WorldWideScience

Sample records for correlating global gene

  1. Resistance Genes in Global Crop Breeding Networks.

    Science.gov (United States)

    Garrett, K A; Andersen, K F; Asche, F; Bowden, R L; Forbes, G A; Kulakow, P A; Zhou, B

    2017-10-01

    Resistance genes are a major tool for managing crop diseases. The networks of crop breeders who exchange resistance genes and deploy them in varieties help to determine the global landscape of resistance and epidemics, an important system for maintaining food security. These networks function as a complex adaptive system, with associated strengths and vulnerabilities, and implications for policies to support resistance gene deployment strategies. Extensions of epidemic network analysis can be used to evaluate the multilayer agricultural networks that support and influence crop breeding networks. Here, we evaluate the general structure of crop breeding networks for cassava, potato, rice, and wheat. All four are clustered due to phytosanitary and intellectual property regulations, and linked through CGIAR hubs. Cassava networks primarily include public breeding groups, whereas others are more mixed. These systems must adapt to global change in climate and land use, the emergence of new diseases, and disruptive breeding technologies. Research priorities to support policy include how best to maintain both diversity and redundancy in the roles played by individual crop breeding groups (public versus private and global versus local), and how best to manage connectivity to optimize resistance gene deployment while avoiding risks to the useful life of resistance genes. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

  2. Full waveform inversion using envelope-based global correlation norm

    Science.gov (United States)

    Oh, Ju-Won; Alkhalifah, Tariq

    2018-05-01

    To increase the feasibility of full waveform inversion on real data, we suggest a new objective function, which is defined as the global correlation of the envelopes of modelled and observed data. The envelope-based global correlation norm has the advantage of the envelope inversion that generates artificial low-frequency information, which provides the possibility to recover long-wavelength structure in an early stage. In addition, the envelope-based global correlation norm maintains the advantage of the global correlation norm, which reduces the sensitivity of the misfit to amplitude errors so that the performance of inversion on real data can be enhanced when the exact source wavelet is not available and more complex physics are ignored. Through the synthetic example for 2-D SEG/EAGE overthrust model with inaccurate source wavelet, we compare the performance of four different approaches, which are the least-squares waveform inversion, least-squares envelope inversion, global correlation norm and envelope-based global correlation norm. Finally, we apply the envelope-based global correlation norm on the 3-D Ocean Bottom Cable (OBC) data from the North Sea. The envelope-based global correlation norm captures the strong reflections from the high-velocity caprock and generates artificial low-frequency reflection energy that helps us recover long-wavelength structure of the model domain in the early stages. From this long-wavelength model, the conventional global correlation norm is sequentially applied to invert for higher-resolution features of the model.

  3. 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

  4. 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

  5. Negatively correlated local and global stock externalities: tax or subsidy?

    International Nuclear Information System (INIS)

    Zili Yang

    2006-01-01

    Fossil fuel combustion generates both CO 2 and SO 2 . CO 2 is the most important greenhouse gas; SO 2 can cause serious local pollution. But it can alleviate the potential global warming because of negative radiative forcing. Such a phenomenon can be characterized as negatively correlated local and global stock externalities. In this paper, we set up an optimal control problem of negatively correlated local and global stock externality provision. The efficiency conditions for this problem are derived. These conditions modify the Samuelson rules for optimal provision of externalities. In addition, we examine several policy related scenarios of negatively correlated local and global stock externality provisions. Finally, we discuss policy implications and limitation of the theoretical results derived in this paper. We also indicate applications of the theoretical results here to empirical research, particularly to economic analysis of multiple-gas issues in climate change. (Author)

  6. The impact of global signal regression on resting state correlations: are anti-correlated networks introduced?

    Science.gov (United States)

    Murphy, Kevin; Birn, Rasmus M; Handwerker, Daniel A; Jones, Tyler B; Bandettini, Peter A

    2009-02-01

    Low-frequency fluctuations in fMRI signal have been used to map several consistent resting state networks in the brain. Using the posterior cingulate cortex as a seed region, functional connectivity analyses have found not only positive correlations in the default mode network but negative correlations in another resting state network related to attentional processes. The interpretation is that the human brain is intrinsically organized into dynamic, anti-correlated functional networks. Global variations of the BOLD signal are often considered nuisance effects and are commonly removed using a general linear model (GLM) technique. This global signal regression method has been shown to introduce negative activation measures in standard fMRI analyses. The topic of this paper is whether such a correction technique could be the cause of anti-correlated resting state networks in functional connectivity analyses. Here we show that, after global signal regression, correlation values to a seed voxel must sum to a negative value. Simulations also show that small phase differences between regions can lead to spurious negative correlation values. A combination breath holding and visual task demonstrates that the relative phase of global and local signals can affect connectivity measures and that, experimentally, global signal regression leads to bell-shaped correlation value distributions, centred on zero. Finally, analyses of negatively correlated networks in resting state data show that global signal regression is most likely the cause of anti-correlations. These results call into question the interpretation of negatively correlated regions in the brain when using global signal regression as an initial processing step.

  7. 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

  8. Dissecting specific and global transcriptional regulation of bacterial gene expression

    NARCIS (Netherlands)

    Gerosa, Luca; Kochanowski, Karl; Heinemann, Matthias; Sauer, Uwe

    Gene expression is regulated by specific transcriptional circuits but also by the global expression machinery as a function of growth. Simultaneous specific and global regulation thus constitutes an additional-but often neglected-layer of complexity in gene expression. Here, we develop an

  9. 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....

  10. 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.

  11. Self-adaptive isogeometric global digital image correlation and digital height correlation

    NARCIS (Netherlands)

    Hoefnagels, J. P M; Kleinendorst, S. M.; Ruybalid, A. P.; Verhoosel, C. V.; Geers, M. G D; Yoshida, S.; Lamberti, L.; Sciammarella, C.

    2017-01-01

    This work explores the full potential of isogeometric shape functions for global digital image correlation. To this end, a novel DIC and DHC (digital height correlation) methodology have been developed based on adaptive refinement of isogeometric shape functions. Non-Uniform Rational B-Spline

  12. 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

  13. Diametrical clustering for identifying anti-correlated gene clusters.

    Science.gov (United States)

    Dhillon, Inderjit S; Marcotte, Edward M; Roshan, Usman

    2003-09-01

    Clustering genes based upon their expression patterns allows us to predict gene function. Most existing clustering algorithms cluster genes together when their expression patterns show high positive correlation. However, it has been observed that genes whose expression patterns are strongly anti-correlated can also be functionally similar. Biologically, this is not unintuitive-genes responding to the same stimuli, regardless of the nature of the response, are more likely to operate in the same pathways. We present a new diametrical clustering algorithm that explicitly identifies anti-correlated clusters of genes. Our algorithm proceeds by iteratively (i). re-partitioning the genes and (ii). computing the dominant singular vector of each gene cluster; each singular vector serving as the prototype of a 'diametric' cluster. We empirically show the effectiveness of the algorithm in identifying diametrical or anti-correlated clusters. Testing the algorithm on yeast cell cycle data, fibroblast gene expression data, and DNA microarray data from yeast mutants reveals that opposed cellular pathways can be discovered with this method. We present systems whose mRNA expression patterns, and likely their functions, oppose the yeast ribosome and proteosome, along with evidence for the inverse transcriptional regulation of a number of cellular systems.

  14. 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....

  15. 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)

  16. Intrinsic limits to gene regulation by global crosstalk

    Science.gov (United States)

    Friedlander, Tamar; Prizak, Roshan; Guet, Călin C.; Barton, Nicholas H.; Tkačik, Gašper

    2016-01-01

    Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. PMID:27489144

  17. Correlation-maximizing surrogate gene space for visual mining of gene expression patterns in developing barley endosperm tissue

    Directory of Open Access Journals (Sweden)

    Usadel Björn

    2007-05-01

    Full Text Available Abstract Background Micro- and macroarray technologies help acquire thousands of gene expression patterns covering important biological processes during plant ontogeny. Particularly, faithful visualization methods are beneficial for revealing interesting gene expression patterns and functional relationships of coexpressed genes. Such screening helps to gain deeper insights into regulatory behavior and cellular responses, as will be discussed for expression data of developing barley endosperm tissue. For that purpose, high-throughput multidimensional scaling (HiT-MDS, a recent method for similarity-preserving data embedding, is substantially refined and used for (a assessing the quality and reliability of centroid gene expression patterns, and for (b derivation of functional relationships of coexpressed genes of endosperm tissue during barley grain development (0–26 days after flowering. Results Temporal expression profiles of 4824 genes at 14 time points are faithfully embedded into two-dimensional displays. Thereby, similar shapes of coexpressed genes get closely grouped by a correlation-based similarity measure. As a main result, by using power transformation of correlation terms, a characteristic cloud of points with bipolar sandglass shape is obtained that is inherently connected to expression patterns of pre-storage, intermediate and storage phase of endosperm development. Conclusion The new HiT-MDS-2 method helps to create global views of expression patterns and to validate centroids obtained from clustering programs. Furthermore, functional gene annotation for developing endosperm barley tissue is successfully mapped to the visualization, making easy localization of major centroids of enriched functional categories possible.

  18. 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...

  19. 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.

  20. 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.

  1. Finding biological process modifications in cancer tissues by mining gene expression correlations

    Directory of Open Access Journals (Sweden)

    Storari Sergio

    2006-01-01

    Full Text Available Abstract Background Through the use of DNA microarrays it is now possible to obtain quantitative measurements of the expression of thousands of genes from a biological sample. This technology yields a global view of gene expression that can be used in several ways. Functional insight into expression profiles is routinely obtained by using Gene Ontology terms associated to the cellular genes. In this paper, we deal with functional data mining from expression profiles, proposing a novel approach that studies the correlations between genes and their relations to Gene Ontology (GO. By using this "functional correlations comparison" we explore all possible pairs of genes identifying the affected biological processes by analyzing in a pair-wise manner gene expression patterns and linking correlated pairs with Gene Ontology terms. Results We apply here this "functional correlations comparison" approach to identify the existing correlations in hepatocarcinoma (161 microarray experiments and to reveal functional differences between normal liver and cancer tissues. The number of well-correlated pairs in each GO term highlights several differences in genetic interactions between cancer and normal tissues. We performed a bootstrap analysis in order to compute false detection rates (FDR and confidence limits. Conclusion Experimental results show the main advantage of the applied method: it both picks up general and specific GO terms (in particular it shows a fine resolution in the specific GO terms. The results obtained by this novel method are highly coherent with the ones proposed by other cancer biology studies. But additionally they highlight the most specific and interesting GO terms helping the biologist to focus his/her studies on the most relevant biological processes.

  2. 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.

  3. 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....

  4. 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

  5. Global gene mining and the pharmaceutical industry

    International Nuclear Information System (INIS)

    Knudsen, Lisbeth E.

    2005-01-01

    Worldwide efforts are ongoing in optimizing medical treatment by searching for the right medicine at the right dose for the individual. Metabolism is regulated by polymorphisms, which may be tested by relatively simple SNP analysis, however requiring DNA from the test individuals. Target genes for the efficiency of a given medicine or predisposition of a given disease are also subject to population studies, e.g., in Iceland, Estonia, Sweden, etc. For hypothesis testing and generation, several bio-banks with samples from patients and healthy persons within the pharmaceutical industry have been established during the past 10 years. Thus, more than 100,000 samples are stored in the freezers of either the pharmaceutical companies or their contractual partners at universities and test institutions. Ethical issues related to data protection of the individuals providing samples to bio-banks are several: nature and extent of information prior to consent, coverage of the consent given by the study person, labeling and storage of the sample and data (coded or anonymized). In general, genetic test data, once obtained, are permanent and cannot be changed. The test data may imply information that is not beneficial to the patient and his/her family (e.g., employment opportunities, insurance, etc.). Furthermore, there may be a long latency between the analysis of the genetic test and the clinical expression of the disease and wide differences in the disease patterns. Consequently, information about some genetic test data may stigmatize patients leading to poor quality of life. This has raised the issue of 'genetic exceptionalism' justifying specific regulation of use of genetic information. Discussions on how to handle sampling and data are ongoing within the industry and the regulatory sphere, the European Agency for the Evaluation of Medicinal Products (EMEA) having issued a position paper, the Council for International Organizations of Medical Sciences (CIOMS) having a working

  6. 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.

  7. Intrinsic limits to gene regulation by global crosstalk

    Science.gov (United States)

    Friedlander, Tamar; Prizak, Roshan; Guet, Calin; Barton, Nicholas H.; Tkacik, Gasper

    Gene activity is mediated by the specificity of binding interactions between special proteins, called transcription factors, and short regulatory sequences on the DNA, where different protein species preferentially bind different DNA targets. Limited interaction specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to spurious interactions or remains erroneously inactive. Since each protein can potentially interact with numerous DNA targets, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyze the effects of global crosstalk on gene regulation, using statistical mechanics. We find that crosstalk in regulatory interactions puts fundamental limits on the reliability of gene regulation that are not easily mitigated by tuning proteins concentrations or by complex regulatory schemes proposed in the literature. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA Grant agreement Nr. 291734 (T.F.) and ERC Grant Nr. 250152 (N.B.).

  8. Correlation analyses revealed global microRNA-mRNA expression associations in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Wang, Lan; Zhu, Jiang; Deng, Fei-Yan; Wu, Long-Fei; Mo, Xing-Bo; Zhu, Xiao-Wei; Xia, Wei; Xie, Fang-Fei; He, Pei; Bing, Peng-Fei; Qiu, Ying-Hua; Lin, Xiang; Lu, Xin; Zhang, Lei; Yi, Neng-Jun; Zhang, Yong-Hong; Lei, Shu-Feng

    2018-02-01

    MicroRNAs (miRNAs) can regulate gene expression through binding to complementary sites in the 3'-untranslated regions of target mRNAs, which will lead to existence of correlation in expression between miRNA and mRNA. However, the miRNA-mRNA correlation patterns are complex and remain largely unclear yet. To establish the global correlation patterns in human peripheral blood mononuclear cells (PBMCs), multiple miRNA-mRNA correlation analyses and expression quantitative trait locus (eQTL) analysis were conducted in this study. We predicted and achieved 861 miRNA-mRNA pairs (65 miRNAs, 412 mRNAs) using multiple bioinformatics programs, and found global negative miRNA-mRNA correlations in PBMC from all 46 study subjects. Among the 861 pairs of correlations, 19.5% were significant (P correlation network was complex and highlighted key miRNAs/genes in PBMC. Some miRNAs, such as hsa-miR-29a, hsa-miR-148a, regulate a cluster of target genes. Some genes, e.g., TNRC6A, are regulated by multiple miRNAs. The identified genes tend to be enriched in molecular functions of DNA and RNA binding, and biological processes such as protein transport, regulation of translation and chromatin modification. The results provided a global view of the miRNA-mRNA expression correlation profile in human PBMCs, which would facilitate in-depth investigation of biological functions of key miRNAs/mRNAs and better understanding of the pathogenesis underlying PBMC-related diseases.

  9. 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.

  10. 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

  11. Why is the correlation between gene importance and gene evolutionary rate so weak?

    Science.gov (United States)

    Wang, Zhi; Zhang, Jianzhi

    2009-01-01

    One of the few commonly believed principles of molecular evolution is that functionally more important genes (or DNA sequences) evolve more slowly than less important ones. This principle is widely used by molecular biologists in daily practice. However, recent genomic analysis of a diverse array of organisms found only weak, negative correlations between the evolutionary rate of a gene and its functional importance, typically measured under a single benign lab condition. A frequently suggested cause of the above finding is that gene importance determined in the lab differs from that in an organism's natural environment. Here, we test this hypothesis in yeast using gene importance values experimentally determined in 418 lab conditions or computationally predicted for 10,000 nutritional conditions. In no single condition or combination of conditions did we find a much stronger negative correlation, which is explainable by our subsequent finding that always-essential (enzyme) genes do not evolve significantly more slowly than sometimes-essential or always-nonessential ones. Furthermore, we verified that functional density, approximated by the fraction of amino acid sites within protein domains, is uncorrelated with gene importance. Thus, neither the lab-nature mismatch nor a potentially biased among-gene distribution of functional density explains the observed weakness of the correlation between gene importance and evolutionary rate. We conclude that the weakness is factual, rather than artifactual. In addition to being weakened by population genetic reasons, the correlation is likely to have been further weakened by the presence of multiple nontrivial rate determinants that are independent from gene importance. These findings notwithstanding, we show that the principle of slower evolution of more important genes does have some predictive power when genes with vastly different evolutionary rates are compared, explaining why the principle can be practically useful

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. An improved Pearson's correlation proximity-based hierarchical clustering for mining biological association between genes.

    Science.gov (United States)

    Booma, P M; Prabhakaran, S; Dhanalakshmi, R

    2014-01-01

    Microarray gene expression datasets has concerned great awareness among molecular biologist, statisticians, and computer scientists. Data mining that extracts the hidden and usual information from datasets fails to identify the most significant biological associations between genes. A search made with heuristic for standard biological process measures only the gene expression level, threshold, and response time. Heuristic search identifies and mines the best biological solution, but the association process was not efficiently addressed. To monitor higher rate of expression levels between genes, a hierarchical clustering model was proposed, where the biological association between genes is measured simultaneously using proximity measure of improved Pearson's correlation (PCPHC). Additionally, the Seed Augment algorithm adopts average linkage methods on rows and columns in order to expand a seed PCPHC model into a maximal global PCPHC (GL-PCPHC) model and to identify association between the clusters. Moreover, a GL-PCPHC applies pattern growing method to mine the PCPHC patterns. Compared to existing gene expression analysis, the PCPHC model achieves better performance. Experimental evaluations are conducted for GL-PCPHC model with standard benchmark gene expression datasets extracted from UCI repository and GenBank database in terms of execution time, size of pattern, significance level, biological association efficiency, and pattern quality.

  19. 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.

  20. 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.

  1. Importance of correlation between gene expression levels: application to the type I interferon signature in rheumatoid arthritis.

    Science.gov (United States)

    Reynier, Frédéric; Petit, Fabien; Paye, Malick; Turrel-Davin, Fanny; Imbert, Pierre-Emmanuel; Hot, Arnaud; Mougin, Bruno; Miossec, Pierre

    2011-01-01

    The analysis of gene expression data shows that many genes display similarity in their expression profiles suggesting some co-regulation. Here, we investigated the co-expression patterns in gene expression data and proposed a correlation-based research method to stratify individuals. Using blood from rheumatoid arthritis (RA) patients, we investigated the gene expression profiles from whole blood using Affymetrix microarray technology. Co-expressed genes were analyzed by a biclustering method, followed by gene ontology analysis of the relevant biclusters. Taking the type I interferon (IFN) pathway as an example, a classification algorithm was developed from the 102 RA patients and extended to 10 systemic lupus erythematosus (SLE) patients and 100 healthy volunteers to further characterize individuals. We developed a correlation-based algorithm referred to as Classification Algorithm Based on a Biological Signature (CABS), an alternative to other approaches focused specifically on the expression levels. This algorithm applied to the expression of 35 IFN-related genes showed that the IFN signature presented a heterogeneous expression between RA, SLE and healthy controls which could reflect the level of global IFN signature activation. Moreover, the monitoring of the IFN-related genes during the anti-TNF treatment identified changes in type I IFN gene activity induced in RA patients. In conclusion, we have proposed an original method to analyze genes sharing an expression pattern and a biological function showing that the activation levels of a biological signature could be characterized by its overall state of correlation.

  2. 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.

  3. 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.

  4. Catecholamine-related gene expression in blood correlates with tic severity in tourette syndrome.

    Science.gov (United States)

    Gunther, Joan; Tian, Yingfang; Stamova, Boryana; Lit, Lisa; Corbett, Blythe; Ander, Brad; Zhan, Xinhua; Jickling, Glen; Bos-Veneman, Netty; Liu, Da; Hoekstra, Pieter; Sharp, Frank

    2012-12-30

    Tourette syndrome (TS) is a heritable disorder characterized by tics that are decreased in some patients by treatment with alpha adrenergic agonists and dopamine receptor blockers. Thus, this study examines the relationship between catecholamine gene expression in blood and tic severity. TS diagnosis was confirmed using Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria and tic severity measured using the Yale Global Tic Severity Scale (YGTSS) for 26 un-medicated subjects with TS. Whole blood was collected and Ribonucleic acid (RNA) processed on Affymetrix Human Exon 1.0 ST arrays. An Analysis of Covariance (ANCOVA) identified 3627 genes correlated with tic severity (pdisorders, Attention Deficit Hyperactivity Disorder (ADHD), and Obsessive-Compulsive Disorder (OCD). Correlation of gene expression in peripheral blood with tic severity may allow inferences about catecholamine pathway dysfunction in TS subjects. Findings built on previous work suggest that at least some genes expressed peripherally are relevant for central nervous system (CNS) pathology in the brain of individuals with TS. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. 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.

  6. 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

  7. 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.

  8. Correlates of eggshell thickness | Okereke | Global Journal of Pure ...

    African Journals Online (AJOL)

    This study discussed the effects of age and genotype of birds and location of farm on eggshell thickness. The ultimate objective of the study is to determine the correlates of eggshell thickness which may be relevant to improve eggshell thickness. Secondary data on eggshell thickness collected from the Agricultural ...

  9. 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

  10. Globally conformal invariant gauge field theory with rational correlation functions

    CERN Document Server

    Nikolov, N M; Todorov, I T; CERN. Geneva; Todorov, Ivan T.

    2003-01-01

    Operator product expansions (OPE) for the product of a scalar field with its conjugate are presented as infinite sums of bilocal fields $V_{\\kappa} (x_1, x_2)$ of dimension $(\\kappa, \\kappa)$. For a {\\it globally conformal invariant} (GCI) theory we write down the OPE of $V_{\\kappa}$ into a series of {\\it twist} (dimension minus rank) $2\\kappa$ symmetric traceless tensor fields with coefficients computed from the (rational) 4-point function of the scalar field. We argue that the theory of a GCI hermitian scalar field ${\\cal L} (x)$ of dimension 4 in $D = 4$ Minkowski space such that the 3-point functions of a pair of ${\\cal L}$'s and a scalar field of dimension 2 or 4 vanish can be interpreted as the theory of local observables of a conformally invariant fixed point in a gauge theory with Lagrangian density ${\\cal L} (x)$.

  11. 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.

  12. Study of formation of green eggshell color in ducks through global gene expression.

    Science.gov (United States)

    Xu, Fa Qiong; Li, Ang; Lan, Jing Jing; Wang, Yue Ming; Yan, Mei Jiao; Lian, Sen Yang; Wu, Xu

    2018-01-01

    The green eggshell color produced by ducks is a threshold trait that can be influenced by various factors, such as hereditary, environment and nutrition. The aim of this study was to investigate the genetic regulation of the formation of eggs with green shells in Youxian ducks. We performed integrative analysis of mRNAs and miRNAs expression profiling in the shell gland samples from ducks by RNA-Seq. We found 124 differentially expressed genes that were associated with various pathways, such as the ATP-binding cassette (ABC) transporter and solute carrier supper family pathways. A total of 31 differentially expressed miRNAs were found between ducks laying green eggs and white eggs. KEGG pathway analysis of the predicted miRNA target genes also indicated the functional characteristics of these miRNAs; they were involved in the ABC transporter pathway and the solute carrier (SLC) supper family. Analysis with qRT-PCR was applied to validate the results of global gene expression, which showed a correlation between results obtained by RNA-seq and RT-qPCR. Moreover, a miRNA-mRNA interaction network was established using correlation analysis of differentially expressed mRNA and miRNA. Compared to ducks that lay white eggs, ducks that lay green eggs include six up-regulated miRNAs that had regulatory effects on 35 down-regulated genes, and seven down-regulated miRNAs which influenced 46 up-regulated genes. For example, the ABC transporter pathway could be regulated by expressing gga-miR-144-3p (up-regulated) with ABCG2 (up-regulated) and other miRNAs and genes. This study provides valuable information about mRNA and miRNA regulation in duck shell gland tissues, and provides foundational information for further study on the eggshell color formation and marker-assisted selection for Youxian duck breeding.

  13. Study of formation of green eggshell color in ducks through global gene expression.

    Directory of Open Access Journals (Sweden)

    Fa Qiong Xu

    Full Text Available The green eggshell color produced by ducks is a threshold trait that can be influenced by various factors, such as hereditary, environment and nutrition. The aim of this study was to investigate the genetic regulation of the formation of eggs with green shells in Youxian ducks. We performed integrative analysis of mRNAs and miRNAs expression profiling in the shell gland samples from ducks by RNA-Seq. We found 124 differentially expressed genes that were associated with various pathways, such as the ATP-binding cassette (ABC transporter and solute carrier supper family pathways. A total of 31 differentially expressed miRNAs were found between ducks laying green eggs and white eggs. KEGG pathway analysis of the predicted miRNA target genes also indicated the functional characteristics of these miRNAs; they were involved in the ABC transporter pathway and the solute carrier (SLC supper family. Analysis with qRT-PCR was applied to validate the results of global gene expression, which showed a correlation between results obtained by RNA-seq and RT-qPCR. Moreover, a miRNA-mRNA interaction network was established using correlation analysis of differentially expressed mRNA and miRNA. Compared to ducks that lay white eggs, ducks that lay green eggs include six up-regulated miRNAs that had regulatory effects on 35 down-regulated genes, and seven down-regulated miRNAs which influenced 46 up-regulated genes. For example, the ABC transporter pathway could be regulated by expressing gga-miR-144-3p (up-regulated with ABCG2 (up-regulated and other miRNAs and genes. This study provides valuable information about mRNA and miRNA regulation in duck shell gland tissues, and provides foundational information for further study on the eggshell color formation and marker-assisted selection for Youxian duck breeding.

