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  1. Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

    DEFF Research Database (Denmark)

    Medina-Gomez, Carolina; Kemp, John P; Dimou, Niki L

    2017-01-01

    Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone...

  2. Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

    NARCIS (Netherlands)

    M.C. Medina-Gomez (Carolina); J.P. Kemp (John); Dimou, N.L. (Niki L.); Kreiner, E. (Eskil); A. Chesi (Alessandra); B.S. Zemel (Babette S.); K. Bønnelykke (Klaus); Boer, C.G. (Cindy G.); T.S. Ahluwalia (Tarunveer Singh); H. Bisgaard; E. Evangelou (Evangelos); D.H.M. Heppe (Denise); Bonewald, L.F. (Lynda F.); Gorski, J.P. (Jeffrey P.); M. Ghanbari (Mohsen); S. Demissie (Serkalem); Duque, G. (Gustavo); M.T. Maurano (Matthew T.); D.P. Kiel (Douglas P.); Y.-H. Hsu (Yi-Hsiang); B.C.J. van der Eerden (Bram); Ackert-Bicknell, C. (Cheryl); S. Reppe (Sjur); K.M. Gautvik (Kaare); Raastad, T. (Truls); D. Karasik (David); J. van de Peppel (Jeroen); V.W.V. Jaddoe (Vincent); A.G. Uitterlinden (André); J.H. Tobias (Jon); S.F.A. Grant (Struan); Bagos, P.G. (Pantelis G.); D.M. Evans (David); F. Rivadeneira Ramirez (Fernando)

    2017-01-01

    markdownabstractBone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body

  3. Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus.

    Science.gov (United States)

    Medina-Gomez, Carolina; Kemp, John P; Dimou, Niki L; Kreiner, Eskil; Chesi, Alessandra; Zemel, Babette S; Bønnelykke, Klaus; Boer, Cindy G; Ahluwalia, Tarunveer S; Bisgaard, Hans; Evangelou, Evangelos; Heppe, Denise H M; Bonewald, Lynda F; Gorski, Jeffrey P; Ghanbari, Mohsen; Demissie, Serkalem; Duque, Gustavo; Maurano, Matthew T; Kiel, Douglas P; Hsu, Yi-Hsiang; C J van der Eerden, Bram; Ackert-Bicknell, Cheryl; Reppe, Sjur; Gautvik, Kaare M; Raastad, Truls; Karasik, David; van de Peppel, Jeroen; Jaddoe, Vincent W V; Uitterlinden, André G; Tobias, Jonathan H; Grant, Struan F A; Bagos, Pantelis G; Evans, David M; Rivadeneira, Fernando

    2017-07-25

    Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34-52%) for TBLH-BMD, and 39% (95% CI: 30-48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29-56%). We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5. Variants in the TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that SREBF1 is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.Bone mineral density and lean skeletal mass are heritable traits. Here, Medina-Gomez and colleagues perform bivariate GWAS analyses of total body lean mass and bone mass density in children, and show genetic loci with pleiotropic effects on both traits.

  4. Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

    DEFF Research Database (Denmark)

    Medina-Gomez, Carolina; Kemp, John P; Dimou, Niki L

    2017-01-01

    Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone...... mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34-52%) for TBLH-BMD, and 39% (95% CI: 30-48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29-56%). We identify variants with pleiotropic effects in eight loci, including seven established...... as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.Bone mineral density and lean skeletal mass are heritable traits. Here, Medina-Gomez and colleagues perform bivariate GWAS analyses of total...

  5. Covariate analysis of bivariate survival data

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, L.E.

    1992-01-01

    The methods developed are used to analyze the effects of covariates on bivariate survival data when censoring and ties are present. The proposed method provides models for bivariate survival data that include differential covariate effects and censored observations. The proposed models are based on an extension of the univariate Buckley-James estimators which replace censored data points by their expected values, conditional on the censoring time and the covariates. For the bivariate situation, it is necessary to determine the expectation of the failure times for one component conditional on the failure or censoring time of the other component. Two different methods have been developed to estimate these expectations. In the semiparametric approach these expectations are determined from a modification of Burke's estimate of the bivariate empirical survival function. In the parametric approach censored data points are also replaced by their conditional expected values where the expected values are determined from a specified parametric distribution. The model estimation will be based on the revised data set, comprised of uncensored components and expected values for the censored components. The variance-covariance matrix for the estimated covariate parameters has also been derived for both the semiparametric and parametric methods. Data from the Demographic and Health Survey was analyzed by these methods. The two outcome variables are post-partum amenorrhea and breastfeeding; education and parity were used as the covariates. Both the covariate parameter estimates and the variance-covariance estimates for the semiparametric and parametric models will be compared. In addition, a multivariate test statistic was used in the semiparametric model to examine contrasts. The significance of the statistic was determined from a bootstrap distribution of the test statistic.

  6. Joint association analysis of bivariate quantitative and qualitative traits.

    Science.gov (United States)

    Yuan, Mengdie; Diao, Guoqing

    2011-11-29

    Univariate genome-wide association analysis of quantitative and qualitative traits has been investigated extensively in the literature. In the presence of correlated phenotypes, it is more intuitive to analyze all phenotypes simultaneously. We describe an efficient likelihood-based approach for the joint association analysis of quantitative and qualitative traits in unrelated individuals. We assume a probit model for the qualitative trait, under which an unobserved latent variable and a prespecified threshold determine the value of the qualitative trait. To jointly model the quantitative and qualitative traits, we assume that the quantitative trait and the latent variable follow a bivariate normal distribution. The latent variable is allowed to be correlated with the quantitative phenotype. Simultaneous modeling of the quantitative and qualitative traits allows us to make more precise inference on the pleiotropic genetic effects. We derive likelihood ratio tests for the testing of genetic effects. An application to the Genetic Analysis Workshop 17 data is provided. The new method yields reasonable power and meaningful results for the joint association analysis of the quantitative trait Q1 and the qualitative trait disease status at SNPs with not too small MAF.

  7. A comparison between multivariate and bivariate analysis used in marketing research

    Directory of Open Access Journals (Sweden)

    Constantin, C.

    2012-01-01

    Full Text Available This paper is about an instrumental research conducted in order to compare the information given by two multivariate data analysis in comparison with the usual bivariate analysis. The outcomes of the research reveal that sometimes the multivariate methods use more information from a certain variable, but sometimes they use only a part of the information considered the most important for certain associations. For this reason, a researcher should use both categories of data analysis in order to obtain entirely useful information.

  8. Bivariate extreme value with application to PM10 concentration analysis

    Science.gov (United States)

    Amin, Nor Azrita Mohd; Adam, Mohd Bakri; Ibrahim, Noor Akma; Aris, Ahmad Zaharin

    2015-05-01

    This study is focus on a bivariate extreme of renormalized componentwise maxima with generalized extreme value distribution as a marginal function. The limiting joint distribution of several parametric models are presented. Maximum likelihood estimation is employed for parameter estimations and the best model is selected based on the Akaike Information Criterion. The weekly and monthly componentwise maxima series are extracted from the original observations of daily maxima PM10 data for two air quality monitoring stations located in Pasir Gudang and Johor Bahru. The 10 years data are considered for both stations from year 2001 to 2010. The asymmetric negative logistic model is found as the best fit bivariate extreme model for both weekly and monthly maxima componentwise series. However the dependence parameters show that the variables for weekly maxima series is more dependence to each other compared to the monthly maxima.

  9. Univariate and Bivariate Empirical Mode Decomposition for Postural Stability Analysis

    Directory of Open Access Journals (Sweden)

    Jacques Duchêne

    2008-05-01

    Full Text Available The aim of this paper was to compare empirical mode decomposition (EMD and two new extended methods of  EMD named complex empirical mode decomposition (complex-EMD and bivariate empirical mode decomposition (bivariate-EMD. All methods were used to analyze stabilogram center of pressure (COP time series. The two new methods are suitable to be applied to complex time series to extract complex intrinsic mode functions (IMFs before the Hilbert transform is subsequently applied on the IMFs. The trace of the analytic IMF in the complex plane has a circular form, with each IMF having its own rotation frequency. The area of the circle and the average rotation frequency of IMFs represent efficient indicators of the postural stability status of subjects. Experimental results show the effectiveness of these indicators to identify differences in standing posture between groups.

  10. Inheritance of dermatoglyphic traits in twins: univariate and bivariate variance decomposition analysis.

    Science.gov (United States)

    Karmakar, Bibha; Malkin, Ida; Kobyliansky, Eugene

    2012-01-01

    Dermatoglyphic traits in a sample of twins were analyzed to estimate the resemblance between MZ and DZ twins and to evaluate the mode of inheritance by using the maximum likelihood-based Variance decomposition analysis. The additive genetic variance component was significant in both sexes for four traits--PII, AB_RC, RC_HB, and ATD_L. AB RC and RC_HB had significant sex differences in means, whereas PII and ATD_L did not. The results of the Bivariate Variance decomposition analysis revealed that PII and RC_HB have a significant correlation in both genetic and residual components. Significant correlation in the additive genetic variance between AB_RC and ATD_L was observed. The same analysis only for the females sub-sample in the three traits RBL, RBR and AB_DIS shows that the additive genetic RBR component was significant and the AB_DIS sibling component was not significant while others cannot be constrained to zero. The additive variance for AB DIS sibling component was not significant. The three components additive, sibling and residual were significantly correlated between each pair of traits revealed by the Bivariate Variance decomposition analysis.

  11. Preparation and bivariate analysis of suspensions of human chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    van den Engh, G.J.; Trask, B.J.; Gray, J.W.; Langlois, R.G.; Yu, L.C.

    1985-01-01

    Chromosomes were isolated from a variety of human cell types using a HEPES-buffered hypotonic solution (pH 8.0) containing KCl, MgSO/sub 4/ dithioerythritol, and RNase. The chromosomes isolated by this procedure could be stained with a variety of fluorescent stains including propidium iodide, chromomycin A3, and Hoeschst 33258. Addition of sodium citrate to the stained chromosomes was found to improve the total fluorescence resolution. High-quality bivariate Hoeschst vs. chromomycin fluorescence distributions were obtained for chromosomes isolated from a human fibroblast cell strain, a human colon carcinoma cell line, and human peripheral blood lymphocyte cultures. Good flow karyotypes were also obtained from primary amniotic cell cultures. The Hoeschst vs. chromomycin flow karyotypes of a given cell line, made at different times and at dye concentrations varying over fourfold ranges, show little variation in the relative peak positions of the chromosomes. The size of the DNA in chromosomes isolated using this procedure ranges from 20 to 50 kilobases. The described isolation procedure is simple, it yields high-quality flow karyotypes, and it can be used to prepare chromosomes from clinical samples. 22 references, 7 figures, 1 table.

  12. A Bivariate Extension to Traditional Empirical Orthogonal Function Analysis

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Hilger, Klaus Baggesen; Andersen, Ole Baltazar

    2002-01-01

    This paper describes the application of canonical correlations analysis to the joint analysis of global monthly mean values of 1996-1997 sea surface temperature (SST) and height (SSH) data. The SST data are considered as one set and the SSH data as another set of multivariate observations, both w...... as for example an increase in the SST will lead to an increase in the SSH. The analysis clearly shows the build-up of one of the largest El Niño events on record. Also the analysis indicates a phase lag of approximately one month between the SST and SSH fields....

  13. Assessing the copula selection for bivariate frequency analysis ...

    Indian Academy of Sciences (India)

    58

    37 frequency analysis methods cannot describe the random variable properties that are correlated. 38. (Sarhadi et al., 2016). This approach can lead to high uncertainty or failure of guidelines in. 39 water resources planning, operation and design of hydraulic structures or creating the flood risk. 40 mapping (Chebana and ...

  14. Bivariable analysis of ventricular late potentials in high resolution ECG records

    International Nuclear Information System (INIS)

    Orosco, L; Laciar, E

    2007-01-01

    In this study the bivariable analysis for ventricular late potentials detection in high-resolution electrocardiographic records is proposed. The standard time-domain analysis and the application of the time-frequency technique to high-resolution ECG records are briefly described as well as their corresponding results. In the proposed technique the time-domain parameter, QRSD and the most significant time-frequency index, EN QRS are used like variables. A bivariable index is defined, that combines the previous parameters. The propose technique allows evaluating the risk of ventricular tachycardia in post-myocardial infarct patients. The results show that the used bivariable index allows discriminating between the patient's population with ventricular tachycardia and the subjects of the control group. Also, it was found that the bivariable technique obtains a good valuation as diagnostic test. It is concluded that comparatively, the valuation of the bivariable technique as diagnostic test is superior to that of the time-domain method and the time-frequency technique evaluated individually

  15. Accuracy of body mass index in predicting pre-eclampsia: bivariate meta-analysis

    NARCIS (Netherlands)

    Cnossen, J. S.; Leeflang, M. M. G.; de Haan, E. E. M.; Mol, B. W. J.; van der Post, J. A. M.; Khan, K. S.; ter Riet, G.

    2007-01-01

    OBJECTIVE: The objective of this study was to determine the accuracy of body mass index (BMI) (pre-pregnancy or at booking) in predicting pre-eclampsia and to explore its potential for clinical application. DESIGN: Systematic review and bivariate meta-analysis. SETTING: Medline, Embase, Cochrane

  16. Meta-analysis of studies with bivariate binary outcomes: a marginal beta-binomial model approach.

    Science.gov (United States)

    Chen, Yong; Hong, Chuan; Ning, Yang; Su, Xiao

    2016-01-15

    When conducting a meta-analysis of studies with bivariate binary outcomes, challenges arise when the within-study correlation and between-study heterogeneity should be taken into account. In this paper, we propose a marginal beta-binomial model for the meta-analysis of studies with binary outcomes. This model is based on the composite likelihood approach and has several attractive features compared with the existing models such as bivariate generalized linear mixed model (Chu and Cole, 2006) and Sarmanov beta-binomial model (Chen et al., 2012). The advantages of the proposed marginal model include modeling the probabilities in the original scale, not requiring any transformation of probabilities or any link function, having closed-form expression of likelihood function, and no constraints on the correlation parameter. More importantly, because the marginal beta-binomial model is only based on the marginal distributions, it does not suffer from potential misspecification of the joint distribution of bivariate study-specific probabilities. Such misspecification is difficult to detect and can lead to biased inference using currents methods. We compare the performance of the marginal beta-binomial model with the bivariate generalized linear mixed model and the Sarmanov beta-binomial model by simulation studies. Interestingly, the results show that the marginal beta-binomial model performs better than the Sarmanov beta-binomial model, whether or not the true model is Sarmanov beta-binomial, and the marginal beta-binomial model is more robust than the bivariate generalized linear mixed model under model misspecifications. Two meta-analyses of diagnostic accuracy studies and a meta-analysis of case-control studies are conducted for illustration. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Bivariate Drought Analysis Using Streamflow Reconstruction with Tree Ring Indices in the Sacramento Basin, California, USA

    Directory of Open Access Journals (Sweden)

    Jaewon Kwak

    2016-03-01

    Full Text Available Long-term streamflow data are vital for analysis of hydrological droughts. Using an artificial neural network (ANN model and nine tree-ring indices, this study reconstructed the annual streamflow of the Sacramento River for the period from 1560 to 1871. Using the reconstructed streamflow data, the copula method was used for bivariate drought analysis, deriving a hydrological drought return period plot for the Sacramento River basin. Results showed strong correlation among drought characteristics, and the drought with a 20-year return period (17.2 million acre-feet (MAF per year in the Sacramento River basin could be considered a critical level of drought for water shortages.

  18. Historical and future drought in Bangladesh using copula-based bivariate regional frequency analysis

    Science.gov (United States)

    Mortuza, Md Rubayet; Moges, Edom; Demissie, Yonas; Li, Hong-Yi

    2018-02-01

    The study aims at regional and probabilistic evaluation of bivariate drought characteristics to assess both the past and future drought duration and severity in Bangladesh. The procedures involve applying (1) standardized precipitation index to identify drought duration and severity, (2) regional frequency analysis to determine the appropriate marginal distributions for both duration and severity, (3) copula model to estimate the joint probability distribution of drought duration and severity, and (4) precipitation projections from multiple climate models to assess future drought trends. Since drought duration and severity in Bangladesh are often strongly correlated and do not follow same marginal distributions, the joint and conditional return periods of droughts are characterized using the copula-based joint distribution. The country is divided into three homogeneous regions using Fuzzy clustering and multivariate discordancy and homogeneity measures. For given severity and duration values, the joint return periods for a drought to exceed both values are on average 45% larger, while to exceed either value are 40% less than the return periods from the univariate frequency analysis, which treats drought duration and severity independently. These suggest that compared to the bivariate drought frequency analysis, the standard univariate frequency analysis under/overestimate the frequency and severity of droughts depending on how their duration and severity are related. Overall, more frequent and severe droughts are observed in the west side of the country. Future drought trend based on four climate models and two scenarios showed the possibility of less frequent drought in the future (2020-2100) than in the past (1961-2010).

  19. Obtaining DDF Curves of Extreme Rainfall Data Using Bivariate Copula and Frequency Analysis

    DEFF Research Database (Denmark)

    Sadri, Sara; Madsen, Henrik; Mikkelsen, Peter Steen

    2009-01-01

    , situated near Copenhagen in Denmark. For rainfall extracted using method 2, the marginal distribution of depth was found to fit the Generalized Pareto distribution while duration was found to fit the Gamma distribution, using the method of L-moments. The volume was fit with a generalized Pareto...... with duration for a given return period and name them DDF (depth-duration-frequency) curves. The copula approach does not assume the rainfall variables are independent or jointly normally distributed. Rainfall series are extracted in three ways: (1) by maximum mean intensity; (2) by depth and duration...... distribution and the duration was fit with a Pearson type III distribution for rainfall extracted using method 3. The Clayton copula was found to be appropriate for bivariate analysis of rainfall depth and duration for both methods 2 and 3. DDF curves derived using the Clayton copula for depth and duration...

  20. A composite likelihood method for bivariate meta-analysis in diagnostic systematic reviews.

    Science.gov (United States)

    Chen, Yong; Liu, Yulun; Ning, Jing; Nie, Lei; Zhu, Hongjian; Chu, Haitao

    2017-04-01

    Diagnostic systematic review is a vital step in the evaluation of diagnostic technologies. In many applications, it involves pooling pairs of sensitivity and specificity of a dichotomized diagnostic test from multiple studies. We propose a composite likelihood (CL) method for bivariate meta-analysis in diagnostic systematic reviews. This method provides an alternative way to make inference on diagnostic measures such as sensitivity, specificity, likelihood ratios, and diagnostic odds ratio. Its main advantages over the standard likelihood method are the avoidance of the nonconvergence problem, which is nontrivial when the number of studies is relatively small, the computational simplicity, and some robustness to model misspecifications. Simulation studies show that the CL method maintains high relative efficiency compared to that of the standard likelihood method. We illustrate our method in a diagnostic review of the performance of contemporary diagnostic imaging technologies for detecting metastases in patients with melanoma.

  1. Bivariate frequency analysis of rainfall intensity and duration for urban stormwater infrastructure design

    Science.gov (United States)

    Jun, Changhyun; Qin, Xiaosheng; Gan, Thian Yew; Tung, Yeou-Koung; De Michele, Carlo

    2017-10-01

    This study presents a storm-event based bivariate frequency analysis approach to determine design rainfalls in which, the number, intensity and duration of actual rainstorm events were considered. To derive more realistic design storms, the occurrence probability of an individual rainstorm event was determined from the joint distribution of storm intensity and duration through a copula model. Hourly rainfall data were used at three climate stations respectively located in Singapore, South Korea and Canada. It was found that the proposed approach could give a more realistic description of rainfall characteristics of rainstorm events and design rainfalls. As results, the design rainfall quantities from actual rainstorm events at the three studied sites are consistently lower than those obtained from the conventional rainfall depth-duration-frequency (DDF) method, especially for short-duration storms (such as 1-h). It results from occurrence probabilities of each rainstorm event and a different angle for rainfall frequency analysis, and could offer an alternative way of describing extreme rainfall properties and potentially help improve the hydrologic design of stormwater management facilities in urban areas.

  2. GIS-based bivariate statistical techniques for groundwater potential analysis (an example of Iran)

    Science.gov (United States)

    Haghizadeh, Ali; Moghaddam, Davoud Davoudi; Pourghasemi, Hamid Reza

    2017-12-01

    Groundwater potential analysis prepares better comprehension of hydrological settings of different regions. This study shows the potency of two GIS-based data driven bivariate techniques namely statistical index (SI) and Dempster-Shafer theory (DST) to analyze groundwater potential in Broujerd region of Iran. The research was done using 11 groundwater conditioning factors and 496 spring positions. Based on the ground water potential maps (GPMs) of SI and DST methods, 24.22% and 23.74% of the study area is covered by poor zone of groundwater potential, and 43.93% and 36.3% of Broujerd region is covered by good and very good potential zones, respectively. The validation of outcomes displayed that area under the curve (AUC) of SI and DST techniques are 81.23% and 79.41%, respectively, which shows SI method has slightly a better performance than the DST technique. Therefore, SI and DST methods are advantageous to analyze groundwater capacity and scrutinize the complicated relation between groundwater occurrence and groundwater conditioning factors, which permits investigation of both systemic and stochastic uncertainty. Finally, it can be realized that these techniques are very beneficial for groundwater potential analyzing and can be practical for water-resource management experts.

  3. Bivariate flow cytometric analysis and sorting of different types of maize starch grains.

    Science.gov (United States)

    Zhang, Xudong; Feng, Jiaojiao; Wang, Heng; Zhu, Jianchu; Zhong, Yuyue; Liu, Linsan; Xu, Shutu; Zhang, Renhe; Zhang, Xinghua; Xue, Jiquan; Guo, Dongwei

    2018-02-01

    Particle-size distribution, granular structure, and composition significantly affect the physicochemical properties, rheological properties, and nutritional function of starch. Flow cytometry and flow sorting are widely considered convenient and efficient ways of classifying and separating natural biological particles or other substances into subpopulations, respectively, based on the differential response of each component to stimulation by a light beam; the results allow for the correlation analysis of parameters. In this study, different types of starches isolated from waxy maize, sweet maize, high-amylose maize, pop maize, and normal maize were initially classified into various subgroups by flow cytometer and then collected through flow sorting to observe their morphology and particle-size distribution. The results showed that a 0.25% Gelzan solution served as an optimal reagent for keeping individual starch particles homogeneously dispersed in suspension for a relatively long time. The bivariate flow cytometric population distributions indicated that the starches of normal maize, sweet maize, and pop maize were divided into two subgroups, whereas high-amylose maize starch had only one subgroup. Waxy maize starch, conversely, showed three subpopulations. The subgroups sorted by flow cytometer were determined and verified in terms of morphology and granule size by scanning electron microscopy and laser particle distribution analyzer. Results showed that flow cytometry can be regarded as a novel method for classifying and sorting starch granules. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  4. Bayesian bivariate meta-analysis of diagnostic test studies using integrated nested Laplace approximations.

    Science.gov (United States)

    Paul, M; Riebler, A; Bachmann, L M; Rue, H; Held, L

    2010-05-30

    For bivariate meta-analysis of diagnostic studies, likelihood approaches are very popular. However, they often run into numerical problems with possible non-convergence. In addition, the construction of confidence intervals is controversial. Bayesian methods based on Markov chain Monte Carlo (MCMC) sampling could be used, but are often difficult to implement, and require long running times and diagnostic convergence checks. Recently, a new Bayesian deterministic inference approach for latent Gaussian models using integrated nested Laplace approximations (INLA) has been proposed. With this approach MCMC sampling becomes redundant as the posterior marginal distributions are directly and accurately approximated. By means of a real data set we investigate the influence of the prior information provided and compare the results obtained by INLA, MCMC, and the maximum likelihood procedure SAS PROC NLMIXED. Using a simulation study we further extend the comparison of INLA and SAS PROC NLMIXED by assessing their performance in terms of bias, mean-squared error, coverage probability, and convergence rate. The results indicate that INLA is more stable and gives generally better coverage probabilities for the pooled estimates and less biased estimates of variance parameters. The user-friendliness of INLA is demonstrated by documented R-code. Copyright (c) 2010 John Wiley & Sons, Ltd.

  5. Effect of catchment properties and flood generation regime on copula selection for bivariate flood frequency analysis

    Science.gov (United States)

    Filipova, Valeriya; Lawrence, Deborah; Klempe, Harald

    2018-02-01

    Applying copula-based bivariate flood frequency analysis is advantageous because the results provide information on both the flood peak and volume. More data are, however, required for such an analysis, and it is often the case that only data series with a limited record length are available. To overcome this issue of limited record length, data regarding climatic and geomorphological properties can be used to complement statistical methods. In this paper, we present a study of 27 catchments located throughout Norway, in which we assess whether catchment properties, flood generation processes and flood regime have an effect on the correlation between flood peak and volume and, in turn, on the selection of copulas. To achieve this, the annual maximum flood events were first classified into events generated primarily by rainfall, snowmelt or a combination of these. The catchments were then classified into flood regime, depending on the predominant flood generation process producing the annual maximum flood events. A contingency table and Fisher's exact test were used to determine the factors that affect the selection of copulas in the study area. The results show that the two-parameter copulas BB1 and BB7 are more commonly selected in catchments with high steepness, high mean annual runoff and rainfall flood regime. These findings suggest that in these types of catchments, the dependence structure between flood peak and volume is more complex and cannot be modeled effectively using a one-parameter copula. The results illustrate that by relating copula types to flood regime and catchment properties, additional information can be supplied for selecting copulas in catchments with limited data.

  6. An improved method for bivariate meta-analysis when within-study correlations are unknown.

    Science.gov (United States)

    Hong, Chuan; D Riley, Richard; Chen, Yong

    2018-03-01

    Multivariate meta-analysis, which jointly analyzes multiple and possibly correlated outcomes in a single analysis, is becoming increasingly popular in recent years. An attractive feature of the multivariate meta-analysis is its ability to account for the dependence between multiple estimates from the same study. However, standard inference procedures for multivariate meta-analysis require the knowledge of within-study correlations, which are usually unavailable. This limits standard inference approaches in practice. Riley et al proposed a working model and an overall synthesis correlation parameter to account for the marginal correlation between outcomes, where the only data needed are those required for a separate univariate random-effects meta-analysis. As within-study correlations are not required, the Riley method is applicable to a wide variety of evidence synthesis situations. However, the standard variance estimator of the Riley method is not entirely correct under many important settings. As a consequence, the coverage of a function of pooled estimates may not reach the nominal level even when the number of studies in the multivariate meta-analysis is large. In this paper, we improve the Riley method by proposing a robust variance estimator, which is asymptotically correct even when the model is misspecified (ie, when the likelihood function is incorrect). Simulation studies of a bivariate meta-analysis, in a variety of settings, show a function of pooled estimates has improved performance when using the proposed robust variance estimator. In terms of individual pooled estimates themselves, the standard variance estimator and robust variance estimator give similar results to the original method, with appropriate coverage. The proposed robust variance estimator performs well when the number of studies is relatively large. Therefore, we recommend the use of the robust method for meta-analyses with a relatively large number of studies (eg, m≥50). When the

  7. Analysis of input variables of an artificial neural network using bivariate correlation and canonical correlation

    International Nuclear Information System (INIS)

    Costa, Valter Magalhaes; Pereira, Iraci Martinez

    2011-01-01

    The monitoring of variables and diagnosis of sensor fault in nuclear power plants or processes industries is very important because a previous diagnosis allows the correction of the fault and, like this, to prevent the production stopped, improving operator's security and it's not provoking economics losses. The objective of this work is to build a set, using bivariate correlation and canonical correlation, which will be the set of input variables of an artificial neural network to monitor the greater number of variables. This methodology was applied to the IEA-R1 Research Reactor at IPEN. Initially, for the input set of neural network we selected the variables: nuclear power, primary circuit flow rate, control/safety rod position and difference in pressure in the core of the reactor, because almost whole of monitoring variables have relation with the variables early described or its effect can be result of the interaction of two or more. The nuclear power is related to the increasing and decreasing of temperatures as well as the amount radiation due fission of the uranium; the rods are controls of power and influence in the amount of radiation and increasing and decreasing of temperatures; the primary circuit flow rate has the function of energy transport by removing the nucleus heat. An artificial neural network was trained and the results were satisfactory since the IEA-R1 Data Acquisition System reactor monitors 64 variables and, with a set of 9 input variables resulting from the correlation analysis, it was possible to monitor 51 variables. (author)

  8. Analysis of input variables of an artificial neural network using bivariate correlation and canonical correlation

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Valter Magalhaes; Pereira, Iraci Martinez, E-mail: valter.costa@usp.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    The monitoring of variables and diagnosis of sensor fault in nuclear power plants or processes industries is very important because a previous diagnosis allows the correction of the fault and, like this, to prevent the production stopped, improving operator's security and it's not provoking economics losses. The objective of this work is to build a set, using bivariate correlation and canonical correlation, which will be the set of input variables of an artificial neural network to monitor the greater number of variables. This methodology was applied to the IEA-R1 Research Reactor at IPEN. Initially, for the input set of neural network we selected the variables: nuclear power, primary circuit flow rate, control/safety rod position and difference in pressure in the core of the reactor, because almost whole of monitoring variables have relation with the variables early described or its effect can be result of the interaction of two or more. The nuclear power is related to the increasing and decreasing of temperatures as well as the amount radiation due fission of the uranium; the rods are controls of power and influence in the amount of radiation and increasing and decreasing of temperatures; the primary circuit flow rate has the function of energy transport by removing the nucleus heat. An artificial neural network was trained and the results were satisfactory since the IEA-R1 Data Acquisition System reactor monitors 64 variables and, with a set of 9 input variables resulting from the correlation analysis, it was possible to monitor 51 variables. (author)

  9. Analysis of Blood Transfusion Data Using Bivariate Zero-Inflated Poisson Model: A Bayesian Approach.

    Science.gov (United States)

    Mohammadi, Tayeb; Kheiri, Soleiman; Sedehi, Morteza

    2016-01-01

    Recognizing the factors affecting the number of blood donation and blood deferral has a major impact on blood transfusion. There is a positive correlation between the variables "number of blood donation" and "number of blood deferral": as the number of return for donation increases, so does the number of blood deferral. On the other hand, due to the fact that many donors never return to donate, there is an extra zero frequency for both of the above-mentioned variables. In this study, in order to apply the correlation and to explain the frequency of the excessive zero, the bivariate zero-inflated Poisson regression model was used for joint modeling of the number of blood donation and number of blood deferral. The data was analyzed using the Bayesian approach applying noninformative priors at the presence and absence of covariates. Estimating the parameters of the model, that is, correlation, zero-inflation parameter, and regression coefficients, was done through MCMC simulation. Eventually double-Poisson model, bivariate Poisson model, and bivariate zero-inflated Poisson model were fitted on the data and were compared using the deviance information criteria (DIC). The results showed that the bivariate zero-inflated Poisson regression model fitted the data better than the other models.

  10. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews

    NARCIS (Netherlands)

    Reitsma, Johannes B.; Glas, Afina S.; Rutjes, Anne W. S.; Scholten, Rob J. P. M.; Bossuyt, Patrick M.; Zwinderman, Aeilko H.

    2005-01-01

    Background and Objectives: Studies of diagnostic accuracy most often report pairs of sensitivity and specificity. We demonstrate the advantage of using bivariate meta-regression models to analyze such data. Methods: We discuss the methodology of both the summary Receiver Operating Characteristic

  11. Global assessment of predictability of water availability: A bivariate probabilistic Budyko analysis

    Science.gov (United States)

    Wang, Weiguang; Fu, Jianyu

    2018-02-01

    Estimating continental water availability is of great importance for water resources management, in terms of maintaining ecosystem integrity and sustaining society development. To more accurately quantify the predictability of water availability, on the basis of univariate probabilistic Budyko framework, a bivariate probabilistic Budyko approach was developed using copula-based joint distribution model for considering the dependence between parameter ω of Wang-Tang's equation and the Normalized Difference Vegetation Index (NDVI), and was applied globally. The results indicate the predictive performance in global water availability is conditional on the climatic condition. In comparison with simple univariate distribution, the bivariate one produces the lower interquartile range under the same global dataset, especially in the regions with higher NDVI values, highlighting the importance of developing the joint distribution by taking into account the dependence structure of parameter ω and NDVI, which can provide more accurate probabilistic evaluation of water availability.

  12. Genetic determinant of trabecular bone score (TBS) and bone mineral density: A bivariate analysis.

    Science.gov (United States)

    Ho-Pham, Lan T; Hans, Didier; Doan, Minh C; Mai, Linh D; Nguyen, Tuan V

    2016-11-01

    This study sought to estimate the extent of genetic influence on the variation in trabecular bone score (TBS). We found that genetic factors accounted for ~45% of variance in TBS, and that the co-variation between TBS and bone density is partially determined by genetic factors. Trabecular bone score has emerged as an important predictor of fragility fracture, but factors underlying the individual differences in TBS have not been explored. In this study, we sought to determine the genetic contribution to the variation of TBS in the general population. The study included 556 women and 189 men from 265 families. The individuals aged 53years (SD 11). We measured lumbar spine bone mineral density (BMD; Hologic Horizon) and then derived the TBS from the same Hologic scan where BMD was derived. A biometric model was applied to the data to partition the variance of TBS into two components: one due to additive genetic factors, and one due to environmental factors. The index of heritability was estimated as the ratio of genetic variance to total variance of a trait. Bivariate genetic analysis was conducted to estimate the genetic correlation between TBS and BMD measurements. TBS was strongly correlated with lumbar spine BMD (r=0.73; P<0.001). On average TBS in men was higher than women, after adjusting age and height which are significantly associated with both TBS and lumbar spine BMD. The age and height adjusted index of heritability of TBS was 0.46 (95% CI, 0.39-0.54), which was not much different from that of LSBMD (0.44; 95% CI, 0.31-0.55). Moreover, the genetic correlation between TBS and LSBMD was 0.35 (95% CI, 0.21-0.46), between TBS and femoral neck BMD was 0.21 (95% CI, 0.10-0.33). Approximately 45% of the variance in TBS is under genetic influence, and this effect magnitude is similar to that of lumbar spine BMD. This finding provides a scientific justification for the search for specific genetic variants that may be associated with TBS and fracture risk

  13. Meta-analysis for diagnostic accuracy studies: a new statistical model using beta-binomial distributions and bivariate copulas.

    Science.gov (United States)

    Kuss, Oliver; Hoyer, Annika; Solms, Alexander

    2014-01-15

    There are still challenges when meta-analyzing data from studies on diagnostic accuracy. This is mainly due to the bivariate nature of the response where information on sensitivity and specificity must be summarized while accounting for their correlation within a single trial. In this paper, we propose a new statistical model for the meta-analysis for diagnostic accuracy studies. This model uses beta-binomial distributions for the marginal numbers of true positives and true negatives and links these margins by a bivariate copula distribution. The new model comes with all the features of the current standard model, a bivariate logistic regression model with random effects, but has the additional advantages of a closed likelihood function and a larger flexibility for the correlation structure of sensitivity and specificity. In a simulation study, which compares three copula models and two implementations of the standard model, the Plackett and the Gauss copula do rarely perform worse but frequently better than the standard model. We use an example from a meta-analysis to judge the diagnostic accuracy of telomerase (a urinary tumor marker) for the diagnosis of primary bladder cancer for illustration. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Bivariate Random Effects Meta-analysis of Diagnostic Studies Using Generalized Linear Mixed Models

    Science.gov (United States)

    GUO, HONGFEI; ZHOU, YIJIE

    2011-01-01

    Bivariate random effect models are currently one of the main methods recommended to synthesize diagnostic test accuracy studies. However, only the logit-transformation on sensitivity and specificity has been previously considered in the literature. In this paper, we consider a bivariate generalized linear mixed model to jointly model the sensitivities and specificities, and discuss the estimation of the summary receiver operating characteristic curve (ROC) and the area under the ROC curve (AUC). As the special cases of this model, we discuss the commonly used logit, probit and complementary log-log transformations. To evaluate the impact of misspecification of the link functions on the estimation, we present two case studies and a set of simulation studies. Our study suggests that point estimation of the median sensitivity and specificity, and AUC is relatively robust to the misspecification of the link functions. However, the misspecification of link functions has a noticeable impact on the standard error estimation and the 95% confidence interval coverage, which emphasizes the importance of choosing an appropriate link function to make statistical inference. PMID:19959794

  15. Bivariate spatial analysis of temperature and precipitation from general circulation models and observation proxies

    KAUST Repository

    Philbin, R.

    2015-05-22

    This study validates the near-surface temperature and precipitation output from decadal runs of eight atmospheric ocean general circulation models (AOGCMs) against observational proxy data from the National Centers for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) reanalysis temperatures and Global Precipitation Climatology Project (GPCP) precipitation data. We model the joint distribution of these two fields with a parsimonious bivariate Matérn spatial covariance model, accounting for the two fields\\' spatial cross-correlation as well as their own smoothnesses. We fit output from each AOGCM (30-year seasonal averages from 1981 to 2010) to a statistical model on each of 21 land regions. Both variance and smoothness values agree for both fields over all latitude bands except southern mid-latitudes. Our results imply that temperature fields have smaller smoothness coefficients than precipitation fields, while both have decreasing smoothness coefficients with increasing latitude. Models predict fields with smaller smoothness coefficients than observational proxy data for the tropics. The estimated spatial cross-correlations of these two fields, however, are quite different for most GCMs in mid-latitudes. Model correlation estimates agree well with those for observational proxy data for Australia, at high northern latitudes across North America, Europe and Asia, as well as across the Sahara, India, and Southeast Asia, but elsewhere, little consistent agreement exists.

  16. The Role of Wealth and Health in Insurance Choice: Bivariate Probit Analysis in China

    Directory of Open Access Journals (Sweden)

    Yiding Yue

    2014-01-01

    Full Text Available This paper captures the correlation between the choices of health insurance and pension insurance using the bivariate probit model and then studies the effect of wealth and health on insurance choice. Our empirical evidence shows that people who participate in a health care program are more likely to participate in a pension plan at the same time, while wealth and health have different effects on the choices of the health care program and the pension program. Generally, the higher an individual’s wealth level is, the more likelihood he will participate in a health care program; but wealth has no effect on the participation of pension. Health status has opposite effects on choices of health care programs and pension plans; the poorer an individual’s health is, the more likely he is to participate in health care programs, while the better health he enjoys, the more likely he is to participate in pension plans. When the investigation scope narrows down to commercial insurance, there is only a significant effect of health status on commercial health insurance. The commercial insurance choice and the insurance choice of the agricultural population are more complicated.

  17. Diagnostic performance of des-γ-carboxy prothrombin (DCP) for hepatocellular carcinoma: a bivariate meta-analysis.

    Science.gov (United States)

    Gao, P; Li, M; Tian, Q B; Liu, Dian-Wu

    2012-01-01

    Serum markers are needed to be developed to specifically diagnose Hepatocellular carcinoma (HCC). Des-γ-carboxy prothrombin (DCP) is a promising tool with limited expense and widely accessibility, but the reported results have been controversial. In order to review the performance of DCP for the diagnosis of HCC, the meta-analysis was performed. After a systematic review of relevant studies, the sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively) were pooled using a bivariate meta-analysis. Potential between-study heterogeneity was explored by meta-regression model. The post-test probability and the likelihood ratio scattergram to evaluate clinical usefulness were calculated. Based on literature review of 20 publications, the overall sensitivity, specificity, PLR and NLR of DCP for the detection of HCC were 67% (95%CI, 58%-74%), 92% (95%CI, 88%-94%), 7.9 (95%CI, 5.6-11.2) and 0.36 (95%CI, 0.29-0.46), respectively. The area under the bivariate summary receiving operating characteristics curve was 0.89 (95%CI, 0.85-0.92). Significant heterogeneity was present. In conclusion, the major role of DCP is the moderate confirmation of HCC. More prospective studies of DCP are needed in future.

  18. Analysis of input variables of an artificial neural network using bivariate correlation and canonical correlation

    International Nuclear Information System (INIS)

    Costa, Valter Magalhaes

    2011-01-01

    was trained and the results were satisfactory since the IEA-R1 Data Acquisition System reactor monitors 64 variables and, with a set of 9 input variables resulting from the correlation analysis, it was possible to monitor 51 variables using neural networks. (author)

  19. Quasi-bivariate variational mode decomposition as a tool of scale analysis in wall-bounded turbulence

    Science.gov (United States)

    Wang, Wenkang; Pan, Chong; Wang, Jinjun

    2018-01-01

    The identification and separation of multi-scale coherent structures is a critical task for the study of scale interaction in wall-bounded turbulence. Here, we propose a quasi-bivariate variational mode decomposition (QB-VMD) method to extract structures with various scales from instantaneous two-dimensional (2D) velocity field which has only one primary dimension. This method is developed from the one-dimensional VMD algorithm proposed by Dragomiretskiy and Zosso (IEEE Trans Signal Process 62:531-544, 2014) to cope with a quasi-2D scenario. It poses the feature of length-scale bandwidth constraint along the decomposed dimension, together with the central frequency re-balancing along the non-decomposed dimension. The feasibility of this method is tested on both a synthetic flow field and a turbulent boundary layer at moderate Reynolds number (Re_{τ } = 3458) measured by 2D particle image velocimetry (PIV). Some other popular scale separation tools, including pseudo-bi-dimensional empirical mode decomposition (PB-EMD), bi-dimensional EMD (B-EMD) and proper orthogonal decomposition (POD), are also tested for comparison. Among all these methods, QB-VMD shows advantages in both scale characterization and energy recovery. More importantly, the mode mixing problem, which degrades the performance of EMD-based methods, is avoided or minimized in QB-VMD. Finally, QB-VMD analysis of the wall-parallel plane in the log layer (at y/δ = 0.12) of the studied turbulent boundary layer shows the coexistence of large- or very large-scale motions (LSMs or VLSMs) and inner-scaled structures, which can be fully decomposed in both physical and spectral domains.

  20. Ordinal Bivariate Inequality

    DEFF Research Database (Denmark)

    Sonne-Schmidt, Christoffer Scavenius; Tarp, Finn; Østerdal, Lars Peter Raahave

    2016-01-01

    This paper introduces a concept of inequality comparisons with ordinal bivariate categorical data. In our model, one population is more unequal than another when they have common arithmetic median outcomes and the first can be obtained from the second by correlation-increasing switches and....../or median-preserving spreads. For the canonical 2 × 2 case (with two binary indicators), we derive a simple operational procedure for checking ordinal inequality relations in practice. As an illustration, we apply the model to childhood deprivation in Mozambique....

  1. Ordinal bivariate inequality

    DEFF Research Database (Denmark)

    Sonne-Schmidt, Christoffer Scavenius; Tarp, Finn; Østerdal, Lars Peter Raahave

    This paper introduces a concept of inequality comparisons with ordinal bivariate categorical data. In our model, one population is more unequal than another when they have common arithmetic median outcomes and the first can be obtained from the second by correlationincreasing switches and/or median......-preserving spreads. For the canonical 2x2 case (with two binary indicators), we derive a simple operational procedure for checking ordinal inequality relations in practice. As an illustration, we apply the model to childhood deprivation in Mozambique....

  2. Effectiveness of enforcement levels of speed limit and drink driving laws and associated factors – Exploratory empirical analysis using a bivariate ordered probit model

    Directory of Open Access Journals (Sweden)

    Behram Wali

    2017-06-01

    Full Text Available The contemporary traffic safety research comprises little information on quantifying the simultaneous association between drink driving and speeding among fatally injured drivers. Potential correlation between driver's drink driving and speeding behavior poses a substantial methodological concern which needs investigation. This study therefore focused on investigating the simultaneous impact of socioeconomic factors, fatalities, vehicle ownership, health services and highway agency road safety policies on enforcement levels of speed limit and drink driving laws. The effectiveness of enforcement levels of speed limit and drink driving laws has been investigated through development of bivariate ordered probit model using data extricated from WHO's global status report on road safety in 2013. The consistent and intuitive parameter estimates along with statistically significant correlation between response outcomes validates the statistical supremacy of bivariate ordered probit model. The results revealed that fatalities per thousand registered vehicles, hospital beds per hundred thousand population and road safety policies are associated with a likely medium or high effectiveness of enforcement levels of speed limit and drink driving laws, respectively. Also, the model encapsulates the effect of several other agency related variables and socio-economic status on the response outcomes. Marginal effects are reported for analyzing the impact of such factors on intermediate categories of response outcomes. The results of this study are expected to provide necessary insights to elemental enforcement programs. Also, marginal effects of explanatory variables may provide useful directions for formulating effective policy countermeasures for overcoming driver's speeding and drink driving behavior.

  3. Monitoring bivariate process

    Directory of Open Access Journals (Sweden)

    Marcela A. G. Machado

    2009-12-01

    Full Text Available The T² chart and the generalized variance |S| chart are the usual tools for monitoring the mean vector and the covariance matrix of multivariate processes. The main drawback of these charts is the difficulty to obtain and to interpret the values of their monitoring statistics. In this paper, we study control charts for monitoring bivariate processes that only requires the computation of sample means (the ZMAX chart for monitoring the mean vector, sample variances (the VMAX chart for monitoring the covariance matrix, or both sample means and sample variances (the MCMAX chart in the case of the joint control of the mean vector and the covariance matrix.Os gráficos de T² e da variância amostral generalizada |S| são as ferramentas usualmente utilizadas no monitoramento do vetor de médias e da matriz de covariâncias de processos multivariados. A principal desvantagem desses gráficos é a dificuldade em obter e interpretar os valores de suas estatísticas de monitoramento. Neste artigo, estudam-se gráficos de controle para o monitoramento de processos bivariados que necessitam somente do cálculo de médias amostrais (gráfico ZMAX para o monitoramento do vetor de médias, ou das variâncias amostrais (gráfico VMAX para o monitoramento da matriz de covariâncias, ou então das médias e variâncias amostrais (gráfico MCMAX para o caso do monitoramento conjunto do vetor de médias e da matriz de covariâncias.

  4. Diagnostic value of sTREM-1 in bronchoalveolar lavage fluid in ICU patients with bacterial lung infections: a bivariate meta-analysis.

    Science.gov (United States)

    Shi, Jia-Xin; Li, Jia-Shu; Hu, Rong; Li, Chun-Hua; Wen, Yan; Zheng, Hong; Zhang, Feng; Li, Qin

    2013-01-01

    The serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a useful biomarker in differentiating bacterial infections from others. However, the diagnostic value of sTREM-1 in bronchoalveolar lavage fluid (BALF) in lung infections has not been well established. We performed a meta-analysis to assess the accuracy of sTREM-1 in BALF for diagnosis of bacterial lung infections in intensive care unit (ICU) patients. We searched PUBMED, EMBASE and Web of Knowledge (from January 1966 to October 2012) databases for relevant studies that reported diagnostic accuracy data of BALF sTREM-1 in the diagnosis of bacterial lung infections in ICU patients. Pooled sensitivity, specificity, and positive and negative likelihood ratios were calculated by a bivariate regression analysis. Measures of accuracy and Q point value (Q*) were calculated using summary receiver operating characteristic (SROC) curve. The potential between-studies heterogeneity was explored by subgroup analysis. Nine studies were included in the present meta-analysis. Overall, the prevalence was 50.6%; the sensitivity was 0.87 (95% confidence interval (CI), 0.72-0.95); the specificity was 0.79 (95% CI, 0.56-0.92); the positive likelihood ratio (PLR) was 4.18 (95% CI, 1.78-9.86); the negative likelihood ratio (NLR) was 0.16 (95% CI, 0.07-0.36), and the diagnostic odds ratio (DOR) was 25.60 (95% CI, 7.28-89.93). The area under the SROC curve was 0.91 (95% CI, 0.88-0.93), with a Q* of 0.83. Subgroup analysis showed that the assay method and cutoff value influenced the diagnostic accuracy of sTREM-1. BALF sTREM-1 is a useful biomarker of bacterial lung infections in ICU patients. Further studies are needed to confirm the optimized cutoff value.

  5. Association of Supply Type with Fecal Contamination of Source Water and Household Stored Drinking Water in Developing Countries: A Bivariate Meta-analysis.

    Science.gov (United States)

    Shields, Katherine F; Bain, Robert E S; Cronk, Ryan; Wright, Jim A; Bartram, Jamie

    2015-12-01

    Access to safe drinking water is essential for health. Monitoring access to drinking water focuses on water supply type at the source, but there is limited evidence on whether quality differences at the source persist in water stored in the household. We assessed the extent of fecal contamination at the source and in household stored water (HSW) and explored the relationship between contamination at each sampling point and water supply type. We performed a bivariate random-effects meta-analysis of 45 studies, identified through a systematic review, that reported either the proportion of samples free of fecal indicator bacteria and/or individual sample bacteria counts for source and HSW, disaggregated by supply type. Water quality deteriorated substantially between source and stored water. The mean percentage of contaminated samples (noncompliance) at the source was 46% (95% CI: 33, 60%), whereas mean noncompliance in HSW was 75% (95% CI: 64, 84%). Water supply type was significantly associated with noncompliance at the source (p water (OR = 0.2; 95% CI: 0.1, 0.5) and HSW (OR = 0.3; 95% CI: 0.2, 0.8) from piped supplies had significantly lower odds of contamination compared with non-piped water, potentially due to residual chlorine. Piped water is less likely to be contaminated compared with other water supply types at both the source and in HSW. A focus on upgrading water services to piped supplies may help improve safety, including for those drinking stored water.

  6. Association of Supply Type with Fecal Contamination of Source Water and Household Stored Drinking Water in Developing Countries: A Bivariate Meta-analysis

    OpenAIRE

    Shields, Katherine F.; Bain, Robert E.S.; Cronk, Ryan; Wright, Jim A.; Bartram, Jamie

    2015-01-01

    Background Access to safe drinking water is essential for health. Monitoring access to drinking water focuses on water supply type at the source, but there is limited evidence on whether quality differences at the source persist in water stored in the household. Objectives We assessed the extent of fecal contamination at the source and in household stored water (HSW) and explored the relationship between contamination at each sampling point and water supply type. Methods We performed a bivari...

  7. Bivariate value-at-risk

    Directory of Open Access Journals (Sweden)

    Giuseppe Arbia

    2007-10-01

    Full Text Available In this paper we extend the concept of Value-at-risk (VaR to bivariate return distributions in order to obtain measures of the market risk of an asset taking into account additional features linked to downside risk exposure. We first present a general definition of risk as the probability of an adverse event over a random distribution and we then introduce a measure of market risk (b-VaR that admits the traditional b of an asset in portfolio management as a special case when asset returns are normally distributed. Empirical evidences are provided by using Italian stock market data.

  8. Accuracy of serum uric acid as a predictive test for maternal complications in pre-eclampsia: Bivariate meta-analysis and decision analysis

    NARCIS (Netherlands)

    Koopmans, Corine M.; van Pampus, Maria G.; Groen, Henk; Aarnoudse, Jan G.; van den Berg, Paul P.; Mol, Ben W. J.

    2009-01-01

    The aim of this study is to determine the accuracy and clinical value of serum uric acid in predicting maternal complications in women with pre-eclampsia. An existing meta-analysis on the subject was updated. The accuracy of serum uric acid for the prediction of maternal complications was assessed

  9. Accuracy of serum uric acid as a predictive test for maternal complications in pre-eclampsia : Bivariate meta-analysis and decision analysis

    NARCIS (Netherlands)

    Koopmans, C.M.; van Pampus, Maria; Groen, H.; Aarnoudse, J.G.; van den Berg, P.P.; Mol, B.W.J.

    The aim of this study is to determine the accuracy and clinical value of serum uric acid in predicting maternal complications in women with pre-eclampsia. An existing meta-analysis on the subject was updated. The accuracy of serum uric acid for the prediction of maternal complications was assessed

  10. Bivariate analysis of the genetic variability among some accessions of African Yam Bean (Sphenostylis stenocarpa (Hochst ex A. RichHarms

    Directory of Open Access Journals (Sweden)

    Solomon Tayo AKINYOSOYE

    2017-12-01

    Full Text Available Variability is an important factor to consider in crop improvement programmes. This study was conducted in two years to assess genetic variability and determine relationship between seed yield, its components and tuber production characters among twelve accessions of African yam bean. Data collected were subjected to combined analysis of variance (ANOVA, Principal Component Analysis (PCA, hierarchical and K-means clustering analyses. Results obtained revealed that genotype by year (G × Y interaction had significant effects on some of variables measured (days to first flowering, days to 50 % flowering, number of pod per plant, pod length, seed yield and tuber yield per plant in this study.The first five principal components (PC with Eigen values greater than 1.0 accounted for about 66.70 % of the total variation, where PC1 and PC 2 accounted for 39.48 % of variation and were associated with seed and tuber yield variables. Three heterotic groups were clearly delineated among genotypes with accessions AY03 and AY10 identified for high seed yield and tuber yield respectively. Non-significant relationship that existed between tuber and seed yield per plant of these accessions was recommended for further test in various agro-ecologies for their suitability, adaptability and possible exploitation of heterosis to further improve the accessions.

  11. Flash flood susceptibility analysis and its mapping using different bivariate models in Iran: a comparison between Shannon's entropy, statistical index, and weighting factor models.

    Science.gov (United States)

    Khosravi, Khabat; Pourghasemi, Hamid Reza; Chapi, Kamran; Bahri, Masoumeh

    2016-12-01

    Flooding is a very common worldwide natural hazard causing large-scale casualties every year; Iran is not immune to this thread as well. Comprehensive flood susceptibility mapping is very important to reduce losses of lives and properties. Thus, the aim of this study is to map susceptibility to flooding by different bivariate statistical methods including Shannon's entropy (SE), statistical index (SI), and weighting factor (Wf). In this regard, model performance evaluation is also carried out in Haraz Watershed, Mazandaran Province, Iran. In the first step, 211 flood locations were identified by the documentary sources and field inventories, of which 70% (151 positions) were used for flood susceptibility modeling and 30% (60 positions) for evaluation and verification of the model. In the second step, ten influential factors in flooding were chosen, namely slope angle, plan curvature, altitude, topographic wetness index (TWI), stream power index (SPI), distance from river, rainfall, geology, land use, and normalized difference vegetation index (NDVI). In the next step, flood susceptibility maps were prepared by these four methods in ArcGIS. As the last step, receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated for quantitative assessment of each model. The results showed that the best model to estimate the susceptibility to flooding in Haraz Watershed was SI model with the prediction and success rates of 99.71 and 98.72%, respectively, followed by Wf and SE models with the AUC values of 98.1 and 96.57% for the success rate, and 97.6 and 92.42% for the prediction rate, respectively. In the SI and Wf models, the highest and lowest important parameters were the distance from river and geology. Flood susceptibility maps are informative for managers and decision makers in Haraz Watershed in order to contemplate measures to reduce human and financial losses.

  12. Landslide susceptibility analysis in central Vietnam based on an incomplete landslide inventory: Comparison of a new method to calculate weighting factors by means of bivariate statistics

    Science.gov (United States)

    Meinhardt, Markus; Fink, Manfred; Tünschel, Hannes

    2015-04-01

    Vietnam is regarded as a country strongly impacted by climate change. Population and economic growth result in additional pressures on the ecosystems in the region. In particular, changes in landuse and precipitation extremes lead to a higher landslide susceptibility in the study area (approx. 12,400 km2), located in central Vietnam and impacted by a tropical monsoon climate. Hence, this natural hazard is a serious problem in the study area. A probability assessment of landslides is therefore undertaken through the use of bivariate statistics. However, the landslide inventory based only on field campaigns does not cover the whole area. To avoid a systematic bias due to the limited mapping area, the investigated regions are depicted as the viewshed in the calculations. On this basis, the distribution of the landslides is evaluated in relation to the maps of 13 parameters, showing the strongest correlation to distance to roads and precipitation increase. An additional weighting of the input parameters leads to better results, since some parameters contribute more to landslides than others. The method developed in this work is based on the validation of different parameter sets used within the statistical index method. It is called "omit error" because always omitting another parameter leads to the weightings, which describe how strong every single parameter improves or reduces the objective function. Furthermore, this approach is used to find a better input parameter set by excluding some parameters. After this optimization, nine input parameters are left, and they are weighted by the omit error method, providing the best susceptibility map with a success rate of 92.9% and a prediction rate of 92.3%. This is an improvement of 4.4% and 4.2%, respectively, compared to the basic statistical index method with the 13 input parameters.

  13. GIS-based bivariate statistical techniques for groundwater potential ...

    Indian Academy of Sciences (India)

    Groundwater potential analysis prepares better comprehension of hydrological settings of different regions. This study shows the potency of two GIS-based data driven bivariate techniques namely statistical index (SI) and Dempster–Shafer theory (DST) to analyze groundwater potential in Broujerd region of Iran.

  14. Bivariate hard thresholding in wavelet function estimation

    OpenAIRE

    Piotr Fryzlewicz

    2007-01-01

    We propose a generic bivariate hard thresholding estimator of the discrete wavelet coefficients of a function contaminated with i.i.d. Gaussian noise. We demonstrate its good risk properties in a motivating example, and derive upper bounds for its mean-square error. Motivated by the clustering of large wavelet coefficients in real-life signals, we propose two wavelet denoising algorithms, both of which use specific instances of our bivariate estimator. The BABTE algorithm uses basis averaging...

  15. Bivariate Correlation Analysis of the Chemometric Profiles of Chinese Wild Salvia miltiorrhiza Based on UPLC-Qqq-MS and Antioxidant Activities

    Directory of Open Access Journals (Sweden)

    Xiaodan Zhang

    2018-02-01

    Full Text Available To better understand the mechanisms underlying the pharmacological actions of Salvia miltiorrhiza, correlation between the chemical profiles and in vitro antioxidant activities in 50 batches of wild S. miltiorrhiza samples was analyzed. Our ultra-performance liquid chromatography–tandem mass spectrometry analysis detected twelve phenolic acids and five tanshinones and obtained various chemical profiles from different origins. In a principal component analysis (PCA and cluster analysis, the tanshinones cryptotanshinone, tanshinone IIA and dihydrotanshinone I exhibited higher weights in PC1, whereas the phenolic acids danshensu, salvianolic acids A and B and lithospermic acid were highly loaded in PC2. All components could be optimized as markers of different locations and might be suitable for S. miltiorrhiza quality analyses. Additionally, the DPPH and ABTS assays used to comprehensively evaluate antioxidant activities indicated large variations, with mean DPPH and ABTS scavenging potencies of 32.24 and 23.39 μg/mL, respectively, among S. miltiorrhiza extract solutions. Notably, samples that exceeded the mean IC50 values had higher phenolic acid contents. A correlation analysis indicated a strong correlation between the antioxidant activities and phenolic acid contents. Caffeic acid, danshensu, rosmarinic acid, lithospermic acid and salvianolic acid B were major contributors to antioxidant activity. In conclusion, phenolic compounds were the predominant antioxidant components in the investigated plant species. These plants may be sources of potent natural antioxidants and beneficial chemopreventive agents.

  16. Influence of Four Radiotracers in PET/CT on Diagnostic Accuracy for Prostate Cancer: A Bivariate Random-Effects Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Junzhong Liu

    2016-07-01

    Full Text Available Background/Aims: To date, several positron emission tomography/computed tomography (PET/CT radiotracers including fluorine-18 fluorodeoxyglucose (18F-FDG, carbon-11 labeled choline (11C-choline, 18-F fluorocholine (18F-FCH and carbon-11 acetate (11C-acetate have already been assessed in the application of prostate cancer (PCa diagnosis to some extent, the diagnostic efficiency of these radiotracers still remain controversial. As a result of this, we carried out this meta-analysis for the purpose of comparing the diagnostic accuracy among four PET/CT radiotracers. Methods: A systematical literature search for articles was performed until July 3, 2015. We implemented all analysis using the statistical software of STATA12 and quality assessment was performed using QUADAS-2. Results: A total of 56 studies containing 3,586 patients were included in this meta-analysis. Parameter estimates of the overall analysis are as follows: sensitivity, 0.80 (95% CI: 0.74-0.85; specificity, 0.84 (95% CI: 0.77-0.89 and area under roc curve-AUC of SROC, 0.89 (95% CI: 0.86-0.91, indicating a relatively high level of accuracy in diagnosis of PCa. When different radiotracers of PET/CT were compared, 18F-FCH-PET/CT was ranked as the most favorable with the highest value of AUC (AUC = 0.94; 95% CI: 0.92-0.96 whereas 18F-FDG was the least favorable (AUC = 0.73, 95% CI: 0.69-0.77. Conclusion: This study suggested that PET/CT imaging plays an invaluable role in the diagnosis of PCa and 18F-FCH-PET/CT was considered as a superior diagnostic tool over other radiotracers. More attention should be paid to the diagnostic efficiency of the four radiotracers particularly for PCa patients with different clinical stages.

  17. Influence of Four Radiotracers in PET/CT on Diagnostic Accuracy for Prostate Cancer: A Bivariate Random-Effects Meta-Analysis.

    Science.gov (United States)

    Liu, Junzhong; Chen, Zhongfeng; Wang, Tianyu; Liu, Li; Zhao, Lei; Guo, Guangtao; Wang, Dongqing

    2016-01-01

    To date, several positron emission tomography/computed tomography (PET/CT) radiotracers including fluorine-18 fluorodeoxyglucose (18F-FDG), carbon-11 labeled choline (11C-choline), 18-F fluorocholine (18F-FCH) and carbon-11 acetate (11C-acetate) have already been assessed in the application of prostate cancer (PCa) diagnosis to some extent, the diagnostic efficiency of these radiotracers still remain controversial. As a result of this, we carried out this meta-analysis for the purpose of comparing the diagnostic accuracy among four PET/CT radiotracers. A systematical literature search for articles was performed until July 3, 2015. We implemented all analysis using the statistical software of STATA12 and quality assessment was performed using QUADAS-2. A total of 56 studies containing 3,586 patients were included in this meta-analysis. Parameter estimates of the overall analysis are as follows: sensitivity, 0.80 (95% CI: 0.74-0.85); specificity, 0.84 (95% CI: 0.77-0.89) and area under roc curve-AUC of SROC, 0.89 (95% CI: 0.86-0.91), indicating a relatively high level of accuracy in diagnosis of PCa. When different radiotracers of PET/CT were compared, 18F-FCH-PET/CT was ranked as the most favorable with the highest value of AUC (AUC = 0.94; 95% CI: 0.92-0.96) whereas 18F-FDG was the least favorable (AUC = 0.73, 95% CI: 0.69-0.77). This study suggested that PET/CT imaging plays an invaluable role in the diagnosis of PCa and 18F-FCH-PET/CT was considered as a superior diagnostic tool over other radiotracers. More attention should be paid to the diagnostic efficiency of the four radiotracers particularly for PCa patients with different clinical stages. © 2016 The Author(s) Published by S. Karger AG, Basel.

  18. A Vehicle for Bivariate Data Analysis

    Science.gov (United States)

    Roscoe, Matt B.

    2016-01-01

    Instead of reserving the study of probability and statistics for special fourth-year high school courses, the Common Core State Standards for Mathematics (CCSSM) takes a "statistics for all" approach. The standards recommend that students in grades 6-8 learn to summarize and describe data distributions, understand probability, draw…

  19. Monosomic analysis reveals duplicated chromosomal segments in ...

    Indian Academy of Sciences (India)

    Monosomic analysis reveals duplicated chromosomal segments in maize genome. MAHESH C. YADAV1,2∗, J. K. S. ... cated chromosomal segments in maize genome. Materials and methods. Development and .... each in chromosomes 2 and 7, while 10 other pairs of du- plicate loci had one copy in chromosome 3 and the ...

  20. Genomics analysis of genes expressed reveals differential ...

    African Journals Online (AJOL)

    Genomics analysis of genes expressed reveals differential responses to low chronic nitrogen stress in maize. ... Most induced clones were largely involved in various metabolism processes including physiological process, organelle regulation of biological process, nutrient reservoir activity, transcription regulator activity and ...

  1. Probability distributions with truncated, log and bivariate extensions

    CERN Document Server

    Thomopoulos, Nick T

    2018-01-01

    This volume presents a concise and practical overview of statistical methods and tables not readily available in other publications. It begins with a review of the commonly used continuous and discrete probability distributions. Several useful distributions that are not so common and less understood are described with examples and applications in full detail: discrete normal, left-partial, right-partial, left-truncated normal, right-truncated normal, lognormal, bivariate normal, and bivariate lognormal. Table values are provided with examples that enable researchers to easily apply the distributions to real applications and sample data. The left- and right-truncated normal distributions offer a wide variety of shapes in contrast to the symmetrically shaped normal distribution, and a newly developed spread ratio enables analysts to determine which of the three distributions best fits a particular set of sample data. The book will be highly useful to anyone who does statistical and probability analysis. This in...

  2. Reliability for some bivariate beta distributions

    Directory of Open Access Journals (Sweden)

    Nadarajah Saralees

    2005-01-01

    Full Text Available In the area of stress-strength models there has been a large amount of work as regards estimation of the reliability R=Pr( Xbivariate distribution with dependence between X and Y . In particular, we derive explicit expressions for R when the joint distribution is bivariate beta. The calculations involve the use of special functions.

  3. Reliability for some bivariate gamma distributions

    Directory of Open Access Journals (Sweden)

    Nadarajah Saralees

    2005-01-01

    Full Text Available In the area of stress-strength models, there has been a large amount of work as regards estimation of the reliability R=Pr( Xbivariate distribution with dependence between X and Y . In particular, we derive explicit expressions for R when the joint distribution is bivariate gamma. The calculations involve the use of special functions.

  4. Financial Applications of Bivariate Markov Processes

    OpenAIRE

    Ortobelli Lozza, Sergio; Angelelli, Enrico; Bianchi, Annamaria

    2011-01-01

    This paper describes a methodology to approximate a bivariate Markov process by means of a proper Markov chain and presents possible financial applications in portfolio theory, option pricing and risk management. In particular, we first show how to model the joint distribution between market stochastic bounds and future wealth and propose an application to large-scale portfolio problems. Secondly, we examine an application to VaR estimation. Finally, we propose a methodology...

  5. Spectral density regression for bivariate extremes

    KAUST Repository

    Castro Camilo, Daniela

    2016-05-11

    We introduce a density regression model for the spectral density of a bivariate extreme value distribution, that allows us to assess how extremal dependence can change over a covariate. Inference is performed through a double kernel estimator, which can be seen as an extension of the Nadaraya–Watson estimator where the usual scalar responses are replaced by mean constrained densities on the unit interval. Numerical experiments with the methods illustrate their resilience in a variety of contexts of practical interest. An extreme temperature dataset is used to illustrate our methods. © 2016 Springer-Verlag Berlin Heidelberg

  6. Bivariate Kumaraswamy Models via Modified FGM Copulas: Properties and Applications

    Directory of Open Access Journals (Sweden)

    Indranil Ghosh

    2017-11-01

    Full Text Available A copula is a useful tool for constructing bivariate and/or multivariate distributions. In this article, we consider a new modified class of FGM (Farlie–Gumbel–Morgenstern bivariate copula for constructing several different bivariate Kumaraswamy type copulas and discuss their structural properties, including dependence structures. It is established that construction of bivariate distributions by this method allows for greater flexibility in the values of Spearman’s correlation coefficient, ρ and Kendall’s τ .

  7. Multiple imputation methods for bivariate outcomes in cluster randomised trials.

    Science.gov (United States)

    DiazOrdaz, K; Kenward, M G; Gomes, M; Grieve, R

    2016-09-10

    Missing observations are common in cluster randomised trials. The problem is exacerbated when modelling bivariate outcomes jointly, as the proportion of complete cases is often considerably smaller than the proportion having either of the outcomes fully observed. Approaches taken to handling such missing data include the following: complete case analysis, single-level multiple imputation that ignores the clustering, multiple imputation with a fixed effect for each cluster and multilevel multiple imputation. We contrasted the alternative approaches to handling missing data in a cost-effectiveness analysis that uses data from a cluster randomised trial to evaluate an exercise intervention for care home residents. We then conducted a simulation study to assess the performance of these approaches on bivariate continuous outcomes, in terms of confidence interval coverage and empirical bias in the estimated treatment effects. Missing-at-random clustered data scenarios were simulated following a full-factorial design. Across all the missing data mechanisms considered, the multiple imputation methods provided estimators with negligible bias, while complete case analysis resulted in biased treatment effect estimates in scenarios where the randomised treatment arm was associated with missingness. Confidence interval coverage was generally in excess of nominal levels (up to 99.8%) following fixed-effects multiple imputation and too low following single-level multiple imputation. Multilevel multiple imputation led to coverage levels of approximately 95% throughout. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

  8. Solving Bivariate Polynomial Systems on a GPU

    International Nuclear Information System (INIS)

    Moreno Maza, Marc; Pan Wei

    2012-01-01

    We present a CUDA implementation of dense multivariate polynomial arithmetic based on Fast Fourier Transforms over finite fields. Our core routine computes on the device (GPU) the subresultant chain of two polynomials with respect to a given variable. This subresultant chain is encoded by values on a FFT grid and is manipulated from the host (CPU) in higher-level procedures. We have realized a bivariate polynomial system solver supported by our GPU code. Our experimental results (including detailed profiling information and benchmarks against a serial polynomial system solver implementing the same algorithm) demonstrate that our strategy is well suited for GPU implementation and provides large speedup factors with respect to pure CPU code.

  9. Bivariate Rayleigh Distribution and its Properties

    Directory of Open Access Journals (Sweden)

    Ahmad Saeed Akhter

    2007-01-01

    Full Text Available Rayleigh (1880 observed that the sea waves follow no law because of the complexities of the sea, but it has been seen that the probability distributions of wave heights, wave length, wave induce pitch, wave and heave motions of the ships follow the Rayleigh distribution. At present, several different quantities are in use for describing the state of the sea; for example, the mean height of the waves, the root mean square height, the height of the “significant waves” (the mean height of the highest one-third of all the waves the maximum height over a given interval of the time, and so on. At present, the ship building industry knows less than any other construction industry about the service conditions under which it must operate. Only small efforts have been made to establish the stresses and motions and to incorporate the result of such studies in to design. This is due to the complexity of the problem caused by the extensive variability of the sea and the corresponding response of the ships. Although the problem appears feasible, yet it is possible to predict service conditions for ships in an orderly and relatively simple manner Rayleigh (1980 derived it from the amplitude of sound resulting from many independent sources. This distribution is also connected with one or two dimensions and is sometimes referred to as “random walk” frequency distribution. The Rayleigh distribution can be derived from the bivariate normal distribution when the variate are independent and random with equal variances. We try to construct bivariate Rayleigh distribution with marginal Rayleigh distribution function and discuss its fundamental properties.

  10. Stress-strength reliability for general bivariate distributions

    Directory of Open Access Journals (Sweden)

    Alaa H. Abdel-Hamid

    2016-10-01

    Full Text Available An expression for the stress-strength reliability R=P(X1bivariate distribution. Such distribution includes bivariate compound Weibull, bivariate compound Gompertz, bivariate compound Pareto, among others. In the parametric case, the maximum likelihood estimates of the parameters and reliability function R are obtained. In the non-parametric case, point and interval estimates of R are developed using Govindarajulu's asymptotic distribution-free method when X1 and X2 are dependent. An example is given when the population distribution is bivariate compound Weibull. Simulation is performed, based on different sample sizes to study the performance of estimates.

  11. STUDI PERBANDINGAN ANTARA ALGORITMA BIVARIATE MARGINAL DISTRIBUTION DENGAN ALGORITMA GENETIKA

    Directory of Open Access Journals (Sweden)

    Chastine Fatichah

    2006-01-01

    Full Text Available Bivariate Marginal Distribution Algorithm is extended from Estimation of Distribution Algorithm. This heuristic algorithm proposes the new approach for recombination of generate new individual that without crossover and mutation process such as genetic algorithm. Bivariate Marginal Distribution Algorithm uses connectivity variable the pair gene for recombination of generate new individual. Connectivity between variable is doing along optimization process. In this research, genetic algorithm performance with one point crossover is compared with Bivariate Marginal Distribution Algorithm performance in case Onemax, De Jong F2 function, and Traveling Salesman Problem. In this research, experimental results have shown performance the both algorithm is dependence of parameter respectively and also population size that used. For Onemax case with size small problem, Genetic Algorithm perform better with small number of iteration and more fast for get optimum result. However, Bivariate Marginal Distribution Algorithm perform better of result optimization for case Onemax with huge size problem. For De Jong F2 function, Genetic Algorithm perform better from Bivariate Marginal Distribution Algorithm of a number of iteration and time. For case Traveling Salesman Problem, Bivariate Marginal Distribution Algorithm have shown perform better from Genetic Algorithm of optimization result. Abstract in Bahasa Indonesia : Bivariate Marginal Distribution Algorithm merupakan perkembangan lebih lanjut dari Estimation of Distribution Algorithm. Algoritma heuristik ini mengenalkan pendekatan baru dalam melakukan rekombinasi untuk membentuk individu baru, yaitu tidak menggunakan proses crossover dan mutasi seperti pada Genetic Algorithm. Bivariate Marginal Distribution Algorithm menggunakan keterkaitan pasangan variabel dalam melakukan rekombinasi untuk membentuk individu baru. Keterkaitan antar variabel tersebut ditemukan selama proses optimasi berlangsung. Aplikasi yang

  12. Quantitative interactome analysis reveals a chemoresistant edgotype.

    Science.gov (United States)

    Chavez, Juan D; Schweppe, Devin K; Eng, Jimmy K; Zheng, Chunxiang; Taipale, Alex; Zhang, Yiyi; Takara, Kohji; Bruce, James E

    2015-08-03

    Chemoresistance is a common mode of therapy failure for many cancers. Tumours develop resistance to chemotherapeutics through a variety of mechanisms, with proteins serving pivotal roles. Changes in protein conformations and interactions affect the cellular response to environmental conditions contributing to the development of new phenotypes. The ability to understand how protein interaction networks adapt to yield new function or alter phenotype is limited by the inability to determine structural and protein interaction changes on a proteomic scale. Here, chemical crosslinking and mass spectrometry were employed to quantify changes in protein structures and interactions in multidrug-resistant human carcinoma cells. Quantitative analysis of the largest crosslinking-derived, protein interaction network comprising 1,391 crosslinked peptides allows for 'edgotype' analysis in a cell model of chemoresistance. We detect consistent changes to protein interactions and structures, including those involving cytokeratins, topoisomerase-2-alpha, and post-translationally modified histones, which correlate with a chemoresistant phenotype.

