WorldWideScience

Sample records for complex traits insights

  1. Local Genetic Correlation Gives Insights into the Shared Genetic Architecture of Complex Traits.

    Science.gov (United States)

    Shi, Huwenbo; Mancuso, Nicholas; Spendlove, Sarah; Pasaniuc, Bogdan

    2017-11-02

    Although genetic correlations between complex traits provide valuable insights into epidemiological and etiological studies, a precise quantification of which genomic regions disproportionately contribute to the genome-wide correlation is currently lacking. Here, we introduce ρ-HESS, a technique to quantify the correlation between pairs of traits due to genetic variation at a small region in the genome. Our approach requires GWAS summary data only and makes no distributional assumption on the causal variant effect sizes while accounting for linkage disequilibrium (LD) and overlapping GWAS samples. We analyzed large-scale GWAS summary data across 36 quantitative traits, and identified 25 genomic regions that contribute significantly to the genetic correlation among these traits. Notably, we find 6 genomic regions that contribute to the genetic correlation of 10 pairs of traits that show negligible genome-wide correlation, further showcasing the power of local genetic correlation analyses. Finally, we report the distribution of local genetic correlations across the genome for 55 pairs of traits that show putative causal relationships. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  2. Hormones and the Evolution of Complex Traits: Insights from Artificial Selection on Behavior.

    Science.gov (United States)

    Garland, Theodore; Zhao, Meng; Saltzman, Wendy

    2016-08-01

    Although behavior may often be a fairly direct target of natural or sexual selection, it cannot evolve without changes in subordinate traits that cause or permit its expression. In principle, changes in endocrine function could be a common mechanism underlying behavioral evolution because they are well positioned to mediate integrated responses to behavioral selection. More specifically, hormones can influence both motivational (e.g., brain) and performance (e.g., muscles) components of behavior simultaneously and in a coordinated fashion. If the endocrine system is often "used" as a general mechanism to effect responses to selection, then correlated responses in other aspects of behavior, life history, and organismal performance (e.g., locomotor abilities) should commonly occur because any cell with appropriate receptors could be affected. Ways in which behavior coadapts with other aspects of the phenotype can be studied directly through artificial selection and experimental evolution. Several studies have targeted rodent behavior for selective breeding and reported changes in other aspects of behavior, life history, and lower-level effectors of these organismal traits, including endocrine function. One example involves selection for high levels of voluntary wheel running, one aspect of physical activity, in four replicate High Runner (HR) lines of mice. Circulating levels of several hormones (including insulin, testosterone, thyroxine, triiodothyronine) have been characterized, three of which-corticosterone, leptin, and adiponectin-differ between HR and control lines, depending on sex, age, and generation. Potential changes in circulating levels of other behaviorally and metabolically relevant hormones, as well as in other components of the endocrine system (e.g., receptors), have yet to be examined. Overall, results to date identify promising avenues for further studies on the endocrine basis of activity levels. © The Author 2016. Published by Oxford University

  3. Structural insight of dopamine β-hydroxylase, a drug target for complex traits, and functional significance of exonic single nucleotide polymorphisms.

    Directory of Open Access Journals (Sweden)

    Abhijeet Kapoor

    Full Text Available Human dopamine β-hydroxylase (DBH is an important therapeutic target for complex traits. Several single nucleotide polymorphisms (SNPs have also been identified in DBH with potential adverse physiological effect. However, difficulty in obtaining diffractable crystals and lack of a suitable template for modeling the protein has ensured that neither crystallographic three-dimensional structure nor computational model for the enzyme is available to aid rational drug design, prediction of functional significance of SNPs or analytical protein engineering.Adequate biochemical information regarding human DBH, structural coordinates for peptidylglycine alpha-hydroxylating monooxygenase and computational data from a partial model of rat DBH were used along with logical manual intervention in a novel way to build an in silico model of human DBH. The model provides structural insight into the active site, metal coordination, subunit interface, substrate recognition and inhibitor binding. It reveals that DOMON domain potentially promotes tetramerization, while substrate dopamine and a potential therapeutic inhibitor nepicastat are stabilized in the active site through multiple hydrogen bonding. Functional significance of several exonic SNPs could be described from a structural analysis of the model. The model confirms that SNP resulting in Ala318Ser or Leu317Pro mutation may not influence enzyme activity, while Gly482Arg might actually do so being in the proximity of the active site. Arg549Cys may cause abnormal oligomerization through non-native disulfide bond formation. Other SNPs like Glu181, Glu250, Lys239 and Asp290 could potentially inhibit tetramerization thus affecting function.The first three-dimensional model of full-length human DBH protein was obtained in a novel manner with a set of experimental data as guideline for consistency of in silico prediction. Preliminary physicochemical tests validated the model. The model confirms, rationalizes and

  4. Structural insight of dopamine β-hydroxylase, a drug target for complex traits, and functional significance of exonic single nucleotide polymorphisms.

    Science.gov (United States)

    Kapoor, Abhijeet; Shandilya, Manish; Kundu, Suman

    2011-01-01

    Human dopamine β-hydroxylase (DBH) is an important therapeutic target for complex traits. Several single nucleotide polymorphisms (SNPs) have also been identified in DBH with potential adverse physiological effect. However, difficulty in obtaining diffractable crystals and lack of a suitable template for modeling the protein has ensured that neither crystallographic three-dimensional structure nor computational model for the enzyme is available to aid rational drug design, prediction of functional significance of SNPs or analytical protein engineering. Adequate biochemical information regarding human DBH, structural coordinates for peptidylglycine alpha-hydroxylating monooxygenase and computational data from a partial model of rat DBH were used along with logical manual intervention in a novel way to build an in silico model of human DBH. The model provides structural insight into the active site, metal coordination, subunit interface, substrate recognition and inhibitor binding. It reveals that DOMON domain potentially promotes tetramerization, while substrate dopamine and a potential therapeutic inhibitor nepicastat are stabilized in the active site through multiple hydrogen bonding. Functional significance of several exonic SNPs could be described from a structural analysis of the model. The model confirms that SNP resulting in Ala318Ser or Leu317Pro mutation may not influence enzyme activity, while Gly482Arg might actually do so being in the proximity of the active site. Arg549Cys may cause abnormal oligomerization through non-native disulfide bond formation. Other SNPs like Glu181, Glu250, Lys239 and Asp290 could potentially inhibit tetramerization thus affecting function. The first three-dimensional model of full-length human DBH protein was obtained in a novel manner with a set of experimental data as guideline for consistency of in silico prediction. Preliminary physicochemical tests validated the model. The model confirms, rationalizes and provides

  5. Managing complexity insights, concepts, applications

    CERN Document Server

    Helbing, Dirk

    2007-01-01

    Each chapter in Managing Complexity focuses on analyzing real-world complex systems and transferring knowledge from the complex-systems sciences to applications in business, industry and society. The interdisciplinary contributions range from markets and production through logistics, traffic control, and critical infrastructures, up to network design, information systems, social conflicts and building consensus. They serve to raise readers' awareness concerning the often counter-intuitive behavior of complex systems and to help them integrate insights gained in complexity research into everyday planning, decision making, strategic optimization, and policy. Intended for a broad readership, the contributions have been kept largely non-technical and address a general, scientifically literate audience involved in corporate, academic, and public institutions.

  6. Relationships between structural complexity, coral traits, and reef fish assemblages

    Science.gov (United States)

    Darling, Emily S.; Graham, Nicholas A. J.; Januchowski-Hartley, Fraser A.; Nash, Kirsty L.; Pratchett, Morgan S.; Wilson, Shaun K.

    2017-06-01

    With the ongoing loss of coral cover and the associated flattening of reef architecture, understanding the links between coral habitat and reef fishes is of critical importance. Here, we investigate whether considering coral traits and functional diversity provides new insights into the relationship between structural complexity and reef fish communities, and whether coral traits and community composition can predict structural complexity. Across 157 sites in Seychelles, Maldives, the Chagos Archipelago, and Australia's Great Barrier Reef, we find that structural complexity and reef zone are the strongest and most consistent predictors of reef fish abundance, biomass, species richness, and trophic structure. However, coral traits, diversity, and life histories provided additional predictive power for models of reef fish assemblages, and were key drivers of structural complexity. Our findings highlight that reef complexity relies on living corals—with different traits and life histories—continuing to build carbonate skeletons, and that these nuanced relationships between coral assemblages and habitat complexity can affect the structure of reef fish assemblages. Seascape-level estimates of structural complexity are rapid and cost effective with important implications for the structure and function of fish assemblages, and should be incorporated into monitoring programs.

  7. Integrative Genomic Analysis of Complex traits

    DEFF Research Database (Denmark)

    Ehsani, Ali Reza

    In the last decade rapid development in biotechnologies has made it possible to extract extensive information about practically all levels of biological organization. An ever-increasing number of studies are reporting miltilayered datasets on the entire DNA sequence, transceroption, protein...... expression, and metabolite abundance of more and more populations in a multitude of invironments. However, a solid model for including all of this complex information in one analysis, to disentangle genetic variation and the underlying genetic architecture of complex traits and diseases, has not yet been...

  8. Structural insights into transcription complexes

    NARCIS (Netherlands)

    Berger, I.; Blanco, A.G.; Boelens, R.; Cavarelli, J.; Coll, M.; Folkers, G.E.; Nie, Y.; Pogenberg, V.; Schultz, P.; Wilmanns, M.; Moras, D.; Poterszman, A.

    2011-01-01

    Control of transcription allows the regulation of cell activity in response to external stimuli and research in the field has greatly benefited from efforts in structural biology. In this review, based on specific examples from the European SPINE2-COMPLEXES initiative, we illustrate the impact of

  9. The Hidden Complexity of Mendelian Traits across Natural Yeast Populations

    Directory of Open Access Journals (Sweden)

    Jing Hou

    2016-07-01

    Full Text Available Mendelian traits are considered to be at the lower end of the complexity spectrum of heritable phenotypes. However, more than a century after the rediscovery of Mendel’s law, the global landscape of monogenic variants, as well as their effects and inheritance patterns within natural populations, is still not well understood. Using the yeast Saccharomyces cerevisiae, we performed a species-wide survey of Mendelian traits across a large population of isolates. We generated offspring from 41 unique parental pairs and analyzed 1,105 cross/trait combinations. We found that 8.9% of the cases were Mendelian. Further tracing of causal variants revealed background-specific expressivity and modified inheritances, gradually transitioning from Mendelian to complex traits in 30% of the cases. In fact, when taking into account the natural population diversity, the hidden complexity of traits could be substantial, confounding phenotypic predictability even for simple Mendelian traits.

  10. Interpersonal Perception: Cognitive Complexity and Trait Implication

    Science.gov (United States)

    Halverson, Charles F., Jr.

    1970-01-01

    Demonstrates that evaluative connotations of personality characteristics have more persuasive effect on interpersonal judgment for persons low in cognitive complexity than for cognitively complex persons. Stresses need for conceptualizing interpersonal judgment as function of interaction between cognitive complexity and evaluative requirements of…

  11. Ubiquitous polygenicity of human complex traits: genome-wide analysis of 49 traits in Koreans.

    Directory of Open Access Journals (Sweden)

    Jian Yang

    Full Text Available Recent studies in population of European ancestry have shown that 30% ~ 50% of heritability for human complex traits such as height and body mass index, and common diseases such as schizophrenia and rheumatoid arthritis, can be captured by common SNPs and that genetic variation attributed to chromosomes are in proportion to their length. Using genome-wide estimation and partitioning approaches, we analysed 49 human quantitative traits, many of which are relevant to human diseases, in 7,170 unrelated Korean individuals genotyped on 326,262 SNPs. For 43 of the 49 traits, we estimated a nominally significant (P<0.05 proportion of variance explained by all SNPs on the Affymetrix 5.0 genotyping array ([Formula: see text]. On average across 47 of the 49 traits for which the estimate of h(G(2 is non-zero, common SNPs explain approximately one-third (range of 7.8% to 76.8% of narrow sense heritability. The estimate of h(G(2 is highly correlated with the proportion of SNPs with association P<0.031 (r(2 = 0.92. Longer genomic segments tend to explain more phenotypic variation, with a correlation of 0.78 between the estimate of variance explained by individual chromosomes and their physical length, and 1% of the genome explains approximately 1% of the genetic variance. Despite the fact that there are a few SNPs with large effects for some traits, these results suggest that polygenicity is ubiquitous for most human complex traits and that a substantial proportion of the "missing heritability" is captured by common SNPs.

  12. Improved understanding of protein complex offers insight into DNA

    Science.gov (United States)

    Summer Science Writing Internship Improved understanding of protein complex offers insight into DNA clearer understanding of the origin recognition complex (ORC) - a protein complex that directs DNA replication - through its crystal structure offers new insight into fundamental mechanisms of DNA replication

  13. Integrating modelling and phenotyping approaches to identify and screen complex traits - Illustration for transpiration efficiency in cereals.

    Science.gov (United States)

    Chenu, K; van Oosterom, E J; McLean, G; Deifel, K S; Fletcher, A; Geetika, G; Tirfessa, A; Mace, E S; Jordan, D R; Sulman, R; Hammer, G L

    2018-02-21

    Following advances in genetics, genomics, and phenotyping, trait selection in breeding is limited by our ability to understand interactions within the plants and with their environments, and to target traits of most relevance for the target population of environments. We propose an integrated approach that combines insights from crop modelling, physiology, genetics, and breeding to identify traits valuable for yield gain in the target population of environments, develop relevant high-throughput phenotyping platforms, and identify genetic controls and their values in production environments. This paper uses transpiration efficiency (biomass produced per unit of water used) as an example of a complex trait of interest to illustrate how the approach can guide modelling, phenotyping, and selection in a breeding program. We believe that this approach, by integrating insights from diverse disciplines, can increase the resource use efficiency of breeding programs for improving yield gains in target populations of environments.

  14. The art of insight in science and engineering mastering complexity

    CERN Document Server

    Mahajan, Sanjoy

    2014-01-01

    In this book, Sanjoy Mahajan shows us that the way to master complexity is through insight rather than precision. Precision can overwhelm us with information, whereas insight connects seemingly disparate pieces of information into a simple picture. Unlike computers, humans depend on insight. Based on the author's fifteen years of teaching at MIT, Cambridge University, and Olin College, The Art of Insight in Science and Engineering shows us how to build insight and find understanding, giving readers tools to help them solve any problem in science and engineering. To master complexity, we can organize it or discard it. The Art of Insight in Science and Engineering first teaches the tools for organizing complexity, then distinguishes the two paths for discarding complexity: with and without loss of information. Questions and problems throughout the text help readers master and apply these groups of tools. Armed with this three-part toolchest, and without complicated mathematics, readers can estimate the flight ...

  15. On the Origin of Complex Adaptive Traits: Progress Since the Darwin Versus Mivart Debate.

    Science.gov (United States)

    Suzuki, Takao K

    2017-06-01

    The evolutionary origin of complex adaptive traits has been a controversial topic in the history of evolutionary biology. Although Darwin argued for the gradual origins of complex adaptive traits within the theory of natural selection, Mivart insisted that natural selection could not account for the incipient stages of complex traits. The debate starting from Darwin and Mivart eventually engendered two opposite views: gradualism and saltationism. Although this has been a long-standing debate, the issue remains unresolved. However, recent studies have interrogated classic examples of complex traits, such as the asymmetrical eyes of flatfishes and leaf mimicry of butterfly wings, whose origins were debated by Darwin and Mivart. Here, I review recent findings as a starting point to provide a modern picture of the evolution of complex adaptive traits. First, I summarize the empirical evidence that unveils the evolutionary steps toward complex traits. I then argue that the evolution of complex traits could be understood within the concept of "reducible complexity." Through these discussions, I propose a conceptual framework for the formation of complex traits, named as reducible-composable multicomponent systems, that satisfy two major characteristics: reducibility into a sum of subcomponents and composability to construct traits from various additional and combinatorial arrangements of the subcomponents. This conceptual framework provides an analytical foundation for exploring evolutionary pathways to build up complex traits. This review provides certain essential avenues for deciphering the origin of complex adaptive traits. © 2017 Wiley Periodicals, Inc.

  16. cis-Acting Complex-Trait-Associated lincRNA Expression Correlates with Modulation of Chromosomal Architecture

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    Jennifer Yihong Tan

    2017-02-01

    Full Text Available Summary: Intergenic long noncoding RNAs (lincRNAs are the largest class of transcripts in the human genome. Although many have recently been linked to complex human traits, the underlying mechanisms for most of these transcripts remain undetermined. We investigated the regulatory roles of a high-confidence and reproducible set of 69 trait-relevant lincRNAs (TR-lincRNAs in human lymphoblastoid cells whose biological relevance is supported by their evolutionary conservation during recent human history and genetic interactions with other trait-associated loci. Their enrichment in enhancer-like chromatin signatures, interactions with nearby trait-relevant protein-coding loci, and preferential location at topologically associated domain (TAD boundaries provide evidence that TR-lincRNAs likely regulate proximal trait-relevant gene expression in cis by modulating local chromosomal architecture. This is consistent with the positive and significant correlation found between TR-lincRNA abundance and intra-TAD DNA-DNA contacts. Our results provide insights into the molecular mode of action by which TR-lincRNAs contribute to complex human traits. : Tan et al. identify and characterize 69 human complex trait/disease-associated lincRNAs in LCLs. They show that these loci are often associated with cis-regulation of gene expression and tend to be localized at TAD boundaries, suggesting that these lincRNAs may influence chromosomal architecture. Keywords: intergenic long noncoding RNA, lincRNA, GWAS, expression quantitative trait loci, eQTL, complex trait and disease, enhancer, cis-regulation, topologically associated domains, TAD

  17. Improving biological understanding and complex trait prediction by integrating prior information in genomic feature models

    DEFF Research Database (Denmark)

    Edwards, Stefan McKinnon

    externally founded information, such as KEGG pathways, Gene Ontology gene sets, or genomic features, and estimate the joint contribution of the genetic variants within these sets to complex trait phenotypes. The analysis of complex trait phenotypes is hampered by the myriad of genes that control the trait...

  18. Contribution of Large Region Joint Associations to Complex Traits Genetics

    Science.gov (United States)

    Paré, Guillaume; Asma, Senay; Deng, Wei Q.

    2015-01-01

    A polygenic model of inheritance, whereby hundreds or thousands of weakly associated variants contribute to a trait’s heritability, has been proposed to underlie the genetic architecture of complex traits. However, relatively few genetic variants have been positively identified so far and they collectively explain only a small fraction of the predicted heritability. We hypothesized that joint association of multiple weakly associated variants over large chromosomal regions contributes to complex traits variance. Confirmation of such regional associations can help identify new loci and lead to a better understanding of known ones. To test this hypothesis, we first characterized the ability of commonly used genetic association models to identify large region joint associations. Through theoretical derivation and simulation, we showed that multivariate linear models where multiple SNPs are included as independent predictors have the most favorable association profile. Based on these results, we tested for large region association with height in 3,740 European participants from the Health and Retirement Study (HRS) study. Adjusting for SNPs with known association with height, we demonstrated clustering of weak associations (p = 2x10-4) in regions extending up to 433.0 Kb from known height loci. The contribution of regional associations to phenotypic variance was estimated at 0.172 (95% CI 0.063-0.279; p < 0.001), which compared favorably to 0.129 explained by known height variants. Conversely, we showed that suggestively associated regions are enriched for known height loci. To extend our findings to other traits, we also tested BMI, HDLc and CRP for large region associations, with consistent results for CRP. Our results demonstrate the presence of large region joint associations and suggest these can be used to pinpoint weakly associated SNPs. PMID:25856144

  19. Genomic prediction of complex human traits: relatedness, trait architecture and predictive meta-models

    Science.gov (United States)

    Spiliopoulou, Athina; Nagy, Reka; Bermingham, Mairead L.; Huffman, Jennifer E.; Hayward, Caroline; Vitart, Veronique; Rudan, Igor; Campbell, Harry; Wright, Alan F.; Wilson, James F.; Pong-Wong, Ricardo; Agakov, Felix; Navarro, Pau; Haley, Chris S.

    2015-01-01

    We explore the prediction of individuals' phenotypes for complex traits using genomic data. We compare several widely used prediction models, including Ridge Regression, LASSO and Elastic Nets estimated from cohort data, and polygenic risk scores constructed using published summary statistics from genome-wide association meta-analyses (GWAMA). We evaluate the interplay between relatedness, trait architecture and optimal marker density, by predicting height, body mass index (BMI) and high-density lipoprotein level (HDL) in two data cohorts, originating from Croatia and Scotland. We empirically demonstrate that dense models are better when all genetic effects are small (height and BMI) and target individuals are related to the training samples, while sparse models predict better in unrelated individuals and when some effects have moderate size (HDL). For HDL sparse models achieved good across-cohort prediction, performing similarly to the GWAMA risk score and to models trained within the same cohort, which indicates that, for predicting traits with moderately sized effects, large sample sizes and familial structure become less important, though still potentially useful. Finally, we propose a novel ensemble of whole-genome predictors with GWAMA risk scores and demonstrate that the resulting meta-model achieves higher prediction accuracy than either model on its own. We conclude that although current genomic predictors are not accurate enough for diagnostic purposes, performance can be improved without requiring access to large-scale individual-level data. Our methodologically simple meta-model is a means of performing predictive meta-analysis for optimizing genomic predictions and can be easily extended to incorporate multiple population-level summary statistics or other domain knowledge. PMID:25918167

  20. Pentacoordinated organoaluminum complexes: A computational insight

    KAUST Repository

    Milione, Stefano

    2012-12-24

    The geometry and the electronic structure of a series of organometallic pentacoordinated aluminum complexes bearing tri- or tetradentate N,O-based ligands have been investigated with theoretical methods. The BP86, B3LYP, and M06 functionals reproduce with low accuracy the geometry of the selected complexes. The worst result was obtained for the complex bearing a Schiff base ligand with a pendant donor arm, aeimpAlMe2 (aeimp = N-2-(dimethylamino)ethyl-(3,5-di-tert-butyl)salicylaldimine). In particular, the Al-Namine bond distance was unacceptably overestimated. This failure suggests a reasonably flat potential energy surface with respect to Al-N elongation, indicating a weak interaction with probably a strong component of dispersion forces. MP2 and M06-2X methods led to an acceptable value for the same Al-N distance. Better results were obtained with the addition of the dispersion correction to the hybrid B3LYP functional (B3LYP-D). Natural bond orbital analysis revealed that the contribution of the d orbital to the bonding is very small, in agreement with several previous studies of hypervalent molecules. The donation of electronic charge from the ligand to metal mainly consists in the interactions of the lone pairs on the donor atoms of the ligands with the s and p valence orbitals of the aluminum. The covalent bonding of the Al with the coordinated ligand is weak, and the interactions between Al and the coordinated ligands are largely ionic. To further explore the geometrical and electronic factors affecting the formation of these pentacoordianted aluminum complexes, we considered the tetracoordinated complex impAlMe2 (imp = N-isopropyl-(3,5-di-tert-butyl)salicylaldimine)), analogous to aeimpAlMe 2, and we investigated the potential energy surface around the aluminum atom corresponding to the approach of NMe3 to the metal center. At the MP2/6-31G(d) level of theory, a weak attraction was revealed only when NMe3 heads toward the metal center through the directions

  1. Pentacoordinated organoaluminum complexes: A computational insight

    KAUST Repository

    Milione, Stefano; Milano, Giuseppe; Cavallo, Luigi

    2012-01-01

    The geometry and the electronic structure of a series of organometallic pentacoordinated aluminum complexes bearing tri- or tetradentate N,O-based ligands have been investigated with theoretical methods. The BP86, B3LYP, and M06 functionals reproduce with low accuracy the geometry of the selected complexes. The worst result was obtained for the complex bearing a Schiff base ligand with a pendant donor arm, aeimpAlMe2 (aeimp = N-2-(dimethylamino)ethyl-(3,5-di-tert-butyl)salicylaldimine). In particular, the Al-Namine bond distance was unacceptably overestimated. This failure suggests a reasonably flat potential energy surface with respect to Al-N elongation, indicating a weak interaction with probably a strong component of dispersion forces. MP2 and M06-2X methods led to an acceptable value for the same Al-N distance. Better results were obtained with the addition of the dispersion correction to the hybrid B3LYP functional (B3LYP-D). Natural bond orbital analysis revealed that the contribution of the d orbital to the bonding is very small, in agreement with several previous studies of hypervalent molecules. The donation of electronic charge from the ligand to metal mainly consists in the interactions of the lone pairs on the donor atoms of the ligands with the s and p valence orbitals of the aluminum. The covalent bonding of the Al with the coordinated ligand is weak, and the interactions between Al and the coordinated ligands are largely ionic. To further explore the geometrical and electronic factors affecting the formation of these pentacoordianted aluminum complexes, we considered the tetracoordinated complex impAlMe2 (imp = N-isopropyl-(3,5-di-tert-butyl)salicylaldimine)), analogous to aeimpAlMe 2, and we investigated the potential energy surface around the aluminum atom corresponding to the approach of NMe3 to the metal center. At the MP2/6-31G(d) level of theory, a weak attraction was revealed only when NMe3 heads toward the metal center through the directions

  2. Complex relationships among personality traits, job characteristics, and work behaviors

    NARCIS (Netherlands)

    van den Berg, P.T.; Feij, J.A.

    2003-01-01

    The aim of the study was to investigate the additive, mediating, and moderating effects of personality traits and job characteristics on work behaviors. Job applicants (N = 161) completed personality questionnaires measuring extraversion, neuroticism, achievement motivation, and experience seeking.

  3. Climatic conditions cause complex patterns of covariation between demographic traits in a long-lived raptor

    NARCIS (Netherlands)

    Herfindal, Ivar; van de Pol, Martijn; Nielsen, Jan Tøttrup; Sæther, Bernt-Erik; Møller, Anders Pape

    2015-01-01

    1.Environmental variation can induce life history changes that can last over a large part of the lifetime of an organism. If multiple demographic traits are affected, expected changes in climate may influence environmental covariances among traits in a complex manner. Thus, examining the

  4. Chaotic, fractional, and complex dynamics new insights and perspectives

    CERN Document Server

    Macau, Elbert; Sanjuan, Miguel

    2018-01-01

    The book presents nonlinear, chaotic and fractional dynamics, complex systems and networks, together with cutting-edge research on related topics. The fifteen chapters – written by leading scientists working in the areas of nonlinear, chaotic and fractional dynamics, as well as complex systems and networks – offer an extensive overview of cutting-edge research on a range of topics, including fundamental and applied research. These include but are not limited to aspects of synchronization in complex dynamical systems, universality features in systems with specific fractional dynamics, and chaotic scattering. As such, the book provides an excellent and timely snapshot of the current state of research, blending the insights and experiences of many prominent researchers.

  5. Statistical power to detect genetic (covariance of complex traits using SNP data in unrelated samples.

    Directory of Open Access Journals (Sweden)

    Peter M Visscher

    2014-04-01

    Full Text Available We have recently developed analysis methods (GREML to estimate the genetic variance of a complex trait/disease and the genetic correlation between two complex traits/diseases using genome-wide single nucleotide polymorphism (SNP data in unrelated individuals. Here we use analytical derivations and simulations to quantify the sampling variance of the estimate of the proportion of phenotypic variance captured by all SNPs for quantitative traits and case-control studies. We also derive the approximate sampling variance of the estimate of a genetic correlation in a bivariate analysis, when two complex traits are either measured on the same or different individuals. We show that the sampling variance is inversely proportional to the number of pairwise contrasts in the analysis and to the variance in SNP-derived genetic relationships. For bivariate analysis, the sampling variance of the genetic correlation additionally depends on the harmonic mean of the proportion of variance explained by the SNPs for the two traits and the genetic correlation between the traits, and depends on the phenotypic correlation when the traits are measured on the same individuals. We provide an online tool for calculating the power of detecting genetic (covariation using genome-wide SNP data. The new theory and online tool will be helpful to plan experimental designs to estimate the missing heritability that has not yet been fully revealed through genome-wide association studies, and to estimate the genetic overlap between complex traits (diseases in particular when the traits (diseases are not measured on the same samples.

  6. Genetic insight into yield-associated traits of wheat grown in multiple rain-fed environments.

    Directory of Open Access Journals (Sweden)

    Xianshan Wu

    Full Text Available BACKGROUND: Grain yield is a key economic driver of successful wheat production. Due to its complex nature, little is known regarding its genetic control. The goal of this study was to identify important quantitative trait loci (QTL directly and indirectly affecting grain yield using doubled haploid lines derived from a cross between Hanxuan 10 and Lumai 14. METHODOLOGY/PRINCIPAL FINDINGS: Ten yield-associated traits, including yield per plant (YP, number of spikes per plant (NSP, number of grains per spike (NGS, one-thousand grain weight (TGW, total number of spikelets per spike (TNSS, number of sterile spikelets per spike (NSSS, proportion of fertile spikelets per spike (PFSS, spike length (SL, density of spikelets per spike (DSS and plant height (PH, were assessed across 14 (for YP to 23 (for TGW year × location × water regime environments in China. Then, the genetic effects were partitioned into additive main effects (a, epistatic main effects (aa and their environment interaction effects (ae and aae by using composite interval mapping in a mixed linear model. CONCLUSIONS/SIGNIFICANCE: Twelve (YP to 33 (PH QTLs were identified on all 21 chromosomes except 6D. QTLs were more frequently observed on chromosomes 1B, 2B, 2D, 5A and 6B, and were concentrated in a few regions on individual chromosomes, exemplified by three striking yield-related QTL clusters on chromosomes 2B, 1B and 4B that explained the correlations between YP and other traits. The additive main-effect QTLs contributed more phenotypic variation than the epistasis and environmental interaction. Consistent with agronomic analyses, a group of progeny derived by selecting TGW and NGS, with higher grain yield, had an increased frequency of QTL for high YP, NGS, TGW, TNSS, PFSS, SL, PH and fewer NSSS, when compared to low yielding progeny. This indicated that it is feasible by marker-assisted selection to facilitate wheat production.

  7. Impacts of population structure and analytical models in genome-wide association studies of complex traits in forest trees: a case study in Eucalyptus globulus.

    Directory of Open Access Journals (Sweden)

    Eduardo P Cappa

    heterozygous forest trees, and provides additional insights into the nature of complex quantitative traits in Eucalyptus.

  8. Impacts of Population Structure and Analytical Models in Genome-Wide Association Studies of Complex Traits in Forest Trees: A Case Study in Eucalyptus globulus

    Science.gov (United States)

    Garcia, Martín N.; Acuña, Cintia; Borralho, Nuno M. G.; Grattapaglia, Dario; Marcucci Poltri, Susana N.

    2013-01-01

    heterozygous forest trees, and provides additional insights into the nature of complex quantitative traits in Eucalyptus. PMID:24282578

  9. Parameters in dynamic models of complex traits are containers of missing heritability.

    Directory of Open Access Journals (Sweden)

    Yunpeng Wang

    Full Text Available Polymorphisms identified in genome-wide association studies of human traits rarely explain more than a small proportion of the heritable variation, and improving this situation within the current paradigm appears daunting. Given a well-validated dynamic model of a complex physiological trait, a substantial part of the underlying genetic variation must manifest as variation in model parameters. These parameters are themselves phenotypic traits. By linking whole-cell phenotypic variation to genetic variation in a computational model of a single heart cell, incorporating genotype-to-parameter maps, we show that genome-wide association studies on parameters reveal much more genetic variation than when using higher-level cellular phenotypes. The results suggest that letting such studies be guided by computational physiology may facilitate a causal understanding of the genotype-to-phenotype map of complex traits, with strong implications for the development of phenomics technology.

  10. A Commentary on Pitfalls of Predicting Complex Traits From SNP's

    DEFF Research Database (Denmark)

    de los Campos, Gustavo; Sorensen, Daniel

    2013-01-01

    As stated by Wray and co-authors1, knowing the proportion of variance of a trait that is explained by regression on markers in the population (h2M) is relevant because, in principle, h2M represents the maximum prediction accuracy (R2TST) that is achievable in testing (TST) data if marker effects...... of h2M (Ref. 5), conseqeuenty, it is not obvious that R2TST can achieve values equal to the finite sample estimate of h2G-BLUP. In a recent article5, we studied the R2TST of G-BLUP and its relationship with h2G-BLUP. We show analytically that mis-specification of the training–testing (TRN–TST) genomic...

  11. Farmers’ Preference for Rice Traits: Insights from Farm Surveys in Central Luzon, Philippines, 1966-2012

    Science.gov (United States)

    Laborte, Alice G.; Paguirigan, Neale C.; Moya, Piedad F.; Nelson, Andrew; Sparks, Adam H.; Gregorio, Glenn B.

    2015-01-01

    Many modern rice varieties (MVs) have been released but only a few have been widely adopted by farmers. To understand farmers’ preferences, we characterized MVs released in the Philippines from 1966 to 2013 and identified important characteristics of the varieties that were widely adopted in Central Luzon using farm surveys conducted in 1966–2012. We found that farmers adopt MVs that are high yielding, mature faster, and have long and slender grains, high milling recovery, and intermediate amylose content. The amylose content of adopted varieties has been declining, suggesting value in developing softer rice. To have a high potential for adoption, new MVs should have characteristics within the ranges of values observed for the adopted MVs. In addition, new MVs should have higher head rice recovery, less chalky grains, and better resistance to pests and diseases. Most MVs released in 2005–2013 compared poorly in these three traits. To reduce the risk of severe outbreaks, broad spectrum resistance should be incorporated into new MVs. This analysis of five decades of farm surveys provides insights into the varietal characteristics preferred by farmers which could contribute to the establishment of a product profile for developing improved MVs that are more targeted and, hence, would have high potential for adoption by farmers in Central Luzon and similar areas. We recommend a similar analysis be done in other major rice growing regions to aid the development of MVs that are more responsive to farmers’ needs and preferences. PMID:26317505

  12. Worms under stress: unravelling genetic complex traits through perturbation

    NARCIS (Netherlands)

    Rodriguez Sanchez, M.

    2014-01-01

    The genetic architecture of an organism could be considered ‘the most amazing piece of engineering’ existing in nature. Looking from a certain distance, the genetic complexity of an organism could be described as an immense jigsaw puzzle. As in a real jigsaw, the connection between two pieces

  13. Inferring genetic architecture of complex traits using Bayesian integrative analysis of genome and transcriptiome data

    DEFF Research Database (Denmark)

    Ehsani, Alireza; Sørensen, Peter; Pomp, Daniel

    2012-01-01

    Background To understand the genetic architecture of complex traits and bridge the genotype-phenotype gap, it is useful to study intermediate -omics data, e.g. the transcriptome. The present study introduces a method for simultaneous quantification of the contributions from single nucleotide......-modal distribution of genomic values collapses, when gene expressions are added to the model Conclusions With increased availability of various -omics data, integrative approaches are promising tools for understanding the genetic architecture of complex traits. Partitioning of explained variances at the chromosome...

  14. Emerging applications of genome-editing technology to examine functionality of GWAS-associated variants for complex traits.

    Science.gov (United States)

    Smith, Andrew J P; Deloukas, Panos; Munroe, Patricia B

    2018-04-13

    Over the last decade, genome-wide association studies (GWAS) have propelled the discovery of thousands of loci associated with complex diseases. The focus is now turning towards the function of these association signals, determining the causal variant(s) amongst those in strong linkage disequilibrium, and identifying their underlying mechanisms, such as long-range gene regulation. Genome-editing techniques utilising zinc-finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs) and clustered regularly-interspaced short palindromic repeats with Cas9 nuclease (CRISPR-Cas9), are becoming the tools of choice to establish functionality for these variants, due to the ability to assess effects of single variants in vivo. This review will discuss examples of how these technologies have begun to aid functional analysis of GWAS loci for complex traits such as cardiovascular disease, type 2 diabetes, cancer, obesity and autoimmune disease. We focus on analysis of variants occurring within non-coding genomic regions, as these comprise the majority of GWAS variants, providing the greatest challenges to determining functionality, and compare editing strategies that provide different levels of evidence for variant functionality. The review describes molecular insights into some of these potentially causal variants, and how these may relate to the pathology of the trait, and look towards future directions for these technologies in post-GWAS analysis, such as base-editing.

  15. The complex jujube genome provides insights into fruit tree biology.

    Science.gov (United States)

    Liu, Meng-Jun; Zhao, Jin; Cai, Qing-Le; Liu, Guo-Cheng; Wang, Jiu-Rui; Zhao, Zhi-Hui; Liu, Ping; Dai, Li; Yan, Guijun; Wang, Wen-Jiang; Li, Xian-Song; Chen, Yan; Sun, Yu-Dong; Liu, Zhi-Guo; Lin, Min-Juan; Xiao, Jing; Chen, Ying-Ying; Li, Xiao-Feng; Wu, Bin; Ma, Yong; Jian, Jian-Bo; Yang, Wei; Yuan, Zan; Sun, Xue-Chao; Wei, Yan-Li; Yu, Li-Li; Zhang, Chi; Liao, Sheng-Guang; He, Rong-Jun; Guang, Xuan-Min; Wang, Zhuo; Zhang, Yue-Yang; Luo, Long-Hai

    2014-10-28

    The jujube (Ziziphus jujuba Mill.), a member of family Rhamnaceae, is a major dry fruit and a traditional herbal medicine for more than one billion people. Here we present a high-quality sequence for the complex jujube genome, the first genome sequence of Rhamnaceae, using an integrated strategy. The final assembly spans 437.65 Mb (98.6% of the estimated) with 321.45 Mb anchored to the 12 pseudo-chromosomes and contains 32,808 genes. The jujube genome has undergone frequent inter-chromosome fusions and segmental duplications, but no recent whole-genome duplication. Further analyses of the jujube-specific genes and transcriptome data from 15 tissues reveal the molecular mechanisms underlying some specific properties of the jujube. Its high vitamin C content can be attributed to a unique high level expression of genes involved in both biosynthesis and regeneration. Our study provides insights into jujube-specific biology and valuable genomic resources for the improvement of Rhamnaceae plants and other fruit trees.

  16. Integrating Nonadditive Genomic Relationship Matrices into the Study of Genetic Architecture of Complex Traits.

    Science.gov (United States)

    Nazarian, Alireza; Gezan, Salvador A

    2016-03-01

    The study of genetic architecture of complex traits has been dramatically influenced by implementing genome-wide analytical approaches during recent years. Of particular interest are genomic prediction strategies which make use of genomic information for predicting phenotypic responses instead of detecting trait-associated loci. In this work, we present the results of a simulation study to improve our understanding of the statistical properties of estimation of genetic variance components of complex traits, and of additive, dominance, and genetic effects through best linear unbiased prediction methodology. Simulated dense marker information was used to construct genomic additive and dominance matrices, and multiple alternative pedigree- and marker-based models were compared to determine if including a dominance term into the analysis may improve the genetic analysis of complex traits. Our results showed that a model containing a pedigree- or marker-based additive relationship matrix along with a pedigree-based dominance matrix provided the best partitioning of genetic variance into its components, especially when some degree of true dominance effects was expected to exist. Also, we noted that the use of a marker-based additive relationship matrix along with a pedigree-based dominance matrix had the best performance in terms of accuracy of correlations between true and estimated additive, dominance, and genetic effects. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Plasticity first: molecular signatures of a complex morphological trait in filamentous cyanobacteria.

    Science.gov (United States)

    Koch, Robin; Kupczok, Anne; Stucken, Karina; Ilhan, Judith; Hammerschmidt, Katrin; Dagan, Tal

    2017-08-31

    Filamentous cyanobacteria that differentiate multiple cell types are considered the peak of prokaryotic complexity and their evolution has been studied in the context of multicellularity origins. Species that form true-branching filaments exemplify the most complex cyanobacteria. However, the mechanisms underlying the true-branching morphology remain poorly understood despite of several investigations that focused on the identification of novel genes or pathways. An alternative route for the evolution of novel traits is based on existing phenotypic plasticity. According to that scenario - termed genetic assimilation - the fixation of a novel phenotype precedes the fixation of the genotype. Here we show that the evolution of transcriptional regulatory elements constitutes a major mechanism for the evolution of new traits. We found that supplementation with sucrose reconstitutes the ancestral branchless phenotype of two true-branching Fischerella species and compared the transcription start sites (TSSs) between the two phenotypic states. Our analysis uncovers several orthologous TSSs whose transcription level is correlated with the true-branching phenotype. These TSSs are found in genes that encode components of the septosome and elongasome (e.g., fraC and mreB). The concept of genetic assimilation supplies a tenable explanation for the evolution of novel traits but testing its feasibility is hindered by the inability to recreate and study the evolution of present-day traits. We present a novel approach to examine transcription data for the plasticity first route and provide evidence for its occurrence during the evolution of complex colony morphology in true-branching cyanobacteria. Our results reveal a route for evolution of the true-branching phenotype in cyanobacteria via modification of the transcription level of pre-existing genes. Our study supplies evidence for the 'plasticity-first' hypothesis and highlights the importance of transcriptional regulation in

  18. Drosophila and genome-wide association studies: a review and resource for the functional dissection of human complex traits

    Science.gov (United States)

    Wangler, Michael F.; Hu, Yanhui

    2017-01-01

    ABSTRACT Human genome-wide association studies (GWAS) have successfully identified thousands of susceptibility loci for common diseases with complex genetic etiologies. Although the susceptibility variants identified by GWAS usually have only modest effects on individual disease risk, they contribute to a substantial burden of trait variation in the overall population. GWAS also offer valuable clues to disease mechanisms that have long proven to be elusive. These insights could lead the way to breakthrough treatments; however, several challenges hinder progress, making innovative approaches to accelerate the follow-up of results from GWAS an urgent priority. Here, we discuss the largely untapped potential of the fruit fly, Drosophila melanogaster, for functional investigation of findings from human GWAS. We highlight selected examples where strong genomic conservation with humans along with the rapid and powerful genetic tools available for flies have already facilitated fine mapping of association signals, elucidated gene mechanisms, and revealed novel disease-relevant biology. We emphasize current research opportunities in this rapidly advancing field, and present bioinformatic analyses that systematically explore the applicability of Drosophila for interrogation of susceptibility signals implicated in more than 1000 human traits, based on all GWAS completed to date. Thus, our discussion is targeted at both human geneticists seeking innovative strategies for experimental validation of findings from GWAS, as well as the Drosophila research community, by whom ongoing investigations of the implicated genes will powerfully inform our understanding of human disease. PMID:28151408

  19. Host Genome Influence on Gut Microbial Composition and Microbial Prediction of Complex Traits in Pigs.

    Science.gov (United States)

    Camarinha-Silva, Amelia; Maushammer, Maria; Wellmann, Robin; Vital, Marius; Preuss, Siegfried; Bennewitz, Jörn

    2017-07-01

    The aim of the present study was to analyze the interplay between gastrointestinal tract (GIT) microbiota, host genetics, and complex traits in pigs using extended quantitative-genetic methods. The study design consisted of 207 pigs that were housed and slaughtered under standardized conditions, and phenotyped for daily gain, feed intake, and feed conversion rate. The pigs were genotyped with a standard 60 K SNP chip. The GIT microbiota composition was analyzed by 16S rRNA gene amplicon sequencing technology. Eight from 49 investigated bacteria genera showed a significant narrow sense host heritability, ranging from 0.32 to 0.57. Microbial mixed linear models were applied to estimate the microbiota variance for each complex trait. The fraction of phenotypic variance explained by the microbial variance was 0.28, 0.21, and 0.16 for daily gain, feed conversion, and feed intake, respectively. The SNP data and the microbiota composition were used to predict the complex traits using genomic best linear unbiased prediction (G-BLUP) and microbial best linear unbiased prediction (M-BLUP) methods, respectively. The prediction accuracies of G-BLUP were 0.35, 0.23, and 0.20 for daily gain, feed conversion, and feed intake, respectively. The corresponding prediction accuracies of M-BLUP were 0.41, 0.33, and 0.33. Thus, in addition to SNP data, microbiota abundances are an informative source of complex trait predictions. Since the pig is a well-suited animal for modeling the human digestive tract, M-BLUP, in addition to G-BLUP, might be beneficial for predicting human predispositions to some diseases, and, consequently, for preventative and personalized medicine. Copyright © 2017 by the Genetics Society of America.

  20. Genetic architecture of complex traits and accuracy of genomic prediction: coat colour, milk-fat percentage, and type in Holstein cattle as contrasting model traits.

    Directory of Open Access Journals (Sweden)

    Ben J Hayes

    2010-09-01

    Full Text Available Prediction of genetic merit using dense SNP genotypes can be used for estimation of breeding values for selection of livestock, crops, and forage species; for prediction of disease risk; and for forensics. The accuracy of these genomic predictions depends in part on the genetic architecture of the trait, in particular number of loci affecting the trait and distribution of their effects. Here we investigate the difference among three traits in distribution of effects and the consequences for the accuracy of genomic predictions. Proportion of black coat colour in Holstein cattle was used as one model complex trait. Three loci, KIT, MITF, and a locus on chromosome 8, together explain 24% of the variation of proportion of black. However, a surprisingly large number of loci of small effect are necessary to capture the remaining variation. A second trait, fat concentration in milk, had one locus of large effect and a host of loci with very small effects. Both these distributions of effects were in contrast to that for a third trait, an index of scores for a number of aspects of cow confirmation ("overall type", which had only loci of small effect. The differences in distribution of effects among the three traits were quantified by estimating the distribution of variance explained by chromosome segments containing 50 SNPs. This approach was taken to account for the imperfect linkage disequilibrium between the SNPs and the QTL affecting the traits. We also show that the accuracy of predicting genetic values is higher for traits with a proportion of large effects (proportion black and fat percentage than for a trait with no loci of large effect (overall type, provided the method of analysis takes advantage of the distribution of loci effects.

  1. Age of Onset of Mood Disorders and Complexity of Personality Traits

    OpenAIRE

    Ostacoli, L.; Zuffranieri, M.; Cavallo, M.; Zennaro, A.; Rainero, I.; Pinessi, L.; Pacchiana Parravicini, M. V.; Ladisa, E.; Furlan, P. M.; Picci, R. L.

    2013-01-01

    Objective. The aim of the present study is to evaluate the link between the age of onset of mood disorders and the complexity of the personality traits. Methods. 209 patients with major depressive or manic/hypomanic episodes were assessed using the Structured Clinical Interview for DSM Axis I diagnoses and the Millon Clinical Multiaxial Inventory-III (MCMI-III). Results. 17.2% of the patients had no elevated MCMI-III scores, 45.9% had one peak, and 36.9% had a complex personality disorder wit...

  2. Insights into physiological traits of Bifidobacterium animalis subsp. lactis BB-12 through membrane proteome analysis

    DEFF Research Database (Denmark)

    Gilad, Ofir; Hjernø, Karin; Østerlund, Eva Christina

    2012-01-01

    Bifidobacterium animalis subsp. lactis BB-12 is a widely used probiotic strain associated with a variety of health-promoting traits. There is, however, only limited knowledge available regarding the membrane proteome and the proteins involved in oligosaccharide transport in BB-12. We applied two...

  3. Decomposing Additive Genetic Variance Revealed Novel Insights into Trait Evolution in Synthetic Hexaploid Wheat

    Directory of Open Access Journals (Sweden)

    Abdulqader Jighly

    2018-02-01

    Full Text Available Whole genome duplication (WGD is an evolutionary phenomenon, which causes significant changes to genomic structure and trait architecture. In recent years, a number of studies decomposed the additive genetic variance explained by different sets of variants. However, they investigated diploid populations only and none of the studies examined any polyploid organism. In this research, we extended the application of this approach to polyploids, to differentiate the additive variance explained by the three subgenomes and seven sets of homoeologous chromosomes in synthetic allohexaploid wheat (SHW to gain a better understanding of trait evolution after WGD. Our SHW population was generated by crossing improved durum parents (Triticum turgidum; 2n = 4x = 28, AABB subgenomes with the progenitor species Aegilops tauschii (syn Ae. squarrosa, T. tauschii; 2n = 2x = 14, DD subgenome. The population was phenotyped for 10 fungal/nematode resistance traits as well as two abiotic stresses. We showed that the wild D subgenome dominated the additive effect and this dominance affected the A more than the B subgenome. We provide evidence that this dominance was not inflated by population structure, relatedness among individuals or by longer linkage disequilibrium blocks observed in the D subgenome within the population used for this study. The cumulative size of the three homoeologs of the seven chromosomal groups showed a weak but significant positive correlation with their cumulative explained additive variance. Furthermore, an average of 69% for each chromosomal group's cumulative additive variance came from one homoeolog that had the highest explained variance within the group across all 12 traits. We hypothesize that structural and functional changes during diploidization may explain chromosomal group relations as allopolyploids keep balanced dosage for many genes. Our results contribute to a better understanding of trait evolution mechanisms in polyploidy

  4. Effects of structural complexity on within-canopy light environments and leaf traits in a northern mixed deciduous forest.

    Science.gov (United States)

    Fotis, Alexander T; Curtis, Peter S

    2017-10-01

    Canopy structure influences forest productivity through its effects on the distribution of radiation and the light-induced changes in leaf physiological traits. Due to the difficulty of accessing and measuring forest canopies, few field-based studies have quantitatively linked these divergent scales of canopy functioning. The objective of our study was to investigate how canopy structure affects light profiles within a forest canopy and whether leaves of mature trees adjust morphologically and biochemically to the light environments characteristic of canopies with different structural complexity. We used a combination of light detection and ranging (LiDAR) data and hemispherical photographs to quantify canopy structure and light environments, respectively, and a telescoping pole to sample leaves. Leaf mass per area (LMA), nitrogen on an area basis (Narea) and chlorophyll on a mass basis (Chlmass) were measured in red maple (Acer rubrum), american beech (Fagus grandifolia), white pine (Pinus strobus), and northern red oak (Quercus rubra) at different heights in plots with similar leaf area index but contrasting canopy complexity (rugosity). We found that more complex canopies had greater porosity and reduced light variability in the midcanopy while total light interception was unchanged relative to less complex canopies. Leaf phenotypes of F. grandifolia, Q. rubra and P. strobus were more sun-acclimated in the midstory of structurally complex canopies while leaf phenotypes of A. rubrum were more shade-acclimated (lower LMA) in the upper canopy of more complex stands, despite no differences in total light interception. Broadleaf species showed further differences in acclimation with increased Narea and reduced Chlmass in leaves with higher LMA, while P. strobus showed no change in Narea and Chlmass with higher LMA. Our results provide new insight on how light distribution and leaf acclimation in mature trees might be altered when natural and anthropogenic

  5. Missing heritability : Is the gap closing? An analysis of 32 complex traits in the Lifelines Cohort Study

    NARCIS (Netherlands)

    Nolte, Ilja M.; van der Most, Peter J.; Alizadeh, Behrooz Z.; de Bakker, Paul I. W.; Boezen, H. Marike; Bruinenberg, Marcel; Franke, Lude; van der Harst, Pim; Navis, Gerjan; Postma, Dirkje S.; Rots, Marianne G.; Stolk, Ronald P.; Swertz, Morris A.; Wolffenbuttel, Bruce H. R.; Wijmenga, Cisca; Snieder, Harold

    Despite the recent explosive rise in number of genetic markers for complex disease traits identified in genome-wide association studies, there is still a large gap between the known heritability of these traits and the part explained by these markers. To gauge whether this 'heritability gap' is

  6. Detection of expression quantitative trait Loci in complex mouse crosses: impact and alleviation of data quality and complex population substructure.

    Science.gov (United States)

    Iancu, Ovidiu D; Darakjian, Priscila; Kawane, Sunita; Bottomly, Daniel; Hitzemann, Robert; McWeeney, Shannon

    2012-01-01

    Complex Mus musculus crosses, e.g., heterogeneous stock (HS), provide increased resolution for quantitative trait loci detection. However, increased genetic complexity challenges detection methods, with discordant results due to low data quality or complex genetic architecture. We quantified the impact of theses factors across three mouse crosses and two different detection methods, identifying procedures that greatly improve detection quality. Importantly, HS populations have complex genetic architectures not fully captured by the whole genome kinship matrix, calling for incorporating chromosome specific relatedness information. We analyze three increasingly complex crosses, using gene expression levels as quantitative traits. The three crosses were an F(2) intercross, a HS formed by crossing four inbred strains (HS4), and a HS (HS-CC) derived from the eight lines found in the collaborative cross. Brain (striatum) gene expression and genotype data were obtained using the Illumina platform. We found large disparities between methods, with concordance varying as genetic complexity increased; this problem was more acute for probes with distant regulatory elements (trans). A suite of data filtering steps resulted in substantial increases in reproducibility. Genetic relatedness between samples generated overabundance of detected eQTLs; an adjustment procedure that includes the kinship matrix attenuates this problem. However, we find that relatedness between individuals is not evenly distributed across the genome; information from distinct chromosomes results in relatedness structure different from the whole genome kinship matrix. Shared polymorphisms from distinct chromosomes collectively affect expression levels, confounding eQTL detection. We suggest that considering chromosome specific relatedness can result in improved eQTL detection.

  7. Directional selection can drive the evolution of modularity in complex traits.

    Science.gov (United States)

    Melo, Diogo; Marroig, Gabriel

    2015-01-13

    Modularity is a central concept in modern biology, providing a powerful framework for the study of living organisms on many organizational levels. Two central and related questions can be posed in regard to modularity: How does modularity appear in the first place, and what forces are responsible for keeping and/or changing modular patterns? We approached these questions using a quantitative genetics simulation framework, building on previous results obtained with bivariate systems and extending them to multivariate systems. We developed an individual-based model capable of simulating many traits controlled by many loci with variable pleiotropic relations between them, expressed in populations subject to mutation, recombination, drift, and selection. We used this model to study the problem of the emergence of modularity, and hereby show that drift and stabilizing selection are inefficient at creating modular variational structures. We also demonstrate that directional selection can have marked effects on the modular structure between traits, actively promoting a restructuring of genetic variation in the selected population and potentially facilitating the response to selection. Furthermore, we give examples of complex covariation created by simple regimes of combined directional and stabilizing selection and show that stabilizing selection is important in the maintenance of established covariation patterns. Our results are in full agreement with previous results for two-trait systems and further extend them to include scenarios of greater complexity. Finally, we discuss the evolutionary consequences of modular patterns being molded by directional selection.

  8. The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

    Science.gov (United States)

    Astle, William J; Elding, Heather; Jiang, Tao; Allen, Dave; Ruklisa, Dace; Mann, Alice L; Mead, Daniel; Bouman, Heleen; Riveros-Mckay, Fernando; Kostadima, Myrto A; Lambourne, John J; Sivapalaratnam, Suthesh; Downes, Kate; Kundu, Kousik; Bomba, Lorenzo; Berentsen, Kim; Bradley, John R; Daugherty, Louise C; Delaneau, Olivier; Freson, Kathleen; Garner, Stephen F; Grassi, Luigi; Guerrero, Jose; Haimel, Matthias; Janssen-Megens, Eva M; Kaan, Anita; Kamat, Mihir; Kim, Bowon; Mandoli, Amit; Marchini, Jonathan; Martens, Joost H A; Meacham, Stuart; Megy, Karyn; O'Connell, Jared; Petersen, Romina; Sharifi, Nilofar; Sheard, Simon M; Staley, James R; Tuna, Salih; van der Ent, Martijn; Walter, Klaudia; Wang, Shuang-Yin; Wheeler, Eleanor; Wilder, Steven P; Iotchkova, Valentina; Moore, Carmel; Sambrook, Jennifer; Stunnenberg, Hendrik G; Di Angelantonio, Emanuele; Kaptoge, Stephen; Kuijpers, Taco W; Carrillo-de-Santa-Pau, Enrique; Juan, David; Rico, Daniel; Valencia, Alfonso; Chen, Lu; Ge, Bing; Vasquez, Louella; Kwan, Tony; Garrido-Martín, Diego; Watt, Stephen; Yang, Ying; Guigo, Roderic; Beck, Stephan; Paul, Dirk S; Pastinen, Tomi; Bujold, David; Bourque, Guillaume; Frontini, Mattia; Danesh, John; Roberts, David J; Ouwehand, Willem H; Butterworth, Adam S; Soranzo, Nicole

    2016-11-17

    Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Translational Insight Into Polycystic Ovary Syndrome (PCOS) From Female Monkeys with PCOS-like Traits

    OpenAIRE

    Abbott, D.H.; Levine, J.E.; Dumesic, D.A.

    2016-01-01

    Genetics-based studies of women with polycystic ovary syndrome (PCOS) implicate >20 PCOS risk genes that collectively account for 90% of PCOS cases. Animal models convincingly demonstrate excess fetal testosterone exposure in females as a reliable, epigenetic, developmental origin for PCOS-like traits. In particular, nonhuman primates (NHPs) provide the most faithful emulation of PCOS-like pathophysiology, likely because of close similarities to humans in genomic, developmental, reproductive ...

  10. Conserving marine biodiversity: insights from life-history trait candidate genes in Atlantic cod (Gadus morhua)

    DEFF Research Database (Denmark)

    Hansen, Jakob Hemmer; Therkildsen, Nina Overgaard; Meldrup, Dorte

    2014-01-01

    Recent technological developments have facilitated an increased focus on identifying genomic regions underlying adaptive trait variation in natural populations, and it has been advocated that this information should be important for designating population units for conservation. In marine fishes...... are under selection in natural populations of Atlantic cod. Furthermore, we find that patterns of variation in outlier markers do not align with those observed at selectively neutral markers, and that outlier markers identify conservation units on finer geographical scales than those revealed when analysing...... only neutral markers. Accordingly, results also suggest that information about adaptive genetic variation will be useful for targeted conservation and management in this and other marine species...

  11. Simple versus complex models of trait evolution and stasis as a response to environmental change

    Science.gov (United States)

    Hunt, Gene; Hopkins, Melanie J.; Lidgard, Scott

    2015-04-01

    Previous analyses of evolutionary patterns, or modes, in fossil lineages have focused overwhelmingly on three simple models: stasis, random walks, and directional evolution. Here we use likelihood methods to fit an expanded set of evolutionary models to a large compilation of ancestor-descendant series of populations from the fossil record. In addition to the standard three models, we assess more complex models with punctuations and shifts from one evolutionary mode to another. As in previous studies, we find that stasis is common in the fossil record, as is a strict version of stasis that entails no real evolutionary changes. Incidence of directional evolution is relatively low (13%), but higher than in previous studies because our analytical approach can more sensitively detect noisy trends. Complex evolutionary models are often favored, overwhelmingly so for sequences comprising many samples. This finding is consistent with evolutionary dynamics that are, in reality, more complex than any of the models we consider. Furthermore, the timing of shifts in evolutionary dynamics varies among traits measured from the same series. Finally, we use our empirical collection of evolutionary sequences and a long and highly resolved proxy for global climate to inform simulations in which traits adaptively track temperature changes over time. When realistically calibrated, we find that this simple model can reproduce important aspects of our paleontological results. We conclude that observed paleontological patterns, including the prevalence of stasis, need not be inconsistent with adaptive evolution, even in the face of unstable physical environments.

  12. Adapting APSIM to model the physiology and genetics of complex adaptive traits in field crops.

    Science.gov (United States)

    Hammer, Graeme L; van Oosterom, Erik; McLean, Greg; Chapman, Scott C; Broad, Ian; Harland, Peter; Muchow, Russell C

    2010-05-01

    Progress in molecular plant breeding is limited by the ability to predict plant phenotype based on its genotype, especially for complex adaptive traits. Suitably constructed crop growth and development models have the potential to bridge this predictability gap. A generic cereal crop growth and development model is outlined here. It is designed to exhibit reliable predictive skill at the crop level while also introducing sufficient physiological rigour for complex phenotypic responses to become emergent properties of the model dynamics. The approach quantifies capture and use of radiation, water, and nitrogen within a framework that predicts the realized growth of major organs based on their potential and whether the supply of carbohydrate and nitrogen can satisfy that potential. The model builds on existing approaches within the APSIM software platform. Experiments on diverse genotypes of sorghum that underpin the development and testing of the adapted crop model are detailed. Genotypes differing in height were found to differ in biomass partitioning among organs and a tall hybrid had significantly increased radiation use efficiency: a novel finding in sorghum. Introducing these genetic effects associated with plant height into the model generated emergent simulated phenotypic differences in green leaf area retention during grain filling via effects associated with nitrogen dynamics. The relevance to plant breeding of this capability in complex trait dissection and simulation is discussed.

  13. Genomic insights into the Saccharomyces sensu stricto complex.

    Science.gov (United States)

    Borneman, Anthony R; Pretorius, Isak S

    2015-02-01

    The Saccharomyces sensu stricto group encompasses species ranging from the industrially ubiquitous yeast Saccharomyces cerevisiae to those that are confined to geographically limited environmental niches. The wealth of genomic data that are now available for the Saccharomyces genus is providing unprecedented insights into the genomic processes that can drive speciation and evolution, both in the natural environment and in response to human-driven selective forces during the historical "domestication" of these yeasts for baking, brewing, and winemaking. Copyright © 2015 by the Genetics Society of America.