  14. Correlation and network analysis of global financial indices.

    Science.gov (United States)

    Kumar, Sunil; Deo, Nivedita

    2012-08-01

    Random matrix theory (RMT) and network methods are applied to investigate the correlation and network properties of 20 financial indices. The results are compared before and during the financial crisis of 2008. In the RMT method, the components of eigenvectors corresponding to the second largest eigenvalue form two clusters of indices in the positive and negative directions. The components of these two clusters switch in opposite directions during the crisis. The network analysis uses the Fruchterman-Reingold layout to find clusters in the network of indices at different thresholds. At a threshold of 0.6, before the crisis, financial indices corresponding to the Americas, Europe, and Asia-Pacific form separate clusters. On the other hand, during the crisis at the same threshold, the American and European indices combine together to form a strongly linked cluster while the Asia-Pacific indices form a separate weakly linked cluster. If the value of the threshold is further increased to 0.9 then the European indices (France, Germany, and the United Kingdom) are found to be the most tightly linked indices. The structure of the minimum spanning tree of financial indices is more starlike before the crisis and it changes to become more chainlike during the crisis. The average linkage hierarchical clustering algorithm is used to find a clearer cluster structure in the network of financial indices. The cophenetic correlation coefficients are calculated and found to increase significantly, which indicates that the hierarchy increases during the financial crisis. These results show that there is substantial change in the structure of the organization of financial indices during a financial crisis.

  15. 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...

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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…

  1. 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.

  2. 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.

  3. 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.

  4. 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)

  5. 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

  6. Two-Way Gene Interaction From Microarray Data Based on Correlation Methods.

    Science.gov (United States)

    Alavi Majd, Hamid; Talebi, Atefeh; Gilany, Kambiz; Khayyer, Nasibeh

    2016-06-01

    Gene networks have generated a massive explosion in the development of high-throughput techniques for monitoring various aspects of gene activity. Networks offer a natural way to model interactions between genes, and extracting gene network information from high-throughput genomic data is an important and difficult task. The purpose of this study is to construct a two-way gene network based on parametric and nonparametric correlation coefficients. The first step in constructing a Gene Co-expression Network is to score all pairs of gene vectors. The second step is to select a score threshold and connect all gene pairs whose scores exceed this value. In the foundation-application study, we constructed two-way gene networks using nonparametric methods, such as Spearman's rank correlation coefficient and Blomqvist's measure, and compared them with Pearson's correlation coefficient. We surveyed six genes of venous thrombosis disease, made a matrix entry representing the score for the corresponding gene pair, and obtained two-way interactions using Pearson's correlation, Spearman's rank correlation, and Blomqvist's coefficient. Finally, these methods were compared with Cytoscape, based on BIND, and Gene Ontology, based on molecular function visual methods; R software version 3.2 and Bioconductor were used to perform these methods. Based on the Pearson and Spearman correlations, the results were the same and were confirmed by Cytoscape and GO visual methods; however, Blomqvist's coefficient was not confirmed by visual methods. Some results of the correlation coefficients are not the same with visualization. The reason may be due to the small number of data.

  7. 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...

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. DNA methylation of PTEN gene promoter region is not correlated ...

    African Journals Online (AJOL)

    Tumor suppressor gene PTEN plays an important role in cell cycle. Disorder of PTEN protein can cause cell growth and division in an uncontrolled way, which can lead to the formation of tumors. It has been proven that epigenetic mechanisms, such as promoter hypermethylation, may account for inactivation of PTEN in a ...

  14. 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.

  15. 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.

  16. 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

  17. Global analysis of differential expressed genes in ECV304 ...

    African Journals Online (AJOL)

    EB

    Abstract. Background: Human cytomegalovirus (HCMV) is a virus which has the potential to alter cellular gene expression through .... and (reverse: 5'-CAG CAC CAT CCT CCT CTT. CCT CT ..... acute respiratory syndrome (SARS) coronavirus.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. Global gene response in Saccharomyces cerevisiae exposed to silver nanoparticles.

    Science.gov (United States)

    Niazi, Javed H; Sang, Byoung-In; Kim, Yeon Seok; Gu, Man Bock

    2011-08-01

    Silver nanoparticles (AgNPs), exhibiting a broad size range and morphologies with highly reactive facets, which are widely applicable in real-life but not fully verified for biosafety and ecotoxicity, were subjected to report transcriptome profile in yeast Saccharomyces cerevisiae. A large number of genes accounted for ∼3% and ∼5% of the genome affected by AgNPs and Ag-ions, respectively. Principal component and cluster analysis suggest that the different physical forms of Ag were the major cause in differential expression profile. Among 90 genes affected by both AgNPs and Ag-ions, metalloprotein mediating high resistance to copper (CUP1-1 and CUP1-2) were strongly induced by AgNPs (∼45-folds) and Ag-ions (∼22-folds), respectively. A total of 17 genes, responsive to chemical stimuli, stress, and transport processes, were differentially induced by AgNPs. The differential expression was also seen with Ag-ions that affected 73 up- and 161 down-regulating genes, and most of these were involved in ion transport and homeostasis. This study provides new information on the knowledge for impact of nanoparticles on living microorganisms that can be extended to other nanoparticles.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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...

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. [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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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)

  9. 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...

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. [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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain.

    Science.gov (United States)

    Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

    2013-01-01

    An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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...

  1. 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.

  2. 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.

  3. 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

  4. Impulsivity across the psychosis spectrum: Correlates of cortical volume, suicidal history, and social and global function.

    Science.gov (United States)

    Nanda, Pranav; Tandon, Neeraj; Mathew, Ian T; Padmanabhan, Jaya L; Clementz, Brett A; Pearlson, Godfrey D; Sweeney, John A; Tamminga, Carol A; Keshavan, Matcheri S

    2016-01-01

    Patients with psychotic disorders appear to exhibit greater impulsivity-related behaviors relative to healthy controls. However, the neural underpinning of this impulsivity remains uncertain. Furthermore, it remains unclear how impulsivity might differ or be conserved between psychotic disorder diagnoses in mechanism and manifestation. In this study, self-reported impulsivity, measured by Barratt Impulsiveness Scale (BIS), was compared between 305 controls (HC), 139 patients with schizophrenia (SZ), 100 with schizoaffective disorder (SZA), and 125 with psychotic bipolar disorder (PBP). In each proband group, impulsivity was associated with regional cortical volumes (using FreeSurfer analysis of T1 MRI scans), suicide attempt history, Global Assessment of Functioning (GAF), and Social Functioning Scale (SFS). BIS scores were found to differ significantly between participant groups, with SZA and PBP exhibiting significantly higher impulsivity than SZ, which exhibited significantly higher impulsivity than HC. BIS scores were significantly related to suicide attempt history, and they were inversely associated with GAF, SFS, and bilateral orbitofrontal cortex (OFC) volume in both SZA and PBP, but not SZ. These findings indicate that psychotic disorders, particularly those with prominent affective symptoms, are characterized by elevated self-reported impulsivity measures. Impulsivity's correlations with suicide attempt history, GAF, and SFS suggest that impulsivity may be a mediator of clinical outcome. The observed impulsivity-OFC correlations corroborate the importance of OFC deficits in impulsivity. These correlations' presence in SZA and PBP but not in SZ suggests that impulsivity may have different underlying mechanisms in affective and non-affective psychotic disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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...

  12. 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

  13. 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/.

  14. 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

  15. 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

  16. 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...

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. Correlation between the GP78 Gene Polymorphism and Coronary Atherosclerotic Heart Disease

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    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

  5. 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...

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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...

  11. 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.

  12. 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

  13. 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...

  14. 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.

  15. 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.

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

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    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.

  17. 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.

  18. 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)

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

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    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.

  20. 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.)

  1. 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.)

  2. 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.

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

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    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.

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

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    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.

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

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    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.

  6. Globalization

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    Tulio Rosembuj

    2006-12-01

    Full Text Available There is no singular globalization, nor is the result of an individual agent. We could start by saying that global action has different angles and subjects who perform it are different, as well as its objectives. The global is an invisible invasion of materials and immediate effects.

  7. Globalization

    OpenAIRE

    Tulio Rosembuj

    2006-01-01

    There is no singular globalization, nor is the result of an individual agent. We could start by saying that global action has different angles and subjects who perform it are different, as well as its objectives. The global is an invisible invasion of materials and immediate effects.

  8. 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.

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

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    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.

  10. 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.

  11. 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

  12. 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.

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

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    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.

  14. 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

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

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    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.

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

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    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.

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

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    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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Globalization

    OpenAIRE

    Andru?cã Maria Carmen

    2013-01-01

    The field of globalization has highlighted an interdependence implied by a more harmonious understanding determined by the daily interaction between nations through the inducement of peace and the management of streamlining and the effectiveness of the global economy. For the functioning of the globalization, the developing countries that can be helped by the developed ones must be involved. The international community can contribute to the institution of the development environment of the gl...

  5. 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

  6. Spatial correlation structure of the ionosphere predicted by geomagnetic indices and application to global field modelling

    Science.gov (United States)

    Holschneider, M.; Ferrat, K.; Lesur, V.; Stolle, C.

    2017-12-01

    Ionospheric fields are modelled in terms of random structures taking into account a mean behaviour as well as random fluctuations which are described through two point correlation kernels. These kernels are estimated from long time series of numerical simulations from various models. These correlations are best expressed in SM system of coordinates. For the moment we limit ourselves to spatial correlations only in this coordinate system. We study the influence of various indices as possible predictor parameters for these correlations as well as seasonal effects. The various time series of ionospheric fields are stored in a HDF5 database which is accessible via a web interface. The obtained correlation structures serve as prior information to separate external and internal field components from observatory based measurements. We present a model that predicts the correlations as a function of time and some geomagnetic indices. First results of the inversion from observatory data are presented.

  7. 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...

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Correlations Between Extreme Atmospheric Hazards and Global Teleconnections: Implications for Multihazard Resilience

    Science.gov (United States)

    Steptoe, H.; Jones, S. E. O.; Fox, H.

    2018-03-01

    Occurrences of concurrent extreme atmospheric hazards represent a significant area of uncertainty for organizations involved in disaster mitigation and risk management. Understanding risks posed by natural disasters and their relationship with global climate drivers is crucial in preparing for extreme events. In this review we quantify the strength of the physical mechanisms linking hazards and atmosphere-ocean processes. We demonstrate how research from the science community may be used to support disaster risk reduction and global sustainable development efforts. We examine peer-reviewed literature connecting 16 regions affected by extreme atmospheric hazards and eight key global drivers of weather and climate. We summarize current understanding of multihazard disaster risk in each of these regions and identify aspects of the global climate system that require further investigation to strengthen our resilience in these areas. We show that some drivers can increase the risk of concurrent hazards across different regions. Organizations that support disaster risk reduction, or underwrite exposure, in multiple regions may have a heightened risk of facing multihazard losses. We find that 15 regional hazards share connections via the El Niño-Southern Oscillation, with the Indian Ocean Dipole, North Atlantic Oscillation, and the Southern Annular Mode being secondary sources of significant regional interconnectivity. From a hazard perspective, rainfall over China shares the most connections with global drivers and has links to both Northern and Southern Hemisphere modes of variability. We use these connections to assess the global likelihood of concurrent hazard occurrence in support of multihazard resilience and disaster risk reduction goals.

  15. 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.

  16. 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.

  17. Population structure from NOS genes correlates with geographical differences in coronary incidence across Europe.

    Science.gov (United States)

    Carreras-Torres, Robert; Ferran, Albert; Zanetti, Daniela; Esteban, Esther; Varesi, Laurent; Pojskic, Naris; Coia, Valentina; Chaabani, Hassen; Via, Marc; Moral, Pedro

    2016-12-01

    The population analysis of cardiovascular risk and non-risk genetic variation can help to identify adaptive or random demographic processes that shaped coronary incidence variation across geography. In this study, 114 single nucleotide polymorphisms and 17 tandem repeat polymorphisms from Nitric Oxide Synthases (NOS) regions were analyzed in 1686 individuals from 35 populations from Europe, North Africa, and the Middle East. NOS genes encode for key enzymes on nitric oxide availability, which is involved in several cardiovascular processes. These genetic variations were used to test for selection and to infer the population structure of NOS regions. Moreover, we tested whether the variation in the incidence of coronary events and in the levels of classical risk factors in 11 of these European populations could be explained by the population structure estimates. Our results supported, first, the absence of clear signs of selection for NOS genetic variants associated with cardiovascular diseases, and second, the presence of a continuous genetic pattern of variation across European and North African populations without a Mediterranean barrier for gene flow. Finally, population structure estimates from NOS regions are closely correlated with coronary event rates and classical risk parameters (explaining 39-98%) among European populations. Our results reinforce the hypothesis that genetic bases of cardiovascular diseases and associated complex phenotypes could be geographically shaped by random demographic processes. © 2016 Wiley Periodicals, Inc.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. Continuous gene flow contributes to low global species abundance and distribution of a marine model diatom

    KAUST Repository

    Rastogi, Achal

    2017-08-15

    Unlike terrestrial ecosystems where geographical isolation often leads to a restricted gene flow between species, genetic admixing in aquatic micro-eukaryotes is likely to be frequent. Diatoms inhabit marine ecosystems since the Mesozoic period and presently constitute one of the major primary producers in the world ocean. They are a highly diversified group of eukaryotic phytoplankton with estimates of up to 200,000 species. Since decades, Phaeodactylum tricornutum is used as a model diatom species to characterize the functional pathways, physiology and evolution of diatoms in general. In the current study, using whole genome sequencing of ten P. tricornutum strains, sampled at broad geospatial and temporal scales, we show a continuous dispersal and genetic admixing between geographically isolated strains. We also describe a very high level of heterozygosity and propose it to be a consequence of frequent ancestral admixture. Our finding that P. tricornutum sequences are plausibly detectable at low but broadly distributed levels in the world ocean further suggests that high admixing between geographically isolated strains may create a significant bottleneck, thus influencing their global abundance and distribution in nature. Finally, in an attempt to understand the functional implications of genetic diversity between different P. tricornutum ecotypes, we show the effects of domestication in inducing changes in the selection pressure on many genes and metabolic pathways. We propose these findings to have significant implications for understanding the genetic structure of diatom populations in nature and provide a framework to assess the genomic underpinnings of their ecological success.

  4. Continuous gene flow contributes to low global species abundance and distribution of a marine model diatom

    KAUST Repository

    Rastogi, Achal; Deton-Cabanillas, Anne-Flore; Rocha Jimenez Vieira, Fabio; Veluchamy, Alaguraj; Cantrel, Catherine; Wang, Gaohong; Vanormelingen, Pieter; Bowler, Chris; Piganeau, Gwenael; Tirichine, Leila; Hu, Hanhua

    2017-01-01

    Unlike terrestrial ecosystems where geographical isolation often leads to a restricted gene flow between species, genetic admixing in aquatic micro-eukaryotes is likely to be frequent. Diatoms inhabit marine ecosystems since the Mesozoic period and presently constitute one of the major primary producers in the world ocean. They are a highly diversified group of eukaryotic phytoplankton with estimates of up to 200,000 species. Since decades, Phaeodactylum tricornutum is used as a model diatom species to characterize the functional pathways, physiology and evolution of diatoms in general. In the current study, using whole genome sequencing of ten P. tricornutum strains, sampled at broad geospatial and temporal scales, we show a continuous dispersal and genetic admixing between geographically isolated strains. We also describe a very high level of heterozygosity and propose it to be a consequence of frequent ancestral admixture. Our finding that P. tricornutum sequences are plausibly detectable at low but broadly distributed levels in the world ocean further suggests that high admixing between geographically isolated strains may create a significant bottleneck, thus influencing their global abundance and distribution in nature. Finally, in an attempt to understand the functional implications of genetic diversity between different P. tricornutum ecotypes, we show the effects of domestication in inducing changes in the selection pressure on many genes and metabolic pathways. We propose these findings to have significant implications for understanding the genetic structure of diatom populations in nature and provide a framework to assess the genomic underpinnings of their ecological success.

  5. 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.

  6. 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

  7. Correlation of Global N-Acetyl Aspartate With Cognitive Impairment in Multiple Sclerosis

    DEFF Research Database (Denmark)

    Kahr Mathiesen, Henrik; Jonsson, Agnete; Tscherning, Thomas

    2006-01-01

    BACKGROUND: Whole-brain N-acetyl aspartate (NAA), a measure of neuronal function, can be assessed by multislice echo-planar spectroscopic imaging. OBJECTIVE: To test the hypothesis that the global brain NAA/creatine (Cr) ratio is a better predictor of cognitive dysfunction in multiple sclerosis...

  8. Neural correlate of autistic-like traits and a common allele in the oxytocin receptor gene.

    Science.gov (United States)

    Saito, Yuki; Suga, Motomu; Tochigi, Mamoru; Abe, Osamu; Yahata, Noriaki; Kawakubo, Yuki; Liu, Xiaoxi; Kawamura, Yoshiya; Sasaki, Tsukasa; Kasai, Kiyoto; Yamasue, Hidenori

    2014-10-01

    Sub-clinical autistic-like traits (ALTs) are continuously distributed in the general population and genetically linked to autism. Although identifying the neurogenetic backgrounds of ALTs might enhance our ability to identify those of autism, they are largely unstudied. Here, we have examined the neuroanatomical basis of ALTs and their association with the oxytocin receptor gene (OXTR) rs2254298A, a known risk allele for autism in Asian populations which has also been implicated in limbic-paralimbic brain structures. First, we extracted a four-factor structure of ALTs, as measured using the Autism-Spectrum Quotient, including 'prosociality', 'communication', 'details/patterns' and 'imagination' in 135 neurotypical adults (79 men, 56 women) to reduce the genetic heterogeneity of ALTs. Then, in the same population, voxel-based morphometry revealed that lower 'prosociality', which indicates strong ALTs, was significantly correlated to smaller regional grey matter volume in the right insula in males. Males with lower 'prosociality' also had less interregional structural coupling between the right insula and the ventral anterior cingulate cortex. Furthermore, males with OXTR rs2254298A had significantly smaller grey matter volume in the right insula. These results show that decreased volume of the insula is a neuroanatomical correlate of ALTs and a potential intermediate phenotype linking ALTs with OXTR in male subjects. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. 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

  10. 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

  11. Global hotspots and correlates of alien species richness across taxonomic groups

    Science.gov (United States)

    Dawson, Wayne; Moser, Dietmar; van Kleunen, Mark; Kreft, Holger; Pergl, Jan; Pysek, Petr; Weigelt, Patrick; Winter, Marten; Lenzner, Bernd; Blackburn, Tim M.; Dyer, Ellie; Cassey, Phillip; Scrivens, Sally-Louise; Economo, Evan P.; Guenard, Benoit; Capinha, Cesar; Seebens, Hanno; Garcia-Diaz, Pablo; Nentwig, Wolfgang; Garcia-Berthou, Emili; Casal, Christine; Mandrak, Nicholas E.; Fuller, Pam; Meyer, Carsten; Essl, Franz

    2017-01-01

    Human-mediated transport beyond biogeographic barriers has led to the introduction and establishment of alien species in new regions worldwide. However, we lack a global picture of established alien species richness for multiple taxonomic groups. Here, we assess global patterns and potential drivers of established alien species richness across eight taxonomic groups (amphibians, ants, birds, freshwater fishes, mammals, vascular plants, reptiles and spiders) for 186 islands and 423 mainland regions. Hotspots of established alien species richness are predominantly island and coastal mainland regions. Regions with greater gross domestic product per capita, human population density, and area have higher established alien richness, with strongest effects emerging for islands. Ants and reptiles, birds and mammals, and vascular plants and spiders form pairs of taxonomic groups with the highest spatial congruence in established alien richness, but drivers explaining richness differ between the taxa in each pair. Across all taxonomic groups, our results highlight the need to prioritize prevention of further alien species introductions to island and coastal mainland regions globally.

  12. 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.

  13. 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

  14. Effects of land use on zoonotic host communities: a global correlative analysis

    Directory of Open Access Journals (Sweden)

    Rory Gibb, MRes

    2018-05-01

    Full Text Available Background: Environmental trade-offs associated with land use—for example, between food security and biodiversity conservation—are crucial dimensions of planetary health. Land use-driven biodiversity change might predictably affect disease risk if reservoir host species are consistently more likely to persist under human disturbance (ie, if ecological communities in modified habitats generally have a higher zoonotic potential than those in unmodified habitats. Such a phenomenon has been observed in specific disease systems, but with substantial change in global land use projected for this century, assessing its global and taxonomic generality would shed light on an important hypothesised driver of environmental synergies or trade-offs between conservation and public health. Methods: We collated data on hosts of human parasites and pathogens from the published literature, and combined these with the Projecting Responses of Ecological Diversity in Changing Terrestrial Systems (PREDICTS global database of local ecological communities and associated land use data. We analysed the effects of land use on host richness and abundance across 7330 sites globally, controlling for disease-related research effort and differences in survey methods. Findings: Ecological communities in anthropogenic land uses (managed and urban ecosystems contained a consistently higher richness and abundance of host species than did communities in nearby primary (undisturbed sites. However, among mammal hosts of zoonotic pathogens, we found considerable taxonomic variation in host responses to land use, with abundances of rodents and bats generally increasing and those of primates and carnivores generally declining in modified landscapes. Interpretation: Our results suggest that future change in global land use has the potential to drive overall increasing contact between people and ecological communities with increased shared pathogen potential (ie, more potential hosts

  15. 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)

  16. Globalization

    DEFF Research Database (Denmark)

    Plum, Maja

    Globalization is often referred to as external to education - a state of affair facing the modern curriculum with numerous challenges. In this paper it is examined as internal to curriculum; analysed as a problematization in a Foucaultian sense. That is, as a complex of attentions, worries, ways...... of reasoning, producing curricular variables. The analysis is made through an example of early childhood curriculum in Danish Pre-school, and the way the curricular variable of the pre-school child comes into being through globalization as a problematization, carried forth by the comparative practices of PISA...

  17. Globalization

    OpenAIRE

    F. Gerard Adams

    2008-01-01

    The rapid globalization of the world economy is causing fundamental changes in patterns of trade and finance. Some economists have argued that globalization has arrived and that the world is “flat†. While the geographic scope of markets has increased, the author argues that new patterns of trade and finance are a result of the discrepancies between “old†countries and “new†. As the differences are gradually wiped out, particularly if knowledge and technology spread worldwide, the t...

  18. The Correlation of Human Development Index on Fertility and Mortality Rate: a Global Ecological Study

    Directory of Open Access Journals (Sweden)

    Amir Almasi-Hashiani

    2016-12-01

    Full Text Available BackgroundSeveral studies have examined the relationship between Human Development Index (HDI and various health outcomes. The aim of this study was to investigate the relationship between HDI, and infant mortality rate, mortality rate of children under one year and under 5 years, maternal mortality rate, and total fertility rate.Materials and MethodsIn this ecologic study, data on HDI, total fertility rate (TFR, maternal mortality rate (MMR, neonatal mortality rate (NMR, infant mortality rate (IMR and mortality rate in children under 5 years of age (< 5MR, were extracted from 188 countries in 2014 in the world. The data required in this study was obtained from the World Bank. Data analysis was performed using Pearson correlation in Stata version 12.0 software. ResultsIn this study, a negative significant correlation was observed between HDI and IMR (r = -0.878, P = 0.001, NMR (r = -0.870, 95% CI: -0.902, -0.828, P = 0.001, ConclusionIMR, children under one year old and under 5 years, and MMR mostly occur in developing countries. There was a correlation between HDI and its components, and the neonatal, infants, children under 5 years, maternal mortality rate and total fertility. The average annual percentage change of HDI also had a correlation with neonatal, infants, children under 5- year mortality rate, total fertility and maternal deaths.

  19. 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

  20. 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.

  1. Global hotspots and correlates of alien species richness across taxonomic groups

    Czech Academy of Sciences Publication Activity Database

    Dawson, W.; Moser, D.; van Kleunen, M.; Kreft, H.; Pergl, Jan; Pyšek, Petr; Weigelt, P.; Winter, M.; Lenzner, B.; Blackburn, T. M.; Dyer, E. E.; Cassey, P.; Scrivens, S. L.; Economo, E. P.; Guénard, B.; Capinha, C.; Seebens, H.; García-Díaz, P.; Nentwig, W.; García-Berthou, E.; Casal, C.; Mandrak, N. E.; Fuller, P.; Meyer, C.; Essl, F.