  13. Approximation of bivariate copulas by patched bivariate Fréchet copulas

    KAUST Repository

    Zheng, Yanting

    2011-03-01

    Bivariate Fréchet (BF) copulas characterize dependence as a mixture of three simple structures: comonotonicity, independence and countermonotonicity. They are easily interpretable but have limitations when used as approximations to general dependence structures. To improve the approximation property of the BF copulas and keep the advantage of easy interpretation, we develop a new copula approximation scheme by using BF copulas locally and patching the local pieces together. Error bounds and a probabilistic interpretation of this approximation scheme are developed. The new approximation scheme is compared with several existing copula approximations, including shuffle of min, checkmin, checkerboard and Bernstein approximations and exhibits better performance, especially in characterizing the local dependence. The utility of the new approximation scheme in insurance and finance is illustrated in the computation of the rainbow option prices and stop-loss premiums. © 2010 Elsevier B.V.

  14. A comparison of bivariate and univariate QTL mapping in livestock populations

    Directory of Open Access Journals (Sweden)

    Sorensen Daniel

    2003-11-01

    Full Text Available Abstract This study presents a multivariate, variance component-based QTL mapping model implemented via restricted maximum likelihood (REML. The method was applied to investigate bivariate and univariate QTL mapping analyses, using simulated data. Specifically, we report results on the statistical power to detect a QTL and on the precision of parameter estimates using univariate and bivariate approaches. The model and methodology were also applied to study the effectiveness of partitioning the overall genetic correlation between two traits into a component due to many genes of small effect, and one due to the QTL. It is shown that when the QTL has a pleiotropic effect on two traits, a bivariate analysis leads to a higher statistical power of detecting the QTL and to a more precise estimate of the QTL's map position, in particular in the case when the QTL has a small effect on the trait. The increase in power is most marked in cases where the contributions of the QTL and of the polygenic components to the genetic correlation have opposite signs. The bivariate REML analysis can successfully partition the two components contributing to the genetic correlation between traits.

  15. Nonlinear cardio-respiratory interactions revealed by time-phase bispectral analysis

    International Nuclear Information System (INIS)

    Jamsek, Janez; Stefanovska, Aneta; McClintock, Peter V E

    2004-01-01

    Bispectral analysis based on high order statistics, introduced recently as a technique for revealing time-phase relationships among interacting noisy oscillators, has been used to study the nature of the coupling between cardiac and respiratory activity. Univariate blood flow signals recorded simultaneously by laser-Doppler flowmetry on both legs and arms were analysed. Coupling between cardiac and respiratory activity was also checked by use of bivariate data and computation of the cross-bispectrum between the ECG and respiratory signals. Measurements were made on six healthy males aged 25-27 years. Recordings were taken during spontaneous breathing (20 min), and during paced respiration at frequencies both lower and higher than that of spontaneous respiration (either two or three recordings with a constant frequency in the interval between 0.09 and 0.35 Hz). At each paced frequency recordings were taken for 12 min. It was confirmed that the dynamics of blood flow can usefully be considered in terms of coupled oscillators, and demonstrated that interactions between the cardiac and respiratory processes are weak and time-varying, and that they can be nonlinear. Nonlinear coupling was revealed to exist during both spontaneous and paced respiration. When present, it was detected in all four blood flow signals and in the cross-bispectrum between the ECG and respiratory signal. The episodes with nonlinear coupling were detected in 11 out of 22 recordings and lasted between 19 s in the case of high frequency (0.34 Hz) and 106 s in the case of low frequency paced respiration (0.11 Hz)

  16. mitants of Order Statistics from Bivariate Inverse Rayleigh Distribution

    Directory of Open Access Journals (Sweden)

    Muhammad Aleem

    2006-01-01

    Full Text Available The probability density function (pdf of the rth, 1 r n and joint pdf of the rth and sth, 1 rBivariate Inverse Rayleigh Distribution and their moments, product moments are obtained. Its percentiles are also obtained.

  17. Dissecting the correlation structure of a bivariate phenotype ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 84; Issue 2. Dissecting the correlation structure of a bivariate phenotype: common genes or shared environment? ... High correlations between two quantitative traits may be either due to common genetic factors or common environmental factors or a combination of both.

  18. Modelling of Uncertainty and Bi-Variable Maps

    Science.gov (United States)

    Nánásiová, Ol'ga; Pykacz, Jarosław

    2016-05-01

    The paper gives an overview and compares various bi-varilable maps from orthomodular lattices into unit interval. It focuses mainly on such bi-variable maps that may be used for constructing joint probability distributions for random variables which are not defined on the same Boolean algebra.

  19. An assessment on the use of bivariate, multivariate and soft ...

    Indian Academy of Sciences (India)

    Conditional probability (CP), logistic regression (LR) and artificial neural networks (ANN) models representing the bivariate, multivariate and soft computing techniques were used in GIS based collapse susceptibility mapping in an area from Sivas basin (Turkey). Collapse-related factors, directly or indirectly related to the ...

  20. An assessment on the use of bivariate, multivariate and soft ...

    Indian Academy of Sciences (India)

    The paper presented herein compares and discusses the use of bivariate, multivariate and soft computing techniques for ... map is a useful tool in urban planning. ..... 381. Table 1. Frequency ratio of geological factors to collapse occurrences and results of the P(A/Bi) obtained from the. Conditional Probability model. Class.

  1. Comparison between two bivariate Poisson distributions through the ...

    African Journals Online (AJOL)

    To remedy this problem, Berkhout and Plug proposed a bivariate Poisson distribution accepting the correlation as well negative, equal to zero, that positive. In this paper, we show that these models are nearly everywhere asymptotically equal. From this survey that the ø-divergence converges toward zero, both models are ...

  2. About some properties of bivariate splines with shape parameters

    Science.gov (United States)

    Caliò, F.; Marchetti, E.

    2017-07-01

    The paper presents and proves geometrical properties of a particular bivariate function spline, built and algorithmically implemented in previous papers. The properties typical of this family of splines impact the field of computer graphics in particular that of the reverse engineering.

  3. Spectrum-based estimators of the bivariate Hurst exponent

    Czech Academy of Sciences Publication Activity Database

    Krištoufek, Ladislav

    2014-01-01

    Roč. 90, č. 6 (2014), art. 062802 ISSN 1539-3755 R&D Projects: GA ČR(CZ) GP14-11402P Institutional support: RVO:67985556 Keywords : bivariate Hurst exponent * power- law cross-correlations * estimation Subject RIV: AH - Economics Impact factor: 2.288, year: 2014 http://library.utia.cas.cz/separaty/2014/E/kristoufek-0436818.pdf

  4. Bivariate return periods of temperature and precipitation explain a large fraction of European crop yields

    Science.gov (United States)

    Zscheischler, Jakob; Orth, Rene; Seneviratne, Sonia I.

    2017-07-01

    Crops are vital for human society. Crop yields vary with climate and it is important to understand how climate and crop yields are linked to ensure future food security. Temperature and precipitation are among the key driving factors of crop yield variability. Previous studies have investigated mostly linear relationships between temperature and precipitation and crop yield variability. Other research has highlighted the adverse impacts of climate extremes, such as drought and heat waves, on crop yields. Impacts are, however, often non-linearly related to multivariate climate conditions. Here we derive bivariate return periods of climate conditions as indicators for climate variability along different temperature-precipitation gradients. We show that in Europe, linear models based on bivariate return periods of specific climate conditions explain on average significantly more crop yield variability (42 %) than models relying directly on temperature and precipitation as predictors (36 %). Our results demonstrate that most often crop yields increase along a gradient from hot and dry to cold and wet conditions, with lower yields associated with hot and dry periods. The majority of crops are most sensitive to climate conditions in summer and to maximum temperatures. The use of bivariate return periods allows the integration of non-linear impacts into climate-crop yield analysis. This offers new avenues to study the link between climate and crop yield variability and suggests that they are possibly more strongly related than what is inferred from conventional linear models.

  5. Multiresolution transmission of the correlation modes between bivariate time series based on complex network theory

    Science.gov (United States)

    Huang, Xuan; An, Haizhong; Gao, Xiangyun; Hao, Xiaoqing; Liu, Pengpeng

    2015-06-01

    This study introduces an approach to study the multiscale transmission characteristics of the correlation modes between bivariate time series. The correlation between the bivariate time series fluctuates over time. The transmission among the correlation modes exhibits a multiscale phenomenon, which provides richer information. To investigate the multiscale transmission of the correlation modes, this paper describes a hybrid model integrating wavelet analysis and complex network theory to decompose and reconstruct the original bivariate time series into sequences in a joint time-frequency domain and defined the correlation modes at each time-frequency domain. We chose the crude oil spot and futures prices as the sample data. The empirical results indicate that the main duration of volatility (32-64 days) for the strongly positive correlation between the crude oil spot price and the futures price provides more useful information for investors. Moreover, the weighted degree, weighted indegree and weighted outdegree of the correlation modes follow power-law distributions. The correlation fluctuation strengthens the extent of persistence over the long term, whereas persistence weakens over the short and medium term. The primary correlation modes dominating the transmission process and the major intermediary modes in the transmission process are clustered both in the short and long term.

  6. Invoking Thomas Kuhn: What Citation Analysis Reveals about Science Education

    Science.gov (United States)

    Loving, Cathleen C.; Cobern, William W.

    This paper analyzes how Thomas Kuhn's writings are used by others, especially science education researchers. Previous research in citation analysis is used to frame questions related to who cites Kuhn, in what manner and why. Research questions first focus on the variety of disciplines invoking Kuhn and to what extent Structure of Scientific Revolutions (SSR) is cited. The Web of Science database provides material from 1982 for this analysis. The science education literature is analyzed using back issues from 1985 of the Journal of Research in Science Teaching and Science Education. An article analysis reveals trends in terms of what Kuhnian ideas are most frequently invoked. Results indicate a wide array of disciplines from beekeeping to law cite Kuhn - especially generic citations to SSR. The science education journal analysis reveals pervasive use of the term paradigm, although use is quite varied. The two areas of research in science education most impacted by Kuhn appear to be conceptual change theory and constructivist epistemologies. Additional uses of Kuhn are discussed. The degree to which Kuhn is invoked in ways supporting the theoretical framework of citation analysis, whether his work is misappropriated, and the impact of Kuhn are discussed.

  7. Assessing the copula selection for bivariate frequency analysis ...

    Indian Academy of Sciences (India)

    58

    upper tail copulas (Frank, Clayton and Gaussian), if there exists asymptotic dependence in the. 24 flood characteristics. ... characteristics and Frank, Clayton and Gaussian copulas are the appropriate copula models in. 30 ..... The mean of daily discharge of Trian stream gauge from 1978 to 2013 is 527.4 m3/s and the. 181.

  8. Computational approach to Thornley's problem by bivariate operational calculus

    Science.gov (United States)

    Bazhlekova, E.; Dimovski, I.

    2012-10-01

    Thornley's problem is an initial-boundary value problem with a nonlocal boundary condition for linear onedimensional reaction-diffusion equation, used as a mathematical model of spiral phyllotaxis in botany. Applying a bivariate operational calculus we find explicit representation of the solution, containing two convolution products of special solutions and the arbitrary initial and boundary functions. We use a non-classical convolution with respect to the space variable, extending in this way the classical Duhamel principle. The special solutions involved are represented in the form of fast convergent series. Numerical examples are considered to show the application of the present technique and to analyze the character of the solution.

  9. Microbiota analysis to reveal temperature abuse of fresh pork

    DEFF Research Database (Denmark)

    Buschhardt, Tasja; Bahl, Martin Iain; Hansen, Tina Beck

    monitored during aerobic chill-storage (4 °C and 7 °C) and temperature abuse (12 °C and 16 °C) for 96 hours, by culture-based methods and 16S rRNA gene sequencing. Bacterial genera that dominated during prolonged temperature abuse were Acinetobacter, Serratia and Pseudomonas, whereas chill-stored meat...... was dominated by Pseudomonas only. We also showed that the initial community affects subsequent changes during storage. The results suggest that principal coordinate analysis of beta diversity could be a useful tool to reveal temperature abused meat. Sequence data and culturing data revealed a strong positive......Violations of temperature regulations in the meat chain may affect meat safety. Methods are lacking to estimate whether meat has been subjected to temperature abuse. Exposure to too high temperatures may lead to systematic changes in the diverse bacterial communities of fresh meat. We investigated...

  10. Microbiota analysis to reveal temperature abuse of fresh pork

    DEFF Research Database (Denmark)

    Buschhardt, Tasja; Bahl, Martin Iain; Hansen, Tina Beck

    2017-01-01

    Violations of temperature regulations in the meat chain may affect meat safety. Methods are lacking to estimate whether meat has been subjected to temperature abuse. Exposure to too high temperatures may lead to systematic changes in the diverse bacterial communities of fresh meat. We investigated...... monitored during aerobic chill-storage (4 °C and 7 °C) and temperature abuse (12 °C and 16 °C) for 96 hours, by culture-based methods and 16S rRNA gene sequencing. Bacterial genera that dominated during prolonged temperature abuse were Acinetobacter, Serratia and Pseudomonas, whereas chill-stored meat...... was dominated by Pseudomonas only. We also showed that the initial community affects subsequent changes during storage. The results suggest that principal coordinate analysis of beta diversity could be a useful tool to reveal temperature abused meat. Sequence data and culturing data revealed a strong positive...

  11. Bivariate generalized Pareto distribution for extreme atmospheric particulate matter

    Science.gov (United States)

    Amin, Nor Azrita Mohd; Adam, Mohd Bakri; Ibrahim, Noor Akma; Aris, Ahmad Zaharin

    2015-02-01

    The high particulate matter (PM10) level is the prominent issue causing various impacts to human health and seriously affecting the economics. The asymptotic theory of extreme value is apply for analyzing the relation of extreme PM10 data from two nearby air quality monitoring stations. The series of daily maxima PM10 for Johor Bahru and Pasir Gudang stations are consider for year 2001 to 2010 databases. The 85% and 95% marginal quantile apply to determine the threshold values and hence construct the series of exceedances over the chosen threshold. The logistic, asymmetric logistic, negative logistic and asymmetric negative logistic models areconsidered as the dependence function to the joint distribution of a bivariate observation. Maximum likelihood estimation is employed for parameter estimations. The best fitted model is chosen based on the Akaike Information Criterion and the quantile plots. It is found that the asymmetric logistic model gives the best fitted model for bivariate extreme PM10 data and shows the weak dependence between two stations.

  12. Bivariate spline solution of time dependent nonlinear PDE for a population density over irregular domains.

    Science.gov (United States)

    Gutierrez, Juan B; Lai, Ming-Jun; Slavov, George

    2015-12-01

    We study a time dependent partial differential equation (PDE) which arises from classic models in ecology involving logistic growth with Allee effect by introducing a discrete weak solution. Existence, uniqueness and stability of the discrete weak solutions are discussed. We use bivariate splines to approximate the discrete weak solution of the nonlinear PDE. A computational algorithm is designed to solve this PDE. A convergence analysis of the algorithm is presented. We present some simulations of population development over some irregular domains. Finally, we discuss applications in epidemiology and other ecological problems. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Efficient estimation of semiparametric copula models for bivariate survival data

    KAUST Repository

    Cheng, Guang

    2014-01-01

    A semiparametric copula model for bivariate survival data is characterized by a parametric copula model of dependence and nonparametric models of two marginal survival functions. Efficient estimation for the semiparametric copula model has been recently studied for the complete data case. When the survival data are censored, semiparametric efficient estimation has only been considered for some specific copula models such as the Gaussian copulas. In this paper, we obtain the semiparametric efficiency bound and efficient estimation for general semiparametric copula models for possibly censored data. We construct an approximate maximum likelihood estimator by approximating the log baseline hazard functions with spline functions. We show that our estimates of the copula dependence parameter and the survival functions are asymptotically normal and efficient. Simple consistent covariance estimators are also provided. Numerical results are used to illustrate the finite sample performance of the proposed estimators. © 2013 Elsevier Inc.

  14. Bell-Type Inequalities for Bivariate Maps on Orthomodular Lattices

    Science.gov (United States)

    Pykacz, Jarosław; Valášková, L'ubica; Nánásiová, Ol'ga

    2015-08-01

    Bell-type inequalities on orthomodular lattices, in which conjunctions of propositions are not modeled by meets but by maps for simultaneous measurements (-maps), are studied. It is shown, that the most simple of these inequalities, that involves only two propositions, is always satisfied, contrary to what happens in the case of traditional version of this inequality in which conjunctions of propositions are modeled by meets. Equivalence of various Bell-type inequalities formulated with the aid of bivariate maps on orthomodular lattices is studied. Our investigations shed new light on the interpretation of various multivariate maps defined on orthomodular lattices already studied in the literature. The paper is concluded by showing the possibility of using -maps and -maps to represent counterfactual conjunctions and disjunctions of non-compatible propositions about quantum systems.

  15. Selection effects in the bivariate brightness distribution for spiral galaxies

    International Nuclear Information System (INIS)

    Phillipps, S.; Disney, M.

    1986-01-01

    The joint distribution of total luminosity and characteristic surface brightness (the bivariate brightness distribution) is investigated for a complete sample of spiral galaxies in the Virgo cluster. The influence of selection and physical limits of various kinds on the apparent distribution are detailed. While the distribution of surface brightness for bright galaxies may be genuinely fairly narrow, faint galaxies exist right across the (quite small) range of accessible surface brightnesses so no statement can be made about the true extent of the distribution. The lack of high surface brightness bright galaxies in the Virgo sample relative to an overall RC2 sample (mostly field galaxies) supports the contention that the star-formation rate is reduced in the inner region of the cluster for environmental reasons. (author)

  16. Single cell transcriptional analysis reveals novel innate immune cell types

    Directory of Open Access Journals (Sweden)

    Linda E. Kippner

    2014-06-01

    Full Text Available Single-cell analysis has the potential to provide us with a host of new knowledge about biological systems, but it comes with the challenge of correctly interpreting the biological information. While emerging techniques have made it possible to measure inter-cellular variability at the transcriptome level, no consensus yet exists on the most appropriate method of data analysis of such single cell data. Methods for analysis of transcriptional data at the population level are well established but are not well suited to single cell analysis due to their dependence on population averages. In order to address this question, we have systematically tested combinations of methods for primary data analysis on single cell transcription data generated from two types of primary immune cells, neutrophils and T lymphocytes. Cells were obtained from healthy individuals, and single cell transcript expression data was obtained by a combination of single cell sorting and nanoscale quantitative real time PCR (qRT-PCR for markers of cell type, intracellular signaling, and immune functionality. Gene expression analysis was focused on hierarchical clustering to determine the existence of cellular subgroups within the populations. Nine combinations of criteria for data exclusion and normalization were tested and evaluated. Bimodality in gene expression indicated the presence of cellular subgroups which were also revealed by data clustering. We observed evidence for two clearly defined cellular subtypes in the neutrophil populations and at least two in the T lymphocyte populations. When normalizing the data by different methods, we observed varying outcomes with corresponding interpretations of the biological characteristics of the cell populations. Normalization of the data by linear standardization taking into account technical effects such as plate effects, resulted in interpretations that most closely matched biological expectations. Single cell transcription

  17. A non-stationary cost-benefit based bivariate extreme flood estimation approach

    Science.gov (United States)

    Qi, Wei; Liu, Junguo

    2018-02-01

    Cost-benefit analysis and flood frequency analysis have been integrated into a comprehensive framework to estimate cost effective design values. However, previous cost-benefit based extreme flood estimation is based on stationary assumptions and analyze dependent flood variables separately. A Non-Stationary Cost-Benefit based bivariate design flood estimation (NSCOBE) approach is developed in this study to investigate influence of non-stationarities in both the dependence of flood variables and the marginal distributions on extreme flood estimation. The dependence is modeled utilizing copula functions. Previous design flood selection criteria are not suitable for NSCOBE since they ignore time changing dependence of flood variables. Therefore, a risk calculation approach is proposed based on non-stationarities in both marginal probability distributions and copula functions. A case study with 54-year observed data is utilized to illustrate the application of NSCOBE. Results show NSCOBE can effectively integrate non-stationarities in both copula functions and marginal distributions into cost-benefit based design flood estimation. It is also found that there is a trade-off between maximum probability of exceedance calculated from copula functions and marginal distributions. This study for the first time provides a new approach towards a better understanding of influence of non-stationarities in both copula functions and marginal distributions on extreme flood estimation, and could be beneficial to cost-benefit based non-stationary bivariate design flood estimation across the world.

  18. An integrated user-friendly ArcMAP tool for bivariate statistical modeling in geoscience applications

    Science.gov (United States)

    Jebur, M. N.; Pradhan, B.; Shafri, H. Z. M.; Yusof, Z.; Tehrany, M. S.

    2014-10-01

    Modeling and classification difficulties are fundamental issues in natural hazard assessment. A geographic information system (GIS) is a domain that requires users to use various tools to perform different types of spatial modeling. Bivariate statistical analysis (BSA) assists in hazard modeling. To perform this analysis, several calculations are required and the user has to transfer data from one format to another. Most researchers perform these calculations manually by using Microsoft Excel or other programs. This process is time consuming and carries a degree of uncertainty. The lack of proper tools to implement BSA in a GIS environment prompted this study. In this paper, a user-friendly tool, BSM (bivariate statistical modeler), for BSA technique is proposed. Three popular BSA techniques such as frequency ratio, weights-of-evidence, and evidential belief function models are applied in the newly proposed ArcMAP tool. This tool is programmed in Python and is created by a simple graphical user interface, which facilitates the improvement of model performance. The proposed tool implements BSA automatically, thus allowing numerous variables to be examined. To validate the capability and accuracy of this program, a pilot test area in Malaysia is selected and all three models are tested by using the proposed program. Area under curve is used to measure the success rate and prediction rate. Results demonstrate that the proposed program executes BSA with reasonable accuracy. The proposed BSA tool can be used in numerous applications, such as natural hazard, mineral potential, hydrological, and other engineering and environmental applications.

  19. Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction.

    Science.gov (United States)

    Ikegami, Keisuke; Yoshimura, Takashi

    2016-02-01

    Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. A bivariate measurement error model for semicontinuous and continuous variables: Application to nutritional epidemiology.

    Science.gov (United States)

    Kipnis, Victor; Freedman, Laurence S; Carroll, Raymond J; Midthune, Douglas

    2016-03-01

    Semicontinuous data in the form of a mixture of a large portion of zero values and continuously distributed positive values frequently arise in many areas of biostatistics. This article is motivated by the analysis of relationships between disease outcomes and intakes of episodically consumed dietary components. An important aspect of studies in nutritional epidemiology is that true diet is unobservable and commonly evaluated by food frequency questionnaires with substantial measurement error. Following the regression calibration approach for measurement error correction, unknown individual intakes in the risk model are replaced by their conditional expectations given mismeasured intakes and other model covariates. Those regression calibration predictors are estimated using short-term unbiased reference measurements in a calibration substudy. Since dietary intakes are often "energy-adjusted," e.g., by using ratios of the intake of interest to total energy intake, the correct estimation of the regression calibration predictor for each energy-adjusted episodically consumed dietary component requires modeling short-term reference measurements of the component (a semicontinuous variable), and energy (a continuous variable) simultaneously in a bivariate model. In this article, we develop such a bivariate model, together with its application to regression calibration. We illustrate the new methodology using data from the NIH-AARP Diet and Health Study (Schatzkin et al., 2001, American Journal of Epidemiology 154, 1119-1125), and also evaluate its performance in a simulation study. © 2015, The International Biometric Society.

  1. Semiparametric probit models with univariate and bivariate current-status data.

    Science.gov (United States)

    Liu, Hao; Qin, Jing

    2018-03-01

    Multivariate current-status data are frequently encountered in biomedical and public health studies. Semiparametric regression models have been extensively studied for univariate current-status data, but most existing estimation procedures are computationally intensive, involving either penalization or smoothing techniques. It becomes more challenging for the analysis of multivariate current-status data. In this article, we study the maximum likelihood estimations for univariate and bivariate current-status data under the semiparametric probit regression models. We present a simple computational procedure combining the expectation-maximization algorithm with the pool-adjacent-violators algorithm for solving the monotone constraint on the baseline function. Asymptotic properties of the maximum likelihood estimators are investigated, including the calculation of the explicit information bound for univariate current-status data, as well as the asymptotic consistency and convergence rate for bivariate current-status data. Extensive simulation studies showed that the proposed computational procedures performed well under small or moderate sample sizes. We demonstrate the estimation procedure with two real data examples in the areas of diabetic and HIV research. © 2017, The International Biometric Society.

  2. A method of moments to estimate bivariate survival functions: the copula approach

    Directory of Open Access Journals (Sweden)

    Silvia Angela Osmetti

    2013-05-01

    Full Text Available In this paper we discuss the problem on parametric and non parametric estimation of the distributions generated by the Marshall-Olkin copula. This copula comes from the Marshall-Olkin bivariate exponential distribution used in reliability analysis. We generalize this model by the copula and different marginal distributions to construct several bivariate survival functions. The cumulative distribution functions are not absolutely continuous and they unknown parameters are often not be obtained in explicit form. In order to estimate the parameters we propose an easy procedure based on the moments. This method consist in two steps: in the first step we estimate only the parameters of marginal distributions and in the second step we estimate only the copula parameter. This procedure can be used to estimate the parameters of complex survival functions in which it is difficult to find an explicit expression of the mixed moments. Moreover it is preferred to the maximum likelihood one for its simplex mathematic form; in particular for distributions whose maximum likelihood parameters estimators can not be obtained in explicit form.

  3. Sequential analysis of the numerical Stroop effect reveals response suppression.

    Science.gov (United States)

    Cohen Kadosh, Roi; Gevers, Wim; Notebaert, Wim

    2011-09-01

    Automatic processing of irrelevant stimulus dimensions has been demonstrated in a variety of tasks. Previous studies have shown that conflict between relevant and irrelevant dimensions can be reduced when a feature of the irrelevant dimension is repeated. The specific level at which the automatic process is suppressed (e.g., perceptual repetition, response repetition), however, is less understood. In the current experiment we used the numerical Stroop paradigm, in which the processing of irrelevant numerical values of 2 digits interferes with the processing of their physical size, to pinpoint the precise level of the suppression. Using a sequential analysis, we dissociated perceptual repetition from response repetition of the relevant and irrelevant dimension. Our analyses of reaction times, error rates, and diffusion modeling revealed that the congruity effect is significantly reduced or even absent when the response sequence of the irrelevant dimension, rather than the numerical value or the physical size, is repeated. These results suggest that automatic activation of the irrelevant dimension is suppressed at the response level. The current results shed light on the level of interaction between numerical magnitude and physical size as well as the effect of variability of responses and stimuli on automatic processing. (c) 2011 APA, all rights reserved.

  4. A bivariate optimal replacement policy for a multistate repairable system

    International Nuclear Information System (INIS)

    Zhang Yuanlin; Yam, Richard C.M.; Zuo, Ming J.

    2007-01-01

    In this paper, a deteriorating simple repairable system with k+1 states, including k failure states and one working state, is studied. It is assumed that the system after repair is not 'as good as new' and the deterioration of the system is stochastic. We consider a bivariate replacement policy, denoted by (T,N), in which the system is replaced when its working age has reached T or the number of failures it has experienced has reached N, whichever occurs first. The objective is to determine the optimal replacement policy (T,N)* such that the long-run expected profit per unit time is maximized. The explicit expression of the long-run expected profit per unit time is derived and the corresponding optimal replacement policy can be determined analytically or numerically. We prove that the optimal policy (T,N)* is better than the optimal policy N* for a multistate simple repairable system. We also show that a general monotone process model for a multistate simple repairable system is equivalent to a geometric process model for a two-state simple repairable system in the sense that they have the same structure for the long-run expected profit (or cost) per unit time and the same optimal policy. Finally, a numerical example is given to illustrate the theoretical results

  5. Epileptic seizure prediction based on a bivariate spectral power methodology.

    Science.gov (United States)

    Bandarabadi, Mojtaba; Teixeira, Cesar A; Direito, Bruno; Dourado, Antonio

    2012-01-01

    The spectral power of 5 frequently considered frequency bands (Alpha, Beta, Gamma, Theta and Delta) for 6 EEG channels is computed and then all the possible pairwise combinations among the 30 features set, are used to create a 435 dimensional feature space. Two new feature selection methods are introduced to choose the best candidate features among those and to reduce the dimensionality of this feature space. The selected features are then fed to Support Vector Machines (SVMs) that classify the cerebral state in preictal and non-preictal classes. The outputs of the SVM are regularized using a method that accounts for the classification dynamics of the preictal class, also known as "Firing Power" method. The results obtained using our feature selection approaches are compared with the ones obtained using minimum Redundancy Maximum Relevance (mRMR) feature selection method. The results in a group of 12 patients of the EPILEPSIAE database, containing 46 seizures and 787 hours multichannel recording for out-of-sample data, indicate the efficiency of the bivariate approach as well as the two new feature selection methods. The best results presented sensitivity of 76.09% (35 of 46 seizures predicted) and a false prediction rate of 0.15(-1).

  6. Isotope analysis reveals foraging area dichotomy for atlantic leatherback turtles.

    Directory of Open Access Journals (Sweden)

    Stéphane Caut

    Full Text Available BACKGROUND: The leatherback turtle (Dermochelys coriacea has undergone a dramatic decline over the last 25 years, and this is believed to be primarily the result of mortality associated with fisheries bycatch followed by egg and nesting female harvest. Atlantic leatherback turtles undertake long migrations across ocean basins from subtropical and tropical nesting beaches to productive frontal areas. Migration between two nesting seasons can last 2 or 3 years, a time period termed the remigration interval (RI. Recent satellite transmitter data revealed that Atlantic leatherbacks follow two major dispersion patterns after nesting season, through the North Gulf Stream area or more eastward across the North Equatorial Current. However, information on the whole RI is lacking, precluding the accurate identification of feeding areas where conservation measures may need to be applied. METHODOLOGY/PRINCIPAL FINDINGS: Using stable isotopes as dietary tracers we determined the characteristics of feeding grounds of leatherback females nesting in French Guiana. During migration, 3-year RI females differed from 2-year RI females in their isotope values, implying differences in their choice of feeding habitats (offshore vs. more coastal and foraging latitude (North Atlantic vs. West African coasts, respectively. Egg-yolk and blood isotope values are correlated in nesting females, indicating that egg analysis is a useful tool for assessing isotope values in these turtles, including adults when not available. CONCLUSIONS/SIGNIFICANCE: Our results complement previous data on turtle movements during the first year following the nesting season, integrating the diet consumed during the year before nesting. We suggest that the French Guiana leatherback population segregates into two distinct isotopic groupings, and highlight the urgent need to determine the feeding habitats of the turtle in the Atlantic in order to protect this species from incidental take by

  7. Mitochondrial Genome Analysis Reveals Historical Lineages in Yellowstone Bison.

    Directory of Open Access Journals (Sweden)

    David Forgacs

    Full Text Available Yellowstone National Park is home to one of the only plains bison populations that have continuously existed on their present landscape since prehistoric times without evidence of domestic cattle introgression. Previous studies characterized the relatively high levels of nuclear genetic diversity in these bison, but little is known about their mitochondrial haplotype diversity. This study assessed mitochondrial genomes from 25 randomly selected Yellowstone bison and found 10 different mitochondrial haplotypes with a haplotype diversity of 0.78 (± 0.06. Spatial analysis of these mitochondrial DNA (mtDNA haplotypes did not detect geographic population subdivision (FST = -0.06, p = 0.76. However, we identified two independent and historically important lineages in Yellowstone bison by combining data from 65 bison (defined by 120 polymorphic sites from across North America representing a total of 30 different mitochondrial DNA haplotypes. Mitochondrial DNA haplotypes from one of the Yellowstone lineages represent descendants of the 22 indigenous bison remaining in central Yellowstone in 1902. The other mitochondrial DNA lineage represents descendants of the 18 females introduced from northern Montana in 1902 to supplement the indigenous bison population and develop a new breeding herd in the northern region of the park. Comparing modern and historical mitochondrial DNA diversity in Yellowstone bison helps uncover a historical context of park restoration efforts during the early 1900s, provides evidence against a hypothesized mitochondrial disease in bison, and reveals the signature of recent hybridization between American plains bison (Bison bison bison and Canadian wood bison (B. b. athabascae. Our study demonstrates how mitochondrial DNA can be applied to delineate the history of wildlife species and inform future conservation actions.

  8. Quantitative flux analysis reveals folate-dependent NADPH production

    Science.gov (United States)

    Fan, Jing; Ye, Jiangbin; Kamphorst, Jurre J.; Shlomi, Tomer; Thompson, Craig B.; Rabinowitz, Joshua D.

    2014-06-01

    ATP is the dominant energy source in animals for mechanical and electrical work (for example, muscle contraction or neuronal firing). For chemical work, there is an equally important role for NADPH, which powers redox defence and reductive biosynthesis. The most direct route to produce NADPH from glucose is the oxidative pentose phosphate pathway, with malic enzyme sometimes also important. Although the relative contribution of glycolysis and oxidative phosphorylation to ATP production has been extensively analysed, similar analysis of NADPH metabolism has been lacking. Here we demonstrate the ability to directly track, by liquid chromatography-mass spectrometry, the passage of deuterium from labelled substrates into NADPH, and combine this approach with carbon labelling and mathematical modelling to measure NADPH fluxes. In proliferating cells, the largest contributor to cytosolic NADPH is the oxidative pentose phosphate pathway. Surprisingly, a nearly comparable contribution comes from serine-driven one-carbon metabolism, in which oxidation of methylene tetrahydrofolate to 10-formyl-tetrahydrofolate is coupled to reduction of NADP+ to NADPH. Moreover, tracing of mitochondrial one-carbon metabolism revealed complete oxidation of 10-formyl-tetrahydrofolate to make NADPH. As folate metabolism has not previously been considered an NADPH producer, confirmation of its functional significance was undertaken through knockdown of methylenetetrahydrofolate dehydrogenase (MTHFD) genes. Depletion of either the cytosolic or mitochondrial MTHFD isozyme resulted in decreased cellular NADPH/NADP+ and reduced/oxidized glutathione ratios (GSH/GSSG) and increased cell sensitivity to oxidative stress. Thus, although the importance of folate metabolism for proliferating cells has been long recognized and attributed to its function of producing one-carbon units for nucleic acid synthesis, another crucial function of this pathway is generating reducing power.

  9. Inland dissolved salt chemistry: statistical evaluation of bivariate and ternary diagram models for surface and subsurface waters

    Directory of Open Access Journals (Sweden)

    Stephen T. THRELKELD

    2000-08-01

    Full Text Available We compared the use of ternary and bivariate diagrams to distinguish the effects of atmospheric precipitation, rock weathering, and evaporation on inland surface and subsurface water chemistry. The three processes could not be statistically differentiated using bivariate models even if large water bodies were evaluated separate from small water bodies. Atmospheric precipitation effects were identified using ternary diagrams in water with total dissolved salts (TDS 1000 mg l-1. A principal components analysis showed that the variability in the relative proportions of the major ions was related to atmospheric precipitation, weathering, and evaporation. About half of the variation in the distribution of inorganic ions was related to rock weathering. By considering most of the important inorganic ions, ternary diagrams are able to distinguish the contributions of atmospheric precipitation, rock weathering, and evaporation to inland water chemistry.

  10. An integrated user-friendly ArcMAP tool for bivariate statistical modelling in geoscience applications

    Science.gov (United States)

    Jebur, M. N.; Pradhan, B.; Shafri, H. Z. M.; Yusoff, Z. M.; Tehrany, M. S.

    2015-03-01

    Modelling and classification difficulties are fundamental issues in natural hazard assessment. A geographic information system (GIS) is a domain that requires users to use various tools to perform different types of spatial modelling. Bivariate statistical analysis (BSA) assists in hazard modelling. To perform this analysis, several calculations are required and the user has to transfer data from one format to another. Most researchers perform these calculations manually by using Microsoft Excel or other programs. This process is time-consuming and carries a degree of uncertainty. The lack of proper tools to implement BSA in a GIS environment prompted this study. In this paper, a user-friendly tool, bivariate statistical modeler (BSM), for BSA technique is proposed. Three popular BSA techniques, such as frequency ratio, weight-of-evidence (WoE), and evidential belief function (EBF) models, are applied in the newly proposed ArcMAP tool. This tool is programmed in Python and created by a simple graphical user interface (GUI), which facilitates the improvement of model performance. The proposed tool implements BSA automatically, thus allowing numerous variables to be examined. To validate the capability and accuracy of this program, a pilot test area in Malaysia is selected and all three models are tested by using the proposed program. Area under curve (AUC) is used to measure the success rate and prediction rate. Results demonstrate that the proposed program executes BSA with reasonable accuracy. The proposed BSA tool can be used in numerous applications, such as natural hazard, mineral potential, hydrological, and other engineering and environmental applications.

  11. Comparison of Model Reliabilities from Single-Step and Bivariate Blending Methods

    DEFF Research Database (Denmark)

    Taskinen, Matti; Mäntysaari, Esa; Lidauer, Martin

    2013-01-01

    the production trait evaluation of Nordic Red dairy cattle. Genotyped bulls with daughters are used as training animals, and genotyped bulls and producing cows as candidate animals. For simplicity, size of the data is chosen so that the full inverses of the mixed model equation coefficient matrices can......Model based reliabilities in genetic evaluation are compared between three methods: animal model BLUP, single-step BLUP, and bivariate blending after genomic BLUP. The original bivariate blending is revised in this work to better account animal models. The study data is extracted from...... be calculated. Model reliabilities by the single-step and the bivariate blending methods were higher than by animal model due to genomic information. Compared to the single-step method, the bivariate blending method reliability estimates were, in general, lower. Computationally bivariate blending method was...

  12. Bivariate return periods of temperature and precipitation explain a large fraction of European crop yields

    Directory of Open Access Journals (Sweden)

    J. Zscheischler

    2017-07-01

    Full Text Available Crops are vital for human society. Crop yields vary with climate and it is important to understand how climate and crop yields are linked to ensure future food security. Temperature and precipitation are among the key driving factors of crop yield variability. Previous studies have investigated mostly linear relationships between temperature and precipitation and crop yield variability. Other research has highlighted the adverse impacts of climate extremes, such as drought and heat waves, on crop yields. Impacts are, however, often non-linearly related to multivariate climate conditions. Here we derive bivariate return periods of climate conditions as indicators for climate variability along different temperature–precipitation gradients. We show that in Europe, linear models based on bivariate return periods of specific climate conditions explain on average significantly more crop yield variability (42 % than models relying directly on temperature and precipitation as predictors (36 %. Our results demonstrate that most often crop yields increase along a gradient from hot and dry to cold and wet conditions, with lower yields associated with hot and dry periods. The majority of crops are most sensitive to climate conditions in summer and to maximum temperatures. The use of bivariate return periods allows the integration of non-linear impacts into climate–crop yield analysis. This offers new avenues to study the link between climate and crop yield variability and suggests that they are possibly more strongly related than what is inferred from conventional linear models.

  13. Subfield profitability analysis reveals an economic case for cropland diversification

    Science.gov (United States)

    Brandes, E.; McNunn, G. S.; Schulte, L. A.; Bonner, I. J.; Muth, D. J.; Babcock, B. A.; Sharma, B.; Heaton, E. A.

    2016-01-01

    Public agencies and private enterprises increasingly desire to achieve ecosystem service outcomes in agricultural systems, but are limited by perceived conflicts between economic and ecosystem service goals and a lack of tools enabling effective operational management. Here we use Iowa—an agriculturally homogeneous state representative of the Maize Belt—to demonstrate an economic rationale for cropland diversification at the subfield scale. We used a novel computational framework that integrates disparate but publicly available data to map ˜3.3 million unique potential management polygons (9.3 Mha) and reveal subfield opportunities to increase overall field profitability. We analyzed subfield profitability for maize/soybean fields during 2010-2013—four of the most profitable years in recent history—and projected results for 2015. While cropland operating at a loss of US 250 ha-1 or more was negligible between 2010 and 2013 at 18 000-190 000 ha (<2% of row-crop land), the extent of highly unprofitable land increased to 2.5 Mha, or 27% of row-crop land, in the 2015 projection. Aggregation of these areas to the township level revealed ‘hotspots’ for potential management change in Western, Central, and Northeast Iowa. In these least profitable areas, incorporating conservation management that breaks even (e.g., planting low-input perennials), into low-yielding portions of fields could increase overall cropland profitability by 80%. This approach is applicable to the broader region and differs substantially from the status quo of ‘top-down’ land management for conservation by harnessing private interest to align profitability with the production of ecosystem services.

  14. A genetic analysis of segregation distortion revealed by molecular ...

    Indian Academy of Sciences (India)

    c Indian Academy of Sciences. RESEARCH NOTE. A genetic analysis of segregation ... 2College of Life Science, Northeast Forest University, Harbin 150040, People's Republic of China. [Cai J., Zhang X., Wang B., Yan M., Qi Y. and Kong L. ... elite agronomic traits (Zhang et al. 2011). However, there is still no report about ...

  15. Network analysis reveals multiscale controls on streamwater chemistry

    Science.gov (United States)

    Kevin J. McGuire; Christian E. Torgersen; Gene E. Likens; Donald C. Buso; Winsor H. Lowe; Scott W. Bailey

    2014-01-01

    By coupling synoptic data from a basin-wide assessment of streamwater chemistry with network-based geostatistical analysis, we show that spatial processes differentially affect biogeochemical condition and pattern across a headwater stream network. We analyzed a high-resolution dataset consisting of 664 water samples collected every 100 m throughout 32 tributaries in...

  16. Revealing the underlying drivers of disaster risk: a global analysis

    Science.gov (United States)

    Peduzzi, Pascal

    2017-04-01

    Disasters events are perfect examples of compound events. Disaster risk lies at the intersection of several independent components such as hazard, exposure and vulnerability. Understanding the weight of each component requires extensive standardisation. Here, I show how footprints of past disastrous events were generated using GIS modelling techniques and used for extracting population and economic exposures based on distribution models. Using past event losses, it was possible to identify and quantify a wide range of socio-politico-economic drivers associated with human vulnerability. The analysis was applied to about nine thousand individual past disastrous events covering earthquakes, floods and tropical cyclones. Using a multiple regression analysis on these individual events it was possible to quantify each risk component and assess how vulnerability is influenced by various hazard intensities. The results show that hazard intensity, exposure, poverty, governance as well as other underlying factors (e.g. remoteness) can explain the magnitude of past disasters. Analysis was also performed to highlight the role of future trends in population and climate change and how this may impacts exposure to tropical cyclones in the future. GIS models combined with statistical multiple regression analysis provided a powerful methodology to identify, quantify and model disaster risk taking into account its various components. The same methodology can be applied to various types of risk at local to global scale. This method was applied and developed for the Global Risk Analysis of the Global Assessment Report on Disaster Risk Reduction (GAR). It was first applied on mortality risk in GAR 2009 and GAR 2011. New models ranging from global assets exposure and global flood hazard models were also recently developed to improve the resolution of the risk analysis and applied through CAPRA software to provide probabilistic economic risk assessments such as Average Annual Losses (AAL

  17. Proteomics Analysis Reveals Previously Uncharacterized Virulence Factors in Vibrio proteolyticus.

    Science.gov (United States)

    Ray, Ann; Kinch, Lisa N; de Souza Santos, Marcela; Grishin, Nick V; Orth, Kim; Salomon, Dor

    2016-07-26

    Members of the genus Vibrio include many pathogens of humans and marine animals that share genetic information via horizontal gene transfer. Hence, the Vibrio pan-genome carries the potential to establish new pathogenic strains by sharing virulence determinants, many of which have yet to be characterized. Here, we investigated the virulence properties of Vibrio proteolyticus, a Gram-negative marine bacterium previously identified as part of the Vibrio consortium isolated from diseased corals. We found that V. proteolyticus causes actin cytoskeleton rearrangements followed by cell lysis in HeLa cells in a contact-independent manner. In search of the responsible virulence factor involved, we determined the V. proteolyticus secretome. This proteomics approach revealed various putative virulence factors, including active type VI secretion systems and effectors with virulence toxin domains; however, these type VI secretion systems were not responsible for the observed cytotoxic effects. Further examination of the V. proteolyticus secretome led us to hypothesize and subsequently demonstrate that a secreted hemolysin, belonging to a previously uncharacterized clan of the leukocidin superfamily, was the toxin responsible for the V. proteolyticus-mediated cytotoxicity in both HeLa cells and macrophages. Clearly, there remains an armory of yet-to-be-discovered virulence factors in the Vibrio pan-genome that will undoubtedly provide a wealth of knowledge on how a pathogen can manipulate host cells. The pan-genome of the genus Vibrio is a potential reservoir of unidentified toxins that can provide insight into how members of this genus have successfully risen as emerging pathogens worldwide. We focused on Vibrio proteolyticus, a marine bacterium that was previously implicated in virulence toward marine animals, and characterized its interaction with eukaryotic cells. We found that this bacterium causes actin cytoskeleton rearrangements and leads to cell death. Using a

  18. Sensitization trajectories in childhood revealed by using a cluster analysis

    DEFF Research Database (Denmark)

    Schoos, Ann-Marie M.; Chawes, Bo L.; Melen, Erik

    2017-01-01

    BACKGROUND: Assessment of sensitization at a single time point during childhood provides limited clinical information. We hypothesized that sensitization develops as specific patterns with respect to age at debut, development over time, and involved allergens and that such patterns might be more...... biologically and clinically relevant. OBJECTIVE: We sought to explore latent patterns of sensitization during the first 6 years of life and investigate whether such patterns associate with the development of asthma, rhinitis, and eczema. METHODS: We investigated 398 children from the at-risk Copenhagen...... Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) birth cohort with specific IgE against 13 common food and inhalant allergens at the ages of ½, 1½, 4, and 6 years. An unsupervised cluster analysis for 3-dimensional data (nonnegative sparse parallel factor analysis) was used to extract latent...

  19. Demographic analysis reveals gradual senescence in the flatworm Macrostomum lignano

    OpenAIRE

    Mouton, Stijn; Willems, Maxime; Back, Patricia; Braeckman, Bart; Borgonie, Gaetan

    2009-01-01

    Abstract Free-living flatworms ("Turbellaria") are appropriate model organisms to gain better insight into the role of stem cells in ageing and rejuvenation. Ageing research in flatworms is, however, still scarce. This is partly due to culture difficulties and the lack of a complete set of demographic data, including parameters such as median lifespan and age-specific mortality rate. In this paper, we report on the first flatworm survival analysis. We used the species Macrostomum lignano, whi...

  20. Proteomics Analysis Reveals Previously Uncharacterized Virulence Factors in Vibrio proteolyticus

    Directory of Open Access Journals (Sweden)

    Ann Ray

    2016-07-01

    Full Text Available Members of the genus Vibrio include many pathogens of humans and marine animals that share genetic information via horizontal gene transfer. Hence, the Vibrio pan-genome carries the potential to establish new pathogenic strains by sharing virulence determinants, many of which have yet to be characterized. Here, we investigated the virulence properties of Vibrio proteolyticus, a Gram-negative marine bacterium previously identified as part of the Vibrio consortium isolated from diseased corals. We found that V. proteolyticus causes actin cytoskeleton rearrangements followed by cell lysis in HeLa cells in a contact-independent manner. In search of the responsible virulence factor involved, we determined the V. proteolyticus secretome. This proteomics approach revealed various putative virulence factors, including active type VI secretion systems and effectors with virulence toxin domains; however, these type VI secretion systems were not responsible for the observed cytotoxic effects. Further examination of the V. proteolyticus secretome led us to hypothesize and subsequently demonstrate that a secreted hemolysin, belonging to a previously uncharacterized clan of the leukocidin superfamily, was the toxin responsible for the V. proteolyticus-mediated cytotoxicity in both HeLa cells and macrophages. Clearly, there remains an armory of yet-to-be-discovered virulence factors in the Vibrio pan-genome that will undoubtedly provide a wealth of knowledge on how a pathogen can manipulate host cells.

  1. Proteomic Analysis of Hylocereus polyrhizus Reveals Metabolic Pathway Changes.

    Science.gov (United States)

    Hua, Qingzhu; Zhou, Qianjun; Gan, Susheng; Wu, Jingyu; Chen, Canbin; Li, Jiaqiang; Ye, Yaoxiong; Zhao, Jietang; Hu, Guibing; Qin, Yonghua

    2016-09-28

    Red dragon fruit or red pitaya ( Hylocereus polyrhizus ) is the only edible fruit that contains betalains. The color of betalains ranges from red and violet to yellow in plants. Betalains may also serve as an important component of health-promoting and disease-preventing functional food. Currently, the biosynthetic and regulatory pathways for betalain production remain to be fully deciphered. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analyses were used to reveal the molecular mechanism of betalain biosynthesis in H. polyrhizus fruits at white and red pulp stages, respectively. A total of 1946 proteins were identified as the differentially expressed between the two samples, and 936 of them were significantly highly expressed at the red pulp stage of H. polyrhizus . RNA-seq and iTRAQ analyses showed that some transcripts and proteins were positively correlated; they belonged to "phenylpropanoid biosynthesis", "tyrosine metabolism", "flavonoid biosynthesis", "ascorbate and aldarate metabolism", "betalains biosynthesis" and "anthocyanin biosynthesis". In betalains biosynthesis pathway, several proteins/enzymes such as polyphenol oxidase, CYP76AD3 and 4,5-dihydroxy-phenylalanine (DOPA) dioxygenase extradiol-like protein were identified. The present study provides a new insight into the molecular mechanism of the betalain biosynthesis at the posttranscriptional level.

  2. Proteomic Analysis of Hylocereus polyrhizus Reveals Metabolic Pathway Changes

    Directory of Open Access Journals (Sweden)

    Qingzhu Hua

    2016-09-01

    Full Text Available Red dragon fruit or red pitaya (Hylocereus polyrhizus is the only edible fruit that contains betalains. The color of betalains ranges from red and violet to yellow in plants. Betalains may also serve as an important component of health-promoting and disease-preventing functional food. Currently, the biosynthetic and regulatory pathways for betalain production remain to be fully deciphered. In this study, isobaric tags for relative and absolute quantitation (iTRAQ-based proteomic analyses were used to reveal the molecular mechanism of betalain biosynthesis in H. polyrhizus fruits at white and red pulp stages, respectively. A total of 1946 proteins were identified as the differentially expressed between the two samples, and 936 of them were significantly highly expressed at the red pulp stage of H. polyrhizus. RNA-seq and iTRAQ analyses showed that some transcripts and proteins were positively correlated; they belonged to “phenylpropanoid biosynthesis”, “tyrosine metabolism”, “flavonoid biosynthesis”, “ascorbate and aldarate metabolism”, “betalains biosynthesis” and “anthocyanin biosynthesis”. In betalains biosynthesis pathway, several proteins/enzymes such as polyphenol oxidase, CYP76AD3 and 4,5-dihydroxy-phenylalanine (DOPA dioxygenase extradiol-like protein were identified. The present study provides a new insight into the molecular mechanism of the betalain biosynthesis at the posttranscriptional level.

  3. Transcriptome network analysis reveals potential candidate genes for ankylosing spondylitis.

    Science.gov (United States)

    Zhu, Z-Q; Tang, J-S; Cao, X-J

    2013-12-01

    Ankylosing spondylitis (AS) is a chronic, inflammatory arthritis and autoimmune disease. The main symptom of AS is inflammatory spinal pain; with time, some patients develop ankylosis and spinal immobility. We aim to find cure available for ankylosing spondylitis. We used the GSE11886 series to identify potential genes that related to AS to construct a regulation network. In the network, some of TFs and target genes have been proved related with AS in previous study, such as NFKB1, STAT1, STAT4, TNFSF10, IL2RA, and IL2RB. We also found some new TFs (Franscription Factors) and target genes response to AS, such as BXDC5, and EGFR. Further analysis indicated some significant pathways are associated with AS, including antigen processing and presentation and cytokine-cytokine receptor interaction, etc.; although not significant, there was evident that they play an important role in AS progression, such as apoptosis and systemic lupus erythematosus. Therefore, it is demonstrated that transcriptome network analysis is useful in identification of the candidate genes in AS.

  4. On the matched pairs sign test using bivariate ranked set sampling ...

    African Journals Online (AJOL)

    BVRSS) is introduced and investigated. We show that this test is asymptotically more efficient than its counterpart sign test based on a bivariate simple random sample (BVSRS). The asymptotic null distribution and the efficiency of the test are derived.

  5. Sensitization trajectories in childhood revealed by using a cluster analysis.

    Science.gov (United States)

    Schoos, Ann-Marie M; Chawes, Bo L; Melén, Erik; Bergström, Anna; Kull, Inger; Wickman, Magnus; Bønnelykke, Klaus; Bisgaard, Hans; Rasmussen, Morten A

    2017-12-01

    Assessment of sensitization at a single time point during childhood provides limited clinical information. We hypothesized that sensitization develops as specific patterns with respect to age at debut, development over time, and involved allergens and that such patterns might be more biologically and clinically relevant. We sought to explore latent patterns of sensitization during the first 6 years of life and investigate whether such patterns associate with the development of asthma, rhinitis, and eczema. We investigated 398 children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC 2000 ) birth cohort with specific IgE against 13 common food and inhalant allergens at the ages of ½, 1½, 4, and 6 years. An unsupervised cluster analysis for 3-dimensional data (nonnegative sparse parallel factor analysis) was used to extract latent patterns explicitly characterizing temporal development of sensitization while clustering allergens and children. Subsequently, these patterns were investigated in relation to asthma, rhinitis, and eczema. Verification was sought in an independent unselected birth cohort (BAMSE) constituting 3051 children with specific IgE against the same allergens at 4 and 8 years of age. The nonnegative sparse parallel factor analysis indicated a complex latent structure involving 7 age- and allergen-specific patterns in the COPSAC 2000 birth cohort data: (1) dog/cat/horse, (2) timothy grass/birch, (3) molds, (4) house dust mites, (5) peanut/wheat flour/mugwort, (6) peanut/soybean, and (7) egg/milk/wheat flour. Asthma was solely associated with pattern 1 (odds ratio [OR], 3.3; 95% CI, 1.5-7.2), rhinitis with patterns 1 to 4 and 6 (OR, 2.2-4.3), and eczema with patterns 1 to 3 and 5 to 7 (OR, 1.6-2.5). All 7 patterns were verified in the independent BAMSE cohort (R 2  > 0.89). This study suggests the presence of specific sensitization patterns in early childhood differentially associated with development of

  6. Genome analysis of the platypus reveals unique signatures of evolution.

    Science.gov (United States)

    Warren, Wesley C; Hillier, LaDeana W; Marshall Graves, Jennifer A; Birney, Ewan; Ponting, Chris P; Grützner, Frank; Belov, Katherine; Miller, Webb; Clarke, Laura; Chinwalla, Asif T; Yang, Shiaw-Pyng; Heger, Andreas; Locke, Devin P; Miethke, Pat; Waters, Paul D; Veyrunes, Frédéric; Fulton, Lucinda; Fulton, Bob; Graves, Tina; Wallis, John; Puente, Xose S; López-Otín, Carlos; Ordóñez, Gonzalo R; Eichler, Evan E; Chen, Lin; Cheng, Ze; Deakin, Janine E; Alsop, Amber; Thompson, Katherine; Kirby, Patrick; Papenfuss, Anthony T; Wakefield, Matthew J; Olender, Tsviya; Lancet, Doron; Huttley, Gavin A; Smit, Arian F A; Pask, Andrew; Temple-Smith, Peter; Batzer, Mark A; Walker, Jerilyn A; Konkel, Miriam K; Harris, Robert S; Whittington, Camilla M; Wong, Emily S W; Gemmell, Neil J; Buschiazzo, Emmanuel; Vargas Jentzsch, Iris M; Merkel, Angelika; Schmitz, Juergen; Zemann, Anja; Churakov, Gennady; Kriegs, Jan Ole; Brosius, Juergen; Murchison, Elizabeth P; Sachidanandam, Ravi; Smith, Carly; Hannon, Gregory J; Tsend-Ayush, Enkhjargal; McMillan, Daniel; Attenborough, Rosalind; Rens, Willem; Ferguson-Smith, Malcolm; Lefèvre, Christophe M; Sharp, Julie A; Nicholas, Kevin R; Ray, David A; Kube, Michael; Reinhardt, Richard; Pringle, Thomas H; Taylor, James; Jones, Russell C; Nixon, Brett; Dacheux, Jean-Louis; Niwa, Hitoshi; Sekita, Yoko; Huang, Xiaoqiu; Stark, Alexander; Kheradpour, Pouya; Kellis, Manolis; Flicek, Paul; Chen, Yuan; Webber, Caleb; Hardison, Ross; Nelson, Joanne; Hallsworth-Pepin, Kym; Delehaunty, Kim; Markovic, Chris; Minx, Pat; Feng, Yucheng; Kremitzki, Colin; Mitreva, Makedonka; Glasscock, Jarret; Wylie, Todd; Wohldmann, Patricia; Thiru, Prathapan; Nhan, Michael N; Pohl, Craig S; Smith, Scott M; Hou, Shunfeng; Nefedov, Mikhail; de Jong, Pieter J; Renfree, Marilyn B; Mardis, Elaine R; Wilson, Richard K

    2008-05-08

    We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation.

  7. Genome analysis of the platypus reveals unique signatures of evolution

    Science.gov (United States)

    Warren, Wesley C.; Hillier, LaDeana W.; Marshall Graves, Jennifer A.; Birney, Ewan; Ponting, Chris P.; Grützner, Frank; Belov, Katherine; Miller, Webb; Clarke, Laura; Chinwalla, Asif T.; Yang, Shiaw-Pyng; Heger, Andreas; Locke, Devin P.; Miethke, Pat; Waters, Paul D.; Veyrunes, Frédéric; Fulton, Lucinda; Fulton, Bob; Graves, Tina; Wallis, John; Puente, Xose S.; López-Otín, Carlos; Ordóñez, Gonzalo R.; Eichler, Evan E.; Chen, Lin; Cheng, Ze; Deakin, Janine E.; Alsop, Amber; Thompson, Katherine; Kirby, Patrick; Papenfuss, Anthony T.; Wakefield, Matthew J.; Olender, Tsviya; Lancet, Doron; Huttley, Gavin A.; Smit, Arian F. A.; Pask, Andrew; Temple-Smith, Peter; Batzer, Mark A.; Walker, Jerilyn A.; Konkel, Miriam K.; Harris, Robert S.; Whittington, Camilla M.; Wong, Emily S. W.; Gemmell, Neil J.; Buschiazzo, Emmanuel; Vargas Jentzsch, Iris M.; Merkel, Angelika; Schmitz, Juergen; Zemann, Anja; Churakov, Gennady; Kriegs, Jan Ole; Brosius, Juergen; Murchison, Elizabeth P.; Sachidanandam, Ravi; Smith, Carly; Hannon, Gregory J.; Tsend-Ayush, Enkhjargal; McMillan, Daniel; Attenborough, Rosalind; Rens, Willem; Ferguson-Smith, Malcolm; Lefèvre, Christophe M.; Sharp, Julie A.; Nicholas, Kevin R.; Ray, David A.; Kube, Michael; Reinhardt, Richard; Pringle, Thomas H.; Taylor, James; Jones, Russell C.; Nixon, Brett; Dacheux, Jean-Louis; Niwa, Hitoshi; Sekita, Yoko; Huang, Xiaoqiu; Stark, Alexander; Kheradpour, Pouya; Kellis, Manolis; Flicek, Paul; Chen, Yuan; Webber, Caleb; Hardison, Ross; Nelson, Joanne; Hallsworth-Pepin, Kym; Delehaunty, Kim; Markovic, Chris; Minx, Pat; Feng, Yucheng; Kremitzki, Colin; Mitreva, Makedonka; Glasscock, Jarret; Wylie, Todd; Wohldmann, Patricia; Thiru, Prathapan; Nhan, Michael N.; Pohl, Craig S.; Smith, Scott M.; Hou, Shunfeng; Renfree, Marilyn B.; Mardis, Elaine R.; Wilson, Richard K.

    2009-01-01

    We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation. PMID:18464734

  8. Changes in cod muscle proteins during frozen storage revealed by proteome analysis and multivariate data analysis

    DEFF Research Database (Denmark)

    Kjærsgård, Inger Vibeke Holst; Nørrelykke, M.R.; Jessen, Flemming

    2006-01-01

    Multivariate data analysis has been combined with proteomics to enhance the recovery of information from 2-DE of cod muscle proteins during different storage conditions. Proteins were extracted according to 11 different storage conditions and samples were resolved by 2-DE. Data generated by 2-DE...... was subjected to principal component analysis (PCA) and discriminant partial least squares regression (DPLSR). Applying PCA to 2-DE data revealed the samples to form groups according to frozen storage time, whereas differences due to different storage temperatures or chilled storage in modified atmosphere...... light chain 1, 2 and 3, triose-phosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, aldolase A and two ?-actin fragments, and a nuclease diphosphate kinase B fragment to change in concentration, during frozen storage. Application of proteomics, multivariate data analysis and MS/MS to analyse...

  9. Interpreting Bivariate Regression Coefficients: Going beyond the Average

    Science.gov (United States)

    Halcoussis, Dennis; Phillips, G. Michael

    2010-01-01

    Statistics, econometrics, investment analysis, and data analysis classes often review the calculation of several types of averages, including the arithmetic mean, geometric mean, harmonic mean, and various weighted averages. This note shows how each of these can be computed using a basic regression framework. By recognizing when a regression model…

  10. Network analysis reveals distinct clinical syndromes underlying acute mountain sickness.

    Directory of Open Access Journals (Sweden)

    David P Hall

    Full Text Available Acute mountain sickness (AMS is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS, we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25. These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes.

  11. Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression.

    Science.gov (United States)

    Fiziev, Petko; Akdemir, Kadir C; Miller, John P; Keung, Emily Z; Samant, Neha S; Sharma, Sneha; Natale, Christopher A; Terranova, Christopher J; Maitituoheti, Mayinuer; Amin, Samirkumar B; Martinez-Ledesma, Emmanuel; Dhamdhere, Mayura; Axelrad, Jacob B; Shah, Amiksha; Cheng, Christine S; Mahadeshwar, Harshad; Seth, Sahil; Barton, Michelle C; Protopopov, Alexei; Tsai, Kenneth Y; Davies, Michael A; Garcia, Benjamin A; Amit, Ido; Chin, Lynda; Ernst, Jason; Rai, Kunal

    2017-04-25

    The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways. Importantly, such acetylation changes were also observed between benign nevi and malignant melanoma human tissues. Intriguingly, only a small fraction of chromatin state transitions correlated with expected changes in gene expression patterns. Restoration of acetylation levels on deacetylated loci by histone deacetylase (HDAC) inhibitors selectively blocked excessive proliferation in tumorigenic cells and human melanoma cells, suggesting functional roles of observed chromatin state transitions in driving hyperproliferative phenotype. Through these results, we define functionally relevant chromatin states associated with melanoma progression. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Interspecific differences revealed with in Drosophila Photometric Analysis

    Directory of Open Access Journals (Sweden)

    Hoenigsberg H. F.

    1964-12-01

    Full Text Available The above refer to experiments present a new method which permits the study of philogenesis in the genus Drosophila. There are several types of results: a close kinship among the various geographical races of  D. melanogaster in the neo-tropics coincides with their spectrophotometric similarities; b the interspecific differences are also identified with the photometric analysis; c finally there are optical density affinities among the various species which belong to the same taxonomic groups.  Acknowledgment. The authors want to express their gratitude to Professor Everet of the physico-chemical laboratory of the National University for the use of his Beckman DU spectrophotometer and for his generous advice. This research is supported by the American Agricultural Research Service grant F. G. Co 107. For technical assistance we are indebted to Miss B. I. Cortés and to Mr. L. Castro.

  13. Network analysis reveals multiscale controls on streamwater chemistry

    Science.gov (United States)

    McGuire, Kevin J.; Torgersen, Christian E.; Likens, Gene E.; Buso, Donald C.; Lowe, Winsor H.; Bailey, Scott W.

    2014-01-01

    By coupling synoptic data from a basin-wide assessment of streamwater chemistry with network-based geostatistical analysis, we show that spatial processes differentially affect biogeochemical condition and pattern across a headwater stream network. We analyzed a high-resolution dataset consisting of 664 water samples collected every 100 m throughout 32 tributaries in an entire fifth-order stream network. These samples were analyzed for an exhaustive suite of chemical constituents. The fine grain and broad extent of this study design allowed us to quantify spatial patterns over a range of scales by using empirical semivariograms that explicitly incorporated network topology. Here, we show that spatial structure, as determined by the characteristic shape of the semivariograms, differed both among chemical constituents and by spatial relationship (flow-connected, flow-unconnected, or Euclidean). Spatial structure was apparent at either a single scale or at multiple nested scales, suggesting separate processes operating simultaneously within the stream network and surrounding terrestrial landscape. Expected patterns of spatial dependence for flow-connected relationships (e.g., increasing homogeneity with downstream distance) occurred for some chemical constituents (e.g., dissolved organic carbon, sulfate, and aluminum) but not for others (e.g., nitrate, sodium). By comparing semivariograms for the different chemical constituents and spatial relationships, we were able to separate effects on streamwater chemistry of (i) fine-scale versus broad-scale processes and (ii) in-stream processes versus landscape controls. These findings provide insight on the hierarchical scaling of local, longitudinal, and landscape processes that drive biogeochemical patterns in stream networks.

  14. Demographic analysis reveals gradual senescence in the flatworm Macrostomum lignano

    Directory of Open Access Journals (Sweden)

    Braeckman Bart P

    2009-07-01

    Full Text Available Abstract Free-living flatworms ("Turbellaria" are appropriate model organisms to gain better insight into the role of stem cells in ageing and rejuvenation. Ageing research in flatworms is, however, still scarce. This is partly due to culture difficulties and the lack of a complete set of demographic data, including parameters such as median lifespan and age-specific mortality rate. In this paper, we report on the first flatworm survival analysis. We used the species Macrostomum lignano, which is an emerging model for studying the reciprocal influence between stem cells, ageing and rejuvenation. This species has a median lifespan of 205 ± 13 days (average ± standard deviation [SD] and a 90th percentile lifespan of 373 ± 32 days. The maximum lifespan, however, is more than 745 days, and the average survival curve is characterised by a long tail because a small number of individuals lives twice as long as 90% of the population. Similar to earlier observations in a wide range of animals, in M. lignano the age-specific mortality rate increases exponentially, but levels off at the oldest ages. To compare the senescence of M. lignano with that of other ageing models, we determined the mortality rate doubling time, which is 0.20 ± 0.02 years. As a result, we can conclude that M. lignano shows gradual senescence at a rate similar to the vertebrate ageing models Rattus norvegicus and Mus musculus. We argue that M. lignano is a suitable model for ageing and rejuvenation research, and especially for the role of stem cells in these processes, due to its accessible stem cell system and regeneration capacity, and the possibility of combining stem cell studies with demographic analyses.

  15. Demographic analysis reveals gradual senescence in the flatworm Macrostomum lignano.

    Science.gov (United States)

    Mouton, Stijn; Willems, Maxime; Back, Patricia; Braeckman, Bart P; Borgonie, Gaetan

    2009-07-30

    Free-living flatworms ("Turbellaria") are appropriate model organisms to gain better insight into the role of stem cells in ageing and rejuvenation. Ageing research in flatworms is, however, still scarce. This is partly due to culture difficulties and the lack of a complete set of demographic data, including parameters such as median lifespan and age-specific mortality rate. In this paper, we report on the first flatworm survival analysis. We used the species Macrostomum lignano, which is an emerging model for studying the reciprocal influence between stem cells, ageing and rejuvenation. This species has a median lifespan of 205 +/- 13 days (average +/- standard deviation [SD]) and a 90th percentile lifespan of 373 +/- 32 days. The maximum lifespan, however, is more than 745 days, and the average survival curve is characterised by a long tail because a small number of individuals lives twice as long as 90% of the population. Similar to earlier observations in a wide range of animals, in M. lignano the age-specific mortality rate increases exponentially, but levels off at the oldest ages. To compare the senescence of M. lignano with that of other ageing models, we determined the mortality rate doubling time, which is 0.20 +/- 0.02 years. As a result, we can conclude that M. lignano shows gradual senescence at a rate similar to the vertebrate ageing models Rattus norvegicus and Mus musculus. We argue that M. lignano is a suitable model for ageing and rejuvenation research, and especially for the role of stem cells in these processes, due to its accessible stem cell system and regeneration capacity, and the possibility of combining stem cell studies with demographic analyses.

  16. Classification of Knee Joint Vibration Signals Using Bivariate Feature Distribution Estimation and Maximal Posterior Probability Decision Criterion

    Directory of Open Access Journals (Sweden)

    Fang Zheng

    2013-04-01

    Full Text Available Analysis of knee joint vibration or vibroarthrographic (VAG signals using signal processing and machine learning algorithms possesses high potential for the noninvasive detection of articular cartilage degeneration, which may reduce unnecessary exploratory surgery. Feature representation of knee joint VAG signals helps characterize the pathological condition of degenerative articular cartilages in the knee. This paper used the kernel-based probability density estimation method to model the distributions of the VAG signals recorded from healthy subjects and patients with knee joint disorders. The estimated densities of the VAG signals showed explicit distributions of the normal and abnormal signal groups, along with the corresponding contours in the bivariate feature space. The signal classifications were performed by using the Fisher’s linear discriminant analysis, support vector machine with polynomial kernels, and the maximal posterior probability decision criterion. The maximal posterior probability decision criterion was able to provide the total classification accuracy of 86.67% and the area (Az of 0.9096 under the receiver operating characteristics curve, which were superior to the results obtained by either the Fisher’s linear discriminant analysis (accuracy: 81.33%, Az: 0.8564 or the support vector machine with polynomial kernels (accuracy: 81.33%, Az: 0.8533. Such results demonstrated the merits of the bivariate feature distribution estimation and the superiority of the maximal posterior probability decision criterion for analysis of knee joint VAG signals.

  17. Perceived social support and academic achievement: cross-lagged panel and bivariate growth curve analyses.

    Science.gov (United States)

    Mackinnon, Sean P

    2012-04-01

    As students transition to post-secondary education, they experience considerable stress and declines in academic performance. Perceived social support is thought to improve academic achievement by reducing stress. Longitudinal designs with three or more waves are needed in this area because they permit stronger causal inferences and help disentangle the direction of relationships. This study uses a cross-lagged panel and a bivariate growth curve analysis with a three-wave longitudinal design. Participants include 10,445 students (56% female; 12.6% born outside of Canada) transitioning to post-secondary education from ages 15-19. Self-report measures of academic achievement and a generalized measure of perceived social support were used. An increase in average relative standing in academic achievement predicted an increase in average relative standing on perceived social support 2 years later, but the reverse was not true. High levels of perceived social support at age 15 did not protect against declines in academic achievement over time. In sum, perceived social support appears to have no bearing on adolescents' future academic performance, despite commonly held assumptions of its importance.

  18. Bivariate empirical mode decomposition for ECG-based biometric identification with emotional data.

    Science.gov (United States)

    Ferdinando, Hany; Seppanen, Tapio; Alasaarela, Esko

    2017-07-01

    Emotions modulate ECG signals such that they might affect ECG-based biometric identification in real life application. It motivated in finding good feature extraction methods where the emotional state of the subjects has minimum impacts. This paper evaluates feature extraction based on bivariate empirical mode decomposition (BEMD) for biometric identification when emotion is considered. Using the ECG signal from the Mahnob-HCI database for affect recognition, the features were statistical distributions of dominant frequency after applying BEMD analysis to ECG signals. The achieved accuracy was 99.5% with high consistency using kNN classifier in 10-fold cross validation to identify 26 subjects when the emotional states of the subjects were ignored. When the emotional states of the subject were considered, the proposed method also delivered high accuracy, around 99.4%. We concluded that the proposed method offers emotion-independent features for ECG-based biometric identification. The proposed method needs more evaluation related to testing with other classifier and variation in ECG signals, e.g. normal ECG vs. ECG with arrhythmias, ECG from various ages, and ECG from other affective databases.

