (i.e., the Tibetan Plateau and northern Africa. Discrepancies in regional O3–CO correlation patterns in the three simulations may be attributed to differences in convective transport, stratospheric influence, and subsidence, among other processes. To

Global analysis of transcriptome responses and gene expression profiles to cold stress of Jatropha curcas L.

Science.gov (United States)

Wang, Haibo; Zou, Zhurong; Wang, Shasha; Gong, Ming

2013-01-01

Jatropha curcas L., also called the Physic nut, is an oil-rich shrub with multiple uses, including biodiesel production, and is currently exploited as a renewable energy resource in many countries. Nevertheless, because of its origin from the tropical MidAmerican zone, J. curcas confers an inherent but undesirable characteristic (low cold resistance) that may seriously restrict its large-scale popularization. This adaptive flaw can be genetically improved by elucidating the mechanisms underlying plant tolerance to cold temperatures. The newly developed Illumina Hiseq™ 2000 RNA-seq and Digital Gene Expression (DGE) are deep high-throughput approaches for gene expression analysis at the transcriptome level, using which we carefully investigated the gene expression profiles in response to cold stress to gain insight into the molecular mechanisms of cold response in J. curcas. In total, 45,251 unigenes were obtained by assembly of clean data generated by RNA-seq analysis of the J. curcas transcriptome. A total of 33,363 and 912 complete or partial coding sequences (CDSs) were determined by protein database alignments and ESTScan prediction, respectively. Among these unigenes, more than 41.52% were involved in approximately 128 known metabolic or signaling pathways, and 4,185 were possibly associated with cold resistance. DGE analysis was used to assess the changes in gene expression when exposed to cold condition (12°C) for 12, 24, and 48 h. The results showed that 3,178 genes were significantly upregulated and 1,244 were downregulated under cold stress. These genes were then functionally annotated based on the transcriptome data from RNA-seq analysis. This study provides a global view of transcriptome response and gene expression profiling of J. curcas in response to cold stress. The results can help improve our current understanding of the mechanisms underlying plant cold resistance and favor the screening of crucial genes for genetically enhancing cold resistance

Diurnal and circadian expression profiles of glycerolipid biosynthetic genes in Arabidopsis.

Science.gov (United States)

Nakamura, Yuki; Andrés, Fernando; Kanehara, Kazue; Liu, Yu-chi; Coupland, George; Dörmann, Peter

2014-01-01

Glycerolipid composition in plant membranes oscillates in response to diurnal change. However, its functional significance remained unclear. A recent discovery that Arabidopsis florigen FT binds diurnally oscillating phosphatidylcholine molecules to promote flowering suggests that diurnal oscillation of glycerolipid composition is an important input in flowering time control. Taking advantage of public microarray data, we globally analyzed the expression pattern of glycerolipid biosynthetic genes in Arabidopsis under long-day, short-day, and continuous light conditions. The results revealed that 12 genes associated with glycerolipid metabolism showed significant oscillatory profiles. Interestingly, expression of most of these genes followed circadian profiles, suggesting that glycerolipid biosynthesis is partially under clock regulation. The oscillating expression profile of one representative gene, PECT1, was analyzed in detail. Expression of PECT1 showed a circadian pattern highly correlated with that of the clock-regulated gene GIGANTEA. Thus, our study suggests that a considerable number of glycerolipid biosynthetic genes are under circadian control.

In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma.

Directory of Open Access Journals (Sweden)

Bekim Sadikovic

Full Text Available Genetic and epigenetic changes contribute to deregulation of gene expression and development of human cancer. Changes in DNA methylation are key epigenetic factors regulating gene expression and genomic stability. Recent progress in microarray technologies resulted in developments of high resolution platforms for profiling of genetic, epigenetic and gene expression changes. OS is a pediatric bone tumor with characteristically high level of numerical and structural chromosomal changes. Furthermore, little is known about DNA methylation changes in OS. Our objective was to develop an integrative approach for analysis of high-resolution epigenomic, genomic, and gene expression profiles in order to identify functional epi/genomic differences between OS cell lines and normal human osteoblasts. A combination of Affymetrix Promoter Tilling Arrays for DNA methylation, Agilent array-CGH platform for genomic imbalance and Affymetrix Gene 1.0 platform for gene expression analysis was used. As a result, an integrative high-resolution approach for interrogation of genome-wide tumour-specific changes in DNA methylation was developed. This approach was used to provide the first genomic DNA methylation maps, and to identify and validate genes with aberrant DNA methylation in OS cell lines. This first integrative analysis of global cancer-related changes in DNA methylation, genomic imbalance, and gene expression has provided comprehensive evidence of the cumulative roles of epigenetic and genetic mechanisms in deregulation of gene expression networks.

Global SUMO proteome responses guide gene regulation, mRNA biogenesis, and plant stress responses

Directory of Open Access Journals (Sweden)

Magdalena eMazur

2012-09-01

Full Text Available Small-ubiquitin-like MOdifier (SUMO is a key regulator of abiotic stress, disease resistance and development in plants. The identification of >350 plant SUMO targets has revealed many processes modulated by SUMO and potential consequences of SUMO on its targets. Importantly, highly related proteins are SUMO-modified in plants, yeast, and metazoans. Overlapping SUMO targets include heat-shock proteins, transcription regulators, histones, histone-modifying enzymes, proteins involved in DNA damage repair, but also proteins involved in mRNA biogenesis and nucleo-cytoplasmic transport. Proteomics studies indicate key roles for SUMO in gene repression by controlling histone (deacetylation activity at genomic loci. The responsible heavily sumoylated transcriptional repressor complexes are recruited by EAR (Ethylene-responsive element binding factor [ERF]-associated Amphiphilic Repression-motif containing transcription factors in plants. These transcription factors are not necessarily themselves a SUMO target. Conversely, SUMO acetylation prevents binding of downstream partners by preventing binding of SIMs (SUMO-interaction peptide motifs presents in these partners, while SUMO acetylation has emerged as mechanism to recruit specifically bromodomains; bromodomain are generally linked with gene activation. These findings strengthen the idea of a bidirectional sumo-/acetylation switch in gene regulation. Quantitative proteomics has highlighted that global sumoylation provides a dynamic response to protein damage involving SUMO chain-mediated protein degradation, but also SUMO E3 ligase-dependent transcription of HSP (Heat-shock protein genes. With these insights in SUMO function and novel technical advancements, we can now study SUMO dynamics in responses to (abiotic stress in plants.

Integrative analysis of genome-wide gene copy number changes and gene expression in non-small cell lung cancer.

Directory of Open Access Journals (Sweden)

Verena Jabs

Full Text Available Non-small cell lung cancer (NSCLC represents a genomically unstable cancer type with extensive copy number aberrations. The relationship of gene copy number alterations and subsequent mRNA levels has only fragmentarily been described. The aim of this study was to conduct a genome-wide analysis of gene copy number gains and corresponding gene expression levels in a clinically well annotated NSCLC patient cohort (n = 190 and their association with survival. While more than half of all analyzed gene copy number-gene expression pairs showed statistically significant correlations (10,296 of 18,756 genes, high correlations, with a correlation coefficient >0.7, were obtained only in a subset of 301 genes (1.6%, including KRAS, EGFR and MDM2. Higher correlation coefficients were associated with higher copy number and expression levels. Strong correlations were frequently based on few tumors with high copy number gains and correspondingly increased mRNA expression. Among the highly correlating genes, GO groups associated with posttranslational protein modifications were particularly frequent, including ubiquitination and neddylation. In a meta-analysis including 1,779 patients we found that survival associated genes were overrepresented among highly correlating genes (61 of the 301 highly correlating genes, FDR adjusted p<0.05. Among them are the chaperone CCT2, the core complex protein NUP107 and the ubiquitination and neddylation associated protein CAND1. In conclusion, in a comprehensive analysis we described a distinct set of highly correlating genes. These genes were found to be overrepresented among survival-associated genes based on gene expression in a large collection of publicly available datasets.

Analysis of global gene expression in Brachypodium distachyon reveals extensive network plasticity in response to abiotic stress.

Directory of Open Access Journals (Sweden)

Henry D Priest

Full Text Available Brachypodium distachyon is a close relative of many important cereal crops. Abiotic stress tolerance has a significant impact on productivity of agriculturally important food and feedstock crops. Analysis of the transcriptome of Brachypodium after chilling, high-salinity, drought, and heat stresses revealed diverse differential expression of many transcripts. Weighted Gene Co-Expression Network Analysis revealed 22 distinct gene modules with specific profiles of expression under each stress. Promoter analysis implicated short DNA sequences directly upstream of module members in the regulation of 21 of 22 modules. Functional analysis of module members revealed enrichment in functional terms for 10 of 22 network modules. Analysis of condition-specific correlations between differentially expressed gene pairs revealed extensive plasticity in the expression relationships of gene pairs. Photosynthesis, cell cycle, and cell wall expression modules were down-regulated by all abiotic stresses. Modules which were up-regulated by each abiotic stress fell into diverse and unique gene ontology GO categories. This study provides genomics resources and improves our understanding of abiotic stress responses of Brachypodium.

Gene expression in chicken reveals correlation with structural genomic features and conserved patterns of transcription in the terrestrial vertebrates.

Directory of Open Access Journals (Sweden)

Haisheng Nie

Full Text Available BACKGROUND: The chicken is an important agricultural and avian-model species. A survey of gene expression in a range of different tissues will provide a benchmark for understanding expression levels under normal physiological conditions in birds. With expression data for birds being very scant, this benchmark is of particular interest for comparative expression analysis among various terrestrial vertebrates. METHODOLOGY/PRINCIPAL FINDINGS: We carried out a gene expression survey in eight major chicken tissues using whole genome microarrays. A global picture of gene expression is presented for the eight tissues, and tissue specific as well as common gene expression were identified. A Gene Ontology (GO term enrichment analysis showed that tissue-specific genes are enriched with GO terms reflecting the physiological functions of the specific tissue, and housekeeping genes are enriched with GO terms related to essential biological functions. Comparisons of structural genomic features between tissue-specific genes and housekeeping genes show that housekeeping genes are more compact. Specifically, coding sequence and particularly introns are shorter than genes that display more variation in expression between tissues, and in addition intergenic space was also shorter. Meanwhile, housekeeping genes are more likely to co-localize with other abundantly or highly expressed genes on the same chromosomal regions. Furthermore, comparisons of gene expression in a panel of five common tissues between birds, mammals and amphibians showed that the expression patterns across tissues are highly similar for orthologous genes compared to random gene pairs within each pair-wise comparison, indicating a high degree of functional conservation in gene expression among terrestrial vertebrates. CONCLUSIONS: The housekeeping genes identified in this study have shorter gene length, shorter coding sequence length, shorter introns, and shorter intergenic regions, there seems

A powerful score-based test statistic for detecting gene-gene co-association.

Science.gov (United States)

Xu, Jing; Yuan, Zhongshang; Ji, Jiadong; Zhang, Xiaoshuai; Li, Hongkai; Wu, Xuesen; Xue, Fuzhong; Liu, Yanxun

2016-01-29

The genetic variants identified by Genome-wide association study (GWAS) can only account for a small proportion of the total heritability for complex disease. The existence of gene-gene joint effects which contains the main effects and their co-association is one of the possible explanations for the "missing heritability" problems. Gene-gene co-association refers to the extent to which the joint effects of two genes differ from the main effects, not only due to the traditional interaction under nearly independent condition but the correlation between genes. Generally, genes tend to work collaboratively within specific pathway or network contributing to the disease and the specific disease-associated locus will often be highly correlated (e.g. single nucleotide polymorphisms (SNPs) in linkage disequilibrium). Therefore, we proposed a novel score-based statistic (SBS) as a gene-based method for detecting gene-gene co-association. Various simulations illustrate that, under different sample sizes, marginal effects of causal SNPs and co-association levels, the proposed SBS has the better performance than other existed methods including single SNP-based and principle component analysis (PCA)-based logistic regression model, the statistics based on canonical correlations (CCU), kernel canonical correlation analysis (KCCU), partial least squares path modeling (PLSPM) and delta-square (δ (2)) statistic. The real data analysis of rheumatoid arthritis (RA) further confirmed its advantages in practice. SBS is a powerful and efficient gene-based method for detecting gene-gene co-association.

Quantitative global and gene-specific promoter methylation in relation to biological properties of neuroblastomas

Directory of Open Access Journals (Sweden)

Kiss Nimrod B

2012-09-01

Full Text Available Abstract Background In this study we aimed to quantify tumor suppressor gene (TSG promoter methylation densities levels in primary neuroblastoma tumors and cell lines. A subset of these TSGs is associated with a CpG island methylator phenotype (CIMP in other tumor types. Methods The study panel consisted of 38 primary tumors, 7 established cell lines and 4 healthy references. Promoter methylation was determined by bisulphate Pyrosequencing for 14 TSGs; and LINE-1 repeat element methylation was used as an indicator of global methylation levels. Results Overall mean TSG Z-scores were significantly increased in cases with adverse outcome, but were unrelated to global LINE-1 methylation. CIMP with hypermethylation of three or more gene promoters was observed in 6/38 tumors and 7/7 cell lines. Hypermethylation of one or more TSG (comprising TSGs BLU, CASP8, DCR2, CDH1, RASSF1A and RASSF2 was evident in 30/38 tumors. By contrast only very low levels of promoter methylation were recorded for APC, DAPK1, NORE1A, P14, P16, TP73, PTEN and RARB. Similar involvements of methylation instability were revealed between cell line models and neuroblastoma tumors. Separate analysis of two proposed CASP8 regulatory regions revealed frequent and significant involvement of CpG sites between exon 4 and 5, but modest involvement of the exon 1 region. Conclusions/significance The results highlight the involvement of TSG methylation instability in neuroblastoma tumors and cell lines using quantitative methods, support the use of DNA methylation analyses as a prognostic tool for this tumor type, and underscore the relevance of developing demethylating therapies for its treatment.

Alternate bearing in citrus: changes in the expression of flowering control genes and in global gene expression in ON- versus OFF-crop trees.

Science.gov (United States)

Shalom, Liron; Samuels, Sivan; Zur, Naftali; Shlizerman, Lyudmila; Zemach, Hanita; Weissberg, Mira; Ophir, Ron; Blumwald, Eduardo; Sadka, Avi

2012-01-01

Alternate bearing (AB) is the process in fruit trees by which cycles of heavy yield (ON crop) one year are followed by a light yield (OFF crop) the next. Heavy yield usually reduces flowering intensity the following year. Despite its agricultural importance, how the developing crop influences the following year's return bloom and yield is not fully understood. It might be assumed that an 'AB signal' is generated in the fruit, or in another organ that senses fruit presence, and moves into the bud to determine its fate-flowering or vegetative growth. The bud then responds to fruit presence by altering regulatory and metabolic pathways. Determining these pathways, and when they are altered, might indicate the nature of this putative AB signal. We studied bud morphology, the expression of flowering control genes, and global gene expression in ON- and OFF-crop buds. In May, shortly after flowering and fruit set, OFF-crop buds were already significantly longer than ON-crop buds. The number of differentially expressed genes was higher in May than at the other tested time points. Processes differentially expressed between ON- and OFF-crop trees included key metabolic and regulatory pathways, such as photosynthesis and secondary metabolism. The expression of genes of trehalose metabolism and flavonoid metabolism was validated by nCounter technology, and the latter was confirmed by metabolomic analysis. Among genes induced in OFF-crop trees was one homologous to SQUAMOSA PROMOTER BINDING-LIKE (SPL), which controls juvenile-to-adult and annual phase transitions, regulated by miR156. The expression pattern of SPL-like, miR156 and other flowering control genes suggested that fruit load affects bud fate, and therefore development and metabolism, a relatively long time before the flowering induction period. Results shed light on some of the metabolic and regulatory processes that are altered in ON and OFF buds.

Global gene analysis of oocytes from early stages in human folliculogenesis shows high expression of novel genes in reproduction

DEFF Research Database (Denmark)

Markholt, Sara; Grøndahl, M L; Ernst, Erik

2012-01-01

The pool of primordial follicles in humans is laid down during embryonic development and follicles can remain dormant for prolonged intervals, often decades, until individual follicles resume growth. The mechanisms that induce growth and maturation of primordial follicles are poorly understood...... but follicles once activated either continue growth or undergo atresia. We have isolated pure populations of oocytes from human primordial, intermediate and primary follicles using laser capture micro-dissection microscopy and evaluated the global gene expression profiles by whole-genome microarray analysis......) and the mitochondrial-encoded ATPase6 (ATP6). Thus, the present study provides not only a technique to capture and perform transcriptome analysis of the sparse material of human oocytes from the earliest follicle stages but further includes a comprehensive basis for our understanding of the regulatory factors...

Differential expression of six genes and correlation with fatness traits in a unique broiler population

Directory of Open Access Journals (Sweden)

Pengcheng Jin

2017-05-01

Full Text Available Previous results from genome wide association studies (GWASs in chickens divergently selected for abdominal fat content of Northeast Agricultural University (NEAUHLF showed that many single nucleotide polymorphism (SNP variants were associated with abdominal fat content. Of them, six top significant SNPs at the genome level were located within SRD5A3, SGCZ, DLC1, GBE1, GALNT9 and DNAJB6 genes. Here, expression levels of these six candidate genes were investigated in abdominal fat and liver tissue between fat and lean broilers from the 14th generation population of NEAUHLF. The results showed that expression levels of SRD5A3, SGCZ and DNAJB6 in the abdominal fat and SRD5A3, DLC1, GALNT9, DNAJB6 and GBE1 in the liver tissue differed significantly between the fat and lean birds, and were correlated with abdominal fat traits. The findings will provide important references for further function investigation of the six candidate genes involved in abdominal fat deposition in chickens.

Calculation of evolutionary correlation between individual genes and full-length genome: a method useful for choosing phylogenetic markers for molecular epidemiology.

Directory of Open Access Journals (Sweden)

Shuai Wang

Full Text Available Individual genes or regions are still commonly used to estimate the phylogenetic relationships among viral isolates. The genomic regions that can faithfully provide assessments consistent with those predicted with full-length genome sequences would be preferable to serve as good candidates of the phylogenetic markers for molecular epidemiological studies of many viruses. Here we employed a statistical method to evaluate the evolutionary relationships between individual viral genes and full-length genomes without tree construction as a way to determine which gene can match the genome well in phylogenetic analyses. This method was performed by calculation of linear correlations between the genetic distance matrices of aligned individual gene sequences and aligned genome sequences. We applied this method to the phylogenetic analyses of porcine circovirus 2 (PCV2, measles virus (MV, hepatitis E virus (HEV and Japanese encephalitis virus (JEV. Phylogenetic trees were constructed for comparisons and the possible factors affecting the method accuracy were also discussed in the calculations. The results revealed that this method could produce results consistent with those of previous studies about the proper consensus sequences that could be successfully used as phylogenetic markers. And our results also suggested that these evolutionary correlations could provide useful information for identifying genes that could be used effectively to infer the genetic relationships.

Transcription profiles of mitochondrial genes correlate with mitochondrial DNA haplotypes in a natural population of Silene vulgaris

Directory of Open Access Journals (Sweden)

Olson Matthew S

2010-01-01

Full Text Available Abstract Background Although rapid changes in copy number and gene order are common within plant mitochondrial genomes, associated patterns of gene transcription are underinvestigated. Previous studies have shown that the gynodioecious plant species Silene vulgaris exhibits high mitochondrial diversity and occasional paternal inheritance of mitochondrial markers. Here we address whether variation in DNA molecular markers is correlated with variation in transcription of mitochondrial genes in S. vulgaris collected from natural populations. Results We analyzed RFLP variation in two mitochondrial genes, cox1 and atp1, in offspring of ten plants from a natural population of S. vulgaris in Central Europe. We also investigated transcription profiles of the atp1 and cox1 genes. Most DNA haplotypes and transcription profiles were maternally inherited; for these, transcription profiles were associated with specific mitochondrial DNA haplotypes. One individual exhibited a pattern consistent with paternal inheritance of mitochondrial DNA; this individual exhibited a transcription profile suggestive of paternal but inconsistent with maternal inheritance. We found no associations between gender and transcript profiles. Conclusions Specific transcription profiles of mitochondrial genes were associated with specific mitochondrial DNA haplotypes in a natural population of a gynodioecious species S. vulgaris. Our findings suggest the potential for a causal association between rearrangements in the plant mt genome and transcription product variation.

Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary

Directory of Open Access Journals (Sweden)

Longo Dan L

2008-06-01

Full Text Available Abstract Background The aging of reproductive organs is not only a major social issue, but of special interest in aging research. A long-standing view of 'immortal germ line versus mortal soma' poses an important question of whether the reproductive tissues age in similar ways to the somatic tissues. As a first step to understand this phenomenon, we examine global changes in gene expression patterns by DNA microarrays in ovaries and testes of C57BL/6 mice at 1, 6, 16, and 24 months of age. In addition, we compared a group of mice on ad libitum (AL feeding with a group on lifespan-extending 40% calorie restriction (CR. Results We found that gene expression changes occurred in aging gonads, but were generally different from those in somatic organs during aging. For example, only two functional categories of genes previously associated with aging in muscle, kidney, and brain were confirmed in ovary: genes associated with complement activation were upregulated, and genes associated with mitochondrial electron transport were downregulated. The bulk of the changes in gonads were mostly related to gonad-specific functions. Ovaries showed extensive gene expression changes with age, especially in the period when ovulation ceases (from 6 to 16 months, whereas testes showed only limited age-related changes. The same trend was seen for the effects of CR: CR-mediated reversal of age-associated gene expression changes, reported in somatic organs previously, was limited to a small number of genes in gonads. Instead, in both ovary and testis, CR caused small and mostly gonad-specific effects: suppression of ovulation in ovary and activation of testis-specific genes in testis. Conclusion Overall, the results are consistent with unique modes of aging and its modification by CR in testis and ovary.

Copper induces expression and methylation changes of early development genes in Crassostrea gigas embryos.