  14. Simultaneous discovery, estimation and prediction analysis of complex traits using a bayesian mixture model.

    Directory of Open Access Journals (Sweden)

    Gerhard Moser

    2015-04-01

    Full Text Available Gene discovery, estimation of heritability captured by SNP arrays, inference on genetic architecture and prediction analyses of complex traits are usually performed using different statistical models and methods, leading to inefficiency and loss of power. Here we use a Bayesian mixture model that simultaneously allows variant discovery, estimation of genetic variance explained by all variants and prediction of unobserved phenotypes in new samples. We apply the method to simulated data of quantitative traits and Welcome Trust Case Control Consortium (WTCCC data on disease and show that it provides accurate estimates of SNP-based heritability, produces unbiased estimators of risk in new samples, and that it can estimate genetic architecture by partitioning variation across hundreds to thousands of SNPs. We estimated that, depending on the trait, 2,633 to 9,411 SNPs explain all of the SNP-based heritability in the WTCCC diseases. The majority of those SNPs (>96% had small effects, confirming a substantial polygenic component to common diseases. The proportion of the SNP-based variance explained by large effects (each SNP explaining 1% of the variance varied markedly between diseases, ranging from almost zero for bipolar disorder to 72% for type 1 diabetes. Prediction analyses demonstrate that for diseases with major loci, such as type 1 diabetes and rheumatoid arthritis, Bayesian methods outperform profile scoring or mixed model approaches.

  15. Translational Insight Into Polycystic Ovary Syndrome (PCOS) From Female Monkeys with PCOS-like Traits.

    Science.gov (United States)

    Abbott, David H; Levine, Jon E; Dumesic, Daniel A

    2016-01-01

    Genetics-based studies of women with polycystic ovary syndrome (PCOS) implicate >20 PCOS risk genes that collectively account for <10% of PCOS. Clinicians now consider that either rare alleles or non-genetic, potentially epigenetic, developmental origins may contribute key pathogenic components to >90% of PCOS cases. Animal models convincingly demonstrate excess fetal testosterone exposure in females as a reliable, epigenetic, developmental origin for PCOS-like traits. In particular, nonhuman primates (NHPs) provide the most faithful emulation of PCOS-like pathophysiology, likely because of close similarities to humans in genomic, developmental, reproductive and metabolic characteristics, as well as aging. Recent appreciation of potential molecular mechanisms contributing to enhanced LH action in both PCOS women (GWAS-based) and PCOS-like monkeys (DNA methylation-based) suggest commonality in pathogenic origins. This review examines the translational relevance of NHP studies to PCOS, identifying characteristics of newborn females at risk for PCOS-like traits and potential prepubertal treatment interventions to ameliorate PCOS onset.

  16. Translational Insight Into Polycystic Ovary Syndrome (PCOS) From Female Monkeys with PCOS-like Traits

    Science.gov (United States)

    Abbott, D.H.; Levine, J.E.; Dumesic, D.A.

    2017-01-01

    Genetics-based studies of women with polycystic ovary syndrome (PCOS) implicate >20 PCOS risk genes that collectively account for PCOS. Clinicians now consider that either rare alleles or non-genetic, potentially epigenetic, developmental origins may contribute key pathogenic components to >90% of PCOS cases. Animal models convincingly demonstrate excess fetal testosterone exposure in females as a reliable, epigenetic, developmental origin for PCOS-like traits. In particular, nonhuman primates (NHPs) provide the most faithful emulation of PCOS-like pathophysiology, likely because of close similarities to humans in genomic, developmental, reproductive and metabolic characteristics, as well as aging. Recent appreciation of potential molecular mechanisms contributing to enhanced LH action in both PCOS women (GWAS-based) and PCOS-like monkeys (DNA methylation-based) suggest commonality in pathogenic origins. This review examines the translational relevance of NHP studies to PCOS, identifying characteristics of newborn females at risk for PCOS-like traits and potential prepubertal treatment interventions to ameliorate PCOS onset. PMID:27426126

  17. Novel insights in agent-based complex automated negotiation

    CERN Document Server

    Lopez-Carmona, Miguel; Ito, Takayuki; Zhang, Minjie; Bai, Quan; Fujita, Katsuhide

    2014-01-01

    This book focuses on all aspects of complex automated negotiations, which are studied in the field of autonomous agents and multi-agent systems. This book consists of two parts. I: Agent-Based Complex Automated Negotiations, and II: Automated Negotiation Agents Competition. The chapters in Part I are extended versions of papers presented at the 2012 international workshop on Agent-Based Complex Automated Negotiation (ACAN), after peer reviews by three Program Committee members. Part II examines in detail ANAC 2012 (The Third Automated Negotiating Agents Competition), in which automated agents that have different negotiation strategies and are implemented by different developers are automatically negotiated in the several negotiation domains. ANAC is an international competition in which automated negotiation strategies, submitted by a number of universities and research institutes across the world, are evaluated in tournament style. The purpose of the competition is to steer the research in the area of bilate...

  18. Structural insight into the UNC-45–myosin complex

    DEFF Research Database (Denmark)

    Fratev, Filip; Jonsdottir, Svava Osk; Pajeva, Ilza

    2013-01-01

    The UNC-45 chaperone protein interacts with and affects the folding, stability, and the ATPase activity of myosins. It plays a critical role in the cardiomyopathy development and in the breast cancer tumor growth. Here we propose the first structural model of the UNC-45–myosin complex using various...... is mainly stabilized by electrostatic interactions. Remarkably, the contact surface area is similar to that of the myosinactin complex. A significant interspecies difference in the myosin binding epitope is observed. Our results reveal the structural basis of MYH7 exons 15–16 hypertrophic cardiomyopathy...... mutations and provide directions for drug targeting. © 2013 Wiley Periodicals, Inc....

  19. An Insight into Pedicularis cheilanthifolia Schrenk Complex (Scrophulariaceae

    Directory of Open Access Journals (Sweden)

    Arti Garg

    2009-09-01

    Full Text Available The taxonomy complexity of Pedicularis cheilanthifolia Schrenk along with its three varieties viz. var. cheilanthifolia, var. purpurea (Pennell Tsoong ex Garg and var. albida (Pennell Tsoong is elucidated and resolved. Key to varieties, morphology, distribution, phenology and ecology is provided to differentiate the varieties. Diagnostic morphological characters supported the transfer of P. purpurea (Pennel Tsoong to P. cheilanthifolia, hence the new combination is made.

  20. Scaling up complex interventions: insights from a realist synthesis.

    Science.gov (United States)

    Willis, Cameron D; Riley, Barbara L; Stockton, Lisa; Abramowicz, Aneta; Zummach, Dana; Wong, Geoff; Robinson, Kerry L; Best, Allan

    2016-12-19

    Preventing chronic diseases, such as cancer, cardiovascular disease and diabetes, requires complex interventions, involving multi-component and multi-level efforts that are tailored to the contexts in which they are delivered. Despite an increasing number of complex interventions in public health, many fail to be 'scaled up'. This study aimed to increase understanding of how and under what conditions complex public health interventions may be scaled up to benefit more people and populations.A realist synthesis was conducted and discussed at an in-person workshop involving practitioners responsible for scaling up activities. Realist approaches view causality through the linkages between changes in contexts (C) that activate mechanisms (M), leading to specific outcomes (O) (CMO configurations). To focus this review, three cases of complex interventions that had been successfully scaled up were included: Vibrant Communities, Youth Build USA and Pathways to Education. A search strategy of published and grey literature related to each case was developed, involving searches of relevant databases and nominations from experts. Data extracted from included documents were classified according to CMO configurations within strategic themes. Findings were compared and contrasted with guidance from diffusion theory, and interpreted with knowledge users to identify practical implications and potential directions for future research.Four core mechanisms were identified, namely awareness, commitment, confidence and trust. These mechanisms were activated within two broad scaling up strategies, those of renewing and regenerating, and documenting success. Within each strategy, specific actions to change contexts included building partnerships, conducting evaluations, engaging political support and adapting funding models. These modified contexts triggered the identified mechanisms, leading to a range of scaling up outcomes, such as commitment of new communities, changes in relevant

  1. Genome-wide association mapping of leaf metabolic profiles for dissecting complex traits in maize.

    Science.gov (United States)

    Riedelsheimer, Christian; Lisec, Jan; Czedik-Eysenberg, Angelika; Sulpice, Ronan; Flis, Anna; Grieder, Christoph; Altmann, Thomas; Stitt, Mark; Willmitzer, Lothar; Melchinger, Albrecht E

    2012-06-05

    The diversity of metabolites found in plants is by far greater than in most other organisms. Metabolic profiling techniques, which measure many of these compounds simultaneously, enabled investigating the regulation of metabolic networks and proved to be useful for predicting important agronomic traits. However, little is known about the genetic basis of metabolites in crops such as maize. Here, a set of 289 diverse maize inbred lines was genotyped with 56,110 SNPs and assayed for 118 biochemical compounds in the leaves of young plants, as well as for agronomic traits of mature plants in field trials. Metabolite concentrations had on average a repeatability of 0.73 and showed a correlation pattern that largely reflected their functional grouping. Genome-wide association mapping with correction for population structure and cryptic relatedness identified for 26 distinct metabolites strong associations with SNPs, explaining up to 32.0% of the observed genetic variance. On nine chromosomes, we detected 15 distinct SNP-metabolite associations, each of which explained more then 15% of the genetic variance. For lignin precursors, including p-coumaric acid and caffeic acid, we found strong associations (P values to ) with a region on chromosome 9 harboring cinnamoyl-CoA reductase, a key enzyme in monolignol synthesis and a target for improving the quality of lignocellulosic biomass by genetic engineering approaches. Moreover, lignin precursors correlated significantly with lignin content, plant height, and dry matter yield, suggesting that metabolites represent promising connecting links for narrowing the genotype-phenotype gap of complex agronomic traits.

  2. Kernel-based whole-genome prediction of complex traits: a review.

    Science.gov (United States)

    Morota, Gota; Gianola, Daniel

    2014-01-01

    Prediction of genetic values has been a focus of applied quantitative genetics since the beginning of the 20th century, with renewed interest following the advent of the era of whole genome-enabled prediction. Opportunities offered by the emergence of high-dimensional genomic data fueled by post-Sanger sequencing technologies, especially molecular markers, have driven researchers to extend Ronald Fisher and Sewall Wright's models to confront new challenges. In particular, kernel methods are gaining consideration as a regression method of choice for genome-enabled prediction. Complex traits are presumably influenced by many genomic regions working in concert with others (clearly so when considering pathways), thus generating interactions. Motivated by this view, a growing number of statistical approaches based on kernels attempt to capture non-additive effects, either parametrically or non-parametrically. This review centers on whole-genome regression using kernel methods applied to a wide range of quantitative traits of agricultural importance in animals and plants. We discuss various kernel-based approaches tailored to capturing total genetic variation, with the aim of arriving at an enhanced predictive performance in the light of available genome annotation information. Connections between prediction machines born in animal breeding, statistics, and machine learning are revisited, and their empirical prediction performance is discussed. Overall, while some encouraging results have been obtained with non-parametric kernels, recovering non-additive genetic variation in a validation dataset remains a challenge in quantitative genetics.

  3. Kernel-based whole-genome prediction of complex traits: a review

    Directory of Open Access Journals (Sweden)

    Gota eMorota

    2014-10-01

    Full Text Available Prediction of genetic values has been a focus of applied quantitative genetics since the beginning of the 20th century, with renewed interest following the advent of the era of whole genome-enabled prediction. Opportunities offered by the emergence of high-dimensional genomic data fueled by post-Sanger sequencing technologies, especially molecular markers, have driven researchers to extend Ronald Fisher and Sewall Wright's models to confront new challenges. In particular, kernel methods are gaining consideration as a regression method of choice for genome-enabled prediction. Complex traits are presumably influenced by many genomic regions working in concert with others (clearly so when considering pathways, thus generating interactions. Motivated by this view, a growing number of statistical approaches based on kernels attempt to capture non-additive effects, either parametrically or non-parametrically. This review centers on whole-genome regression using kernel methods applied to a wide range of quantitative traits of agricultural importance in animals and plants. We discuss various kernel-based approaches tailored to capturing total genetic variation, with the aim of arriving at an enhanced predictive performance in the light of available genome annotation information. Connections between prediction machines born in animal breeding, statistics, and machine learning are revisited, and their empirical prediction performance is discussed. Overall, while some encouraging results have been obtained with non-parametric kernels, recovering non-additive genetic variation in a validation dataset remains a challenge in quantitative genetics.

  4. Endurance Exercise Ability in the Horse: A Trait with Complex Polygenic Determinism

    Directory of Open Access Journals (Sweden)

    Anne Ricard

    2017-06-01

    fibroblasts. This lncRNA could be one element of the cardiac rhythm regulation. Our GWAS revealed that equine performance during endurance races is a complex polygenic trait, and is partially governed by at least 5 QTL: two coding genes involved in neuronal tissues and three other loci with many regulatory functions such as slowing down heart rate.

  5. Endurance Exercise Ability in the Horse: A Trait with Complex Polygenic Determinism.

    Science.gov (United States)

    Ricard, Anne; Robert, Céline; Blouin, Christine; Baste, Fanny; Torquet, Gwendoline; Morgenthaler, Caroline; Rivière, Julie; Mach, Nuria; Mata, Xavier; Schibler, Laurent; Barrey, Eric

    2017-01-01

    . This lncRNA could be one element of the cardiac rhythm regulation. Our GWAS revealed that equine performance during endurance races is a complex polygenic trait, and is partially governed by at least 5 QTL: two coding genes involved in neuronal tissues and three other loci with many regulatory functions such as slowing down heart rate.

  6. The search for Pleiades in trait constellations: functional integration and phenotypic selection in the complex flowers of Morrenia brachystephana (Apocynaceae).

    Science.gov (United States)

    Baranzelli, M C; Sérsic, A N; Cocucci, A A

    2014-04-01

    Pollinator-mediated natural selection on single traits, such as corolla tube or spur length, has been well documented. However, flower phenotypes are usually complex, and selection is expected to act on several traits that functionally interact rather than on a single isolated trait. Despite the fact that selection on complex phenotypes is expectedly widespread, multivariate selection modelling on such phenotypes still remains under-explored in plants. Species of the subfamily Asclepiadoideae (Apocynaceae) provide an opportunity to study such complex flower contrivances integrated by fine-scaled organs from disparate developmental origin. We studied the correlation structure among linear floral traits (i) by testing a priori morphological, functional or developmental hypotheses among traits and (ii) by exploring the organization of flower covariation, considering alternative expectations of modular organization or whole flower integration through conditional dependence analysis (CDA) and integration matrices. The phenotypic selection approach was applied to determine whether floral traits involved in the functioning of the pollination mechanism were affected by natural selection. Floral integration was low, suggesting that flowers are organized in more than just one correlation pleiad; our hypothetical functional correlation matrix was significantly correlated with the empirical matrix, and the CDA revealed three putative modules. Analyses of phenotypic selection showed significant linear and correlational gradients, lending support to expectations of functional interactions between floral traits. Significant correlational selection gradients found involved traits of different floral whorls, providing evidence for the existence of functional integration across developmental domains. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  7. Prediction of Complex Human Traits Using the Genomic Best Linear Unbiased Predictor

    DEFF Research Database (Denmark)

    de los Campos, Gustavo; Vazquez, Ana I; Fernando, Rohan

    2013-01-01

    Despite important advances from Genome Wide Association Studies (GWAS), for most complex human traits and diseases, a sizable proportion of genetic variance remains unexplained and prediction accuracy (PA) is usually low. Evidence suggests that PA can be improved using Whole-Genome Regression (WGR......) models where phenotypes are regressed on hundreds of thousands of variants simultaneously. The Genomic Best Linear Unbiased Prediction G-BLUP, a ridge-regression type method) is a commonly used WGR method and has shown good predictive performance when applied to plant and animal breeding populations....... However, breeding and human populations differ greatly in a number of factors that can affect the predictive performance of G-BLUP. Using theory, simulations, and real data analysis, we study the erformance of G-BLUP when applied to data from related and unrelated human subjects. Under perfect linkage...

  8. Genomic Selection in the Era of Next Generation Sequencing for Complex Traits in Plant Breeding.

    Science.gov (United States)

    Bhat, Javaid A; Ali, Sajad; Salgotra, Romesh K; Mir, Zahoor A; Dutta, Sutapa; Jadon, Vasudha; Tyagi, Anshika; Mushtaq, Muntazir; Jain, Neelu; Singh, Pradeep K; Singh, Gyanendra P; Prabhu, K V

    2016-01-01

    Genomic selection (GS) is a promising approach exploiting molecular genetic markers to design novel breeding programs and to develop new markers-based models for genetic evaluation. In plant breeding, it provides opportunities to increase genetic gain of complex traits per unit time and cost. The cost-benefit balance was an important consideration for GS to work in crop plants. Availability of genome-wide high-throughput, cost-effective and flexible markers, having low ascertainment bias, suitable for large population size as well for both model and non-model crop species with or without the reference genome sequence was the most important factor for its successful and effective implementation in crop species. These factors were the major limitations to earlier marker systems viz., SSR and array-based, and was unimaginable before the availability of next-generation sequencing (NGS) technologies which have provided novel SNP genotyping platforms especially the genotyping by sequencing. These marker technologies have changed the entire scenario of marker applications and made the use of GS a routine work for crop improvement in both model and non-model crop species. The NGS-based genotyping have increased genomic-estimated breeding value prediction accuracies over other established marker platform in cereals and other crop species, and made the dream of GS true in crop breeding. But to harness the true benefits from GS, these marker technologies will be combined with high-throughput phenotyping for achieving the valuable genetic gain from complex traits. Moreover, the continuous decline in sequencing cost will make the WGS feasible and cost effective for GS in near future. Till that time matures the targeted sequencing seems to be more cost-effective option for large scale marker discovery and GS, particularly in case of large and un-decoded genomes.

  9. Heritability and demographic analyses in the large isolated population of Val Borbera suggest advantages in mapping complex traits genes.

    Directory of Open Access Journals (Sweden)

    Michela Traglia

    2009-10-01

    Full Text Available Isolated populations are a useful resource for mapping complex traits due to shared stable environment, reduced genetic complexity and extended Linkage Disequilibrium (LD compared to the general population. Here we describe a large genetic isolate from the North West Apennines, the mountain range that runs through Italy from the North West Alps to the South.The study involved 1,803 people living in 7 villages of the upper Borbera Valley. For this large population cohort, data from genealogy reconstruction, medical questionnaires, blood, anthropometric and bone status QUS parameters were evaluated. Demographic and epidemiological analyses indicated a substantial genetic component contributing to each trait variation as well as overlapping genetic determinants and family clustering for some traits.The data provide evidence for significant heritability of medical relevant traits that will be important in mapping quantitative traits. We suggest that this population isolate is suitable to identify rare variants associated with complex phenotypes that may be difficult to study in larger but more heterogeneous populations.

  10. An atlas of genetic correlations across human diseases and traits

    DEFF Research Database (Denmark)

    Bulik-Sullivan, Brendan; Finucane, Hilary K; Anttila, Verneri

    2015-01-01

    Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are t...

  11. Genetic Marker Discovery in Complex Traits: A Field Example on Fat Content and Composition in Pigs

    Directory of Open Access Journals (Sweden)

    Ramona Natacha Pena

    2016-12-01

    Full Text Available Among the large number of attributes that define pork quality, fat content and composition have attracted the attention of breeders in the recent years due to their interaction with human health and technological and sensorial properties of meat. In livestock species, fat accumulates in different depots following a temporal pattern that is also recognized in humans. Intramuscular fat deposition rate and fatty acid composition change with life. Despite indication that it might be possible to select for intramuscular fat without affecting other fat depots, to date only one depot-specific genetic marker (PCK1 c.2456C>A has been reported. In contrast, identification of polymorphisms related to fat composition has been more successful. For instance, our group has described a variant in the stearoyl-coA desaturase (SCD gene that improves the desaturation index of fat without affecting overall fatness or growth. Identification of mutations in candidate genes can be a tedious and costly process. Genome-wide association studies can help in narrowing down the number of candidate genes by highlighting those which contribute most to the genetic variation of the trait. Results from our group and others indicate that fat content and composition are highly polygenic and that very few genes explain more than 5% of the variance of the trait. Moreover, as the complexity of the genome emerges, the role of non-coding genes and regulatory elements cannot be disregarded. Prediction of breeding values from genomic data is discussed in comparison with conventional best linear predictors of breeding values. An example based on real data is given, and the implications in phenotype prediction are discussed in detail. The benefits and limitations of using large SNP sets versus a few very informative markers as predictors of genetic merit of breeding candidates are evaluated using field data as an example.

  12. Using a system of differential equations that models cattle growth to uncover the genetic basis of complex traits.

    Science.gov (United States)

    Freua, Mateus Castelani; Santana, Miguel Henrique de Almeida; Ventura, Ricardo Vieira; Tedeschi, Luis Orlindo; Ferraz, José Bento Sterman

    2017-08-01

    The interplay between dynamic models of biological systems and genomics is based on the assumption that genetic variation of the complex trait (i.e., outcome of model behavior) arises from component traits (i.e., model parameters) in lower hierarchical levels. In order to provide a proof of concept of this statement for a cattle growth model, we ask whether model parameters map genomic regions that harbor quantitative trait loci (QTLs) already described for the complex trait. We conducted a genome-wide association study (GWAS) with a Bayesian hierarchical LASSO method in two parameters of the Davis Growth Model, a system of three ordinary differential equations describing DNA accretion, protein synthesis and degradation, and fat synthesis. Phenotypic and genotypic data were available for 893 Nellore (Bos indicus) cattle. Computed values for parameter k 1 (DNA accretion rate) ranged from 0.005 ± 0.003 and for α (constant for energy for maintenance requirement) 0.134 ± 0.024. The expected biological interpretation of the parameters is confirmed by QTLs mapped for k 1 and α. QTLs within genomic regions mapped for k 1 are expected to be correlated with the DNA pool: body size and weight. Single nucleotide polymorphisms (SNPs) which were significant for α mapped QTLs that had already been associated with residual feed intake, feed conversion ratio, average daily gain (ADG), body weight, and also dry matter intake. SNPs identified for k 1 were able to additionally explain 2.2% of the phenotypic variability of the complex ADG, even when SNPs for k 1 did not match the genomic regions associated with ADG. Although improvements are needed, our findings suggest that genomic analysis on component traits may help to uncover the genetic basis of more complex traits, particularly when lower biological hierarchies are mechanistically described by mathematical simulation models.

  13. Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement

    Directory of Open Access Journals (Sweden)

    Nelson eColihueque

    2014-08-01

    Full Text Available Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years.

  14. Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement

    Science.gov (United States)

    Colihueque, Nelson; Araneda, Cristian

    2014-01-01

    Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years. PMID:25140172

  15. Complexity of International Sign for inexperienced interpreters: Insights From a Deaf IS Instructor

    NARCIS (Netherlands)

    Oyserman, J.; Rosenstock, R.; Napier, J.

    2016-01-01

    In lieu of an abstract, here is a brief excerpt of the content: 192 Complexity of International Sign for Inexperienced Interpreters: Insights From a Deaf IS Instructor Joni Oyserman In this chapter, I focus on how inexperienced interpreters view, acquire, and use International Sign (IS). A profile

  16. The genetic architecture of a complex ecological trait: host plant use in the specialist moth, HELIOTHIS SUBFLEXA

    Science.gov (United States)

    The study of the genetic basis of ecological adaptation remains in its infancy, and most studies have focused on phenotypically simple traits. Host plant use by herbivorous insects is phenotypically complex. While research has illuminated the evolutionary determinants of host use, knowledge of its...

  17. A comparison of graph- and kernel-based -omics data integration algorithms for classifying complex traits.

    Science.gov (United States)

    Yan, Kang K; Zhao, Hongyu; Pang, Herbert

    2017-12-06

    High-throughput sequencing data are widely collected and analyzed in the study of complex diseases in quest of improving human health. Well-studied algorithms mostly deal with single data source, and cannot fully utilize the potential of these multi-omics data sources. In order to provide a holistic understanding of human health and diseases, it is necessary to integrate multiple data sources. Several algorithms have been proposed so far, however, a comprehensive comparison of data integration algorithms for classification of binary traits is currently lacking. In this paper, we focus on two common classes of integration algorithms, graph-based that depict relationships with subjects denoted by nodes and relationships denoted by edges, and kernel-based that can generate a classifier in feature space. Our paper provides a comprehensive comparison of their performance in terms of various measurements of classification accuracy and computation time. Seven different integration algorithms, including graph-based semi-supervised learning, graph sharpening integration, composite association network, Bayesian network, semi-definite programming-support vector machine (SDP-SVM), relevance vector machine (RVM) and Ada-boost relevance vector machine are compared and evaluated with hypertension and two cancer data sets in our study. In general, kernel-based algorithms create more complex models and require longer computation time, but they tend to perform better than graph-based algorithms. The performance of graph-based algorithms has the advantage of being faster computationally. The empirical results demonstrate that composite association network, relevance vector machine, and Ada-boost RVM are the better performers. We provide recommendations on how to choose an appropriate algorithm for integrating data from multiple sources.

  18. Primary care physician insights into a typology of the complex patient in primary care.

    Science.gov (United States)

    Loeb, Danielle F; Binswanger, Ingrid A; Candrian, Carey; Bayliss, Elizabeth A

    2015-09-01

    Primary care physicians play unique roles caring for complex patients, often acting as the hub for their care and coordinating care among specialists. To inform the clinical application of new models of care for complex patients, we sought to understand how these physicians conceptualize patient complexity and to develop a corresponding typology. We conducted qualitative in-depth interviews with internal medicine primary care physicians from 5 clinics associated with a university hospital and a community health hospital. We used systematic nonprobabilistic sampling to achieve an even distribution of sex, years in practice, and type of practice. The interviews were analyzed using a team-based participatory general inductive approach. The 15 physicians in this study endorsed a multidimensional concept of patient complexity. The physicians perceived patients to be complex if they had an exacerbating factor-a medical illness, mental illness, socioeconomic challenge, or behavior or trait (or some combination thereof)-that complicated care for chronic medical illnesses. This perspective of primary care physicians caring for complex patients can help refine models of complexity to design interventions or models of care that improve outcomes for these patients. © 2015 Annals of Family Medicine, Inc.

  19. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

    NARCIS (Netherlands)

    S.I. Berndt (Sonja); S. Gustafsson (Stefan); R. Mägi (Reedik); A. Ganna (Andrea); E. Wheeler (Eleanor); M.F. Feitosa (Mary Furlan); A.E. Justice (Anne); K.L. Monda (Keri); D.C. Croteau-Chonka (Damien); F.R. Day (Felix); T. Esko (Tõnu); M. Fall (Magnus); T. Ferreira (Teresa); D. Gentilini (Davide); A.U. Jackson (Anne); J. Luan; J.C. Randall (Joshua); S. Vedantam (Sailaja); C.J. Willer (Cristen); T.W. Winkler (Thomas); A.R. Wood (Andrew); T. Workalemahu (Tsegaselassie); Y.-J. Hu (Yi-Juan); S.H. Lee (Sang Hong); L. Liang (Liming); D.Y. Lin (Dan); J. Min (Josine); B.M. Neale (Benjamin); G. Thorleifsson (Gudmar); J. Yang (Jian); E. Albrecht (Eva); N. Amin (Najaf); J.L. Bragg-Gresham (Jennifer L.); G. Cadby (Gemma); M. den Heijer (Martin); N. Eklund (Niina); K. Fischer (Krista); A. Goel (Anuj); J.J. Hottenga (Jouke Jan); J.E. Huffman (Jennifer); I. Jarick (Ivonne); A. Johansson (Åsa); T. Johnson (Toby); S. Kanoni (Stavroula); M.E. Kleber (Marcus); I.R. König (Inke); K. Kristiansson (Kati); Z. Kutalik (Zoltán); C. Lamina (Claudia); C. Lecoeur (Cécile); G. Li (Guo); M. Mangino (Massimo); W.L. McArdle (Wendy); M.C. Medina-Gomez (Carolina); M. Müller-Nurasyid (Martina); J.S. Ngwa; I.M. Nolte (Ilja); L. Paternoster (Lavinia); S. Pechlivanis (Sonali); M. Perola (Markus); M.J. Peters (Marjolein); M. Preuss (Michael); L.M. Rose (Lynda); J. Shi (Jianxin); D. Shungin (Dmitry); G.D. Smith; R.J. Strawbridge (Rona); I. Surakka (Ida); A. Teumer (Alexander); M.D. Trip (Mieke); J.P. Tyrer (Jonathan); J.V. van Vliet-Ostaptchouk (Jana); L. Vandenput (Liesbeth); L. Waite (Lindsay); J.H. Zhao (Jing Hua); D. Absher (Devin); F.W. Asselbergs (Folkert); M. Atalay (Mustafa); A.P. Attwood (Antony); A.J. Balmforth (Anthony); D.C.G. Basart (Dick); J.P. Beilby (John); L.L. Bonnycastle (Lori); P. Brambilla (Paolo); M. Bruinenberg (M.); H. Campbell (Harry); D.I. Chasman (Daniel); P.S. Chines (Peter); F.S. Collins (Francis); J. Connell (John); W. O Cookson (William); U. de Faire (Ulf); F. de Vegt (Femmie); M. Dei (Mariano); M. Dimitriou (Maria); T. Edkins (Ted); K. Estrada Gil (Karol); D.M. Evans (David); M. Farrall (Martin); F. Ferrario (Franco); J. Ferrières (Jean); L. Franke (Lude); F. Frau (Francesca); P.V. Gejman (Pablo); H. Grallert (Harald); H. Grönberg (Henrik); V. Gudnason (Vilmundur); A. Hall (Anne); A.S. Hall (Alistair); A.L. Hartikainen; C. Hayward (Caroline); N.L. Heard-Costa (Nancy); A.C. Heath (Andrew); J. Hebebrand (Johannes); G. Homuth (Georg); F.B. Hu (Frank); S.E. Hunt (Sarah); E. Hyppönen (Elina); C. Iribarren (Carlos); K.B. Jacobs (Kevin); J.-O. Jansson (John-Olov); A. Jula (Antti); M. Kähönen (Mika); S. Kathiresan (Sekar); F. Kee (F.); K-T. Khaw (Kay-Tee); M. Kivimaki (Mika); W. Koenig (Wolfgang); A. Kraja (Aldi); M. Kumari (Meena); K. Kuulasmaa (Kari); J. Kuusisto (Johanna); J. Laitinen (Jaana); T.A. Lakka (Timo); C. Langenberg (Claudia); L.J. Launer (Lenore); L. Lind (Lars); J. Lindstrom (Jaana); J. Liu (Jianjun); A. Liuzzi (Antonio); M.L. Lokki; M. Lorentzon (Mattias); P.A. Madden (Pamela); P.K. Magnusson (Patrik); P. Manunta (Paolo); D. Marek (Diana); W. März (Winfried); I.M. Leach (Irene Mateo); B. McKnight (Barbara); S.E. Medland (Sarah Elizabeth); E. Mihailov (Evelin); L. Milani (Lili); G.W. Montgomery (Grant); V. Mooser (Vincent); T.W. Mühleisen (Thomas); P. Munroe (Patricia); A.W. Musk (Arthur); N. Narisu (Narisu); G. Navis (Gerjan); G. Nicholson (Ggeorge); C. Nohr (Christian); K. Ong (Ken); B.A. Oostra (Ben); C.N.A. Palmer (Colin); A. Palotie (Aarno); J. Peden (John); N. Pedersen; A. Peters (Annette); O. Polasek (Ozren); A. Pouta (Anneli); P.P. Pramstaller (Peter Paul); I. Prokopenko (Inga); C. Pütter (Carolin); A. Radhakrishnan (Aparna); O. Raitakari (Olli); A. Rendon (Augusto); F. Rivadeneira Ramirez (Fernando); I. Rudan (Igor); T. Saaristo (Timo); J.G. Sambrook (Jennifer); A.R. Sanders (Alan); S. Sanna (Serena); J. Saramies (Jouko); S. Schipf (Sabine); S. Schreiber (Stefan); H. Schunkert (Heribert); S.-Y. Shin; S. Signorini (Stefano); J. Sinisalo (Juha); B. Skrobek (Boris); N. Soranzo (Nicole); A. Stancáková (Alena); K. Stark (Klaus); J. Stephens (Jonathan); K. Stirrups (Kathy); R.P. Stolk (Ronald); M. Stumvoll (Michael); A.J. Swift (Amy); E.V. Theodoraki (Eirini); B. Thorand (Barbara); D.-A. Tregouet (David-Alexandre); E. Tremoli (Elena); M.M. van der Klauw (Melanie); J.B.J. van Meurs (Joyce); S.H.H.M. Vermeulen (Sita); J. Viikari (Jorma); J. Virtamo (Jarmo); V. Vitart (Veronique); G. Waeber (Gérard); Z. Wang (Zhaoming); E. Widen (Elisabeth); S.H. Wild (Sarah); G.A.H.M. Willemsen (Gonneke); B. Winkelmann; J.C.M. Witteman (Jacqueline); B.H.R. Wolffenbuttel (Bruce); A. Wong (Andrew); A.F. Wright (Alan); M.C. Zillikens (Carola); P. Amouyel (Philippe); B.O. Boehm (Bernhard); E.A. Boerwinkle (Eric); D.I. Boomsma (Dorret); M. Caulfield (Mark); S.J. Chanock (Stephen); L.A. Cupples (Adrienne); D. Cusi (Daniele); G.V. Dedoussis (George); J. Erdmann (Jeanette); J.G. Eriksson (Johan); P.W. Franks (Paul); P. Froguel (Philippe); C. Gieger (Christian); U. Gyllensten (Ulf); A. Hamsten (Anders); T.B. Harris (Tamara); C. Hengstenberg (Christian); A.A. Hicks (Andrew); A. Hingorani (Aroon); A. Hinney (Anke); A. Hofman (Albert); G.K. Hovingh (Kees); K. Hveem (Kristian); T. Illig (Thomas); M.-R. Jarvelin (Marjo-Riitta); K.-H. Jöckel (Karl-Heinz); S. Keinanen-Kiukaanniemi (Sirkka); L.A.L.M. Kiemeney (Bart); D. Kuh (Diana); M. Laakso (Markku); T. Lehtimäki (Terho); D.F. Levinson (Douglas); N.G. Martin (Nicholas); A. Metspalu (Andres); A.D. Morris (Andrew); M.S. Nieminen (Markku); I. Njølstad (Inger); C. Ohlsson (Claes); A.J. Oldehinkel (Albertine); W.H. Ouwehand (Willem); C. Palmer (Cameron); B.W.J.H. Penninx (Brenda); C. Power (Christopher); M.A. Province (Mike); B.M. Psaty (Bruce); L. Qi (Lu); R. Rauramaa (Rainer); P.M. Ridker (Paul); S. Ripatti (Samuli); V. Salomaa (Veikko); N.J. Samani (Nilesh); H. Snieder (Harold); H.G. Sorensen; T.D. Spector (Timothy); J-A. Zwart (John-Anker); A. Tönjes (Anke); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); M. Uusitupa (Matti); P. van der Harst (Pim); P. Vollenweider (Peter); H. Wallaschofski (Henri); N.J. Wareham (Nick); H. Watkins (Hugh); H.E. Wichmann (Heinz Erich); J.F. Wilson (James F); G.R. Abecasis (Gonçalo); T.L. Assimes (Themistocles); I.E. Barroso (Inês); M. Boehnke (Michael); I.B. Borecki (Ingrid); P. Deloukas (Panagiotis); C. Fox (Craig); T.M. Frayling (Timothy); L. Groop (Leif); T. Haritunian (Talin); I.M. Heid (Iris); D. Hunter (David); R.C. Kaplan (Robert); F. Karpe (Fredrik); M.F. Moffatt (Miriam); K.L. Mohlke (Karen); J.R. O´Connell; Y. Pawitan (Yudi); E.E. Schadt (Eric); D. Schlessinger (David); V. Steinthorsdottir (Valgerdur); D.P. Strachan (David); U. Thorsteinsdottir (Unnur); C.M. van Duijn (Cornelia); P.M. Visscher (Peter); A.M. Di Blasio (Anna Maria); J.N. Hirschhorn (Joel); C.M. Lindgren (Cecilia); A.D. Morris (Andrew); D. Meyre (David); A. Scherag (Andre); M.I. McCarthy (Mark); E.K. Speliotes (Elizabeth); K.E. North (Kari); R.J.F. Loos (Ruth); E. Ingelsson (Erik)

    2013-01-01

    textabstractApproaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of

  20. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

    NARCIS (Netherlands)

    Berndt, Sonja I; Gustafsson, Stefan; Mägi, Reedik; Ganna, Andrea; Wheeler, Eleanor; Feitosa, Mary F; Justice, Anne E; Monda, Keri L; Croteau-Chonka, Damien C; Day, Felix R; Esko, Tõnu; Fall, Tove; Ferreira, Teresa; Gentilini, Davide; Jackson, Anne U; Luan, Jian'an; Randall, Joshua C; Vedantam, Sailaja; Willer, Cristen J; Winkler, Thomas W; Wood, Andrew R; Workalemahu, Tsegaselassie; Hu, Yi-Juan; Lee, Sang Hong; Liang, Liming; Lin, Dan-Yu; Min, Josine L; Neale, Benjamin M; Thorleifsson, Gudmar; Yang, Jian; Albrecht, Eva; Amin, Najaf; Bragg-Gresham, Jennifer L; Cadby, Gemma; den Heijer, Martin; Eklund, Niina; Fischer, Krista; Goel, Anuj; Hottenga, Jouke-Jan; Huffman, Jennifer E; Jarick, Ivonne; Johansson, Åsa; Johnson, Toby; Kanoni, Stavroula; Kleber, Marcus E; König, Inke R; Kristiansson, Kati; Kutalik, Zoltán; Lamina, Claudia; Lecoeur, Cecile; Li, Guo; Mangino, Massimo; McArdle, Wendy L; Medina-Gomez, Carolina; Müller-Nurasyid, Martina; Ngwa, Julius S; Nolte, Ilja M; Paternoster, Lavinia; Pechlivanis, Sonali; Perola, Markus; Peters, Marjolein J; Preuss, Michael; Rose, Lynda M; Shi, Jianxin; Shungin, Dmitry; Smith, Albert Vernon; Strawbridge, Rona J; Surakka, Ida; Teumer, Alexander; Trip, Mieke D; Tyrer, Jonathan; Van Vliet-Ostaptchouk, Jana V; Vandenput, Liesbeth; Waite, Lindsay L; Zhao, Jing Hua; Absher, Devin; Asselbergs, Folkert W; Atalay, Mustafa; Attwood, Antony P; Balmforth, Anthony J; Basart, Hanneke; Beilby, John; Bonnycastle, Lori L; Brambilla, Paolo; Bruinenberg, Marcel; Campbell, Harry; Chasman, Daniel I; Chines, Peter S; Collins, Francis S; Connell, John M; Cookson, William O; de Faire, Ulf; de Vegt, Femmie; Dei, Mariano; Dimitriou, Maria; Edkins, Sarah; Estrada, Karol; Evans, David M; Farrall, Martin; Ferrario, Marco M; Ferrières, Jean; Franke, Lude; Frau, Francesca; Gejman, Pablo V; Grallert, Harald; Grönberg, Henrik; Gudnason, Vilmundur; Hall, Alistair S; Hall, Per; Hartikainen, Anna-Liisa; Hayward, Caroline; Heard-Costa, Nancy L; Heath, Andrew C; Hebebrand, Johannes; Homuth, Georg; Hu, Frank B; Hunt, Sarah E; Hyppönen, Elina; Iribarren, Carlos; Jacobs, Kevin B; Jansson, John-Olov; Jula, Antti; Kähönen, Mika; Kathiresan, Sekar; Kee, Frank; Khaw, Kay-Tee; Kivimäki, Mika; Koenig, Wolfgang; Kraja, Aldi T; Kumari, Meena; Kuulasmaa, Kari; Kuusisto, Johanna; Laitinen, Jaana H; Lakka, Timo A; Langenberg, Claudia; Launer, Lenore J; Lind, Lars; Lindström, Jaana; Liu, Jianjun; Liuzzi, Antonio; Lokki, Marja-Liisa; Lorentzon, Mattias; Madden, Pamela A; Magnusson, Patrik K; Manunta, Paolo; Marek, Diana; März, Winfried; Mateo Leach, Irene; McKnight, Barbara; Medland, Sarah E; Mihailov, Evelin; Milani, Lili; Montgomery, Grant W; Mooser, Vincent; Mühleisen, Thomas W; Munroe, Patricia B; Musk, Arthur W; Narisu, Narisu; Navis, Gerjan; Nicholson, George; Nohr, Ellen A; Ong, Ken K; Oostra, Ben A; Palmer, Colin N A; Palotie, Aarno; Peden, John F; Pedersen, Nancy; Peters, Annette; Polasek, Ozren; Pouta, Anneli; Pramstaller, Peter P; Prokopenko, Inga; Pütter, Carolin; Radhakrishnan, Aparna; Raitakari, Olli; Rendon, Augusto; Rivadeneira, Fernando; Rudan, Igor; Saaristo, Timo E; Sambrook, Jennifer G; Sanders, Alan R; Sanna, Serena; Saramies, Jouko; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Shin, So-Youn; Signorini, Stefano; Sinisalo, Juha; Skrobek, Boris; Soranzo, Nicole; Stančáková, Alena; Stark, Klaus; Stephens, Jonathan C; Stirrups, Kathleen; Stolk, Ronald P; Stumvoll, Michael; Swift, Amy J; Theodoraki, Eirini V; Thorand, Barbara; Tregouet, David-Alexandre; Tremoli, Elena; Van der Klauw, Melanie M; van Meurs, Joyce B J; Vermeulen, Sita H; Viikari, Jorma; Virtamo, Jarmo; Vitart, Veronique; Waeber, Gérard; Wang, Zhaoming; Widén, Elisabeth; Wild, Sarah H; Willemsen, Gonneke; Winkelmann, Bernhard R; Witteman, Jacqueline C M; Wolffenbuttel, Bruce H R; Wong, Andrew; Wright, Alan F; Zillikens, M Carola; Amouyel, Philippe; Boehm, Bernhard O; Boerwinkle, Eric; Boomsma, Dorret I; Caulfield, Mark J; Chanock, Stephen J; Cupples, L Adrienne; Cusi, Daniele; Dedoussis, George V; Erdmann, Jeanette; Eriksson, Johan G; Franks, Paul W; Froguel, Philippe; Gieger, Christian; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B; Hengstenberg, Christian; Hicks, Andrew A; Hingorani, Aroon; Hinney, Anke; Hofman, Albert; Hovingh, Kees G; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Keinanen-Kiukaanniemi, Sirkka M; Kiemeney, Lambertus A; Kuh, Diana; Laakso, Markku; Lehtimäki, Terho; Levinson, Douglas F; Martin, Nicholas G; Metspalu, Andres; Morris, Andrew D; Nieminen, Markku S; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J; Ouwehand, Willem H; Palmer, Lyle J; Penninx, Brenda; Power, Chris; Province, Michael A; Psaty, Bruce M; Qi, Lu; Rauramaa, Rainer; Ridker, Paul M; Ripatti, Samuli; Salomaa, Veikko; Samani, Nilesh J; Snieder, Harold; Sørensen, Thorkild I A; Spector, Timothy D; Stefansson, Kari; Tönjes, Anke; Tuomilehto, Jaakko; Uitterlinden, André G; Uusitupa, Matti; van der Harst, Pim; Vollenweider, Peter; Wallaschofski, Henri; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Wilson, James F; Abecasis, Goncalo R; Assimes, Themistocles L; Barroso, Inês; Boehnke, Michael; Borecki, Ingrid B; Deloukas, Panos; Fox, Caroline S; Frayling, Timothy; Groop, Leif C; Haritunian, Talin; Heid, Iris M; Hunter, David; Kaplan, Robert C; Karpe, Fredrik; Moffatt, Miriam F; Mohlke, Karen L; O'Connell, Jeffrey R; Pawitan, Yudi; Schadt, Eric E; Schlessinger, David; Steinthorsdottir, Valgerdur; Strachan, David P; Thorsteinsdottir, Unnur; van Duijn, Cornelia M; Visscher, Peter M; Di Blasio, Anna Maria; Hirschhorn, Joel N; Lindgren, Cecilia M; Morris, Andrew P; Meyre, David; Scherag, André; McCarthy, Mark I; Speliotes, Elizabeth K; North, Kari E; Loos, Ruth J F; Ingelsson, Erik

    Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass

  1. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

    NARCIS (Netherlands)

    Berndt, Sonja I.; Gustafsson, Stefan; Mägi, Reedik; Ganna, Andrea; Wheeler, Eleanor; Feitosa, Mary F.; Justice, Anne E.; Monda, Keri L.; Croteau-Chonka, Damien C.; Day, Felix R.; Esko, Tõnu; Fall, Tove; Ferreira, Teresa; Gentilini, Davide; Jackson, Anne U.; Luan, Jian'an; Randall, Joshua C.; Vedantam, Sailaja; Willer, Cristen J.; Winkler, Thomas W.; Wood, Andrew R.; Workalemahu, Tsegaselassie; Hu, Yi-Juan; Lee, Sang Hong; Liang, Liming; Lin, Dan-Yu; Min, Josine L.; Neale, Benjamin M.; Thorleifsson, Gudmar; Yang, Jian; Albrecht, Eva; Amin, Najaf; Bragg-Gresham, Jennifer L.; Cadby, Gemma; den Heijer, Martin; Eklund, Niina; Fischer, Krista; Goel, Anuj; Hottenga, Jouke-Jan; Huffman, Jennifer E.; Jarick, Ivonne; Johansson, Asa; Johnson, Toby; Kanoni, Stavroula; Kleber, Marcus E.; König, Inke R.; Kristiansson, Kati; Kutalik, Zoltán; Lamina, Claudia; Lecoeur, Cecile; Li, Guo; Mangino, Massimo; McArdle, Wendy L.; Medina-Gomez, Carolina; Müller-Nurasyid, Martina; Ngwa, Julius S.; Nolte, Ilja M.; Paternoster, Lavinia; Pechlivanis, Sonali; Perola, Markus; Peters, Marjolein J.; Preuss, Michael; Rose, Lynda M.; Shi, Jianxin; Shungin, Dmitry; Smith, Albert Vernon; Strawbridge, Rona J.; Surakka, Ida; Teumer, Alexander; Trip, Mieke D.; Tyrer, Jonathan; van Vliet-Ostaptchouk, Jana V.; Vandenput, Liesbeth; Waite, Lindsay L.; Zhao, Jing Hua; Absher, Devin; Asselbergs, Folkert W.; Atalay, Mustafa; Attwood, Antony P.; Balmforth, Anthony J.; Basart, Hanneke; Beilby, John; Bonnycastle, Lori L.; Brambilla, Paolo; Bruinenberg, Marcel; Campbell, Harry; Chasman, Daniel I.; Chines, Peter S.; Collins, Francis S.; Connell, John M.; Cookson, William O.; de Faire, Ulf; de Vegt, Femmie; dei, Mariano; Dimitriou, Maria; Edkins, Sarah; Estrada, Karol; Evans, David M.; Farrall, Martin; Ferrario, Marco M.; Ferrières, Jean; Franke, Lude; Frau, Francesca; Gejman, Pablo V.; Grallert, Harald; Grönberg, Henrik; Gudnason, Vilmundur; Hall, Alistair S.; Hall, Per; Hartikainen, Anna-Liisa; Hayward, Caroline; Heard-Costa, Nancy L.; Heath, Andrew C.; Hebebrand, Johannes; Homuth, Georg; Hu, Frank B.; Hunt, Sarah E.; Hyppönen, Elina; Iribarren, Carlos; Jacobs, Kevin B.; Jansson, John-Olov; Jula, Antti; Kähönen, Mika; Kathiresan, Sekar; Kee, Frank; Khaw, Kay-Tee; Kivimäki, Mika; Koenig, Wolfgang; Kraja, Aldi T.; Kumari, Meena; Kuulasmaa, Kari; Kuusisto, Johanna; Laitinen, Jaana H.; Lakka, Timo A.; Langenberg, Claudia; Launer, Lenore J.; Lind, Lars; Lindström, Jaana; Liu, Jianjun; Liuzzi, Antonio; Lokki, Marja-Liisa; Lorentzon, Mattias; Madden, Pamela A.; Magnusson, Patrik K.; Manunta, Paolo; Marek, Diana; März, Winfried; Mateo Leach, Irene; McKnight, Barbara; Medland, Sarah E.; Mihailov, Evelin; Milani, Lili; Montgomery, Grant W.; Mooser, Vincent; Mühleisen, Thomas W.; Munroe, Patricia B.; Musk, Arthur W.; Narisu, Narisu; Navis, Gerjan; Nicholson, George; Nohr, Ellen A.; Ong, Ken K.; Oostra, Ben A.; Palmer, Colin N. A.; Palotie, Aarno; Peden, John F.; Pedersen, Nancy; Peters, Annette; Polasek, Ozren; Pouta, Anneli; Pramstaller, Peter P.; Prokopenko, Inga; Pütter, Carolin; Radhakrishnan, Aparna; Raitakari, Olli; Rendon, Augusto; Rivadeneira, Fernando; Rudan, Igor; Saaristo, Timo E.; Sambrook, Jennifer G.; Sanders, Alan R.; Sanna, Serena; Saramies, Jouko; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Shin, So-Youn; Signorini, Stefano; Sinisalo, Juha; Skrobek, Boris; Soranzo, Nicole; Stančáková, Alena; Stark, Klaus; Stephens, Jonathan C.; Stirrups, Kathleen; Stolk, Ronald P.; Stumvoll, Michael; Swift, Amy J.; Theodoraki, Eirini V.; Thorand, Barbara; Tregouet, David-Alexandre; Tremoli, Elena; van der Klauw, Melanie M.; van Meurs, Joyce B. J.; Vermeulen, Sita H.; Viikari, Jorma; Virtamo, Jarmo; Vitart, Veronique; Waeber, Gérard; Wang, Zhaoming; Widén, Elisabeth; Wild, Sarah H.; Willemsen, Gonneke; Winkelmann, Bernhard R.; Witteman, Jacqueline C. M.; Wolffenbuttel, Bruce H. R.; Wong, Andrew; Wright, Alan F.; Zillikens, M. Carola; Amouyel, Philippe; Boehm, Bernhard O.; Boerwinkle, Eric; Boomsma, Dorret I.; Caulfield, Mark J.; Chanock, Stephen J.; Cupples, L. Adrienne; Cusi, Daniele; Dedoussis, George V.; Erdmann, Jeanette; Eriksson, Johan G.; Franks, Paul W.; Froguel, Philippe; Gieger, Christian; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hengstenberg, Christian; Hicks, Andrew A.; Hingorani, Aroon; Hinney, Anke; Hofman, Albert; Hovingh, Kees G.; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Keinanen-Kiukaanniemi, Sirkka M.; Kiemeney, Lambertus A.; Kuh, Diana; Laakso, Markku; Lehtimäki, Terho; Levinson, Douglas F.; Martin, Nicholas G.; Metspalu, Andres; Morris, Andrew D.; Nieminen, Markku S.; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J.; Ouwehand, Willem H.; Palmer, Lyle J.; Penninx, Brenda; Power, Chris; Province, Michael A.; Psaty, Bruce M.; Qi, Lu; Rauramaa, Rainer; Ridker, Paul M.; Ripatti, Samuli; Salomaa, Veikko; Samani, Nilesh J.; Snieder, Harold; Sørensen, Thorkild I. A.; Spector, Timothy D.; Stefansson, Kari; Tönjes, Anke; Tuomilehto, Jaakko; Uitterlinden, André G.; Uusitupa, Matti; van der Harst, Pim; Vollenweider, Peter; Wallaschofski, Henri; Wareham, Nicholas J.; Watkins, Hugh; Wichmann, H.-Erich; Wilson, James F.; Abecasis, Goncalo R.; Assimes, Themistocles L.; Barroso, Inês; Boehnke, Michael; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Frayling, Timothy; Groop, Leif C.; Haritunian, Talin; Heid, Iris M.; Hunter, David; Kaplan, Robert C.; Karpe, Fredrik; Moffatt, Miriam F.; Mohlke, Karen L.; O'Connell, Jeffrey R.; Pawitan, Yudi; Schadt, Eric E.; Schlessinger, David; Steinthorsdottir, Valgerdur; Strachan, David P.; Thorsteinsdottir, Unnur; van Duijn, Cornelia M.; Visscher, Peter M.; Di Blasio, Anna Maria; Hirschhorn, Joel N.; Lindgren, Cecilia M.; Morris, Andrew P.; Meyre, David; Scherag, André; McCarthy, Mark I.; Speliotes, Elizabeth K.; North, Kari E.; Loos, Ruth J. F.; Ingelsson, Erik

    2013-01-01

    Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass

  2. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

    DEFF Research Database (Denmark)

    Berndt, Sonja I; Gustafsson, Stefan; Mägi, Reedik

    2013-01-01

    Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass ...

  3. Cell–cell signaling drives the evolution of complex traits: introduction—lung evo-devo

    Science.gov (United States)

    Torday, John S.; Rehan, V. K.

    2009-01-01

    an evolutionary vertical integration of cell-to-tissue-to-organ-to-physiology of intrinsic cell–cell signaling and extrinsic factors is the reverse of the “top-down” conventional way in which physiologic systems are usually regarded. This novel mechanistic approach, incorporating a “middle-out” cell–cell signaling component, will lead to a readily available algorithm for integrating genes and phenotypes. This symposium surveyed the phylogenetic origins of such vertically integrated mechanisms for the evolution of cell–cell communication as the basis for complex physiologic traits, from sponges to man. PMID:20607136

  4. Ethics in Publishing: Complexity Science and Human Factors Offer Insights to Develop a Just Culture.

    Science.gov (United States)

    Saurin, Tarcisio Abreu

    2016-12-01

    While ethics in publishing has been increasingly debated, there seems to be a lack of a theoretical framework for making sense of existing rules of behavior as well as for designing, managing and enforcing such rules. This letter argues that systems-oriented disciplines, such as complexity science and human factors, offer insights into new ways of dealing with ethics in publishing. Some examples of insights are presented. Also, a call is made for empirical studies that unveil the context and details of both retracted papers and the process of writing and publishing academic papers. This is expected to shed light on the complexity of the publication system as well as to support the development of a just culture, in which all participants are accountable.

  5. HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease.

    Science.gov (United States)

    Ward, Lucas D; Kellis, Manolis

    2016-01-04

    More than 90% of common variants associated with complex traits do not affect proteins directly, but instead the circuits that control gene expression. This has increased the urgency of understanding the regulatory genome as a key component for translating genetic results into mechanistic insights and ultimately therapeutics. To address this challenge, we developed HaploReg (http://compbio.mit.edu/HaploReg) to aid the functional dissection of genome-wide association study (GWAS) results, the prediction of putative causal variants in haplotype blocks, the prediction of likely cell types of action, and the prediction of candidate target genes by systematic mining of comparative, epigenomic and regulatory annotations. Since first launching the website in 2011, we have greatly expanded HaploReg, increasing the number of chromatin state maps to 127 reference epigenomes from ENCODE 2012 and Roadmap Epigenomics, incorporating regulator binding data, expanding regulatory motif disruption annotations, and integrating expression quantitative trait locus (eQTL) variants and their tissue-specific target genes from GTEx, Geuvadis, and other recent studies. We present these updates as HaploReg v4, and illustrate a use case of HaploReg for attention deficit hyperactivity disorder (ADHD)-associated SNPs with putative brain regulatory mechanisms. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Identification of candidate genes for dissecting complex branch number trait in chickpea.

    Science.gov (United States)

    Bajaj, Deepak; Upadhyaya, Hari D; Das, Shouvik; Kumar, Vinod; Gowda, C L L; Sharma, Shivali; Tyagi, Akhilesh K; Parida, Swarup K

    2016-04-01

    The present study exploited integrated genomics-assisted breeding strategy for genetic dissection of complex branch number quantitative trait in chickpea. Candidate gene-based association analysis in a branch number association panel was performed by utilizing the genotyping data of 401 SNP allelic variants mined from 27 known cloned branch number gene orthologs of chickpea. The genome-wide association study (GWAS) integrating both genome-wide GBS- (4556 SNPs) and candidate gene-based genotyping information of 4957 SNPs in a structured population of 60 sequenced desi and kabuli accessions (with 350-400 kb LD decay), detected 11 significant genomic loci (genes) associated (41% combined PVE) with branch number in chickpea. Of these, seven branch number-associated genes were further validated successfully in two inter (ICC 4958 × ICC 17160)- and intra (ICC 12299 × ICC 8261)-specific mapping populations. The axillary meristem and shoot apical meristem-specific expression, including differential up- and down-regulation (4-5 fold) of the validated seven branch number-associated genes especially in high branch number as compared to the low branch number-containing parental accessions and homozygous individuals of two aforesaid mapping populations was apparent. Collectively, this combinatorial genomic approach delineated diverse naturally occurring novel functional SNP allelic variants in seven potential known/candidate genes [PIN1 (PIN-FORMED protein 1), TB1 (teosinte branched 1), BA1/LAX1 (BARREN STALK1/LIKE AUXIN1), GRAS8 (gibberellic acid insensitive/GAI, Repressor of ga13/RGA and Scarecrow8/SCR8), ERF (ethylene-responsive element-binding factor), MAX2 (more axillary growth 2) and lipase] governing chickpea branch number. The useful information generated from this study have potential to expedite marker-assisted genetic enhancement by developing high-yielding cultivars with more number of productive (pods and seeds) branches in chickpea. Copyright © 2016 Elsevier

  7. Conventional and phenomics characterization provides insight into the diversity and relationships of hypervariable scarlet (Solanum aethiopicum L. and gboma (S. macrocarpon L. eggplant complexes

    Directory of Open Access Journals (Sweden)

    Mariola ePlazas

    2014-07-01

    Full Text Available Scarlet (Solanum aethiopicum and gboma (S. macrocarpon eggplants are major vegetable crops in sub-Saharan Africa. Together with their respective wild ancestors (S. anguivi and S. dasyphyllum and intermediate cultivated-wild forms they constitute the so-called scarlet and gboma eggplant complexes. We used conventional descriptors and the high-throughput phenomics tool Tomato Analyzer for characterizing 63 accessions of the scarlet eggplant complex, including the four S. aethiopicum cultivar groups (Aculeatum, Gilo, Kumba, and Shum, Intermediate S. aethiopicum-S. anguivi forms, and S. anguivi, and 12 cultivated and wild accessions of the gboma eggplant complex. A large diversity was found between both complexes, showing that they are very well differentiated from each other. Within the scarlet eggplant complex, many significant differences were also found among cultivar groups, but more differences were found for fruit traits evaluated with Tomato Analyzer than with conventional descriptors. In particular, Tomato Analyzer phenomics characterization was useful for distinguishing small fruited groups (Shum, Intermediate, and S. anguivi, as well as groups for which few or no significant differences were observed for plant traits. Multivariate principal components analysis (PCA separated well all groups, except the Intermediate group which plotted between S. anguivi and small fruited S. aethiopicum accessions. For the gboma eggplant complex, S. dasyphyllum was clearly distinguished from S. macrocarpon and an important diversity was found in the latter. The results have shown that both complexes are hypervariable and have provided insight into their diversity and relationships. The information obtained has important implications for the conservation and management of genetic resources as well as for the selection and breeding of both scarlet and gboma eggplants.

  8. Studies on fluctuating asymmetry (FA for certain morphological traits in four species of the Drosophila bipectinata complex

    Directory of Open Access Journals (Sweden)

    Banerjee Parul

    2015-01-01

    Full Text Available Fluctuating asymmetry (FA is defined as subtle deviations from perfect bilateral symmetry, evident in differences between the right and the left sides of any given trait. It is a pattern of variation between sides and measures developmental instability. Differences in the level of FA may be used for comparing developmental precision among closely related species and thus may give an idea whether developmental stability was affected during the divergence and separation of populations into distinct species. Keeping this in view, FA was studied in four species of the Drosophila bipectinata complex i.e. D. bipectinata, D. parabipectinata, D. malerkotliana and D. pseudoananassae. In females of all the four species, FA values did not vary significantly for any of the traits considered. However, in case of males, they varied significantly for Wing length (WL and sex comb tooth number (SCTN. Also, while in females Composite fluctuating asymmetry (CFA did not exhibit significant variation, in males it was found to vary significantly across the four species. However, Bonferroni t-tests did not reveal any consistent difference in FA levels between any two species. The magnitude of FA was found to differ significantly among traits and CFA values were found to be higher for males than females in all the four species. Therefore, it may be concluded that the level of FA shows trait specific variations and males are more prone to developmental perturbations. However, the FA levels are more or less similar in all the four species of this complex. Thus, developmental precision remains nearly same in all the four species of this complex irrespective of the degree of evolutionary divergence reached.