  19. A note on finding peakedness in bivariate normal distribution using Mathematica

    Directory of Open Access Journals (Sweden)

    Anwer Khurshid

    2007-07-01

    Full Text Available Peakedness measures the concentration around the central value. A classical standard measure of peakedness is kurtosis which is the degree of peakedness of a probability distribution. In view of inconsistency of kurtosis in measuring of the peakedness of a distribution, Horn (1983 proposed a measure of peakedness for symmetrically unimodal distributions. The objective of this paper is two-fold. First, Horn’s method has been extended for bivariate normal distribution. Secondly, to show that computer algebra system Mathematica can be extremely useful tool for all sorts of computation related to bivariate normal distribution. Mathematica programs are also provided.

  20. Causal networks clarify productivity-richness interrelations, bivariate plots do not

    Science.gov (United States)

    Grace, James B.; Adler, Peter B.; Harpole, W. Stanley; Borer, Elizabeth T.; Seabloom, Eric W.

    2014-01-01

    Perhaps no other pair of variables in ecology has generated as much discussion as species richness and ecosystem productivity, as illustrated by the reactions by Pierce (2013) and others to Adler et al.'s (2011) report that empirical patterns are weak and inconsistent. Adler et al. (2011) argued we need to move beyond a focus on simplistic bivariate relationships and test mechanistic, multivariate causal hypotheses. We feel the continuing debate over productivity–richness relationships (PRRs) provides a focused context for illustrating the fundamental difficulties of using bivariate relationships to gain scientific understanding.

  1. New Colors for Histology: Optimized Bivariate Color Maps Increase Perceptual Contrast in Histological Images.

    Directory of Open Access Journals (Sweden)

    Jakob Nikolas Kather

    Full Text Available Accurate evaluation of immunostained histological images is required for reproducible research in many different areas and forms the basis of many clinical decisions. The quality and efficiency of histopathological evaluation is limited by the information content of a histological image, which is primarily encoded as perceivable contrast differences between objects in the image. However, the colors of chromogen and counterstain used for histological samples are not always optimally distinguishable, even under optimal conditions.In this study, we present a method to extract the bivariate color map inherent in a given histological image and to retrospectively optimize this color map. We use a novel, unsupervised approach based on color deconvolution and principal component analysis to show that the commonly used blue and brown color hues in Hematoxylin-3,3'-Diaminobenzidine (DAB images are poorly suited for human observers. We then demonstrate that it is possible to construct improved color maps according to objective criteria and that these color maps can be used to digitally re-stain histological images.To validate whether this procedure improves distinguishability of objects and background in histological images, we re-stain phantom images and N = 596 large histological images of immunostained samples of human solid tumors. We show that perceptual contrast is improved by a factor of 2.56 in phantom images and up to a factor of 2.17 in sets of histological tumor images.Thus, we provide an objective and reliable approach to measure object distinguishability in a given histological image and to maximize visual information available to a human observer. This method could easily be incorporated in digital pathology image viewing systems to improve accuracy and efficiency in research and diagnostics.

  2. New Colors for Histology: Optimized Bivariate Color Maps Increase Perceptual Contrast in Histological Images.

    Science.gov (United States)

    Kather, Jakob Nikolas; Weis, Cleo-Aron; Marx, Alexander; Schuster, Alexander K; Schad, Lothar R; Zöllner, Frank Gerrit

    2015-01-01

    Accurate evaluation of immunostained histological images is required for reproducible research in many different areas and forms the basis of many clinical decisions. The quality and efficiency of histopathological evaluation is limited by the information content of a histological image, which is primarily encoded as perceivable contrast differences between objects in the image. However, the colors of chromogen and counterstain used for histological samples are not always optimally distinguishable, even under optimal conditions. In this study, we present a method to extract the bivariate color map inherent in a given histological image and to retrospectively optimize this color map. We use a novel, unsupervised approach based on color deconvolution and principal component analysis to show that the commonly used blue and brown color hues in Hematoxylin-3,3'-Diaminobenzidine (DAB) images are poorly suited for human observers. We then demonstrate that it is possible to construct improved color maps according to objective criteria and that these color maps can be used to digitally re-stain histological images. To validate whether this procedure improves distinguishability of objects and background in histological images, we re-stain phantom images and N = 596 large histological images of immunostained samples of human solid tumors. We show that perceptual contrast is improved by a factor of 2.56 in phantom images and up to a factor of 2.17 in sets of histological tumor images. Thus, we provide an objective and reliable approach to measure object distinguishability in a given histological image and to maximize visual information available to a human observer. This method could easily be incorporated in digital pathology image viewing systems to improve accuracy and efficiency in research and diagnostics.

  3. Parameter estimation and statistical test of geographically weighted bivariate Poisson inverse Gaussian regression models

    Science.gov (United States)

    Amalia, Junita; Purhadi, Otok, Bambang Widjanarko

    2017-11-01

    Poisson distribution is a discrete distribution with count data as the random variables and it has one parameter defines both mean and variance. Poisson regression assumes mean and variance should be same (equidispersion). Nonetheless, some case of the count data unsatisfied this assumption because variance exceeds mean (over-dispersion). The ignorance of over-dispersion causes underestimates in standard error. Furthermore, it causes incorrect decision in the statistical test. Previously, paired count data has a correlation and it has bivariate Poisson distribution. If there is over-dispersion, modeling paired count data is not sufficient with simple bivariate Poisson regression. Bivariate Poisson Inverse Gaussian Regression (BPIGR) model is mix Poisson regression for modeling paired count data within over-dispersion. BPIGR model produces a global model for all locations. In another hand, each location has different geographic conditions, social, cultural and economic so that Geographically Weighted Regression (GWR) is needed. The weighting function of each location in GWR generates a different local model. Geographically Weighted Bivariate Poisson Inverse Gaussian Regression (GWBPIGR) model is used to solve over-dispersion and to generate local models. Parameter estimation of GWBPIGR model obtained by Maximum Likelihood Estimation (MLE) method. Meanwhile, hypothesis testing of GWBPIGR model acquired by Maximum Likelihood Ratio Test (MLRT) method.

  4. The Effects of Selection Strategies for Bivariate Loglinear Smoothing Models on NEAT Equating Functions

    Science.gov (United States)

    Moses, Tim; Holland, Paul W.

    2010-01-01

    In this study, eight statistical strategies were evaluated for selecting the parameterizations of loglinear models for smoothing the bivariate test score distributions used in nonequivalent groups with anchor test (NEAT) equating. Four of the strategies were based on significance tests of chi-square statistics (Likelihood Ratio, Pearson,…

  5. First-order dominance: stronger characterization and a bivariate checking algorithm

    DEFF Research Database (Denmark)

    Range, Troels Martin; Østerdal, Lars Peter Raahave

    2018-01-01

    distributions. Utilizing that this problem can be formulated as a transportation problem with a special structure, we provide a stronger characterization of multivariate first-order dominance and develop a linear time complexity checking algorithm for the bivariate case. We illustrate the use of the checking...

  6. On the Construction of Bivariate Exponential Distributions with an Arbitrary Correlation Coefficient

    DEFF Research Database (Denmark)

    Bladt, Mogens; Nielsen, Bo Friis

    2010-01-01

    In this article we use the concept of multivariate phase-type distributions to define a class of bivariate exponential distributions. This class has the following three appealing properties. Firstly, we may construct a pair of exponentially distributed random variables with any feasible correlation...

  7. Semi-automated detection of aberrant chromosomes in bivariate flow karyotypes

    NARCIS (Netherlands)

    Boschman, G. A.; Manders, E. M.; Rens, W.; Slater, R.; Aten, J. A.

    1992-01-01

    A method is described that is designed to compare, in a standardized procedure, bivariate flow karyotypes of Hoechst 33258 (HO)/Chromomycin A3 (CA) stained human chromosomes from cells with aberrations with a reference flow karyotype of normal chromosomes. In addition to uniform normalization of

  8. A simple approximation to the bivariate normal distribution with large correlation coefficient

    NARCIS (Netherlands)

    Albers, Willem/Wim; Kallenberg, W.C.M.

    1994-01-01

    The bivariate normal distribution function is approximated with emphasis on situations where the correlation coefficient is large. The high accuracy of the approximation is illustrated by numerical examples. Moreover, exact upper and lower bounds are presented as well as asymptotic results on the

  9. Glycoproteomic analysis of seven major allergenic proteins reveals novel post-translational modifications

    DEFF Research Database (Denmark)

    Halim, Adnan; Carlsson, Michael C; Mathiesen, Caroline Benedicte K

    2015-01-01

    characterization by bottom-up analysis. In addition, top-down mass spectrometry is utilized for targeted analysis of individual proteins, revealing hitherto unknown PTMs of HDM allergens. We demonstrate the presence of lysine-linked polyhexose glycans and asparagine-linked N-acetylhexosamine glycans on HDM...

  10. A bivariate model for analyzing recurrent multi-type automobile failures

    Science.gov (United States)

    Sunethra, A. A.; Sooriyarachchi, M. R.

    2017-09-01

    The failure mechanism in an automobile can be defined as a system of multi-type recurrent failures where failures can occur due to various multi-type failure modes and these failures are repetitive such that more than one failure can occur from each failure mode. In analysing such automobile failures, both the time and type of the failure serve as response variables. However, these two response variables are highly correlated with each other since the timing of failures has an association with the mode of the failure. When there are more than one correlated response variables, the fitting of a multivariate model is more preferable than separate univariate models. Therefore, a bivariate model of time and type of failure becomes appealing for such automobile failure data. When there are multiple failure observations pertaining to a single automobile, such data cannot be treated as independent data because failure instances of a single automobile are correlated with each other while failures among different automobiles can be treated as independent. Therefore, this study proposes a bivariate model consisting time and type of failure as responses adjusted for correlated data. The proposed model was formulated following the approaches of shared parameter models and random effects models for joining the responses and for representing the correlated data respectively. The proposed model is applied to a sample of automobile failures with three types of failure modes and up to five failure recurrences. The parametric distributions that were suitable for the two responses of time to failure and type of failure were Weibull distribution and multinomial distribution respectively. The proposed bivariate model was programmed in SAS Procedure Proc NLMIXED by user programming appropriate likelihood functions. The performance of the bivariate model was compared with separate univariate models fitted for the two responses and it was identified that better performance is secured by

  11. Transcriptome analysis reveals key differentially expressed genes involved in wheat grain development

    Directory of Open Access Journals (Sweden)

    Yonglong Yu

    2016-04-01

    Full Text Available Wheat seed development is an important physiological process of seed maturation and directly affects wheat yield and quality. In this study, we performed dynamic transcriptome microarray analysis of an elite Chinese bread wheat cultivar (Jimai 20 during grain development using the GeneChip Wheat Genome Array. Grain morphology and scanning electron microscope observations showed that the period of 11–15 days post-anthesis (DPA was a key stage for the synthesis and accumulation of seed starch. Genome-wide transcriptional profiling and significance analysis of microarrays revealed that the period from 11 to 15 DPA was more important than the 15–20 DPA stage for the synthesis and accumulation of nutritive reserves. Series test of cluster analysis of differential genes revealed five statistically significant gene expression profiles. Gene ontology annotation and enrichment analysis gave further information about differentially expressed genes, and MapMan analysis revealed expression changes within functional groups during seed development. Metabolic pathway network analysis showed that major and minor metabolic pathways regulate one another to ensure regular seed development and nutritive reserve accumulation. We performed gene co-expression network analysis to identify genes that play vital roles in seed development and identified several key genes involved in important metabolic pathways. The transcriptional expression of eight key genes involved in starch and protein synthesis and stress defense was further validated by qRT-PCR. Our results provide new insight into the molecular mechanisms of wheat seed development and the determinants of yield and quality.

  12. Bivariate functional data clustering: grouping streams based on a varying coefficient model of the stream water and air temperature relationship

    Science.gov (United States)

    H. Li; X. Deng; Andy Dolloff; E. P. Smith

    2015-01-01

    A novel clustering method for bivariate functional data is proposed to group streams based on their water–air temperature relationship. A distance measure is developed for bivariate curves by using a time-varying coefficient model and a weighting scheme. This distance is also adjusted by spatial correlation of streams via the variogram. Therefore, the proposed...

  13. Proteomic analysis of three gonad types of swamp eel reveals genes differentially expressed during sex reversal

    OpenAIRE

    Yue Sheng; Wei Zhao; Ying Song; Zhigang Li; Majing Luo; Quan Lei; Hanhua Cheng; Rongjia Zhou

    2015-01-01

    A variety of mechanisms are engaged in sex determination in vertebrates. The teleost fish swamp eel undergoes sex reversal naturally and is an ideal model for vertebrate sexual development. However, the importance of proteome-wide scanning for gonad reversal was not previously determined. We report a 2-D electrophoresis analysis of three gonad types of proteomes during sex reversal. MS/MS analysis revealed a group of differentially expressed proteins during ovary to ovotestis to testis transf...

  14. Bivariate Developmental Relations between Calculations and Word Problems: A Latent Change Approach.

    Science.gov (United States)

    Gilbert, Jennifer K; Fuchs, Lynn S

    2017-10-01

    The relation between 2 forms of mathematical cognition, calculations and word problems, was examined. Across grades 2-3, performance of 328 children (mean starting age 7.63 [ SD =0.43]) was assessed 3 times. Comparison of a priori latent change score models indicated a dual change model, with consistently positive but slowing growth, described development in each domain better than a constant or proportional change model. The bivariate model including change models for both calculations and word problems indicated prior calculation performance and change were not predictors of subsequent word-problem change, and prior word-problem performance and change were not predictors of subsequent calculation change. Results were comparable for boys versus girls. The bivariate model, along with correlations among intercepts and slopes, suggest calculation and word-problem development are related, but through an external set of overlapping factors. Exploratory supplemental analyses corroborate findings and provide direction for future study.

  15. Using risk analysis to reveal opportunities for the management of unplanned ignitions in wilderness

    Science.gov (United States)

    Kevin Barnett; Carol Miller; Tyron J. Venn

    2016-01-01

    A goal of fire management in wilderness is to allow fire to play its natural ecological role without intervention. Unfortunately, most unplanned ignitions in wilderness are suppressed, in part because of the risk they might pose to values outside of the wilderness. We capitalize on recent advances in fire risk analysis to demonstrate a risk-based approach for revealing...

  16. Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit

    Science.gov (United States)

    Ashoori, Maryam; Burns, Catherine M.; d'Entremont, Barbara; Momtahan, Kathryn

    2014-01-01

    Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamworkand leverage the existing CWA approaches to analyse team interactions. Team CWA is explained and contrasted with prior approaches to CWA. Team CWA does not replace CWA, but supplements traditional CWA to more easily reveal team information. As a result, Team CWA may be a useful approach to enhance CWA in complex environments where effective teamwork is required. Practitioner Summary: This paper looks at ways of analysing cognitive work in healthcare teams. Team Cognitive Work Analysis, when used to supplement traditional Cognitive Work Analysis, revealed more team information than traditional Cognitive Work Analysis. Team Cognitive Work Analysis should be considered when studying teams PMID:24837514

  17. Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit.

    Science.gov (United States)

    Ashoori, Maryam; Burns, Catherine M; d'Entremont, Barbara; Momtahan, Kathryn

    2014-01-01

    Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamwork and leverage the existing CWA approaches to analyse team interactions. Team CWA is explained and contrasted with prior approaches to CWA. Team CWA does not replace CWA, but supplements traditional CWA to more easily reveal team information. As a result, Team CWA may be a useful approach to enhance CWA in complex environments where effective teamwork is required. This paper looks at ways of analysing cognitive work in healthcare teams. Team Cognitive Work Analysis, when used to supplement traditional Cognitive Work Analysis, revealed more team information than traditional Cognitive Work Analysis. Team Cognitive Work Analysis should be considered when studying teams.

  18. Can the bivariate Hurst exponent be higher than an average of the separate Hurst exponents?

    Czech Academy of Sciences Publication Activity Database

    Krištoufek, Ladislav

    2015-01-01

    Roč. 431, č. 1 (2015), s. 124-127 ISSN 0378-4371 R&D Projects: GA ČR(CZ) GP14-11402P Institutional support: RVO:67985556 Keywords : Correlations * Power- law cross-correlations * Bivariate Hurst exponent * Spectrum coherence Subject RIV: AH - Economics Impact factor: 1.785, year: 2015 http://library.utia.cas.cz/separaty/2015/E/kristoufek-0452314.pdf

  19. The approximation of bivariate Chlodowsky-Sz?sz-Kantorovich-Charlier-type operators

    OpenAIRE

    Agrawal, Purshottam Narain; Baxhaku, Behar; Chauhan, Ruchi

    2017-01-01

    Abstract In this paper, we introduce a bivariate Kantorovich variant of combination of Szász and Chlodowsky operators based on Charlier polynomials. Then, we study local approximation properties for these operators. Also, we estimate the approximation order in terms of Peetre’s K-functional and partial moduli of continuity. Furthermore, we introduce the associated GBS-case (Generalized Boolean Sum) of these operators and study the degree of approximation by means of the Lipschitz class of Bög...

  20. On minimum divergence adaptation of discrete bivariate distributions to given marginals

    Czech Academy of Sciences Publication Activity Database

    Vajda, Igor; van der Meulen, E. C.

    2005-01-01

    Roč. 51, č. 1 (2005), s. 313-320 ISSN 0018-9448 R&D Projects: GA ČR GA201/02/1391; GA MŠk 1M0572 Institutional research plan: CEZ:AV0Z10750506 Keywords : approximation of contingency tables * bivariate discrete distributions * minimization of divergences Subject RIV: BD - Theory of Information Impact factor: 2.183, year: 2005

  1. Robust bivariate error detection in skewed data with application to historical radiosonde winds

    KAUST Repository

    Sun, Ying

    2017-01-18

    The global historical radiosonde archives date back to the 1920s and contain the only directly observed measurements of temperature, wind, and moisture in the upper atmosphere, but they contain many random errors. Most of the focus on cleaning these large datasets has been on temperatures, but winds are important inputs to climate models and in studies of wind climatology. The bivariate distribution of the wind vector does not have elliptical contours but is skewed and heavy-tailed, so we develop two methods for outlier detection based on the bivariate skew-t (BST) distribution, using either distance-based or contour-based approaches to flag observations as potential outliers. We develop a framework to robustly estimate the parameters of the BST and then show how the tuning parameter to get these estimates is chosen. In simulation, we compare our methods with one based on a bivariate normal distribution and a nonparametric approach based on the bagplot. We then apply all four methods to the winds observed for over 35,000 radiosonde launches at a single station and demonstrate differences in the number of observations flagged across eight pressure levels and through time. In this pilot study, the method based on the BST contours performs very well.

  2. EXPLORATORY DATA ANALYSIS AND MULTIVARIATE STRATEGIES FOR REVEALING MULTIVARIATE STRUCTURES IN CLIMATE DATA

    Directory of Open Access Journals (Sweden)

    2016-12-01

    Full Text Available This paper is on data analysis strategy in a complex, multidimensional, and dynamic domain. The focus is on the use of data mining techniques to explore the importance of multivariate structures; using climate variables which influences climate change. Techniques involved in data mining exercise vary according to the data structures. The multivariate analysis strategy considered here involved choosing an appropriate tool to analyze a process. Factor analysis is introduced into data mining technique in order to reveal the influencing impacts of factors involved as well as solving for multicolinearity effect among the variables. The temporal nature and multidimensionality of the target variables is revealed in the model using multidimensional regression estimates. The strategy of integrating the method of several statistical techniques, using climate variables in Nigeria was employed. R2 of 0.518 was obtained from the ordinary least square regression analysis carried out and the test was not significant at 5% level of significance. However, factor analysis regression strategy gave a good fit with R2 of 0.811 and the test was significant at 5% level of significance. Based on this study, model building should go beyond the usual confirmatory data analysis (CDA, rather it should be complemented with exploratory data analysis (EDA in order to achieve a desired result.

  3. Maximum Entropy-Copula Method for Hydrological Risk Analysis under Uncertainty: A Case Study on the Loess Plateau, China

    Directory of Open Access Journals (Sweden)

    Aijun Guo

    2017-11-01

    Full Text Available Copula functions have been extensively used to describe the joint behaviors of extreme hydrological events and to analyze hydrological risk. Advanced marginal distribution inference, for example, the maximum entropy theory, is particularly beneficial for improving the performance of the copulas. The goal of this paper, therefore, is twofold; first, to develop a coupled maximum entropy-copula method for hydrological risk analysis through deriving the bivariate return periods, risk, reliability and bivariate design events; and second, to reveal the impact of marginal distribution selection uncertainty and sampling uncertainty on bivariate design event identification. Particularly, the uncertainties involved in the second goal have not yet received significant consideration. The designed framework for hydrological risk analysis related to flood and extreme precipitation events is exemplarily applied in two catchments of the Loess plateau, China. Results show that (1 distribution derived by the maximum entropy principle outperforms the conventional distributions for the probabilistic modeling of flood and extreme precipitation events; (2 the bivariate return periods, risk, reliability and bivariate design events are able to be derived using the coupled entropy-copula method; (3 uncertainty analysis highlights the fact that appropriate performance of marginal distribution is closely related to bivariate design event identification. Most importantly, sampling uncertainty causes the confidence regions of bivariate design events with return periods of 30 years to be very large, overlapping with the values of flood and extreme precipitation, which have return periods of 10 and 50 years, respectively. The large confidence regions of bivariate design events greatly challenge its application in practical engineering design.

  4. Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells.

    Science.gov (United States)

    Roellig, Daniela; Tan-Cabugao, Johanna; Esaian, Sevan; Bronner, Marianne E

    2017-03-29

    The 'neural plate border' of vertebrate embryos contains precursors of neural crest and placode cells, both defining vertebrate characteristics. How these lineages segregate from neural and epidermal fates has been a matter of debate. We address this by performing a fine-scale quantitative temporal analysis of transcription factor expression in the neural plate border of chick embryos. The results reveal significant overlap of transcription factors characteristic of multiple lineages in individual border cells from gastrula through neurula stages. Cell fate analysis using a Sox2 (neural) enhancer reveals that cells that are initially Sox2+ cells can contribute not only to neural tube but also to neural crest and epidermis. Moreover, modulating levels of Sox2 or Pax7 alters the apportionment of neural tube versus neural crest fates. Our results resolve a long-standing question and suggest that many individual border cells maintain ability to contribute to multiple ectodermal lineages until or beyond neural tube closure.

  5. Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi.

    Science.gov (United States)

    Zhao, Zhongtao; Liu, Huiquan; Wang, Chenfang; Xu, Jin-Rong

    2013-04-23

    Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 103 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed. Importantly, cellulases of some GH families are present in fungi that are not known to have cellulose-degrading ability. In addition, our results also showed that in general, plant pathogenic fungi have the highest number of CAZymes. Biotrophic fungi tend to have fewer CAZymes than necrotrophic and hemibiotrophic fungi. Pathogens of dicots often contain more pectinases than fungi infecting monocots. Interestingly, besides yeasts, many saprophytic fungi that are highly active in degrading plant biomass contain fewer CAZymes than plant pathogenic fungi. Furthermore, analysis of the gene expression profile of the wheat scab fungus Fusarium graminearum revealed that most of the CAZyme genes related to cell wall degradation were up-regulated during plant infection. Phylogenetic analysis also revealed a complex

  6. Enlarging the collective model of household behaviour: a revealed preference analysis

    OpenAIRE

    d'Aspremont-Lynden, Claude; Dos Santos Ferreira, Rodolphe

    2017-01-01

    We use a comprehensive model of strategic household behaviour in which the spouses' expenditure on each public good is decomposed into autonomous spending and coordinated spending à la Lindahl. We obtain a continuum of semi-cooperative regimes parameterized by the relative weights put on autonomous spending, by each spouse and for each public good, nesting full cooperative and non-cooperative regimes as limit cases. Testing is approached through revealed preference analysis, by looking for ra...

  7. Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi

    Science.gov (United States)

    2013-01-01

    Background Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. Results In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 103 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed. Importantly, cellulases of some GH families are present in fungi that are not known to have cellulose-degrading ability. In addition, our results also showed that in general, plant pathogenic fungi have the highest number of CAZymes. Biotrophic fungi tend to have fewer CAZymes than necrotrophic and hemibiotrophic fungi. Pathogens of dicots often contain more pectinases than fungi infecting monocots. Interestingly, besides yeasts, many saprophytic fungi that are highly active in degrading plant biomass contain fewer CAZymes than plant pathogenic fungi. Furthermore, analysis of the gene expression profile of the wheat scab fungus Fusarium graminearum revealed that most of the CAZyme genes related to cell wall degradation were up-regulated during plant infection. Phylogenetic analysis also

  8. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways

    OpenAIRE

    M?ller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. ...

  9. Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids

    Directory of Open Access Journals (Sweden)

    Caroline H. Johnson

    2017-10-01

    Full Text Available Abstract Background Cancer cells that enter the metastatic cascade require traits that allow them to survive within the circulation and colonize distant organ sites. As disseminating cancer cells adapt to their changing microenvironments, they also modify their metabolism and metabolite production. Methods A mouse xenograft model of spontaneous tumor metastasis was used to determine the metabolic rewiring that occurs between primary cancers and their metastases. An “autonomous” mass spectrometry-based untargeted metabolomic workflow with integrative metabolic pathway analysis revealed a number of differentially regulated metabolites in primary mammary fat pad (MFP tumors compared to microdissected paired lung metastases. The study was further extended to analyze metabolites in paired normal tissues which determined the potential influence of metabolites from the microenvironment. Results Metabolomic analysis revealed that multiple metabolites were increased in metastases, including cholesterol sulfate and phospholipids (phosphatidylglycerols and phosphatidylethanolamine. Metabolite analysis of normal lung tissue in the mouse model also revealed increased levels of these metabolites compared to tissues from normal MFP and primary MFP tumors, indicating potential extracellular uptake by cancer cells in lung metastases. These results indicate a potential functional importance of cholesterol sulfate and phospholipids in propagating metastasis. In addition, metabolites involved in DNA/RNA synthesis and the TCA cycle were decreased in lung metastases compared to primary MFP tumors. Conclusions Using an integrated metabolomic workflow, this study identified a link between cholesterol sulfate and phospholipids, metabolic characteristics of the metastatic niche, and the capacity of tumor cells to colonize distant sites.

  10. Eigen-analysis reveals components supporting super-resolution imaging of blinking fluorophores.

    Science.gov (United States)

    Agarwal, Krishna; Prasad, Dilip K

    2017-06-30

    This paper presents eigen-analysis of image stack of blinking fluorophores to identify the components that enable super-resolved imaging of blinking fluorophores. Eigen-analysis reveals that the contributions of spatial distribution of fluorophores and their temporal photon emission characteristics can be completely separated. While cross-emitter cross-pixel information of spatial distribution that permits super-resolution is encoded in two matrices, temporal statistics weigh the contribution of these matrices to the measured data. The properties and conditions of exploitation of these matrices are investigated. Con-temporary super-resolution imaging methods that use blinking for super-resolution are studied in the context of the presented analysis. Besides providing insight into the capabilities and limitations of existing super-resolution methods, the analysis shall help in designing better super-resolution techniques that directly exploit these matrices.

  11. A COMPARISON OF SOME ROBUST BIVARIATE CONTROL CHARTS FOR INDIVIDUAL OBSERVATIONS

    Directory of Open Access Journals (Sweden)

    Moustafa Omar Ahmed Abu - Shawiesh

    2014-06-01

    Full Text Available This paper proposed and considered some bivariate control charts to monitor individual observations from a statistical process control. Usual control charts which use mean and variance-covariance estimators are sensitive to outliers. We consider the following robust alternatives to the classical Hoteling's T2: T2MedMAD, T2MCD, T2MVE a simulation study has been conducted to compare the performance of these control charts. Two real life data are analyzed to illustrate the application of these robust alternatives.

  12. The approximation of bivariate Chlodowsky-Szász-Kantorovich-Charlier-type operators

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    Purshottam Narain Agrawal

    2017-08-01

    Full Text Available Abstract In this paper, we introduce a bivariate Kantorovich variant of combination of Szász and Chlodowsky operators based on Charlier polynomials. Then, we study local approximation properties for these operators. Also, we estimate the approximation order in terms of Peetre’s K-functional and partial moduli of continuity. Furthermore, we introduce the associated GBS-case (Generalized Boolean Sum of these operators and study the degree of approximation by means of the Lipschitz class of Bögel continuous functions. Finally, we present some graphical examples to illustrate the rate of convergence of the operators under consideration.

  13. On the construction of bivariate exponential distributions with an arbitrary correlation coefficient

    DEFF Research Database (Denmark)

    Bladt, Mogens; Nielsen, Bo Friis

    coefficient (also negative). Secondly, the class satisfies that any linear combination (projection) of the marginal random variables is a phase {type distributions, The latter property is potentially important for the development hypothesis testing in linear models. Thirdly, it is very easy to simulate......In this paper we use a concept of multivariate phase-type distributions to define a class of bivariate exponential distributions. This class has the following three appealing properties. Firstly, we may construct a pair of exponentially distributed random variables with any feasible correlation...

  14. The approximation of bivariate Chlodowsky-Szász-Kantorovich-Charlier-type operators.

    Science.gov (United States)

    Agrawal, Purshottam Narain; Baxhaku, Behar; Chauhan, Ruchi

    2017-01-01

    In this paper, we introduce a bivariate Kantorovich variant of combination of Szász and Chlodowsky operators based on Charlier polynomials. Then, we study local approximation properties for these operators. Also, we estimate the approximation order in terms of Peetre's K-functional and partial moduli of continuity. Furthermore, we introduce the associated GBS-case (Generalized Boolean Sum) of these operators and study the degree of approximation by means of the Lipschitz class of Bögel continuous functions. Finally, we present some graphical examples to illustrate the rate of convergence of the operators under consideration.

  15. An efficient algorithm for generating random number pairs drawn from a bivariate normal distribution

    Science.gov (United States)

    Campbell, C. W.

    1983-01-01

    An efficient algorithm for generating random number pairs from a bivariate normal distribution was developed. Any desired value of the two means, two standard deviations, and correlation coefficient can be selected. Theoretically the technique is exact and in practice its accuracy is limited only by the quality of the uniform distribution random number generator, inaccuracies in computer function evaluation, and arithmetic. A FORTRAN routine was written to check the algorithm and good accuracy was obtained. Some small errors in the correlation coefficient were observed to vary in a surprisingly regular manner. A simple model was developed which explained the qualities aspects of the errors.

  16. Meta-analysis of small RNA-sequencing errors reveals ubiquitous post-transcriptional RNA modifications.

    Science.gov (United States)

    Ebhardt, H Alexander; Tsang, Herbert H; Dai, Denny C; Liu, Yifeng; Bostan, Babak; Fahlman, Richard P

    2009-05-01

    Recent advances in DNA-sequencing technology have made it possible to obtain large datasets of small RNA sequences. Here we demonstrate that not all non-perfectly matched small RNA sequences are simple technological sequencing errors, but many hold valuable biological information. Analysis of three small RNA datasets originating from Oryza sativa and Arabidopsis thaliana small RNA-sequencing projects demonstrates that many single nucleotide substitution errors overlap when aligning homologous non-identical small RNA sequences. Investigating the sites and identities of substitution errors reveal that many potentially originate as a result of post-transcriptional modifications or RNA editing. Modifications include N1-methyl modified purine nucleotides in tRNA, potential deamination or base substitutions in micro RNAs, 3' micro RNA uridine extensions and 5' micro RNA deletions. Additionally, further analysis of large sequencing datasets reveal that the combined effects of 5' deletions and 3' uridine extensions can alter the specificity by which micro RNAs associate with different Argonaute proteins. Hence, we demonstrate that not all sequencing errors in small RNA datasets are technical artifacts, but that these actually often reveal valuable biological insights to the sites of post-transcriptional RNA modifications.

  17. Bivariate tensor product [Formula: see text]-analogue of Kantorovich-type Bernstein-Stancu-Schurer operators.

    Science.gov (United States)

    Cai, Qing-Bo; Xu, Xiao-Wei; Zhou, Guorong

    2017-01-01

    In this paper, we construct a bivariate tensor product generalization of Kantorovich-type Bernstein-Stancu-Schurer operators based on the concept of [Formula: see text]-integers. We obtain moments and central moments of these operators, give the rate of convergence by using the complete modulus of continuity for the bivariate case and estimate a convergence theorem for the Lipschitz continuous functions. We also give some graphs and numerical examples to illustrate the convergence properties of these operators to certain functions.

  18. Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death.

    Directory of Open Access Journals (Sweden)

    Marie-Noëlle Delyfer

    Full Text Available BACKGROUND: Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome. METHODOLOGY/PRINCIPAL FINDINGS: Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here. CONCLUSIONS/SIGNIFICANCE: This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery.

  19. The Revealed Competitiveness of Major Ports in the East Asian Region: An Additive Market Share Analysis

    Directory of Open Access Journals (Sweden)

    Tae Seung Kim

    2015-12-01

    Full Text Available In the single cargo market, the ordinary market share analysis method has been the representative tool for revealed competitiveness analysis. This paper develops and employs an applied market share index called the additive market share (AMS. Data are collected from 15 major container ports for the 1998-2013 period. In comparison to the results of an ordinary market share analysis, the highest AMS is observed for the Bohai Rim port cluster from 2008, not for the Yangtze River cluster or the Pearl River cluster. There are substitutable relationships between Yangtze River and non-Chinese ports and between Pearl River and Bohai Rim ports from 2001. Finally, there is an internal competition at Pearl River and Yangtze River ports, whereas Bohai Rim and non-Chinese ports show internally complementary relationships.

  20. Network analysis of oyster transcriptome revealed a cascade of cellular responses during recovery after heat shock.

    Directory of Open Access Journals (Sweden)

    Lingling Zhang

    Full Text Available Oysters, as a major group of marine bivalves, can tolerate a wide range of natural and anthropogenic stressors including heat stress. Recent studies have shown that oysters pretreated with heat shock can result in induced heat tolerance. A systematic study of cellular recovery from heat shock may provide insights into the mechanism of acquired thermal tolerance. In this study, we performed the first network analysis of oyster transcriptome by reanalyzing microarray data from a previous study. Network analysis revealed a cascade of cellular responses during oyster recovery after heat shock and identified responsive gene modules and key genes. Our study demonstrates the power of network analysis in a non-model organism with poor gene annotations, which can lead to new discoveries that go beyond the focus on individual genes.

  1. Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells

    DEFF Research Database (Denmark)

    Larsen, Sara C; Sylvestersen, Kathrine B; Mund, Andreas

    2016-01-01

    The posttranslational modification of proteins by arginine methylation is functionally important, yet the breadth of this modification is not well characterized. Using high-resolution mass spectrometry, we identified 8030 arginine methylation sites within 3300 human proteins in human embryonic...... kidney 293 cells, indicating that the occurrence of this modification is comparable to phosphorylation and ubiquitylation. A site-level conservation analysis revealed that arginine methylation sites are less evolutionarily conserved compared to arginines that were not identified as modified...... as coactivator-associated arginine methyltransferase 1 (CARM1)] or PRMT1 increased the RNA binding function of HNRNPUL1. High-content single-cell imaging additionally revealed that knocking down CARM1 promoted the nuclear accumulation of SRSF2, independent of cell cycle phase. Collectively, the presented human...

  2. Proteomic and genomic analysis reveals novel Campylobacter jejuni outer membrane proteins and potential heterogeneity

    Directory of Open Access Journals (Sweden)

    Eleanor Watson

    2014-09-01

    Full Text Available Gram-negative bacterial outer membrane proteins play important roles in the interaction of bacteria with their environment including nutrient acquisition, adhesion and invasion, and antibiotic resistance. In this study we identified 47 proteins within the Sarkosyl-insoluble fraction of Campylobacter jejuni 81-176, using LC–ESI-MS/MS. Comparative analysis of outer membrane protein sequences was visualised to reveal protein distribution within a panel of Campylobacter spp., identifying several C. jejuni-specific proteins. Smith–Waterman analyses of C. jejuni homologues revealed high sequence conservation amongst a number of hypothetical proteins, sequence heterogeneity of other proteins and several proteins which are absent in a proportion of strains.

  3. A bivariate space-time downscaler under space and time misalignment.

    Science.gov (United States)

    Berrocal, Veronica J; Gelfand, Alan E; Holland, David M

    2010-12-01

    Ozone and particulate matter PM(2.5) are co-pollutants that have long been associated with increased public health risks. Information on concentration levels for both pollutants come from two sources: monitoring sites and output from complex numerical models that produce concentration surfaces over large spatial regions. In this paper, we offer a fully-model based approach for fusing these two sources of information for the pair of co-pollutants which is computationally feasible over large spatial regions and long periods of time. Due to the association between concentration levels of the two environmental contaminants, it is expected that information regarding one will help to improve prediction of the other. Misalignment is an obvious issue since the monitoring networks for the two contaminants only partly intersect and because the collection rate for PM(2.5) is typically less frequent than that for ozone.Extending previous work in Berrocal et al. (2009), we introduce a bivariate downscaler that provides a flexible class of bivariate space-time assimilation models. We discuss computational issues for model fitting and analyze a dataset for ozone and PM(2.5) for the ozone season during year 2002. We show a modest improvement in predictive performance, not surprising in a setting where we can anticipate only a small gain.

  4. Probabilistic modeling using bivariate normal distributions for identification of flow and displacement intervals in longwall overburden

    Energy Technology Data Exchange (ETDEWEB)

    Karacan, C.O.; Goodman, G.V.R. [NIOSH, Pittsburgh, PA (United States). Off Mine Safety & Health Research

    2011-01-15

    Gob gas ventholes (GGV) are used to control methane emissions in longwall mines by capturing it within the overlying fractured strata before it enters the work environment. In order for GGVs to effectively capture more methane and less mine air, the length of the slotted sections and their proximity to top of the coal bed should be designed based on the potential gas sources and their locations, as well as the displacements in the overburden that will create potential flow paths for the gas. In this paper, an approach to determine the conditional probabilities of depth-displacement, depth-flow percentage, depth-formation and depth-gas content of the formations was developed using bivariate normal distributions. The flow percentage, displacement and formation data as a function of distance from coal bed used in this study were obtained from a series of borehole experiments contracted by the former US Bureau of Mines as part of a research project. Each of these parameters was tested for normality and was modeled using bivariate normal distributions to determine all tail probabilities. In addition, the probability of coal bed gas content as a function of depth was determined using the same techniques. The tail probabilities at various depths were used to calculate conditional probabilities for each of the parameters. The conditional probabilities predicted for various values of the critical parameters can be used with the measurements of flow and methane percentage at gob gas ventholes to optimize their performance.

  5. Xp21 contiguous gene syndromes: Deletion quantitation with bivariate flow karyotyping allows mapping of patient breakpoints

    Energy Technology Data Exchange (ETDEWEB)

    McCabe, E.R.B.; Towbin, J.A. (Baylor College of Medicine, Houston, TX (United States)); Engh, G. van den; Trask, B.J. (Lawrence Livermore National Lab., CA (United States))

    1992-12-01

    Bivariate flow karyotyping was used to estimate the deletion sizes for a series of patients with Xp21 contiguous gene syndromes. The deletion estimates were used to develop an approximate scale for the genomic map in Xp21. The bivariate flow karyotype results were compared with clinical and molecular genetic information on the extent of the patients' deletions, and these various types of data were consistent. The resulting map spans >15 Mb, from the telomeric interval between DXS41 (99-6) and DXS68 (1-4) to a position centromeric to the ornithine transcarbamylase locus. The deletion sizing was considered to be accurate to [plus minus]1 Mb. The map provides information on the relative localization of genes and markers within this region. For example, the map suggests that the adrenal hypoplasia congenita and glycerol kinase genes are physically close to each other, are within 1-2 Mb of the telomeric end of the Duchenne muscular dystrophy (DMD) gene, and are nearer to the DMD locus than to the more distal marker DXS28 (C7). Information of this type is useful in developing genomic strategies for positional cloning in Xp21. These investigations demonstrate that the DNA from patients with Xp21 contiguous gene syndromes can be valuable reagents, not only for ordering loci and markers but also for providing an approximate scale to the map of the Xp21 region surrounding DMD. 44 refs., 3 figs.

  6. Bivariate pointing movements on large touch screens: investigating the validity of a refined Fitts' Law.

    Science.gov (United States)

    Bützler, Jennifer; Vetter, Sebastian; Jochems, Nicole; Schlick, Christopher M

    2012-01-01

    On the basis of three empirical studies Fitts' Law was refined for bivariate pointing tasks on large touch screens. In the first study different target width parameters were investigated. The second study considered the effect of the motion angle. Based on the results of the two studies a refined model for movement time in human-computer interaction was formulated. A third study, which is described here in detail, concerns the validation of the refined model. For the validation study 20 subjects had to execute a bivariate pointing task on a large touch screen. In the experimental task 250 rectangular target objects were displayed at a randomly chosen position on the screen covering a broad range of ID values (ID= [1.01; 4.88]). Compared to existing refinements of Fitts' Law, the new model shows highest predictive validity. A promising field of application of the model is the ergonomic design and evaluation of project management software. By using the refined model, software designers can calculate a priori the appropriate angular position and the size of buttons, menus or icons.

  7. Phylogenomic Analysis Reveals Extensive Phylogenetic Mosaicism in the Human GPCR Superfamily

    Directory of Open Access Journals (Sweden)

    Mathew Woodwark

    2007-01-01

    Full Text Available A novel high throughput phylogenomic analysis (HTP was applied to the rhodopsin G-protein coupled receptor (GPCR family. Instances of phylogenetic mosaicism between receptors were found to be frequent, often as instances of correlated mosaicism and repeated mosaicism. A null data set was constructed with the same phylogenetic topology as the rhodopsin GPCRs. Comparison of the two data sets revealed that mosaicism was found in GPCRs in a higher frequency than would be expected by homoplasy or the effects of topology alone. Various evolutionary models of differential conservation, recombination and homoplasy are explored which could result in the patterns observed in this analysis. We find that the results are most consistent with frequent recombination events. A complex evolutionary history is illustrated in which it is likely frequent recombination has endowed GPCRs with new functions. The pattern of mosaicism is shown to be informative for functional prediction for orphan receptors. HTP analysis is complementary to conventional phylogenomic analyses revealing mosaicism that would not otherwise have been detectable through conventional phylogenetics.

  8. Multilocus sequence analysis of nectar pseudomonads reveals high genetic diversity and contrasting recombination patterns.

    Science.gov (United States)

    Alvarez-Pérez, Sergio; de Vega, Clara; Herrera, Carlos M

    2013-01-01

    The genetic and evolutionary relationships among floral nectar-dwelling Pseudomonas 'sensu stricto' isolates associated to South African and Mediterranean plants were investigated by multilocus sequence analysis (MLSA) of four core housekeeping genes (rrs, gyrB, rpoB and rpoD). A total of 35 different sequence types were found for the 38 nectar bacterial isolates characterised. Phylogenetic analyses resulted in the identification of three main clades [nectar groups (NGs) 1, 2 and 3] of nectar pseudomonads, which were closely related to five intrageneric groups: Pseudomonas oryzihabitans (NG 1); P. fluorescens, P. lutea and P. syringae (NG 2); and P. rhizosphaerae (NG 3). Linkage disequilibrium analysis pointed to a mostly clonal population structure, even when the analysis was restricted to isolates from the same floristic region or belonging to the same NG. Nevertheless, signatures of recombination were observed for NG 3, which exclusively included isolates retrieved from the floral nectar of insect-pollinated Mediterranean plants. In contrast, the other two NGs comprised both South African and Mediterranean isolates. Analyses relating diversification to floristic region and pollinator type revealed that there has been more unique evolution of the nectar pseudomonads within the Mediterranean region than would be expected by chance. This is the first work analysing the sequence of multiple loci to reveal geno- and ecotypes of nectar bacteria.

  9. High-speed image analysis reveals chaotic vibratory behaviors of pathological vocal folds

    International Nuclear Information System (INIS)

    Zhang Yu; Shao Jun; Krausert, Christopher R.; Zhang Sai; Jiang, Jack J.

    2011-01-01

    Research highlights: → Low-dimensional human glottal area data. → Evidence of chaos in human laryngeal activity from high-speed digital imaging. → Traditional perturbation analysis should be cautiously applied to aperiodic high speed image signals. → Nonlinear dynamic analysis may be helpful for understanding disordered behaviors in pathological laryngeal systems. - Abstract: Laryngeal pathology is usually associated with irregular dynamics of laryngeal activity. High-speed imaging facilitates direct observation and measurement of vocal fold vibrations. However, chaotic dynamic characteristics of aperiodic high-speed image data have not yet been investigated in previous studies. In this paper, we will apply nonlinear dynamic analysis and traditional perturbation methods to quantify high-speed image data from normal subjects and patients with various laryngeal pathologies including vocal fold nodules, polyps, bleeding, and polypoid degeneration. The results reveal the low-dimensional dynamic characteristics of human glottal area data. In comparison to periodic glottal area series from a normal subject, aperiodic glottal area series from pathological subjects show complex reconstructed phase space, fractal dimension, and positive Lyapunov exponents. The estimated positive Lyapunov exponents provide the direct evidence of chaos in pathological human vocal folds from high-speed digital imaging. Furthermore, significant differences between the normal and pathological groups are investigated for nonlinear dynamic and perturbation analyses. Jitter in the pathological group is significantly higher than in the normal group, but shimmer does not show such a difference. This finding suggests that the traditional perturbation analysis should be cautiously applied to high speed image signals. However, the correlation dimension and the maximal Lyapunov exponent reveal a statistically significant difference between normal and pathological groups. Nonlinear dynamic

  10. Correction: Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi

    Science.gov (United States)

    2014-01-01

    Abstract The version of this article published in BMC Genomics 2013, 14: 274, contains 9 unpublished genomes (Botryobasidium botryosum, Gymnopus luxurians, Hypholoma sublateritium, Jaapia argillacea, Hebeloma cylindrosporum, Conidiobolus coronatus, Laccaria amethystina, Paxillus involutus, and P. rubicundulus) downloaded from JGI website. In this correction, we removed these genomes after discussion with editors and data producers whom we should have contacted before downloading these genomes. Removing these data did not alter the principle results and conclusions of our original work. The relevant Figures 1, 2, 3, 4 and 6; and Table 1 have been revised. Additional files 1, 3, 4, and 5 were also revised. We would like to apologize for any confusion or inconvenience this may have caused. Background Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. Results In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 94 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed

  11. Correction: Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi.

    Science.gov (United States)

    Zhao, Zhongtao; Liu, Huiquan; Wang, Chenfang; Xu, Jin-Rong

    2014-01-03

    The version of this article published in BMC Genomics 2013, 14: 274, contains 9 unpublished genomes (Botryobasidium botryosum, Gymnopus luxurians, Hypholoma sublateritium, Jaapia argillacea, Hebeloma cylindrosporum, Conidiobolus coronatus, Laccaria amethystina, Paxillus involutus, and P. rubicundulus) downloaded from JGI website. In this correction, we removed these genomes after discussion with editors and data producers whom we should have contacted before downloading these genomes. Removing these data did not alter the principle results and conclusions of our original work. The relevant Figures 1, 2, 3, 4 and 6; and Table 1 have been revised. Additional files 1, 3, 4, and 5 were also revised. We would like to apologize for any confusion or inconvenience this may have caused. Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 94 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed. Importantly, cellulases of some GH

  12. VNTR analysis reveals unexpected genetic diversity within Mycoplasma agalactiae, the main causative agent of contagious agalactia

    Directory of Open Access Journals (Sweden)

    Ayling Roger D

    2008-11-01

    Full Text Available Abstract Background Mycoplasma agalactiae is the main cause of contagious agalactia, a serious disease of sheep and goats, which has major clinical and economic impacts. Previous studies of M. agalactiae have shown it to be unusually homogeneous and there are currently no available epidemiological techniques which enable a high degree of strain differentiation. Results We have developed variable number tandem repeat (VNTR analysis using the sequenced genome of the M. agalactiae type strain PG2. The PG2 genome was found to be replete with tandem repeat sequences and 4 were chosen for further analysis. VNTR 5 was located within the hypothetical protein MAG6170 a predicted lipoprotein. VNTR 14 was intergenic between the hypothetical protein MAG3350 and the hypothetical protein MAG3340. VNTR 17 was intergenic between the hypothetical protein MAG4060 and the hypothetical protein MAG4070 and VNTR 19 spanned the 5' end of the pseudogene for a lipoprotein MAG4310 and the 3' end of the hypothetical lipoprotein MAG4320. We have investigated the genetic diversity of 88 M. agalactiae isolates of wide geographic origin using VNTR analysis and compared it with pulsed field gel electrophoresis (PFGE and random amplified polymorphic DNA (RAPD analysis. Simpson's index of diversity was calculated to be 0.324 for PFGE and 0.574 for VNTR analysis. VNTR analysis revealed unexpected diversity within M. agalactiae with 9 different VNTR types discovered. Some correlation was found between geographical origin and the VNTR type of the isolates. Conclusion VNTR analysis represents a useful, rapid first-line test for use in molecular epidemiological analysis of M. agalactiae for outbreak tracing and control.

  13. Proteomic analysis reveals novel proteins associated with progression and differentiation of colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Yi Gan

    2014-01-01

    Full Text Available Aim: The objective of this study is to characterize differential proteomic expression among well-differentiation and poor-differentiation colorectal carcinoma tissues and normal mucous epithelium. Materials and Methods: The study is based on quantitative 2-dimensional gel electrophoresis and analyzed by PDquest. Results: Excluding redundancies due to proteolysis and posttranslational modified isoforms of over 600 protein spots, 11 proteins were revealed as regulated with statistical variance being within the 95 th confidence level and were identified by peptide mass fingerprinting in matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Progression-associated proteins belong to the functional complexes of tumorigenesis, proliferation, differentiation, metabolism, and the regulation of major histocompatibility complex processing and other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in CRC. Among various differentiation stage of CRC tissues, we identified calreticulin precursor, MHC class I antigen (human leukocyte antigen A , glutathione S-transferase pi1, keratin 8, heat shock protein 27, tubulin beta chain, triosephosphate, fatty acid-binding protein, hemoglobin (deoxy mutant with val b 1 replaced by met (HBB, and zinc finger protein 312 (FEZF2. Conclusions: Their functional networks were analyzed by Ingenuity systems Ingenuity Pathways Analysis and revealed the potential roles as novel biomarkers for progression in various differentiation stages of CRC.

  14. Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina

    DEFF Research Database (Denmark)

    Gallo, G.; Renzone, G.; Alduina, R.

    2010-01-01

    A differential proteomic analysis, based on 2-DE and MS procedures, was performed on Amycolatopsis balhimycina DSM5908, the actinomycete producing the vancomycin-like antibiotic balhimycin. A comparison of proteomic profiles before and during balhimycin production characterized differentially...... available over the World Wide Web as interactive web pages (http://www.unipa.it/ampuglia/Abal-proteome-maps). Functional clustering analysis revealed that differentially expressed proteins belong to functional groups involved in central carbon metabolism, amino acid metabolism and protein biosynthesis......, energetic and redox balance, sugar/amino sugar metabolism, balhimycin biosynthesis and transcriptional regulation or with hypothetical and/or unknown function. Interestingly, proteins involved in the biosynthesis of balhimycin precursors, such as amino acids, amino sugars and central carbon metabolism...

  15. Proteomic analysis of three gonad types of swamp eel reveals genes differentially expressed during sex reversal.

    Science.gov (United States)

    Sheng, Yue; Zhao, Wei; Song, Ying; Li, Zhigang; Luo, Majing; Lei, Quan; Cheng, Hanhua; Zhou, Rongjia

    2015-05-18

    A variety of mechanisms are engaged in sex determination in vertebrates. The teleost fish swamp eel undergoes sex reversal naturally and is an ideal model for vertebrate sexual development. However, the importance of proteome-wide scanning for gonad reversal was not previously determined. We report a 2-D electrophoresis analysis of three gonad types of proteomes during sex reversal. MS/MS analysis revealed a group of differentially expressed proteins during ovary to ovotestis to testis transformation. Cbx3 is up-regulated during gonad reversal and is likely to have a role in spermatogenesis. Rab37 is down-regulated during the reversal and is mainly associated with oogenesis. Both Cbx3 and Rab37 are linked up in a protein network. These datasets in gonadal proteomes provide a new resource for further studies in gonadal development.

  16. A beamformer analysis of MEG data reveals frontal generators of the musically elicited mismatch negativity.

    Directory of Open Access Journals (Sweden)

    Claudia Lappe

    Full Text Available To localize the neural generators of the musically elicited mismatch negativity with high temporal resolution we conducted a beamformer analysis (Synthetic Aperture Magnetometry, SAM on magnetoencephalography (MEG data from a previous musical mismatch study. The stimuli consisted of a six-tone melodic sequence comprising broken chords in C- and G-major. The musical sequence was presented within an oddball paradigm in which the last tone was lowered occasionally (20% by a minor third. The beamforming analysis revealed significant right hemispheric neural activation in the superior temporal (STC, inferior frontal (IFC, superior frontal (SFC and orbitofrontal (OFC cortices within a time window of 100-200 ms after the occurrence of a deviant tone. IFC and SFC activation was also observed in the left hemisphere. The pronounced early right inferior frontal activation of the auditory mismatch negativity has not been shown in MEG studies so far. The activation in STC and IFC is consistent with earlier electroencephalography (EEG, optical imaging and functional magnetic resonance imaging (fMRI studies that reveal the auditory and inferior frontal cortices as main generators of the auditory MMN. The observed right hemispheric IFC is also in line with some previous music studies showing similar activation patterns after harmonic syntactic violations. The results demonstrate that a deviant tone within a musical sequence recruits immediately a distributed neural network in frontal and prefrontal areas suggesting that top-down processes are involved when expectation violation occurs within well-known stimuli.

  17. Archetypal analysis of diverse Pseudomonas aeruginosa transcriptomes reveals adaptation in cystic fibrosis airways

    Science.gov (United States)

    2013-01-01

    Background Analysis of global gene expression by DNA microarrays is widely used in experimental molecular biology. However, the complexity of such high-dimensional data sets makes it difficult to fully understand the underlying biological features present in the data. The aim of this study is to introduce a method for DNA microarray analysis that provides an intuitive interpretation of data through dimension reduction and pattern recognition. We present the first “Archetypal Analysis” of global gene expression. The analysis is based on microarray data from five integrated studies of Pseudomonas aeruginosa isolated from the airways of cystic fibrosis patients. Results Our analysis clustered samples into distinct groups with comprehensible characteristics since the archetypes representing the individual groups are closely related to samples present in the data set. Significant changes in gene expression between different groups identified adaptive changes of the bacteria residing in the cystic fibrosis lung. The analysis suggests a similar gene expression pattern between isolates with a high mutation rate (hypermutators) despite accumulation of different mutations for these isolates. This suggests positive selection in the cystic fibrosis lung environment, and changes in gene expression for these isolates are therefore most likely related to adaptation of the bacteria. Conclusions Archetypal analysis succeeded in identifying adaptive changes of P. aeruginosa. The combination of clustering and matrix factorization made it possible to reveal minor similarities among different groups of data, which other analytical methods failed to identify. We suggest that this analysis could be used to supplement current methods used to analyze DNA microarray data. PMID:24059747

  18. Pretreatment and integrated analysis of spectral data reveal seaweed similarities based on chemical diversity.

    Science.gov (United States)

    Wei, Feifei; Ito, Kengo; Sakata, Kenji; Date, Yasuhiro; Kikuchi, Jun

    2015-03-03

    Extracting useful information from high dimensionality and large data sets is a major challenge for data-driven approaches. The present study was aimed at developing novel integrated analytical strategies for comprehensively characterizing seaweed similarities based on chemical diversity. The chemical compositions of 107 seaweed and 2 seagrass samples were analyzed using multiple techniques, including Fourier transform infrared (FT-IR) and solid- and solution-state nuclear magnetic resonance (NMR) spectroscopy, thermogravimetry-differential thermal analysis (TG-DTA), inductively coupled plasma-optical emission spectrometry (ICP-OES), CHNS/O total elemental analysis, and isotope ratio mass spectrometry (IR-MS). The spectral data were preprocessed using non-negative matrix factorization (NMF) and NMF combined with multivariate curve resolution-alternating least-squares (MCR-ALS) methods in order to separate individual component information from the overlapping and/or broad spectral peaks. Integrated analysis of the preprocessed chemical data demonstrated distinct discrimination of differential seaweed species. Further network analysis revealed a close correlation between the heavy metal elements and characteristic components of brown algae, such as cellulose, alginic acid, and sulfated mucopolysaccharides, providing a componential basis for its metal-sorbing potential. These results suggest that this integrated analytical strategy is useful for extracting and identifying the chemical characteristics of diverse seaweeds based on large chemical data sets, particularly complicated overlapping spectral data.

  19. A Bivariate Chebyshev Spectral Collocation Quasilinearization Method for Nonlinear Evolution Parabolic Equations

    Directory of Open Access Journals (Sweden)

    S. S. Motsa

    2014-01-01

    Full Text Available This paper presents a new method for solving higher order nonlinear evolution partial differential equations (NPDEs. The method combines quasilinearisation, the Chebyshev spectral collocation method, and bivariate Lagrange interpolation. In this paper, we use the method to solve several nonlinear evolution equations, such as the modified KdV-Burgers equation, highly nonlinear modified KdV equation, Fisher's equation, Burgers-Fisher equation, Burgers-Huxley equation, and the Fitzhugh-Nagumo equation. The results are compared with known exact analytical solutions from literature to confirm accuracy, convergence, and effectiveness of the method. There is congruence between the numerical results and the exact solutions to a high order of accuracy. Tables were generated to present the order of accuracy of the method; convergence graphs to verify convergence of the method and error graphs are presented to show the excellent agreement between the results from this study and the known results from literature.

  20. Comparison between different uncertainty propagation methods in multivariate analysis: An application in the bivariate case

    International Nuclear Information System (INIS)

    Mullor, R.; Sanchez, A.; Martorell, S.; Martinez-Alzamora, N.

    2011-01-01

    Safety related systems performance optimization is classically based on quantifying the effects that testing and maintenance activities have on reliability and cost (R+C). However, R+C quantification is often incomplete in the sense that important uncertainties may not be considered. An important number of studies have been published in the last decade in the field of R+C based optimization considering uncertainties. They have demonstrated that inclusion of uncertainties in the optimization brings the decision maker insights concerning how uncertain the R+C results are and how this uncertainty does matter as it can result in differences in the outcome of the decision making process. Several methods of uncertainty propagation based on the theory of tolerance regions have been proposed in the literature depending on the particular characteristics of the variables in the output and their relations. In this context, the objective of this paper focuses on the application of non-parametric and parametric methods to analyze uncertainty propagation, which will be implemented on a multi-objective optimization problem where reliability and cost act as decision criteria and maintenance intervals act as decision variables. Finally, a comparison of results of these applications and the conclusions obtained are presented.

  1. Comparison between different uncertainty propagation methods in multivariate analysis: An application in the bivariate case

    Energy Technology Data Exchange (ETDEWEB)

    Mullor, R. [Dpto. Estadistica e Investigacion Operativa, Universidad Alicante (Spain); Sanchez, A., E-mail: aisanche@eio.upv.e [Dpto. Estadistica e Investigacion Operativa Aplicadas y Calidad, Universidad Politecnica Valencia, Camino de Vera s/n 46022 (Spain); Martorell, S. [Dpto. Ingenieria Quimica y Nuclear, Universidad Politecnica Valencia (Spain); Martinez-Alzamora, N. [Dpto. Estadistica e Investigacion Operativa Aplicadas y Calidad, Universidad Politecnica Valencia, Camino de Vera s/n 46022 (Spain)

    2011-06-15

    Safety related systems performance optimization is classically based on quantifying the effects that testing and maintenance activities have on reliability and cost (R+C). However, R+C quantification is often incomplete in the sense that important uncertainties may not be considered. An important number of studies have been published in the last decade in the field of R+C based optimization considering uncertainties. They have demonstrated that inclusion of uncertainties in the optimization brings the decision maker insights concerning how uncertain the R+C results are and how this uncertainty does matter as it can result in differences in the outcome of the decision making process. Several methods of uncertainty propagation based on the theory of tolerance regions have been proposed in the literature depending on the particular characteristics of the variables in the output and their relations. In this context, the objective of this paper focuses on the application of non-parametric and parametric methods to analyze uncertainty propagation, which will be implemented on a multi-objective optimization problem where reliability and cost act as decision criteria and maintenance intervals act as decision variables. Finally, a comparison of results of these applications and the conclusions obtained are presented.

  2. Bivariate analysis of basal serum anti-Mullerian hormone measurements and human blastocyst development after IVF

    LENUS (Irish Health Repository)

    Sills, E Scott

    2011-12-02

    Abstract Background To report on relationships among baseline serum anti-Müllerian hormone (AMH) measurements, blastocyst development and other selected embryology parameters observed in non-donor oocyte IVF cycles. Methods Pre-treatment AMH was measured in patients undergoing IVF (n = 79) and retrospectively correlated to in vitro embryo development noted during culture. Results Mean (+\\/- SD) age for study patients in this study group was 36.3 ± 4.0 (range = 28-45) yrs, and mean (+\\/- SD) terminal serum estradiol during IVF was 5929 +\\/- 4056 pmol\\/l. A moderate positive correlation (0.49; 95% CI 0.31 to 0.65) was noted between basal serum AMH and number of MII oocytes retrieved. Similarly, a moderate positive correlation (0.44) was observed between serum AMH and number of early cleavage-stage embryos (95% CI 0.24 to 0.61), suggesting a relationship between serum AMH and embryo development in IVF. Of note, serum AMH levels at baseline were significantly different for patients who did and did not undergo blastocyst transfer (15.6 vs. 10.9 pmol\\/l; p = 0.029). Conclusions While serum AMH has found increasing application as a predictor of ovarian reserve for patients prior to IVF, its roles to estimate in vitro embryo morphology and potential to advance to blastocyst stage have not been extensively investigated. These data suggest that baseline serum AMH determinations can help forecast blastocyst developmental during IVF. Serum AMH measured before treatment may assist patients, clinicians and embryologists as scheduling of embryo transfer is outlined. Additional studies are needed to confirm these correlations and to better define the role of baseline serum AMH level in the prediction of blastocyst formation.

  3. Attenuation of vagal modulation with aging: Univariate and bivariate analysis of HRV.

    Science.gov (United States)

    Junior, E C; Oliveira, F M

    2017-07-01

    The aging process leads to diverse changes in the human organism, including in autonomic system modulation. In this study, we calculated indices of HRV in frequency (power spectral density, PSD) and time (the impulse response (IR) method) domains, using data from healthy young and elderly volunteers (Fantasia database from Physionet). The results obtained showed that aging leads to an attenuation of vagal modulation of elderly individuals when compared to young volunteers.

  4. Metagenomic and network analysis reveal wide distribution and co-occurrence of environmental antibiotic resistance genes.

    Science.gov (United States)

    Li, Bing; Yang, Ying; Ma, Liping; Ju, Feng; Guo, Feng; Tiedje, James M; Zhang, Tong

    2015-11-01

    A metagenomic approach and network analysis was used to investigate the wide-spectrum profiles of antibiotic resistance genes (ARGs) and their co-occurrence patterns in 50 samples from 10 typical environments. In total, 260 ARG subtypes belonging to 18 ARG types were detected with an abundance range of 5.4 × 10(-6)-2.2 × 10(-1) copy of ARG per copy of 16S-rRNA gene. The trend of the total ARG abundances in environments matched well with the levels of anthropogenic impacts on these environments. From the less impacted environments to the seriously impacted environments, the total ARG abundances increased up to three orders of magnitude, that is, from 3.2 × 10(-3) to 3.1 × 10(0) copy of ARG per copy of 16S-rRNA gene. The abundant ARGs were associated with aminoglycoside, bacitracin, β-lactam, chloramphenicol, macrolide-lincosamide-streptogramin, quinolone, sulphonamide and tetracycline, in agreement with the antibiotics extensively used in human medicine or veterinary medicine/promoters. The widespread occurrences and abundance variation trend of vancomycin resistance genes in different environments might imply the spread of vancomycin resistance genes because of the selective pressure resulting from vancomycin use. The simultaneous enrichment of 12 ARG types in adult chicken faeces suggests the coselection of multiple ARGs in this production system. Non-metric multidimensional scaling analysis revealed that samples belonging to the same environment generally possessed similar ARG compositions. Based on the co-occurrence pattern revealed by network analysis, tetM and aminoglycoside resistance protein, the hubs of the ARG network, are proposed to be indicators to quantitatively estimate the abundance of 23 other co-occurring ARG subtypes by power functions.

  5. Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality.

    Science.gov (United States)

    Jiang, Yue; Xiong, Xuejian; Danska, Jayne; Parkinson, John

    2016-01-12

    Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. Metatranscriptomic datasets exhibited distinct taxonomic and functional signatures. From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. At the same time, our findings show how microbiome complexity and availability of

  6. An association network analysis among microeukaryotes and bacterioplankton reveals algal bloom dynamics.

    Science.gov (United States)

    Tan, Shangjin; Zhou, Jin; Zhu, Xiaoshan; Yu, Shichen; Zhan, Wugen; Wang, Bo; Cai, Zhonghua

    2015-02-01

    Algal blooms are a worldwide phenomenon and the biological interactions that underlie their regulation are only just beginning to be understood. It is established that algal microorganisms associate with many other ubiquitous, oceanic organisms, but the interactions that lead to the dynamics of bloom formation are currently unknown. To address this gap, we used network approaches to investigate the association patterns among microeukaryotes and bacterioplankton in response to a natural Scrippsiella trochoidea bloom. This is the first study to apply network approaches to bloom dynamics. To this end, terminal restriction fragment (T-RF) length polymorphism analysis showed dramatic changes in community compositions of microeukaryotes and bacterioplankton over the blooming period. A variance ratio test revealed significant positive overall associations both within and between microeukaryotic and bacterioplankton communities. An association network generated from significant correlations between T-RFs revealed that S. trochoidea had few connections to other microeukaryotes and bacterioplankton and was placed on the edge. This lack of connectivity allowed for the S. trochoidea sub-network to break off from the overall network. These results allowed us to propose a conceptual model for explaining how changes in microbial associations regulate the dynamics of an algal bloom. In addition, key T-RFs were screened by principal components analysis, correlation coefficients, and network analysis. Dominant T-RFs were then identified through 18S and 16S rRNA gene clone libraries. Results showed that microeukaryotes clustered predominantly with Dinophyceae and Perkinsea while the majority of bacterioplankton identified were Alphaproteobacteria, Gammaproteobacteria, and Bacteroidetes. The ecologi-cal roles of both were discussed in the context of these findings. © 2014 Phycological Society of America.

  7. Association genetics and transcriptome analysis reveal a gibberellin-responsive pathway involved in regulating photosynthesis.

    Science.gov (United States)

    Xie, Jianbo; Tian, Jiaxing; Du, Qingzhang; Chen, Jinhui; Li, Ying; Yang, Xiaohui; Li, Bailian; Zhang, Deqiang

    2016-05-01

    Gibberellins (GAs) regulate a wide range of important processes in plant growth and development, including photosynthesis. However, the mechanism by which GAs regulate photosynthesis remains to be understood. Here, we used multi-gene association to investigate the effect of genes in the GA-responsive pathway, as constructed by RNA sequencing, on photosynthesis, growth, and wood property traits, in a population of 435 Populus tomentosa By analyzing changes in the transcriptome following GA treatment, we identified many key photosynthetic genes, in agreement with the observed increase in measurements of photosynthesis. Regulatory motif enrichment analysis revealed that 37 differentially expressed genes related to photosynthesis shared two essential GA-related cis-regulatory elements, the GA response element and the pyrimidine box. Thus, we constructed a GA-responsive pathway consisting of 47 genes involved in regulating photosynthesis, including GID1, RGA, GID2, MYBGa, and 37 photosynthetic differentially expressed genes. Single nucleotide polymorphism (SNP)-based association analysis showed that 142 SNPs, representing 40 candidate genes in this pathway, were significantly associated with photosynthesis, growth, and wood property traits. Epistasis analysis uncovered interactions between 310 SNP-SNP pairs from 37 genes in this pathway, revealing possible genetic interactions. Moreover, a structural gene-gene matrix based on a time-course of transcript abundances provided a better understanding of the multi-gene pathway affecting photosynthesis. The results imply a functional role for these genes in mediating photosynthesis, growth, and wood properties, demonstrating the potential of combining transcriptome-based regulatory pathway construction and genetic association approaches to detect the complex genetic networks underlying quantitative traits. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights

  8. Proteomics and bioinformatics analysis reveal underlying pathways of infection associated histologic chorioamnionitis in pPROM.

    Science.gov (United States)

    Tambor, V; Kacerovsky, M; Lenco, J; Bhat, G; Menon, R

    2013-02-01

    The presence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) is associated with adverse neonatal outcomes in pregnancies complicated by preterm prelabor rupture of membranes (pPROM). Therefore, there is an urgent need to identify new biomarkers revealing these conditions. The objective of this study is to identify possible biomarkers and their underlying biofunctions in pPROM pregnancies with and without MIAC and HCA. A total of 72 women with pPROM were recruited. Only women with both MIAC and HCA (n = 19) and all women without these complications (n = 19) having the same range of gestational ages at sampling were included in the study. Samples of amniotic fluid were obtained by transabdominal amniocentesis, processed and analyzed using quantitative shotgun proteomics. Ingenuity pathway analysis was used to identify molecular networks that involve altered proteins. Network interaction identified by ingenuity pathway analysis revealed immunological disease and the inflammatory response as the top functions and disease associated with pPROM in the presence of MIAC and HCA. The proteins involved in these pathways were significantly altered between the groups with and without the presence of both MIAC and HCA. Proteins involved included histones H3, H4, H2B, cathelicidin antimicrobial peptide, myeloperoxidase, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, peptidoglycan recognition protein-1 and neutrophil defensin 1, all of which were found to be up-regulated in the presence of MIAC and HCA. Bioinformatic analysis of proteomics data allowed us to project likely biomolecular pathology resulting in pPROM complicated by MIAC and HCA. As inflammation is not a homogeneous phenomenon, we provide evidence for oxidative-stress-associated DNA damage and biomarkers of reactive oxygen species generation as factors associated with inflammation and proteolysis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia.

    Science.gov (United States)

    Damaraju, E; Allen, E A; Belger, A; Ford, J M; McEwen, S; Mathalon, D H; Mueller, B A; Pearlson, G D; Potkin, S G; Preda, A; Turner, J A; Vaidya, J G; van Erp, T G; Calhoun, V D

    2014-01-01

    Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical-subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group

  10. Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia

    Directory of Open Access Journals (Sweden)

    E. Damaraju

    2014-01-01

    Full Text Available Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length, and a dynamic sense, computed using sliding windows (44 s in length and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual, as well as reduced connectivity (hypoconnectivity between sensory networks from all modalities. Dynamic analysis suggests that (1, on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2, that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical–subcortical antagonism (anti-correlations and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity

  11. Structural connectivity analysis reveals abnormal brain connections in agenesis of the corpus callosum in children.

    Science.gov (United States)

    Meoded, Avner; Katipally, Rohan; Bosemani, Thangamadhan; Huisman, Thierry A G M; Poretti, Andrea

    2015-05-01

    Structural connectivity analysis is an ideal tool to study connections in brain malformations. We aimed to characterize the topological network measures and study sub-networks in children with agenesis of the corpus callosum (AgCC). We hypothesized a more segregated structural network in children with AgCC. Structural connectivity analysis including topology analysis and network-based-statistics was applied in children with AgCC and age-matched controls. Probabilistic-tractography and brain segmentation into 108 regions were performed. For controls, structural connectivity has been analyzed after excluding the callosal connections ('virtual callosotomy'). Ten patients (six males, mean age 6.5 years, SD 4.5 years) and ten controls (mean age 5.9 years, SD 4.7 years) were included. In patients, topology analysis revealed higher clustering coefficient and transitivity and lower small world index and assortativity compared to controls. The bilateral insula were identified as hubs in patients, whereas the cerebellum was detected as a hub only in controls. Three sub-networks of increased connectivity were identified in patients. We found reduced global and increased local connectivity in children with AgCC compared to controls. Neural plasticity in AgCC may attempt to increase the interhemispheric connectivity through alternative decussating pathways other than the corpus callosum. • The structural connectivity analysis quantifies white-matter networks within the brain • In callosal agenesis there is reduced global and increased local connectivity • In callosal agenesis, alternative decussating pathways are used for interhemispheric connectivity.

  12. Comparative Analysis of 35 Basidiomycete Genomes Reveals Diversity and Uniqueness of the Phylum

    Energy Technology Data Exchange (ETDEWEB)

    Riley, Robert; Salamov, Asaf; Otillar, Robert; Fagnan, Kirsten; Boussau, Bastien; Brown, Daren; Henrissat, Bernard; Levasseur, Anthony; Held, Benjamin; Nagy, Laszlo; Floudas, Dimitris; Morin, Emmanuelle; Manning, Gerard; Baker, Scott; Martin, Francis; Blanchette, Robert; Hibbett, David; Grigoriev, Igor V.