    2017-01-01

    Roč. 1, č. 7 (2017), s. 1-7, č. článku no.0186. E-ISSN 2397-334X R&D Projects: GA ČR GB14-36079G Grant - others:AV ČR(CZ) AP1002; COST(XE) TD1209 Program:Akademická prémie - Praemium Academiae; FA Institutional support: RVO:67985939 Keywords : biological invasions * plants and animals * global patterns Subject RIV: EH - Ecology, Behaviour OBOR OECD: Ecology

  2. 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

  3. 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.

  4. Independent Origin and Global Distribution of Distinct Plasmodium vivax Duffy Binding Protein Gene Duplications.

    Directory of Open Access Journals (Sweden)

    Jessica B Hostetler

    2016-10-01

    Full Text Available Plasmodium vivax causes the majority of malaria episodes outside Africa, but remains a relatively understudied pathogen. The pathology of P. vivax infection depends critically on the parasite's ability to recognize and invade human erythrocytes. This invasion process involves an interaction between P. vivax Duffy Binding Protein (PvDBP in merozoites and the Duffy antigen receptor for chemokines (DARC on the erythrocyte surface. Whole-genome sequencing of clinical isolates recently established that some P. vivax genomes contain two copies of the PvDBP gene. The frequency of this duplication is particularly high in Madagascar, where there is also evidence for P. vivax infection in DARC-negative individuals. The functional significance and global prevalence of this duplication, and whether there are other copy number variations at the PvDBP locus, is unknown.Using whole-genome sequencing and PCR to study the PvDBP locus in P. vivax clinical isolates, we found that PvDBP duplication is widespread in Cambodia. The boundaries of the Cambodian PvDBP duplication differ from those previously identified in Madagascar, meaning that current molecular assays were unable to detect it. The Cambodian PvDBP duplication did not associate with parasite density or DARC genotype, and ranged in prevalence from 20% to 38% over four annual transmission seasons in Cambodia. This duplication was also present in P. vivax isolates from Brazil and Ethiopia, but not India.PvDBP duplications are much more widespread and complex than previously thought, and at least two distinct duplications are circulating globally. The same duplication boundaries were identified in parasites from three continents, and were found at high prevalence in human populations where DARC-negativity is essentially absent. It is therefore unlikely that PvDBP duplication is associated with infection of DARC-negative individuals, but functional tests will be required to confirm this hypothesis.

  5. Adult onset global loss of the fto gene alters body composition and metabolism in the mouse.

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    Fiona McMurray

    Full Text Available The strongest BMI-associated GWAS locus in humans is the FTO gene. Rodent studies demonstrate a role for FTO in energy homeostasis and body composition. The phenotypes observed in loss of expression studies are complex with perinatal lethality, stunted growth from weaning, and significant alterations in body composition. Thus understanding how and where Fto regulates food intake, energy expenditure, and body composition is a challenge. To address this we generated a series of mice with distinct temporal and spatial loss of Fto expression. Global germline loss of Fto resulted in high perinatal lethality and a reduction in body length, fat mass, and lean mass. When ratio corrected for lean mass, mice had a significant increase in energy expenditure, but more appropriate multiple linear regression normalisation showed no difference in energy expenditure. Global deletion of Fto after the in utero and perinatal period, at 6 weeks of age, removed the high lethality of germline loss. However, there was a reduction in weight by 9 weeks, primarily as loss of lean mass. Over the subsequent 10 weeks, weight converged, driven by an increase in fat mass. There was a switch to a lower RER with no overall change in food intake or energy expenditure. To test if the phenotype can be explained by loss of Fto in the mediobasal hypothalamus, we sterotactically injected adeno-associated viral vectors encoding Cre recombinase to cause regional deletion. We observed a small reduction in food intake and weight gain with no effect on energy expenditure or body composition. Thus, although hypothalamic Fto can impact feeding, the effect of loss of Fto on body composition is brought about by its actions at sites elsewhere. Our data suggest that Fto may have a critical role in the control of lean mass, independent of its effect on food intake.

  6. 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....

  7. Efficiency and cross-correlation in equity market during global financial crisis: Evidence from China

    Science.gov (United States)

    Ma, Pengcheng; Li, Daye; Li, Shuo

    2016-02-01

    Using one minute high-frequency data of the Shanghai Composite Index (SHCI) and the Shenzhen Composite Index (SZCI) (2007-2008), we employ the detrended fluctuation analysis (DFA) and the detrended cross correlation analysis (DCCA) with rolling window approach to observe the evolution of market efficiency and cross-correlation in pre-crisis and crisis period. Considering the fat-tail distribution of return time series, statistical test based on shuffling method is conducted to verify the null hypothesis of no long-term dependence. Our empirical research displays three main findings. First Shanghai equity market efficiency deteriorated while Shenzhen equity market efficiency improved with the advent of financial crisis. Second the highly positive dependence between SHCI and SZCI varies with time scale. Third financial crisis saw a significant increase of dependence between SHCI and SZCI at shorter time scales but a lack of significant change at longer time scales, providing evidence of contagion and absence of interdependence during crisis.

  8. 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.

  9. Antibiotics and antibiotic resistance genes in global lakes: A review and meta-analysis.

    Science.gov (United States)

    Yang, Yuyi; Song, Wenjuan; Lin, Hui; Wang, Weibo; Du, Linna; Xing, Wei

    2018-04-10

    Lakes are an important source of freshwater, containing nearly 90% of the liquid surface fresh water worldwide. Long retention times in lakes mean pollutants from discharges slowly circulate around the lakes and may lead to high ecological risk for ecosystem and human health. In recent decades, antibiotics and antibiotic resistance genes (ARGs) have been regarded as emerging pollutants. The occurrence and distribution of antibiotics and ARGs in global freshwater lakes are summarized to show the pollution level of antibiotics and ARGs and to identify some of the potential risks to ecosystem and human health. Fifty-seven antibiotics were reported at least once in the studied lakes. Our meta-analysis shows that sulfamethoxazole, sulfamerazine, sulfameter, tetracycline, oxytetracycline, erythromycin, and roxithromycin were found at high concentrations in both lake water and lake sediment. There is no significant difference in the concentration of sulfonamides in lake water from China and that from other countries worldwide; however, there was a significant difference in quinolones. Erythromycin had the lowest predicted hazardous concentration for 5% of the species (HC 5 ) and the highest ecological risk in lakes. There was no significant difference in the concentration of sulfonamide resistance genes (sul1 and sul2) in lake water and river water. There is surprisingly limited research on the role of aquatic biota in propagation of ARGs in freshwater lakes. As an environment that is susceptible to cumulative build-up of pollutants, lakes provide an important environment to study the fate of antibiotics and transport of ARGs with a broad range of niches including bacterial community, aquatic plants and animals. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

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    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.

  11. Prediction of essential proteins based on subcellular localization and gene expression correlation.

    Science.gov (United States)

    Fan, Yetian; Tang, Xiwei; Hu, Xiaohua; Wu, Wei; Ping, Qing

    2017-12-01

    Essential proteins are indispensable to the survival and development process of living organisms. To understand the functional mechanisms of essential proteins, which can be applied to the analysis of disease and design of drugs, it is important to identify essential proteins from a set of proteins first. As traditional experimental methods designed to test out essential proteins are usually expensive and laborious, computational methods, which utilize biological and topological features of proteins, have attracted more attention in recent years. Protein-protein interaction networks, together with other biological data, have been explored to improve the performance of essential protein prediction. The proposed method SCP is evaluated on Saccharomyces cerevisiae datasets and compared with five other methods. The results show that our method SCP outperforms the other five methods in terms of accuracy of essential protein prediction. In this paper, we propose a novel algorithm named SCP, which combines the ranking by a modified PageRank algorithm based on subcellular compartments information, with the ranking by Pearson correlation coefficient (PCC) calculated from gene expression data. Experiments show that subcellular localization information is promising in boosting essential protein prediction.

  12. Genes: Interactions with Language on Three Levels—Inter-Individual Variation, Historical Correlations and Genetic Biasing

    Science.gov (United States)

    Dediu, Dan

    The complex inter-relationships between genetics and linguistics encompass all four scales highlighted by the contributions to this book and, together with cultural transmission, the genetics of language holds the promise to offer a unitary understanding of this fascinating phenomenon. There are inter-individual differences in genetic makeup which contribute to the obvious fact that we are not identical in the way we understand and use language and, by studying them, we will be able to both better treat and enhance ourselves. There are correlations between the genetic configuration of human groups and their languages, reflecting the historical processes shaping them, and there also seem to exist genes which can influence some characteristics of language, biasing it towards or against certain states by altering the way language is transmitted across generations. Besides the joys of pure knowledge, the understanding of these three aspects of genetics relevant to language will potentially trigger advances in medicine, linguistics, psychology or the understanding of our own past and, last but not least, a profound change in the way we regard one of the emblems of being human: our capacity for language.

  13. 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

  14. 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.

  15. Global diversification of a tropical plant growth form: environmental correlates and historical contingencies in climbing palms.

    Science.gov (United States)

    Couvreur, Thomas L P; Kissling, W Daniel; Condamine, Fabien L; Svenning, Jens-Christian; Rowe, Nick P; Baker, William J

    2014-01-01

    Tropical rain forests (TRF) are the most diverse terrestrial biome on Earth, but the diversification dynamics of their constituent growth forms remain largely unexplored. Climbing plants contribute significantly to species diversity and ecosystem processes in TRF. We investigate the broad-scale patterns and drivers of species richness as well as the diversification history of climbing and non-climbing palms (Arecaceae). We quantify to what extent macroecological diversity patterns are related to contemporary climate, forest canopy height, and paleoclimatic changes. We test whether diversification rates are higher for climbing than non-climbing palms and estimate the origin of the climbing habit. Climbers account for 22% of global palm species diversity, mostly concentrated in Southeast Asia. Global variation in climbing palm species richness can be partly explained by past and present-day climate and rain forest canopy height, but regional differences in residual species richness after accounting for current and past differences in environment suggest a strong role of historical contingencies in climbing palm diversification. Climbing palms show a higher net diversification rate than non-climbers. Diversification analyses of palms detected a diversification rate increase along the branches leading to the most species-rich clade of climbers. Ancestral character reconstructions revealed that the climbing habit originated between early Eocene and Miocene. These results imply that changes from non-climbing to climbing habits may have played an important role in palm diversification, resulting in the origin of one fifth of all palm species. We suggest that, in addition to current climate and paleoclimatic changes after the late Neogene, present-day diversity of climbing palms can be explained by morpho-anatomical innovations, the biogeographic history of Southeast Asia, and/or ecological opportunities due to the diversification of high-stature dipterocarps in Asian TRFs.

  16. Extensive gene content variation in the Brachypodium distachyon pan-genome correlates with population structure.

    Science.gov (United States)

    Gordon, Sean P; Contreras-Moreira, Bruno; Woods, Daniel P; Des Marais, David L; Burgess, Diane; Shu, Shengqiang; Stritt, Christoph; Roulin, Anne C; Schackwitz, Wendy; Tyler, Ludmila; Martin, Joel; Lipzen, Anna; Dochy, Niklas; Phillips, Jeremy; Barry, Kerrie; Geuten, Koen; Budak, Hikmet; Juenger, Thomas E; Amasino, Richard; Caicedo, Ana L; Goodstein, David; Davidson, Patrick; Mur, Luis A J; Figueroa, Melania; Freeling, Michael; Catalan, Pilar; Vogel, John P

    2017-12-19

    While prokaryotic pan-genomes have been shown to contain many more genes than any individual organism, the prevalence and functional significance of differentially present genes in eukaryotes remains poorly understood. Whole-genome de novo assembly and annotation of 54 lines of the grass Brachypodium distachyon yield a pan-genome containing nearly twice the number of genes found in any individual genome. Genes present in all lines are enriched for essential biological functions, while genes present in only some lines are enriched for conditionally beneficial functions (e.g., defense and development), display faster evolutionary rates, lie closer to transposable elements and are less likely to be syntenic with orthologous genes in other grasses. Our data suggest that differentially present genes contribute substantially to phenotypic variation within a eukaryote species, these genes have a major influence in population genetics, and transposable elements play a key role in pan-genome evolution.

  17. [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.

  18. 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.

  19. 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'…

  20. 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

  1. 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.

  2. Characterization of the global profile of genes expressed in cervical epithelium by Serial Analysis of Gene Expression (SAGE

    Directory of Open Access Journals (Sweden)

    Piña-Sanchez Patricia

    2005-09-01

    Full Text Available Abstract Background Serial Analysis of Gene Expression (SAGE is a new technique that allows a detailed and profound quantitative and qualitative knowledge of gene expression profile, without previous knowledge of sequence of analyzed genes. We carried out a modification of SAGE methodology (microSAGE, useful for the analysis of limited quantities of tissue samples, on normal human cervical tissue obtained from a donor without histopathological lesions. Cervical epithelium is constituted mainly by cervical keratinocytes which are the targets of human papilloma virus (HPV, where persistent HPV infection of cervical epithelium is associated with an increase risk for developing cervical carcinomas (CC. Results We report here a transcriptome analysis of cervical tissue by SAGE, derived from 30,418 sequenced tags that provide a wealth of information about the gene products involved in normal cervical epithelium physiology, as well as genes not previously found in uterine cervix tissue involved in the process of epidermal differentiation. Conclusion This first comprehensive and profound analysis of uterine cervix transcriptome, should be useful for the identification of genes involved in normal cervix uterine function, and candidate genes associated with cervical carcinoma.

  3. "Every Gene Is Everywhere but the Environment Selects": Global Geolocalization of Gene Sharing in Environmental Samples through Network Analysis.

    Science.gov (United States)

    Fondi, Marco; Karkman, Antti; Tamminen, Manu V; Bosi, Emanuele; Virta, Marko; Fani, Renato; Alm, Eric; McInerney, James O

    2016-05-13

    The spatial distribution of microbes on our planet is famously formulated in the Baas Becking hypothesis as "everything is everywhere but the environment selects." While this hypothesis does not strictly rule out patterns caused by geographical effects on ecology and historical founder effects, it does propose that the remarkable dispersal potential of microbes leads to distributions generally shaped by environmental factors rather than geographical distance. By constructing sequence similarity networks from uncultured environmental samples, we show that microbial gene pool distributions are not influenced nearly as much by geography as ecology, thus extending the Bass Becking hypothesis from whole organisms to microbial genes. We find that gene pools are shaped by their broad ecological niche (such as sea water, fresh water, host, and airborne). We find that freshwater habitats act as a gene exchange bridge between otherwise disconnected habitats. Finally, certain antibiotic resistance genes deviate from the general trend of habitat specificity by exhibiting a high degree of cross-habitat mobility. The strong cross-habitat mobility of antibiotic resistance genes is a cause for concern and provides a paradigmatic example of the rate by which genes colonize new habitats when new selective forces emerge. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  4. Trans-Pacific ENSO teleconnections pose a correlated risk to global agriculture

    Science.gov (United States)

    Anderson, W. B.; Seager, R.; Cane, M. A.; Baethgen, W.

    2017-12-01

    The El Niño Southern Oscillation (ENSO) is a major source of interannual climate variability, particularly in the Pacific Basin. ENSO life-cycles tend to evolve over multiple years, as do the associated trans-Pacific ENSO teleconnections. This analysis, however, represents the first attempt to characterize the structure of the risk posed by ENSO to wheat, maize and soybean production across the Pacific Basin. Our results indicate that most ENSO teleconnections relevant for crop flowering seasons are the result of a single trans-Pacific circulation anomaly that develops in boreal summer and persists through the spring. During the late summer and early fall of a developing ENSO event, the tropical Pacific forces an atmospheric anomaly in the midlatitudes that spans the Pacific Basin. This teleconnection directly links the soybean and maize growing seasons of the US, Mexico and China. It also connects the wheat growing seasons of Argentina, southern Brazil and Australia. The ENSO event peaks in boreal winter, when the atmospheric circulation anomalies intensify and affect maize and soybeans in southeast South America. As the event decays, the ENSO-induced circulation anomalies persist through the wheat flowering seasons in China and the US. While the prospect of ENSO forcing simultaneous droughts in major food producing regions seems disastrous, there may be a silver lining from the perspective of global food security: trans-Pacific ENSO teleconnections to yields are often offsetting between major producing regions in the eastern and western portions of the Pacific Basin. El Niños tend to create good maize and soybean growing conditions in the US and southeast South America, but poor growing conditions in China, Mexico and northeast Brazil. The opposite is true during La Niña. Wheat growing conditions in southeast South America generally have the opposite sign of those in Australia. Finally, we investigate how trade networks interact with this structure of ENSO

  5. Global Pattern of Nasopharyngeal Cancer: Correlation of Outcome With Access to Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lam, Ka-On [Clinical Oncology Center, University of Hong Kong-Shenzhen Hospital, Shenzhen (China); Lee, Anne W.M., E-mail: annelee@hku-szh.org [Clinical Oncology Center, University of Hong Kong-Shenzhen Hospital, Shenzhen (China); Choi, Cheuk-Wai [Department of Systems Engineering and Engineering Management, City University of Hong Kong, Hong Kong (China); Sze, Henry C.K. [Clinical Oncology Center, University of Hong Kong-Shenzhen Hospital, Shenzhen (China); Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Hopkins, Kirsten I.; Rosenblatt, Eduardo [International Atomic Energy Agency, Vienna (Austria)

    2016-04-01

    Purpose: This study aimed to estimate the treatment outcome of nasopharyngeal cancer (NPC) across the world and its correlation with access to radiation therapy (RT). Methods and Materials: The age-standardized mortality (ASM) and age-standardized incidence (ASI) rates of NPC from GLOBOCAN (2012) were summarized, and [1−(ASM/ASI)] was computed to give the proxy relative survival (RS). Data from the International Atomic Energy Agency (IAEA) and the World Bank were used to assess the availability of RT in surrogate terms: the number of RT equipment units and radiation oncologists per million population. Results: A total of 112 countries with complete valid data were analyzed, and the proxy RS varied widely from 0% to 83% (median, 50%). Countries were categorized into Good, Median, and Poor outcome groups on the basis of their proxy RS (<45%, 45%-55%, and >55%). Eighty percent of new cases occurred in the Poor outcome group. Univariable linear regression showed a significant correlation between outcome and the availability of RT: proxy RS increased at 3.4% (P<.001) and 1.5% (P=.001) per unit increase in RT equipment and oncologist per million population, respectively. The median number of RT equipment units per million population increased significantly from 0.5 in the Poor, to 1.5 in the Median, to 4.6 in the Good outcome groups, and the corresponding number of oncologists increased from 1.1 to 3.3 to 7.1 (P<.001). Conclusions: Nasopharyngeal cancer is a highly treatable disease, but the outcome varies widely across the world. The current study shows a significant correlation between survival and access to RT based on available surrogate indicators. However, the possible reasons for poor outcome are likely to be multifactorial and complex. Concerted international efforts are needed not only to address the fundamental requirement for adequate RT access but also to obtain more comprehensive and accurate data for research to improve cancer outcome.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Obesity in BSB mice is correlated with expression of genes foriron homeostasis and leptin

    Energy Technology Data Exchange (ETDEWEB)

    Farahani, Poupak; Chiu, Sally; Bowlus, Christopher L.; Boffelli,Dario; Lee, Eric; Fisler, Janis S.; Krauss, Ronald M.; Warden, Craig H.

    2003-04-01

    Obesity is a complex disease. To date, over 100 chromosomal loci for body weight, body fat, regional white adipose tissue weight, and other obesity-related traits have been identified in humans and in animal models. For most loci, the underlying genes are not yet identified; some of these chromosomal loci will be alleles of known obesity genes, whereas many will represent alleles of unknown genes. Microarray analysis allows simultaneous multiple gene and pathway discovery. cDNA and oligonucleotide arrays are commonly used to identify differentially expressed genes by surveys of large numbers of known and unnamed genes. Two papers previously identified genes differentially expressed in adipose tissue of mouse models of obesity and diabetes by analysis of hybridization to Affymetrix oligonucleotide chips.

  11. Automatic extraction of gene ontology annotation and its correlation with clusters in protein networks

    Directory of Open Access Journals (Sweden)

    Mazo Ilya

    2007-07-01

    Full Text Available Abstract Background Uncovering cellular roles of a protein is a task of tremendous importance and complexity that requires dedicated experimental work as well as often sophisticated data mining and processing tools. Protein functions, often referred to as its annotations, are believed to manifest themselves through topology of the networks of inter-proteins interactions. In particular, there is a growing body of evidence that proteins performing the same function are more likely to interact with each other than with proteins with other functions. However, since functional annotation and protein network topology are often studied separately, the direct relationship between them has not been comprehensively demonstrated. In addition to having the general biological significance, such demonstration would further validate the data extraction and processing methods used to compose protein annotation and protein-protein interactions datasets. Results We developed a method for automatic extraction of protein functional annotation from scientific text based on the Natural Language Processing (NLP technology. For the protein annotation extracted from the entire PubMed, we evaluated the precision and recall rates, and compared the performance of the automatic extraction technology to that of manual curation used in public Gene Ontology (GO annotation. In the second part of our presentation, we reported a large-scale investigation into the correspondence between communities in the literature-based protein networks and GO annotation groups of functionally related proteins. We found a comprehensive two-way match: proteins within biological annotation groups form significantly denser linked network clusters than expected by chance and, conversely, densely linked network communities exhibit a pronounced non-random overlap with GO groups. We also expanded the publicly available GO biological process annotation using the relations extracted by our NLP technology

  12. Cross-species global and subset gene expression profiling identifies genes involved in prostate cancer response to selenium

    Directory of Open Access Journals (Sweden)

    Dhir Rajiv

    2004-08-01

    Full Text Available Abstract Background Gene expression technologies have the ability to generate vast amounts of data, yet there often resides only limited resources for subsequent validation studies. This necessitates the ability to perform sorting and prioritization of the output data. Previously described methodologies have used functional pathways or transcriptional regulatory grouping to sort genes for further study. In this paper we demonstrate a comparative genomics based method to leverage data from animal models to prioritize genes for validation. This approach allows one to develop a disease-based focus for the prioritization of gene data, a process that is essential for systems that lack significant functional pathway data yet have defined animal models. This method is made possible through the use of highly controlled spotted cDNA slide production and the use of comparative bioinformatics databases without the use of cross-species slide hybridizations. Results Using gene expression profiling we have demonstrated a similar whole transcriptome gene expression patterns in prostate cancer cells from human and rat prostate cancer cell lines both at baseline expression levels and after treatment with physiologic concentrations of the proposed chemopreventive agent Selenium. Using both the human PC3 and rat PAII prostate cancer cell lines have gone on to identify a subset of one hundred and fifty-four genes that demonstrate a similar level of differential expression to Selenium treatment in both species. Further analysis and data mining for two genes, the Insulin like Growth Factor Binding protein 3, and Retinoic X Receptor alpha, demonstrates an association with prostate cancer, functional pathway links, and protein-protein interactions that make these genes prime candidates for explaining the mechanism of Selenium's chemopreventive effect in prostate cancer. These genes are subsequently validated by western blots showing Selenium based induction and using

  13. Decreased blood riboflavin levels are correlated with defective expression of RFT2 gene in gastric cancer

    Science.gov (United States)

    Eli, Maynur; Li, De-Sheng; Zhang, Wei-Wei; Kong, Bing; Du, Chen-Song; Wumar, Maimaitiaili; Mamtimin, Batur; Sheyhidin, Ilyar; Hasim, Ayshamgul

    2012-01-01

    AIM: To investigate the relationship between blood riboflavin levels and riboflavin transporter 2 (RFT2) gene expression in gastric carcinoma (GC) development. METHODS: High-performance liquid chromatography was used to detect blood riboflavin levels in patients with GC. Real-time fluorogenic quantitative polymerase chain reaction and immunohistochemistry were used to analyze the expression of RFT2 mRNA and protein in samples from 60 GC patients consisting of both tumor and normal tissue. RESULTS: A significant decrease in the RFT2 mRNA levels was detected in GC samples compared with those in the normal mucous membrane (0.398 ± 0.149 vs 1.479 ± 0.587; P = 0.040). Tumors exhibited low RFT2 protein expression (75%, 16.7%, 8.3% and 0% for no RFT2 staining, weak staining, medium staining and strong staining, respectively), which was significantly lower than that in the normal mucous membrane (10%, 16.7%, 26.7% and 46.7% for no RFT2 staining, weak staining, medium staining and strong staining, respectively; P riboflavin levels were reverse correlated with development of GC (1.2000 ± 0.97 569 ng/mL in high tumor stage patients vs 2.5980 ± 1.31 129 ng/mL in low tumor stage patients; P riboflavin levels with defective expression of RFT2 protein was found in GC patients (χ2 = 2.619; P = 0.019). CONCLUSION: Defective expression of RFT2 is associated with the development of GC and this may represent a mechanism underlying the decreased plasma riboflavin levels in GC. PMID:22791947

  14. Fractures of the proximal femur: correlation with vitamin D receptor gene polymorphism

    Directory of Open Access Journals (Sweden)

    A.C. Ramalho

    1998-07-01

    Full Text Available Fractures are the feared consequences of osteoporosis and fractures of the proximal femur (FPF are those that involve the highest morbidity and mortality. Thus far, evaluation of bone mineral density (BMD is the best way to determine the risk of fracture. Genetic inheritance, in turn, is one of the major determinants of BMD. A correlation between different genotypes of the vitamin D receptor (VDR and BMD has been recently reported. On this basis, we decided to determine the importance of the determination of VDR genotype in the presence of an osteoporotic FPF in a Brazilian population. We studied three groups: group I consisted of 73 elderly subjects older than 65 years (78.5 ± 7.2 years hospitalized for nonpathological FPF; group II consisted of 50 individuals older than 65 years (72.9 ± 5.2 years without FPF and group III consisted of 98 young normal Brazilian individuals aged 32.6 ± 6.6 years (mean ± SD. Analysis of VDR gene polymorphism by restriction fragment length polymorphism (RFLP was performed by PCR amplification followed by BsmI digestion of DNA isolated from peripheral leukocytes. The genotype distribution in group I was 20.5% BB, 42.5% Bb and 37% bb and did not differ significantly from the values obtained for group II (16% BB, 36% Bb and 48% bb or for group III (10.2% BB, 47.6% Bb and 41.8% bb. No differences in genotype distribution were observed between sexes or between the young and elderly groups. We conclude that determination of VDR polymorphism is of no practical use for the prediction of FPF. Other nongenetic factors probably start to affect bone mass, the risk to fall and consequently the occurrence of osteoporotic fractures with advancing age.