Science.gov (United States)

Sussarellu, Rossana; Lebreton, Morgane; Rouxel, Julien; Akcha, Farida; Rivière, Guillaume

2018-03-01

Copper contamination is widespread along coastal areas and exerts adverse effects on marine organisms such as mollusks. In the Pacific oyster, copper induces severe developmental abnormalities during early life stages; however, the underlying molecular mechanisms are largely unknown. This study aims to better understand whether the embryotoxic effects of copper in Crassostrea gigas could be mediated by alterations in gene expression, and the putative role of DNA methylation, which is known to contribute to gene regulation in early embryo development. For that purpose, oyster embryos were exposed to 4 nominal copper concentrations (0.1, 1, 10 and 20 μg L -1 Cu 2+ ) during early development assays. Embryotoxicity was monitored through the oyster embryo-larval bioassay at the D-larva stage 24 h post fertilization (hpf) and genotoxicity at gastrulation 7 hpf. In parallel, the relative expression of 15 genes encoding putative homeotic, biomineralization and DNA methylation proteins was measured at three developmental stages (3 hpf morula stage, 7 hpf gastrula stage, 24 hpf D-larvae stage) using RT-qPCR. Global DNA content in methylcytosine and hydroxymethylcytosine were measured by HPLC and gene-specific DNA methylation levels were monitored using MeDIP-qPCR. A significant increase in larval abnormalities was observed from copper concentrations of 10 μg L -1 , while significant genotoxic effects were detected at 1 μg L -1 and above. All the selected genes presented a stage-dependent expression pattern, which was impaired for some homeobox and DNA methylation genes (Notochord, HOXA1, HOX2, Lox5, DNMT3b and CXXC-1) after copper exposure. While global DNA methylation (5-methylcytosine) at gastrula stage didn't show significant changes between experimental conditions, 5-hydroxymethylcytosine, its degradation product, decreased upon copper treatment. The DNA methylation of exons and the transcript levels were correlated in control samples for HOXA1 but such

Links between Friends' Physical Aggression and Adolescents' Physical Aggression: What Happens If Gene-Environment Correlations are Controlled?

Science.gov (United States)

Vitaro, Frank; Brendgen, Mara; Girard, Alain; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

2016-01-01

Exposure to deviant friends has been found to be a powerful source of influence on children's and adolescents' aggressive behavior. However, the contribution of deviant friends may have been overestimated because of a possible non-accounted gene-environment correlation (rGE). In this study, we used a cross-lagged design to test whether friends'…

Global cognitive impairment should be taken into account in SPECT-neuropsychology correlations: the example of verbal memory in very mild Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Rodriguez, G.; Brugnolo, A.; Girtler, N.; Nobili, F. [University of Genoa, Clinical Neurophysiology, Department of Endocrinological and Metabolic Sciences, Genoa (Italy); Morbelli, S.; Piccardo, A. [University of Genoa, Section of Nuclear Medicine, Department of Internal Medicine, Genoa (Italy); Calvini, P. [University of Genoa, INFN and Department of Physics, Genoa (Italy); Dougall, N.J.; Ebmeier, K.P. [University of Edinburgh, Division of Psychiatry, Edinburgh (United Kingdom); Baron, J.C. [University of Cambridge, Department of Clinical Neurosciences and Stroke Unit, Addenbrooke' s Hospital, Cambridge (United Kingdom)

2005-10-01

To examine the impact of severity of global cognitive impairment on SPECT-neuropsychology correlations, we correlated a verbal memory test with brain perfusion in patients with very mild Alzheimer's disease (AD), taking into account the Mini-Mental State Examination (MMSE) score as an index of global cognitive impairment. Twenty-nine outpatients (mean age 78.2{+-}5.5 years) affected by very mild, probable AD underwent brain SPECT with {sup 99m}Tc-ethylcysteinate dimer and a word list learning test. SPM99 was used for voxel-based correlation analysis after normalisation to mean cerebellar counts (height threshold: p<0.01). In a first analysis, only age and years of education were inserted as nuisance covariates, while in a second analysis the MMSE score was inserted as well. In the first analysis, two clusters of significant correlation were found in both hemispheres, mainly including regions of the right hemisphere, such as the inferior parietal lobule, the middle temporal gyrus and the posterior cingulate. Significant correlation in the left hemisphere was observed in the lingual lobule, the parietal precuneus and the posterior cingulate. After taking into consideration the MMSE, the largest cluster of correlation was found in the left hemisphere, including the parietal gyrus angularis, the posterior cingulate and the middle temporal gyrus. (orig.)

WDR1 and CLNK gene polymorphisms correlate with serum glucose and high-density lipoprotein levels in Tibetan gout patients.

Science.gov (United States)

Lan, Bing; Chen, Peng; Jiri, Mutu; He, Na; Feng, Tian; Liu, Kai; Jin, Tianbo; Kang, Longli

2016-03-01

Current evidence suggests heredity and metabolic syndrome contributes to gout progression. Specifically, the WDR1 and CLNK genes may play a role in gout progression in European ancestry populations. However, no studies have focused on Chinese populations, especially Tibetan individuals. This study aims to determine whether variations in these two genes correlate with gout-related indices in Chinese-Tibetan gout patients. Eleven single-nucleotide polymorphisms in the WDR1 and CLNK genes were detected in 319 Chinese-Tibetan gout patients and 318 controls. We used one-way analysis of variance to evaluate the polymorphisms' effects on gout based on mean serum levels of metabolism indicators, such as albumin, glucose (GLU), triglycerides, cholesterol, high-density lipoproteins (HDL-C), creatinine, and uric acid, from fasting venous blood samples. All p values were Bonferroni corrected. Polymorphisms of the WDR1 and CLNK genes affected multiple risk factors for gout development. Significant differences in serum GLU levels were detected between different genotypic groups with WDRI polymorphisms rs4604059 (p = 0.005) and rs12498927 (p = 0.005). In addition, significant differences in serum HDL-C levels were detected between different genotypic groups with the CLNK polymorphism rs2041215 (p = 0.001). Polymorphisms of CLNK also affected levels of albumin, triglycerides, and creatinine. This study is the first to investigate and identify positive correlations between WDR1 and CLNK gene polymorphisms in Chinese-Tibetan populations. Our findings provide significant evidence for the effect of genetic polymorphisms on gout-related factors in Chinese-Tibetan populations.

Reconstructing gene regulatory networks from knock-out data using Gaussian Noise Model and Pearson Correlation Coefficient.

Science.gov (United States)

Mohamed Salleh, Faridah Hani; Arif, Shereena Mohd; Zainudin, Suhaila; Firdaus-Raih, Mohd

2015-12-01

A gene regulatory network (GRN) is a large and complex network consisting of interacting elements that, over time, affect each other's state. The dynamics of complex gene regulatory processes are difficult to understand using intuitive approaches alone. To overcome this problem, we propose an algorithm for inferring the regulatory interactions from knock-out data using a Gaussian model combines with Pearson Correlation Coefficient (PCC). There are several problems relating to GRN construction that have been outlined in this paper. We demonstrated the ability of our proposed method to (1) predict the presence of regulatory interactions between genes, (2) their directionality and (3) their states (activation or suppression). The algorithm was applied to network sizes of 10 and 50 genes from DREAM3 datasets and network sizes of 10 from DREAM4 datasets. The predicted networks were evaluated based on AUROC and AUPR. We discovered that high false positive values were generated by our GRN prediction methods because the indirect regulations have been wrongly predicted as true relationships. We achieved satisfactory results as the majority of sub-networks achieved AUROC values above 0.5. Copyright © 2015 Elsevier Ltd. All rights reserved.

Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

Science.gov (United States)

Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

2014-10-01

Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc

SNPexp - A web tool for calculating and visualizing correlation between HapMap genotypes and gene expression levels

Directory of Open Access Journals (Sweden)

Franke Andre

2010-12-01

Full Text Available Abstract Background Expression levels for 47294 transcripts in lymphoblastoid cell lines from all 270 HapMap phase II individuals, and genotypes (both HapMap phase II and III of 3.96 million single nucleotide polymorphisms (SNPs in the same individuals are publicly available. We aimed to generate a user-friendly web based tool for visualization of the correlation between SNP genotypes within a specified genomic region and a gene of interest, which is also well-known as an expression quantitative trait locus (eQTL analysis. Results SNPexp is implemented as a server-side script, and publicly available on this website: http://tinyurl.com/snpexp. Correlation between genotype and transcript expression levels are calculated by performing linear regression and the Wald test as implemented in PLINK and visualized using the UCSC Genome Browser. Validation of SNPexp using previously published eQTLs yielded comparable results. Conclusions SNPexp provides a convenient and platform-independent way to calculate and visualize the correlation between HapMap genotypes within a specified genetic region anywhere in the genome and gene expression levels. This allows for investigation of both cis and trans effects. The web interface and utilization of publicly available and widely used software resources makes it an attractive supplement to more advanced bioinformatic tools. For the advanced user the program can be used on a local computer on custom datasets.

Global isolation by distance despite strong regional phylogeography in a small metazoan

Directory of Open Access Journals (Sweden)

Mills Scott

2007-11-01

Full Text Available Abstract Background Small vagile eukaryotic organisms, which comprise a large proportion of the Earth's biodiversity, have traditionally been thought to lack the extent of population structuring and geographic speciation observed in larger taxa. Here we investigate the patterns of genetic diversity, amongst populations of the salt lake microscopic metazoan Brachionus plicatilis s. s. (sensu stricto (Rotifera: Monogononta on a global scale. We examine the phylogenetic relationships of geographic isolates from four continents using a 603 bp fragment of the mitochondrial COI gene to investigate patterns of phylogeographic subdivision in this species. In addition we investigate the relationship between genetic and geographic distances on a global scale to try and reconcile the paradox between the high vagility of this species and the previously reported patterns of restricted gene flow, even over local spatial scales. Results Analysis of global sequence diversity of B. plicatilis s. s. reveals the presence of four allopatric genetic lineages: North American-Far East Asian, Western Mediterranean, Australian, and an Eastern Mediterranean lineage represented by a single isolate. Geographically orientated substructure is also apparent within the three best sampled lineages. Surprisingly, given this strong phylogeographic structure, B. plicatilis s. s. shows a significant correlation between geographic and genetic distance on a global scale ('isolation by distance' – IBD. Conclusion Despite its cosmopolitan distribution and potential for high gene flow, B. plicatilis s. s. is strongly structured at a global scale. IBD patterns have traditionally been interpreted to indicate migration-drift equilibrium, although in this system equilibrium conditions are incompatible with the observed genetic structure. Instead, we suggest the pattern may have arisen through persistent founder effects, acting in a similar fashion to geographic barriers for larger

Global isolation by distance despite strong regional phylogeography in a small metazoan

Science.gov (United States)

Mills, Scott; Lunt, David H; Gómez, Africa

2007-01-01

Background Small vagile eukaryotic organisms, which comprise a large proportion of the Earth's biodiversity, have traditionally been thought to lack the extent of population structuring and geographic speciation observed in larger taxa. Here we investigate the patterns of genetic diversity, amongst populations of the salt lake microscopic metazoan Brachionus plicatilis s. s. (sensu stricto) (Rotifera: Monogononta) on a global scale. We examine the phylogenetic relationships of geographic isolates from four continents using a 603 bp fragment of the mitochondrial COI gene to investigate patterns of phylogeographic subdivision in this species. In addition we investigate the relationship between genetic and geographic distances on a global scale to try and reconcile the paradox between the high vagility of this species and the previously reported patterns of restricted gene flow, even over local spatial scales. Results Analysis of global sequence diversity of B. plicatilis s. s. reveals the presence of four allopatric genetic lineages: North American-Far East Asian, Western Mediterranean, Australian, and an Eastern Mediterranean lineage represented by a single isolate. Geographically orientated substructure is also apparent within the three best sampled lineages. Surprisingly, given this strong phylogeographic structure, B. plicatilis s. s. shows a significant correlation between geographic and genetic distance on a global scale ('isolation by distance' – IBD). Conclusion Despite its cosmopolitan distribution and potential for high gene flow, B. plicatilis s. s. is strongly structured at a global scale. IBD patterns have traditionally been interpreted to indicate migration-drift equilibrium, although in this system equilibrium conditions are incompatible with the observed genetic structure. Instead, we suggest the pattern may have arisen through persistent founder effects, acting in a similar fashion to geographic barriers for larger organisms. Our data indicates

Correlation Analysis Between Expression Levels of Hepatic Growth Hormone Receptor, Janus Kinase 2, Insulin-Like Growth Factor-I Genes and Dwarfism Phenotype in Bama Minipig.

Science.gov (United States)

Yang, Haowen; Jiang, Qinyang; Wu, Dan; Lan, Ganqiu; Fan, Jing; Guo, Yafen; Chen, Baojian; Yang, Xiurong; Jiang, Hesheng

2015-02-01

Animal growth and development are complex and sophisticated biological metabolic processes, in which genes plays an important role. In this paper, we employed real-time quantitative PCR (RT-qPCR) to analyze the expression levels of hepatic GHR, JAK2 and IGF-I genes in 1, 30, 180 day of Bama minipig and Landrace with attempt to verify the correlation between the expression of these growth-associated genes and the dwarfism phenotype of Bama minipig. The results showed that the expression levels of these 3 genes in Bama minipigs were down-regulated expressed from 1 day to 30 day, and which was up-regulated expressed in Landrace. The expression levels of the 3 genes on 1, 30, 180 day were prominently higher in Landrace than in Bama minipigs. The significant differences of the 3 genes expression levels on 1 day between this two breeds indicate that different expressions of these genes might occur before birth. It is speculated that the down-regulated expression of the 3 genes may have a close correlation with the dwarfism phenotype of Bama minipig. More investigations in depth of this study is under progress with the help of biochip nanotechnology.

Novel gene sets improve set-level classification of prokaryotic gene expression data.

Science.gov (United States)

Holec, Matěj; Kuželka, Ondřej; Železný, Filip

2015-10-28

Set-level classification of gene expression data has received significant attention recently. In this setting, high-dimensional vectors of features corresponding to genes are converted into lower-dimensional vectors of features corresponding to biologically interpretable gene sets. The dimensionality reduction brings the promise of a decreased risk of overfitting, potentially resulting in improved accuracy of the learned classifiers. However, recent empirical research has not confirmed this expectation. Here we hypothesize that the reported unfavorable classification results in the set-level framework were due to the adoption of unsuitable gene sets defined typically on the basis of the Gene ontology and the KEGG database of metabolic networks. We explore an alternative approach to defining gene sets, based on regulatory interactions, which we expect to collect genes with more correlated expression. We hypothesize that such more correlated gene sets will enable to learn more accurate classifiers. We define two families of gene sets using information on regulatory interactions, and evaluate them on phenotype-classification tasks using public prokaryotic gene expression data sets. From each of the two gene-set families, we first select the best-performing subtype. The two selected subtypes are then evaluated on independent (testing) data sets against state-of-the-art gene sets and against the conventional gene-level approach. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. Novel gene sets defined on the basis of regulatory interactions improve set-level classification of gene expression data. The experimental scripts and other material needed to reproduce the experiments are available at http://ida.felk.cvut.cz/novelgenesets.tar.gz.

Global gene expression changes in human urothelial cells exposed to low-level monomethylarsonous acid

International Nuclear Information System (INIS)

Medeiros, Matthew; Zheng, Xinghui; Novak, Petr; Wnek, Shawn M.; Chyan, Vivian; Escudero-Lourdes, Claudia; Gandolfi, A. Jay

2012-01-01

Highlights: ► Chronic exposure to 50 nM monomethylarsonous acid in UROtsa was investigated. ► At 3 months of exposure substantial changes were observed in gene expression. ► Notable changes occurred in mitogenic signaling, stress, immune and inflammatory responses. ► Gene expression changes correlate with phenotypic changes from previous studies. -- Abstract: Bladder cancer has been associated with chronic arsenic exposure. Monomethylarsonous acid [MMA(III)] is a metabolite of inorganic arsenic and has been shown to transform an immortalized urothelial cell line (UROtsa) at concentrations 20-fold less than arsenite. MMA(III) was used as a model arsenical to examine the mechanisms of arsenical-induced transformation of urothelium. A microarray analysis was performed to assess the transcriptional changes in UROtsa during the critical window of chronic 50 nM MMA(III) exposure that leads to transformation at 3 months of exposure. The analysis revealed only minor changes in gene expression at 1 and 2 months of exposure, contrasting with substantial changes observed at 3 months of exposure. The gene expression changes at 3 months were analyzed showing distinct alterations in biological processes and pathways such as a response to oxidative stress, enhanced cell proliferation, anti-apoptosis, MAPK signaling, as well as inflammation. Twelve genes selected as markers of these particular biological processes were used to validate the microarray and these genes showed a time-dependent changes at 1 and 2 months of exposure, with the most substantial changes occurring at 3 months of exposure. These results indicate that there is a strong association between the acquired phenotypic changes that occur with chronic MMA(III) exposure and the observed gene expression patterns that are indicative of a malignant transformation. Although the substantial changes that occur at 3 months of exposure may be a consequence of transformation, there are common occurrences of altered

Expression of Genes Involved in Cellular Adhesion and Extracellular Matrix Remodeling Correlates with Poor Survival of Patients with Renal Cancer.

Science.gov (United States)

Boguslawska, Joanna; Kedzierska, Hanna; Poplawski, Piotr; Rybicka, Beata; Tanski, Zbigniew; Piekielko-Witkowska, Agnieszka

2016-06-01

Renal cell carcinoma is the most common highly metastatic kidney malignancy. Adhesion has a crucial role in the metastatic process. TGF (transforming growth factor)-β1 is a pleiotropic cytokine that influences cancerous transformation. We hypothesized that 1) changes in the expression of adhesion related genes may influence survival rate of patients with renal cell carcinoma and 2) TGF-β1 may contribute to changed expression of adhesion related genes. Two-step quantitative real-time polymerase chain reaction arrays were used to analyze the expression of adhesion related genes in 77 tumors and matched pair controls. The prognostic significance of genes was evaluated in TCGA (The Cancer Genome Atlas) data on 468 patients with renal cell carcinoma. Quantitative real-time polymerase chain reaction and Western blot were applied for TGF-β1 analysis. TGF-β1 mediated regulation of gene expression was analyzed by TGF-β1 supplementation of Caki-2 cells and quantitative real-time polymerase chain reaction. The expression of 19 genes related to adhesion and extracellular matrix remodeling was statistically significantly disturbed in renal cell carcinoma compared with controls. The 10-gene expression signature (COL1A1, COL5A1, COL11A1, FN1, ICAM1, ITGAL, ITGAM, ITGB2, THBS2 and TIMP1) correlated with poor survival (HR 2.85, p = 5.7e-10). TGF-β1 expression was 22 times higher in renal cell carcinoma than in controls (p adhesion and extracellular matrix remodeling develops early during renal cell carcinoma carcinogenesis and correlates with poor survival. TGF-β1 contributes to changed expression of extracellular matrix and adhesion related genes. Bioinformatic analysis performed on a broad panel of cancers of nonkidney origin suggests that disturbed expression of genes related to extracellular matrix and adhesion may be a universal feature of cancerous progression. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All

Global analysis of transcriptome responses and gene expression profiles to cold stress of Jatropha curcas L.

Directory of Open Access Journals (Sweden)

Haibo Wang

Full Text Available BACKGROUND: Jatropha curcas L., also called the Physic nut, is an oil-rich shrub with multiple uses, including biodiesel production, and is currently exploited as a renewable energy resource in many countries. Nevertheless, because of its origin from the tropical MidAmerican zone, J. curcas confers an inherent but undesirable characteristic (low cold resistance that may seriously restrict its large-scale popularization. This adaptive flaw can be genetically improved by elucidating the mechanisms underlying plant tolerance to cold temperatures. The newly developed Illumina Hiseq™ 2000 RNA-seq and Digital Gene Expression (DGE are deep high-throughput approaches for gene expression analysis at the transcriptome level, using which we carefully investigated the gene expression profiles in response to cold stress to gain insight into the molecular mechanisms of cold response in J. curcas. RESULTS: In total, 45,251 unigenes were obtained by assembly of clean data generated by RNA-seq analysis of the J. curcas transcriptome. A total of 33,363 and 912 complete or partial coding sequences (CDSs were determined by protein database alignments and ESTScan prediction, respectively. Among these unigenes, more than 41.52% were involved in approximately 128 known metabolic or signaling pathways, and 4,185 were possibly associated with cold resistance. DGE analysis was used to assess the changes in gene expression when exposed to cold condition (12°C for 12, 24, and 48 h. The results showed that 3,178 genes were significantly upregulated and 1,244 were downregulated under cold stress. These genes were then functionally annotated based on the transcriptome data from RNA-seq analysis. CONCLUSIONS: This study provides a global view of transcriptome response and gene expression profiling of J. curcas in response to cold stress. The results can help improve our current understanding of the mechanisms underlying plant cold resistance and favor the screening of

Activation of the alpha-globin gene expression correlates with dramatic upregulation of nearby non-globin genes and changes in local and large-scale chromatin spatial structure.

Science.gov (United States)

Ulianov, Sergey V; Galitsyna, Aleksandra A; Flyamer, Ilya M; Golov, Arkadiy K; Khrameeva, Ekaterina E; Imakaev, Maxim V; Abdennur, Nezar A; Gelfand, Mikhail S; Gavrilov, Alexey A; Razin, Sergey V

2017-07-11

In homeotherms, the alpha-globin gene clusters are located within permanently open genome regions enriched in housekeeping genes. Terminal erythroid differentiation results in dramatic upregulation of alpha-globin genes making their expression comparable to the rRNA transcriptional output. Little is known about the influence of the erythroid-specific alpha-globin gene transcription outburst on adjacent, widely expressed genes and large-scale chromatin organization. Here, we have analyzed the total transcription output, the overall chromatin contact profile, and CTCF binding within the 2.7 Mb segment of chicken chromosome 14 harboring the alpha-globin gene cluster in cultured lymphoid cells and cultured erythroid cells before and after induction of terminal erythroid differentiation. We found that, similarly to mammalian genome, the chicken genomes is organized in TADs and compartments. Full activation of the alpha-globin gene transcription in differentiated erythroid cells is correlated with upregulation of several adjacent housekeeping genes and the emergence of abundant intergenic transcription. An extended chromosome region encompassing the alpha-globin cluster becomes significantly decompacted in differentiated erythroid cells, and depleted in CTCF binding and CTCF-anchored chromatin loops, while the sub-TAD harboring alpha-globin gene cluster and the upstream major regulatory element (MRE) becomes highly enriched with chromatin interactions as compared to lymphoid and proliferating erythroid cells. The alpha-globin gene domain and the neighboring loci reside within the A-like chromatin compartment in both lymphoid and erythroid cells and become further segregated from the upstream gene desert upon terminal erythroid differentiation. Our findings demonstrate that the effects of tissue-specific transcription activation are not restricted to the host genomic locus but affect the overall chromatin structure and transcriptional output of the encompassing

Mutations of 3c and spike protein genes correlate with the occurrence of feline infectious peritonitis.