    2013-03-11

    Fungi of the phylum Basidiomycota (basidiomycetes), make up some 37percent of the described fungi, and are important in forestry, agriculture, medicine, and bioenergy. This diverse phylum includes symbionts, pathogens, and saprobes including wood decaying fungi. To better understand the diversity of this phylum we compared the genomes of 35 basidiomycete fungi including 6 newly sequenced genomes. The genomes of basidiomycetes span extremes of genome size, gene number, and repeat content. A phylogenetic tree of Basidiomycota was generated using the Phyldog software, which uses all available protein sequence data to simultaneously infer gene and species trees. Analysis of core genes reveals that some 48percent of basidiomycete proteins are unique to the phylum with nearly half of those (22percent) comprising proteins found in only one organism. Phylogenetic patterns of plant biomass-degrading genes suggest a continuum rather than a sharp dichotomy between the white rot and brown rot modes of wood decay among the members of Agaricomycotina subphylum. There is a correlation of the profile of certain gene families to nutritional mode in Agaricomycotina. Based on phylogenetically-informed PCA analysis of such profiles, we predict that that Botryobasidium botryosum and Jaapia argillacea have properties similar to white rot species, although neither has liginolytic class II fungal peroxidases. Furthermore, we find that both fungi exhibit wood decay with white rot-like characteristics in growth assays. Analysis of the rate of discovery of proteins with no or few homologs suggests the high value of continued sequencing of basidiomycete fungi.

  13. Comprehensive DNA Adduct Analysis Reveals Pulmonary Inflammatory Response Contributes to Genotoxic Action of Magnetite Nanoparticles

    Directory of Open Access Journals (Sweden)

    Kousuke Ishino

    2015-02-01

    Full Text Available Nanosized-magnetite (MGT is widely utilized in medicinal and industrial fields; however, its toxicological properties are not well documented. In our previous report, MGT showed genotoxicity in both in vitro and in vivo assay systems, and it was suggested that inflammatory responses exist behind the genotoxicity. To further clarify mechanisms underlying the genotoxicity, a comprehensive DNA adduct (DNA adductome analysis was conducted using DNA samples derived from the lungs of mice exposed to MGT. In total, 30 and 42 types of DNA adducts were detected in the vehicle control and MGT-treated groups, respectively. Principal component analysis (PCA against a subset of DNA adducts was applied and several adducts, which are deduced to be formed by inflammation or oxidative stress, as the case of etheno-deoxycytidine (εdC, revealed higher contributions to MGT exposure. By quantitative-LC-MS/MS analysis, εdC levels were significantly higher in MGT-treated mice than those of the vehicle control. Taken together with our previous data, it is suggested that inflammatory responses might be involved in the genotoxicity induced by MGT in the lungs of mice.

  14. Comprehensive genetic analysis of OEIS complex reveals no evidence for a recurrent microdeletion or duplication.

    Science.gov (United States)

    Vlangos, Christopher N; Siuniak, Amanda; Ackley, Todd; van Bokhoven, Hans; Veltman, Joris; Iyer, Ram; Park, John M; Keppler-Noreuil, Kim; Keegan, Catherine E

    2011-01-01

    Omphalocele-exstrophy of the bladder-imperforate anus-spinal defects (OEIS) complex, or cloacal exstrophy (EC), is a rare constellation of malformations in humans involving the urogenital, gastrointestinal, and skeletal systems, and less commonly the central nervous system. Although OEIS complex is well-recognized in the clinical setting, there remains a significant lack of understanding of this condition at both the developmental and the genetic level. While most cases are sporadic, familial cases have been reported, suggesting that one or more specific genes may play a significant role in this condition. Several developmental mechanisms have been proposed to explain the etiology of OEIS complex, and it is generally considered to be a defect early in caudal mesoderm development and ventral body wall closure. The goal of this study was to identify genetic aberrations in 13 patients with OEIS/EC using a combination of candidate gene analysis and microarray studies. Analysis of 14 candidate genes in combination with either high resolution SNP or oligonucleotide microarray did not reveal any disease-causing mutations, although novel variants were identified in five patients. To our knowledge, this is the most comprehensive genetic analysis of patients with OEIS complex to date. We conclude that OEIS is a complex disorder from an etiological perspective, likely involving a combination of genetic and environmental predispositions. Based on our data, OEIS complex is unlikely to be caused by a recurrent chromosomal aberration. Copyright © 2010 Wiley-Liss, Inc.

  15. REVEAL - A tool for rule driven analysis of safety critical software

    International Nuclear Information System (INIS)

    Miedl, H.; Kersken, M.

    1998-01-01

    As the determination of ultrahigh reliability figures for safety critical software is hardly possible, national and international guidelines and standards give mainly requirements for the qualitative evaluation of software. An analysis whether all these requirements are fulfilled is time and effort consuming and prone to errors, if performed manually by analysts, and should instead be dedicated to tools as far as possible. There are many ''general-purpose'' software analysis tools, both static and dynamic, which help analyzing the source code. However, they are not designed to assess the adherence to specific requirements of guidelines and standards in the nuclear field. Against the background of the development of I and C systems in the nuclear field which are based on digital techniques and implemented in high level language, it is essential that the assessor or licenser has a tool with which he can automatically and uniformly qualify as many aspects as possible of the high level language software. For this purpose the software analysis tool REVEAL has been developed at ISTec and the Halden Reactor Project. (author)

  16. In vivo dynamics of skeletal muscle Dystrophin in zebrafish embryos revealed by improved FRAP analysis.

    Science.gov (United States)

    Bajanca, Fernanda; Gonzalez-Perez, Vinicio; Gillespie, Sean J; Beley, Cyriaque; Garcia, Luis; Theveneau, Eric; Sear, Richard P; Hughes, Simon M

    2015-10-13

    Dystrophin forms an essential link between sarcolemma and cytoskeleton, perturbation of which causes muscular dystrophy. We analysed Dystrophin binding dynamics in vivo for the first time. Within maturing fibres of host zebrafish embryos, our analysis reveals a pool of diffusible Dystrophin and complexes bound at the fibre membrane. Combining modelling, an improved FRAP methodology and direct semi-quantitative analysis of bleaching suggests the existence of two membrane-bound Dystrophin populations with widely differing bound lifetimes: a stable, tightly bound pool, and a dynamic bound pool with high turnover rate that exchanges with the cytoplasmic pool. The three populations were found consistently in human and zebrafish Dystrophins overexpressed in wild-type or dmd(ta222a/ta222a) zebrafish embryos, which lack Dystrophin, and in Gt(dmd-Citrine)(ct90a) that express endogenously-driven tagged zebrafish Dystrophin. These results lead to a new model for Dystrophin membrane association in developing muscle, and highlight our methodology as a valuable strategy for in vivo analysis of complex protein dynamics.

  17. Systematic analysis of essential genes reveals important regulators of G protein signaling.

    Science.gov (United States)

    Cappell, Steven D; Baker, Rachael; Skowyra, Dorota; Dohlman, Henrik G

    2010-06-11

    The yeast pheromone pathway consists of a canonical heterotrimeric G protein and MAP kinase cascade. To identify additional signaling components, we systematically evaluated 870 essential genes using a library of repressible-promoter strains. Quantitative transcription-reporter and MAPK activity assays were used to identify strains that exhibit altered pheromone sensitivity. Of the 92 newly identified essential genes required for proper G protein signaling, those involved with protein degradation were most highly represented. Included in this group are members of the Skp, Cullin, F box (SCF) ubiquitin ligase complex. Further genetic and biochemical analysis reveals that SCF(Cdc4) acts together with the Cdc34 ubiquitin-conjugating enzyme at the level of the G protein; promotes degradation of the G protein alpha subunit, Gpa1, in vivo; and catalyzes Gpa1 ubiquitination in vitro. These insights to the G protein signaling network reveal the essential genome as an untapped resource for identifying new components and regulators of signal transduction pathways. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  18. Quantitative proteomic analysis reveals that transmissible gastroenteritis virus activates the JAK-STAT1 signaling pathway.

    Science.gov (United States)

    An, Kang; Fang, Liurong; Luo, Rui; Wang, Dang; Xie, Lilan; Yang, Jing; Chen, Huanchun; Xiao, Shaobo

    2014-12-05

    Transmissible gastroenteritis virus (TGEV), a porcine enteropathogenic coronavirus, causes lethal watery diarrhea and severe dehydration in piglets. In this study, liquid chromatography-tandem mass spectrometry coupled to isobaric tags for relative and absolute quantification labeling was used to quantitatively identify differentially expressed cellular proteins after TGEV infection in PK-15 cells. In total, 162 differentially expressed cellular proteins were identified, including 60 upregulated proteins and 102 downregulated proteins. These differentially expressed proteins were involved in the cell cycle, cellular growth and proliferation, the innate immune response, etc. Interestingly, many upregulated proteins were associated with interferon signaling, especially signal transducer and activator of transcription 1 (STAT1) and interferon-stimulated genes (ISGs). Immunoblotting and real-time quantitative reverse transcription polymerase chain reaction demonstrated that TGEV infection induces STAT1 phosphorylation and nuclear translocation, as well as ISG expression. This study for the first time reveals that TGEV induces interferon signaling from the point of proteomic analysis.

  19. Peptidomic analysis reveals proteolytic activity of kefir microorganisms on bovine milk proteins.

    Science.gov (United States)

    Dallas, David C; Citerne, Florine; Tian, Tian; Silva, Vitor L M; Kalanetra, Karen M; Frese, Steven A; Robinson, Randall C; Mills, David A; Barile, Daniela

    2016-04-15

    The microorganisms that make up kefir grains are well known for lactose fermentation, but the extent to which they hydrolyze and consume milk proteins remains poorly understood. Peptidomics technologies were used to examine the proteolytic activity of kefir grains on bovine milk proteins. Gel electrophoresis revealed substantial digestion of milk proteins by kefir grains, with mass spectrometric analysis showing the release of 609 protein fragments and alteration of the abundance of >1500 peptides that derived from 27 milk proteins. Kefir contained 25 peptides identified from the literature as having biological activity, including those with antihypertensive, antimicrobial, immunomodulatory, opioid and anti-oxidative functions. 16S rRNA and shotgun metagenomic sequencing identified the principle taxa in the culture as Lactobacillus species. The model kefir sample contained thousands of protein fragments released in part by kefir microorganisms and in part by native milk proteases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Metagenomic analysis of the pinewood nematode microbiome reveals a symbiotic relationship critical for xenobiotics degradation

    Science.gov (United States)

    Cheng, Xin-Yue; Tian, Xue-Liang; Wang, Yun-Sheng; Lin, Ren-Miao; Mao, Zhen-Chuan; Chen, Nansheng; Xie, Bing-Yan

    2013-01-01

    Our recent research revealed that pinewood nematode (PWN) possesses few genes encoding enzymes for degrading α-pinene, which is the main compound in pine resin. In this study, we examined the role of PWN microbiome in xenobiotics detoxification by metagenomic and bacteria culture analyses. Functional annotation of metagenomes illustrated that benzoate degradation and its related metabolisms may provide the main metabolic pathways for xenobiotics detoxification in the microbiome, which is obviously different from that in PWN that uses cytochrome P450 metabolism as the main pathway for detoxification. The metabolic pathway of degrading α-pinene is complete in microbiome, but incomplete in PWN genome. Experimental analysis demonstrated that most of tested cultivable bacteria can not only survive the stress of 0.4% α-pinene, but also utilize α-pinene as carbon source for their growth. Our results indicate that PWN and its microbiome have established a potentially mutualistic symbiotic relationship with complementary pathways in detoxification metabolism. PMID:23694939

  1. Global analysis of asymmetric RNA enrichment in oocytes reveals low conservation between closely related Xenopus species

    Science.gov (United States)

    Claußen, Maike; Lingner, Thomas; Pommerenke, Claudia; Opitz, Lennart; Salinas, Gabriela; Pieler, Tomas

    2015-01-01

    RNAs that localize to the vegetal cortex during Xenopus laevis oogenesis have been reported to function in germ layer patterning, axis determination, and development of the primordial germ cells. Here we report on the genome-wide, comparative analysis of differentially localizing RNAs in Xenopus laevis and Xenopus tropicalis oocytes, revealing a surprisingly weak degree of conservation in respect to the identity of animally as well as vegetally enriched transcripts in these closely related species. Heterologous RNA injections and protein binding studies indicate that the different RNA localization patterns in these two species are due to gain/loss of cis-acting localization signals rather than to differences in the RNA-localizing machinery. PMID:26337391

  2. Comparative Analysis of Four Calypogeia Species Revealed Unexpected Change in Evolutionarily-Stable Liverwort Mitogenomes

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    Monika Ślipiko

    2017-12-01

    Full Text Available Liverwort mitogenomes are considered to be evolutionarily stable. A comparative analysis of four Calypogeia species revealed differences compared to previously sequenced liverwort mitogenomes. Such differences involve unexpected structural changes in the two genes, cox1 and atp1, which have lost three and two introns, respectively. The group I introns in the cox1 gene are proposed to have been lost by two-step localized retroprocessing, whereas one-step retroprocessing could be responsible for the disappearance of the group II introns in the atp1 gene. These cases represent the first identified losses of introns in mitogenomes of leafy liverworts (Jungermanniopsida contrasting the stability of mitochondrial gene order with certain changes in the gene content and intron set in liverworts.

  3. Bifidobacterium asteroides PRL2011 genome analysis reveals clues for colonization of the insect gut.

    Science.gov (United States)

    Bottacini, Francesca; Milani, Christian; Turroni, Francesca; Sánchez, Borja; Foroni, Elena; Duranti, Sabrina; Serafini, Fausta; Viappiani, Alice; Strati, Francesco; Ferrarini, Alberto; Delledonne, Massimo; Henrissat, Bernard; Coutinho, Pedro; Fitzgerald, Gerald F; Margolles, Abelardo; van Sinderen, Douwe; Ventura, Marco

    2012-01-01

    Bifidobacteria are known as anaerobic/microaerophilic and fermentative microorganisms, which commonly inhabit the gastrointestinal tract of various animals and insects. Analysis of the 2,167,301 bp genome of Bifidobacterium asteroides PRL2011, a strain isolated from the hindgut of Apis mellifera var. ligustica, commonly known as the honey bee, revealed its predicted capability for respiratory metabolism. Conservation of the latter gene clusters in various B. asteroides strains enforces the notion that respiration is a common metabolic feature of this ancient bifidobacterial species, which has been lost in currently known mammal-derived Bifidobacterium species. In fact, phylogenomic based analyses suggested an ancient origin of B. asteroides and indicates it as an ancestor of the genus Bifidobacterium. Furthermore, the B. asteroides PRL2011 genome encodes various enzymes for coping with toxic products that arise as a result of oxygen-mediated respiration.

  4. Conformational Dynamics of apo-GlnBP Revealed by Experimental and Computational Analysis

    KAUST Repository

    Feng, Yitao

    2016-10-13

    The glutamine binding protein (GlnBP) binds l-glutamine and cooperates with its cognate transporters during glutamine uptake. Crystal structure analysis has revealed an open and a closed conformation for apo- and holo-GlnBP, respectively. However, the detailed conformational dynamics have remained unclear. Herein, we combined NMR spectroscopy, MD simulations, and single-molecule FRET techniques to decipher the conformational dynamics of apo-GlnBP. The NMR residual dipolar couplings of apo-GlnBP were in good agreement with a MD-derived structure ensemble consisting of four metastable states. The open and closed conformations are the two major states. This four-state model was further validated by smFRET experiments and suggests the conformational selection mechanism in ligand recognition of GlnBP. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

  5. EEG Cortical Connectivity Analysis of Working Memory Reveals Topological Reorganization in Theta and Alpha Bands

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    Zhongxiang Dai

    2017-05-01

    Full Text Available Numerous studies have revealed various working memory (WM-related brain activities that originate from various cortical regions and oscillate at different frequencies. However, multi-frequency band analysis of the brain network in WM in the cortical space remains largely unexplored. In this study, we employed a graph theoretical framework to characterize the topological properties of the brain functional network in the theta and alpha frequency bands during WM tasks. Twenty-eight subjects performed visual n-back tasks at two difficulty levels, i.e., 0-back (control task and 2-back (WM task. After preprocessing, Electroencephalogram (EEG signals were projected into the source space and 80 cortical brain regions were selected for further analysis. Subsequently, the theta- and alpha-band networks were constructed by calculating the Pearson correlation coefficients between the power series (obtained by concatenating the power values of all epochs in each session of all pairs of brain regions. Graph theoretical approaches were then employed to estimate the topological properties of the brain networks at different WM tasks. We found higher functional integration in the theta band and lower functional segregation in the alpha band in the WM task compared with the control task. Moreover, compared to the 0-back task, altered regional centrality was revealed in the 2-back task in various brain regions that mainly resided in the frontal, temporal and occipital lobes, with distinct presentations in the theta and alpha bands. In addition, significant negative correlations were found between the reaction time with the average path length of the theta-band network and the local clustering of the alpha-band network, which demonstrates the potential for using the brain network metrics as biomarkers for predicting the task performance during WM tasks.

  6. Cluster analysis reveals a binary effect of storage on boar sperm motility function.

    Science.gov (United States)

    Henning, Heiko; Petrunkina, Anna M; Harrison, Robin A P; Waberski, Dagmar

    2014-06-01

    Storage of liquid-preserved boar spermatozoa is associated with a loss of fertilising ability of the preserved spermatozoa, which standard semen parameters barely reflect. Monitoring responses to molecular effectors of sperm function (e.g. bicarbonate) has proven to be a more sensitive approach to investigating storage effects. Bicarbonate not only initiates capacitation in spermatozoa, but also induces motility activation. This occurs at ejaculation, but also happens throughout passage through the oviduct. In the present study we tested whether the specific response of boar sperm subpopulations to bicarbonate, as assessed by motility activation, is altered with the duration of storage in vitro. Three ejaculates from each of seven boars were diluted in Beltsville thawing solution and stored at 17°C. Only minor changes in the parameters of diluted semen were revealed over a period of 72h storage. For assessment of bicarbonate responses, subsamples of diluted spermatozoa were centrifuged through a discontinuous Percoll gradient after 12, 24 and 72h storage. Subsequently, spermatozoa were incubated in two Ca2+-free variants of Tyrode's medium either without (TyrControl) or with (TyrBic) 15mM bicarbonate, and computer-aided sperm analysis motility measurements were made. Cluster analysis of imaging data from motile spermatozoa revealed the presence of five major sperm subpopulations with distinct motility characteristics, differing between TyrBic and TyrControl at any given time (Pfunction in both media, bicarbonate induced an increase in a 'fast linear' cohort of spermatozoa in TyrBic regardless of storage (66.4% at 12h and 63.9% at 72h). These results imply a binary pattern in response of sperm motility function descriptors to storage: although the quantitative descriptor (percentage of motile spermatozoa) declines in washed semen samples, the qualitative descriptor (percentage of spermatozoa stimulated into fast linear motion by bicarbonate) is sustained

  7. Comparative transcriptional analysis reveals differential gene expression between asymmetric and symmetric zygotic divisions in tobacco.

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    Tian-Xiang Hu

    Full Text Available Asymmetric cell divisions occur widely during many developmental processes in plants. In most angiosperms, the first zygotic cell division is asymmetric resulting in two daughter cells of unequal size and with distinct fates. However, the critical molecular mechanisms regulating this division remain unknown. Previously we showed that treatment of tobacco zygotes with beta-glucosyl Yariv (βGlcY could dramatically alter the first zygotic asymmetric division to produce symmetric two-celled proembryos. In the present study, we isolated zygotes and two-celled asymmetric proembryos in vivo by micromanipulation, and obtained symmetric, two-celled proembryos by in vitro cell cultures. Using suppression-subtractive hybridization (SSH and macroarray analysis differential gene expression between the zygote and the asymmetric and symmetric two-celled proembryos was investigated. After sequencing of the differentially expressed clones, a total of 1610 EST clones representing 685 non-redundant transcripts were obtained. Gene ontology (GO term analysis revealed that these transcripts include those involved in physiological processes such as response to stimulus, regulation of gene expression, and localization and formation of anatomical structures. A homology search against known genes from Arabidopsis indicated that some of the above transcripts are involved in asymmetric cell division and embryogenesis. Quantitative real-time PCR confirmed the up- or down-regulation of the selected candidate transcripts during zygotic division. A few of these transcripts were expressed exclusively in the zygote, or in either type of the two-celled proembryos. Expression analyses of select genes in different tissues and organs also revealed potential roles of these transcripts in fertilization, seed maturation and organ development. The putative roles of few of the identified transcripts in the regulation of zygotic division are discussed. Further functional work on these

  8. Comparative Transcriptomic Analysis Reveals Similarities and Dissimilarities in Saccharomyces cerevisiae Wine Strains Response to Nitrogen Availability

    Science.gov (United States)

    Barbosa, Catarina; García-Martínez, José; Pérez-Ortín, José E.; Mendes-Ferreira, Ana

    2015-01-01

    Nitrogen levels in grape-juices are of major importance in winemaking ensuring adequate yeast growth and fermentation performance. Here we used a comparative transcriptome analysis to uncover wine yeasts responses to nitrogen availability during fermentation. Gene expression was assessed in three genetically and phenotypically divergent commercial wine strains (CEG, VL1 and QA23), under low (67 mg/L) and high nitrogen (670 mg/L) regimes, at three time points during fermentation (12h, 24h and 96h). Two-way ANOVA analysis of each fermentation condition led to the identification of genes whose expression was dependent on strain, fermentation stage and on the interaction of both factors. The high fermenter yeast strain QA23 was more clearly distinct from the other two strains, by differential expression of genes involved in flocculation, mitochondrial functions, energy generation and protein folding and stabilization. For all strains, higher transcriptional variability due to fermentation stage was seen in the high nitrogen fermentations. A positive correlation between maximum fermentation rate and the expression of genes involved in stress response was observed. The finding of common genes correlated with both fermentation activity and nitrogen up-take underlies the role of nitrogen on yeast fermentative fitness. The comparative analysis of genes differentially expressed between both fermentation conditions at 12h, where the main difference was the level of nitrogen available, showed the highest variability amongst strains revealing strain-specific responses. Nevertheless, we were able to identify a small set of genes whose expression profiles can quantitatively assess the common response of the yeast strains to varying nitrogen conditions. The use of three contrasting yeast strains in gene expression analysis prompts the identification of more reliable, accurate and reproducible biomarkers that will facilitate the diagnosis of deficiency of this nutrient in the grape

  9. Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus.

    Science.gov (United States)

    Vecsey, Christopher G; Peixoto, Lucia; Choi, Jennifer H K; Wimmer, Mathieu; Jaganath, Devan; Hernandez, Pepe J; Blackwell, Jennifer; Meda, Karuna; Park, Alan J; Hannenhalli, Sridhar; Abel, Ted

    2012-10-17

    Sleep deprivation is a common problem of considerable health and economic impact in today's society. Sleep loss is associated with deleterious effects on cognitive functions such as memory and has a high comorbidity with many neurodegenerative and neuropsychiatric disorders. Therefore, it is crucial to understand the molecular basis of the effect of sleep deprivation in the brain. In this study, we combined genome-wide and traditional molecular biological approaches to determine the cellular and molecular impacts of sleep deprivation in the mouse hippocampus, a brain area crucial for many forms of memory. Microarray analysis examining the effects of 5 h of sleep deprivation on gene expression in the mouse hippocampus found 533 genes with altered expression. Bioinformatic analysis revealed that a prominent effect of sleep deprivation was to downregulate translation, potentially mediated through components of the insulin signaling pathway such as the mammalian target of rapamycin (mTOR), a key regulator of protein synthesis. Consistent with this analysis, sleep deprivation reduced levels of total and phosphorylated mTOR, and levels returned to baseline after 2.5 h of recovery sleep. Our findings represent the first genome-wide analysis of the effects of sleep deprivation on the mouse hippocampus, and they suggest that the detrimental effects of sleep deprivation may be mediated by reductions in protein synthesis via downregulation of mTOR. Because protein synthesis and mTOR activation are required for long-term memory formation, our study improves our understanding of the molecular mechanisms underlying the memory impairments induced by sleep deprivation.

  10. Comparative transcriptomic analysis reveals similarities and dissimilarities in Saccharomyces cerevisiae wine strains response to nitrogen availability.

    Directory of Open Access Journals (Sweden)

    Catarina Barbosa

    Full Text Available Nitrogen levels in grape-juices are of major importance in winemaking ensuring adequate yeast growth and fermentation performance. Here we used a comparative transcriptome analysis to uncover wine yeasts responses to nitrogen availability during fermentation. Gene expression was assessed in three genetically and phenotypically divergent commercial wine strains (CEG, VL1 and QA23, under low (67 mg/L and high nitrogen (670 mg/L regimes, at three time points during fermentation (12 h, 24 h and 96 h. Two-way ANOVA analysis of each fermentation condition led to the identification of genes whose expression was dependent on strain, fermentation stage and on the interaction of both factors. The high fermenter yeast strain QA23 was more clearly distinct from the other two strains, by differential expression of genes involved in flocculation, mitochondrial functions, energy generation and protein folding and stabilization. For all strains, higher transcriptional variability due to fermentation stage was seen in the high nitrogen fermentations. A positive correlation between maximum fermentation rate and the expression of genes involved in stress response was observed. The finding of common genes correlated with both fermentation activity and nitrogen up-take underlies the role of nitrogen on yeast fermentative fitness. The comparative analysis of genes differentially expressed between both fermentation conditions at 12 h, where the main difference was the level of nitrogen available, showed the highest variability amongst strains revealing strain-specific responses. Nevertheless, we were able to identify a small set of genes whose expression profiles can quantitatively assess the common response of the yeast strains to varying nitrogen conditions. The use of three contrasting yeast strains in gene expression analysis prompts the identification of more reliable, accurate and reproducible biomarkers that will facilitate the diagnosis of deficiency of this

  11. A Systemic Analysis of Transcriptomic and Epigenomic Data To Reveal Regulation Patterns for Complex Disease.

    Science.gov (United States)

    Xu, Chao; Zhang, Ji-Gang; Lin, Dongdong; Zhang, Lan; Shen, Hui; Deng, Hong-Wen

    2017-07-05

    Integrating diverse genomics data can provide a global view of the complex biological processes related to the human complex diseases. Although substantial efforts have been made to integrate different omics data, there are at least three challenges for multi-omics integration methods: (i) How to simultaneously consider the effects of various genomic factors, since these factors jointly influence the phenotypes; (ii) How to effectively incorporate the information from publicly accessible databases and omics datasets to fully capture the interactions among (epi)genomic factors from diverse omics data; and (iii) Until present, the combination of more than two omics datasets has been poorly explored. Current integration approaches are not sufficient to address all of these challenges together. We proposed a novel integrative analysis framework by incorporating sparse model, multivariate analysis, Gaussian graphical model, and network analysis to address these three challenges simultaneously. Based on this strategy, we performed a systemic analysis for glioblastoma multiforme (GBM) integrating genome-wide gene expression, DNA methylation, and miRNA expression data. We identified three regulatory modules of genomic factors associated with GBM survival time and revealed a global regulatory pattern for GBM by combining the three modules, with respect to the common regulatory factors. Our method can not only identify disease-associated dysregulated genomic factors from different omics, but more importantly, it can incorporate the information from publicly accessible databases and omics datasets to infer a comprehensive interaction map of all these dysregulated genomic factors. Our work represents an innovative approach to enhance our understanding of molecular genomic mechanisms underlying human complex diseases. Copyright © 2017 Xu et al.

  12. Bach Is the Father of Harmony: Revealed by a 1/f Fluctuation Analysis across Musical Genres.

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    Dan Wu

    Full Text Available Harmony is a fundamental attribute of music. Close connections exist between music and mathematics since both pursue harmony and unity. In music, the consonance of notes played simultaneously partly determines our perception of harmony; associates with aesthetic responses; and influences the emotion expression. The consonance could be considered as a window to understand and analyze harmony. Here for the first time we used a 1/f fluctuation analysis to investigate whether the consonance fluctuation structure in music with a wide range of composers and genres followed the scale free pattern that has been found for pitch, melody, rhythm, human body movements, brain activity, natural images and geographical features. We then used a network graph approach to investigate which composers were the most influential both within and across genres. Our results showed that patterns of consonance in music did follow scale-free characteristics, suggesting that this feature is a universally evolved one in both music and the living world. Furthermore, our network analysis revealed that Bach's harmony patterns were having the most influence on those used by other composers, followed closely by Mozart.

  13. Bach Is the Father of Harmony: Revealed by a 1/f Fluctuation Analysis across Musical Genres.

    Science.gov (United States)

    Wu, Dan; Kendrick, Keith M; Levitin, Daniel J; Li, Chaoyi; Yao, Dezhong

    2015-01-01

    Harmony is a fundamental attribute of music. Close connections exist between music and mathematics since both pursue harmony and unity. In music, the consonance of notes played simultaneously partly determines our perception of harmony; associates with aesthetic responses; and influences the emotion expression. The consonance could be considered as a window to understand and analyze harmony. Here for the first time we used a 1/f fluctuation analysis to investigate whether the consonance fluctuation structure in music with a wide range of composers and genres followed the scale free pattern that has been found for pitch, melody, rhythm, human body movements, brain activity, natural images and geographical features. We then used a network graph approach to investigate which composers were the most influential both within and across genres. Our results showed that patterns of consonance in music did follow scale-free characteristics, suggesting that this feature is a universally evolved one in both music and the living world. Furthermore, our network analysis revealed that Bach's harmony patterns were having the most influence on those used by other composers, followed closely by Mozart.

  14. Intestinal transcriptome analysis revealed differential salinity adaptation between two tilapiine species.

    Science.gov (United States)

    Ronkin, Dana; Seroussi, Eyal; Nitzan, Tali; Doron-Faigenboim, Adi; Cnaani, Avner

    2015-03-01

    Tilapias are a group of freshwater species, which vary in their ability to adapt to high salinity water. Osmotic regulation in fish is conducted mainly in the gills, kidney, and gastrointestinal tract (GIT). The mechanisms involved in ion and water transport through the GIT is not well-characterized, with only a few described complexes. Comparing the transcriptome of the anterior and posterior intestinal sections of a freshwater and saltwater adapted fish by deep-sequencing, we examined the salinity adaptation of two tilapia species: the high salinity-tolerant Oreochromis mossambicus (Mozambique tilapia), and the less salinity-tolerant Oreochromis niloticus (Nile tilapia). This comparative analysis revealed high similarity in gene expression response to salinity change between species in the posterior intestine and large differences in the anterior intestine. Furthermore, in the anterior intestine 68 genes were saltwater up-regulated in one species and down-regulated in the other species (47 genes up-regulated in O. niloticus and down-regulated in O. mossambicus, with 21 genes showing the reverse pattern). Gene ontology (GO) analysis showed a high proportion of transporter and ion channel function among these genes. The results of this study point to a group of genes that differed in their salinity-dependent regulation pattern in the anterior intestine as potentially having a role in the differential salinity tolerance of these two closely related species. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Comparative Transcriptome Analysis Reveals Different Silk Yields of Two Silkworm Strains.

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    Juan Li

    Full Text Available Cocoon and silk yields are the most important characteristics of sericulture. However, few studies have examined the genes that modulate these features. Further studies of these genes will be useful for improving the products of sericulture. JingSong (JS and Lan10 (L10 are two strains having significantly different cocoon and silk yields. In the current study, RNA-Seq and quantitative polymerase chain reaction (qPCR were performed on both strains in order to determine divergence of the silk gland, which controls silk biosynthesis in silkworms. Compared with L10, JS had 1375 differentially expressed genes (DEGs; 738 up-regulated genes and 673 down-regulated genes. Nine enriched gene ontology (GO terms were identified by GO enrichment analysis based on these DEGs. KEGG enrichment analysis results showed that the DEGs were enriched in three pathways, which were mainly associated with the processing and biosynthesis of proteins. The representative genes in the enrichment pathways and ten significant DEGs were further verified by qPCR, the results of which were consistent with the RNA-Seq data. Our study has revealed differences in silk glands between the two silkworm strains and provides a perspective for understanding the molecular mechanisms determining silk yield.

  16. Social phenotype extended to communities: expanded multilevel social selection analysis reveals fitness consequences of interspecific interactions.

    Science.gov (United States)

    Campobello, Daniela; Hare, James F; Sarà, Maurizio

    2015-04-01

    In social species, fitness consequences are associated with both individual and social phenotypes. Social selection analysis has quantified the contribution of conspecific social traits to individual fitness. There has been no attempt, however, to apply a social selection approach to quantify the fitness implications of heterospecific social phenotypes. Here, we propose a novel social selection based approach integrating the role of all social interactions at the community level. We extended multilevel selection analysis by including a term accounting for the group phenotype of heterospecifics. We analyzed nest activity as a model social trait common to two species, the lesser kestrel (Falco naumanni) and jackdaw (Corvus monedula), nesting in either single- or mixed-species colonies. By recording reproductive outcome as a measure of relative fitness, our results reveal an asymmetric system wherein only jackdaw breeding performance was affected by the activity phenotypes of both conspecific and heterospecific neighbors. Our model incorporating heterospecific social phenotypes is applicable to animal communities where interacting species share a common social trait, thus allowing an assessment of the selection pressure imposed by interspecific interactions in nature. Finally, we discuss the potential role of ecological limitations accounting for random or preferential assortments among interspecific social phenotypes, and the implications of such processes to community evolution. © 2015 The Author(s).

  17. Proteomic Analysis of a Novel Bacillus Jumbo Phage Revealing Glycoside Hydrolase As Structural Component.

    Science.gov (United States)

    Yuan, Yihui; Gao, Meiying

    2016-01-01

    Tailed phages with genomes of larger than 200 kbp are classified as Jumbo phages and exhibited extremely high uncharted diversity. The genomic annotation of Jumbo phage is often disappointing because most of the predicted proteins, including structural proteins, failed to make good hits to the sequences in the databases. In this study, 23 proteins of a novel Bacillus Jumbo phage, vB_BpuM_BpSp, were identified as phage structural proteins by the structural proteome analysis, including 14 proteins of unknown function, 5 proteins with predicted function as structural proteins, a glycoside hydrolase, a Holliday junction resolvase, a RNA-polymerase β-subunit, and a host-coding portal protein, which might be hijacked from the host strain during phage virion assembly. The glycoside hydrolase (Gp255) was identified as phage virion component and was found to interact with the phage baseplate protein. Gp255 shows specific lytic activity against the phage host strain GR8 and has high temperature tolerance. In situ peptidoglycan-hydrolyzing activities analysis revealed that the expressed Gp255 and phage structural proteome exhibited glycoside hydrolysis activity against the tested GR8 cell extracts. This study identified the first functional individual structural glycoside hydrolase in phage virion. The presence of activated glycoside hydrolase in phage virions might facilitate the injection of the phage genome during infection by forming pores on the bacterial cell wall.

  18. Heterogeneity of large macromolecular complexes revealed by 3-D cryo-EM variance analysis

    Science.gov (United States)

    Zhang, Wei; Kimmel, Marek; Spahn, Christian M.T.; Penczek, Pawel A.

    2008-01-01

    Macromolecular structure determination by cryo-electron microscopy (EM) and single particle analysis are based on the assumption that imaged molecules have identical structure. With the increased size of processed datasets it becomes apparent that many complexes coexist in a mixture of conformational states or contain flexible regions. As the cryo-EM data is collected in form of projections of imaged molecules, the information about variability of reconstructed density maps is not directly available. To address this problem, we describe a new implementation of the bootstrap resampling technique that yields estimates of voxel-by-voxel variance of a structure reconstructed from the set of its projections. We introduced a novel highly efficient reconstruction algorithm that is based on direct Fourier inversion and which incorporates correction for the transfer function of the microscope, thus extending the resolution limits of variance estimation. We also describe a validation method to determine the number of resampled volumes required to achieve stable estimate of the variance. The proposed bootstrap method was applied to a dataset of 70S ribosome complexed with tRNA and the elongation factor G. The variance map revealed regions of high variability: the L1 protein, the EF-G and the 30S head and the ratchet-like subunit rearrangement. The proposed method of variance estimation opens new possibilities for single particle analysis, by extending applicability of the technique to heterogeneous datasets of macromolecules, and to complexes with significant conformational variability. PMID:19081053

  19. Pan-genome analysis of Clostridium botulinum reveals unique targets for drug development.

    Science.gov (United States)

    Bhardwaj, Tulika; Somvanshi, Pallavi

    2017-08-05

    Clostridium botulinum, a formidable pathogen is responsible for the emerging cause of food poisoning cases on the global canvas. The endemicity of bacterium Clostridium botulinum is reflected by the sudden hospital outbreaks and increased resistance towards multiple drugs. Therefore, a combined approach of in-silico comparative genomic analysis with statistical analysis was applied to overcome the limitation of bench-top technologies. Owing to the paucity of genomic data available by the advent of third generation sequencing technologies, several 'omics' technologies were applied to understand the underlying evolutionary pattern and lifestyle of the bacterial pathogen using phylogenomics. The calculation of pan-genome, core genome and singletons provides view of genetic repertoire of the bacterial pathogen lineage at the successive level, orthology shared and specific gene subsets. In addition, assessment of pathogenomic potential, resistome, toxin/antitoxin family in successive pathogenic strains of Clostridium botulinum aids in revealing more specific targets for drug design and development. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Early Development of Functional Network Segregation Revealed by Connectomic Analysis of the Preterm Human Brain.

    Science.gov (United States)

    Cao, Miao; He, Yong; Dai, Zhengjia; Liao, Xuhong; Jeon, Tina; Ouyang, Minhui; Chalak, Lina; Bi, Yanchao; Rollins, Nancy; Dong, Qi; Huang, Hao

    2017-03-01

    Human brain functional networks are topologically organized with nontrivial connectivity characteristics such as small-worldness and densely linked hubs to support highly segregated and integrated information processing. However, how they emerge and change at very early developmental phases remains poorly understood. Here, we used resting-state functional MRI and voxel-based graph theory analysis to systematically investigate the topological organization of whole-brain networks in 40 infants aged around 31 to 42 postmenstrual weeks. The functional connectivity strength and heterogeneity increased significantly in primary motor, somatosensory, visual, and auditory regions, but much less in high-order default-mode and executive-control regions. The hub and rich-club structures in primary regions were already present at around 31 postmenstrual weeks and exhibited remarkable expansions with age, accompanied by increased local clustering and shortest path length, indicating a transition from a relatively random to a more organized configuration. Moreover, multivariate pattern analysis using support vector regression revealed that individual brain maturity of preterm babies could be predicted by the network connectivity patterns. Collectively, we highlighted a gradually enhanced functional network segregation manner in the third trimester, which is primarily driven by the rapid increases of functional connectivity of the primary regions, providing crucial insights into the topological development patterns prior to birth. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Comparative functional genomic analysis of two Vibrio phages reveals complex metabolic interactions with the host cell

    Directory of Open Access Journals (Sweden)

    Dimitrios Skliros

    2016-11-01

    Full Text Available Sequencing and annotation was performed for two giant double stranded DNA bacteriophages, φGrn1 and φSt2 of the Myoviridae family, considered to be of great interest for phage therapy against Vibrios in aquaculture live feeds. In addition, phage-host metabolic interactions and exploitation was studied by transcript profiling of selected viral and host genes. Comparative genomic analysis with other giant Vibrio phages was also performed to establish the presence and location of homing endonucleases highlighting distinct features for both phages. Phylogenetic analysis revealed that they belong to the schizoT4like clade. Although many reports of newly sequenced viruses have provided a large set of information, basic research related to the shift of the bacterial metabolism during infection remains stagnant. The function of many viral protein products in the process of infection is still unknown. Genome annotation identified the presence of several viral ORFs participating in metabolism, including a Sir2/cobB (sirtuin protein and a number of genes involved in auxiliary NAD+ and nucleotide biosynthesis, necessary for phage DNA replication. Key genes were subsequently selected for detail study of their expression levels during infection. This work suggests a complex metabolic interaction and exploitation of the host metabolic pathways and biochemical processes, including a possible post-translational protein modification, by the virus during infection.

  2. Metagenomic analysis reveals that bacteriophages are reservoirs of antibiotic resistance genes.

    Science.gov (United States)

    Subirats, Jéssica; Sànchez-Melsió, Alexandre; Borrego, Carles M; Balcázar, José Luis; Simonet, Pascal

    2016-08-01

    A metagenomics approach was applied to explore the presence of antibiotic resistance genes (ARGs) in bacteriophages from hospital wastewater. Metagenomic analysis showed that most phage sequences affiliated to the order Caudovirales, comprising the tailed phage families Podoviridae, Siphoviridae and Myoviridae. Moreover, the relative abundance of ARGs in the phage DNA fraction (0.26%) was higher than in the bacterial DNA fraction (0.18%). These differences were particularly evident for genes encoding ATP-binding cassette (ABC) and resistance-nodulation-cell division (RND) proteins, phosphotransferases, β-lactamases and plasmid-mediated quinolone resistance. Analysis of assembled contigs also revealed that blaOXA-10, blaOXA-58 and blaOXA-24 genes belonging to class D β-lactamases as well as a novel blaTEM (98.9% sequence similarity to the blaTEM-1 gene) belonging to class A β-lactamases were detected in a higher proportion in phage DNA. Although preliminary, these findings corroborate the role of bacteriophages as reservoirs of resistance genes and thus highlight the necessity to include them in future studies on the emergence and spread of antibiotic resistance in the environment. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  3. Genetic analysis of hyperemesis gravidarum reveals association with intracellular calcium release channel (RYR2).

    Science.gov (United States)

    Fejzo, Marlena Schoenberg; Myhre, Ronny; Colodro-Conde, Lucía; MacGibbon, Kimber W; Sinsheimer, Janet S; Reddy, M V Prasad Linga; Pajukanta, Päivi; Nyholt, Dale R; Wright, Margaret J; Martin, Nicholas G; Engel, Stephanie M; Medland, Sarah E; Magnus, Per; Mullin, Patrick M

    2017-01-05

    Hyperemesis Gravidarum (HG), severe nausea/vomiting in pregnancy (NVP), can cause poor maternal/fetal outcomes. Genetic predisposition suggests the genetic component is essential in discovering an etiology. We performed whole-exome sequencing of 5 families followed by analysis of variants in 584 cases/431 controls. Variants in RYR2 segregated with disease in 2 families. The novel variant L3277R was not found in any case/control. The rare variant, G1886S was more common in cases (p = 0.046) and extreme cases (p = 0.023). Replication of G1886S using Norwegian/Australian data was supportive. Common variants rs790899 and rs1891246 were significantly associated with HG and weight loss. Copy-number analysis revealed a deletion in a patient. RYR2 encodes an intracellular calcium release channel involved in vomiting, cyclic-vomiting syndrome, and is a thyroid hormone target gene. Additionally, RYR2 is a downstream drug target of Inderal, used to treat HG and CVS. Thus, herein we provide genetic evidence for a pathway and therapy for HG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Proteomic analysis reveals the diversity and complexity of membrane proteins in chickpea (Cicer arietinum L.

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    Jaiswal Dinesh Kumar

    2012-10-01

    Full Text Available Abstract Background Compartmentalization is a unique feature of eukaryotes that helps in maintaining cellular homeostasis not only in intra- and inter-organellar context, but also between the cells and the external environment. Plant cells are highly compartmentalized with a complex metabolic network governing various cellular events. The membranes are the most important constituents in such compartmentalization, and membrane-associated proteins play diverse roles in many cellular processes besides being part of integral component of many signaling cascades. Results To obtain valuable insight into the dynamic repertoire of membrane proteins, we have developed a proteome reference map of a grain legume, chickpea, using two-dimensional gel electrophoresis. MALDI-TOF/TOF and LC-ESI-MS/MS analysis led to the identification of 91 proteins involved in a variety of cellular functions viz., bioenergy, stress-responsive and signal transduction, metabolism, protein synthesis and degradation, among others. Significantly, 70% of the identified proteins are putative integral membrane proteins, possessing transmembrane domains. Conclusions The proteomic analysis revealed many resident integral membrane proteins as well as membrane-associated proteins including those not reported earlier. To our knowledge, this is the first report of membrane proteome from aerial tissues of a crop plant. The findings may provide a better understanding of the biochemical machinery of the plant membranes at the molecular level that might help in functional genomics studies of different developmental pathways and stress-responses.

  5. Proteome analysis of schizophrenia patients Wernicke's area reveals an energy metabolism dysregulation

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    Marangoni Sérgio

    2009-04-01

    Full Text Available Abstract Background Schizophrenia is likely to be a consequence of DNA alterations that, together with environmental factors, will lead to protein expression differences and the ultimate establishment of the illness. The superior temporal gyrus is implicated in schizophrenia and executes functions such as the processing of speech, language skills and sound processing. Methods We performed an individual comparative proteome analysis using two-dimensional gel electrophoresis of 9 schizophrenia and 6 healthy control patients' left posterior superior temporal gyrus (Wernicke's area – BA22p identifying by mass spectrometry several protein expression alterations that could be related to the disease. Results Our analysis revealed 11 downregulated and 14 upregulated proteins, most of them related to energy metabolism. Whereas many of the identified proteins have been previously implicated in schizophrenia, such as fructose-bisphosphate aldolase C, creatine kinase and neuron-specific enolase, new putative disease markers were also identified such as dihydrolipoyl dehydrogenase, tropomyosin 3, breast cancer metastasis-suppressor 1, heterogeneous nuclear ribonucleoproteins C1/C2 and phosphate carrier protein, mitochondrial precursor. Besides, the differential expression of peroxiredoxin 6 (PRDX6 and glial fibrillary acidic protein (GFAP were confirmed by western blot in schizophrenia prefrontal cortex. Conclusion Our data supports a dysregulation of energy metabolism in schizophrenia as well as suggests new markers that may contribute to a better understanding of this complex disease.

  6. Comparative Genomic Analysis of Lactococcus garvieae Strains Isolated from Different Sources Reveals Candidate Virulence Genes

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    Eiji Miyauchi

    2012-01-01

    Full Text Available Lactococcus garvieae is a major pathogen for fish. Two complete (ATCC 49156 and Lg2 and three draft (UNIUD074, 8831, and 21881 genome sequences of L. garvieae have recently been released. We here present the results of a comparative genomic analysis of these fish and human isolates of L. garvieae. The pangenome comprised 1,542 core and 1,378 dispensable genes. The sequenced L. garvieae strains shared most of the possible virulence genes, but the capsule gene cluster was found only in fish-pathogenic strain Lg2. The absence of the capsule gene cluster in other nonpathogenic strains isolated from mastitis and vegetable was also confirmed by PCR. The fish and human isolates of L. garvieae contained the specific two and four adhesin genes, respectively, indicating that these adhesion proteins may be involved in the host specificity differences of L. garvieae. The discoveries revealed by the pangenomic analysis may provide significant insights into the biology of L. garvieae.

  7. Dynamic allostery in the methionine repressor revealed by force distribution analysis.

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    Wolfram Stacklies

    2009-11-01

    Full Text Available Many fundamental cellular processes such as gene expression are tightly regulated by protein allostery. Allosteric signal propagation from the regulatory to the active site requires long-range communication, the molecular mechanism of which remains a matter of debate. A classical example for long-range allostery is the activation of the methionine repressor MetJ, a transcription factor. Binding of its co-repressor SAM increases its affinity for DNA several-fold, but has no visible conformational effect on its DNA binding interface. Our molecular dynamics simulations indicate correlated domain motions within MetJ, and quenching of these dynamics upon SAM binding entropically favors DNA binding. From monitoring conformational fluctuations alone, it is not obvious how the presence of SAM is communicated through the largely rigid core of MetJ and how SAM thereby is able to regulate MetJ dynamics. We here directly monitored the propagation of internal forces through the MetJ structure, instead of relying on conformational changes as conventionally done. Our force distribution analysis successfully revealed the molecular network for strain propagation, which connects collective domain motions through the protein core. Parts of the network are directly affected by SAM binding, giving rise to the observed quenching of fluctuations. Our results are in good agreement with experimental data. The force distribution analysis suggests itself as a valuable tool to gain insight into the molecular function of a whole class of allosteric proteins.

  8. Comprehensive Proteomics Analysis of Laticifer Latex Reveals New Insights into Ethylene Stimulation of Natural Rubber Production.

    Science.gov (United States)

    Wang, Xuchu; Wang, Dan; Sun, Yong; Yang, Qian; Chang, Lili; Wang, Limin; Meng, Xueru; Huang, Qixing; Jin, Xiang; Tong, Zheng

    2015-09-08

    Ethylene is a stimulant to increase natural rubber latex. After ethylene application, both fresh yield and dry matter of latex are substantially improved. Moreover, we found that ethylene improves the generation of small rubber particles. However, most genes involved in rubber biosynthesis are inhibited by exogenous ethylene. Therefore, we conducted a proteomics analysis of ethylene-stimulated rubber latex, and identified 287 abundant proteins as well as 143 ethylene responsive latex proteins (ERLPs) with mass spectrometry from the 2-DE and DIGE gels, respectively. In addition, more than 1,600 proteins, including 404 ERLPs, were identified by iTRAQ. Functional classification of ERLPs revealed that enzymes involved in post-translational modification, carbohydrate metabolism, hydrolase activity, and kinase activity were overrepresented. Some enzymes for rubber particle aggregation were inhibited to prolong latex flow, and thus finally improved latex production. Phosphoproteomics analysis identified 59 differential phosphoproteins; notably, specific isoforms of rubber elongation factor and small rubber particle protein that were phosphorylated mainly at serine residues. This post-translational modification and isoform-specific phosphorylation might be important for ethylene-stimulated latex production. These results not only deepen our understanding of the rubber latex proteome but also provide new insights into the use of ethylene to stimulate rubber latex production.

  9. Large-scale analysis by SAGE reveals new mechanisms of v-erbA oncogene action

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    Faure Claudine

    2007-10-01

    Full Text Available Abstract Background: The v-erbA oncogene, carried by the Avian Erythroblastosis Virus, derives from the c-erbAα proto-oncogene that encodes the nuclear receptor for triiodothyronine (T3R. v-ErbA transforms erythroid progenitors in vitro by blocking their differentiation, supposedly by interference with T3R and RAR (Retinoic Acid Receptor. However, v-ErbA target genes involved in its transforming activity still remain to be identified. Results: By using Serial Analysis of Gene Expression (SAGE, we identified 110 genes deregulated by v-ErbA and potentially implicated in the transformation process. Bioinformatic analysis of promoter sequence and transcriptional assays point out a potential role of c-Myb in the v-ErbA effect. Furthermore, grouping of newly identified target genes by function revealed both expected (chromatin/transcription and unexpected (protein metabolism functions potentially deregulated by v-ErbA. We then focused our study on 15 of the new v-ErbA target genes and demonstrated by real time PCR that in majority their expression was activated neither by T3, nor RA, nor during differentiation. This was unexpected based upon the previously known role of v-ErbA. Conclusion: This paper suggests the involvement of a wealth of new unanticipated mechanisms of v-ErbA action.

  10. Metagenomic analysis reveals wastewater treatment plants as hotspots of antibiotic resistance genes and mobile genetic elements.

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    Guo, Jianhua; Li, Jie; Chen, Hui; Bond, Philip L; Yuan, Zhiguo

    2017-10-15

    The intensive use of antibiotics results in their continuous release into the environment and the subsequent widespread occurrence of antibiotic resistant bacteria (ARB), antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). This study used Illumina high-throughput sequencing to investigate the broad-spectrum profiles of both ARGs and MGEs in activated sludge and anaerobically digested sludge from a full-scale wastewater treatment plant. A pipeline for identifying antibiotic resistance determinants was developed that consisted of four categories: gene transfer potential, ARG potential, ARGs pathway and ARGs phylogenetic origin. The metagenomic analysis showed that the activated sludge and the digested sludge exhibited different microbial communities and changes in the types and occurrence of ARGs and MGEs. In total, 42 ARGs subtypes were identified in the activated sludge, while 51 ARG subtypes were detected in the digested sludge. Additionally, MGEs including plasmids, transposons, integrons (intI1) and insertion sequences (e.g. ISSsp4, ISMsa21 and ISMba16) were abundant in the two sludge samples. The co-occurrence pattern between ARGs and microbial taxa revealed by network analysis indicated that some environmental bacteria (e.g. Clostridium and Nitrosomonas) might be potential hosts of multiple ARGs. The findings increase our understanding of WWTPs as hotspots of ARGs and MGEs, and contribute towards preventing their release into the downstream environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Comparative Transcriptome Analysis Reveals Different Silk Yields of Two Silkworm Strains.

    Science.gov (United States)

    Li, Juan; Qin, Sheng; Yu, Huanjun; Zhang, Jing; Liu, Na; Yu, Ye; Hou, Chengxiang; Li, Muwang

    2016-01-01

    Cocoon and silk yields are the most important characteristics of sericulture. However, few studies have examined the genes that modulate these features. Further studies of these genes will be useful for improving the products of sericulture. JingSong (JS) and Lan10 (L10) are two strains having significantly different cocoon and silk yields. In the current study, RNA-Seq and quantitative polymerase chain reaction (qPCR) were performed on both strains in order to determine divergence of the silk gland, which controls silk biosynthesis in silkworms. Compared with L10, JS had 1375 differentially expressed genes (DEGs; 738 up-regulated genes and 673 down-regulated genes). Nine enriched gene ontology (GO) terms were identified by GO enrichment analysis based on these DEGs. KEGG enrichment analysis results showed that the DEGs were enriched in three pathways, which were mainly associated with the processing and biosynthesis of proteins. The representative genes in the enrichment pathways and ten significant DEGs were further verified by qPCR, the results of which were consistent with the RNA-Seq data. Our study has revealed differences in silk glands between the two silkworm strains and provides a perspective for understanding the molecular mechanisms determining silk yield.

  12. Sweet Potato Value Chain Analysis Reveals Opportunities for Increased Income and Food Security in Northern Ghana

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    Issah Sugri

    2017-01-01

    Full Text Available Sweet potato has gained prominence due to its ability to adapt to wide production ecologies and yield response to minimal external inputs. Orange-fleshed cultivars in particular have immense potential to improve household income and nutrition in sub-Saharan Africa. However, the sweet potato value chain (SPVC is not well-developed in many producing countries. The study was conducted in two regions to characterize the production operations as well as identify opportunities to propel the SPVC in Northern Ghana. Data were collected using mixed methods including structured questionnaires via face-to-face interviews. Analysis of strengths, weaknesses, opportunities, and threats (SWOT was conducted at multistakeholder platforms with different actors. Gross margin profit and benefit-cost ratios were determined by using six cost variables. Overall, the industry was largely a fresh produce market, targeting food vendors, processors, and direct selling to wholesalers, retailers, and household consumers. The SWOT analysis revealed wide-ranging opportunities including favourable production ecologies, processing options, and insatiable local and international markets. The institutional actors need to network the primary actors to synergistically operate with a collective profit motive. The most prioritized production constraints such as access to seed, cost of chemical fertilizer, short shelf-life, field pests and diseases, and declining soil fertility should be addressed.

  13. Metagenomic analysis reveals symbiotic relationship among bacteria in Microcystis-dominated community

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    Meili eXie

    2016-02-01

    Full Text Available Microcystis bloom, a cyanobacterial mass occurrence often found in eutrophicated water bodies, is one of the most serious threats to freshwater ecosystems worldwide. In nature, Microcystis forms aggregates or colonies that contain heterotrophic bacteria. The Microcystis-bacteria colonies were persistent even when they were maintained in lab culture for a long period. The relationship between Microcystis and the associated bacteria was investigated by a metagenomic approach in this study. We developed a visualization-guided method of binning for genome assembly after total colony DNA sequencing. We found that the method was effective in grouping sequences and it did not require reference genome sequence. Individual genomes of the colony bacteria were obtained and they provided valuable insights into microbial community structures. Analysis of metabolic pathways based on these genomes revealed that while all heterotrophic bacteria were dependent upon Microcystis for carbon and energy, Vitamin B12 biosynthesis, which is required for growth by Microcystis, was accomplished in a cooperative fashion among the bacteria. Our analysis also suggests that individual bacteria in the colony community contributed a complete pathway for degradation of benzoate, which is inhibitory to the cyanobacterial growth, and its ecological implication for Microcystis bloom is discussed.

  14. Critical genes of hepatocellular carcinoma revealed by network and module analysis of RNA-seq data.

    Science.gov (United States)

    Yang, M-R; Zhang, Y; Wu, X-X; Chen, W

    2016-10-01

    RNA-seq data of hepatocellular carcinoma (HCC) was analyzed to identify critical genes related to the pathogenesis and prognosis. Three RNA-seq datasets of HCC (GSE69164, GSE63863 and GSE55758) were downloaded from Gene Expression Omnibus (GEO), while another dataset including 54 HCC cases with survival time was obtained from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) were identified by significant analysis of microarrays (SAM) method using package samr of R. As followed, we constructed a protein-protein interaction (PPI) network based on the information in Human Protein Reference Database (HPRD). Modules in the PPI network were identified with MCODE method using plugin clusterViz of CytoScape. Gene Ontology (GO) enrichment analysis and pathway enrichment analysis were performed with DAVID. The difference in survival curves was analyzed with Kaplan-Meier (K-M) method using package survival. A total of 2572 DEGs were identified in the 3 datasets from GEO (GSE69164, GSE63863 and GSE55758). The PPI network was constructed including 660 nodes and 1008 edges, and 4 modules were disclosed in the network. Module A (containing 244 DEGs) was found to related to HCC closely, which genes were involved in transcription factor binding, protein metabolism as well as regulation of apoptosis. Nine hub genes were identified in the module A, including PRKCA, YWHAZ, KRT18, NDRG1, HSPA1A, HSP90AA1, HSF1, IKGKB and UBE21. The network provides the protein-protein interaction of these critical genes, which were implicated in the pathogenesis of HCC. Survival analysis showed that there is a significant difference between two groups classified by the genes in module A. Further Univariate Cox regression analysis showed that 72 genes were associated with survival time significantly, such as NPM1, PRKDC, SPARC, HMGA1, COL1A1 and COL1A2. Nine critical genes related to the pathogenesis and 72 potential prognostic markers were revealed in HCC by the network and module

  15. Bivariate tensor product ( p , q $(p, q$ -analogue of Kantorovich-type Bernstein-Stancu-Schurer operators

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    Qing-Bo Cai

    2017-11-01

    Full Text Available Abstract In this paper, we construct a bivariate tensor product generalization of Kantorovich-type Bernstein-Stancu-Schurer operators based on the concept of ( p , q $(p, q$ -integers. We obtain moments and central moments of these operators, give the rate of convergence by using the complete modulus of continuity for the bivariate case and estimate a convergence theorem for the Lipschitz continuous functions. We also give some graphs and numerical examples to illustrate the convergence properties of these operators to certain functions.

  16. Bioinformatic analysis of the neprilysin (M13 family of peptidases reveals complex evolutionary and functional relationships

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    Pinney John W

    2008-01-01

    Full Text Available Abstract Background The neprilysin (M13 family of endopeptidases are zinc-metalloenzymes, the majority of which are type II integral membrane proteins. The best characterised of this family is neprilysin, which has important roles in inactivating signalling peptides involved in modulating neuronal activity, blood pressure and the immune system. Other family members include the endothelin converting enzymes (ECE-1 and ECE-2, which are responsible for the final step in the synthesis of potent vasoconstrictor endothelins. The ECEs, as well as neprilysin, are considered valuable therapeutic targets for treating cardiovascular disease. Other members of the M13 family have not been functionally characterised, but are also likely to have biological roles regulating peptide signalling. The recent sequencing of animal genomes has greatly increased the number of M13 family members in protein databases, information which can be used to reveal evolutionary relationships and to gain insight into conserved biological roles. Results The phylogenetic analysis successfully resolved vertebrate M13 peptidases into seven classes, one of which appears to be specific to mammals, and insect genes into five functional classes and a series of expansions, which may include inactive peptidases. Nematode genes primarily resolved into groups containing no other taxa, bar the two nematode genes associated with Drosophila DmeNEP1 and DmeNEP4. This analysis reconstructed only one relationship between chordate and invertebrate clusters, that of the ECE sub-group and the DmeNEP3 related genes. Analysis of amino acid utilisation in the active site of M13 peptidases reveals a basis for their biochemical properties. A relatively invariant S1' subsite gives the majority of M13 peptidases their strong preference for hydrophobic residues in P1' position. The greater variation in the S2' subsite may be instrumental in determining the specificity of M13 peptidases for their substrates

  17. Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails.

    Science.gov (United States)

    Mu, Huawei; Sun, Jin; Cheung, Siu Gin; Fang, Ling; Zhou, Haiyun; Luan, Tiangang; Zhang, Huoming; Wong, Chris K C; Qiu, Jian-Wen

    2018-02-10

    Although high-throughput proteomics has been widely applied to study mechanisms of environmental adaptation, the conclusions from studies that are based on one species can be confounded by phylogeny. We compare the freshwater snail Pomacea canaliculata (a notorious invasive species) and its congener Pomacea diffusa (a non-invasive species) to understand the molecular mechanisms of their differential resistance to hypoxia. A 72-h acute exposure experiment showed that P. canaliculata is more tolerant to hypoxia than P. diffusa. The two species were then exposed to three levels of dissolved oxygen (6.7, 2.0 and 1.0mgL -1 ) for 8h, and their gill proteins were analyzed using iTRAQ-coupled LC-MS/MS. The two species showed striking differences in protein expression profiles, with the more hypoxia tolerant P. canaliculata having more up-regulated proteins in signal transduction and down-regulated proteins in glycolysis and the tricarboxylic acid cycle. Evolutionary analysis revealed five orthologous genes encoding differentially expressed proteins having clear signal of positive selection, indicating selection has acted on some of the hypoxia responsive genes. Our case study has highlighted the potential of integrated proteomics and comparative evolutionary analysis for understanding the genetic basis of adaptation to global environmental change in non-model species. Rapid globalization in recent decades has greatly facilitated species introduction around the world. Successfully established introduced species, so-called invasive species, have threatened the invaded ecosystems. There has been substantial interest in studying how invasive species respond to extreme environmental conditions because the results can help not only predict their range of expansion and manage their impact, but also may reveal the adaptive mechanisms underlying their invasiveness. Our study has adopted a comparative approach to study the differential physiological and proteomic responses of two

  18. Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails

    KAUST Repository

    Mu, Huawei

    2017-11-06

    Although high-throughput proteomics has been widely applied to study mechanisms of environmental adaptation, the conclusions from studies that are based on one species can be confounded by phylogeny. We compare the freshwater snail Pomacea canaliculata (a notorious invasive species) and its congener Pomacea diffusa (a non-invasive species) to understand the molecular mechanisms of their differential resistance to hypoxia. A 72-h acute exposure experiment showed that P. canaliculata is more tolerant to hypoxia than P. diffusa. The two species were then exposed to three levels of dissolved oxygen (6.7, 2.0 and 1.0mgL−1) for 8h, and their gill proteins were analyzed using iTRAQ-coupled LC-MS/MS. The two species showed striking differences in protein expression profiles, with the more hypoxia tolerant P. canaliculata having more up-regulated proteins in signal transduction and down-regulated proteins in glycolysis and the tricarboxylic acid cycle. Evolutionary analysis revealed five orthologous genes encoding differentially expressed proteins having clear signal of positive selection, indicating selection has acted on some of the hypoxia responsive genes. Our case study has highlighted the potential of integrated proteomics and comparative evolutionary analysis for understanding the genetic basis of adaptation to global environmental change in non-model species. SignificanceRapid globalization in recent decades has greatly facilitated species introduction around the world. Successfully established introduced species, so-called invasive species, have threatened the invaded ecosystems. There has been substantial interest in studying how invasive species respond to extreme environmental conditions because the results can help not only predict their range of expansion and manage their impact, but also may reveal the adaptive mechanisms underlying their invasiveness. Our study has adopted a comparative approach to study the differential physiological and proteomic

  19. Bioinformatics analysis of RNA-seq data revealed critical genes in colon adenocarcinoma.

    Science.gov (United States)

    Xi, W-D; Liu, Y-J; Sun, X-B; Shan, J; Yi, L; Zhang, T-T

    2017-07-01

    RNA-seq data of colon adenocarcinoma (COAD) were analyzed with bioinformatics tools to discover critical genes in the disease. Relevant small molecule drugs, transcription factors (TFs) and microRNAs (miRNAs) were also investigated. RNA-seq data of COAD were downloaded from The Cancer Genome Atlas (TCGA). Differential analysis was performed with package edgeR. False positive discovery (FDR) 1 were set as the cut-offs to screen out differentially expressed genes (DEGs). Gene coexpression network was constructed with package Ebcoexpress. GO enrichment analysis was performed for the DEGs in the gene coexpression network with DAVID. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was also performed for the genes with KOBASS 2.0. Modules were identified with MCODE of Cytoscape. Relevant small molecules drugs were predicted by Connectivity map. Relevant miRNAs and TFs were searched by WebGestalt. A total of 457 DEGs, including 255 up-regulated and 202 down-regulated genes, were identified from 437 COAD and 39 control samples. A gene coexpression network was constructed containing 40 DEGs and 101 edges. The genes were mainly associated with collagen fibril organization, extracellular matrix organization and translation. Two modules were identified from the gene coexpression network, which were implicated in muscle contraction and extracellular matrix organization, respectively. Several critical genes were disclosed, such as MYH11, COL5A2 and ribosomal proteins. Nine relevant small molecule drugs were identified, such as scriptaid and STOCK1N-35874. Accordingly, a total of 17 TFs and 10 miRNAs related to COAD were acquired, such as ETS2, NFAT, AP4, miR-124A, MiR-9, miR-96 and let-7. Several critical genes and relevant drugs, TFs and miRNAs were revealed in COAD. These findings could advance the understanding of the disease and benefit therapy development.

  20. Transcriptional regulation of rod photoreceptor homeostasis revealed by in vivo NRL targetome analysis.

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    Hong Hao

    Full Text Available A stringent control of homeostasis is critical for functional maintenance and survival of neurons. In the mammalian retina, the basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate and activates the expression of many rod-specific genes. Here, we report an integrated analysis of NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq data from Illumina and ABI platforms with global expression profiling and in vivo knockdown studies. We identified approximately 300 direct NRL target genes. Of these, 22 NRL targets are associated with human retinal dystrophies, whereas 95 mapped to regions of as yet uncloned retinal disease loci. In silico analysis of NRL ChIP-Seq peak sequences revealed an enrichment of distinct sets of transcription factor binding sites. Specifically, we discovered that genes involved in photoreceptor function include binding sites for both NRL and homeodomain protein CRX. Evaluation of 26 ChIP-Seq regions validated their enhancer functions in reporter assays. In vivo knockdown of 16 NRL target genes resulted in death or abnormal morphology of rod photoreceptors, suggesting their importance in maintaining retinal function. We also identified histone demethylase Kdm5b as a novel secondary node in NRL transcriptional hierarchy. Exon array analysis of flow-sorted photoreceptors in which Kdm5b was knocked down by shRNA indicated its role in regulating rod-expressed genes. Our studies identify candidate genes for retinal dystrophies, define cis-regulatory module(s for photoreceptor-expressed genes and provide a framework for decoding transcriptional regulatory networks that dictate rod homeostasis.

  1. Single-base methylome analysis reveals dynamic epigenomic differences associated with water deficit in apple.

    Science.gov (United States)

    Xu, Jidi; Zhou, Shasha; Gong, Xiaoqing; Song, Yi; van Nocker, Steve; Ma, Fengwang; Guan, Qingmei

    2018-02-01

    Cytosine methylation is an essential feature of epigenetic regulation and is involved in various biological processes. Although cytosine methylation has been analysed at the genomic scale for several plant species, there is a general lack of understanding of the dynamics of global and genic DNA methylation in plants growing in environments challenged with biotic and abiotic stresses. In this study, we mapped cytosine methylation at single-base resolution in the genome of commercial apple (Malus x domestica), and analysed changes in methylation patterns associated with water deficit in representative drought-sensitive and drought-tolerant cultivars. We found that the apple genome exhibits ~54%, ~38% and ~8.5% methylation at CG, CHG and CHH sequence contexts, respectively. We additionally documented changes in gene expression associated with water deficit in an attempt to link methylation and gene expression changes. Global methylation and transcription analysis revealed that promoter-unmethylated genes showed higher expression levels than promoter-methylated genes. Gene body methylation appears to be positively correlated with gene expression. Water deficit stress was associated with changes in methylation at a multitude of genes, including those encoding transcription factors (TFs) and transposable elements (TEs). These results present a methylome map of the apple genome and reveal widespread DNA methylation alterations in response to water deficit stress. These data will be helpful for understanding potential linkages between DNA methylation and gene expression in plants growing in natural environments and challenged with abiotic and biotic stresses. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  2. Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes.

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    Peter Hevezi

    Full Text Available Efforts to unravel the mechanisms underlying taste sensation (gustation have largely focused on rodents. Here we present the first comprehensive characterization of gene expression in primate taste buds. Our findings reveal unique new insights into the biology of taste buds. We generated a taste bud gene expression database using laser capture microdissection (LCM procured fungiform (FG and circumvallate (CV taste buds from primates. We also used LCM to collect the top and bottom portions of CV taste buds. Affymetrix genome wide arrays were used to analyze gene expression in all samples. Known taste receptors are preferentially expressed in the top portion of taste buds. Genes associated with the cell cycle and stem cells are preferentially expressed in the bottom portion of taste buds, suggesting that precursor cells are located there. Several chemokines including CXCL14 and CXCL8 are among the highest expressed genes in taste buds, indicating that immune system related processes are active in taste buds. Several genes expressed specifically in endocrine glands including growth hormone releasing hormone and its receptor are also strongly expressed in taste buds, suggesting a link between metabolism and taste. Cell type-specific expression of transcription factors and signaling molecules involved in cell fate, including KIT, reveals the taste bud as an active site of cell regeneration, differentiation, and development. IKBKAP, a gene mutated in familial dysautonomia, a disease that results in loss of taste buds, is expressed in taste cells that communicate with afferent nerve fibers via synaptic transmission. This database highlights the power of LCM coupled with transcriptional profiling to dissect the molecular composition of normal tissues, represents the most comprehensive molecular analysis of primate taste buds to date, and provides a foundation for further studies in diverse aspects of taste biology.

  3. Three-dimensional Crustal Structure beneath the Tibetan Plateau Revealed by Multi-scale Gravity Analysis

    Science.gov (United States)

    Xu, C.; Luo, Z.; Sun, R.; Li, Q.

    2017-12-01

    The Tibetan Plateau, the largest and highest plateau on Earth, was uplifted, shorten and thicken by the collision and continuous convergence of the Indian and Eurasian plates since 50 million years ago, the Eocene epoch. Fine three-dimensional crustal structure of the Tibetan Plateau is helpful in understanding the tectonic development. At present, the ordinary method used for revealing crustal structure is seismic method, which is inhibited by poor seismic station coverage, especially in the central and western plateau primarily due to the rugged terrain. Fortunately, with the implementation of satellite gravity missions, gravity field models have demonstrated unprecedented global-scale accuracy and spatial resolution, which can subsequently be employed to study the crustal structure of the entire Tibetan Plateau. This study inverts three-dimensional crustal density and Moho topography of the Tibetan Plateau from gravity data using multi-scale gravity analysis. The inverted results are in agreement with those provided by the previous works. Besides, they can reveal rich tectonic development of the Tibetan Plateau: (1) The low-density channel flow can be observed from the inverted crustal density; (2) The Moho depth in the west is deeper than that in the east, and the deepest Moho, which is approximately 77 km, is located beneath the western Qiangtang Block; (3) The Moho fold, the directions of which are in agreement with the results of surface movement velocities estimated from Global Positioning System, exists clearly on the Moho topography.This study is supported by the National Natural Science Foundation of China (Grant No. 41504015), the China Postdoctoral Science Foundation (Grant No. 2015M572146), and the Surveying and Mapping Basic Research Programme of the National Administration of Surveying, Mapping and Geoinformation (Grant No. 15-01-08).

  4. Analysis of SSH library of rice variety Aganni reveals candidate gall midge resistance genes.

    Science.gov (United States)

    Divya, Dhanasekar; Singh, Y Tunginba; Nair, Suresh; Bentur, J S

    2016-03-01

    The Asian rice gall midge, Orseolia oryzae, is a serious insect pest causing extensive yield loss. Interaction between the gall midge and rice genotypes is known to be on a gene-for-gene basis. Here, we report molecular basis of HR- (hypersensitive reaction-negative) type of resistance in Aganni (an indica rice variety possessing gall midge resistance gene Gm8) through the construction and analysis of a suppressive subtraction hybridization (SSH) cDNA library. In all, 2,800 positive clones were sequenced and analyzed. The high-quality ESTs were assembled into 448 non-redundant gene sequences. Homology search with the NCBI databases, using BlastX and BlastN, revealed that 73% of the clones showed homology to genes with known function and majority of ESTs belonged to the gene ontology category 'biological process'. Validation of 27 putative candidate gall midge resistance genes through real-time PCR, following gall midge infestation, in contrasting parents and their derived pre-NILs (near isogenic lines) revealed induction of specific genes related to defense and metabolism. Interestingly, four genes, belonging to families of leucine-rich repeat (LRR), heat shock protein (HSP), pathogenesis related protein (PR), and NAC domain-containing protein, implicated in conferring HR+ type of resistance, were found to be up-regulated in Aganni. Two of the reactive oxygen intermediates (ROI)-scavenging-enzyme-coding genes Cytosolic Ascorbate Peroxidase1, 2 (OsAPx1 and OsAPx2) were found up-regulated in Aganni in incompatible interaction possibly suppressing HR. We suggest that Aganni has a deviant form of inducible, salicylic acid (SA)-mediated resistance but without HR.