  9. Towards reconstructing herbaceous biome dynamics and associated precipitation in Africa: insights from the classification of grass morphological traits

    Science.gov (United States)

    Pasturel, Marine; Alexandre, Anne; Novello, Alice; Moctar Dieye, Amadou; Wele, Abdoulaye; Paradis, Laure; Hely, Christelle

    2014-05-01

    Inter-tropical herbaceous ecosystems occupy a 1/5th of terrestrial surface, a half of the African continent, and are expected to extend in the next decades. Dynamic of these ecosystems is simulated with poor accuracy by Dynamic Global Vegetation Models (DGVMs). One of the bias results from the fact that the diversity of the grass layer dominating these herbaceous ecosystems is poorly taken into account. Mean annual precipitation and the length of the dry season are the main constrains of the dynamics of these ecosystems. Conversely, changes in vegetation affect the water cycle. Inaccuracy in herbaceous ecosystem simulation thus impacts simulations of the water cycle (including precipitation) and vice versa. In order to increase our knowledge of the relationships between grass morphological traits, taxonomy, biomes and climatic niches in Western and South Africa, a 3-step methodology was followed: i) values of culm height, leaf length and width of dominant grass species from Senegal were gathered from flora and clustered using the Partition Around Medoids (PAM) method; ii) trait group ability to sign climatic domains and biomes was assessed using Kruskal-Wallis tests; iii) genericity and robustness of the trait groups were evaluated through their application to Chadian and South African botanical datasets. Results show that 8 grass trait groups are present either in Senegal, Chad or South Africa. These 8 trait groups are distributed along mean annual precipitation and dry season length gradients. The combination of three of them allow to discriminate mean annual precipitation domains (1000 mm) and herbaceous biomes (steppes, savannas, South African grasslands and Nama-Karoo). With these results in hand, grass Plant Functional Types (PFTs) of the DGMV LPJ-GUESS will be re-parameterized and particular attention will be given to the herbaceous biomass assigned to each grass trait group. Simultaneously, relationships between grass trait groups and phytolith vegetation

  10. Comparison of gene-based rare variant association mapping methods for quantitative traits in a bovine population with complex familial relationships

    NARCIS (Netherlands)

    Zhang, Qianqian; Guldbrandtsen, Bernt; Calus, Mario P.L.; Lund, Mogens Sandø; Sahana, Goutam

    2016-01-01

    Background: There is growing interest in the role of rare variants in the variation of complex traits due to increasing evidence that rare variants are associated with quantitative traits. However, association methods that are commonly used for mapping common variants are not effective to map

  11. Biological and Psychosocial Processes in the Development of Children’s Appetitive Traits: Insights from Developmental Theory and Research

    Directory of Open Access Journals (Sweden)

    Catherine G. Russell

    2018-05-01

    Full Text Available There has been increasing concern expressed about children’s food intakes and dietary patterns. These are closely linked to children’s appetitive traits (such as disinhibited eating and food fussiness/neophobia. Research has examined both biological and psychosocial correlates or predictors of these traits. There has been less focus on possible processes or mechanisms associated with children’s development of these traits and research that links biological and psychosocial factors. There is an absence of research that links biological and psychosocial factors. In the present article, we outline a model intended to facilitate theory and research on the development of appetitive traits. It is based on scholarship from developmental theory and research and incorporates biological factors such as genetic predispositions and temperament as well as psychosocial factors in terms of parent cognitions, feeding styles and feeding practices. Particular attention is directed to aspects such as emotional eating and feeding, self-regulation of energy intake, and non-shared family environments. We highlight the opportunity for longitudinal research that examines bidirectional, transactional and cascade processes and uses a developmental framework. The model provides a basis for connecting the biological foundations of appetitive traits to system-level analysis in the family. Knowledge generated through the application of the model should lead to more effective prevention and intervention initiatives.

  12. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

    Science.gov (United States)

    Berndt, Sonja I.; Gustafsson, Stefan; Mägi, Reedik; Ganna, Andrea; Wheeler, Eleanor; Feitosa, Mary F.; Justice, Anne E.; Monda, Keri L.; Croteau-Chonka, Damien C.; Day, Felix R.; Esko, Tõnu; Fall, Tove; Ferreira, Teresa; Gentilini, Davide; Jackson, Anne U.; Luan, Jian’an; Randall, Joshua C.; Vedantam, Sailaja; Willer, Cristen J.; Winkler, Thomas W.; Wood, Andrew R.; Workalemahu, Tsegaselassie; Hu, Yi-Juan; Lee, Sang Hong; Liang, Liming; Lin, Dan-Yu; Min, Josine L.; Neale, Benjamin M.; Thorleifsson, Gudmar; Yang, Jian; Albrecht, Eva; Amin, Najaf; Bragg-Gresham, Jennifer L.; Cadby, Gemma; den Heijer, Martin; Eklund, Niina; Fischer, Krista; Goel, Anuj; Hottenga, Jouke-Jan; Huffman, Jennifer E.; Jarick, Ivonne; Johansson, Åsa; Johnson, Toby; Kanoni, Stavroula; Kleber, Marcus E.; König, Inke R.; Kristiansson, Kati; Kutalik, Zoltán; Lamina, Claudia; Lecoeur, Cecile; Li, Guo; Mangino, Massimo; McArdle, Wendy L.; Medina-Gomez, Carolina; Müller-Nurasyid, Martina; Ngwa, Julius S.; Nolte, Ilja M.; Paternoster, Lavinia; Pechlivanis, Sonali; Perola, Markus; Peters, Marjolein J.; Preuss, Michael; Rose, Lynda M.; Shi, Jianxin; Shungin, Dmitry; Smith, Albert Vernon; Strawbridge, Rona J.; Surakka, Ida; Teumer, Alexander; Trip, Mieke D.; Tyrer, Jonathan; Van Vliet-Ostaptchouk, Jana V.; Vandenput, Liesbeth; Waite, Lindsay L.; Zhao, Jing Hua; Absher, Devin; Asselbergs, Folkert W.; Atalay, Mustafa; Attwood, Antony P.; Balmforth, Anthony J.; Basart, Hanneke; Beilby, John; Bonnycastle, Lori L.; Brambilla, Paolo; Bruinenberg, Marcel; Campbell, Harry; Chasman, Daniel I.; Chines, Peter S.; Collins, Francis S.; Connell, John M.; Cookson, William; de Faire, Ulf; de Vegt, Femmie; Dei, Mariano; Dimitriou, Maria; Edkins, Sarah; Estrada, Karol; Evans, David M.; Farrall, Martin; Ferrario, Marco M.; Ferrières, Jean; Franke, Lude; Frau, Francesca; Gejman, Pablo V.; Grallert, Harald; Grönberg, Henrik; Gudnason, Vilmundur; Hall, Alistair S.; Hall, Per; Hartikainen, Anna-Liisa; Hayward, Caroline; Heard-Costa, Nancy L.; Heath, Andrew C.; Hebebrand, Johannes; Homuth, Georg; Hu, Frank B.; Hunt, Sarah E.; Hyppönen, Elina; Iribarren, Carlos; Jacobs, Kevin B.; Jansson, John-Olov; Jula, Antti; Kähönen, Mika; Kathiresan, Sekar; Kee, Frank; Khaw, Kay-Tee; Kivimaki, Mika; Koenig, Wolfgang; Kraja, Aldi T.; Kumari, Meena; Kuulasmaa, Kari; Kuusisto, Johanna; Laitinen, Jaana H.; Lakka, Timo A.; Langenberg, Claudia; Launer, Lenore J.; Lind, Lars; Lindström, Jaana; Liu, Jianjun; Liuzzi, Antonio; Lokki, Marja-Liisa; Lorentzon, Mattias; Madden, Pamela A.; Magnusson, Patrik K.; Manunta, Paolo; Marek, Diana; März, Winfried; Mateo Leach, Irene; McKnight, Barbara; Medland, Sarah E.; Mihailov, Evelin; Milani, Lili; Montgomery, Grant W.; Mooser, Vincent; Mühleisen, Thomas W.; Munroe, Patricia B.; Musk, Arthur W.; Narisu, Narisu; Navis, Gerjan; Nicholson, George; Nohr, Ellen A.; Ong, Ken K.; Oostra, Ben A.; Palmer, Colin N.A.; Palotie, Aarno; Peden, John F.; Pedersen, Nancy; Peters, Annette; Polasek, Ozren; Pouta, Anneli; Pramstaller, Peter P.; Prokopenko, Inga; Pütter, Carolin; Radhakrishnan, Aparna; Raitakari, Olli; Rendon, Augusto; Rivadeneira, Fernando; Rudan, Igor; Saaristo, Timo E.; Sambrook, Jennifer G.; Sanders, Alan R.; Sanna, Serena; Saramies, Jouko; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Shin, So-Youn; Signorini, Stefano; Sinisalo, Juha; Skrobek, Boris; Soranzo, Nicole; Stančáková, Alena; Stark, Klaus; Stephens, Jonathan C.; Stirrups, Kathleen; Stolk, Ronald P.; Stumvoll, Michael; Swift, Amy J.; Theodoraki, Eirini V.; Thorand, Barbara; Tregouet, David-Alexandre; Tremoli, Elena; Van der Klauw, Melanie M.; van Meurs, Joyce B.J.; Vermeulen, Sita H.; Viikari, Jorma; Virtamo, Jarmo; Vitart, Veronique; Waeber, Gérard; Wang, Zhaoming; Widén, Elisabeth; Wild, Sarah H.; Willemsen, Gonneke; Winkelmann, Bernhard R.; Witteman, Jacqueline C.M.; Wolffenbuttel, Bruce H.R.; Wong, Andrew; Wright, Alan F.; Zillikens, M. Carola; Amouyel, Philippe; Boehm, Bernhard O.; Boerwinkle, Eric; Boomsma, Dorret I.; Caulfield, Mark J.; Chanock, Stephen J.; Cupples, L. Adrienne; Cusi, Daniele; Dedoussis, George V.; Erdmann, Jeanette; Eriksson, Johan G.; Franks, Paul W.; Froguel, Philippe; Gieger, Christian; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hengstenberg, Christian; Hicks, Andrew A.; Hingorani, Aroon; Hinney, Anke; Hofman, Albert; Hovingh, Kees G.; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Keinanen-Kiukaanniemi, Sirkka M.; Kiemeney, Lambertus A.; Kuh, Diana; Laakso, Markku; Lehtimäki, Terho; Levinson, Douglas F.; Martin, Nicholas G.; Metspalu, Andres; Morris, Andrew D.; Nieminen, Markku S.; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J.; Ouwehand, Willem H.; Palmer, Lyle J.; Penninx, Brenda; Power, Chris; Province, Michael A.; Psaty, Bruce M.; Qi, Lu; Rauramaa, Rainer; Ridker, Paul M.; Ripatti, Samuli; Salomaa, Veikko; Samani, Nilesh J.; Snieder, Harold; Sørensen, Thorkild I.A.; Spector, Timothy D.; Stefansson, Kari; Tönjes, Anke; Tuomilehto, Jaakko; Uitterlinden, André G.; Uusitupa, Matti; van der Harst, Pim; Vollenweider, Peter; Wallaschofski, Henri; Wareham, Nicholas J.; Watkins, Hugh; Wichmann, H.-Erich; Wilson, James F.; Abecasis, Goncalo R.; Assimes, Themistocles L.; Barroso, Inês; Boehnke, Michael; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Frayling, Timothy; Groop, Leif C.; Haritunian, Talin; Heid, Iris M.; Hunter, David; Kaplan, Robert C.; Karpe, Fredrik; Moffatt, Miriam; Mohlke, Karen L.; O’Connell, Jeffrey R.; Pawitan, Yudi; Schadt, Eric E.; Schlessinger, David; Steinthorsdottir, Valgerdur; Strachan, David P.; Thorsteinsdottir, Unnur; van Duijn, Cornelia M.; Visscher, Peter M.; Di Blasio, Anna Maria; Hirschhorn, Joel N.; Lindgren, Cecilia M.; Morris, Andrew P.; Meyre, David; Scherag, André; McCarthy, Mark I.; Speliotes, Elizabeth K.; North, Kari E.; Loos, Ruth J.F.; Ingelsson, Erik

    2014-01-01

    Approaches exploiting extremes of the trait distribution may reveal novel loci for common traits, but it is unknown whether such loci are generalizable to the general population. In a genome-wide search for loci associated with upper vs. lower 5th percentiles of body mass index, height and waist-hip ratio, as well as clinical classes of obesity including up to 263,407 European individuals, we identified four new loci (IGFBP4, H6PD, RSRC1, PPP2R2A) influencing height detected in the tails and seven new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3, ZZZ3) for clinical classes of obesity. Further, we show that there is large overlap in terms of genetic structure and distribution of variants between traits based on extremes and the general population and little etiologic heterogeneity between obesity subgroups. PMID:23563607

  13. The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

    NARCIS (Netherlands)

    Astle, William J.; Elding, Heather; Jiang, Tao; Allen, Dave; Ruklisa, Dace; Mann, Alice L.; Mead, Daniel; Bouman, Heleen; Riveros-Mckay, Fernando; Kostadima, Myrto A.; Lambourne, John J.; Sivapalaratnam, Suthesh; Downes, Kate; Kundu, Kousik; Bomba, Lorenzo; Berentsen, Kim; Bradley, John R.; Daugherty, Louise C.; Delaneau, Olivier; Freson, Kathleen; Garner, Stephen F.; Grassi, Luigi; Guerrero, Jose; Haimel, Matthias; Janssen-Megens, Eva M.; Kaan, Anita; Kamat, Mihir; Kim, Bowon; Mandoli, Amit; Marchini, Jonathan; Martens, Joost H. A.; Meacham, Stuart; Megy, Karyn; O'Connell, Jared; Petersen, Romina; Sharifi, Nilofar; Sheard, Simon M.; Staley, James R.; Tuna, Salih; van der Ent, Martijn; Walter, Klaudia; Wang, Shuang-Yin; Wheeler, Eleanor; Wilder, Steven P.; Iotchkova, Valentina; Moore, Carmel; Sambrook, Jennifer; Stunnenberg, Hendrik G.; Di Angelantonio, Emanuele; Kaptoge, Stephen; Kuijpers, Taco W.; Carrillo-de-Santa-Pau, Enrique; Juan, David; Rico, Daniel; Valencia, Alfonso; Chen, Lu; Ge, Bing; Vasquez, Louella; Kwan, Tony; Garrido-Martín, Diego; Watt, Stephen; Yang, Ying; Guigo, Roderic; Beck, Stephan; Paul, Dirk S.; Pastinen, Tomi; Bujold, David; Bourque, Guillaume; Frontini, Mattia; Danesh, John; Roberts, David J.; Ouwehand, Willem H.; Butterworth, Adam S.; Soranzo, Nicole

    2016-01-01

    Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell,

  14. Complex pedigree analysis to detect quantitative trait loci in dairy cattle

    NARCIS (Netherlands)

    Bink, M.C.A.M.

    1998-01-01

    In dairy cattle, many quantitative traits of economic importance show phenotypic variation. For breeding purposes the analysis of this phenotypic variation and uncovering the contribution of genetic factors is very important. Usually, the individual gene effects contributing to the

  15. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    DEFF Research Database (Denmark)

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes...

  16. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    NARCIS (Netherlands)

    Scott, Robert A.; Lagou, Vasiliki; Welch, Ryan P.; Wheeler, Eleanor; Montasser, May E.; Luan, Jian'an; Mägi, Reedik; Strawbridge, Rona J.; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J.; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C. D.; Jukema, J. Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V.; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J.; Evans, David M.; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S.; Hui, Jennie; Bielak, Lawrence F.; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O'Connell, Jeffrey R.; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tõnu; Mihailov, Evelin; Fraser, Ross M.; Fall, Tove; Voight, Benjamin F.; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M.; Morris, Andrew P.; Rayner, Nigel W.; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S.; Willems, Sara M.; Chines, Peter S.; Jackson, Anne U.; Kang, Hyun Min; Stringham, Heather M.; Song, Kijoung; Tanaka, Toshiko; Peden, John F.; Goel, Anuj; Hicks, Andrew A.; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J.; Bruinenberg, Marcel; Pankow, James S.; North, Kari E.; Forouhi, Nita G.; Loos, Ruth J. F.; Edkins, Sarah; Varga, Tibor V.; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J. L.; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B.; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L.; Rivadeneira, Fernando; Uitterlinden, Andre G.; Palmer, Colin N. A.; Doney, Alex S. F.; Willemsen, Gonneke; Smit, Johannes H.; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L.; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L.; Fowkes, Gerard R.; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H.; Basart, Hanneke V.; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E.; Boehm, Bernhard O.; Peters, Annette; Pramstaller, Peter P.; Province, Michael A.; Borecki, Ingrid B.; Hastie, Nicholas D.; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M.; Bergman, Richard N.; Collins, Francis S.; Tuomilehto, Jaakko; Watanabe, Richard M.; de Geus, Eco J. C.; Penninx, Brenda W.; Hofman, Albert; Oostra, Ben A.; Psaty, Bruce M.; Vollenweider, Peter; Wilson, James F.; Wright, Alan F.; Hovingh, G. Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K. E.; Kyvik, Kirsten O.; Kaprio, Jaakko; Price, Jackie F.; Dedoussis, George V.; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R.; van Duijn, Cornelia M.; Morris, Andrew D.; Toenjes, Anke; Peyser, Patricia A.; Beilby, John P.; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R.; Schwarz, Peter E. H.; Lakka, Timo A.; Rauramaa, Rainer; Adair, Linda S.; Smith, George Davey; Spector, Tim D.; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M.; Saaristo, Timo E.; Boomsma, Dorret I.; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L.; Sattar, Naveed; Harris, Tamara B.; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L.; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J.; Bouatia-Naji, Nabila; McCarthy, Mark I.; Franks, Paul W.; Meigs, James B.; Teslovich, Tanya M.; Florez, Jose C.; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes

  17. New insights into roles of acidocalcisomes and contractile vacuole complex in osmoregulation in protists.

    Science.gov (United States)

    Docampo, Roberto; Jimenez, Veronica; Lander, Noelia; Li, Zhu-Hong; Niyogi, Sayantanee

    2013-01-01

    While free-living protists are usually subjected to hyposmotic environments, parasitic protists are also in contact with hyperosmotic habitats. Recent work in one of these parasites, Trypanosoma cruzi, has revealed that its contractile vacuole complex, which usually collects and expels excess water as a mechanism of regulatory volume decrease after hyposmotic stress, has also a role in cell shrinking when the cells are submitted to hyperosmotic stress. Trypanosomes also have an acidic calcium store rich in polyphosphate (polyP), named the acidocalcisome, which is involved in their response to osmotic stress. Here, we review newly emerging insights on the role of acidocalcisomes and the contractile vacuole complex in the cellular response to hyposmotic and hyperosmotic stresses. We also review the current state of knowledge on the composition of these organelles and their other roles in calcium homeostasis and protein trafficking. © 2013, Elsevier Inc. All Rights Reserved.

  18. New Insights into the Roles of Acidocalcisomes and the Contractile Vacuole Complex in Osmoregulation in Protists

    Science.gov (United States)

    Docampo, Roberto; Jimenez, Veronica; Lander, Noelia; Li, Zhu-Hong; Niyogi, Sayantanee

    2013-01-01

    While free-living protists are usually subjected to hyposmotic environments, parasitic protists are also in contact with hyperosmotic habitats. Recent work in one of these parasites, Trypanosoma cruzi, has revealed that its contractile vacuole complex, which usually collects and expels excess water as a mechanism of regulatory volume decrease after hyposmotic stress, has also a role in cell shrinking when the cells are submitted to hyperosmotic stress. Trypanosomes also have an acidic calcium store rich in polyphosphate (polyP), named the acidocalcisome, which is involved in their response to osmotic stress. Here, we review newly emerging insights on the role of acidocalcisomes and the contractile vacuole complex in the cellular response to hyposmotic and hyperosmotic stresses. We also review the current state of knowledge on the composition of these organelles and their other roles in calcium homeostasis and protein trafficking. PMID:23890380

  19. Large-scale in silico mapping of complex quantitative traits in inbred mice.

    Directory of Open Access Journals (Sweden)

    Pengyuan Liu

    2007-07-01

    Full Text Available Understanding the genetic basis of common disease and disease-related quantitative traits will aid in the development of diagnostics and therapeutics. The processs of gene discovery can be sped up by rapid and effective integration of well-defined mouse genome and phenome data resources. We describe here an in silico gene-discovery strategy through genome-wide association (GWA scans in inbred mice with a wide range of genetic variation. We identified 937 quantitative trait loci (QTLs from a survey of 173 mouse phenotypes, which include models of human disease (atherosclerosis, cardiovascular disease, cancer and obesity as well as behavioral, hematological, immunological, metabolic, and neurological traits. 67% of QTLs were refined into genomic regions <0.5 Mb with approximately 40-fold increase in mapping precision as compared with classical linkage analysis. This makes for more efficient identification of the genes that underlie disease. We have identified two QTL genes, Adam12 and Cdh2, as causal genetic variants for atherogenic diet-induced obesity. Our findings demonstrate that GWA analysis in mice has the potential to resolve multiple tightly linked QTLs and achieve single-gene resolution. These high-resolution QTL data can serve as a primary resource for positional cloning and gene identification in the research community.

  20. Regression-based approach for testing the association between multi-region haplotype configuration and complex trait

    Directory of Open Access Journals (Sweden)

    Zhao Hongbo

    2009-09-01

    Full Text Available Abstract Background It is quite common that the genetic architecture of complex traits involves many genes and their interactions. Therefore, dealing with multiple unlinked genomic regions simultaneously is desirable. Results In this paper we develop a regression-based approach to assess the interactions of haplotypes that belong to different unlinked regions, and we use score statistics to test the null hypothesis of non-genetic association. Additionally, multiple marker combinations at each unlinked region are considered. The multiple tests are settled via the minP approach. The P value of the "best" multi-region multi-marker configuration is corrected via Monte-Carlo simulations. Through simulation studies, we assess the performance of the proposed approach and demonstrate its validity and power in testing for haplotype interaction association. Conclusion Our simulations showed that, for binary trait without covariates, our proposed methods prove to be equal and even more powerful than htr and hapcc which are part of the FAMHAP program. Additionally, our model can be applied to a wider variety of traits and allow adjustment for other covariates. To test the validity, our methods are applied to analyze the association between four unlinked candidate genes and pig meat quality.

  1. A power study of bivariate LOD score analysis of a complex trait and fear/discomfort with strangers.

    Science.gov (United States)

    Ji, Fei; Lee, Dayoung; Mendell, Nancy Role

    2005-12-30

    Complex diseases are often reported along with disease-related traits (DRT). Sometimes investigators consider both disease and DRT phenotypes separately and sometimes they consider individuals as affected if they have either the disease or the DRT, or both. We propose instead to consider the joint distribution of the disease and the DRT and do a linkage analysis assuming a pleiotropic model. We evaluated our results through analysis of the simulated datasets provided by Genetic Analysis Workshop 14. We first conducted univariate linkage analysis of the simulated disease, Kofendrerd Personality Disorder and one of its simulated associated traits, phenotype b (fear/discomfort with strangers). Subsequently, we considered the bivariate phenotype, which combined the information on Kofendrerd Personality Disorder and fear/discomfort with strangers. We developed a program to perform bivariate linkage analysis using an extension to the Elston-Stewart peeling method of likelihood calculation. Using this program we considered the microsatellites within 30 cM of the gene pleiotropic for this simulated disease and DRT. Based on 100 simulations of 300 families we observed excellent power to detect linkage within 10 cM of the disease locus using the DRT and the bivariate trait.

  2. Genome-enabled Modeling of Microbial Biogeochemistry using a Trait-based Approach. Does Increasing Metabolic Complexity Increase Predictive Capabilities?

    Science.gov (United States)

    King, E.; Karaoz, U.; Molins, S.; Bouskill, N.; Anantharaman, K.; Beller, H. R.; Banfield, J. F.; Steefel, C. I.; Brodie, E.

    2015-12-01

    The biogeochemical functioning of ecosystems is shaped in part by genomic information stored in the subsurface microbiome. Cultivation-independent approaches allow us to extract this information through reconstruction of thousands of genomes from a microbial community. Analysis of these genomes, in turn, gives an indication of the organisms present and their functional roles. However, metagenomic analyses can currently deliver thousands of different genomes that range in abundance/importance, requiring the identification and assimilation of key physiologies and metabolisms to be represented as traits for successful simulation of subsurface processes. Here we focus on incorporating -omics information into BioCrunch, a genome-informed trait-based model that represents the diversity of microbial functional processes within a reactive transport framework. This approach models the rate of nutrient uptake and the thermodynamics of coupled electron donors and acceptors for a range of microbial metabolisms including heterotrophs and chemolithotrophs. Metabolism of exogenous substrates fuels catabolic and anabolic processes, with the proportion of energy used for cellular maintenance, respiration, biomass development, and enzyme production based upon dynamic intracellular and environmental conditions. This internal resource partitioning represents a trade-off against biomass formation and results in microbial community emergence across a fitness landscape. Biocrunch was used here in simulations that included organisms and metabolic pathways derived from a dataset of ~1200 non-redundant genomes reflecting a microbial community in a floodplain aquifer. Metagenomic data was directly used to parameterize trait values related to growth and to identify trait linkages associated with respiration, fermentation, and key enzymatic functions such as plant polymer degradation. Simulations spanned a range of metabolic complexities and highlight benefits originating from simulations

  3. Insights into bioassessment of marine pollution using body-size distinctness of planktonic ciliates based on a modified trait hierarchy.

    Science.gov (United States)

    Xu, Henglong; Jiang, Yong; Xu, Guangjian

    2016-06-15

    Based on a modified trait hierarchy of body-size units, the feasibility for bioassessment of water pollution using body-size distinctness of planktonic ciliates was studied in a semi-enclosed bay, northern China. An annual dataset was collected at five sampling stations within a gradient of heavy metal contaminants. Results showed that: (1) in terms of probability density, the body-size spectra of the ciliates represented significant differences among the five stations; (2) bootstrap average analysis demonstrated a spatial variation in body-size rank patterns in response to pollution stress due to heavy metals; and (3) the average body-size distinctness (Δz(+)) and variation in body-size distinctness (Λz(+)), based on the modified trait hierarchy, revealed a clear departure pattern from the expected body-size spectra in areas with pollutants. These results suggest that the body-size diversity measures based on the modified trait hierarchy of the ciliates may be used as a potential indicator of marine pollution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Insights into the development and evolution of exaggerated traits using de novo transcriptomes of two species of horned scarab beetles.

    Directory of Open Access Journals (Sweden)

    Ian A Warren

    Full Text Available Scarab beetles exhibit an astonishing variety of rigid exo-skeletal outgrowths, known as "horns". These traits are often sexually dimorphic and vary dramatically across species in size, shape, location, and allometry with body size. In many species, the horn exhibits disproportionate growth resulting in an exaggerated allometric relationship with body size, as compared to other traits, such as wings, that grow proportionately with body size. Depending on the species, the smallest males either do not produce a horn at all, or they produce a disproportionately small horn for their body size. While the diversity of horn shapes and their behavioural ecology have been reasonably well studied, we know far less about the proximate mechanisms that regulate horn growth. Thus, using 454 pyrosequencing, we generated transcriptome profiles, during horn growth and development, in two different scarab beetle species: the Asian rhinoceros beetle, Trypoxylus dichotomus, and the dung beetle, Onthophagus nigriventris. We obtained over half a million reads for each species that were assembled into over 6,000 and 16,000 contigs respectively. We combined these data with previously published studies to look for signatures of molecular evolution. We found a small subset of genes with horn-biased expression showing evidence for recent positive selection, as is expected with sexual selection on horn size. We also found evidence of relaxed selection present in genes that demonstrated biased expression between horned and horn-less morphs, consistent with the theory of developmental decoupling of phenotypically plastic traits.

  5. Environmental drivers defining linkages among life-history traits: mechanistic insights from a semiterrestrial amphipod subjected to macroscale gradients.

    Science.gov (United States)

    Gómez, Julio; Barboza, Francisco R; Defeo, Omar

    2013-10-01

    Determining the existence of interconnected responses among life-history traits and identifying underlying environmental drivers are recognized as key goals for understanding the basis of phenotypic variability. We studied potentially interconnected responses among senescence, fecundity, embryos size, weight of brooding females, size at maturity and sex ratio in a semiterrestrial amphipod affected by macroscale gradients in beach morphodynamics and salinity. To this end, multiple modelling processes based on generalized additive mixed models were used to deal with the spatio-temporal structure of the data obtained at 10 beaches during 22 months. Salinity was the only nexus among life-history traits, suggesting that this physiological stressor influences the energy balance of organisms. Different salinity scenarios determined shifts in the weight of brooding females and size at maturity, having consequences in the number and size of embryos which in turn affected sex determination and sex ratio at the population level. Our work highlights the importance of analysing field data to find the variables and potential mechanisms that define concerted responses among traits, therefore defining life-history strategies.

  6. Insights into the development and evolution of exaggerated traits using de novo transcriptomes of two species of horned scarab beetles.

    Science.gov (United States)

    Warren, Ian A; Vera, J Cristobal; Johns, Annika; Zinna, Robert; Marden, James H; Emlen, Douglas J; Dworkin, Ian; Lavine, Laura C

    2014-01-01

    Scarab beetles exhibit an astonishing variety of rigid exo-skeletal outgrowths, known as "horns". These traits are often sexually dimorphic and vary dramatically across species in size, shape, location, and allometry with body size. In many species, the horn exhibits disproportionate growth resulting in an exaggerated allometric relationship with body size, as compared to other traits, such as wings, that grow proportionately with body size. Depending on the species, the smallest males either do not produce a horn at all, or they produce a disproportionately small horn for their body size. While the diversity of horn shapes and their behavioural ecology have been reasonably well studied, we know far less about the proximate mechanisms that regulate horn growth. Thus, using 454 pyrosequencing, we generated transcriptome profiles, during horn growth and development, in two different scarab beetle species: the Asian rhinoceros beetle, Trypoxylus dichotomus, and the dung beetle, Onthophagus nigriventris. We obtained over half a million reads for each species that were assembled into over 6,000 and 16,000 contigs respectively. We combined these data with previously published studies to look for signatures of molecular evolution. We found a small subset of genes with horn-biased expression showing evidence for recent positive selection, as is expected with sexual selection on horn size. We also found evidence of relaxed selection present in genes that demonstrated biased expression between horned and horn-less morphs, consistent with the theory of developmental decoupling of phenotypically plastic traits.

  7. KMgene: a unified R package for gene-based association analysis for complex traits.

    Science.gov (United States)

    Yan, Qi; Fang, Zhou; Chen, Wei; Stegle, Oliver

    2018-02-09

    In this report, we introduce an R package KMgene for performing gene-based association tests for familial, multivariate or longitudinal traits using kernel machine (KM) regression under a generalized linear mixed model (GLMM) framework. Extensive simulations were performed to evaluate the validity of the approaches implemented in KMgene. http://cran.r-project.org/web/packages/KMgene. qi.yan@chp.edu or wei.chen@chp.edu. Supplementary data are available at Bioinformatics online. © The Author(s) 2018. Published by Oxford University Press.

  8. "Are we there yet?": Deciding when one has demonstrated specific genetic causation in complex diseases and quantitative traits.

    Science.gov (United States)

    Page, Grier P; George, Varghese; Go, Rodney C; Page, Patricia Z; Allison, David B

    2003-10-01

    Although mathematical relationships can be proven by deductive logic, biological relationships can only be inferred from empirical observations. This is a distinct disadvantage for those of us who strive to identify the genes involved in complex diseases and quantitative traits. If causation cannot be proven, however, what does constitute sufficient evidence for causation? The philosopher Karl Popper said, "Our belief in a hypothesis can have no stronger basis than our repeated unsuccessful critical attempts to refute it." We believe that to establish causation, as scientists, we must make a serious attempt to refute our own hypotheses and to eliminate all known sources of bias before association becomes causation. In addition, we suggest that investigators must provide sufficient data and evidence of their unsuccessful efforts to find any confounding biases. In this editorial, we discuss what "causation" means in the context of complex diseases and quantitative traits, and we suggest guidelines for steps that may be taken to address possible confounders of association before polymorphisms may be called "causative."

  9. Peptide biomarkers used for the selective breeding of a complex polygenic trait in honey bees.

    Science.gov (United States)

    Guarna, M Marta; Hoover, Shelley E; Huxter, Elizabeth; Higo, Heather; Moon, Kyung-Mee; Domanski, Dominik; Bixby, Miriam E F; Melathopoulos, Andony P; Ibrahim, Abdullah; Peirson, Michael; Desai, Suresh; Micholson, Derek; White, Rick; Borchers, Christoph H; Currie, Robert W; Pernal, Stephen F; Foster, Leonard J

    2017-08-21

    We present a novel way to select for highly polygenic traits. For millennia, humans have used observable phenotypes to selectively breed stronger or more productive livestock and crops. Selection on genotype, using single-nucleotide polymorphisms (SNPs) and genome profiling, is also now applied broadly in livestock breeding programs; however, selection on protein/peptide or mRNA expression markers has not yet been proven useful. Here we demonstrate the utility of protein markers to select for disease-resistant hygienic behavior in the European honey bee (Apis mellifera L.). Robust, mechanistically-linked protein expression markers, by integrating cis- and trans- effects from many genomic loci, may overcome limitations of genomic markers to allow for selection. After three generations of selection, the resulting marker-selected stock outperformed an unselected benchmark stock in terms of hygienic behavior, and had improved survival when challenged with a bacterial disease or a parasitic mite, similar to bees selected using a phenotype-based assessment for this trait. This is the first demonstration of the efficacy of protein markers for industrial selective breeding in any agricultural species, plant or animal.

  10. Efficient algorithms for multidimensional global optimization in genetic mapping of complex traits

    Directory of Open Access Journals (Sweden)

    Kajsa Ljungberg

    2010-10-01

    Full Text Available Kajsa Ljungberg1, Kateryna Mishchenko2, Sverker Holmgren11Division of Scientific Computing, Department of Information Technology, Uppsala University, Uppsala, Sweden; 2Department of Mathematics and Physics, Mälardalen University College, Västerås, SwedenAbstract: We present a two-phase strategy for optimizing a multidimensional, nonconvex function arising during genetic mapping of quantitative traits. Such traits are believed to be affected by multiple so called QTL, and searching for d QTL results in a d-dimensional optimization problem with a large number of local optima. We combine the global algorithm DIRECT with a number of local optimization methods that accelerate the final convergence, and adapt the algorithms to problem-specific features. We also improve the evaluation of the QTL mapping objective function to enable exploitation of the smoothness properties of the optimization landscape. Our best two-phase method is demonstrated to be accurate in at least six dimensions and up to ten times faster than currently used QTL mapping algorithms.Keywords: global optimization, QTL mapping, DIRECT 

  11. Limits to behavioral evolution: the quantitative genetics of a complex trait under directional selection.

    Science.gov (United States)

    Careau, Vincent; Wolak, Matthew E; Carter, Patrick A; Garland, Theodore

    2013-11-01

    Replicated selection experiments provide a powerful way to study how "multiple adaptive solutions" may lead to differences in the quantitative-genetic architecture of selected traits and whether this may translate into differences in the timing at which evolutionary limits are reached. We analyze data from 31 generations (n=17,988) of selection on voluntary wheel running in house mice. The rate of initial response, timing of selection limit, and height of the plateau varied significantly between sexes and among the four selected lines. Analyses of litter size and realized selection differentials seem to rule out counterposing natural selection as a cause of the selection limits. Animal-model analyses showed that although the additive genetic variance was significantly lower in selected than control lines, both before and after the limits, the decrease was not sufficient to explain the limits. Moreover, directional selection promoted a negative covariance between additive and maternal genetic variance over the first 10 generations. These results stress the importance of replication in selection studies of higher-level traits and highlight the fact that long-term predictions of response to selection are not necessarily expected to be linear because of the variable effects of selection on additive genetic variance and maternal effects. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  12. In Vivo fitness associated with high virulence in a vertebrate virus is a complex trait regulated by host entry, replication, and shedding

    Science.gov (United States)

    Wargo, Andrew R.; Kurath, Gael

    2011-01-01

    The relationship between pathogen fitness and virulence is typically examined by quantifying only one or two pathogen fitness traits. More specifically, it is regularly assumed that within-host replication, as a precursor to transmission, is the driving force behind virulence. In reality, many traits contribute to pathogen fitness, and each trait could drive the evolution of virulence in different ways. Here, we independently quantified four viral infection cycle traits, namely, host entry, within-host replication, within-host coinfection fitness, and shedding, in vivo, in the vertebrate virus Infectious hematopoietic necrosis virus (IHNV). We examined how each of these stages of the viral infection cycle contributes to the fitness of IHNV genotypes that differ in virulence in rainbow trout. This enabled us to determine how infection cycle fitness traits are independently associated with virulence. We found that viral fitness was independently regulated by each of the traits examined, with the largest impact on fitness being provided by within-host replication. Furthermore, the more virulent of the two genotypes of IHNV we used had advantages in all of the traits quantified. Our results are thus congruent with the assumption that virulence and within-host replication are correlated but suggest that infection cycle fitness is complex and that replication is not the only trait associated with virulence.

  13. Investigation of obsessive-compulsive disorder and assessment of obsessionality as a personality trait in patients with complex partial seizure

    Directory of Open Access Journals (Sweden)

    Banihashemian K

    2010-05-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Behavioral changes in patients with epilepsy could cause comorbid psychiatric disorders such as anxiety disorders. This study is concerned with investigation of obsessive-compulsive disorders and assessment of obsessionality as a personality trait in patients with complex partial seizure. "n"nMethods: Seventy six patients with complex partial seizure, 74 patients with generalized epilepsy that referred to Shiraz psychiatric professional center during three month (from July to September 2009, and 76 matched healthy controls were randomly selected and evaluated using the Yale-Brown obsessive compulsive scale (Y-BOCS, short form of Minnesota multiphasic personality inventory (MMPI and clinical interview. "n"nResults: Complex partial seizure and obsessive-compulsive disorder (%13.15 are significantly more prevalent than generalized seizure (%2.70 and than control groups (%1.31 (p<0.001, and mean of psychasthenia scale (Pt scale scores in patients with complex partial seizure is more than mean of Pt scores in generalized epilepsy and control groups (p<0.001. There is significant relationship between total score of Yale-Brown scale and Pt scale in MMPI (r=0.79, p<0.01."n"nConclusions: Patients with complex

  14. Microscopic insight into thermodynamics of conformational changes of SAP-SLAM complex in signal transduction cascade

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2017-04-01

    The signalling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, associate with SLAM-associated protein (SAP)-related molecules, composed of single SH2 domain architecture. SAP activates Src-family kinase Fyn after SLAM ligation, resulting in a SLAM-SAP-Fyn complex, where, SAP binds the Fyn SH3 domain that does not involve canonical SH3 or SH2 interactions. This demands insight into this SAP mediated signalling cascade. Thermodynamics of the conformational changes are extracted from the histograms of dihedral angles obtained from the all-atom molecular dynamics simulations of this structurally well characterized SAP-SLAM complex. The results incorporate the binding induced thermodynamic changes of individual amino acid as well as the secondary structural elements of the protein and the solvent. Stabilization of the peptide partially comes through a strong hydrogen bonding network with the protein, while hydrophobic interactions also play a significant role where the peptide inserts itself into a hydrophobic cavity of the protein. SLAM binding widens SAP's second binding site for Fyn, which is the next step in the signal transduction cascade. The higher stabilization and less fluctuation of specific residues of SAP in the Fyn binding site, induced by SAP-SLAM complexation, emerge as the key structural elements to trigger the recognition of SAP by the SH3 domain of Fyn. The thermodynamic quantification of the protein due to complexation not only throws deeper understanding in the established mode of SAP-SLAM interaction but also assists in the recognition of the relevant residues of the protein responsible for alterations in its activity.

  15. Using Models to Inform Policy: Insights from Modeling the Complexities of Global Polio Eradication

    Science.gov (United States)

    Thompson, Kimberly M.

    Drawing on over 20 years of experience modeling risks in complex systems, this talk will challenge SBP participants to develop models that provide timely and useful answers to critical policy questions when decision makers need them. The talk will include reflections on the opportunities and challenges associated with developing integrated models for complex problems and communicating their results effectively. Dr. Thompson will focus the talk largely on collaborative modeling related to global polio eradication and the application of system dynamics tools. After successful global eradication of wild polioviruses, live polioviruses will still present risks that could potentially lead to paralytic polio cases. This talk will present the insights of efforts to use integrated dynamic, probabilistic risk, decision, and economic models to address critical policy questions related to managing global polio risks. Using a dynamic disease transmission model combined with probabilistic model inputs that characterize uncertainty for a stratified world to account for variability, we find that global health leaders will face some difficult choices, but that they can take actions that will manage the risks effectively. The talk will emphasize the need for true collaboration between modelers and subject matter experts, and the importance of working with decision makers as partners to ensure the development of useful models that actually get used.

  16. Complex dynamics of our economic life on different scales: insights from search engine query data.

    Science.gov (United States)

    Preis, Tobias; Reith, Daniel; Stanley, H Eugene

    2010-12-28

    Search engine query data deliver insight into the behaviour of individuals who are the smallest possible scale of our economic life. Individuals are submitting several hundred million search engine queries around the world each day. We study weekly search volume data for various search terms from 2004 to 2010 that are offered by the search engine Google for scientific use, providing information about our economic life on an aggregated collective level. We ask the question whether there is a link between search volume data and financial market fluctuations on a weekly time scale. Both collective 'swarm intelligence' of Internet users and the group of financial market participants can be regarded as a complex system of many interacting subunits that react quickly to external changes. We find clear evidence that weekly transaction volumes of S&P 500 companies are correlated with weekly search volume of corresponding company names. Furthermore, we apply a recently introduced method for quantifying complex correlations in time series with which we find a clear tendency that search volume time series and transaction volume time series show recurring patterns.

  17. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    Science.gov (United States)

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian’an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O’Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tönu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have raised the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q fasting insulin showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional follow-up of these newly discovered loci will further improve our understanding of glycemic control. PMID:22885924

  18. Comparative genomics of plant-associated Pseudomonas spp.: insights into diversity and inheritance of traits involved in multitrophic interactions.

    Directory of Open Access Journals (Sweden)

    Joyce E Loper

    2012-07-01

    Full Text Available We provide here a comparative genome analysis of ten strains within the Pseudomonas fluorescens group including seven new genomic sequences. These strains exhibit a diverse spectrum of traits involved in biological control and other multitrophic interactions with plants, microbes, and insects. Multilocus sequence analysis placed the strains in three sub-clades, which was reinforced by high levels of synteny, size of core genomes, and relatedness of orthologous genes between strains within a sub-clade. The heterogeneity of the P. fluorescens group was reflected in the large size of its pan-genome, which makes up approximately 54% of the pan-genome of the genus as a whole, and a core genome representing only 45-52% of the genome of any individual strain. We discovered genes for traits that were not known previously in the strains, including genes for the biosynthesis of the siderophores achromobactin and pseudomonine and the antibiotic 2-hexyl-5-propyl-alkylresorcinol; novel bacteriocins; type II, III, and VI secretion systems; and insect toxins. Certain gene clusters, such as those for two type III secretion systems, are present only in specific sub-clades, suggesting vertical inheritance. Almost all of the genes associated with multitrophic interactions map to genomic regions present in only a subset of the strains or unique to a specific strain. To explore the evolutionary origin of these genes, we mapped their distributions relative to the locations of mobile genetic elements and repetitive extragenic palindromic (REP elements in each genome. The mobile genetic elements and many strain-specific genes fall into regions devoid of REP elements (i.e., REP deserts and regions displaying atypical tri-nucleotide composition, possibly indicating relatively recent acquisition of these loci. Collectively, the results of this study highlight the enormous heterogeneity of the P. fluorescens group and the importance of the variable genome in tailoring

  19. Epistasis × environment interactions among Arabidopsis thaliana glucosinolate genes impact complex traits and fitness in the field.

    Science.gov (United States)

    Kerwin, Rachel E; Feusier, Julie; Muok, Alise; Lin, Catherine; Larson, Brandon; Copeland, Daniel; Corwin, Jason A; Rubin, Matthew J; Francisco, Marta; Li, Baohua; Joseph, Bindu; Weinig, Cynthia; Kliebenstein, Daniel J

    2017-08-01

    Despite the growing number of studies showing that genotype × environment and epistatic interactions control fitness, the influences of epistasis × environment interactions on adaptive trait evolution remain largely uncharacterized. Across three field trials, we quantified aliphatic glucosinolate (GSL) defense chemistry, leaf damage, and relative fitness using mutant lines of Arabidopsis thaliana varying at pairs of causal aliphatic GSL defense genes to test the impact of epistatic and epistasis × environment interactions on adaptive trait variation. We found that aliphatic GSL accumulation was primarily influenced by additive and epistatic genetic variation, leaf damage was primarily influenced by environmental variation and relative fitness was primarily influenced by epistasis and epistasis × environment interactions. Epistasis × environment interactions accounted for up to 48% of the relative fitness variation in the field. At a single field site, the impact of epistasis on relative fitness varied significantly over 2 yr, showing that epistasis × environment interactions within a location can be temporally dynamic. These results suggest that the environmental dependency of epistasis can profoundly influence the response to selection, shaping the adaptive trajectories of natural populations in complex ways, and deserves further consideration in future evolutionary studies. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  20. Spatial Patterns in Herbivory on a Coral Reef Are Influenced by Structural Complexity but Not by Algal Traits

    Science.gov (United States)

    Vergés, Adriana; Vanderklift, Mathew A.; Doropoulos, Christopher; Hyndes, Glenn A.

    2011-01-01

    Background Patterns of herbivory can alter the spatial structure of ecosystems, with important consequences for ecosystem functions and biodiversity. While the factors that drive spatial patterns in herbivory in terrestrial systems are well established, comparatively less is known about what influences the distribution of herbivory in coral reefs. Methodology and Principal Findings We quantified spatial patterns of macroalgal consumption in a cross-section of Ningaloo Reef (Western Australia). We used a combination of descriptive and experimental approaches to assess the influence of multiple macroalgal traits and structural complexity in establishing the observed spatial patterns in macroalgal herbivory, and to identify potential feedback mechanisms between herbivory and macroalgal nutritional quality. Spatial patterns in macroalgal consumption were best explained by differences in structural complexity among habitats. The biomass of herbivorous fish, and rates of herbivory were always greater in the structurally-complex coral-dominated outer reef and reef flat habitats, which were also characterised by high biomass of herbivorous fish, low cover and biomass of macroalgae and the presence of unpalatable algae species. Macroalgal consumption decreased to undetectable levels within 75 m of structurally-complex reef habitat, and algae were most abundant in the structurally-simple lagoon habitats, which were also characterised by the presence of the most palatable algae species. In contrast to terrestrial ecosystems, herbivory patterns were not influenced by the distribution, productivity or nutritional quality of resources (macroalgae), and we found no evidence of a positive feedback between macroalgal consumption and the nitrogen content of algae. Significance This study highlights the importance of seascape-scale patterns in structural complexity in determining spatial patterns of macroalgal consumption by fish. Given the importance of herbivory in maintaining the

  1. Spatial patterns in herbivory on a coral reef are influenced by structural complexity but not by algal traits.

    Directory of Open Access Journals (Sweden)

    Adriana Vergés

    2011-02-01

    Full Text Available Patterns of herbivory can alter the spatial structure of ecosystems, with important consequences for ecosystem functions and biodiversity. While the factors that drive spatial patterns in herbivory in terrestrial systems are well established, comparatively less is known about what influences the distribution of herbivory in coral reefs.We quantified spatial patterns of macroalgal consumption in a cross-section of Ningaloo Reef (Western Australia. We used a combination of descriptive and experimental approaches to assess the influence of multiple macroalgal traits and structural complexity in establishing the observed spatial patterns in macroalgal herbivory, and to identify potential feedback mechanisms between herbivory and macroalgal nutritional quality. Spatial patterns in macroalgal consumption were best explained by differences in structural complexity among habitats. The biomass of herbivorous fish, and rates of herbivory were always greater in the structurally-complex coral-dominated outer reef and reef flat habitats, which were also characterised by high biomass of herbivorous fish, low cover and biomass of macroalgae and the presence of unpalatable algae species. Macroalgal consumption decreased to undetectable levels within 75 m of structurally-complex reef habitat, and algae were most abundant in the structurally-simple lagoon habitats, which were also characterised by the presence of the most palatable algae species. In contrast to terrestrial ecosystems, herbivory patterns were not influenced by the distribution, productivity or nutritional quality of resources (macroalgae, and we found no evidence of a positive feedback between macroalgal consumption and the nitrogen content of algae.This study highlights the importance of seascape-scale patterns in structural complexity in determining spatial patterns of macroalgal consumption by fish. Given the importance of herbivory in maintaining the ability of coral reefs to reorganise and

  2. Relationship between social-cognitive and social-perceptual aspects of theory of mind and neurocognitive deficits, insight level and schizotypal traits in obsessive-compulsive disorder.

    Science.gov (United States)

    Mısır, Emre; Bora, Emre; Akdede, Berna Binnur

    2018-05-01

    The primary aim of the current study was to investigate different aspects of theory of mind (ToM), including social-cognitive (ToM-reasoning) and social-perceptual (ToM-decoding) in obsessive-compulsive disorder (OCD). We also aimed to investigate the relationship between ToM, neurocognition and a number of clinical variables including overvalued ideas, schizotypal personality traits, level of insight, and disease severity. Thirty-four patients who have been diagnosed with OCD according to DSM-IV and 30 healthy controls were included in the study. All participants were given a neuropsychological battery including tasks measuring ToM-reasoning, ToM-decoding and other neurocognitive functions. Schizotypal Personality Questionnaire (SPQ), Yale Brown Obsession and Compulsion Scale (YBOC-S) and Overvalued Ideas Scale (OVIS) were also administered to the participants. Patients with OCD showed significant deficits in both aspects of ToM. ToM performances of patients showed a significant positive correlation with neurocognitive functions. When controlled for general cognition factor, patient-control difference for ToM-reasoning (F = 3,917; p = 0,05), but not ToM-decoding, remained statistically significant. ToM-reasoning impairment of patients was significantly related to the severity of OCD symptoms and poor insight (p = 0,026 and p = 0,045, respectively). On the other hand, general cognitive factor (β = 0,778; t = 3,146; p = 0,04) was found to be the only significant predictor of ToM-reasoning in OCD patients in the multiple linear regression model. OCD is associated with ToM impairment, which is related to schizotypal traits, disease severity and poor insight, yet neurocognitive deficits also significantly contribute to this finding. However, ToM-reasoning impairment could be considered as a relatively distinct feature of OCD, which is partly separate from general cognitive deficits. Copyright © 2018. Published by Elsevier Inc.

  3. Protein quantitative trait locus study in obesity during weight-loss identifies a leptin regulator

    DEFF Research Database (Denmark)

    Carayol, Jérôme; Chabert, Christian; Di Cara, Alessandro

    2017-01-01

    of an organism. Proteome analysis especially can provide new insights into the molecular mechanisms of complex traits like obesity. The role of genetic variation in determining protein level variation has not been assessed in obesity. To address this, we design a large-scale protein quantitative trait locus (p...

  4. Use of biological priors enhances understanding of genetic architecture and genomic prediction of complex traits within and between dairy cattle breeds.

    Science.gov (United States)

    Fang, Lingzhao; Sahana, Goutam; Ma, Peipei; Su, Guosheng; Yu, Ying; Zhang, Shengli; Lund, Mogens Sandø; Sørensen, Peter

    2017-08-10

    A better understanding of the genetic architecture underlying complex traits (e.g., the distribution of causal variants and their effects) may aid in the genomic prediction. Here, we hypothesized that the genomic variants of complex traits might be enriched in a subset of genomic regions defined by genes grouped on the basis of "Gene Ontology" (GO), and that incorporating this independent biological information into genomic prediction models might improve their predictive ability. Four complex traits (i.e., milk, fat and protein yields, and mastitis) together with imputed sequence variants in Holstein (HOL) and Jersey (JER) cattle were analysed. We first carried out a post-GWAS analysis in a HOL training population to assess the degree of enrichment of the association signals in the gene regions defined by each GO term. We then extended the genomic best linear unbiased prediction model (GBLUP) to a genomic feature BLUP (GFBLUP) model, including an additional genomic effect quantifying the joint effect of a group of variants located in a genomic feature. The GBLUP model using a single random effect assumes that all genomic variants contribute to the genomic relationship equally, whereas GFBLUP attributes different weights to the individual genomic relationships in the prediction equation based on the estimated genomic parameters. Our results demonstrate that the immune-relevant GO terms were more associated with mastitis than milk production, and several biologically meaningful GO terms improved the prediction accuracy with GFBLUP for the four traits, as compared with GBLUP. The improvement of the genomic prediction between breeds (the average increase across the four traits was 0.161) was more apparent than that it was within the HOL (the average increase across the four traits was 0.020). Our genomic feature modelling approaches provide a framework to simultaneously explore the genetic architecture and genomic prediction of complex traits by taking advantage of

  5. Cortical dysplasia and autistic trait severity in children with Tuberous Sclerosis Complex : A clinical epidemiological study

    NARCIS (Netherlands)

    S.E. Mous (Sabine); I.E. Overwater (Iris); R. Vidal Gato (Rita); J. Duvekot (Jorieke); L.W. ten Hoopen (Leontine); M. Leguin (Maarten); M.C.Y. de Wit (Marie Claire); G.C. Dieleman (Gwen)

    2017-01-01

    textabstractTuberous Sclerosis Complex (TSC) is characterized by a high prevalence of autism spectrum disorders (ASD). Little is known about the relation between cortical dysplasia and ASD severity in TSC. We assessed ASD severity (using the Autism Diagnostic Observation Scale), tuber and radial

  6. Use of biological priors enhances understanding of genetic architecture and genomic prediction of complex traits within and between dairy cattle breeds

    DEFF Research Database (Denmark)

    Fang, Lingzhao; Sahana, Goutam; Ma, Peipei

    2017-01-01

    sequence variants in Holstein (HOL) and Jersey (JER) cattle were analysed. We first carried out a post-GWAS analysis in a HOL training population to assess the degree of enrichment of the association signals in the gene regions defined by each GO term. We then extended the genomic best linear unbiased......BACKGROUND: A better understanding of the genetic architecture underlying complex traits (e.g., the distribution of causal variants and their effects) may aid in the genomic prediction. Here, we hypothesized that the genomic variants of complex traits might be enriched in a subset of genomic...

  7. First insights into circulating Mycobacterium tuberculosis complex lineages and drug resistance in Guinea

    Science.gov (United States)

    Ejo, Mebrat; Gehre, Florian; Barry, Mamadou Dian; Sow, Oumou; Bah, Nene Mamata; Camara, Mory; Bah, Boubacar; Uwizeye, Cecile; Nduwamahoro, Elie; Fissette, Kristina; Rijk, Pim De; Merle, Corinne; Olliaro, Piero; Burgos, Marcos; Lienhardt, Christian; Rigouts, Leen; de Jong, Bouke C.

    2015-01-01

    In this study we assessed first-line anti-tuberculosis drug resistance and the genotypic distribution of Mycobacterium tuberculosis complex (MTBC) isolates that had been collected from consecutive new tuberculosis patients enrolled in two clinical trials conducted in Guinea between 2005 and 2010. Among the total 359 MTBC strains that were analyzed in this study, 22.8% were resistant to at least one of the first line anti-tuberculosis drugs, including 2.5% multidrug resistance and 17.5% isoniazid resistance, with or without other drugs. In addition, further characterization of isolates from a subset of the two trials (n = 184) revealed a total of 80 different spoligotype patterns, 29 “orphan” and 51 shared patterns. We identified the six major MTBC lineages of human relevance, with predominance of the Euro-American lineage. In total, 132 (71.7%) of the strains were genotypically clustered, and further analysis (using the DESTUS model) suggesting significantly faster spread of LAM10_CAM family (p = 0.00016). In conclusion, our findings provide a first insight into drug resistance and the population structure of the MTBC in Guinea, with relevance for public health scientists in tuberculosis control programs. PMID:26004194

  8. Phenotypic differentiation in love song traits among sibling species of the Lutzomyia longipalpis complex in Brazil.

    Science.gov (United States)

    Vigoder, Felipe M; Souza, Nataly A; Brazil, Reginaldo P; Bruno, Rafaela V; Costa, Pietra L; Ritchie, Michael G; Klaczko, Louis B; Peixoto, Alexandre A

    2015-05-28

    Brazilian populations of Lutzomyia longipalpis may constitute a complex of cryptic species, and this report investigates the distribution and number of potential sibling species. One of the main differences observed among Brazilian populations is the type of acoustic signal produced by males during copulation. These copulation song differences seem to be evolving faster than neutral molecular markers and have been suggested to contribute to insemination failure observed in crosses between these sibling species. In previous studies, two main types of copulation songs were found, burst-type and pulse-type. The latter type can, in turn, be further subdivided into five different patterns. We recorded male song from 13 new populations of the L. longipalpis complex from Brazil and compared the songs with 12 already available. Out of these 25 populations, 16 produce burst-type and 9 produce pulse-type songs. We performed a principal component analysis in these two main groups separately and an additional discriminant analysis in the pulse-type group. The pulse-type populations showed a clear separation between the five known patterns with a high correspondence of individuals to their correct group, confirming the differentiation between them. The distinctiveness of the burst-type subgroups was much lower than that observed among the pulse-type groups and no clear population structure was observed. This suggests that the burst-type populations represent a single species. Overall, our results are consistent with the existence in Brazil of at least six species of the L. longipalpis complex, one with a wide distribution comprising all the populations with burst-type songs, and five more closely related allopatric siblings with different pulse-type song patterns and more restricted distribution ranges.

  9. A power set-based statistical selection procedure to locate susceptible rare variants associated with complex traits with sequencing data.

    Science.gov (United States)

    Sun, Hokeun; Wang, Shuang

    2014-08-15

    Existing association methods for rare variants from sequencing data have focused on aggregating variants in a gene or a genetic region because of the fact that analysing individual rare variants is underpowered. However, these existing rare variant detection methods are not able to identify which rare variants in a gene or a genetic region of all variants are associated with the complex diseases or traits. Once phenotypic associations of a gene or a genetic region are identified, the natural next step in the association study with sequencing data is to locate the susceptible rare variants within the gene or the genetic region. In this article, we propose a power set-based statistical selection procedure that is able to identify the locations of the potentially susceptible rare variants within a disease-related gene or a genetic region. The selection performance of the proposed selection procedure was evaluated through simulation studies, where we demonstrated the feasibility and superior power over several comparable existing methods. In particular, the proposed method is able to handle the mixed effects when both risk and protective variants are present in a gene or a genetic region. The proposed selection procedure was also applied to the sequence data on the ANGPTL gene family from the Dallas Heart Study to identify potentially susceptible rare variants within the trait-related genes. An R package 'rvsel' can be downloaded from http://www.columbia.edu/∼sw2206/ and http://statsun.pusan.ac.kr. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. A multilevel trait-based approach to the ecological performance of Microcystis aeruginosa complex from headwaters to the ocean.

    Science.gov (United States)

    Kruk, Carla; Segura, Angel M; Nogueira, Lucía; Alcántara, Ignacio; Calliari, Danilo; Martínez de la Escalera, Gabriela; Carballo, Carmela; Cabrera, Carolina; Sarthou, Florencia; Scavone, Paola; Piccini, Claudia

    2017-12-01

    The Microcystis aeruginosa complex (MAC) clusters cosmopolitan and conspicuous harmful bloom-forming cyanobacteria able to produce cyanotoxins. It is hypothesized that low temperatures and brackish salinities are the main barriers to MAC proliferation. Here, patterns at multiple levels of organization irrespective of taxonomic identity (i.e. a trait-based approach) were analyzed. MAC responses from the intracellular (e.g. respiratory activity) to the ecosystem level (e.g. blooms) were evaluated in wide environmental gradients. Experimental results on buoyancy and respiratory activity in response to increased salinity (0-35) and a literature review of maximum growth rates under different temperatures and salinities were combined with field sampling from headwaters (800km upstream) to the marine end of the Rio de la Plata estuary (Uruguay-South America). Salinity and temperature were the major variables affecting MAC responses. Experimentally, freshwater MAC cells remained active for 24h in brackish waters (salinity=15) while colonies increased their flotation velocity. At the population level, maximum growth rate decreased with salinity and presented a unimodal exponential response with temperature, showing an optimum at 27.5°C and a rapid decrease thereafter. At the community and ecosystem levels, MAC occurred from fresh to marine waters (salinity 30) with a sustained relative increase of large mucilaginous colonies biovolume with respect to individual cells. Similarly, total biomass and, specific and morphological richness decreased with salinity while blooms were only detected in freshwater both at high (33°C) and low (11°C) temperatures. In brackish waters, large mucilaginous colonies presented advantages under osmotic restrictive conditions. These traits values have also been associated with higher toxicity potential. This suggest salinity or low temperatures would not represent effective barriers for the survival and transport of potentially toxic MAC under

  11. Discovery of rare variants via sequencing: implications for the design of complex trait association studies.

    Directory of Open Access Journals (Sweden)

    Bingshan Li

    2009-05-01

    Full Text Available There is strong evidence that rare variants are involved in complex disease etiology. The first step in implicating rare variants in disease etiology is their identification through sequencing in both randomly ascertained samples (e.g., the 1,000 Genomes Project and samples ascertained according to disease status. We investigated to what extent rare variants will be observed across the genome and in candidate genes in randomly ascertained samples, the magnitude of variant enrichment in diseased individuals, and biases that can occur due to how variants are discovered. Although sequencing cases can enrich for casual variants, when a gene or genes are not involved in disease etiology, limiting variant discovery to cases can lead to association studies with dramatically inflated false positive rates.

  12. Mapping epistasis and environment × QTX interaction based on four -omics genotypes for the detected QTX loci controlling complex traits in tobacco

    Directory of Open Access Journals (Sweden)

    Liyuan Zhou

    2013-12-01

    Full Text Available Using newly developed methods and software, association mapping was conducted for chromium content and total sugar in tobacco leaf, based on four -omics datasets. Our objective was to collect data on genotype and phenotype for 60 leaf samples at four developmental stages, from three plant architectural positions and for three cultivars that were grown in two locations. Association mapping was conducted to detect genetic variants at quantitative trait SNP (QTS loci, quantitative trait transcript (QTT differences, quantitative trait protein (QTP variability, and quantitative trait metabolite (QTM changes, which can be summarized as QTX locus variation. The total heritabilities of the four -omics loci for both traits tested were 23.60% for epistasis and 15.26% for treatment interaction. Epistasis and environment × treatment interaction had important impacts on complex traits at all -omics levels. For decreasing chromium content and increasing total sugar in tobacco leaf, six methylated loci can be directly used for marker-assisted selection, and expression of ten QTTs, seven QTPs and six QTMs can be modified by selection or cultivation.