Science.gov (United States)

Bank-Wolf, Barbara Regina; Stallkamp, Iris; Wiese, Svenja; Moritz, Andreas; Tekes, Gergely; Thiel, Heinz-Jürgen

2014-10-10

The genes encoding accessory proteins 3a, 3b, 3c, 7a and 7b, the S2 domain of the spike (S) protein gene and the membrane (M) protein gene of feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV) samples were amplified, cloned and sequenced. For this faeces and/or ascites samples from 19 cats suffering from feline infectious peritonitis (FIP) as well as from 20 FECV-infected healthy cats were used. Sequence comparisons revealed that 3c genes of animals with FIP were heavily affected by nucleotide deletions and point mutations compared to animals infected with FECV; these alterations resulted either in early termination or destruction of the translation initiation codon. Two ascites-derived samples of cats with FIP which displayed no alterations of ORF3c harboured mutations in the S2 domain of the S protein gene which resulted in amino acid exchanges or deletions. Moreover, changes in 3c were often accompanied by mutations in S2. In contrast, in samples obtained from faeces of healthy cats, the ORF3c was never affected by such mutations. Similarly ORF3c from faecal samples of the cats with FIP was mostly intact and showed only in a few cases the same mutations found in the respective ascites samples. The genes encoding 3a, 3b, 7a and 7b displayed no mutations linked to the feline coronavirus (FCoV) biotype. The M protein gene was found to be conserved between FECV and FIPV samples. Our findings suggest that mutations of 3c and spike protein genes correlate with the occurrence of FIP. Copyright © 2014 Elsevier B.V. All rights reserved.

Distributions of positive correlations in sectoral value added growth in the global economic network*

Science.gov (United States)

Maluck, Julian; Donner, Reik V.

2017-02-01

International trade has grown considerably during the process of globalization. Complex supply chains for the production of goods have resulted in an increasingly connected International Trade Network (ITN). Traditionally, direct trade relations between industries have been regarded as mediators of supply and demand spillovers. With increasing network connectivity the question arises if higher-order relations become more important in explaining a national sector's susceptibility to supply and demand changes of its trading partner. In this study we address this question by investigating empirically to what extent the topological properties of the ITN provide information about positive correlations in the production of two industry sectors. We observe that although direct trade relations between industries serve as important indicators for correlations in the industries' value added growth, opportunities of substitution for required production inputs as well as second-order trade relations cannot be neglected. Our results contribute to a better understanding of the relation between trade and economic productivity and can serve as a basis for the improvement of crisis spreading models that evaluate contagion threats in the case of a node's failure in the ITN.

Comparison of subset-based local and FE-based global digital image correlation: Theoretical error analysis and validation

KAUST Repository

Pan, B.

2016-03-22

Subset-based local and finite-element-based (FE-based) global digital image correlation (DIC) approaches are the two primary image matching algorithms widely used for full-field displacement mapping. Very recently, the performances of these different DIC approaches have been experimentally investigated using numerical and real-world experimental tests. The results have shown that in typical cases, where the subset (element) size is no less than a few pixels and the local deformation within a subset (element) can be well approximated by the adopted shape functions, the subset-based local DIC outperforms FE-based global DIC approaches because the former provides slightly smaller root-mean-square errors and offers much higher computation efficiency. Here we investigate the theoretical origin and lay a solid theoretical basis for the previous comparison. We assume that systematic errors due to imperfect intensity interpolation and undermatched shape functions are negligibly small, and perform a theoretical analysis of the random errors or standard deviation (SD) errors in the displacements measured by two local DIC approaches (i.e., a subset-based local DIC and an element-based local DIC) and two FE-based global DIC approaches (i.e., Q4-DIC and Q8-DIC). The equations that govern the random errors in the displacements measured by these local and global DIC approaches are theoretically derived. The correctness of the theoretically predicted SD errors is validated through numerical translation tests under various noise levels. We demonstrate that the SD errors induced by the Q4-element-based local DIC, the global Q4-DIC and the global Q8-DIC are 4, 1.8-2.2 and 1.2-1.6 times greater, respectively, than that associated with the subset-based local DIC, which is consistent with our conclusions from previous work. © 2016 Elsevier Ltd. All rights reserved.

GSTM1 Gene Expression Correlates to Leiomyoma Volume Regression in Response to Mifepristone Treatment

Science.gov (United States)

Engman, Mikael; Varghese, Suby; Lagerstedt Robinson, Kristina; Malmgren, Helena; Hammarsjö, Anna; Byström, Birgitta; L Lalitkumar, Parameswaran Grace; Gemzell-Danielsson, Kristina

2013-01-01

Progesterone receptor modulators, such as mifepristone are useful and well tolerated in reducing leiomyoma volume although with large individual variation. The objective of this study was to investigate the molecular basis for the observed leiomyoma volume reduction, in response to mifepristone treatment and explore a possible molecular marker for the selective usage of mifepristone in leiomyoma patients. Premenopausal women (N = 14) were treated with mifepristone 50 mg, every other day for 12 weeks prior to surgery. Women were arbitrarily sub-grouped as good (N = 4), poor (N = 4) responders to treatment or intermediate respondents (N = 3). Total RNA was extracted from leiomyoma tissue, after surgical removal of the tumour and the differential expression of genes were analysed by microarray. The results were analysed using Ingenuity Pathway Analysis software. The glutathione pathway was the most significantly altered canonical pathway in which the glutathione-s transferase mu 1 (GSTM1) gene was significantly over expressed (+8.03 folds) among the good responders compared to non responders. This was further confirmed by Real time PCR (p = 0.024). Correlation of immunoreactive scores (IRS) for GSTM1 accumulation in leiomyoma tissue was seen with base line volume change of leiomyoma R = −0.8 (p = 0.011). Furthermore the accumulation of protein GSTM1 analysed by Western Blot correlated significantly with the percentual leiomyoma volume change R = −0.82 (p = 0.004). Deletion of the GSTM1 gene in leiomyoma biopsies was found in 50% of the mifepristone treated cases, with lower presence of the GSTM1 protein. The findings support a significant role for GSTM1 in leiomyoma volume reduction induced by mifepristone and explain the observed individual variation in this response. Furthermore the finding could be useful to further explore GSTM1 as a biomarker for tailoring medical treatment of uterine leiomyomas for optimizing the response

In-silico gene co-expression network analysis in Paracoccidioides brasiliensis with reference to haloacid dehalogenase superfamily hydrolase gene

Directory of Open Access Journals (Sweden)

Raghunath Satpathy

2015-01-01

Full Text Available Context: Paracoccidioides brasiliensis, a dimorphic fungus is the causative agent of paracoccidioidomycosis, a disease globally affecting millions of people. The haloacid dehalogenase (HAD superfamily hydrolases enzyme in the fungi, in particular, is known to be responsible in the pathogenesis by adhering to the tissue. Hence, identification of novel drug targets is essential. Aims: In-silico based identification of co-expressed genes along with HAD superfamily hydrolase in P. brasiliensis during the morphogenesis from mycelium to yeast to identify possible genes as drug targets. Materials and Methods: In total, four datasets were retrieved from the NCBI-gene expression omnibus (GEO database, each containing 4340 genes, followed by gene filtration expression of the data set. Further co-expression (CE study was performed individually and then a combination these genes were visualized in the Cytoscape 2. 8.3. Statistical Analysis Used: Mean and standard deviation value of the HAD superfamily hydrolase gene was obtained from the expression data and this value was subsequently used for the CE calculation purpose by selecting specific correlation power and filtering threshold. Results: The 23 genes that were thus obtained are common with respect to the HAD superfamily hydrolase gene. A significant network was selected from the Cytoscape network visualization that contains total 7 genes out of which 5 genes, which do not have significant protein hits, obtained from gene annotation of the expressed sequence tags by BLAST X. For all the protein PSI-BLAST was performed against human genome to find the homology. Conclusions: The gene co-expression network was obtained with respect to HAD superfamily dehalogenase gene in P. Brasiliensis.

Altered gene activity correlated with long-term memory formation of conditioned taste aversion in Lymnaea.

Science.gov (United States)

Azami, Sachiyo; Wagatsuma, Akiko; Sadamoto, Hisayo; Hatakeyama, Dai; Usami, Takeshi; Fujie, Manabu; Koyanagi, Ryo; Azumi, Kaoru; Fujito, Yutaka; Lukowiak, Ken; Ito, Etsuro

2006-11-15

The pond snail Lymnaea stagnalis is capable of learning conditioned taste aversion (CTA) and then consolidating that learning into long-term memory (LTM) that persists for at least 1 month. LTM requires de novo protein synthesis and altered gene activity. Changes in gene activity in Lymnaea that are correlated with, much less causative, memory formation have not yet been identified. As a first step toward rectifying this situation, we constructed a cDNA microarray with mRNAs extracted from the central nervous system (CNS) of Lymnaea. We then, using this microarray assay, identified genes whose activity either increased or decreased following CTA memory consolidation. We also identified genes whose expression levels were altered after inhibition of the cyclic AMP response element-binding protein (CREB) that is hypothesized to be a key transcription factor for CTA memory. We found that the molluscan insulin-related peptide II (MIP II) was up-regulated during CTA-LTM, whereas the gene encoding pedal peptide preprohormone (Pep) was down-regulated by CREB2 RNA interference. We next examined mRNAs of MIP II and Pep using real-time RT-PCR with SYBR Green. The MIP II mRNA level in the CNS of snails exhibiting "good" memory for CTA was confirmed to be significantly higher than that from the CNS of snails exhibiting "poor" memory. In contrast, there was no significant difference in expression levels of the Pep mRNA between "good" and "poor" performers. These data suggest that in Lymnaea MIP II may play a role in the consolidation process that forms LTM following CTA training.

Immunohistochemical expression of EGFR in colorectal carcinoma correlates with high but not low level gene amplification, as demonstrated by CISH.

Science.gov (United States)

Hemmings, Chris; Broomfield, Amy; Bean, Elaine; Whitehead, Martin; Yip, Desmond

2009-01-01

To assess and compare immunohistochemical expression of epidermal growth factor receptor (EGFR) with gene amplification as demonstrated by chromogenic in situ hybridisation (CISH), in colorectal adenocarcinoma. Sections from 100 consecutive colorectal cancer resection specimens were stained for EGFR using immunohistochemistry and CISH. Immunohistochemical assessment was independently performed at two laboratories, using the same antibody and protocols. With immunohistochemistry, strong circumferential membrane staining (3+ staining) was demonstrated in only 5% of cases, and this was only focal in three of five cases. At one laboratory, weak or incomplete staining (1+ or 2+) was observed in five further cases (5%), which had been negative at the other laboratory. CISH demonstrated high level gene amplification (>10 copies/nucleus) in the same five cases which had demonstrated 3+ staining with immunohistochemistry, and in those cases where the staining was focal, the amplification was demonstrated in the same foci of the tumour. Five further cases (5%) had low level amplification (5-10 copies per nucleus); these cases did not exhibit significant positive staining with immunohistochemistry. All the cases which demonstrated gene amplification (high or low level) arose in the distal colon. There was no correlation between gene amplification status and a variety of other variables, including stage at diagnosis, mucinous differentiation, neuroendocrine differentiation, or loss of expression of mismatch repair proteins. Immunohistochemical expression of EGFR is variable between laboratories, even using standardised protocols. 3+ staining is predictive of high level gene amplification, but correlates very poorly with low level amplification, which may still be clinically significant. In some cases gene amplification was only focal, offering a potential explanation for poor response to targeted therapy in patients with EGFR positive tumours.

ppGpp Controls Global Gene Expression in Light and in Darkness in S. elongatus

Directory of Open Access Journals (Sweden)

Anna M. Puszynska

2017-12-01

Full Text Available The bacterial and plant stringent response involves production of the signaling molecules guanosine tetraphosphate and guanosine pentaphosphate ((pppGpp, leading to global reorganization of gene expression. The function of the stringent response has been well characterized in stress conditions, but its regulatory role during unstressed growth is less studied. Here, we demonstrate that (pppGpp-deficient strains of S. elongatus have globally deregulated biosynthetic capacity, with increased transcription rate, translation rate, and cell size in unstressed conditions in light and impaired viability in darkness. Synthetic restoration of basal guanosine tetraphosphate (ppGpp levels is sufficient to recover transcriptional balance and appropriate cell size in light and to rescue viability in light/dark conditions, but it is insufficient to enable efficient dark-induced transcriptional shutdown. Our work underscores the importance of basal ppGpp signaling for regulation of cyanobacterial physiology in the absence of stress and for viability in energy-limiting conditions, highlighting that basal (pppGpp level is essential in cyanobacteria in the environmental light/dark cycle.

Colony-level behavioural variation correlates with differences in expression of the foraging gene in red imported fire ants.

Science.gov (United States)

Bockoven, Alison A; Coates, Craig J; Eubanks, Micky D

2017-11-01

Among social insects, colony-level variation is likely to be widespread and has significant ecological consequences. Very few studies, however, have documented how genetic factors relate to behaviour at the colony level. Differences in expression of the foraging gene have been associated with differences in foraging and activity of a wide variety of organisms. We quantified expression of the red imported fire ant foraging gene (sifor) in workers from 21 colonies collected across the natural range of Texas fire ant populations, but maintained under standardized, environmentally controlled conditions. Colonies varied significantly in their behaviour. The most active colonies had up to 10 times more active foragers than the least active colony and more than 16 times as many workers outside the nest. Expression differences among colonies correlated with this colony-level behavioural variation. Colonies with higher sifor expression in foragers had, on average, significantly higher foraging activity, exploratory activity and recruitment to nectar than colonies with lower expression. Expression of sifor was also strongly correlated with worker task (foraging vs. working in the interior of the nest). These results provide insight into the genetic and physiological processes underlying collective differences in social behaviour. Quantifying variation in expression of the foraging gene may provide an important tool for understanding and predicting the ecological consequences of colony-level behavioural variation. © 2017 John Wiley & Sons Ltd.

Significance levels for studies with correlated test statistics.

Science.gov (United States)

Shi, Jianxin; Levinson, Douglas F; Whittemore, Alice S

2008-07-01

When testing large numbers of null hypotheses, one needs to assess the evidence against the global null hypothesis that none of the hypotheses is false. Such evidence typically is based on the test statistic of the largest magnitude, whose statistical significance is evaluated by permuting the sample units to simulate its null distribution. Efron (2007) has noted that correlation among the test statistics can induce substantial interstudy variation in the shapes of their histograms, which may cause misleading tail counts. Here, we show that permutation-based estimates of the overall significance level also can be misleading when the test statistics are correlated. We propose that such estimates be conditioned on a simple measure of the spread of the observed histogram, and we provide a method for obtaining conditional significance levels. We justify this conditioning using the conditionality principle described by Cox and Hinkley (1974). Application of the method to gene expression data illustrates the circumstances when conditional significance levels are needed.

Effect of Correlated Noises in a Genetic Model

International Nuclear Information System (INIS)

Li, Zhang; Li, Cao

2010-01-01

The Stratonovich stochastic differential equation is used to analyze genotype selection in the presence of correlated Gaussian white noises. We study the steady state properties of the genotype selection and discuss the effects of the correlated noises. It is found that the degree of correlation of the noises can be used to select one type of genes from another type of mixing genes. The strong selection of genes caused by a large value of multiplicative noise intensity can be weakened by the intensive negative correlation. (general)

Pantoea ananatis Genetic Diversity Analysis Reveals Limited Genomic Diversity as Well as Accessory Genes Correlated with Onion Pathogenicity

Directory of Open Access Journals (Sweden)

Shaun P. Stice

2018-02-01

Full Text Available Pantoea ananatis is a member of the family Enterobacteriaceae and an enigmatic plant pathogen with a broad host range. Although P. ananatis strains can be aggressive on onion causing foliar necrosis and onion center rot, previous genomic analysis has shown that P. ananatis lacks the primary virulence secretion systems associated with other plant pathogens. We assessed a collection of fifty P. ananatis strains collected from Georgia over three decades to determine genetic factors that correlated with onion pathogenic potential. Previous genetic analysis studies have compared strains isolated from different hosts with varying diseases potential and isolation sources. Strains varied greatly in their pathogenic potential and aggressiveness on different cultivated Allium species like onion, leek, shallot, and chive. Using multi-locus sequence analysis (MLSA and repetitive extragenic palindrome repeat (rep-PCR techniques, we did not observe any correlation between onion pathogenic potential and genetic diversity among strains. Whole genome sequencing and pan-genomic analysis of a sub-set of 10 strains aided in the identification of a novel series of genetic regions, likely plasmid borne, and correlating with onion pathogenicity observed on single contigs of the genetic assemblies. We named these loci Onion Virulence Regions (OVR A-D. The OVR loci contain genes involved in redox regulation as well as pectate lyase and rhamnogalacturonase genes. Previous studies have not identified distinct genetic loci or plasmids correlating with onion foliar pathogenicity or pathogenicity on a single host pathosystem. The lack of focus on a single host system for this phytopathgenic disease necessitates the pan-genomic analysis performed in this study.

QTL global meta-analysis: are trait determining genes clustered?

Directory of Open Access Journals (Sweden)

Adelson David L

2009-04-01

Full Text Available Abstract Background A key open question in biology is if genes are physically clustered with respect to their known functions or phenotypic effects. This is of particular interest for Quantitative Trait Loci (QTL where a QTL region could contain a number of genes that contribute to the trait being measured. Results We observed a significant increase in gene density within QTL regions compared to non-QTL regions and/or the entire bovine genome. By grouping QTL from the Bovine QTL Viewer database into 8 categories of non-redundant regions, we have been able to analyze gene density and gene function distribution, based on Gene Ontology (GO with relation to their location within QTL regions, outside of QTL regions and across the entire bovine genome. We identified a number of GO terms that were significantly over represented within particular QTL categories. Furthermore, select GO terms expected to be associated with the QTL category based on common biological knowledge have also proved to be significantly over represented in QTL regions. Conclusion Our analysis provides evidence of over represented GO terms in QTL regions. This increased GO term density indicates possible clustering of gene functions within QTL regions of the bovine genome. Genes with similar functions may be grouped in specific locales and could be contributing to QTL traits. Moreover, we have identified over-represented GO terminology that from a biological standpoint, makes sense with respect to QTL category type.

Altered AKT1 and MAPK1 Gene Expression on Peripheral Blood Mononuclear Cells and Correlation with T-Helper-Transcription Factors in Systemic Lupus Erythematosus Patients

Directory of Open Access Journals (Sweden)

Sonia Garcia-Rodriguez

2012-01-01

Full Text Available Kinases have been implicated in the immunopathological mechanisms of Systemic Lupus Erythematosus (SLE. v-akt murine-thymoma viral-oncogene-homolog 1 (AKT1 and mitogen-activated-protein-kinase 1 (MAPK1 gene expressions in peripheral mononuclear cells from thirteen SLE patients with inactive or mild disease were evaluated using quantitative real-time reverse-transcription polymerase-chain-reaction and analyzed whether there was any correlation with T-helper (Th transcription factors (TF gene expression, cytokines, and S100A8/S100A9-(Calprotectin. Age- and gender-matched thirteen healthy controls were examined. AKT1 and MAPK1 expressions were upregulated in SLE patients and correlated with Th17-(Retinoic acid-related orphan receptor (ROR-C, T-regulatory-(Treg-(Transforming Growth Factor Beta (TGFB-2, and Th2-(interleukin (IL-5-related genes. MAPK1 expression correlated with Th1-(IL-12A, T-box TF-(T-bet, Th2-(GATA binding protein-(GATA-3, and IL-10 expressions. IL-10 expression was increased and correlated with plasma Tumor Necrosis Factor (TNF-α and Th0-(IL-2, Th1-(IL-12A, T-bet, GATA3, Treg-(Forkhead/winged-helix transcription factor- (FOXP-3, and IL-6 expressions. FOXP3 expression, FOXP3/RORC, and FOXP3/GATA3 expression ratios were increased. Plasma IL-1β, IL-12(p70, Interferon-(IFN-γ, and IL-6 cytokines were augmented. Plasma IL-1β, IL-6, IL-2, IFN-γ, TNF-α, IL-10, and IL-13 correlated with C-reactive protein, respectively. Increased Calprotectin correlated with neutrophils. Conclusion, SLE patients presented a systemic immunoinflammatory activity, augmented AKT1 and MAPK1 expressions, proinflammatory cytokines, and Calprotectin, together with increased expression of Treg-related genes, suggesting a regulatory feedback opposing the inflammatory activity.

Estrogenic effect of soy isoflavones on mammary gland morphogenesis and gene expression profile

DEFF Research Database (Denmark)

Thomsen, Anni R.; Almstrup, Kristian; Nielsen, John E.

2006-01-01

We examined the effect of 17 beta-estradiol (E2) and soy isoflavones' exposure on morphogenesis and global gene expression in the murine mammary gland. Three exposure regimens were applied: isoflavones added to the diet throughout either the lactational period (via the dams) or the postweaning...... period and E2 administered orally during the lactational period. Whole mounts of mammary glands were evaluated both in juvenile and adult animals with respect to branching morphogenesis and terminal end bud (TEB) formation. At postnatal day (PND) 28, we observed a significant increase in branching...... isoflavone and E2 exposure was further substantiated by changes in gene expression, since the same groups of genes were up- and downregulated, particularly in the E2 and postweaning isoflavone regimen. All changes in gene expression correlated with changes in the cellular composition of the gland, i.e., more...

Global discriminative learning for higher-accuracy computational gene prediction.

Directory of Open Access Journals (Sweden)

Axel Bernal

2007-03-01

Full Text Available Most ab initio gene predictors use a probabilistic sequence model, typically a hidden Markov model, to combine separately trained models of genomic signals and content. By combining separate models of relevant genomic features, such gene predictors can exploit small training sets and incomplete annotations, and can be trained fairly efficiently. However, that type of piecewise training does not optimize prediction accuracy and has difficulty in accounting for statistical dependencies among different parts of the gene model. With genomic information being created at an ever-increasing rate, it is worth investigating alternative approaches in which many different types of genomic evidence, with complex statistical dependencies, can be integrated by discriminative learning to maximize annotation accuracy. Among discriminative learning methods, large-margin classifiers have become prominent because of the success of support vector machines (SVM in many classification tasks. We describe CRAIG, a new program for ab initio gene prediction based on a conditional random field model with semi-Markov structure that is trained with an online large-margin algorithm related to multiclass SVMs. Our experiments on benchmark vertebrate datasets and on regions from the ENCODE project show significant improvements in prediction accuracy over published gene predictors that use intrinsic features only, particularly at the gene level and on genes with long introns.

A power law global error model for the identification of differentially expressed genes in microarray data

Directory of Open Access Journals (Sweden)

Granucci Francesca

2004-12-01

Full Text Available Abstract Background High-density oligonucleotide microarray technology enables the discovery of genes that are transcriptionally modulated in different biological samples due to physiology, disease or intervention. Methods for the identification of these so-called "differentially expressed genes" (DEG would largely benefit from a deeper knowledge of the intrinsic measurement variability. Though it is clear that variance of repeated measures is highly dependent on the average expression level of a given gene, there is still a lack of consensus on how signal reproducibility is linked to signal intensity. The aim of this study was to empirically model the variance versus mean dependence in microarray data to improve the performance of existing methods for identifying DEG. Results In the present work we used data generated by our lab as well as publicly available data sets to show that dispersion of repeated measures depends on location of the measures themselves following a power law. This enables us to construct a power law global error model (PLGEM that is applicable to various Affymetrix GeneChip data sets. A new DEG identification method is therefore proposed, consisting of a statistic designed to make explicit use of model-derived measurement spread estimates and a resampling-based hypothesis testing algorithm. Conclusions The new method provides a control of the false positive rate, a good sensitivity vs. specificity trade-off and consistent results with varying number of replicates and even using single samples.