  5. Genomic analysis of a cardinalfish with larval homing potential reveals genetic admixture in the Okinawa Islands.

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    Gould, A L; Dunlap, P V

    2017-08-01

    Discrepancies between potential and observed dispersal distances of reef fish indicate the need for a better understanding of the influence of larval behaviour on recruitment and dispersal. Population genetic studies can provide insight on the degree to which populations are connected, and the development of restriction site-associated sequencing (RAD-Seq) methods has made such studies of nonmodel organisms more accessible. We applied double-digest RAD-Seq methods to test for population differentiation in the coral reef-dwelling cardinalfish, Siphamia tubifer, which based on behavioural studies, have the potential to use navigational cues to return to natal reefs. Analysis of 11,836 SNPs from fish collected at coral reefs in Okinawa, Japan, from eleven locations over 3 years reveals little genetic differentiation between groups of S. tubifer at spatial scales from 2 to 140 km and between years at one location: pairwise F ST values were between 0.0116 and 0.0214. These results suggest that the Kuroshio Current largely influences larval dispersal in the region, and in contrast to expectations based on studies of other cardinalfishes, there is no evidence of population structure for S. tubifer at the spatial scales examined. However, analyses of outlier loci putatively under selection reveal patterns of temporal differentiation that indicate high population turnover and variable larval supply from divergent source populations between years. These findings highlight the need for more studies of fishes across various geographic regions that also examine temporal patterns of genetic differentiation to better understand the potential connections between early life-history traits and connectivity of reef fish populations. © 2017 John Wiley & Sons Ltd.

  6. Thyroid transcriptome analysis reveals different adaptive responses to cold environmental conditions between two chicken breeds.

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    Xie, Shanshan; Yang, Xukai; Wang, Dehe; Zhu, Feng; Yang, Ning; Hou, Zhuocheng; Ning, Zhonghua

    2018-01-01

    Selection for cold tolerance in chickens is important for improving production performance and animal welfare. The identification of chicken breeds with higher cold tolerance and production performance will help to target candidates for the selection. The thyroid gland plays important roles in thermal adaptation, and its function is influenced by breed differences and transcriptional plasticity, both of which remain largely unknown in the chicken thyroid transcriptome. In this study, we subjected Bashang Long-tail (BS) and Rhode Island Red (RIR) chickens to either cold or warm environments for 21 weeks and investigated egg production performance, body weight changes, serum thyroid hormone concentrations, and thyroid gland transcriptome profiles. RIR chickens had higher egg production than BS chickens under warm conditions, but BS chickens produced more eggs than RIRs under cold conditions. Furthermore, BS chickens showed stable body weight gain under cold conditions while RIRs did not. These results suggested that BS breed is a preferable candidate for cold-tolerance selection and that the cold adaptability of RIRs should be improved in the future. BS chickens had higher serum thyroid hormone concentrations than RIRs under both environments. RNA-Seq generated 344.3 million paired-end reads from 16 sequencing libraries, and about 90% of the processed reads were concordantly mapped to the chicken reference genome. Differential expression analysis identified 46-1,211 genes in the respective comparisons. With regard to breed differences in the thyroid transcriptome, BS chickens showed higher cell replication and development, and immune response-related activity, while RIR chickens showed higher carbohydrate and protein metabolism activity. The cold environment reduced breed differences in the thyroid transcriptome compared with the warm environment. Transcriptional plasticity analysis revealed different adaptive responses in BS and RIR chickens to cope with the cold

  7. Biophysical analysis of HTLV-1 particles reveals novel insights into particle morphology and Gag stochiometry

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    Fogarty Keir H

    2010-09-01

    Full Text Available Abstract Background Human T-lymphotropic virus type 1 (HTLV-1 is an important human retrovirus that is a cause of adult T-cell leukemia/lymphoma. While an important human pathogen, the details regarding virus replication cycle, including the nature of HTLV-1 particles, remain largely unknown due to the difficulties in propagating the virus in tissue culture. In this study, we created a codon-optimized HTLV-1 Gag fused to an EYFP reporter as a model system to quantitatively analyze HTLV-1 particles released from producer cells. Results The codon-optimized Gag led to a dramatic and highly robust level of Gag expression as well as virus-like particle (VLP production. The robust level of particle production overcomes previous technical difficulties with authentic particles and allowed for detailed analysis of particle architecture using two novel methodologies. We quantitatively measured the diameter and morphology of HTLV-1 VLPs in their native, hydrated state using cryo-transmission electron microscopy (cryo-TEM. Furthermore, we were able to determine HTLV-1 Gag stoichiometry as well as particle size with the novel biophysical technique of fluorescence fluctuation spectroscopy (FFS. The average HTLV-1 particle diameter determined by cryo-TEM and FFS was 71 ± 20 nm and 75 ± 4 nm, respectively. These values are significantly smaller than previous estimates made of HTLV-1 particles by negative staining TEM. Furthermore, cryo-TEM reveals that the majority of HTLV-1 VLPs lacks an ordered structure of the Gag lattice, suggesting that the HTLV-1 Gag shell is very likely to be organized differently compared to that observed with HIV-1 Gag in immature particles. This conclusion is supported by our observation that the average copy number of HTLV-1 Gag per particle is estimated to be 510 based on FFS, which is significantly lower than that found for HIV-1 immature virions. Conclusions In summary, our studies represent the first quantitative biophysical

  8. Semiparametric bivariate zero-inflated Poisson models with application to studies of abundance for multiple species

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    Arab, Ali; Holan, Scott H.; Wikle, Christopher K.; Wildhaber, Mark L.

    2012-01-01

    Ecological studies involving counts of abundance, presence–absence or occupancy rates often produce data having a substantial proportion of zeros. Furthermore, these types of processes are typically multivariate and only adequately described by complex nonlinear relationships involving externally measured covariates. Ignoring these aspects of the data and implementing standard approaches can lead to models that fail to provide adequate scientific understanding of the underlying ecological processes, possibly resulting in a loss of inferential power. One method of dealing with data having excess zeros is to consider the class of univariate zero-inflated generalized linear models. However, this class of models fails to address the multivariate and nonlinear aspects associated with the data usually encountered in practice. Therefore, we propose a semiparametric bivariate zero-inflated Poisson model that takes into account both of these data attributes. The general modeling framework is hierarchical Bayes and is suitable for a broad range of applications. We demonstrate the effectiveness of our model through a motivating example on modeling catch per unit area for multiple species using data from the Missouri River Benthic Fishes Study, implemented by the United States Geological Survey.

  9. Modeling both of the number of pausibacillary and multibacillary leprosy patients by using bivariate poisson regression

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    Winahju, W. S.; Mukarromah, A.; Putri, S.

    2015-03-01

    Leprosy is a chronic infectious disease caused by bacteria of leprosy (Mycobacterium leprae). Leprosy has become an important thing in Indonesia because its morbidity is quite high. Based on WHO data in 2014, in 2012 Indonesia has the highest number of new leprosy patients after India and Brazil with a contribution of 18.994 people (8.7% of the world). This number makes Indonesia automatically placed as the country with the highest number of leprosy morbidity of ASEAN countries. The province that most contributes to the number of leprosy patients in Indonesia is East Java. There are two kind of leprosy. They consist of pausibacillary and multibacillary. The morbidity of multibacillary leprosy is higher than pausibacillary leprosy. This paper will discuss modeling both of the number of multibacillary and pausibacillary leprosy patients as responses variables. These responses are count variables, so modeling will be conducted by using bivariate poisson regression method. Unit experiment used is in East Java, and predictors involved are: environment, demography, and poverty. The model uses data in 2012, and the result indicates that all predictors influence significantly.

  10. Improved deadzone modeling for bivariate wavelet shrinkage-based image denoising

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    DelMarco, Stephen

    2016-05-01

    Modern image processing performed on-board low Size, Weight, and Power (SWaP) platforms, must provide high- performance while simultaneously reducing memory footprint, power consumption, and computational complexity. Image preprocessing, along with downstream image exploitation algorithms such as object detection and recognition, and georegistration, place a heavy burden on power and processing resources. Image preprocessing often includes image denoising to improve data quality for downstream exploitation algorithms. High-performance image denoising is typically performed in the wavelet domain, where noise generally spreads and the wavelet transform compactly captures high information-bearing image characteristics. In this paper, we improve modeling fidelity of a previously-developed, computationally-efficient wavelet-based denoising algorithm. The modeling improvements enhance denoising performance without significantly increasing computational cost, thus making the approach suitable for low-SWAP platforms. Specifically, this paper presents modeling improvements to the Sendur-Selesnick model (SSM) which implements a bivariate wavelet shrinkage denoising algorithm that exploits interscale dependency between wavelet coefficients. We formulate optimization problems for parameters controlling deadzone size which leads to improved denoising performance. Two formulations are provided; one with a simple, closed form solution which we use for numerical result generation, and the second as an integral equation formulation involving elliptic integrals. We generate image denoising performance results over different image sets drawn from public domain imagery, and investigate the effect of wavelet filter tap length on denoising performance. We demonstrate denoising performance improvement when using the enhanced modeling over performance obtained with the baseline SSM model.

  11. Multiscale Fluctuation Features of the Dynamic Correlation between Bivariate Time Series

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    Meihui Jiang

    2016-01-01

    Full Text Available The fluctuation of the dynamic correlation between bivariate time series has some special features on the time-frequency domain. In order to study these fluctuation features, this paper built the dynamic correlation network models using two kinds of time series as sample data. After studying the dynamic correlation networks at different time-scales, we found that the correlation between time series is a dynamic process. The correlation is strong and stable in the long term, but it is weak and unstable in the short and medium term. There are key correlation modes which can effectively indicate the trend of the correlation. The transmission characteristics of correlation modes show that it is easier to judge the trend of the fluctuation of the correlation between time series from the short term to long term. The evolution of media capability of the correlation modes shows that the transmission media in the long term have higher value to predict the trend of correlation. This work does not only propose a new perspective to analyze the correlation between time series but also provide important information for investors and decision makers.

  12. Bivariate Gaussian bridges: directional factorization of diffusion in Brownian bridge models.

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    Kranstauber, Bart; Safi, Kamran; Bartumeus, Frederic

    2014-01-01

    In recent years high resolution animal tracking data has become the standard in movement ecology. The Brownian Bridge Movement Model (BBMM) is a widely adopted approach to describe animal space use from such high resolution tracks. One of the underlying assumptions of the BBMM is isotropic diffusive motion between consecutive locations, i.e. invariant with respect to the direction. Here we propose to relax this often unrealistic assumption by separating the Brownian motion variance into two directional components, one parallel and one orthogonal to the direction of the motion. Our new model, the Bivariate Gaussian bridge (BGB), tracks movement heterogeneity across time. Using the BGB and identifying directed and non-directed movement within a trajectory resulted in more accurate utilisation distributions compared to dynamic Brownian bridges, especially for trajectories with a non-isotropic diffusion, such as directed movement or Lévy like movements. We evaluated our model with simulated trajectories and observed tracks, demonstrating that the improvement of our model scales with the directional correlation of a correlated random walk. We find that many of the animal trajectories do not adhere to the assumptions of the BBMM. The proposed model improves accuracy when describing the space use both in simulated correlated random walks as well as observed animal tracks. Our novel approach is implemented and available within the "move" package for R.

  13. Neural Systems with Numerically Matched Input-Output Statistic: Isotonic Bivariate Statistical Modeling

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    Simone Fiori

    2007-07-01

    Full Text Available Bivariate statistical modeling from incomplete data is a useful statistical tool that allows to discover the model underlying two data sets when the data in the two sets do not correspond in size nor in ordering. Such situation may occur when the sizes of the two data sets do not match (i.e., there are “holes” in the data or when the data sets have been acquired independently. Also, statistical modeling is useful when the amount of available data is enough to show relevant statistical features of the phenomenon underlying the data. We propose to tackle the problem of statistical modeling via a neural (nonlinear system that is able to match its input-output statistic to the statistic of the available data sets. A key point of the new implementation proposed here is that it is based on look-up-table (LUT neural systems, which guarantee a computationally advantageous way of implementing neural systems. A number of numerical experiments, performed on both synthetic and real-world data sets, illustrate the features of the proposed modeling procedure.

  14. A Basic Bivariate Structure of Personality Attributes Evident Across Nine Languages.

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    Saucier, Gerard; Thalmayer, Amber Gayle; Payne, Doris L; Carlson, Robert; Sanogo, Lamine; Ole-Kotikash, Leonard; Church, A Timothy; Katigbak, Marcia S; Somer, Oya; Szarota, Piotr; Szirmák, Zsofia; Zhou, Xinyue

    2014-02-01

    Here, two studies seek to characterize a parsimonious common-denominator personality structure with optimal cross-cultural replicability. Personality differences are observed in all human populations and cultures, but lexicons for personality attributes contain so many distinctions that parsimony is lacking. Models stipulating the most important attributes have been formulated by experts or by empirical studies drawing on experience in a very limited range of cultures. Factor analyses of personality lexicons of nine languages of diverse provenance (Chinese, Korean, Filipino, Turkish, Greek, Polish, Hungarian, Maasai, and Senoufo) were examined, and their common structure was compared to that of several prominent models in psychology. A parsimonious bivariate model showed evidence of substantial convergence and ubiquity across cultures. Analyses involving key markers of these dimensions in English indicate that they are broad dimensions involving the overlapping content of the interpersonal circumplex, models of communion and agency, and morality/warmth and competence. These "Big Two" dimensions-Social Self-Regulation and Dynamism-provide a common-denominator model involving the two most crucial axes of personality variation, ubiquitous across cultures. The Big Two might serve as an umbrella model serving to link diverse theoretical models and associated research literatures. © 2013 Wiley Periodicals, Inc.

  15. Comparative Genomic Analysis of Clinical and Environmental Vibrio Vulnificus Isolates Revealed Biotype 3 Evolutionary Relationships

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    Yael eKotton

    2015-01-01

    Full Text Available In 1996 a common-source outbreak of severe soft tissue and bloodstream infections erupted among Israeli fish farmers and fish consumers due to changes in fish marketing policies. The causative pathogen was a new strain of Vibrio vulnificus, named biotype 3, which displayed a unique biochemical and genotypic profile. Initial observations suggested that the pathogen erupted as a result of genetic recombination between two distinct populations. We applied a whole genome shotgun sequencing approach using several V. vulnificus strains from Israel in order to study the pan genome of V. vulnificus and determine the phylogenetic relationship of biotype 3 with existing populations. The core genome of V. vulnificus based on 16 draft and complete genomes consisted of 3068 genes, representing between 59% and 78% of the whole genome of 16 strains. The accessory genome varied in size from 781 kbp to 2044 kbp. Phylogenetic analysis based on whole, core, and accessory genomes displayed similar clustering patterns with two main clusters, clinical (C and environmental (E, all biotype 3 strains formed a distinct group within the E cluster. Annotation of accessory genomic regions found in biotype 3 strains and absent from the core genome yielded 1732 genes, of which the vast majority encoded hypothetical proteins, phage-related proteins, and mobile element proteins. A total of 1916 proteins (including 713 hypothetical proteins were present in all human pathogenic strains (both biotype 3 and non-biotype 3 and absent from the environmental strains. Clustering analysis of the non-hypothetical proteins revealed 148 protein clusters shared by all human pathogenic strains; these included transcriptional regulators, arylsulfatases, methyl-accepting chemotaxis proteins, acetyltransferases, GGDEF family proteins, transposases, type IV secretory system (T4SS proteins, and integrases. Our study showed that V. vulnificus biotype 3 evolved from environmental populations and

  16. Comparative transcriptome analysis reveals differentially expressed genes associated with sex expression in garden asparagus (Asparagus officinalis).

    Science.gov (United States)

    Li, Shu-Fen; Zhang, Guo-Jun; Zhang, Xue-Jin; Yuan, Jin-Hong; Deng, Chuan-Liang; Gao, Wu-Jun

    2017-08-22

    Garden asparagus (Asparagus officinalis) is a highly valuable vegetable crop of commercial and nutritional interest. It is also commonly used to investigate the mechanisms of sex determination and differentiation in plants. However, the sex expression mechanisms in asparagus remain poorly understood. De novo transcriptome sequencing via Illumina paired-end sequencing revealed more than 26 billion bases of high-quality sequence data from male and female asparagus flower buds. A total of 72,626 unigenes with an average length of 979 bp were assembled. In comparative transcriptome analysis, 4876 differentially expressed genes (DEGs) were identified in the possible sex-determining stage of female and male/supermale flower buds. Of these DEGs, 433, including 285 male/supermale-biased and 149 female-biased genes, were annotated as flower related. Of the male/supermale-biased flower-related genes, 102 were probably involved in anther development. In addition, 43 DEGs implicated in hormone response and biosynthesis putatively associated with sex expression and reproduction were discovered. Moreover, 128 transcription factor (TF)-related genes belonging to various families were found to be differentially expressed, and this finding implied the essential roles of TF in sex determination or differentiation in asparagus. Correlation analysis indicated that miRNA-DEG pairs were also implicated in asparagus sexual development. Our study identified a large number of DEGs involved in the sex expression and reproduction of asparagus, including known genes participating in plant reproduction, plant hormone signaling, TF encoding, and genes with unclear functions. We also found that miRNAs might be involved in the sex differentiation process. Our study could provide a valuable basis for further investigations on the regulatory networks of sex determination and differentiation in asparagus and facilitate further genetic and genomic studies on this dioecious species.

  17. Gene array analysis of PD-1H overexpressing monocytes reveals a pro-inflammatory profile

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    Preeti Bharaj

    2018-02-01

    Full Text Available We have previously reported that overexpression of Programmed Death -1 Homolog (PD-1H in human monocytes leads to activation and spontaneous secretion of multiple pro inflammatory cytokines. Here we evaluate changes in monocytes gene expression after enforced PD-1H expression by gene array. The results show that there are significant alterations in 51 potential candidate genes that relate to immune response, cell adhesion and metabolism. Genes corresponding to pro-inflammatory cytokines showed the highest upregulation, 7, 3.2, 3.0, 5.8, 4.4 and 3.1 fold upregulation of TNF-α, IL-1 β, IFN-α, γ, λ and IL-27 relative to vector control. The data are in agreement with cytometric bead array analysis showing induction of proinflammatory cytokines, IL-6, IL-1β and TNF-α by PD-1H. Other genes related to inflammation, include transglutaminase 2 (TG2, NF-κB (p65 and p50 and toll like receptors (TLR 3 and 4 were upregulated 5, 4.5 and 2.5 fold, respectively. Gene set enrichment analysis (GSEA also revealed that signaling pathways related to inflammatory response, such as NFκB, AT1R, PYK2, MAPK, RELA, TNFR1, MTOR and proteasomal degradation, were significantly upregulated in response to PD-1H overexpression. We validated the results utilizing a standard inflammatory sepsis model in humanized BLT mice, finding that PD-1H expression was highly correlated with proinflammatory cytokine production. We therefore conclude that PD-1H functions to enhance monocyte activation and the induction of a pro-inflammatory gene expression profile.

  18. Proteomic analysis of Ketogulonicigenium vulgare under glutathione reveals high demand for thiamin transport and antioxidant protection.

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    Qian Ma

    Full Text Available Ketogulonicigenium vulgare, though grows poorly when mono-cultured, has been widely used in the industrial production of the precursor of vitamin C with the coculture of Bacillus megaterium. Various efforts have been made to clarify the synergic pattern of this artificial microbial community and to improve the growth and production ability of K. vulgare, but there is still no sound explanation. In previous research, we found that the addition of reduced glutathione into K. vulgare monoculture could significantly improve its growth and productivity. By performing SEM and TEM, we observed that after adding GSH into K. vulgare monoculture, cells became about 4-6 folds elongated, and formed intracytoplasmic membranes (ICM. To explore the molecular mechanism and provide insights into the investigation of the synergic pattern of the co-culture system, we conducted a comparative iTRAQ-2-D-LC-MS/MS-based proteomic analysis of K. vulgare grown under reduced glutathione. Principal component analysis of proteomic data showed that after the addition of glutathione, proteins for thiamin/thiamin pyrophosphate (TPP transport, glutathione transport and the maintenance of membrane integrity, together with several membrane-bound dehydrogenases had significant up-regulation. Besides, several proteins participating in the pentose phosphate pathway and tricarboxylic acid cycle were also up-regulated. Additionally, proteins combating intracellular reactive oxygen species were also up-regulated, which similarly occurred in K. vulgare when the co-cultured B. megaterium cells lysed from our former research results. This study reveals the demand for transmembrane transport of substrates, especially thiamin, and the demand for antioxidant protection of K. vulgare.

  19. RNA-Seq analysis reveals a six-gene SoxR regulon in Streptomyces coelicolor.

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    Nawar Naseer

    Full Text Available The redox-regulated transcription factor SoxR is conserved in diverse bacteria, but emerging studies suggest that this protein plays distinct physiological roles in different bacteria. SoxR regulates a global oxidative stress response (involving > 100 genes against exogenous redox-cycling drugs in Escherichia coli and related enterics. In the antibiotic producers Streptomyces coelicolor and Pseudomonas aeruginosa, however, SoxR regulates a smaller number of genes that encode membrane transporters and proteins with homology to antibiotic-tailoring enzymes. In both S. coelicolor and P. aeruginosa, SoxR-regulated genes are expressed in stationary phase during the production of endogenously-produced redox-active antibiotics. These observations suggest that SoxR evolved to sense endogenous secondary metabolites and activate machinery to process and transport them in antibiotic-producing bacteria. Previous bioinformatics analysis that searched the genome for SoxR-binding sites in putative promoters defined a five-gene SoxR regulon in S. coelicolor including an ABC transporter, two oxidoreductases, a monooxygenase and an epimerase/dehydratase. Since this in silico screen may have missed potential SoxR-targets, we conducted a whole genome transcriptome comparison of wild type S. coelicolor and a soxR-deficient mutant in stationary phase using RNA-Seq. Our analysis revealed a sixth SoxR-regulated gene in S. coelicolor that encodes a putative quinone oxidoreductase. Knowledge of the full complement of genes regulated by SoxR will facilitate studies to elucidate the function of this regulatory molecule in antibiotic producers.

  20. Proteomic analysis of chromoplasts from six crop species reveals insights into chromoplast function and development.

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    Wang, Yong-Qiang; Yang, Yong; Fei, Zhangjun; Yuan, Hui; Fish, Tara; Thannhauser, Theodore W; Mazourek, Michael; Kochian, Leon V; Wang, Xiaowu; Li, Li

    2013-02-01

    Chromoplasts are unique plastids that accumulate massive amounts of carotenoids. To gain a general and comparative characterization of chromoplast proteins, this study performed proteomic analysis of chromoplasts from six carotenoid-rich crops: watermelon, tomato, carrot, orange cauliflower, red papaya, and red bell pepper. Stromal and membrane proteins of chromoplasts were separated by 1D gel electrophoresis and analysed using nLC-MS/MS. A total of 953-2262 proteins from chromoplasts of different crop species were identified. Approximately 60% of the identified proteins were predicted to be plastid localized. Functional classification using MapMan bins revealed large numbers of proteins involved in protein metabolism, transport, amino acid metabolism, lipid metabolism, and redox in chromoplasts from all six species. Seventeen core carotenoid metabolic enzymes were identified. Phytoene synthase, phytoene desaturase, ζ-carotene desaturase, 9-cis-epoxycarotenoid dioxygenase, and carotenoid cleavage dioxygenase 1 were found in almost all crops, suggesting relative abundance of them among the carotenoid pathway enzymes. Chromoplasts from different crops contained abundant amounts of ATP synthase and adenine nucleotide translocator, which indicates an important role of ATP production and transport in chromoplast development. Distinctive abundant proteins were observed in chromoplast from different crops, including capsanthin/capsorubin synthase and fibrillins in pepper, superoxide dismutase in watermelon, carrot, and cauliflower, and glutathione-S-transferease in papaya. The comparative analysis of chromoplast proteins among six crop species offers new insights into the general metabolism and function of chromoplasts as well as the uniqueness of chromoplasts in specific crop species. This work provides reference datasets for future experimental study of chromoplast biogenesis, development, and regulation in plants.

  1. Population genomic analysis of elongated skulls reveals extensive female-biased immigration in Early Medieval Bavaria.

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    Veeramah, Krishna R; Rott, Andreas; Groß, Melanie; van Dorp, Lucy; López, Saioa; Kirsanow, Karola; Sell, Christian; Blöcher, Jens; Wegmann, Daniel; Link, Vivian; Hofmanová, Zuzana; Peters, Joris; Trautmann, Bernd; Gairhos, Anja; Haberstroh, Jochen; Päffgen, Bernd; Hellenthal, Garrett; Haas-Gebhard, Brigitte; Harbeck, Michaela; Burger, Joachim

    2018-03-12

    Modern European genetic structure demonstrates strong correlations with geography, while genetic analysis of prehistoric humans has indicated at least two major waves of immigration from outside the continent during periods of cultural change. However, population-level genome data that could shed light on the demographic processes occurring during the intervening periods have been absent. Therefore, we generated genomic data from 41 individuals dating mostly to the late 5th/early 6th century AD from present-day Bavaria in southern Germany, including 11 whole genomes (mean depth 5.56×). In addition we developed a capture array to sequence neutral regions spanning a total of 5 Mb and 486 functional polymorphic sites to high depth (mean 72×) in all individuals. Our data indicate that while men generally had ancestry that closely resembles modern northern and central Europeans, women exhibit a very high genetic heterogeneity; this includes signals of genetic ancestry ranging from western Europe to East Asia. Particularly striking are women with artificial skull deformations; the analysis of their collective genetic ancestry suggests an origin in southeastern Europe. In addition, functional variants indicate that they also differed in visible characteristics. This example of female-biased migration indicates that complex demographic processes during the Early Medieval period may have contributed in an unexpected way to shape the modern European genetic landscape. Examination of the panel of functional loci also revealed that many alleles associated with recent positive selection were already at modern-like frequencies in European populations ∼1,500 years ago. Copyright © 2018 the Author(s). Published by PNAS.

  2. Interspecies insertion polymorphism analysis reveals recent activity of transposable elements in extant coelacanths.

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    Magali Naville

    Full Text Available Coelacanths are lobe-finned fish represented by two extant species, Latimeria chalumnae in South Africa and Comoros and L. menadoensis in Indonesia. Due to their intermediate phylogenetic position between ray-finned fish and tetrapods in the vertebrate lineage, they are of great interest from an evolutionary point of view. In addition, extant specimens look similar to 300 million-year-old fossils; because of their apparent slowly evolving morphology, coelacanths have been often described as « living fossils ». As an underlying cause of such a morphological stasis, several authors have proposed a slow evolution of the coelacanth genome. Accordingly, sequencing of the L. chalumnae genome has revealed a globally low substitution rate for protein-coding regions compared to other vertebrates. However, genome and gene evolution can also be influenced by transposable elements, which form a major and dynamic part of vertebrate genomes through their ability to move, duplicate and recombine. In this work, we have searched for evidence of transposition activity in coelacanth genomes through the comparative analysis of orthologous genomic regions from both Latimeria species. Comparison of 5.7 Mb (0.2% of the L. chalumnae genome with orthologous Bacterial Artificial Chromosome clones from L. menadoensis allowed the identification of 27 species-specific transposable element insertions, with a strong relative contribution of CR1 non-LTR retrotransposons. Species-specific homologous recombination between the long terminal repeats of a new coelacanth endogenous retrovirus was also detected. Our analysis suggests that transposon activity is responsible for at least 0.6% of genome divergence between both Latimeria species. Taken together, this study demonstrates that coelacanth genomes are not evolutionary inert: they contain recently active transposable elements, which have significantly contributed to post-speciation genome divergence in Latimeria.

  3. Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells.

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    Li, Yuanyuan; Wang, Ran; Qiao, Nan; Peng, Guangdun; Zhang, Ke; Tang, Ke; Han, Jing-Dong J; Jing, Naihe

    2017-12-01

    Proper neural commitment is essential for ensuring the appropriate development of the human brain and for preventing neurodevelopmental diseases such as autism spectrum disorders, schizophrenia, and intellectual disorders. However, the molecular mechanisms underlying the neural commitment in humans remain elusive. Here, we report the establishment of a neural differentiation system based on human embryonic stem cells (hESCs) and on comprehensive RNA sequencing analysis of transcriptome dynamics during early hESC differentiation. Using weighted gene co-expression network analysis, we reveal that the hESC neurodevelopmental trajectory has five stages: pluripotency (day 0); differentiation initiation (days 2, 4, and 6); neural commitment (days 8-10); neural progenitor cell proliferation (days 12, 14, and 16); and neuronal differentiation (days 18, 20, and 22). These stages were characterized by unique module genes, which may recapitulate the early human cortical development. Moreover, a comparison of our RNA-sequencing data with several other transcriptome profiling datasets from mice and humans indicated that Module 3 associated with the day 8-10 stage is a critical window of fate switch from the pluripotency to the neural lineage. Interestingly, at this stage, no key extrinsic signals were activated. In contrast, using CRISPR/Cas9-mediated gene knockouts, we also found that intrinsic hub transcription factors, including the schizophrenia-associated SIX3 gene and septo-optic dysplasia-related HESX1 gene, are required to program hESC neural determination. Our results improve the understanding of the mechanism of neural commitment in the human brain and may help elucidate the etiology of human mental disorders and advance therapies for managing these conditions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Grapevine immune signaling network in response to drought stress as revealed by transcriptomic analysis.

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    Haider, Muhammad S; Kurjogi, Mahantesh M; Khalil-Ur-Rehman, M; Fiaz, Muhammad; Pervaiz, Tariq; Jiu, Songtao; Haifeng, Jia; Chen, Wang; Fang, Jinggui

    2017-12-01

    Drought is a ubiquitous abiotic factor that severely impedes growth and development of horticulture crops. The challenge postured by global climate change is the evolution of drought-tolerant cultivars that could cope with concurrent stress. Hence, in this study, biochemical, physiological and transcriptome analysis were investigated in drought-treated grapevine leaves. The results revealed that photosynthetic activity and reducing sugars were significantly diminished which were positively correlated with low stomatal conductance and CO 2 exchange in drought-stressed leaves. Further, the activities of superoxide dismutase, peroxidase, and catalase were significantly actuated in the drought-responsive grapevine leaves. Similarly, the levels of abscisic acid and jasmonic acid were also significantly increased in the drought-stressed leaves. In transcriptome analysis, 12,451 differentially-expressed genes (DEGs) were annotated, out of which 8021 DEGs were up-regulated and 4430 DEGs were down-regulated in response to drought stress. In addition, the genes encoding pathogen-associated molecular pattern (PAMP) triggered immunity (PTI), including calcium signals, protein phosphatase 2C, calcineurin B-like proteins, MAPKs, and phosphorylation (FLS2 and MEKK1) cascades were up-regulated in response to drought stress. Several genes related to plant-pathogen interaction pathway (RPM1, PBS1, RPS5, RIN4, MIN7, PR1, and WRKYs) were also found up-regulated in response to drought stress. Overall the results of present study showed the dynamic interaction of DEG in grapevine physiology which provides the premise for selection of defense-related genes against drought stress for subsequent grapevine breeding programs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Analysis of transcriptome data reveals multifactor constraint on codon usage in Taenia multiceps.

    Science.gov (United States)

    Huang, Xing; Xu, Jing; Chen, Lin; Wang, Yu; Gu, Xiaobin; Peng, Xuerong; Yang, Guangyou

    2017-04-20

    Codon usage bias (CUB) is an important evolutionary feature in genomes that has been widely observed in many organisms. However, the synonymous codon usage pattern in the genome of T. multiceps remains to be clarified. In this study, we analyzed the codon usage of T. multiceps based on the transcriptome data to reveal the constraint factors and to gain an improved understanding of the mechanisms that shape synonymous CUB. Analysis of a total of 8,620 annotated mRNA sequences from T. multiceps indicated only a weak codon bias, with mean GC and GC3 content values of 49.29% and 51.43%, respectively. Our analysis indicated that nucleotide composition, mutational pressure, natural selection, gene expression level, amino acids with grand average of hydropathicity (GRAVY) and aromaticity (Aromo) and the effective selection of amino-acids all contributed to the codon usage in T. multiceps. Among these factors, natural selection was implicated as the major factor affecting the codon usage variation in T. multiceps. The codon usage of ribosome genes was affected mainly by mutations, while the essential genes were affected mainly by selection. In addition, 21codons were identified as "optimal codons". Overall, the optimal codons were GC-rich (GC:AU, 41:22), and ended with G or C (except CGU). Furthermore, different degrees of variation in codon usage were found between T. multiceps and Escherichia coli, yeast, Homo sapiens. However, little difference was found between T. multiceps and Taenia pisiformis. In this study, the codon usage pattern of T. multiceps was analyzed systematically and factors affected CUB were also identified. This is the first study of codon biology in T. multiceps. Understanding the codon usage pattern in T. multiceps can be helpful for the discovery of new genes, molecular genetic engineering and evolutionary studies.

  6. Network Analysis Reveals Putative Genes Affecting Meat Quality in Angus Cattle

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    Raluca G. Mateescu

    2017-11-01

    Full Text Available Improvements in eating satisfaction will benefit consumers and should increase beef demand which is of interest to the beef industry. Tenderness, juiciness, and flavor are major determinants of the palatability of beef and are often used to reflect eating satisfaction. Carcass qualities are used as indicator traits for meat quality, with higher quality grade carcasses expected to relate to more tender and palatable meat. However, meat quality is a complex concept determined by many component traits making interpretation of genome-wide association studies (GWAS on any one component challenging to interpret. Recent approaches combining traditional GWAS with gene network interactions theory could be more efficient in dissecting the genetic architecture of complex traits. Phenotypic measures of 23 traits reflecting carcass characteristics, components of meat quality, along with mineral and peptide concentrations were used along with Illumina 54k bovine SNP genotypes to derive an annotated gene network associated with meat quality in 2,110 Angus beef cattle. The efficient mixed model association (EMMAX approach in combination with a genomic relationship matrix was used to directly estimate the associations between 54k SNP genotypes and each of the 23 component traits. Genomic correlated regions were identified by partial correlations which were further used along with an information theory algorithm to derive gene network clusters. Correlated SNP across 23 component traits were subjected to network scoring and visualization software to identify significant SNP. Significant pathways implicated in the meat quality complex through GO term enrichment analysis included angiogenesis, inflammation, transmembrane transporter activity, and receptor activity. These results suggest that network analysis using partial correlations and annotation of significant SNP can reveal the genetic architecture of complex traits and provide novel information regarding

  7. Social phobia subtypes in the general population revealed by cluster analysis.

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    Furmark, T; Tillfors, M; Stattin, H; Ekselius, L; Fredrikson, M

    2000-11-01

    Epidemiological data on subtypes of social phobia are scarce and their defining features are debated. Hence, the present study explored the prevalence and descriptive characteristics of empirically derived social phobia subgroups in the general population. To reveal subtypes, data on social distress, functional impairment, number of social fears and criteria fulfilled for avoidant personality disorder were extracted from a previously published epidemiological study of 188 social phobics and entered into an hierarchical cluster analysis. Criterion validity was evaluated by comparing clusters on the Social Phobia Scale (SPS) and the Social Interaction Anxiety Scale (SIAS). Finally, profile analyses were performed in which clusters were compared on a set of sociodemographic and descriptive characteristics. Three clusters emerged, consisting of phobics scoring either high (generalized subtype), intermediate (non-generalized subtype) or low (discrete subtype) on all variables. Point prevalence rates were 2.0%, 5.9% and 7.7% respectively. All subtypes were distinguished on both SPS and SIAS. Generalized or severe social phobia tended to be over-represented among individuals with low levels of educational attainment and social support. Overall, public-speaking was the most common fear. Although categorical distinctions may be used, the present data suggest that social phobia subtypes in the general population mainly differ dimensionally along a mild moderate-severe continuum, and that the number of cases declines with increasing severity.

  8. Genetic analysis of paramyxovirus isolates from pacific salmon reveals two independently co-circulating lineages

    Science.gov (United States)

    Batts, W.N.; Falk, K.; Winton, J.R.

    2008-01-01

    Viruses with the morphological and biochemical characteristics of the family Paramyxoviridae (paramyxoviruses) have been isolated from adult salmon returning to rivers along the Pacific coast of North America since 1982. These Pacific salmon paramyxoviruses (PSPV), which have mainly been isolated from Chinook salmon Oncorhynchus tshawytscha, grow slowly in established fish cell lines and have not been associated with disease. Genetic analysis of a 505-base-pair region of the polymerase gene from 47 PsPV isolates produced 17 nucleotide sequence types that could be grouped into two major sublineages, designated A and B. The two independently co-circulating sublineages differed by 12.1-13.9% at the nucleotide level but by only 1.2% at the amino acid level. Isolates of PSPV from adult Pacific salmon returning to rivers from Alaska to California over a 25-year period showed little evidence of geographic or temporal grouping. Phylogenetic analyses revealed that these paramyxoviruses of Pacific salmon were most closely related to the Atlantic salmon paramyxovirus (ASPV) from Norway, having a maximum nucleotide diversity of 26.1 % and an amino acid diversity of 19.0%. When compared with homologous sequences of other paramyxoviruses, PSPV and ASPV were sufficiently distinct to suggest that they are not clearly members of any of the established genera in the family Paramyxoviridae. in the course of this study, a polymerase chain reaction assay was developed that can be used for confirmatory identification of PSPV. ?? Copyright by the American Fisheries Society 2008.

  9. A pangenomic analysis of the Nannochloropsis organellar genomes reveals novel genetic variations in key metabolic genes.

    Science.gov (United States)

    Starkenburg, Shawn R; Kwon, Kyungyoon J; Jha, Ramesh K; McKay, Cedar; Jacobs, Michael; Chertkov, Olga; Twary, Scott; Rocap, Gabrielle; Cattolico, Rose Ann

    2014-03-19

    Microalgae in the genus Nannochloropsis are photosynthetic marine Eustigmatophytes of significant interest to the bioenergy and aquaculture sectors due to their ability to efficiently accumulate biomass and lipids for utilization in renewable transportation fuels, aquaculture feed, and other useful bioproducts. To better understand the genetic complement that drives the metabolic processes of these organisms, we present the assembly and comparative pangenomic analysis of the chloroplast and mitochondrial genomes from Nannochloropsis salina CCMP1776. The chloroplast and mitochondrial genomes of N. salina are 98.4% and 97% identical to their counterparts in Nannochloropsis gaditana. Comparison of the Nannochloropsis pangenome to other algae within and outside of the same phyla revealed regions of significant genetic divergence in key genes that encode proteins needed for regulation of branched chain amino synthesis (acetohydroxyacid synthase), carbon fixation (RuBisCO activase), energy conservation (ATP synthase), protein synthesis and homeostasis (Clp protease, ribosome). Many organellar gene modifications in Nannochloropsis are unique and deviate from conserved orthologs found across the tree of life. Implementation of secondary and tertiary structure prediction was crucial to functionally characterize many proteins and therefore should be implemented in automated annotation pipelines. The exceptional similarity of the N. salina and N. gaditana organellar genomes suggests that N. gaditana be reclassified as a strain of N. salina.

  10. Alanine Enhances Aminoglycosides-Induced ROS Production as Revealed by Proteomic Analysis

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    Jin-zhou Ye

    2018-01-01

    Full Text Available Metabolite-enabled killing of antibiotic-resistant pathogens by antibiotics is an attractive strategy to manage antibiotic resistance. Our previous study demonstrated that alanine or/and glucose increased the killing efficacy of kanamycin on antibiotic-resistant bacteria, whose action is through up-regulating TCA cycle, increasing proton motive force and enhancing antibiotic uptake. Despite the fact that alanine altered several metabolic pathways, other mechanisms could be potentially involved in alanine-mediated kanamycin killing of bacteria which remains to be explored. In the present study, we adopted proteomic approach to analyze the proteome changes induced by exogenous alanine. Our results revealed that the expression of three outer membrane proteins was altered and the deletion of nagE and fadL decreased the intracellular kanamycin concentration, implying their possible roles in mediating kanamycin transport. More importantly, the integrated analysis of proteomic and metabolomic data pointed out that alanine metabolism could connect to riboflavin metabolism that provides the source for reactive oxygen species (ROS production. Functional studies confirmed that alanine treatment together with kanamycin could promote ROS production that in turn potentiates the killing of antibiotic-resistant bacteria. Further investigation showed that alanine repressed the transcription of antioxidant-encoding genes, and alanine metabolism to riboflavin metabolism connected with riboflavin metabolism through TCA cycle, glucogenesis pathway and pentose phosphate pathway. Our results suggest a novel mechanism by which alanine facilitates kanamycin killing of antibiotic-resistant bacteria via promoting ROS production.

  11. Metabolomics analysis reveals the metabolic and functional roles of flavonoids in light-sensitive tea leaves.

    Science.gov (United States)

    Zhang, Qunfeng; Liu, Meiya; Ruan, Jianyun

    2017-03-20

    As the predominant secondary metabolic pathway in tea plants, flavonoid biosynthesis increases with increasing temperature and illumination. However, the concentration of most flavonoids decreases greatly in light-sensitive tea leaves when they are exposed to light, which further improves tea quality. To reveal the metabolism and potential functions of flavonoids in tea leaves, a natural light-sensitive tea mutant (Huangjinya) cultivated under different light conditions was subjected to metabolomics analysis. The results showed that chlorotic tea leaves accumulated large amounts of flavonoids with ortho-dihydroxylated B-rings (e.g., catechin gallate, quercetin and its glycosides etc.), whereas total flavonoids (e.g., myricetrin glycoside, epigallocatechin gallate etc.) were considerably reduced, suggesting that the flavonoid components generated from different metabolic branches played different roles in tea leaves. Furthermore, the intracellular localization of flavonoids and the expression pattern of genes involved in secondary metabolic pathways indicate a potential photoprotective function of dihydroxylated flavonoids in light-sensitive tea leaves. Our results suggest that reactive oxygen species (ROS) scavenging and the antioxidation effects of flavonoids help chlorotic tea plants survive under high light stress, providing new evidence to clarify the functional roles of flavonoids, which accumulate to high levels in tea plants. Moreover, flavonoids with ortho-dihydroxylated B-rings played a greater role in photo-protection to improve the acclimatization of tea plants.

  12. Gamma-Tocotrienol Modulated Gene Expression in Senescent Human Diploid Fibroblasts as Revealed by Microarray Analysis

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    Suzana Makpol

    2013-01-01

    Full Text Available The effect of γ-tocotrienol, a vitamin E isomer, in modulating gene expression in cellular aging of human diploid fibroblasts was studied. Senescent cells at passage 30 were incubated with 70 μM of γ-tocotrienol for 24 h. Gene expression patterns were evaluated using Sentrix HumanRef-8 Expression BeadChip from Illumina, analysed using GeneSpring GX10 software, and validated using quantitative RT-PCR. A total of 100 genes were differentially expressed (P<0.001 by at least 1.5 fold in response to γ-tocotrienol treatment. Amongst the genes were IRAK3, SelS, HSPA5, HERPUD1, DNAJB9, SEPR1, C18orf55, ARF4, RINT1, NXT1, CADPS2, COG6, and GLRX5. Significant gene list was further analysed by Gene Set Enrichment Analysis (GSEA, and the Normalized Enrichment Score (NES showed that biological processes such as inflammation, protein transport, apoptosis, and cell redox homeostasis were modulated in senescent fibroblasts treated with γ-tocotrienol. These findings revealed that γ-tocotrienol may prevent cellular aging of human diploid fibroblasts by modulating gene expression.

  13. Genomic analysis reveals the molecular basis for capsule loss in the group B Streptococcus population.

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    Roberto Rosini

    Full Text Available The human and bovine bacterial pathogen Streptococcus agalactiae (Group B Streptococcus, GBS expresses a thick polysaccharide capsule that constitutes a major virulence factor and vaccine target. GBS can be classified into ten distinct serotypes differing in the chemical composition of their capsular polysaccharide. However, non-typeable strains that do not react with anti-capsular sera are frequently isolated from colonized and infected humans and cattle. To gain a comprehensive insight into the molecular basis for the loss of capsule expression in GBS, a collection of well-characterized non-typeable strains was investigated by genome sequencing. Genome based phylogenetic analysis extended to a wide population of sequenced strains confirmed the recently observed high clonality among GBS lineages mainly containing human strains, and revealed a much higher degree of diversity in the bovine population. Remarkably, non-typeable strains were equally distributed in all lineages. A number of distinct mutations in the cps operon were identified that were apparently responsible for inactivation of capsule synthesis. The most frequent genetic alterations were point mutations leading to stop codons in the cps genes, and the main target was found to be cpsE encoding the portal glycosyl transferase of capsule biosynthesis. Complementation of strains carrying missense mutations in cpsE with a wild-type gene restored capsule expression allowing the identification of amino acid residues essential for enzyme activity.

  14. Latent physiological factors of complex human diseases revealed by independent component analysis of clinarrays

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    Chen David P

    2010-10-01

    Full Text Available Abstract Background Diagnosis and treatment of patients in the clinical setting is often driven by known symptomatic factors that distinguish one particular condition from another. Treatment based on noticeable symptoms, however, is limited to the types of clinical biomarkers collected, and is prone to overlooking dysfunctions in physiological factors not easily evident to medical practitioners. We used a vector-based representation of patient clinical biomarkers, or clinarrays, to search for latent physiological factors that underlie human diseases directly from clinical laboratory data. Knowledge of these factors could be used to improve assessment of disease severity and help to refine strategies for diagnosis and monitoring disease progression. Results Applying Independent Component Analysis on clinarrays built from patient laboratory measurements revealed both known and novel concomitant physiological factors for asthma, types 1 and 2 diabetes, cystic fibrosis, and Duchenne muscular dystrophy. Serum sodium was found to be the most significant factor for both type 1 and type 2 diabetes, and was also significant in asthma. TSH3, a measure of thyroid function, and blood urea nitrogen, indicative of kidney function, were factors unique to type 1 diabetes respective to type 2 diabetes. Platelet count was significant across all the diseases analyzed. Conclusions The results demonstrate that large-scale analyses of clinical biomarkers using unsupervised methods can offer novel insights into the pathophysiological basis of human disease, and suggest novel clinical utility of established laboratory measurements.

  15. Highly distinct chromosomal structures in cowpea (Vigna unguiculata), as revealed by molecular cytogenetic analysis.

    Science.gov (United States)

    Iwata-Otsubo, Aiko; Lin, Jer-Young; Gill, Navdeep; Jackson, Scott A

    2016-05-01

    Cowpea (Vigna unguiculata (L.) Walp) is an important legume, particularly in developing countries. However, little is known about its genome or chromosome structure. We used molecular cytogenetics to characterize the structure of pachytene chromosomes to advance our knowledge of chromosome and genome organization of cowpea. Our data showed that cowpea has highly distinct chromosomal structures that are cytologically visible as brightly DAPI-stained heterochromatic regions. Analysis of the repetitive fraction of the cowpea genome present at centromeric and pericentromeric regions confirmed that two retrotransposons are major components of pericentromeric regions and that a 455-bp tandem repeat is found at seven out of 11 centromere pairs in cowpea. These repeats likely evolved after the divergence of cowpea from common bean and form chromosomal structure unique to cowpea. The integration of cowpea genetic and physical chromosome maps reveals potential regions of suppressed recombination due to condensed heterochromatin and a lack of pairing in a few chromosomal termini. This study provides fundamental knowledge on cowpea chromosome structure and molecular cytogenetics tools for further chromosome studies.

  16. A quorum-sensing factor in vegetative Dictyostelium discoideum cells revealed by quantitative migration analysis.

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    Laurent Golé

    Full Text Available BACKGROUND: Many cells communicate through the production of diffusible signaling molecules that accumulate and once a critical concentration has been reached, can activate or repress a number of target genes in a process termed quorum sensing (QS. In the social amoeba Dictyostelium discoideum, QS plays an important role during development. However little is known about its effect on cell migration especially in the growth phase. METHODS AND FINDINGS: To investigate the role of cell density on cell migration in the growth phase, we use multisite timelapse microscopy and automated cell tracking. This analysis reveals a high heterogeneity within a given cell population, and the necessity to use large data sets to draw reliable conclusions on cell motion. In average, motion is persistent for short periods of time (t ≤ 5 min, but normal diffusive behavior is recovered over longer time periods. The persistence times are positively correlated with the migrated distances. Interestingly, the migrated distance decreases as well with cell density. The adaptation of cell migration to cell density highlights the role of a secreted quorum sensing factor (QSF on cell migration. Using a simple model describing the balance between the rate of QSF generation and the rate of QSF dilution, we were able to gather all experimental results into a single master curve, showing a sharp cell transition between high and low motile behaviors with increasing QSF. CONCLUSION: This study unambiguously demonstrates the central role played by QSF on amoeboid motion in the growth phase.

  17. Transcriptomic Analysis of Leaf in Tree Peony Reveals Differentially Expressed Pigments Genes.

    Science.gov (United States)

    Luo, Jianrang; Shi, Qianqian; Niu, Lixin; Zhang, Yanlong

    2017-02-20

    Tree peony (Paeonia suffruticosa Andrews) is an important traditional flower in China. Besides its beautiful flower, the leaf of tree peony has also good ornamental value owing to its leaf color change in spring. So far, the molecular mechanism of leaf color change in tree peony is unclear. In this study, the pigment level and transcriptome of three different color stages of tree peony leaf were analyzed. The purplish red leaf was rich in anthocyanin, while yellowish green leaf was rich in chlorophyll and carotenoid. Transcriptome analysis revealed that 4302 differentially expressed genes (DEGs) were upregulated, and 4225 were downregulated in the purplish red leaf vs. yellowish green leaf. Among these DEGs, eight genes were predicted to participate in anthocyanin biosynthesis, eight genes were predicted involved in porphyrin and chlorophyll metabolism, and 10 genes were predicted to participate in carotenoid metabolism. In addition, 27 MYBs, 20 bHLHs, 36 WD40 genes were also identified from DEGs. Anthocyanidin synthase (ANS) is the key gene that controls the anthocyanin level in tree peony leaf. Protochlorophyllide oxido-reductase (POR) is the key gene which regulated the chlorophyll content in tree peony leaf.

  18. Proteomics analysis reveals the molecular mechanism underlying the transition from primary to secondary growth of poplar.

    Science.gov (United States)

    Li, Yuan; Jin, Feng; Chao, Qing; Wang, Bai-Chen

    2017-06-01

    Wood is the most important natural source of energy and also provides fuel and fiber. Considering the significant role of wood, it is critical to understand how wood is formed. Integration of knowledge about wood development at the cellular and molecular levels will allow more comprehensive understanding of this complex process. In the present study, we used a comparative proteomic approach to investigate the differences in protein profiles between primary and secondary growth in young poplar stems using tandem mass tag (TMT)-labeling. More than 10,816 proteins were identified, and, among these, 3106 proteins were differentially expressed during primary to secondary growth. Proteomic data were validated using a combination of histochemical staining, enzyme activity assays, and quantitative real-time PCR. Bioinformatics analysis revealed that these differentially expressed proteins are related to various metabolic pathways, mainly including signaling, phytohormones, cell cycle, cell wall, secondary metabolism, carbohydrate and energy metabolism, and protein metabolism as well as redox and stress pathways. This large proteomics dataset will be valuable for uncovering the molecular changes occurring during the transition from primary to secondary growth. Further, it provides new and accurate information for tree breeding to modify wood properties. Copyright © 2017 Elsevier GmbH. All rights reserved.

  19. Metagenomic Analysis of Apple Orchard Soil Reveals Antibiotic Resistance Genes Encoding Predicted Bifunctional Proteins▿

    Science.gov (United States)

    Donato, Justin J.; Moe, Luke A.; Converse, Brandon J.; Smart, Keith D.; Berklein, Flora C.; McManus, Patricia S.; Handelsman, Jo

    2010-01-01

    To gain insight into the diversity and origins of antibiotic resistance genes, we identified resistance genes in the soil in an apple orchard using functional metagenomics, which involves inserting large fragments of foreign DNA into Escherichia coli and assaying the resulting clones for expressed functions. Among 13 antibiotic-resistant clones, we found two genes that encode bifunctional proteins. One predicted bifunctional protein confers resistance to ceftazidime and contains a natural fusion between a predicted transcriptional regulator and a β-lactamase. Sequence analysis of the entire metagenomic clone encoding the predicted bifunctional β-lactamase revealed a gene potentially involved in chloramphenicol resistance as well as a predicted transposase. A second clone that encodes a predicted bifunctional protein confers resistance to kanamycin and contains an aminoglycoside acetyltransferase domain fused to a second acetyltransferase domain that, based on nucleotide sequence, was predicted not to be involved in antibiotic resistance. This is the first report of a transcriptional regulator fused to a β-lactamase and of an aminoglycoside acetyltransferase fused to an acetyltransferase not involved in antibiotic resistance. PMID:20453147

  20. Network analysis reveals seasonal variation of co-occurrence correlations between Cyanobacteria and other bacterioplankton.

    Science.gov (United States)

    Zhao, Dayong; Shen, Feng; Zeng, Jin; Huang, Rui; Yu, Zhongbo; Wu, Qinglong L

    2016-12-15

    Association network approaches have recently been proposed as a means for exploring the associations between bacterial communities. In the present study, high-throughput sequencing was employed to investigate the seasonal variations in the composition of bacterioplankton communities in six eutrophic urban lakes of Nanjing City, China. Over 150,000 16S rRNA sequences were derived from 52 water samples, and correlation-based network analyses were conducted. Our results demonstrated that the architecture of the co-occurrence networks varied in different seasons. Cyanobacteria played various roles in the ecological networks during different seasons. Co-occurrence patterns revealed that members of Cyanobacteria shared a very similar niche and they had weak positive correlations with other phyla in summer. To explore the effect of environmental factors on species-species co-occurrence networks and to determine the most influential environmental factors, the original positive network was simplified by module partitioning and by calculating module eigengenes. Module eigengene analysis indicated that temperature only affected some Cyanobacteria; the rest were mainly affected by nitrogen associated factors throughout the year. Cyanobacteria were dominant in summer which may result from strong co-occurrence patterns and suitable living conditions. Overall, this study has improved our understanding of the roles of Cyanobacteria and other bacterioplankton in ecological networks. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Integrated Analysis of Alzheimer's Disease and Schizophrenia Dataset Revealed Different Expression Pattern in Learning and Memory.

    Science.gov (United States)

    Li, Wen-Xing; Dai, Shao-Xing; Liu, Jia-Qian; Wang, Qian; Li, Gong-Hua; Huang, Jing-Fei

    2016-01-01

    Alzheimer's disease (AD) and schizophrenia (SZ) are both accompanied by impaired learning and memory functions. This study aims to explore the expression profiles of learning or memory genes between AD and SZ. We downloaded 10 AD and 10 SZ datasets from GEO-NCBI for integrated analysis. These datasets were processed using RMA algorithm and a global renormalization for all studies. Then Empirical Bayes algorithm was used to find the differentially expressed genes between patients and controls. The results showed that most of the differentially expressed genes were related to AD whereas the gene expression profile was little affected in the SZ. Furthermore, in the aspects of the number of differentially expressed genes, the fold change and the brain region, there was a great difference in the expression of learning or memory related genes between AD and SZ. In AD, the CALB1, GABRA5, and TAC1 were significantly downregulated in whole brain, frontal lobe, temporal lobe, and hippocampus. However, in SZ, only two genes CRHBP and CX3CR1 were downregulated in hippocampus, and other brain regions were not affected. The effect of these genes on learning or memory impairment has been widely studied. It was suggested that these genes may play a crucial role in AD or SZ pathogenesis. The different gene expression patterns between AD and SZ on learning and memory functions in different brain regions revealed in our study may help to understand the different mechanism between two diseases.

  2. Revealing spatio-spectral electroencephalographic dynamics of musical mode and tempo perception by independent component analysis.

    Science.gov (United States)

    Lin, Yuan-Pin; Duann, Jeng-Ren; Feng, Wenfeng; Chen, Jyh-Horng; Jung, Tzyy-Ping

    2014-02-28

    Music conveys emotion by manipulating musical structures, particularly musical mode- and tempo-impact. The neural correlates of musical mode and tempo perception revealed by electroencephalography (EEG) have not been adequately addressed in the literature. This study used independent component analysis (ICA) to systematically assess spatio-spectral EEG dynamics associated with the changes of musical mode and tempo. Empirical results showed that music with major mode augmented delta-band activity over the right sensorimotor cortex, suppressed theta activity over the superior parietal cortex, and moderately suppressed beta activity over the medial frontal cortex, compared to minor-mode music, whereas fast-tempo music engaged significant alpha suppression over the right sensorimotor cortex. The resultant EEG brain sources were comparable with previous studies obtained by other neuroimaging modalities, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). In conjunction with advanced dry and mobile EEG technology, the EEG results might facilitate the translation from laboratory-oriented research to real-life applications for music therapy, training and entertainment in naturalistic environments.

  3. Phenotypic factor analysis of psychopathology reveals a new body-related transdiagnostic factor.

    Science.gov (United States)

    Pezzoli, Patrizia; Antfolk, Jan; Santtila, Pekka

    2017-01-01

    Comorbidity challenges the notion of mental disorders as discrete categories. An increasing body of literature shows that symptoms cut across traditional diagnostic boundaries and interact in shaping the latent structure of psychopathology. Using exploratory and confirmatory factor analysis, we reveal the latent sources of covariation among nine measures of psychopathological functioning in a population-based sample of 13024 Finnish twins and their siblings. By implementing unidimensional, multidimensional, second-order, and bifactor models, we illustrate the relationships between observed variables, specific, and general latent factors. We also provide the first investigation to date of measurement invariance of the bifactor model of psychopathology across gender and age groups. Our main result is the identification of a distinct "Body" factor, alongside the previously identified Internalizing and Externalizing factors. We also report relevant cross-disorder associations, especially between body-related psychopathology and trait anger, as well as substantial sex and age differences in observed and latent means. The findings expand the meta-structure of psychopathology, with implications for empirical and clinical practice, and demonstrate shared mechanisms underlying attitudes towards nutrition, self-image, sexuality and anger, with gender- and age-specific features.

  4. Molecular systematic analysis reveals cryptic tertiary diversification of a widespread tropical rain forest tree.

    Science.gov (United States)

    Dick, Christopher W; Abdul-Salim, Kobinah; Bermingham, Eldredge

    2003-12-01

    The broad geographic range of many Neotropical rain forest tree species implies excellent dispersal abilities or range establishment that preceded the formation of current dispersal barriers. In order to initiate historical analyses of such widespread Neotropical trees, we sequenced the nuclear ribosomal spacer (ITS) region of Symphonia globulifera L. f. (Clusiaceae) from populations spanning the Neotropics and western Africa. This rain forest tree has left unmistakable Miocene fossils in Mesoamerica (15.5-18.2 Ma) and in South America ( approximately 15 Ma). Although marine dispersal of S. globulifera is considered improbable, our study establishes three marine dispersal events leading to the colonization of Mesoamerica, the Amazon basin, and the West Indies, thus supporting the paleontological data. Our phylogeographic analysis revealed the spatial extent of the three Neotropical S. globulifera clades, which represent trans-Andes (Mesoamerica+west Ecuador), cis-Andes (Amazonia+Guiana), and the West Indies. Strong phylogeographic structure found among trans-Andean populations of S. globulifera stands in contrast to an absence of ITS nucleotide variation across the Amazon basin and indicates profound regional differences in the demographic history of this rain forest tree. Drawing from these results, we provide a historical biogeographic hypothesis to account for differences in the patterns of beta diversity within Mesoamerican and Amazonian forests.

  5. Raman spectroscopic analysis of Lactobacillus rhamnosus GG in response to dehydration reveals DNA conformation changes.

    Science.gov (United States)

    Myintzu Hlaing, Mya; Wood, Bayden; McNaughton, Don; Ying, DanYan; Augustin, Mary Ann

    2017-04-01

    Dehydration of bacterial cells elicits cellular stress responses in bacteria. Microencapsulation has been used to protect cells against the environmental stress. In this study, Confocal Raman Spectroscopy was used to examine DNA changes in the chemical composition of non-encapsulated and microencapsulated Lactobacillus rhamnosus GG and the reversibility of these changes upon freeze drying and rehydration. The viability of cells upon freeze drying was also enumerated using culture methods and membrane integrity was measured using BacLight Live/Dead staining. Raman analyses show changes in the spectral features associated with various biochemical compounds, which are interpreted as the result of detrimental freeze drying effects on the bacterial cells. Specifically, analyses based on Principal Components Analysis (PCA) of Raman spectra, confirm that microencapsulation protects cells from environmental stress. The results also reveal a B- to A-like DNA conformation change in dormant cells that provided insights into the extent of reversibility of this transition upon rehydration. The extent of this reversibility is less in non-encapsulated than in microencapsulated cells. These findings indicate the potential application of Raman spectroscopy in rapid sensing of microbial dehydration stress responses. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. A Simple Geotracer Compositional Correlation Analysis Reveals Oil Charge and Migration Pathways.

    Science.gov (United States)

    Yang, Yunlai; Arouri, Khaled

    2016-03-11

    A novel approach, based on geotracer compositional correlation analysis is reported, which reveals the oil charge sequence and migration pathways for five oil fields in Saudi Arabia. The geotracers utilised are carbazoles, a family of neutral pyrrolic nitrogen compounds known to occur naturally in crude oils. The approach is based on the concept that closely related fields, with respect to filling sequence, will show a higher carbazole compositional correlation, than those fields that are less related. That is, carbazole compositional correlation coefficients can quantify the charge and filling relationships among different fields. Consequently, oil migration pathways can be defined based on the established filling relationships. The compositional correlation coefficients of isomers of C1 and C2 carbazoles, and benzo[a]carbazole for all different combination pairs of the five fields were found to vary extremely widely (0.28 to 0.94). A wide range of compositional correlation coefficients allows adequate differentiation of separate filling relationships. Based on the established filling relationships, three distinct migration pathways were inferred, with each apparently being charged from a different part of a common source kitchen. The recognition of these charge and migration pathways will greatly aid the search for new accumulations.

  7. A Simple Geotracer Compositional Correlation Analysis Reveals Oil Charge and Migration Pathways

    Science.gov (United States)

    Yang, Yunlai; Arouri, Khaled

    2016-03-01

    A novel approach, based on geotracer compositional correlation analysis is reported, which reveals the oil charge sequence and migration pathways for five oil fields in Saudi Arabia. The geotracers utilised are carbazoles, a family of neutral pyrrolic nitrogen compounds known to occur naturally in crude oils. The approach is based on the concept that closely related fields, with respect to filling sequence, will show a higher carbazole compositional correlation, than those fields that are less related. That is, carbazole compositional correlation coefficients can quantify the charge and filling relationships among different fields. Consequently, oil migration pathways can be defined based on the established filling relationships. The compositional correlation coefficients of isomers of C1 and C2 carbazoles, and benzo[a]carbazole for all different combination pairs of the five fields were found to vary extremely widely (0.28 to 0.94). A wide range of compositional correlation coefficients allows adequate differentiation of separate filling relationships. Based on the established filling relationships, three distinct migration pathways were inferred, with each apparently being charged from a different part of a common source kitchen. The recognition of these charge and migration pathways will greatly aid the search for new accumulations.

  8. Rapid Holocene coastal change revealed by high-resolution micropaleontological analysis, Pamlico Sound, North Carolina, USA

    Science.gov (United States)

    Grand, Pre C.; Culver, S.J.; Mallinson, D.J.; Farrell, K.M.; Corbett, D.R.; Horton, B.P.; Hillier, C.; Riggs, S.R.; Snyder, S.W.; Buzas, M.A.

    2011-01-01

    Foraminiferal analyses of 404 contiguous samples, supported by diatom, lithologic, geochronologic and seismic data, reveal both rapid and gradual Holocene paleoenvironmental changes in an 8.21-m vibracore taken from southern Pamlico Sound, North Carolina. Data record initial flooding of a latest Pleistocene river drainage and the formation of an estuary 9000. yr ago. Estuarine conditions were punctuated by two intervals of marine influence from approximately 4100 to 3700 and 1150 to 500. cal. yr BP. Foraminiferal assemblages in the muddy sand facies that accumulated during these intervals contain many well-preserved benthic foraminiferal species, which occur today in open marine settings as deep as the mid shelf, and significant numbers of well-preserved planktonic foraminifera, some typical of Gulf Stream waters. We postulate that these marine-influenced units resulted from temporary destruction of the southern Outer Banks barrier islands by hurricanes. The second increase in marine influence is coeval with increased rate of sea-level rise and a peak in Atlantic tropical cyclone activity during the Medieval Climate Anomaly. This high-resolution analysis demonstrates the range of environmental variability and the rapidity of coastal change that can result from the interplay of changing climate, sea level and geomorphology in an estuarine setting. ?? 2011 University of Washington.

  9. Transcriptome analysis reveals positive selection on the divergent between topmouth culter and zebrafish.

    Science.gov (United States)

    Ren, Li; Tan, Xing-Jun; Xiong, Ya-Feng; Xu, Kang; Zhou, Yi; Zhong, Huan; Liu, Yun; Hong, Yun-Han; Liu, Shao-Jun

    2014-12-01

    The topmouth culter (Erythroculter ilishaeformis) is a predatory cyprinid fish that distributes widely in the East Asia. Here we report the liver transcriptome in this organism as a model of predatory fish. Sequencing of 5 Gb raw reads led to 27,741 unigenes and produced 11,131 annotatable genes. A total of 7093 (63.7%) genes were found to have putative functions by gene ontology analysis. Importantly, a blast search revealed 4033 culter genes that were orthologous to the zebrafish. Extracted from 38 candidate positive selection genes, 4 genes exhibit strong positive selection based on the ratio of nonsynonymous (Ka) to synonymous substitutions (Ks). In addition, the four genes also indicated the strong positive selection by comparing them between blunt snout bream (Megalobrama amblycephala) and zebrafish. These genes were involved in activator of gene expression, metabolic processes and development. The transcriptome variation may be reflective of natural selection in the early life history of Cyprinidae. Based on Ks ratios, date of the separation between topmouth culter and zebrafish is approximately 64 million years ago. We conclude that natural selection acts in diversifying the genomes between topmouth culter and zebrafish. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Transcriptome analysis of Phytophthora litchii reveals pathogenicity arsenals and confirms taxonomic status.

    Science.gov (United States)

    Sun, Jinhua; Gao, Zhaoyin; Zhang, Xinchun; Zou, Xiaoxiao; Cao, Lulu; Wang, Jiabao

    2017-01-01

    Litchi downy blight, caused by Peronophythora litchii, is one of the major diseases of litchi and has caused severe economic losses. P. litchii has the unique ability to produce downy mildew like sporangiophores under artificial culture. The pathogen had been placed in a new family Peronophytophthoraceae by some authors. In this study, the whole transcriptome of P. litchii from mycelia, sporangia, and zoospores was sequenced for the first time. A set of 23637 transcripts with an average length of 1284 bp was assembled. Using six open reading frame (ORF) predictors, 19267 representative ORFs were identified and were annotated by searching against several public databases. There were 4666 conserved gene families and various sets of lineage-specific genes among P. litchii and other four closely related oomycetes. In silico analyses revealed 490 pathogen-related proteins including 128 RXLR and 22 CRN effector candidates. Based on the phylogenetic analysis of 164 single copy orthologs from 22 species, it is validated that P. litchii is in the genus Phytophthora. Our work provides valuable data to elucidate the pathogenicity basis and ascertain the taxonomic status of P. litchii.

  11. Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum.

    Science.gov (United States)

    Kenyon, Amy; Gavriouchkina, Daria; Zorman, Jernej; Napolitani, Giorgio; Cerundolo, Vincenzo; Sauka-Spengler, Tatjana

    2017-07-26

    The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β. Crispr/Cas9-mediated knockout of caspase b, which acts by proteolytic processing of il1β, results in increased bacterial burden and less infiltration of macrophages to sites of mycobacterial infection, thus impairing granuloma development. We also show that a number of immediate early response genes (IEGs) are responsible for orchestrating the initial neutrophil response to mycobacterial infection. Further perturbation of the IEGs exposes egr3 as a key transcriptional regulator controlling il1β transcription.

  12. The Immersive Virtual Reality Experience: A Typology of Users Revealed Through Multiple Correspondence Analysis Combined with Cluster Analysis Technique.

    Science.gov (United States)

    Rosa, Pedro J; Morais, Diogo; Gamito, Pedro; Oliveira, Jorge; Saraiva, Tomaz

    2016-03-01

    Immersive virtual reality is thought to be advantageous by leading to higher levels of presence. However, and despite users getting actively involved in immersive three-dimensional virtual environments that incorporate sound and motion, there are individual factors, such as age, video game knowledge, and the predisposition to immersion, that may be associated with the quality of virtual reality experience. Moreover, one particular concern for users engaged in immersive virtual reality environments (VREs) is the possibility of side effects, such as cybersickness. The literature suggests that at least 60% of virtual reality users report having felt symptoms of cybersickness, which reduces the quality of the virtual reality experience. The aim of this study was thus to profile the right user to be involved in a VRE through head-mounted display. To examine which user characteristics are associated with the most effective virtual reality experience (lower cybersickness), a multiple correspondence analysis combined with cluster analysis technique was performed. Results revealed three distinct profiles, showing that the PC gamer profile is more associated with higher levels of virtual reality effectiveness, that is, higher predisposition to be immersed and reduced cybersickness symptoms in the VRE than console gamer and nongamer. These findings can be a useful orientation in clinical practice and future research as they help identify which users are more predisposed to benefit from immersive VREs.

  13. Comparative Genomic Analysis Reveals Habitat-Specific Genes and Regulatory Hubs within the GenusNovosphingobium.

    Science.gov (United States)

    Kumar, Roshan; Verma, Helianthous; Haider, Shazia; Bajaj, Abhay; Sood, Utkarsh; Ponnusamy, Kalaiarasan; Nagar, Shekhar; Shakarad, Mallikarjun N; Negi, Ram Krishan; Singh, Yogendra; Khurana, J P; Gilbert, Jack A; Lal, Rup

    2017-01-01

    Species belonging to the genus Novosphingobium are found in many different habitats and have been identified as metabolically versatile. Through comparative genomic analysis, we identified habitat-specific genes and regulatory hubs that could determine habitat selection for Novosphingobium spp. Genomes from 27 Novosphingobium strains isolated from diverse habitats such as rhizosphere soil, plant surfaces, heavily contaminated soils, and marine and freshwater environments were analyzed. Genome size and coding potential were widely variable, differing significantly between habitats. Phylogenetic relationships between strains were less likely to describe functional genotype similarity than the habitat from which they were isolated. In this study, strains (19 out of 27) with a recorded habitat of isolation, and at least 3 representative strains per habitat, comprised four ecological groups-rhizosphere, contaminated soil, marine, and freshwater. Sulfur acquisition and metabolism were the only core genomic traits to differ significantly in proportion between these ecological groups; for example, alkane sulfonate ( ssuABCD ) assimilation was found exclusively in all of the rhizospheric isolates. When we examined osmolytic regulation in Novosphingobium spp. through ectoine biosynthesis, which was assumed to be marine habitat specific, we found that it was also present in isolates from contaminated soil, suggesting its relevance beyond the marine system. Novosphingobium strains were also found to harbor a wide variety of mono- and dioxygenases, responsible for the metabolism of several aromatic compounds, suggesting their potential to act as degraders of a variety of xenobiotic compounds. Protein-protein interaction analysis revealed β-barrel outer membrane proteins as habitat-specific hubs in each of the four habitats-freshwater (Saro_1868), marine water (PP1Y_AT17644), rhizosphere (PMI02_00367), and soil (V474_17210). These outer membrane proteins could play a key role

  14. Proteomic analysis reveals changes in carbohydrate and protein metabolism associated with broiler breast myopathy.

    Science.gov (United States)

    Kuttappan, Vivek A; Bottje, Walter; Ramnathan, Ranjith; Hartson, Steven D; Coon, Craig N; Kong, Byung-Whi; Owens, Casey M; Vazquez-Añon, Mercedes; Hargis, Billy M

    2017-08-01

    White Striping (WS) and Woody Breast (WB) are 2 conditions that adversely affect consumer acceptance as well as quality of poultry meat and meat products. Both WS and WB are characterized with degenerative myopathic changes. Previous studies showed that WS and WB in broiler fillets could result in higher ultimate pH, increased drip loss, and decreased marinade uptake. The main objective of the present study was to compare the proteomic profiles of muscle tissue (n = 5 per group) with either NORM (no or few minor myopathic lesions) or SEV (with severe myopathic changes). Proteins were extracted from these samples and analyzed using a hybrid LTQ-OrbitrapXL mass spectrometer (LC-MS/MS). Over 800 proteins were identified in the muscle samples, among which 141 demonstrated differential (P < 0.05) expression between NORM and SEV. The set of differentially (P < 0.05) expressed proteins was uploaded to Ingenuity Pathway Analysis® (IPA) software to determine the associated biological networks and pathways. The IPA analysis showed that eukaryotic initiation factor-2 (eIF-2) signaling, mechanistic target of rapamycin (mTOR) signaling, as well as regulation of eIF4 and p70S6K signaling were the major canonical pathways up-regulated (P < 0.05) in SEV muscle compared to NORM. The up-regulation of these pathways indicate an increase in protein synthesis which could be part of the rapid growth as well as cellular stress associated with ongoing muscle degeneration and the attempt to repair tissue damage in SEV birds. Furthermore, IPA analysis revealed that glycolysis and gluconeogenesis were the major down-regulated (P < 0.05) canonical pathways in SEV with respect to NORM muscle. Down-regulation of these pathways could be the reason for higher ultimate pH seen in SEV muscle samples indicating reduced glycolytic potential. In conclusion, comparison of proteomic profiles of NORM and SEV muscle samples showed differences in protein profile which explains some of the observed

  15. Proteomic and bioinformatic analysis of epithelial tight junction reveals an unexpected cluster of synaptic molecules

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    Tang Vivian W

    2006-12-01

    Full Text Available Abstract Background Zonula occludens, also known as the tight junction, is a specialized cell-cell interaction characterized by membrane "kisses" between epithelial cells. A cytoplasmic plaque of ~100 nm corresponding to a meshwork of densely packed proteins underlies the tight junction membrane domain. Due to its enormous size and difficulties in obtaining a biochemically pure fraction, the molecular composition of the tight junction remains largely unknown. Results A novel biochemical purification protocol has been developed to isolate tight junction protein complexes from cultured human epithelial cells. After identification of proteins by mass spectroscopy and fingerprint analysis, candidate proteins are scored and assessed individually. A simple algorithm has been devised to incorporate transmembrane domains and protein modification sites for scoring membrane proteins. Using this new scoring system, a total of 912 proteins have been identified. These 912 hits are analyzed using a bioinformatics approach to bin the hits in 4 categories: configuration, molecular function, cellular function, and specialized process. Prominent clusters of proteins related to the cytoskeleton, cell adhesion, and vesicular traffic have been identified. Weaker clusters of proteins associated with cell growth, cell migration, translation, and transcription are also found. However, the strongest clusters belong to synaptic proteins and signaling molecules. Localization studies of key components of synaptic transmission have confirmed the presence of both presynaptic and postsynaptic proteins at the tight junction domain. To correlate proteomics data with structure, the tight junction has been examined using electron microscopy. This has revealed many novel structures including end-on cytoskeletal attachments, vesicles fusing/budding at the tight junction membrane domain, secreted substances encased between the tight junction kisses, endocytosis of tight junction

  16. Bivariate genome-wide association analyses identified genetic pleiotropic effects for bone mineral density and alcohol drinking in Caucasians.