  13. An insight into the complex prion-prion interaction network in the budding yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Du, Zhiqiang; Valtierra, Stephanie; Li, Liming

    2014-01-01

    The budding yeast Saccharomyces cerevisiae is a valuable model system for studying prion-prion interactions as it contains multiple prion proteins. A recent study from our laboratory showed that the existence of Swi1 prion ([SWI(+)]) and overproduction of Swi1 can have strong impacts on the formation of 2 other extensively studied yeast prions, [PSI(+)] and [PIN(+)] ([RNQ(+)]) (Genetics, Vol. 197, 685-700). We showed that a single yeast cell is capable of harboring at least 3 heterologous prion elements and these prions can influence each other's appearance positively and/or negatively. We also showed that during the de novo [PSI(+)] formation process upon Sup35 overproduction, the aggregation patterns of a preexisting inducer ([RNQ(+)] or [SWI(+)]) can undergo significant remodeling from stably transmitted dot-shaped aggregates to aggregates that co-localize with the newly formed Sup35 aggregates that are ring/ribbon/rod- shaped. Such co-localization disappears once the newly formed [PSI(+)] prion stabilizes. Our finding provides strong evidence supporting the "cross-seeding" model for prion-prion interactions and confirms earlier reports that the interactions among different prions and their prion proteins mostly occur at the initiation stages of prionogenesis. Our results also highlight a complex prion interaction network in yeast. We believe that elucidating the mechanism underlying the yeast prion-prion interaction network will not only provide insight into the process of prion de novo generation and propagation in yeast but also shed light on the mechanisms that govern protein misfolding, aggregation, and amyloidogenesis in higher eukaryotes.

  14. Cynefin as Reference Framework to Facilitate Insight and Decision-Making in Complex Contexts of Biomedical Research

    Directory of Open Access Journals (Sweden)

    Gerd Kempermann

    2017-11-01

    Full Text Available The Cynefin scheme is a concept of knowledge management, originally devised to support decision making in management, but more generally applicable to situations, in which complexity challenges the quality of insight, prediction, and decision. Despite the fact that life itself, and especially the brain and its diseases, are complex to the extent that complexity could be considered their cardinal feature, complex problems in biomedicine are often treated as if they were actually not more than the complicated sum of solvable sub-problems. Because of the emergent properties of complex contexts this is not correct. With a set of clear criteria Cynefin helps to set apart complex problems from “simple/obvious,” “complicated,” “chaotic,” and “disordered” contexts in order to avoid misinterpreting the relevant causality structures. The distinction comes with the insight, which specific kind of knowledge is possible in each of these categories and what are the consequences for resulting decisions and actions. From student's theses over the publication and grant writing process to research politics, misinterpretation of complexity can have problematic or even dangerous consequences, especially in clinical contexts. Conceptualization of problems within a straightforward reference language like Cynefin improves clarity and stringency within projects and facilitates communication and decision-making about them.

  15. The use of genome-wide eQTL associations in lymphoblastoid cell lines to identify novel genetic pathways involved in complex traits.

    Directory of Open Access Journals (Sweden)

    Josine L Min

    Full Text Available The integrated analysis of genotypic and expression data for association with complex traits could identify novel genetic pathways involved in complex traits. We profiled 19,573 expression probes in Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs from 299 twins and correlated these with 44 quantitative traits (QTs. For 939 expressed probes correlating with more than one QT, we investigated the presence of eQTL associations in three datasets of 57 CEU HapMap founders and 86 unrelated twins. Genome-wide association analysis of these probes with 2.2 m SNPs revealed 131 potential eQTLs (1,989 eQTL SNPs overlapping between the HapMap datasets, five of which were in cis (58 eQTL SNPs. We then tested 535 SNPs tagging the eQTL SNPs, for association with the relevant QT in 2,905 twins. We identified nine potential SNP-QT associations (P<0.01 but none significantly replicated in five large consortia of 1,097-16,129 subjects. We also failed to replicate previous reported eQTL associations with body mass index, plasma low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides levels derived from lymphocytes, adipose and liver tissue. Our results and additional power calculations suggest that proponents may have been overoptimistic in the power of LCLs in eQTL approaches to elucidate regulatory genetic effects on complex traits using the small datasets generated to date. Nevertheless, larger tissue-specific expression data sets relevant to specific traits are becoming available, and should enable the adoption of similar integrated analyses in the near future.

  16. Beyond disease susceptibility-Leveraging genome-wide association studies for new insights into complex disease biology.

    Science.gov (United States)

    Lee, J C

    2017-12-01

    Genetic studies in complex diseases have been highly successful, but have also been largely one-dimensional: predominantly focusing on the genetic contribution to disease susceptibility. While this is undoubtedly important-indeed it is a pre-requisite for understanding the mechanisms underlying disease development-there are many other important aspects of disease biology that have received comparatively little attention. In this review, I will discuss how existing genetic data can be leveraged to provide new insights into other aspects of disease biology, why such insights could change the way we think about complex disease, and how this could provide opportunities for better therapies and/or facilitate personalised medicine. To do this, I will use the example of Crohn's disease-a chronic form of inflammatory bowel disease that has been one of the main success stories in complex disease genetics. Indeed, thanks to genetic studies, we now have a much more detailed understanding of the processes involved in Crohn's disease development, but still know relatively little about what determines the subsequent disease course (prognosis) and why this differs so considerably between individuals. I will discuss how we came to realise that genetic variation plays an important role in determining disease prognosis and how this has changed the way we think about Crohn's disease genetics. This will illustrate how phenotypic data can be used to leverage new insights from genetic data and will provide a broadly applicable framework that could yield new insights into the biology of multiple diseases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Insight into the structures and stabilities of Tc and Re DMSA complexes: A computational study

    International Nuclear Information System (INIS)

    Blanco González, Alejandro; Hernández Valdés, Daniel; García Fleitas, Ariel; Rodríguez Riera, Zalua; Jáuregui Haza, Ulises

    2016-01-01

    Meso-2,3-dimercaptosuccinic acid (DMSA) is used in nuclear medicine as ligand for preparation of radiopharmaceuticals for diagnostic and therapy. DMSA has been the subject of numerous investigations during the past three decades and new and significant information of the chemistry and pharmacology of DMSA complexes have emerged. In comparison to other ligands, the structure of some DMSA complexes is unclear up today. The structures and applications of DMSA complexes are strictly dependent on the chemical conditions of their preparation, especially pH and the ratio of components. A computational study of M-DMSA (M = Tc, Re) complexes has been performed using density functional theory. Different isomers for M(V) and M(III) complexes were study. The pH influence over ligand structures was taken into account and the solvent effect was evaluated using an implicit solvation model. The fully optimized complex syn-endo Re(V)-DMSA shows a geometry similar to the X-ray data and was used to validate the methodology. Moreover, new alternative structures for the renal agent 99mTc(III)-DMSA were proposed and computationally studied. For two complex structures, a larger stability respect to that proposed in the literature was obtained. Furthermore, Tc(V)-DMSA complexes are more stable than the Tc(III)-DMSA proposed structures. In general, Re complexes are more stables than the corresponding Tc ones. (author)

  18. Crystal Structure of the Herpesvirus Nuclear Egress Complex Provides Insights into Inner Nuclear Membrane Remodeling

    NARCIS (Netherlands)

    Zeev-Ben-Mordehai, Tzviya; Weberruss, Marion; Lorenz, Michael; Cheleski, Juliana; Hellberg, Teresa; Whittle, Cathy; El Omari, Kamel; Vasishtan, Daven; Dent, Kyle C.; Harlos, Karl; Franzke, Kati; Hagen, Christoph; Klupp, Barbara G.; Antonin, Wolfram; Mettenleiter, Thomas C.; Gruenewald, Kay

    2015-01-01

    Although nucleo-cytoplasmic transport is typically mediated through nuclear pore complexes, herpesvirus capsids exit the nucleus via a unique vesicular pathway. Together, the conserved herpesvirus proteins pUL31 and pUL34 form the heterodimeric nuclear egress complex (NEC), which, in turn, mediates

  19. Plutonium(IV) complexation by diglycolamide ligands - coordination chemistry insight into TODGA-based actinide separations

    NARCIS (Netherlands)

    Reilly, S.D.; Gaunt, A.J.; Scott, B.L.; Modolo, G.; Iqbal, M.; Verboom, Willem; Sarsfield, M.J.

    2012-01-01

    Complexation of Pu(IV) with TMDGA, TEDGA, and TODGA diglycolamide ligands was followed by vis-NIR spectroscopy. A crystal structure determination reveals that TMDGA forms a 1:3 homoleptic Pu(IV) complex with the nitrate anions forced into the outer coordination sphere

  20. Structure of an APC3-APC16 complex: Insights into assembly of the Anaphase Promoting Complex/Cyclosome

    OpenAIRE

    Yamaguchi, Masaya; Yu, Shanshan; Qiao, Renping; Weissmann, Florian; Miller, Darcie J.; VanderLinden, Ryan; Brown, Nicholas G.; Frye, Jeremiah J.; Peters, Jan-Michael; Schulman, Brenda A.

    2014-01-01

    The Anaphase Promoting Complex/Cyclosome (APC/C) is a massive E3 ligase that controls mitosis by catalyzing ubiquitination of key cell cycle regulatory proteins. The APC/C assembly contains two subcomplexes: the “Platform” centers around a cullin-RING-like E3 ligase catalytic core; the “Arc Lamp” is a hub that mediates transient association with regulators and ubiquitination substrates. The Arc Lamp contains the small subunits APC16, CDC26, and APC13, and tetratricopeptide repeat (TPR) protei...

  1. The Evolutionary Logic of the Obsessive Trait Complex: Obsessive Compulsive Personality Disorder as a Complementary Behavioral Syndrome

    Directory of Open Access Journals (Sweden)

    Steven Charles Hertler

    2015-04-01

    Full Text Available Freud noted that the obsessive traits of orderliness, parsimony, and obstinacy incontestably belonged together. This observation has been unfailingly justified, but unsatisfactorily explained. Being a highly heritable pattern essentially unaffected by parental influence, it is counterfactual to continue to explain the obsessive trait constellation as a pathological signature of harsh, authoritarian parenting. Alternatively, the present paper, building upon a previously promulgated evolutionary etiological model, describes how obsessive traits work in unison to enable survival within harsh northerly climates. What appears to be a loosely federated inventory of pathology, after the application of evolutionary reasoning, becomes a coherent behavioral package, adaptive suite, or behavioral syndrome. All three of these terms, taken from behavioral biology, suggest that traits strategically covary, such that the adaptive value of each trait is enhanced by the presence of the others. In this vein, the union of anxious tension and conscientiousness drives the obsessive personality to labor incessantly. The fruits of obsessive labor are then conserved through parsimoniousness, hoarding, vigilance, and niggardliness. And so, obsessive personality is a coherent behavioral package in that the drive to work towards the acquisition of necessities is paired with the drive to conserve and defend them.

  2. Insights into the Halogen Oxidative Addition Reaction to Dinuclear Gold(I) Di(NHC) Complexes

    KAUST Repository

    Baron, Marco

    2016-06-14

    Gold(I) dicarbene complexes [Au2(MeIm-Y-ImMe)2](PF6)2(Y=CH2(1), (CH2)2(2), (CH2)4(4), MeIm=1-methylimidazol-2-ylidene) react with iodine to give the mixed-valence complex [Au(MeIm-CH2-ImMe)2AuI2](PF6)2(1 aI) and the gold(III) complexes [Au2I4(MeIm-Y-ImMe)2](PF6)2(2 cIand 4 cI). Reaction of complexes 1 and 2 with an excess of ICl allows the isolation of the tetrachloro gold(III) complexes [Au2Cl4(MeIm-CH2-ImMe)2](PF6)2(1 cCl) and [Au2Cl4(MeIm-(CH2)2-ImMe)2](Cl)2(2 cCl-Cl) (as main product); remarkably in the case of complex 2, the X-ray molecular structure of the crystals also shows the presence of I-Au-Cl mixed-sphere coordination. The same type of coordination has been observed in the main product of the reaction of complexes 3 or 4 with ICl. The study of the reactivity towards the oxidative addition of halogens to a large series of dinuclear bis(dicarbene) gold(I) complexes has been extended and reviewed. The complexes react with Cl2, Br2and I2to give the successive formation of the mixed-valence gold(I)/gold(III) n aXand gold(III) n cX(excluding compound 1 cI) complexes. However, complex 3 affords with Cl2and Br2the gold(II) complex 3 bX[Au2X2(MeIm-(CH2)3-ImMe)2](PF6)2(X=Cl, Br), which is the predominant species over compound 3 cXeven in the presence of free halogen. The observed different relative stabilities of the oxidised complexes of compounds 1 and 3 have also been confirmed by DFT calculations. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping.

    Science.gov (United States)

    Klein, Christopher J; Lennon, Vanda A; Aston, Paula A; McKeon, Andrew; O'Toole, Orna; Quek, Amy; Pittock, Sean J

    2013-02-01

    To determine, in patients identified as seropositive for neuronal voltage-gated potassium channel (VGKC) complex autoantibodies, the spectrum of clinical presentations and frequency of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as defined antigenic neuronal targets in the VGKC macromolecular complex. Retrospective cohort study. Clinical practice, Mayo Clinic Neuroimmunology Laboratory and Department of Neurology. A total of 54 853 patients were evaluated, of whom 1992 were found to be VGKC complex IgG positive. From June 1, 2008, to June 30, 2010, comprehensive service serologic evaluation performed on 54853 patients with unexplained neurologic symptoms identified 1992 patients (4%) who were positive for VGKC complex IgG (values ≥ 0.03 nmol/L). Among 316 seropositive patients evaluated clinically at our institution, 82 (26%) were seropositive for LGI1 IgG and/or CASPR2 IgG. Of these 82 patients, 27% had low (0.03-0.09 nmol/L), 51% had medium (0.10-0.99 nmol/L), and 22% had high (≥ 1.00 nmol/L) VGKC complex IgG values. Leucine-rich glioma-inactivated protein 1 IgG positivity was associated with higher VGKC complex IgG values (PVGKC complex IgG values and varying LGI1 IgG and CASPR2 IgG specificities. The frequent occurrence of LGI1 IgG and CASPR2 IgG in serum samples with low and medium VGKC complex IgG values supports the clinical significance of low values in clinical evaluation. Additional antigenic components of VGKC macromolecular complexes remain to be defined.

  4. The IgA nephropathy Biobank. An important starting point for the genetic dissection of a complex trait

    Directory of Open Access Journals (Sweden)

    Alexopoulos Efstathios

    2005-12-01

    from the study of Mendelian diseases has shown that the genetic dissection of a complex trait is more powerful when combined linkage-based, association-based, and sequence-based approaches are performed. This Biobank continuously expanded contains a sample size of adequately matched IgAN patients and healthy subjects, extended multiplex pedigrees, parent-child trios, thus permitting the combined genetic approaches with collaborative studies.

  5. Insights into the Halogen Oxidative Addition Reaction to Dinuclear Gold(I) Di(NHC) Complexes

    KAUST Repository

    Baron, Marco; Tubaro, Cristina; Basato, Marino; Isse, Abdirisak Ahmed; Gennaro, Armando; Cavallo, Luigi; Graiff, Claudia; Dolmella, Alessandro; Falivene, Laura; Caporaso, Lucia

    2016-01-01

    Gold(I) dicarbene complexes [Au2(MeIm-Y-ImMe)2](PF6)2(Y=CH2(1), (CH2)2(2), (CH2)4(4), MeIm=1-methylimidazol-2-ylidene) react with iodine to give the mixed-valence complex [Au(MeIm-CH2-ImMe)2AuI2](PF6)2(1 aI) and the gold(III) complexes [Au2I4(Me

  6. New Insights into the Role of Pb-BHA Complexes in the Flotation of Tungsten Minerals

    Science.gov (United States)

    Yue, Tong; Han, Haisheng; Hu, Yuehua; Sun, Wei; Li, Xiaodong; Liu, Runqing; Gao, Zhiyong; Wang, Li; Chen, Pan; Zhang, Chenyang; Tian, Mengjie

    2017-11-01

    Lead ions (lead nitrate) were introduced to modify the surface properties of tungsten minerals, effectively improving the floatability, with benzohydroxamic acid (BHA) serving as the collector. Flotation tests indicated that Pb-BHA complexes were the active species responsible for flotation of the tungsten minerals. The developed Pb-BHA complexes and the novel flotation process effectively increased the recovery of scheelite and wolframite, simplified the technological process, and led to reduced costs. Fourier transform infrared spectra data showed the presence of adsorbed Pb-BHA complexes on the surface of the minerals. The characteristic peaks of BHA shifted by a considerable extent, indicating that chemical adsorption plays an important role in the flotation process. Zeta potential results confirmed physical adsorption of the positively charged Pb-BHA complexes on the mineral surfaces. The synergistic effect between chemical and physical adsorption facilitated the maximum flotation recovery of scheelite and wolframite.

  7. First insights into the evolutionary history of the Davallia repens complex

    NARCIS (Netherlands)

    Chen, C.-W.; Ngan, L.T.; Hidayat, A.; Evangelista, L.; Nooteboom, H.P.; Chiou, W.-L.

    2014-01-01

    Davallia repens and its close relatives have been identified as a species complex in this study because of the existence of continuously morphological variation. To decipher its evolutionary history, integrated methodologies were applied in this study including morphology, cytology, reproductive

  8. Uranium sorption to natural substrates-insights provided by isotope exchange, selective extraction and surface complexation modelling approaches

    International Nuclear Information System (INIS)

    Waite, T.D.; Payne T.E.; Davis, J.A.

    1993-01-01

    An extensive experimental program has been conducted over the last three years into the interaction of U(VI) with both single oxides and clays and complex natural substrates from the weathered zone in the vicinity of a uranium ore body in northern Australia. While iron oxides have frequently been considered to account for much of the uptake on such natural substrates, the results of laboratory open-quotes pH edgeclose quotes studies and of isotope exchange and selective extraction studies suggest that other phases must also play a significant role in controlling the partitioning of U(VI) between solid and solution phases. Supporting studies on kaolinite, the dominant clay in this system, provide insight into the most appropriate method of modelling the interaction of U(VI) with these natural substrates. The problems still remaining in adequately describing sorption of radionuclides and trace elements to complex natural substrates are discussed

  9. Atomic level insights into realistic molecular models of dendrimer-drug complexes through MD simulations

    Science.gov (United States)

    Jain, Vaibhav; Maiti, Prabal K.; Bharatam, Prasad V.

    2016-09-01

    Computational studies performed on dendrimer-drug complexes usually consider 1:1 stoichiometry, which is far from reality, since in experiments more number of drug molecules get encapsulated inside a dendrimer. In the present study, molecular dynamic (MD) simulations were implemented to characterize the more realistic molecular models of dendrimer-drug complexes (1:n stoichiometry) in order to understand the effect of high drug loading on the structural properties and also to unveil the atomistic level details. For this purpose, possible inclusion complexes of model drug Nateglinide (Ntg) (antidiabetic, belongs to Biopharmaceutics Classification System class II) with amine- and acetyl-terminated G4 poly(amidoamine) (G4 PAMAM(NH2) and G4 PAMAM(Ac)) dendrimers at neutral and low pH conditions are explored in this work. MD simulation analysis on dendrimer-drug complexes revealed that the drug encapsulation efficiency of G4 PAMAM(NH2) and G4 PAMAM(Ac) dendrimers at neutral pH was 6 and 5, respectively, while at low pH it was 12 and 13, respectively. Center-of-mass distance analysis showed that most of the drug molecules are located in the interior hydrophobic pockets of G4 PAMAM(NH2) at both the pH; while in the case of G4 PAMAM(Ac), most of them are distributed near to the surface at neutral pH and in the interior hydrophobic pockets at low pH. Structural properties such as radius of gyration, shape, radial density distribution, and solvent accessible surface area of dendrimer-drug complexes were also assessed and compared with that of the drug unloaded dendrimers. Further, binding energy calculations using molecular mechanics Poisson-Boltzmann surface area approach revealed that the location of drug molecules in the dendrimer is not the decisive factor for the higher and lower binding affinity of the complex, but the charged state of dendrimer and drug, intermolecular interactions, pH-induced conformational changes, and surface groups of dendrimer do play an

  10. Evaluation of Two Statistical Methods Provides Insights into the Complex Patterns of Alternative Polyadenylation Site Switching

    Science.gov (United States)

    Li, Jie; Li, Rui; You, Leiming; Xu, Anlong; Fu, Yonggui; Huang, Shengfeng

    2015-01-01

    Switching between different alternative polyadenylation (APA) sites plays an important role in the fine tuning of gene expression. New technologies for the execution of 3’-end enriched RNA-seq allow genome-wide detection of the genes that exhibit significant APA site switching between different samples. Here, we show that the independence test gives better results than the linear trend test in detecting APA site-switching events. Further examination suggests that the discrepancy between these two statistical methods arises from complex APA site-switching events that cannot be represented by a simple change of average 3’-UTR length. In theory, the linear trend test is only effective in detecting these simple changes. We classify the switching events into four switching patterns: two simple patterns (3’-UTR shortening and lengthening) and two complex patterns. By comparing the results of the two statistical methods, we show that complex patterns account for 1/4 of all observed switching events that happen between normal and cancerous human breast cell lines. Because simple and complex switching patterns may convey different biological meanings, they merit separate study. We therefore propose to combine both the independence test and the linear trend test in practice. First, the independence test should be used to detect APA site switching; second, the linear trend test should be invoked to identify simple switching events; and third, those complex switching events that pass independence testing but fail linear trend testing can be identified. PMID:25875641

  11. Structural insights into the p97-Ufd1-Npl4 complex

    Science.gov (United States)

    Pye, Valerie E.; Beuron, Fabienne; Keetch, Catherine A.; McKeown, Ciaran; Robinson, Carol V.; Meyer, Hemmo H.; Zhang, Xiaodong; Freemont, Paul S.

    2007-01-01

    p97/VCP (Cdc48 in yeast) is an essential and abundant member of the AAA+ family of ATPases and is involved in a number of diverse cellular pathways through interactions with different adaptor proteins. The two most characterized adaptors for p97 are p47 and the Ufd1 (ubiquitin fusion degradation 1)-Npl4 (nuclear protein localization 4) complex. p47 directs p97 to membrane fusion events and has been shown to be involved in protein degradation. The Ufd1-Npl4 complex directs p97 to an essential role in endoplasmic reticulum-associated degradation and an important role in mitotic spindle disassembly postmitosis. Here we describe the structural features of the Ufd1-Npl4 complex and its interaction with p97 with the aid of EM and other biophysical techniques. The Ufd1-Npl4 heterodimer has an elongated bilobed structure that is ≈80 × 30 Å in dimension. One Ufd1-Npl4 heterodimer is shown to interact with one p97 hexamer to form the p97-Ufd1-Npl4 complex. The Ufd1-Npl4 heterodimer emanates from one region on the periphery of the N-D1 plane of the p97 hexamer. Intriguingly, the p97-p47 and the p97-Ufd1-Npl4 complexes are significantly different in stoichiometry, symmetry, and quaternary arrangement, reflecting their specific actions and their ability to interact with additional cofactors that cooperate with p97 in diverse cellular pathways. PMID:17202270

  12. Epistasis × environment interactions among Arabidopsis thaliana glucosinolate genes impact complex traits and fitness in the field

    DEFF Research Database (Denmark)

    Kerwin, Rachel E.; Feusier, Julie; Muok, Alise

    2017-01-01

    (GSL) defense chemistry, leaf damage, and relative fitness using mutant lines of Arabidopsis thaliana varying at pairs of causal aliphatic GSL defense genes to test the impact of epistatic and epistasis × environment interactions on adaptive trait variation. We found that aliphatic GSL accumulation...

  13. Quantitative Trait Loci in Inbred Lines

    NARCIS (Netherlands)

    Jansen, R.C.

    2001-01-01

    Quantitative traits result from the influence of multiple genes (quantitative trait loci) and environmental factors. Detecting and mapping the individual genes underlying such 'complex' traits is a difficult task. Fortunately, populations obtained from crosses between inbred lines are relatively

  14. Phylogenetic relationships in the Festuca-Lolium complex (Loliinae; Poaceae: New insights from chloroplast sequences

    Directory of Open Access Journals (Sweden)

    Yajuan Cheng

    2016-07-01

    Full Text Available The species within the Lolium/Festuca grass complex have dispersed and colonized large areas of temperate global grasslands both naturally and by human intervention. The species within this grass complex represent some of the most important grass species both for amenity and agricultural use worldwide. There has been renewed interest by grass breeders in producing hybrid combinations between these species and several countries now market Festulolium varieties as a combination of genes from both genera. The two genera have been differentiated by their inflorescence structure, but controversy has surrounded the taxonomic classification of the Lolium-Festuca complex species for several decades. In order to better understand the complexities within the Lolium/Festuca complex and their genetic background, the phylogeny of important examplers from the Lolium-Festuca complex were reconstructed. In total 40 taxa representing the Festuca and Lolium species with Vulpia myuros and Brachypodium distachyon as outgroups were sampled, using two noncoding intergenic spacers (trnQ-rps16, trnH-psbA and one coding gene (rbcL. Maximum parsimony (MP, Bayesian inference (BI analyses based on each partition and combined plastid DNA dataset, and median-jointing network analysis were employed. The outcomes strongly suggested that the subgen. Schedonorus has a close relationship to Lolium, and it is also proposed to move the sect. Leucopoa from subgen. Leucopoa to Subgen. Schedonorus and to separate sect. Breviaristatae from the subgen. Leucopoa. We found that F. californica could be a lineage of hybrid origin because of its intermediate placement between the broad-leaved and fine-leaved clade.

  15. Structural insights into SUN-KASH complexes across the nuclear envelope

    Institute of Scientific and Technical Information of China (English)

    Wenjia Wang; Zhaocai Zhou; Zhubing Shi; Shi Jiao; Cuicui Chen; Huizhen Wang; Guoguang Liu; Qiang Wang; Yun Zhao; Mark I Greene

    2012-01-01

    Linker of the nucleoskeleton and the cytoskeleton (LINC) complexes are composed of SUN and KASH domaincontaining proteins and bridge the inner and outer membranes of the nuclear envelope.LINC complexes play critical roles in nuclear positioning,cell polarization and cellular stiffness.Previously,we reported the homotrimeric structure of human SUN2.We have now determined the crystal structure of the human SUN2-KASH complex.In the complex structure,the SUN domain homotrimer binds to three independent "hook"-like KASH peptides.The overall conformation of the SUN domain in the complex closely resembles the SUN domain in its apo state.A major conformational change involves the AA'-loop of KASH-bound SUN domain,which rearranges to form a mini β-sheet that interacts with the KASH peptide.The PPPT motif of the KASH domain fits tightly into a hydrophobic pocket on the homotrimeric interface of the SUN domain,which we termed the BI-pocket.Moreover,two adjacent protomers of the SUN domain homotrimer sandwich the KASH domain by hydrophobic interaction and hydrogen bonding.Mutations of these binding sites disrupt or reduce the association between the SUN and KASH domains in vitro.In addition,transfection of wild-type,but not mutant,SUN2 promotes cell migration in Ovcar-3 cells.These results provide a structural model of the LINC complex,which is essential for additional study of the physical and functional coupling between the cytoplasm and the nucleoplasm.

  16. Insights into functional-group-tolerant polymerization catalysis with phosphine-sulfonamide palladium (II) complexes

    KAUST Repository

    Jian, Zhongbao; Falivene, Laura; Wucher, Philipp; Roesle, Philipp; Caporaso, Lucia; Cavallo, Luigi; Gç ttker-Schnetmann, Inigo; Mecking, Stefan

    2014-01-01

    Two series of cationic palladium(II) methyl complexes {[(2-MeOC6H4)2PC6H4SO2NHC6H3(2,6-R1,R2)]PdMe}2[A]2 (X1+-A: R1=R2=H: H1+-A; R1=R2=CH(CH3)2: DIPP1+-A; R1=H, R2=CF3: CF31+-A; A=BF4 or SbF6) and neutral palladium(II) methyl complexes {[(2-MeOC6H4

  17. New insights into sucking, swallowing and breathing central generators: A complexity analysis of rhythmic motor behaviors.

    Science.gov (United States)

    Samson, Nathalie; Praud, Jean-Paul; Quenet, Brigitte; Similowski, Thomas; Straus, Christian

    2017-01-18

    Sucking, swallowing and breathing are dynamic motor behaviors. Breathing displays features of chaos-like dynamics, in particular nonlinearity and complexity, which take their source in the automatic command of breathing. In contrast, buccal/gill ventilation in amphibians is one of the rare motor behaviors that do not display nonlinear complexity. This study aimed at assessing whether sucking and swallowing would also follow nonlinear complex dynamics in the newborn lamb. Breathing movements were recorded before, during and after bottle-feeding. Sucking pressure and the integrated EMG of the thyroartenoid muscle, as an index of swallowing, were recorded during bottle-feeding. Nonlinear complexity of the whole signals was assessed through the calculation of the noise limit value (NL). Breathing and swallowing always exhibited chaos-like dynamics. The NL of breathing did not change significantly before, during or after bottle-feeding. On the other hand, sucking inconsistently and significantly less frequently than breathing exhibited a chaos-like dynamics. Therefore, the central pattern generator (CPG) that drives sucking may be functionally different from the breathing CPG. Furthermore, the analogy between buccal/gill ventilation and sucking suggests that the latter may take its phylogenetic origin in the gill ventilation CPG of the common ancestor of extant amphibians and mammals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. New insight into the ternary complexes of uranyl carbonate in seawater.

    Science.gov (United States)

    Beccia, M R; Matara-Aho, M; Reeves, B; Roques, J; Solari, P L; Monfort, M; Moulin, C; Den Auwer, C

    2017-11-01

    Uranium is naturally present in seawater at trace levels and may in some cases be present at higher concentrations, due to anthropogenic nuclear activities. Understanding uranium speciation in seawater is thus essential for predicting and controlling its behavior in this specific environmental compartment and consequently, its possible impact on living organisms. The carbonato calcic complex Ca 2 UO 2 (CO 3 ) 3 was previously identified as the main uranium species in natural seawater, together with CaUO 2 (CO 3 ) 3 2- . In this work, we further investigate the role of the alkaline earth cation in the structure of the ternary uranyl-carbonate complexes. For this purpose, artificial seawater, free of Mg 2+ and Ca 2+ , using Sr 2+ as a spectroscopic probe was prepared. Combining TRLIF and EXAFS spectroscopy, together with DFT and theoretical thermodynamic calculations, evidence for the presence of Sr alkaline earth counter ion in the complex structure can be asserted. Furthermore, data suggest that when Ca 2+ is replaced by Sr 2+ , SrUO 2 (CO 3 ) 3 2- is the main complex in solution and it occurs with the presence of at least one monodentate carbonate in the uranyl coordination sphere. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Complex Reaction Environments and Competing Reaction Mechanisms in Zeolite Catalysis: Insights from Advanced Molecular Dynamics

    NARCIS (Netherlands)

    De Wispelaere, K.; Ensing, B.; Ghysels, A.; Meijer, E.J.; van Van Speybroeck, V.

    2015-01-01

    The methanol-to-olefin process is a showcase example of complex zeolite-catalyzed chemistry. At real operating conditions, many factors affect the reactivity, such as framework flexibility, adsorption of various guest molecules, and competitive reaction pathways. In this study, the strength of first

  20. Metamorphic complexes in accretionary orogens: Insights from the Beishan collage, southern Central Asian Orogenic Belt

    Science.gov (United States)

    Song, Dongfang; Xiao, Wenjiao; Windley, Brian F.; Han, Chunming; Yang, Lei

    2016-10-01

    The sources of ancient zircons and the tectonic attributions and origins of metamorphic complexes in Phanerozoic accretionary orogens have long been difficult issues. Situated between the Tianshan and Inner Mongolia orogens, the Beishan orogenic collage (BOC) plays a pivotal role in understanding the accretionary processes of the southern Central Asian Orogenic Belt (CAOB), particularly the extensive metamorphic and high-strained complexes on the southern margin. Despite their importance in understanding the basic architecture of the southern CAOB, little consensus has been reached on their ages and origins. Our new structural, LA-ICP-MS zircon U-Pb and Hf isotopic data from the Baidunzi, Shibandun, Qiaowan and Wutongjing metamorphic complexes resolve current controversial relations. The metamorphic complexes have varied lithologies and structures. Detrital zircons from five para-metamorphic rocks yield predominantly Phanerozoic ages with single major peaks at ca. 276 Ma, 286 Ma, 427 Ma, 428 Ma and 461 Ma. Two orthogneisses have weighted mean ages of 294 ± 2 Ma and 304 ± 2 Ma with no Precambrian inherited zircons. Most Phanerozoic zircons show positive εHf(t) values indicating significant crustal growth in the Ordovician, Silurian and Permian. The imbricated fold-thrust deformation style combined with diagnostic zircon U-Pb-Hf isotopic data demonstrate that the metamorphic rocks developed in a subduction-accretion setting on an arc or active continental margin. This setting and conclusion are supported by the nearby occurrence of Ordovician-Silurian adakites, Nb-rich basalts, Carboniferous-Permian ophiolitic mélanges, and trench-type turbidites. Current data do not support the presence of a widespread Precambrian basement in the evolution of the BOC; the accretionary processes may have continued to the early Permian in this part of the CAOB. These relationships have meaningful implications for the interpretation of the tectonic attributions and origins of other

  1. Mechanistic insights into validoxylamine A 7'-phosphate synthesis by VldE using the structure of the entire product complex.

    Directory of Open Access Journals (Sweden)

    Michael C Cavalier

    Full Text Available The pseudo-glycosyltransferase VldE catalyzes non-glycosidic C-N coupling between an unsaturated cyclitol and a saturated aminocyclitol with the conservation of the stereochemical configuration of the substrates to form validoxylamine A 7'-phosphate, the biosynthetic precursor of the antibiotic validamycin A. To study the molecular basis of its mechanism, the three-dimensional structures of VldE from Streptomyces hygroscopicus subsp. limoneus was determined in apo form, in complex with GDP, in complex with GDP and validoxylamine A 7'-phosphate, and in complex with GDP and trehalose. The structure of VldE with the catalytic site in both an "open" and "closed" conformation is also described. With these structures, the preferred binding of the guanine moiety by VldE, rather than the uracil moiety as seen in OtsA could be explained. The elucidation of the VldE structure in complex with the entirety of its products provides insight into the internal return mechanism by which catalysis occurs with a net retention of the stereochemical configuration of the donated cyclitol.

  2. Insights into functional-group-tolerant polymerization catalysis with phosphine-sulfonamide palladium (II) complexes

    KAUST Repository

    Jian, Zhongbao

    2014-12-08

    Two series of cationic palladium(II) methyl complexes {[(2-MeOC6H4)2PC6H4SO2NHC6H3(2,6-R1,R2)]PdMe}2[A]2 (X1+-A: R1=R2=H: H1+-A; R1=R2=CH(CH3)2: DIPP1+-A; R1=H, R2=CF3: CF31+-A; A=BF4 or SbF6) and neutral palladium(II) methyl complexes {[(2-MeOC6H4)2PC6H4SO2NC6H3(2,6-R1,R2)]PdMe(L)} (X1-acetone: L=acetone; X1-dmso: L=dimethyl sulfoxide; X1-pyr: L=pyridine) chelated by a phosphine-sulfonamide were synthesized and fully characterized. Stoichiometric insertion of methyl acrylate (MA) into all complexes revealed that a 2,1 regiochemistry dominates in the first insertion of MA. Subsequently, for the cationic complexes X1+-A, β-H elimination from the 2,1-insertion product X2+-AMA-2,1 is overwhelmingly favored over a second MA insertion to yield two major products X4+-AMA-1,2 and X5+-AMA. By contrast, for the weakly coordinated neutral complexes X1-acetone and X1-dmso, a second MA insertion of the 2,1-insertion product X2MA-2,1 is faster than β-H elimination and gives X3MA as major products. For the strongly coordinated neutral complexes X1-pyr, no second MA insertion and no β-H elimination (except for DIPP2-pyrMA-2,1) were observed for the 2,1-insertion product X2-pyrMA-2,1. The cationic complexes X1+-A exhibited high catalytic activities for ethylene dimerization, affording butenes (C4) with a high selectivity of up to 97.7% (1-butene: 99.3%). Differences in activities and selectivities suggest that the phosphine-sulfonamide ligands remain coordinated to the metal center in a bidentate fashion in the catalytically active species. By comparison, the neutral complexes X1-acetone, X1-dmso, and X1-pyr showed very low activity towards ethylene to give traces of oligomers. DFT analyses taking into account the two possible coordination modes (O or N) of the sulfonamide ligand for the cationic system CF31+ suggested that the experimentally observed high activity in ethylene dimerization is the result of a facile first ethylene insertion into the O-coordinated PdMe isomer and

  3. Effect of preparation processes and structural insight into the supermolecular system: Bisacodyl and β-cyclodextrin inclusion complex

    International Nuclear Information System (INIS)

    Li, Shanshan; Zhai, Yuanming; Yan, Jin; Wang, Lili; Xu, Kailin; Li, Hui

    2016-01-01

    In this study, β-cyclodextrin (β-CD) and bisacodyl were chosen as model host and guest molecule to explore the effect of preparation processes on the physicochemical properties of inclusion complexes (ICs) and to gain an insight into the structure of ICs. The influence of temperature and pH on complexation was studied by multiple temperature–pH phase solubility analysis. The most favorable conformation was predicted by molecular modeling using AutoDock. "1H nuclear magnetic resonance and rotating frame nuclear Overhauser effect spectroscopy further confirmed the structure. Moreover, bisacodyl·β-CD ICs in solid state were successfully prepared via three different procedures (co-crystallization, co-evaporation, and co-grinding) and fully characterized by several solid-state techniques, namely, Fourier transform infrared spectroscopy, X-ray powder diffraction, thermogravimetric analysis, differential scanning calorimetry, solid-state NMR spectroscopy, and scanning electron microscopy. It was found that acid solution and low temperature were unfavorable for formation of bisacodyl·β-CD. The pyridine moiety was suggested to be enclosed in the hydrophobic cavity of β-CD. The complexes prepared using co-crystallization showed properties similar to those prepared using co-evaporation. Moreover, ICs obtained by co-evaporation and co-grinding had higher loading efficiency, water solubility, and dissolution rate than ICs obtained by co-crystallization. - Highlights: • The structure of inclusion complex-bisacodyl·β-CD was determined. • Thermodynamic behaviors of complexation under different conditions were discussed. • Products from three different preparation methods were systemically compared. • Co-crystallization and co-evaporation produced similar complexes. • Co-evaporation and co-grinding had better effects than co-crystallization.

  4. Effect of preparation processes and structural insight into the supermolecular system: Bisacodyl and β-cyclodextrin inclusion complex

    Energy Technology Data Exchange (ETDEWEB)

    Li, Shanshan [College of Chemical Engineering, Sichuan University, Chengdu 610065 (China); Zhai, Yuanming [Analytical and Testing Center, Sichuan University, Chengdu 610064 (China); Yan, Jin; Wang, Lili; Xu, Kailin [College of Chemical Engineering, Sichuan University, Chengdu 610065 (China); Li, Hui, E-mail: lihuilab@sina.com [College of Chemical Engineering, Sichuan University, Chengdu 610065 (China)

    2016-01-01

    In this study, β-cyclodextrin (β-CD) and bisacodyl were chosen as model host and guest molecule to explore the effect of preparation processes on the physicochemical properties of inclusion complexes (ICs) and to gain an insight into the structure of ICs. The influence of temperature and pH on complexation was studied by multiple temperature–pH phase solubility analysis. The most favorable conformation was predicted by molecular modeling using AutoDock. {sup 1}H nuclear magnetic resonance and rotating frame nuclear Overhauser effect spectroscopy further confirmed the structure. Moreover, bisacodyl·β-CD ICs in solid state were successfully prepared via three different procedures (co-crystallization, co-evaporation, and co-grinding) and fully characterized by several solid-state techniques, namely, Fourier transform infrared spectroscopy, X-ray powder diffraction, thermogravimetric analysis, differential scanning calorimetry, solid-state NMR spectroscopy, and scanning electron microscopy. It was found that acid solution and low temperature were unfavorable for formation of bisacodyl·β-CD. The pyridine moiety was suggested to be enclosed in the hydrophobic cavity of β-CD. The complexes prepared using co-crystallization showed properties similar to those prepared using co-evaporation. Moreover, ICs obtained by co-evaporation and co-grinding had higher loading efficiency, water solubility, and dissolution rate than ICs obtained by co-crystallization. - Highlights: • The structure of inclusion complex-bisacodyl·β-CD was determined. • Thermodynamic behaviors of complexation under different conditions were discussed. • Products from three different preparation methods were systemically compared. • Co-crystallization and co-evaporation produced similar complexes. • Co-evaporation and co-grinding had better effects than co-crystallization.

  5. Aryl-NHC-group 13 trimethyl complexes: structural, stability and bonding insights

    KAUST Repository

    Wu, Melissa M.

    2016-12-14

    Treatment of aromatic N-substituted N-heterocyclic carbenes (NHCs) with trimethyl-gallium and -indium yielded the new Lewis acid-base adducts, IMes·GaMe3 (1), SIMes·GaMe3 (2), IPr·GaMe3 (3), SIPr·GaMe3 (4), IMes·InMe3 (5), SIMes·InMe3 (6), IPr·InMe3 (7), and SIPr·InMe3 (8), with all complexes being identified by X-ray diffraction, IR, and multinuclear NMR analyses. Complex stability was found to be largely dependent on the nature of the constituent NHC ligands. Percent buried volume (%VBur) and topographic steric map analyses were employed to quantify and elucidate the observed trends. Additionally, a detailed bond snapping energy (BSE) decomposition analysis focusing on both steric and orbital interactions of the M-NHC bond (M = Al, Ga and In) has been performed.

  6. Aryl-NHC-group 13 trimethyl complexes: structural, stability and bonding insights

    KAUST Repository

    Wu, Melissa M.; Gill, Arran M.; Yunpeng, Lu; Yongxin, Li; Ganguly, Rakesh; Falivene, Laura; Garcí a, Felipe

    2016-01-01

    Treatment of aromatic N-substituted N-heterocyclic carbenes (NHCs) with trimethyl-gallium and -indium yielded the new Lewis acid-base adducts, IMes·GaMe3 (1), SIMes·GaMe3 (2), IPr·GaMe3 (3), SIPr·GaMe3 (4), IMes·InMe3 (5), SIMes·InMe3 (6), IPr·InMe3 (7), and SIPr·InMe3 (8), with all complexes being identified by X-ray diffraction, IR, and multinuclear NMR analyses. Complex stability was found to be largely dependent on the nature of the constituent NHC ligands. Percent buried volume (%VBur) and topographic steric map analyses were employed to quantify and elucidate the observed trends. Additionally, a detailed bond snapping energy (BSE) decomposition analysis focusing on both steric and orbital interactions of the M-NHC bond (M = Al, Ga and In) has been performed.

  7. Coupling of terminal alkynes and isonitriles by organo-actinide complexes: Scope and mechanistic insights

    International Nuclear Information System (INIS)

    Barnea, E.; Andrea, T.; Eisen, M. S.; Berthet, J.C.; Ephritikhine, M.

    2008-01-01

    The coupling reaction of terminal alkynes with several isonitriles, catalyzed by the neutral organo-actinide complexes Cp * 2 AnMe 2 (Cp * = C 5 Me 5 , An = Th, U) or the cationic complex [(Et 2 N) 3 U][BPh 4 ], yielded substituted α, β-acetylenic aldimines, in good to excellent yields. The reaction proceeded via a 1,1-insertion of the isonitrile carbon into a metal-acetylide bond, followed by a protonolysis by the acidic proton of the terminal alkyne. Additional insertion products were obtained by altering the catalyst and the reactant ratios. A plausible mechanism for the catalytic reaction is also presented, based on kinetics measurements and thermodynamic studies of the coupling reaction with Cp * 2 ThMe 2 or [(Et 2 N) 3 U][BPh 4 ] as catalysts. The reaction is first-order in catalyst and isonitrile and zero-order in alkyne. (authors)

  8. Insights into functional-group-tolerant polymerization catalysis with phosphine-sulfonamide palladium(II) complexes.

    Science.gov (United States)

    Jian, Zhongbao; Falivene, Laura; Wucher, Philipp; Roesle, Philipp; Caporaso, Lucia; Cavallo, Luigi; Göttker-Schnetmann, Inigo; Mecking, Stefan

    2015-01-26

    Two series of cationic palladium(II) methyl complexes {[(2-MeOC6 H4 )2 PC6 H4 SO2 NHC6 H3 (2,6-R(1) ,R(2) )]PdMe}2 [A]2 ((X) 1(+) -A: R(1) =R(2) =H: (H) 1(+) -A; R(1) =R(2) =CH(CH3 )2 : (DIPP) 1(+) -A; R(1) =H, R(2) =CF3 : (CF3) 1(+) -A; A=BF4 or SbF6 ) and neutral palladium(II) methyl complexes {[(2-MeOC6 H4 )2 PC6 H4 SO2 NC6 H3 (2,6-R(1) ,R(2) )]PdMe(L)} ((X) 1-acetone: L=acetone; (X) 1-dmso: L=dimethyl sulfoxide; (X) 1-pyr: L=pyridine) chelated by a phosphine-sulfonamide were synthesized and fully characterized. Stoichiometric insertion of methyl acrylate (MA) into all complexes revealed that a 2,1 regiochemistry dominates in the first insertion of MA. Subsequently, for the cationic complexes (X) 1(+) -A, β-H elimination from the 2,1-insertion product (X) 2(+) -AMA-2,1 is overwhelmingly favored over a second MA insertion to yield two major products (X) 4(+) -AMA-1,2 and (X) 5(+) -AMA . By contrast, for the weakly coordinated neutral complexes (X) 1-acetone and (X) 1-dmso, a second MA insertion of the 2,1-insertion product (X) 2MA-2,1 is faster than β-H elimination and gives (X) 3MA as major products. For the strongly coordinated neutral complexes (X) 1-pyr, no second MA insertion and no β-H elimination (except for (DIPP) 2-pyrMA-2,1 ) were observed for the 2,1-insertion product (X) 2-pyrMA-2,1 . The cationic complexes (X) 1(+) -A exhibited high catalytic activities for ethylene dimerization, affording butenes (C4 ) with a high selectivity of up to 97.7 % (1-butene: 99.3 %). Differences in activities and selectivities suggest that the phosphine-sulfonamide ligands remain coordinated to the metal center in a bidentate fashion in the catalytically active species. By comparison, the neutral complexes (X) 1-acetone, (X) 1-dmso, and (X) 1-pyr showed very low activity towards ethylene to give traces of oligomers. DFT analyses taking into account the two possible coordination modes (O or N) of the sulfonamide ligand for the cationic system (CF3) 1(+) suggested

  9. Structural and functional insights into the malaria parasite moving junction complex.

    Directory of Open Access Journals (Sweden)

    Brigitte Vulliez-Le Normand

    Full Text Available Members of the phylum Apicomplexa, which include the malaria parasite Plasmodium, share many features in their invasion mechanism in spite of their diverse host cell specificities and life cycle characteristics. The formation of a moving junction (MJ between the membranes of the invading apicomplexan parasite and the host cell is common to these intracellular pathogens. The MJ contains two key parasite components: the surface protein Apical Membrane Antigen 1 (AMA1 and its receptor, the Rhoptry Neck Protein (RON complex, which is targeted to the host cell membrane during invasion. In particular, RON2, a transmembrane component of the RON complex, interacts directly with AMA1. Here, we report the crystal structure of AMA1 from Plasmodium falciparum in complex with a peptide derived from the extracellular region of PfRON2, highlighting clear specificities of the P. falciparum RON2-AMA1 interaction. The receptor-binding site of PfAMA1 comprises the hydrophobic groove and a region that becomes exposed by displacement of the flexible Domain II loop. Mutations of key contact residues of PfRON2 and PfAMA1 abrogate binding between the recombinant proteins. Although PfRON2 contacts some polymorphic residues, binding studies with PfAMA1 from different strains show that these have little effect on affinity. Moreover, we demonstrate that the PfRON2 peptide inhibits erythrocyte invasion by P. falciparum merozoites and that this strong inhibitory potency is not affected by AMA1 polymorphisms. In parallel, we have determined the crystal structure of PfAMA1 in complex with the invasion-inhibitory peptide R1 derived by phage display, revealing an unexpected structural mimicry of the PfRON2 peptide. These results identify the key residues governing the interactions between AMA1 and RON2 in P. falciparum and suggest novel approaches to antimalarial therapeutics.

  10. Novel complex MAD phasing and RNase H structural insights using selenium oligonucleotides

    Energy Technology Data Exchange (ETDEWEB)

    Abdur, Rob; Gerlits, Oksana O.; Gan, Jianhua; Jiang, Jiansheng; Salon, Jozef; Kovalevsky, Andrey Y.; Chumanevich, Alexander A.; Weber, Irene T.; Huang, Zhen, E-mail: huang@gsu.edu [Georgia State University, Atlanta, GA 30303 (United States)

    2014-02-01

    Selenium-derivatized oligonucleotides may facilitate phase determination and high-resolution structure determination for protein–nucleic acid crystallography. The Se atom-specific mutagenesis (SAM) strategy may also enhance the study of nuclease catalysis. The crystal structures of protein–nucleic acid complexes are commonly determined using selenium-derivatized proteins via MAD or SAD phasing. Here, the first protein–nucleic acid complex structure determined using selenium-derivatized nucleic acids is reported. The RNase H–RNA/DNA complex is used as an example to demonstrate the proof of principle. The high-resolution crystal structure indicates that this selenium replacement results in a local subtle unwinding of the RNA/DNA substrate duplex, thereby shifting the RNA scissile phosphate closer to the transition state of the enzyme-catalyzed reaction. It was also observed that the scissile phosphate forms a hydrogen bond to the water nucleophile and helps to position the water molecule in the structure. Consistently, it was discovered that the substitution of a single O atom by a Se atom in a guide DNA sequence can largely accelerate RNase H catalysis. These structural and catalytic studies shed new light on the guide-dependent RNA cleavage.

  11. Crystal Structure of the Herpesvirus Nuclear Egress Complex Provides Insights into Inner Nuclear Membrane Remodeling

    Directory of Open Access Journals (Sweden)

    Tzviya Zeev-Ben-Mordehai

    2015-12-01

    Full Text Available Although nucleo-cytoplasmic transport is typically mediated through nuclear pore complexes, herpesvirus capsids exit the nucleus via a unique vesicular pathway. Together, the conserved herpesvirus proteins pUL31 and pUL34 form the heterodimeric nuclear egress complex (NEC, which, in turn, mediates the formation of tight-fitting membrane vesicles around capsids at the inner nuclear membrane. Here, we present the crystal structure of the pseudorabies virus NEC. The structure revealed that a zinc finger motif in pUL31 and an extensive interaction network between the two proteins stabilize the complex. Comprehensive mutational analyses, characterized both in situ and in vitro, indicated that the interaction network is not redundant but rather complementary. Fitting of the NEC crystal structure into the recently determined cryoEM-derived hexagonal lattice, formed in situ by pUL31 and pUL34, provided details on the molecular basis of NEC coat formation and inner nuclear membrane remodeling.

  12. Quantum-Chemical Insights into the Self-Assembly of Carbon-Based Supramolecular Complexes

    Directory of Open Access Journals (Sweden)

    Joaquín Calbo

    2018-01-01

    Full Text Available Understanding how molecular systems self-assemble to form well-organized superstructures governed by noncovalent interactions is essential in the field of supramolecular chemistry. In the nanoscience context, the self-assembly of different carbon-based nanoforms (fullerenes, carbon nanotubes and graphene with, in general, electron-donor molecular systems, has received increasing attention as a means of generating potential candidates for technological applications. In these carbon-based systems, a deep characterization of the supramolecular organization is crucial to establish an intimate relation between supramolecular structure and functionality. Detailed structural information on the self-assembly of these carbon-based nanoforms is however not always accessible from experimental techniques. In this regard, quantum chemistry has demonstrated to be key to gain a deep insight into the supramolecular organization of molecular systems of high interest. In this review, we intend to highlight the fundamental role that quantum-chemical calculations can play to understand the supramolecular self-assembly of carbon-based nanoforms through a limited selection of supramolecular assemblies involving fullerene, fullerene fragments, nanotubes and graphene with several electron-rich π-conjugated systems.

  13. A Chromosome Segment Substitution Library of Weedy Rice for Genetic Dissection of Complex Agronomic and Domestication Traits.

    Directory of Open Access Journals (Sweden)

    Prasanta K Subudhi

    Full Text Available Chromosome segment substitution lines (CSSLs are a powerful alternative for locating quantitative trait loci (QTL, analyzing gene interactions, and providing starting materials for map-based cloning projects. We report the development and characterization of a CSSL library of a U.S. weedy rice accession 'PSRR-1' with genome-wide coverage in an adapted rice cultivar 'Bengal' background. The majority of the CSSLs carried a single defined weedy rice segment with an average introgression segment of 2.8 % of the donor genome. QTL mapping results for several agronomic and domestication traits from the CSSL population were compared with those obtained from two recombinant inbred line (RIL populations involving the same weedy rice accession. There was congruence of major effect QTLs between both types of populations, but new and additional QTLs were detected in the CSSL population. Although, three major effect QTLs for plant height were detected on chromosomes 1, 4, and 8 in the CSSL population, the latter two escaped detection in both RIL populations. Since this was observed for many traits, epistasis may play a major role for the phenotypic variation observed in weedy rice. High levels of shattering and seed dormancy in weedy rice might result from an accumulation of many small effect QTLs. Several CSSLs with desirable agronomic traits (e.g. longer panicles, longer grains, and higher seed weight identified in this study could be useful for rice breeding. Since weedy rice is a reservoir of genes for many weedy and agronomic attributes, the CSSL library will serve as a valuable resource to discover latent genetic diversity for improving crop productivity and understanding the plant domestication process through cloning and characterization of the underlying genes.

  14. Assessing the value of phenotypic information from non-genotyped animals for QTL mapping of complex traits in real and simulated populations.

    Science.gov (United States)

    Melo, Thaise P; Takada, Luciana; Baldi, Fernando; Oliveira, Henrique N; Dias, Marina M; Neves, Haroldo H R; Schenkel, Flavio S; Albuquerque, Lucia G; Carvalheiro, Roberto

    2016-06-21

    QTL mapping through genome-wide association studies (GWAS) is challenging, especially in the case of low heritability complex traits and when few animals possess genotypic and phenotypic information. When most of the phenotypic information is from non-genotyped animals, GWAS can be performed using the weighted single-step GBLUP (WssGBLUP) method, which permits to combine all available information, even that of non-genotyped animals. However, it is not clear to what extent phenotypic information from non-genotyped animals increases the power of QTL detection, and whether factors such as the extent of linkage disequilibrium (LD) in the population and weighting SNPs in WssGBLUP affect the importance of using information from non-genotyped animals in GWAS. These questions were investigated in this study using real and simulated data. Analysis of real data showed that the use of phenotypes of non-genotyped animals affected SNP effect estimates and, consequently, QTL mapping. Despite some coincidence, the most important genomic regions identified by the analyses, either using or ignoring phenotypes of non-genotyped animals, were not the same. The simulation results indicated that the inclusion of all available phenotypic information, even that of non-genotyped animals, tends to improve QTL detection for low heritability complex traits. For populations with low levels of LD, this trend of improvement was less pronounced. Stronger shrinkage on SNPs explaining lower variance was not necessarily associated with better QTL mapping. The use of phenotypic information from non-genotyped animals in GWAS may improve the ability to detect QTL for low heritability complex traits, especially in populations in which the level of LD is high.

  15. The Fanconi anemia DNA repair pathway: structural and functional insights into a complex disorder.

    Science.gov (United States)

    Walden, Helen; Deans, Andrew J

    2014-01-01

    Mutations in any of at least sixteen FANC genes (FANCA-Q) cause Fanconi anemia, a disorder characterized by sensitivity to DNA interstrand crosslinking agents. The clinical features of cytopenia, developmental defects, and tumor predisposition are similar in each group, suggesting that the gene products participate in a common pathway. The Fanconi anemia DNA repair pathway consists of an anchor complex that recognizes damage caused by interstrand crosslinks, a multisubunit ubiquitin ligase that monoubiquitinates two substrates, and several downstream repair proteins including nucleases and homologous recombination enzymes. We review progress in the use of structural and biochemical approaches to understanding how each FANC protein functions in this pathway.

  16. Mechanistic insights on the cycloisomerization of polyunsaturated precursors catalyzed by platinum and gold complexes.

    Science.gov (United States)

    Soriano, Elena; Marco-Contelles, José

    2009-08-18

    Organometallic chemistry provides powerful tools for the stereocontrolled synthesis of heterocycles and carbocycles. The electrophilic transition metals Pt(II) and Au(I, III) are efficient catalysts in these transitions and promote a variety of organic transformations of unsaturated precursors. These reactions produce functionalized cyclic and acyclic scaffolds for the synthesis of natural and non-natural products efficiently, under mild conditions, and with excellent chemoselectivity. Because these transformations are strongly substrate-dependent, they are versatile and may yield diverse molecular scaffolds. Therefore, synthetic chemists need a mechanistic interpretation to optimize this reaction process and design a new generation of catalysts. However, so far, no intermediate species has been isolated or characterized, so the formulated mechanistic hypotheses have been primarily based on labeling studies or trapping reactions. Recently, theoretical DFT studies have become a useful tool in our research, giving us insights into the key intermediates and into a variety of plausible reaction pathways. In this Account, we present a comprehensive mechanistic overview of transformations promoted by Pt and Au in a non-nucleophilic medium based on quantum-mechanical studies. The calculations are consistent with the experimental observations and provide fundamental insights into the versatility of these reaction processes. The reactivity of these metals results from their peculiar Lewis acid properties: the alkynophilic character of these soft metals and the pi-acid activation of unsaturated groups promotes the intra- or intermolecular attack of a nucleophile. 1,n-Enynes (n = 3-8) are particularly important precursors, and their transformation may yield a variety of cycloadducts depending on the molecular structure. However, the calculations suggest that these different cyclizations would have closely related reaction mechanisms, and we propose a unified mechanistic

  17. Knowledge to action for solving complex problems: insights from a review of nine international cases.

    Science.gov (United States)

    Riley, B L; Robinson, K L; Gamble, J; Finegood, D T; Sheppard, D; Penney, T L; Best, A

    2015-05-01

    Solving complex problems such as preventing chronic diseases introduces unique challenges for the creation and application of knowledge, or knowledge to action (KTA). KTA approaches that apply principles of systems thinking are thought to hold promise, but practical strategies for their application are not well understood. In this paper we report the results of a scan of systems approaches to KTA with a goal to identify how to optimize their implementation and impact. A 5-person advisory group purposefully selected 9 initiatives to achieve diversity on issues addressed and organizational forms. Information on each case was gathered from documents and through telephone interviews with primary contacts within each organization. Following verification of case descriptions, an inductive analysis was conducted within and across cases. The cases revealed 5 guidelines for moving from conceiving KTA systems to implementing them: (1) establish and nurture relationships, (2) co-produce and curate knowledge, (3) create feedback loops, (4) frame as systems interventions rather than projects, and (5) consider variations across time and place. Results from the environmental scan are a modest start to translating systems concepts for KTA into practice. Use of the strategies revealed in the scan may improve KTA for solving complex public health problems. The strategies themselves will benefit from the development of a science that aims to understand adaptation and ongoing learning from policy and practice interventions, strengthens enduring relationships, and fills system gaps in addition to evidence gaps. Systems approaches to KTA will also benefit from robust evaluations.

  18. Studies of lysine cyclodeaminase from Streptomyces pristinaespiralis: Insights into the complex transition NAD+ state.

    Science.gov (United States)

    Ying, Hanxiao; Wang, Jing; Shi, Ting; Zhao, Yilei; Wang, Xin; Ouyang, Pingkai; Chen, Kequan

    2018-01-01

    Lysine cyclodeaminase (LCD) catalyzes the piperidine ring formation in macrolide-pipecolate natural products metabolic pathways from a lysine substrate through a combination of cyclization and deamination. This enzyme belongs to a unique enzyme class, which uses NAD + as the catalytic prosthetic group instead of as the co-substrate. To understand the molecular details of NAD + functions in lysine cyclodeaminase, we have determined four ternary crystal structure complexes of LCD-NAD + with pipecolic acid (LCD-PA), lysine (LCD-LYS), and an intermediate (LCD-INT) as ligands at 2.26-, 2.00-, 2.17- and 1.80 Å resolutions, respectively. By combining computational studies, a NAD + -mediated "gate keeper" function involving NAD + /NADH and Arg49 that control the binding and entry of the ligand lysine was revealed, confirming the critical roles of NAD + in the substrate access process. Further, in the gate opening form, a substrate delivery tunnel between ε-carboxyl moiety of Glu264 and the α-carboxyl moiety of Asp236 was observed through a comparison of four structure complexes. The LCD structure details including NAD + -mediated "gate keeper" and substrate tunnel may assist in the exploration the NAD + function in this unique enzyme class, and in regulation of macrolide-pipecolate natural product synthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures

    Energy Technology Data Exchange (ETDEWEB)

    Hubin, Elizabeth A.; Lilic, Mirjana; Darst, Seth A.; Campbell, Elizabeth A.