Correlation between phenotypic antibiotic susceptibility and the resistome in Pseudomonas aeruginosa.

Science.gov (United States)

Jaillard, Magali; van Belkum, Alex; Cady, Kyle C; Creely, David; Shortridge, Dee; Blanc, Bernadette; Barbu, E Magda; Dunne, W Michael; Zambardi, Gilles; Enright, Mark; Mugnier, Nathalie; Le Priol, Christophe; Schicklin, Stéphane; Guigon, Ghislaine; Veyrieras, Jean-Baptiste

2017-08-01

Genetic determinants of antibiotic resistance (AR) have been extensively investigated. High-throughput sequencing allows for the assessment of the relationship between genotype and phenotype. A panel of 672 Pseudomonas aeruginosa strains was analysed, including representatives of globally disseminated multidrug-resistant and extensively drug-resistant clones; genomes and multiple antibiograms were available. This panel was annotated for AR gene presence and polymorphism, defining a resistome in which integrons were included. Integrons were present in >70 distinct cassettes, with In5 being the most prevalent. Some cassettes closely associated with clonal complexes, whereas others spread across the phylogenetic diversity, highlighting the importance of horizontal transfer. A resistome-wide association study (RWAS) was performed for clinically relevant antibiotics by correlating the variability in minimum inhibitory concentration (MIC) values with resistome data. Resistome annotation identified 147 loci associated with AR. These loci consisted mainly of acquired genomic elements and intrinsic genes. The RWAS allowed for correct identification of resistance mechanisms for meropenem, amikacin, levofloxacin and cefepime, and added 46 novel mutations. Among these, 29 were variants of the oprD gene associated with variation in meropenem MIC. Using genomic and MIC data, phenotypic AR was successfully correlated with molecular determinants at the whole-genome sequence level. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Gene expression analysis identifies global gene dosage sensitivity in cancer

DEFF Research Database (Denmark)

Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata

2015-01-01

Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gen...

Up-regulation of leucocytes genes implicated in telomere dysfunction and cellular senescence correlates with depression and anxiety severity scores.

Directory of Open Access Journals (Sweden)

Jean-Raymond Teyssier

Full Text Available BACKGROUND: Major depressive disorder (MDD is frequently associated with chronic medical illness responsible of increased disability and mortality. Inflammation and oxidative stress are considered to be the major mediators of the allostatic load, and has been shown to correlate with telomere erosion in the leucocytes of MDD patients, leading to the model of accelerated aging. However, the significance of telomere length as an exclusive biomarker of aging has been questioned on both methodological and biological grounds. Furthermore, telomeres significantly shorten only in patients with long lasting MDD. Sensitive and dynamic functional biomarkers of aging would be clinically useful to evaluate the somatic impact of MDD. METHODOLOGY: To address this issue we have measured in the blood leucocytes of MDD patients (N=17 and controls (N=16 the expression of two genes identified as robust biomarkers of human aging and telomere dysfunction: p16(INK4a and STMN1. We have also quantified the transcripts of genes involved in the repair of oxidative DNA damage at telomeres (OGG1, telomere regulation and elongation (TERT, and in the response to biopsychological stress (FOS and DUSP1. RESULTS: The OGG1, p16(INK4a, and STMN1 gene were significantly up-regulated (25 to 100% in the leucocytes of MDD patients. Expression of p16(INK4a and STMN1 was directly correlated with anxiety scores in the depression group, and that of p16(INK4a, STMN and TERT with the depression and anxiety scores in the combined sample (MDD plus controls. Furthermore, we identified a unique correlative pattern of gene expression in the leucocytes of MDD subjects. CONCLUSIONS: Expression of p16(INK4 and STMN1 is a promising biomarker for future epidemiological assessment of the somatic impact of depressive and anxious symptoms, at both clinical and subclinical level in both depressive patients and general population.

Detecting subnetwork-level dynamic correlations.

Science.gov (United States)

Yan, Yan; Qiu, Shangzhao; Jin, Zhuxuan; Gong, Sihong; Bai, Yun; Lu, Jianwei; Yu, Tianwei

2017-01-15

The biological regulatory system is highly dynamic. The correlations between many functionally related genes change over different biological conditions. Finding dynamic relations on the existing biological network may reveal important regulatory mechanisms. Currently no method is available to detect subnetwork-level dynamic correlations systematically on the genome-scale network. Two major issues hampered the development. The first is gene expression profiling data usually do not contain time course measurements to facilitate the analysis of dynamic relations, which can be partially addressed by using certain genes as indicators of biological conditions. Secondly, it is unclear how to effectively delineate subnetworks, and define dynamic relations between them. Here we propose a new method named LANDD (Liquid Association for Network Dynamics Detection) to find subnetworks that show substantial dynamic correlations, as defined by subnetwork A is concentrated with Liquid Association scouting genes for subnetwork B. The method produces easily interpretable results because of its focus on subnetworks that tend to comprise functionally related genes. Also, the collective behaviour of genes in a subnetwork is a much more reliable indicator of underlying biological conditions compared to using single genes as indicators. We conducted extensive simulations to validate the method's ability to detect subnetwork-level dynamic correlations. Using a real gene expression dataset and the human protein-protein interaction network, we demonstrate the method links subnetworks of distinct biological processes, with both confirmed relations and plausible new functional implications. We also found signal transduction pathways tend to show extensive dynamic relations with other functional groups. The R package is available at https://cran.r-project.org/web/packages/LANDD CONTACTS: yunba@pcom.edu, jwlu33@hotmail.com or tianwei.yu@emory.eduSupplementary information: Supplementary data

A hybrid correlation analysis with application to imaging genetics

Science.gov (United States)

Hu, Wenxing; Fang, Jian; Calhoun, Vince D.; Wang, Yu-Ping

2018-03-01

Investigating the association between brain regions and genes continues to be a challenging topic in imaging genetics. Current brain region of interest (ROI)-gene association studies normally reduce data dimension by averaging the value of voxels in each ROI. This averaging may lead to a loss of information due to the existence of functional sub-regions. Pearson correlation is widely used for association analysis. However, it only detects linear correlation whereas nonlinear correlation may exist among ROIs. In this work, we introduced distance correlation to ROI-gene association analysis, which can detect both linear and nonlinear correlations and overcome the limitation of averaging operations by taking advantage of the information at each voxel. Nevertheless, distance correlation usually has a much lower value than Pearson correlation. To address this problem, we proposed a hybrid correlation analysis approach, by applying canonical correlation analysis (CCA) to the distance covariance matrix instead of directly computing distance correlation. Incorporating CCA into distance correlation approach may be more suitable for complex disease study because it can detect highly associated pairs of ROI and gene groups, and may improve the distance correlation level and statistical power. In addition, we developed a novel nonlinear CCA, called distance kernel CCA, which seeks the optimal combination of features with the most significant dependence. This approach was applied to imaging genetic data from the Philadelphia Neurodevelopmental Cohort (PNC). Experiments showed that our hybrid approach produced more consistent results than conventional CCA across resampling and both the correlation and statistical significance were increased compared to distance correlation analysis. Further gene enrichment analysis and region of interest (ROI) analysis confirmed the associations of the identified genes with brain ROIs. Therefore, our approach provides a powerful tool for finding

Global gene expression changes in human embryonic lung fibroblasts induced by organic extracts from respirable air particles

Directory of Open Access Journals (Sweden)

Líbalová Helena

2012-01-01

Full Text Available Abstract Background Recently, we used cell-free assays to demonstrate the toxic effects of complex mixtures of organic extracts from urban air particles (PM2.5 collected in four localities of the Czech Republic (Ostrava-Bartovice, Ostrava-Poruba, Karvina and Trebon which differed in the extent and sources of air pollution. To obtain further insight into the biological mechanisms of action of the extractable organic matter (EOM from ambient air particles, human embryonic lung fibroblasts (HEL12469 were treated with the same four EOMs to assess changes in the genome-wide expression profiles compared to DMSO treated controls. Method For this purpose, HEL cells were incubated with subtoxic EOM concentrations of 10, 30, and 60 μg EOM/ml for 24 hours and global gene expression changes were analyzed using human whole genome microarrays (Illumina. The expression of selected genes was verified by quantitative real-time PCR. Results Dose-dependent increases in the number of significantly deregulated transcripts as well as dose-response relationships in the levels of individual transcripts were observed. The transcriptomic data did not differ substantially between the localities, suggesting that the air pollution originating mainly from various sources may have similar biological effects. This was further confirmed by the analysis of deregulated pathways and by identification of the most contributing gene modulations. The number of significantly deregulated KEGG pathways, as identified by Goeman's global test, varied, depending on the locality, between 12 to 29. The Metabolism of xenobiotics by cytochrome P450 exhibited the strongest upregulation in all 4 localities and CYP1B1 had a major contribution to the upregulation of this pathway. Other important deregulated pathways in all 4 localities were ABC transporters (involved in the translocation of exogenous and endogenous metabolites across membranes and DNA repair, the Wnt and TGF-β signaling pathways

Sequential Analysis of Global Gene Expression Profiles in Immature and In vitro Matured Bovine Oocytes: Potential Molecular Markers of Oocyte Maturation

LENUS (Irish Health Repository)

Mamo, Solomon

2011-03-16

Abstract Background Without intensive selection, the majority of bovine oocytes submitted to in vitro embryo production (IVP) fail to develop to the blastocyst stage. This is attributed partly to their maturation status and competences. Using the Affymetrix GeneChip Bovine Genome Array, global mRNA expression analysis of immature (GV) and in vitro matured (IVM) bovine oocytes was carried out to characterize the transcriptome of bovine oocytes and then use a variety of approaches to determine whether the observed transcriptional changes during IVM was real or an artifact of the techniques used during analysis. Results 8489 transcripts were detected across the two oocyte groups, of which ~25.0% (2117 transcripts) were differentially expressed (p < 0.001); corresponding to 589 over-expressed and 1528 under-expressed transcripts in the IVM oocytes compared to their immature counterparts. Over expression of transcripts by IVM oocytes is particularly interesting, therefore, a variety of approaches were employed to determine whether the observed transcriptional changes during IVM were real or an artifact of the techniques used during analysis, including the analysis of transcript abundance in oocytes in vitro matured in the presence of α-amanitin. Subsets of the differentially expressed genes were also validated by quantitative real-time PCR (qPCR) and the gene expression data was classified according to gene ontology and pathway enrichment. Numerous cell cycle linked (CDC2, CDK5, CDK8, HSPA2, MAPK14, TXNL4B), molecular transport (STX5, STX17, SEC22A, SEC22B), and differentiation (NACA) related genes were found to be among the several over-expressed transcripts in GV oocytes compared to the matured counterparts, while ANXA1, PLAU, STC1and LUM were among the over-expressed genes after oocyte maturation. Conclusion Using sequential experiments, we have shown and confirmed transcriptional changes during oocyte maturation. This dataset provides a unique reference resource

A stochastic approach to multi-gene expression dynamics

International Nuclear Information System (INIS)

Ochiai, T.; Nacher, J.C.; Akutsu, T.

2005-01-01

In the last years, tens of thousands gene expression profiles for cells of several organisms have been monitored. Gene expression is a complex transcriptional process where mRNA molecules are translated into proteins, which control most of the cell functions. In this process, the correlation among genes is crucial to determine the specific functions of genes. Here, we propose a novel multi-dimensional stochastic approach to deal with the gene correlation phenomena. Interestingly, our stochastic framework suggests that the study of the gene correlation requires only one theoretical assumption-Markov property-and the experimental transition probability, which characterizes the gene correlation system. Finally, a gene expression experiment is proposed for future applications of the model

The correlation between dual-color chromogenic in situ hybridization and fluorescence in situ hybridization in assessing HER2 gene amplification in breast cancer.

Science.gov (United States)

Pedersen, Marianne; Rasmussen, Birgitte Bruun

2009-06-01

Fluorescence in situ hybridization (FISH) is regarded as the gold standard method for detecting HER2 gene amplification. Chromogenic in situ hybridization (CISH) is a promising alternative to FISH because CISH has the advantages of being a method evaluated by bright-field microscopy and the generated chromogenic signals are also stable. This study presents a dual color CISH for simultaneous detection of the HER2 gene and chromosome 17. The CISH method performs a chromogenic detection "on top" of the Food and Drug Administration (FDA)-approved HER2 FISH pharmDx method, where the fluorochrome-labeled probes are detected using enzyme-labeled antibodies and visualized by chromogenic enzymatic reactions. The HER2 status (amplified/not amplified and HER2 ratios) was evaluated by the CISH method and compared with results obtained by the FDA-approved FISH method. Of the 72 successfully investigated invasive breast carcinomas, both FISH and CISH detected HER2 amplification in 24 cases and nonamplification was detected in 47 cases. One case showed a discrepancy between FISH and CISH. The concordance between CISH and FISH was found to be almost perfect (98.6%). The correlation between the HER2 ratios obtained by the 2 methods showed excellent correlation (correlation coefficient 0.95). In conclusion, it is possible by dual-color CISH method to demonstrate HER2 genes and chromosome 17 genes, in the same tissue section and reliably assess HER2 status. The CISH method is a very promising alternative to the FISH method.

Biogeography of photosynthetic light-harvesting genes in marine phytoplankton.

Directory of Open Access Journals (Sweden)

Thomas S Bibby

Full Text Available BACKGROUND: Photosynthetic light-harvesting proteins are the mechanism by which energy enters the marine ecosystem. The dominant prokaryotic photoautotrophs are the cyanobacterial genera Prochlorococcus and Synechococcus that are defined by two distinct light-harvesting systems, chlorophyll-bound protein complexes or phycobilin-bound protein complexes, respectively. Here, we use the Global Ocean Sampling (GOS Project as a unique and powerful tool to analyze the environmental diversity of photosynthetic light-harvesting genes in relation to available metadata including geographical location and physical and chemical environmental parameters. METHODS: All light-harvesting gene fragments and their metadata were obtained from the GOS database, aligned using ClustalX and classified phylogenetically. Each sequence has a name indicative of its geographic location; subsequent biogeographical analysis was performed by correlating light-harvesting gene budgets for each GOS station with surface chlorophyll concentration. CONCLUSION/SIGNIFICANCE: Using the GOS data, we have mapped the biogeography of light-harvesting genes in marine cyanobacteria on ocean-basin scales and show that an environmental gradient exists in which chlorophyll concentration is correlated to diversity of light-harvesting systems. Three functionally distinct types of light-harvesting genes are defined: (1 the phycobilisome (PBS genes of Synechococcus; (2 the pcb genes of Prochlorococcus; and (3 the iron-stress-induced (isiA genes present in some marine Synechococcus. At low chlorophyll concentrations, where nutrients are limited, the Pcb-type light-harvesting system shows greater genetic diversity; whereas at high chlorophyll concentrations, where nutrients are abundant, the PBS-type light-harvesting system shows higher genetic diversity. We interpret this as an environmental selection of specific photosynthetic strategy. Importantly, the unique light-harvesting system isiA is found

Methylation of Promoter Regions of Genes of the Human Intrauterine Renin Angiotensin System and Their Expression

Directory of Open Access Journals (Sweden)

Shane D. Sykes

2015-01-01

Full Text Available The intrauterine renin angiotensin system (RAS is implicated in placentation and labour onset. Here we investigate whether promoter methylation of RAS genes changes with gestation or labour and if it affects gene expression. Early gestation amnion and placenta were studied, as were term amnion, decidua, and placenta collected before labour (at elective caesarean section or after spontaneous labour and delivery. The expression and degree of methylation of the prorenin receptor (ATP6AP2, angiotensin converting enzyme (ACE, angiotensin II type 1 receptor (AGTR1, and two proteases that can activate prorenin (kallikrein, KLK1, and cathepsin D, CTSD were measured by qPCR and a DNA methylation array. There was no effect of gestation or labour on the methylation of RAS genes and CTSD. Amnion and decidua displayed strong correlations between the percent hypermethylation of RAS genes and CTSD, suggestive of global methylation. There were no correlations between the degree of methylation and mRNA abundance of any genes studied. KLK1 was the most methylated gene and the proportion of hypermethylated KLK1 alleles was lower in placenta than decidua. The presence of intermediate methylated alleles of KLK1 in early gestation placenta and in amnion after labour suggests that KLK1 methylation is uniquely dynamic in these tissues.

The Fanconi anemia family of genes and its correlation with breast cancer susceptibility and breast cancer features.

Science.gov (United States)

Barroso, E; Pita, G; Arias, J I; Menendez, P; Zamora, P; Blanco, M; Benitez, J; Ribas, G

2009-12-01

Fanconi anemia (FA) family of proteins participates in the DNA repair pathway by homologous recombination, and it is currently formed by 13 genes. Some of these proteins also confer susceptibility to hereditary breast and ovarian cancer (HBOC), since FANCD1 is the BRCA2 breast cancer susceptibility gene, and FANCN/PALB2 and FANCJ/BRIP1 explain 2% of non-BRCA1/2 HBOC families. Thus, there is an important connection between FA and BRCA pathways. In a previous case-control association study analysing FANCA, FANCD2 and FANCL, we reported an association between FANCD2 and sporadic breast cancer (BC) risk (OR = 1.35). In order to know whether variants in other FA genes could also be involved in this association, we have extended our study with the rest of FA genes and some others implicated in the BRCA pathway. We have also analyzed the correlation with survival, nodal metastasis and hormonal receptors (ER- and PR-). A total of 61 SNPs in ten FA genes (FANC-B, -C, -D1, -E, -F, -G, -I, -J, -M, -N) and five FA related genes (ATM, ATR, BRCA1, H2AX and USP1) were studied in a total of 547 consecutive and nonrelated sporadic BC cases and 552 unaffected controls from the Spanish population. Association analyses reported marginal statistically significant results with the minor allele of intronic SNPs in three genes: BRCA1, BRCA2/FANCD1, and ATM. Survival association with SNPs on FANCC and BRCA2/FANCD1 genes were also reported. Sub-group analyses revealed associations between SNPs on FANCI and ATM and nodal metastasis status and between FANCJ/BRIP1 and FANCN/PALB2 and PR- status.

Molecular signatures in childhood acute leukemia and their correlations to expression patterns in normal hematopoietic subpopulations.

Science.gov (United States)

Andersson, Anna; Olofsson, Tor; Lindgren, David; Nilsson, Björn; Ritz, Cecilia; Edén, Patrik; Lassen, Carin; Råde, Johan; Fontes, Magnus; Mörse, Helena; Heldrup, Jesper; Behrendtz, Mikael; Mitelman, Felix; Höglund, Mattias; Johansson, Bertil; Fioretos, Thoas

2005-12-27

Global expression profiles of a consecutive series of 121 childhood acute leukemias (87 B lineage acute lymphoblastic leukemias, 11 T cell acute lymphoblastic leukemias, and 23 acute myeloid leukemias), six normal bone marrows, and 10 normal hematopoietic subpopulations of different lineages and maturations were ascertained by using 27K cDNA microarrays. Unsupervised analyses revealed segregation according to lineages and primary genetic changes, i.e., TCF3(E2A)/PBX1, IGH@/MYC, ETV6(TEL)/RUNX1(AML1), 11q23/MLL, and hyperdiploidy (>50 chromosomes). Supervised discriminatory analyses were used to identify differentially expressed genes correlating with lineage and primary genetic change. The gene-expression profiles of normal hematopoietic cells were also studied. By using principal component analyses (PCA), a differentiation axis was exposed, reflecting lineages and maturation stages of normal hematopoietic cells. By applying the three principal components obtained from PCA of the normal cells on the leukemic samples, similarities between malignant and normal cell lineages and maturations were investigated. Apart from showing that leukemias segregate according to lineage and genetic subtype, we provide an extensive study of the genes correlating with primary genetic changes. We also investigated the expression pattern of these genes in normal hematopoietic cells of different lineages and maturations, identifying genes preferentially expressed by the leukemic cells, suggesting an ectopic activation of a large number of genes, likely to reflect regulatory networks of pathogenetic importance that also may provide attractive targets for future directed therapies.

An Analysis of Historical Global Warming and Social Engagement

OpenAIRE

Train, Joseph; Roizenman, David; Damiani, Seth; Rochwerg, Ronny

2018-01-01

The goal of this paper is to determine whether there is a correlation between awareness of global warming, and where global warming occurs. This theory is carried out by analyzing maps containing various forms of data that have to do with global warming, such as precipitation and surface temperature, and comparing it with a map of engagement from tweets which mention global warming. This paper found that there is no solid correlation between mentioning global warming in tweets and global warm...

A quadratically regularized functional canonical correlation analysis for identifying the global structure of pleiotropy with NGS data.

Science.gov (United States)

Lin, Nan; Zhu, Yun; Fan, Ruzong; Xiong, Momiao

2017-10-01

Investigating the pleiotropic effects of genetic variants can increase statistical power, provide important information to achieve deep understanding of the complex genetic structures of disease, and offer powerful tools for designing effective treatments with fewer side effects. However, the current multiple phenotype association analysis paradigm lacks breadth (number of phenotypes and genetic variants jointly analyzed at the same time) and depth (hierarchical structure of phenotype and genotypes). A key issue for high dimensional pleiotropic analysis is to effectively extract informative internal representation and features from high dimensional genotype and phenotype data. To explore correlation information of genetic variants, effectively reduce data dimensions, and overcome critical barriers in advancing the development of novel statistical methods and computational algorithms for genetic pleiotropic analysis, we proposed a new statistic method referred to as a quadratically regularized functional CCA (QRFCCA) for association analysis which combines three approaches: (1) quadratically regularized matrix factorization, (2) functional data analysis and (3) canonical correlation analysis (CCA). Large-scale simulations show that the QRFCCA has a much higher power than that of the ten competing statistics while retaining the appropriate type 1 errors. To further evaluate performance, the QRFCCA and ten other statistics are applied to the whole genome sequencing dataset from the TwinsUK study. We identify a total of 79 genes with rare variants and 67 genes with common variants significantly associated with the 46 traits using QRFCCA. The results show that the QRFCCA substantially outperforms the ten other statistics.

Divergence of gene body DNA methylation and evolution of plant duplicate genes.