  15. Correlation of expression of BP1, a homeobox gene, with estrogen receptor status in breast cancer

    International Nuclear Information System (INIS)

    Fu, Sidney W; Poola, Indira; Stephan, Dietrich A; Berg, Patricia E; Schwartz, Arnold; Stevenson, Holly; Pinzone, Joseph J; Davenport, Gregory J; Orenstein, Jan M; Gutierrez, Peter; Simmens, Samuel J; Abraham, Jessy

    2003-01-01

    BP1 is a novel homeobox gene cloned in our laboratory. Our previous studies in leukemia demonstrated that BP1 has oncogenic properties, including as a modulator of cell survival. Here BP1 expression was examined in breast cancer, and the relationship between BP1 expression and clinicopathological data was determined. Total RNA was isolated from cell lines, tumors, and matched normal adjacent tissue or tissue from autopsy. Reverse transcription polymerase chain reaction was performed to evaluate BP1 expression. Statistical analysis was accomplished with SAS. Analysis of 46 invasive ductal breast tumors demonstrated BP1 expression in 80% of them, compared with a lack of expression in six normal breast tissues and low-level expression in one normal breast tissue. Remarkably, 100% of tumors that were negative for the estrogen receptor (ER) were BP1-positive, whereas 73% of ER-positive tumors expressed BP1 (P = 0.03). BP1 expression was also associated with race: 89% of the tumors of African American women were BP1-positive, whereas 57% of those from Caucasian women expressed BP1 (P = 0.04). However, there was no significant difference in BP1 expression between grades I, II, and III tumors. Interestingly, BP1 mRNA expression was correlated with the ability of malignant cell lines to cause breast cancer in mice. Because BP1 is expressed abnormally in breast tumors, it could provide a useful target for therapy, particularly in patients with ER-negative tumors. The frequent expression of BP1 in all tumor grades suggests that activation of BP1 is an early event

  16. 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.

  17. 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

  18. 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.

  19. 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...

  20. 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.

  1. Global Gene Expression Analysis of Cross-Protected Phenotype of Pectobacterium atrosepticum.

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    Vladimir Gorshkov

    Full Text Available The ability to adapt to adverse conditions permits many bacterial species to be virtually ubiquitous and survive in a variety of ecological niches. This ability is of particular importance for many plant pathogenic bacteria that should be able to exist, except for their host plants, in different environments e.g. soil, water, insect-vectors etc. Under some of these conditions, bacteria encounter absence of nutrients and persist, acquiring new properties related to resistance to a variety of stress factors (cross-protection. Although many studies describe the phenomenon of cross-protection and several regulatory components that induce the formation of resistant cells were elucidated, the global comparison of the physiology of cross-protected phenotype and growing cells has not been performed. In our study, we took advantage of RNA-Seq technology to gain better insights into the physiology of cross-protected cells on the example of a harmful phytopathogen, Pectobacterium atrosepticum (Pba that causes crop losses all over the world. The success of this bacterium in plant colonization is related to both its virulence potential and ability to persist effectively under various stress conditions (including nutrient deprivation retaining the ability to infect plants afterwards. In our previous studies, we showed Pba to be advanced in applying different adaptive strategies that led to manifestation of cell resistance to multiple stress factors. In the present study, we determined the period necessary for the formation of cross-protected Pba phenotype under starvation conditions, and compare the transcriptome profiles of non-adapted growing cells and of adapted cells after the cross-protective effect has reached the maximal level. The obtained data were verified using qRT-PCR. Genes that were expressed differentially (DEGs in two cell types were classified into functional groups and categories using different approaches. As a result, we portrayed

  2. Sexuality generates diversity in the aflatoxin gene cluster: evidence on a global scale.

    Directory of Open Access Journals (Sweden)

    Geromy G Moore

    Full Text Available Aflatoxins are produced by Aspergillus flavus and A. parasiticus in oil-rich seed and grain crops and are a serious problem in agriculture, with aflatoxin B₁ being the most carcinogenic natural compound known. Sexual reproduction in these species occurs between individuals belonging to different vegetative compatibility groups (VCGs. We examined natural genetic variation in 758 isolates of A. flavus, A. parasiticus and A. minisclerotigenes sampled from single peanut fields in the United States (Georgia, Africa (Benin, Argentina (Córdoba, Australia (Queensland and India (Karnataka. Analysis of DNA sequence variation across multiple intergenic regions in the aflatoxin gene clusters of A. flavus, A. parasiticus and A. minisclerotigenes revealed significant linkage disequilibrium (LD organized into distinct blocks that are conserved across different localities, suggesting that genetic recombination is nonrandom and a global occurrence. To assess the contributions of asexual and sexual reproduction to fixation and maintenance of toxin chemotype diversity in populations from each locality/species, we tested the null hypothesis of an equal number of MAT1-1 and MAT1-2 mating-type individuals, which is indicative of a sexually recombining population. All samples were clone-corrected using multi-locus sequence typing which associates closely with VCG. For both A. flavus and A. parasiticus, when the proportions of MAT1-1 and MAT1-2 were significantly different, there was more extensive LD in the aflatoxin cluster and populations were fixed for specific toxin chemotype classes, either the non-aflatoxigenic class in A. flavus or the B₁-dominant and G₁-dominant classes in A. parasiticus. A mating type ratio close to 1∶1 in A. flavus, A. parasiticus and A. minisclerotigenes was associated with higher recombination rates in the aflatoxin cluster and less pronounced chemotype differences in populations. This work shows that the reproductive nature of

  3. 3D spatially-adaptive canonical correlation analysis: Local and global methods.

    Science.gov (United States)

    Yang, Zhengshi; Zhuang, Xiaowei; Sreenivasan, Karthik; Mishra, Virendra; Curran, Tim; Byrd, Richard; Nandy, Rajesh; Cordes, Dietmar

    2018-04-01

    Local spatially-adaptive canonical correlation analysis (local CCA) with spatial constraints has been introduced to fMRI multivariate analysis for improved modeling of activation patterns. However, current algorithms require complicated spatial constraints that have only been applied to 2D local neighborhoods because the computational time would be exponentially increased if the same method is applied to 3D spatial neighborhoods. In this study, an efficient and accurate line search sequential quadratic programming (SQP) algorithm has been developed to efficiently solve the 3D local CCA problem with spatial constraints. In addition, a spatially-adaptive kernel CCA (KCCA) method is proposed to increase accuracy of fMRI activation maps. With oriented 3D spatial filters anisotropic shapes can be estimated during the KCCA analysis of fMRI time courses. These filters are orientation-adaptive leading to rotational invariance to better match arbitrary oriented fMRI activation patterns, resulting in improved sensitivity of activation detection while significantly reducing spatial blurring artifacts. The kernel method in its basic form does not require any spatial constraints and analyzes the whole-brain fMRI time series to construct an activation map. Finally, we have developed a penalized kernel CCA model that involves spatial low-pass filter constraints to increase the specificity of the method. The kernel CCA methods are compared with the standard univariate method and with two different local CCA methods that were solved by the SQP algorithm. Results show that SQP is the most efficient algorithm to solve the local constrained CCA problem, and the proposed kernel CCA methods outperformed univariate and local CCA methods in detecting activations for both simulated and real fMRI episodic memory data. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease.

    Science.gov (United States)

    Modena, Brian D; Bleecker, Eugene R; Busse, William W; Erzurum, Serpil C; Gaston, Benjamin M; Jarjour, Nizar N; Meyers, Deborah A; Milosevic, Jadranka; Tedrow, John R; Wu, Wei; Kaminski, Naftali; Wenzel, Sally E

    2017-06-01

    Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Identify networks of genes reflective of underlying biological processes that define SA. Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12-21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes.

  5. 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).

  6. Toxoplasmosis – A Global Threat. Correlation of Latent Toxoplasmosis with Specific Disease Burden in a Set of 88 Countries

    Science.gov (United States)

    Flegr, Jaroslav; Prandota, Joseph; Sovičková, Michaela; Israili, Zafar H.

    2014-01-01

    Background Toxoplasmosis is becoming a global health hazard as it infects 30–50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this ‘asymptomatic infection’ may also lead to development of other human pathologies. Aims of the Study The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries. Methods and Findings Prevalence data published between 1995–2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (ptoxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented. Conclusions The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more

  7. Toxoplasmosis--a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries.

    Science.gov (United States)

    Flegr, Jaroslav; Prandota, Joseph; Sovičková, Michaela; Israili, Zafar H

    2014-01-01

    Toxoplasmosis is becoming a global health hazard as it infects 30-50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this 'asymptomatic infection' may also lead to development of other human pathologies. The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries. Prevalence data published between 1995-2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (ptoxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented. The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more attention and financial support both in everyday medical practice and

  8. Chronology of Eocene-Miocene sequences on the New Jersey shallow shelf: implications for regional, interregional, and global correlations

    Science.gov (United States)

    Browning, James V.; Miller, Kenneth G.; Sugarman, Peter J.; Barron, John; McCarthy, Francine M.G.; Kulhanek, Denise K.; Katz, Miriam E.; Feigenson, Mark D.

    2013-01-01

    Integrated Ocean Drilling Program Expedition 313 continuously cored and logged latest Eocene to early-middle Miocene sequences at three sites (M27, M28, and M29) on the inner-middle continental shelf offshore New Jersey, providing an opportunity to evaluate the ages, global correlations, and significance of sequence boundaries. We provide a chronology for these sequences using integrated strontium isotopic stratigraphy and biostratigraphy (primarily calcareous nannoplankton, diatoms, and dinocysts [dinoflagellate cysts]). Despite challenges posed by shallow-water sediments, age resolution is typically ±0.5 m.y. and in many sequences is as good as ±0.25 m.y. Three Oligocene sequences were sampled at Site M27 on sequence bottomsets. Fifteen early to early-middle Miocene sequences were dated at Sites M27, M28, and M29 across clinothems in topsets, foresets (where the sequences are thickest), and bottomsets. A few sequences have coarse (∼1 m.y.) or little age constraint due to barren zones; we constrain the age estimates of these less well dated sequences by applying the principle of superposition, i.e., sediments above sequence boundaries in any site are younger than the sediments below the sequence boundaries at other sites. Our age control provides constraints on the timing of deposition in the clinothem; sequences on the topsets are generally the youngest in the clinothem, whereas the bottomsets generally are the oldest. The greatest amount of time is represented on foresets, although we have no evidence for a correlative conformity. Our chronology provides a baseline for regional and interregional correlations and sea-level reconstructions: (1) we correlate a major increase in sedimentation rate precisely with the timing of the middle Miocene climate changes associated with the development of a permanent East Antarctic Ice Sheet; and (2) the timing of sequence boundaries matches the deep-sea oxygen isotopic record, implicating glacioeustasy as a major driver

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

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    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

  10. 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

  11. Correlation between Left Ventricular Global and Regional Longitudinal Systolic Strain and Impaired Microcirculation in Patients with Acute Myocardial Infarction

    DEFF Research Database (Denmark)

    Løgstrup, Brian B; Høfsten, Dan Eik; Christophersen, Thomas Brøcher

    2012-01-01

    investigated if LRS and GLS imaging is superior to conventional measures of left ventricle (LV) function. Methods: In a consecutive population of first time AMI patients, who underwent successful revascularization, we performed comprehensive TTE. GLS and LRS were obtained from the three standard apical views...... elevation myocardial infarction. The GLS was -15.2 [-19.3;-10.1]% in the total population of 183 patients. Total wall motion score index (WMSI) in the population was 1.19 [1;1.5]. Eighty-five patients suffered from culprit lesion in left anterior descending artery (LAD). The CFR in these patients was 1......Objectives: We investigated the correlation between left ventricular global and regional longitudinal systolic strain (GLS and LRS) and coronary flow reserve (CFR) assessed by transthoracic echocardiography (TTE) in patients with a recent acute myocardial infarction (AMI). Furthermore, we...

  12. Global gene expression analysis of apple fruit development from the floral bud to ripe fruit

    Directory of Open Access Journals (Sweden)

    McArtney Steve

    2008-02-01

    Full Text Available Abstract Background Apple fruit develop over a period of 150 days from anthesis to fully ripe. An array representing approximately 13000 genes (15726 oligonucleotides of 45–55 bases designed from apple ESTs has been used to study gene expression over eight time points during fruit development. This analysis of gene expression lays the groundwork for a molecular understanding of fruit growth and development in apple. Results Using ANOVA analysis of the microarray data, 1955 genes showed significant changes in expression over this time course. Expression of genes is coordinated with four major patterns of expression observed: high in floral buds; high during cell division; high when starch levels and cell expansion rates peak; and high during ripening. Functional analysis associated cell cycle genes with early fruit development and three core cell cycle genes are significantly up-regulated in the early stages of fruit development. Starch metabolic genes were associated with changes in starch levels during fruit development. Comparison with microarrays of ethylene-treated apple fruit identified a group of ethylene induced genes also induced in normal fruit ripening. Comparison with fruit development microarrays in tomato has been used to identify 16 genes for which expression patterns are similar in apple and tomato and these genes may play fundamental roles in fruit development. The early phase of cell division and tissue specification that occurs in the first 35 days after pollination has been associated with up-regulation of a cluster of genes that includes core cell cycle genes. Conclusion Gene expression in apple fruit is coordinated with specific developmental stages. The array results are reproducible and comparisons with experiments in other species has been used to identify genes that may play a fundamental role in fruit development.

  13. Genes for Hereditary Sensory and Autonomic Neuropathies: A Genotype-Phenotype Correlation

    Science.gov (United States)

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

    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"…

  14. 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.

  15. 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.

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

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    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.

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

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    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.

  18. Global alteration in gene expression profiles of deciduas from women with idiopathic recurrent pregnancy loss.

    Science.gov (United States)

    Krieg, S A; Fan, X; Hong, Y; Sang, Q-X; Giaccia, A; Westphal, L M; Lathi, R B; Krieg, A J; Nayak, N R

    2012-09-01

    Recurrent pregnancy loss (RPL) occurs in ∼5% of women. However, the etiology is still poorly understood. Defects in decidualization of the endometrium during early pregnancy contribute to several pregnancy complications, such as pre-eclampsia and intrauterine growth restriction (IUGR), and are believed to be important in the pathogenesis of idiopathic RPL. We performed microarray analysis to identify gene expression alterations in the deciduas of idiopathic RPL patients. Control patients had one antecedent term delivery, but were undergoing dilation and curettage for current aneuploid miscarriage. Gene expression differences were evaluated using both pathway and gene ontology (GO) analysis. Selected genes were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A total of 155 genes were found to be significantly dysregulated in the deciduas of RPL patients (>2-fold change, P genes up-regulated and 133 genes down-regulated. GO analysis linked a large percentage of genes to discrete biological functions, including immune response (23%), cell signaling (18%) and cell invasion (17.1%), and pathway analysis revealed consistent changes in both the interleukin 1 (IL-1) and IL-8 pathways. All genes in the IL-8 pathway were up-regulated while genes in the IL-1 pathway were down-regulated. Although both pathways can promote inflammation, IL-1 pathway activity is important for normal implantation. Additionally, genes known to be critical for degradation of the extracellular matrix, including matrix metalloproteinase 26 and serine peptidase inhibitor Kazal-type 1, were also highly up-regulated. In this first microarray approach to decidual gene expression in RPL patients, our data suggest that dysregulation of genes associated with cell invasion and immunity may contribute significantly to idiopathic recurrent miscarriage.

  19. 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...

  20. 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.

  1. An adaptive least-squares global sensitivity method and application to a plasma-coupled combustion prediction with parametric correlation

    Science.gov (United States)

    Tang, Kunkun; Massa, Luca; Wang, Jonathan; Freund, Jonathan B.

    2018-05-01

    We introduce an efficient non-intrusive surrogate-based methodology for global sensitivity analysis and uncertainty quantification. Modified covariance-based sensitivity indices (mCov-SI) are defined for outputs that reflect correlated effects. The overall approach is applied to simulations of a complex plasma-coupled combustion system with disparate uncertain parameters in sub-models for chemical kinetics and a laser-induced breakdown ignition seed. The surrogate is based on an Analysis of Variance (ANOVA) expansion, such as widely used in statistics, with orthogonal polynomials representing the ANOVA subspaces and a polynomial dimensional decomposition (PDD) representing its multi-dimensional components. The coefficients of the PDD expansion are obtained using a least-squares regression, which both avoids the direct computation of high-dimensional integrals and affords an attractive flexibility in choosing sampling points. This facilitates importance sampling using a Bayesian calibrated posterior distribution, which is fast and thus particularly advantageous in common practical cases, such as our large-scale demonstration, for which the asymptotic convergence properties of polynomial expansions cannot be realized due to computation expense. Effort, instead, is focused on efficient finite-resolution sampling. Standard covariance-based sensitivity indices (Cov-SI) are employed to account for correlation of the uncertain parameters. Magnitude of Cov-SI is unfortunately unbounded, which can produce extremely large indices that limit their utility. Alternatively, mCov-SI are then proposed in order to bound this magnitude ∈ [ 0 , 1 ]. The polynomial expansion is coupled with an adaptive ANOVA strategy to provide an accurate surrogate as the union of several low-dimensional spaces, avoiding the typical computational cost of a high-dimensional expansion. It is also adaptively simplified according to the relative contribution of the different polynomials to the total

  2. 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.

  3. 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.

  4. Common changes in global gene expression induced by RNA polymerase inhibitors in Shigella flexneri.

    Directory of Open Access Journals (Sweden)

    Hua Fu

    Full Text Available Characterization of expression profile of organisms in response to antimicrobials provides important information on the potential mechanism of action of the drugs. The special expression signature can be used to predict whether other drugs act on the same target. Here, the common response of Shigella flexneri to two inhibitors of RNA polymerase was examined using gene expression profiling. Consistent with similar effects of the two drugs, the gene expression profiles indicated that responses of the bacteria to these drugs were roughly the same, with 225 genes affected commonly. Of them, 88 were induced and 137 were repressed. Real-time PCR was performed for selected genes to verify the microarray results. Analysis of the expression data revealed that more than 30% of the plasmid-encoded genes on the array were up-regulated by the antibiotics including virF regulon, other virulence-related genes, and genes responsible for plasmid replication, maintenance, and transfer. In addition, some chromosome-encoded genes involved in virulence and genes acquired from horizontal transfer were also significantly up-regulated. However, the expression of genes encoding the beta-subunit of RNA polymerase was increased moderately. The repressed genes include those that code for products associated with the ribosome, citrate cycle, glycolysis, thiamine biosynthesis, purine metabolism, fructose metabolism, mannose metabolism, and cold shock proteins. This study demonstrates that the two antibiotics induce rapid cessation of RNA synthesis resulting in inhibition of translation components. It also indicates that the production of virulence factors involved in intercellular dissemination, tissue invasion and inflammatory destruction may be enhanced through derepressing horizontal transfer genes by the drugs.

  5. RAPTOR gene polymorphism is independently correlated with urothelial cancer susceptibility compared with environmental toxin exposure

    Directory of Open Access Journals (Sweden)

    Hao Lun Luo

    2017-12-01

    Conclusion: RAPTOR gene polymorphisms are important SNPs with significantly association with the risk of urothelial cancer in Taiwan. Further researches about raptor-mTOR complex interfering malignant transformation of urothelium is worthy of further investigation.

  6. Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Putnik, Milica, E-mail: milica.putnik@ki.se [Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge S-14183 (Sweden); Zhao, Chunyan, E-mail: chunyan.zhao@ki.se [Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge S-14183 (Sweden); Gustafsson, Jan-Ake, E-mail: jan-ake.gustafsson@ki.se [Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge S-14183 (Sweden); Department of Biology and Biochemistry, Science and Engineering Research Center Bldg, University of Houston, Houston, TX 77204-5056 (United States); Dahlman-Wright, Karin, E-mail: karin.dahlman-wright@ki.se [Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge S-14183 (Sweden)

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer Estrogen signaling and demethylation can both control gene expression in breast cancers. Black-Right-Pointing-Pointer Cross-talk between these mechanisms is investigated in human MCF-7 breast cancer cells. Black-Right-Pointing-Pointer 137 genes are influenced by both 17{beta}-estradiol and demethylating agent 5-aza-2 Prime -deoxycytidine. Black-Right-Pointing-Pointer A set of genes is identified as targets of both estrogen signaling and demethylation. Black-Right-Pointing-Pointer There is no direct molecular interplay of mediators of estrogen and epigenetic signaling. -- Abstract: Estrogen signaling and epigenetic modifications, in particular DNA methylation, are involved in regulation of gene expression in breast cancers. Here we investigated a potential regulatory cross-talk between these two pathways by identifying their common target genes and exploring underlying molecular mechanisms in human MCF-7 breast cancer cells. Gene expression profiling revealed that the expression of approximately 140 genes was influenced by both 17{beta}-estradiol (E2) and a demethylating agent 5-aza-2 Prime -deoxycytidine (DAC). Gene ontology (GO) analysis suggests that these genes are involved in intracellular signaling cascades, regulation of cell proliferation and apoptosis. Based on previously reported association with breast cancer, estrogen signaling and/or DNA methylation, CpG island prediction and GO analysis, we selected six genes (BTG3, FHL2, PMAIP1, BTG2, CDKN1A and TGFB2) for further analysis. Tamoxifen reverses the effect of E2 on the expression of all selected genes, suggesting that they are direct targets of estrogen receptor. Furthermore, DAC treatment reactivates the expression of all selected genes in a dose-dependent manner. Promoter CpG island methylation status analysis revealed that only the promoters of BTG3 and FHL2 genes are methylated, with DAC inducing demethylation, suggesting DNA methylation directs repression of

  7. Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Putnik, Milica; Zhao, Chunyan; Gustafsson, Jan-Åke; Dahlman-Wright, Karin

    2012-01-01

    Highlights: ► Estrogen signaling and demethylation can both control gene expression in breast cancers. ► Cross-talk between these mechanisms is investigated in human MCF-7 breast cancer cells. ► 137 genes are influenced by both 17β-estradiol and demethylating agent 5-aza-2′-deoxycytidine. ► A set of genes is identified as targets of both estrogen signaling and demethylation. ► There is no direct molecular interplay of mediators of estrogen and epigenetic signaling. -- Abstract: Estrogen signaling and epigenetic modifications, in particular DNA methylation, are involved in regulation of gene expression in breast cancers. Here we investigated a potential regulatory cross-talk between these two pathways by identifying their common target genes and exploring underlying molecular mechanisms in human MCF-7 breast cancer cells. Gene expression profiling revealed that the expression of approximately 140 genes was influenced by both 17β-estradiol (E2) and a demethylating agent 5-aza-2′-deoxycytidine (DAC). Gene ontology (GO) analysis suggests that these genes are involved in intracellular signaling cascades, regulation of cell proliferation and apoptosis. Based on previously reported association with breast cancer, estrogen signaling and/or DNA methylation, CpG island prediction and GO analysis, we selected six genes (BTG3, FHL2, PMAIP1, BTG2, CDKN1A and TGFB2) for further analysis. Tamoxifen reverses the effect of E2 on the expression of all selected genes, suggesting that they are direct targets of estrogen receptor. Furthermore, DAC treatment reactivates the expression of all selected genes in a dose-dependent manner. Promoter CpG island methylation status analysis revealed that only the promoters of BTG3 and FHL2 genes are methylated, with DAC inducing demethylation, suggesting DNA methylation directs repression of these genes in MCF-7 cells. In a further analysis of the potential interplay between estrogen signaling and DNA methylation, E2 treatment

  8. 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

  9. 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

  10. Molecular pathways to parallel evolution: I. Gene nexuses and their morphological correlates.

    Science.gov (United States)

    Zuckerkandl, E

    1994-12-01

    Aspects of the regulatory interactions among genes are probably as old as most genes are themselves. Correspondingly, similar predispositions to changes in such interactions must have existed for long evolutionary periods. Features of the structure and the evolution of the system of gene regulation furnish the background necessary for a molecular understanding of parallel evolution. Patently "unrelated" organs, such as the fat body of a fly and the liver of a mammal, can exhibit fractional homology, a fraction expected to become subject to quantitation. This also seems to hold for different organs in the same organism, such as wings and legs of a fly. In informational macromolecules, on the other hand, homology is indeed all or none. In the quite different case of organs, analogy is expected usually to represent attenuated homology. Many instances of putative convergence are likely to turn out to be predominantly parallel evolution, presumably including the case of the vertebrate and cephalopod eyes. Homology in morphological features reflects a similarity in networks of active genes. Similar nexuses of active genes can be established in cells of different embryological origins. Thus, parallel development can be considered a counterpart to parallel evolution. Specific macromolecular interactions leading to the regulation of the c-fos gene are given as an example of a "controller node" defined as a regulatory unit. Quantitative changes in gene control are distinguished from relational changes, and frequent parallelism in quantitative changes is noted in Drosophila enzymes. Evolutionary reversions in quantitative gene expression are also expected. The evolution of relational patterns is attributed to several distinct mechanisms, notably the shuffling of protein domains. The growth of such patterns may in part be brought about by a particular process of compensation for "controller gene diseases," a process that would spontaneously tend to lead to increased regulatory

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs

    DEFF Research Database (Denmark)

    Khan, Aly A; Betel, Doron; Miller, Martin L

    2009-01-01

    Transfection of small RNAs (such as small interfering RNAs (siRNAs) and microRNAs (miRNAs)) into cells typically lowers expression of many genes. Unexpectedly, increased expression of genes also occurs. We investigated whether this upregulation results from a saturation effect--that is, competiti...