    2017-07-13

    The mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against tuberculosis, motivating structure/function studies. Here we report a 3.2 Å-resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter complex (RPo), along with structural analysis of the Msm RPo and a previously reported 2.76 Å-resolution crystal structure of an Msm transcription initiation complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP α-subunit C-terminal domain (αCTD) with DNA, and we provide evidence that the αCTD may play a role in Mtb transcription regulation. Our results reveal the structure of an Actinobacteria-unique insert of the RNAP β' subunit. Finally, our analysis reveals the disposition of the N-terminal segment of Msm σA, which may comprise an intrinsically disordered protein domain unique to mycobacteria. The clade-specific features of the mycobacteria RNAP provide clues to the profound instability of mycobacteria RPo compared with E. coli.

  20. Structural insights into RNA processing by the human RISC-loading complex.

    Science.gov (United States)

    Wang, Hong-Wei; Noland, Cameron; Siridechadilok, Bunpote; Taylor, David W; Ma, Enbo; Felderer, Karin; Doudna, Jennifer A; Nogales, Eva

    2009-11-01

    Targeted gene silencing by RNA interference (RNAi) requires loading of a short guide RNA (small interfering RNA (siRNA) or microRNA (miRNA)) onto an Argonaute protein to form the functional center of an RNA-induced silencing complex (RISC). In humans, Argonaute2 (AGO2) assembles with the guide RNA-generating enzyme Dicer and the RNA-binding protein TRBP to form a RISC-loading complex (RLC), which is necessary for efficient transfer of nascent siRNAs and miRNAs from Dicer to AGO2. Here, using single-particle EM analysis, we show that human Dicer has an L-shaped structure. The RLC Dicer's N-terminal DExH/D domain, located in a short 'base branch', interacts with TRBP, whereas its C-terminal catalytic domains in the main body are proximal to AGO2. A model generated by docking the available atomic structures of Dicer and Argonaute homologs into the RLC reconstruction suggests a mechanism for siRNA transfer from Dicer to AGO2.

  1. Rheo-NMR - how nuclear magnetic resonance is providing new insight regarding complex fluid rheology

    International Nuclear Information System (INIS)

    Callaghan, P.T.

    2000-01-01

    Over the past five decades, NMR has revolutionised chemistry, and has found widespread application in condensed matter physics, in molecular biology, in medicine and in food technology. Most recently NMR has made a significant impact in chemical engineering, where it is being extensively used for the non-invasive study of dispersion and flow in porous media. One of the most recent applications of NMR in materials science concerns its use in the study of the mechanical properties of complex fluids. This particular aspect of NMR has been extensively developed in research carried out at Massey University in New Zealand. In this short article, some of the ideas behind this work and the applications which have resulted, will be described. These examples provide a glimpse of possible applications of Nuclear Magnetic Resonance to the study of complex fluid rheology. While this is a very new field of research in which only a handful of groups presently participate, the potential exists for a substantial increase in Rheo-NMR research activity. Systems studied to date include polymer melts and semi-dilute solutions, thermotropic and lyotropic liquid crystals and liquid crystalline polymers, micellar solutions, food materials and colloidal suspensions. Rheo-NMR suffers in a number of respects by comparison with optical methods. It is expensive, it is difficult to use, it suffers from poor signal-to-noise ratios and the effective interpretation of spectra often depends on familiarity with the nuclear spin Hamiltonian and the associated effects of spin dynamics. Nonetheless NMR offers some unique advantages, including the ability to work with opaque materials, the ability to combine velocimetry with localised spectroscopy, and the ability to access a wide range of molecular properties relating to organisation, orientation and dynamics. Rheo-NMR has been able to provide a direct window on a variety of behaviours, including slip, shear-thinning, shear banding, yield stress

  2. Gaining insight into the physics of dynamic atomic force microscopy in complex environments using the VEDA simulator

    Science.gov (United States)

    Kiracofe, Daniel; Melcher, John; Raman, Arvind

    2012-01-01

    Dynamic atomic force microscopy (dAFM) continues to grow in popularity among scientists in many different fields, and research on new methods and operating modes continues to expand the resolution, capabilities, and types of samples that can be studied. But many promising increases in capability are accompanied by increases in complexity. Indeed, interpreting modern dAFM data can be challenging, especially on complicated material systems, or in liquid environments where the behavior is often contrary to what is known in air or vacuum environments. Mathematical simulations have proven to be an effective tool in providing physical insight into these non-intuitive systems. In this article we describe recent developments in the VEDA (virtual environment for dynamic AFM) simulator, which is a suite of freely available, open-source simulation tools that are delivered through the cloud computing cyber-infrastructure of nanoHUB (www.nanohub.org). Here we describe three major developments. First, simulations in liquid environments are improved by enhancements in the modeling of cantilever dynamics, excitation methods, and solvation shell forces. Second, VEDA is now able to simulate many new advanced modes of operation (bimodal, phase-modulation, frequency-modulation, etc.). Finally, nineteen different tip-sample models are available to simulate the surface physics of a wide variety different material systems including capillary, specific adhesion, van der Waals, electrostatic, viscoelasticity, and hydration forces. These features are demonstrated through example simulations and validated against experimental data, in order to provide insight into practical problems in dynamic AFM.

  3. Water Complexes of Cytochrome P450: Insights from Energy Decomposition Analysis

    Directory of Open Access Journals (Sweden)

    Hajime Hirao

    2013-06-01

    Full Text Available Water is a small molecule that nevertheless perturbs, sometimes significantly, the electronic properties of an enzyme’s active site. In this study, interactions of a water molecule with the ferric heme and the compound I (Cpd I intermediate of cytochrome P450 are studied. Energy decomposition analysis (EDA schemes are used to investigate the physical origins of these interactions. Localized molecular orbital EDA (LMOEDA implemented in the quantum chemistry software GAMESS and the EDA method implemented in the ADF quantum chemistry program are used. EDA reveals that the electrostatic and polarization effects act as the major driving force in both of these interactions. The hydrogen bonding in the Cpd I•••H2O complex is similar to that in the water dimer; however, the relative importance of the electrostatic effect is somewhat larger in the water dimer.

  4. Limnephilid taxa revised by speciation traits: Rhadicoleptus, Isogamus, Melampophylax genera, Chaetopteryx rugulosa, Psilopteryx psorosa species groups, Drusus bolivari, Annitella kosciuszkii species complexes (Trichoptera: Limnephilidae

    Directory of Open Access Journals (Sweden)

    Oláh, J.

    2015-06-01

    Full Text Available Speciation traits of paramere, paraproct and aedeagus were applied to find initial split criteria with fine structure analysis in order to prepare diverged trait matrices for delimiting phylogenetic incipient species of unsettled limnephilid taxa in the early stages of reproductive isolation. A brief history is presented how this phenotypic taxonomic tool of the speciation traits was discovered and applied in caddisfly taxonomy. The theoretical basis was elaborated for the phenotypic speciation trait by reviewing several relevant topics in the sciences of taxonomy, molecular genetics and phylogenetics. Perspectives of integrative taxonomy is discussed in context of phenotype versus genotype, immensely complex phenotype versus phenomic challenge, taxonomic impediment versus genetic expedient, taxonomic adaptation of genetic vocabulary versus genetic sophistication and virtualization, New Systematics of Huxley and Mayr versus New Taxonomy of Wheeler. Debates on magic trait, speciation phenotype, speciation trait and super traits are discussed concluding that evolution works with phenotype and why the cryptic species concept is irrelevant. Briefly summarized how speciation traits evolve in sexual selection, through accelerated reproductive isolation with genital evolution through sex-limited speciation traits, including minor sex chromosomes. Why neutral molecular markers are blind compared to the adaptive speciation traits sensitized by fine structure analysis and backed by the potential of high-tech and high-throughput phenotyping and cyber-infrastructure broadly accessible and fed by computable phenotype descriptions. What sort of genetics could really help taxonomy to describe biodiversity of the over 100 million unknown taxa? Collecting new and re-examining old type materials deposited in various collections, the following taxonomic actions were elaborated by speciation traits. Drusus bolivari new species complex has been erected with

  5. An insight into the thermodynamic characteristics of human thrombopoietin complexation with TN1 antibody

    Science.gov (United States)

    Shibazaki, Chie; Adachi, Motoyasu; Honjo, Eijiro; Tamada, Taro; Maeda, Yoshitake; Tahara, Tomoyuki; Kato, Takashi; Miyazaki, Hiroshi; Blaber, Michael; Kuroki, Ryota

    2016-01-01

    Abstract Human thrombopoietin (hTPO) primarily stimulates megakaryocytopoiesis and platelet production and is neutralized by the mouse TN1 antibody. The thermodynamic characteristics of TN1 antibody–hTPO complexation were analyzed by isothermal titration calorimetry (ITC) using an antigen‐binding fragment (Fab) derived from the TN1 antibody (TN1‐Fab). To clarify the mechanism by which hTPO is recognized by TN1‐Fab the conformation of free TN1‐Fab was determined to a resolution of 2.0 Å using X‐ray crystallography and compared with the hTPO‐bound form of TN1‐Fab determined by a previous study. This structural comparison revealed that the conformation of TN1‐Fab does not substantially change after hTPO binding and a set of 15 water molecules is released from the antigen‐binding site (paratope) of TN1‐Fab upon hTPO complexation. Interestingly, the heat capacity change (ΔCp) measured by ITC (−1.52 ± 0.05 kJ mol−1 K−1) differed significantly from calculations based upon the X‐ray structure data of the hTPO‐bound and unbound forms of TN1‐Fab (−1.02 ∼ 0.25 kJ mol−1 K−1) suggesting that hTPO undergoes an induced‐fit conformational change combined with significant desolvation upon TN1‐Fab binding. The results shed light on the structural biology associated with neutralizing antibody recognition. PMID:27419667

  6. Interdependence of free zinc changes and protein complex assembly - insights into zinc signal regulation.

    Science.gov (United States)

    Kocyła, Anna; Adamczyk, Justyna; Krężel, Artur

    2018-01-24

    Cellular zinc (Zn(ii)) is bound with proteins that are part of the proteomes of all domains of life. It is mostly utilized as a catalytic or structural protein cofactor, which results in a vast number of binding architectures. The Zn(ii) ion is also important for the formation of transient protein complexes with a Zn(ii)-dependent quaternary structure that is formed upon cellular zinc signals. The mechanisms by which proteins associate with and dissociate from Zn(ii) and the connection with cellular Zn(ii) changes remain incompletely understood. In this study, we aimed to examine how zinc protein domains with various Zn(ii)-binding architectures are formed under free Zn(ii) concentration changes and how formation of the Zn(ii)-dependent assemblies is related to the protein concentration and reactivity. To accomplish these goals we chose four zinc domains with different Zn(ii)-to-protein binding stoichiometries: classical zinc finger (ZnP), LIM domain (Zn 2 P), zinc hook (ZnP 2 ) and zinc clasp (ZnP 1 P 2 ) folds. Our research demonstrated a lack of changes in the saturation level of intraprotein zinc binding sites, despite various peptide concentrations, while homo- and heterodimers indicated a concentration-dependent tendency. In other words, at a certain free Zn(ii) concentration, the fraction of a formed dimeric complex increases or decreases with subunit concentration changes. Secondly, even small or local changes in free Zn(ii) may significantly affect protein saturation depending on its architecture, function and subcellular concentration. In our paper, we indicate the importance of interdependence of free Zn(ii) availability and protein subunit concentrations for cellular zinc signal regulation.

  7. miR-34 and p53: New Insights into a Complex Functional Relationship.

    Directory of Open Access Journals (Sweden)

    Francisco Navarro

    Full Text Available miR-34, a tumor suppressor miRNA family transcriptionally activated by p53, is considered a critical mediator of p53 function. However, knockout of the mouse miR-34 family has little or no effect on the p53 response. The relative contribution of different miR-34 family members to p53 function or how much p53 relies on miR-34 in human cells is unclear. Here we show that miR-34a has a complex effect on the p53 response in human cells. In HCT116 cells miR-34a overexpression enhances p53 transcriptional activity, but the closely related family members, miR-34b and miR-34c, even when over-expressed, have little effect. Both TP53 itself and MDM4, a strong p53 transactivation inhibitor, are direct targets of miR-34a. The genes regulated by miR-34a also include four other post-translational inhibitors of p53. miR-34a overexpression leads to variable effects on p53 levels in p53-sufficient human cancer cell lines. In HCT116, miR-34a overexpression increases p53 protein levels and stability. About a quarter of all mRNAs that participate in the human p53 network bind to biotinylated miR-34a, suggesting that many are direct miR-34a targets. However, only about a fifth of the mRNAs that bind to miR-34a also bind to miR-34b or miR-34c. Two human cell lines knocked out for miR-34a have unimpaired p53-mediated responses to genotoxic stress, like mouse cells. The complex positive and negative effects of miR-34 on the p53 network suggest that rather than simply promoting the p53 response, miR-34a might act at a systems level to stabilize the robustness of the p53 response to genotoxic stress.

  8. Structural insights into a high affinity nanobody:antigen complex by homology modelling.

    Science.gov (United States)

    Skottrup, Peter Durand

    2017-09-01

    Porphyromonas gingivalis is a major periodontitis-causing pathogens. P. gingivalis secrete a cysteine protease termed RgpB, which is specific for Arg-Xaa bonds in substrates. Recently, a nanobody-based assay was used to demonstrate that RgpB could represent a novel diagnostic target, thereby simplifying. P. gingivalis detection. The nanobody, VHH7, had a high binding affinity and was specific for RgpB, when tested towards the highly identical RgpA. In this study a homology model of VHH7 was build. The complementarity determining regions (CDR) comprising the paratope residues responsible for RgpB binding were identified and used as input to the docking. Furthermore, residues likely involved in the RgpB epitope was identified based upon RgpB:RgpA alignment and analysis of residue surface accessibility. CDR residues and putitative RgpB epitope residues were used as input to an information-driven flexible docking approach using the HADDOCK server. Analysis of the VHH7:RgpB model demonstrated that the epitope was found in the immunoglobulin-like domain and residue pairs located at the molecular paratope:epitope interface important for complex stability was identified. Collectively, the VHH7 homology model and VHH7:RgpB docking supplies knowledge of the residues involved in the high affinity interaction. This information could prove valuable in the design of an antibody-drug conjugate for specific RgpB targeting. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. First insights on the molybdenum-copper Bled M'Dena complex (Eglab massif, Algeria)

    Science.gov (United States)

    Lagraa, Karima; Salvi, Stefano; Béziat, Didier; Debat, Pierre; Kolli, Omar

    2017-03-01

    Molybdenum-Copper showings in the Eglab massif (eastern part of the Reguibat rise of Algeria), are found in quartz-monzodiorite and granodiorite of the Bled M'Dena complex, a Paleoproterozoic circular structure of ∼5 km in diameter, comprising volcanic and intrusive suites. The latter consist of quartz-diorite, quartz-monzodiorite and granodiorite with a metaluminous normative composition. They display an "adakitic character" with moderate light rare-earth element (LREE) enrichment, minor Eu anomalies, high Sr/Y ratio and low Yb concentration, suggestive of a hydrous, arc magma of volcanic-arc affinity. The mineralization occurs mostly in quartz + molybdenite + chalcopyrite stockwork veins marked by widespread propylitic alteration along the selvages. Molybdenite and chalcopyrite are commonly associated with calcite, which precipitated at relatively late stages of the hydrothermal alteration. Fluid inclusions related to the mineralization stage, range from aqueous to aqueous-carbonic to solid bearing. The latter inclusions have the highest homogenization temperature (up to ∼400 °C), are salt saturated, and commonly contain molybdenite and/or chalcopyrite crystals. The petrology and geochemistry of the host rocks, the style of the hydrothermal alteration, the ore mineral associations, and the characteristics of the fluid inclusions, are all coherent in indicating that the Bled M'Dena represents a Paleoproterozoic porphyry style Mo mineralization, which is far unreported in the African continent.

  10. New insights on the structure of the picloram-montmorillonite surface complexes.

    Science.gov (United States)

    Marco-Brown, Jose L; Trinelli, María Alcira; Gaigneaux, Eric M; Sánchez, Rosa M Torres; Afonso, María dos Santos

    2015-04-15

    The environmental mobility and bioavailability of Picloram (PCM) are determined by the amine and carboxylate chemical groups interaction with the soils mineral phases. Clay particles, such as montmorillonite (Mt), and the pH value of the media could play an important role in adsorption processes. Thus, the study of the role of soil components other than organic matter deserves further investigation for a more accurate assessment of the risk of groundwater contamination. Samples with PCM adsorbed on Mt dispersions were prepared at pH 3-9. Subsequently, the dispersions were separated, washed, centrifuged and stored at room temperature. Picloram (PCM) herbicide interaction with surface groups of montmorillonite (Mt) was studied using XRD, DTA, FTIR and XPS techniques. The entrance of PCM into the Mt basal space, in two different arrangements, perpendicular and planar, is proposed and the final arrangement depends on PCM concentration. The interaction of PCM with Mt surface sites through the nitrogen of the pyridine ring and carboxylic group of PCM, forming bidentate and bridge inner-sphere complexes was confirmed by FTIR and XPS analysis. The acidity constant of the PCM adsorbed on the Mt surface was calculated. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Structural insights into Rhino-Deadlock complex for germline piRNA cluster specification.

    Science.gov (United States)

    Yu, Bowen; Lin, Yu An; Parhad, Swapnil S; Jin, Zhaohui; Ma, Jinbiao; Theurkauf, William E; Zhang, Zz Zhao; Huang, Ying

    2018-06-01

    PIWI-interacting RNAs (piRNAs) silence transposons in germ cells to maintain genome stability and animal fertility. Rhino, a rapidly evolving heterochromatin protein 1 (HP1) family protein, binds Deadlock in a species-specific manner and so defines the piRNA-producing loci in the Drosophila genome. Here, we determine the crystal structures of Rhino-Deadlock complex in Drosophila melanogaster and simulans In both species, one Rhino binds the N-terminal helix-hairpin-helix motif of one Deadlock protein through a novel interface formed by the beta-sheet in the Rhino chromoshadow domain. Disrupting the interface leads to infertility and transposon hyperactivation in flies. Our structural and functional experiments indicate that electrostatic repulsion at the interaction interface causes cross-species incompatibility between the sibling species. By determining the molecular architecture of this piRNA-producing machinery, we discover a novel HP1-partner interacting mode that is crucial to piRNA biogenesis and transposon silencing. We thus explain the cross-species incompatibility of two sibling species at the molecular level. © 2018 The Authors.

  12. “Are We There Yet?”: Deciding When One Has Demonstrated Specific Genetic Causation in Complex Diseases and Quantitative Traits

    Science.gov (United States)

    Page, Grier P.; George, Varghese; Go, Rodney C.; Page, Patricia Z.; Allison, David B.

    2003-01-01

    Although mathematical relationships can be proven by deductive logic, biological relationships can only be inferred from empirical observations. This is a distinct disadvantage for those of us who strive to identify the genes involved in complex diseases and quantitative traits. If causation cannot be proven, however, what does constitute sufficient evidence for causation? The philosopher Karl Popper said, “Our belief in a hypothesis can have no stronger basis than our repeated unsuccessful critical attempts to refute it.” We believe that to establish causation, as scientists, we must make a serious attempt to refute our own hypotheses and to eliminate all known sources of bias before association becomes causation. In addition, we suggest that investigators must provide sufficient data and evidence of their unsuccessful efforts to find any confounding biases. In this editorial, we discuss what “causation” means in the context of complex diseases and quantitative traits, and we suggest guidelines for steps that may be taken to address possible confounders of association before polymorphisms may be called “causative.” PMID:13680525

  13. Structure of a Human Astrovirus Capsid-Antibody Complex and Mechanistic Insights into Virus Neutralization

    Energy Technology Data Exchange (ETDEWEB)

    Bogdanoff, Walter A.; Campos, Jocelyn; Perez, Edmundo I.; Yin, Lu; Alexander, David L.; DuBois, Rebecca M. (UCSC)

    2016-11-02

    ABSTRACT

    Human astroviruses (HAstVs) are a leading cause of viral diarrhea in young children, the immunocompromised, and the elderly. There are no vaccines or antiviral therapies against HAstV disease. Several lines of evidence point to the presence of protective antibodies in healthy adults as a mechanism governing protection against reinfection by HAstV. However, development of anti-HAstV therapies is hampered by the gap in knowledge of protective antibody epitopes on the HAstV capsid surface. Here, we report the structure of the HAstV capsid spike domain bound to the neutralizing monoclonal antibody PL-2. The antibody uses all six complementarity-determining regions to bind to a quaternary epitope on each side of the dimeric capsid spike. We provide evidence that the HAstV capsid spike is a receptor-binding domain and that the antibody neutralizes HAstV by blocking virus attachment to cells. We identify patches of conserved amino acids that overlap the antibody epitope and may comprise a receptor-binding site. Our studies provide a foundation for the development of therapies to prevent and treat HAstV diarrheal disease.

    IMPORTANCEHuman astroviruses (HAstVs) infect nearly every person in the world during childhood and cause diarrhea, vomiting, and fever. Despite the prevalence of this virus, little is known about how antibodies in healthy adults protect them against reinfection. Here, we determined the crystal structure of a complex of the HAstV capsid protein and a virus-neutralizing antibody. We show that the antibody binds to the outermost spike domain of the capsid, and we provide evidence that the antibody blocks virus attachment to human cells. Importantly, our findings suggest that a subunit-based vaccine focusing the immune system on the HAstV capsid spike domain could be effective in protecting children against HAstV disease.

  14. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    Energy Technology Data Exchange (ETDEWEB)

    Cros, C., E-mail: caroline.cros@hotmail.co.uk [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Skinner, M., E-mail: Matthew.Skinner@astrazeneca.com [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Moors, J. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Lainee, P. [Sanofi-Aventis R and D, 371, rue du Pr Joseph Blayac, 34184 Montpellier Cedex 04 (France); Valentin, J.P. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom)

    2012-12-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I{sub Na}) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I{sub Na}, this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E{sub max} 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two

  15. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    International Nuclear Information System (INIS)

    Cros, C.; Skinner, M.; Moors, J.; Lainee, P.; Valentin, J.P.

    2012-01-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I Na ) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I Na , this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E max 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two out of three

  16. Sodium montmorillonite/amine-containing drugs complexes: new insights on intercalated drugs arrangement into layered carrier material.

    Directory of Open Access Journals (Sweden)

    Murilo L Bello

    Full Text Available Layered drug delivery carriers are current targets of nanotechnology studies since they are able to accommodate pharmacologically active substances and are effective at modulating drug release. Sodium montmorillonite (Na-MMT is a clay that has suitable properties for developing new pharmaceutical materials due to its high degree of surface area and high capacity for cation exchange. Therefore Na-MMT is a versatile material for the preparation of new drug delivery systems, especially for slow release of protonable drugs. Herein, we describe the intercalation of several amine-containing drugs with Na-MMT so we can derive a better understanding of how these drugs molecules interact with and distribute throughout the Na-MMT interlayer space. Therefore, for this purpose nine sodium montmorillonite/amine-containing drugs complexes (Na-MMT/drug were prepared and characterized. In addition, the physicochemical properties of the drugs molecules in combination with different experimental conditions were assessed to determine how these factors influenced experimental outcomes (e.g. increase of the interlayer spacing versus drugs arrangement and orientation. We also performed a molecular modeling study of these amine-containing drugs associated with different Na-MMT/drug complex models to analyze the orientation and arrangement of the drugs molecules in the complexes studied. Six amine-containing drugs (rivastigmine, doxazosin, 5-fluorouracil, chlorhexidine, dapsone, nystatin were found to successfully intercalate Na-MMT. These findings provide important insights on the interlayer aspect of the molecular systems formed and may contribute to produce more efficient drug delivery nanosystems.

  17. Systems Biology for Smart Crops and Agricultural Innovation: Filling the Gaps between Genotype and Phenotype for Complex Traits Linked with Robust Agricultural Productivity and Sustainability

    Science.gov (United States)

    Pathak, Rajesh Kumar; Gupta, Sanjay Mohan; Gaur, Vikram Singh; Pandey, Dinesh

    2015-01-01

    Abstract In recent years, rapid developments in several omics platforms and next generation sequencing technology have generated a huge amount of biological data about plants. Systems biology aims to develop and use well-organized and efficient algorithms, data structure, visualization, and communication tools for the integration of these biological data with the goal of computational modeling and simulation. It studies crop plant systems by systematically perturbing them, checking the gene, protein, and informational pathway responses; integrating these data; and finally, formulating mathematical models that describe the structure of system and its response to individual perturbations. Consequently, systems biology approaches, such as integrative and predictive ones, hold immense potential in understanding of molecular mechanism of agriculturally important complex traits linked to agricultural productivity. This has led to identification of some key genes and proteins involved in networks of pathways involved in input use efficiency, biotic and abiotic stress resistance, photosynthesis efficiency, root, stem and leaf architecture, and nutrient mobilization. The developments in the above fields have made it possible to design smart crops with superior agronomic traits through genetic manipulation of key candidate genes. PMID:26484978

  18. Longitudinal and cross-sectional changes with age in selected anthropometric and physiological traits in hospitalized adults: an insight from the Polish Longitudinal Study of Aging (PLSA

    Directory of Open Access Journals (Sweden)

    Chmielewski Piotr

    2015-12-01

    Full Text Available Longitudinal studies of aging concerning individuals with comparable lifestyle, diet, health profile, socioeconomic status, and income remain extraordinarily rare. The purposes of our ongoing project are as follows: (i to collect extensive data on biological and medical aspects of aging in the Polish population, (ii to determine factors affecting the rate and course of aging, (iii to understand how aging unfolds as a dynamic and malleable process in ontogeny, and (iv to find novel predictors of longevity. Our investigation followed 142 physically healthy asylum inmates, including 68 males and 74 females, for at least 25 years from the age of 45 years onward. Cross-sectional assessment involved 225 inmates, including 113 males and 112 females. All the patients lived for a very long time under similar and good environmental conditions at the hospital in Cibórz, Lubuskie Province. They maintained virtually the same daily schedule and lifestyle. The rate and direction of changes with age in selected anthropometric and physiological traits were determined using ANOVA, t-test, and regression analysis. There were sex differences in the rate and pattern of age-related changes in certain characteristics such as relative weight, red blood cell count, monocyte count, thymol turbidity value, systolic blood pressure, and body temperature. Body weight, the body mass index (BMI, and total bilirubin level increased with advancing age, while body height decreased with age in both sexes. In conclusion, the aging process was associated with many regressive alterations in biological traits in both sexes but the rate and pattern of these changes depended on biological factors such as age and sex. There were only few characteristics which did not change significantly during the period under study. On the basis of comparison between the pattern of longitudinal changes with aging and the pattern of cross-sectional changes with age in the analyzed traits, we were able

  19. Genomic prediction in contrast to a genome-wide association study in explaining heritable variation of complex growth traits in breeding populations of Eucalyptus.

    Science.gov (United States)

    Müller, Bárbara S F; Neves, Leandro G; de Almeida Filho, Janeo E; Resende, Márcio F R; Muñoz, Patricio R; Dos Santos, Paulo E T; Filho, Estefano Paludzyszyn; Kirst, Matias; Grattapaglia, Dario

    2017-07-11

    capture large proportions of trait heritability and predict growth traits in trees with accuracies equal or better than those attainable by phenotypic selection. Additionally, our results document the superiority of the whole-genome regression approach in accounting for large proportions of the heritability of complex traits such as growth in contrast to the limited value of the local GWAS approach toward breeding applications in forest trees.

  20. A Flexible Computational Framework Using R and Map-Reduce for Permutation Tests of Massive Genetic Analysis of Complex Traits.

    Science.gov (United States)

    Mahjani, Behrang; Toor, Salman; Nettelblad, Carl; Holmgren, Sverker

    2017-01-01

    In quantitative trait locus (QTL) mapping significance of putative QTL is often determined using permutation testing. The computational needs to calculate the significance level are immense, 10 4 up to 10 8 or even more permutations can be needed. We have previously introduced the PruneDIRECT algorithm for multiple QTL scan with epistatic interactions. This algorithm has specific strengths for permutation testing. Here, we present a flexible, parallel computing framework for identifying multiple interacting QTL using the PruneDIRECT algorithm which uses the map-reduce model as implemented in Hadoop. The framework is implemented in R, a widely used software tool among geneticists. This enables users to rearrange algorithmic steps to adapt genetic models, search algorithms, and parallelization steps to their needs in a flexible way. Our work underlines the maturity of accessing distributed parallel computing for computationally demanding bioinformatics applications through building workflows within existing scientific environments. We investigate the PruneDIRECT algorithm, comparing its performance to exhaustive search and DIRECT algorithm using our framework on a public cloud resource. We find that PruneDIRECT is vastly superior for permutation testing, and perform 2 ×10 5 permutations for a 2D QTL problem in 15 hours, using 100 cloud processes. We show that our framework scales out almost linearly for a 3D QTL search.

  1. The drug-eluting resorbable magnesium vascular scaffold in complex coronary bifurcations: insights from an in vivo multimodality imaging study.

    Science.gov (United States)

    Bennett, Johan; Vanhaverbeke, Maarten; Vanden Driessche, Nina; Hiltrop, Nick; Adriaenssens, Tom; Desmet, Walter; Sinnaeve, Peter; Dubois, Christophe

    2018-04-20

    This acute in vivo study sought to provide insights regarding the feasibility of performing complex bifurcation stenting with Magmaris magnesium alloy bioresorbable scaffolds (Biotronik, Bulach, Switzerland). Twenty-five New Zealand White rabbits underwent stenting of non-diseased aorto-iliac bifurcations with the Magmaris using provisional (PS; n=5), culotte (n=6), modified T (n=6), or T and protrusion (TAP, n=8) stenting techniques. Angiography, optical coherence tomography and micro-computed tomography were performed. Angiographic results were good without evidence of side branch (SB) compromise. In 9/25 procedures, strut fractures were identified with minimal luminal compromise in two cases. PS opened the SB optimally without evidence of scaffold compromise. Culotte resulted in complete bifurcation coverage and good scaffold expansion; single strut fractures were present in three out of six and double fractures in one out of six procedures. Modified T and TAP resulted in complete bifurcation coverage, minimal neocarina double-strut layers and good expansion. In two out of six modified T procedures, strut fractures were present with SB scaffold deformity present in an additional two out of six procedures. In three out of eight TAP procedures, strut fractures were present without compromising overall scaffold integrity. Bifurcation stenting using Magmaris appears feasible. PS with additional TAP whenever needed seems a reasonable approach. Whenever a two-stent technique is planned, TAP appears most favourable whilst modified T and culotte stenting should probably be avoided.

  2. Crystal Structure of the FGFR4/LY2874455 Complex Reveals Insights into the Pan-FGFR Selectivity of LY2874455.

    Science.gov (United States)

    Wu, Daichao; Guo, Ming; Philips, Michael A; Qu, Lingzhi; Jiang, Longying; Li, Jun; Chen, Xiaojuan; Chen, Zhuchu; Chen, Lin; Chen, Yongheng

    2016-01-01

    Aberrant FGFR4 signaling has been documented abundantly in various human cancers. The majority of FGFR inhibitors display significantly reduced potency toward FGFR4 compared to FGFR1-3. However, LY2874455 has similar inhibition potency for FGFR1-4 with IC50 less than 6.4 nM. To date, there is no published crystal structure of LY2874455 in complex with any kinase. To better understand the pan-FGFR selectivity of LY2874455, we have determined the crystal structure of the FGFR4 kinase domain bound to LY2874455 at a resolution of 2.35 Å. LY2874455, a type I inhibitor for FGFR4, binds to the ATP-binding pocket of FGFR4 in a DFG-in active conformation with three hydrogen bonds and a number of van der Waals contacts. After alignment of the kinase domain sequence of 4 FGFRs, and superposition of the ATP binding pocket of 4 FGFRs, our structural analyses reveal that the interactions of LY2874455 to FGFR4 are largely conserved in 4 FGFRs, explaining at least partly, the broad inhibitory activity of LY2874455 toward 4 FGFRs. Consequently, our studies reveal new insights into the pan-FGFR selectivity of LY2874455 and provide a structural basis for developing novel FGFR inhibitors that target FGFR1-4 broadly.

  3. Freshwater Biological Traits Database (Traits)

    Science.gov (United States)

    The traits database was compiled for a project on climate change effects on river and stream ecosystems. The traits data, gathered from multiple sources, focused on information published or otherwise well-documented by trustworthy sources.

  4. Limnephilid taxa revised by speciation traits: Rhadicoleptus, Isogamus, Melampophylax genera, Chaetopteryx rugulosa, Psilopteryx psorosa species groups, Drusus bolivari, Annitella kosciuszkii species complexes (Trichoptera: Limnephilidae)

    Czech Academy of Sciences Publication Activity Database

    Oláh, J.; Chvojka, P.; Coppa, G.; Godunko, Roman J.; Lodovici, O.; Majecka, K.; Majecki, J.; Szczęsny, B.; Urbanic, G.; Valle, M.

    2015-01-01

    Roč. 46, č. 1 (2015), s. 3-117 ISSN 0237-5419 Institutional support: RVO:60077344 Keywords : speciation traits * neutral and adaptive molecular markers * neutral and adaptive traits Subject RIV: EG - Zoology

  5. Comparative sequence analyses of the major quantitative trait locus phosphorus uptake 1 (Pup1) reveal a complex genetic structure.

    Science.gov (United States)

    Heuer, Sigrid; Lu, Xiaochun; Chin, Joong Hyoun; Tanaka, Juan Pariasca; Kanamori, Hiroyuki; Matsumoto, Takashi; De Leon, Teresa; Ulat, Victor Jun; Ismail, Abdelbagi M; Yano, Masahiro; Wissuwa, Matthias

    2009-06-01

    The phosphorus uptake 1 (Pup1) locus was identified as a major quantitative trait locus (QTL) for tolerance of phosphorus deficiency in rice. Near-isogenic lines with the Pup1 region from tolerant donor parent Kasalath typically show threefold higher phosphorus uptake and grain yield in phosphorus-deficient field trials than the intolerant parent Nipponbare. In this study, we report the fine mapping of the Pup1 locus to the long arm of chromosome 12 (15.31-15.47 Mb). Genes in the region were initially identified on the basis of the Nipponbare reference genome, but did not reveal any obvious candidate genes related to phosphorus uptake. Kasalath BAC clones were therefore sequenced and revealed a 278-kbp sequence significantly different from the syntenic regions in Nipponbare (145 kb) and in the indica reference genome of 93-11 (742 kbp). Size differences are caused by large insertions or deletions (INDELs), and an exceptionally large number of retrotransposon and transposon-related elements (TEs) present in all three sequences (45%-54%). About 46 kb of the Kasalath sequence did not align with the entire Nipponbare genome, and only three Nipponbare genes (fatty acid alpha-dioxygenase, dirigent protein and aspartic proteinase) are highly conserved in Kasalath. Two Nipponbare genes (expressed proteins) might have evolved by at least three TE integrations in an ancestor gene that is still present in Kasalath. Several predicted Kasalath genes are novel or unknown genes that are mainly located within INDEL regions. Our results highlight the importance of sequencing QTL regions in the respective donor parent, as important genes might not be present in the current reference genomes.

  6. Insights from gas and water chemistry on the geothermal system of the Domuyo volcanic complex (Patagonia, Argentina)

    Science.gov (United States)

    Tassi, F.; Liccioli, C.; Chiodini, G.; Agusto, M.; Caselli, A. T.; Caliro, S.; Vaselli, O.; Pecoraino, G.

    2015-12-01

    This study focuses on the geochemistry of geothermal fluids discharging from the western flank of the Domuyo volcanic complex (Argentina), which is hosted within an extensional basins that interrupts the Andes at latitudes comprises between 35° and 39°S. The analytical results of gas and water samples collected during three sampling campaigns (2013, 2014 and 2015) are presented and discussed in order to: i) evaluate the equilibrium temperature(s) of the main fluid reservoir, ii) provide information on the origin of the fluid discharges and the secondary processes controlling their chemistry. Geothermometry based on the chemical composition of thermal waters indicates a maximum equilibrium temperature of 220 °C. This temperature, coupled with the measured amount of discharged Cl, suggest that the total energy released from this system is 1.1±0.2 GW. Atmospheric gases from a thick shallow aquifer contaminate most gas emissions, masking the chemical features of the deep fluid component, with the only exception of a jet fumarole located at 3,000 m a.s.l. (Bramadora). The H2O-CO2-CH4-H2-CO-C3H6-C3H8 composition of this gas emission was used to construct a geochemical conceptual model showing that the hydrothermal reservoir is liquid-dominated and thermally stratified, with temperatures ranging from 180 to 270 °C. The helium isotopic ratios (up to 6.8 Ra) and the δ13C-CO2 values (from -7.05 to -7.75 ‰ V-PDB) indicate that mantle degassing represents the dominant primary source for this dormant volcano. These results highlight the huge potential of this system as energy resource for the region. Accordingly, the regional authorities have recently planned and approved an investigation project aimed to provide further insights into the fluid geochemistry and the geostructural assessment in this promising area.

  7. Complexities in barrier island response to sea level rise: Insights from numerical model experiments, North Carolina Outer Banks

    Science.gov (United States)

    Moore, Laura J.; List, Jeffrey H.; Williams, S. Jeffress; Stolper, David

    2010-09-01

    .g., previous slopes, sediment budgets, etc.) in determining migration trajectories and therefore how a barrier island will respond to sea level rise. Although simple analytical calculations may predict barrier response in simplified coastal environments (e.g., constant slope, constant sea level rise rate, etc.), our model experiments demonstrate that morphological-behavior modeling is necessary to provide critical insights regarding changes that may occur in environments having complex geometries, especially when multiple parameters change simultaneously.

  8. Structure and tectonic evolution of the southwestern Trinidad dome, Escambray complex, Central Cuba: Insights into deformation in an accretionary wedge

    Science.gov (United States)

    Despaigne-Díaz, Ana Ibis; García Casco, Antonio; Cáceres Govea, Dámaso; Wilde, Simon A.; Millán Trujillo, Guillermo

    2017-10-01

    The Trinidad dome, Escambray complex, Cuba, forms part of an accretionary wedge built during intra-oceanic subduction in the Caribbean from the Late Cretaceous to Cenozoic. The structure reflects syn-subduction exhumation during thickening of the wedge, followed by extension. Field mapping, metamorphic and structural analysis constrain the tectonic evolution into five stages. Three ductile deformation events (D1, D2 and D3) are related to metamorphism in a compressional setting and formation of several nappes. D1 subduction fabrics are only preserved as relict S1 foliation and rootless isoclinal folds strongly overprinted by the main S2 foliation. The S2 foliation is parallel to sheared serpentinised lenses that define tectonic contacts, suggesting thrust stacks and underthrusting at mantle depths. Thrusting caused an inverted metamorphic structure with higher-grade on top of lower-grade nappes. Exhumation started during D2 when the units were incorporated into the growing accretionary wedge along NNE-directed thrust faults and was accompanied by substantial decompression and cooling. Folding and thrusting continued during D3 and marks the transition from ductile to brittle-ductile conditions at shallower crustal levels. The D4-5 events are related to extension and contributed to the final exhumation (likely as a core complex). D4 is associated with a regional spaced S4 cleavage, late open folds, and numerous extension veins, whereas D5 is recorded by normal and strike-slip faults affecting all nappes. The P-t path shows rapid exhumation during D2 and slower rates during D3 when the units were progressively incorporated into the accretionary prism. The domal shape formed in response to tectonic denudation assisted by normal faulting and erosion at the surface during the final stages of structural development. These results support tectonic models of SW subduction of the Proto-Caribbean crust under the Caribbean plate during the latest Cretaceous and provide

  9. Complexities in barrier island response to sea level rise: Insights from numerical model experiments, North Carolina Outer Banks

    Science.gov (United States)

    Moore, Laura J.; List, Jeffrey H.; Williams, S. Jeffress; Stolper, David

    2010-01-01

    .g., previous slopes, sediment budgets, etc.) in determining migration trajectories and therefore how a barrier island will respond to sea level rise. Although simple analytical calculations may predict barrier response in simplified coastal environments (e.g., constant slope, constant sea level rise rate, etc.), our model experiments demonstrate that morphological-behavior modeling is necessary to provide critical insights regarding changes that may occur in environments having complex geometries, especially when multiple parameters change simultaneously.

  10. Comparison of gene-based rare variant association mapping methods for quantitative traits in a bovine population with complex familial relationships.

    Science.gov (United States)

    Zhang, Qianqian; Guldbrandtsen, Bernt; Calus, Mario P L; Lund, Mogens Sandø; Sahana, Goutam

    2016-08-17

    There is growing interest in the role of rare variants in the variation of complex traits due to increasing evidence that rare variants are associated with quantitative traits. However, association methods that are commonly used for mapping common variants are not effective to map rare variants. Besides, livestock populations have large half-sib families and the occurrence of rare variants may be confounded with family structure, which makes it difficult to disentangle their effects from family mean effects. We compared the power of methods that are commonly applied in human genetics to map rare variants in cattle using whole-genome sequence data and simulated phenotypes. We also studied the power of mapping rare variants using linear mixed models (LMM), which are the method of choice to account for both family relationships and population structure in cattle. We observed that the power of the LMM approach was low for mapping a rare variant (defined as those that have frequencies lower than 0.01) with a moderate effect (5 to 8 % of phenotypic variance explained by multiple rare variants that vary from 5 to 21 in number) contributing to a QTL with a sample size of 1000. In contrast, across the scenarios studied, statistical methods that are specialized for mapping rare variants increased power regardless of whether multiple rare variants or a single rare variant underlie a QTL. Different methods for combining rare variants in the test single nucleotide polymorphism set resulted in similar power irrespective of the proportion of total genetic variance explained by the QTL. However, when the QTL variance is very small (only 0.1 % of the total genetic variance), these specialized methods for mapping rare variants and LMM generally had no power to map the variants within a gene with sample sizes of 1000 or 5000. We observed that the methods that combine multiple rare variants within a gene into a meta-variant generally had greater power to map rare variants compared

  11. High-resolution mapping of a fruit firmness-related quantitative trait locus in tomato reveals epistatic interactions associated with a complex combinatorial locus.

    Science.gov (United States)

    Chapman, Natalie H; Bonnet, Julien; Grivet, Laurent; Lynn, James; Graham, Neil; Smith, Rebecca; Sun, Guiping; Walley, Peter G; Poole, Mervin; Causse, Mathilde; King, Graham J; Baxter, Charles; Seymour, Graham B

    2012-08-01

    Fruit firmness in tomato (Solanum lycopersicum) is determined by a number of factors including cell wall structure, turgor, and cuticle properties. Firmness is a complex polygenic trait involving the coregulation of many genes and has proved especially challenging to unravel. In this study, a quantitative trait locus (QTL) for fruit firmness was mapped to tomato chromosome 2 using the Zamir Solanum pennellii interspecific introgression lines (ILs) and fine-mapped in a population consisting of 7,500 F2 and F3 lines from IL 2-3 and IL 2-4. This firmness QTL contained five distinct subpeaks, Fir(s.p.)QTL2.1 to Fir(s.p.)QTL2.5, and an effect on a distal region of IL 2-4 that was nonoverlapping with IL 2-3. All these effects were located within an 8.6-Mb region. Using genetic markers, each subpeak within this combinatorial locus was mapped to a physical location within the genome, and an ethylene response factor (ERF) underlying Fir(s.p.)QTL2.2 and a region containing three pectin methylesterase (PME) genes underlying Fir(s.p.)QTL2.5 were nominated as QTL candidate genes. Statistical models used to explain the observed variability between lines indicated that these candidates and the nonoverlapping portion of IL 2-4 were sufficient to account for the majority of the fruit firmness effects. Quantitative reverse transcription-polymerase chain reaction was used to quantify the expression of each candidate gene. ERF showed increased expression associated with soft fruit texture in the mapping population. In contrast, PME expression was tightly linked with firm fruit texture. Analysis of a range of recombinant lines revealed evidence for an epistatic interaction that was associated with this combinatorial locus.

  12. Transcriptomic analysis of short-fruit 1 (sf1) reveals new insights into the variation of fruit-related traits in Cucumis sativus.

    Science.gov (United States)

    Wang, Lina; Cao, Chenxing; Zheng, Shuangshuang; Zhang, Haiyang; Liu, Panjing; Ge, Qian; Li, Jinrui; Ren, Zhonghai

    2017-06-07

    Fruit size is an important quality trait in different market classes of Cucumis sativus L., an economically important vegetable cultivated worldwide, but the genetic and molecular mechanisms that control fruit size are largely unknown. In this study, we isolated a natural cucumber mutant, short fruit 1 (sf1), caused by a single recessive Mendelian factor, from the North China-type inbred line CNS2. In addition to significantly decreased fruit length, other fruit-related phenotypic variations were also observed in sf1 compared to the wild-type (WT) phenotype, indicating that sf1 might have pleiotropic effects. Microscopic imaging showed that fruit cell size in sf1 was much larger than that in WT, suggesting that the short fruit phenotype in sf1 is caused by decreased cell number. Fine mapping revealed that sf1 was localized to a 174.3 kb region on chromosome 6. Similarly, SNP association analysis of bulked segregant RNA-Seq data showed increased SNP frequency in the same region of chromosome 6. In addition, transcriptomic analysis revealed that sf1 might control fruit length through the fine-tuning of cytokinin and auxin signalling, gibberellin biosynthesis and signal transduction in cucumber fruits. Overall, our results provide important information for further study of fruit length and other fruit-related features in cucumber.

  13. TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits.

    Directory of Open Access Journals (Sweden)

    Dorothée Diogo

    Full Text Available Despite the success of genome-wide association studies (GWAS in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples, Exomechip genotyping (n = 18,409 case/control samples and targeted exon-sequencing (n = 2,236 case/controls samples to demonstrate that three protein-coding variants in TYK2 (tyrosine kinase 2 independently protect against RA: P1104A (rs34536443, OR = 0.66, P = 2.3 x 10(-21, A928V (rs35018800, OR = 0.53, P = 1.2 x 10(-9, and I684S (rs12720356, OR = 0.86, P = 4.6 x 10(-7. Second, we show that the same three TYK2 variants protect against systemic lupus erythematosus (SLE, Pomnibus = 6 x 10(-18, and provide suggestive evidence that two of the TYK2 variants (P1104A and A928V may also protect against inflammatory bowel disease (IBD; P(omnibus = 0.005. Finally, in a phenome-wide association study (PheWAS assessing >500 phenotypes using electronic medical records (EMR in >29,000 subjects, we found no convincing evidence for association of P1104A and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug target for the treatment of autoimmune diseases.

  14. GENERAL AND SPECIFIC COMBINING ABILITY OF INITIAL PARENTAL FORMS IN TOMATO FOR COMPLEX OF ECONOMICALLY VALUABLE TRAITS TO DEVELOP HYBRIDS F1 OF CHERRY AND COCKTAIL TYPES

    Directory of Open Access Journals (Sweden)

    R. K. Rechets

    2017-01-01

    Full Text Available Results of estimation of general and specific combining ability of male and female parental tomato forms were given for complex of traits. The estimation was carried out according to incomplete diallel crosses 15x15. Such varities   as   ‘Trapeza’,  Rosovaya  kapelka’,  ‘Seniorita’, ‘Ocharovanie’,  ‘Tigris’   ‘Vishnya  Zheltaya’  (Gavrish, ‘Denezhnoye Derevo’ (national breeding, and  lines: ‘46/06’,  ‘49/09’,  ‘295/09’,  ‘336/11’,  ‘354/11’,  ‘357/11’, ‘388/09’ (nor, ‘498’ (selection of TARI were used as intial breeding accessions, differing in bush type (determinate and indeterminate, duration of vegetative phase (ultraearly,  early, medium early, middle-ripening, fruit  shape (rounded, oval, fruit color (red, pink, black, orange, tiger and with the gene nor, fruit weight (10 g. and more, brush structure (dense, friable. As a results, ‘Trapeza’, ‘Vishnya Zheltaya’, ‘Ocharovaniye’, ‘Seniorita’, and lines: ‘295/10’, ‘49/09’,  ‘498’,  ‘357/11’,  ‘354/11’,  ‘388/09’  (nor were selected and recommended to be used in breeding program for development of heterotic hybrids with high fruit setting and generative bush type. The promising hybrids F1 with high constants of specific combining ability for a complex of economically valuable traits have been observed. Because of different lines and accessions were used in crossings, these hybrids varied in internode length of cluster type, classical or shorten; rounded or oval fruit shape; fruit  color, red (F1   combinations ‘354/11’ х ‘Seniorita’, ‘Trapeza’ х  ‘L.49/09’,  L.  ‘49/09’  х  L.354/11, pink (F1 combination ‘Rosovaya Kapelka’ х ‘L.354/11’, yellow (F1 combination ‘Ocharovaniye’ х  ‘Vishiya Zheltaya’, deep brown (F1 combination  ‘L.357/11’ х ‘L.354/11’.

  15. Predicting complex traits using a diffusion kernel on genetic markers with an application to dairy cattle and wheat data

    Science.gov (United States)

    2013-01-01

    Background Arguably, genotypes and phenotypes may be linked in functional forms that are not well addressed by the linear additive models that are standard in quantitative genetics. Therefore, developing statistical learning models for predicting phenotypic values from all available molecular information that are capable of capturing complex genetic network architectures is of great importance. Bayesian kernel ridge regression is a non-parametric prediction model proposed for this purpose. Its essence is to create a spatial distance-based relationship matrix called a kernel. Although the set of all single nucleotide polymorphism genotype configurations on which a model is built is finite, past research has mainly used a Gaussian kernel. Results We sought to investigate the performance of a diffusion kernel, which was specifically developed to model discrete marker inputs, using Holstein cattle and wheat data. This kernel can be viewed as a discretization of the Gaussian kernel. The predictive ability of the diffusion kernel was similar to that of non-spatial distance-based additive genomic relationship kernels in the Holstein data, but outperformed the latter in the wheat data. However, the difference in performance between the diffusion and Gaussian kernels was negligible. Conclusions It is concluded that the ability of a diffusion kernel to capture the total genetic variance is not better than that of a Gaussian kernel, at least for these data. Although the diffusion kernel as a choice of basis function may have potential for use in whole-genome prediction, our results imply that embedding genetic markers into a non-Euclidean metric space has very small impact on prediction. Our results suggest that use of the black box Gaussian kernel is justified, given its connection to the diffusion kernel and its similar predictive performance. PMID:23763755

  16. Insights into aquatic toxicities of the antibiotics oxytetracycline and ciprofloxacin in the presence of metal: Complexation versus mixture

    International Nuclear Information System (INIS)

    Zhang Yu; Cai Xiyun; Lang Xianming; Qiao Xianliang; Li Xuehua; Chen Jingwen

    2012-01-01

    Co-contamination of ligand-like antibiotics (e.g., tetracyclines and quinolones) and heavy metals prevails in the environment, and thus the complexation between them is involved in environmental risks of antibiotics. To understand toxicological significance of the complex, effects of metal coordination on antibiotics' toxicity were investigated. The complexation of two antibiotics, oxytetracycline and ciprofloxacin, with three heavy metals, copper, zinc, and cadmium, was verified by spectroscopic techniques. The antibiotics bound metals via multiple coordination sites and rendered a mixture of various complexation speciations. Toxicity analysis indicated that metal coordination did modify the toxicity of the antibiotics and that antibiotic, metal, and their complex acted primarily as concentration addition. Comparison of EC 50 values revealed that the complex commonly was highest toxic and predominately correlated in toxicity to the mixture. Finally, environmental scenario analysis demonstrated that ignoring complexation would improperly classify environmental risks of the antibiotics. - Highlights: ► The complex of antibiotic with metal is a mixture of various complexation modes. ► Antibiotic and metal act as various combined interactions when their complexation is ignored. ► Antibiotic, metal, and their complex act as concentration addition interaction. ► Complex commonly is the highest toxicant. ► Neglecting complexation renders improper classification of risks for antibiotics. - Antibiotic, heavy metal and their complex act primarily as concentration addition interaction and the complex commonly is highest toxic.

  17. Insights into aquatic toxicities of the antibiotics oxytetracycline and ciprofloxacin in the presence of metal: Complexation versus mixture

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Zhang [Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024 (China); Cai Xiyun, E-mail: xiyuncai@dlut.edu.cn [Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024 (China); Xianming, Lang [Liaoning Academy of Environmental Sciences, Shenyang 110031 (China); Xianliang, Qiao; Xuehua, Li; Jingwen, Chen [Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024 (China)

    2012-07-15

    Co-contamination of ligand-like antibiotics (e.g., tetracyclines and quinolones) and heavy metals prevails in the environment, and thus the complexation between them is involved in environmental risks of antibiotics. To understand toxicological significance of the complex, effects of metal coordination on antibiotics' toxicity were investigated. The complexation of two antibiotics, oxytetracycline and ciprofloxacin, with three heavy metals, copper, zinc, and cadmium, was verified by spectroscopic techniques. The antibiotics bound metals via multiple coordination sites and rendered a mixture of various complexation speciations. Toxicity analysis indicated that metal coordination did modify the toxicity of the antibiotics and that antibiotic, metal, and their complex acted primarily as concentration addition. Comparison of EC{sub 50} values revealed that the complex commonly was highest toxic and predominately correlated in toxicity to the mixture. Finally, environmental scenario analysis demonstrated that ignoring complexation would improperly classify environmental risks of the antibiotics. - Highlights: Black-Right-Pointing-Pointer The complex of antibiotic with metal is a mixture of various complexation modes. Black-Right-Pointing-Pointer Antibiotic and metal act as various combined interactions when their complexation is ignored. Black-Right-Pointing-Pointer Antibiotic, metal, and their complex act as concentration addition interaction. Black-Right-Pointing-Pointer Complex commonly is the highest toxicant. Black-Right-Pointing-Pointer Neglecting complexation renders improper classification of risks for antibiotics. - Antibiotic, heavy metal and their complex act primarily as concentration addition interaction and the complex commonly is highest toxic.

  18. Simple, standardized incorporation of genetic risk into non-genetic risk prediction tools for complex traits: coronary heart disease as an example

    Directory of Open Access Journals (Sweden)

    Benjamin A Goldstein

    2014-08-01

    Full Text Available Purpose: Genetic risk assessment is becoming an important component of clinical decision-making. Genetic Risk Scores (GRSs allow the composite assessment of genetic risk in complex traits. A technically and clinically pertinent question is how to most easily and effectively combine a GRS with an assessment of clinical risk derived from established non-genetic risk factors as well as to clearly present this information to patient and health care providers. Materials & Methods: We illustrate a means to combine a GRS with an independent assessment of clinical risk using a log-link function. We apply the method to the prediction of coronary heart disease (CHD in the Atherosclerosis Risk in Communities (ARIC cohort. We evaluate different constructions based on metrics of effect change, discrimination, and calibration.Results: The addition of a GRS to a clinical risk score (CRS improves both discrimination and calibration for CHD in ARIC. Results are similar regardless of whether external vs. internal coefficients are used for the CRS, risk factor SNPs are included in the GRS, or subjects with diabetes at baseline are excluded. We outline how to report the construction and the performance of a GRS using our method and illustrate a means to present genetic risk information to subjects and/or their health care provider. Conclusion: The proposed method facilitates the standardized incorporation of a GRS in risk assessment.

  19. Biochemical and genetic analyses of the oomycete Pythium insidiosum provide new insights into clinical identification and urease-based evolution of metabolism-related traits

    Directory of Open Access Journals (Sweden)

    Theerapong Krajaejun

    2018-06-01

    biochemical characteristics and drew new insights into clinical identification and urease-related evolution of P. insidiosum.

  20. Social traits, social networks and evolutionary biology.

    Science.gov (United States)

    Fisher, D N; McAdam, A G

    2017-12-01

    effects) provides the potential to understand how entire networks of social interactions in populations influence phenotypes and predict how these traits may evolve. By theoretical integration of social network analysis and quantitative genetics, we hope to identify areas of compatibility and incompatibility and to direct research efforts towards the most promising areas. Continuing this synthesis could provide important insights into the evolution of traits expressed in a social context and the evolutionary consequences of complex and nuanced social phenotypes. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  1. Heteroleptic Copper(I) Complexes of "Scorpionate" Bis-pyrazolyl Carboxylate Ligand with Auxiliary Phosphine as Potential Anticancer Agents: An Insight into Cytotoxic Mode.

    Science.gov (United States)

    Khan, Rais Ahmad; Usman, Mohammad; Dhivya, Rajakumar; Balaji, Perumalsamy; Alsalme, Ali; AlLohedan, Hamad; Arjmand, Farukh; AlFarhan, Khalid; Akbarsha, Mohammad Abdulkader; Marchetti, Fabio; Pettinari, Claudio; Tabassum, Sartaj

    2017-03-24

    New copper(I) complexes [CuCl(PPh 3 )(L)] (1: L = L A  = 4-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane; (2: L = L B  = 3-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane) were prepared and characterised by elemental analysis and various spectroscopic techniques such as FT-IR, NMR, UV-Vis, and ESI-MS. The molecular structures of complexes 1 and 2 were analyzed by theoretical B3LYP/DFT method. Furthermore, in vitro DNA binding studies were carried out to check the ability of complexes 1 and 2 to interact with native calf thymus DNA (CT-DNA) using absorption titration, fluorescence quenching and circular dichroism, which is indicative of more avid binding of the complex 1. Moreover, DNA mobility assay was also conducted to study the concentration-dependent cleavage pattern of pBR322 DNA by complex 1, and the role of ROS species to have a mechanistic insight on the cleavage pattern, which ascertained substantial roles by both hydrolytic and oxidative pathways. Additionally, we analyzed the potential of the interaction of complex 1 with DNA and enzyme (Topo I and II) with the aid of molecular modeling. Furthermore, cytotoxic activity of complex 1 was tested against HepG2 cancer cell lines. Thus, the potential of the complex 1 is promising though further in vivo investigations may be required before subjecting it to clinical trials.

  2. Unified analysis of ensemble and single-complex optical spectral data from light-harvesting complex-2 chromoproteins for gaining deeper insight into bacterial photosynthesis

    Science.gov (United States)

    Pajusalu, Mihkel; Kunz, Ralf; Rätsep, Margus; Timpmann, Kõu; Köhler, Jürgen; Freiberg, Arvi

    2015-11-01

    Bacterial light-harvesting pigment-protein complexes are very efficient at converting photons into excitons and transferring them to reaction centers, where the energy is stored in a chemical form. Optical properties of the complexes are known to change significantly in time and also vary from one complex to another; therefore, a detailed understanding of the variations on the level of single complexes and how they accumulate into effects that can be seen on the macroscopic scale is required. While experimental and theoretical methods exist to study the spectral properties of light-harvesting complexes on both individual complex and bulk ensemble levels, they have been developed largely independently of each other. To fill this gap, we simultaneously analyze experimental low-temperature single-complex and bulk ensemble optical spectra of the light-harvesting complex-2 (LH2) chromoproteins from the photosynthetic bacterium Rhodopseudomonas acidophila in order to find a unique theoretical model consistent with both experimental situations. The model, which satisfies most of the observations, combines strong exciton-phonon coupling with significant disorder, characteristic of the proteins. We establish a detailed disorder model that, in addition to containing a C2-symmetrical modulation of the site energies, distinguishes between static intercomplex and slow conformational intracomplex disorders. The model evaluations also verify that, despite best efforts, the single-LH2-complex measurements performed so far may be biased toward complexes with higher Huang-Rhys factors.

  3. Insights into the Intramolecular Properties of η6-Arene-Ru-Based Anticancer Complexes Using Quantum Calculations

    Directory of Open Access Journals (Sweden)

    Adebayo A. Adeniyi

    2013-01-01

    Full Text Available The factors that determine the stability and the effects of noncovalent interaction on the η6-arene ruthenium anticancer complexes are determined using DFT method. The intramolecular and intra-atomic properties were computed for two models of these half-sandwich ruthenium anticancer complexes and their respective hydrated forms. The results showed that the stability of these complexes depends largely on the network of hydrogen bonds (HB, strong nature of charge transfer, polarizability, and electrostatic energies that exist within the complexes. The hydrogen bonds strength was found to be related to the reported anticancer activities and the activation of the complexes by hydration. The metal–ligand bonds were found to be closed shell systems that are characterised by high positive Laplacian values of electron density. Two of the complexes are found to be predominantly characterised by LMCT while the other two are predominately characterised by MLCT.

  4. Genetic and QTL analyses of yield and a set of physiological traits in pepper

    NARCIS (Netherlands)

    Alimi, N.A.; Bink, M.C.A.M.; Dieleman, J.A.; Nicolaï, M.; Wubs, M.; Heuvelink, E.; Magan, J.; Voorrips, R.E.; Jansen, J.; Rodrigues, P.C.; Heijden, van der G.W.A.M.; Vercauteren, A.; Vuylsteke, M.; Song, Y.; Glasbey, C.; Barocsi, A.; Lefebvre, V.; Palloix, A.; Eeuwijk, van F.A.

    2013-01-01

    An interesting strategy for improvement of a complex trait dissects the complex trait in a number of physiological component traits, with the latter having hopefully a simple genetic basis. The complex trait is then improved via improvement of its component traits. As first part of such a strategy

  5. Are Model Transferability And Complexity Antithetical? Insights From Validation of a Variable-Complexity Empirical Snow Model in Space and Time

    Science.gov (United States)

    Lute, A. C.; Luce, Charles H.