Directory of Open Access Journals (Sweden)

Jun Wang

Full Text Available It has been shown that gene body DNA methylation is associated with gene expression. However, whether and how deviation of gene body DNA methylation between duplicate genes can influence their divergence remains largely unexplored. Here, we aim to elucidate the potential role of gene body DNA methylation in the fate of duplicate genes. We identified paralogous gene pairs from Arabidopsis and rice (Oryza sativa ssp. japonica genomes and reprocessed their single-base resolution methylome data. We show that methylation in paralogous genes nonlinearly correlates with several gene properties including exon number/gene length, expression level and mutation rate. Further, we demonstrated that divergence of methylation level and pattern in paralogs indeed positively correlate with their sequence and expression divergences. This result held even after controlling for other confounding factors known to influence the divergence of paralogs. We observed that methylation level divergence might be more relevant to the expression divergence of paralogs than methylation pattern divergence. Finally, we explored the mechanisms that might give rise to the divergence of gene body methylation in paralogs. We found that exonic methylation divergence more closely correlates with expression divergence than intronic methylation divergence. We show that genomic environments (e.g., flanked by transposable elements and repetitive sequences of paralogs generated by various duplication mechanisms are associated with the methylation divergence of paralogs. Overall, our results suggest that the changes in gene body DNA methylation could provide another avenue for duplicate genes to develop differential expression patterns and undergo different evolutionary fates in plant genomes.

Global transcriptome analysis of Huperzia serrata and identification of critical genes involved in the biosynthesis of huperzine A.

Science.gov (United States)

Yang, Mengquan; You, Wenjing; Wu, Shiwen; Fan, Zhen; Xu, Baofu; Zhu, Mulan; Li, Xuan; Xiao, Youli

2017-03-22

Huperzia serrata (H. serrata) is an economically important traditional Chinese herb with the notably medicinal value. As a representative member of the Lycopodiaceae family, the H. serrata produces various types of effectively bioactive lycopodium alkaloids, especially the huperzine A (HupA) which is a promising drug for Alzheimer's disease. Despite their medicinal importance, the public genomic and transcriptomic resources are very limited and the biosynthesis of HupA is largely unknown. Previous studies on comparison of 454-ESTs from H. serrata and Phlegmariurus carinatus predicted putative genes involved in lycopodium alkaloid biosynthesis, such as lysine decarboxylase like (LDC-like) protein and some CYP450s. However, these gene annotations were not carried out with further biochemical characterizations. To understand the biosynthesis of HupA and its regulation in H. serrata, a global transcriptome analysis on H. Serrata tissues was performed. In this study, we used the Illumina Highseq4000 platform to generate a substantial RNA sequencing dataset of H. serrata. A total of 40.1 Gb clean data was generated from four different tissues: root, stem, leaf, and sporangia and assembled into 181,141 unigenes. The total length, average length, N50 and GC content of unigenes were 219,520,611 bp, 1,211 bp, 2,488 bp and 42.51%, respectively. Among them, 105,516 unigenes (58.25%) were annotated by seven public databases (NR, NT, Swiss-Prot, KEGG, COG, Interpro, GO), and 54 GO terms and 3,391 transcription factors (TFs) were functionally classified, respectively. KEGG pathway analysis revealed that 72,230 unigenes were classified into 21 functional pathways. Three types of candidate enzymes, LDC, CAO and PKS, responsible for the biosynthesis of precursors of HupA were all identified in the transcripts. Four hundred and fifty-seven CYP450 genes in H. serrata were also analyzed and compared with tissue-specific gene expression. Moreover, two key classes of CYP450 genes BBE

Genome-wide Annotation, Identification, and Global Transcriptomic Analysis of Regulatory or Small RNA Gene Expression in Staphylococcus aureus.

Science.gov (United States)

Carroll, Ronan K; Weiss, Andy; Broach, William H; Wiemels, Richard E; Mogen, Austin B; Rice, Kelly C; Shaw, Lindsey N

2016-02-09

In Staphylococcus aureus, hundreds of small regulatory or small RNAs (sRNAs) have been identified, yet this class of molecule remains poorly understood and severely understudied. sRNA genes are typically absent from genome annotation files, and as a consequence, their existence is often overlooked, particularly in global transcriptomic studies. To facilitate improved detection and analysis of sRNAs in S. aureus, we generated updated GenBank files for three commonly used S. aureus strains (MRSA252, NCTC 8325, and USA300), in which we added annotations for >260 previously identified sRNAs. These files, the first to include genome-wide annotation of sRNAs in S. aureus, were then used as a foundation to identify novel sRNAs in the community-associated methicillin-resistant strain USA300. This analysis led to the discovery of 39 previously unidentified sRNAs. Investigating the genomic loci of the newly identified sRNAs revealed a surprising degree of inconsistency in genome annotation in S. aureus, which may be hindering the analysis and functional exploration of these elements. Finally, using our newly created annotation files as a reference, we perform a global analysis of sRNA gene expression in S. aureus and demonstrate that the newly identified tsr25 is the most highly upregulated sRNA in human serum. This study provides an invaluable resource to the S. aureus research community in the form of our newly generated annotation files, while at the same time presenting the first examination of differential sRNA expression in pathophysiologically relevant conditions. Despite a large number of studies identifying regulatory or small RNA (sRNA) genes in Staphylococcus aureus, their annotation is notably lacking in available genome files. In addition to this, there has been a considerable lack of cross-referencing in the wealth of studies identifying these elements, often leading to the same sRNA being identified multiple times and bearing multiple names. In this work

Gene and protein expression of epidermal growth factor measured on the kidney 24 hours after irradiation correlates to late radiation damage

International Nuclear Information System (INIS)

Otsuka, Makoto; Hatakenaka, Masamitsu

2001-01-01

This study was designed to evaluate the proliferative response of epidermal growth factor (EGF) gene expression as an early indicator of late renal radiation damage. EGF gene expression was measured in the irradiated left kidney of C3H/HeSlc mice using RT-PCR 24 hours after radiation doses of 9, 12, or 15 Gy. In a second experiment, the same radiation doses were administered to the right kidney plus the lower half of the left kidney. The partly irradiated left kidneys were harvested and EGF gene expression was measured. The irradiated whole right kidneys were subjected to immunohistochemical staining for EGF protein. In a third experiment, 12 Gy was administered to the right kidney plus the lower half of the left kidney. The mice underwent left nephrectomy 24 hours after radiation, and the EGF gene expression in the kidney was correlated with the blood urea nitrogen (BUN) level representing late renal functional damage. EGF expression increased in 1 of 10 control mice and in 9 of 10 mice that received 15 Gy. The extent of increase of EGF was dependent on radiation dose. In mice having an increased BUN level after irradiation, 7 of 10 had EGF positive irradiated kidneys. All six mice whose BUN levels were unchanged had EGF-negative irradiated kidneys. EGF protein staining was observed in tubule cells only, not in glomerular cells. The amount of EGF protein staining correlated with radiation dose to some extent. EGF gene expression seems to be a very early indicator of late radiation damage to the kidney. (author)

The transcriptional and gene regulatory network of Lactococcus lactis MG1363 during growth in milk.

Directory of Open Access Journals (Sweden)

Anne de Jong

Full Text Available In the present study we examine the changes in the expression of genes of Lactococcus lactis subspecies cremoris MG1363 during growth in milk. To reveal which specific classes of genes (pathways, operons, regulons, COGs are important, we performed a transcriptome time series experiment. Global analysis of gene expression over time showed that L. lactis adapted quickly to the environmental changes. Using upstream sequences of genes with correlated gene expression profiles, we uncovered a substantial number of putative DNA binding motifs that may be relevant for L. lactis fermentative growth in milk. All available novel and literature-derived data were integrated into network reconstruction building blocks, which were used to reconstruct and visualize the L. lactis gene regulatory network. This network enables easy mining in the chrono-transcriptomics data. A freely available website at http://milkts.molgenrug.nl gives full access to all transcriptome data, to the reconstructed network and to the individual network building blocks.

Correlation Between ISAba1 Upstream ampC Gene and Resistance to Cefotaxime in Acinetobacter baumannii: A Serious Threat to Nosocomial Infections

Directory of Open Access Journals (Sweden)

Rezaee

2016-01-01

Full Text Available Background Infections due to Acinetobacter baumannii have become a significant challenge in modern healthcare systems. The global upsurge of multidrug resistance in A. baumannii has created widespread problems in the treatment of patients. Objectives We examined the prevalence ISAmpC and its correlation with cefotaxime resistance. Materials and Methods Standard biochemical tests were used to identify isolates. Genomic species of the genus Acinetobacter were confirmed by Amplified Ribosomal DNA Restriction Analysis (ARDRA. The susceptibility of 50 A. baumannii isolates to a variety of antimicrobial agents was determined using the disk diffusion method and E-test strips. PCR was used to investigate the connection of insertion sequences and the ampC gene. Clonal relatedness was determined by Repetitive Extragenic Palindromic PCR. Results ISAba1 located upstream of blaampC was found in 24 (48% of the A. baumannii isolates. In all of the studied isolates that had ISAmpC, the MIC for cefotaxime was 64 - 256 μg/mL. Based on the REP-PCR patterns among the resistant isolates, the highest number of ISAmpC positive isolates belonged to type B (n = 19 and type C (n = 12. Conclusions ISAba1 has become an important factor in A. baumannii’s resistance to cefotaxime.

A canonical correlation analysis-based dynamic bayesian network prior to infer gene regulatory networks from multiple types of biological data.

Science.gov (United States)

Baur, Brittany; Bozdag, Serdar

2015-04-01

One of the challenging and important computational problems in systems biology is to infer gene regulatory networks (GRNs) of biological systems. Several methods that exploit gene expression data have been developed to tackle this problem. In this study, we propose the use of copy number and DNA methylation data to infer GRNs. We developed an algorithm that scores regulatory interactions between genes based on canonical correlation analysis. In this algorithm, copy number or DNA methylation variables are treated as potential regulator variables, and expression variables are treated as potential target variables. We first validated that the canonical correlation analysis method is able to infer true interactions in high accuracy. We showed that the use of DNA methylation or copy number datasets leads to improved inference over steady-state expression. Our results also showed that epigenetic and structural information could be used to infer directionality of regulatory interactions. Additional improvements in GRN inference can be gleaned from incorporating the result in an informative prior in a dynamic Bayesian algorithm. This is the first study that incorporates copy number and DNA methylation into an informative prior in dynamic Bayesian framework. By closely examining top-scoring interactions with different sources of epigenetic or structural information, we also identified potential novel regulatory interactions.

Big Data Solution for CTBT Monitoring Using Global Cross Correlation

Science.gov (United States)

Gaillard, P.; Bobrov, D.; Dupont, A.; Grenouille, A.; Kitov, I. O.; Rozhkov, M.

2014-12-01

Due to the mismatch between data volume and the performance of the Information Technology infrastructure used in seismic data centers, it becomes more and more difficult to process all the data with traditional applications in a reasonable elapsed time. To fulfill their missions, the International Data Centre of the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO/IDC) and the Département Analyse Surveillance Environnement of Commissariat à l'Energie atomique et aux énergies alternatives (CEA/DASE) collect, process and produce complex data sets whose volume is growing exponentially. In the medium term, computer architectures, data management systems and application algorithms will require fundamental changes to meet the needs. This problem is well known and identified as a "Big Data" challenge. To tackle this major task, the CEA/DASE takes part during two years to the "DataScale" project. Started in September 2013, DataScale gathers a large set of partners (research laboratories, SMEs and big companies). The common objective is to design efficient solutions using the synergy between Big Data solutions and the High Performance Computing (HPC). The project will evaluate the relevance of these technological solutions by implementing a demonstrator for seismic event detections thanks to massive waveform correlations. The IDC has developed an expertise on such techniques leading to an algorithm called "Master Event" and provides a high-quality dataset for an extensive cross correlation study. The objective of the project is to enhance the Master Event algorithm and to reanalyze 10 years of waveform data from the International Monitoring System (IMS) network thanks to a dedicated HPC infrastructure operated by the "Centre de Calcul Recherche et Technologie" at the CEA of Bruyères-le-Châtel. The dataset used for the demonstrator includes more than 300,000 seismic events, tens of millions of raw detections and more than 30 terabytes of continuous seismic data

WGCNA: an R package for weighted correlation network analysis.

Science.gov (United States)

Langfelder, Peter; Horvath, Steve

2008-12-29

Correlation networks are increasingly being used in bioinformatics applications. For example, weighted gene co-expression network analysis is a systems biology method for describing the correlation patterns among genes across microarray samples. Weighted correlation network analysis (WGCNA) can be used for finding clusters (modules) of highly correlated genes, for summarizing such clusters using the module eigengene or an intramodular hub gene, for relating modules to one another and to external sample traits (using eigengene network methodology), and for calculating module membership measures. Correlation networks facilitate network based gene screening methods that can be used to identify candidate biomarkers or therapeutic targets. These methods have been successfully applied in various biological contexts, e.g. cancer, mouse genetics, yeast genetics, and analysis of brain imaging data. While parts of the correlation network methodology have been described in separate publications, there is a need to provide a user-friendly, comprehensive, and consistent software implementation and an accompanying tutorial. The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis. The package includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software. Along with the R package we also present R software tutorials. While the methods development was motivated by gene expression data, the underlying data mining approach can be applied to a variety of different settings. The WGCNA package provides R functions for weighted correlation network analysis, e.g. co-expression network analysis of gene expression data. The R package along with its source code and additional material are freely available at http://www.genetics.ucla.edu/labs/horvath/CoexpressionNetwork/Rpackages/WGCNA.

Coamplification of human acetylcholinesterase and butyrylcholinesterase genes in blood cells: Correlation with various leukemias and abnormal megakaryocytopoiesis

International Nuclear Information System (INIS)

Lapidot-Lifson, Y.; Prody, C.A.; Ginzberg, D.; Meytes, D.; Zakut, H.; Soreq, H.

1989-01-01

To study the yet unknown role of the ubiquitous family of cholinesterases (ChoEases) in developing blood cells, the recently isolated cDNAs encoding human acetylcholinesterase and butyrylcholinesterase were used in blot hybridization with peripheral blood DNA from various leukemic patients. Hybridization signals and modified restriction patterns were observed with both cDNA probes in 4 of the 16 leukemia DNA preparations examined. These reflected the amplification of the corresponding AcCho-Ease and BtChoEase genes (ACHE and CHE) and alteration in their structure. Parallel analysis of 30 control samples revealed nonpolymorphic, much weaker hybridization signals for each of the probes. In view of previous reports on the effect of acetylcholine analogs and ChoEase inhibitors in the induction of megakaryocytopoiesis and production of platelets in the mouse. The authors further searched for such phenomena in nonleukemic patients with platelet production disorders. Amplifications of both ACHE and CHE genes were found in 2 of the 4 patients so far examined. Pronounced coamplification of these two related but distinct genes in correlation with pathological production of blood cells suggests a functional role for members of the ChoEase family in megakaryocytopoiesis and raises the question whether the coamplification of these genes could be casually involved in the etiology of hemocytopoietic disorders

Correlation of ophthalmic examination with carrier status in females potentially harboring a severe Norrie disease gene mutation.

Science.gov (United States)

Khan, Arif O; Aldahmesh, Mohammed A; Meyer, Brian

2008-04-01

To correlate ophthalmic findings with carrier status for a severe Norrie disease (ND) gene mutation (C95F). Prospective interventional case series. Six potential carriers and 1 obligate carrier from a family harboring the mutation. An ophthalmologist blind to the pedigree performed a full ophthalmic examination for the 7 asymptomatic family members. A peripheral blood sample was collected from each for ND gene sequencing. Ophthalmic examination findings (with attention to the presence or absence of retinal findings) and results of ND gene sequencing. Three carriers were identified by molecular genetics, and all 3 of them had peripheral retinal abnormality. However, 3 of the 4 genetically identified noncarriers also exhibited peripheral retinal abnormality. Two of these noncarriers with retinal findings were the offspring of a confirmed noncarrier. The genetically identified noncarrier with a normal peripheral retinal examination was the daughter of an obligate carrier. The presence of peripheral retinal changes was not useful for carrier prediction in a family harboring ND. There are likely additional loci responsible for phenotypic expression.

Genome-wide analysis of the expansin gene superfamily reveals grapevine-specific structural and functional characteristics.

Directory of Open Access Journals (Sweden)

Silvia Dal Santo

Full Text Available BACKGROUND: Expansins are proteins that loosen plant cell walls in a pH-dependent manner, probably by increasing the relative movement among polymers thus causing irreversible expansion. The expansin superfamily (EXP comprises four distinct families: expansin A (EXPA, expansin B (EXPB, expansin-like A (EXLA and expansin-like B (EXLB. There is experimental evidence that EXPA and EXPB proteins are required for cell expansion and developmental processes involving cell wall modification, whereas the exact functions of EXLA and EXLB remain unclear. The complete grapevine (Vitis vinifera genome sequence has allowed the characterization of many gene families, but an exhaustive genome-wide analysis of expansin gene expression has not been attempted thus far. METHODOLOGY/PRINCIPAL FINDINGS: We identified 29 EXP superfamily genes in the grapevine genome, representing all four EXP families. Members of the same EXP family shared the same exon-intron structure, and phylogenetic analysis confirmed a closer relationship between EXP genes from woody species, i.e. grapevine and poplar (Populus trichocarpa, compared to those from Arabidopsis thaliana and rice (Oryza sativa. We also identified grapevine-specific duplication events involving the EXLB family. Global gene expression analysis confirmed a strong correlation among EXP genes expressed in mature and green/vegetative samples, respectively, as reported for other gene families in the recently-published grapevine gene expression atlas. We also observed the specific co-expression of EXLB genes in woody organs, and the involvement of certain grapevine EXP genes in berry development and post-harvest withering. CONCLUSION: Our comprehensive analysis of the grapevine EXP superfamily confirmed and extended current knowledge about the structural and functional characteristics of this gene family, and also identified properties that are currently unique to grapevine expansin genes. Our data provide a model for the

Polymorphisms of two neuroendocrine–correlated genes associated ...

African Journals Online (AJOL)

Administrator

2011-09-19

Sep 19, 2011 ... genes associated with body weight and reproductive traits in Jinghai ... 3Jiangsu Jinghai Poultry Group Co., Ltd., Nantong, 226103, China. Accepted 18 .... Birds had access to feed [commercial corn-soybean diets meeting.

Rift Valley fever virus NS{sub S} gene expression correlates with a defect in nuclear mRNA export

Energy Technology Data Exchange (ETDEWEB)

Copeland, Anna Maria; Van Deusen, Nicole M.; Schmaljohn, Connie S., E-mail: Connie.s.schmaljohn.civ@mail.mil

2015-12-15

We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NS{sub S} gene, but not the N, G{sub N} or NS{sub M} genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NS{sub S}, confirming that expression of NS{sub S} is likely responsible for this phenomenon. - Highlights: • Rift Valley fever virus (RVFV) infection alters the localization of host mRNA. • mRNA accumulates in the nuclei of RVFV-infected but not mock-infected cells. • NS{sub S} is likely responsible for mRNA relocalization to the nucleus.

First cellular approach of the effects of global warming on groundwater organisms: a study of the HSP70 gene expression.

Science.gov (United States)

Colson-Proch, Céline; Morales, Anne; Hervant, Frédéric; Konecny, Lara; Moulin, Colette; Douady, Christophe J

2010-05-01

Whereas the consequences of global warming at population or community levels are well documented, studies at the cellular level are still scarce. The study of the physiological or metabolic effects of such small increases in temperature (between +2 degrees C and +6 degrees C) is difficult because they are below the amplitude of the daily or seasonal thermal variations occurring in most environments. In contrast, subterranean biotopes are highly thermally buffered (+/-1 degrees C within a year), and underground water organisms could thus be particularly well suited to characterise cellular responses of global warming. To this purpose, we studied genes encoding chaperone proteins of the HSP70 family in amphipod crustaceans belonging to the ubiquitous subterranean genus Niphargus. An HSP70 sequence was identified in eight populations of two complexes of species of the Niphargus genus (Niphargus rhenorhodanensis and Niphargus virei complexes). Expression profiles were determined for one of these by reverse transcription and quantitative polymerase chain reaction, confirming the inducible nature of this gene. An increase in temperature of 2 degrees C seemed to be without effect on N. rhenorhodanensis physiology, whereas a heat shock of +6 degrees C represented an important thermal stress for these individuals. Thus, this study shows that although Niphargus individuals do not undergo any daily or seasonal thermal variations in underground water, they display an inducible HSP70 heat shock response. This controlled laboratory-based physiological experiment constitutes a first step towards field investigations of the cellular consequences of global warming on subterranean organisms.

De novo Transcriptome Assembly of Chinese Kale and Global Expression Analysis of Genes Involved in Glucosinolate Metabolism in Multiple Tissues

Science.gov (United States)

Wu, Shuanghua; Lei, Jianjun; Chen, Guoju; Chen, Hancai; Cao, Bihao; Chen, Changming

2017-01-01

Chinese kale, a vegetable of the cruciferous family, is a popular crop in southern China and Southeast Asia due to its high glucosinolate content and nutritional qualities. However, there is little research on the molecular genetics and genes involved in glucosinolate metabolism and its regulation in Chinese kale. In this study, we sequenced and characterized the transcriptomes and expression profiles of genes expressed in 11 tissues of Chinese kale. A total of 216 million 150-bp clean reads were generated using RNA-sequencing technology. From the sequences, 98,180 unigenes were assembled for the whole plant, and 49,582~98,423 unigenes were assembled for each tissue. Blast analysis indicated that a total of 80,688 (82.18%) unigenes exhibited similarity to known proteins. The functional annotation and classification tools used in this study suggested that genes principally expressed in Chinese kale, were mostly involved in fundamental processes, such as cellular and molecular functions, the signal transduction, and biosynthesis of secondary metabolites. The expression levels of all unigenes were analyzed in various tissues of Chinese kale. A large number of candidate genes involved in glucosinolate metabolism and its regulation were identified, and the expression patterns of these genes were analyzed. We found that most of the genes involved in glucosinolate biosynthesis were highly expressed in the root, petiole, and in senescent leaves. The expression patterns of ten glucosinolate biosynthetic genes from RNA-seq were validated by quantitative RT-PCR in different tissues. These results provided an initial and global overview of Chinese kale gene functions and expression activities in different tissues. PMID:28228764

A practical platform for blood biomarker study by using global gene expression profiling of peripheral whole blood.

Directory of Open Access Journals (Sweden)

Ze Tian

Full Text Available Although microarray technology has become the most common method for studying global gene expression, a plethora of technical factors across the experiment contribute to the variable of genome gene expression profiling using peripheral whole blood. A practical platform needs to be established in order to obtain reliable and reproducible data to meet clinical requirements for biomarker study.We applied peripheral whole blood samples with globin reduction and performed genome-wide transcriptome analysis using Illumina BeadChips. Real-time PCR was subsequently used to evaluate the quality of array data and elucidate the mode in which hemoglobin interferes in gene expression profiling. We demonstrated that, when applied in the context of standard microarray processing procedures, globin reduction results in a consistent and significant increase in the quality of beadarray data. When compared to their pre-globin reduction counterparts, post-globin reduction samples show improved detection statistics, lowered variance and increased sensitivity. More importantly, gender gene separation is remarkably clearer in post-globin reduction samples than in pre-globin reduction samples. Our study suggests that the poor data obtained from pre-globin reduction samples is the result of the high concentration of hemoglobin derived from red blood cells either interfering with target mRNA binding or giving the pseudo binding background signal.We therefore recommend the combination of performing globin mRNA reduction in peripheral whole blood samples and hybridizing on Illumina BeadChips as the practical approach for biomarker study.