  17. A Unique Evolution of the S2 Gene of Equine Infectious Anemia Virus in Hosts Correlated with Particular Infection Statuses

    Science.gov (United States)

    Wang, Xue-Feng; Wang, Shuai; Liu, Qiang; Lin, Yue-Zhi; Du, Cheng; Tang, Yan-Dong; Na, Lei; Wang, Xiaojun; Zhou, Jian-Hua

    2014-01-01

    Equine infectious anemia virus (EIAV) is a member of the Lentivirus genus in the Retroviridae family that exhibits a genomic structure similar to that of HIV-1. The S2 accessory proteins play important roles in viral replication in vivo and in viral pathogenicity; however, studies on S2 evolution in vivo are limited. This study analyzed the evolutionary characteristics of the S2 gene of a pathogenic EIAV strain, EIAVLN40, in four experimentally infected horses. The results demonstrated that 14.7% (10 of 68 residues) of the stable amino acid mutations occurred longitudinally in S2 during a 150-day infection period. Further analysis revealed that six of the ten mutated residues were positively selected during the infection. Alignment and phylogenetic analyses showed that the S2 gene sequences of viruses isolated from the infected horses at the early stage of EIAVLN40 infection were highly homologous and similar to the vaccine-specific sequence. The S2 gene variants isolated from the febrile episodes and late phase of infection became homologous to the S2 gene sequence of the inoculating EIAVLN40 strain. Our results indicate that the S2 gene evolves in diversity and divergence in vivo in different stages of EIAV infection and that this evolution correlates with the pathogenicity of the virus. PMID:25390683

  18. Association of Genetic Polymorphism in the Interleukin-8 Gene with Risk of Oral Cancer and Its Correlation with Pain.

    Science.gov (United States)

    Singh, Prithvi Kumar; Chandra, Girish; Bogra, Jaishri; Gupta, Rajni; Kumar, Vijay; Hussain, Syed Rizwan; Jain, Amita; Mahdi, Abbas Ali; Ahmad, Mohammad Kaleem

    2016-02-01

    Oral cancer is a multifactorial disease process and involves complex interactions between gene to gene and gene to environmental factors. Interleukin 8 (IL-8), a pro-inflammatory cytokine, having angiogenic activity with elevated expression in tumor cells, is reported to play an essential role in oral cancer development. This study was conducted with the aim to investigate the role of IL-8 (-A251T) gene polymorphism in susceptibility, progression, and self-reporting pain in oral cancer. The single nucleotide polymorphisms of the IL-8 (-A251T) gene were screened in 300 patients with oral cancer and 300 healthy controls, by polymerase chain reaction-restriction fragment length polymorphism. Genotype and allele frequencies were evaluated by chi-square test and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. The results of the study demonstrated that IL-8 (-A251T) gene polymorphism was significantly associated with susceptibility of oral cancer, whereas its correlation with clinico-pathological status or pain due to oral cancer could not be established. The AT heterozygous (OR 5.31; CI 3.38-8.34; p 0.0001) and AA homozygous (OR 2.89; CI 1.76-4.75; p 0.0001) had a greater risk for oral cancer compared to TT homozygous. Furthermore, significantly increased values of A allele frequencies compared to T allele were observed in all patients (OR 1.56; CI 1.24-1.96; p 0.0002). Tobacco chewing and smoking were also found to influence the development of oral cancer and increased the incidence of pain in oral cancer patients. The findings of this study suggest that the IL-8 (-A251T) gene polymorphism may be associated with increased risk of oral cancer.

  19. Observed correlation between the depth to base and top of gas hydrate occurrence from review of global drilling data

    Science.gov (United States)

    Riedel, M.; Collett, T. S.

    2017-07-01

    A global inventory of data from gas hydrate drilling expeditions is used to develop relationships between the base of structure I gas hydrate stability, top of gas hydrate occurrence, sulfate-methane transition depth, pressure (water depth), and geothermal gradients. The motivation of this study is to provide first-order estimates of the top of gas hydrate occurrence and associated thickness of the gas hydrate occurrence zone for climate-change scenarios, global carbon budget analyses, or gas hydrate resource assessments. Results from publically available drilling campaigns (21 expeditions and 52 drill sites) off Cascadia, Blake Ridge, India, Korea, South China Sea, Japan, Chile, Peru, Costa Rica, Gulf of Mexico, and Borneo reveal a first-order linear relationship between the depth to the top and base of gas hydrate occurrence. The reason for these nearly linear relationships is believed to be the strong pressure and temperature dependence of methane solubility in the absence of large difference in thermal gradients between the various sites assessed. In addition, a statistically robust relationship was defined between the thickness of the gas hydrate occurrence zone and the base of gas hydrate stability (in meters below seafloor). The relationship developed is able to predict the depth of the top of gas hydrate occurrence zone using observed depths of the base of gas hydrate stability within less than 50 m at most locations examined in this study. No clear correlation of the depth to the top and base of gas hydrate occurrences with geothermal gradient and sulfate-methane transition depth was identified.

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

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    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.

  1. 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.

  2. A hemocyte gene expression signature correlated with predictive capacity of oysters to survive Vibrio infections

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    Rosa Rafael

    2012-06-01

    Full Text Available Abstract Background The complex balance between environmental and host factors is an important determinant of susceptibility to infection. Disturbances of this equilibrium may result in multifactorial diseases as illustrated by the summer mortality syndrome, a worldwide and complex phenomenon that affects the oysters, Crassostrea gigas. The summer mortality syndrome reveals a physiological intolerance making this oyster species susceptible to diseases. Exploration of genetic basis governing the oyster resistance or susceptibility to infections is thus a major goal for understanding field mortality events. In this context, we used high-throughput genomic approaches to identify genetic traits that may characterize inherent survival capacities in C. gigas. Results Using digital gene expression (DGE, we analyzed the transcriptomes of hemocytes (immunocompetent cells of oysters able or not able to survive infections by Vibrio species shown to be involved in summer mortalities. Hemocytes were nonlethally collected from oysters before Vibrio experimental infection, and two DGE libraries were generated from individuals that survived or did not survive. Exploration of DGE data and microfluidic qPCR analyses at individual level showed an extraordinary polymorphism in gene expressions, but also a set of hemocyte-expressed genes whose basal mRNA levels discriminate oyster capacity to survive infections by the pathogenic V. splendidus LGP32. Finally, we identified a signature of 14 genes that predicted oyster survival capacity. Their expressions are likely driven by distinct transcriptional regulation processes associated or not associated to gene copy number variation (CNV. Conclusions We provide here for the first time in oyster a gene expression survival signature that represents a useful tool for understanding mortality events and for assessing genetic traits of interest for disease resistance selection programs.

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

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    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.

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

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    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.

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

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    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.

  6. Prevalence and correlates of cigarette smoking among adolescents in Malawi: results from the Global Youth Tobacco Survey 2005.

    Science.gov (United States)

    Muula, A S; Siziya, S; Rudatsikira, E

    2008-07-01

    The majority of adults who smoke cigarettes initiated the habit when they were adolescents or young adults. While rates of smoking and associated factors are known among 13-15 year olds in Malawi, correlates of cigarette smoking among adolescents in a national representative sample in Malawi have not been studied. We, therefore, carried out this study to estimate the prevalence of current smoking and determine its correlates in a nationally representative sample of in-school adolescents in Malawi. An analysis of the Malawi Global Youth Tobacco Survey (GYTS) 2005 was conducted. Using logistic regression analysis, we estimated the association between current cigarette smoking and potential explanatory variables. Overall, 2.5% of adolescents (3.2% among males, and 1.8% among females) were current cigarette smokers. Smoking among parents was 9.6% with no significant difference between males and females (10.3% versus 10.1%). Stronger associations with smoking were observed for friends smoking status (AOR=3.07, 95%CI 2.99, 3.16), receiving pocket money (AOR=3.06, 95%CI 2.98, 3.14), and perception that smoking increases body weight (AOR=2.98, 95%CI 2.81, 3.16). Students who thought that cigarette smoking is harmful to health were 56% (AOR=0.44, 95%CI 0.43, 0.45) less likely to smoke than students who thought otherwise. Despite being the world's second leading grower of tobacco, the prevalence of cigarette smoking among adolescent is lower than has been reported elsewhere.

  7. Catecholamine-related gene expression in blood correlates with tic severity in tourette syndrome

    NARCIS (Netherlands)

    Gunther, Joan; Tian, Yingfang; Stamova, Boryana; Lit, Lisa; Corbett, Blythe; Ander, Brad; Zhan, Xinhua; Jickling, Glen; Bos-Veneman, Netty; Liu, Da; Hoekstra, Pieter; Sharp, Frank

    2012-01-01

    Tourette syndrome (TS) is a heritable disorder characterized by tics that are decreased in some patients by treatment with alpha adrenergic agonists and dopamine receptor blockers. Thus, this study examines the relationship between catecholamine gene expression in blood and tic severity. TS

  8. Polymorphisms in Renal Ammonia Metabolism Genes Correlate With 24-Hour Urine pH

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    Benjamin K. Canales

    2017-11-01

    Discussion: Overall, these findings suggest that variants in common genes involved in ammonia metabolism may substantively contribute to basal urine pH regulation. These variations might influence the likelihood of developing disease conditions associated with altered urine pH, such as uric acid or calcium phosphate kidney stones.

  9. 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.

  10. 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.

  11. Global gene expression and comparison between multiple populations in the mouse epidermis

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    Anders Patrik Gunnarsson

    2016-07-01

    Our data shows that flow cytometry using multicolor panels can identify further subsets of cells within the epidermis and also highlights a marked discrepancy in gene expression between directly isolated cells and tissue cultured cells.

  12. Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids

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    Tetu Bernard

    2008-02-01

    Full Text Available Abstract Background Chemotherapy (CT resistance in ovarian cancer (OC is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155, following treatment with 10,0 μM cisplatin, 2,5 μM paclitaxel or 5,0 μM topotecan for 72 hours. Results Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism, signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes, cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Conclusion Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular

  13. Global Metabolic Reconstruction and Metabolic Gene Evolution in the Cattle Genome

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    Kim, Woonsu; Park, Hyesun; Seo, Seongwon

    2016-01-01

    The sequence of cattle genome provided a valuable opportunity to systematically link genetic and metabolic traits of cattle. The objectives of this study were 1) to reconstruct genome-scale cattle-specific metabolic pathways based on the most recent and updated cattle genome build and 2) to identify duplicated metabolic genes in the cattle genome for better understanding of metabolic adaptations in cattle. A bioinformatic pipeline of an organism for amalgamating genomic annotations from multiple sources was updated. Using this, an amalgamated cattle genome database based on UMD_3.1, was created. The amalgamated cattle genome database is composed of a total of 33,292 genes: 19,123 consensus genes between NCBI and Ensembl databases, 8,410 and 5,493 genes only found in NCBI or Ensembl, respectively, and 266 genes from NCBI scaffolds. A metabolic reconstruction of the cattle genome and cattle pathway genome database (PGDB) was also developed using Pathway Tools, followed by an intensive manual curation. The manual curation filled or revised 68 pathway holes, deleted 36 metabolic pathways, and added 23 metabolic pathways. Consequently, the curated cattle PGDB contains 304 metabolic pathways, 2,460 reactions including 2,371 enzymatic reactions, and 4,012 enzymes. Furthermore, this study identified eight duplicated genes in 12 metabolic pathways in the cattle genome compared to human and mouse. Some of these duplicated genes are related with specific hormone biosynthesis and detoxifications. The updated genome-scale metabolic reconstruction is a useful tool for understanding biology and metabolic characteristics in cattle. There has been significant improvements in the quality of cattle genome annotations and the MetaCyc database. The duplicated metabolic genes in the cattle genome compared to human and mouse implies evolutionary changes in the cattle genome and provides a useful information for further research on understanding metabolic adaptations of cattle. PMID

  14. Global gene expression under nitrogen starvation in Xylella fastidiosa: contribution of the σ54 regulon

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    da Silva Neto José F

    2010-08-01

    Full Text Available Abstract Background Xylella fastidiosa, a Gram-negative fastidious bacterium, grows in the xylem of several plants causing diseases such as citrus variegated chlorosis. As the xylem sap contains low concentrations of amino acids and other compounds, X. fastidiosa needs to cope with nitrogen limitation in its natural habitat. Results In this work, we performed a whole-genome microarray analysis of the X. fastidiosa nitrogen starvation response. A time course experiment (2, 8 and 12 hours of cultures grown in defined medium under nitrogen starvation revealed many differentially expressed genes, such as those related to transport, nitrogen assimilation, amino acid biosynthesis, transcriptional regulation, and many genes encoding hypothetical proteins. In addition, a decrease in the expression levels of many genes involved in carbon metabolism and energy generation pathways was also observed. Comparison of gene expression profiles between the wild type strain and the rpoN null mutant allowed the identification of genes directly or indirectly induced by nitrogen starvation in a σ54-dependent manner. A more complete picture of the σ54 regulon was achieved by combining the transcriptome data with an in silico search for potential σ54-dependent promoters, using a position weight matrix approach. One of these σ54-predicted binding sites, located upstream of the glnA gene (encoding glutamine synthetase, was validated by primer extension assays, confirming that this gene has a σ54-dependent promoter. Conclusions Together, these results show that nitrogen starvation causes intense changes in the X. fastidiosa transcriptome and some of these differentially expressed genes belong to the σ54 regulon.

  15. Global Gene Expression Analysis of Yeast Cells during Sake Brewing▿ †

    Science.gov (United States)

    Wu, Hong; Zheng, Xiaohong; Araki, Yoshio; Sahara, Hiroshi; Takagi, Hiroshi; Shimoi, Hitoshi

    2006-01-01

    During the brewing of Japanese sake, Saccharomyces cerevisiae cells produce a high concentration of ethanol compared with other ethanol fermentation methods. We analyzed the gene expression profiles of yeast cells during sake brewing using DNA microarray analysis. This analysis revealed some characteristics of yeast gene expression during sake brewing and provided a scaffold for a molecular level understanding of the sake brewing process. PMID:16997994

  16. Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.

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    Carolyn Glass

    Full Text Available The ecotropic virus integration site 1 (EVI1 transcription factor is associated with human myeloid malignancy of poor prognosis and is overexpressed in 8-10% of adult AML and strikingly up to 27% of pediatric MLL-rearranged leukemias. For the first time, we report comprehensive genomewide EVI1 binding and whole transcriptome gene deregulation in leukemic cells using a combination of ChIP-Seq and RNA-Seq expression profiling. We found disruption of terminal myeloid differentiation and cell cycle regulation to be prominent in EVI-induced leukemogenesis. Specifically, we identified EVI1 directly binds to and downregulates the master myeloid differentiation gene Cebpe and several of its downstream gene targets critical for terminal myeloid differentiation. We also found EVI1 binds to and downregulates Serpinb2 as well as numerous genes involved in the Jak-Stat signaling pathway. Finally, we identified decreased expression of several ATP-dependent P2X purinoreceptors genes involved in apoptosis mechanisms. These findings provide a foundation for future study of potential therapeutic gene targets for EVI1-induced leukemia.

  17. Correlates of cigarette smoking among school-going adolescents in Thailand: findings from the Thai global youth tobacco survey 2005

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    Rudatsikira Emmanuel

    2008-06-01

    Full Text Available Abstract Background Many studies examining the social correlates of tobacco use among adolescents fail to recognise theories of health behaviour and health promotion in their analysis. Using the Socio-Ecologiocal Model (SEM we assessed the demographic and social factors associated with current cigarette smoking among adolescents in Thailand. Method A secondary analysis of cross-sectional data from the Thai Global Youth Tobacco Survey (Thai GYTS 2005 was analysed to obtain prevalence of selected attributes and assess factors associated with current cigarette smoking. Current cigarette smoking was defined as having smoked a cigarette, even a single puff, in the last 30 days. Logistic regression was conducted to estimate the level of association between the explanatory variables and current smoking. Results Of the 18,368 respondents, 22.0% males and 5.2% females reported being current smokers (p Conclusion Current cigarette smoking was associated with male gender, smoking parents or closest peers. Perception that smoking was harmful to health was associated with less likelihood of being a current smoker.

  18. Chromatin status of apoptosis genes correlates with sensitivity to chemo-, immune- and radiation therapy in colorectal cancer cell lines.

    Science.gov (United States)

    Benard, Anne; Janssen, Connie M; van den Elsen, Peter J; van Eggermond, Marja C J A; Hoon, Dave S B; van de Velde, Cornelis J H; Kuppen, Peter J K

    2014-12-01

    The apoptosis pathway of programmed cell death is frequently deregulated in cancer. An intact apoptosis pathway is required for proper response to anti-cancer treatment. We investigated the chromatin status of key apoptosis genes in the apoptosis pathway in colorectal cancer cell lines in relation to apoptosis induced by chemo-, immune- or radiation therapy. Using chromatin immunoprecipitation (ChIP), we measured the presence of transcription-activating histone modifications H3Ac and H3K4me3 and silencing modifications H3K9me3 and H3K27me3 at the gene promoter regions of key apoptosis genes Bax, Bcl2, Caspase-9, Fas (CD95) and p53. Cell lines DLD1, SW620, Colo320, Caco2, Lovo and HT29 were treated with cisplatin, anti-Fas or radiation. The apoptotic response was measured by flow cytometry using propidium iodide and annexin V-FITC. The chromatin status of the apoptosis genes reflected the activation status of the intrinsic (Bax, Bcl2, Caspase-9 and p53) and extrinsic (Fas) pathways. An active intrinsic apoptotic pathway corresponded to sensitivity to cisplatin and radiation treatment of cell lines DLD1, SW620 and Colo320. An active Fas promoter corresponded to an active extrinsic apoptotic pathway in cell line DLD1. mRNA expression data correlated with the chromatin status of the apoptosis genes as measured by ChIP. In conclusion, the results presented in this study indicate that the balance between activating and silencing histone modifications, reflecting the chromatin status of apoptosis genes, can be used to predict the response of tumor cells to different anti-cancer therapies and could provide a novel target to sensitize tumors to obtain adequate treatment responses.

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

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    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.

  20. Investigating Correlation between Protein Sequence Similarity and Semantic Similarity Using Gene Ontology Annotations.

    Science.gov (United States)

    Ikram, Najmul; Qadir, Muhammad Abdul; Afzal, Muhammad Tanvir

    2018-01-01

    Sequence similarity is a commonly used measure to compare proteins. With the increasing use of ontologies, semantic (function) similarity is getting importance. The correlation between these measures has been applied in the evaluation of new semantic similarity methods, and in protein function prediction. In this research, we investigate the relationship between the two similarity methods. The results suggest absence of a strong correlation between sequence and semantic similarities. There is a large number of proteins with low sequence similarity and high semantic similarity. We observe that Pearson's correlation coefficient is not sufficient to explain the nature of this relationship. Interestingly, the term semantic similarity values above 0 and below 1 do not seem to play a role in improving the correlation. That is, the correlation coefficient depends only on the number of common GO terms in proteins under comparison, and the semantic similarity measurement method does not influence it. Semantic similarity and sequence similarity have a distinct behavior. These findings are of significant effect for future works on protein comparison, and will help understand the semantic similarity between proteins in a better way.

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

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    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.

  2. Correlation of in vitro lymphocyte radiosensitivity and gene expression with late normal tissue reactions following curative radiotherapy for breast cancer

    International Nuclear Information System (INIS)

    Finnon, Paul; Kabacik, Sylwia; MacKay, Alan; Raffy, Claudine; A’Hern, Roger; Owen, Roger; Badie, Christophe; Yarnold, John; Bouffler, Simon

    2012-01-01

    Background and purpose: Identification of mechanisms of late normal tissue responses to curative radiotherapy that discriminate individuals with marked or mild responses would aid response prediction. This study aimed to identify differences in gene expression, apoptosis, residual DNA double strand breaks and chromosomal damage after in vitro irradiation of lymphocytes in a series of patients with marked (31 cases) or mild (28 controls) late adverse reaction to adjuvant breast radiotherapy. Materials and methods: Gene expression arrays, residual γH2AX, apoptosis, G2 chromosomal radiosensitivity and G0 micronucleus assay were used to compare case and control lymphocyte radiation responses. Results: Five hundred and thirty genes were up-regulated and 819 down-regulated by ionising radiation. Irradiated samples were identified with an overall cross-validated error rate of 3.4%. Prediction analyses to classify cases and controls using unirradiated (0 Gy), irradiated (4 Gy) or radiation response (4–0 Gy) expression profiles correctly identified samples with, respectively, 25%, 22% or 18.5% error rates. Significant inter-sample variation was observed for all cellular endpoints but cases and controls could not be distinguished. Conclusions: Variation in lymphocyte radiosensitivity does not necessarily correlate with normal tissue response to radiotherapy. Gene expression analysis can predict of radiation exposure and may in the future help prediction of normal tissue radiosensitivity.

  3. 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

  4. 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.

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

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    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.

  6. The effects of MicroRNA transfections on global patterns of gene expression in ovarian cancer cells are functionally coordinated

    Directory of Open Access Journals (Sweden)

    Shahab Shubin W

    2012-08-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are a class of small RNAs that have been linked to a number of diseases including cancer. The potential application of miRNAs in the diagnostics and therapeutics of ovarian and other cancers is an area of intense interest. A current challenge is the inability to accurately predict the functional consequences of exogenous modulations in the levels of potentially therapeutic miRNAs. Methods In an initial effort to systematically address this issue, we conducted miRNA transfection experiments using two miRNAs (miR-7, miR-128. We monitored the consequent changes in global patterns of gene expression by microarray and quantitative (real-time polymerase chain reaction. Network analysis of the expression data was used to predict the consequence of each transfection on cellular function and these predictions were experimentally tested. Results While ~20% of the changes in expression patterns of hundreds to thousands of genes could be attributed to direct miRNA-mRNA interactions, the majority of the changes are indirect, involving the downstream consequences of miRNA-mediated changes in regulatory gene expression. The changes in gene expression induced by individual miRNAs are functionally coordinated but distinct between the two miRNAs. MiR-7 transfection into ovarian cancer cells induces changes in cell adhesion and other developmental networks previously associated with epithelial-mesenchymal transitions (EMT and other processes linked with metastasis. In contrast, miR-128 transfection induces changes in cell cycle control and other processes commonly linked with cellular replication. Conclusions The functionally coordinated patterns of gene expression displayed by different families of miRNAs have the potential to provide clinicians with a strategy to treat cancers from a systems rather than a single gene perspective.

  7. 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.

  8. 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.

  9. Global gene expression analysis in a mouse model for Norrie disease: late involvement of photoreceptor cells.

    Science.gov (United States)

    Lenzner, Steffen; Prietz, Sandra; Feil, Silke; Nuber, Ulrike A; Ropers, H-Hilger; Berger, Wolfgang

    2002-09-01

    Mutations in the NDP gene give rise to a variety of eye diseases, including classic Norrie disease (ND), X-linked exudative vitreoretinopathy (EVRX), retinal telangiectasis (Coats disease), and advanced retinopathy of prematurity (ROP). The gene product is a cystine-knot-containing extracellular signaling molecule of unknown function. In the current study, gene expression was determined in a mouse model of ND, to unravel disease-associated mechanisms at the molecular level. Gene transcription in the eyes of 2-year-old Ndp knockout mice was compared with that in the eyes of age-matched wild-type control animals, by means of cDNA subtraction and microarrays. Clones (n = 3072) from the cDNA subtraction libraries were spotted onto glass slides and hybridized with fluorescently labeled RNA-derived targets. More than 230 differentially expressed clones were sequenced, and their expression patterns were verified by virtual Northern blot analysis. Numerous gene transcripts that are absent or downregulated in the eye of Ndp knockout mice are photoreceptor cell specific. In younger Ndp knockout mice (up to 1 year old), however, all these transcripts were found to be expressed at normal levels. The identification of numerous photoreceptor cell-specific transcripts with a reduced expression in 2-year-old, but not in young, Ndp knockout mice indicates that normal gene expression in these light-sensitive cells of mutant mice is established and maintained over a long period and that rods and cones are affected relatively late in the mouse model of ND. Obviously, the absence of the Ndp gene product is not compatible with long-term survival of photoreceptor cells in the mouse.