    2017-11-01

    The related challenges of predictions in ungauged basins and predictions in ungauged climates point to the need to develop environmental models that are transferable across both space and time. Hydrologic modeling has historically focused on modelling one or only a few basins using highly parameterized conceptual or physically based models. However, model parameters and structures have been shown to change significantly when calibrated to new basins or time periods, suggesting that model complexity and model transferability may be antithetical. Empirical space-for-time models provide a framework within which to assess model transferability and any tradeoff with model complexity. Using 497 SNOTEL sites in the western U.S., we develop space-for-time models of April 1 SWE and Snow Residence Time based on mean winter temperature and cumulative winter precipitation. The transferability of the models to new conditions (in both space and time) is assessed using non-random cross-validation tests with consideration of the influence of model complexity on transferability. As others have noted, the algorithmic empirical models transfer best when minimal extrapolation in input variables is required. Temporal split-sample validations use pseudoreplicated samples, resulting in the selection of overly complex models, which has implications for the design of hydrologic model validation tests. Finally, we show that low to moderate complexity models transfer most successfully to new conditions in space and time, providing empirical confirmation of the parsimony principal.

  6. Delimiting Species Boundaries within a Paraphyletic Species Complex: Insights from Morphological, Genetic, and Molecular Data on Paramecium sonneborni (Paramecium aurelia species complex, Ciliophora, Protozoa).

    Science.gov (United States)

    Przyboś, Ewa; Tarcz, Sebastian; Rautian, Maria; Sawka, Natalia

    2015-09-01

    The demarcation of boundaries between protist species is often problematic because of the absence of a uniform species definition, the abundance of cryptic diversity, and the occurrence of convergent morphology. The ciliates belonging to the Paramecium aurelia complex, consisting of 15 species, are a good model for such systematic and evolutionary studies. One member of the complex is P. sonneborni, previously known only from one stand in Texas (USA), but recently found in two new sampling sites in Cyprus (creeks running to Salt Lake and Oroklini Lake near Larnaca). The studied Paramecium sonneborni strains (from the USA and Cyprus) reveal low viability in the F1 and F2 generations of interstrain hybrids and may be an example of ongoing allopatric speciation. Despite its molecular distinctiveness, we postulate that P. sonneborni should remain in the P. aurelia complex, making it a paraphyletic taxon. Morphological studies have revealed that some features of the nuclear apparatus of P. sonneborni correspond to the P. aurelia spp. complex, while others are similar to P. jenningsi and P. schewiakoffi. The observed discordance indicates rapid splitting of the P. aurelia-P. jenningsi-P. schewiakoffi group, in which genetic, morphological, and molecular boundaries between species are not congruent. Copyright © 2015 Elsevier GmbH. All rights reserved.

  7. Insight into regulation of emission color and photodeactivation process from heteroleptic to homoleptic Ir(III) complexes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xin; Zheng, Danning; Feng, Songyan; Wang, Li, E-mail: chemwangl@henu.edu.cn; Li, Junfeng, E-mail: jfli@theochem.kth.se; Zhang, Jinglai, E-mail: zhangjinglai@henu.edu.cn

    2017-03-15

    The phosphorescent process of two heteroleptic ((DMDPI){sub 2}Ir(tftap) and (tftap){sub 2}Ir(DMDPI)) and one homoleptic (Ir(DMDPI){sub 3}) Ir(III) complexes (See ) is theoretically investigated by density functional theory (DFT) and quadratic response (QR) time-dependent density functional theory (TDDFT) calculations including spin-orbit coupling (SOC). Two or three triplet excited states are confirmed for three complexes, respectively. On the basis of the respective optimized triplet geometry, the emissive wavelength is determined by the ΔSCF-DFT method. Furthermore, the radiative rate constant (k{sub r}) is also calculated corresponding to each triplet state. Combination of k{sub r} and emissive energy, the emission rule is determined. It is found that complex (DMDPI){sub 2}Ir(tftap) follows the dual emission scenarios, while complexes (tftap){sub 2}Ir(DMDPI) and Ir(DMDPI){sub 3} obey the Kasha rule. The nonradiative rate constant (k{sub nr}) is qualitatively evaluated by the construction of triplet potential surface via metal centered ({sup 3}MC d-d) state. Finally, the sequence of quantum yield is compared by both k{sub r} and k{sub nr}. The quantum yield of homoleptic Ir(III) complex Ir(DMDPI){sub 3} is higher than that of heteroleptic Ir(III) complexes (DMDPI){sub 2}Ir(tftap) and (tftap){sub 2}Ir(DMDPI). However, the emissive wavelength of Ir(DMDPI){sub 3} is in the red color region rather than blue color.

  8. Software errors and complexity: An empirical investigation

    Science.gov (United States)

    Basili, Victor R.; Perricone, Berry T.

    1983-01-01

    The distributions and relationships derived from the change data collected during the development of a medium scale satellite software project show that meaningful results can be obtained which allow an insight into software traits and the environment in which it is developed. Modified and new modules were shown to behave similarly. An abstract classification scheme for errors which allows a better understanding of the overall traits of a software project is also shown. Finally, various size and complexity metrics are examined with respect to errors detected within the software yielding some interesting results.

  9. Structural insights into calcium-bound S100P and the V domain of the RAGE complex.

    Directory of Open Access Journals (Sweden)

    Srinivasa R Penumutchu

    Full Text Available The S100P protein is a member of the S100 family of calcium-binding proteins and possesses both intracellular and extracellular functions. Extracellular S100P binds to the cell surface receptor for advanced glycation end products (RAGE and activates its downstream signaling cascade to meditate tumor growth, drug resistance and metastasis. Preventing the formation of this S100P-RAGE complex is an effective strategy to treat various disease conditions. Despite its importance, the detailed structural characterization of the S100P-RAGE complex has not yet been reported. In this study, we report that S100P preferentially binds to the V domain of RAGE. Furthermore, we characterized the interactions between the RAGE V domain and Ca(2+-bound S100P using various biophysical techniques, including isothermal titration calorimetry (ITC, fluorescence spectroscopy, multidimensional NMR spectroscopy, functional assays and site-directed mutagenesis. The entropy-driven binding between the V domain of RAGE and Ca(+2-bound S100P was found to lie in the micromolar range (Kd of ∼ 6 µM. NMR data-driven HADDOCK modeling revealed the putative sites that interact to yield a proposed heterotetrameric model of the S100P-RAGE V domain complex. Our study on the spatial structural information of the proposed protein-protein complex has pharmaceutical relevance and will significantly contribute toward drug development for the prevention of RAGE-related multifarious diseases.

  10. Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Das, Kalyan; Martinez, Sergio E.; Arnold, Eddy

    2017-04-10

    HIV-1 reverse transcriptase (RT) is targeted by multiple drugs. RT mutations that confer resistance to nucleoside RT inhibitors (NRTIs) emerge during clinical use. Q151M and four associated mutations, A62V, V75I, F77L, and F116Y, were detected in patients failing therapies with dideoxynucleosides (didanosine [ddI], zalcitabine [ddC]) and/or zidovudine (AZT). The cluster of the five mutations is referred to as the Q151M complex (Q151Mc), and an RT or virus containing Q151Mc exhibits resistance to multiple NRTIs. To understand the structural basis for Q151M and Q151Mc resistance, we systematically determined the crystal structures of the wild-type RT/double-stranded DNA (dsDNA)/dATP (complex I), wild-type RT/dsDNA/ddATP (complex II), Q151M RT/dsDNA/dATP (complex III), Q151Mc RT/dsDNA/dATP (complex IV), and Q151Mc RT/dsDNA/ddATP (complex V) ternary complexes. The structures revealed that the deoxyribose rings of dATP and ddATP have 3'-endo and 3'-exo conformations, respectively. The single mutation Q151M introduces conformational perturbation at the deoxynucleoside triphosphate (dNTP)-binding pocket, and the mutated pocket may exist in multiple conformations. The compensatory set of mutations in Q151Mc, particularly F116Y, restricts the side chain flexibility of M151 and helps restore the DNA polymerization efficiency of the enzyme. The altered dNTP-binding pocket in Q151Mc RT has the Q151-R72 hydrogen bond removed and has a switched conformation for the key conserved residue R72 compared to that in wild-type RT. On the basis of a modeled structure of hepatitis B virus (HBV) polymerase, the residues R72, Y116, M151, and M184 in Q151Mc HIV-1 RT are conserved in wild-type HBV polymerase as residues R41, Y89, M171, and M204, respectively; functionally, both Q151Mc HIV-1 and wild-type HBV are resistant to dideoxynucleoside analogs.

  11. Induction and Rationalization of Supramolecular Chirality in the Tweezer-Diamine Complexes: Insights from Experimental and DFT Studies.

    Science.gov (United States)

    Dhamija, Avinash; Ikbal, Sk Asif; Rath, Sankar Prasad

    2016-12-19

    A series of supramolecular chiral 1:1 sandwich complexes (1 M ·L and 2 M ·L) consisting of diphenylether/ethane bridged metallobisporphyrin host (1 M and 2 M ; M: Zn/Mg) and chiral diamine guest (L) have been presented. The host-guest complexes are compared just upon changing the metal ion (Mg vs Zn) or the bridge (highly flexible ethane vs rigid diphenylether) keeping other factors similar. The factors that would influence the chirality induction process along with their contributions toward the sign and intensity of the CD couplet of the overall complex have been analyzed. Larger CD amplitude was observed in the host-guest complex with the more flexible ethane bridge as compared to the rigid diphenylether bridged one, irrespective of the metal ion used. Also, Zn complexes have displayed larger CD amplitude because of their stronger binding with the chiral diamines. A fairly linear dependence between the binding constant (K) and CD amplitude has been observed. Moreover, the amplitude of the CD couplet has been correlated with the relative steric bulk of the substituent at the stereogenic center: with increasing the bulk, CD intensity gradually increases. However, large increase of steric hindrance, after a threshold value, has diminished the intensity. The observation of a weak positive CD couplet between (1R,2R)-DPEA guest and Zn-bisporphyrin hosts indicates that the clockwise-twisted (steric-controlled) conformer is more populated as compared to the anticlockwise (chirality-controlled) one. In contrast, amplitude of the positive CD couplets is larger with Mg-bisporphyrin hosts, suggesting almost exclusive contribution of the clockwise-twisted conformer guided solely by sterics. DFT calculations support the experimental observations and have displayed the possible interconversion between clockwise and anticlockwise twisted conformers just upon changing the bulk of the substituent irrespective of the nature of chirality at the stereogenic center.

  12. The Complex Interplay Between Depression/Anxiety and Executive Functioning: Insights From the ECAS in a Large ALS Population

    Science.gov (United States)

    Solca, Federica; Faini, Andrea; Madotto, Fabiana; Lafronza, Annalisa; Monti, Alessia; Zago, Stefano; Doretti, Alberto; Ciammola, Andrea; Ticozzi, Nicola; Silani, Vincenzo; Poletti, Barbara

    2018-01-01

    Introduction: The observed association between depressive symptoms and cognitive performances has not been previously clarified in patients with amyotrophic lateral sclerosis (pALS). In fact, the use of cognitive measures often not accommodating for motor disability has led to heterogeneous and not conclusive findings about this issue. The aim of the present study was to evaluate the relationship between cognitive and depressive/anxiety symptoms by means of the recently developed Edinburgh Cognitive and Behavioral ALS Screen (ECAS), a brief assessment specifically designed for pALS. Methods: Sample included 168 pALS (114 males, 54 females); they were administered two standard cognitive screening tools (FAB; MoCA) and the ECAS, assessing different cognitive domains, including ALS-specific (executive functions, verbal fluency, and language tests) and ALS non-specific subtests (memory and visuospatial tests). Two psychological questionnaires for depression and anxiety (BDI; STAI/Y) were also administered to patients. Pearson’s correlation coefficient was used to assess the degree of association between cognitive and psychological measures. Results: Depression assessment negatively correlated with the ECAS, more significantly with regard to the executive functions subdomain. In particular, Sentence Completion and Social Cognition subscores were negatively associated with depression levels measured by BDI total score and Somatic-Performance symptoms subscore. Conversely, no significant correlations were observed between depression level and cognitive functions as measured by traditional screening tools for frontal abilities (FAB) and global cognition (MoCA) assessment. Finally, no significant correlations were observed between state/trait anxiety and the ECAS. Discussion and conclusion: This represents the first study focusing on the relationship between cognitive and psychological components in pALS by means of the ECAS, the current gold standard for ALS cognitive

  13. Mechanistic Insights into Validoxylamine A 7'-Phosphate Synthesis by VldE Using the Structure of the Entire Product Complex

    Energy Technology Data Exchange (ETDEWEB)

    Cavalier, Michael C.; Yim, Young-Sun; Asamizu, Shumpei; Neau, David; Almabruk, Khaled H.; Mahmud, Taifo; Lee, Yong-Hwan [Oregon State U.; (Cornell); (LSU)

    2013-09-09

    The pseudo-glycosyltransferase VldE catalyzes non-glycosidic C-N coupling between an unsaturated cyclitol and a saturated aminocyclitol with the conservation of the stereochemical configuration of the substrates to form validoxylamine A 7'-phosphate, the biosynthetic precursor of the antibiotic validamycin A. To study the molecular basis of its mechanism, the three-dimensional structures of VldE from Streptomyces hygroscopicus subsp. limoneus was determined in apo form, in complex with GDP, in complex with GDP and validoxylamine A 7'-phosphate, and in complex with GDP and trehalose. The structure of VldE with the catalytic site in both an “open” and “closed” conformation is also described. With these structures, the preferred binding of the guanine moiety by VldE, rather than the uracil moiety as seen in OtsA could be explained. The elucidation of the VldE structure in complex with the entirety of its products provides insight into the internal return mechanism by which catalysis occurs with a net retention of the stereochemical configuration of the donated cyclitol.

  14. New Insights Into the Mechanisms and Biological Roles of D-Amino Acids in Complex Eco-Systems

    Science.gov (United States)

    Aliashkevich, Alena; Alvarez, Laura; Cava, Felipe

    2018-01-01

    In the environment bacteria share their habitat with a great diversity of organisms, from microbes to humans, animals and plants. In these complex communities, the production of extracellular effectors is a common strategy to control the biodiversity by interfering with the growth and/or viability of nearby microbes. One of such effectors relies on the production and release of extracellular D-amino acids which regulate diverse cellular processes such as cell wall biogenesis, biofilm integrity, and spore germination. Non-canonical D-amino acids are mainly produced by broad spectrum racemases (Bsr). Bsr’s promiscuity allows it to generate high concentrations of D-amino acids in environments with variable compositions of L-amino acids. However, it was not clear until recent whether these molecules exhibit divergent functions. Here we review the distinctive biological roles of D-amino acids, their mechanisms of action and their modulatory properties of the biodiversity of complex eco-systems. PMID:29681896

  15. Structure and dynamics of a complex of cellulose with EDA: insights into the action of amines on cellulose

    Energy Technology Data Exchange (ETDEWEB)

    Sawada, Daisuke [ORNL; Nishiyama, Yoshiharu [Centre de Recherches sur les Macromolecules Vegetales (CERMAV-CNRS); Petridis, Loukas [ORNL; Parthasarathi, R. [Los Alamos National Laboratory (LANL); Gnanakaran, S [Los Alamos National Laboratory (LANL); Forsyth, V. T. [Institut Laue Langevin and Keele University; Wada, Masahisa [University of Tokyo, Japan; Langan, Paul [ORNL

    2013-01-01

    The neutron structure of a complex of EDA with cellulose has been determined to reveal the location of hydrogen atoms involved in hydrogen bonding. EDA disrupts the hydrogen bonding pattern of naturally occurring cellulose by accepting a strong hydrogen bond from the O6 hydroxymethyl group as the conformation of this group is rotated from tg to gt. The O3-H O5 intrachain hydrogen bond commonly found in cellulose allomorphs is observed to be disordered in the neutron structure, and quantum chemistry and molecular dynamics calculations show that O3 prefers to donate to EDA. The hydrogen bonding arrangement is highly dynamic with bonds continually being formed and broken thus explaining the difficulty in locating all of the hydrogen atoms in the neutron scattering density maps. Comparison with other polysaccharide-amine complexes supports a common underlying mechanism for amine disruption of cellulose.

  16. Application of Metagenomic Analyses in Dentistry as a Novel Strategy Enabling Complex Insight into Microbial Diversity of the Oral Cavity.

    Science.gov (United States)

    Burczynska, Aleksandra; Dziewit, Lukasz; Decewicz, Przemysław; Struzycka, Izabela; Wroblewska, Marta

    2017-03-30

    The composition of the oral microbiome in healthy individuals is complex and dynamic, and depends on many factors, such as anatomical location in the oral cavity, diet, oral hygiene habits or host immune responses. It is estimated at present that worldwide about 2 billion people suffer from diseases of the oral cavity, mainly periodontal disease and dental caries. Importantly, the oral microflora involved in local infections may spread and cause systemic, even life-threatening infections. In search for etiological agents of infections in dentistry, traditional approaches are not sufficient, as about 50% of oral bacteria are not cultivable. Instead, metagenomic analyses are particularly useful for studies of the complex oral microbiome - both in healthy individuals, and in patients with oral and dental diseases. In this paper we review the current and future applications of metagenomic studies in evaluation of both the composition of the oral microbiome as well as its potential pathogenic role in infections in dentistry.

  17. Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1 subcomplex.

    Science.gov (United States)

    Alqarni, Saad S M; Murthy, Andal; Zhang, Wei; Przewloka, Marcin R; Silva, Ana P G; Watson, Aleksandra A; Lejon, Sara; Pei, Xue Y; Smits, Arne H; Kloet, Susan L; Wang, Hongxin; Shepherd, Nicholas E; Stokes, Philippa H; Blobel, Gerd A; Vermeulen, Michiel; Glover, David M; Mackay, Joel P; Laue, Ernest D

    2014-08-08

    The nucleosome remodeling and deacetylase (NuRD) complex is a widely conserved transcriptional co-regulator that harbors both nucleosome remodeling and histone deacetylase activities. It plays a critical role in the early stages of ES cell differentiation and the reprogramming of somatic to induced pluripotent stem cells. Abnormalities in several NuRD proteins are associated with cancer and aging. We have investigated the architecture of NuRD by determining the structure of a subcomplex comprising RbAp48 and MTA1. Surprisingly, RbAp48 recognizes MTA1 using the same site that it uses to bind histone H4, showing that assembly into NuRD modulates RbAp46/48 interactions with histones. Taken together with other results, our data show that the MTA proteins act as scaffolds for NuRD complex assembly. We further show that the RbAp48-MTA1 interaction is essential for the in vivo integration of RbAp46/48 into the NuRD complex. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Costs of storing colour and complex shape in visual working memory: Insights from pupil size and slow waves.

    Science.gov (United States)

    Kursawe, Michael A; Zimmer, Hubert D

    2015-06-01

    We investigated the impact of perceptual processing demands on visual working memory of coloured complex random polygons during change detection. Processing load was assessed by pupil size (Exp. 1) and additionally slow wave potentials (Exp. 2). Task difficulty was manipulated by presenting different set sizes (1, 2, 4 items) and by making different features (colour, shape, or both) task-relevant. Memory performance in the colour condition was better than in the shape and both condition which did not differ. Pupil dilation and the posterior N1 increased with set size independent of type of feature. In contrast, slow waves and a posterior P2 component showed set size effects but only if shape was task-relevant. In the colour condition slow waves did not vary with set size. We suggest that pupil size and N1 indicates different states of attentional effort corresponding to the number of presented items. In contrast, slow waves reflect processes related to encoding and maintenance strategies. The observation that their potentials vary with the type of feature (simple colour versus complex shape) indicates that perceptual complexity already influences encoding and storage and not only comparison of targets with memory entries at the moment of testing. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Insight to structural subsite recognition in plant thiol protease-inhibitor complexes : Understanding the basis of differential inhibition and the role of water

    Directory of Open Access Journals (Sweden)

    Mukhopadhayay Bishnu P

    2001-09-01

    Full Text Available Abstract Background This work represents an extensive MD simulation / water-dynamics studies on a series of complexes of inhibitors (leupeptin, E-64, E-64-C, ZPACK and plant cysteine proteases (actinidin, caricain, chymopapain, calotropin DI of papain family to understand the various interactions, water binding mode, factors influencing it and the structural basis of differential inhibition. Results The tertiary structure of the enzyme-inhibitor complexes were built by visual interactive modeling and energy minimization followed by dynamic simulation of 120 ps in water environment. DASA study with and without the inhibitor revealed the potential subsite residues involved in inhibition. Though the interaction involving main chain atoms are similar, critical inspection of the complexes reveal significant differences in the side chain interactions in S2-P2 and S3-P3 pairs due to sequence differences in the equivalent positions of respective subsites leading to differential inhibition. Conclusion The key finding of the study is a conserved site of a water molecule near oxyanion hole of the enzyme active site, which is found in all the modeled complexes and in most crystal structures of papain family either native or complexed. Conserved water molecules at the ligand binding sites of these homologous proteins suggest the structural importance of the water, which changes the conventional definition of chemical geometry of inhibitor binding domain, its shape and complimentarity. The water mediated recognition of inhibitor to enzyme subsites (Pn...H2O....Sn of leupeptin acetyl oxygen to caricain, chymopapain and calotropinDI is an additional information and offer valuable insight to potent inhibitor design.

  20. Lack of FTSH4 Protease Affects Protein Carbonylation, Mitochondrial Morphology, and Phospholipid Content in Mitochondria of Arabidopsis: New Insights into a Complex Interplay.

    Science.gov (United States)

    Smakowska, Elwira; Skibior-Blaszczyk, Renata; Czarna, Malgorzata; Kolodziejczak, Marta; Kwasniak-Owczarek, Malgorzata; Parys, Katarzyna; Funk, Christiane; Janska, Hanna

    2016-08-01

    FTSH4 is one of the inner membrane-embedded ATP-dependent metalloproteases in mitochondria of Arabidopsis (Arabidopsis thaliana). In mutants impaired to express FTSH4, carbonylated proteins accumulated and leaf morphology was altered when grown under a short-day photoperiod, at 22°C, and a long-day photoperiod, at 30°C. To provide better insight into the function of FTSH4, we compared the mitochondrial proteomes and oxyproteomes of two ftsh4 mutants and wild-type plants grown under conditions inducing the phenotypic alterations. Numerous proteins from various submitochondrial compartments were observed to be carbonylated in the ftsh4 mutants, indicating a widespread oxidative stress. One of the reasons for the accumulation of carbonylated proteins in ftsh4 was the limited ATP-dependent proteolytic capacity of ftsh4 mitochondria, arising from insufficient ATP amount, probably as a result of an impaired oxidative phosphorylation (OXPHOS), especially complex V. In ftsh4, we further observed giant, spherical mitochondria coexisting among normal ones. Both effects, the increased number of abnormal mitochondria and the decreased stability/activity of the OXPHOS complexes, were probably caused by the lower amount of the mitochondrial membrane phospholipid cardiolipin. We postulate that the reduced cardiolipin content in ftsh4 mitochondria leads to perturbations within the OXPHOS complexes, generating more reactive oxygen species and less ATP, and to the deregulation of mitochondrial dynamics, causing in consequence the accumulation of oxidative damage. © 2016 American Society of Plant Biologists. All Rights Reserved.

  1. Crystal structure of lactose permease in complex with an affinity inactivator yields unique insight into sugar recognition

    Energy Technology Data Exchange (ETDEWEB)

    Chaptal, Vincent; Kwon, Seunghyug; Sawaya, Michael R.; Guan, Lan; Kaback, H. Ronald; Abramson, Jeff (UCLA); (TTU)

    2011-08-29

    Lactose permease of Escherichia coli (LacY) with a single-Cys residue in place of A122 (helix IV) transports galactopyranosides and is specifically inactivated by methanethiosulfonyl-galactopyranosides (MTS-gal), which behave as unique suicide substrates. In order to study the mechanism of inactivation more precisely, we solved the structure of single-Cys122 LacY in complex with covalently bound MTS-gal. This structure exhibits an inward-facing conformation similar to that observed previously with a slight narrowing of the cytoplasmic cavity. MTS-gal is bound covalently, forming a disulfide bond with C122 and positioned between R144 and W151. E269, a residue essential for binding, coordinates the C-4 hydroxyl of the galactopyranoside moiety. The location of the sugar is in accord with many biochemical studies.

  2. Role of competing ions in the mobilization of arsenic in groundwater of Bengal Basin: insight from surface complexation modeling.

    Science.gov (United States)

    Biswas, Ashis; Gustafsson, Jon Petter; Neidhardt, Harald; Halder, Dipti; Kundu, Amit K; Chatterjee, Debashis; Berner, Zsolt; Bhattacharya, Prosun

    2014-05-15

    This study assesses the role of competing ions in the mobilization of arsenic (As) by surface complexation modeling of the temporal variability of As in groundwater. The potential use of two different surface complexation models (SCMs), developed for ferrihydrite and goethite, has been explored to account for the temporal variation of As(III) and As(V) concentration, monitored in shallow groundwater of Bengal Basin over a period of 20 months. The SCM for ferrihydrite appears as the better predictor of the observed variation in both As(III) and As(V) concentrations in the study sites. It is estimated that among the competing ions, PO4(3-) is the major competitor of As(III) and As(V) adsorption onto Fe oxyhydroxide, and the competition ability decreases in the order PO4(3-) ≫ Fe(II) > H4SiO4 = HCO3(-). It is further revealed that a small change in pH can also have a significant effect on the mobility of As(III) and As(V) in the aquifers. A decrease in pH increases the concentration of As(III), whereas it decreases the As(V) concentration and vice versa. The present study suggests that the reductive dissolution of Fe oxyhydroxide alone cannot explain the observed high As concentration in groundwater of the Bengal Basin. This study supports the view that the reductive dissolution of Fe oxyhydroxide followed by competitive sorption reactions with the aquifer sediment is the processes responsible for As enrichment in groundwater. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. How new concepts become universal scientific approaches: insights from citation network analysis of agent-based complex systems science.

    Science.gov (United States)

    Vincenot, Christian E

    2018-03-14

    Progress in understanding and managing complex systems comprised of decision-making agents, such as cells, organisms, ecosystems or societies, is-like many scientific endeavours-limited by disciplinary boundaries. These boundaries, however, are moving and can actively be made porous or even disappear. To study this process, I advanced an original bibliometric approach based on network analysis to track and understand the development of the model-based science of agent-based complex systems (ACS). I analysed research citations between the two communities devoted to ACS research, namely agent-based (ABM) and individual-based modelling (IBM). Both terms refer to the same approach, yet the former is preferred in engineering and social sciences, while the latter prevails in natural sciences. This situation provided a unique case study for grasping how a new concept evolves distinctly across scientific domains and how to foster convergence into a universal scientific approach. The present analysis based on novel hetero-citation metrics revealed the historical development of ABM and IBM, confirmed their past disjointedness, and detected their progressive merger. The separation between these synonymous disciplines had silently opposed the free flow of knowledge among ACS practitioners and thereby hindered the transfer of methodological advances and the emergence of general systems theories. A surprisingly small number of key publications sparked the ongoing fusion between ABM and IBM research. Beside reviews raising awareness of broad-spectrum issues, generic protocols for model formulation and boundary-transcending inference strategies were critical means of science integration. Accessible broad-spectrum software similarly contributed to this change. From the modelling viewpoint, the discovery of the unification of ABM and IBM demonstrates that a wide variety of systems substantiate the premise of ACS research that microscale behaviours of agents and system-level dynamics

  4. Insights on novel particulate self-assembled drug delivery beads based on partial inclusion complexes between triglycerides and cyclodextrins.

    Science.gov (United States)

    Aburahma, Mona Hassan

    2016-09-01

    Most of the newly designed drug molecules are lipophilic in nature and often encounter erratic absorption and low bioavailability after oral administration. Finding ways to enhance the absorption and bioavailability of these lipophilic drugs is one of the major challenges that face pharmaceutical industry nowadays. In view of that, the purpose of this review is to shed some light on a novel particulate self-assembling system named "beads" than can act as a safe carrier for delivering lipophilic drugs. The beads are prepared simply by mixing oils with cyclodextrin (CD) aqueous solution in mild conditions. A unique interaction between oil components and CD molecules occurs to form in situ surface-active complexes which are prerequisites for beads formation. This review mainly focuses on the fundamentals of beads preparation through reviewing present, yet scarce, literature. The key methods used for beads characterization are discussed in details. Also, the potential mechanisms by which beads increase the bioavailability of lipophilic drugs are illustrated. Finally, the related research areas that needs to be addressed in future for optimizing this promising delivery system are briefly outlined.

  5. Theoretical insight into the solvent effect of H2O and formamide on the cooperativity effect in HMX complex.

    Science.gov (United States)

    Meng, Rui-Hong; Cao, Xiong; Hu, Shuang-Qi; Hu, Li-Shuang

    2017-08-01

    The cooperativity effects of the H-bonding interactions in HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane)∙∙∙HMX∙∙∙FA (formamide), HMX∙∙∙HMX∙∙∙H 2 O and HMX∙∙∙HMX∙∙∙HMX complexes involving the chair and chair-chair HMX are investigated by using the ONIOM2 (CAM-B3LYP/6-31++G(d,p):PM3) and ONIOM2 (M06-2X/6-31++G(d,p):PM3) methods. The solvent effect of FA or H 2 O on the cooperativity effect in HMX∙∙∙HMX∙∙∙HMX are evaluated by the integral equation formalism polarized continuum model. The results show that the cooperativity and anti-cooperativity effects are not notable in all the systems. Although the effect of solvation on the binding energy of ternary system HMX∙∙∙HMX∙∙∙HMX is not large, that on the cooperativity of H-bonds is notable, which leads to the mutually strengthened H-bonding interaction in solution. This is perhaps the reason for the formation of different conformation of HMX in different solvent. Surface electrostatic potential and reduced density gradient are used to reveal the nature of the solvent effect on cooperativity effect in HMX∙∙∙HMX∙∙∙HMX. Graphical abstract RDG isosurface and electrostatic potential surface of HMX∙∙∙HMX∙∙∙HMX.

  6. Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome.

    Science.gov (United States)

    Sun, Ji; MacKinnon, Roderick

    2017-06-01

    KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I Ks ) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present the cryoelectron microscopy (cryo-EM) structure of a KCNQ1/calmodulin (CaM) complex. The conformation corresponds to an "uncoupled," PIP 2 -free state of KCNQ1, with activated voltage sensors and a closed pore. Unique structural features within the S4-S5 linker permit uncoupling of the voltage sensor from the pore in the absence of PIP 2 . CaM contacts the KCNQ1 voltage sensor through a specific interface involving a residue on CaM that is mutated in a form of inherited LQTS. Using an electrophysiological assay, we find that this mutation on CaM shifts the KCNQ1 voltage-activation curve. This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP 2 , and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Structure and dynamics of the uranyl tricarbonate complex in aqueous solution: insights from quantum mechanical charge field molecular dynamics.

    Science.gov (United States)

    Tirler, Andreas O; Hofer, Thomas S

    2014-11-13

    This investigation presents the characterization of structural and dynamical properties of uranyl tricarbonate in aqueous solution employing an extended hybrid quantum mechanical/molecular mechanical (QM/MM) approach. It is shown that the inclusion of explicit solvent molecules in the quantum chemical treatment is essential to mimic the complex interaction occurring in an aqueous environment. Thus, in contrast to gas phase cluster calculations on a quantum chemical level proposing a 6-fold coordination of the three carbonates, the QMCF MD simulation proposes a 5-fold coordination. An extensive comparison of the simulation results to structural and dynamical data available in the literature was found to be in excellent agreement. Furthermore, this work is the first theoretical study on a quantum chemical level of theory able to observe the conversion of carbonate (CO₃²⁻) to bicarbonate (HCO₃⁻) in the equatorial coordination sphere of the uranyl ion. From a comparison of the free energy ΔG values for the unprotonated educt [UO₂(CO₃)₃]⁴⁻ and the protonated [UO₂(CO₃)₂(HCO₃)]³⁻, it could be concluded that the reaction equilibrium is strongly shifted toward the product state confirming the benignity for the observed protonation reaction. Structural properties and the three-dimensional arrangement of carbonate ligands were analyzed via pair-, three-body, and angular distributions, the dynamical properties were evaluated by hydrogen-bond correlation functions and vibrational power spectra.

  8. The Mediator complex of Caenorhabditis elegans: insights into the developmental and physiological roles of a conserved transcriptional coregulator.

    Science.gov (United States)

    Grants, Jennifer M; Goh, Grace Y S; Taubert, Stefan

    2015-02-27

    The Mediator multiprotein complex ('Mediator') is an important transcriptional coregulator that is evolutionarily conserved throughout eukaryotes. Although some Mediator subunits are essential for the transcription of all protein-coding genes, others influence the expression of only subsets of genes and participate selectively in cellular signaling pathways. Here, we review the current knowledge of Mediator subunit function in the nematode Caenorhabditis elegans, a metazoan in which established and emerging genetic technologies facilitate the study of developmental and physiological regulation in vivo. In this nematode, unbiased genetic screens have revealed critical roles for Mediator components in core developmental pathways such as epidermal growth factor (EGF) and Wnt/β-catenin signaling. More recently, important roles for C. elegans Mediator subunits have emerged in the regulation of lipid metabolism and of systemic stress responses, engaging conserved transcription factors such as nuclear hormone receptors (NHRs). We emphasize instances where similar functions for individual Mediator subunits exist in mammals, highlighting parallels between Mediator subunit action in nematode development and in human cancer biology. We also discuss a parallel between the association of the Mediator subunit MED12 with several human disorders and the role of its C. elegans ortholog mdt-12 as a regulatory hub that interacts with numerous signaling pathways. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. The Axl kinase domain in complex with a macrocyclic inhibitor offers first structural insights into an active TAM receptor kinase.

    Science.gov (United States)

    Gajiwala, Ketan S; Grodsky, Neil; Bolaños, Ben; Feng, Junli; Ferre, RoseAnn; Timofeevski, Sergei; Xu, Meirong; Murray, Brion W; Johnson, Ted W; Stewart, Al

    2017-09-22

    The receptor tyrosine kinase family consisting of Tyro3, Axl, and Mer (TAM) is one of the most recently identified receptor tyrosine kinase families. TAM receptors are up-regulated postnatally and maintained at high levels in adults. They all play an important role in immunity, but Axl has also been implicated in cancer and therefore is a target in the discovery and development of novel therapeutics. However, of the three members of the TAM family, the Axl kinase domain is the only one that has so far eluded structure determination. To this end, using differential scanning fluorimetry and hydrogen-deuterium exchange mass spectrometry, we show here that a lower stability and greater dynamic nature of the Axl kinase domain may account for its poor crystallizability. We present the first structural characterization of the Axl kinase domain in complex with a small-molecule macrocyclic inhibitor. The Axl crystal structure revealed two distinct conformational states of the enzyme, providing a first glimpse of what an active TAM receptor kinase may look like and suggesting a potential role for the juxtamembrane region in enzyme activity. We noted that the ATP/inhibitor-binding sites of the TAM members closely resemble each other, posing a challenge for the design of a selective inhibitor. We propose that the differences in the conformational dynamics among the TAM family members could potentially be exploited to achieve inhibitor selectivity for targeted receptors. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. New insights into the transposition mechanisms of IS6110 and its dynamic distribution between Mycobacterium tuberculosis Complex lineages.

    Science.gov (United States)

    Gonzalo-Asensio, Jesús; Pérez, Irene; Aguiló, Nacho; Uranga, Santiago; Picó, Ana; Lampreave, Carlos; Cebollada, Alberto; Otal, Isabel; Samper, Sofía; Martín, Carlos

    2018-04-01

    The insertion Sequence IS6110, only present in the pathogens of the Mycobacterium tuberculosis Complex (MTBC), has been the gold-standard epidemiological marker for TB for more than 25 years, but biological implications of IS6110 transposition during MTBC adaptation to humans remain elusive. By studying 2,236 clinical isolates typed by IS6110-RFLP and covering the MTBC, we remarked a lineage-specific content of IS6110 being higher in modern globally distributed strains. Once observed the IS6110 distribution in the MTBC, we selected representative isolates and found a correlation between the normalized expression of IS6110 and its abundance in MTBC chromosomes. We also studied the molecular regulation of IS6110 transposition and we found a synergistic action of two post-transcriptional mechanisms: a -1 ribosomal frameshift and a RNA pseudoknot which interferes translation. The construction of a transcriptionally active transposase resulted in 20-fold increase of the transposition frequency. Finally, we examined transposition in M. bovis and M. tuberculosis during laboratory starvation and in a mouse infection model of TB. Our results shown a higher transposition in M. tuberculosis, that preferably happens during TB infection in mice and after one year of laboratory culture, suggesting that IS6110 transposition is dynamically adapted to the host and to adverse growth conditions.

  11. Mechanistic Insights from the Crystal Structure of Bacillus subtilis o-Succinylbenzoyl-CoA Synthetase Complexed with the Adenylate Intermediate.

    Science.gov (United States)

    Chen, Yaozong; Jiang, Yiping; Guo, Zhihong

    2016-12-06

    o-Succinylbenzoyl-CoA (OSB-CoA) synthetase, or MenE, catalyzes an essential step in vitamin K biosynthesis and is a valuable drug target. Like many other adenylating enzymes, it changes its structure to accommodate substrate binding, catalysis, and product release along the path of a domain alternation catalytic mechanism. We have determined the crystal structure of its complex with the adenylation product, o-succinylbenzoyl-adenosine monophosphate (OSB-AMP), and captured a new postadenylation state. This structure presents unique features such as a strained conformation for the bound adenylate intermediate to indicate that it represents the enzyme state after completion of the adenylation reaction but before release of the C domain in its transition to the thioesterification conformation. By comparison to the ATP-bound preadenylation conformation, structural changes are identified in both the reactants and the active site to allow inference about how these changes accommodate and facilitate the adenylation reaction and to directly support an in-line backside attack nucleophilic substitution mechanism for the first half-reaction. Mutational analysis suggests that the conserved His196 plays an important role in desolvation of the active site rather than stabilizing the transition state of the adenylation reaction. In addition, comparison of the new structure with a previously determined OSB-AMP-bound structure of the same enzyme allows us to propose a release mechanism of the C domain in its alteration to form the thioesterification conformation. These findings allow us to better understand the domain alternation catalytic mechanism of MenE as well as many other adenylating enzymes.

  12. New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes

    Directory of Open Access Journals (Sweden)

    Sabiha Abekhoukh

    2017-04-01

    Full Text Available Cytoplasmic FMRP interacting protein 1 (CYFIP1 is a candidate gene for intellectual disability (ID, autism, schizophrenia and epilepsy. It is a member of a family of proteins that is highly conserved during evolution, sharing high homology with its Drosophila homolog, dCYFIP. CYFIP1 interacts with the Fragile X mental retardation protein (FMRP, encoded by the FMR1 gene, whose absence causes Fragile X syndrome, and with the translation initiation factor eIF4E. It is a member of the WAVE regulatory complex (WRC, thus representing a link between translational regulation and the actin cytoskeleton. Here, we present data showing a correlation between mRNA levels of CYFIP1 and other members of the WRC. This suggests a tight regulation of the levels of the WRC members, not only by post-translational mechanisms, as previously hypothesized. Moreover, we studied the impact of loss of function of both CYFIP1 and FMRP on neuronal growth and differentiation in two animal models – fly and mouse. We show that these two proteins antagonize each other's function not only during neuromuscular junction growth in the fly but also during new neuronal differentiation in the olfactory bulb of adult mice. Mechanistically, FMRP and CYFIP1 modulate mTor signaling in an antagonistic manner, likely via independent pathways, supporting the results obtained in mouse as well as in fly at the morphological level. Collectively, our results illustrate a new model to explain the cellular roles of FMRP and CYFIP1 and the molecular significance of their interaction.

  13. Geological Mapping of Impact Melt Deposits at Lunar Complex Craters: New Insights into Morphological Diversity, Distribution and the Cratering Process

    Science.gov (United States)

    Dhingra, D.; Head, J. W., III; Pieters, C. M.

    2014-12-01

    We have completed high resolution geological mapping of impact melt deposits at the young lunar complex craters (wall and rim impact melt units and their relation to floor units have also been mapped. Among the distinctive features of these impact melt deposits are: 1) Impact Melt Wave Fronts: These are extensive (sometimes several kilometers in length) and we have documented their occurrence and distribution in different parts of the crater floor at Jackson and Tycho. These features emphasize melt mobility and style of emplacement during the modification stage of the craters. 2) Variations in Floor Elevations: Spatially extensive and coherent sections of crater floors have different elevations at all the three craters. The observed elevation differences could be caused by subsidence due to cooling of melt and/or structural failure, together with a contribution from regional slope. 3) Melt-Covered Megablocks: We also observe large blocks/rock-fragments (megablocks) covered in impact melt, which could be sections of collapsed wall or in some cases, subdued sections of central peaks. 4) Melt-Covered Central Peaks: Impact melt has also been mapped on the central peaks but varies in spatial extent among the craters. The presence of melt on peaks must be taken into account when interpreting peak mineralogy as exposures of deeper crust. 5) Boulder Distribution: Interesting trends are observed in the distribution of boulder units of various sizes; some impact melt units have spatially extensive boulders, while boulder distribution is very scarce in other units on the floor. We interpret these distributions to be influenced by a) the differential collapse of the crater walls during the modification stage, and b) the amount of relative melt volume retained in different parts of the crater floor. These observations provide important documentation of the morphological diversity and better understanding of the emplacement and final distribution of impact melt deposits.

  14. Kinetic effects of sulfur oxidation on catalytic nitrile hydration: nitrile hydratase insights from bioinspired ruthenium(II) complexes.

    Science.gov (United States)

    Kumar, Davinder; Nguyen, Tho N; Grapperhaus, Craig A

    2014-12-01

    Kinetic investigations inspired by the metalloenzyme nitrile hydratase were performed on a series of ruthenium(II) complexes to determine the effect of sulfur oxidation on catalytic nitrile hydration. The rate of benzonitrile hydration was quantified as a function of catalyst, nitrile, and water concentrations. Precatalysts L(n)RuPPh3 (n = 1-3; L(1) = 4,7-bis(2'-methyl-2'-mercapto-propyl)-1-thia-4,7-diazacyclononane; L(2) = 4-(2'-methyl-2'-sulfinatopropyl)-7-(2'-methyl-2'-mercapto-propyl)-1-thia-4,7-diazacyclononane; L(3) = 4-(2'-methyl-2'-sulfinatopropyl)-7-(2'-methyl-2'-sulfenato-propyl)-1-thia-4,7-diazacyclononane) were activated by substitution of triphenylphosphine with substrate in hot dimethylformamide solution. Rate measurements are consistent with a dynamic equilibrium between inactive aqua (L(n)Ru-OH2) and active nitrile (L(n)Ru-NCR) derivatives with K = 21 ± 1, 9 ± 0.9, and 23 ± 3 for L(1) to L(3), respectively. Subsequent hydration of the L(n)Ru-NCR intermediate yields the amide product with measured hydration rate constants (k's) of 0.37 ± 0.01, 0.82 ± 0.07, and 1.59 ± 0.12 M(-1) h(-1) for L(1) to L(3), respectively. Temperature dependent studies reveal that sulfur oxidation lowers the enthalpic barrier by 27 kJ/mol, but increases the entropic barrier by 65 J/(mol K). Density functional theory (DFT) calculations (B3LYP/LanL2DZ (Ru); 6-31G(d) (all other atoms)) support a nitrile bound catalytic cycle with lowering of the reaction barrier as a consequence of sulfur oxidation through enhanced nitrile binding and attack of the water nucleophile through a highly organized transition state.

  15. Molecular insight into γ-γ tubulin lateral interactions within the γ-tubulin ring complex (γ-TuRC)

    Science.gov (United States)

    Suri, Charu; Hendrickson, Triscia W.; Joshi, Harish C.; Naik, Pradeep Kumar

    2014-09-01

    γ-tubulin is essential for the nucleation and organization of mitotic microtubules in dividing cells. It is localized at the microtubule organizing centers and mitotic spindle fibres. The most well accepted hypothesis for the initiation of microtubule polymerization is that α/β-tubulin dimers add onto a γ-tubulin ring complex (γTuRC), in which adjacent γ-tubulin subunits bind to the underlying non-tubulin components of the γTuRC. This template thus determines the resulting microtubule lattice. In this study we use molecular modelling and molecular dynamics simulations, combined with computational MM-PBSA/MM-GBSA methods, to determine the extent of the lateral atomic interaction between two adjacent γ-tubulins within the γTuRC. To do this we simulated a γ-γ homodimer for 10 ns and calculated the ensemble average of binding free energies of -107.76 kcal/mol by the MM-PBSA method and of -87.12 kcal/mol by the MM-GBSA method. These highly favourable binding free energy values imply robust lateral interactions between adjacent γ-tubulin subunits in addition to their end-interactions longitudinally with other proteins of γTuRC. Although the functional reconstitution of γ-TuRC subunits and their stepwise in vitro assembly from purified components is not yet feasible, we nevertheless wanted to recognize hotspot amino acids responsible for key γ-γ interactions. Our free energy decomposition data from converting a compendium of amino acid residues identified an array of hotspot amino acids. A subset of such mutants can be expressed in vivo in living yeast. Because γTuRC is important for the growth of yeast, we could test whether this subset of the hotspot mutations support growth of yeast. Consistent with our model, γ-tubulin mutants that fall into our identified hotspot do not support yeast growth.

  16. Identification of loci governing eight agronomic traits using a GBS-GWAS approach and validation by QTL mapping in soya bean.

    Science.gov (United States)

    Sonah, Humira; O'Donoughue, Louise; Cober, Elroy; Rajcan, Istvan; Belzile, François

    2015-02-01

    Soya bean is a major source of edible oil and protein for human consumption as well as animal feed. Understanding the genetic basis of different traits in soya bean will provide important insights for improving breeding strategies for this crop. A genome-wide association study (GWAS) was conducted to accelerate molecular breeding for the improvement of agronomic traits in soya bean. A genotyping-by-sequencing (GBS) approach was used to provide dense genome-wide marker coverage (>47,000 SNPs) for a panel of 304 short-season soya bean lines. A subset of 139 lines, representative of the diversity among these, was characterized phenotypically for eight traits under six environments (3 sites × 2 years). Marker coverage proved sufficient to ensure highly significant associations between the genes known to control simple traits (flower, hilum and pubescence colour) and flanking SNPs. Between one and eight genomic loci associated with more complex traits (maturity, plant height, seed weight, seed oil and protein) were also identified. Importantly, most of these GWAS loci were located within genomic regions identified by previously reported quantitative trait locus (QTL) for these traits. In some cases, the reported QTLs were also successfully validated by additional QTL mapping in a biparental population. This study demonstrates that integrating GBS and GWAS can be used as a powerful complementary approach to classical biparental mapping for dissecting complex traits in soya bean. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  17. Structural and Functional Studies of a Bothropic Myotoxin Complexed to Rosmarinic Acid: New Insights into Lys49-PLA2 Inhibition

    Science.gov (United States)

    dos Santos, Juliana I.; Cardoso, Fábio F.; Soares, Andreimar M.; dal Pai Silva, Maeli; Gallacci, Márcia; Fontes, Marcos R. M.

    2011-01-01

    Snakebite envenoming is an important public health problem in many tropical and subtropical countries, and is considered a neglected tropical disease by the World Health Organization. Most severe cases are inflicted by species of the families Elapidae and Viperidae, and lead to a number of systemic and local effects in the victim. One of the main problems regarding viperidic accidents is prominent local tissue damage whose pathogenesis is complex and involves the combined actions of a variety of venom components. Phospholipases A2 (PLA2s) are the most abundant muscle-damaging components of these venoms. Herein, we report functional and structural studies of PrTX-I, a Lys49-PLA2 from Bothops pirajai snake venom, and the influence of rosmarinic acid (RA) upon this toxin's activities. RA is a known active component of some plant extracts and has been reported as presenting anti-myotoxic properties related to bothopic envenomation. The myotoxic activity of Lys49-PLA2s is well established in the literature and although no in vivo neurotoxicity has been observed among these toxins, in vitro neuromuscular blockade has been reported for some of these proteins. Our in vitro studies show that RA drastically reduces both the muscle damage and the neuromuscular blockade exerted by PrTX-I on mice neuromuscular preparations (by ∼80% and ∼90%, respectively). These results support the hypothesis that the two effects are closely related and lead us to suggest that they are consequences of the muscle membrane-destabilizing activity of the Lys49-PLA2. Although the C-terminal region of these proteins has been reported to comprise the myotoxic site, we demonstrate by X-ray crystallographic studies that RA interacts with PrTX-I in a different region. Consequently, a new mode of Lys49-PLA2 inhibition is proposed. Comparison of our results with others in the literature suggests possible new ways to inhibit bothropic snake venom myotoxins and improve serum therapy. PMID:22205953

  18. Molecular fingerprinting of complex grass allergoids: size assessments reveal new insights in epitope repertoires and functional capacities.

    Science.gov (United States)

    Starchenka, S; Bell, A J; Mwange, J; Skinner, M A; Heath, M D

    2017-01-01

    Subcutaneous allergen immunotherapy (SCIT) is a well-documented treatment for allergic disease which involves injections of native allergen or modified (allergoid) extracts. The use of allergoid vaccines is a growing sector of the allergy immunotherapy market, associated with shorter-course therapy. The aim of this study was the structural and immunological characterisation of group 1 (Lol p 1) IgG-binding epitopes within a complex mix grass allergoid formulation containing rye grass. HP-SEC was used to resolve a mix grass allergoid preparation of high molecular weight into several distinct fractions with defined molecular weight and elution profiles. Allergen verification of the HP-SEC allergoid fractions was confirmed by mass spectrometry analysis. IgE and IgG immunoreactivity of the allergoid preparations was explored and Lol p 1 specific IgG-binding epitopes mapped by SPOT synthesis technology (PepSpot™) with structural analysis based on a Lol p 1 homology model. Grass specific IgE reactivity of the mix grass modified extract (allergoid) was diminished in comparison with the mix grass native extract. A difference in IgG profiles was observed between an intact mix grass allergoid preparation and HP-SEC allergoid fractions, which indicated enhancement of accessible reactive IgG epitopes across size distribution profiles of the mix grass allergoid formulation. Detailed analysis of the epitope specificity showed retention of six Lol p 1 IgG-binding epitopes in the mix grass modified extract. The structural and immunological changes which take place following the grass allergen modification process was further unravelled revealing distinct IgG immunological profiles. All epitopes were mapped on the solvent exposed area of Lol p 1 homology model accessible for IgG binding. One of the epitopes was identified as an 'immunodominant' Lol p 1 IgG-binding epitope (62-IFKDGRGCGSCFEIK-76) and classified as a novel epitope. The results from this study support the concept

  19. Genome-wide association studies dissect the genetic networks underlying agronomical traits in soybean.

    Science.gov (United States)

    Fang, Chao; Ma, Yanming; Wu, Shiwen; Liu, Zhi; Wang, Zheng; Yang, Rui; Hu, Guanghui; Zhou, Zhengkui; Yu, Hong; Zhang, Min; Pan, Yi; Zhou, Guoan; Ren, Haixiang; Du, Weiguang; Yan, Hongrui; Wang, Yanping; Han, Dezhi; Shen, Yanting; Liu, Shulin; Liu, Tengfei; Zhang, Jixiang; Qin, Hao; Yuan, Jia; Yuan, Xiaohui; Kong, Fanjiang; Liu, Baohui; Li, Jiayang; Zhang, Zhiwu; Wang, Guodong; Zhu, Baoge; Tian, Zhixi

    2017-08-24

    Soybean (Glycine max [L.] Merr.) is one of the most important oil and protein crops. Ever-increasing soybean consumption necessitates the improvement of varieties for more efficient production. However, both correlations among different traits and genetic interactions among genes that affect a single trait pose a challenge to soybean breeding. To understand the genetic networks underlying phenotypic correlations, we collected 809 soybean accessions worldwide and phenotyped them for two years at three locations for 84 agronomic traits. Genome-wide association studies identified 245 significant genetic loci, among which 95 genetically interacted with other loci. We determined that 14 oil synthesis-related genes are responsible for fatty acid accumulation in soybean and function in line with an additive model. Network analyses demonstrated that 51 traits could be linked through the linkage disequilibrium of 115 associated loci and these links reflect phenotypic correlations. We revealed that 23 loci, including the known Dt1, E2, E1, Ln, Dt2, Fan, and Fap loci, as well as 16 undefined associated loci, have pleiotropic effects on different traits. This study provides insights into the genetic correlation among complex traits and will facilitate future soybean functional studies and breeding through molecular design.

  20. Neutral Theory: From Complex Population History to Natural Selection and Sociocultural Phenomena in Human Populations.

    Science.gov (United States)

    Austerlitz, Frédéric; Heyer, Evelyne

    2018-06-01

    Here, we present a synthetic view on how Kimura's Neutral theory has helped us gaining insight on the different evolutionary forces that shape human evolution. We put this perspective in the frame of recent emerging challenges: the use of whole genome data for reconstructing population histories, natural selection on complex polygenic traits, and integrating cultural processes in human evolution.

  1. Brief Report: Effect of Spatial Complexity on Visual Short-Term Memory and Self-Reported Autistic-Like Traits in Typically Developed Individuals

    Science.gov (United States)

    Takahashi, Junichi; Gyoba, Jiro; Yamawaki, Nozomi

    2013-01-01

    This report examines effects of the spatial complexity of configurations on visual short-term memory (VSTM) capacity for individuals from the general population differing on autism-spectrum quotient (AQ) scores. During each trial, nine-line segments with various orientations were arrayed in simple or complex configurations and presented in both…

  2. Molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase – inhibitor complex in leishmaniasis: Insight into the structure based drug design [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Vineetha Mandlik

    2016-09-01

    Full Text Available Inositol phosphorylceramide synthase (IPCS has emerged as an important, interesting and attractive target in the sphingolipid metabolism of Leishmania. IPCS catalyzes the conversion of ceramide to IPC which forms the most predominant sphingolipid in Leishmania. IPCS has no mammalian equivalent and also plays an important role in maintaining the infectivity and viability of the parasite. The present study explores the possibility of targeting IPCS; development of suitable inhibitors for the same would serve as a treatment strategy for the infectious disease leishmaniasis. Five coumarin derivatives were developed as inhibitors of IPCS protein. Molecular dynamics simulations of the complexes of IPCS with these inhibitors were performed which provided insights into the binding modes of the inhibitors. In vitro screening of the top three compounds has resulted in the identification of one of the compounds (compound 3 which shows little cytotoxic effects. This compound therefore represents a good starting point for further in vivo experimentation and could possibly serve as an important drug candidate for the treatment of leishmaniasis.

  3. Landscape-Scale Disturbance: Insights into the Complexity of Catchment Hydrology in the Mountaintop Removal Mining Region of the Eastern United States

    Directory of Open Access Journals (Sweden)

    Andrew J. Miller

    2016-07-01

    Full Text Available Few land disturbances impact watersheds at the scale and extent of mountaintop removal mining (MTM. This practice removes forests, soils and bedrock to gain access to underground coal that results in likely permanent and wholesale changes that impact catchment hydrology, geochemistry and ecosystem health. MTM is the dominant driver of land cover changes in the central Appalachian Mountains region of the United States, converting forests to mine lands and burying headwater streams. Despite its dominance on the landscape, determining the hydrological impacts of MTM is complicated by underground coal mines that significantly alter groundwater hydrology. To provide insight into how coal mining impacts headwater catchments, we compared the hydrologic responses of an MTM and forested catchment using event rainfall-runoff analysis, modeling and isotopic approaches. Despite similar rainfall characteristics, hydrology in the two catchments differed in significant ways, but both catchments demonstrated threshold-mediated hydrologic behavior that was attributed to transient storage and the release of runoff from underground mines. Results suggest that underground mines are important controls for runoff generation in both obviously disturbed and seemingly undisturbed catchments and interact in uncertain ways with disturbance from MTM. This paper summarizes our results and demonstrates the complexity of catchment hydrology in the MTM region.

  4. The morphology and distribution of submerged reefs in the Maui-Nui Complex, Hawaii: New insights into their evolution since the Early Pleistocene

    Science.gov (United States)

    Faichney, Iain D.E.; Webster, James M.; Clague, David A.; Kelley, Chris; Applegate, Bruce; Moore, James G.

    2009-01-01

    Reef drowning and backstepping have long been recognised as reef responses to sea-level rise on subsiding margins. During the Late Pleistocene (~500–14 ka) Hawaiian reefs grew in response to rapid subsidence and 120 m 100 kyr sea-level cycles, with recent work on the submerged drowned reefs around the big island of Hawaii, and in other locations from the last deglacial, providing insight into reef development under these conditions. In contrast, reefs of the Early Pleistocene (~1.8–0.8 Ma) remain largely unexplored despite developing in response to significantly different 60–70 m 41 kyr sea-level cycles. The Maui-Nui Complex (MNC — forming the islands of Maui, Molokai, Lanai and Kahoolawe), provides a natural laboratory to study reef evolution throughout this time period as recent data indicate the reefs grew from 1.1 to 0.5 Ma. We use new high resolution bathymetric and backscatter data as well as sub-bottom profiling seismic data and field observations from ROV and submersible dives to make a detailed analysis of reef morphology and structure around the MNC. We focus specifically on the south-central region of the complex that provides the best reef exposure and find that the morphology of the reefs varies both regionally and temporally within this region. Barrier and pinnacle features dominate the steeper margins in the north of the study area whilst broad backstepping of the reefs is observed in the south. Within the Au'au channel in the central region between the islands, closely spaced reef and karst morphology indicates repeated subaerial exposure. We propose that this variation in the morphology and structure of the reefs within the MNC has been controlled by three main factors; the subsidence rate of the complex, the amplitude and period of eustatic sea-level cycles, and the slope and continuity of the basement substrate. We provide a model of reef development within the MNC over the last 1.2 Ma highlighting the effect that the interaction

  5. The impact of sex-role reversal on the diversity of the major histocompatibility complex: insights from the seahorse (Hippocampus abdominalis).

    Science.gov (United States)

    Bahr, Angela; Wilson, Anthony B

    2011-05-10

    Both natural and sexual selection are thought to influence genetic diversity, but the study of the relative importance of these two factors on ecologically-relevant traits has traditionally focused on species with conventional sex-roles, with male-male competition and female-based mate choice. With its high variability and significance in both immune function and olfactory-mediated mate choice, the major histocompatibility complex (MHC/MH) is an ideal system in which to evaluate the relative contributions of these two selective forces to genetic diversity. Intrasexual competition and mate choice are both reversed in sex-role reversed species, and sex-related differences in the detection and use of MH-odor cues are expected to influence the intensity of sexual selection in such species. The seahorse, Hippocampus abdominalis, has an exceptionally highly developed form of male parental care, with female-female competition and male mate choice. Here, we demonstrate that the sex-role reversed seahorse has a single MH class II beta-chain gene and that the diversity of the seahorse MHIIβ locus and its pattern of variation are comparable to those detected in species with conventional sex roles. Despite the presence of only a single gene copy, intralocus MHIIβ allelic diversity in this species exceeds that observed in species with multiple copies of this locus. The MHIIβ locus of the seahorse exhibits a novel expression domain in the male brood pouch. The high variation found at the seahorse MHIIβ gene indicates that sex-role reversed species are capable of maintaining the high MHC diversity typical in most vertebrates.Whether such species have evolved the capacity to use MH-odor cues during mate choice is presently being investigated using mate choice experiments. If this possibility can be rejected, such systems would offer an exceptional opportunity to study the effects of natural selection in isolation, providing powerful comparative models for understanding the

  6. The impact of sex-role reversal on the diversity of the major histocompatibility complex: Insights from the seahorse (Hippocampus abdominalis

    Directory of Open Access Journals (Sweden)

    Wilson Anthony B

    2011-05-01

    Full Text Available Abstract Background Both natural and sexual selection are thought to influence genetic diversity, but the study of the relative importance of these two factors on ecologically-relevant traits has traditionally focused on species with conventional sex-roles, with male-male competition and female-based mate choice. With its high variability and significance in both immune function and olfactory-mediated mate choice, the major histocompatibility complex (MHC/MH is an ideal system in which to evaluate the relative contributions of these two selective forces to genetic diversity. Intrasexual competition and mate choice are both reversed in sex-role reversed species, and sex-related differences in the detection and use of MH-odor cues are expected to influence the intensity of sexual selection in such species. The seahorse, Hippocampus abdominalis, has an exceptionally highly developed form of male parental care, with female-female competition and male mate choice. Results Here, we demonstrate that the sex-role reversed seahorse has a single MH class II beta-chain gene and that the diversity of the seahorse MHIIβ locus and its pattern of variation are comparable to those detected in species with conventional sex roles. Despite the presence of only a single gene copy, intralocus MHIIβ allelic diversity in this species exceeds that observed in species with multiple copies of this locus. The MHIIβ locus of the seahorse exhibits a novel expression domain in the male brood pouch. Conclusions The high variation found at the seahorse MHIIβ gene indicates that sex-role reversed species are capable of maintaining the high MHC diversity typical in most vertebrates. Whether such species have evolved the capacity to use MH-odor cues during mate choice is presently being investigated using mate choice experiments. If this possibility can be rejected, such systems would offer an exceptional opportunity to study the effects of natural selection in isolation

  7. TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits

    NARCIS (Netherlands)

    Diogo, Dorothée; Bastarache, Lisa; Liao, Katherine P.; Graham, Robert R.; Fulton, Robert S.; Greenberg, Jeffrey D.; Eyre, Steve; Bowes, John; Cui, Jing; Lee, Annette; Pappas, Dimitrios A.; Kremer, Joel M.; Barton, Anne; Coenen, Marieke J. H.; Franke, Barbara; Kiemeney, Lambertus A.; Mariette, Xavier; Richard-Miceli, Corrine; Canhão, Helena; Fonseca, João E.; de Vries, Niek; Tak, Paul P.; Crusius, J. Bart A.; Nurmohamed, Michael T.; Kurreeman, Fina; Mikuls, Ted R.; Okada, Yukinori; Stahl, Eli A.; Larson, David E.; Deluca, Tracie L.; O'Laughlin, Michelle; Fronick, Catrina C.; Fulton, Lucinda L.; Kosoy, Roman; Ransom, Michael; Bhangale, Tushar R.; Ortmann, Ward; Cagan, Andrew; Gainer, Vivian; Karlson, Elizabeth W.; Kohane, Isaac; Murphy, Shawn N.; Martin, Javier; Zhernakova, Alexandra; Klareskog, Lars; Padyukov, Leonid; Worthington, Jane; Mardis, Elaine R.; Seldin, Michael F.; Gregersen, Peter K.; Behrens, Timothy; Raychaudhuri, Soumya; Denny, Joshua C.; Plenge, Robert M.