    Science.gov (United States)

    Lu, Shan; Zhao, Lan-Juan; Chen, Xiang-Ding; Papasian, Christopher J; Wu, Ke-Hao; Tan, Li-Jun; Wang, Zhuo-Er; Pei, Yu-Fang; Tian, Qing; Deng, Hong-Wen

    2017-11-01

    Several studies indicated bone mineral density (BMD) and alcohol intake might share common genetic factors. The study aimed to explore potential SNPs/genes related to both phenotypes in US Caucasians at the genome-wide level. A bivariate genome-wide association study (GWAS) was performed in 2069 unrelated participants. Regular drinking was graded as 1, 2, 3, 4, 5, or 6, representing drinking alcohol never, less than once, once or twice, three to six times, seven to ten times, or more than ten times per week respectively. Hip, spine, and whole body BMDs were measured. The bivariate GWAS was conducted on the basis of a bivariate linear regression model. Sex-stratified association analyses were performed in the male and female subgroups. In males, the most significant association signal was detected in SNP rs685395 in DYNC2H1 with bivariate spine BMD and alcohol drinking (P = 1.94 × 10 -8 ). SNP rs685395 and five other SNPs, rs657752, rs614902, rs682851, rs626330, and rs689295, located in the same haplotype block in DYNC2H1 were the top ten most significant SNPs in the bivariate GWAS in males. Additionally, two SNPs in GRIK4 in males and three SNPs in OPRM1 in females were suggestively associated with BMDs (of the hip, spine, and whole body) and alcohol drinking. Nine SNPs in IL1RN were only suggestively associated with female whole body BMD and alcohol drinking. Our study indicated that DYNC2H1 may contribute to the genetic mechanisms of both spine BMD and alcohol drinking in male Caucasians. Moreover, our study suggested potential pleiotropic roles of OPRM1 and IL1RN in females and GRIK4 in males underlying variation of both BMD and alcohol drinking.

  17. Image Restoration and Analysis of Influenza Virions Binding to Membrane Receptors Reveal Adhesion-Strengthening Kinetics.

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    Donald W Lee

    Full Text Available With the development of single-particle tracking (SPT microscopy and host membrane mimics called supported lipid bilayers (SLBs, stochastic virus-membrane binding interactions can be studied in depth while maintaining control over host receptor type and concentration. However, several experimental design challenges and quantitative image analysis limitations prevent the widespread use of this approach. One main challenge of SPT studies is the low signal-to-noise ratio of SPT videos, which is sometimes inevitable due to small particle sizes, low quantum yield of fluorescent dyes, and photobleaching. These situations could render current particle tracking software to yield biased binding kinetic data caused by intermittent tracking error. Hence, we developed an effective image restoration algorithm for SPT applications called STAWASP that reveals particles with a signal-to-noise ratio of 2.2 while preserving particle features. We tested our improvements to the SPT binding assay experiment and imaging procedures by monitoring X31 influenza virus binding to α2,3 sialic acid glycolipids. Our interests lie in how slight changes to the peripheral oligosaccharide structures can affect the binding rate and residence times of viruses. We were able to detect viruses binding weakly to a glycolipid called GM3, which was undetected via assays such as surface plasmon resonance. The binding rate was around 28 folds higher when the virus bound to a different glycolipid called GD1a, which has a sialic acid group extending further away from the bilayer surface than GM3. The improved imaging allowed us to obtain binding residence time distributions that reflect an adhesion-strengthening mechanism via multivalent bonds. We empirically fitted these distributions using a time-dependent unbinding rate parameter, koff, which diverges from standard treatment of koff as a constant. We further explain how to convert these models to fit ensemble-averaged binding data

  18. Proteomic analysis reveals differential protein expression in variants of papillary thyroid carcinoma

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    Yasemin Ucal

    2017-12-01

    Full Text Available Introduction: Fine Needle Aspiration Biopsy (FNAB allows the cytological differentiation of benign and malignant thyroid nodules. However, the method itself is not adequate in determining some cases. For example, the diagnosis of Follicular Variant Papillary Thyroid Carcinoma (FV-PTC can be challenging. In the current study we investigate the protein profiles of FV-PTC and classical variant PTC (CV-PTC with no lymph node metastasis and compare it with benign thyroid tissue. Method: We used CV-PTC (n = 6, FV-PTC (n = 6 and benign thyroid tissues (n = 6 to prepare tissue lysates. Proteins from each group were trypsin and lys-C digested. The samples were analyzed on a Q Exactive Orbitrap mass spectrometer. Results: We identified 2560 proteins across all 18 specimens. Protein profiles revealed that there was no clear distinction between benign and FV-PTC samples. However, further examination of our data showed that proteins in energy metabolism have altered in FV-PTC. Proteomic pathway analysis showed marked alteration of the actin cytoskeleton proteins, especially several members of Arp2/3 complex were significantly increased in CV-PTC. We made the novel observation that IQGAP1 protein was significantly increased in CV-PTC, whereas IQGAP2 protein was highly expressed in FV-PTC lesions, suggesting differential roles of IQGAP proteins in thyroid pathology. Conclusion: In the present study, mass spectrometry based label free quantification approach was applied to investigate the protein profiles of FV-PTC, CV-PTC and benign thyroid tissues. This study pointed out that actin cytoskeleton proteins, IQGAP proteins and changes in energy metabolism play predominant roles in thyroid pathology. Keywords: Papillary thyroid carcinoma, IQGAP, Proteomics, Mass spectrometry

  19. Evolutionary history of barley cultivation in Europe revealed by genetic analysis of extant landraces

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    Jones Huw

    2011-11-01

    Full Text Available Abstract Background Understanding the evolution of cultivated barley is important for two reasons. First, the evolutionary relationships between different landraces might provide information on the spread and subsequent development of barley cultivation, including the adaptation of the crop to new environments and its response to human selection. Second, evolutionary information would enable landraces with similar traits but different genetic backgrounds to be identified, providing alternative strategies for the introduction of these traits into modern germplasm. Results The evolutionary relationships between 651 barley landraces were inferred from the genotypes for 24 microsatellites. The landraces could be divided into nine populations, each with a different geographical distribution. Comparisons with ear row number, caryopsis structure, seasonal growth habit and flowering time revealed a degree of association between population structure and phenotype, and analysis of climate variables indicated that the landraces are adapted, at least to some extent, to their environment. Human selection and/or environmental adaptation may therefore have played a role in the origin and/or maintenance of one or more of the barley landrace populations. There was also evidence that at least some of the population structure derived from geographical partitioning set up during the initial spread of barley cultivation into Europe, or reflected the later introduction of novel varieties. In particular, three closely-related populations were made up almost entirely of plants with the daylength nonresponsive version of the photoperiod response gene PPD-H1, conferring adaptation to the long annual growth season of northern Europe. These three populations probably originated in the eastern Fertile Crescent and entered Europe after the initial spread of agriculture. Conclusions The discovery of population structure, combined with knowledge of associated phenotypes and

  20. Genetic Mapping and Phylogenetic Analysis Reveal Intraspecific Variation in Sex Chromosomes of the Virginian Strawberry.

    Science.gov (United States)

    Wei, Na; Govindarajulu, Rajanikanth; Tennessen, Jacob A; Liston, Aaron; Ashman, Tia-Lynn

    2017-10-30

    With their extraordinary diversity in sexual systems, flowering plants offer unparalleled opportunities to understand sex determination and to reveal generalities in the evolution of sex chromosomes. Comparative genetic mapping of related taxa with good phylogenetic resolution can delineate the extent of sex chromosome diversity within plant groups, and lead the way to understanding the evolutionary drivers of such diversity. The North American octoploid wild strawberries provide such an opportunity. We performed linkage mapping using targeted sequence capture for the subdioecious western Fragaria virginiana ssp. platypetala and compared the location of its sex-determining region (SDR) to those of 2 other (sub)dioecious species, the eastern subspecies, F. virginiana ssp. virginiana (whose SDR is at 0-5.5 Mb on chromosome VI of the B2 subgenome), and the sister species F. chiloensis (whose SDR is at 37 Mb on chromosome VI of the Av subgenome). Male sterility was dominant in F. virginiana ssp. platypetala and mapped to a chromosome also in homeologous group VI. Likewise, one major quantitative trait locus (QTL) for female fertility overlapped the male sterility region. However, the SDR mapped to yet another subgenome (B1), and to a different location (13 Mb), but similar to the location inferred in one population of the naturally occurring hybrid between F. chiloensis and F. virginiana (F. ×ananassa ssp. cuneifolia). Phylogenetic analysis of chromosomes across the octoploid taxa showed consistent subgenomic composition reflecting shared evolutionary history but also reinforced within-species variation in the SDR-carrying chromosome, suggesting either repeated evolution, or recent turnovers in SDR. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Sequence analysis of mtDNA COI barcode region revealed three haplotypes within Culex pipiens assemblage.

    Science.gov (United States)

    Koosha, Mona; Oshaghi, Mohammad Ali; Sedaghat, Mohammad Mehdi; Vatandoost, Hassan; Azari-Hamidian, Shahyad; Abai, Mohammad Reza; Hanafi-Bojd, Ahmad Ali; Mohtarami, Fatemeh

    2017-10-01

    Members of the Culex (Culex) pipiens assemblage are known vectors of deadly encephalitides, periodic filariasis, and West Nile virus throughout the world. However, members of this assemblage are morphologically indistinguishable or hard to distinguish and play distinct roles in transmission of the diseases. The current study aimed to provide further evidence on utility of the two most popular nuclear (ITS2-rDNA) and mitochondrial (COI barcode region) genetic markers to identify members of the assemblage. Culex pipiens assemblage specimens from different climate zones of Iran were collected and identified to species level based on morphological characteristics. Nucleotide sequences of the loci for the specimens plus available data in the GenBank were analyzed to find species specific genetic structures useful for diagnosis purposes. ITS2 region was highly divergent within species or populations suggesting lack of consistency as a reliable molecular marker. In contrast, sequence analysis of 710 bp of COI gene revealed three fixed haplotypes named here "C, T, H" within the assemblage which can be distinguished by HaeIII and AluI enzymes. There were a correlation between the haplotypes and the world climate regions, where the haplotypes H/T and C are present mainly in temperate and tropical regions of the world, respectively. In the New world, Australia, and Japan only haplotype H is found. In conjunction between tropical and temperate regions such Iran, China, and Turkey, a mix of C/H or C/H/T are present. Although, the haplotypes are not strictly species-specific, however, Cx. quinquefasciatus was mainly of haplotype C. Due to the lack of mating barrier and questionable taxonomic situation of the complex members, the mentioned haplotypes in combination with other morphological and molecular characters might be used to address the genetic structure of the studied populations. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Molecular determinants of juvenile hormone action as revealed by 3D QSAR analysis in Drosophila.

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    Denisa Liszeková

    Full Text Available BACKGROUND: Postembryonic development, including metamorphosis, of many animals is under control of hormones. In Drosophila and other insects these developmental transitions are regulated by the coordinate action of two principal hormones, the steroid ecdysone and the sesquiterpenoid juvenile hormone (JH. While the mode of ecdysone action is relatively well understood, the molecular mode of JH action remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: To gain more insights into the molecular mechanism of JH action, we have tested the biological activity of 86 structurally diverse JH agonists in Drosophila melanogaster. The results were evaluated using 3D QSAR analyses involving CoMFA and CoMSIA procedures. Using this approach we have generated both computer-aided and species-specific pharmacophore fingerprints of JH and its agonists, which revealed that the most active compounds must possess an electronegative atom (oxygen or nitrogen at both ends of the molecule. When either of these electronegative atoms are replaced by carbon or the distance between them is shorter than 11.5 A or longer than 13.5 A, their biological activity is dramatically decreased. The presence of an electron-deficient moiety in the middle of the JH agonist is also essential for high activity. CONCLUSIONS/SIGNIFICANCE: The information from 3D QSAR provides guidelines and mechanistic scope for identification of steric and electrostatic properties as well as donor and acceptor hydrogen-bonding that are important features of the ligand-binding cavity of a JH target protein. In order to refine the pharmacophore analysis and evaluate the outcomes of the CoMFA and CoMSIA study we used pseudoreceptor modeling software PrGen to generate a putative binding site surrogate that is composed of eight amino acid residues corresponding to the defined molecular interactions.

  3. Comparative genome analysis reveals metabolic versatility and environmental adaptations of Sulfobacillus thermosulfidooxidans strain ST.

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    Xue Guo

    Full Text Available The genus Sulfobacillus is a cohort of mildly thermophilic or thermotolerant acidophiles within the phylum Firmicutes and requires extremely acidic environments and hypersalinity for optimal growth. However, our understanding of them is still preliminary partly because few genome sequences are available. Here, the draft genome of Sulfobacillus thermosulfidooxidans strain ST was deciphered to obtain a comprehensive insight into the genetic content and to understand the cellular mechanisms necessary for its survival. Furthermore, the expressions of key genes related with iron and sulfur oxidation were verified by semi-quantitative RT-PCR analysis. The draft genome sequence of Sulfobacillus thermosulfidooxidans strain ST, which encodes 3225 predicted coding genes on a total length of 3,333,554 bp and a 48.35% G+C, revealed the high degree of heterogeneity with other Sulfobacillus species. The presence of numerous transposases, genomic islands and complete CRISPR/Cas defence systems testifies to its dynamic evolution consistent with the genome heterogeneity. As expected, S. thermosulfidooxidans encodes a suit of conserved enzymes required for the oxidation of inorganic sulfur compounds (ISCs. The model of sulfur oxidation in S. thermosulfidooxidans was proposed, which showed some different characteristics from the sulfur oxidation of Gram-negative A. ferrooxidans. Sulfur oxygenase reductase and heterodisulfide reductase were suggested to play important roles in the sulfur oxidation. Although the iron oxidation ability was observed, some key proteins cannot be identified in S. thermosulfidooxidans. Unexpectedly, a predicted sulfocyanin is proposed to transfer electrons in the iron oxidation. Furthermore, its carbon metabolism is rather flexible, can perform the transformation of pentose through the oxidative and non-oxidative pentose phosphate pathways and has the ability to take up small organic compounds. It encodes a multitude of heavy metal

  4. Metabolite analysis of Mycobacterium species under aerobic and hypoxic conditions reveals common metabolic traits.

    Science.gov (United States)

    Drapal, Margit; Wheeler, Paul R; Fraser, Paul D

    2016-08-01

    A metabolite profiling approach has been implemented to elucidate metabolic adaptation at set culture conditions in five Mycobacterium species (two fast- and three slow-growing) with the potential to act as model organisms for Mycobacterium tuberculosis (Mtb). Analysis has been performed over designated growth phases and under representative environments (nutrient and oxygen depletion) experienced by Mtb during infection. The procedure was useful in determining a range of metabolites (60-120 compounds) covering nucleotides, amino acids, organic acids, saccharides, fatty acids, glycerols, -esters, -phosphates and isoprenoids. Among these classes of compounds, key biomarker metabolites, which can act as indicators of pathway/process activity, were identified. In numerous cases, common metabolite traits were observed for all five species across the experimental conditions (e.g. uracil indicating DNA repair). Amino acid content, especially glutamic acid, highlighted the different properties between the fast- and slow-growing mycobacteria studied (e.g. nitrogen assimilation). The greatest similarities in metabolite composition between fast- and slow-growing mycobacteria were apparent under hypoxic conditions. A comparison to previously reported transcriptomic data revealed a strong correlation between changes in transcription and metabolite content. Collectively, these data validate the changes in the transcription at the metabolite level, suggesting transcription exists as one of the predominant modes of cellular regulation in Mycobacterium. Sectors with restricted correlation between metabolites and transcription (e.g. hypoxic cultivation) warrant further study to elucidate and exploit post-transcriptional modes of regulation. The strong correlation between the laboratory conditions used and data derived from in vivo conditions, indicate that the approach applied is a valuable addition to our understanding of cell regulation in these Mycobacterium species.

  5. Proteomic analysis reveals metabolic and regulatory systems involved the syntrophic and axenic lifestyle of Syntrophomonas wolfei.

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    Jessica Rhea Sieber

    2015-02-01

    Full Text Available Microbial syntrophy is a vital metabolic interaction necessary for the complete oxidation of organic biomass to methane in all-anaerobic ecosystems. However, this process is thermodynamically constrained and represents an ecosystem-level metabolic bottleneck. To gain insight into the physiology of this process, a shotgun proteomic approach was used to quantify the protein landscape of the model syntrophic metabolizer, Syntrophomonas wolfei, grown axenically and syntrophically with Methanospirillum hungatei. Remarkably, the abundance of most proteins as represented by normalized spectral abundance factor (NSAF value changed very little between the pure and coculture growth conditions. Among the most abundant proteins detected were GroEL and GroES chaperonins, a small heat shock protein, and proteins involved in electron transfer, beta-oxidation, and ATP synthesis. Several putative energy conservation enzyme systems that utilize NADH and ferredoxin were present. The abundance of an EtfAB2 and the membrane-bound iron-sulfur oxidoreductase (Swol_0698 gene product delineated a potential conduit for electron transfer between acyl-CoA dehydrogenases and membrane redox carriers. Proteins detected only when S. wolfei was grown with M. hungatei included a zinc-dependent dehydrogenase with a GroES domain, whose gene is present in genomes in many organisms capable of syntrophy, and transcriptional regulators responsive to environmental stimuli or the physiological status of the cell. The proteomic analysis revealed an emphasis macromolecular stability and energy metabolism to S. wolfei and presence of regulatory mechanisms responsive to external stimuli and cellular physiological status.

  6. Network analysis reveals a causal role of mitochondrial gene activity in atherosclerotic lesion formation.

    Science.gov (United States)

    Vilne, Baiba; Skogsberg, Josefin; Foroughi Asl, Hassan; Talukdar, Husain Ahammad; Kessler, Thorsten; Björkegren, Johan L M; Schunkert, Heribert

    2017-12-01

    Mitochondrial damage and augmented production of reactive oxygen species (ROS) may represent an intermediate step by which hypercholesterolemia exacerbates atherosclerotic lesion formation. To test this hypothesis, in mice with severe but genetically reversible hypercholesterolemia (i.e. the so called Reversa mouse model), we performed time-resolved analyses of mitochondrial transcriptome in the aortic arch employing a systems-level network approach. During hypercholesterolemia, we observed a massive down-regulation (>28%) of mitochondrial genes, specifically at the time of rapid atherosclerotic lesion expansion and foam cell formation, i.e. between 30 and 40 weeks of age. Both phenomena - down-regulation of mitochondrial genes and lesion expansion - were largely reversible by genetically lowering plasma cholesterol (by >80%, from 427 to 54 ± 31 mg/L) at 30 weeks. Co-expression network analysis revealed that both mitochondrial signature genes were highly connected in two modules, negatively correlating with lesion size and supported as causal for coronary artery disease (CAD) in humans, as expression-associated single nucleotide polymorphisms (eSNPs) representing their genes overlapped markedly with established disease risk loci. Within these modules, we identified the transcription factor estrogen related receptor (ERR)-α and its co-factors PGC1-α and -β, i.e. two members of the peroxisome proliferator-activated receptor γ co-activator 1 family of transcription regulators, as key regulatory genes. Together, these factors are known as major orchestrators of mitochondrial biogenesis and antioxidant responses. Using a network approach, we demonstrate how hypercholesterolemia could hamper mitochondrial activity during atherosclerosis progression and pinpoint potential therapeutic targets to counteract these processes. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Phylogenomic analysis reveals dynamic evolutionary history of the Drosophila heterochromatin protein 1 (HP1 gene family.

    Directory of Open Access Journals (Sweden)

    Mia T Levine

    Full Text Available Heterochromatin is the gene-poor, satellite-rich eukaryotic genome compartment that supports many essential cellular processes. The functional diversity of proteins that bind and often epigenetically define heterochromatic DNA sequence reflects the diverse functions supported by this enigmatic genome compartment. Moreover, heterogeneous signatures of selection at chromosomal proteins often mirror the heterogeneity of evolutionary forces that act on heterochromatic DNA. To identify new such surrogates for dissecting heterochromatin function and evolution, we conducted a comprehensive phylogenomic analysis of the Heterochromatin Protein 1 gene family across 40 million years of Drosophila evolution. Our study expands this gene family from 5 genes to at least 26 genes, including several uncharacterized genes in Drosophila melanogaster. The 21 newly defined HP1s introduce unprecedented structural diversity, lineage-restriction, and germline-biased expression patterns into the HP1 family. We find little evidence of positive selection at these HP1 genes in both population genetic and molecular evolution analyses. Instead, we find that dynamic evolution occurs via prolific gene gains and losses. Despite this dynamic gene turnover, the number of HP1 genes is relatively constant across species. We propose that karyotype evolution drives at least some HP1 gene turnover. For example, the loss of the male germline-restricted HP1E in the obscura group coincides with one episode of dramatic karyotypic evolution, including the gain of a neo-Y in this lineage. This expanded compendium of ovary- and testis-restricted HP1 genes revealed by our study, together with correlated gain/loss dynamics and chromosome fission/fusion events, will guide functional analyses of novel roles supported by germline chromatin.

  8. MultipleLegionella pneumophilaeffector virulence phenotypes revealed through high-throughput analysis of targeted mutant libraries.

    Science.gov (United States)

    Shames, Stephanie R; Liu, Luying; Havey, James C; Schofield, Whitman B; Goodman, Andrew L; Roy, Craig R

    2017-11-28

    Legionella pneumophila is the causative agent of a severe pneumonia called Legionnaires' disease. A single strain of L. pneumophila encodes a repertoire of over 300 different effector proteins that are delivered into host cells by the Dot/Icm type IV secretion system during infection. The large number of L. pneumophila effectors has been a limiting factor in assessing the importance of individual effectors for virulence. Here, a transposon insertion sequencing technology called INSeq was used to analyze replication of a pool of effector mutants in parallel both in a mouse model of infection and in cultured host cells. Loss-of-function mutations in genes encoding effector proteins resulted in host-specific or broad virulence phenotypes. Screen results were validated for several effector mutants displaying different virulence phenotypes using genetic complementation studies and infection assays. Specifically, loss-of-function mutations in the gene encoding LegC4 resulted in enhanced L. pneumophila in the lungs of infected mice but not within cultured host cells, which indicates LegC4 augments bacterial clearance by the host immune system. The effector proteins RavY and Lpg2505 were important for efficient replication within both mammalian and protozoan hosts. Further analysis of Lpg2505 revealed that this protein functions as a metaeffector that counteracts host cytotoxicity displayed by the effector protein SidI. Thus, this study identified a large cohort of effectors that contribute to L. pneumophila virulence positively or negatively and has demonstrated regulation of effector protein activities by cognate metaeffectors as being critical for host pathogenesis.

  9. Analysis of newly established EST databases reveals similarities between heart regeneration in newt and fish

    Directory of Open Access Journals (Sweden)

    Weis Patrick

    2010-01-01

    Full Text Available Abstract Background The newt Notophthalmus viridescens possesses the remarkable ability to respond to cardiac damage by formation of new myocardial tissue. Surprisingly little is known about changes in gene activities that occur during the course of regeneration. To begin to decipher the molecular processes, that underlie restoration of functional cardiac tissue, we generated an EST database from regenerating newt hearts and compared the transcriptional profile of selected candidates with genes deregulated during zebrafish heart regeneration. Results A cDNA library of 100,000 cDNA clones was generated from newt hearts 14 days after ventricular injury. Sequencing of 11520 cDNA clones resulted in 2894 assembled contigs. BLAST searches revealed 1695 sequences with potential homology to sequences from the NCBI database. BLAST searches to TrEMBL and Swiss-Prot databases assigned 1116 proteins to Gene Ontology terms. We also identified a relatively large set of 174 ORFs, which are likely to be unique for urodele amphibians. Expression analysis of newt-zebrafish homologues confirmed the deregulation of selected genes during heart regeneration. Sequences, BLAST results and GO annotations were visualized in a relational web based database followed by grouping of identified proteins into clusters of GO Terms. Comparison of data from regenerating zebrafish hearts identified biological processes, which were uniformly overrepresented during cardiac regeneration in newt and zebrafish. Conclusion We concluded that heart regeneration in newts and zebrafish led to the activation of similar sets of genes, which suggests that heart regeneration in both species might follow similar principles. The design of the newly established newt EST database allows identification of molecular pathways important for heart regeneration.

  10. Diversity in a Polymicrobial Community Revealed by Analysis of Viromes, Endolysins and CRISPR Spacers.

    Directory of Open Access Journals (Sweden)

    Michelle Davison

    Full Text Available The polymicrobial biofilm communities in Mushroom and Octopus Spring in Yellowstone National Park (YNP are well characterized, yet little is known about the phage populations. Dominant species, Synechococcus sp. JA-2-3B'a(2-13, Synechococcus sp. JA-3-3Ab, Chloroflexus sp. Y-400-fl, and Roseiflexus sp. RS-1, contain multiple CRISPR-Cas arrays, suggesting complex interactions with phage predators. To analyze phage populations from Octopus Spring biofilms, we sequenced a viral enriched fraction. To assemble and analyze phage metagenomic data, we developed a custom module, VIRITAS, implemented within the MetAMOS framework. This module bins contigs into groups based on tetranucleotide frequencies and CRISPR spacer-protospacer matching and ORF calling. Using this pipeline we were able to assemble phage sequences into contigs and bin them into three clusters that corroborated with their potential host range. The virome contained 52,348 predicted ORFs; some were clearly phage-like; 9319 ORFs had a recognizable Pfam domain while the rest were hypothetical. Of the recognized domains with CRISPR spacer matches, was the phage endolysin used by lytic phage to disrupt cells. Analysis of the endolysins present in the thermophilic cyanophage contigs revealed a subset of characterized endolysins as well as a Glyco_hydro_108 (PF05838 domain not previously associated with sequenced cyanophages. A search for CRISPR spacer matches to all identified phage endolysins demonstrated that a majority of endolysin domains were targets. This strategy provides a general way to link host and phage as endolysins are known to be widely distributed in bacteriophage. Endolysins can also provide information about host cell wall composition and have the additional potential to be used as targets for novel therapeutics.

  11. Metabolomics analysis reveals large effect of roughage types on rumen microbial metabolic profile in dairy cows.

    Science.gov (United States)

    Zhao, S; Zhao, J; Bu, D; Sun, P; Wang, J; Dong, Z

    2014-07-01

    The aim of our study was to determine the effect of diets with different types of roughage on the ruminal microbial metabolite profile in dairy cows. Holstein dairy cows were fed a diet containing either corn stover (CS group) or a mixture of alfalfa hay, Leymus chinensis hay and corn silage (MF group) at 0700 and 1900 h daily. Rumen fluid was sampled from each cow through a ruminal cannula at 0630 and 1030 h, and the mixed ruminal fluid from 3 day in each cow was analysed using nuclear magnetic resonance (NMR) spectroscopy. A multivariate analysis revealed a significant difference between the ruminal metabolome of the CS and MF groups at both time points. The MF group had higher levels of acetate, valerate, hydrocinnamate and methylamine and lower levels of glucose, glycine, propionate and isovalerate than those in the CS group. Our results showed that different types of roughages can significantly influence the ruminal microbial metabolome, especially with regard to organic acids, amines and amino acids. The microbial metabolites in the rumen provide nutritional precursors that are critical for general health and milk production in dairy cows. However, studies of the effect of diet on ruminal microbial metabolism are scant. In our current study, we analysed the ruminal microbial metabolite profile of cows fed different types of roughage. We found that the ruminal microbial metabolite profile of cows fed a mixed-roughage diet differed significantly from that of cows fed a single type of roughage. Certain metabolites, such as acetate, hydrocinnamate and methylamine, were closely correlated with specific types of roughage. Our findings provide insight into the effects of different roughages on ruminal microbial fermentation in dairy cows. © 2014 The Society for Applied Microbiology.

  12. System-wide analysis reveals intrinsically disordered proteins are prone to ubiquitylation after misfolding stress.

    Science.gov (United States)

    Ng, Alex H M; Fang, Nancy N; Comyn, Sophie A; Gsponer, Jörg; Mayor, Thibault

    2013-09-01

    Damaged and misfolded proteins that are no longer functional in the cell need to be eliminated. Failure to do so might lead to their accumulation and aggregation, a hallmark of many neurodegenerative diseases. Protein quality control pathways play a major role in the degradation of these proteins, which is mediated mainly by the ubiquitin proteasome system. Despite significant focus on identifying ubiquitin ligases involved in these pathways, along with their substrates, a systems-level understanding of these pathways has been lacking. For instance, as misfolded proteins are rapidly ubiquitylated, unconjugated ubiquitin is rapidly depleted from the cell upon misfolding stress; yet it is unknown whether certain targets compete more efficiently to be ubiquitylated. Using a system-wide approach, we applied statistical and computational methods to identify characteristics enriched among proteins that are further ubiquitylated after heat shock. We discovered that distinct populations of structured and, surprisingly, intrinsically disordered proteins are prone to ubiquitylation. Proteomic analysis revealed that abundant and highly structured proteins constitute the bulk of proteins in the low-solubility fraction after heat shock, but only a portion is ubiquitylated. In contrast, ubiquitylated, intrinsically disordered proteins are enriched in the low-solubility fraction after heat shock. These proteins have a very low abundance in the cell, are rarely encoded by essential genes, and are enriched in binding motifs. In additional experiments, we confirmed that several of the identified intrinsically disordered proteins were ubiquitylated after heat shock and demonstrated for two of them that their disordered regions are important for ubiquitylation after heat shock. We propose that intrinsically disordered regions may be recognized by the protein quality control machinery and thereby facilitate the ubiquitylation of proteins after heat shock.

  13. A novel network profiling analysis reveals system changes in epithelial-mesenchymal transition.

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    Teppei Shimamura

    Full Text Available Patient-specific analysis of molecular networks is a promising strategy for making individual risk predictions and treatment decisions in cancer therapy. Although systems biology allows the gene network of a cell to be reconstructed from clinical gene expression data, traditional methods, such as bayesian networks, only provide an averaged network for all samples. Therefore, these methods cannot reveal patient-specific differences in molecular networks during cancer progression. In this study, we developed a novel statistical method called NetworkProfiler, which infers patient-specific gene regulatory networks for a specific clinical characteristic, such as cancer progression, from gene expression data of cancer patients. We applied NetworkProfiler to microarray gene expression data from 762 cancer cell lines and extracted the system changes that were related to the epithelial-mesenchymal transition (EMT. Out of 1732 possible regulators of E-cadherin, a cell adhesion molecule that modulates the EMT, NetworkProfiler, identified 25 candidate regulators, of which about half have been experimentally verified in the literature. In addition, we used NetworkProfiler to predict EMT-dependent master regulators that enhanced cell adhesion, migration, invasion, and metastasis. In order to further evaluate the performance of NetworkProfiler, we selected Krueppel-like factor 5 (KLF5 from a list of the remaining candidate regulators of E-cadherin and conducted in vitro validation experiments. As a result, we found that knockdown of KLF5 by siRNA significantly decreased E-cadherin expression and induced morphological changes characteristic of EMT. In addition, in vitro experiments of a novel candidate EMT-related microRNA, miR-100, confirmed the involvement of miR-100 in several EMT-related aspects, which was consistent with the predictions obtained by NetworkProfiler.

  14. Assessing protein conformational sampling methods based on bivariate lag-distributions of backbone angles

    KAUST Repository

    Maadooliat, Mehdi

    2012-08-27

    Despite considerable progress in the past decades, protein structure prediction remains one of the major unsolved problems in computational biology. Angular-sampling-based methods have been extensively studied recently due to their ability to capture the continuous conformational space of protein structures. The literature has focused on using a variety of parametric models of the sequential dependencies between angle pairs along the protein chains. In this article, we present a thorough review of angular-sampling-based methods by assessing three main questions: What is the best distribution type to model the protein angles? What is a reasonable number of components in a mixture model that should be considered to accurately parameterize the joint distribution of the angles? and What is the order of the local sequence-structure dependency that should be considered by a prediction method? We assess the model fits for different methods using bivariate lag-distributions of the dihedral/planar angles. Moreover, the main information across the lags can be extracted using a technique called Lag singular value decomposition (LagSVD), which considers the joint distribution of the dihedral/planar angles over different lags using a nonparametric approach and monitors the behavior of the lag-distribution of the angles using singular value decomposition. As a result, we developed graphical tools and numerical measurements to compare and evaluate the performance of different model fits. Furthermore, we developed a web-tool (http://www.stat.tamu. edu/~madoliat/LagSVD) that can be used to produce informative animations. © The Author 2012. Published by Oxford University Press.

  15. Students' concept patterns revealed by computer analysis of language-constrained science concept maps

    Science.gov (United States)

    Fife, Barbara Mae

    This dissertation consists of four studies that develop a computer-based methodology to construct and evaluate concept maps to explore commonalities in students' representation of ideas in a domain. It also explores whether a progression in learning is evident in concept maps of cross-age students who have experienced a similar curriculum. The first two studies determine the validity and reliability of the language-constrained concept mapping using The Computer-assisted Concept Mapper as a software analog to traditional concept mapping. Students manipulate teacher-provided concepts and linking phrases; the program encodes each concept map to preserve the relations and equivalent topology. Validity and reliability of this approach is confirmed. The third study explores the ability of The Concept Map Analyzer hypercard stack to analyze a large number of concept maps and discriminate groups of similar maps. Three hundred seventy-eight sixth, ninth, and twelfth grade students in one school district created concept maps selecting from thirty provided concepts and ten linking phrases related to the water cycle. All pairs of maps are compared for similarities in concepts used and concepts-connected. The algorithm, based on the Pathfinder analysis C-measure, divides the set of common elements by the set of all elements in both concept maps. The similarity ratios which define the congruence between each pair of maps are subjected to cluster analysis to identify groups of similar maps. The number of concepts used and concepts-connected increases from sixth through twelfth grade; however, all three grade levels are represented in each of the seven clusters. The fourth study explores represented levels of understanding. Software provides a graphic composite of each cluster that shows relations selected by at least the specified percentage of students. The complexity and richness of composite maps generally increases with grade level; however, grade-level composites in this

  16. Relative Quantitative Proteomic Analysis of Brucella abortus Reveals Metabolic Adaptation to Multiple Environmental Stresses

    Science.gov (United States)

    Zai, Xiaodong; Yang, Qiaoling; Yin, Ying; Li, Ruihua; Qian, Mengying; Zhao, Taoran; Li, Yaohui; Zhang, Jun; Fu, Ling; Xu, Junjie; Chen, Wei

    2017-01-01

    Brucella spp. are facultative intracellular pathogens that cause chronic brucellosis in humans and animals. The virulence of Brucella primarily depends on its successful survival and replication in host cells. During invasion of the host tissue, Brucella is simultaneously subjected to a variety of harsh conditions, including nutrient limitation, low pH, antimicrobial defenses, and extreme levels of reactive oxygen species (ROS) via the host immune response. This suggests that Brucella may be able to regulate its metabolic adaptation in response to the distinct stresses encountered during its intracellular infection of the host. An investigation into the differential proteome expression patterns of Brucella grown under the relevant stress conditions may contribute toward a better understanding of its pathogenesis and adaptive response. Here, we utilized a mass spectrometry-based label-free relative quantitative proteomics approach to investigate and compare global proteomic changes in B. abortus in response to eight different stress treatments. The 3 h short-term in vitro single-stress and multi-stress conditions mimicked the in vivo conditions of B. abortus under intracellular infection, with survival rates ranging from 3.17 to 73.17%. The proteomic analysis identified and quantified a total of 2,272 proteins and 74% of the theoretical proteome, thereby providing wide coverage of the B. abortus proteome. By including eight distinct growth conditions and comparing these with a control condition, we identified a total of 1,221 differentially expressed proteins (DEPs) that were significantly changed under the stress treatments. Pathway analysis revealed that most of the proteins were involved in oxidative phosphorylation, ABC transporters, two-component systems, biosynthesis of secondary metabolites, the citrate cycle, thiamine metabolism, and nitrogen metabolism; constituting major response mechanisms toward the reconstruction of cellular homeostasis and metabolic

  17. Genomic Analysis of Hospital Plumbing Reveals Diverse Reservoir of Bacterial Plasmids Conferring Carbapenem Resistance.

    Science.gov (United States)

    Weingarten, Rebecca A; Johnson, Ryan C; Conlan, Sean; Ramsburg, Amanda M; Dekker, John P; Lau, Anna F; Khil, Pavel; Odom, Robin T; Deming, Clay; Park, Morgan; Thomas, Pamela J; Henderson, David K; Palmore, Tara N; Segre, Julia A; Frank, Karen M

    2018-02-06

    The hospital environment is a potential reservoir of bacteria with plasmids conferring carbapenem resistance. Our Hospital Epidemiology Service routinely performs extensive sampling of high-touch surfaces, sinks, and other locations in the hospital. Over a 2-year period, additional sampling was conducted at a broader range of locations, including housekeeping closets, wastewater from hospital internal pipes, and external manholes. We compared these data with previously collected information from 5 years of patient clinical and surveillance isolates. Whole-genome sequencing and analysis of 108 isolates provided comprehensive characterization of bla KPC / bla NDM -positive isolates, enabling an in-depth genetic comparison. Strikingly, despite a very low prevalence of patient infections with bla KPC -positive organisms, all samples from the intensive care unit pipe wastewater and external manholes contained carbapenemase-producing organisms (CPOs), suggesting a vast, resilient reservoir. We observed a diverse set of species and plasmids, and we noted species and susceptibility profile differences between environmental and patient populations of CPOs. However, there were plasmid backbones common to both populations, highlighting a potential environmental reservoir of mobile elements that may contribute to the spread of resistance genes. Clear associations between patient and environmental isolates were uncommon based on sequence analysis and epidemiology, suggesting reasonable infection control compliance at our institution. Nonetheless, a probable nosocomial transmission of Leclercia sp. from the housekeeping environment to a patient was detected by this extensive surveillance. These data and analyses further our understanding of CPOs in the hospital environment and are broadly relevant to the design of infection control strategies in many infrastructure settings. IMPORTANCE Carbapenemase-producing organisms (CPOs) are a global concern because of the morbidity and

  18. Deep sequencing analysis of the developing mouse brain reveals a novel microRNA

    Directory of Open Access Journals (Sweden)

    Piltz Sandra

    2011-04-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are small non-coding RNAs that can exert multilevel inhibition/repression at a post-transcriptional or protein synthesis level during disease or development. Characterisation of miRNAs in adult mammalian brains by deep sequencing has been reported previously. However, to date, no small RNA profiling of the developing brain has been undertaken using this method. We have performed deep sequencing and small RNA analysis of a developing (E15.5 mouse brain. Results We identified the expression of 294 known miRNAs in the E15.5 developing mouse brain, which were mostly represented by let-7 family and other brain-specific miRNAs such as miR-9 and miR-124. We also discovered 4 putative 22-23 nt miRNAs: mm_br_e15_1181, mm_br_e15_279920, mm_br_e15_96719 and mm_br_e15_294354 each with a 70-76 nt predicted pre-miRNA. We validated the 4 putative miRNAs and further characterised one of them, mm_br_e15_1181, throughout embryogenesis. Mm_br_e15_1181 biogenesis was Dicer1-dependent and was expressed in E3.5 blastocysts and E7 whole embryos. Embryo-wide expression patterns were observed at E9.5 and E11.5 followed by a near complete loss of expression by E13.5, with expression restricted to a specialised layer of cells within the developing and early postnatal brain. Mm_br_e15_1181 was upregulated during neurodifferentiation of P19 teratocarcinoma cells. This novel miRNA has been identified as miR-3099. Conclusions We have generated and analysed the first deep sequencing dataset of small RNA sequences of the developing mouse brain. The analysis revealed a novel miRNA, miR-3099, with potential regulatory effects on early embryogenesis, and involvement in neuronal cell differentiation/function in the brain during late embryonic and early neonatal development.

  19. Global proteomic analysis in trypanosomes reveals unique proteins and conserved cellular processes impacted by arginine methylation.

    Science.gov (United States)

    Lott, Kaylen; Li, Jun; Fisk, John C; Wang, Hao; Aletta, John M; Qu, Jun; Read, Laurie K

    2013-10-08

    Arginine methylation is a common posttranslational modification with reported functions in transcription, RNA processing and translation, and DNA repair. Trypanosomes encode five protein arginine methyltransferases, suggesting that arginine methylation exerts widespread impacts on the biology of these organisms. Here, we performed a global proteomic analysis of Trypanosoma brucei to identify arginine methylated proteins and their sites of modification. Using an approach entailing two-dimensional chromatographic separation and alternating electron transfer dissociation and collision induced dissociation, we identified 1332 methylarginines in 676 proteins. The resulting data set represents the largest compilation of arginine methylated proteins in any organism to date. Functional classification revealed numerous arginine methylated proteins involved in flagellar function, RNA metabolism, DNA replication and repair, and intracellular protein trafficking. Thus, arginine methylation has the potential to impact aspects of T. brucei gene expression, cell biology, and pathogenesis. Interestingly, pathways with known methylated proteins in higher eukaryotes were identified in this study, but often different components of the pathway were methylated in trypanosomes. Methylarginines were often identified in glycine rich contexts, although exceptions to this rule were detected. Collectively, these data inform on a multitude of aspects of trypanosome biology and serve as a guide for the identification of homologous arginine methylated proteins in higher eukaryotes. T. brucei is a protozoan parasite that causes lethal African sleeping sickness in humans and nagana in livestock, thereby imposing a significant medical and economic burden on sub-Saharan Africa. The parasite encounters very different environments as it cycles between mammalian and insect hosts, and must exert cellular responses to these varying milieus. One mechanism by which all cells respond to changing

  20. Properties of galaxies around AGNs with the most massive supermassive black holes revealed by clustering analysis

    Science.gov (United States)

    Shirasaki, Yuji; Komiya, Yutaka; Ohishi, Masatoshi; Mizumoto, Yoshihiko

    2016-04-01

    We present results of the clustering analysis between active galactic nuclei (AGNs) and galaxies at redshift 0.1-1.0, which was performed to investigate the properties of galaxies associated with the AGNs and reveal the nature of the fueling mechanism of supermassive black holes (SMBHs). We used 8059 AGNs/quasi-stellar objects (QSOs) for which virial masses of individual SMBHs were measured, and divided them into four mass groups.Cross-correlation analysis was performed to reconfirm our previous result that cross-correlation length increases with SMBH mass MBH; we obtained consistent results. A linear bias of AGN for each mass group was measured as 1.47 for MBH = 107.5-108.2 M⊙ and 3.08 for MBH = 109-1010 M⊙. The averaged color and luminosity distributions of galaxies around the AGNs/QSOs were also derived for each mass group. The galaxy color Dopt-IR was estimated from a spectral energy distribution (SED) constructed from a catalog derived by merging the Sloan Digital Sky Survey (SDSS) and the UKIRT Infrared Deep Sky Survey (UKIDSS) catalogs. The distributions of color and luminosity were derived by a subtraction method, which does not require redshift information of galaxies. The main results of this work are as follows. (1) A linear bias increases by a factor of two from the lower-mass group to the highest-mass group. (2) The environment around AGNs with the most massive SMBHs (MBH > 109 M⊙) is dominated by red sequence galaxies. (3) Marginal indication of decline in luminosity function at dimmer side of MIR > -19.5 is found for galaxies around AGNs with MBH = 108.2-109 M⊙ and nearest redshift group (z = 0.1-0.3). These results indicate that AGNs with the most massive SMBHs reside in haloes where a large fraction of galaxies have been transited to the red sequence. The accretion of hot halo gas as well as recycled gas from evolving stars can be one of the plausible mechanisms to fuel the SMBHs above ˜ 109 M⊙.

  1. Relative Quantitative Proteomic Analysis of Brucella abortus Reveals Metabolic Adaptation to Multiple Environmental Stresses.

    Science.gov (United States)

    Zai, Xiaodong; Yang, Qiaoling; Yin, Ying; Li, Ruihua; Qian, Mengying; Zhao, Taoran; Li, Yaohui; Zhang, Jun; Fu, Ling; Xu, Junjie; Chen, Wei

    2017-01-01

    Brucella spp. are facultative intracellular pathogens that cause chronic brucellosis in humans and animals. The virulence of Brucella primarily depends on its successful survival and replication in host cells. During invasion of the host tissue, Brucella is simultaneously subjected to a variety of harsh conditions, including nutrient limitation, low pH, antimicrobial defenses, and extreme levels of reactive oxygen species (ROS) via the host immune response. This suggests that Brucella may be able to regulate its metabolic adaptation in response to the distinct stresses encountered during its intracellular infection of the host. An investigation into the differential proteome expression patterns of Brucella grown under the relevant stress conditions may contribute toward a better understanding of its pathogenesis and adaptive response. Here, we utilized a mass spectrometry-based label-free relative quantitative proteomics approach to investigate and compare global proteomic changes in B. abortus in response to eight different stress treatments. The 3 h short-term in vitro single-stress and multi-stress conditions mimicked the in vivo conditions of B. abortus under intracellular infection, with survival rates ranging from 3.17 to 73.17%. The proteomic analysis identified and quantified a total of 2,272 proteins and 74% of the theoretical proteome, thereby providing wide coverage of the B. abortus proteome. By including eight distinct growth conditions and comparing these with a control condition, we identified a total of 1,221 differentially expressed proteins (DEPs) that were significantly changed under the stress treatments. Pathway analysis revealed that most of the proteins were involved in oxidative phosphorylation, ABC transporters, two-component systems, biosynthesis of secondary metabolites, the citrate cycle, thiamine metabolism, and nitrogen metabolism; constituting major response mechanisms toward the reconstruction of cellular homeostasis and metabolic

  2. Genome-wide analysis reveals population structure and selection in Chinese indigenous sheep breeds.

    Science.gov (United States)

    Wei, Caihong; Wang, Huihua; Liu, Gang; Wu, Mingming; Cao, Jiaxve; Liu, Zhen; Liu, Ruizao; Zhao, Fuping; Zhang, Li; Lu, Jian; Liu, Chousheng; Du, Lixin

    2015-03-17

    Traditionally, Chinese indigenous sheep were classified geographically and morphologically into three groups: Mongolian, Kazakh and Tibetan. Herein, we aimed to evaluate the population structure and genome selection among 140 individuals from ten representative Chinese indigenous sheep breeds: Ujimqin, Hu, Tong, Large-Tailed Han and Lop breed (Mongolian group); Duolang and Kazakh (Kazakh group); and Diqing, Plateau-type Tibetan, and Valley-type Tibetan breed (Tibetan group). We analyzed the population using principal component analysis (PCA), STRUCTURE and a Neighbor-Joining (NJ)-tree. In PCA plot, the Tibetan and Mongolian groups were clustered as expected; however, Duolang and Kazakh (Kazakh group) were segregated. STRUCTURE analyses suggested two subpopulations: one from North China (Kazakh and Mongolian groups) and the other from the Southwest (Tibetan group). In the NJ-tree, the Tibetan group formed an independent branch and the Kazakh and Mongolian groups were mixed. We then used the d i statistic approach to reveal selection in Chinese indigenous sheep breeds. Among the 599 genome sequence windows analyzed, sixteen (2.7%) exhibited signatures of selection in four or more breeds. We detected three strong selection windows involving three functional genes: RXFP2, PPP1CC and PDGFD. PDGFD, one of the four subfamilies of PDGF, which promotes proliferation and inhibits differentiation of preadipocytes, was significantly selected in fat type breeds by the Rsb (across pairs of populations) approach. Two consecutive selection regions in Duolang sheep were obviously different to other breeds. One region was in OAR2 including three genes (NPR2, SPAG8 and HINT2) the influence growth traits. The other region was in OAR 6 including four genes (PKD2, SPP1, MEPE, and IBSP) associated with a milk production quantitative trait locus. We also identified known candidate genes such as BMPR1B, MSRB3, and three genes (KIT, MC1R, and FRY) that influence lambing percentage, ear size

  3. Evolutionary analysis of TLR9 genes reveals the positive selection of extant teleosts in Perciformes.

    Science.gov (United States)

    Zhu, Zhihuang; Sun, Yuena; Wang, Rixin; Xu, Tianjun

    2013-08-01

    The innate immune system can recognize non-self through pattern recognition receptors. Toll-like receptors were the best-known members of these receptors, and they could sense, recognize, and bind pathogen-associated molecular patterns. TLRs played an important role in innate immune system and were conserved in both invertebrate and vertebrate lineages. Thereinto, TLR9 could detect unmethylated CpG motifs in dsDNA and was expected to undergo coevolution with its microbial ligands. It was known that aquatic and terrestrial organisms dwelled in different environments which contained different pathogens, and they had to adapt to their local environmental conditions. Therefore, we collected TLR9 genes from invertebrate to vertebrate to further explore whether the huge differences between aquatic and terrestrial environments affected the TLR9s evolution between aquatic and terrestrial organisms. Molecular evolution analysis detected positively selected sites in the ancestral lineages of vertebrates, teleosts, and Perciformes but not in the ancestral lineage of mammals. In PAML, site model revealed that extant mammalian TLR9 genes underwent positive selection. However, the positive selection of extant teleosts appeared primarily in Perciformes in which there were 14 positively selected sites. Among these sites, two of them were located on the amino acid insertions of the leucine-rich repeats which could create DNA binding sites, three were found on the convex surface which might possibly affect the flexibility of the TLR solenoids, and six were located on the β-face of concave surface which contained the ligand-binding sites of the TLR solenoids. In other ML methods, we also found three sites under selection that coincided with the codons identified by M8 and these sites were all located in LRRs. The diverse aquatic and terrestrial environments might possess different pathogens to make the living organisms adapt to their local environmental conditions. The positive

  4. Comparative analysis of alfalfa (Medicago sativa L.) leaf transcriptomes reveals genotype-specific salt tolerance mechanisms.

    Science.gov (United States)

    Lei, Yunting; Xu, Yuxing; Hettenhausen, Christian; Lu, Chengkai; Shen, Guojing; Zhang, Cuiping; Li, Jing; Song, Juan; Lin, Honghui; Wu, Jianqiang

    2018-02-15

    Soil salinity is an important factor affecting growth, development, and productivity of almost all land plants, including the forage crop alfalfa (Medicago sativa). However, little is known about how alfalfa responds and adapts to salt stress, particularly among different salt-tolerant cultivars. Among seven alfalfa cultivars, we found that Zhongmu-1 (ZM) is relatively salt-tolerant and Xingjiang Daye (XJ) is salt-sensitive. Compared to XJ, ZM showed slower growth under low-salt conditions, but exhibited stronger tolerance to salt stress. RNA-seq analysis revealed 2237 and 1125 differentially expressed genes (DEGs) between ZM and XJ in the presence and absence of salt stress, among which many genes are involved in stress-related pathways. After salt treatment, compared with the controls, the number of DEGs in XJ (19373) was about four times of that in ZM (4833). We also detected specific differential gene expression patterns: In response to salt stress, compared with XJ, ZM maintained relatively more stable expression levels of genes related to the ROS and Ca 2+ pathways, phytohormone biosynthesis, and Na + /K + transport. Notably, several salt resistance-associated genes always showed greater levels of expression in ZM than in XJ, including a transcription factor. Consistent with the suppression of plant growth resulting from salt stress, the expression of numerous photosynthesis- and growth hormone-related genes decreased more dramatically in XJ than in ZM. By contrast, the expression levels of photosynthetic genes were lower in ZM under low-salt conditions. Compared with XJ, ZM is a salt-tolerant alfalfa cultivar possessing specific regulatory mechanisms conferring exceptional salt tolerance, likely by maintaining high transcript levels of abiotic and biotic stress resistance-related genes. Our results suggest that maintaining this specific physiological status and/or plant adaptation to salt stress most likely arises by inhibition of plant growth in ZM through

  5. Neuronal networks in west syndrome as revealed by source analysis and renormalized partial directed coherence.

    Science.gov (United States)

    Japaridze, Natia; Muthuraman, Muthuraman; Moeller, Friederike; Boor, Rainer; Anwar, Abdul Rauf; Deuschl, Günther; Stephani, Urlich; Raethjen, Jan; Siniatchkin, Michael

    2013-01-01

    West syndrome is a severe epileptic encephalopathy of infancy with a poor developmental outcome. This syndrome is associated with the pathognomonic EEG feature of hypsarrhythmia. The aim of the study was to describe neuronal networks underlying hypsarrhythmia using the source analysis method (dynamic imaging of coherent sources or DICS) which represents an inverse solution algorithm in the frequency domain. In order to investigate the interaction within the detected network, a renormalized partial directed coherence (RPDC) method was also applied as a measure of the directionality of information flow between the source signals. Both DICS and RPDC were performed for EEG delta activity (1-4 Hz) in eight patients with West syndrome and in eight patients with partial epilepsies (control group). The brain area with the strongest power in the given frequency range was defined as the reference region. The coherence between this reference region and the entire brain was computed using DICS. After that, the RPDC was applied to the source signals estimated by DICS. The results of electrical source imaging were compared to results of a previous EEG-fMRI study which had been carried out using the same cohort of patients. As revealed by DICS, delta activity in hypsarrhythmia was associated with coherent sources in the occipital cortex (main source) as well as the parietal cortex, putamen, caudate nucleus and brainstem. In patients with partial epilepsies, delta activity could be attributed to sources in the occipital, parietal and sensory-motor cortex. In West syndrome, RPDC showed the strongest and most significant direction of ascending information flow from the brainstem towards the putamen and cerebral cortex. The neuronal network underlying hypsarrhythmia in this study resembles the network which was described in previous EEG-fMRI and PET studies with involvement of the brainstem, putamen and cortical regions in the generation of hypsarrhythmia. The RPDC suggests that

  6. Long-lead station-scale prediction of hydrological droughts in South Korea based on bivariate pattern-based downscaling

    Science.gov (United States)

    Sohn, Soo-Jin; Tam, Chi-Yung

    2016-05-01

    Capturing climatic variations in boreal winter to spring (December-May) is essential for properly predicting droughts in South Korea. This study investigates the variability and predictability of the South Korean climate during this extended season, based on observations from 60 station locations and multi-model ensemble (MME) hindcast experiments (1983/1984-2005/2006) archived at the APEC Climate Center (APCC). Multivariate empirical orthogonal function (EOF) analysis results based on observations show that the first two leading modes of winter-to-spring precipitation and temperature variability, which together account for ~80 % of the total variance, are characterized by regional-scale anomalies covering the whole South Korean territory. These modes were also closely related to some of the recurrent large-scale circulation changes in the northern hemisphere during the same season. Consistent with the above, examination of the standardized precipitation evapotranspiration index (SPEI) indicates that drought conditions in South Korea tend to be accompanied by regional-to-continental-scale circulation anomalies over East Asia to the western north Pacific. Motivated by the aforementioned findings on the spatial-temporal coherence among station-scale precipitation and temperature anomalies, a new bivariate and pattern-based downscaling method was developed. The novelty of this method is that precipitation and temperature data were first filtered using multivariate EOFs to enhance their spatial-temporal coherence, before being linked to large-scale circulation variables using canonical correlation analysis (CCA). To test its applicability and to investigate its related potential predictability, a perfect empirical model was first constructed with observed datasets as predictors. Next, a model output statistics (MOS)-type hybrid dynamical-statistical model was developed, using products from nine one-tier climate models as inputs. It was found that, with model sea

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

    Directory of Open Access Journals (Sweden)

    Henry D Priest

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

  8. A non-parametric conditional bivariate reference region with an application to height/weight measurements on normal girls

    DEFF Research Database (Denmark)

    Petersen, Jørgen Holm

    2009-01-01

    A conceptually simple two-dimensional conditional reference curve is described. The curve gives a decision basis for determining whether a bivariate response from an individual is "normal" or "abnormal" when taking into account that a third (conditioning) variable may influence the bivariate...... response. The reference curve is not only characterized analytically but also by geometric properties that are easily communicated to medical doctors - the users of such curves. The reference curve estimator is completely non-parametric, so no distributional assumptions are needed about the two......-dimensional response. An example that will serve to motivate and illustrate the reference is the study of the height/weight distribution of 7-8-year-old Danish school girls born in 1930, 1950, or 1970....

  9. Bivariate Extension of the Quadrature Method of Moments for Modeling Simultaneous Coagulation and Sintering of Particle Populations.

    Science.gov (United States)

    Wright, Douglas L.; McGraw, Robert; Rosner, Daniel E.

    2001-04-15

    We extendthe application of moment methods to multivariate suspended particle population problems-those for which size alone is insufficient to specify the state of a particle in the population. Specifically, a bivariate extension of the quadrature method of moments (QMOM) (R. McGraw, Aerosol Sci. Technol. 27, 255 (1997)) is presented for efficiently modeling the dynamics of a population of inorganic nanoparticles undergoing simultaneous coagulation and particle sintering. Continuum regime calculations are presented for the Koch-Friedlander-Tandon-Rosner model, which includes coagulation by Brownian diffusion (evaluated for particle fractal dimensions, D(f), in the range 1.8-3) and simultaneous sintering of the resulting aggregates (P. Tandon and D. E. Rosner, J. Colloid Interface Sci. 213, 273 (1999)). For evaluation purposes, and to demonstrate the computational efficiency of the bivariate QMOM, benchmark calculations are carried out using a high-resolution discrete method to evolve the particle distribution function n(nu, a) for short to intermediate times (where nu and a are particle volume and surface area, respectively). Time evolution of a selected set of 36 low-order mixed moments is obtained by integration of the full bivariate distribution and compared with the corresponding moments obtained directly using two different extensions of the QMOM. With the more extensive treatment, errors of less than 1% are obtained over substantial aerosol evolution, while requiring only a few minutes (rather than days) of CPU time. Longer time QMOM simulations lend support to the earlier finding of a self-preserving limit for the dimensionless joint (nu, a) particle distribution function under simultaneous coagulation and sintering (Tandon and Rosner, 1999; D. E. Rosner and S. Yu, AIChE J., 47 (2001)). We demonstrate that, even in the bivariate case, it is possible to use the QMOM to rapidly model the approach to asymptotic behavior, allowing an immediate assessment of

  10. Bacterial adaptation during chronic infection revealed by independent component analysis of transcriptomic data

    DEFF Research Database (Denmark)

    Yang, Lei; Rau, Martin Holm; Yang, Liang

    2011-01-01

    , principle component analysis (PCA) and independent component analysis (ICA), to extract and characterize the most informative features from transcriptomic dataset generated from cystic fibrosis (CF) Pseudomonas aeruginosa isolates. ICA was shown to be able to efficiently extract biological meaningful...

  11. CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

    DEFF Research Database (Denmark)

    Macé, Aurélien; Tuke, Marcus A; Deelen, Patrick

    2017-01-01

    There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations ...

  12. Comparing Johnson’s SBB, Weibull and Logit-Logistic bivariate distributions for modeling tree diameters and heights using copulas

    Directory of Open Access Journals (Sweden)

    Jose Javier Gorgoso-Varela

    2016-04-01

    Full Text Available Aim of study: In this study we compare the accuracy of three bivariate distributions: Johnson’s SBB, Weibull-2P and LL-2P functions for characterizing the joint distribution of tree diameters and heights.Area of study: North-West of Spain.Material and methods: Diameter and height measurements of 128 plots of pure and even-aged Tasmanian blue gum (Eucalyptus globulus Labill. stands located in the North-west of Spain were considered in the present study. The SBB bivariate distribution was obtained from SB marginal distributions using a Normal Copula based on a four-parameter logistic transformation. The Plackett Copula was used to obtain the bivariate models from the Weibull and Logit-logistic univariate marginal distributions. The negative logarithm of the maximum likelihood function was used to compare the results and the Wilcoxon signed-rank test was used to compare the related samples of these logarithms calculated for each sample plot and each distribution.Main results: The best results were obtained by using the Plackett copula and the best marginal distribution was the Logit-logistic.Research highlights: The copulas used in this study have shown a good performance for modeling the joint distribution of tree diameters and heights. They could be easily extended for modelling multivariate distributions involving other tree variables, such as tree volume or biomass.

  13. Comparing Johnson’s SBB, Weibull and Logit-Logistic bivariate distributions for modeling tree diameters and heights using copulas

    Energy Technology Data Exchange (ETDEWEB)

    Cardil Forradellas, A.; Molina Terrén, D.M.; Oliveres, J.; Castellnou, M.

    2016-07-01

    Aim of study: In this study we compare the accuracy of three bivariate distributions: Johnson’s SBB, Weibull-2P and LL-2P functions for characterizing the joint distribution of tree diameters and heights. Area of study: North-West of Spain. Material and methods: Diameter and height measurements of 128 plots of pure and even-aged Tasmanian blue gum (Eucalyptus globulus Labill.) stands located in the North-west of Spain were considered in the present study. The SBB bivariate distribution was obtained from SB marginal distributions using a Normal Copula based on a four-parameter logistic transformation. The Plackett Copula was used to obtain the bivariate models from the Weibull and Logit-logistic univariate marginal distributions. The negative logarithm of the maximum likelihood function was used to compare the results and the Wilcoxon signed-rank test was used to compare the related samples of these logarithms calculated for each sample plot and each distribution. Main results: The best results were obtained by using the Plackett copula and the best marginal distribution was the Logit-logistic. Research highlights: The copulas used in this study have shown a good performance for modeling the joint distribution of tree diameters and heights. They could be easily extended for modelling multivariate distributions involving other tree variables, such as tree volume or biomass. (Author)

  14. Phylogeographic analysis reveals significant spatial genetic structure of Incarvillea sinensis as a product of mountain building

    Directory of Open Access Journals (Sweden)

    Chen Shaotian

    2012-04-01

    Full Text Available Abstract Background Incarvillea sinensis is widely distributed from Southwest China to Northeast China and in the Russian Far East. The distribution of this species was thought to be influenced by the uplift of the Qinghai-Tibet Plateau and Quaternary glaciation. To reveal the imprints of geological events on the spatial genetic structure of Incarvillea sinensis, we examined two cpDNA segments ( trnH- psbA and trnS- trnfM in 705 individuals from 47 localities. Results A total of 16 haplotypes was identified, and significant genetic differentiation was revealed (GST =0.843, NST = 0.975, P  Conclusions The results revealed that the uplift of the Qinghai-Tibet Plateau likely resulted in the significant divergence between the lineage in the eastern Qinghai-Tibet Plateau and the other one outside this area. The diverse niches in the eastern Qinghai-Tibet Plateau created a wide spectrum of habitats to accumulate and accommodate new mutations. The features of genetic diversity of populations outside the eastern Qinghai-Tibet Plateau seemed to reveal the imprints of extinction during the Glacial and the interglacial and postglacial recolonization. Our study is a typical case of the significance of the uplift of the Qinghai-Tibet Plateau and the Quaternary Glacial in spatial genetic structure of eastern Asian plants, and sheds new light on the evolution of biodiversity in the Qinghai-Tibet Plateau at the intraspecies level.

  15. Glycomics meets artificial intelligence - Potential of glycan analysis for identification of seropositive and seronegative rheumatoid arthritis patients revealed.

    Science.gov (United States)

    Chocholova, Erika; Bertok, Tomas; Jane, Eduard; Lorencova, Lenka; Holazova, Alena; Belicka, Ludmila; Belicky, Stefan; Mislovicova, Danica; Vikartovska, Alica; Imrich, Richard; Kasak, Peter; Tkac, Jan

    2018-02-25

    In this study, one hundred serum samples from healthy people and patients with rheumatoid arthritis (RA) were analyzed. Standard immunoassays for detection of 10 different RA markers and analysis of glycan markers on antibodies in 10 different assay formats with several lectins were applied for each serum sample. A dataset containing 2000 data points was data mined using artificial neural networks (ANN). We identified key RA markers, which can discriminate between healthy people and seropositive RA patients (serum containing autoantibodies) with accuracy of 83.3%. Combination of RA markers with glycan analysis provided much better discrimination accuracy of 92.5%. Immunoassays completely failed to identify seronegative RA patients (serum not containing autoantibodies), while glycan analysis correctly identified 43.8% of these patients. Further, we revealed other critical parameters for successful glycan analysis such as type of a sample, format of analysis and orientation of captured antibodies for glycan analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Editing site analysis in a gymnosperm mitochondrial genome reveals similarities with angiosperm mitochondrial genomes

    OpenAIRE

    Salmans, Michael Lee; Chaw, Shu-Miaw; Lin, Ching-Ping; Shih, Arthur Chun-Chieh; Wu, Yu-Wei; Mulligan, R. Michael

    2010-01-01

    Sequence analysis of organelle genomes and comprehensive analysis of C-to-U editing sites from flowering and non-flowering plants have provided extensive sequence information from diverse taxa. This study includes the first comprehensive analysis of RNA editing sites from a gymnosperm mitochondrial genome, and utilizes informatics analyses to determine conserved features in the RNA sequence context around editing sites. We have identified 565 editing sites in 21 full-length and 4 partial cDNA...

  17. Decision Makers Use Norms, Not Cost-Benefit Analysis, When Choosing to Conceal or Reveal Unfair Rewards

    Science.gov (United States)

    Heimann, Marco; Girotto, Vittorio; Legrenzi, Paolo; Bonnefon, Jean-François

    2013-01-01

    We introduce the Conceal or Reveal Dilemma, in which individuals receive unfair benefits, and must decide whether to conceal or to reveal this unfair advantage. This dilemma has two important characteristics: it does not lend itself easily to cost-benefit analysis, neither to the application of any strong universal norm. As a consequence, it is ideally suited to the study of interindividual and intercultural variations in moral-economic norms. In this paper we focus on interindividual variations, and we report four studies showing that individuals cannot be swayed by financial incentives to conceal or to reveal, and follow instead fixed, idiosyncratic strategies. We discuss how this result can be extended to individual and cultural variations in the tendency to display or to hide unfair rewards. PMID:24066040

  18. Quantitative morphological analysis reveals ultrastructural diversity of amyloid fibrils from alpha-synuclein mutants

    NARCIS (Netherlands)

    van Raaij, Martijn E; Segers-Nolten, Ine M J; Subramaniam, Vinod

    2006-01-01

    High resolution atomic force microscopy is a powerful tool to characterize nanoscale morphological features of protein amyloid fibrils. Comparison of fibril morphological properties between studies has been hampered by differences in analysis procedures and measurement error determination used by

  19. Archetypal analysis of diverse Pseudomonas aeruginosa transcriptomes reveals adaptation in cystic fibrosis airways

    DEFF Research Database (Denmark)

    Thøgersen, Juliane Charlotte; Mørup, Morten; Pedersen, Søren Damkiær

    2013-01-01

    is to introduce a method for DNA microarray analysis that provides an intuitive interpretation of data through dimension reduction and pattern recognition. We present the first “Archetypal Analysis” of global gene expression. The analysis is based on microarray data from five integrated studies of Pseudomonas...... aeruginosa isolated from the airways of cystic fibrosis patients. RESULTS: Our analysis clustered samples into distinct groups with comprehensible characteristics since the archetypes representing the individual groups are closely related to samples present in the data set. Significant changes in gene....... This suggests positive selection in the cystic fibrosis lung environment, and changes in gene expression for these isolates are therefore most likely related to adaptation of the bacteria. CONCLUSIONS: Archetypal analysis succeeded in identifying adaptive changes of P. aeruginosa. The combination of clustering...

  20. Analysis of image versus position, scale and direction reveals pattern texture anisotropy

    OpenAIRE

    Roland eLehoucq; Jerome eWeiss; Berengere eDubrulle; Axelle eAmon; Antoine eLe Bouil; Jerome eCrassous; David eAmitrano; Francois eGraner

    2015-01-01

    Pattern heterogeneities and anisotropies often carry significant physical information. We provide a toolbox which: (i) cumulates analysis in terms of position, direction and scale; (ii) is as general as possible; (iii) is simple and fast to understand, implement, execute and exploit.It consists in dividing the image into analysis boxes at a chosen scale; in each box an ellipse (the inertia tensor) is fitted to the signal and thus determines the direction in which the signal is more present. ...

  1. Transcriptomic Analysis Reveals Selective Metabolic Adaptation of Streptococcus suis to Porcine Blood and Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Anna Koczula

    2017-02-01

    Full Text Available Streptococcus suis is a zoonotic pathogen that can cause severe pathologies such as septicemia and meningitis in its natural porcine host as well as in humans. Establishment of disease requires not only virulence of the infecting strain but also an appropriate metabolic activity of the pathogen in its host environment. However, it is yet largely unknown how the streptococcal metabolism adapts to the different host niches encountered during infection. Our previous isotopologue profiling studies on S. suis grown in porcine blood and cerebrospinal fluid (CSF revealed conserved activities of central carbon metabolism in both body fluids. On the other hand, they suggested differences in the de novo amino acid biosynthesis. This prompted us to further dissect S. suis adaptation to porcine blood and CSF by RNA deep sequencing (RNA-seq. In blood, the majority of differentially expressed genes were associated with transport of alternative carbohydrate sources and the carbohydrate metabolism (pentose phosphate pathway, glycogen metabolism. In CSF, predominantly genes involved in the biosynthesis of branched-chain and aromatic amino acids were differentially expressed. Especially, isoleucine biosynthesis seems to be of major importance for S. suis in CSF because several related biosynthetic genes were more highly expressed. In conclusion, our data revealed niche-specific metabolic gene activity which emphasizes a selective adaptation of S. suis to host environments.

  2. Adaptations to a Subterranean Environment and Longevity Revealed by the Analysis of Mole Rat Genomes

    Directory of Open Access Journals (Sweden)

    Xiaodong Fang

    2014-09-01

    Full Text Available Subterranean mammals spend their lives in dark, unventilated environments that are rich in carbon dioxide and ammonia and low in oxygen. Many of these animals are also long-lived and exhibit reduced aging-associated diseases, such as neurodegenerative disorders and cancer. We sequenced the genome of the Damaraland mole rat (DMR, Fukomys damarensis and improved the genome assembly of the naked mole rat (NMR, Heterocephalus glaber. Comparative genome analyses, along with the transcriptomes of related subterranean rodents, revealed candidate molecular adaptations for subterranean life and longevity, including a divergent insulin peptide, expression of oxygen-carrying globins in the brain, prevention of high CO2-induced pain perception, and enhanced ammonia detoxification. Juxtaposition of the genomes of DMR and other more conventional animals with the genome of NMR revealed several truly exceptional NMR features: unusual thermogenesis, an aberrant melatonin system, pain insensitivity, and unique processing of 28S rRNA. Together, these genomes and transcriptomes extend our understanding of subterranean adaptations, stress resistance, and longevity.

  3. Comparative genomic analysis reveals a distant liver enhancer upstream of the COUP-TFII gene

    Energy Technology Data Exchange (ETDEWEB)

    Baroukh, Nadine; Ahituv, Nadav; Chang, Jessie; Shoukry, Malak; Afzal, Veena; Rubin, Edward M.; Pennacchio, Len A.

    2004-08-20

    COUP-TFII is a central nuclear hormone receptor that tightly regulates the expression of numerous target lipid metabolism genes in vertebrates. However, it remains unclear how COUP-TFII itself is transcriptionally controlled since studies with its promoter and upstream region fail to recapitulate the genes liver expression. In an attempt to identify liver enhancers in the vicinity of COUP-TFII, we employed a comparative genomic approach. Initial comparisons between humans and mice of the 3,470kb gene poor region surrounding COUP-TFII revealed 2,023 conserved non-coding elements. To prioritize a subset of these elements for functional studies, we performed further genomic comparisons with the orthologous pufferfish (Fugu rubripes) locus and uncovered two anciently conserved non-coding sequences (CNS) upstream of COUP-TFII (CNS-62kb and CNS-66kb). Testing these two elements using reporter constructs in liver (HepG2) cells revealed that CNS-66kb, but not CNS-62kb, yielded robust in vitro enhancer activity. In addition, an in vivo reporter assay using naked DNA transfer with CNS-66kb linked to luciferase displayed strong reproducible liver expression in adult mice, further supporting its role as a liver enhancer. Together, these studies further support the utility of comparative genomics to uncover gene regulatory sequences based on evolutionary conservation and provide the substrates to better understand the regulation and expression of COUP-TFII.