  10. 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

  11. 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.

  12. [Correlation analysis between single nucleotide polymorphism of FGF5 gene and wool yield in rabbits].

    Science.gov (United States)

    Li, Chun-Xiao; Jiang, Mei-Shan; Chen, Shi-Yi; Lai, Song-Jia

    2008-07-01

    Single nucleotide polymorphism (SNP) in exon 1 and 3 of fibroblast growth factor (FGF5) gene was studied by DNA sequencing in Yingjing angora rabbit, Tianfu black rabbit and California rabbit. A frameshift mutation (TCT insert) at base position 217 (site A) of exon 1 and a T/C missense mutation at base position 59 (site B) of exon 3 were found in Yingjing angora rabbit with a high frequency; a T/C same-sense mutation at base position 3 (site C) of exon 3 was found with similar frequency in three rabbit breeds. Least square analysis showed that different genotypes had no significant association with wool yield in site A, and had high significant association with wool yield in site B (Plink with the major gene, and polymorphic loci B and C may be used as molecular markers for im-proving wool yield in angora rabbits.

  13. Global analysis of gene expression in the developing brain of Gtf2ird1 knockout mice.

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    Jennifer O'Leary

    Full Text Available Williams-Beuren Syndrome (WBS is a neurodevelopmental disorder caused by a hemizygous deletion of a 1.5 Mb region on chromosome 7q11.23 encompassing 26 genes. One of these genes, GTF2IRD1, codes for a putative transcription factor that is expressed throughout the brain during development. Genotype-phenotype studies in patients with atypical deletions of 7q11.23 implicate this gene in the neurological features of WBS, and Gtf2ird1 knockout mice show reduced innate fear and increased sociability, consistent with features of WBS. Multiple studies have identified in vitro target genes of GTF2IRD1, but we sought to identify in vivo targets in the mouse brain.We performed the first in vivo microarray screen for transcriptional targets of Gtf2ird1 in brain tissue from Gtf2ird1 knockout and wildtype mice at embryonic day 15.5 and at birth. Changes in gene expression in the mutant mice were moderate (0.5 to 2.5 fold and of candidate genes with altered expression verified using real-time PCR, most were located on chromosome 5, within 10 Mb of Gtf2ird1. siRNA knock-down of Gtf2ird1 in two mouse neuronal cell lines failed to identify changes in expression of any of the genes identified from the microarray and subsequent analysis showed that differences in expression of genes on chromosome 5 were the result of retention of that chromosome region from the targeted embryonic stem cell line, and so were dependent upon strain rather than Gtf2ird1 genotype. In addition, specific analysis of genes previously identified as direct in vitro targets of GTF2IRD1 failed to show altered expression.We have been unable to identify any in vivo neuronal targets of GTF2IRD1 through genome-wide expression analysis, despite widespread and robust expression of this protein in the developing rodent brain.

  14. 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...

  15. Global Analysis of Differentially Expressed Genes and Proteins in the Wheat Callus Infected by Agrobacterium tumefaciens

    Science.gov (United States)

    Zhou, Xiaohong; Wang, Ke; Lv, Dongwen; Wu, Chengjun; Li, Jiarui; Zhao, Pei; Lin, Zhishan; Du, Lipu; Yan, Yueming; Ye, Xingguo

    2013-01-01

    Agrobacterium-mediated plant transformation is an extremely complex and evolved process involving genetic determinants of both the bacteria and the host plant cells. However, the mechanism of the determinants remains obscure, especially in some cereal crops such as wheat, which is recalcitrant for Agrobacterium-mediated transformation. In this study, differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were analyzed in wheat callus cells co-cultured with Agrobacterium by using RNA sequencing (RNA-seq) and two-dimensional electrophoresis (2-DE) in conjunction with mass spectrometry (MS). A set of 4,889 DEGs and 90 DEPs were identified, respectively. Most of them are related to metabolism, chromatin assembly or disassembly and immune defense. After comparative analysis, 24 of the 90 DEPs were detected in RNA-seq and proteomics datasets simultaneously. In addition, real-time RT-PCR experiments were performed to check the differential expression of the 24 genes, and the results were consistent with the RNA-seq data. According to gene ontology (GO) analysis, we found that a big part of these differentially expressed genes were related to the process of stress or immunity response. Several putative determinants and candidate effectors responsive to Agrobacterium mediated transformation of wheat cells were discussed. We speculate that some of these genes are possibly related to Agrobacterium infection. Our results will help to understand the interaction between Agrobacterium and host cells, and may facilitate developing efficient transformation strategies in cereal crops. PMID:24278131

  16. Global Screening of Antiviral Genes that Suppress Baculovirus Transgene Expression in Mammalian Cells.

    Science.gov (United States)

    Wang, Chia-Hung; Naik, Nenavath Gopal; Liao, Lin-Li; Wei, Sung-Chan; Chao, Yu-Chan

    2017-09-15

    Although baculovirus has been used as a safe and convenient gene delivery vector in mammalian cells, baculovirus-mediated transgene expression is less effective in various mammalian cell lines. Identification of the negative regulators in host cells is necessary to improve baculovirus-based expression systems. Here, we performed high-throughput shRNA library screening, targeting 176 antiviral innate immune genes, and identified 43 host restriction factor genes in a human A549 lung carcinoma cell line. Among them, suppression of receptor interaction protein kinase 1 (RIP1, also known as RIPK1) significantly increased baculoviral transgene expression without resulting in significant cell death. Silencing of RIP1 did not affect viral entry or cell viability, but it did inhibit nuclear translocation of the IRF3 and NF-κB transcription factors. Also, activation of downstream signaling mediators (such as TBK1 and IRF7) was affected, and subsequent interferon and cytokine gene expression levels were abolished. Further, Necrostatin-1 (Nec-1)-an inhibitor of RIP1 kinase activity-dramatically increased baculoviral transgene expression in RIP1-silenced cells. Using baculovirus as a model system, this study presents an initial investigation of large numbers of human cell antiviral innate immune response factors against a "nonadaptive virus." In addition, our study has made baculovirus a more efficient gene transfer vector for some of the most frequently used mammalian cell systems.

  17. Global analysis of differentially expressed genes and proteins in the wheat callus infected by Agrobacterium tumefaciens.

    Directory of Open Access Journals (Sweden)

    Xiaohong Zhou

    Full Text Available Agrobacterium-mediated plant transformation is an extremely complex and evolved process involving genetic determinants of both the bacteria and the host plant cells. However, the mechanism of the determinants remains obscure, especially in some cereal crops such as wheat, which is recalcitrant for Agrobacterium-mediated transformation. In this study, differentially expressed genes (DEGs and differentially expressed proteins (DEPs were analyzed in wheat callus cells co-cultured with Agrobacterium by using RNA sequencing (RNA-seq and two-dimensional electrophoresis (2-DE in conjunction with mass spectrometry (MS. A set of 4,889 DEGs and 90 DEPs were identified, respectively. Most of them are related to metabolism, chromatin assembly or disassembly and immune defense. After comparative analysis, 24 of the 90 DEPs were detected in RNA-seq and proteomics datasets simultaneously. In addition, real-time RT-PCR experiments were performed to check the differential expression of the 24 genes, and the results were consistent with the RNA-seq data. According to gene ontology (GO analysis, we found that a big part of these differentially expressed genes were related to the process of stress or immunity response. Several putative determinants and candidate effectors responsive to Agrobacterium mediated transformation of wheat cells were discussed. We speculate that some of these genes are possibly related to Agrobacterium infection. Our results will help to understand the interaction between Agrobacterium and host cells, and may facilitate developing efficient transformation strategies in cereal crops.

  18. Global gene expression profiling in human lung cells exposed to cobalt

    Energy Technology Data Exchange (ETDEWEB)

    Malard, V.; Berenguer, F.; Prat, O.; Ruat, S.; Steinmetz, G.; Quemeneur, E. [CEA VALRHO, Serv Biochim and Toxicol Nucl, DSV, iBEB, F-30207 Bagnols Sur Ceze (France)

    2007-06-06

    It has been estimated that more than 1 million workers in the United States are exposed to cobalt. Occupational exposure to {sup 59}Co occurs mainly via inhalation and leads to various lung diseases. Cobalt is classified by the IARC as a possible human carcinogen (group 2B). Although there is evidence for in vivo and in vitro toxicity, the mechanisms of cobalt-induced lung toxicity are not fully known. The purpose of this work was to identify potential signatures of acute cobalt exposure using a toxico-genomic approach. Data analysis focused on some cellular processes and protein targets that are thought to be relevant for carcinogenesis, transport and bio-marker research. Results: A time course transcriptome analysis was performed on A549 human pulmonary cells, leading to the identification of 85 genes which are repressed or induced in response to soluble 59 Co. A group of 29 of these genes, representing the main biological functions, was assessed by quantitative RT-PCR. The expression profiles of six of them were then tested by quantitative RT-PCR in a time-dependent manner and three modulations were confirmed by Western blotting. The 85 modulated genes include potential cobalt carriers (FBXL2, ZNT1, SLC12A5), tumor suppressors or transcription factors (MAZ, DLG1, MYC, AXL) and genes linked to the stress response (UBC, HSPCB, BN1P3L). We also identified nine genes coding for secreted proteins as candidates for bio-marker research. Of those, T1MP2 was found to be down-regulated and this modulation was confirmed, in a dose-dependent manner, at protein level in the supernatant of exposed cells. Conclusion: Most of these genes have never been described as related to cobalt stress and provide original hypotheses for further study of the effects of this metal ion on human lung epithelial cells. A putative bio-marker of cobalt toxicity was identified. (authors)

  19. Global Transcriptomic Analysis of Targeted Silencing of Two Paralogous ACC Oxidase Genes in Banana

    Science.gov (United States)

    Xia, Yan; Kuan, Chi; Chiu, Chien-Hsiang; Chen, Xiao-Jing; Do, Yi-Yin; Huang, Pung-Ling

    2016-01-01

    Among 18 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase homologous genes existing in the banana genome there are two genes, Mh-ACO1 and Mh-ACO2, that participate in banana fruit ripening. To better understand the physiological functions of Mh-ACO1 and Mh-ACO2, two hairpin-type siRNA expression vectors targeting both the Mh-ACO1 and Mh-ACO2 were constructed and incorporated into the banana genome by Agrobacterium-mediated transformation. The generation of Mh-ACO1 and Mh-ACO2 RNAi transgenic banana plants was confirmed by Southern blot analysis. To gain insights into the functional diversity and complexity between Mh-ACO1 and Mh-ACO2, transcriptome sequencing of banana fruits using the Illumina next-generation sequencer was performed. A total of 32,093,976 reads, assembled into 88,031 unigenes for 123,617 transcripts were obtained. Significantly enriched Gene Oncology (GO) terms and the number of differentially expressed genes (DEGs) with GO annotation were ‘catalytic activity’ (1327, 56.4%), ‘heme binding’ (65, 2.76%), ‘tetrapyrrole binding’ (66, 2.81%), and ‘oxidoreductase activity’ (287, 12.21%). Real-time RT-PCR was further performed with mRNAs from both peel and pulp of banana fruits in Mh-ACO1 and Mh-ACO2 RNAi transgenic plants. The results showed that expression levels of genes related to ethylene signaling in ripening banana fruits were strongly influenced by the expression of genes associated with ethylene biosynthesis. PMID:27681726

  20. [Correlation of polymorphisms of adiponectin receptor 2 gene +33371Gln/Arg, cytochrome P4502E1 gene Rsa I and smoking with nonalcoholic fatty liver disease].

    Science.gov (United States)

    Zhang, Chaoxian; Guo, Like

    2014-10-01

    To investigate the correlation of the polymorphisms of adiponectin receptor 2 (AdipoR2) gene +33371Gln/;Arg and cytochromes P4502E1 gene Rsa I (CYP2E1-Rsa I) as well as smoking with nonalcoholic fatty liver disease (NAFLD). The polymorphisms of AdipoR2 gene +33371Gln/Arg and CYP2E1-Rsa I were analyzed with PCR technique in peripheral blood leukocytes from 750 NAFLD cases and 750 healthy subjects. The frequencies of AdipoR2 gene +33371Gln/Arg (A/A) and CYP2E1-Rsa I (c2/c2 ) were 39.20% and 71.73% in NAFLD cases, respectively, significantly higher than those in healthy subjects (21.07% and 43.07%, respectively, PRsa I (c2/c2) (OR=3.3547, 95% CI=1.9182-4.5057). Combined analysis of the polymorphisms showed that the percentage of +33371Gln/Arg (A/A)/CYP2E1-Rsa I (c2/c2) was 32. 67% in NAFLD cases, significantly higher than that in the healthy subjects (6.40%, PRsa I (c2/c2) had a high risk of NAFLD (OR=9.9264, 95% CI=4.2928-12.4241). The smoking rate was significantly higher in the case group than in the control group (OR=2.5919, 95% CI=1.4194-4. 9527, PRsa I (c2/c2) to increase the risk of NAFLD (OR=34.6764, 95% CI=18.9076-61.5825). +33371Gln/Arg (A/A), CYP2E1-Rsa I (c2/c2 ) and smoking are risk factors for NAFLD and coordinately contribute to the occurrence of NAFLD.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. Genome-wide study of correlations between genomic features and their relationship with the regulation of gene expression.

    Science.gov (United States)

    Kravatsky, Yuri V; Chechetkin, Vladimir R; Tchurikov, Nikolai A; Kravatskaya, Galina I

    2015-02-01

    The broad class of tasks in genetics and epigenetics can be reduced to the study of various features that are distributed over the genome (genome tracks). The rapid and efficient processing of the huge amount of data stored in the genome-scale databases cannot be achieved without the software packages based on the analytical criteria. However, strong inhomogeneity of genome tracks hampers the development of relevant statistics. We developed the criteria for the assessment of genome track inhomogeneity and correlations between two genome tracks. We also developed a software package, Genome Track Analyzer, based on this theory. The theory and software were tested on simulated data and were applied to the study of correlations between CpG islands and transcription start sites in the Homo sapiens genome, between profiles of protein-binding sites in chromosomes of Drosophila melanogaster, and between DNA double-strand breaks and histone marks in the H. sapiens genome. Significant correlations between transcription start sites on the forward and the reverse strands were observed in genomes of D. melanogaster, Caenorhabditis elegans, Mus musculus, H. sapiens, and Danio rerio. The observed correlations may be related to the regulation of gene expression in eukaryotes. Genome Track Analyzer is freely available at http://ancorr.eimb.ru/. © The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  7. Studies of metabolic phenotypic correlates of 15 obesity associated gene variants

    DEFF Research Database (Denmark)

    Sandholt, Camilla Helene; Vestmar, Marie Aare; Bille, Dorthe Sadowa

    2011-01-01

    associate with type 2 diabetes and to elucidate potential underlying metabolic mechanisms. Methods: 15 gene variants in 14 loci including TMEM18 (rs7561317), SH2B1 (rs7498665), KCTD15 (rs29941), NEGR1 (rs2568958), ETV5 (rs7647305), BDNF (rs4923461, rs925946), SEC16B (rs10913469), FAIM2 (rs7138803), GNPDA2......, which could suggest neuronal and peripheral distinctive ways of actions for the protein. SH2B1 rs7498665 associated with type 2 diabetes independently of BMI....

  8. 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.

  9. Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters

    NARCIS (Netherlands)

    Cimermancic, P.; Medema, Marnix; Claesen, J.; Kurika, K.; Wieland Brown, L.C.; Mavrommatis, K.; Pati, A.; Godfrey, P.A.; Koehrsen, M.; Clardy, J.; Birren, B. W.; Takano, Eriko; Sali, A.; Linington, R.G.; Fischbach, M.A.

    2014-01-01

    Although biosynthetic gene clusters (BGCs) have been discovered for hundreds of bacterial metabolites, our knowledge of their diversity remains limited. Here, we used a novel algorithm to systematically identify BGCs in the extensive extant microbial sequencing data. Network analysis of the

  10. Global Features of Gene Expression on the Proteome and Transcriptome Levels in S. coelicolor during Germination

    Czech Academy of Sciences Publication Activity Database

    Straková, Eva; Bobek, Jan; Ziková, Alice; Vohradský, Jiří

    2013-01-01

    Roč. 8, č. 9 (2013) E-ISSN 1932-6203 R&D Projects: GA ČR GAP302/11/0229; GA ČR GAP302/10/0468 Institutional support: RVO:61388971 Keywords : Streptomycetes * Gene expression * s. coelicolor Subject RIV: EE - Microbiology, Virology Impact factor: 3.534, year: 2013

  11. Causal correlations between genes and linguistic features: The mechanism of gradual language evolution

    OpenAIRE

    Dediu, D.

    2008-01-01

    The causal correlations between human genetic variants and linguistic (typological) features could represent the mechanism required for gradual, accretionary models of language evolution. The causal link is mediated by the process of cultural transmission of language across generations in a population of genetically biased individuals. The particular case of Tone, ASPM and Microcephalin is discussed as an illustration. It is proposed that this type of genetically-influenced linguistic bias, c...

  12. 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

  13. 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)

  14. Genome Plasticity and Polymorphisms in Critical Genes Correlate with Increased Virulence of Dutch Outbreak-Related Coxiella burnetii Strains

    Directory of Open Access Journals (Sweden)

    Runa Kuley

    2017-08-01

    Full Text Available Coxiella burnetii is an obligate intracellular bacterium and the etiological agent of Q fever. During 2007–2010 the largest Q fever outbreak ever reported occurred in The Netherlands. It is anticipated that strains from this outbreak demonstrated an increased zoonotic potential as more than 40,000 individuals were assumed to be infected. The acquisition of novel genetic factors by these C. burnetii outbreak strains, such as virulence-related genes, has frequently been proposed and discussed, but is not proved yet. In the present study, the whole genome sequence of several Dutch strains (CbNL01 and CbNL12 genotypes, a few additionally selected strains from different geographical locations and publicly available genome sequences were used for a comparative bioinformatics approach. The study focuses on the identification of specific genetic differences in the outbreak related CbNL01 strains compared to other C. burnetii strains. In this approach we investigated the phylogenetic relationship and genomic aspects of virulence and host-specificity. Phylogenetic clustering of whole genome sequences showed a genotype-specific clustering that correlated with the clustering observed using Multiple Locus Variable-number Tandem Repeat Analysis (MLVA. Ortholog analysis on predicted genes and single nucleotide polymorphism (SNP analysis of complete genome sequences demonstrated the presence of genotype-specific gene contents and SNP variations in C. burnetii strains. It also demonstrated that the currently used MLVA genotyping methods are highly discriminatory for the investigated outbreak strains. In the fully reconstructed genome sequence of the Dutch outbreak NL3262 strain of the CbNL01 genotype, a relatively large number of transposon-linked genes were identified as compared to the other published complete genome sequences of C. burnetii. Additionally, large numbers of SNPs in its membrane proteins and predicted virulence-associated genes were identified

  15. Correlation between ability of biofilm formation with their responsible genes and MDR patterns in clinical and environmental Acinetobacter baumannii isolates.

    Science.gov (United States)

    Bardbari, Ali Mohammadi; Arabestani, Mohammad Reza; Karami, Manoochehr; Keramat, Fariba; Alikhani, Mohammad Yousef; Bagheri, Kamran Pooshang

    2017-07-01

    Acinetobacter baumannii potential to form biofilm and exhibit multiple antibiotic resistances may be responsible in its survival in hospital environment. Accordingly, our study was aimed to determine the correlation between ability of biofilm formation and the frequency of biofilm related genes with antibiotic resistance phenotypes, and also the categorization of their patterns in clinical and environmental isolates. A total of 75 clinical and 32 environmental strains of the A. baumannii were collected and identified via API 20NE. Antibiotic susceptibility was evaluated by disk diffusion and microdilution broth methods. Biofilm formation assay was performed by microtiter plate method. OXA types and biofilm related genes including Bla OXA-51 , Bla OXA-23 , Bla OXA-24 , Bla OXA-58 , bap, bla PER-1 , and ompA were amplified by PCR. The rate of MDR A. baumannii in clinical isolates (100%) was higher than environmental (81.2%) isolates (p baumannii isolates was associated with biofilm formation. There was a significant correlation between multiple drug resistance and biofilm formation. The clinical isolates had a higher ability to form strong biofilms compared to the environmental samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. 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.

  17. p53 immunostaining is correlated with reduced survival and is not correlated with gene mutations in resected pulmonary large cell carcinomas

    Directory of Open Access Journals (Sweden)

    L.M. Massoni Neto

    2007-08-01

    Full Text Available Malignancy of pulmonary large cell carcinomas (LCC increases from classic LCC through LCC with neuroendocrine morphology (LCCNM to large cell neuroendocrine carcinomas (LCNEC. However, the histological classification has sometimes proved to be difficult. Because the malignancy of LCC is highly dependent on proteins with functions in the cell cycle, DNA repair, and apoptosis, p53 has been targeted as a potentially useful biological marker. p53 mutations in lung cancers have been shown to result in expression and protein expression also occurs in the absence of mutations. To validate the importance of both p53 protein expression (by immunostaining and p53 gene mutations in lung LCC (by PCR-single strand conformational polymorphism analysis of exons 5, 6, 7, and 8 and to study their relationships with clinical factors and sub-classification we investigated the correlation of p53 abnormalities in 15 patients with LCC (5 classic LCC, 5 LCNEC, and 5 LCCNM who had undergone resection with curative intent. Of these patients, 5/15 expressed p53 and none had mutant p53 sequences. There was a negative survival correlation with positive p53 immunostaining (P = 0.05. After adjustment for stage, age, gender, chemotherapy, radiotherapy, and histological subtypes by multivariate analysis, p53 expression had an independent impact on survival. The present study indicates that p53 assessment may provide an objective marker for the prognosis of LCC irrespective of morphological variants and suggests that p53 expression is important for outcome prediction in patients with the early stages of LCC. The results reported here should be considered to be initial results because tumors from only 15 patients were studied: 5 each from LCC, LCNEC and LCCNM. This was due to the rarity of these specific diseases.

  18. 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.)

  19. 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.)

  20. Spaceflight Alters Bacterial Gene Expression and Virulence and Reveals Role for Global Regulator Hfq

    Science.gov (United States)

    Wilson, J. W.; Ott, C. M.; zuBentrup, K. Honer; Ramamurthy R.; Quick, L.; Porwollik, S.; Cheng, P.; McClellan, M.; Tsaprailis, G.; Radabaugh, T.; hide

    2007-01-01

    A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the spaceflight environment has never been accomplished due to significant technological and logistical hurdles. Moreover, the effects of spaceflight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared to identical ground control cultures. Global microarray and proteomic analyses revealed 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground based microgravity culture model. Spaceflight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during spaceflight missions and provide novel therapeutic options on Earth.

  1. Los orígenes del debate sobre la justicia global

    Directory of Open Access Journals (Sweden)

    Peña Echeverría, Javier

    2010-12-01

    Full Text Available The notion of global justice and the theory of justice attached to it are new in the current moral and political philosophy. However, this paper aims to show that the present debate on global justice is partially based upon problems and concepts that had previously been an issue of reflection and controversy in the history of the philosophical and juridical thinking. In particular, it tries to be a reflection on the following three ideas: first, on a universal human community conceived of as a framework that coexists with the fact of being a member of particular political societies; second, on the distinctions between perfect and imperfect rights and duties, as well as between requirements of justice and beneficence; and finally, on justification, conditions, and limits for communication, trade and property among members of different political societies.

    La idea de una justicia global y el enfoque desde ese punto de vista de la teoría de la justicia son novedosos en la filosofía moral y política actual. Sin embargo, este artículo trata de mostrar que el debate actual sobre la justicia global se sustenta en parte sobre conceptos y problemas que fueron anteriormente objeto de reflexión y controversia en la historia del pensamiento filosófico y jurídico: la idea de una comunidad humana universal como marco de referencia que convive con la pertenencia a sociedades políticas particulares; la distinción entre derechos y deberes perfectos e imperfectos, así como entre exigencias de justicia y de beneficencia; y la justificación, condiciones y límites de la comunicación, el comercio y la propiedad entre miembros de distintas sociedades políticas.