    2015-01-01

    Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease

  8. Gene Co-expression Analysis to Characterize Genes Related to Marbling Trait in Hanwoo (Korean) Cattle.

    Science.gov (United States)

    Lim, Dajeong; Lee, Seung-Hwan; Kim, Nam-Kuk; Cho, Yong-Min; Chai, Han-Ha; Seong, Hwan-Hoo; Kim, Heebal

    2013-01-01

    Marbling (intramuscular fat) is an important trait that affects meat quality and is a casual factor determining the price of beef in the Korean beef market. It is a complex trait and has many biological pathways related to muscle and fat. There is a need to identify functional modules or genes related to marbling traits and investigate their relationships through a weighted gene co-expression network analysis based on the system level. Therefore, we investigated the co-expression relationships of genes related to the 'marbling score' trait and systemically analyzed the network topology in Hanwoo (Korean cattle). As a result, we determined 3 modules (gene groups) that showed statistically significant results for marbling score. In particular, one module (denoted as red) has a statistically significant result for marbling score (p = 0.008) and intramuscular fat (p = 0.02) and water capacity (p = 0.006). From functional enrichment and relationship analysis of the red module, the pathway hub genes (IL6, CHRNE, RB1, INHBA and NPPA) have a direct interaction relationship and share the biological functions related to fat or muscle, such as adipogenesis or muscle growth. This is the first gene network study with m.logissimus in Hanwoo to observe co-expression patterns in divergent marbling phenotypes. It may provide insights into the functional mechanisms of the marbling trait.

  9. Linguistic Diversity and Traffic Accidents: Lessons from Statistical Studies of Cultural Traits

    Science.gov (United States)

    Roberts, Seán; Winters, James

    2013-01-01

    The recent proliferation of digital databases of cultural and linguistic data, together with new statistical techniques becoming available has lead to a rise in so-called nomothetic studies [1]–[8]. These seek relationships between demographic variables and cultural traits from large, cross-cultural datasets. The insights from these studies are important for understanding how cultural traits evolve. While these studies are fascinating and are good at generating testable hypotheses, they may underestimate the probability of finding spurious correlations between cultural traits. Here we show that this kind of approach can find links between such unlikely cultural traits as traffic accidents, levels of extra-martial sex, political collectivism and linguistic diversity. This suggests that spurious correlations, due to historical descent, geographic diffusion or increased noise-to-signal ratios in large datasets, are much more likely than some studies admit. We suggest some criteria for the evaluation of nomothetic studies and some practical solutions to the problems. Since some of these studies are receiving media attention without a widespread understanding of the complexities of the issue, there is a risk that poorly controlled studies could affect policy. We hope to contribute towards a general skepticism for correlational studies by demonstrating the ease of finding apparently rigorous correlations between cultural traits. Despite this, we see well-controlled nomothetic studies as useful tools for the development of theories. PMID:23967132

  10. Gene Co-expression Analysis to Characterize Genes Related to Marbling Trait in Hanwoo (Korean Cattle

    Directory of Open Access Journals (Sweden)

    Dajeong Lim

    2013-01-01

    Full Text Available Marbling (intramuscular fat is an important trait that affects meat quality and is a casual factor determining the price of beef in the Korean beef market. It is a complex trait and has many biological pathways related to muscle and fat. There is a need to identify functional modules or genes related to marbling traits and investigate their relationships through a weighted gene co-expression network analysis based on the system level. Therefore, we investigated the co-expression relationships of genes related to the ‘marbling score’ trait and systemically analyzed the network topology in Hanwoo (Korean cattle. As a result, we determined 3 modules (gene groups that showed statistically significant results for marbling score. In particular, one module (denoted as red has a statistically significant result for marbling score (p = 0.008 and intramuscular fat (p = 0.02 and water capacity (p = 0.006. From functional enrichment and relationship analysis of the red module, the pathway hub genes (IL6, CHRNE, RB1, INHBA and NPPA have a direct interaction relationship and share the biological functions related to fat or muscle, such as adipogenesis or muscle growth. This is the first gene network study with m.logissimus in Hanwoo to observe co-expression patterns in divergent marbling phenotypes. It may provide insights into the functional mechanisms of the marbling trait.

  11. Linguistic diversity and traffic accidents: lessons from statistical studies of cultural traits.

    Directory of Open Access Journals (Sweden)

    Seán Roberts

    Full Text Available The recent proliferation of digital databases of cultural and linguistic data, together with new statistical techniques becoming available has lead to a rise in so-called nomothetic studies [1]-[8]. These seek relationships between demographic variables and cultural traits from large, cross-cultural datasets. The insights from these studies are important for understanding how cultural traits evolve. While these studies are fascinating and are good at generating testable hypotheses, they may underestimate the probability of finding spurious correlations between cultural traits. Here we show that this kind of approach can find links between such unlikely cultural traits as traffic accidents, levels of extra-martial sex, political collectivism and linguistic diversity. This suggests that spurious correlations, due to historical descent, geographic diffusion or increased noise-to-signal ratios in large datasets, are much more likely than some studies admit. We suggest some criteria for the evaluation of nomothetic studies and some practical solutions to the problems. Since some of these studies are receiving media attention without a widespread understanding of the complexities of the issue, there is a risk that poorly controlled studies could affect policy. We hope to contribute towards a general skepticism for correlational studies by demonstrating the ease of finding apparently rigorous correlations between cultural traits. Despite this, we see well-controlled nomothetic studies as useful tools for the development of theories.

  12. Linguistic diversity and traffic accidents: lessons from statistical studies of cultural traits.

    Science.gov (United States)

    Roberts, Seán; Winters, James

    2013-01-01

    The recent proliferation of digital databases of cultural and linguistic data, together with new statistical techniques becoming available has lead to a rise in so-called nomothetic studies [1]-[8]. These seek relationships between demographic variables and cultural traits from large, cross-cultural datasets. The insights from these studies are important for understanding how cultural traits evolve. While these studies are fascinating and are good at generating testable hypotheses, they may underestimate the probability of finding spurious correlations between cultural traits. Here we show that this kind of approach can find links between such unlikely cultural traits as traffic accidents, levels of extra-martial sex, political collectivism and linguistic diversity. This suggests that spurious correlations, due to historical descent, geographic diffusion or increased noise-to-signal ratios in large datasets, are much more likely than some studies admit. We suggest some criteria for the evaluation of nomothetic studies and some practical solutions to the problems. Since some of these studies are receiving media attention without a widespread understanding of the complexities of the issue, there is a risk that poorly controlled studies could affect policy. We hope to contribute towards a general skepticism for correlational studies by demonstrating the ease of finding apparently rigorous correlations between cultural traits. Despite this, we see well-controlled nomothetic studies as useful tools for the development of theories.

  13. Genome-wide association study of anthropometric traits and evidence of interactions with age and study year in Filipino women.

    Science.gov (United States)

    Croteau-Chonka, Damien C; Marvelle, Amanda F; Lange, Ethan M; Lee, Nanette R; Adair, Linda S; Lange, Leslie A; Mohlke, Karen L

    2011-05-01

    Increased values of multiple adiposity-related anthropometric traits are important risk factors for many common complex diseases. We performed a genome-wide association (GWA) study for four quantitative traits related to body size and adiposity (BMI, weight, waist circumference, and height) in a cohort of 1,792 adult Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). This is the first GWA study of anthropometric traits in Filipinos, a population experiencing a rapid transition into a more obesogenic environment. In addition to identifying suggestive evidence of additional single-nucleotide polymorphism (SNP) association signals (P Filipinos and provide further insight into the effects of BDNF, FTO, and MC4R on BMI.

  14. Unraveling the Quaternary river incision in the Moselle valley (Rhenish Massif, Germany): new insights from cosmogenic nuclide dating (10Be/26Al) of the Main Terrace complex

    Science.gov (United States)

    Rixhon, Gilles; Cordier, Stéphane; Harmand, Dominique; May, Simon Matthias; Kelterbaum, Daniel; Dunai, Tibor; Binnie, Steven; Brückner, Helmut

    2014-05-01

    Throughout the whole river network of the Rhenish Massif, the terrace complex of the so-called Main Terrace forms the morphological transition between a wide upper palaeovalley (plateau valley) and a deeply incised lower valley. The youngest level of this Main Terrace complex (YMT), directly located at the edge of the incised valley, represents a dominant geomorphic feature in the terrace flight; it is often used as a reference level to identify the start of the main middle Pleistocene incision episode (Demoulin & Hallot, 2009). The latter probably reflects the major tectonic pulse that affected the whole Massif and was related to an acceleration of the uplift rates (Demoulin & Hallot, 2009). The Main terraces are particularly well preserved in the lower Moselle valley and are characterized by a constant absolute elevation of their base along a 150 km-long reach. Despite that various hypotheses have been proposed to explain this horizontality (updoming, faulting...), all studies assumed an age of ca. 800 ka for the YMT, mainly based on the questionable extrapolation of palaeomagnetic data obtained in the Rhine valley. Therefore, a reliable chronological framework is still required to unravel the spatio-temporal characteristics of the Pleistocene evolution of the Moselle valley. In this study, we apply cosmogenic nuclide dating (10Be/26Al) to fluvial sediments pertaining to the Main Terrace complex or to the upper Middle Terraces. Several sites along the lower Moselle were sampled following two distinct sampling strategies: (i) depth profiles where the original terrace (palaeo-)surface is well preserved and did not experience much postdepositional burial (e.g., loess cover); and (ii) the isochron technique where the sediment thickness exceeds 3 m. Cosmogenic nuclide ages recently obtained for three rivers in the Meuse catchment in the western Rhenish Massif demonstrated that the Main Terraces were younger than expected and their abandonment was diachronic along the

  15. Genetic Characterization of Dog Personality Traits.

    Science.gov (United States)

    Ilska, Joanna; Haskell, Marie J; Blott, Sarah C; Sánchez-Molano, Enrique; Polgar, Zita; Lofgren, Sarah E; Clements, Dylan N; Wiener, Pamela

    2017-06-01

    The genetic architecture of behavioral traits in dogs is of great interest to owners, breeders, and professionals involved in animal welfare, as well as to scientists studying the genetics of animal (including human) behavior. The genetic component of dog behavior is supported by between-breed differences and some evidence of within-breed variation. However, it is a challenge to gather sufficiently large datasets to dissect the genetic basis of complex traits such as behavior, which are both time-consuming and logistically difficult to measure, and known to be influenced by nongenetic factors. In this study, we exploited the knowledge that owners have of their dogs to generate a large dataset of personality traits in Labrador Retrievers. While accounting for key environmental factors, we demonstrate that genetic variance can be detected for dog personality traits assessed using questionnaire data. We identified substantial genetic variance for several traits, including fetching tendency and fear of loud noises, while other traits revealed negligibly small heritabilities. Genetic correlations were also estimated between traits; however, due to fairly large SEs, only a handful of trait pairs yielded statistically significant estimates. Genomic analyses indicated that these traits are mainly polygenic, such that individual genomic regions have small effects, and suggested chromosomal associations for six of the traits. The polygenic nature of these traits is consistent with previous behavioral genetics studies in other species, for example in mouse, and confirms that large datasets are required to quantify the genetic variance and to identify the individual genes that influence behavioral traits. Copyright © 2017 by the Genetics Society of America.

  16. Whole Trait Theory

    Science.gov (United States)

    Fleeson, William; Jayawickreme, Eranda

    2014-01-01

    Personality researchers should modify models of traits to include mechanisms of differential reaction to situations. Whole Trait Theory does so via five main points. First, the descriptive side of traits should be conceptualized as density distributions of states. Second, it is important to provide an explanatory account of the Big 5 traits. Third, adding an explanatory account to the Big 5 creates two parts to traits, an explanatory part and a descriptive part, and these two parts should be recognized as separate entities that are joined into whole traits. Fourth, Whole Trait Theory proposes that the explanatory side of traits consists of social-cognitive mechanisms. Fifth, social-cognitive mechanisms that produce Big-5 states should be identified. PMID:26097268

  17. Major-histocompatibility-complex-associated variation in secondary sexual traits of white-tailed deer (Odocoileus virginianus): evidence for good-genes advertisement.

    Science.gov (United States)

    Ditchkoff, S S; Lochmiller, R L; Masters, R E; Hoofer, S R; Van Den Bussche, R A

    2001-03-01

    Good-genes hypotheses predict that development of secondary sexual characters can be an honest advertisement of heritable male quality. We explored this hypothesis using a cervid model (adult, male white-tailed deer, Odocoileus virginianus) to determine whether antler development could provide an honest signal of a male's genetic quality and condition to adversaries. We compared antler, morphometric, hormonal, and parasitic data collected from hunter-harvested deer to characteristics of the Mhc-DRB (Odvi), the most widely studied gene of the major histocompatibility complex (MHC) in Artiodactyla. We detected associations between genetic characteristics at Odvi-DRB and antler development and body mass, suggesting that antler development and body mass may be associated with pathogen resistance in deer and thus may be an honest signal of genetic quality. We also detected associations between Odvi-DRB characteristics and serum testosterone during the breeding season, suggesting that certain MHC characteristics may help deer cope with stresses related to breeding activity. In addition, we observed a negative relationship between degree of antler development and overall abundance of abomasal helminths. Our observations provide support for the hypothesis that antler development in white-tailed deer is an honest signal of quality.

  18. Traits traded off

    NARCIS (Netherlands)

    Rueffler, Claus

    2006-01-01

    The course of evolution is restricted by constraints. A special type of constraint is a trade-off where different traits are negatively correlated. In this situation a mutant type that shows an improvement in one trait suffers from a decreased performance through another trait. In a fixed fitness

  19. Methods for meta-analysis of multiple traits using GWAS summary statistics.

    Science.gov (United States)

    Ray, Debashree; Boehnke, Michael

    2018-03-01

    Genome-wide association studies (GWAS) for complex diseases have focused primarily on single-trait analyses for disease status and disease-related quantitative traits. For example, GWAS on risk factors for coronary artery disease analyze genetic associations of plasma lipids such as total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides (TGs) separately. However, traits are often correlated and a joint analysis may yield increased statistical power for association over multiple univariate analyses. Recently several multivariate methods have been proposed that require individual-level data. Here, we develop metaUSAT (where USAT is unified score-based association test), a novel unified association test of a single genetic variant with multiple traits that uses only summary statistics from existing GWAS. Although the existing methods either perform well when most correlated traits are affected by the genetic variant in the same direction or are powerful when only a few of the correlated traits are associated, metaUSAT is designed to be robust to the association structure of correlated traits. metaUSAT does not require individual-level data and can test genetic associations of categorical and/or continuous traits. One can also use metaUSAT to analyze a single trait over multiple studies, appropriately accounting for overlapping samples, if any. metaUSAT provides an approximate asymptotic P-value for association and is computationally efficient for implementation at a genome-wide level. Simulation experiments show that metaUSAT maintains proper type-I error at low error levels. It has similar and sometimes greater power to detect association across a wide array of scenarios compared to existing methods, which are usually powerful for some specific association scenarios only. When applied to plasma lipids summary data from the METSIM and the T2D-GENES studies, metaUSAT detected genome-wide significant loci beyond the ones identified by univariate analyses

  20. Physiology insights

    DEFF Research Database (Denmark)

    Watanabe, Richard M; Hansen, Torben

    2016-01-01

    In recent years, the search for genetic determinants of type 2 diabetes has resulted in identification of numerous type 2 diabetes-associated loci as well as a number of loci associating with related prediabetic traits. These findings have illuminated new biological pathways contributing to the p......In recent years, the search for genetic determinants of type 2 diabetes has resulted in identification of numerous type 2 diabetes-associated loci as well as a number of loci associating with related prediabetic traits. These findings have illuminated new biological pathways contributing...... insulin levels. Combined, these loci only account for a fraction of the observed familial clustering of type 2 diabetes and only up to about 10 % of the variation in prediabetic quantitative traits. Improved methods are needed to dig deeper into a biological understanding of the pathophysiology of type 2...

  1. An extensive microarray analysis of AAL-toxin-induced cell death in Arabidopsis thaliana brings new insights into the complexity of programmed cell death in plants

    NARCIS (Netherlands)

    Gechev, T.S.; Gadjev, I.Z.; Hille, J.

    2004-01-01

    A T-DNA knockout of the Arabidopsis homologue of the tomato disease resistance gene Asc was obtained. The asc gene renders plants sensitive to programmed cell death (PCD) triggered by the fungal AAL toxin. To obtain more insights into the nature of AAL-toxin-induced cell death and to identify genes

  2. Role of DNA conformation & energetic insights in Msx-1-DNA recognition as revealed by molecular dynamics studies on specific and nonspecific complexes.

    Science.gov (United States)

    Kachhap, Sangita; Singh, Balvinder

    2015-01-01

    In most of homeodomain-DNA complexes, glutamine or lysine is present at 50th position and interacts with 5th and 6th nucleotide of core recognition region. Molecular dynamics simulations of Msx-1-DNA complex (Q50-TG) and its variant complexes, that is specific (Q50K-CC), nonspecific (Q50-CC) having mutation in DNA and (Q50K-TG) in protein, have been carried out. Analysis of protein-DNA interactions and structure of DNA in specific and nonspecific complexes show that amino acid residues use sequence-dependent shape of DNA to interact. The binding free energies of all four complexes were analysed to define role of amino acid residue at 50th position in terms of binding strength considering the variation in DNA on stability of protein-DNA complexes. The order of stability of protein-DNA complexes shows that specific complexes are more stable than nonspecific ones. Decomposition analysis shows that N-terminal amino acid residues have been found to contribute maximally in binding free energy of protein-DNA complexes. Among specific protein-DNA complexes, K50 contributes more as compared to Q50 towards binding free energy in respective complexes. The sequence dependence of local conformation of DNA enables Q50/Q50K to make hydrogen bond with nucleotide(s) of DNA. The changes in amino acid sequence of protein are accommodated and stabilized around TAAT core region of DNA having variation in nucleotides.

  3. Insights into the catalytic activity of [Pd(NHC)(cin)Cl] (NHC = IPr, IPrCl, IPrBr) complexes in the Suzuki-Miyaura reaction

    KAUST Repository

    Nolan, Steven Patrick; Izquierdo, Frederic; Zinser, Caroline; Minenkov, Yury; Cordes, David; Slawin, Alexandra; Cavallo, Luigi; Nahra, Fady; Cazin, Catherine

    2017-01-01

    The influence of C4,5-halogenation on palladium N-heterocyclic carbene complexes and their activity in the Suzuki-Miyaura reaction have been investigated. Two [Pd(NHC)(cin)Cl] complexes bearing IPrCl and IPrBr ligands were synthesized. After

  4. Integrative Systems Biology: Elucidating Complex Traits

    DEFF Research Database (Denmark)

    Pers, Tune Hannes

    . In section ., I outline results from our bioinformaticsbased analysis of the FTO locus. Genetic variation within the FTO locus provides the hitherto strongest association between common SNPs and obesity, but the mechanisms leading to this association are still unknown. In Paper III, we demonstrate...

  5. Association of candidate genes with drought tolerance traits in diverse perennial ryegrass accessions

    Science.gov (United States)

    Xiaoqing Yu; Guihua Bai; Shuwei Liu; Na Luo; Ying Wang; Douglas S. Richmond; Paula M. Pijut; Scott A. Jackson; Jianming Yu; Yiwei. Jiang

    2013-01-01

    Drought is a major environmental stress limiting growth of perennial grasses in temperate regions. Plant drought tolerance is a complex trait that is controlled by multiple genes. Candidate gene association mapping provides a powerful tool for dissection of complex traits. Candidate gene association mapping of drought tolerance traits was conducted in 192 diverse...

  6. New insights into the coordination chemistry of Schiff bases derived from amino acids: Planar [Ni4] complexes with tyrosine side-chains

    Science.gov (United States)

    Muche, Simon; Hołyńska, Małgorzata

    2017-08-01

    Structure and properties of a rare metal complex of the chiral Schiff base ligand derived from ortho-vanillin and L-tyrosine are presented. This study is a continuation of research on ligands containing biologically compatible moieties. The ligand is also fully characterized in form of a sodium salt, in particular in solution, for the first time. The metal complex contains a unique bowl-shaped [Ni4] core. Its structure is investigated both in solution (ESI-MS, NMR) and in solid state (X-ray diffraction studies). Under certain conditions the complex can be isolated as crystalline DMF solvate which is studied in solid state.

  7. Crustal-Scale Fault Interaction at Rifted Margins and the Formation of Domain-Bounding Breakaway Complexes: Insights From Offshore Norway

    Science.gov (United States)

    Osmundsen, P. T.; Péron-Pinvidic, G.

    2018-03-01

    The large-magnitude faults that control crustal thinning and excision at rifted margins combine into laterally persistent structural boundaries that separate margin domains of contrasting morphology and structure. We term them breakaway complexes. At the Mid-Norwegian margin, we identify five principal breakaway complexes that separate the proximal, necking, distal, and outer margin domains. Downdip and lateral interactions between the faults that constitute breakaway complexes became fundamental to the evolution of the 3-D margin architecture. Different types of fault interaction are observed along and between these faults, but simple models for fault growth will not fully describe their evolution. These structures operate on the crustal scale, cut large thicknesses of heterogeneously layered lithosphere, and facilitate fundamental margin processes such as deformation coupling and exhumation. Variations in large-magnitude fault geometry, erosional footwall incision, and subsequent differential subsidence along the main breakaway complexes likely record the variable efficiency of these processes.

  8. the relationship between insight and psychosis in state patients with ...

    African Journals Online (AJOL)

    understanding of problems and personality traits as applied to the self, but also an ... between insight scores and the severity of the mental disorder were measured. ..... namely psychopathology (for instance paranoia, hostility, perplexity and ...

  9. Mononuclear late first row transition metal complexes of ONO donor hydrazone ligand: Synthesis, characterization, crystallographic insight, in vivo and in vitro anti-inflammatory activity

    Science.gov (United States)

    Kendur, Umashri; Chimmalagi, Geeta H.; Patil, Sunil M.; Gudasi, Kalagouda B.; Frampton, Christopher S.; Mangannavar, Chandrashekhar V.; Muchchandi, Iranna S.

    2018-02-01

    Air and moisture stable coordination compounds of late first row transition metal ions, viz., Co(II), Ni(II), Cu(II) and Zn(II) with a newly designed ligand, (E)-2-amino-N'-(1-(2-hydroxy-6-methyl-4-oxo-4H-pyran-3-yl)ethylidene)benzohydrazide (H2L) were prepared and extensively characterized using various spectro-analytical techniques. The ligand acts both in mono as well as doubly deprotonated manner. The ligand to metal stoichiometry was found to be 1:2 in case of complexes using chloride salts, whereas 1:1 in case of copper (II) complex using its acetate salt. The molecular structures of H2L, nickel and copper complexes were unambiguously determined by single-crystal X-ray diffraction studies reveal that H2L exists in a zwitterionic form while copper complex has copper centre in a distorted square planar environment. On the other hand, cobalt, nickel and zinc complexes display distorted octahedral coordination around the metal ion. In case of [Ni(HL)2].H2O, intramolecular Csbnd H⋯π stacking interaction were observed between the centroid of five membered chelate ring and phenyl proton C5sbnd H5 and intermolecular Csbnd H⋯π stacking interaction between the centroid of phenyl ring, dehydroacetic acid (DHA) ring and phenyl protons. The [Cu(L)DMF] complex is stabilized by intramolecular hydrogen bonding N1H⋯N2 and by intermolecular hydrogen bonding N1H⋯O4. Intermolecular interactions were investigated by Hirshfeld surfaces. Further, H2L and its metal complexes were screened for their in vivo and in vitro anti-inflammatory activities. The activity of the ligand has enhanced on coordination with transition metals. The tested compounds have shown excellent activity, which is almost equipotent to the standard used in the study.

  10. Cuticular Compounds Bring New Insight in the Post-Glacial Recolonization of a Pyrenean Area: Deutonura deficiens Deharveng, 1979 Complex, a Case Study

    Science.gov (United States)

    Porco, David; Bedos, Anne; Deharveng, Louis

    2010-01-01

    Background In most Arthropod groups, the study of systematics and evolution rely mostly on neutral characters, in this context cuticular compounds, as non-neutral characters, represent an underexplored but potentially informative type of characters at the infraspecific level as they have been routinely proven to be involved in sexual attraction. Methods and Findings The collembolan species complex Deutonura deficiens was chosen as a model in order to test the utility of these characters for delineating four infraspecific entities of this group. Specimens were collected for three subspecies (D. d. deficiens, D. d. meridionalis, D. d. sylvatica) and two morphotypes (D. d. sylvatica morphoype A and B) of the complex; an additional species D. monticola was added. Cuticular compounds were extracted and separated by gas chromatography for each individual. Our results demonstrate that cuticular compounds succeeded in separating the different elements of this complex. Those data allowed also the reconstruction of the phylogenetic relationships among them. Conclusions The discriminating power of cuticular compounds is directly related to their involvement in sexual attraction and mate recognition. These findings allowed a discussion on the potential involvement of intrinsic and paleoclimatic factors in the origin and the diversification of this complex in the Pyrenean zone. This character type brings the first advance from pattern to process concerning the origin of this species complex. PMID:21209797

  11. Fundamental insights into conformational stability and orbital interactions of antioxidant (+)-catechin species and complexation of (+)-catechin with zinc(II) and oxovanadium(IV)

    Science.gov (United States)

    Yasarawan, Nuttawisit; Thipyapong, Khajadpai; Sirichai, Somsak; Ruangpornvisuti, Vithaya

    2013-09-01

    Conformational stability of (+)-catechin species in water has been examined with density functional theory, associated with the polarizable continuum model (PCM) of solvation. Factors such as electron delocalization, lone-pair electron donation and intramolecular hydrogen bonding substantially contribute to the conformational stabilization. Upon deprotonation, the HOMO and LUMO energies for (+)-catechin are both elevated; the energy gaps for the deprotonated species are narrower than the energy gap for the neutral species. The preferential deprotonation occurs at the C3'-, C5-, C7- and C4'-OH groups successively. The pKa value at 9.3 predicted for the most acidic OH group agrees well with previous experimental data; however the values are overestimated for the less acidic OH groups due to limitations of the PCM for charged solutes and/or complex nature of true deprotonation pathways. Formation of hydrogen radicals should be promoted at high pH values following the bond dissociation enthalpies. Complexation of (+)-catechin with either zinc(II) or oxovanadium(IV) is favored at the 1:1 metal-to-ligand (M:L) mole ratio, with the oxovanadium(IV) complex showing higher reaction preference. At M:L = 1:2, formation of two isomeric complexes are plausible for each type of metal ion. Effects of stoichiometry and isomerism on the computational spectral features of the possibly formed metal complexes have been described.

  12. Cuticular compounds bring new insight in the post-glacial recolonization of a Pyrenean area: Deutonura deficiens Deharveng, 1979 complex, a case study.

    Science.gov (United States)

    Porco, David; Bedos, Anne; Deharveng, Louis

    2010-12-21

    In most Arthropod groups, the study of systematics and evolution rely mostly on neutral characters, in this context cuticular compounds, as non-neutral characters, represent an underexplored but potentially informative type of characters at the infraspecific level as they have been routinely proven to be involved in sexual attraction. The collembolan species complex Deutonura deficiens was chosen as a model in order to test the utility of these characters for delineating four infraspecific entities of this group. Specimens were collected for three subspecies (D. d. deficiens, D. d. meridionalis, D. d. sylvatica) and two morphotypes (D. d. sylvatica morphoype A and B) of the complex; an additional species D. monticola was added. Cuticular compounds were extracted and separated by gas chromatography for each individual. Our results demonstrate that cuticular compounds succeeded in separating the different elements of this complex. Those data allowed also the reconstruction of the phylogenetic relationships among them. The discriminating power of cuticular compounds is directly related to their involvement in sexual attraction and mate recognition. These findings allowed a discussion on the potential involvement of intrinsic and paleoclimatic factors in the origin and the diversification of this complex in the Pyrenean zone. This character type brings the first advance from pattern to process concerning the origin of this species complex.

  13. An insight into the complexation of trivalent americium vis-a-vis lanthanides with bis(1,2,4-triazinyl)bipyridine derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharyya, Arunasis; Mohapatra, Manoj; Mohapatra, Prasanta K. [Bhabha Atomic Research Centre, Trombay, Mumbai (India). Radiochemistry Div.; Gadly, Trilochan; Ghosh, Sunil K. [Bhabha Atomic Research Centre, Trombay, Mumbai (India). Bioorganic Div.; Manna, Debashree; Ghanty, Tapan K. [Bhabha Atomic Research Centre, Trombay, Mumbai (India). Theoretical Chemistry Section; Rawat, Neetika; Tomar, Bhupendra S. [Bhabha Atomic Research Centre, Trombay, Mumbai (India). Radioanalytical Chemistry Div.

    2017-01-26

    Complexation of Am{sup 3+} and Ln{sup 3+} (La{sup 3+}, Eu{sup 3+}, and Er{sup 3+}) with two bis(1,2,4-triazinyl)bipyridine (C{sub 2}BTBP, C{sub 5}BTBP) derivatives has been studied in acetonitrile medium with use of various experimental techniques such as electrospray ionization mass spectrometry (ESI-MS), time-resolved fluorescence spectroscopy (TRFS), UV/Vis spectrophotometry, and solution calorimetry. Metal-ligand stoichiometries and conditional stability constants of these complexes were determined. To the best of our knowledge, this is the first report on the complexation of Am{sup 3+} with any of the BTBP derivatives with use of UV/Vis spectrophotometric titration to determine the conditional stability constants. Density functional theory (DFT) calculations are carried out on the An{sup 3+} (U{sup 3+} and Am{sup 3+}) and Ln{sup 3+} (La{sup 3+}, Nd{sup 3+}, Eu{sup 3+}, Er{sup 3+}, and Lu{sup 3+}) complexes of BTBP in order to understand the difference between the bonding in actinide and lanthanide complexes. The results indicate a stronger covalent interaction in the An-N bonds as compared to the Ln-N bonds, which leads to an actinide selectivity of this class of ligands. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  14. Insights on the identities of sharks of the Rhizoprionodon acutus (Elasmobranchii: Carcharhiniformes) species complex based on three new species of Phoreiobothrium (Cestoda: Onchoproteocephalidea).

    Science.gov (United States)

    Caira, J N; Jensen, K

    2015-12-22

    Recent molecular work on milk sharks (Rhizoprionodon acutus [Rüppell]) suggests that, rather than a single widely distributed species, R. acutus represents a complex of four narrowly distributed cryptic species. Examination of the cestodes in three of the four members of that complex globally led to the discovery and description of three new species in the onchoproteocephalidean genus Phoreiobothrium Linton, 1889. The host associations and geographic distributions of the new species are fully congruent with the geographic distributions and species boundaries inferred for the sharks from molecular data: Phoreiobothrium jahki n. sp. parasitizes Rhizoprionodon cf. acutus 3 off Borneo, P. nadiae n. sp. parasitizes R. cf. acutus 1 off Senegal, and P. swaki n. sp. parasitizes R. cf. acutus 2 off northern Australia. The new cestodes differ from one another and from their 11 valid congeners in morphological features such as sublocular configuration and number, hook size, and testis number. Given the notoriously oioxenous nature of elasmobranch-hosted onchoproteocephalidean cestodes, these results provide further support for recognition of the milk shark species complex. This work also raises questions about the Phoreiobothrium species reported in cursory descriptions from India; further examination of these cestodes is key because they are potentially hosted by the fourth member of the R. acutus complex. To encourage future taxonomic work on the morphology of sharks in this complex, comparative photographs of representatives of the four potential host species are provided.

  15. QTL analyses on genotype-specific component traits in a crop simulation model for capsicum annuum L.

    NARCIS (Netherlands)

    Wubs, A.M.; Heuvelink, E.; Dieleman, J.A.; Magan, J.J.; Palloix, A.; Eeuwijk, van F.A.

    2012-01-01

    Abstract: QTL for a complex trait like yield tend to be unstable across environments and show QTL by environment interaction. Direct improvement of complex traits by selecting on QTL is therefore difficult. For improvement of complex traits, crop growth models can be useful, as such models can

  16. Insights into the catalytic activity of [Pd(NHC)(cin)Cl] (NHC = IPr, IPrCl, IPrBr) complexes in the Suzuki-Miyaura reaction

    KAUST Repository

    Nolan, Steven Patrick

    2017-09-06

    The influence of C4,5-halogenation on palladium N-heterocyclic carbene complexes and their activity in the Suzuki-Miyaura reaction have been investigated. Two [Pd(NHC)(cin)Cl] complexes bearing IPrCl and IPrBr ligands were synthesized. After determining electronic and steric properties of these ligands, their properties were compared to those of [Pd(IPr)(cin)Cl]. The three palladium complexes were studied using DFT calculations to delineate their behaviour in the activation step leading to the putative 12-electron active catalyst. Experimentally, their catalytic activity in the Suzuki-Miyaura reaction involving a wide range of coupling partners (30 entries) at low catalyst loading was studied.

  17. The Ru-NO bonding in nitrosyl-[poly(1-pyrazolyl)borate]ruthenium complexes: a theoretical insight based on EDA

    Energy Technology Data Exchange (ETDEWEB)

    Caramori, Giovanni F.; Kunitz, Andre G.; Coimbra, Daniel F.; Garcia, Leone C.; Fonseca, David E.P., E-mail: giovanni.caramori@ufsc.br [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Centro de Ciencias Fisicas e Matematicas. Dept. de Quimica

    2013-09-15

    The lability of NO{sup +} group in [TpRuCl{sub 2}(NO)]{sup q} (Tp = BL(pyrazol-1-yl){sub 3}) complexes was evaluated at the light of energy decomposition analysis (Su-Li EDA). The electronic effects of different pseudoaxial substituents (L = H, pyrazolyl anion, pyrazole, isoxazole and isothiazole) on the nature of Ru-NO bonding were evaluated considering complexes in ground (GS) and in metastable (MS1 and MS2) states. (Ru-NO){sup 6} bond nature in [TpRuCl{sub 2}(NO)]{sup q} (Tp = BL(pyrazol-1-yl){sub 3}) complexes is in essence covalent, but with a still significant electrostatic character. The nature of pseudoaxial substituents has a direct effect on the magnitude of (Ru-NO){sup 6} bonds. (author)

  18. Structure-guided approach identifies a novel class of HIV-1 ribonuclease H inhibitors: binding mode insights through magnesium complexation and site-directed mutagenesis studies

    DEFF Research Database (Denmark)

    Poongavanam, Vasanthanathan; Corona, Angela; Steinmann, Casper

    2018-01-01

    is a long and expensive process that can be speeded up by in silico methods. In the present study, a structure-guided screening is coupled with a similarity-based search on the Specs database to identify a new class of HIV-1 RNase H inhibitors. Out of the 45 compounds selected for experimental testing, 15...... inhibited the RNase H function below 100 μM with three hits exhibiting IC50 values active compound, AA, inhibits HIV-1 RNase H with an IC50 of 5.1 μM and exhibits a Mg-independent mode of inhibition. Site-directed mutagenesis studies provide valuable insight into the binding mode of newly...

  19. Africa Insight

    African Journals Online (AJOL)

    Africa Insight is a quarterly, peer-reviewed journal of the Africa Institute of South Africa. It is accredited by the South African National Department of Higher Education and Training (DHET) and is indexed in the International Bibliography of Social Science (IBSS). It is a multi-disciplinary journal primarily focusing on African ...

  20. Evolution in Australia's mesic biome under past and future climates: Insights from a phylogenetic study of the Australian Rock Orchids (Dendrobium speciosum complex, Orchidaceae).

    Science.gov (United States)

    Simpson, Lalita; Clements, Mark A; Crayn, Darren M; Nargar, Katharina

    2018-01-01

    The Australian mesic biome spans c. 33° of latitude along Australia's east coast and ranges and is dissected by historical and contemporary biogeographical barriers. To investigate the impact of these barriers on evolutionary diversification and to predict the impact of future climate change on the distribution of species and genetic diversity within this biome, we inferred phylogenetic relationships within the Dendrobium speciosum complex (Orchidaceae) across its distribution and undertook environmental niche modelling (ENM) under past, contemporary and projected future climates. Neighbor Joining tree inference, NeighborNet and Structure analyses of Amplified Fragment Length Polymorphism (AFLP) profiles for D. speciosum sampled from across its distribution showed that the complex consists of two highly supported main groups that are geographically separated by the St. Lawrence gap, an area of dry sclerophyll forest and woodland. The presence of several highly admixed individuals identified by the Structure analysis provided evidence of genetic exchange between the two groups across this gap. Whereas previous treatments have recognised between one to eleven species, the molecular results support the taxonomic treatment of the complex as a single species with two subspecies. The ENM analysis supported the hypothesis that lineage divergence within the complex was driven by past climatic changes. The St. Lawrence gap represented a stronger biogeographic barrier for the D. speciosum complex during the cool and dry glacial climatic conditions of the Pleistocene than under today's interglacial conditions. Shallow genetic divergence was found within the two lineages, which mainly corresponded to three other biogeographic barriers: the Black Mountain Corridor, Glass House Mountains and the Hunter Valley. Our ENM analyses provide further support for the hypothesis that biogeographic barriers along Australia's east coast were somewhat permeable to genetic exchange due to

  1. Environmental sensitivity in dairy cattle with focus on fertility traits

    DEFF Research Database (Denmark)

    Ismael, Ahmed; Løvendahl, Peter; Strandberg, Erling

    2012-01-01

    Dairy cattle differ in production, fertility, health, and other important traits in the different environment as both the phenopypic and genetic level (Winding et la., 2005 and Calus et al., 2005). Fertility of Nordic dairy cattle breeds (Holstein, Red, Jersey) is a complex trait and the heritabi...

  2. Structural styles and zircon ages of the South Tianshan accretionary complex, Atbashi Ridge, Kyrgyzstan: Insights for the anatomy of ocean plate stratigraphy and accretionary processes

    Science.gov (United States)

    Sang, Miao; Xiao, Wenjiao; Orozbaev, Rustam; Bakirov, Apas; Sakiev, Kadyrbek; Pak, Nikolay; Ivleva, Elena; Zhou, Kefa; Ao, Songjian; Qiao, Qingqing; Zhang, Zhixin

    2018-03-01

    The anatomy of an ancient accretionary complex has a significance for a better understanding of the tectonic processes of accretionary orogens and complex because of its complicated compositions and strong deformation. With a thorough structural and geochronological study of a fossil accretionary complex in the Atbashi Ridge, South Tianshan (Kyrgyzstan), we analyze the structure and architecture of ocean plate stratigraphy in the western Central Asian Orogenic Belt. The architecture of the Atbashi accretionary complex is subdivisible into four lithotectonic assemblages, some of which are mélanges with "block-in-matrix" structure: (1) North Ophiolitic Mélange; (2) High-pressure (HP)/Ultra-high-pressure (UHP) Metamorphic Assemblage; (3) Coherent & Mélange Assemblage; and (4) South Ophiolitic Mélange. Relationships between main units are tectonic contacts presented by faults. The major structures and lithostratigraphy of these units are thrust-fold nappes, thrusted duplexes, and imbricated ocean plate stratigraphy. All these rock units are complicatedly stacked in 3-D with the HP/UHP rocks being obliquely southwestward extruded. Detrital zircon ages of meta-sediments provide robust constraints on their provenance from the Ili-Central Tianshan Arc. The isotopic ages of the youngest components of the four units are Late Permian, Early-Middle Triassic, Early Carboniferous, and Early Triassic, respectively. We present a new tectonic model of the South Tianshan; a general northward subduction polarity led to final closure of the South Tianshan Ocean in the End-Permian to Late Triassic. These results help to resolve the long-standing controversy regarding the subduction polarity and the timing of the final closure of the South Tianshan Ocean. Finally, our work sheds lights on the use of ocean plate stratigraphy in the analysis of the tectonic evolution of accretionary orogens.

  3. Insight to the interaction of the dihydrolipoamide acetyltransferase (E2) core with the peripheral components in the Escherichia coli pyruvate dehydrogenase complex via multifaceted structural approaches.

    Science.gov (United States)

    Chandrasekhar, Krishnamoorthy; Wang, Junjie; Arjunan, Palaniappa; Sax, Martin; Park, Yun-Hee; Nemeria, Natalia S; Kumaran, Sowmini; Song, Jaeyoung; Jordan, Frank; Furey, William

    2013-05-24

    Multifaceted structural approaches were undertaken to investigate interaction of the E2 component with E3 and E1 components from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), as a representative of the PDHc from Gram-negative bacteria. The crystal structure of E3 at 2.5 Å resolution reveals similarity to other E3 structures and was an important starting point for understanding interaction surfaces between E3 and E2. Biochemical studies revealed that R129E-E2 and R150E-E2 substitutions in the peripheral subunit-binding domain (PSBD) of E2 greatly diminished PDHc activity, affected interactions with E3 and E1 components, and affected reductive acetylation of E2. Because crystal structures are unavailable for any complete E2-containing complexes, peptide-specific hydrogen/deuterium exchange mass spectrometry was used to identify loci of interactions between 3-lipoyl E2 and E3. Two peptides from the PSBD, including Arg-129, and three peptides from E3 displayed statistically significant reductions in deuterium uptake resulting from interaction between E3 and E2. Of the peptides identified on E3, two were from the catalytic site, and the third was from the interface domain, which for all known E3 structures is believed to interact with the PSBD. NMR clearly demonstrates that there is no change in the lipoyl domain structure on complexation with E3. This is the first instance where the entire wild-type E2 component was employed to understand interactions with E3. A model for PSBD-E3 binding was independently constructed and found to be consistent with the importance of Arg-129, as well as revealing other electrostatic interactions likely stabilizing this complex.

  4. Insight to the Interaction of the Dihydrolipoamide Acetyltransferase (E2) Core with the Peripheral Components in the Escherichia coli Pyruvate Dehydrogenase Complex via Multifaceted Structural Approaches*

    Science.gov (United States)

    Chandrasekhar, Krishnamoorthy; Wang, Junjie; Arjunan, Palaniappa; Sax, Martin; Park, Yun-Hee; Nemeria, Natalia S.; Kumaran, Sowmini; Song, Jaeyoung; Jordan, Frank; Furey, William

    2013-01-01

    Multifaceted structural approaches were undertaken to investigate interaction of the E2 component with E3 and E1 components from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), as a representative of the PDHc from Gram-negative bacteria. The crystal structure of E3 at 2.5 Å resolution reveals similarity to other E3 structures and was an important starting point for understanding interaction surfaces between E3 and E2. Biochemical studies revealed that R129E-E2 and R150E-E2 substitutions in the peripheral subunit-binding domain (PSBD) of E2 greatly diminished PDHc activity, affected interactions with E3 and E1 components, and affected reductive acetylation of E2. Because crystal structures are unavailable for any complete E2-containing complexes, peptide-specific hydrogen/deuterium exchange mass spectrometry was used to identify loci of interactions between 3-lipoyl E2 and E3. Two peptides from the PSBD, including Arg-129, and three peptides from E3 displayed statistically significant reductions in deuterium uptake resulting from interaction between E3 and E2. Of the peptides identified on E3, two were from the catalytic site, and the third was from the interface domain, which for all known E3 structures is believed to interact with the PSBD. NMR clearly demonstrates that there is no change in the lipoyl domain structure on complexation with E3. This is the first instance where the entire wild-type E2 component was employed to understand interactions with E3. A model for PSBD-E3 binding was independently constructed and found to be consistent with the importance of Arg-129, as well as revealing other electrostatic interactions likely stabilizing this complex. PMID:23580650

  5. A Genetic Epidemiological Study of Behavioral Traits

    NARCIS (Netherlands)

    N. Amin (Najaf)

    2011-01-01

    textabstractHuman behavioural genetics aims to unravel the genetic and environmental contributions to variations in human behaviour. Behaviour is a complex trait, involving multiple genes that are affected by a variety of other factors. Genetic epidemiological research of behaviour goes back to

  6. The politics of insight

    OpenAIRE

    Salvi, Carola; Cristofori, Irene; Grafman, Jordan; Beeman, Mark

    2016-01-01

    Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insig...

  7. Developing Leadership Traits.

    Science.gov (United States)

    Hall, Susan King

    1980-01-01

    Defines six leadership traits that are necessary to and fostered by editing a college newspaper: delegating authority, developing subordinates, motivating others, being approachable, commanding respect, and bringing out optimum performances in others. (TJ)

  8. Characterising the continental crust factory: new insights into the roots of an island arc from Hf isotopes in rutile (Kohistan complex, Pakistan)

    Science.gov (United States)

    Ewing, Tanya; Müntener, Othmar; Schaltegger, Urs

    2017-04-01

    Island arcs are one of the primary sites of generation of new continental crust. As such, a question of fundamental importance to models of continental growth is to what extent island arc magmas are strictly juvenile melts derived directly from the mantle, versus potentially incorporating a significant recycled continental component, for example from subducted sediment. The Kohistan complex (northeastern Pakistan) preserves a remarkably complete ˜50 km thick cross-section through an exhumed Jurassic-Cretaceous island arc. It affords a rare opportunity to study the evolution of island arc magmatism from subduction initiation, through intra-oceanic subduction, to arc-continent collision. In this study, we investigate the ultramafic-mafic Jijal Complex, which preserves part of the plutonic roots of the Kohistan complex formed over ˜20 Ma of intra-oceanic subduction. The Jijal Complex is volumetrically dominated by ultramafic rocks and garnet-bearing gabbros whose petrogenesis is controversial. Garnet formation has variously been attributed a prograde metamorphic origin1, a magmatic origin recording crystallisation at high pressures2,3, or a restitic origin following partial melting4. We have characterised the source of the Jijal Complex using in situ LA-MC-ICPMS determination of the Hf isotope composition of rutile from garnet gabbros, which are zircon-free. This work exploits the superior sensitivity of the Neptune Plus, coupled with an improved analytical protocol, to improve precision of this novel technique and permit in situ analysis of rutile with only ˜10-30 ppm Hf. Rutile occurs included in early-formed minerals such as clinopyroxene and garnet, indicating crystallisation at high pressures and temperatures. Rutile from all samples, collected across ˜3 km of former crustal depth, has indistinguishable Hf isotope compositions close to depleted mantle values. Integrating the new Hf isotope data for rutile with previously published whole rock Nd-Sr isotope

  9. Structural and dynamical insights on HLA-DR2 complexes that confer susceptibility to multiple sclerosis in Sardinia: a molecular dynamics simulation study.

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    Full Text Available Sardinia is a major Island in the Mediterranean with a high incidence of multiple sclerosis, a chronic autoimmune inflammatory disease of the central nervous system. Disease susceptibility in Sardinian population has been associated with five alleles of major histocompatibility complex (MHC class II DRB1 gene. We performed 120 ns of molecular dynamics simulation on one predisposing and one protective alleles, unbound and in complex with the two relevant peptides: Myelin Basic Protein and Epstein Barr Virus derived peptide. In particular we focused on the MHC peptide binding groove dynamics. The predisposing allele was found to form a stable complex with both the peptides, while the protective allele displayed stability only when bound with myelin peptide. The local flexibility of the MHC was probed dividing the binding groove into four compartments covering the well known peptide anchoring pockets. The predisposing allele in the first half cleft exhibits a narrower and more rigid groove conformation in the presence of myelin peptide. The protective allele shows a similar behavior, while in the second half cleft it displays a narrower and more flexible groove conformation in the presence of viral peptide. We further characterized these dynamical differences by evaluating H-bonds, hydrophobic and stacking interaction networks, finding striking similarities with super-type patterns emerging in other autoimmune diseases. The protective allele shows a defined preferential binding to myelin peptide, as confirmed by binding free energy calculations. All together, we believe the presented molecular analysis could help to design experimental assays, supports the molecular mimicry hypothesis and suggests that propensity to multiple sclerosis in Sardinia could be partly linked to distinct peptide-MHC interaction and binding characteristics of the antigen presentation mechanism.

  10. Crystal structure of LGR4-Rspo1 complex: insights into the divergent mechanisms of ligand recognition by leucine-rich repeat G-protein-coupled receptors (LGRs).

    Science.gov (United States)

    Xu, Jin-Gen; Huang, Chunfeng; Yang, Zhengfeng; Jin, Mengmeng; Fu, Panhan; Zhang, Ni; Luo, Jian; Li, Dali; Liu, Mingyao; Zhou, Yan; Zhu, Yongqun

    2015-01-23

    Leucine-rich repeat G-protein-coupled receptors (LGRs) are a unique class of G-protein-coupled receptors characterized by a large extracellular domain to recognize ligands and regulate many important developmental processes. Among the three groups of LGRs, group B members (LGR4-6) recognize R-spondin family proteins (Rspo1-4) to stimulate Wnt signaling. In this study, we successfully utilized the "hybrid leucine-rich repeat technique," which fused LGR4 with the hagfish VLR protein, to obtain two recombinant human LGR4 proteins, LGR415 and LGR49. We determined the crystal structures of ligand-free LGR415 and the LGR49-Rspo1 complex. LGR4 exhibits a twisted horseshoe-like structure. Rspo1 adopts a flat and β-fold architecture and is bound in the concave surface of LGR4 in the complex through electrostatic and hydrophobic interactions. All the Rspo1-binding residues are conserved in LGR4-6, suggesting that LGR4-6 bind R-spondins through an identical surface. Structural analysis of our LGR4-Rspo1 complex with the previously determined LGR4 and LGR5 structures revealed that the concave surface of LGR4 is the sole binding site for R-spondins, suggesting a one-site binding model of LGR4-6 in ligand recognition. The molecular mechanism of LGR4-6 is distinct from the two-step mechanism of group A receptors LGR1-3 and the multiple-interface binding model of group C receptors LGR7-8, suggesting LGRs utilize the divergent mechanisms for ligand recognition. Our structures, together with previous reports, provide a comprehensive understanding of the ligand recognition by LGRs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Structural and biochemical analyses reveal insights into covalent flavinylation of the Escherichia coli Complex II homolog quinol:fumarate reductase

    Energy Technology Data Exchange (ETDEWEB)

    Starbird, C.A.; Maklashina, Elena; Sharma, Pankaj; Qualls-Histed, Susan; Cecchini, Gary; Iverson, T.M. (VA); (UCSF); (Vanderbilt)

    2017-06-14

    The Escherichia coli Complex II homolog quinol:fumarate reductase (QFR, FrdABCD) catalyzes the interconversion of fumarate and succinate at a covalently attached FAD within the FrdA subunit. The SdhE assembly factor enhances covalent flavinylation of Complex II homologs, but the mechanisms underlying the covalent attachment of FAD remain to be fully elucidated. Here, we explored the mechanisms of covalent flavinylation of the E. coli QFR FrdA subunit. Using a ΔsdhE E. coli strain, we show that the requirement for the assembly factor depends on the cellular redox environment. We next identified residues important for the covalent attachment and selected the FrdAE245 residue, which contributes to proton shuttling during fumarate reduction, for detailed biophysical and structural characterization. We found that QFR complexes containing FrdAE245Q have a structure similar to that of the WT flavoprotein, but lack detectable substrate binding and turnover. In the context of the isolated FrdA subunit, the anticipated assembly intermediate during covalent flavinylation, FrdAE245 variants had stability similar to that of WT FrdA, contained noncovalent FAD, and displayed a reduced capacity to interact with SdhE. However, small-angle X-ray scattering (SAXS) analysis of WT FrdA cross-linked to SdhE suggested that the FrdAE245 residue is unlikely to contribute directly to the FrdA-SdhE protein-protein interface. We also found that no auxiliary factor is absolutely required for flavinylation, indicating that the covalent flavinylation is autocatalytic. We propose that multiple factors, including the SdhE assembly factor and bound dicarboxylates, stimulate covalent flavinylation by preorganizing the active site to stabilize the quinone-methide intermediate.

  12. Chromosomal characterization of the three subgenomes in the polyploids of Hordeum murinum L.: new insight into the evolution of this complex.

    Directory of Open Access Journals (Sweden)

    Ángeles Cuadrado

    Full Text Available Hordeum murinum L. is a species complex composed of related taxa, including the subspecies glaucum, murinum and leporinum. However, the phylogenetic relationships between the different taxa and their cytotypes, and the origin of the polyploid forms, remain points of controversy. The present work reports a comparative karyotype analysis of seven accessions of the H. murinum complex representing all subspecies and cytotypes. The karyotypes were determined by examining the distribution of the repetitive Triticeae DNA sequences pTa71, pTa794, pSc119.2, pAs1 and pHch950, the simple sequence repeats (SSRs (AG10, (AAC5, (AAG5, (ACT5, (ATC5, and (CCCTAAA3 via in situ hybridization. The chromosomes of the three subgenomes involved in the polyploids were identified. All tetraploids of all subspecies shared the same two subgenomes (thus suggesting them to in fact belong to the same taxon, the result of hybridization between two diploid ancestors. One of the subgenomes present in all tetraploids of all subspecies was found to be very similar (though not identical to the chromosome complement of the diploid glaucum. The hexaploid form of leporinum came about through a cross between a tetraploid and a third diploid form. Exclusively bivalent associations among homologous chromosomes were observed when analyzing pollen mother cells of tetraploid taxa. In conclusion, the present results identify all the individual chromosomes within the H. murinum complex, reveal its genome structure and phylogeny, and explain the appearance of the different cytotypes. Three cryptic species are proposed according to ploidy level that may deserve full taxonomic recognition.

  13. Synthesis and structure of 1,3-dimethyl-5-(p-sulfonamide-phenylazo)-6-aminouracil and its Ni(II) complex: Topological insights and investigation for noncovalent interactions

    Science.gov (United States)

    Debnath, Diptanu; Roy, Subhadip; Purkayastha, Atanu; Bauzá, Antonio; Choudhury, Rupasree; Ganguly, Rakesh; Frontera, Antonio; Misra, Tarun Kumar

    2017-08-01

    The azo-derivative, 1,3-dimethyl-5-(p-sulfonamide-phenylazo)-6-aminouracil (HL) containing 6-aminouracil (a biomolecule) and sulfonamide functionality (commonly found in sulfa-drugs), and its Ni(II) complex, NiIIL2 were synthesized. Single-crystal X-ray diffraction studies show that the ligand (HL) consists of an E conformation about the azo-linkage with a nearly planar geometry and the complex possesses distorted square planar geometry. The H-bonded underlying networks of HL and NiIIL2 were topologically classified revealing distinct topological types, namely tts and hxl, respectively. Moreover, topology of molecular packings in HL and NiIIL2 has also been discussed. Density functional theory (DFT) calculations, at the M06-2X/def2TZVP level of theory, are employed to characterize a great variety of non-covalent interactions that explicitly show the importance of antiparallel stacking interactions established by π--π+ interactions and H-bonds in the self-assembled dimmers in HL and lp-π/C-H⋯π interactions in NiIIL2. The results of NMR and UV-vis spectroscopies evidence that the ligand exists in hydrazone-imine-keto (B) tautomeric form in solution. The ligand absorption bands consist of the overlapping bands of π→π* and n→π* transitions. The complex experiences electronic transitions that consist of basically ILCT in character with some sort of participation of the atomic d-orbitals of the nickel. The pKa value of the ligand is found to be 4.09.

  14. Evo-Devo insights from pathological networks: exploring craniosynostosis as a developmental mechanism for modularity and complexity in the human skull.

    Science.gov (United States)

    Esteve-Altava, Borja; Rasskin-Gutman, Diego

    2015-07-20

    Bone fusion has occurred repeatedly during skull evolution in all tetrapod lineages, leading to a reduction in the number of bones and an increase in their morphological complexity. The ontogeny of the human skull includes also bone fusions as part of its normal developmental process. However, several disruptions might cause premature closure of cranial sutures (craniosynostosis), reducing the number of bones and producing new skull growth patterns that causes shape changes. Here, we compare skull network models of a normal newborn with different craniosynostosis conditions, the normal adult stage, and phylogenetically reconstructed forms of a primitive tetrapod, a synapsid, and a placental mammal. Changes in morphological complexity of newborn-to-synostosed skulls are two to three times less than in newborn-to-adult; and even smaller when we compare them to the increases among the reconstructed ancestors in the evolutionary transitions. In addition, normal, synostosed, and adult human skulls show the same connectivity modules: facial and cranial. Differences arise in the internal structure of these modules. In the adult skull the facial module has an internal hierarchical organization, whereas the cranial module has a regular network organization. However, all newborn forms, normal and synostosed, do not reach such kind of internal organization. We conclude that the subtle changes in skull complexity at the developmental scale can change the modular substructure of the newborn skull to more integrated modules in the adult skull, but is not enough to generate radical changes as it occurs at a macroevolutionary scale. The timing of closure of craniofacial sutures, together with the conserved patterns of morphological modularity, highlights a potential relation between the premature fusion of bones and the evolution of the shape of the skull in hominids.

  15. Same Traits, Different Variance

    Directory of Open Access Journals (Sweden)

    Jamie S. Churchyard

    2014-02-01

    Full Text Available Personality trait questionnaires are regularly used in individual differences research to examine personality scores between participants, although trait researchers tend to place little value on intra-individual variation in item ratings within a measured trait. The few studies that examine variability indices have not considered how they are related to a selection of psychological outcomes, so we recruited 160 participants (age M = 24.16, SD = 9.54 who completed the IPIP-HEXACO personality questionnaire and several outcome measures. Heterogenous within-subject differences in item ratings were found for every trait/facet measured, with measurement error that remained stable across the questionnaire. Within-subject standard deviations, calculated as measures of individual variation in specific item ratings within a trait/facet, were related to outcomes including life satisfaction and depression. This suggests these indices represent valid constructs of variability, and that researchers administering behavior statement trait questionnaires with outcome measures should also apply item-level variability indices.

  16. New insights into the Hendra virus attachment and entry process from structures of the virus G glycoprotein and its complex with Ephrin-B2.

    Directory of Open Access Journals (Sweden)

    Kai Xu

    Full Text Available Hendra virus and Nipah virus, comprising the genus Henipavirus, are recently emerged, highly pathogenic and often lethal zoonotic agents against which there are no approved therapeutics. Two surface glycoproteins, the attachment (G and fusion (F, mediate host cell entry. The crystal structures of the Hendra G glycoprotein alone and in complex with the ephrin-B2 receptor reveal that henipavirus uses Tryptophan 122 on ephrin-B2/B3 as a "latch" to facilitate the G-receptor association. Structural-based mutagenesis of residues in the Hendra G glycoprotein at the receptor binding interface document their importance for viral attachments and entry, and suggest that the stability of the Hendra-G-ephrin attachment complex does not strongly correlate with the efficiency of viral entry. In addition, our data indicates that conformational rearrangements of the G glycoprotein head domain upon receptor binding may be the trigger leading to the activation of the viral F fusion glycoprotein during virus infection.

  17. A quantum mechanical analysis of the light-harvesting complex 2 (LH2) from purple photosynthetic bacteria: insights into the electrostatic effects of transmembrane helices.

    Science.gov (United States)

    Pichierri, Fabio

    2011-02-01

    We perform a quantum mechanical study of the peptides that are part of the LH2 complex from Rhodopseudomonas acidophila, a non-sulfur purple bacteria that has the ability of producing chemical energy from photosynthesis. The electronic structure calculations indicate that the transmembrane helices of these peptides are characterized by dipole moments with a magnitude of about 150D. When the full nonamer assembly made of 18 peptides is considered, then a macrodipole of magnitude 806D is built up from the vector sum of each monomer dipole. The macrodipole is oriented normal to the membrane plane and with the positive tip toward the cytoplasm thereby indicating that the electronic charge of the protein scaffold is polarized toward the periplasm. The results obtained here suggest that the asymmetric charge distribution of the protein scaffold contributes an anisotropic electrostatic environment which differentiates the absorption properties of the bacteriochlorophyll pigments, B800 and B850, embedded in the LH2 complex. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  18. High-Order Ca(II)-Chloro Complexes in Mixed CaCl2-LiCl Aqueous Solution: Insights from Density Functional Theory and Molecular Dynamics Simulations.