  4. Phylogenetic analysis of New Zealand earthworms (Oligochaeta: Megascolecidae) reveals ancient clades and cryptic taxonomic diversity.

    Science.gov (United States)

    Buckley, Thomas R; James, Sam; Allwood, Julia; Bartlam, Scott; Howitt, Robyn; Prada, Diana

    2011-01-01

    We have constructed the first ever phylogeny for the New Zealand earthworm fauna (Megascolecinae and Acanthodrilinae) including representatives from other major continental regions. Bayesian and maximum likelihood phylogenetic trees were constructed from 427 base pairs from the mitochondrial large subunit (16S) rRNA gene and 661 base pairs from the nuclear large subunit (28S) rRNA gene. Within the Acanthodrilinae we were able to identify a number of well-supported clades that were restricted to continental landmasses. Estimates of nodal support for these major clades were generally high, but relationships among clades were poorly resolved. The phylogenetic analyses revealed several independent lineages in New Zealand, some of which had a comparable phylogenetic depth to monophyletic groups sampled from Madagascar, Africa, North America and Australia. These results are consistent with at least some of these clades having inhabited New Zealand since rifting from Gondwana in the Late Cretaceous. Within the New Zealand Acanthodrilinae, major clades tended to be restricted to specific regions of New Zealand, with the central North Island and Cook Strait representing major biogeographic boundaries. Our field surveys of New Zealand and subsequent identification has also revealed extensive cryptic taxonomic diversity with approximately 48 new species sampled in addition to the 199 species recognized by previous authors. Our results indicate that further survey and taxonomic work is required to establish a foundation for future biogeographic and ecological research on this vitally important component of the New Zealand biota. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. Statistical strategies to reveal potential vibrational markers for in vivo analysis by confocal Raman spectroscopy

    Science.gov (United States)

    Oliveira Mendes, Thiago de; Pinto, Liliane Pereira; Santos, Laurita dos; Tippavajhala, Vamshi Krishna; Téllez Soto, Claudio Alberto; Martin, Airton Abrahão

    2016-07-01

    The analysis of biological systems by spectroscopic techniques involves the evaluation of hundreds to thousands of variables. Hence, different statistical approaches are used to elucidate regions that discriminate classes of samples and to propose new vibrational markers for explaining various phenomena like disease monitoring, mechanisms of action of drugs, food, and so on. However, the technical statistics are not always widely discussed in applied sciences. In this context, this work presents a detailed discussion including the various steps necessary for proper statistical analysis. It includes univariate parametric and nonparametric tests, as well as multivariate unsupervised and supervised approaches. The main objective of this study is to promote proper understanding of the application of various statistical tools in these spectroscopic methods used for the analysis of biological samples. The discussion of these methods is performed on a set of in vivo confocal Raman spectra of human skin analysis that aims to identify skin aging markers. In the Appendix, a complete routine of data analysis is executed in a free software that can be used by the scientific community involved in these studies.

  6. Complete genome sequence analysis of novel human bocavirus reveals genetic recombination between human bocavirus 2 and human bocavirus 4.

    Science.gov (United States)

    Khamrin, Pattara; Okitsu, Shoko; Ushijima, Hiroshi; Maneekarn, Niwat

    2013-07-01

    Epidemiological surveillance of human bocavirus (HBoV) was conducted on fecal specimens collected from hospitalized children with diarrhea in Chiang Mai, Thailand in 2011. By partial sequence analysis of VP1 gene, an unusual strain of HBoV (CMH-S011-11), was initially identified as HBoV4. The complete genome sequence of CMH-S011-11 was performed and analyzed further to clarify whether it was a recombinant strain or a new HBoV variant. Analysis of complete genome sequence revealed that the coding sequence starting from NS1, NP1 to VP1/VP2 was 4795 nucleotides long. Interestingly, the nucleotide sequence of NS1 gene of CMH-S011-11 was most closely related to the HBoV2 reference strains detected in Pakistan, which contradicted to the initial genotyping result of the partial VP1 region in the previous study. In addition, comparison of NP1 nucleotide sequence of CMH-S011-11 with those of other HBoV1-4 reference strains also revealed a high level of sequence identity with HBoV2. On the other hand, nucleotide sequence of VP1/VP2 gene of CMH-S011-11 was most closely related to those of HBoV4 reference strains detected in Nigeria. The overall full-length sequence analysis revealed that this CMH-S011-11 was grouped within HBoV4 species, but located in a separate branch from other HBoV4 prototype strains. Recombination analysis revealed that CMH-S011-11 was the result of recombination between HBoV2 and HBoV4 strains with the break point located near the start codon of VP2. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Siderophile element concentrations in magnetic spherules from deep sea sediments revealed by instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    Nogami, Ken-ichi; Shimamura, Tadashi; Tazawa, Yuji; Yamakoshi, Kazuo.

    1980-01-01

    For the purpose of deciding the extraterrestrial origin of the magnetic spherules found in deep sea sediments, the siderophile elements Co, Ni, Ir and/or Au etc., were measured by instrumental neutron activation analysis. Spherules were collected from red clay samples which were dredged from Mid Pacific Ocean. Only spherules which had smooth surfaces and relatively high specific gravities were chosen for analysis. Existence of Co, Ni and Ir in most spherules suggests the possibility of an extraterrestrial origin for these spherules. It is not clear whether these spherules are droplets ablated from iron meteorites entering into the Earth's atmosphere or they are cosmic iron grains themselves. X-ray diffraction analysis suggested that these spherules are the products of rapid cooling materials. (author)

  8. A structural homologue of colipase in black mamba venom revealed by NMR floating disulphide bridge analysis.

    Science.gov (United States)

    Boisbouvier, J; Albrand, J P; Blackledge, M; Jaquinod, M; Schweitz, H; Lazdunski, M; Marion, D

    1998-01-01

    The solution structure of mamba intestinal toxin 1 (MIT1), isolated from Dendroaspis polylepis polylepis venom, has been determined. This molecule is a cysteine-rich polypeptide exhibiting no recognised family membership. Resistance to MIT1 to classical specific endoproteases produced contradictory NMR and biochemical information concerning disulphide-bridge topology. We have used distance restraints allowing ambiguous partners between S atoms in combination with NMR-derived structural information, to correctly determine the disulphide-bridge topology. The resultant solution structure of MIT1, determined to a resolution of 0.5 A, reveals an unexpectedly similar global fold with respect to colipase, a protein involved in fatty acid digestion. Colipase exhibits an analogous resistance to endoprotease activity, indicating for the first time the possible topological origins of this biochemical property. The biochemical and structural homology permitted us to propose a mechanically related digestive function for MIT1 and provides novel information concerning snake venom protein evolution. Copyright 1998 Academic Press.

  9. DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity

    DEFF Research Database (Denmark)

    Gupta, Rajat; Somyajit, Kumar; Narita, Takeo

    2018-01-01

    -switch recombination (CSR), and fusion of unprotected telomeres. Shieldin functions as a downstream effector of 53BP1-RIF1 in restraining DNA end resection and in sensitizing BRCA1-deficient cells to PARP inhibitors. These findings have implications for understanding cancer-associated PARPi resistance...... expressed DNA repair factors 53BP1, BRCA1, and MDC1. Our spatially resolved interaction maps reveal rich network intricacies, identify shared and bait-specific interaction modules, and implicate previously concealed regulators in this process. We identified a novel vertebrate-specific protein complex......, shieldin, comprising REV7 plus three previously uncharacterized proteins, RINN1 (CTC-534A2.2), RINN2 (FAM35A), and RINN3 (C20ORF196). Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class...

  10. What Do Women's Advertised Mate Preferences Reveal? An Analysis of Video Dating Profiles

    Directory of Open Access Journals (Sweden)

    Cari D. Goetz

    2013-04-01

    Full Text Available This study examined women's video dating profiles to determine what their advertised mate preferences revealed about their mate value and relationship interests. Women created a one-minute long video dating profile for a hypothetical dating website. The videos were content analyzed into four categories of stated mate preferences: 1 “good genes” indicators 2 good resource investment potential indicators 3 good parenting indicators and 4 good partner indicators. Long-term mating interest was positively correlated with describing good partner indicators and self-perceived mate value was positively correlated with describing good genes indicators. Short-term mating interest was negatively correlated with describing any mate preferences while attractiveness was positively correlated with doing so. Results suggest that women's advertised mate preferences provide clues to their underlying relationship interests and mate value.

  11. Integrated analysis of multiple data sources reveals modular structure of biological networks

    International Nuclear Information System (INIS)

    Lu Hongchao; Shi Baochen; Wu Gaowei; Zhang Yong; Zhu Xiaopeng; Zhang Zhihua; Liu Changning; Zhao, Yi; Wu Tao; Wang Jie; Chen Runsheng

    2006-01-01

    It has been a challenging task to integrate high-throughput data into investigations of the systematic and dynamic organization of biological networks. Here, we presented a simple hierarchical clustering algorithm that goes a long way to achieve this aim. Our method effectively reveals the modular structure of the yeast protein-protein interaction network and distinguishes protein complexes from functional modules by integrating high-throughput protein-protein interaction data with the added subcellular localization and expression profile data. Furthermore, we take advantage of the detected modules to provide a reliably functional context for the uncharacterized components within modules. On the other hand, the integration of various protein-protein association information makes our method robust to false-positives, especially for derived protein complexes. More importantly, this simple method can be extended naturally to other types of data fusion and provides a framework for the study of more comprehensive properties of the biological network and other forms of complex networks

  12. Network Analysis Reveals the Recognition Mechanism for Mannose-binding Lectins

    Science.gov (United States)

    Zhao, Yunjie; Jian, Yiren; Zeng, Chen; Computational Biophysics Lab Team

    The specific carbohydrate binding of mannose-binding lectin (MBL) protein in plants makes it a very useful molecular tool for cancer cell detection and other applications. The biological states of most MBL proteins are dimeric. Using dynamics network analysis on molecular dynamics (MD) simulations on the model protein of MBL, we elucidate the short- and long-range driving forces behind the dimer formation. The results are further supported by sequence coevolution analysis. We propose a general framework for deciphering the recognition mechanism underlying protein-protein interactions that may have potential applications in signaling pathways.

  13. Crystal structure analysis reveals functional flexibility in the selenocysteine-specific tRNA from mouse.

    Directory of Open Access Journals (Sweden)

    Oleg M Ganichkin

    Full Text Available Selenocysteine tRNAs (tRNA(Sec exhibit a number of unique identity elements that are recognized specifically by proteins of the selenocysteine biosynthetic pathways and decoding machineries. Presently, these identity elements and the mechanisms by which they are interpreted by tRNA(Sec-interacting factors are incompletely understood.We applied rational mutagenesis to obtain well diffracting crystals of murine tRNA(Sec. tRNA(Sec lacking the single-stranded 3'-acceptor end ((ΔGCCARNA(Sec yielded a crystal structure at 2.0 Å resolution. The global structure of (ΔGCCARNA(Sec resembles the structure of human tRNA(Sec determined at 3.1 Å resolution. Structural comparisons revealed flexible regions in tRNA(Sec used for induced fit binding to selenophosphate synthetase. Water molecules located in the present structure were involved in the stabilization of two alternative conformations of the anticodon stem-loop. Modeling of a 2'-O-methylated ribose at position U34 of the anticodon loop as found in a sub-population of tRNA(Secin vivo showed how this modification favors an anticodon loop conformation that is functional during decoding on the ribosome. Soaking of crystals in Mn(2+-containing buffer revealed eight potential divalent metal ion binding sites but the located metal ions did not significantly stabilize specific structural features of tRNA(Sec.We provide the most highly resolved structure of a tRNA(Sec molecule to date and assessed the influence of water molecules and metal ions on the molecule's conformation and dynamics. Our results suggest how conformational changes of tRNA(Sec support its interaction with proteins.

  14. Stable carbon isotope analysis reveals widespread drought stress in boreal black spruce forests.

    Science.gov (United States)

    Walker, Xanthe J; Mack, Michelle C; Johnstone, Jill F

    2015-08-01

    Unprecedented rates of climate warming over the past century have resulted in increased forest stress and mortality worldwide. Decreased tree growth in association with increasing temperatures is generally accepted as a signal of temperature-induced drought stress. However, variations in tree growth alone do not reveal the physiological mechanisms behind recent changes in tree growth. Examining stable carbon isotope composition of tree rings in addition to tree growth can provide a secondary line of evidence for physiological drought stress. In this study, we examined patterns of black spruce growth and carbon isotopic composition in tree rings in response to climate warming and drying in the boreal forest of interior Alaska. We examined trees at three nested scales: landscape, toposequence, and a subsample of trees within the toposequence. At each scale, we studied the potential effects of differences in microclimate and moisture availability by sampling on northern and southern aspects. We found that black spruce radial growth responded negatively to monthly metrics of temperature at all examined scales, and we examined ∆(13)C responses on a subsample of trees as representative of the wider region. The negative ∆(13)C responses to temperature reveal that black spruce trees are experiencing moisture stress on both northern and southern aspects. Contrary to our expectations, ∆(13)C from trees on the northern aspect exhibited the strongest drought signal. Our results highlight the prominence of drought stress in the boreal forest of interior Alaska. We conclude that if temperatures continue to warm, we can expect drought-induced productivity declines across large regions of the boreal forest, even for trees located in cool and moist landscape positions. © 2015 John Wiley & Sons Ltd.

  15. Genomic Analysis of Two Phylogenetically DistinctNitrospiraSpecies Reveals Their Genomic Plasticity and Functional Diversity.

    Science.gov (United States)

    Ushiki, Norisuke; Fujitani, Hirotsugu; Shimada, Yu; Morohoshi, Tomohiro; Sekiguchi, Yuji; Tsuneda, Satoshi

    2017-01-01

    The genus Nitrospira represents a dominant group of nitrite-oxidizing bacteria in natural and engineered ecosystems. This genus is phylogenetically divided into six lineages, for which vast phylogenetic and functional diversity has been revealed by recent molecular ecophysiological analyses. However, the genetic basis underlying these phenotypic differences remains largely unknown because of the lack of genome sequences representing their diversity. To gain a more comprehensive understanding of Nitrospira , we performed genomic comparisons between two Nitrospira strains (ND1 and NJ1 belonging to lineages I and II, respectively) previously isolated from activated sludge. In addition, the genomes of these strains were systematically compared with previously reported six Nitrospira genomes to reveal their similarity and presence/absence of several functional genes/operons. Comparisons of Nitrospira genomes indicated that their genomic diversity reflects phenotypic differences and versatile nitrogen metabolisms. Although most genes involved in key metabolic pathways were conserved between strains ND1 and NJ1, assimilatory nitrite reduction pathways of the two Nitrospira strains were different. In addition, the genomes of both strains contain a phylogenetically different urease locus and we confirmed their ureolytic activity. During gene annotation of strain NJ1, we found a gene cluster encoding a quorum-sensing system. From the enriched supernatant of strain NJ1, we successfully identified seven types of acyl-homoserine lactones with a range of C10-C14. In addition, the genome of strain NJ1 lacks genes relevant to flagella and the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas (CRISPR-associated genes) systems, whereas most nitrifying bacteria including strain ND1 possess these genomic elements. These findings enhance our understanding of genomic plasticity and functional diversity among members of the genus Nitrospira .

  16. Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential

    Science.gov (United States)

    Hurley, Jennifer M.; Dasgupta, Arko; Emerson, Jillian M.; Zhou, Xiaoying; Ringelberg, Carol S.; Knabe, Nicole; Lipzen, Anna M.; Lindquist, Erika A.; Daum, Christopher G.; Barry, Kerrie W.; Grigoriev, Igor V.; Smith, Kristina M.; Galagan, James E.; Bell-Pedersen, Deborah; Freitag, Michael; Cheng, Chao; Loros, Jennifer J.; Dunlap, Jay C.

    2014-01-01

    Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation–based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset of ccg promoters, including those of many transcription factors. High temporal resolution (2-h) sampling over 48 h using RNA sequencing (RNA-Seq) identified circadianly expressed genes in Neurospora, revealing that from ∼10% to as much 40% of the transcriptome can be expressed under circadian control. Functional classifications of these genes revealed strong enrichment in pathways involving metabolism, protein synthesis, and stress responses; in broad terms, daytime metabolic potential favors catabolism, energy production, and precursor assembly, whereas night activities favor biosynthesis of cellular components and growth. Discriminative regular expression motif elicitation (DREME) identified key promoter motifs highly correlated with the temporal regulation of ccgs. Correlations between ccg abundance from RNA-Seq, the degree of ccg-promoter activation as reported by ccg-promoter–luciferase fusions, and binding of WCC as measured by ChIP-Seq, are not strong. Therefore, although circadian activation is critical to ccg rhythmicity, posttranscriptional regulation plays a major role in determining rhythmicity at the mRNA level. PMID:25362047

  17. Metabolomics Analysis Reveals that AICAR Affects Glycerolipid, Ceramide and Nucleotide Synthesis Pathways in INS-1 Cells.

    Science.gov (United States)

    ElAzzouny, Mahmoud A; Evans, Charles R; Burant, Charles F; Kennedy, Robert T

    2015-01-01

    AMPK regulates many metabolic pathways including fatty acid and glucose metabolism, both of which are closely associated with insulin secretion in pancreatic β-cells. Insulin secretion is regulated by metabolic coupling factors such as ATP/ADP ratio and other metabolites generated by the metabolism of nutrients such as glucose, fatty acid and amino acids. However, the connection between AMPK activation and insulin secretion in β-cells has not yet been fully elucidated at a metabolic level. To study the effect of AMPK activation on glucose stimulated insulin secretion, we applied the pharmacological activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to an INS-1 (832/13) β-cell line. We measured the change in 66 metabolites in the presence or absence of AICAR using different stable isotopic labeled nutrients to probe selected pathways. AMPK activation by AICAR increased basal insulin secretion and reduced the glucose stimulation index. Although ATP/ADP ratios were not strongly affected by AICAR, several other metabolites and pathways important for insulin secretion were affected by AICAR treatment including long-chain CoAs, malonyl-CoA, 3-hydroxy-3 methylglutaryl CoA, diacylglycerol, and farnesyl pyrophosphate. Tracer studies using 13C-glucose revealed lower glucose flux in the purine and pyrimidine pathway and in the glycerolipid synthesis pathway. Untargeted metabolomics revealed reduction in ceramides caused by AICAR that may explain the beneficial role of AMPK in protecting β-cells from lipotoxicity. Taken together, the results provide an overall picture of the metabolic changes associated with AICAR treatment and how it modulates insulin secretion and β-cell survival.

  18. Genome wide analysis reveals Zic3 interaction with distal regulatory elements of stage specific developmental genes in zebrafish.

    Directory of Open Access Journals (Sweden)

    Cecilia L Winata

    2013-10-01

    Full Text Available Zic3 regulates early embryonic patterning in vertebrates. Loss of Zic3 function is known to disrupt gastrulation, left-right patterning, and neurogenesis. However, molecular events downstream of this transcription factor are poorly characterized. Here we use the zebrafish as a model to study the developmental role of Zic3 in vivo, by applying a combination of two powerful genomics approaches--ChIP-seq and microarray. Besides confirming direct regulation of previously implicated Zic3 targets of the Nodal and canonical Wnt pathways, analysis of gastrula stage embryos uncovered a number of novel candidate target genes, among which were members of the non-canonical Wnt pathway and the neural pre-pattern genes. A similar analysis in zic3-expressing cells obtained by FACS at segmentation stage revealed a dramatic shift in Zic3 binding site locations and identified an entirely distinct set of target genes associated with later developmental functions such as neural development. We demonstrate cis-regulation of several of these target genes by Zic3 using in vivo enhancer assay. Analysis of Zic3 binding sites revealed a distribution biased towards distal intergenic regions, indicative of a long distance regulatory mechanism; some of these binding sites are highly conserved during evolution and act as functional enhancers. This demonstrated that Zic3 regulation of developmental genes is achieved predominantly through long distance regulatory mechanism and revealed that developmental transitions could be accompanied by dramatic changes in regulatory landscape.

  19. Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes

    DEFF Research Database (Denmark)

    Zhao, Xiaolu; Leon, Ileana R; Bak, Steffen

    2011-01-01

    . In skeletal muscle, mitochondrial dysfunction is linked to insulin resistance in humans with obesity and type 2 diabetes. We performed a phosphoproteomic study of functional mitochondria isolated from human muscle biopsies with the aim to obtain a comprehensive overview of mitochondrial phosphoproteins....... Future comparative phosphoproteome analysis of mitochondria from healthy and diseased individuals will provide insights into the role of abnormal phosphorylation in pathologies, such as type 2 diabetes....... in insulin resistance. We also assigned phosphorylation sites in mitochondrial proteins involved in amino acid degradation, importers and transporters, calcium homeostasis, and apoptosis. Bioinformatics analysis of kinase motifs revealed that many of these mitochondrial phosphoproteins are substrates...

  20. Predicting the Size of Sunspot Cycle 24 on the Basis of Single- and Bi-Variate Geomagnetic Precursor Methods

    Science.gov (United States)

    Wilson, Robert M.; Hathaway, David H.

    2009-01-01

    Examined are single- and bi-variate geomagnetic precursors for predicting the maximum amplitude (RM) of a sunspot cycle several years in advance. The best single-variate fit is one based on the average of the ap index 36 mo prior to cycle minimum occurrence (E(Rm)), having a coefficient of correlation (r) equal to 0.97 and a standard error of estimate (se) equal to 9.3. Presuming cycle 24 not to be a statistical outlier and its minimum in March 2008, the fit suggests cycle 24 s RM to be about 69 +/- 20 (the 90% prediction interval). The weighted mean prediction of 11 statistically important single-variate fits is 116 +/- 34. The best bi-variate fit is one based on the maximum and minimum values of the 12-mma of the ap index; i.e., APM# and APm*, where # means the value post-E(RM) for the preceding cycle and * means the value in the vicinity of cycle minimum, having r = 0.98 and se = 8.2. It predicts cycle 24 s RM to be about 92 +/- 27. The weighted mean prediction of 22 statistically important bi-variate fits is 112 32. Thus, cycle 24's RM is expected to lie somewhere within the range of about 82 to 144. Also examined are the late-cycle 23 behaviors of geomagnetic indices and solar wind velocity in comparison to the mean behaviors of cycles 2023 and the geomagnetic indices of cycle 14 (RM = 64.2), the weakest sunspot cycle of the modern era.

  1. Risk analysis reveals global hotspots for marine debris ingestion by sea turtles

    NARCIS (Netherlands)

    Schuyler, Qamar A.; Wilcox, Chris; Townsend, Kathy A.; Wedemeyer-Strombel, Kathryn R.; Balazs, George; van Sebille, Erik|info:eu-repo/dai/nl/304831921; Hardesty, Britta Denise

    2016-01-01

    Plastic marine debris pollution is rapidly becoming one of the critical environmental concerns facing wildlife in the 21st century. Here we present a risk analysis for plastic ingestion by sea turtles on a global scale. We combined global marine plastic distributions based on ocean drifter data with

  2. Revealing and Quantifying the Impaired Phonological Analysis Underpinning Impaired Comprehension in Wernicke's Aphasia

    Science.gov (United States)

    Robson, Holly; Keidel, James L.; Lambon Ralph, Matthew A.; Sage, Karen

    2012-01-01

    Wernicke's aphasia is a condition which results in severely disrupted language comprehension following a lesion to the left temporo-parietal region. A phonological analysis deficit has traditionally been held to be at the root of the comprehension impairment in Wernicke's aphasia, a view consistent with current functional neuroimaging which finds…

  3. Genome-wide analysis of Rad52 foci reveals diverse mechanisms impacting recombination

    DEFF Research Database (Denmark)

    Alvaro, David; Lisby, Michael; Rothstein, Rodney

    2007-01-01

    to humans. Along with genes involved in DNA replication, repair, and chromatin remodeling, we found 22 previously uncharacterized open reading frames. Analysis of recombination rates and synthetic genetic interactions with rad52Delta suggests that multiple mechanisms are responsible for elevated levels...

  4. Transcriptional Network Analysis Reveals Drought Resistance Mechanisms of AP2/ERF Transgenic Rice

    Directory of Open Access Journals (Sweden)

    Hongryul Ahn

    2017-06-01

    Full Text Available This study was designed to investigate at the molecular level how a transgenic version of rice “Nipponbare” obtained a drought-resistant phenotype. Using multi-omics sequencing data, we compared wild-type rice (WT and a transgenic version (erf71 that had obtained a drought-resistant phenotype by overexpressing OsERF71, a member of the AP2/ERF transcription factor (TF family. A comprehensive bioinformatics analysis pipeline, including TF networks and a cascade tree, was developed for the analysis of multi-omics data. The results of the analysis showed that the presence of OsERF71 at the source of the network controlled global gene expression levels in a specific manner to make erf71 survive longer than WT. Our analysis of the time-series transcriptome data suggests that erf71 diverted more energy to survival-critical mechanisms related to translation, oxidative response, and DNA replication, while further suppressing energy-consuming mechanisms, such as photosynthesis. To support this hypothesis further, we measured the net photosynthesis level under physiological conditions, which confirmed the further suppression of photosynthesis in erf71. In summary, our work presents a comprehensive snapshot of transcriptional modification in transgenic rice and shows how this induced the plants to acquire a drought-resistant phenotype.

  5. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

    DEFF Research Database (Denmark)

    Hoadley, Katherine A; Yau, Christina; Wolf, Denise M

    2014-01-01

    Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform o...

  6. In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling

    DEFF Research Database (Denmark)

    Lundby, Alicia; Andersen, Martin N; Steffensen, Annette B

    2013-01-01

    -X-X-pS/T), and integrative analysis of sequence motifs and interaction networks suggested that the kinases AMPK (adenosine 5'-monophosphate-activated protein kinase), Akt, and mTOR (mammalian target of rapamycin) mediate βAR signaling, in addition to the well-established pathways mediated by PKA (cyclic adenosine...

  7. Comprehensive analysis of RNA-Seq data reveals extensive RNA editing in a human transcriptome

    DEFF Research Database (Denmark)

    Peng, Zhiyu; Cheng, Yanbing; Tan, Bertrand Chin-Ming

    2012-01-01

    RNA editing is a post-transcriptional event that recodes hereditary information. Here we describe a comprehensive profile of the RNA editome of a male Han Chinese individual based on analysis of ∼767 million sequencing reads from poly(A)(+), poly(A)(-) and small RNA samples. We developed...

  8. Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance

    DEFF Research Database (Denmark)

    Du, Peina; Huang, Peide; Huang, Xuanlin

    2017-01-01

    was relatively small, and the molecular basis of ESCC has not been fully elucidated. Here, we performed an integrated analysis of 490 tumours by combining the genomic data from 7 previous ESCC projects. We identified 18 significantly mutated genes (SMGs). PTEN, DCDC1 and CUL3 were first reported as SMGs in ESCC...

  9. Gene Coexpression Analysis Reveals Complex Metabolism of the Monoterpene Alcohol Linalool in Arabidopsis FlowersW

    NARCIS (Netherlands)

    Ginglinger, J.F.; Boachon, B.; Hofer, R.; Paetz, C.; Kollner, T.G.; Miesch, L.; Lugan, R.; Baltenweck, R.; Mutterer, J.; Ullman, P.; Verstappen, F.W.A.; Bouwmeester, H.J.

    2013-01-01

    The cytochrome P450 family encompasses the largest family of enzymes in plant metabolism, and the functions of many of its members in Arabidopsis thaliana are still unknown. Gene coexpression analysis pointed to two P450s that were coexpressed with two monoterpene synthases in flowers and were thus

  10. Proteomic analysis reveals that iron availability alters the metabolic status of the pathogenic fungus Paracoccidioides brasiliensis.

    Directory of Open Access Journals (Sweden)

    Ana F A Parente

    Full Text Available Paracoccidioides brasiliensis is a thermodimorphic fungus and the causative agent of paracoccidioidomycosis (PCM. The ability of P. brasiliensis to uptake nutrients is fundamental for growth, but a reduction in the availability of iron and other nutrients is a host defense mechanism many pathogenic fungi must overcome. Thus, fungal mechanisms that scavenge iron from host may contribute to P. brasiliensis virulence. In order to better understand how P. brasiliensis adapts to iron starvation in the host we compared the two-dimensional (2D gel protein profile of yeast cells during iron starvation to that of iron rich condition. Protein spots were selected for comparative analysis based on the protein staining intensity as determined by image analysis. A total of 1752 protein spots were selected for comparison, and a total of 274 out of the 1752 protein spots were determined to have changed significantly in abundance due to iron depletion. Ninety six of the 274 proteins were grouped into the following functional categories; energy, metabolism, cell rescue, virulence, cell cycle, protein synthesis, protein fate, transcription, cellular communication, and cell fate. A correlation between protein and transcript levels was also discovered using quantitative RT-PCR analysis from RNA obtained from P. brasiliensis under iron restricting conditions and from yeast cells isolated from infected mouse spleens. In addition, western blot analysis and enzyme activity assays validated the differential regulation of proteins identified by 2-D gel analysis. We observed an increase in glycolytic pathway protein regulation while tricarboxylic acid cycle, glyoxylate and methylcitrate cycles, and electron transport chain proteins decreased in abundance under iron limiting conditions. These data suggest a remodeling of P. brasiliensis metabolism by prioritizing iron independent pathways.

  11. Powerful bivariate genome-wide association analyses suggest the SOX6 gene influencing both obesity and osteoporosis phenotypes in males.

    Directory of Open Access Journals (Sweden)

    Yao-Zhong Liu

    2009-08-01

    Full Text Available Current genome-wide association studies (GWAS are normally implemented in a univariate framework and analyze different phenotypes in isolation. This univariate approach ignores the potential genetic correlation between important disease traits. Hence this approach is difficult to detect pleiotropic genes, which may exist for obesity and osteoporosis, two common diseases of major public health importance that are closely correlated genetically.To identify such pleiotropic genes and the key mechanistic links between the two diseases, we here performed the first bivariate GWAS of obesity and osteoporosis. We searched for genes underlying co-variation of the obesity phenotype, body mass index (BMI, with the osteoporosis risk phenotype, hip bone mineral density (BMD, scanning approximately 380,000 SNPs in 1,000 unrelated homogeneous Caucasians, including 499 males and 501 females. We identified in the male subjects two SNPs in intron 1 of the SOX6 (SRY-box 6 gene, rs297325 and rs4756846, which were bivariately associated with both BMI and hip BMD, achieving p values of 6.82x10(-7 and 1.47x10(-6, respectively. The two SNPs ranked at the top in significance for bivariate association with BMI and hip BMD in the male subjects among all the approximately 380,000 SNPs examined genome-wide. The two SNPs were replicated in a Framingham Heart Study (FHS cohort containing 3,355 Caucasians (1,370 males and 1,985 females from 975 families. In the FHS male subjects, the two SNPs achieved p values of 0.03 and 0.02, respectively, for bivariate association with BMI and femoral neck BMD. Interestingly, SOX6 was previously found to be essential to both cartilage formation/chondrogenesis and obesity-related insulin resistance, suggesting the gene's dual role in both bone and fat.Our findings, together with the prior biological evidence, suggest the SOX6 gene's importance in co-regulation of obesity and osteoporosis.

  12. miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology

    Directory of Open Access Journals (Sweden)

    Claudio Guedes Salgado

    2018-03-01

    Full Text Available Leprosy remains as a public health problem and its physiopathology is still not fully understood. MicroRNAs (miRNA are small RNA non-coding that can interfere with mRNA to regulate gene expression. A few studies using DNA chip microarrays have explored the expression of miRNA in leprosy patients using a predetermined set of genes as targets, providing interesting findings regarding the regulation of immune genes. However, using a predetermined set of genes restricted the possibility of finding new miRNAs that might be involved in different mechanisms of disease. Thus, we examined the miRNome of tuberculoid (TT and lepromatous (LL patients using both blood and lesional biopsies from classical leprosy patients (LP who visited the Dr. Marcello Candia Reference Unit in Sanitary Dermatology in the State of Pará and compared them with healthy subjects. Using a set of tools to correlate significantly differentially expressed miRNAs with their gene targets, we identified possible interactions and networks of miRNAs that might be involved in leprosy immunophysiopathology. Using this approach, we showed that the leprosy miRNA profile in blood is distinct from that in lesional skin as well as that four main groups of genes are the targets of leprosy miRNA: (1 recognition and phagocytosis, with activation of immune effector cells, where the immunosuppressant profile of LL and immunoresponsive profile of TT are clearly affected by miRNA expression; (2 apoptosis, with supportive data for an antiapoptotic leprosy profile based on BCL2, MCL1, and CASP8 expression; (3 Schwann cells (SCs, demyelination and epithelial–mesenchymal transition (EMT, supporting a role for different developmental or differentiation gene families, such as Sox, Zeb, and Hox; and (4 loss of sensation and neuropathic pain, revealing that RHOA, ROCK1, SIGMAR1, and aquaporin-1 (AQP1 may be involved in the loss of sensation or leprosy pain, indicating possible new therapeutic targets

  13. Integration of differences in EEG analysis reveals changes in human EEG caused by microwave.

    Science.gov (United States)

    Bachmann, Maie; Lass, Jaanus; Kalda, Jaan; Säkki, Maksim; Tomson, Ruth; Tuulik, Viiu; Hinrikus, Hiie

    2006-01-01

    Three different methods in combination with integration of differences in signals were applied for EEG analysis to distinguish changes in EEG caused by microwave: S-parameter, power spectral density and length distribution of low variability periods. The experiments on the effect of modulated low-level microwaves on human EEG were carried out on four different groups of healthy volunteers exposed to 450 MHz microwave radiation modulated with 7 Hz, 14 Hz, 21 Hz, 40 Hz, 70 Hz, 217 or 1000 Hz frequencies. The field power density at the scalp was 0.16 mW/cm2. The EEG analysis performed for individuals with three different methods showed that statistically significant changes occur in the EEG rhythms energy and dynamics between 12% and 30% of subjects.

  14. Histopathological and ultrastructural analysis of vestibular endorgans in Meniere's disease reveals basement membrane pathology

    Directory of Open Access Journals (Sweden)

    McCall Andrew A

    2009-06-01

    Full Text Available Abstract Background We report the systematic analysis of the ultrastructural and cytological histopathology of vestibular endorgans acquired from labyrinthectomy in Meniere's disease. Methods 17 subjects with intractable Meniere's disease and ipsilateral non-serviceable hearing presenting to the Neurotology Clinic from 1997 to 2006 who chose ablative labyrinthectomy (average age = 62 years; range 29–83 years participated. The average duration of symptoms prior to surgery was 7 years (range 1–20 years. Results Nearly all vestibular endorgans demonstrated varying degrees of degeneration. A monolayer of epithelial cells occurred significantly more frequently in the horizontal cristae (12/13 = 92% (p Conclusion Systematic histopathological analysis of the vestibular endorgans from Meniere's disease demonstrated neuroepithelial degeneration which was highly correlated with an associated BM thickening. Other findings included hair cell and supporting cell microvessicles, increased intercellular clear spaces in the stroma, and endothelial cell vacuolization and stromal perivascular BM thickening.

  15. Reaction trajectory revealed by a joint analysis of protein data bank.

    Science.gov (United States)

    Ren, Zhong

    2013-01-01

    Structural motions along a reaction pathway hold the secret about how a biological macromolecule functions. If each static structure were considered as a snapshot of the protein molecule in action, a large collection of structures would constitute a multidimensional conformational space of an enormous size. Here I present a joint analysis of hundreds of known structures of human hemoglobin in the Protein Data Bank. By applying singular value decomposition to distance matrices of these structures, I demonstrate that this large collection of structural snapshots, derived under a wide range of experimental conditions, arrange orderly along a reaction pathway. The structural motions along this extensive trajectory, including several helical transformations, arrive at a reverse engineered mechanism of the cooperative machinery (Ren, companion article), and shed light on pathological properties of the abnormal homotetrameric hemoglobins from α-thalassemia. This method of meta-analysis provides a general approach to structural dynamics based on static protein structures in this post genomics era.

  16. Sunflower mega-environments in Serbia revealed by GGE biplot analysis

    Directory of Open Access Journals (Sweden)

    Balalić Igor

    2013-01-01

    Full Text Available Sunflower mega-environment analysis was conducted for the grain yield data of 20 hybrids and 19 test locations during 2006, and 20 hybrids and 16 test locations during 2007. Combined data included 15 hybrids and 9 test locations common for both years and it was analyzed as balanced experiment. The analysis of variance components showed that hybrid by location interaction explained 2.74, 5.8, and 3.72 times more variation than hybrid, for grain yield, for 2006, 2007, combined data, respectively, and indicated potential mega-environment existence. Our results showed the existence of two mega-environments in Serbia sunflower growing region: (1 Kula Vitovnica, Aleksa Šantić, Sombor and (2 Rimski Šančevi, Kikinda. It has been concluded that if we want promising sunflower hybrids to be optimally used, they should be cropped differently for the two determined mega-environments.

  17. Analysis of the Yeast Kinome Reveals a Network of Regulated Protein Localization during Filamentous Growth

    OpenAIRE

    Bharucha, Nikë; Ma, Jun; Dobry, Craig J.; Lawson, Sarah K.; Yang, Zhifen; Kumar, Anuj

    2008-01-01

    The subcellular distribution of kinases and other signaling proteins is regulated in response to cellular cues; however, the extent of this regulation has not been investigated for any gene set in any organism. Here, we present a systematic analysis of protein kinases in the budding yeast, screening for differential localization during filamentous growth. Filamentous growth is an important stress response involving mitogen-activated protein kinase and cAMP-dependent protein kinase signaling m...

  18. Chromatin organization at the nuclear periphery as revealed by image analysis of structured illumination microscopy data

    Czech Academy of Sciences Publication Activity Database

    Fišerová, Jindřiška; Efenberková, Michaela; Sieger, T.; Maninová, Miloslava; Uhlířová, Jana; Hozák, Pavel

    2017-01-01

    Roč. 130, č. 12 (2017), s. 2066-2077 ISSN 0021-9533 R&D Projects: GA ČR GJ15-08835Y; GA MŠk(CZ) LM2015062 Institutional support: RVO:68378050 Keywords : Structured illumination * Image analysis * Chromation * Nucleus * Histone modification * Nuclear pore complexes Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 4.431, year: 2016

  19. Meta-analysis of small RNA-sequencing errors reveals ubiquitous post-transcriptional RNA modifications

    OpenAIRE

    Ebhardt, H. Alexander; Tsang, Herbert H.; Dai, Denny C.; Liu, Yifeng; Bostan, Babak; Fahlman, Richard P.

    2009-01-01

    Recent advances in DNA-sequencing technology have made it possible to obtain large datasets of small RNA sequences. Here we demonstrate that not all non-perfectly matched small RNA sequences are simple technological sequencing errors, but many hold valuable biological information. Analysis of three small RNA datasets originating from Oryza sativa and Arabidopsis thaliana small RNA-sequencing projects demonstrates that many single nucleotide substitution errors overlap when aligning homologous...

  20. Active tectonics revealed by isobase surfaces analysis from South Rifian Ridges, Northern Morocco

    OpenAIRE

    Amine, Afaf; El Ouardi, Hmidou

    2017-01-01

    The analysis of isobase maps, as one of surface dynamic parameters , helps understanding the tectonic geomorphology of South Rifian Ridges, Northern Morocco . The automatic generation of morphostructural map of 2nd and 3rd order channels is based on 30-grid Digital Elevation Modelin to Geographic Information System environment presents good results, supporting previous studies. Comparing to the western ridges, the eastern ones, specially Moulay Idriss massif, evidence neotectonic activity tri...

  1. Analysis of image versus position, scale and direction reveals pattern texture anisotropy

    Directory of Open Access Journals (Sweden)

    Roland eLehoucq

    2015-01-01

    Full Text Available Pattern heterogeneities and anisotropies often carry significant physical information. We provide a toolbox which: (i cumulates analysis in terms of position, direction and scale; (ii is as general as possible; (iii is simple and fast to understand, implement, execute and exploit.It consists in dividing the image into analysis boxes at a chosen scale; in each box an ellipse (the inertia tensor is fitted to the signal and thus determines the direction in which the signal is more present. This tensor can be averaged in position and/or be used to study the dependence with scale. This choice is formally linked with Leray transforms and anisotropic wavelet analysis. Such protocol is intutively interpreted and consistent with what the eye detects: relevant scales, local variations in space, priviledged directions. It is fast and parallelizable.Its several variants are adaptable to the user's data and needs. It is useful to statistically characterize anisotropies of 2D or 3D patterns in which individual objects are not easily distinguished, with only minimal pre-processing of the raw image, and more generally applies to data in higher dimensions.It is less sensitive to edge effects, and thus better adapted for a multiscale analysis down to small scale boxes, than pair correlation function or Fourier transform.Easy to understand and implement,it complements more sophisticated methods such as Hough transform or diffusion tensor imaging.We use it on various fracture patterns (sea ice cover, thin sections of granite, granular materials, to pinpoint the maximal anisotropy scales. The results are robust to noise and to user choices. This toolbox could turn also useful for granular materials, hard condensed matter, geophysics, thin films, statistical mechanics, characterisation of networks, fluctuating amorphous systems, inhomogeneous and disordered systems, or medical imaging, among others.

  2. Global transcriptome analysis of spore formation in Myxococcus xanthus reveals a locus necessary for cell differentiation

    Directory of Open Access Journals (Sweden)

    Treuner-Lange Anke

    2010-04-01

    Full Text Available Abstract Background Myxococcus xanthus is a Gram negative bacterium that can differentiate into metabolically quiescent, environmentally resistant spores. Little is known about the mechanisms involved in differentiation in part because sporulation is normally initiated at the culmination of a complex starvation-induced developmental program and only inside multicellular fruiting bodies. To obtain a broad overview of the sporulation process and to identify novel genes necessary for differentiation, we instead performed global transcriptome analysis of an artificial chemically-induced sporulation process in which addition of glycerol to vegetatively growing liquid cultures of M. xanthus leads to rapid and synchronized differentiation of nearly all cells into myxospore-like entities. Results Our analyses identified 1 486 genes whose expression was significantly regulated at least two-fold within four hours of chemical-induced differentiation. Most of the previously identified sporulation marker genes were significantly upregulated. In contrast, most genes that are required to build starvation-induced multicellular fruiting bodies, but which are not required for sporulation per se, were not significantly regulated in our analysis. Analysis of functional gene categories significantly over-represented in the regulated genes, suggested large rearrangements in core metabolic pathways, and in genes involved in protein synthesis and fate. We used the microarray data to identify a novel operon of eight genes that, when mutated, rendered cells unable to produce viable chemical- or starvation-induced spores. Importantly, these mutants displayed no defects in building fruiting bodies, suggesting these genes are necessary for the core sporulation process. Furthermore, during the starvation-induced developmental program, these genes were expressed in fruiting bodies but not in peripheral rods, a subpopulation of developing cells which do not sporulate

  3. Wavelet-based regularity analysis reveals recurrent spatiotemporal behavior in resting-state fMRI.

    Science.gov (United States)

    Smith, Robert X; Jann, Kay; Ances, Beau; Wang, Danny J J

    2015-09-01

    One of the major findings from multimodal neuroimaging studies in the past decade is that the human brain is anatomically and functionally organized into large-scale networks. In resting state fMRI (rs-fMRI), spatial patterns emerge when temporal correlations between various brain regions are tallied, evidencing networks of ongoing intercortical cooperation. However, the dynamic structure governing the brain's spontaneous activity is far less understood due to the short and noisy nature of the rs-fMRI signal. Here, we develop a wavelet-based regularity analysis based on noise estimation capabilities of the wavelet transform to measure recurrent temporal pattern stability within the rs-fMRI signal across multiple temporal scales. The method consists of performing a stationary wavelet transform to preserve signal structure, followed by construction of "lagged" subsequences to adjust for correlated features, and finally the calculation of sample entropy across wavelet scales based on an "objective" estimate of noise level at each scale. We found that the brain's default mode network (DMN) areas manifest a higher level of irregularity in rs-fMRI time series than rest of the brain. In 25 aged subjects with mild cognitive impairment and 25 matched healthy controls, wavelet-based regularity analysis showed improved sensitivity in detecting changes in the regularity of rs-fMRI signals between the two groups within the DMN and executive control networks, compared with standard multiscale entropy analysis. Wavelet-based regularity analysis based on noise estimation capabilities of the wavelet transform is a promising technique to characterize the dynamic structure of rs-fMRI as well as other biological signals. © 2015 Wiley Periodicals, Inc.

  4. Analysis of image versus position, scale and direction reveals pattern texture anisotropy

    Science.gov (United States)

    Lehoucq, Roland; Weiss, Jerome; Dubrulle, Berengere; Amon, Axelle; Le Bouil, Antoine; Crassous, Jerome; Amitrano, David; Graner, Francois

    2014-12-01

    Pattern heterogeneities and anisotropies often carry significant physical information. We provide a toolbox which: (i) cumulates analysis in terms of position, direction and scale; (ii) is as general as possible; (iii) is simple and fast to understand, implement, execute and exploit. It consists in dividing the image into analysis boxes at a chosen scale; in each box an ellipse (the inertia tensor) is fitted to the signal and thus determines the direction in which the signal is more present. This tensor can be averaged in position and/or be used to study the dependence with scale. This choice is formally linked with Leray transforms and anisotropic wavelet analysis. Such protocol is intutively interpreted and consistent with what the eye detects: relevant scales, local variations in space, priviledged directions. It is fast and parallelizable. Its several variants are adaptable to the user's data and needs. It is useful to statistically characterize anisotropies of 2D or 3D patterns in which individual objects are not easily distinguished, with only minimal pre-processing of the raw image, and more generally applies to data in higher dimensions. It is less sensitive to edge effects, and thus better adapted for a multiscale analysis down to small scale boxes, than pair correlation function or Fourier transform. Easy to understand and implement, it complements more sophisticated methods such as Hough transform or diffusion tensor imaging. We use it on various fracture patterns (sea ice cover, thin sections of granite, granular materials), to pinpoint the maximal anisotropy scales. The results are robust to noise and to user choices. This toolbox could turn also useful for granular materials, hard condensed matter, geophysics, thin films, statistical mechanics, characterisation of networks, fluctuating amorphous systems, inhomogeneous and disordered systems, or medical imaging, among others.

  5. Protein-Protein Interaction on Lysozyme Crystallization Revealed by Rotational Diffusion Analysis

    OpenAIRE

    Takahashi, Daisuke; Nishimoto, Etsuko; Murase, Tadashi; Yamashita, Shoji

    2008-01-01

    Intermolecular interactions between protein molecules diffusing in various environments underlie many biological processes as well as control protein crystallization, which is a crucial step in x-ray protein structure determinations. Protein interactions were investigated through protein rotational diffusion analysis. First, it was confirmed that tetragonal lysozyme crystals containing fluorescein-tagged lysozyme were successfully formed with the same morphology as that of native protein. Usi...

  6. Polymorphism in mitochondrial DNA of humans as revealed by restriction endonuclease analysis.

    OpenAIRE

    Brown, W M

    1980-01-01

    Mitochondrial DNA samples from each of 21 humans of diverse racial and geographic origin were digested with each of 18 restriction endonucleases. The sizes of the resulting DNA fragments were compared after gel electrophoresis. No differences among the samples were detected in digest with 7 of the enzymes. Analysis of digests with the remaining enzymes showed one or more differences. Each of the 21 samples could be characterized individually on the basis of these digests. All between-sample d...

  7. Mitochondrial DNA differentiation in the Japanese brown frog Rana japonica as revealed by restriction endonuclease analysis.

    Science.gov (United States)

    Sumida, M

    1997-04-01

    To elucidate mtDNA differentiation in the Japanese brown frog Rana japonica, and compare it with results from allozyme analysis and crossing experiments, RFLP analysis was conducted on 78 frogs from 16 populations in Honshu. Purified mtDNA was digested with eight six-base recognizing restriction enzymes and analyzed by 1% agarose-slab gel electrophoresis. Cleavage patterns of the mtDNA showed three distinct genome size classes: small (18.5 kb), middle (20.0 kb) and large (21.5 kb). Ten haplotypes (I approximately X) were observed among the 16 populations. The expected nucleotide divergences within populations ranged from 0 to 0.47% with a mean of 0.08%. The net nucleotide divergences among 16 populations ranged from 0 to 7.74% with a mean of 3.49%. The UPGMA dendrogram and NJ tree, which were constructed based on the net nucleotide divergences, showed that R. japonica diverged first into the eastern and western groups. The eastern group subsequently differentiated into a subgroup containing six populations and the Akita population, and the western group divided into several subgroups. These results, as well as the results of allozyme analysis and crossing experiments, suggest the the eastern and western groups have experienced secondary contact, and introgression has occurred in the Akita population.

  8. Resting-state time-varying analysis reveals aberrant variations of functional connectivity in autism

    Directory of Open Access Journals (Sweden)

    Zhijun Yao

    2016-09-01

    Full Text Available Recently, studies based on time-varying functional connectivity have unveiled brain states diversity in some neuropsychiatric disorders, such as schizophrenia and major depressive disorder. However, time-varying functional connectivity analysis of resting-state functional Magnetic Resonance Imaging (fMRI have been rarely performed on the Autism Spectrum Disorder (ASD. Hence, we performed time-varying connectivity analysis on resting-state fMRI data to investigate brain states mutation in ASD children. ASD showed an imbalance of connectivity state and aberrant ratio of connectivity with different strengths in the whole brain network, and decreased connectivity associated precuneus/posterior cingulate gyrus with medial prefrontal gyrus in default mode network. As compared to typical development children, weak relevance condition (the strength of a large number of connectivities in the state was less than means minus standard deviation of all connection strength was maintained for a longer time between brain areas of ASD children, and ratios of weak connectivity in brain states varied dramatically in the ASD. In the ASD, the abnormal brain state might be related to repetitive behaviors and stereotypical interests, and macroscopically reflect disruption of gamma-aminobutyric acid at the cellular level. The detection of brain states based on time-varying functional connectivity analysis of resting-state fMRI might be conducive for diagnosis and early intervention of ASD before obvious clinical symptoms.

  9. Comparative Genome Analysis of Filamentous Fungi Reveals Gene Family Expansions Associated with Fungal Pathogenesis

    Science.gov (United States)

    Soanes, Darren M.; Alam, Intikhab; Cornell, Mike; Wong, Han Min; Hedeler, Cornelia; Paton, Norman W.; Rattray, Magnus; Hubbard, Simon J.; Oliver, Stephen G.; Talbot, Nicholas J.

    2008-01-01

    Fungi and oomycetes are the causal agents of many of the most serious diseases of plants. Here we report a detailed comparative analysis of the genome sequences of thirty-six species of fungi and oomycetes, including seven plant pathogenic species, that aims to explore the common genetic features associated with plant disease-causing species. The predicted translational products of each genome have been clustered into groups of potential orthologues using Markov Chain Clustering and the data integrated into the e-Fungi object-oriented data warehouse (http://www.e-fungi.org.uk/). Analysis of the species distribution of members of these clusters has identified proteins that are specific to filamentous fungal species and a group of proteins found only in plant pathogens. By comparing the gene inventories of filamentous, ascomycetous phytopathogenic and free-living species of fungi, we have identified a set of gene families that appear to have expanded during the evolution of phytopathogens and may therefore serve important roles in plant disease. We have also characterised the predicted set of secreted proteins encoded by each genome and identified a set of protein families which are significantly over-represented in the secretomes of plant pathogenic fungi, including putative effector proteins that might perturb host cell biology during plant infection. The results demonstrate the potential of comparative genome analysis for exploring the evolution of eukaryotic microbial pathogenesis. PMID:18523684

  10. Time Correlations of Lightning Flash Sequences in Thunderstorms Revealed by Fractal Analysis

    Science.gov (United States)

    Gou, Xueqiang; Chen, Mingli; Zhang, Guangshu

    2018-01-01

    By using the data of lightning detection and ranging system at the Kennedy Space Center, the temporal fractal and correlation of interevent time series of lightning flash sequences in thunderstorms have been investigated with Allan factor (AF), Fano factor (FF), and detrended fluctuation analysis (DFA) methods. AF, FF, and DFA methods are powerful tools to detect the time-scaling structures and correlations in point processes. Totally 40 thunderstorms with distinguishing features of a single-cell storm and apparent increase and decrease in the total flash rate were selected for the analysis. It is found that the time-scaling exponents for AF (αAF) and FF (αFF) analyses are 1.62 and 0.95 in average, respectively, indicating a strong time correlation of the lightning flash sequences. DFA analysis shows that there is a crossover phenomenon—a crossover timescale (τc) ranging from 54 to 195 s with an average of 114 s. The occurrence of a lightning flash in a thunderstorm behaves randomly at timescales τc but shows strong time correlation at scales >τc. Physically, these may imply that the establishment of an extensive strong electric field necessary for the occurrence of a lightning flash needs a timescale >τc, which behaves strongly time correlated. But the initiation of a lightning flash within a well-established extensive strong electric field may involve the heterogeneities of the electric field at a timescale τc, which behave randomly.

  11. Stable isotope analysis of precipitation samples obtained via crowdsourcing reveals the spatiotemporal evolution of Superstorm Sandy.

    Directory of Open Access Journals (Sweden)

    Stephen P Good

    Full Text Available Extra-tropical cyclones, such as 2012 Superstorm Sandy, pose a significant climatic threat to the northeastern United Sates, yet prediction of hydrologic and thermodynamic processes within such systems is complicated by their interaction with mid-latitude water patterns as they move poleward. Fortunately, the evolution of these systems is also recorded in the stable isotope ratios of storm-associated precipitation and water vapor, and isotopic analysis provides constraints on difficult-to-observe cyclone dynamics. During Superstorm Sandy, a unique crowdsourced approach enabled 685 precipitation samples to be obtained for oxygen and hydrogen isotopic analysis, constituting the largest isotopic sampling of a synoptic-scale system to date. Isotopically, these waters span an enormous range of values (> 21‰ for δ(18O, > 160‰ for δ(2H and exhibit strong spatiotemporal structure. Low isotope ratios occurred predominantly in the west and south quadrants of the storm, indicating robust isotopic distillation that tracked the intensity of the storm's warm core. Elevated values of deuterium-excess (> 25‰ were found primarily in the New England region after Sandy made landfall. Isotope mass balance calculations and Lagrangian back-trajectory analysis suggest that these samples reflect the moistening of dry continental air entrained from a mid-latitude trough. These results demonstrate the power of rapid-response isotope monitoring to elucidate the structure and dynamics of water cycling within synoptic-scale systems and improve our understanding of storm evolution, hydroclimatological impacts, and paleo-storm proxies.

  12. Stable isotope analysis of precipitation samples obtained via crowdsourcing reveals the spatiotemporal evolution of Superstorm Sandy.

    Science.gov (United States)

    Good, Stephen P; Mallia, Derek V; Lin, John C; Bowen, Gabriel J

    2014-01-01

    Extra-tropical cyclones, such as 2012 Superstorm Sandy, pose a significant climatic threat to the northeastern United Sates, yet prediction of hydrologic and thermodynamic processes within such systems is complicated by their interaction with mid-latitude water patterns as they move poleward. Fortunately, the evolution of these systems is also recorded in the stable isotope ratios of storm-associated precipitation and water vapor, and isotopic analysis provides constraints on difficult-to-observe cyclone dynamics. During Superstorm Sandy, a unique crowdsourced approach enabled 685 precipitation samples to be obtained for oxygen and hydrogen isotopic analysis, constituting the largest isotopic sampling of a synoptic-scale system to date. Isotopically, these waters span an enormous range of values (> 21‰ for δ(18)O, > 160‰ for δ(2)H) and exhibit strong spatiotemporal structure. Low isotope ratios occurred predominantly in the west and south quadrants of the storm, indicating robust isotopic distillation that tracked the intensity of the storm's warm core. Elevated values of deuterium-excess (> 25‰) were found primarily in the New England region after Sandy made landfall. Isotope mass balance calculations and Lagrangian back-trajectory analysis suggest that these samples reflect the moistening of dry continental air entrained from a mid-latitude trough. These results demonstrate the power of rapid-response isotope monitoring to elucidate the structure and dynamics of water cycling within synoptic-scale systems and improve our understanding of storm evolution, hydroclimatological impacts, and paleo-storm proxies.

  13. Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions.

    Science.gov (United States)

    Akiba, Hiroki; Tsumoto, Kouhei

    2015-07-01

    Antibodies (immunoglobulins) bind specific molecules (i.e. antigens) with high affinity and specificity. In order to understand their mechanisms of recognition, interaction analysis based on thermodynamic and kinetic parameters, as well as structure determination is crucial. In this review, we focus on mutational analysis which gives information about the role of each amino acid residue in antibody-antigen interaction. Taking anti-hen egg lysozyme antibodies and several anti-small molecule antibodies, the energetic contribution of hot-spot and non-hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics of the contribution from aromatic, charged and hydrogen bond-forming amino acids are discussed, and their different characteristics have been elucidated. The information gives fundamental understanding of the antibody-antigen interaction. Furthermore, the consequences of antibody engineering are analysed from thermodynamic viewpoints: humanization to reduce immunogenicity and rational design to improve affinity. Amino acid residues outside hot-spots in the interface play important roles in these cases, and thus thermodynamic and kinetic parameters give much information about the antigen recognition. Thermodynamic analysis of mutant antibodies thus should lead to advanced strategies to design and select antibodies with high affinity. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  14. Whole genome analysis of linezolid resistance in Streptococcus pneumoniae reveals resistance and compensatory mutations

    Directory of Open Access Journals (Sweden)

    Légaré Danielle

    2011-10-01

    Full Text Available Abstract Background Several mutations were present in the genome of Streptococcus pneumoniae linezolid-resistant strains but the role of several of these mutations had not been experimentally tested. To analyze the role of these mutations, we reconstituted resistance by serial whole genome transformation of a novel resistant isolate into two strains with sensitive background. We sequenced the parent mutant and two independent transformants exhibiting similar minimum inhibitory concentration to linezolid. Results Comparative genomic analyses revealed that transformants acquired G2576T transversions in every gene copy of 23S rRNA and that the number of altered copies correlated with the level of linezolid resistance and cross-resistance to florfenicol and chloramphenicol. One of the transformants also acquired a mutation present in the parent mutant leading to the overexpression of an ABC transporter (spr1021. The acquisition of these mutations conferred a fitness cost however, which was further enhanced by the acquisition of a mutation in a RNA methyltransferase implicated in resistance. Interestingly, the fitness of the transformants could be restored in part by the acquisition of altered copies of the L3 and L16 ribosomal proteins and by mutations leading to the overexpression of the spr1887 ABC transporter that were present in the original linezolid-resistant mutant. Conclusions Our results demonstrate the usefulness of whole genome approaches at detecting major determinants of resistance as well as compensatory mutations that alleviate the fitness cost associated with resistance.

  15. Ancient DNA and morphometric analysis reveal extinction and replacement of New Zealand's unique black swans.

    Science.gov (United States)

    Rawlence, Nicolas J; Kardamaki, Afroditi; Easton, Luke J; Tennyson, Alan J D; Scofield, R Paul; Waters, Jonathan M

    2017-07-26

    Prehistoric human impacts on megafaunal populations have dramatically reshaped ecosystems worldwide. However, the effects of human exploitation on smaller species, such as anatids (ducks, geese, and swans) are less clear. In this study we apply ancient DNA and osteological approaches to reassess the history of Australasia's iconic black swans ( Cygnus atratus ) including the palaeo-behaviour of prehistoric populations. Our study shows that at the time of human colonization, New Zealand housed a genetically, morphologically, and potentially ecologically distinct swan lineage ( C. sumnerensis , Poūwa), divergent from modern (Australian) C. atratus Morphological analyses indicate C. sumnerensis exhibited classic signs of the 'island rule' effect, being larger, and likely flight-reduced compared to C. atratus Our research reveals sudden extinction and replacement events within this anatid species complex, coinciding with recent human colonization of New Zealand. This research highlights the role of anthropogenic processes in rapidly reshaping island ecosystems and raises new questions for avian conservation, ecosystem re-wilding, and de-extinction. © 2017 The Author(s).

  16. Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism.

    Science.gov (United States)

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill; Ruckerbauer, David E; Hannibal-Bach, Hans Kristian; Zanghellini, Jürgen; Jensen, Ole N; Ejsing, Christer S

    2015-03-19

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular architecture and processes during physiological adaptations in yeast. Our results reveal that activation of cardiolipin synthesis and remodeling supports mitochondrial biogenesis in the transition from fermentative to respiratory metabolism, that down-regulation of de novo sterol synthesis machinery prompts differential turnover of lipid droplet-associated triacylglycerols and sterol esters during respiratory growth, that sphingolipid metabolism is regulated in a previously unrecognized growth stage-specific manner, and that endogenous synthesis of unsaturated fatty acids constitutes an in vivo upstream activator of peroxisomal biogenesis, via the heterodimeric Oaf1/Pip2 transcription factor. Our work demonstrates the pivotal role of lipid metabolism in adaptive processes and provides a resource to investigate its regulation at the cellular level. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus

    Science.gov (United States)

    Price, Jordan V.; Haddon, David J.; Kemmer, Dodge; Delepine, Guillaume; Mandelbaum, Gil; Jarrell, Justin A.; Gupta, Rohit; Balboni, Imelda; Chakravarty, Eliza F.; Sokolove, Jeremy; Shum, Anthony K.; Anderson, Mark S.; Cheng, Mickie H.; Robinson, William H.; Browne, Sarah K.; Holland, Steven M.; Baechler, Emily C.; Utz, Paul J.

    2013-01-01

    Autoantibodies against cytokines, chemokines, and growth factors inhibit normal immunity and are implicated in inflammatory autoimmune disease and diseases of immune deficiency. In an effort to evaluate serum from autoimmune and immunodeficient patients for Abs against cytokines, chemokines, and growth factors in a high-throughput and unbiased manner, we constructed a multiplex protein microarray for detection of serum factor–binding Abs and used the microarray to detect autoantibody targets in SLE. We designed a nitrocellulose-surface microarray containing human cytokines, chemokines, and other circulating proteins and demonstrated that the array permitted specific detection of serum factor–binding probes. We used the arrays to detect previously described autoantibodies against cytokines in samples from individuals with autoimmune polyendocrine syndrome type 1 and chronic mycobacterial infection. Serum profiling from individuals with SLE revealed that among several targets, elevated IgG autoantibody reactivity to B cell–activating factor (BAFF) was associated with SLE compared with control samples. BAFF reactivity correlated with the severity of disease-associated features, including IFN-α–driven SLE pathology. Our results showed that serum factor protein microarrays facilitate detection of autoantibody reactivity to serum factors in human samples and that BAFF-reactive autoantibodies may be associated with an elevated inflammatory disease state within the spectrum of SLE. PMID:24270423

  18. Proteomic Analysis of Fetal Ovaries Reveals That Primordial Follicle Formation and Transition Are Differentially Regulated

    Directory of Open Access Journals (Sweden)

    Mengmeng Xu

    2017-01-01

    Full Text Available Primordial follicle formation represents a critical phase of the initiation of embryonic reproductive organ development, while the primordial follicle transition into primary follicle determines whether oestrus or ovulation will occur in female animals. To identify molecular mechanism of new proteins which are involved in ovarian development, we employed 2D-DIGE to compare the protein expression profiles of primordial follicles and primary follicles of fetal ovaries in pigs. Fetal ovaries were collected at distinct time-points of the gestation cycle (g55 and g90. The identified proteins at the g55 time-point are mainly involved in the development of anatomical structures [reticulocalbin-1 (RCN1, reticulocalbin-3 (RCN3], cell differentiation (actin, and stress response [heterogeneous nuclear ribonucleoprotein K (HNRNPK]. Meanwhile, at the g90 stage, the isolated proteins with altered expression levels were mainly associated with cell proliferation [major vault protein (MVP] and stress response [heat shock-related 70 kDa protein 2 (HSPA2]. In conclusion, our work revealed that primordial follicle formation is regulated by RCN1, RCN3, actin, and HNRNPK, while the primordial follicle transformation to primary follicle is regulated by MVP and HSPA2. Therefore, our results provide further information for the prospective understanding of the molecular mechanism(s involved in the regulation of the ovarian follicle development.

  19. Alteration in Fluidity of Cell Plasma Membrane in Huntington Disease Revealed by Spectral Phasor Analysis.

    Science.gov (United States)

    Sameni, Sara; Malacrida, Leonel; Tan, Zhiqun; Digman, Michelle A

    2018-01-15

    Huntington disease (HD) is a late-onset genetic neurodegenerative disorder caused by expansion of cytosine-adenine-guanine (CAG) trinucleotide in the exon 1 of the gene encoding the polyglutamine (polyQ). It has been shown that protein degradation and lipid metabolism is altered in HD. In many neurodegenerative disorders, impaired lipid homeostasis is one of the early events in the disease onset. Yet, little is known about how mutant huntingtin may affect phospholipids membrane fluidity. Here, we investigated how membrane fluidity in the living cells (differentiated PC12 and HEK293 cell lines) are affected using a hyperspectral imaging of widely used probes, LAURDAN. Using phasor approach, we characterized the fluorescence of LAURDAN that is sensitive to the polarity of the immediate environment. LAURDAN is affected by the physical order of phospholipids (lipid order) and reports the membrane fluidity. We also validated our results using a different fluorescent membrane probe, Nile Red (NR). The plasma membrane in the cells expressing expanded polyQ shows a shift toward increased membrane fluidity revealed by both LAURDAN and NR spectral phasors. This finding brings a new perspective in the understanding of the early stages of HD that can be used as a target for drug screening.

  20. Comparative Transcriptome Analysis to Reveal Genes Involved in Wheat Hybrid Necrosis

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2014-12-01

    Full Text Available Wheat hybrid necrosis is an interesting genetic phenomenon that is found frequently and results in gradual death or loss of productivity of wheat. However, the molecular basis and mechanisms of this genetic phenomenon are still not well understood. In this study, the transcriptomes of wheat hybrid necrosis F1 and its parents (Neimai 8 and II469 were investigated using digital gene expression (DGE. A total of 1300 differentially expressed genes were identified, indicating that the response to hybrid necrosis in wheat is complicated. The assignments of the annotated genes based on Gene Ontology (GO revealed that most of the up-regulated genes belong to “universal stress related”, “DNA/RNA binding”, “protein degradation” functional groups, while the down-regulated genes belong to “carbohydrate metabolism” and “translation regulation” functional groups. These findings suggest that these pathways were affected by hybrid necrosis. Our results provide preliminarily new insight into the underlying molecular mechanisms of hybrid necrosis and will help to identify important candidate genes involved in wheat hybrid necrosis.

  1. Comparative transcriptome analysis to reveal genes involved in wheat hybrid necrosis.

    Science.gov (United States)

    Zhang, Yong; Cheng, Yan; Guo, Jiahui; Yang, Ennian; Liu, Cheng; Zheng, Xuelian; Deng, Kejun; Zhou, Jianping

    2014-12-16

    Wheat hybrid necrosis is an interesting genetic phenomenon that is found frequently and results in gradual death or loss of productivity of wheat. However, the molecular basis and mechanisms of this genetic phenomenon are still not well understood. In this study, the transcriptomes of wheat hybrid necrosis F1 and its parents (Neimai 8 and II469) were investigated using digital gene expression (DGE). A total of 1300 differentially expressed genes were identified, indicating that the response to hybrid necrosis in wheat is complicated. The assignments of the annotated genes based on Gene Ontology (GO) revealed that most of the up-regulated genes belong to "universal stress related", "DNA/RNA binding", "protein degradation" functional groups, while the down-regulated genes belong to "carbohydrate metabolism" and "translation regulation" functional groups. These findings suggest that these pathways were affected by hybrid necrosis. Our results provide preliminarily new insight into the underlying molecular mechanisms of hybrid necrosis and will help to identify important candidate genes involved in wheat hybrid necrosis.

  2. Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins.

    Directory of Open Access Journals (Sweden)

    Eric K Johnson

    Full Text Available Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies.

  3. Proteomic Analysis of Lysine Acetylation Sites in Rat Tissues Reveals Organ Specificity and Subcellular Patterns

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    Alicia Lundby

    2012-08-01

    Full Text Available Lysine acetylation is a major posttranslational modification involved in a broad array of physiological functions. Here, we provide an organ-wide map of lysine acetylation sites from 16 rat tissues analyzed by high-resolution tandem mass spectrometry. We quantify 15,474 modification sites on 4,541 proteins and provide the data set as a web-based database. We demonstrate that lysine acetylation displays site-specific sequence motifs that diverge between cellular compartments, with a significant fraction of nuclear sites conforming to the consensus motifs G-AcK and AcK-P. Our data set reveals that the subcellular acetylation distribution is tissue-type dependent and that acetylation targets tissue-specific pathways involved in fundamental physiological processes. We compare lysine acetylation patterns for rat as well as human skeletal muscle biopsies and demonstrate its general involvement in muscle contraction. Furthermore, we illustrate that acetylation of fructose-bisphosphate aldolase and glycerol-3-phosphate dehydrogenase serves as a cellular mechanism to switch off enzymatic activity.

  4. In vivo single cell analysis reveals Gata2 dynamics in cells transitioning to hematopoietic fate.

    Science.gov (United States)

    Eich, Christina; Arlt, Jochen; Vink, Chris S; Solaimani Kartalaei, Parham; Kaimakis, Polynikis; Mariani, Samanta A; van der Linden, Reinier; van Cappellen, Wiggert A; Dzierzak, Elaine

    2018-01-02

    Cell fate is established through coordinated gene expression programs in individual cells. Regulatory networks that include the Gata2 transcription factor play central roles in hematopoietic fate establishment. Although Gata2 is essential to the embryonic development and function of hematopoietic stem cells that form the adult hierarchy, little is known about the in vivo expression dynamics of Gata2 in single cells. Here, we examine Gata2 expression in single aortic cells as they establish hematopoietic fate in Gata2Venus mouse embryos. Time-lapse imaging reveals rapid pulsatile level changes in Gata2 reporter expression in cells undergoing endothelial-to-hematopoietic transition. Moreover, Gata2 reporter pulsatile expression is dramatically altered in Gata2 +/- aortic cells, which undergo fewer transitions and are reduced in hematopoietic potential. Our novel finding of dynamic pulsatile expression of Gata2 suggests a highly unstable genetic state in single cells concomitant with their transition to hematopoietic fate. This reinforces the notion that threshold levels of Gata2 influence fate establishment and has implications for transcription factor-related hematologic dysfunctions. © 2018 Eich et al.

  5. A specific indel marker for the Philippines Schistosoma japonicum revealed by analysis of mitochondrial genome sequences.

    Science.gov (United States)

    Li, Juan; Chen, Fen; Sugiyama, Hiromu; Blair, David; Lin, Rui-Qing; Zhu, Xing-Quan

    2015-07-01

    In the present study, near-complete mitochondrial (mt) genome sequences for Schistosoma japonicum from different regions in the Philippines and Japan were amplified and sequenced. Comparisons among S. japonicum from the Philippines, Japan, and China revealed a geographically based length difference in mt genomes, but the mt genomic organization and gene arrangement were the same. Sequence differences among samples from the Philippines and all samples from the three endemic areas were 0.57-2.12 and 0.76-3.85 %, respectively. The most variable part of the mt genome was the non-coding region. In the coding portion of the genome, protein-coding genes varied more than rRNA genes and tRNAs. The near-complete mt genome sequences for Philippine specimens were identical in length (14,091 bp) which was 4 bp longer than those of S. japonicum samples from Japan and China. This indel provides a unique genetic marker for S. japonicum samples from the Philippines. Phylogenetic analyses based on the concatenated amino acids of 12 protein-coding genes showed that samples of S. japonicum clustered according to their geographical origins. The identified mitochondrial indel marker will be useful for tracing the source of S. japonicum infection in humans and animals in Southeast Asia.

  6. Chicken genome analysis reveals novel genes encoding biotin-binding proteins related to avidin family

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    Nordlund Henri R

    2005-03-01

    Full Text Available Abstract Background A chicken egg contains several biotin-binding proteins (BBPs, whose complete DNA and amino acid sequences are not known. In order to identify and characterise these genes and proteins we studied chicken cDNAs and genes available in the NCBI database and chicken genome database using the reported N-terminal amino acid sequences of chicken egg-yolk BBPs as search strings. Results Two separate hits showing significant homology for these N-terminal sequences were discovered. For one of these hits, the chromosomal location in the immediate proximity of the avidin gene family was found. Both of these hits encode proteins having high sequence similarity with avidin suggesting that chicken BBPs are paralogous to avidin family. In particular, almost all residues corresponding to biotin binding in avidin are conserved in these putative BBP proteins. One of the found DNA sequences, however, seems to encode a carboxy-terminal extension not present in avidin. Conclusion We describe here the predicted properties of the putative BBP genes and proteins. Our present observations link BBP genes together with avidin gene family and shed more light on the genetic arrangement and variability of this family. In addition, comparative modelling revealed the potential structural elements important for the functional and structural properties of the putative BBP proteins.