Global gene expression analysis for evaluation and design of biomaterials

Directory of Open Access Journals (Sweden)

Nobutaka Hanagata, Taro Takemura and Takashi Minowa

2010-01-01

Full Text Available Comprehensive gene expression analysis using DNA microarrays has become a widespread technique in molecular biological research. In the biomaterials field, it is used to evaluate the biocompatibility or cellular toxicity of metals, polymers and ceramics. Studies in this field have extracted differentially expressed genes in the context of differences in cellular responses among multiple materials. Based on these genes, the effects of materials on cells at the molecular level have been examined. Expression data ranging from several to tens of thousands of genes can be obtained from DNA microarrays. For this reason, several tens or hundreds of differentially expressed genes are often present in different materials. In this review, we outline the principles of DNA microarrays, and provide an introduction to methods of extracting information which is useful for evaluating and designing biomaterials from comprehensive gene expression data.

Global gene expression analysis for evaluation and design of biomaterials

International Nuclear Information System (INIS)

Hanagata, Nobutaka; Takemura, Taro; Minowa, Takashi

2010-01-01

Comprehensive gene expression analysis using DNA microarrays has become a widespread technique in molecular biological research. In the biomaterials field, it is used to evaluate the biocompatibility or cellular toxicity of metals, polymers and ceramics. Studies in this field have extracted differentially expressed genes in the context of differences in cellular responses among multiple materials. Based on these genes, the effects of materials on cells at the molecular level have been examined. Expression data ranging from several to tens of thousands of genes can be obtained from DNA microarrays. For this reason, several tens or hundreds of differentially expressed genes are often present in different materials. In this review, we outline the principles of DNA microarrays, and provide an introduction to methods of extracting information which is useful for evaluating and designing biomaterials from comprehensive gene expression data. (topical review)

Investigating the radial structure of axisymmetric fluctuations in the TCV tokamak with local and global gyrokinetic GENE simulations

Science.gov (United States)

Merlo, G.; Brunner, S.; Huang, Z.; Coda, S.; Görler, T.; Villard, L.; Bañón Navarro, A.; Dominski, J.; Fontana, M.; Jenko, F.; Porte, L.; Told, D.

2018-03-01

Axisymmetric (n = 0) density fluctuations measured in the TCV tokamak are observed to possess a frequency f 0 which is either varying (radially dispersive oscillations) or a constant over a large fraction of the plasma minor radius (radially global oscillations) as reported in a companion paper (Z Huang et al, this issue). Given that f 0 scales with the sound speed and given the poloidal structure of density fluctuations, these oscillations were interpreted as Geodesic Acoustic Modes, even though f 0 is in fact smaller than the local linear GAM frequency {f}{GAM}. In this work we employ the Eulerian gyrokinetic code GENE to simulate TCV relevant conditions and investigate the nature and properties of these oscillations, in particular their relation to the safety factor profile. Local and global simulations are carried out and a good qualitative agreement is observed between experiments and simulations. By varying also the plasma temperature and density profiles, we conclude that a variation of the edge safety factor alone is not sufficient to induce a transition from global to radially inhomogeneous oscillations, as was initially suggested by experimental results. This transition appears instead to be the combined result of variations in the different plasma profiles, collisionality and finite machine size effects. Simulations also show that radially global GAM-like oscillations can be observed in all fluxes and fluctuation fields, suggesting that they are the result of a complex nonlinear process involving also finite toroidal mode numbers and not just linear global GAM eigenmodes.

The effect of the CCR5-delta32 deletion on global gene expression considering immune response and inflammation

Directory of Open Access Journals (Sweden)

Hütter Gero

2011-10-01

Full Text Available Abstract Background The natural function of the C-C chemokine receptor type 5 (CCR5 is poorly understood. A 32 base pair deletion in the CCR5 gene (CCR5-delta32 located on chromosome 3 results in a non-functional protein. It is supposed that this deletion causes an alteration in T-cell response to inflammation. For example, the presence of the CCR5-delta32 allele in recipients of allografts constitutes as an independent and protective factor associated with a decreased risk of graft-versus-host disease (GVHD and graft rejection. However, the mechanism of this beneficial effect of the deletion regarding GVHD is unknown. In this survey we searched for a CCR5-delta32 associated regulation of critical genes involved in the immune response and the development of GVHD. Methods We examined CD34+ hematopoietic progenitor cells derived from bone marrow samples from 19 healthy volunteers for the CCR5-delta32 deletion with a genomic PCR using primers flanking the site of the deletion. Results 12 individuals were found to be homozygous for CCR5 WT and 7 carried the CCR5-delta32 deletion heterozygously. Global gene expression analysis led to the identification of 11 differentially regulated genes. Six of them are connected with mechanisms of immune response and control: LRG1, CXCR2, CCRL2, CD6, CD7, WD repeat domain, and CD30L. Conclusions Our data indicate that the CCR5-delta32 mutation may be associated with differential gene expression. Some of these genes are critical for immune response, in the case of CD30L probably protective in terms of GVHD.

Correlation of HAMP gene polymorphisms and expression with the susceptibility and length of hospital stays in Taiwanese children with Kawasaki disease

Science.gov (United States)

Lu, Hsing-Fang; Wong, Henry Sung-Ching; Yu, Hong-Ren; Kuo, Hsing-Chun; Huang, Fu-Chen; Lo, Mao-Hung; Hsieh, Kai-Sheng; Chen, Su-Fen; Chang, Wei-Chiao; Kuo, Ho-Chang

2017-01-01

Kawasaki disease (KD) is a form of systemic vasculitis. Regarding its pathogenesis, HAMP gene encoding hepcidin, which is significant for iron metabolism, has a vital function. In this study, we recruited a total of 381 KD patients for genotyping. Data from 997 subjects (500 subjects from cohort 1; 497 subjects from cohort 2) were used for analysis. Using TaqMan allelic discrimination, we determined five tag SNPs (rs916145, rs10421768, rs3817623, rs7251432, and rs2293689). Treatment outcome data related to such clinical phenotypes as coronary artery lesions (CAL), coronary artery aneurysms (CAA), and intravenous immunoglobulin (IVIG) effects were also collected. Furthermore, we measured plasma hepcidin levels with an enzyme-linked immunosorbent assay. We found that HAMP gene polymorphism (rs7251432, and rs2293689) was significantly correlated with KD risk and that plasma hepcidin levels both before and after IVIG treatment had a significantly positive correlation with length of hospital stays (R = 0.217, p = 0.046 and R = 0.381, p < 0.0001, respectively). In contrast, plasma hepcidin levels has a negative correlation with KD patients’ albumin levels (R = −0.27, p < 0.001) prior to IVIG treatment. This study's findings indicate that HAMP might have a role in the disease susceptibility, as well as its expressions correlated length of hospital stays, and albumin levels in Taiwanese children with KD. PMID:28881695

Patterns of evolutionary conservation of essential genes correlate with their compensability.

Directory of Open Access Journals (Sweden)

Tobias Bergmiller

2012-06-01

Full Text Available Essential genes code for fundamental cellular functions required for the viability of an organism. For this reason, essential genes are often highly conserved across organisms. However, this is not always the case: orthologues of genes that are essential in one organism are sometimes not essential in other organisms or are absent from their genomes. This suggests that, in the course of evolution, essential genes can be rendered nonessential. How can a gene become non-essential? Here we used genetic manipulation to deplete the products of 26 different essential genes in Escherichia coli. This depletion results in a lethal phenotype, which could often be rescued by the overexpression of a non-homologous, non-essential gene, most likely through replacement of the essential function. We also show that, in a smaller number of cases, the essential genes can be fully deleted from the genome, suggesting that complete functional replacement is possible. Finally, we show that essential genes whose function can be replaced in the laboratory are more likely to be non-essential or not present in other taxa. These results are consistent with the notion that patterns of evolutionary conservation of essential genes are influenced by their compensability-that is, by how easily they can be functionally replaced, for example through increased expression of other genes.

Global Variation of Human Papillomavirus Genotypes and Selected Genes Involved in Cervical Malignancies.

Science.gov (United States)

Husain, R S Akram; Ramakrishnan, V

2015-01-01

Carcinoma of the cervix is ranked second among the top 5 cancers affecting women globally. Parallel to other cancers, it is also a complex disease involving numerous factors such as human papillomavirus (HPV) infection followed by the activity of oncogenes and environmental factors. The incidence rate of the disease remains high in developing countries due to lack of awareness, followed by mass screening programs, various socioeconomic issues, and low usage of preventive vaccines. Over the past 3 decades, extensive research has taken place in cervical malignancy to elucidate the role of host genes in the pathogenesis of the disease, yet it remains one of the most prevalent diseases. It is imperative that recent genome-wide techniques be used to determine whether carcinogenesis of oncogenes is associated with cervical cancer at the molecular level and to translate that knowledge into developing diagnostic and therapeutic tools. The aim of this study was to discuss HPV predominance with their genotype distribution worldwide, and in India, as well as to discuss the newly identified oncogenes related to cervical cancer in current scenario. Using data from various databases and robust technologies, oncogenes associated with cervical malignancies were identified and are explained in concise manner. Due to the advent of recent technologies, new candidate genes are explored and can be used as precise biomarkers for screening and developing drug targets. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

High Levels of Antibiotic Resistance Genes and Their Correlations with Bacterial Community and Mobile Genetic Elements in Pharmaceutical Wastewater Treatment Bioreactors.

Directory of Open Access Journals (Sweden)

Wenda Tao

Full Text Available To understand the diversity and abundance of antibiotic resistance genes (ARGs in pharmaceutical wastewater treatment bioreactors, the ARGs in sludge from two full-scale pharmaceutical wastewater treatment plants (PWWTPs were investigated and compared with sludge samples from three sewage treatment plants (STPs using metagenomic approach. The results showed that the ARG abundances in PWWTP sludge ranged from 54.7 to 585.0 ppm, which were higher than those in STP sludge (27.2 to 86.4 ppm. Moreover, the diversity of ARGs in PWWTP aerobic sludge (153 subtypes was higher than that in STP aerobic sludge (118 subtypes. In addition, it was found that the profiles of ARGs in PWWTP aerobic sludge were similar to those in STP aerobic sludge but different from those in PWWTP anaerobic sludge, suggesting that dissolve oxygen (DO could be one of the important factors affecting the profiles of ARGs. In PWWTP aerobic sludge, aminoglycoside, sulfonamide and multidrug resistance genes were frequently detected. While, tetracycline, macrolide-lincosamide-streptogramin and polypeptide resistance genes were abundantly present in PWWTP anaerobic sludge. Furthermore, we investigated the microbial community and the correlation between microbial community and ARGs in PWWTP sludge. And, significant correlations between ARG types and seven bacterial genera were found. In addition, the mobile genetic elements (MGEs were also examined and correlations between the ARGs and MGEs in PWWTP sludge were observed. Collectively, our results suggested that the microbial community and MGEs, which could be affected by DO, might be the main factors shaping the profiles of ARGs in PWWTP sludge.

Self-Orientation Modulates the Neural Correlates of Global and Local Processing.

Science.gov (United States)

Liddell, Belinda J; Das, Pritha; Battaglini, Eva; Malhi, Gin S; Felmingham, Kim L; Whitford, Thomas J; Bryant, Richard A

2015-01-01

Differences in self-orientation (or "self-construal") may affect how the visual environment is attended, but the neural and cultural mechanisms that drive this remain unclear. Behavioral studies have demonstrated that people from Western backgrounds with predominant individualistic values are perceptually biased towards local-level information; whereas people from non-Western backgrounds that support collectivist values are preferentially focused on contextual and global-level information. In this study, we compared two groups differing in predominant individualistic (N = 15) vs collectivistic (N = 15) self-orientation. Participants completed a global/local perceptual conflict task whilst undergoing functional Magnetic Resonance Imaging (fMRI) scanning. When participants high in individualistic values attended to the global level (ignoring the local level), greater activity was observed in the frontoparietal and cingulo-opercular networks that underpin attentional control, compared to the match (congruent) baseline. Participants high in collectivistic values activated similar attentional control networks o only when directly compared with global processing. This suggests that global interference was stronger than local interference in the conflict task in the collectivistic group. Both groups showed increased activity in dorsolateral prefrontal regions involved in resolving perceptual conflict during heightened distractor interference. The findings suggest that self-orientation may play an important role in driving attention networks to facilitate interaction with the visual environment.

Global gene expression analysis of peripheral blood mononuclear cells in rhesus monkey infants with CA16 infection-induced HFMD.

Science.gov (United States)

Song, Jie; Hu, Yajie; Hu, Yunguang; Wang, Jingjing; Zhang, Xiaolong; Wang, Lichun; Guo, Lei; Wang, Yancui; Ning, Ruotong; Liao, Yun; Zhang, Ying; Zheng, Huiwen; Shi, Haijing; He, Zhanlong; Li, Qihan; Liu, Longding

2016-03-02

Coxsackievirus A16 (CA16) is a dominant pathogen that results in hand, foot, and mouth disease and causes outbreaks worldwide, particularly in the Asia-Pacific region. However, the underlying molecular mechanisms remain unclear. Our previous study has demonstrated that the basic CA16 pathogenic process was successfully mimicked in rhesus monkey infant. The present study focused on the global gene expression changes in peripheral blood mononuclear cells of rhesus monkey infants with hand, foot, and mouth disease induced by CA16 infection at different time points. Genome-wide expression analysis was performed with Agilent whole-genome microarrays and established bioinformatics tools. Nine hundred and forty-eight significant differentially expressed genes that were associated with 5 gene ontology categories, including cell communication, cell cycle, immune system process, regulation of transcription and metabolic process were identified. Subsequently, the mapping of genes related to the immune system process by PANTHER pathway analysis revealed the predominance of inflammation mediated by chemokine and cytokine signaling pathways and the interleukin signaling pathway. Ultimately, co-expressed genes and their networks were analyzed. The results revealed the gene expression profile of the immune system in response to CA16 in rhesus monkey infants and suggested that such an immune response was generated as a result of the positive mobilization of the immune system. This initial microarray study will provide insights into the molecular mechanism of CA16 infection and will facilitate the identification of biomarkers for the evaluation of vaccines against this virus. Copyright © 2016 Elsevier B.V. All rights reserved.

Structure of Rot, a global regulator of virulence genes in Staphylococcus aureus.

Science.gov (United States)

Zhu, Yuwei; Fan, Xiaojiao; Zhang, Xu; Jiang, Xuguang; Niu, Liwen; Teng, Maikun; Li, Xu

2014-09-01

Staphylococcus aureus is a highly versatile pathogen that can infect human tissue by producing a large arsenal of virulence factors that are tightly regulated by a complex regulatory network. Rot, which shares sequence similarity with SarA homologues, is a global regulator that regulates numerous virulence genes. However, the recognition model of Rot for the promoter region of target genes and the putative regulation mechanism remain elusive. In this study, the 1.77 Å resolution X-ray crystal structure of Rot is reported. The structure reveals that two Rot molecules form a compact homodimer, each of which contains a typical helix-turn-helix module and a β-hairpin motif connected by a flexible loop. Fluorescence polarization results indicate that Rot preferentially recognizes AT-rich dsDNA with ~30-base-pair nucleotides and that the conserved positively charged residues on the winged-helix motif are vital for binding to the AT-rich dsDNA. It is proposed that the DNA-recognition model of Rot may be similar to that of SarA, SarR and SarS, in which the helix-turn-helix motifs of each monomer interact with the major grooves of target dsDNA and the winged motifs contact the minor grooves. Interestingly, the structure shows that Rot adopts a novel dimerization model that differs from that of other SarA homologues. As expected, perturbation of the dimer interface abolishes the dsDNA-binding ability of Rot, suggesting that Rot functions as a dimer. In addition, the results have been further confirmed in vivo by measuring the transcriptional regulation of α-toxin, a major virulence factor produced by most S. aureus strains.

Global solutions of restricted open-shell Hartree-Fock theory from semidefinite programming with applications to strongly correlated quantum systems.

Science.gov (United States)

Veeraraghavan, Srikant; Mazziotti, David A

2014-03-28

We present a density matrix approach for computing global solutions of restricted open-shell Hartree-Fock theory, based on semidefinite programming (SDP), that gives upper and lower bounds on the Hartree-Fock energy of quantum systems. While wave function approaches to Hartree-Fock theory yield an upper bound to the Hartree-Fock energy, we derive a semidefinite relaxation of Hartree-Fock theory that yields a rigorous lower bound on the Hartree-Fock energy. We also develop an upper-bound algorithm in which Hartree-Fock theory is cast as a SDP with a nonconvex constraint on the rank of the matrix variable. Equality of the upper- and lower-bound energies guarantees that the computed solution is the globally optimal solution of Hartree-Fock theory. The work extends a previously presented method for closed-shell systems [S. Veeraraghavan and D. A. Mazziotti, Phys. Rev. A 89, 010502-R (2014)]. For strongly correlated systems the SDP approach provides an alternative to the locally optimized Hartree-Fock energies and densities with a certificate of global optimality. Applications are made to the potential energy curves of C2, CN, Cr2, and NO2.

The analysis of correlation between IL-1B gene expression and genotyping in multiple sclerosis patients.

Science.gov (United States)

Heidary, Masoumeh; Rakhshi, Nahid; Pahlevan Kakhki, Majid; Behmanesh, Mehrdad; Sanati, Mohammad Hossein; Sanadgol, Nima; Kamaladini, Hossein; Nikravesh, Abbas

2014-08-15

IL-1B is released by monocytes, astrocytes and brain endothelial cells and seems to be involved in inflammatory reactions of the central nervous system (CNS) in multiple sclerosis (MS). This study aims to evaluate the expression level of IL-1B mRNA in peripheral blood mononuclear cells (PBMCs), genotype the rs16944 SNP and find out the role of this SNP on the expression level of IL-1B in MS patients. We found that the expression level of IL-1B in MS patients increased 3.336 times more than controls in PBMCs but the rs16944 SNP in the promoter region of IL-1B did not affect the expression level of this gene and there was not association of this SNP with MS in the examined population. Also, our data did not reveal any correlation between normalized expressions of IL-1B gene with age of participants, age of onset, and disease duration. Copyright © 2014 Elsevier B.V. All rights reserved.

Protein Homeostasis Imposes a Barrier on Functional Integration of Horizontally Transferred Genes in Bacteria.

Science.gov (United States)

Bershtein, Shimon; Serohijos, Adrian W R; Bhattacharyya, Sanchari; Manhart, Michael; Choi, Jeong-Mo; Mu, Wanmeng; Zhou, Jingwen; Shakhnovich, Eugene I

2015-10-01

Horizontal gene transfer (HGT) plays a central role in bacterial evolution, yet the molecular and cellular constraints on functional integration of the foreign genes are poorly understood. Here we performed inter-species replacement of the chromosomal folA gene, encoding an essential metabolic enzyme dihydrofolate reductase (DHFR), with orthologs from 35 other mesophilic bacteria. The orthologous inter-species replacements caused a marked drop (in the range 10-90%) in bacterial growth rate despite the fact that most orthologous DHFRs are as stable as E.coli DHFR at 37°C and are more catalytically active than E. coli DHFR. Although phylogenetic distance between E. coli and orthologous DHFRs as well as their individual molecular properties correlate poorly with growth rates, the product of the intracellular DHFR abundance and catalytic activity (kcat/KM), correlates strongly with growth rates, indicating that the drop in DHFR abundance constitutes the major fitness barrier to HGT. Serial propagation of the orthologous strains for ~600 generations dramatically improved growth rates by largely alleviating the fitness barriers. Whole genome sequencing and global proteome quantification revealed that the evolved strains with the largest fitness improvements have accumulated mutations that inactivated the ATP-dependent Lon protease, causing an increase in the intracellular DHFR abundance. In one case DHFR abundance increased further due to mutations accumulated in folA promoter, but only after the lon inactivating mutations were fixed in the population. Thus, by apparently distinguishing between self and non-self proteins, protein homeostasis imposes an immediate and global barrier to the functional integration of foreign genes by decreasing the intracellular abundance of their products. Once this barrier is alleviated, more fine-tuned evolution occurs to adjust the function/expression of the transferred proteins to the constraints imposed by the intracellular

Protein Homeostasis Imposes a Barrier on Functional Integration of Horizontally Transferred Genes in Bacteria.

Directory of Open Access Journals (Sweden)

Shimon Bershtein

2015-10-01

Full Text Available Horizontal gene transfer (HGT plays a central role in bacterial evolution, yet the molecular and cellular constraints on functional integration of the foreign genes are poorly understood. Here we performed inter-species replacement of the chromosomal folA gene, encoding an essential metabolic enzyme dihydrofolate reductase (DHFR, with orthologs from 35 other mesophilic bacteria. The orthologous inter-species replacements caused a marked drop (in the range 10-90% in bacterial growth rate despite the fact that most orthologous DHFRs are as stable as E.coli DHFR at 37°C and are more catalytically active than E. coli DHFR. Although phylogenetic distance between E. coli and orthologous DHFRs as well as their individual molecular properties correlate poorly with growth rates, the product of the intracellular DHFR abundance and catalytic activity (kcat/KM, correlates strongly with growth rates, indicating that the drop in DHFR abundance constitutes the major fitness barrier to HGT. Serial propagation of the orthologous strains for ~600 generations dramatically improved growth rates by largely alleviating the fitness barriers. Whole genome sequencing and global proteome quantification revealed that the evolved strains with the largest fitness improvements have accumulated mutations that inactivated the ATP-dependent Lon protease, causing an increase in the intracellular DHFR abundance. In one case DHFR abundance increased further due to mutations accumulated in folA promoter, but only after the lon inactivating mutations were fixed in the population. Thus, by apparently distinguishing between self and non-self proteins, protein homeostasis imposes an immediate and global barrier to the functional integration of foreign genes by decreasing the intracellular abundance of their products. Once this barrier is alleviated, more fine-tuned evolution occurs to adjust the function/expression of the transferred proteins to the constraints imposed by the

Optimising parallel R correlation matrix calculations on gene expression data using MapReduce.