  2. Twist and YB-1 gene expression in cervical cancer and precancerous tissue and their correlation with cell invasion

    Directory of Open Access Journals (Sweden)

    Qin Tian

    2017-04-01

    Full Text Available Objective: To study the correlation of Twist and YB-1 gene expression in cervical cancer and precancerous tissue with cell invasion. Methods: Cervical cancer tissue, precancerous tissue and normal cervical tissue surgically removed in our hospital between May 2013 and April 2015 were collected; immunohistochemical staining kits were used to detect the positive protein expression rate of Twist and YB-1 gene; fluorescence quantitative PCR kits were used to detect Twist, YB-1 and invasion gene mRNA expression. Results: Twist and YB-1 mRNA expression and positive protein expression rate as well as USP22, Rab11, Rac1 and ANXA5 mRNA expression in cervical cancer tissue and precancerous tissue were significantly higher than those in normal cervical tissue, Twist and YB-1 mRNA expression and positive protein expression rate as well as USP22, Rab11, Rac1 and ANXA5 mRNA expression in cervical cancer tissue were significantly higher than those in precancerous tissue; USP22, Rab11, Rac1 and ANXA5 mRNA expression in cervical cancer tissue and precancerous tissue with positive Twist and YB-1 expression were significantly higher than those in cervical cancer tissue and precancerous tissue with negative Twist and YB-1 expression. Conclusion: Highly expressed Twist and YB-1 in cervical cancer and precancerous tissue can promote cell invasion.

  3. 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.

  4. 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.

  5. 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

  6. Correlation of EGFR expression, gene copy number and clinicopathological status in NSCLC.

    Science.gov (United States)

    Gaber, Rania; Watermann, Iris; Kugler, Christian; Reinmuth, Nils; Huber, Rudolf M; Schnabel, Philipp A; Vollmer, Ekkehard; Reck, Martin; Goldmann, Torsten

    2014-09-17

    Epidermal Growth Factor Receptor (EGFR) targeting therapies are currently of great relevance for the treatment of lung cancer. For this reason, in addition to mutational analysis immunohistochemistry (IHC) of EGFR in lung cancer has been discussed for the decision making of according therapeutic strategies. The aim of this study was to obtain standardization of EGFR-expression methods for the selection of patients who might benefit of EGFR targeting therapies. As a starting point of a broad investigation, aimed at elucidating the expression of EGFR on different biological levels, four EGFR specific antibodies were analyzed concerning potential differences in expression levels by Immunohistochemistry (IHC) and correlated with fluorescence in situ hybridization (FISH) analysis and clinicopathological data. 206 tumor tissues were analyzed in a tissue microarray format employing immunohistochemistry with four different antibodies including Dako PharmDx kit (clone 2-18C9), clone 31G7, clone 2.1E1 and clone SP84 using three different scoring methods. Protein expression was compared to FISH utilizing two different probes. EGFR protein expression determined by IHC with Dako PharmDx kit, clone 31G7 and clone 2.1E1 (p ≤ 0.05) correlated significantly with both FISH probes independently of the three scoring methods; best correlation is shown for 31G7 using the scoring method that defined EGFR positivity when ≥ 10% of the tumor cells show membranous staining of moderate and severe intensity (p=0.001). Overall, our data show differences in EGFR expression determined by IHC, due to the applied antibody. Highest concordance with FISH is shown for antibody clone 31G7, evaluated with score B (p=0.001). On this account, this antibody clone might by utilized for standard evaluation of EGFR expression by IHC. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_165.

  7. Global transcriptional regulatory network for Escherichia coli robustly connects gene expression to transcription factor activities

    Science.gov (United States)

    Fang, Xin; Sastry, Anand; Mih, Nathan; Kim, Donghyuk; Tan, Justin; Lloyd, Colton J.; Gao, Ye; Yang, Laurence; Palsson, Bernhard O.

    2017-01-01

    Transcriptional regulatory networks (TRNs) have been studied intensely for >25 y. Yet, even for the Escherichia coli TRN—probably the best characterized TRN—several questions remain. Here, we address three questions: (i) How complete is our knowledge of the E. coli TRN; (ii) how well can we predict gene expression using this TRN; and (iii) how robust is our understanding of the TRN? First, we reconstructed a high-confidence TRN (hiTRN) consisting of 147 transcription factors (TFs) regulating 1,538 transcription units (TUs) encoding 1,764 genes. The 3,797 high-confidence regulatory interactions were collected from published, validated chromatin immunoprecipitation (ChIP) data and RegulonDB. For 21 different TF knockouts, up to 63% of the differentially expressed genes in the hiTRN were traced to the knocked-out TF through regulatory cascades. Second, we trained supervised machine learning algorithms to predict the expression of 1,364 TUs given TF activities using 441 samples. The algorithms accurately predicted condition-specific expression for 86% (1,174 of 1,364) of the TUs, while 193 TUs (14%) were predicted better than random TRNs. Third, we identified 10 regulatory modules whose definitions were robust against changes to the TRN or expression compendium. Using surrogate variable analysis, we also identified three unmodeled factors that systematically influenced gene expression. Our computational workflow comprehensively characterizes the predictive capabilities and systems-level functions of an organism’s TRN from disparate data types. PMID:28874552

  8. Global and disease-associated genetic variation in the human Fanconi anemia gene family.

    Science.gov (United States)

    Rogers, Kai J; Fu, Wenqing; Akey, Joshua M; Monnat, Raymond J

    2014-12-20

    Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57,240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Global and disease-associated genetic variation in the human Fanconi anemia gene family

    OpenAIRE

    Rogers, Kai J.; Fu, Wenqing; Akey, Joshua M.; Monnat, Raymond J.

    2014-01-01

    Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population gen...

  10. 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

  11. 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.

  12. Operating Characteristics of Statistical Methods for Detecting Gene-by-Measured Environment Interaction in the Presence of Gene-Environment Correlation under Violations of Distributional Assumptions.

    Science.gov (United States)

    Van Hulle, Carol A; Rathouz, Paul J

    2015-02-01

    Accurately identifying interactions between genetic vulnerabilities and environmental factors is of critical importance for genetic research on health and behavior. In the previous work of Van Hulle et al. (Behavior Genetics, Vol. 43, 2013, pp. 71-84), we explored the operating characteristics for a set of biometric (e.g., twin) models of Rathouz et al. (Behavior Genetics, Vol. 38, 2008, pp. 301-315), for testing gene-by-measured environment interaction (GxM) in the presence of gene-by-measured environment correlation (rGM) where data followed the assumed distributional structure. Here we explore the effects that violating distributional assumptions have on the operating characteristics of these same models even when structural model assumptions are correct. We simulated N = 2,000 replicates of n = 1,000 twin pairs under a number of conditions. Non-normality was imposed on either the putative moderator or on the ultimate outcome by ordinalizing or censoring the data. We examined the empirical Type I error rates and compared Bayesian information criterion (BIC) values. In general, non-normality in the putative moderator had little impact on the Type I error rates or BIC comparisons. In contrast, non-normality in the outcome was often mistaken for or masked GxM, especially when the outcome data were censored.

  13. Influence of correlation between HLA-G polymorphism and Interleukin-6 (IL6) gene expression on the risk of schizophrenia.

    Science.gov (United States)

    Shivakumar, Venkataram; Debnath, Monojit; Venugopal, Deepthi; Rajasekaran, Ashwini; Kalmady, Sunil V; Subbanna, Manjula; Narayanaswamy, Janardhanan C; Amaresha, Anekal C; Venkatasubramanian, Ganesan

    2018-07-01

    Converging evidence suggests important implications of immuno-inflammatory pathway in the risk and progression of schizophrenia. Prenatal infection resulting in maternal immune activation and developmental neuroinflammation reportedly increases the risk of schizophrenia in the offspring by generating pro-inflammatory cytokines including IL-6. However, it is not known how prenatal infection can induce immuno-inflammatory responses despite the presence of immuno-inhibitory Human Leukocyte Antigen-G (HLA-G) molecules. To address this, the present study was aimed at examining the correlation between 14 bp Insertion/Deletion (INDEL) polymorphism of HLA-G and IL-6 gene expression in schizophrenia patients. The 14 bp INDEL polymorphism was studied by PCR amplification/direct sequencing and IL-6 gene expression was quantified by using real-time RT-PCR in 56 schizophrenia patients and 99 healthy controls. We observed significantly low IL6 gene expression in the peripheral mononuclear cells (PBMCs) of schizophrenia patients (t = 3.8, p = .004) compared to the controls. In addition, schizophrenia patients carrying Del/Del genotype of HLA-G 14 bp INDEL exhibited significantly lower IL6 gene expression (t = 3.1; p = .004) than the Del/Ins as well as Ins/Ins carriers. Our findings suggest that presence of "high-expressor" HLA-G 14 bp Del/Del genotype in schizophrenia patients could attenuate IL-6 mediated inflammation in schizophrenia. Based on these findings it can be assumed that HLA-G and cytokine interactions might play an important role in the immunological underpinnings of schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. 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.)

  15. 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.)

  16. Genes, isotopes, and ecosystem biogeochemistry. Dissecting methane flux at the leading edge of global change

    Energy Technology Data Exchange (ETDEWEB)

    Saleska, Scott [Univ. of Arizona, Tucson, AZ (United States); Rich, Virginia [The Ohio State Univ., Columbus, OH (United States); Tyson, Gene [Univ. of Queensland, St. Lucia (Australia); Chanton, Jeff [Florida State Univ., Tallahassee, FL (United States); Crill, Patrick [Stockholm Univ. (Sweden); Li, Changshen [Univ. of New Hampshire, Durham, NH (United States)

    2016-02-22

    This project integrates across three fields (microbiology, biogeochemistry, and modeling) to understand the mechanisms of methane cycling in thawing permafrost. We have made substantial progress in each area, and in cross-cutting interdisciplinary synthesis. Large releases of CH4 from thawing permafrost to the atmosphere, a strong positive feedback to global warming, are plausible but little is known about the controls on such release. Our project (“IsoGenie”) addresses the key question: What is the interplay of microbial communities and soil organic matter composition in the decomposition of organic C to CH4 across a permafrost thaw gradient?

  17. Global methylation silencing of clustered proto-cadherin genes in cervical cancer: serving as diagnostic markers comparable to HPV

    International Nuclear Information System (INIS)

    Wang, Kai-Hung; Lin, Cuei-Jyuan; Liu, Chou-Jen; Liu, Dai-Wei; Huang, Rui-Lan; Ding, Dah-Ching; Weng, Ching-Feng; Chu, Tang-Yuan

    2015-01-01

    Epigenetic remodeling of cell adhesion genes is a common phenomenon in cancer invasion. This study aims to investigate global methylation of cell adhesion genes in cervical carcinogenesis and to apply them in early detection of cancer from cervical scraping. Genome-wide methylation array was performed on an investigation cohort, including 16 cervical intraepithelial neoplasia 3 (CIN3) and 20 cervical cancers (CA) versus 12 each of normal, inflammation and CIN1 as controls. Twelve members of clustered proto-cadherin (PCDH) genes were collectively methylated and silenced, which were validated in cancer cells of the cervix, endometrium, liver, head and neck, breast, and lung. In an independent cohort including 107 controls, 66 CIN1, 85 CIN2/3, and 38 CA, methylated PCDHA4 and PCDHA13 were detected in 2.8%, 24.2%, 52.9%, and 84.2% (P < 10 −25 ), and 2.8%, 24.2%, 50.6%, and 94.7% (P < 10 −29 ), respectively. In diagnosis of CIN2 or more severe lesion of the cervix, a combination test of methylated PCDHA4 or PCDHA13 from cervical scraping had a sensitivity, specificity, positive predictive value, and negative predictive value of 74.8%, 80.3%, 73%, and 81.8%, respectively. Testing of this combination from cervical scraping is equally sensitive but more specific than human papillomavirus (HPV) test in diagnosis of CIN2 or more severe lesions. The study disclosed a collective methylation of PCDH genes in cancer of cervix and other sites. At least two of them can be promising diagnostic markers for cervical cancer noninferior to HPV

  18. Fungal Biodegradative Oxidants in Lignocellulose: Fluorescence Mapping and Correlation With Gene Expression

    Energy Technology Data Exchange (ETDEWEB)

    Hammel, Kenneth E. [Univ. of Wisconsin, Madison, WI (United States); Ralph, John [Univ. of Wisconsin, Madison, WI (United States); Hunt, Christopher G. [U.S. Forest Products Lab., Madison, WI (United States); Houtman, Carl J. [U.S. Forest Products Lab., Madison, WI (United States)

    2016-09-06

    This work focused on new methods for the detection of oxidation in natural substrates during the deconstruction of lignocellulose by microoganisms. Oxidation was the focus because all known biological systems that degrade lignin are oxidative. The detection methods involved the used of (a) micrometer-scale beads carrying a fluorescent dye that is sensitive to oxidation, (b) 13C-labeled synthetic lignins whose breakdown products can be assessed using mass spectrometry and nuclear magnetic resonance spectroscopy, and (c) a fluorometric stain that is highly sensitive to incipient oxidation during microbial attack. The results showed (a) that one white rot fungus, Phanerochaete chrysosporium, produces diffusible oxidants on wood, and that the onset of oxidation is coincident with the marked up-regulation of genes that encode ligninolytic peroxidases and auxiliary oxidative enzymes; (b) that a more selectively ligninolytic white rot fungus, Ceriporiopsis subvermispora, produces a highly diastereoselective oxidative system for attack on lignin; (c) that a brown rot fungus, Serpula lacrymans, uses extracellular hydroquinone metabolites to drive the production of lignocellulose-oxidizing free radicals; (d) that both white rot and brown rot fungi produce highly diffusible mild oxidants that modify lignocellulose at the earliest stage of substrate deconstruction; and (e) that lignin degradation in a tropical soil is not inhibited as much as expected during periods of flooding-induced hypoxia, which indicates that unknown mechanisms for attack on lignin remain to be discovered.

  19. Reduced methylation of the thromboxane synthase gene is correlated with its increased vascular expression in preeclampsia.

    Science.gov (United States)

    Mousa, Ahmad A; Strauss, Jerome F; Walsh, Scott W

    2012-06-01

    Preeclampsia is characterized by increased thromboxane and decreased prostacyclin levels, which predate symptoms, and can explain some of the clinical manifestations of preeclampsia, including hypertension and thrombosis. In this study, we examined DNA methylation of the promoter region of the thromboxane synthase gene (TBXAS1) and the expression of thromboxane synthase in systemic blood vessels of normal pregnant and preeclamptic women. Thromboxane synthase is responsible for the synthesis of thromboxane A(2), a potent vasoconstrictor and activator of platelets. We also examined the effect of experimentally induced DNA hypomethylation on the expression of thromboxane synthase in a neutrophil-like cell line (HL-60 cells) and in cultured vascular smooth muscle and endothelial cells. We found that DNA methylation of the TBXAS1 promoter was decreased and thromboxane synthase expression was increased in omental arteries of preeclamptic women as compared with normal pregnant women. Increased thromboxane synthase expression was observed in vascular smooth muscles cells, endothelial cells, and infiltrating neutrophils. Experimentally induced DNA hypomethylation only increased expression of thromboxane synthase in the neutrophil-like cell line, whereas tumor necrosis factor-α, a neutrophil product, increased its expression in cultured vascular smooth muscle cells. Our study suggests that epigenetic mechanisms and release of tumor necrosis factor-α by infiltrating neutrophils could contribute to the increased expression of thromboxane synthase in maternal systemic blood vessels, contributing to the hypertension and coagulation abnormalities associated with preeclampsia.

  20. Global gene expression patterns in the post-pneumonectomy lung of adult mice

    Directory of Open Access Journals (Sweden)

    Ingenito Edward P

    2009-10-01

    Full Text Available Abstract Background Adult mice have a remarkable capacity to regenerate functional alveoli following either lung resection or injury that exceeds the regenerative capacity observed in larger adult mammals. The molecular basis for this unique capability in mice is largely unknown. We examined the transcriptomic responses to single lung pneumonectomy in adult mice in order to elucidate prospective molecular signaling mechanisms used in this species during lung regeneration. Methods Unilateral left pneumonectomy or sham thoracotomy was performed under general anesthesia (n = 8 mice per group for each of the four time points. Total RNA was isolated from the remaining lung tissue at four time points post-surgery (6 hours, 1 day, 3 days, 7 days and analyzed using microarray technology. Results The observed transcriptomic patterns revealed mesenchymal cell signaling, including up-regulation of genes previously associated with activated fibroblasts (Tnfrsf12a, Tnc, Eln, Col3A1, as well as modulation of Igf1-mediated signaling. The data set also revealed early down-regulation of pro-inflammatory cytokine transcripts and up-regulation of genes involved in T cell development/function, but few similarities to transcriptomic patterns observed during embryonic or post-natal lung development. Immunohistochemical analysis suggests that early fibroblast but not myofibroblast proliferation is important during lung regeneration and may explain the preponderance of mesenchymal-associated genes that are over-expressed in this model. This again appears to differ from embryonic alveologenesis. Conclusion These data suggest that modulation of mesenchymal cell transcriptome patterns and proliferation of S100A4 positive mesenchymal cells, as well as modulation of pro-inflammatory transcriptome patterns, are important during post-pneumonectomy lung regeneration in adult mice.

  1. 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.

  2. The Number of Overlapping AID Hotspots in Germline IGHV Genes Is Inversely Correlated with Mutation Frequency in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Yuan, Chaohui; Chu, Charles C; Yan, Xiao-Jie; Bagnara, Davide; Chiorazzi, Nicholas; MacCarthy, Thomas

    2017-01-01

    The targeting of mutations by Activation-Induced Deaminase (AID) is a key step in generating antibody diversity at the Immunoglobulin (Ig) loci but is also implicated in B-cell malignancies such as chronic lymphocytic leukemia (CLL). AID has previously been shown to preferentially deaminate WRC (W = A/T, R = A/G) hotspots. WGCW sites, which contain an overlapping WRC hotspot on both DNA strands, mutate at much higher frequency than single hotspots. Human Ig heavy chain (IGHV) genes differ in terms of WGCW numbers, ranging from 4 for IGHV3-48*03 to as many as 12 in IGHV1-69*01. An absence of V-region mutations in CLL patients ("IGHV unmutated", or U-CLL) is associated with a poorer prognosis compared to "IGHV mutated" (M-CLL) patients. The reasons for this difference are still unclear, but it has been noted that particular IGHV genes associate with U-CLL vs M-CLL. For example, patients with IGHV1-69 clones tend to be U-CLL with a poor prognosis, whereas patients with IGHV3-30 tend to be M-CLL and have a better prognosis. Another distinctive feature of CLL is that ~30% of (mostly poor prognosis) patients can be classified into "stereotyped" subsets, each defined by HCDR3 similarity, suggesting selection, possibly for a self-antigen. We analyzed >1000 IGHV genes from CLL patients and found a highly significant statistical relationship between the number of WGCW hotspots in the germline V-region and the observed mutation frequency in patients. However, paradoxically, this correlation was inverse, with V-regions with more WGCW hotspots being less likely to be mutated, i.e., more likely to be U-CLL. The number of WGCW hotspots in particular, are more strongly correlated with mutation frequency than either non-overlapping (WRC) hotspots or more general models of mutability derived from somatic hypermutation data. Furthermore, this correlation is not observed in sequences from the B cell repertoires of normal individuals and those with autoimmune diseases.

  3. 17α-Ethinylestradiol (EE2) effect on global gene expression in primary rainbow trout (Oncorhynchus mykiss) hepatocytes.

    Science.gov (United States)

    Hultman, Maria T; Song, You; Tollefsen, Knut Erik

    2015-12-01

    The potential impact of endocrine disrupting chemicals (EDCs) in the aquatic environment has driven the development of screening assays to evaluate the estrogenic properties of chemicals and their effects on aquatic organisms such as fish. However, obtaining full concentration-response relationships in animal (in vivo) exposure studies are laborious, costly and unethical, hence a need for developing feasible alternative (non-animal) methods. Use of in vitro bioassays such as primary fish hepatocytes, which retain many of the native properties of the liver, has been proposed for in vitro screening of estrogen receptor (ER) agonists and antagonists. The aim of present study was to characterize the molecular mode of action (MoA) of the ER agonist 17α-ethinylestradiol (EE2) in primary rainbow trout (Oncorhynchus mykiss) hepatocytes. A custom designed salmonid 60,000-feature (60k) oligonucleotide microarray was used to characterize the potential MoAs after 48h exposure to EE2. The microarray analysis revealed several concentration-dependent gene expression alterations including classical estrogen sensitive biomarker gene expression (e.g. estrogen receptor α, vitellogenin, zona radiata). Gene Ontology (GO) analysis displayed transcriptional changes suggesting interference of cellular growth, fatty acid and lipid metabolism potentially mediated through the estrogen receptor (ER), which were proposed to be associated with modulation of genes involved in endocrine function and reproduction. Pathway analysis supported the identified GOs and revealed modulation of additional genes associated with apoptosis and cholesterol biosynthesis. Differentially expressed genes (DEGs) related to impaired lipid metabolism (e.g. peroxisome proliferator-activated receptor α and γ), growth (e.g. insulin growth factor protein 1), phase I and II biotransformation (e.g. cytochrome P450 1A, sulfotransferase, UDP-glucuronosyltransferase and glutathione S-transferase) provided additional

  4. 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

  5. Global Gene Expression Differences in Joints of Mice with Divergent Post Traumatic Osteoarthritis Phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Kibui, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-07-28

    Osteoarthritis (OA) is a debilitating joint disease characterized by cartilage degradation which prompts pain, stiffness and swelling. Contributing factors include age, genetics, obesity, injury and overuse of joints. OA is defined by an acute phase and a chronic phase whereby inflammation and degeneration of articular cartilage and other tissues is followed by joint pain and limited mobility. Patients remain asymptomatic until substantial joint damage has occurred and therefore rely on long term surgical joint replacement and pain management as their sole treatment options. For this reason, there is an increasing need to identify early stage osteoarthritis biomarkers. Our study aimed to identify and characterize gene expression variances in 3 different mouse strains (STR/ort, C57BL/6 and MRL/MpJ) with different susceptibility to post traumatic osteoarthritis (PTOA). Through RNA sequence analysis of whole knee joint RNA, we identified differentially expressed genes associated with the initial stages of PTOA in relation to mice with divergent phenotypes. These results will help elucidate potential mechanisms responsible for PTOA outcomes.

  6. DNA microarray global gene expression analysis of influenza virus-infected chicken and duck cells

    Directory of Open Access Journals (Sweden)

    Suresh V. Kuchipudi

    2015-06-01

    Full Text Available The data described in this article pertain to the article by Kuchipudi et al. (2014 titled “Highly Pathogenic Avian Influenza Virus Infection in Chickens But Not Ducks Is Associated with Elevated Host Immune and Pro-inflammatory Responses” [1]. While infection of chickens with highly pathogenic avian influenza (HPAI H5N1 virus subtypes often leads to 100% mortality within 1 to 2 days, infection of ducks in contrast causes mild or no clinical signs. The rapid onset of fatal disease in chickens, but with no evidence of severe clinical symptoms in ducks, suggests underlying differences in their innate immune mechanisms. We used Chicken Genechip microarrays (Affymetrix to analyse the gene expression profiles of primary chicken and duck lung cells infected with a low pathogenic avian influenza (LPAI H2N3 virus and two HPAI H5N1 virus subtypes to understand the molecular basis of host susceptibility and resistance in chickens and ducks. Here, we described the experimental design, quality control and analysis that were performed on the data set. The data are publicly available through the Gene Expression Omnibus (GEOdatabase with accession number GSE33389, and the analysis and interpretation of these data are included in Kuchipudi et al. (2014 [1].

  7. 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

  8. Regional mantle upwelling on Venus: The Beta-Atla-Themis anomaly and correlation with global tectonic patterns

    Science.gov (United States)

    Crumpler, L. S.; Head, J. W.; Aubele, Jayne C.

    1993-01-01

    The morphology and global distribution of volcanic centers and their association with other geological characteristics offers significant insight into the global patterns of geology, tectonic style, thermal state, and interior dynamics of Venus. Magellan data permit the detailed geological interpretation necessary to address questions about interior dynamics of Venus particularly as they reflect relatively physical, chemical, and thermal conditions of the interior. This paper focuses on the distribution of anomalous concentrations of volcanic centers on Venus and regional patterns of tectonic deformation as it may relate to the identification of global internal anomalies, including mantle dynamic, petrological, or thermal patterns.

  9. A mathematical correlation between variations in solar radiation parameters. 2. Global radiation, air temperature and specific humidity

    International Nuclear Information System (INIS)

    Njau, E.C.