  7. Insight into octoploid strawberry (Fragaria) subgenome composition revealed by GISH analysis of pentaploid hybrids.

    Science.gov (United States)

    Liu, Bo; Poulsen, Elizabeth G; Davis, Thomas M

    2016-02-01

    As the product of interspecific hybridization between its two ancestral octoploid (2n = 8x = 56) species (Fragaria chiloensis and F. virginiana), the cultivated strawberry (F. ×ananassa) is among the most genomically complex of crop plants, harboring subgenomic components derived from as many as four different diploid ancestors. To physically visualize the octoploids' subgenome composition(s), we launched molecular cytogenetic studies using genomic in situ hybridization (GISH), comparative GISH (cGISH), and rDNA-FISH techniques. First, GISH resolution in Fragaria was tested by using diploid and triploid hybrids with predetermined genome compositions. Then, observation of an octoploid genome was implemented by hybridizing chromosomes of pentaploid (2n = 5x = 35) hybrids from F. vesca × F. virginiana with genomic DNA probes derived from diploids (2n = 2x = 14) F. vesca and F. iinumae, which have been proposed by phylogenetic studies to be closely related to the octoploids yet highly divergent from each other. GISH and cGISH results indicated that octoploid-derived gametes (n = 4x = 28) carried seven chromosomes with hybridization affinities to F. vesca, while the remaining 21 chromosomes displayed varying affinities to F. iinumae, indicating differing degrees of subgenomic contribution to the octoploids by these two putatively ancestral diploids. Combined rDNA-FISH revealed severe 25S rDNA loss in both the F. vesca- and F. iinumae-like chromosome groups, while only the prior group retained its 5S loci.

  8. Metagenomic analysis reveals that modern microbialites and polar microbial mats have similar taxonomic and functional potential

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    Richard Allen White III

    2015-09-01

    Full Text Available Within the subarctic climate of Clinton Creek, Yukon, Canada, lies an abandoned and flooded open-pit asbestos mine that harbors rapidly growing microbialites. To understand their formation we completed a metagenomic community profile of the microbialites and their surrounding sediments. Assembled metagenomic data revealed that bacteria within the phylum Proteobacteria numerically dominated this system, although the relative abundances of taxa within the phylum varied among environments. Bacteria belonging to Alphaproteobacteria and Gammaproteobacteria were dominant in the microbialites and sediments, respectively. The microbialites were also home to many other groups associated with microbialite formation including filamentous cyanobacteria and dissimilatory sulfate-reducing Deltaproteobacteria, consistent with the idea of a shared global microbialite microbiome. Other members were present that are typically not associated with microbialites including Gemmatimonadetes and iron-oxidizing Betaproteobacteria, which participate in carbon metabolism and iron cycling. Compared to the sediments, the microbialite microbiome has significantly more genes associated with photosynthetic processes (e.g., photosystem II reaction centers, carotenoid and chlorophyll biosynthesis and carbon fixation (e.g., CO dehydrogenase. The Clinton Creek microbialite communities had strikingly similar functional potentials to non-lithifying microbial mats from the Canadian High Arctic and Antarctica, but are functionally distinct, from non-lithifying mats or biofilms from Yellowstone. Clinton Creek microbialites also share metabolic genes (R2 0.900. These metagenomic profiles from an anthropogenic microbialite-forming ecosystem provide context to microbialite formation on a human-relevant timescale.

  9. Genome-wide analysis reveals the extent of EAV-HP integration in domestic chicken.

    Science.gov (United States)

    Wragg, David; Mason, Andrew S; Yu, Le; Kuo, Richard; Lawal, Raman A; Desta, Takele Taye; Mwacharo, Joram M; Cho, Chang-Yeon; Kemp, Steve; Burt, David W; Hanotte, Olivier

    2015-10-14

    EAV-HP is an ancient retrovirus pre-dating Gallus speciation, which continues to circulate in modern chicken populations, and led to the emergence of avian leukosis virus subgroup J causing significant economic losses to the poultry industry. We mapped EAV-HP integration sites in Ethiopian village chickens, a Silkie, Taiwan Country chicken, red junglefowl Gallus gallus and several inbred experimental lines using whole-genome sequence data. An average of 75.22 ± 9.52 integration sites per bird were identified, which collectively group into 279 intervals of which 5 % are common to 90 % of the genomes analysed and are suggestive of pre-domestication integration events. More than a third of intervals are specific to individual genomes, supporting active circulation of EAV-HP in modern chickens. Interval density is correlated with chromosome length (P < 2.31(-6)), and 27 % of intervals are located within 5 kb of a transcript. Functional annotation clustering of genes reveals enrichment for immune-related functions (P < 0.05). Our results illustrate a non-random distribution of EAV-HP in the genome, emphasising the importance it may have played in the adaptation of the species, and provide a platform from which to extend investigations on the co-evolutionary significance of endogenous retroviral genera with their hosts.

  10. Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species

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    Kim-Chung Lee

    2015-06-01

    Full Text Available Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu–Glu–Leu–Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxybenzoic acid and (sulfooxybenzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxybenzoic acid possesses a structure similar to those of aspirin [2-(acetoxybenzoic acid] and salicylic acid (2-hydroxybenzoic acid. Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu–Glu–Leu–Glu, hydroxy-(sulfooxybenzoic acid and (sulfooxybenzoic acid are virulent factors of the pathogenic Aspergillus species.

  11. A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies.

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    Masakazu Kohda

    2016-01-01

    Full Text Available Mitochondrial disorders have the highest incidence among congenital metabolic disorders characterized by biochemical respiratory chain complex deficiencies. It occurs at a rate of 1 in 5,000 births, and has phenotypic and genetic heterogeneity. Mutations in about 1,500 nuclear encoded mitochondrial proteins may cause mitochondrial dysfunction of energy production and mitochondrial disorders. More than 250 genes that cause mitochondrial disorders have been reported to date. However exact genetic diagnosis for patients still remained largely unknown. To reveal this heterogeneity, we performed comprehensive genomic analyses for 142 patients with childhood-onset mitochondrial respiratory chain complex deficiencies. The approach includes whole mtDNA and exome analyses using high-throughput sequencing, and chromosomal aberration analyses using high-density oligonucleotide arrays. We identified 37 novel mutations in known mitochondrial disease genes and 3 mitochondria-related genes (MRPS23, QRSL1, and PNPLA4 as novel causative genes. We also identified 2 genes known to cause monogenic diseases (MECP2 and TNNI3 and 3 chromosomal aberrations (6q24.3-q25.1, 17p12, and 22q11.21 as causes in this cohort. Our approaches enhance the ability to identify pathogenic gene mutations in patients with biochemically defined mitochondrial respiratory chain complex deficiencies in clinical settings. They also underscore clinical and genetic heterogeneity and will improve patient care of this complex disorder.

  12. Metagenomic Analysis Reveals Presence of Treponema denticola in a Tissue Biopsy of the Iceman

    Science.gov (United States)

    Cipollini, Giovanna; Widder, Stefanie

    2014-01-01

    Ancient hominoid genome studies can be regarded by definition as metagenomic analyses since they represent a mixture of both hominoid and microbial sequences in an environment. Here, we report the molecular detection of the oral spirochete Treponema denticola in ancient human tissue biopsies of the Iceman, a 5,300-year-old Copper Age natural ice mummy. Initially, the metagenomic data of the Iceman’s genomic survey was screened for bacterial ribosomal RNA (rRNA) specific reads. Through ranking the reads by abundance a relatively high number of rRNA reads most similar to T. denticola was detected. Mapping of the metagenome sequences against the T. denticola genome revealed additional reads most similar to this opportunistic pathogen. The DNA damage pattern of specifically mapped reads suggests an ancient origin of these sequences. The haematogenous spread of bacteria of the oral microbiome often reported in the recent literature could already explain the presence of metagenomic reads specific for T. denticola in the Iceman’s bone biopsy. We extended, however, our survey to an Iceman gingival tissue sample and a mouth swab sample and could thereby detect T. denticola and Porphyrimonas gingivalis, another important member of the human commensal oral microflora. Taken together, this study clearly underlines the opportunity to detect disease-associated microorganisms when applying metagenomics- enabled approaches on datasets of ancient human remains. PMID:24941044

  13. Structure-guided mutational analysis reveals the functional requirements for product specificity of DOT1 enzymes.

    Science.gov (United States)

    Dindar, Gülcin; Anger, Andreas M; Mehlhorn, Christine; Hake, Sandra B; Janzen, Christian J

    2014-11-12

    DOT1 enzymes are conserved methyltransferases that catalyse the methylation of lysine 79 on histone H3 (H3K79). Most eukaryotes contain one DOT1 enzyme, whereas African trypanosomes have two homologues, DOT1A and DOT1B, with different enzymatic activities. DOT1A mediates mono- and dimethylation of H3K76, the homologue of H3K79 in other organisms, whereas DOT1B additionally catalyses H3K76 trimethylation. However, it is unclear how these different enzymatic activities are achieved. Here we employ a trypanosomal nucleosome reconstitution system and structure-guided homology modelling to identify critical residues within and outside the catalytic centre that modulate product specificity. Exchange of these residues transfers the product specificity from one enzyme to the other, and reveals the existence of distinct regulatory domains adjacent to the catalytic centre. Our study provides the first evidence that a few crucial residues in DOT1 enzymes are sufficient to catalyse methyl-state-specific reactions. These results might also have far-reaching consequences for the functional understanding of homologous enzymes in higher eukaryotes.

  14. Proteomic Analysis Reveals New Cardiac-Specific Dystrophin-Associated Proteins

    Science.gov (United States)

    Johnson, Eric K.; Zhang, Liwen; Adams, Marvin E.; Phillips, Alistair; Freitas, Michael A.; Froehner, Stanley C.; Green-Church, Kari B.; Montanaro, Federica

    2012-01-01

    Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies. PMID:22937058

  15. Market organization and animal genetic resource management: a revealed preference analysis of sheep pricing.

    Science.gov (United States)

    Tindano, K; Moula, N; Leroy, P; Traoré, A; Antoine-Moussiaux, N

    2017-10-01

    Farm animal genetic resources are threatened worldwide. Participation in markets, while representing a crucial way out of poverty for many smallholders, affects genetic management choices with associated sustainability concerns. This paper proposes a contextualized study of the interactions between markets and animal genetic resources management, in the case of sheep markets in Ouagadougou, Burkina Faso. It focusses on the organization of marketing chains and the valuation of genetic characteristics by value chain actors. Marketing chain characterization was tackled through semi-structured interviews with 25 exporters and 15 butchers, both specialized in sheep. Moreover, revealed preference methods were applied to analyse the impact of animals' attributes on market pricing. Data were collected from 338 transactions during three different periods: Eid al-Adha, Christmas and New Year period, and a neutral period. The neutral period is understood as a period not close to any event likely to influence the demand for sheep. The results show that physical characteristics such as live weight, height at withers and coat colour have a strong influence on the animals' prices. Live weight has also had an increasing marginal impact on price. The different markets (local butcher, feasts, export market, sacrifices) represent distinct demands for genetic characteristics, entailing interesting consequences for animal genetic resource management. Any breeding programme should therefore take this diversity into account to allow this sector to contribute better to a sustainable development of the country.

  16. Service innovation management practices in the telecommunications industry: what does cross country analysis reveal?

    Science.gov (United States)

    Rahman, Syed Abidur; Taghizadeh, Seyedeh Khadijeh; Ramayah, T; Ahmad, Noor Hazlina

    2015-01-01

    Service innovation management practice is currently being widely scrutinized mainly in the developed countries, where it has been initiated. The current study attempts to propose a framework and empirically validate and explain the service innovation practices for successful performance in the telecommunications industry of two developing countries, Malaysia and Bangladesh. The research framework proposes relationships among organisational culture, operating core (innovation process, cross-functional organisation, and implementation of tools/technology), competition-informed pricing, and performance. A total of 176 usable data from both countries are analysed for the purpose of the research. The findings show that organisational culture tends to be more influential on innovation process and cross-functional organisation in Malaysian telecommunication industry. In contrast, implementation of tools/technology plays a more instrumental role in competition-informed pricing practices in Bangladesh. This study revealed few differences in the innovation management practices between two developing countries. The findings have strategic implications for the service sectors in both the developing countries regarding implementation of innovative enterprises, especially in Bangladesh where innovation is the basis for survival. Testing the innovation management practices in the developing countries perhaps contains uniqueness in the field of innovation management.

  17. Proteomic analysis reveals a novel function of the kinase Sat4p in Saccharomyces cerevisiae mitochondria.

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    Uta Gey

    Full Text Available The Saccharomyces cerevisiae kinase Sat4p has been originally identified as a protein involved in salt tolerance and stabilization of plasma membrane transporters, implicating a cytoplasmic localization. Our study revealed an additional mitochondrial (mt localization, suggesting a dual function for Sat4p. While no mt related phenotype was observed in the absence of Sat4p, its overexpression resulted in significant changes of a specific mitochondrial subproteome. As shown by a comparative two dimensional difference gel electrophoresis (2D-DIGE approach combined with mass spectrometry, particularly two groups of proteins were affected: the iron-sulfur containing aconitase-type proteins (Aco1p, Lys4p and the lipoamide-containing subproteome (Lat1p, Kgd2p and Gcv3p. The lipoylation sites of all three proteins could be assigned by nanoLC-MS/MS to Lys75 (Lat1p, Lys114 (Kgd2p and Lys102 (Gcv3p, respectively. Sat4p overexpression resulted in accumulation of the delipoylated protein variants and in reduced levels of aconitase-type proteins, accompanied by a decrease in the activities of the respective enzyme complexes. We propose a regulatory role of Sat4p in the late steps of the maturation of a specific subset of mitochondrial iron-sulfur cluster proteins, including Aco1p and lipoate synthase Lip5p. Impairment of the latter enzyme may account for the observed lipoylation defects.

  18. LC-MS-MS quantitative analysis reveals the association between FTO and DNA methylation.

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    Yuting Zhu

    Full Text Available Fat mass and obesity-associated protein (FTO is α-ketoglutarate-dependent dioxygenase and responsible for demethylating N6-methyladenosine (m6A in mRNA, 3-methylthymine (m3T in single-stranded DNA (ssDNA and 3-methyluracil (m3U in single-stranded RNA (ssRNA. Its other function remains unknown but thousands of mammalian DNA show 5-methyl-2'-deoxycytidine (5mdC modification and 5mdC demethylases are required for mammalian energy homeostasis and fertility. Here, we aimed to confirm whether FTO proteins can demethylate 5mdC in DNA. However, we found that FTO exhibits no potent demethylation activity against 5mdC in vitro and in vivo by using liquid chromatography-tandem mass spectrometry (LC-MS-MS. The result showed FTO demethylase has the characteristics of high substrates specificity and selectivity. In addition, we also used immunofluorescence technique to demonstrate overexpression of wild type TET2, but not FTO and mutant TET2 in Hela cells results in higher levels of 5-hydroxymethyl-2'-deoxycytidine (5hmdC generated from 5mdC. In conclusion, our results not only reveal the enzymatic activity of FTO, but also may facilitate the future discovery of proteins involved in epigenetic modification function.

  19. Modelling the vicious circle between obesity and physical activity in children and adolescents using a bivariate probit model with endogenous regressors.

    Science.gov (United States)

    Yeh, C-Y; Chen, L-J; Ku, P-W; Chen, C-M

    2015-01-01

    The increasing prevalence of obesity in children and adolescents has become one of the most important public health issues around the world. Lack of physical activity is a risk factor for obesity, while being obese could reduce the likelihood of participating in physical activity. Failing to account for the endogeneity between obesity and physical activity would result in biased estimation. This study investigates the relationship between overweight and physical activity by taking endogeneity into consideration. It develops an endogenous bivariate probit model estimated by the maximum likelihood method. The data included 4008 boys and 4197 girls in the 5th-9th grades in Taiwan in 2007-2008. The relationship between overweight and physical activity is significantly negative in the endogenous model, but insignificant in the comparative exogenous model. This endogenous relationship presents a vicious circle in which lower levels of physical activity lead to overweight, while those who are already overweight engage in less physical activity. The results not only reveal the importance of endogenous treatment, but also demonstrate the robust negative relationship between these two factors. An emphasis should be put on overweight and obese children and adolescents in order to break the vicious circle. Promotion of physical activity by appropriate counselling programmes and peer support could be effective in reducing the prevalence of obesity in children and adolescents.

  20. Revealing the association between cerebrovascular accidents and ambient temperature: a meta-analysis

    Science.gov (United States)

    Zorrilla-Vaca, Andrés; Healy, Ryan Jacob; Silva-Medina, Melissa M.

    2017-05-01

    The association between cerebrovascular accidents (CVA) and weather has been described across several studies showing multiple conflicting results. In this paper, we aim to conduct a meta-analysis to further clarify this association, as well as to find the potential sources of heterogeneity. PubMed, EMBASE, and Google Scholar were searched from inception through 2015, for articles analyzing the correlation between the incidence of CVA and temperature. A pooled effect size (ES) was estimated using random effects model and expressed as absolute values. Subgroup analyses by type of CVA were also performed. Heterogeneity and influence of covariates—including geographic latitude of the study site, male percentage, average temperature, and time interval—were assessed by meta-regression analysis. Twenty-six articles underwent full data extraction and scoring. A total of 19,736 subjects with CVA from 12 different countries were included and grouped as ischemic strokes (IS; n = 14,199), intracerebral hemorrhages (ICH; n = 3798), and subarachnoid hemorrhages (SAH; n = 1739). Lower ambient temperature was significantly associated with increase in incidence of overall CVA when using unadjusted (pooled ES = 0.23, P < 0.001) and adjusted data (pooled ES = 0.03, P = 0.003). Subgroup analyses showed that lower temperature has higher impact on the incidence of ICH (pooled ES = 0.34, P < 0.001), than that of IS (pooled ES = 0.22, P < 0.001) and SAH (pooled ES = 0.11, P = 0.012). In meta-regression analysis, the geographic latitude of the study site was the most influencing factor on this association ( Z-score = 8.68). Synthesis of the existing data provides evidence supporting that a lower ambient temperature increases the incidence of CVA. Further population-based studies conducted at negative latitudes are needed to clarify the influence of this factor.

  1. Centromere Locations in Brassica A and C Genomes Revealed Through Half-Tetrad Analysis.

    Science.gov (United States)

    Mason, Annaliese S; Rousseau-Gueutin, Mathieu; Morice, Jérôme; Bayer, Philipp E; Besharat, Naghmeh; Cousin, Anouska; Pradhan, Aneeta; Parkin, Isobel A P; Chèvre, Anne-Marie; Batley, Jacqueline; Nelson, Matthew N

    2016-02-01

    Locating centromeres on genome sequences can be challenging. The high density of repetitive elements in these regions makes sequence assembly problematic, especially when using short-read sequencing technologies. It can also be difficult to distinguish between active and recently extinct centromeres through sequence analysis. An effective solution is to identify genetically active centromeres (functional in meiosis) by half-tetrad analysis. This genetic approach involves detecting heterozygosity along chromosomes in segregating populations derived from gametes (half-tetrads). Unreduced gametes produced by first division restitution mechanisms comprise complete sets of nonsister chromatids. Along these chromatids, heterozygosity is maximal at the centromeres, and homologous recombination events result in homozygosity toward the telomeres. We genotyped populations of half-tetrad-derived individuals (from Brassica interspecific hybrids) using a high-density array of physically anchored SNP markers (Illumina Brassica 60K Infinium array). Mapping the distribution of heterozygosity in these half-tetrad individuals allowed the genetic mapping of all 19 centromeres of the Brassica A and C genomes to the reference Brassica napus genome. Gene and transposable element density across the B. napus genome were also assessed and corresponded well to previously reported genetic map positions. Known centromere-specific sequences were located in the reference genome, but mostly matched unanchored sequences, suggesting that the core centromeric regions may not yet be assembled into the pseudochromosomes of the reference genome. The increasing availability of genetic markers physically anchored to reference genomes greatly simplifies the genetic and physical mapping of centromeres using half-tetrad analysis. We discuss possible applications of this approach, including in species where half-tetrads are currently difficult to isolate. Copyright © 2016 by the Genetics Society of America.

  2. Large-scale transcriptome analysis reveals arabidopsis metabolic pathways are frequently influenced by different pathogens.

    Science.gov (United States)

    Jiang, Zhenhong; He, Fei; Zhang, Ziding

    2017-07-01

    Through large-scale transcriptional data analyses, we highlighted the importance of plant metabolism in plant immunity and identified 26 metabolic pathways that were frequently influenced by the infection of 14 different pathogens. Reprogramming of plant metabolism is a common phenomenon in plant defense responses. Currently, a large number of transcriptional profiles of infected tissues in Arabidopsis (Arabidopsis thaliana) have been deposited in public databases, which provides a great opportunity to understand the expression patterns of metabolic pathways during plant defense responses at the systems level. Here, we performed a large-scale transcriptome analysis based on 135 previously published expression samples, including 14 different pathogens, to explore the expression pattern of Arabidopsis metabolic pathways. Overall, metabolic genes are significantly changed in expression during plant defense responses. Upregulated metabolic genes are enriched on defense responses, and downregulated genes are enriched on photosynthesis, fatty acid and lipid metabolic processes. Gene set enrichment analysis (GSEA) identifies 26 frequently differentially expressed metabolic pathways (FreDE_Paths) that are differentially expressed in more than 60% of infected samples. These pathways are involved in the generation of energy, fatty acid and lipid metabolism as well as secondary metabolite biosynthesis. Clustering analysis based on the expression levels of these 26 metabolic pathways clearly distinguishes infected and control samples, further suggesting the importance of these metabolic pathways in plant defense responses. By comparing with FreDE_Paths from abiotic stresses, we find that the expression patterns of 26 FreDE_Paths from biotic stresses are more consistent across different infected samples. By investigating the expression correlation between transcriptional factors (TFs) and FreDE_Paths, we identify several notable relationships. Collectively, the current study

  3. Comparative genome analysis of entomopathogenic fungi reveals a complex set of secreted proteins.

    Science.gov (United States)

    Staats, Charley Christian; Junges, Angela; Guedes, Rafael Lucas Muniz; Thompson, Claudia Elizabeth; de Morais, Guilherme Loss; Boldo, Juliano Tomazzoni; de Almeida, Luiz Gonzaga Paula; Andreis, Fábio Carrer; Gerber, Alexandra Lehmkuhl; Sbaraini, Nicolau; da Paixão, Rana Louise de Andrade; Broetto, Leonardo; Landell, Melissa; Santi, Lucélia; Beys-da-Silva, Walter Orlando; Silveira, Carolina Pereira; Serrano, Thaiane Rispoli; de Oliveira, Eder Silva; Kmetzsch, Lívia; Vainstein, Marilene Henning; de Vasconcelos, Ana Tereza Ribeiro; Schrank, Augusto

    2014-09-29

    Metarhizium anisopliae is an entomopathogenic fungus used in the biological control of some agricultural insect pests, and efforts are underway to use this fungus in the control of insect-borne human diseases. A large repertoire of proteins must be secreted by M. anisopliae to cope with the various available nutrients as this fungus switches through different lifestyles, i.e., from a saprophytic, to an infectious, to a plant endophytic stage. To further evaluate the predicted secretome of M. anisopliae, we employed genomic and transcriptomic analyses, coupled with phylogenomic analysis, focusing on the identification and characterization of secreted proteins. We determined the M. anisopliae E6 genome sequence and compared this sequence to other entomopathogenic fungi genomes. A robust pipeline was generated to evaluate the predicted secretomes of M. anisopliae and 15 other filamentous fungi, leading to the identification of a core of secreted proteins. Transcriptomic analysis using the tick Rhipicephalus microplus cuticle as an infection model during two periods of infection (48 and 144 h) allowed the identification of several differentially expressed genes. This analysis concluded that a large proportion of the predicted secretome coding genes contained altered transcript levels in the conditions analyzed in this study. In addition, some specific secreted proteins from Metarhizium have an evolutionary history similar to orthologs found in Beauveria/Cordyceps. This similarity suggests that a set of secreted proteins has evolved to participate in entomopathogenicity. The data presented represents an important step to the characterization of the role of secreted proteins in the virulence and pathogenicity of M. anisopliae.

  4. Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases.

    Science.gov (United States)

    Bauer-Mehren, Anna; Bundschus, Markus; Rautschka, Michael; Mayer, Miguel A; Sanz, Ferran; Furlong, Laura I

    2011-01-01

    Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases. The

  5. Metagenomic and network analysis reveal wide distribution and co-occurrence of environmental antibiotic resistance genes

    OpenAIRE

    Li, Bing; Yang, Ying; Ma, Liping; Ju, Feng; Guo, Feng; Tiedje, James M; Zhang, Tong

    2015-01-01

    A metagenomic approach and network analysis was used to investigate the wide-spectrum profiles of antibiotic resistance genes (ARGs) and their co-occurrence patterns in 50 samples from 10 typical environments. In total, 260 ARG subtypes belonging to 18 ARG types were detected with an abundance range of 5.4 × 10−6–2.2 × 10−1 copy of ARG per copy of 16S-rRNA gene. The trend of the total ARG abundances in environments matched well with the levels of anthropogenic impacts on these environments. F...

  6. Pan-cancer analysis of TCGA data reveals notable signaling pathways

    International Nuclear Information System (INIS)

    Neapolitan, Richard; Horvath, Curt M.; Jiang, Xia

    2015-01-01

    A signal transduction pathway (STP) is a network of intercellular information flow initiated when extracellular signaling molecules bind to cell-surface receptors. Many aberrant STPs have been associated with various cancers. To develop optimal treatments for cancer patients, it is important to discover which STPs are implicated in a cancer or cancer-subtype. The Cancer Genome Atlas (TCGA) makes available gene expression level data on cases and controls in ten different types of cancer including breast cancer, colon adenocarcinoma, glioblastoma, kidney renal papillary cell carcinoma, low grade glioma, lung adenocarcinoma, lung squamous cell carcinoma, ovarian carcinoma, rectum adenocarcinoma, and uterine corpus endometriod carcinoma. Signaling Pathway Impact Analysis (SPIA) is a software package that analyzes gene expression data to identify whether a pathway is relevant in a given condition. We present the results of a study that uses SPIA to investigate all 157 signaling pathways in the KEGG PATHWAY database. We analyzed each of the ten cancer types mentioned above separately, and we perform a pan-cancer analysis by grouping the data for all the cancer types. In each analysis several pathways were found to be markedly more significant than all the other pathways. We call them notable. Research has already established a connection between many of these pathways and the corresponding cancer type. However, some of our discovered pathways appear to be new findings. Altogether there were 37 notable findings in the separate analyses, 26 of them occurred in 7 pathways. These 7 pathways included the 4 notable pathways discovered in the pan-cancer analysis. So, our results suggest that these 7 pathways account for much of the mechanisms of cancer. Furthermore, by looking at the overlap among pathways, we identified possible regions on the pathways where the aberrant activity is occurring. We obtained 37 notable findings concerning 18 pathways. Some of them appear to be

  7. Molecular and ultrastructural analysis of forisome subunits reveals the principles of forisome assembly

    Science.gov (United States)

    Müller, Boje; Groscurth, Sira; Menzel, Matthias; Rüping, Boris A.; Twyman, Richard M.; Prüfer, Dirk; Noll, Gundula A.

    2014-01-01

    Background and Aims Forisomes are specialized structural phloem proteins that mediate sieve element occlusion after wounding exclusively in papilionoid legumes, but most studies of forisome structure and function have focused on the Old World clade rather than the early lineages. A comprehensive phylogenetic, molecular, structural and functional analysis of forisomes from species covering a broad spectrum of the papilionoid legumes was therefore carried out, including the first analysis of Dipteryx panamensis forisomes, representing the earliest branch of the Papilionoideae lineage. The aim was to study the molecular, structural and functional conservation among forisomes from different tribes and to establish the roles of individual forisome subunits. Methods Sequence analysis and bioinformatics were combined with structural and functional analysis of native forisomes and artificial forisome-like protein bodies, the latter produced by expressing forisome genes from different legumes in a heterologous background. The structure of these bodies was analysed using a combination of confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and the function of individual subunits was examined by combinatorial expression, micromanipulation and light microscopy. Key Results Dipteryx panamensis native forisomes and homomeric protein bodies assembled from the single sieve element occlusion by forisome (SEO-F) subunit identified in this species were structurally and functionally similar to forisomes from the Old World clade. In contrast, homomeric protein bodies assembled from individual SEO-F subunits from Old World species yielded artificial forisomes differing in proportion to their native counterparts, suggesting that multiple SEO-F proteins are required for forisome assembly in these plants. Structural differences between Medicago truncatula native forisomes, homomeric protein bodies and heteromeric bodies

  8. Phylogenetic analysis reveals the taxonomically diverse distribution of the Pseudomonas putida group.

    Science.gov (United States)

    Yonezuka, Kenta; Shimodaira, Jun; Tabata, Michiro; Ohji, Shoko; Hosoyama, Akira; Kasai, Daisuke; Yamazoe, Atsushi; Fujita, Nobuyuki; Ezaki, Takayuki; Fukuda, Masao

    2017-03-17

    Pseudomonas putida is well-known for degradation activities for a variety of compounds and its infections have been reported. Thus, P. putida includes both clinical and nonclinical isolates. To date, no reports have examined the phylogenetic relationship between clinical and nonclinical isolates of the P. putida group. In this study, fifty-nine strains of P. putida group containing twenty-six clinical, and thirty-three nonclinical, isolates, were subjected to phylogenetic and taxonomic analyses based on 16S rRNA gene sequences and nine housekeeping gene sequences, including argS, dnaN, dnaQ, era, gltA, gyrB, ppnK, rpoB, and rpoD, to obtain insights into the diversity of species in this group. More than 97.6% similarity was observed among the 16S rRNA gene sequences of all the strains examined, indicating that the resolution of 16S rRNA gene sequences is inadequate. Phylogenetic analysis based on the individual housekeeping genes listed above improved the resolution of the phylogenetic trees, which are different from each other. Multilocus sequence analysis (MLSA) based on the concatenated sequences of the nine genes significantly improved the resolution of the phylogenetic tree, and yielded approximately the same results as average nucleotide identity (ANI) analysis, suggesting its high reliability. ANI analysis classified the fifty-nine strains into twenty-six species containing seventeen singletons and nine strain clusters based on the 95% threshold. It also indicated the mixed distribution of clinical and nonclinical isolates in the six clusters, suggesting that the genomic difference between clinical and nonclinical isolates of the P. putida group is subtle. The P. putida type strain NBRC 14164 T is a singleton that is independently located from the P. putida strains distributed among the six clusters, suggesting that the classification of these strains and the differentiation of species in the P. putida group should be re-examined. This study greatly expands

  9. Deep sequencing analysis of the developing mouse brain reveals a novel microRNA

    OpenAIRE

    Ling, King-Hwa; Brautigan, Peter J; Hahn, Christopher N; Daish, Tasman; Rayner, John R; Cheah, Pike-See; Raison, Joy M; Piltz, Sandra; Mann, Jeffrey R; Mattiske, Deidre M; Thomas, Paul Q; Adelson, David L; Scott, Hamish S

    2011-01-01

    Abstract Background MicroRNAs (miRNAs) are small non-coding RNAs that can exert multilevel inhibition/repression at a post-transcriptional or protein synthesis level during disease or development. Characterisation of miRNAs in adult mammalian brains by deep sequencing has been reported previously. However, to date, no small RNA profiling of the developing brain has been undertaken using this method. We have performed deep sequencing and small RNA analysis of a developing (E15.5) mouse brain. ...

  10. Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw

    Science.gov (United States)

    MacKelprang, R.; Waldrop, M.P.; Deangelis, K.M.; David, M.M.; Chavarria, K.L.; Blazewicz, S.J.; Rubin, E.M.; Jansson, J.K.

    2011-01-01

    Permafrost contains an estimated 1672????????Pg carbon (C), an amount roughly equivalent to the total currently contained within land plants and the atmosphere. This reservoir of C is vulnerable to decomposition as rising global temperatures cause the permafrost to thaw. During thaw, trapped organic matter may become more accessible for microbial degradation and result in greenhouse gas emissions. Despite recent advances in the use of molecular tools to study permafrost microbial communities, their response to thaw remains unclear. Here we use deep metagenomic sequencing to determine the impact of thaw on microbial phylogenetic and functional genes, and relate these data to measurements of methane emissions. Metagenomics, the direct sequencing of DNA from the environment, allows the examination of whole biochemical pathways and associated processes, as opposed to individual pieces of the metabolic puzzle. Our metagenome analyses reveal that during transition from a frozen to a thawed state there are rapid shifts in many microbial, phylogenetic and functional gene abundances and pathways. After one week of incubation at 5 ??C, permafrost metagenomes converge to be more similar to each other than while they are frozen. We find that multiple genes involved in cycling of C and nitrogen shift rapidly during thaw. We also construct the first draft genome from a complex soil metagenome, which corresponds to a novel methanogen. Methane previously accumulated in permafrost is released during thaw and subsequently consumed by methanotrophic bacteria. Together these data point towards the importance of rapid cycling of methane and nitrogen in thawing permafrost. ?? 2011 Macmillan Publishers Limited. All rights reserved.

  11. Analysis of genome sequences from plant pathogenic Rhodococcus reveals genetic novelties in virulence loci.

    Directory of Open Access Journals (Sweden)

    Allison L Creason

    Full Text Available Members of Gram-positive Actinobacteria cause economically important diseases to plants. Within the Rhodococcus genus, some members can cause growth deformities and persist as pathogens on a wide range of host plants. The current model predicts that phytopathogenic isolates require a cluster of three loci present on a linear plasmid, with the fas operon central to virulence. The Fas proteins synthesize, modify, and activate a mixture of growth regulating cytokinins, which cause a hormonal imbalance in plants, resulting in abnormal growth. We sequenced and compared the genomes of 20 isolates of Rhodococcus to gain insights into the mechanisms and evolution of virulence in these bacteria. Horizontal gene transfer was identified as critical but limited in the scale of virulence evolution, as few loci are conserved and exclusive to phytopathogenic isolates. Although the fas operon is present in most phytopathogenic isolates, it is absent from phytopathogenic isolate A21d2. Instead, this isolate has a horizontally acquired gene chimera that encodes a novel fusion protein with isopentyltransferase and phosphoribohydrolase domains, predicted to be capable of catalyzing and activating cytokinins, respectively. Cytokinin profiling of the archetypal D188 isolate revealed only one activate cytokinin type that was specifically synthesized in a fas-dependent manner. These results suggest that only the isopentenyladenine cytokinin type is synthesized and necessary for Rhodococcus phytopathogenicity, which is not consistent with the extant model stating that a mixture of cytokinins is necessary for Rhodococcus to cause leafy gall symptoms. In all, data indicate that only four horizontally acquired functions are sufficient to confer the trait of phytopathogenicity to members of the genetically diverse clade of Rhodococcus.

  12. Genetic origin of goat populations in Oman revealed by mitochondrial DNA analysis.

    Directory of Open Access Journals (Sweden)

    Nasser Ali Al-Araimi

    Full Text Available The Sultanate of Oman has a complex mosaic of livestock species and production systems, but the genetic diversity, demographic history or origins of these Omani animals has not been expensively studied. Goats might constitute one of the most abundant and important domestic livestock species since the Neolithic transition. Here, we examined the genetic diversity, origin, population structure and demographic history of Omani goats. Specifically, we analyzed a 525-bp fragment of the first hypervariable region of the mitochondrial DNA (mtDNA control region from 69 Omani individuals and compared this fragment with 17 mtDNA sequences from Somalia and Yemen as well as 18 wild goat species and 1,198 previously published goat sequences from neighboring countries. The studied goat breeds show substantial diversity. The haplotype and nucleotide diversities of Omani goats were found equal to 0.983 ± 0.006 and 0.0284 ± 0.014, respectively. The phylogenetic analyses allowed us to classify Omani goats into three mtDNA haplogroups (A, B and G: haplogroup A was found to be predominant and widely distributed and accounted for 80% of all samples, and haplogroups B and G exhibited low frequencies. Phylogenetic comparisons with wild goats revealed that five of the native Omani goat populations originate from Capra aegagrus. Furthermore, most comparisons of pairwise population FST values within and between these five Omani goat breeds as well as between Omani goats and nine populations from nearby countries were not significant. These results suggest strong gene flow among goat populations caused by the extensive transport of goats and the frequent movements of human populations in ancient Arabia. The findings improve our understanding of the migration routes of modern goats from their region of domestication into southeastern Arabia and thereby shed light on human migratory and commercial networks during historical times.

  13. Analysis of surface protein expression reveals the growth pattern of the gram-negative outer membrane.

    Directory of Open Access Journals (Sweden)

    Tristan S Ursell

    Full Text Available The outer membrane (OM of Gram-negative bacteria is a complex bilayer composed of proteins, phospholipids, lipoproteins, and lipopolysaccharides. Despite recent advances revealing the molecular pathways underlying protein and lipopolysaccharide incorporation into the OM, the spatial distribution and dynamic regulation of these processes remain poorly understood. Here, we used sequence-specific fluorescent labeling to map the incorporation patterns of an OM-porin protein, LamB, by labeling proteins only after epitope exposure on the cell surface. Newly synthesized LamB appeared in discrete puncta, rather than evenly distributed over the cell surface. Further growth of bacteria after labeling resulted in divergence of labeled LamB puncta, consistent with a spatial pattern of OM growth in which new, unlabeled material was also inserted in patches. At the poles, puncta remained relatively stationary through several rounds of division, a salient characteristic of the OM protein population as a whole. We propose a biophysical model of growth in which patches of new OM material are added in discrete bursts that evolve in time according to Stokes flow and are randomly distributed over the cell surface. Simulations based on this model demonstrate that our experimental observations are consistent with a bursty insertion pattern without spatial bias across the cylindrical cell surface, with approximately one burst of ≈ 10(-2 µm(2 of OM material per two minutes per µm(2. Growth by insertion of discrete patches suggests that stochasticity plays a major role in patterning and material organization in the OM.

  14. Analysis on Population Level Reveals Trappability of Wild Rodents Is Determined by Previous Trap Occupant.

    Directory of Open Access Journals (Sweden)

    Marc J Brouard

    Full Text Available Live trapping is central to the study of small mammals. Thus, any bias needs to be understood and accounted for in subsequent analyses to ensure accurate population estimates. One rarely considered bias is the behavioural response of individuals to the trap, in particular the olfactory cues left behind by previous occupants (PO. We used a data set of 8,115 trap nights spanning 17 separate trapping sessions between August 2002 and November 2013 in Wytham Woods, Oxfordshire, UK to examine if the decision to enter a trap was affected by the PO, if this was detectable in traditional Capture-Mark-Recapture trapping data (i.e., individuals not uniquely marked, and if it was possible for this effect to bias the population estimates obtained. Data were collected on Apodemus sylvaticus, Myodes glareolus, and Microtus agrestis. Three Generalised Linear Models revealed a significant tendency for the three species to enter traps with same-species PO. With, for example, A. sylvaticus 9.1 times more likely to enter a same species PO trap compared to one that contained a M. agrestis in the grassland during the nocturnal period. Simulation highlighted that, when all other factors are equal, the species with the highest PO effect will have the highest capture rate and therefore return more accurate population estimates. Despite the large dataset, certain species-, sex-, and/ or age-combinations were under-represented, and thus no effects of any additional individual-specific characteristics could be evaluated. Uniquely marking individuals would allow for the PO effect to be disentangled from other biases such as trap-shyness and spatial heterogeneity, but may not be possible in all cases and will depend on the aims of the study and the resources available.

  15. Subtractive transcriptome analysis of leaf and rhizome reveals differentially expressed transcripts in Panax sokpayensis.

    Science.gov (United States)

    Gurung, Bhusan; Bhardwaj, Pardeep K; Talukdar, Narayan C

    2016-11-01

    In the present study, suppression subtractive hybridization (SSH) strategy was used to identify rare and differentially expressed transcripts in leaf and rhizome tissues of Panax sokpayensis. Out of 1102 randomly picked clones, 513 and 374 high quality expressed sequenced tags (ESTs) were generated from leaf and rhizome subtractive libraries, respectively. Out of them, 64.92 % ESTs from leaf and 69.26 % ESTs from rhizome SSH libraries were assembled into different functional categories, while others were of unknown function. In particular, ESTs encoding galactinol synthase 2, ribosomal RNA processing Brix domain protein, and cell division cycle protein 20.1, which are involved in plant growth and development, were most abundant in the leaf SSH library. Other ESTs encoding protein KIAA0664 homologue, ubiquitin-activating enzyme e11, and major latex protein, which are involved in plant immunity and defense response, were most abundant in the rhizome SSH library. Subtractive ESTs also showed similarity with genes involved in ginsenoside biosynthetic pathway, namely farnesyl pyrophosphate synthase, squalene synthase, and dammarenediol synthase. Expression profiles of selected ESTs validated the quality of libraries and confirmed their differential expression in the leaf, stem, and rhizome tissues. In silico comparative analyses revealed that around 13.75 % of unigenes from the leaf SSH library were not represented in the available leaf transcriptome of Panax ginseng. Similarly, around 18.12, 23.75, 25, and 6.25 % of unigenes from the rhizome SSH library were not represented in available root/rhizome transcriptomes of P. ginseng, Panax notoginseng, Panax quinquefolius, and Panax vietnamensis, respectively, indicating a major fraction of novel ESTs. Therefore, these subtractive transcriptomes provide valuable resources for gene discovery in P. sokpayensis and would complement the available transcriptomes from other Panax species.

  16. Comparative genome analysis reveals a conserved family of actin-like proteins in apicomplexan parasites

    Directory of Open Access Journals (Sweden)

    Sibley L David

    2005-12-01

    Full Text Available Abstract Background The phylum Apicomplexa is an early-branching eukaryotic lineage that contains a number of important human and animal pathogens. Their complex life cycles and unique cytoskeletal features distinguish them from other model eukaryotes. Apicomplexans rely on actin-based motility for cell invasion, yet the regulation of this system remains largely unknown. Consequently, we focused our efforts on identifying actin-related proteins in the recently completed genomes of Toxoplasma gondii, Plasmodium spp., Cryptosporidium spp., and Theileria spp. Results Comparative genomic and phylogenetic studies of apicomplexan genomes reveals that most contain only a single conventional actin and yet they each have 8–10 additional actin-related proteins. Among these are a highly conserved Arp1 protein (likely part of a conserved dynactin complex, and Arp4 and Arp6 homologues (subunits of the chromatin-remodeling machinery. In contrast, apicomplexans lack canonical Arp2 or Arp3 proteins, suggesting they lost the Arp2/3 actin polymerization complex on their evolutionary path towards intracellular parasitism. Seven of these actin-like proteins (ALPs are novel to apicomplexans. They show no phylogenetic associations to the known Arp groups and likely serve functions specific to this important group of intracellular parasites. Conclusion The large diversity of actin-like proteins in apicomplexans suggests that the actin protein family has diverged to fulfill various roles in the unique biology of intracellular parasites. Conserved Arps likely participate in vesicular transport and gene expression, while apicomplexan-specific ALPs may control unique biological traits such as actin-based gliding motility.

  17. Bioinformatic Analysis Reveals Archaeal tRNATyr and tRNATrp Identities in Bacteria

    Directory of Open Access Journals (Sweden)

    Takahito Mukai

    2017-02-01

    Full Text Available The tRNA identity elements for some amino acids are distinct between the bacterial and archaeal domains. Searching in recent genomic and metagenomic sequence data, we found some candidate phyla radiation (CPR bacteria with archaeal tRNA identity for Tyr-tRNA and Trp-tRNA synthesis. These bacteria possess genes for tyrosyl-tRNA synthetase (TyrRS and tryptophanyl-tRNA synthetase (TrpRS predicted to be derived from DPANN superphylum archaea, while the cognate tRNATyr and tRNATrp genes reveal bacterial or archaeal origins. We identified a trace of domain fusion and swapping in the archaeal-type TyrRS gene of a bacterial lineage, suggesting that CPR bacteria may have used this mechanism to create diverse proteins. Archaeal-type TrpRS of bacteria and a few TrpRS species of DPANN archaea represent a new phylogenetic clade (named TrpRS-A. The TrpRS-A open reading frames (ORFs are always associated with another ORF (named ORF1 encoding an unknown protein without global sequence identity to any known protein. However, our protein structure prediction identified a putative HIGH-motif and KMSKS-motif as well as many α-helices that are characteristic of class I aminoacyl-tRNA synthetase (aaRS homologs. These results provide another example of the diversity of molecular components that implement the genetic code and provide a clue to the early evolution of life and the genetic code.

  18. Analysis of genome sequences from plant pathogenic Rhodococcus reveals genetic novelties in virulence loci.

    Science.gov (United States)

    Creason, Allison L; Vandeputte, Olivier M; Savory, Elizabeth A; Davis, Edward W; Putnam, Melodie L; Hu, Erdong; Swader-Hines, David; Mol, Adeline; Baucher, Marie; Prinsen, Els; Zdanowska, Magdalena; Givan, Scott A; El Jaziri, Mondher; Loper, Joyce E; Mahmud, Taifo; Chang, Jeff H

    2014-01-01

    Members of Gram-positive Actinobacteria cause economically important diseases to plants. Within the Rhodococcus genus, some members can cause growth deformities and persist as pathogens on a wide range of host plants. The current model predicts that phytopathogenic isolates require a cluster of three loci present on a linear plasmid, with the fas operon central to virulence. The Fas proteins synthesize, modify, and activate a mixture of growth regulating cytokinins, which cause a hormonal imbalance in plants, resulting in abnormal growth. We sequenced and compared the genomes of 20 isolates of Rhodococcus to gain insights into the mechanisms and evolution of virulence in these bacteria. Horizontal gene transfer was identified as critical but limited in the scale of virulence evolution, as few loci are conserved and exclusive to phytopathogenic isolates. Although the fas operon is present in most phytopathogenic isolates, it is absent from phytopathogenic isolate A21d2. Instead, this isolate has a horizontally acquired gene chimera that encodes a novel fusion protein with isopentyltransferase and phosphoribohydrolase domains, predicted to be capable of catalyzing and activating cytokinins, respectively. Cytokinin profiling of the archetypal D188 isolate revealed only one activate cytokinin type that was specifically synthesized in a fas-dependent manner. These results suggest that only the isopentenyladenine cytokinin type is synthesized and necessary for Rhodococcus phytopathogenicity, which is not consistent with the extant model stating that a mixture of cytokinins is necessary for Rhodococcus to cause leafy gall symptoms. In all, data indicate that only four horizontally acquired functions are sufficient to confer the trait of phytopathogenicity to members of the genetically diverse clade of Rhodococcus.

  19. Toxicogenomic analysis reveals profibrogenic effects of trichloroethylene in autoimmune-mediated cholangitis in mice.

    Science.gov (United States)

    Kopec, Anna K; Sullivan, Bradley P; Kassel, Karen M; Joshi, Nikita; Luyendyk, James P

    2014-10-01

    Epidemiological studies suggest that exposure to environmental chemicals increases the risk of developing autoimmune liver disease. However, the identity of specific chemical perpetrators and the mechanisms whereby environmental chemicals modify liver disease is unclear. Previous studies link exposure to trichloroethylene (TCE) with the development of autoimmune liver disease and exacerbation of autoimmunity in lupus-prone MRL mice. In this study, we utilized NOD.c3c4 mice, which spontaneously develop autoimmune cholangitis bearing resemblance to some features of primary biliary cirrhosis. Nine-week-old female NOD.c3c4 mice were given TCE (0.5 mg/ml) or its vehicle (1% Cremophor-EL) in drinking water for 4 weeks. TCE had little effect on clinical chemistry, biliary cyst formation, or hepatic CD3+ T-cell accumulation. Hepatic microarray profiling revealed a dramatic suppression of early growth response 1 (EGR1) mRNA in livers of TCE-treated mice, which was verified by qPCR and immunohistochemical staining. Consistent with a reported link between reduced EGR1 expression and liver fibrosis, TCE increased hepatic type I collagen (COL1A1) mRNA and protein levels in livers of NOD.c3c4 mice. In contrast, TCE did not increase COL1A1 expression in NOD.ShiLtJ mice, which do not develop autoimmune cholangitis. These results suggest that in the context of concurrent autoimmune liver disease with a genetic basis, modification of hepatic gene expression by TCE may increase profibrogenic signaling in the liver. Moreover, these studies suggest that NOD.c3c4 mice may be a novel model to study gene-environment interactions critical for the development of autoimmune liver disease. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Network analysis reveals contrasting effects of intraspecific competition on individual vs. population diets.

    Science.gov (United States)

    Araújo, Márcio S; Guimarães, Paulo R; Svanbäck, Richard; Pinheiro, Aluisio; Guimarães, Paulo; Dos Reis, Sérgio F; Bolnick, Daniel I

    2008-07-01

    Optimal foraging theory predicts that individuals should become more opportunistic when intraspecific competition is high and preferred resources are scarce. This density-dependent diet shift should result in increased diet breadth for individuals as they add previously unused prey to their repertoire. As a result, the niche breadth of the population as a whole should increase. In a recent study, R. Svanbäck and D. I. Bolnick confirmed that intraspecific competition led to increased population diet breadth in threespine stickleback (Gasterosteus aculeatus). However, individual diet breadth did not expand as resource levels declined. Here, we present a new method based on complex network theory that moves beyond a simple measure of diet breadth, and we use the method to reexamine the stickleback experiment. This method reveals that the population as a whole added new types of prey as stickleback density was increased. However, whereas foraging theory predicts that niche expansion is achieved by individuals accepting new prey in addition to previously preferred prey, we found that a subset of individuals ceased to use their previously preferred prey, even though other members of their population continued to specialize on the original prey types. As a result, populations were subdivided into groups of ecologically similar individuals, with diet variation among groups reflecting phenotype-dependent changes in foraging behavior as prey density declined. These results are consistent with foraging theory if we assume that quantitative trait variation among consumers affects prey preferences, and if cognitive constraints prevent individuals from continuing to use their formerly preferred prey while adding new prey.

  1. Genome-wide analysis reveals novel genes essential for heme homeostasis in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Scott Severance

    2010-07-01

    Full Text Available Heme is a cofactor in proteins that function in almost all sub-cellular compartments and in many diverse biological processes. Heme is produced by a conserved biosynthetic pathway that is highly regulated to prevent the accumulation of heme--a cytotoxic, hydrophobic tetrapyrrole. Caenorhabditis elegans and related parasitic nematodes do not synthesize heme, but instead require environmental heme to grow and develop. Heme homeostasis in these auxotrophs is, therefore, regulated in accordance with available dietary heme. We have capitalized on this auxotrophy in C. elegans to study gene expression changes associated with precisely controlled dietary heme concentrations. RNA was isolated from cultures containing 4, 20, or 500 microM heme; derived cDNA probes were hybridized to Affymetrix C. elegans expression arrays. We identified 288 heme-responsive genes (hrgs that were differentially expressed under these conditions. Of these genes, 42% had putative homologs in humans, while genomes of medically relevant heme auxotrophs revealed homologs for 12% in both Trypanosoma and Leishmania and 24% in parasitic nematodes. Depletion of each of the 288 hrgs by RNA-mediated interference (RNAi in a transgenic heme-sensor worm strain identified six genes that regulated heme homeostasis. In addition, seven membrane-spanning transporters involved in heme uptake were identified by RNAi knockdown studies using a toxic heme analog. Comparison of genes that were positive in both of the RNAi screens resulted in the identification of three genes in common that were vital for organismal heme homeostasis in C. elegans. Collectively, our results provide a catalog of genes that are essential for metazoan heme homeostasis and demonstrate the power of C. elegans as a genetic animal model to dissect the regulatory circuits which mediate heme trafficking in both vertebrate hosts and their parasites, which depend on environmental heme for survival.

  2. Quantitative Genetic Analysis Reveals Potential to Genetically Improve Fruit Yield and Drought Resistance Simultaneously in Coriander.

    Science.gov (United States)

    Khodadadi, Mostafa; Dehghani, Hamid; Jalali Javaran, Mokhtar

    2017-01-01

    Enhancing water use efficiency of coriander ( Coriandrum sativum L.) is a major focus for coriander breeding to cope with drought stress. The purpose of this study was; (a) to identify the predominant mechanism(s) of drought resistance in coriander and (b) to evaluate the genetic control mechanism(s) of traits associated with drought resistance and higher fruit yield. To reach this purpose, 15 half-diallel hybrids of coriander and their six parents were evaluated under well-watered and water deficit stressed (WDS) in both glasshouse lysimetric and field conditions. The parents were selected for their different response to water deficit stress following preliminary experiments. Results revealed that the genetic control mechanism of fruit yield is complex, variable and highly affected by environment. The mode of inheritance and nature of gene action for percent assimilate partitioned to fruits were similar to those for flowering time in both well-watered and WDS conditions. A significant negative genetic linkage was found between fruit yield and percent assimilate partitioned to root, percent assimilate partitioned to shoot, root number, root diameter, root dry mass, root volume, and early flowering. Thus, to improve fruit yield under water deficit stress, selection of low values of these traits could be used. In contrast, a significant positive genetic linkage between fruit yield and percent assimilate partitioned to fruits, leaf relative water content and chlorophyll content indicate selection for high values of these traits. These secondary or surrogate traits could be selected during early segregating generations. The early ripening parent (P 1 ; TN-59-230) contained effective genes involved in preferred percent assimilate partitioning to fruit and drought stress resistance. In conclusion, genetic improvement of fruit yield and drought resistance could be simultaneously gained in coriander when breeding for drought resistance.

  3. Fine Mapping and Transcriptome Analysis Reveal Candidate Genes Associated with Hybrid Lethality in Cabbage (Brassica Oleracea).

    Science.gov (United States)

    Xiao, Zhiliang; Hu, Yang; Zhang, Xiaoli; Xue, Yuqian; Fang, Zhiyuan; Yang, Limei; Zhang, Yangyong; Liu, Yumei; Li, Zhansheng; Liu, Xing; Liu, Zezhou; Lv, Honghao; Zhuang, Mu

    2017-06-05

    Hybrid lethality is a deleterious phenotype that is vital to species evolution. We previously reported hybrid lethality in cabbage ( Brassica oleracea ) and performed preliminary mapping of related genes. In the present study, the fine mapping of hybrid lethal genes revealed that BoHL1 was located on chromosome C1 between BoHLTO124 and BoHLTO130, with an interval of 101 kb. BoHL2 was confirmed to be between insertion-deletion (InDels) markers HL234 and HL235 on C4, with a marker interval of 70 kb. Twenty-eight and nine annotated genes were found within the two intervals of BoHL1 and BoHL2 , respectively. We also applied RNA-Seq to analyze hybrid lethality in cabbage. In the region of BoHL1 , seven differentially expressed genes (DEGs) and five resistance (R)-related genes (two in common, i.e., Bo1g153320 and Bo1g153380 ) were found, whereas in the region of BoHL2 , two DEGs and four R-related genes (two in common, i.e., Bo4g173780 and Bo4g173810 ) were found. Along with studies in which R genes were frequently involved in hybrid lethality in other plants, these interesting R-DEGs may be good candidates associated with hybrid lethality. We also used SNP/InDel analyses and quantitative real-time PCR to confirm the results. This work provides new insight into the mechanisms of hybrid lethality in cabbage.

  4. Quantitative X-ray Diffraction (QXRD) analysis for revealing thermal transformations of red mud.

    Science.gov (United States)

    Liao, Chang-Zhong; Zeng, Lingmin; Shih, Kaimin

    2015-07-01

    Red mud is a worldwide environmental problem, and many authorities are trying to find an economic solution for its beneficial application or/and safe disposal. Ceramic production is one of the potential waste-to-resource strategies for using red mud as a raw material. Before implementing such a strategy, an unambiguous understanding of the reaction behavior of red mud under thermal conditions is essential. In this study, the phase compositions and transformation processes were revealed for the Pingguo red mud (PRM) heat-treated at different sintering temperatures. Hematite, perovskite, andradite, cancrinite, kaolinite, diaspore, gibbsite and calcite phases were observed in the samples. However, unlike those red mud samples from the other regions, no TiO2 (rutile or anatase) or quartz were observed. Titanium was found to exist mainly in perovskite and andradite while the iron mainly existed in hematite and andradite. A new silico-ferrite of calcium and aluminum (SFCA) phase was found in samples treated at temperatures above 1100°C, and two possible formation pathways for SFCA were suggested. This is the first SFCA phase to be reported in thermally treated red mud, and this finding may turn PRM waste into a material resource for the iron-making industry. Titanium was found to be enriched in the perovskite phase after 1200°C thermal treatment, and this observation indicated a potential strategy for the recovery of titanium from PRM. In addition to noting these various resource recovery opportunities, this is also the first study to quantitatively summarize the reaction details of PRM phase transformations at various temperatures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Crystallization of Probucol in Nanoparticles Revealed by AFM Analysis in Aqueous Solution.

    Science.gov (United States)

    Egami, Kiichi; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2015-08-03

    The crystallization behavior of a pharmaceutical drug in nanoparticles was directly evaluated by atomic force microscopy (AFM) force curve measurements in aqueous solution. A ternary spray-dried sample (SPD) was prepared by spray drying the organic solvent containing probucol (PBC), hypromellose (HPMC), and sodium dodecyl sulfate (SDS). The amorphization of PBC in the ternary SPD was confirmed by powder X-ray diffraction (PXRD) and solid-state 13C NMR measurements. A nanosuspension containing quite small particles of 25 nm in size was successfully prepared immediately after dispersion of the ternary SPD into water. Furthermore, solution-state 1H NMR measurements revealed that a portion of HPMC coexisted with PBC as a mixed state in the freshly prepared nanosuspension particles. After storing the nanosuspension at 25 °C, a gradual increase in the size of the nanoparticles was observed, and the particle size changed to 93.9 nm after 7 days. AFM enabled the direct observation of the morphology and agglomeration behavior of the nanoparticles in water. Moreover, AFM force-distance curves were changed from (I) to (IV), depending on the storage period, as follows: (I) complete indentation within an applied force of 1 nN, (II) complete indentation with an applied force of 1-5 nN, (III) partial indentation with an applied force of 5 nN, and (IV) nearly no indentation with an applied force of 5 nN. This stiffness increase of the nanoparticles was attributed to gradual changes in the molecular state of PBC from the amorphous to the crystal state. Solid-state 13C NMR measurements of the freeze-dried samples demonstrated the presence of metastable PBC Form II crystals in the stored nanosuspension, strongly supporting the AFM results.

  6. Genomic Analysis of the Basal Lineage Fungus Rhizopus oryzae Reveals a Whole-Genome Duplication

    Science.gov (United States)

    Ma, Li-Jun; Ibrahim, Ashraf S.; Skory, Christopher; Grabherr, Manfred G.; Burger, Gertraud; Butler, Margi; Elias, Marek; Idnurm, Alexander; Lang, B. Franz; Sone, Teruo; Abe, Ayumi; Calvo, Sarah E.; Corrochano, Luis M.; Engels, Reinhard; Fu, Jianmin; Hansberg, Wilhelm; Kim, Jung-Mi; Kodira, Chinnappa D.; Koehrsen, Michael J.; Liu, Bo; Miranda-Saavedra, Diego; O'Leary, Sinead; Ortiz-Castellanos, Lucila; Poulter, Russell; Rodriguez-Romero, Julio; Ruiz-Herrera, José; Shen, Yao-Qing; Zeng, Qiandong; Galagan, James; Birren, Bruce W.

    2009-01-01

    Rhizopus oryzae is the primary cause of mucormycosis, an emerging, life-threatening infection characterized by rapid angioinvasive growth with an overall mortality rate that exceeds 50%. As a representative of the paraphyletic basal group of the fungal kingdom called “zygomycetes,” R. oryzae is also used as a model to study fungal evolution. Here we report the genome sequence of R. oryzae strain 99–880, isolated from a fatal case of mucormycosis. The highly repetitive 45.3 Mb genome assembly contains abundant transposable elements (TEs), comprising approximately 20% of the genome. We predicted 13,895 protein-coding genes not overlapping TEs, many of which are paralogous gene pairs. The order and genomic arrangement of the duplicated gene pairs and their common phylogenetic origin provide evidence for an ancestral whole-genome duplication (WGD) event. The WGD resulted in the duplication of nearly all subunits of the protein complexes associated with respiratory electron transport chains, the V-ATPase, and the ubiquitin–proteasome systems. The WGD, together with recent gene duplications, resulted in the expansion of multiple gene families related to cell growth and signal transduction, as well as secreted aspartic protease and subtilase protein families, which are known fungal virulence factors. The duplication of the ergosterol biosynthetic pathway, especially the major azole target, lanosterol 14α-demethylase (ERG11), could contribute to the variable responses of R. oryzae to different azole drugs, including voriconazole and posaconazole. Expanded families of cell-wall synthesis enzymes, essential for fungal cell integrity but absent in mammalian hosts, reveal potential targets for novel and R. oryzae-specific diagnostic and therapeutic treatments. PMID:19578406

  7. Rangewide genetic analysis of Lesser Prairie-Chicken reveals population structure, range expansion, and possible introgression

    Science.gov (United States)

    Oyler-McCance, Sara J.; DeYoung, Randall W; Fike, Jennifer; Hagen, Christian A.; Johnson, Jeff A.; Larsson, Lena C.; Patten, Michael

    2016-01-01

    The distribution of the Lesser Prairie-Chicken (Tympanuchus pallidicinctus) has been markedly reduced due to loss and fragmentation of habitat. Portions of the historical range, however, have been recolonized and even expanded due to planting of conservation reserve program (CRP) fields that provide favorable vegetation structure for Lesser Prairie-Chickens. The source population(s) feeding the range expansion is unknown, yet has resulted in overlap between Lesser and Greater Prairie-Chickens (T. cupido) increasing the potential for hybridization. Our objectives were to characterize connectivity and genetic diversity among populations, identify source population(s) of recent range expansion, and examine hybridization with the Greater Prairie-Chicken. We analyzed 640 samples from across the range using 13 microsatellites. We identified three to four populations corresponding largely to ecoregions. The Shinnery Oak Prairie and Sand Sagebrush Prairie represented genetically distinct populations (F ST > 0.034 and F ST > 0.023 respectively). The Shortgrass/CRP Mosaic and Mixed Grass ecoregions appeared admixed (F ST = 0.009). Genetic diversity was similar among ecoregions and N e ranged from 142 (95 % CI 99–236) for the Shortgrass/CRP Mosaic to 296 (95 % CI 233–396) in the Mixed Grass Prairie. No recent migration was detected among ecoregions, except asymmetric dispersal from both the Mixed Grass Prairie and to a lesser extent the Sand Sagebrush Prairie north into adjacent Shortgrass/CRP Mosaic (m = 0.207, 95 % CI 0.116–0.298, m = 0.097, 95 % CI 0.010–0.183, respectively). Indices investigating potential hybridization in the Shortgrass/CRP Mosaic revealed that six of the 13 individuals with hybrid phenotypes were significantly admixed suggesting hybridization. Continued monitoring of diversity within and among ecoregions is warranted as are actions promoting genetic connectivity and range expansion.

  8. Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome

    Science.gov (United States)

    Pride, David T; Salzman, Julia; Haynes, Matthew; Rohwer, Forest; Davis-Long, Clara; White, Richard A; Loomer, Peter; Armitage, Gary C; Relman, David A

    2012-01-01

    Viruses are the most abundant known infectious agents on the planet and are significant drivers of diversity in a variety of ecosystems. Although there have been numerous studies of viral communities, few have focused on viruses within the indigenous human microbiota. We analyzed 2 267 695 virome reads from viral particles and compared them with 263 516 bacterial 16S rRNA gene sequences from the saliva of five healthy human subjects over a 2- to 3-month period, in order to improve our understanding of the role viruses have in the complex oral ecosystem. Our data reveal viral communities in human saliva dominated by bacteriophages whose constituents are temporally distinct. The preponderance of shared homologs between the salivary viral communities in two unrelated subjects in the same household suggests that environmental factors are determinants of community membership. When comparing salivary viromes to those from human stool and the respiratory tract, each group was distinct, further indicating that habitat is of substantial importance in shaping human viromes. Compared with coexisting bacteria, there was concordance among certain predicted host–virus pairings such as Veillonella and Streptococcus, whereas there was discordance among others such as Actinomyces. We identified 122 728 virulence factor homologs, suggesting that salivary viruses may serve as reservoirs for pathogenic gene function in the oral environment. That the vast majority of human oral viruses are bacteriophages whose putative gene function signifies some have a prominent role in lysogeny, suggests these viruses may have an important role in helping shape the microbial diversity in the human oral cavity. PMID:22158393

  9. Dominating clasp of the financial sector revealed by partial correlation analysis of the stock market.

    Science.gov (United States)

    Kenett, Dror Y; Tumminello, Michele; Madi, Asaf; Gur-Gershgoren, Gitit; Mantegna, Rosario N; Ben-Jacob, Eshel

    2010-12-20

    What are the dominant stocks which drive the correlations present among stocks traded in a stock market? Can a correlation analysis provide an answer to this question? In the past, correlation based networks have been proposed as a tool to uncover the underlying backbone of the market. Correlation based networks represent the stocks and their relationships, which are then investigated using different network theory methodologies. Here we introduce a new concept to tackle the above question--the partial correlation network. Partial correlation is a measure of how the correlation between two variables, e.g., stock returns, is affected by a third variable. By using it we define a proxy of stock influence, which is then used to construct partial correlation networks. The empirical part of this study is performed on a specific financial system, namely the set of 300 highly capitalized stocks traded at the New York Stock Exchange, in the time period 2001-2003. By constructing the partial correlation network, unlike the case of standard correlation based networks, we find that stocks belonging to the financial sector and, in particular, to the investment services sub-sector, are the most influential stocks affecting the correlation profile of the system. Using a moving window analysis, we find that the strong influence of the financial stocks is conserved across time for the investigated trading period. Our findings shed a new light on the underlying mechanisms and driving forces controlling the correlation profile observed in a financial market.

  10. Eating or meeting? Cluster analysis reveals intricacies of white shark (Carcharodon carcharias migration and offshore behavior.

    Directory of Open Access Journals (Sweden)

    Salvador J Jorgensen

    Full Text Available Elucidating how mobile ocean predators utilize the pelagic environment is vital to understanding the dynamics of oceanic species and ecosystems. Pop-up archival transmitting (PAT tags have emerged as an important tool to describe animal migrations in oceanic environments where direct observation is not feasible. Available PAT tag data, however, are for the most part limited to geographic position, swimming depth and environmental temperature, making effective behavioral observation challenging. However, novel analysis approaches have the potential to extend the interpretive power of these limited observations. Here we developed an approach based on clustering analysis of PAT daily time-at-depth histogram records to distinguish behavioral modes in white sharks (Carcharodon carcharias. We found four dominant and distinctive behavioral clusters matching previously described behavioral patterns, including two distinctive offshore diving modes. Once validated, we mapped behavior mode occurrence in space and time. Our results demonstrate spatial, temporal and sex-based structure in the diving behavior of white sharks in the northeastern Pacific previously unrecognized including behavioral and migratory patterns resembling those of species with lek mating systems. We discuss our findings, in combination with available life history and environmental data, and propose specific testable hypotheses to distinguish between mating and foraging in northeastern Pacific white sharks that can provide a framework for future work. Our methodology can be applied to similar datasets from other species to further define behaviors during unobservable phases.

  11. Relationships between some Thai cultivars of pineapple (Ananas comosus revealed by RAPD analysis

    Directory of Open Access Journals (Sweden)

    Siam Popluechai

    2007-11-01

    Full Text Available RAPD analysis of nine Thai pineapple cultivars, including 'Phulae', 'Sawee', 'Tradsithong', 'Phuket', 'Pattavia', 'Intrachitdang', 'Intrachitkhow', 'Petburi No.1', and 'Nanglae', showed that, of 40 arbitrary 10- mer primers, 17 primers gave 206 DNA fragments ranging from 510 to 4,700 bp. One hundred and forty-five (70.4% of the amplified fragments were polymorphic. RAPD analysis using NTSYS-pc Version 2.01e also showed that the similarity coefficients among the cultivars were 0.643-0. 963. The dendrogram indicated that the cultivars were clustered into 3 groups, consistent with the morphological data. The first group, consisting of 'Phuket', 'Phulae', 'Tradsithong', 'Sawee', and 'Petburi No.1', had morphological characteristics of the Queen group, while those of the second ('Intrachitdang' and 'Intrachitkow' and the third ('Nanglae' and 'Pattavia' groups could be determined morphologically to be members of the Spanish and Cayenne groups, respectively. 'Intrachitdang' and 'Intrachitkow' have similarity coefficient of 0.963, while that of 'Phulae' and 'Phuket' is 0.950. These pairs of cultivars are probably the same cultivars. The morphological differences between them are probably caused by mutations, differences in environment and agricultural practices, or combinations of these factors.

  12. Muscle contraction phenotypic analysis enabled by optogenetics reveals functional relationships of sarcomere components in Caenorhabditis elegans

    Science.gov (United States)

    Hwang, Hyundoo; Barnes, Dawn E.; Matsunaga, Yohei; Benian, Guy M.; Ono, Shoichiro; Lu, Hang

    2016-01-01

    The sarcomere, the fundamental unit of muscle contraction, is a highly-ordered complex of hundreds of proteins. Despite decades of genetics work, the functional relationships and the roles of those sarcomeric proteins in animal behaviors remain unclear. In this paper, we demonstrate that optogenetic activation of the motor neurons that induce muscle contraction can facilitate quantitative studies of muscle kinetics in C. elegans. To increase the throughput of the study, we trapped multiple worms in parallel in a microfluidic device and illuminated for photoactivation of channelrhodopsin-2 to induce contractions in body wall muscles. Using image processing, the change in body size was quantified over time. A total of five parameters including rate constants for contraction and relaxation were extracted from the optogenetic assay as descriptors of sarcomere functions. To potentially relate the genes encoding the sarcomeric proteins functionally, a hierarchical clustering analysis was conducted on the basis of those parameters. Because it assesses physiological output different from conventional assays, this method provides a complement to the phenotypic analysis of C. elegans muscle mutants currently performed in many labs; the clusters may provide new insights and drive new hypotheses for functional relationships among the many sarcomere components.

  13. Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data

    Directory of Open Access Journals (Sweden)

    Biecek Przemysław

    2011-06-01

    Full Text Available Abstract Background Deregulation between two different cell populations manifests itself in changing gene expression patterns and changing regulatory interactions. Accumulating knowledge about biological networks creates an opportunity to study these changes in their cellular context. Results We analyze re-wiring of regulatory networks based on cell population-specific perturbation data and knowledge about signaling pathways and their target genes. We quantify deregulation by merging regulatory signal from the two cell populations into one score. This joint approach, called JODA, proves advantageous over separate analysis of the cell populations and analysis without incorporation of knowledge. JODA is implemented and freely available in a Bioconductor package 'joda'. Conclusions Using JODA, we show wide-spread re-wiring of gene regulatory networks upon neocarzinostatin-induced DNA damage in Human cells. We recover 645 deregulated genes in thirteen functional clusters performing the rich program of response to damage. We find that the clusters contain many previously characterized neocarzinostatin target genes. We investigate connectivity between those genes, explaining their cooperation in performing the common functions. We review genes with the most extreme deregulation scores, reporting their involvement in response to DNA damage. Finally, we investigate the indirect impact of the ATM pathway on the deregulated genes, and build a hypothetical hierarchy of direct regulation. These results prove that JODA is a step forward to a systems level, mechanistic understanding of changes in gene regulation between different cell populations.

  14. Bayesian change-point analysis reveals developmental change in a classic theory of mind task.

    Science.gov (United States)

    Baker, Sara T; Leslie, Alan M; Gallistel, C R; Hood, Bruce M

    2016-12-01

    Although learning and development reflect changes situated in an individual brain, most discussions of behavioral change are based on the evidence of group averages. Our reliance on group-averaged data creates a dilemma. On the one hand, we need to use traditional inferential statistics. On the other hand, group averages are highly ambiguous when we need to understand change in the individual; the average pattern of change may characterize all, some, or none of the individuals in the group. Here we present a new method for statistically characterizing developmental change in each individual child we study. Using false-belief tasks, fifty-two children in two cohorts were repeatedly tested for varying lengths of time between 3 and 5 years of age. Using a novel Bayesian change point analysis, we determined both the presence and-just as importantly-the absence of change in individual longitudinal cumulative records. Whenever the analysis supports a change conclusion, it identifies in that child's record the most likely point at which change occurred. Results show striking variability in patterns of change and stability across individual children. We then group the individuals by their various patterns of change or no change. The resulting patterns provide scarce support for sudden changes in competence and shed new light on the concepts of "passing" and "failing" in developmental studies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Time-series metagenomic analysis reveals robustness of soil microbiome against chemical disturbance

    Science.gov (United States)

    Kato, Hiromi; Mori, Hiroshi; Maruyama, Fumito; Toyoda, Atsushi; Oshima, Kenshiro; Endo, Ryo; Fuchu, Genki; Miyakoshi, Masatoshi; Dozono, Ayumi; Ohtsubo, Yoshiyuki; Nagata, Yuji; Hattori, Masahira; Fujiyama, Asao; Kurokawa, Ken; Tsuda, Masataka

    2015-01-01

    Soil microbial communities have great potential for bioremediation of recalcitrant aromatic compounds. However, it is unclear which taxa and genes in the communities, and how they contribute to the bioremediation in the polluted soils. To get clues about this funda