Science.gov (United States)

Wang, Shicai; Pandis, Ioannis; Johnson, David; Emam, Ibrahim; Guitton, Florian; Oehmichen, Axel; Guo, Yike

2014-11-05

High-throughput molecular profiling data has been used to improve clinical decision making by stratifying subjects based on their molecular profiles. Unsupervised clustering algorithms can be used for stratification purposes. However, the current speed of the clustering algorithms cannot meet the requirement of large-scale molecular data due to poor performance of the correlation matrix calculation. With high-throughput sequencing technologies promising to produce even larger datasets per subject, we expect the performance of the state-of-the-art statistical algorithms to be further impacted unless efforts towards optimisation are carried out. MapReduce is a widely used high performance parallel framework that can solve the problem. In this paper, we evaluate the current parallel modes for correlation calculation methods and introduce an efficient data distribution and parallel calculation algorithm based on MapReduce to optimise the correlation calculation. We studied the performance of our algorithm using two gene expression benchmarks. In the micro-benchmark, our implementation using MapReduce, based on the R package RHIPE, demonstrates a 3.26-5.83 fold increase compared to the default Snowfall and 1.56-1.64 fold increase compared to the basic RHIPE in the Euclidean, Pearson and Spearman correlations. Though vanilla R and the optimised Snowfall outperforms our optimised RHIPE in the micro-benchmark, they do not scale well with the macro-benchmark. In the macro-benchmark the optimised RHIPE performs 2.03-16.56 times faster than vanilla R. Benefiting from the 3.30-5.13 times faster data preparation, the optimised RHIPE performs 1.22-1.71 times faster than the optimised Snowfall. Both the optimised RHIPE and the optimised Snowfall successfully performs the Kendall correlation with TCGA dataset within 7 hours. Both of them conduct more than 30 times faster than the estimated vanilla R. The performance evaluation found that the new MapReduce algorithm and its

A Meta-analysis on the correlation between the polymorphism of angiotensin converting enzyme gene and hypertrophic cardiomyopathy

Directory of Open Access Journals (Sweden)

Ling CHEN

2014-01-01

Full Text Available Objective　To systematically investigate the correlation between the polymorphism of angiotensin converting enzyme (ACE gene I/D and hypertrophic cardiomyopathy. Methods　The databases, such as PubMed, Embase, OVID, Web of Science, Cochrane library, CNKI, WanFang Data and VIP, were searched to collect the studies on the correlation between ACE I/D polymorphism and hypertrophic cardiomyopathy susceptibility. Studies that met the inclusion criteria were Meta-analyzed using Stata 11.0 software. Results　Fifteen articles were collected including 1114 cases and 1648 controls. The Meta-analysis indicated that there was significant correlation between the 4 models of ACE I/D polymorphism and hypertrophic cardiomyopathy susceptibility [D vs I: OR=1.49, 95%CI (1.20, 1.84; DD vs (ID+II: OR=1.56, 95%CI (1.17, 2.08; (DD+ID vs II: OR=1.76, 95%CI (1.30, 2.38; DD vs II: OR=2.20, 95%CI (1.44, 3.37]. In subgroup analysis, the significant difference existed in Asian population, but no significance was found in European population (P<0.05. Conclusions　There is a positive correlation between hypertrophic cardiomyopathy and ACE I/D polymorphism in population, and D allele and DD genotype are likely to be the risk factors of hypertrophic cardiomyopathy. But such correlation does not exist in European population. DOI: 10.11855/j.issn.0577-7402.2013.12.07

Gene expression correlated with delay in shell formation in larval Pacific oysters (Crassostrea gigas) exposed to experimental ocean acidification provides insights into shell formation mechanisms.

Science.gov (United States)

De Wit, Pierre; Durland, Evan; Ventura, Alexander; Langdon, Chris J

2018-02-22

Despite recent work to characterize gene expression changes associated with larval development in oysters, the mechanism by which the larval shell is first formed is still largely unknown. In Crassostrea gigas, this shell forms within the first 24 h post fertilization, and it has been demonstrated that changes in water chemistry can cause delays in shell formation, shell deformations and higher mortality rates. In this study, we use the delay in shell formation associated with exposure to CO 2 -acidified seawater to identify genes correlated with initial shell deposition. By fitting linear models to gene expression data in ambient and low aragonite saturation treatments, we are able to isolate 37 annotated genes correlated with initial larval shell formation, which can be categorized into 1) ion transporters, 2) shell matrix proteins and 3) protease inhibitors. Clustering of the gene expression data into co-expression networks further supports the result of the linear models, and also implies an important role of dynein motor proteins as transporters of cellular components during the initial shell formation process. Using an RNA-Seq approach with high temporal resolution allows us to identify a conceptual model for how oyster larval calcification is initiated. This work provides a foundation for further studies on how genetic variation in these identified genes could affect fitness of oyster populations subjected to future environmental changes, such as ocean acidification.

A newly designed 45 to 60 mer oligonucleotide Agilent platform microarray for global gene expression studies of Synechocystis PCC6803: example salt stress experiment

NARCIS (Netherlands)

Aguirre von Wobeser, E.; Huisman, J.; Ibelings, B.; Matthijs, H.C.P.; Matthijs, H.C.P.

2005-01-01

A newly designed 45 to 60 mer oligonucleotide Agilent platform microarray for global gene expression studies of Synechocystis PCC6803: example salt stress experiment Eneas Aguirre-von-Wobeser 1, Jef Huisman1, Bas Ibelings2 and Hans C.P. Matthijs1 1 Universiteit van Amsterdam, Amsterdam, The

The global prevalence and correlates of skin bleaching: a meta-analysis and meta-regression analysis.

Science.gov (United States)

Sagoe, Dominic; Pallesen, Ståle; Dlova, Ncoza C; Lartey, Margaret; Ezzedine, Khaled; Dadzie, Ophelia

2018-06-11

To estimate and investigate the global lifetime prevalence and correlates of skin bleaching. A meta-analysis and meta-regression analysis was performed based on a systematic and comprehensive literature search conducted in Google Scholar, ISI Web of Science, ProQuest, PsycNET, PubMed, and other relevant websites and reference lists. A total of 68 studies (67,665 participants) providing original data on the lifetime prevalence of skin bleaching were included. Publication bias was corrected using the trim and fill procedure. The pooled (imputed) lifetime prevalence of skin bleaching was 27.7% (95% CI: 19.6-37.5, I 2  = 99.6, P < 0.01). The highest significant prevalences were associated with: males (28.0%), topical corticosteroid use (51.8%), Africa (27.1%), persons aged ≤30 years (55.9%), individuals with only primary school education (31.6%), urban or semiurban residents (74.9%), patients (21.3%), data from 2010-2017 (26.8%), dermatological evaluation and testing-based assessment (24.9%), random sampling methods (29.2%), and moderate quality studies (32.3%). The proportion of females in study samples was significantly related to skin bleaching prevalence. Despite some limitations, our results indicate that the practice of skin bleaching is a serious global public health issue that should be addressed through appropriate public health interventions. © 2018 The International Society of Dermatology.

Modulation of histone methylation and MLH1 gene silencing by hexavalent chromium

International Nuclear Information System (INIS)

Sun Hong; Zhou Xue; Chen Haobin; Li Qin; Costa, Max

2009-01-01

Hexavalent chromium [Cr(VI)] is a mutagen and carcinogen, and occupational exposure can lead to lung cancers and other adverse health effects. Genetic changes resulting from DNA damage have been proposed as an important mechanism that mediates chromate's carcinogenicity. Here we show that chromate exposure of human lung A549 cells increased global levels of di- and tri-methylated histone H3 lysine 9 (H3K9) and lysine 4 (H3K4) but decreased the levels of tri-methylated histone H3 lysine 27 (H3K27) and di-methylated histone H3 arginine 2 (H3R2). Most interestingly, H3K9 dimethylation was enriched in the human MLH1 gene promoter following chromate exposure and this was correlated with decreased MLH1 mRNA expression. Chromate exposure increased the protein as well as mRNA levels of G9a a histone methyltransferase that specifically methylates H3K9. This Cr(VI)-induced increase in G9a may account for the global elevation of H3K9 dimethylation. Furthermore, supplementation with ascorbate, the primary reductant of Cr(VI) and also an essential cofactor for the histone demethylase activity, partially reversed the H3K9 dimethylation induced by chromate. Thus our studies suggest that Cr(VI) may target histone methyltransferases and demethylases, which in turn affect both global and gene promoter specific histone methylation, leading to the silencing of specific tumor suppressor genes such as MLH1.

From Gene Expression to the Earth System: Isotopic Constraints on Nitrogen Cycling Across Scales

Science.gov (United States)

Houlton, B. Z.

2015-12-01

A central motivation of the Biogeosciences is to understand the cycling of biologically essential elements over multiple scales of space and time. This charge is vital to basic knowledge of Earth system functioning. It is also relevant to many of the global challenges we face, such as climate change, biodiversity conservation, and the multifaceted role of global fertilizer use in maximizing human health and well-being. Nitrogen is connected to all of these; yet it has been one of the more vexing elements to quantitatively appraise across systems and scales. Here I discuss how research in my group has been exploring the use of natural nitrogen isotope abundance (15N/14N) as a biogeochemical tracer - from the level of gene expression to nitrogen's role in global climate change. First, I present evidence for a positive correlation between the bacterial genes that encode for gaseous nitrogen production (i.e., nirS) and the 15N/14N of soil extractable nitrate pools across an array of terrestrial ecosystems. Second, I demonstrate how these local-scale results fit with our work on ecosystem-scale nitrogen isotope budgets, where we quantify a uniformly small isotope effect (i.e., supports the working hypothesis that bacterial denitrification is the major fractionating pathway of nitrogen loss from the terrestrial biosphere, much like the global ocean.

Cosmic microwave background constraints for global strings and global monopoles

International Nuclear Information System (INIS)

Lopez-Eiguren, Asier; Lizarraga, Joanes; Urrestilla, Jon; Hindmarsh, Mark

2017-01-01

We present the first cosmic microwave background (CMB) power spectra from numerical simulations of the global O( N ) linear σ-model, with N =2,3, which have global strings and monopoles as topological defects. In order to compute the CMB power spectra we compute the unequal time correlators (UETCs) of the energy-momentum tensor, showing that they fall off at high wave number faster than naive estimates based on the geometry of the defects, indicating non-trivial (anti-)correlations between the defects and the surrounding Goldstone boson field. We obtain source functions for Einstein-Boltzmann solvers from the UETCs, using a recently developed method that improves the modelling at the radiation-matter transition. We show that the interpolation function that mimics the transition is similar to other defect models, but not identical, confirming the non-universality of the interpolation function. The CMB power spectra for global strings and global monopoles have the same overall shape as those obtained using the non-linear σ-model approximation, which is well captured by a large- N calculation. However, the amplitudes are larger than the large- N calculation would naively predict, and in the case of global strings much larger: a factor of 20 at the peak. Finally we compare the CMB power spectra with the latest CMB data in other to put limits on the allowed contribution to the temperature power spectrum at multipole l = 10 of 1.7% for global strings and 2.4% for global monopoles. These limits correspond to symmetry-breaking scales of 2.9× 10 15 GeV (6.3× 10 14 GeV with the expected logarithmic scaling of the effective string tension between the simulation time and decoupling) and 6.4× 10 15 GeV respectively. The bound on global strings is a significant one for the ultra-light axion scenario with axion masses m a ∼< 10 −28 eV . These upper limits indicate that gravitational waves from global topological defects will not be observable at the gravitational wave

Correlation between rpoB gene mutation in Mycobacterium avium subspecies paratuberculosis and clinical rifabutin and rifampicin resistance for treatment of Crohn’s disease

OpenAIRE

Beckler, Daniel R; Elwasila, Sammer; Ghobrial, George; Valentine, John F; Naser, Saleh A

2008-01-01

AIM: To investigate overlapping regions of the rpoB gene previously involved with rifamycin resistance in M. tuberculosis and seek correlation between rpoB mutations in clinical MAP strains with susceptibility to RIF and RFB.

Global quantum discord in multipartite systems

Energy Technology Data Exchange (ETDEWEB)

Rulli, C. C.; Sarandy, M. S. [Instituto de Fisica, Universidade Federal Fluminense, Av. Gal. Milton Tavares de Souza s/n, Gragoata, 24210-346 Niteroi, RJ (Brazil)

2011-10-15

We propose a global measure for quantum correlations in multipartite systems, which is obtained by suitably recasting the quantum discord in terms of relative entropy and local von Neumann measurements. The measure is symmetric with respect to subsystem exchange and is shown to be nonnegative for an arbitrary state. As an illustration, we consider tripartite correlations in the Werner-GHZ (Greenberger-Horne-Zeilinger) state and multipartite correlations at quantum criticality. In particular, in contrast with the pairwise quantum discord, we show that the global quantum discord is able to characterize the infinite-order quantum phase transition in the Ashkin-Teller spin chain.

Applicability of empirical correlations for estimating global solar radiation

International Nuclear Information System (INIS)

Gopinathan, K.K.; Baholo, M.

1987-01-01

Three empirical models suggested by different investigators, for estimating monthly mean daily global radiation on a horizontal surface, are compared statistically to test their universal applicability. The models thus compared are those suggested by Rietveld, Glover and McCulloch and Gopinathan. The models are compared by calculating the root mean square error, mean bias error and mean relative percentage error values. The model suggested by Gopinathan yields the best results in terms of root mean square, mean bias and mean percentage errors. The model by Rietveld is the second best and the model by Glover and McCulloch comes at third place. However, the differences in the magnitude of errors among the three models are very small and all the three models can be considered to be accurate for global radiation estimation for any location in the world

Culture–gene coevolution of individualism–collectivism and the serotonin transporter gene

Science.gov (United States)

Chiao, Joan Y.; Blizinsky, Katherine D.

2010-01-01

Culture–gene coevolutionary theory posits that cultural values have evolved, are adaptive and influence the social and physical environments under which genetic selection operates. Here, we examined the association between cultural values of individualism–collectivism and allelic frequency of the serotonin transporter functional polymorphism (5-HTTLPR) as well as the role this culture–gene association may play in explaining global variability in prevalence of pathogens and affective disorders. We found evidence that collectivistic cultures were significantly more likely to comprise individuals carrying the short (S) allele of the 5-HTTLPR across 29 nations. Results further show that historical pathogen prevalence predicts cultural variability in individualism–collectivism owing to genetic selection of the S allele. Additionally, cultural values and frequency of S allele carriers negatively predict global prevalence of anxiety and mood disorder. Finally, mediation analyses further indicate that increased frequency of S allele carriers predicted decreased anxiety and mood disorder prevalence owing to increased collectivistic cultural values. Taken together, our findings suggest culture–gene coevolution between allelic frequency of 5-HTTLPR and cultural values of individualism–collectivism and support the notion that cultural values buffer genetically susceptible populations from increased prevalence of affective disorders. Implications of the current findings for understanding culture–gene coevolution of human brain and behaviour as well as how this coevolutionary process may contribute to global variation in pathogen prevalence and epidemiology of affective disorders, such as anxiety and depression, are discussed. PMID:19864286

Culture-gene coevolution of individualism-collectivism and the serotonin transporter gene.

Science.gov (United States)

Chiao, Joan Y; Blizinsky, Katherine D

2010-02-22

Culture-gene coevolutionary theory posits that cultural values have evolved, are adaptive and influence the social and physical environments under which genetic selection operates. Here, we examined the association between cultural values of individualism-collectivism and allelic frequency of the serotonin transporter functional polymorphism (5-HTTLPR) as well as the role this culture-gene association may play in explaining global variability in prevalence of pathogens and affective disorders. We found evidence that collectivistic cultures were significantly more likely to comprise individuals carrying the short (S) allele of the 5-HTTLPR across 29 nations. Results further show that historical pathogen prevalence predicts cultural variability in individualism-collectivism owing to genetic selection of the S allele. Additionally, cultural values and frequency of S allele carriers negatively predict global prevalence of anxiety and mood disorder. Finally, mediation analyses further indicate that increased frequency of S allele carriers predicted decreased anxiety and mood disorder prevalence owing to increased collectivistic cultural values. Taken together, our findings suggest culture-gene coevolution between allelic frequency of 5-HTTLPR and cultural values of individualism-collectivism and support the notion that cultural values buffer genetically susceptible populations from increased prevalence of affective disorders. Implications of the current findings for understanding culture-gene coevolution of human brain and behaviour as well as how this coevolutionary process may contribute to global variation in pathogen prevalence and epidemiology of affective disorders, such as anxiety and depression, are discussed.

STAT5A and STAT5B have opposite correlations with drug response gene expression

International Nuclear Information System (INIS)

Lamba, V.; Jia, B.; Liang, F.

2016-01-01

Introduction: STAT5A and STAT5B are important transcription factors that play a key role in regulation of several important physiological processes including proliferation, survival, mediation of responses to cytokines and in regulating gender differences in drug response genes such as the hepatic cytochrome P450s (CYPs) that are responsible for a large majority of drug metabolism reactions in the human body. STAT5A and STAT5b have a high degree of sequence homology and have been reported to have largely similar functions. Recent studies have, however, indicated that they can also often have distinct and unique roles in regulating gene expression. Objective: In this study, we evaluated the association of STAT5A and STAT5B mRNA expression levels with those of several key hepatic cytochrome P450s (CYPs) and hepatic transcription factors (TFs) and evaluated the potential roles of STAT5A and 5b in mediating gender differences in these CYPs and TFs. Methods: Expression profiling for major hepatic CYP isoforms and transcription factors was performed using RNA sequencing (RNA-seq) in 102 human liver samples (57 female, 45 male). Real time PCR gene expression data for selected CYPs and TFs was available on a subset of 50 human liver samples (25 female, 25 male) and was used to validate the RNA-seq findings. Results: While STAT5A demonstrated significant negative correlation with expression levels of multiple hepatic transcription factors (including NR1I2 and HNF4A) and DMEs such as CYP3A4 and CYP2C19, STAT5B expression was observed to demonstrate positive associations with several CYPs and TFs analyzed. As STAT5A and STAT5B have been shown to be important in regulation of gender differences in CYPs, we also analyzed STAT5A and 5b associations with CYPs and TFs separately in males and females and observed gender dependent differential associations of STATs with several CYPs and TFs. Results from the real time PCR validation largely supported our RNA-seq findings

Effects of Long Chain Fatty Acid Synthesis and Associated Gene Expression in Microalga Tetraselmis sp.

Directory of Open Access Journals (Sweden)

T. Catalina Adarme-Vega

2014-06-01

Full Text Available With the depletion of global fish stocks, caused by high demand and effective fishing techniques, alternative sources for long chain omega-3 fatty acids are required for human nutrition and aquaculture feeds. Recent research has focused on land-based cultivation of microalgae, the primary producers of omega-3 fatty acids in the marine food web. The effect of salinity on fatty acids and related gene expression was studied in the model marine microalga, Tetraselmis sp. M8. Correlations were found for specific fatty acid biosynthesis and gene expression according to salinity and the growth phase. Low salinity was found to increase the conversion of C18:4 stearidonic acid (SDA to C20:4 eicosatetraenoic acid (ETA, correlating with increased transcript abundance of the Δ-6-elongase-encoding gene in salinities of 5 and 10 ppt compared to higher salinity levels. The expression of the gene encoding β-ketoacyl-coenzyme was also found to increase at lower salinities during the nutrient deprivation phase (Day 4, but decreased with further nutrient stress. Nutrient deprivation also triggered fatty acids synthesis at all salinities, and C20:5 eicosapentaenoic acid (EPA increased relative to total fatty acids, with nutrient starvation achieving a maximum of 7% EPA at Day 6 at a salinity of 40 ppt.

Enriching the gene set analysis of genome-wide data by incorporating directionality of gene expression and combining statistical hypotheses and methods

Science.gov (United States)

Väremo, Leif; Nielsen, Jens; Nookaew, Intawat

2013-01-01

Gene set analysis (GSA) is used to elucidate genome-wide data, in particular transcriptome data. A multitude of methods have been proposed for this step of the analysis, and many of them have been compared and evaluated. Unfortunately, there is no consolidated opinion regarding what methods should be preferred, and the variety of available GSA software and implementations pose a difficulty for the end-user who wants to try out different methods. To address this, we have developed the R package Piano that collects a range of GSA methods into the same system, for the benefit of the end-user. Further on we refine the GSA workflow by using modifications of the gene-level statistics. This enables us to divide the resulting gene set P-values into three classes, describing different aspects of gene expression directionality at gene set level. We use our fully implemented workflow to investigate the impact of the individual components of GSA by using microarray and RNA-seq data. The results show that the evaluated methods are globally similar and the major separation correlates well with our defined directionality classes. As a consequence of this, we suggest to use a consensus scoring approach, based on multiple GSA runs. In combination with the directionality classes, this constitutes a more thorough basis for an enriched biological interpretation. PMID:23444143

Gene Expression of Glucose Transporter 1 (GLUT1, Hexokinase 1 and Hexokinase 2 in Gastroenteropancreatic Neuroendocrine Tumors: Correlation with F-18-fluorodeoxyglucose Positron Emission Tomography and Cellular Proliferation

Directory of Open Access Journals (Sweden)

Andreas Kjaer

2013-10-01

Full Text Available Neoplastic tissue exhibits high glucose utilization and over-expression of glucose transporters (GLUTs and hexokinases (HKs, which can be imaged by 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET. The aim of the present study was to investigate the expression of glycolysis-associated genes and to compare this with FDG-PET imaging as well as with the cellular proliferation index in two cancer entities with different malignant potential. Using real-time PCR, gene expression of GLUT1, HK1 and HK2 were studied in 34 neuroendocrine tumors (NETs in comparison with 14 colorectal adenocarcinomas (CRAs. The Ki67 proliferation index and, when available, FDG-PET imaging was compared with gene expression. Overexpression of GLUT1 gene expression was less frequent in NETs (38% compared to CRAs (86%, P = 0.004. HK1 was overexpressed in 41% and 71% of NETs and CRAs, respectively (P = 0.111 and HK2 was overexpressed in 50% and 64% of NETs and CRAs, respectively (P = 0.53. There was a significant correlation between the Ki67 proliferation index and GLUT1 gene expression for the NETs (R = 0.34, P = 0.047, but no correlation with the hexokinases. FDG-PET identified foci in significantly fewer NETs (36% than CRAs (86%, (P = 0.04. The gene expression results, with less frequent GLUT1 and HK1 upregulation in NETs, confirmed the lower metabolic activity of NETs compared to the more aggressive CRAs. In accordance with this, fewer NETs were FDG-PET positive compared to CRA tumors and FDG uptake correlated with GLUT1 gene expression.