    1988-06-01

    We derive from first principles, an equation which expresses global radiation as a function of specific humidity and air temperature at screen height. The practical validity of this equation is tested by using humidity, air temperature and global radiation data from Tanzania. It is shown that global radiation values calculated on the basis of the derived equation agree with measured radiation values to within ± 8% as long as the prevalent (horizontal) winds are either calm or light. It is noted that the equation is equally valid at times of strong horizontal winds provided that the temperature and humidity measuring site is sufficiently shielded from the winds. This implies that meteorological stations that are (for some unavoidable reasons) unable to stock pyranometers can still procure reasonable estimates of local global radiation as long as they can, at least, stock the relatively cheaper barometers and wet- and dry-bulb psychrometers. (author). 12 refs, 1 fig., 4 tabs

  10. Planar cell polarity gene expression correlates with tumor cell viability and prognostic outcome in neuroblastoma

    International Nuclear Information System (INIS)

    Dyberg, Cecilia; Papachristou, Panagiotis; Haug, Bjørn Helge; Lagercrantz, Hugo; Kogner, Per; Ringstedt, Thomas; Wickström, Malin; Johnsen, John Inge

    2016-01-01

    The non-canonical Wnt/Planar cell polarity (PCP) signaling pathway is a major player in cell migration during embryonal development and has recently been implicated in tumorigenesis. Transfections with cDNA plasmids or siRNA were used to increase and suppress Prickle1 and Vangl2 expression in neuroblastoma cells and in non-tumorigenic cells. Cell viability was measured by trypan blue exclusion and protein expression was determined with western blotting. Transcriptional activity was studied with luciferase reporter assay and mRNA expression with real-time RT-PCR. Immunofluorescence stainings were used to study the effects of Vangl2 overexpression in non-tumorigenic embryonic cells. Statistical significance was tested with t-test or one-way ANOVA. Here we show that high expression of the PCP core genes Prickle1 and Vangl2 is associated with low-risk neuroblastoma, suppression of neuroblastoma cell growth and decreased Wnt/β-catenin signaling. Inhibition of Rho-associated kinases (ROCKs) that are important in mediating non-canonical Wnt signaling resulted in increased expression of Prickle1 and inhibition of β-catenin activity in neuroblastoma cells. In contrast, overexpression of Vangl2 in MYC immortalized neural stem cells induced accumulation of active β-catenin and decreased the neural differentiation marker Tuj1. Similarly, genetically modified mice with forced overexpression of Vangl2 in nestin-positive cells showed decreased Tuj1 differentiation marker during embryonal development. Our experimental data demonstrate that high expression of Prickle1 and Vangl2 reduce the growth of neuroblastoma cells and indicate different roles of PCP proteins in tumorigenic cells compared to normal cells. These results suggest that the activity of the non-canonical Wnt/PCP signaling pathway is important for neuroblastoma development and that manipulation of the Wnt/PCP pathway provides a possible therapy for neuroblastoma. The online version of this article (doi:10.1186/s

  11. Global gene expression profiling of asymptomatic bacteriuria Escherichia coli during biofilm growth in human urine

    DEFF Research Database (Denmark)

    Hancock, Viktoria; Klemm, Per

    2007-01-01

    Urinary tract infection (UTI) is an important health problem worldwide, with many millions of cases each year, and Escherichia coli is the most common organism causing UTI in humans. Also, E. coli is responsible for most infections in patients with chronic indwelling bladder catheter. The two...... asymptomatic bacteriuria (ABU) E. coli strains 83972 and VR50 are significantly better biofilm formers in their natural growth medium, human urine, than the two uropathogenic E. coli isolates CFT073 and 536. We used DNA microarrays to monitor the expression profile during biofilm growth in urine of the two ABU...... strains 83972 and VR50. Significant differences in expression levels were seen between the biofilm expression profiles of the two strains with the corresponding planktonic expression profiles in morpholinepropanesulfonic acid minimal laboratory medium and human urine; 417 and 355 genes were up- and down...

  12. Haptoglobin genotyping of Vietnamese: global distribution of HP del, complete deletion allele of the HP gene.

    Science.gov (United States)

    Soejima, Mikiko; Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Lan, Vi Thi Mai; Minh, Tu Binh; Takahashi, Shin; Trang, Pham Thi Kim; Viet, Pham Hung; Tanabe, Shinsuke; Koda, Yoshiro

    2015-01-01

    The haptoglobin (HP) gene deletion allele (HP(del)) is responsible for anhaptoglobinemia and a genetic risk factor for anaphylaxis reaction after transfusion due to production of the anti-HP antibody. The distribution of this allele has been explored by several groups including ours. Here, we studied the frequency of HP(del) in addition to the distribution of common HP genotypes in 293 Vietnamese. The HP(del) was encountered with the frequency of 0.020. The present result suggested that this deletion allele is restricted to East and Southeast Asians. Thus, this allele seems to be a potential ancestry informative marker for these populations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Global analysis of biosynthetic gene clusters reveals vast potential of secondary metabolite production in Penicillium species

    DEFF Research Database (Denmark)

    Nielsen, Jens Christian; Grijseels, Sietske; Prigent, Sylvain

    2017-01-01

    Filamentous fungi produce a wide range of bioactive compounds with important pharmaceutical applications, such as antibiotic penicillins and cholesterol-lowering statins. However, less attention has been paid to fungal secondary metabolites compared to those from bacteria. In this study, we...... sequenced the genomes of 9 Penicillium species and, together with 15 published genomes, we investigated the secondary metabolism of Penicillium and identified an immense, unexploited potential for producing secondary metabolites by this genus. A total of 1,317 putative biosynthetic gene clusters (BGCs) were......-referenced the predicted pathways with published data on the production of secondary metabolites and experimentally validated the production of antibiotic yanuthones in Penicillia and identified a previously undescribed compound from the yanuthone pathway. This study is the first genus-wide analysis of the genomic...

  14. Phenotype/genotype correlation in a case series of Stargardt's patients identifies novel mutations in the ABCA4 gene.

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2013-11-01

    To investigate phenotypic variability in terms of best-corrected visual acuity (BCVA) in patients with Stargardt disease (STGD) and confirmed ABCA4 mutations. Entire coding region analysis of the ABCA4 gene by direct sequencing of seven patients with clinical findings of STGD seen in the Retina Clinics of Southampton Eye Unit between 2002 and 2011.Phenotypic variables recorded were BCVA, fluorescein angiographic appearance, electrophysiology, and visual fields. All patients had heterozygous amino acid-changing variants (missense mutations) in the ABCA4 gene. A splice sequence change was found in a 30-year-old patient with severly affected vision. Two novel sequence changes were identified: a missense mutation in a mildly affected 44-year-old patient and a frameshift mutation in a severly affected 34-year-old patient. The identified ABCA4 mutations were compatible with the resulting phenotypes in terms of BCVA. Higher BCVAs were recorded in patients with missense mutations. Sequence changes, predicted to have more deleterious effect on protein function, resulted in a more severe phenotype. This case series of STGD patients demonstrates novel genotype/phenotype correlations, which may be useful to counselling of patients. This information may prove useful in selection of candidates for clinical trials in ABCA4 disease.

  15. CYP1B1 gene polymorphisms correlate with an increased risk of urinary bladder cancer in India.

    Science.gov (United States)

    Sankhwar, Monica; Sankhwar, Satya Narayan; Abhishek, Amar; Gupta, Nishi; Rajender, Singh

    2016-04-01

    The urinary bladder is the target of several toxic compounds, which makes the bladder more prone to cancer. Cytochrome P450 1B1 enzyme is present in tumor tissues and metabolizes the polyaromatic carcinogens and activates several procarcinogens that cause DNA damage. We examined the functional single-nucleotide polymorphisms in the CYP1B1 gene to study their association with the urinary bladder cancer. We recruited 234 cases of pure urothelial and 258 bladder cancer-free control samples from the individuals visiting the clinic for various investigations. We genotyped 4 CYP1B1 single-nucleotide polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism analysis. The genotype data were analyzed by the Chi-square test. Haplotypes were constructed to evaluate the joint effect of the 4 polymorphisms. Overall, 3 polymorphisms-rs10012, rs150799650, and rs1056827 (odds ratio [OR] = 2.34, CI: 1.59-3.45, Pbladder cancer. Haplotype analysis suggested GTTC, GTTG, and ATGC to be the risk factors for bladder cancer. Overall, 3 polymorphisms, rs10012, rs1056827, and rs150799650 in the CYP1B1 gene correlate with urinary bladder cancer significantly in the Indo-European population of Uttar Pradesh, India. Further investigations in other populations are advised. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Recent urbanization in China is correlated with a Westernized microbiome encoding increased virulence and antibiotic resistance genes.

    Science.gov (United States)

    Winglee, Kathryn; Howard, Annie Green; Sha, Wei; Gharaibeh, Raad Z; Liu, Jiawu; Jin, Donghui; Fodor, Anthony A; Gordon-Larsen, Penny

    2017-09-15

    Urbanization is associated with an increased risk for a number of diseases, including obesity, diabetes, and cancer, which all also show associations with the microbiome. While microbial community composition has been shown to vary across continents and in traditional versus Westernized societies, few studies have examined urban-rural differences in neighboring communities within a single country undergoing rapid urbanization. In this study, we compared the gut microbiome, plasma metabolome, dietary habits, and health biomarkers of rural and urban people from a single Chinese province. We identified significant differences in the microbiota and microbiota-related plasma metabolites in rural versus recently urban subjects from the Hunan province of China. Microbes with higher relative abundance in Chinese urban samples have been associated with disease in other studies and were substantially more prevalent in the Human Microbiome Project cohort of American subjects. Furthermore, using whole metagenome sequencing, we found that urbanization was associated with a loss of microbial diversity and changes in the relative abundances of Viruses, Archaea, and Bacteria. Gene diversity, however, increased with urbanization, along with the proportion of reads associated with antibiotic resistance and virulence, which were strongly correlated with the presence of Escherichia and Shigella. Our data suggest that urbanization has produced convergent evolution of the gut microbial composition in American and urban Chinese populations, resulting in similar compositional patterns of abundant microbes through similar lifestyles on different continents, including a loss of potentially beneficial bacteria and an increase in potentially harmful genes via increased relative abundance of Escherichia and Shigella.

  17. Correlation between HFE gene polymorphisms and increased risk of coronary artery disease among patients with type 2 diabetes in Iran.

    Science.gov (United States)

    Saremi, Leila; Saremi, Marzieh; Lotfipanah, Shirin; İmani, Saber; Fu, Junjiang; Zhang, Tianyu

    2016-04-19

    Diabetes mellitus is a risk factor for cardiovascular diseases (CVDs), which are among the major causes of deaths in type 2 diabetes (T2D). The purpose of the present study was to determine the association of C282Y and H63D mutations in the HFE gene with increased risk of coronary artery disease (CAD) in T2D patients. Two hundred and ninety individuals were divided into two groups: a case group and a control group. Genomic DNA of peripheral venous blood cells was extracted and the HFE gene mutations were analyzed using the PCR-RFLP technique. Data analysis revealed a significant difference between the allele frequencies of H63D and C282Y mutations between the case group and the controls (P 0.05). Using a logistic regression model, BMI, FBS, HDL, and total cholesterol levels were significantly different with independent predictors of CVD (P < 0.05). Our results revealed a significant correlation between C282Y and H63D mutations and the development of CAD in T2D patients.

  18. Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of se-deficient chicks.

    Science.gov (United States)

    Yao, Hai-Dong; Wu, Qiong; Zhang, Zi-Wei; Zhang, Jiu-Li; Li, Shu; Huang, Jia-Qiang; Ren, Fa-Zheng; Xu, Shi-Wen; Wang, Xiao-Long; Lei, Xin Gen

    2013-05-01

    Dietary selenium (Se) deficiency causes muscular dystrophy in various species, but the molecular mechanism remains unclear. Our objectives were to investigate: 1) if dietary Se deficiency induced different amounts of oxidative stress, lipid peroxidation, and cell apoptosis in 3 skeletal muscles; and 2) if the distribution and expression of 4 endoplasmic reticulum (ER) resident selenoprotein genes (Sepn1, Selk, Sels, and Selt) were related to oxidative damages in these muscles. Two groups of day-old layer chicks (n = 60/group) were fed a corn-soy basal diet (33 μg Se/kg; produced in the Se-deficient area of Heilongjiang, China) or the diet supplemented with Se (as sodium selenite) at 0.15 mg/kg for 55 d. Dietary Se deficiency resulted in accelerated (P muscles. All these responses were stronger in the pectoral muscle than in the thigh and wing muscles (P muscles. Expression of Sepn1, Sels, and Selt in these muscles was correlated with (r > 0.72; P muscle demonstrated unique expression patterns of the ER resident selenoprotein genes and GPx activity, along with elevated susceptibility to oxidative cell death, compared with the other skeletal muscles. These features might help explain why it is a primary target of Se deficiency diseases in chicks.

  19. Positron Emission Tomography Imaging Demonstrates Correlation between Behavioral Recovery and Correction of Dopamine Neurotransmission after Gene Therapy

    International Nuclear Information System (INIS)

    Leriche, L.; Besret, L.; Gregoire, M.C.; Deglon, N.; Hantraye, Ph.; Leriche, L.; Besret, L.; Gregoire, M.C.; Deglon, N.; Hantraye, Ph.; Bjorklund, T.; Breysse, N.; Carlsson, T.; Kirik, D.; Dolle, F.; Mandel, R.J.; Kirik, D.

    2009-01-01

    In vivo gene transfer using viral vectors is an emerging therapy for neuro-degenerative diseases with a clinical impact recently demonstrated in Parkinson's disease patients. Recombinant adeno-associated viral (rAAV) vectors, in particular, provide an excellent tool for long-term expression of therapeutic genes in the brain. Here we used the [ 11 C]raclopride [(S)-(-)-3, 5-dichloro-N-((1-ethyl-2-pyrrolidinyl)methyl)-2-hydroxy- 6-methoxybenzamide] micro-positron emission tomography (PET) technique to demonstrate that delivery of the tyrosine hydroxylase (TH) and GTP-cyclohydrolase 1 (GCH1) enzymes using an rAAV5 vector normalizes the increased [ 11 C]raclopride binding in hemi-parkinsonian rats. Importantly, we show in vivo by micro-PET imaging and postmortem by classical binding assays performed in the very same animals that the changes in [ 11 C]raclopride after viral vector-based enzyme replacement therapy is attributable to a decrease in the affinity of the tracer binding to the D2 receptors, providing evidence for reconstitution of a functional pool of endogenous dopamine in the striatum. Moreover, the extent of the normalization in this non-invasive imaging measure was highly correlated with the functional recovery in motor behavior. The PET imaging protocol used in this study is fully adaptable to humans and thus can serve as an in vivo imaging technique to follow TH+GCH1 gene therapy in PD patients and provide an additional objective measure to a potential clinical trial using rAAV vectors to deliver L-3, 4-dihydroxyphenylalanine in the brain. (authors)

  20. Correlation of plasma nitrite/nitrate levels and inducible nitric oxide gene expression among women with cervical abnormalities and cancer.

    Science.gov (United States)

    Sowjanya, A Pavani; Rao, Meera; Vedantham, Haripriya; Kalpana, Basany; Poli, Usha Rani; Marks, Morgan A; Sujatha, M

    2016-01-30

    Cervical cancer is caused by infection with high risk human papillomavirus (HR-HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in chronic inflammation, may modulate cervical cancer risk among HPV infected women. The aim of the study was to measure and correlate plasma nitrite/nitrate levels with tissue specific expression of iNOS mRNA among women with different grades of cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and invasive cancer) and 35 women without cervical abnormalities. Inducible nitric oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the same study subjects were measured. Single nucleotide polymorphism (SNP) analysis was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels were compared across disease stage using linear and logistic regression analysis. Compared to normal controls, women diagnosed with HSIL or invasive cancer had a significantly higher concentration of plasma nitrite/nitrate and a higher median fold-change in iNOS mRNA gene expression. Genotyping of the promoter region showed three different variations: A pentanucleotide repeat (CCTTT) n, -1026T > G (rs2779249) and a novel variant -1153T > A. These variants were associated with increased levels of plasma nitrite/nitrate across all disease stages. The higher expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous lesions suggests a role for nitric oxide in the natural history of cervical cancer. Copyright © 2015. Published by Elsevier Inc.

  1. Intergenerational Effect of Early Life Exposure to Permethrin: Changes in Global DNA Methylation and in Nurr1 Gene Expression

    Directory of Open Access Journals (Sweden)

    Laura Bordoni

    2015-11-01

    Full Text Available Environmental exposure to pesticides during the early stages of development represents an important risk factor for the onset of neurodegenerative diseases in adult age. Neonatal exposure to Permethrin (PERM, a member of the family of synthetic pyrethroids, can induce a Parkinson-like disease and cause some alterations in striatum of rats, involving both genetic and epigenetic pathways. Through gene expression analysis and global DNA methylation assessment in both PERM-treated parents and their untreated offspring, we investigated on the prospective intergenerational effect of this pesticide. Thirty-three percent of progeny presents the same Nurr1 alteration as rats exposed to permethrin in early life. A decrease in global genome-wide DNA methylation was measured in mothers exposed in early life to permethrin as well as in their offspring, whereas untreated rats have a hypermethylated genomic DNA. Further studies are however needed to elucidate the molecular mechanisms, but, despite this, an intergenerational PERM-induced damage on progenies has been identified for the first time.

  2. 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.

  3. Correlation between occurrence of leprosy and fossil fuels: role of fossil fuel bacteria in the origin and global epidemiology of leprosy.

    Science.gov (United States)

    Chakrabarty, A N; Dastidar, S G

    1989-06-01

    On the basis of correlative data on the global distribution of leprosy, its bacteria metabolizing fossil fuels (FF), and the FF themselves, the origin of leprosy in the world as a whole, and in the leprosy-free countries, in particular, as indigenous cases, appeared to be primarily due to a soil-to-man, and secondarily due to a man-to-man infection. These findings helped to elucidate similar problems of animal leprosies and nocardial diseases.

  4. Suppressing Sorbitol Synthesis Substantially Alters the Global Expression Profile of Stress Response Genes in Apple (Malus domestica) Leaves.

    Science.gov (United States)

    Wu, Ting; Wang, Yi; Zheng, Yi; Fei, Zhangjun; Dandekar, Abhaya M; Xu, Kenong; Han, Zhenhai; Cheng, Lailiang

    2015-09-01

    Sorbitol is a major product of photosynthesis in apple (Malus domestica) that is involved in carbohydrate metabolism and stress tolerance. However, little is known about how the global transcript levels in apple leaves respond to decreased sorbitol synthesis. In this study we used RNA sequencing (RNA-seq) profiling to characterize the transcriptome of leaves from transgenic lines of the apple cultivar 'Greensleeves' exhibiting suppressed expression of aldose-6-phosphate reductase (A6PR) to gain insights into sorbitol function and the consequences of decreased sorbitol synthesis on gene expression. We observed that, although the leaves of the low sorbitol transgenic lines accumulate higher levels of various primary metabolites, only very limited changes were found in the levels of transcripts associated with primary metabolism. We suggest that this is indicative of post-transcriptional and/or post-translational regulation of primary metabolite accumulation and central carbon metabolism. However, we identified significantly enriched gene ontology terms belonging to the 'stress related process' category in the antisense lines (P-value sorbitol plays a role in the responses of apple trees to abiotic and biotic stresses. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. The global nitrogen regulator, FNR1, regulates fungal nutrition-genes and fitness during Fusarium oxysporum pathogenesis.

    Science.gov (United States)

    Divon, Hege Hvattum; Ziv, Carmit; Davydov, Olga; Yarden, Oded; Fluhr, Robert

    2006-11-01

    SUMMARY Fusarium oxysporum is a soil-borne pathogen that infects plants through the roots and uses the vascular system for host ingress. Specialized for this route of infection, F. oxysporum is able to adapt to the scarce nutrient environment in the xylem vessels. Here we report the cloning of the F. oxysporum global nitrogen regulator, Fnr1, and show that it is one of the determinants for fungal fitness during in planta growth. The Fnr1 gene has a single conserved GATA-type zinc finger domain and is 96% and 48% identical to AREA-GF from Gibberella fujikuroi, and NIT2 from Neurospora crassa, respectively. Fnr1 cDNA, expressed under a constitutive promoter, was able to complement functionally an N. crassa nit-2(RIP) mutant, restoring the ability of the mutant to utilize nitrate. Fnr1 disruption mutants showed high tolerance to chlorate and reduced ability to utilize several secondary nitrogen sources such as amino acids, hypoxanthine and uric acid, whereas growth on favourable nitrogen sources was not affected. Fnr1 disruption also abolished in vitro expression of nutrition genes, normally induced during the early phase of infection. In an infection assay on tomato seedlings, infection rate of disruption mutants was significantly delayed in comparison with the parental strain. Our results indicate that FNR1 mediates adaptation to nitrogen-poor conditions in planta through the regulation of secondary nitrogen acquisition, and as such acts as a determinant for fungal fitness during infection.

  6. Global gene expression profiles of MT knockout and wild-type mice in the condition of doxorubicin-induced cardiomyopathy.

    Science.gov (United States)

    Shuai, Yi; Guo, Jun; Dong, Yansheng; Zhong, Weijian; Xiao, Ping; Zhou, Tong; Zhang, Lishi; Peng, Shuangqing

    2011-01-15

    Increasing evidence from in vivo and in vitro studies has indicated that MT exerts protective effects against DOX-induced cardiotoxicity; however the underlying precise mechanisms still remain an enigma. Therefore, the present study was designed using MT knockout mice in concert with genomic approaches to explore the possible molecular and cellular mechanisms in terms of the genetic network changes. MT-I/II null (MT⁻/⁻) mice and corresponding wild-type mice (MT+/+) were administrated with a single dose of DOX (15 mg/kg, i.p.) or equal volume of saline. Animals were sacrificed on the 4th day after DOX administration and samples were collected for further analyses. Global gene expression profiles of cardiac mRNA from two genotype mice revealed that 381 characteristically MT-responsive genes were identified between MT+/+ mice and MT⁻/⁻ mice in response to DOX, including fos, ucp3, car3, atf3, map3k6, etc. Functional analysis implied MAPK signaling pathway, p53 signaling pathway, Jak-STAT signaling pathway, PPAR signaling pathway, Wnt signaling pathway, etc. might be involved to mediate the protection of DOX cardiomyopathy by MT. Results from the present study not only validated the previously reported possible mechanisms of MT protection against DOX toxicity, but also provided new clues into the molecular mechanisms involved in this process. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  7. Can intrinsic human tissue radiosensitivity be correlated with late responding gene RNA expression in white blood cells using a 96 gene micro-array?

    International Nuclear Information System (INIS)

    Schmidt, D.; Streeter, O.; Dagliyan, G.; Hill, C.K.; Williams-Hill, D.M.

    2003-01-01

    Radiation is widely used in the treatment of cancers. It is generally believed there is a sigmoid relationship between radiation dose and probability of cure. There is also a sigmoid relationship between radiation dose and normal tissue response. Generally total radiation dose to a tumor is limited by normal tissue tolerance. It has been postulated that up to 70% of inter-individual differences in radiosensitivity may be due to genetic predisposition (Tureson I. Et al, IJROBP, 1996;36:1065). However, to date, clinicians have no way of estimating or predicting an individual's normal tissue response to radiation exposure. Thus the prescribed dose cannot be tailored to an individuals actual expected response but is an empirically derived compromise based on experience. Although a number of studies using cellular techniques have shown that human cell radiosensitivity can be measured, none of these can be performed quick enough to be used in the clinic. In this study we are looking at gene expression that occurs some 24 hours after an exposure compared to expression before any exposure in peripheral white blood cells from patients undergoing radiotherapy for various tumors. The patients will be followed for overt radiation sensitivity by standard criteria by clinicians in the Department. The main aims are: does RNA expression level in a 96 gene micro-array vary before and after radiation and do these changes in RNA expression correlate with the objective measurements of acute radiation response observed by the clinicians in the patients. The USC IRB recently approved the protocol and human consent for this study to enter 50 patients in the next 12 months using mostly head and neck and endometrial cancer patients where we can get a normal tissue sample to examine as well as the blood sample. We will present the rationale, protocol, methods and early results in detail

  8. 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

  9. 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.

  10. 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.

  11. [Correlation between EGLN1 gene, protein express in lung tissue of rats and pulmonary artery pressure at different altitude].

    Science.gov (United States)

    Li, S H; Li, S; Sun, L; Bai, Z Z; Yang, Q Y; Ga, Q; Jin, G E

    2016-08-23

    To investigate the correlation between pulmonary artery pressure (PAP) and the expression level of Egl nine homologue 1 (EGLN1) gene or its protein in lung tissue of rats at different altitudes. Totally 121 male Wistar rats were randomly divided into low altitude group (n=11), moderate altitude group and high altitude group, the rats in moderate altitude and high altitude group were further divided into 1(st) day, 3(rd) days, 7(th) days, 15(th) day and 30(th) day group according to the exposure time to hypoxic environment, each group 11 rats. The low altitude group, the PAP of rats were determined by physiological signal acquisition system, and tissue samples were collected in liquid nitrogen container for storage at an altitude of 498 m area. Moderate altitude group rats were placed in altitude of 2 260 meters of natural environment, 5 high altitude groups rats were placed in the hypobaric hypoxic chamber, simulating altitude of 4 500 meters. The PAP of rats in moderate altitude group and high altitude group were also determined by physiological signal acquisition system, and tissue samples were collected when rats were exposed to hypoxia at 1(st), 3(rd), 7(th), 15(th) and 30(th) day; Western blot was used to determine expression levels of EGLN1 protein, and person correlation analysis was used to analyze whether the protein was related to the formation of pulmonary arterial hypertension (PH) under hypoxia. Real-time quantitive PCR method determined expression levels of EGLN1 mRNA in lung tissues, and the relative expression method was used to analyze PCR data, and finally assess whether the EGLN1 gene was the initial cause of the formation of PH during hypoxia. The mean PAP of rats was (20.0±3.2) mmHg (1 mmHg=0.133 kPa) in low altitude group; in moderate altitude group, mean PAP began to increase slightly when rats were exposed to hypoxia on the 15(th) day and reached at (22.7±4.1) mmHg on hypoxic 30(th) day, but compared with the low a