Expression of antiapoptosis gene survivin in luteinized ovarian granulosa cells of women undergoing IVF or ICSI and embryo transfer: clinical correlations

Directory of Open Access Journals (Sweden)

Varras Michail

2012-09-01

Full Text Available Abstract Background The purpose of the study was to determine the incidence of survivin gene expression in human granulosa cells during ovarian stimulation in Greek women with normal FSH levels, undergoing IVF or ICSI and to discover any correlation between levels of gene expression and clinical parameters, efficacy of ovulation or outcomes of assisted reproduction. Methods Twenty nine women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded and the granulosa cells were analyzed for each patient separately using quantitative reverse transcription polymerase chain reaction analysis for survivin gene expression with internal standard the ABL gene. Results The ABL and survivin mRNA were detected in granulosa cells in 93.1%. The expression levels of survivin were significantly lower in normal women (male infertility factor compared to women with tubal infertility factor (p = 0.007. There was no additional statistically significant correlation between levels of survivin expression and estradiol levels or dosage of FSH for ovulation induction or number of dominant follicles aspirated or number of retrieved oocytes or embryo grade or clinical pregnancy rates respectively. Conclusions High levels of survivin mRNA expression in luteinized granulosa cells in cases with tubal infertility seem to protect ovaries from follicular apoptosis. A subpopulation of patients with low levels of survivin mRNA in granulosa cells might benefit with ICSI treatment to bypass possible natural barriers of sperm-oocyte interactions.

Hox gene colinear expression in the avian medulla oblongata is correlated with pseudorhombomeric domains.

Science.gov (United States)

Marín, Faustino; Aroca, Pilar; Puelles, Luis

2008-11-15

The medulla oblongata (or caudal hindbrain) is not overtly segmented, since it lacks observable interrhombomeric boundaries. However, quail-chick fate maps showed that it is formed by 5 pseudorhombomeres (r7-r11) which were empirically found to be delimited consistently at planes crossing through adjacent somites (Cambronero and Puelles, 2000). We aimed to reexamine the possible segmentation or rostrocaudal regionalisation of this brain region attending to molecular criteria. To this end, we studied the expression of Hox genes from groups 3 to 7 correlative to the differentiating nuclei of the medulla oblongata. Our results show that these genes are differentially expressed in the mature medulla oblongata, displaying instances of typical antero-posterior (3' to 5') Hox colinearity. The different sensory and motor columns, as well as the reticular formation, appear rostrocaudally regionalised according to spaced steps in their Hox expression pattern. The anterior limits of the respective expression domains largely fit boundaries defined between the experimental pseudorhombomeres. Therefore the medulla oblongata shows a Hox-related rostrocaudal molecular regionalisation comparable to that found among rhombomeres, and numerically consistent with the pseudorhombomere list. This suggests that medullary pseudorhombomeres share some AP patterning mechanisms with the rhombomeres present in the rostral, overtly-segmented hindbrain, irrespective of variant boundary properties.

Study on the correlation between KCNJ11 gene polymorphism and metabolic syndrome in the elderly.

Science.gov (United States)

Jiang, Fan; Liu, Ning; Chen, Xiao Zhuang; Han, Kun Yuan; Zhu, Cai Zhong

2017-09-01

The aim of the study was to examine the correlation between KCNJ11 gene polymorphism and metabolic syndrome in elderly patients. From January 2014 to January 2015, 54 elderly patients with metabolic syndrome were enrolled in this study as the observation group. During the same period, 46 healthy elderly individuals were enrolled in this study as the control group. KCNJ11 gene polymorphism (rs28502) was analyzed using polymerase chain reaction-restriction fragment length polymorphism. The expression levels of mRNA in different genotypes were detected using FQ-PCR. ELISA was used to evaluate the KCNJ11 protein expression in different genotypes. KCNJ11 gene polymorphism and metabolic syndrome was studied by measuring the blood pressure levels in patients with different genotypes. Three genotypes of KCNJ11 gene in rs28502 were CC, CT and TT. The CC, CT and TT genotype frequencies in healthy population were 8.5, 9.2 and 82.2%, respectively, while the genotype frequencies in patients with metabolic syndrome were 42.4, 49.8 and 7.8%, respectively. There were significant differences between groups (P≤0.05). However, the genotype frequencies of C/T in healthy individuals and metabolic syndrome patients were 35.3 and 38.3%, respectively. There were no significant differences between groups (P>0.05). FQ-PCR results showed that the KCNJ11 mRNA expression levels in the control and observation groups had no significant differences (P>0.05). However, the results obtained from ELISA analysis revealed that KCNJ11 protein expression level in the observation group was significantly higher than that in the control group (Pmetabolic syndrome in the elderly. Elderly patients with the CC and TT genotypes are more likely to develop metabolic syndrome.

Structure-function correlation of chloroquine and analogues as transgene expression enhancers in nonviral gene delivery.

Science.gov (United States)

Cheng, Jianjun; Zeidan, Ryan; Mishra, Swaroop; Liu, Aijie; Pun, Suzie H; Kulkarni, Rajan P; Jensen, Gregory S; Bellocq, Nathalie C; Davis, Mark E

2006-11-02

To understand how chloroquine (CQ) enhances transgene expression in polycation-based, nonviral gene delivery systems, a number of CQ analogues with variations in the aliphatic amino side chain or in the aromatic ring are synthesized and investigated. Our studies indicate that the aliphatic amino moiety of CQ is essential to provide increased gene expression. Further, the enhancements are more dramatically affected by changes to the aromatic ring and are positively correlated to the strength of intercalation between DNA and the CQ analogues. Quinacrine (QC), a CQ analogue with a fused acridinyl structure that can strongly intercalate DNA, enhances transfection similarly to CQ at a concentration 10 times lower, while N(4)-(4-pyridinyl)-N(1),N(1)-diethyl-1,4-pentanediamine (CP), a CQ analogue that has a weakly intercalating pyridinyl ring, shows no effect on gene expression. Subtle change on the 7-substituent of the chloroquine aromatic structure can also greatly affect the ability of the CQ analogues to enhance transgene expression. Transfection in the presence of N(4)-(7-trifluoromethyl-4-quinolinyl)-N(1),N(1)-diethyl-1,4-pentanediamin e (CQ7a) shows expression efficiency 10 times higher than in the presence of CQ at same concentration, while transfection in the presence of N(4)-(4-quinolinyl)-N(1),N(1)-diethyl-1,4-pentanediamine (CQ7b) does not reveal any enhancing effects on expression. Through a number of comparative studies with CQ and its analogues, we conclude that there are at least three mechanistic features of CQ that lead to the enhancement in gene expression: (i) pH buffering in endocytic vesicles, (ii) displacement of polycations from the nucleic acids in polyplexes, and (iii) alteration of the biophysical properties of the released nucleic acid.

Mithramycin is a gene-selective Sp1 inhibitor that identifies a biological intersection between cancer and neurodegeneration.

Science.gov (United States)

Sleiman, Sama F; Langley, Brett C; Basso, Manuela; Berlin, Jill; Xia, Li; Payappilly, Jimmy B; Kharel, Madan K; Guo, Hengchang; Marsh, J Lawrence; Thompson, Leslie Michels; Mahishi, Lata; Ahuja, Preeti; MacLellan, W Robb; Geschwind, Daniel H; Coppola, Giovanni; Rohr, Jürgen; Ratan, Rajiv R

2011-05-04

Oncogenic transformation of postmitotic neurons triggers cell death, but the identity of genes critical for degeneration remain unclear. The antitumor antibiotic mithramycin prolongs survival of mouse models of Huntington's disease in vivo and inhibits oxidative stress-induced death in cortical neurons in vitro. We had correlated protection by mithramycin with its ability to bind to GC-rich DNA and globally displace Sp1 family transcription factors. To understand how antitumor drugs prevent neurodegeneration, here we use structure-activity relationships of mithramycin analogs to discover that selective DNA-binding inhibition of the drug is necessary for its neuroprotective effect. We identify several genes (Myc, c-Src, Hif1α, and p21(waf1/cip1)) involved in neoplastic transformation, whose altered expression correlates with protective doses of mithramycin or its analogs. Most interestingly, inhibition of one these genes, Myc, is neuroprotective, whereas forced expression of Myc induces Rattus norvegicus neuronal cell death. These results support a model in which cancer cell transformation shares key genetic components with neurodegeneration.

Global biogeography of Prochlorococcus genome diversity in the surface ocean.

Science.gov (United States)

Kent, Alyssa G; Dupont, Chris L; Yooseph, Shibu; Martiny, Adam C

2016-08-01

Prochlorococcus, the smallest known photosynthetic bacterium, is abundant in the ocean's surface layer despite large variation in environmental conditions. There are several genetically divergent lineages within Prochlorococcus and superimposed on this phylogenetic diversity is extensive gene gain and loss. The environmental role in shaping the global ocean distribution of genome diversity in Prochlorococcus is largely unknown, particularly in a framework that considers the vertical and lateral mechanisms of evolution. Here we show that Prochlorococcus field populations from a global circumnavigation harbor extensive genome diversity across the surface ocean, but this diversity is not randomly distributed. We observed a significant correspondence between phylogenetic and gene content diversity, including regional differences in both phylogenetic composition and gene content that were related to environmental factors. Several gene families were strongly associated with specific regions and environmental factors, including the identification of a set of genes related to lower nutrient and temperature regions. Metagenomic assemblies of natural Prochlorococcus genomes reinforced this association by providing linkage of genes across genomic backbones. Overall, our results show that the phylogeography in Prochlorococcus taxonomy is echoed in its genome content. Thus environmental variation shapes the functional capabilities and associated ecosystem role of the globally abundant Prochlorococcus.

Regulation of MicroRNAs, and the Correlations of MicroRNAs and Their Targeted Genes by Zinc Oxide Nanoparticles in Ovarian Granulosa Cells.

Directory of Open Access Journals (Sweden)

Yong Zhao

Full Text Available Zinc oxide (ZnO nanoparticles (NPs have been applied in numerous industrial products and personal care products like sunscreens and cosmetics. The released ZnO NPs from consumer and household products into the environment might pose potential health issues for animals and humans. In this study the expression of microRNAs and the correlations of microRNAs and their targeted genes in ZnO NPs treated chicken ovarian granulosa cells were investigated. ZnSO4 was used as the sole Zn2+ provider to differentiate the effects of NPs from Zn2+. It was found that ZnO-NP-5 μg/ml specifically regulated the expression of microRNAs involved in embryonic development although ZnO-NP-5 μg/ml and ZnSO4-10 μg/ml treatments produced the same intracellular Zn concentrations and resulted in similar cell growth inhibition. And ZnO-NP-5 μg/ml also specifically regulated the correlations of microRNAs and their targeted genes. This is the first investigation that intact NPs in ZnO-NP-5 μg/ml treatment specifically regulated the expression of microRNAs, and the correlations of microRNAs and their targeted genes compared to that by Zn2+. This expands our knowledge for biological effects of ZnO NPs and at the same time it raises the health concerns that ZnO NPs might adversely affect our biological systems, even the reproductive systems through regulation of specific signaling pathways.

Genomewide Expression and Functional Interactions of Genes under Drought Stress in Maize

Directory of Open Access Journals (Sweden)

Nepolean Thirunavukkarasu

2017-01-01

Full Text Available A genomewide transcriptome assay of two subtropical genotypes of maize was used to observe the expression of genes at seedling stage of drought stress. The number of genes expressed differentially was greater in HKI1532 (a drought tolerant genotype than in PC3 (a drought sensitive genotype, indicating primary differences at the transcriptional level in stress tolerance. The global coexpression networks of the two genotypes differed significantly with respect to the number of modules and the coexpression pattern within the modules. A total of 174 drought-responsive genes were selected from HKI1532, and their coexpression network revealed key correlations between different adaptive pathways, each cluster of the network representing a specific biological function. Transcription factors related to ABA-dependent stomatal closure, signalling, and phosphoprotein cascades work in concert to compensate for reduced photosynthesis. Under stress, water balance was maintained by coexpression of the genes involved in osmotic adjustments and transporter proteins. Metabolism was maintained by the coexpression of genes involved in cell wall modification and protein and lipid metabolism. The interaction of genes involved in crucial biological functions during stress was identified and the results will be useful in targeting important gene interactions to understand drought tolerance in greater detail.

DNA micro array analysis of yeast global genome expression in response to ELF-MF exposure

International Nuclear Information System (INIS)

Shimizu, K.; Yamamoto, T.; Ishibashi, T.; Kyoh, B.

2002-01-01

There is wide spread public concern over the possible health risk of ELF-MF. Electromagnetic fields may produce a variety of effects in several biological systems, including the elevation of cancer risk and reduction of cell growth. Epidemiological studies have shown weak correlations between the exposure to ELF and the incidence of several cancers, but negative studies have also been reported. Moreover, there are some reports that basic biological events such as the cell cycle and DNA replication were affected by exposure to MF. However, to date the molecular mechanism of the MF effect on living organism is not clear. In this study, we used yeast DNA micro array to examine the transcriptional profile of all genes in response to ELF-MF. A few years ago it was difficult to carry out a global gene expression study to identify important genes regarding ELF-MF, however, today DNA micro arrays allow gene regulation in response to high density ELF-MF exposure. Thus we used micro array to analyze changes in mRNA abundance during ELF-MF exposure

Disease association with two Helicobacter pylori duplicate outer membrane protein genes, homB and homA.

Science.gov (United States)

Oleastro, Monica; Cordeiro, Rita; Yamaoka, Yoshio; Queiroz, Dulciene; Mégraud, Francis; Monteiro, Lurdes; Ménard, Armelle

2009-06-22

homB encodes a Helicobacter pylori outer membrane protein. This gene was previously associated with peptic ulcer disease (PUD) and was shown to induce activation of interleukin-8 secretion in vitro, as well as contributing to bacterial adherence. Its 90%-similar gene, homA, was previously correlated with gastritis. The present study aimed to evaluate the gastric disease association with homB and homA, as well as with the H. pylori virulence factors cagA, babA and vacA, in 415 H. pylori strains isolated from patients from East Asian and Western countries. The correlation among these genotypes was also evaluated. Both homB and homA genes were heterogeneously distributed worldwide, with a marked difference between East Asian and Western strains. In Western strains (n = 234, 124 PUD and 110 non-ulcer dyspepsia (NUD), homB, cagA and vacA s1 were all significantly associated with PUD (p = 0.025, p = 0.014, p = 0.039, respectively), and homA was closely correlated with NUD (p = 0.072). In East Asian strains (n = 138, 73 PUD and 65 NUD), homB was found more frequently than homA, and none of these genes was associated with the clinical outcome. Overall, homB was associated with the presence of cagA (p = 0.043) and vacA s1 (p homA was found more frequently in cagA-negative (p = 0.062) and vacA s2 (p homA copy number were observed, with a clear geographical specificity, suggesting an involvement of these genes in host adaptation. A correlation between the homB two-copy genotype and PUD was also observed, emphasizing the role of homB in the virulence of the strain. The global results suggest that homB and homA contribute to the determination of clinical outcome.

A mathematical correlation between variations in solar radiation parameters - I: Daily sums of global radiation and midday global radiation

International Nuclear Information System (INIS)

Njau, E.C.

1987-11-01

An equation that simply relates variations in the daily sums of global radiation and the corresponding midday global radiation data over an arbitrarily chosen location on the Earth is derived from first principles. Although this equation is specifically tailored for periods incorporating only cloudless days, it is modified slightly in order also to suit any period that incorporates either cloudless days or consistently cloudy days or days characterised by consistently distributed cloud patches or any combination of these. Global radiation data for Dar es Salaam, Tanzania, calculated on the basis of the slightly modified version of the equation mentioned above agree with actual measurements to at least 89% if each of the days involved is either fairly cloudless or consistently cloudy or is characterised by fairly consistent cloud patches from sunrise to sunset. This clearly demonstrates that it is quite possible to work out reasonable estimates of the overall global radiation incident on a given area using only the corresponding midday global radiation data for that particular area. (author). 6 refs, 1 fig, 3 tabs

Nitrogenase gene amplicons from global marine surface waters are dominated by genes of non-cyanobacteria

DEFF Research Database (Denmark)

Farnelid, Hanna; Andersson, Anders F.; Bertilsson, Stefan

2011-01-01

analysis of 79,090 nitrogenase (nifH) PCR amplicons encoding 7,468 unique proteins from surface samples (ten DNA samples and two RNA samples) collected at ten marine locations world-wide provides the first in-depth survey of a functional bacterial gene and yield insights into the composition and diversity...... by unicellular cyanobacteria, 42% of the identified non-cyanobacterial nifH clusters from the corresponding DNA samples were also detected in cDNA. The study indicates that non-cyanobacteria account for a substantial part of the nifH gene pool in marine surface waters and that these genes are at least...

Expression of fatty acid synthesis genes and fatty acid accumulation in haematococcus pluvialis under different stressors

Directory of Open Access Journals (Sweden)

Lei Anping

2012-03-01

Full Text Available Abstract Background Biofuel has been the focus of intensive global research over the past few years. The development of 4th generation biofuel production (algae-to-biofuels based on metabolic engineering of algae is still in its infancy, one of the main barriers is our lacking of understanding of microalgal growth, metabolism and biofuel production. Although fatty acid (FA biosynthesis pathway genes have been all cloned and biosynthesis pathway was built up in some higher plants, the molecular mechanism for its regulation in microalgae is far away from elucidation. Results We cloned main key genes for FA biosynthesis in Haematococcus pluvialis, a green microalga as a potential biodiesel feedstock, and investigated the correlations between their expression alternation and FA composition and content detected by GC-MS under different stress treatments, such as nitrogen depletion, salinity, high or low temperature. Our results showed that high temperature, high salinity, and nitrogen depletion treatments played significant roles in promoting microalgal FA synthesis, while FA qualities were not changed much. Correlation analysis showed that acyl carrier protein (ACP, 3-ketoacyl-ACP-synthase (KAS, and acyl-ACP thioesterase (FATA gene expression had significant correlations with monounsaturated FA (MUFA synthesis and polyunsaturated FA (PUFA synthesis. Conclusions We proposed that ACP, KAS, and FATA in H. pluvialis may play an important role in FA synthesis and may be rate limiting genes, which probably could be modified for the further study of metabolic engineering to improve microalgal biofuel quality and production.

Did Globalization Influence Credit Market Deregulation

OpenAIRE

Eppinger, Peter; Potrafke, Niklas

2015-01-01

We investigate whether globalization influenced credit market deregulation over the period 1970-2010. Globalization is measured by the KOF indices of globalization. Credit market deregulation is measured by the credit market freedom indicators of the Fraser Institute. The results from both cross-sectional and panel regressions using ordinary least squares indicate a positive correlation between globalization and credit market deregulation. We account for reverse causality by using predicted t...

Global Transcriptome Analysis of Aedes aegypti Mosquitoes in Response to Zika Virus Infection.

Science.gov (United States)

Etebari, Kayvan; Hegde, Shivanand; Saldaña, Miguel A; Widen, Steven G; Wood, Thomas G; Asgari, Sassan; Hughes, Grant L

2017-01-01

Zika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquito Aedes aegypti , which is also the vector of dengue virus; however, little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of whole A. aegypti mosquitoes in response to ZIKV infection at 2, 7, and 14 days postinfection using transcriptome sequencing. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic processes, cellular processes, and proteolysis. In addition, 486 long intergenic noncoding RNAs that were altered upon ZIKV infection were identified. Further, we found changes of a number of potential mRNA target genes correlating with those of altered host microRNAs. The outcomes provide a basic understanding of A. aegypti responses to ZIKV and help to determine host factors involved in replication or mosquito host antiviral response against the virus. IMPORTANCE Vector-borne viruses pose great risks to human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes in both coding and long noncoding RNAs. Analysis of these genes showed similarities with other flaviviruses, including

Horizontal gene transfer and nucleotide compositional anomaly in large DNA viruses

Directory of Open Access Journals (Sweden)

Ogata Hiroyuki

2007-12-01

Full Text Available Abstract Background DNA viruses have a wide range of genome sizes (5 kb up to 1.2 Mb, compared to 0.16 Mb to 1.5 Mb for obligate parasitic bacteria that do not correlate with their virulence or the taxonomic distribution of their hosts. The reasons for such large variation are unclear. According to the traditional view of viruses as gifted "gene pickpockets", large viral genome sizes could originate from numerous gene acquisitions from their hosts. We investigated this hypothesis by studying 67 large DNA viruses with genome sizes larger than 150 kb, including the recently characterized giant mimivirus. Given that horizontally transferred DNA often have anomalous nucleotide compositions differing from the rest of the genome, we conducted a detailed analysis of the inter- and intra-genome compositional properties of these viruses. We then interpreted their compositional heterogeneity in terms of possible causes, including strand asymmetry, gene function/expression, and horizontal transfer. Results We first show that the global nucleotide composition and nucleotide word usage of viral genomes are species-specific and distinct from those of their hosts. Next, we identified compositionally anomalous (cA genes in viral genomes, using a method based on Bayesian inference. The proportion of cA genes is highly variable across viruses and does not exhibit a significant correlation with genome size. The vast majority of the cA genes were of unknown function, lacking homologs in the databases. For genes with known homologs, we found a substantial enrichment of cA genes in specific functional classes for some of the viruses. No significant association was found between cA genes and compositional strand asymmetry. A possible exogenous origin for a small fraction of the cA genes could be confirmed by phylogenetic reconstruction. Conclusion At odds with the traditional dogma, our results argue against frequent genetic transfers to large DNA viruses from their

Field Strain Measurement on the Fiber Scale in Carbon Fiber Reinforced Polymers Using Global Finite-Element Based Digital Image Correlation

KAUST Repository

Tao, Ran

2015-05-01

Laminated composites are materials with complex architecture made of continuous fibers embedded within a polymeric resin. The properties of the raw materials can vary from one point to another due to different local processing conditions or complex geometrical features for example. A first step towards the identification of these spatially varying material parameters is to image with precision the displacement fields in this complex microstructure when subjected to mechanical loading. This thesis is aimed to accurately measure the displacement and strain fields at the fiber-matrix scale in a cross-ply composite. First, the theories of both local subset-based digital image correlation (DIC) and global finite-element based DIC are outlined. Second, in-situ secondary electron tensile images obtained by scanning electron microscopy (SEM) are post-processed by both DIC techniques. Finally, it is shown that when global DIC is applied with a conformal mesh, it can capture more accurately sharp local variations in the strain fields as it takes into account the underlying microstructure. In comparison to subset-based local DIC, finite-element based global DIC is better suited for capturing gradients across the fiber-matrix interfaces.

Chronic ethanol exposure produces time- and brain region-dependent changes in gene coexpression networks.

Directory of Open Access Journals (Sweden)

Elizabeth A Osterndorff-Kahanek

Full Text Available Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY, nucleus accumbens (NAC, prefrontal cortex (PFC, and liver after four weekly cycles of chronic intermittent ethanol (CIE vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000 at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600. Within each region, there was little gene overlap across time (~20%. All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global 'rewiring' of coexpression systems involving glial and immune signaling as well as neuronal genes.

Independent replication of a melanoma subtype gene signature and evaluation of its prognostic value and biological correlates in a population cohort.

Science.gov (United States)