    Science.gov (United States)

    Wang, Yu-Lin; Wang, Ying; Yi, Hai-Bo

    2016-07-21

    In this study, the structural characteristics of high-coordinated Ca-Cl complexes present in mixed CaCl2-LiCl aqueous solution were investigated using density functional theory (DFT) and molecular dynamics (MD) simulations. The DFT results show that [CaClx](2-x) (x = 4-6) clusters are quite unstable in the gas phase, but these clusters become metastable when hydration is considered. The MD simulations show that high-coordinated Ca-chloro complexes are possible transient species that exist for up to nanoseconds in concentrated (11.10 mol·kg(-1)) Cl(-) solution at 273 and 298 K. As the temperature increases to 423 K, these high-coordinated structures tend to disassociate and convert into smaller clusters and single free ions. The presence of high-order Ca-Cl species in concentrated LiCl solution can be attributed to their enhanced hydration shell and the inadequate hydration of ions. The probability of the [CaClx](2-x)aq (x = 4-6) species being present in concentrated LiCl solution decreases greatly with increasing temperature, which also indicates that the formation of the high-coordinated Ca-Cl structure is related to its hydration characteristics.

  19. New insights on the spectrophotometric determination of melatonin pKa values and melatonin-βCD inclusion complex formation constant

    Science.gov (United States)

    Zafra-Roldán, A.; Corona-Avendaño, S.; Montes-Sánchez, R.; Palomar-Pardavé, M.; Romero-Romo, M.; Ramírez-Silva, M. T.

    2018-02-01

    Using UV-Vis spectrophotometry a stability study of melatonin at different pH values was done in aqueous media, finding that at acidic pH melatonin is unstable when interacting with the environment, however it becomes stable protecting it from light and oxygen. From the UV-Vis spectra and SQUAD software, melatonin pKa values, in a completely protected aqueous medium, were estimated as 5.777 ± 0.011 and 10.201 ± 0.024. Using the same techniques, the melatonin and β-cyclodextrin inclusion complex formation constants were assessed at pH 3, 7 and 11.5, giving the values of log β = (3.07 ± 0.06), (2.94 ± 0.01) and (3.07 ± 0.06) M- 1, respectively. From the global acidity formation constants and the complexes' formation constants, the molar fractions were determined for each species of MT and MT - βCD, to build the molar fraction-[βCD]-pH 3D diagram and the molar fraction-pH 2D diagrams, where it was possible to observe the predominance of the MT species with and without βCD. A voltammetric study at pH 3, allowed obtaining a value of log β = (3.15 ± 0.01) M- 1, which corroborates that obtained through UV-Vis spectrophotometry, supporting strongly the rationale behind using simple, straightforward techniques.

  20. Insight in Schizophrenia : Involvement of Self-Reflection Networks?

    NARCIS (Netherlands)

    van der Meer, Lisette; de Vos, Annerieke E.; Stiekema, Annemarie P. M.; Pijnenborg, Gerdina H. M.; van Tol, Marie-Jose; Nolen, Willem A.; David, Anthony S.; Aleman, Andre

    2013-01-01

    Background: Impaired insight is a common feature in psychosis and an important predictor of variables such as functional outcome, prognosis, and treatment adherence. A cognitive process that may underlie insight in psychosis is self-reflection, or the conscious evaluation of one's traits and

  1. Plasticity Regulators Modulate Specific Root Traits in Discrete Nitrogen Environments

    Science.gov (United States)

    Gifford, Miriam L.; Banta, Joshua A.; Katari, Manpreet S.; Hulsmans, Jo; Chen, Lisa; Ristova, Daniela; Tranchina, Daniel; Purugganan, Michael D.; Coruzzi, Gloria M.; Birnbaum, Kenneth D.

    2013-01-01

    Plant development is remarkably plastic but how precisely can the plant customize its form to specific environments? When the plant adjusts its development to different environments, related traits can change in a coordinated fashion, such that two traits co-vary across many genotypes. Alternatively, traits can vary independently, such that a change in one trait has little predictive value for the change in a second trait. To characterize such “tunability” in developmental plasticity, we carried out a detailed phenotypic characterization of complex root traits among 96 accessions of the model Arabidopsis thaliana in two nitrogen environments. The results revealed a surprising level of independence in the control of traits to environment – a highly tunable form of plasticity. We mapped genetic architecture of plasticity using genome-wide association studies and further used gene expression analysis to narrow down gene candidates in mapped regions. Mutants in genes implicated by association and expression analysis showed precise defects in the predicted traits in the predicted environment, corroborating the independent control of plasticity traits. The overall results suggest that there is a pool of genetic variability in plants that controls traits in specific environments, with opportunity to tune crop plants to a given environment. PMID:24039603

  2. Crystal structure of human cyclin-dependent kinase-2 complex with MK2 inhibitor TEI-I01800: insight into the selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Fujino, Aiko; Fukushima, Kei; Kubota, Takaharu; Kosugi, Tomomi; Takimoto-Kamimura, Midori, E-mail: m.kamimura@teijin.co.jp [Teijin Pharma Limited, 4-3-2 Asahigaoka, Hino-shi, Tokyo 191-8512 (Japan)

    2013-11-01

    The Gly-rich loop of cyclin-dependent kinase 2 (CDK2) bound to TEI-I01800 as an MK2 specific inhibitor forms a β-sheet which is a common structure in CDK2–ligand complexes. Here, the reason why TEI-I01800 does not become a strong inhibitor against CDK2 based on the conformation of TEI-I01800 is presented. Mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAP-K2) is a Ser/Thr kinase from the p38 mitogen-activated protein kinase signalling pathway and plays an important role in inflammatory diseases. The crystal structure of the MK2–TEI-I01800 complex has been reported; its Gly-rich loop was found to form an α-helix, not a β-sheet as has been observed for other Ser/Thr kinases. TEI-I01800 is 177-fold selective against MK2 compared with CDK2; in order to understand the inhibitory mechanism of TEI-I01800, the cyclin-dependent kinase 2 (CDK2) complex structure with TEI-I01800 was determined at 2.0 Å resolution. Interestingly, the Gly-rich loop of CDK2 formed a β-sheet that was different from that of MK2. In MK2, TEI-I01800 changed the secondary structure of the Gly-rich loop from a β-sheet to an α-helix by collision between Leu70 and a p-ethoxyphenyl group at the 7-position and bound to MK2. However, for CDK2, TEI-I01800 bound to CDK2 without this structural change and lost the interaction with the substituent at the 7-position. In summary, the results of this study suggest that the reason for the selectivity of TEI-I01800 is the favourable conformation of TEI-I01800 itself, making it suitable for binding to the α-form MK2.

  3. Design of a multi-agent hydroeconomic model to simulate a complex human-water system: Early insights from the Jordan Water Project

    Science.gov (United States)

    Yoon, J.; Klassert, C. J. A.; Lachaut, T.; Selby, P. D.; Knox, S.; Gorelick, S.; Rajsekhar, D.; Tilmant, A.; Avisse, N.; Harou, J. J.; Gawel, E.; Klauer, B.; Mustafa, D.; Talozi, S.; Sigel, K.

    2015-12-01

    Our work focuses on development of a multi-agent, hydroeconomic model for purposes of water policy evaluation in Jordan. The model adopts a modular approach, integrating biophysical modules that simulate natural and engineered phenomena with human modules that represent behavior at multiple levels of decision making. The hydrologic modules are developed using spatially-distributed groundwater and surface water models, which are translated into compact simulators for efficient integration into the multi-agent model. For the groundwater model, we adopt a response matrix method approach in which a 3-dimensional MODFLOW model of a complex regional groundwater system is converted into a linear simulator of groundwater response by pre-processing drawdown results from several hundred numerical simulation runs. Surface water models for each major surface water basin in the country are developed in SWAT and similarly translated into simple rainfall-runoff functions for integration with the multi-agent model. The approach balances physically-based, spatially-explicit representation of hydrologic systems with the efficiency required for integration into a complex multi-agent model that is computationally amenable to robust scenario analysis. For the multi-agent model, we explicitly represent human agency at multiple levels of decision making, with agents representing riparian, management, supplier, and water user groups. The agents' decision making models incorporate both rule-based heuristics as well as economic optimization. The model is programmed in Python using Pynsim, a generalizable, open-source object-oriented code framework for modeling network-based water resource systems. The Jordan model is one of the first applications of Pynsim to a real-world water management case study. Preliminary results from a tanker market scenario run through year 2050 are presented in which several salient features of the water system are investigated: competition between urban and

  4. Power and Autistic Traits

    Directory of Open Access Journals (Sweden)

    Geir Overskeid

    2016-08-01

    Full Text Available Autistic traits can help people gain and sustain power, and has probably done so throughout history, says the present paper. A number of testable claims follow from this assumption. First, the powerful should have more autistic traits than others – which they do appear to have. Among other things, powerful people, and those with many autistic traits, tend to prefer solitary activities and are often aloof. Moreover, they are often rigid and socially insensitive, low on empathy and with low scores on the trait of agreeableness -- and as a rule they do not have many friends. Both groups are also more self-centered than others, more honest, less submissive, more sensitive to slights, and with a stronger tendency to engage in abstract thinking. They tend to behave in bossy or dominant ways, and their moral judgment is more based on rules than on feelings. In addition to experimental evidence, I cite biographies showing that a surprising number of presidents, prime ministers and other powerful people seem to have had traits like those in question – and interestingly, in animals, leaders are often rigid and insensitive to group members’ needs and feelings, mostly acting the way they are themselves inclined to, not responding much to others. Problem solving is important in leadership, and people with many autistic traits appear often to be better thinkers than typical subjects with similar IQs. However, these and other congruities could be coincidences. Hence the question of whether traits the two groups have in common also have a common cause constitutes a strong test of the paper’s thesis – and a common cause does appear to exist, in the form of testosterone’s effects on the central nervous system. Finally, there is evidence that, other things equal, powerful men have more reproductive success than others. If men wielding power do indeed have more autistic traits than those less powerful, this will lead to, other things equal, such traits

  5. Power and Autistic Traits

    Science.gov (United States)

    Overskeid, Geir

    2016-01-01

    Autistic traits can help people gain and sustain power, and has probably done so throughout history, says the present paper. A number of testable claims follow from this assumption. First, the powerful should have more autistic traits than others – which they do appear to have. Among other things, powerful people, and those with many autistic traits, tend to prefer solitary activities and are often aloof. Moreover, they are often rigid and socially insensitive, low on empathy and with low scores on the trait of agreeableness – and as a rule they do not have many friends. Both groups are also more self-centered than others, more honest, less submissive, more sensitive to slights, and with a stronger tendency to engage in abstract thinking. They tend to behave in bossy or dominant ways, and their moral judgment is more based on rules than on feelings. In addition to experimental evidence, I cite biographies showing that a surprising number of presidents, prime ministers and other powerful people seem to have had traits like those in question – and interestingly, in animals, leaders are often rigid and insensitive to group members’ needs and feelings, mostly acting the way they are themselves inclined to, not responding much to others. Problem solving is important in leadership, and people with many autistic traits appear often to be better thinkers than typical subjects with similar IQs. However, these and other congruities could be coincidences. Hence the question of whether traits the two groups have in common also have a common cause constitutes a strong test of the paper’s thesis – and a common cause does appear to exist, in the form of testosterone’s effects on the central nervous system. Finally, there is evidence that, other things equal, powerful men have more reproductive success than others. If men wielding power do indeed have more autistic traits than those less powerful, this will lead to, other things equal, such traits becoming more

  6. Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation.

    Science.gov (United States)

    Corrada, Dario; Soshilov, Anatoly A; Denison, Michael S; Bonati, Laura

    2016-06-01

    The Aryl hydrocarbon Receptor (AhR) is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in understanding its molecular mechanisms of activation. Since dimerization with the AhR Nuclear Translocator (ARNT) protein, occurring through the Helix-Loop-Helix (HLH) and PER-ARNT-SIM (PAS) domains, is needed to convert the AhR into its transcriptionally active form, deciphering the AhR:ARNT dimerization mode would provide insights into the mechanisms of AhR transformation. Here we present homology models of the murine AhR:ARNT PAS domain dimer developed using recently available X-ray structures of other bHLH-PAS protein dimers. Due to the different reciprocal orientation and interaction surfaces in the different template dimers, two alternative models were developed for both the PAS-A and PAS-B dimers and they were characterized by combining a number of computational evaluations. Both well-established hot spot prediction methods and new approaches to analyze individual residue and residue-pairwise contributions to the MM-GBSA binding free energies were adopted to predict residues critical for dimer stabilization. On this basis, a mutagenesis strategy for both the murine AhR and ARNT proteins was designed and ligand-dependent DNA binding ability of the AhR:ARNT heterodimer mutants was evaluated. While functional analysis disfavored the HIF2α:ARNT heterodimer-based PAS-B model, most mutants derived from the CLOCK:BMAL1-based AhR:ARNT dimer models of both the PAS-A and the PAS-B dramatically decreased the levels of DNA binding, suggesting this latter model as the most suitable for describing AhR:ARNT dimerization. These novel results open new research directions focused at elucidating basic molecular mechanisms underlying the

  7. Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation.

    Directory of Open Access Journals (Sweden)

    Dario Corrada

    2016-06-01

    Full Text Available The Aryl hydrocarbon Receptor (AhR is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in understanding its molecular mechanisms of activation. Since dimerization with the AhR Nuclear Translocator (ARNT protein, occurring through the Helix-Loop-Helix (HLH and PER-ARNT-SIM (PAS domains, is needed to convert the AhR into its transcriptionally active form, deciphering the AhR:ARNT dimerization mode would provide insights into the mechanisms of AhR transformation. Here we present homology models of the murine AhR:ARNT PAS domain dimer developed using recently available X-ray structures of other bHLH-PAS protein dimers. Due to the different reciprocal orientation and interaction surfaces in the different template dimers, two alternative models were developed for both the PAS-A and PAS-B dimers and they were characterized by combining a number of computational evaluations. Both well-established hot spot prediction methods and new approaches to analyze individual residue and residue-pairwise contributions to the MM-GBSA binding free energies were adopted to predict residues critical for dimer stabilization. On this basis, a mutagenesis strategy for both the murine AhR and ARNT proteins was designed and ligand-dependent DNA binding ability of the AhR:ARNT heterodimer mutants was evaluated. While functional analysis disfavored the HIF2α:ARNT heterodimer-based PAS-B model, most mutants derived from the CLOCK:BMAL1-based AhR:ARNT dimer models of both the PAS-A and the PAS-B dramatically decreased the levels of DNA binding, suggesting this latter model as the most suitable for describing AhR:ARNT dimerization. These novel results open new research directions focused at elucidating basic molecular mechanisms

  8. Insight in schizophrenia: a review.

    Science.gov (United States)

    Dam, Jesper

    2006-01-01

    The issue of insight in schizophrenia must be assumed to be one of the most important aspects of the clinical examination. Comprehensive studies have shown that between 50% and 80% of all patients suffering from schizophrenia do not believe that they have a disorder. In recent years, poor insight in schizophrenia has been the subject of increasing interest, as manifested in a number of studies discussed in the present review. Some of these studies focus on insight correlated to various parameters such as psychopathology, neuropsychology, clinical relevance and compliance. Other studies refer to more theoretical implications, among these the issue of defining the concept of insight: whether insight can be seen as a "primary" phenomenon in schizophrenia, and whether insight may be graduated, dimensioned or increased. Several authors have developed rating scales in an attempt to obtain a measure for the degree or dimension of insight. Here, the range of parameters employed gives an excellent impression of the complexity of the concept of insight. In the concluding discussion, a phenomenological aspect is brought in, in an attempt to place the concept of insight in relation to disturbances of the self in schizophrenia and to primary symptoms in schizophrenia, amongst these autism.

  9. New insights into the complex regulation of the glycolytic pathway in Lactococcus lactis. I. Construction and diagnosis of a comprehensive dynamic model.

    Science.gov (United States)

    Dolatshahi, Sepideh; Fonseca, Luis L; Voit, Eberhard O

    2016-01-01

    This article and the companion paper use computational systems modeling to decipher the complex coordination of regulatory signals controlling the glycolytic pathway in the dairy bacterium Lactococcus lactis. In this first article, the development of a comprehensive kinetic dynamic model is described. The model is based on in vivo NMR data that consist of concentration trends in key glycolytic metabolites and cofactors. The model structure and parameter values are identified with a customized optimization strategy that uses as its core the method of dynamic flux estimation. For the first time, a dynamic model with a single parameter set fits all available glycolytic time course data under anaerobic operation. The model captures observations that had not been addressed so far and suggests the existence of regulatory effects that had been observed in other species, but not in L. lactis. The companion paper uses this model to analyze details of the dynamic control of glycolysis under aerobic and anaerobic conditions.

  10. Genetic structure offers insights into the evolution of migration and the taxonomy of the Barred Long-tailed Cuckoo Cercococcyx montanus species complex

    DEFF Research Database (Denmark)

    Engel, Joshua I.; Byamana, Kizungu; Kahindo, Charles

    2014-01-01

    and argue that migration was gained and then lost in the C. montanus complex. Based on consistent morphological and genetic differences, we suggest that Barred Long-tailed Cuckoo is best treated as two species, one of which (C. montanus) is a non-migratory Albertine Rift endemic.......Barred Long-tailed Cuckoo (Cercococcyx montanus) currently comprises two morphologically distinct subspecies, one resident in the Albertine Rift (montanus) and one in east and southeast Africa (patulus) in which there are migrations that are poorly understood. Based on nuclear and mitochondrial DNA...... sequences, we find that two specimens collected in relatively low-elevation forest in the Albertine Rift were correctly identified from plumage as the migratory subspecies whose closest known breeding area is > 800 km to the east. We discuss ways in which this unique migratory pattern could have evolved...

  11. Structure of HLA-A*0301 in complex with a peptide of proteolipid protein: insights into the role of HLA-A alleles in susceptibility to multiple sclerosis

    International Nuclear Information System (INIS)

    McMahon, Róisín M.; Friis, Lone; Siebold, Christian; Friese, Manuel A.; Fugger, Lars; Jones, E. Yvonne

    2011-01-01

    The structure of the human major histocompatability (MHC) class I molecule HLA-A*0301 (HLA-A3) in complex with a nonameric peptide (KLIETYFSK) has been determined by X-ray crystallography to 2.7 Å resolution. The structure of the human major histocompatability (MHC) class I molecule HLA-A*0301 (HLA-A3) in complex with a nonameric peptide (KLIETYFSK) has been determined by X-ray crystallography to 2.7 Å resolution. HLA-A3 is a predisposing allele for multiple sclerosis (MS), an autoimmune disease of the central nervous system. The KLIETYFSK peptide is a naturally processed epitope of proteolipid protein, a myelin protein and candidate target for immune-mediated myelin destruction in MS. Comparison of the structure of HLA-A3 with that of HLA-A2, an MHC class I molecule which is protective against MS, indicates that both MHC class I molecules present very similar faces for T-cell receptor recognition whilst differing in the specificity of their peptide-binding grooves. These characteristics may underlie the opposing (predisposing versus protective) associations that they exhibit both in humans and in mouse models of MS-like disease. Furthermore, subtle alterations within the peptide-binding groove of HLA-A3 and other A3-like MHC class I molecules, members of the so-called A3 superfamily, may be sufficient to alter their presentation of autoantigen peptides such as KLIETYFSK. This in turn may modulate their contribution to the associated risk of autoimmune disease

  12. The complex role of social care services in supporting the development of sustainable identities: Insights from the experiences of British South Asian women with intellectual disabilities.

    Science.gov (United States)

    Malik, Kulsoom Jawaid; Unwin, Gemma; Larkin, Michael; Kroese, Biza Stenfert; Rose, John

    2017-04-01

    Carers and service users with intellectual disabilities from minority ethnic groups have typically been reported to be dissatisfied with the social care services they receive. However, service users themselves have rarely been asked directly about their experiences of social care. This paper aims to understand the meaning of social care services in the lives of South Asian women with intellectual disabilities, in the United Kingdom. 10 British South Asian women with mild-moderate intellectual disabilities were interviewed about their experiences of social care services. The transcripts were analysed using interpretative phenomenological analysis. The analysis produced three super-ordinate themes, which focus on how services facilitate the development of complex identities, how the participants explored their sense of being 'stuck' between cultures as they negotiated their journeys towards independence, and the triple disadvantage which they experienced as a consequence of the intersection between gender, ethnicity and disability. The participants were broadly satisfied with the role which services played in these domains, and appeared to find them valuable and helpful. The results suggest that the participants successfully managed complex identity issues, such as acculturation processes, with the support of services. It may be helpful to give more explicit consideration to the positive role which good services can play in supporting people with intellectual disabilities in the development of their identities and goals, alongside the more traditionally 'concrete' objectives of such social care. Engagement with families in 'positive risk-taking' is likely to be an important component of success. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Connections and consequences in complex systems: insights from a case study of the emergence and local impact of crisis resolution and home treatment services.

    Science.gov (United States)

    Hannigan, Ben

    2013-09-01

    In this article the broad contours of a complexity perspective are outlined. Complexity ideas are then drawn on to frame an empirical examination of the connections running between different levels of organisation in health and social care, and to underpin investigation into the intended and unintended local system consequences of service development. Data are used from a study conducted in the UK's mental health field. Here, macro-level policy has led to the supplementing of longstanding community mental health teams by newer, more specialised, services. An example includes teams providing crisis resolution and home treatment (CRHT) care as an alternative to hospital admission. Using an embedded case study design, where 'the case' examined was a new CRHT team set in its surrounding organisational environment, ethnographic data (with interviews predominating) were generated in a single site in Wales over 18 months from the middle of 2007. In a large-scale context favourable to local decision-making, and against a background of a partial and disputed evidence base, the move to establish the new standalone service was contested. Whilst users valued the work of the team, and local practitioners recognised the quality of its contribution, powerful effects were also triggered across the locality's horizontal interfaces. Participants described parts of the interconnected system being closed to release resources, staff gravitating to new crisis services leaving holes elsewhere, and the most needy service users being cared for by the least experienced workers. Some community mental health team staff described unexpected increases in workload, and disputes over eligibility for crisis care with implications for system-wide working relations. Detailed data extracts are used to illustrate these connections and consequences. Concluding lessons are drawn on the use of evidence to inform policy, on the significance of local contexts and system interfaces, and on anticipating the

  14. Contemporary Ecological Interactions Improve Models of Past Trait Evolution.

    Science.gov (United States)

    Hutchinson, Matthew C; Gaiarsa, Marília P; Stouffer, Daniel B

    2018-02-20

    Despite the fact that natural selection underlies both traits and interactions, evolutionary models often neglect that ecological interactions may, and in many cases do, influence the evolution of traits. Here, we explore the interdependence of ecological interactions and functional traits in the pollination associations of hawkmoths and flowering plants. Specifically, we develop an adaptation of the Ornstein-Uhlenbeck model of trait evolution that allows us to study the influence of plant corolla depth and observed hawkmoth-plant interactions on the evolution of hawkmoth proboscis length. Across diverse modelling scenarios, we find that the inclusion of contemporary interactions can provide a better description of trait evolution than the null expectation. Moreover, we show that the pollination interactions provide more-likely models of hawkmoth trait evolution when interactions are considered at increasingly finescale groups of hawkmoths. Finally, we demonstrate how the results of best-fit modelling approaches can implicitly support the association between interactions and trait evolution that our method explicitly examines. In showing that contemporary interactions can provide insight into the historical evolution of hawkmoth proboscis length, we demonstrate the clear utility of incorporating additional ecological information to models designed to study past trait evolution.

  15. Sexual selection and magic traits in speciation with gene flow

    Directory of Open Access Journals (Sweden)

    Maria R. SERVEDIO, Michael KOPP

    2012-06-01

    Full Text Available The extent to which sexual selection is involved in speciation with gene flow remains an open question and the subject of much research. Here, we propose that some insight can be gained from considering the concept of magic traits (i.e., traits involved in both reproductive isolation and ecological divergence. Both magic traits and other, “non-magic”, traits can contribute to speciation via a number of specific mechanisms. We argue that many of these mechanisms are likely to differ widely in the extent to which they involve sexual selection. Furthermore, in some cases where sexual selection is present, it may be prone to inhibit rather than drive speciation. Finally, there are a priori reasons to believe that certain categories of traits are much more effective than others in driving speciation. The combination of these points suggests a classification of traits that may shed light on the broader role of sexual selection in speciation with gene flow. In particular, we suggest that sexual selection can act as a driver of speciation in some scenarios, but may play a negligible role in potentially common categories of magic traits, and may be likely to inhibit speciation in common categories of non-magic traits [Current Zoology 58 (3: 507–513, 2012].

  16. Independence among physiological traits suggests flexibility in the face of ecological demands on phenotypes

    NARCIS (Netherlands)

    Buehler, D.M.; Vézina, F.; Goymann, W.; Schwabl, I.; Versteegh, M.; Tieleman, B.I.; Piersma, T.

    2012-01-01

    Phenotypic flexibility allows animals to adjust their physiology to diverse environmental conditions encountered over the year. Examining how these varying traits covary gives insights into potential constraints or freedoms that may shape evolutionary trajectories. In this study, we examined

  17. Quantitative trait loci and metabolic pathways

    Science.gov (United States)

    McMullen, M. D.; Byrne, P. F.; Snook, M. E.; Wiseman, B. R.; Lee, E. A.; Widstrom, N. W.; Coe, E. H.

    1998-01-01

    The interpretation of quantitative trait locus (QTL) studies is limited by the lack of information on metabolic pathways leading to most economic traits. Inferences about the roles of the underlying genes with a pathway or the nature of their interaction with other loci are generally not possible. An exception is resistance to the corn earworm Helicoverpa zea (Boddie) in maize (Zea mays L.) because of maysin, a C-glycosyl flavone synthesized in silks via a branch of the well characterized flavonoid pathway. Our results using flavone synthesis as a model QTL system indicate: (i) the importance of regulatory loci as QTLs, (ii) the importance of interconnecting biochemical pathways on product levels, (iii) evidence for “channeling” of intermediates, allowing independent synthesis of related compounds, (iv) the utility of QTL analysis in clarifying the role of specific genes in a biochemical pathway, and (v) identification of a previously unknown locus on chromosome 9S affecting flavone level. A greater understanding of the genetic basis of maysin synthesis and associated corn earworm resistance should lead to improved breeding strategies. More broadly, the insights gained in relating a defined genetic and biochemical pathway affecting a quantitative trait should enhance interpretation of the biological basis of variation for other quantitative traits. PMID:9482823

  18. Synthesis, Structure Elucidation, and Redox Properties of (superscript 99)Tc Complexes of Lacunary Wells-Dawson Polyoxometalates: Insights into Molecular (superscript 99)Tc-Metal Oxide Interactions

    International Nuclear Information System (INIS)

    McGregor, Donna; Burton-Pye, Benjamin P.; Howell, Robertha C.; Mbomekalle, Israel M.; Lukens, Wayne W. Jr.; Bian, Fang; Mausolf, Edward; Poineau, Frederic; Czerwinski, Kenneth R.; Francesconi, Lynn C.

    2011-01-01

    The isotope 99 Tc (β max , 293.7; half-life, 2.1 x 10 5 years) is an abundant product of uranium-235 fission in nuclear reactors and is present throughout the radioactive waste stored in underground tanks at the Hanford and Savannah River sites. Understanding and controlling the extensive redox chemistry of 99 Tc is important in identifying tunable strategies to separate 99 Tc from spent fuel and from waste tanks and, once separated, to identify and develop an appropriately stable waste form for 99 Tc. Polyoxometalates (POMs), nanometer-sized models for metal oxide solid-state materials, are used in this study to provide a molecular level understanding of the speciation and redox chemistry of incorporated 99 Tc. In this study, 99 Tc complexes of the (α 2 -P 2 W 17 O 61 ) 10- and (α 1 -P 2 W 17 O 61 ) 10- isomers were prepared. Ethylene glycol was used as a 'transfer ligand' to minimize the formation of TcO 2 · xH 2 O. The solution structures, formulations, and purity of TcVO(α 1 /α 2 -P 2 W 17 O 61 ) 7- were determined by multinuclear NMR. X-ray absorption spectroscopy of the complexes is in agreement with the formulation and structures determined from 31 P and 183 W NMR. Preliminary electrochemistry results are consistent with the EXAFS results, showing a facile reduction of the TcVO(α 1 -P 2 W 17 O 61 ) 7- species compared to the TcVO(α 2 -P 2 W 17 O 61 ) 7- analog. The α 1 defect is unique in that a basic oxygen atom is positioned toward the α 1 site, and the Tc V O center appears to form a dative metal-metal bond with a framework W site. These attributes may lead to the assistance of protonation events that facilitate reduction. Electrochemistry comparison shows that the ReV analogs are about 200 mV more difficult to reduce in accordance with periodic trends.

  19. Synthesis, structure elucidation and redox properties of 99Tc complexes of lacunary Wells Dawson polyoxometalates: insights into molecular 99Tc - metal oxide interactions

    International Nuclear Information System (INIS)

    McGregor, Donna; Burton-Pye, Benjamin P.; Howell, Robertha C.; Mbomekalle, Israel M.; Lukens, Wayne W. Jr; Bian, Fang; Mausolf, Edward; Poineau, Frederic; Czerwinski, Kenneth R; Francesconi, Lynn C.

    2011-01-01

    The isotope 99 Tc (β max : 250 keV, half-life: 2 x 10 5 year) is an abundant product of uranium-235 fission in nuclear reactors and is present throughout the radioactive waste stored in underground tanks at Hanford and Savannah River. Understanding and controlling the extensive redox chemistry of 99 Tc is important to identify tunable strategies to separate 99 Tc from spent fuel and from waste tanks and once separated, to identify and develop an appropriately stable waste-form for 99 Tc. Polyoxometalates (POMs), nanometer sized models for metal oxide solid-state materials, are used in this study to provide a molecular level understanding of the speciation and redox chemistry of incorporated 99 Tc. In this study, 99 Tc complexes of the (α 2 -P 2 W 17 O 61 ) 10- and (α 1 -P 2 W 17 O 61 ) 10- isomers were prepared. Ethylene glycol was used as a 'transfer ligand' to minimize the formation of TcO 2 · xH 2 O. The solution structures, formulations, and purity of Tc V O(α 1 /α 2 -P 2 W 17 O 61 ) 7- were determined by multinuclear NMR. X-ray Absorption Spectroscopy of the complexes are in agreement with the formulation and structures determined from 31 P and 183 W NMR. Preliminary electrochemistry results are consistent with the EXAFS results, showing a facile reduction of the Tc V O(α 1 -P 2 W 17 O 61 ) 7- species compared to the Tc V O(α 2 -P 2 W 17 O 61 ) 7- analog. The α 1 -defect is unique in that a basic oxygen atom is positioned toward the α 1 -site and the Tc V O center appears to form a dative metal-metal bond with a framework W site. These attributes may lead to the assistance of protonation events that facilitate reduction. Electrochemistry comparison shows that the Re V analogs are about 200 mV more difficult to reduce in accordance with periodic trends.

  20. The role of particle jamming on the formation and stability of step-pool morphology: insight from a reduced-complexity model

    Science.gov (United States)

    Saletti, M.; Molnar, P.; Hassan, M. A.

    2017-12-01

    Granular processes have been recognized as key drivers in earth surface dynamics, especially in steep landscapes because of the large size of sediment found in channels. In this work we focus on step-pool morphologies, studying the effect of particle jamming on step formation. Starting from the jammed-state hypothesis, we assume that grains generate steps because of particle jamming and those steps are inherently more stable because of additional force chains in the transversal direction. We test this hypothesis with a particle-based reduced-complexity model, CAST2, where sediment is organized in patches and entrainment, transport and deposition of grains depend on flow stage and local topography through simplified phenomenological rules. The model operates with 2 grain sizes: fine grains, that can be mobilized both my large and moderate flows, and coarse grains, mobile only during large floods. First, we identify the minimum set of processes necessary to generate and maintain steps in a numerical channel: (a) occurrence of floods, (b) particle jamming, (c) low sediment supply, and (d) presence of sediment with different entrainment probabilities. Numerical results are compared with field observations collected in different step-pool channels in terms of step density, a variable that captures the proportion of the channel occupied by steps. Not only the longitudinal profiles of numerical channels display step sequences similar to those observed in real step-pool streams, but also the values of step density are very similar when all the processes mentioned before are considered. Moreover, with CAST2 it is possible to run long simulations with repeated flood events, to test the effect of flood frequency on step formation. Numerical results indicate that larger step densities belong to system more frequently perturbed by floods, compared to system having a lower flood frequency. Our results highlight the important interactions between external hydrological forcing and

  1. Structural context and variation of ocean plate stratigraphy, Franciscan Complex, California: insight into mélange origins and subduction-accretion processes

    Science.gov (United States)

    Wakabayashi, John

    2017-12-01

    The transfer (accretion) of materials from a subducting oceanic plate to a subduction-accretionary complex has produced rock assemblages recording the history of the subducted oceanic plate from formation to arrival at the trench. These rock assemblages, comprising oceanic igneous rocks progressively overlain by pelagic sedimentary rocks (chert and/or limestone) and trench-fill clastic sedimentary rocks (mostly sandstone, shale/mudstone), have been called ocean plate stratigraphy (OPS). During accretion of OPS, megathrust slip is accommodated by imbricate faults and penetrative strain, shortening the unit and leading to tectonic repetition of the OPS sequence, whereas OPS accreted at different times are separated by non-accretionary megathrust horizons. The Franciscan subduction complex of California accreted episodically over a period of over 150 million years and incorporated OPS units with a variety of characteristics separated by non-accretionary megathrust horizons. Most Franciscan OPS comprises MORB (mid-ocean-ridge basalt) progressively overlain by chert and trench-fill clastic sedimentary rocks that are composed of variable proportions of turbidites and siliciclastic and serpentinite-matrix olistostromes (sedimentary mélanges). Volumetrically, the trench-fill component predominates in most Franciscan OPS, but some units have a significant component of igneous and pelagic rocks. Ocean island basalt (OIB) overlain by limestone is less common than MORB-chert assemblages, as are abyssal serpentinized peridotite slabs. The earliest accreted OPS comprises metabasite of supra-subduction zone affinity imbricated with smaller amounts of metaultramafic rocks and metachert, but lacking a clastic component. Most deformation of Franciscan OPS is localized along discrete faults rather than being distributed in the form of penetrative strain. This deformation locally results in block-in-matrix tectonic mélanges, in contrast to the sedimentary mélanges making up part of

  2. Chromosomes 3B and 4D are associated with several milling and baking quality traits in a soft white spring wheat (Triticum aestivum L.) population.

    Science.gov (United States)

    Carter, A H; Garland-Campbell, K; Morris, C F; Kidwell, K K

    2012-04-01

    Wheat is marketed based on end-use quality characteristics and better knowledge of the underlying genetics of specific quality parameters is essential to enhance the breeding process. A set of 188 recombinant inbred lines from a 'Louise' by 'Penawawa' mapping population was grown in two crop years at two locations in the Pacific Northwest region of the United States and data were collected on 17 end-use quality traits using established quality analysis protocols. Using an established genetic linkage map, composite interval mapping was used to identify QTL associated with 16 of the 17 quality traits. QTL were found on 13 of the 21 wheat chromosomes. A large number of QTL were located on chromosomes 3B and 4D and coincided with traits for milling quality and starch functionality. Chromosome 3B contained 10 QTL, which were localized to a 26.2 cM region. Chromosome 4D contained 7 QTL, all of which were located on an 18.8 cM region of this chromosome. The majority of the alleles for superior end-use quality were associated with the cultivar Louise. The identified QTL detected remained highly significant independent of grain yield and protein quantity. The identification of these QTL for end-use quality gives key insight into the relationship and complexity of end-use quality traits. It also improves our understanding of these relationships, thereby allowing plant breeders to make valuable gains from selection for these important traits.

  3. Root traits contributing to plant productivity under drought

    Directory of Open Access Journals (Sweden)

    Louise eComas

    2013-11-01

    Full Text Available Geneticists and breeders are positioned to breed plants with root traits that improve productivity under drought. However, a better understanding of root functional traits and how traits are related to whole plant strategies to increase crop productivity under different drought conditions is needed. Root traits associated with maintaining plant productivity under drought include small fine root diameters, long specific root length (SRL, and considerable root length density, especially at depths in soil with available water. In environments with late season water deficits, small xylem diameters in targeted seminal roots save soil water deep in the soil profile for use during crop maturation and result in improved yields. Capacity for deep root growth and large xylem diameters in deep roots may also improve root acquisition of water when ample water at depth is available. Xylem pit anatomy that makes xylem less ‘leaky’ and prone to cavitation warrants further exploration holding promise that such traits may improve plant productivity in water-limited environments without negatively impacting yield under adequate water conditions. Rapid resumption of root growth following soil rewetting may improve plant productivity under episodic drought. Genetic control of many of these traits through breeding appears feasible. Several recent reviews have covered methods for screening root traits but an appreciation for the complexity of root systems (e.g. functional differences between fine and coarse roots needs to be paired with these methods to successfully identify relevant traits for crop improvement. Screening of root traits at early stages in plant development can proxy traits at mature stages but verification is needed on a case by case basis that traits are linked to increased crop productivity under drought. Examples in lesquerella (Physaria and rice (Oryza show approaches to phenotyping of root traits and current understanding of root trait

  4. Multi-locus sequence typing provides epidemiological insights for diseased sharks infected with fungi belonging to the Fusarium solani species complex.

    Science.gov (United States)

    Desoubeaux, Guillaume; Debourgogne, Anne; Wiederhold, Nathan P; Zaffino, Marie; Sutton, Deanna; Burns, Rachel E; Frasca, Salvatore; Hyatt, Michael W; Cray, Carolyn

    2018-07-01

    Fusarium spp. are saprobic moulds that are responsible for severe opportunistic infections in humans and animals. However, we need epidemiological tools to reliably trace the circulation of such fungal strains within medical or veterinary facilities, to recognize environmental contaminations that might lead to infection and to improve our understanding of factors responsible for the onset of outbreaks. In this study, we used molecular genotyping to investigate clustered cases of Fusarium solani species complex (FSSC) infection that occurred in eight Sphyrnidae sharks under managed care at a public aquarium. Genetic relationships between fungal strains were determined by multi-locus sequence typing (MLST) analysis based on DNA sequencing at five loci, followed by comparison with sequences of 50 epidemiologically unrelated FSSC strains. Our genotyping approach revealed that F. keratoplasticum and F. solani haplotype 9x were most commonly isolated. In one case, the infection proved to be with another Hypocrealian rare opportunistic pathogen Metarhizium robertsii. Twice, sharks proved to be infected with FSSC strains with the same MLST sequence type, supporting the hypothesis the hypothesis that common environmental populations of fungi existed for these sharks and would suggest the longtime persistence of the two clonal strains within the environment, perhaps in holding pools and life support systems of the aquarium. This study highlights how molecular tools like MLST can be used to investigate outbreaks of microbiological disease. This work reinforces the need for regular controls of water quality to reduce microbiological contamination due to waterborne microorganisms.

  5. Crystal Structure of the Homo sapiens Kynureninase-3-Hydroxyhippuric Acid Inhibitor Complex: Insights into the Molecular Basis Of Kynureninase Substrate Specificity

    Energy Technology Data Exchange (ETDEWEB)

    Lima,Santiago; Kumar,Sunil; Gawandi,Vijay; Momany,Cory; Phillips,Robert S.; (Georgia)

    2009-02-23

    Homo sapiens kynureninase is a pyridoxal-5'-phosphate dependent enzyme that catalyzes the hydrolytic cleavage of 3-hydroxykynurenine to yield 3-hydroxyanthranilate and L-alanine as part of the tryptophan catabolic pathway leading to the de novo biosynthesis of NAD{sup +}. This pathway results in quinolinate, an excitotoxin that is an NMDA receptor agonist. High levels of quinolinate have been correlated with the etiology of neurodegenerative disorders such as AIDS-related dementia and Alzheimer's disease. We have synthesized a novel kynureninase inhibitor, 3-hydroxyhippurate, cocrystallized it with human kynureninase, and solved the atomic structure. On the basis of an analysis of the complex, we designed a series of His-102, Ser-332, and Asn-333 mutants. The H102W/N333T and H102W/S332G/N333T mutants showed complete reversal of substrate specificity between 3-hydroxykynurenine and L-kynurenine, thus defining the primary residues contributing to substrate specificity in kynureninases.

  6. Evolution of phosphorus complexation and mineralogy during (hydro)thermal treatments of activated and anaerobically digested sludge: Insights from sequential extraction and P K-edge XANES.

    Science.gov (United States)

    Huang, Rixiang; Tang, Yuanzhi

    2016-09-01

    (Hydro)thermal treatments of sewage sludge is a promising option that can simultaneously target safe waste disposal, energy recovery, and nutrient recovery/recycling. The speciation of phosphorus (P) in sludge is of great relevance to P reclamation/recycling and soil application of sludge-derived products, thus it is critical to understand the effects of different treatment techniques and conditions on P speciation. This study systematically characterized P speciation (i.e. complexation and mineral forms) in chars derived from pyrolysis and hydrothermal carbonization (HTC) of municipal sewage sludges. Combined sequential extraction and P K-edge X-ray absorption near edge structure (XANES) spectroscopy analysis revealed the dependence of P transformation on treatment conditions and metal composition in the feedstocks. Pyrolysis of sludges decreased the relative abundance of phytic acid while increased the abundance of Al-associated P. HTC thoroughly homogenized and exposed P for interaction with various metals/minerals, with the final P speciation closely related to the composition/speciation of metals and their affinities to P. Results from this study revealed the mechanisms of P transformation during (hydro)thermal treatments of sewage sludges, and might be applicable to other biosolids. It also provided fundamental knowledge basis for the design and selection of waste management strategies for better P (re)cycling and reclamation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Glycoconjugate Oxime Formation Catalyzed at Neutral pH: Mechanistic Insights and Applications of 1,4-Diaminobenzene as a Superior Catalyst for Complex Carbohydrates.

    Science.gov (United States)

    Østergaard, Mads; Christensen, Niels Johan; Hjuler, Christian T; Jensen, Knud J; Thygesen, Mikkel B

    2018-04-18

    The reaction of unprotected carbohydrates with aminooxy reagents to provide oximes is a key method for the construction of glycoconjugates. Aniline and derivatives serve as organocatalysts for the formation of oximes from simple aldehydes, and we have previously reported that aniline also catalyzes the formation of oximes from the more complex aldehydes, carbohydrates. Here, we present a comprehensive study of the effect of aniline analogues on the formation of carbohydrate oximes and related glycoconjugates depending on organocatalyst structure, pH, nucleophile, and carbohydrate, covering more than 150 different reaction conditions. The observed superiority of the 1,4-diaminobenzene (PDA) catalyst at neutral pH is rationalized by NMR analyses and DFT studies of reaction intermediates. Carbohydrate oxime formation at pH 7 is demonstrated by the formation of a bioactive glycoconjugate from a labile, decorated octasaccharide originating from exopolysaccharides of the soil bacterium Mesorhizobium loti. This study of glycoconjugate formation includes the first direct comparison of aniline-catalyzed reaction rates and equilibrium constants for different classes of nucleophiles, including primary oxyamines, secondary N-alkyl oxyamines, as well as aryl and arylsulfonyl hydrazides. We identified 1,4-diaminobenzene as a superior catalyst for the construction of oxime-linked glycoconjugates under mild conditions.

  8. Structure-based in silico identification of ubiquitin-binding domains provides insights into the ALIX-V:ubiquitin complex and retrovirus budding

    Science.gov (United States)

    Keren-Kaplan, Tal; Attali, Ilan; Estrin, Michael; Kuo, Lillian S; Farkash, Efrat; Jerabek-Willemsen, Moran; Blutraich, Noa; Artzi, Shay; Peri, Aviyah; Freed, Eric O; Wolfson, Haim J; Prag, Gali

    2013-01-01

    The ubiquitylation signal promotes trafficking of endogenous and retroviral transmembrane proteins. The signal is decoded by a large set of ubiquitin (Ub) receptors that tether Ub-binding domains (UBDs) to the trafficking machinery. We developed a structure-based procedure to scan the protein data bank for hidden UBDs. The screen retrieved many of the known UBDs. Intriguingly, new potential UBDs were identified, including the ALIX-V domain. Pull-down, cross-linking and E3-independent ubiquitylation assays biochemically corroborated the in silico findings. Guided by the output model, we designed mutations at the postulated ALIX-V:Ub interface. Biophysical affinity measurements using microscale-thermophoresis of wild-type and mutant proteins revealed some of the interacting residues of the complex. ALIX-V binds mono-Ub with a Kd of 119 μM. We show that ALIX-V oligomerizes with a Hill coefficient of 5.4 and IC50 of 27.6 μM and that mono-Ub induces ALIX-V oligomerization. Moreover, we show that ALIX-V preferentially binds K63 di-Ub compared with mono-Ub and K48 di-Ub. Finally, an in vivo functionality assay demonstrates the significance of ALIX-V:Ub interaction in equine infectious anaemia virus budding. These results not only validate the new procedure, but also demonstrate that ALIX-V directly interacts with Ub in vivo and that this interaction can influence retroviral budding. PMID:23361315

  9. Structure-based in silico identification of ubiquitin-binding domains provides insights into the ALIX-V:ubiquitin complex and retrovirus budding.

    Science.gov (United States)

    Keren-Kaplan, Tal; Attali, Ilan; Estrin, Michael; Kuo, Lillian S; Farkash, Efrat; Jerabek-Willemsen, Moran; Blutraich, Noa; Artzi, Shay; Peri, Aviyah; Freed, Eric O; Wolfson, Haim J; Prag, Gali

    2013-02-20

    The ubiquitylation signal promotes trafficking of endogenous and retroviral transmembrane proteins. The signal is decoded by a large set of ubiquitin (Ub) receptors that tether Ub-binding domains (UBDs) to the trafficking machinery. We developed a structure-based procedure to scan the protein data bank for hidden UBDs. The screen retrieved many of the known UBDs. Intriguingly, new potential UBDs were identified, including the ALIX-V domain. Pull-down, cross-linking and E3-independent ubiquitylation assays biochemically corroborated the in silico findings. Guided by the output model, we designed mutations at the postulated ALIX-V:Ub interface. Biophysical affinity measurements using microscale-thermophoresis of wild-type and mutant proteins revealed some of the interacting residues of the complex. ALIX-V binds mono-Ub with a K(d) of 119 μM. We show that ALIX-V oligomerizes with a Hill coefficient of 5.4 and IC(50) of 27.6 μM and that mono-Ub induces ALIX-V oligomerization. Moreover, we show that ALIX-V preferentially binds K63 di-Ub compared with mono-Ub and K48 di-Ub. Finally, an in vivo functionality assay demonstrates the significance of ALIX-V:Ub interaction in equine infectious anaemia virus budding. These results not only validate the new procedure, but also demonstrate that ALIX-V directly interacts with Ub in vivo and that this interaction can influence retroviral budding.

  10. Insights into the mechanism of drug resistance: X-ray structure analysis of G48V/C95F tethered HIV-1 protease dimer/saquinavir complex

    International Nuclear Information System (INIS)

    Prashar, Vishal; Bihani, Subhash C.; Das, Amit; Rao, D.R.; Hosur, M.V.

    2010-01-01

    The mutation G48V in HIV-1 protease is a major resistance mutation against the drug saquinavir. Recently, G48V mutation is found to co-exist with the mutation C95F in AIDS patients treated with saquinavir. We report here the three-dimensional crystal structure of G48V/C95F tethered HIV-1 protease/saquinavir complex. The structure indicates following as the possible causes of drug resistance: (1) loss of direct van der Waals interactions between saquinavir and enzyme residues PHE-53 and PRO-1081, (2) loss of water-mediated hydrogen bonds between the carbonyl oxygen atoms in saquinavir and amide nitrogen atoms of flap residues 50 and 1050, (3) changes in inter-monomer interactions, which could affect the energetics of domain movements associated with inhibitor-binding, and (4) significant reduction in the stability of the mutant dimer. The present structure also provides a rationale for the clinical observation that the resistance mutations C95F/G48V/V82A occur as a cluster in AIDS patients.

  11. Getting an Insight into the Complexity of Major Chronic Inflammatory and Degenerative Diseases: A Potential New Systemic Approach to Their Treatment.

    Science.gov (United States)

    Biava, Pier M; Norbiato, Guido

    2015-01-01

    As the modern society is troubled by multi-factorial diseases, research has been conducted on complex realities including chronic inflammation, cancer, obesity, HIV infection, metabolic syndrome and its detrimental cardiovascular complications as well as depression and other brain disorders. Deterioration of crucial homeostatic mechanisms in such diseases invariably results in activation of inflammatory mediators, chronic inflammation, loss in immunological function, increased susceptibility to diseases, alteration of metabolism, decrease of energy production and neuro-cognitive decline. Regulation of genes expression by epigenetic code is the dominant mechanism for the transduction of environmental inputs, such as stress and inflammation to lasting physiological changes. Acute and chronic stress determines DNA methylation and histone modifications in brain regions which may contribute to neuro-degenerative disorders. Nuclear glucocorticoids receptor interacts with the epigenoma resulting in a cortisol resistance status associated with a deterioration of the metabolic and immune functions. Gonadal steroids receptors have a similar capacity to produce epigenomic reorganization of chromatine structure. Epigenomic-induced reduction in immune cells telomeres length has been observed in many degenerative diseases, including all types of cancer. The final result of these epigenetic alterations is a serious damage to the neuro-endocrine-immune-metabolic adaptive systems. In this study, we propose a treatment with stem cells differentiation stage factors taken from zebrafish embryos which are able to regulate the genes expression of normal and pathological stem cells in a different specific way.

  12. Structure of a bacterial glycoside hydrolase family 63 enzyme in complex with its glycosynthase product, and insights into the substrate specificity.

    Science.gov (United States)

    Miyazaki, Takatsugu; Ichikawa, Megumi; Yokoi, Gaku; Kitaoka, Motomitsu; Mori, Haruhide; Kitano, Yoshikazu; Nishikawa, Atsushi; Tonozuka, Takashi

    2013-09-01

    Proteins belonging to glycoside hydrolase family 63 (GH63) are found in bacteria, archaea and eukaryotes. Although the eukaryotic GH63 proteins have been identified as processing α-glucosidase I, the substrate specificities of the bacterial and archaeal GH63 proteins are not clear. Here, we converted a bacterial GH63 enzyme, Escherichia coli YgjK, to a glycosynthase to probe its substrate specificity. Two mutants of YgjK (E727A and D324N) were constructed, and both mutants showed glycosynthase activity. The reactions of E727A with β-D-glucosyl fluoride and monosaccharides showed that the largest amount of glycosynthase product accumulated when galactose was employed as an acceptor molecule. The crystal structure of E727A complexed with the reaction product indicated that the disaccharide bound at the active site was 2-O-α-D-glucopyranosyl-α-D-galactopyranose (Glc12Gal). A comparison of the structures of E727A-Glc12Gal and D324N-melibiose showed that there were two main types of conformation: the open and closed forms. The structure of YgjK adopted the closed form when subsite -1 was occupied by glucose. These results suggest that sugars containing the Glc12Gal structure are the most likely candidates for natural substrates of YgjK. © 2013 FEBS.

  13. Trait plasticity in species interactions: a driving force of community dynamics.

    NARCIS (Netherlands)

    Berg, M.P.; Ellers, J.

    2010-01-01

    Evolutionary community ecology is an emerging field of study that includes evolutionary principles such as individual trait variation and plasticity of traits to provide a more mechanistic insight as to how species diversity is maintained and community processes are shaped across time and space. In

  14. Genome-wide association study for behavior, type traits, and muscular development in Charolais beef cattle

    NARCIS (Netherlands)

    Vallée, A.; Daures, J.; Arendonk, van J.A.M.; Bovenhuis, H.

    2016-01-01

    Behavior, type traits, and muscular development are of interest for beef cattle breeding. Genome-wide association studies (GWAS) enable the identification of candidate genes, which enables genebased selection and provides insight in the genetic architecture of these traits. The objective of the

  15. Cerebellum and personality traits.

    Science.gov (United States)

    Petrosini, Laura; Cutuli, Debora; Picerni, Eleonora; Laricchiuta, Daniela

    2015-02-01

    Personality traits are multidimensional traits comprising cognitive, emotional, and behavioral characteristics, and a wide array of cerebral structures mediate individual variability. Differences in personality traits covary with brain morphometry in specific brain regions. A cerebellar role in emotional and affective processing and on personality characteristics has been suggested. In a large sample of healthy subjects of both sexes and differently aged, the macro- and micro-structural variations of the cerebellum were correlated with the scores obtained in the Temperament and Character Inventory (TCI) by Cloninger. Cerebellar volumes were associated positively with Novelty Seeking scores and negatively with Harm Avoidance scores. Given the cerebellar contribution in personality traits and emotional processing, we investigated the cerebellar involvement even in alexithymia, construct of personality characterized by impairment in cognitive, emotional, and affective processing. Interestingly, the subjects with high alexithymic traits had larger volumes in the bilateral Crus 1. The cerebellar substrate for some personality dimensions extends the relationship between personality and brain areas to a structure up to now thought to be involved mainly in motor and cognitive functions, much less in emotional processes and even less in personality individual differences. The enlarged volumes of Crus 1 in novelty seekers and alexithymics support the tendency to action featuring both personality constructs. In fact, Novelty Seeking and alexithymia are rooted in behavior and inescapably have a strong action component, resulting in stronger responses in the structures more focused on action and embodiment, as the cerebellum is.

  16. Adrenal cortex expression quantitative trait loci in a German Holstein × Charolais cross.

    Science.gov (United States)

    Brand, Bodo; Scheinhardt, Markus O; Friedrich, Juliane; Zimmer, Daisy; Reinsch, Norbert; Ponsuksili, Siriluck; Schwerin, Manfred; Ziegler, Andreas

    2016-10-06

    insight into the molecular and genetic background of complex traits in cattle and will help to understand molecular networks involved.

  17. Linking the southern West Junggar terrane to the Yili Block: Insights from the oldest accretionary complexes in West Junggar, NW China

    Science.gov (United States)

    Ren, Rong; Han, Bao-Fu; Guan, Shu-Wei; Liu, Bo; Wang, Zeng-Zhen

    2018-06-01

    West Junggar is known to tectonically correlate with East Kazakhstan; however, the tectonic link of the southern West Junggar terrane to adjacent regions still remains uncertain. Here, we examined the oldest accretionary complexes, thus constraining its tectonic evolution and link during the Early-Middle Paleozoic. They have contrasting lithologic, geochemical, and geochronological features and thus, provenances and tectonic settings. The Laba Unit was derived from the Late Ordovician-Early Devonian continental arc system (peaking at 450-420 Ma) with Precambrian substrate, which formed as early as the Early Devonian and metamorphosed during the Permian; however, the Kekeshayi Unit was accumulated in an intra-oceanic arc setting, and includes the pre-Late Silurian and Late Silurian subunits with or without Precambrian sources. Integrated with the regional data, the southern West Junggar terrane revealed a tectonic link to the northern Yili Block during the Late Silurian to Early Devonian, as suggested by the comparable Precambrian zircon age spectra between the southern West Junggar terrane and the micro-continents in the southern Kazakhstan Orocline, the proximal accumulation of the Laba Unit in the continental arc atop the Yili Block, and the sudden appearance of Precambrian zircons in the Kekeshayi Unit during the Late Silurian. This link rejects the proposals of the southern West Junggar terrane as an extension of the northern Kazakhstan Orocline and the Middle Paleozoic amalgamation of West Junggar. A new linking model is thus proposed, in which the southern West Junggar terrane first evolved individually, and then collided with the Yili Block to constitute the Kazakhstan continent during the Late Silurian. The independent and contrasting intra-oceanic and continental arcs also support the Paleozoic archipelago-type evolution of the Central Asian Orogenic Belt.

  18. Giant panda genomic data provide insight into the birth-and-death process of mammalian major histocompatibility complex class II genes.

    Directory of Open Access Journals (Sweden)

    Qiu-Hong Wan

    Full Text Available To gain an understanding of the genomic structure and evolutionary history of the giant panda major histocompatibility complex (MHC genes, we determined a 636,503-bp nucleotide sequence spanning the MHC class II region. Analysis revealed that the MHC class II region from this rare species contained 26 loci (17 predicted to be expressed, of which 10 are classical class II genes (1 DRA, 2 DRB, 2 DQA, 3 DQB, 1 DYB, 1 DPA, and 2 DPB and 4 are non-classical class II genes (1 DOA, 1 DOB, 1 DMA, and 1 DMB. The presence of DYB, a gene specific to ruminants, prompted a comparison of the giant panda class II sequence with those of humans, cats, dogs, cattle, pigs, and mice. The results indicated that birth and death events within the DQ and DRB-DY regions led to major lineage differences, with absence of these regions in the cat and in humans and mice respectively. The phylogenetic trees constructed using all expressed alpha and beta genes from marsupials and placental mammals showed that: (1 because marsupials carry loci corresponding to DR, DP, DO and DM genes, those subregions most likely developed before the divergence of marsupials and placental mammals, approximately 150 million years ago (MYA; (2 conversely, the DQ and DY regions must have evolved later, but before the radiation of placental mammals (100 MYA. As a result, the typical genomic structure of MHC class II genes for the giant panda is similar to that of the other placental mammals and corresponds to BTNL2 approximately DR1 approximately DQ approximately DR2 approximately DY approximately DO_box approximately DP approximately COL11A2. Over the past 100 million years, there has been birth and death of mammalian DR, DQ, DY, and DP genes, an evolutionary process that has brought about the current species-specific genomic structure of the MHC class II region. Furthermore, facing certain similar pathogens, mammals have adopted intra-subregion (DR and DQ and inter-subregion (between DQ and DP

  19. A first insight on the population structure of Mycobacterium tuberculosis complex as studied by spoligotyping and MIRU-VNTRs in Santiago, Chile.

    Science.gov (United States)

    Balcells, María Elvira; García, Patricia; Meza, Paulina; Peña, Carlos; Cifuentes, Marcela; Couvin, David; Rastogi, Nalin

    2015-01-01

    Tuberculosis (TB) remains a significant public health problem worldwide, but the ecology of the prevalent mycobacterial strains, and their transmission, can vary depending on country and region. Chile is a country with low incidence of TB, that has a geographically isolated location in relation to the rest of South American countries due to the Andes Mountains, but recent migration from neighboring countries has changed this situation. We aimed to assess the genotypic diversity of Mycobacterium tuberculosis complex (MTBC) strains in Santiago, Chile, and compare with reports from other Latin-American countries. We analyzed MTBC isolates from pulmonary tuberculosis cases collected between years 2008 and 2013 in Central Santiago, using two genotyping methods: spoligotyping and 12-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTRs). Data obtained were analyzed and compared to the SITVIT2 database. Mean age of the patients was 47.5 years and 61% were male; 11.6% were migrants. Of 103 strains (1 isolate/patient) included, there were 56 distinct spoligotype patterns. Of these, 16 strains (15.5%) corresponded to orphan strains in the SITVIT2 database, not previously reported. Latin American and Mediterranean (LAM) (34%) and T (33%) lineages were the most prevalent strains, followed by Haarlem lineage (16.5%). Beijing family was scarcely represented with only two cases (1.9%), one of them isolated from a Peruvian migrant. The most frequent clustered spoligotypes were SIT33/LAM3 (10.7%), SIT53/T1 (8.7%), SIT50/H3 (7.8%), and SIT37/T3 (6.8%). We conclude that LAM and T genotypes are the most prevalent genotypes of MTBC in Santiago, Chile, and together correspond to almost two thirds of analyzed strains, which is similar to strain distribution reported from other countries of Latin America. Nevertheless, the high proportion of SIT37/T3, which was rarely found in other Latin American countries, may underline a specific history or

  20. Response of methane emissions from wetlands to the Last Glacial Maximum and an idealized Dansgaard–Oeschger climate event: insights from two models of different complexity

    Directory of Open Access Journals (Sweden)

    B. Ringeval

    2013-01-01

    Full Text Available The role of different sources and sinks of CH4 in changes in atmospheric methane ([CH4] concentration during the last 100 000 yr is still not fully understood. In particular, the magnitude of the change in wetland CH4 emissions at the Last Glacial Maximum (LGM relative to the pre-industrial period (PI, as well as during abrupt climatic warming or Dansgaard–Oeschger (D–O events of the last glacial period, is largely unconstrained. In the present study, we aim to understand the uncertainties related to the parameterization of the wetland CH4 emission models relevant to these time periods by using two wetland models of different complexity (SDGVM and ORCHIDEE. These models have been forced by identical climate fields from low-resolution coupled atmosphere–ocean general circulation model (FAMOUS simulations of these time periods. Both emission models simulate a large decrease in emissions during LGM in comparison to PI consistent with ice core observations and previous modelling studies. The global reduction is much larger in ORCHIDEE than in SDGVM (respectively −67 and −46%, and whilst the differences can be partially explained by different model sensitivities to temperature, the major reason for spatial differences between the models is the inclusion of freezing of soil water in ORCHIDEE and the resultant impact on methanogenesis substrate availability in boreal regions. Besides, a sensitivity test performed with ORCHIDEE in which the methanogenesis substrate sensitivity to the precipitations is modified to be more realistic gives a LGM reduction of −36%. The range of the global LGM decrease is still prone to uncertainty, and here we underline its sensitivity to different process parameterizations. Over the course of an idealized D–O warming, the magnitude of the change in wetland CH4 emissions simulated by the two models at global scale is very similar at around 15 Tg yr−1, but this is only around 25% of the ice-core measured

  1. The Dovyren Intrusive Complex (Southern Siberia, Russia): Insights into dynamics of an open magma chamber with implications for parental magma origin, composition, and Cu-Ni-PGE fertility

    Science.gov (United States)

    Ariskin, Alexey; Danyushevsky, Leonid; Nikolaev, Georgy; Kislov, Evgeny; Fiorentini, Marco; McNeill, Andrew; Kostitsyn, Yuri; Goemann, Karsten; Feig, Sandrin T.; Malyshev, Alexey

    2018-03-01

    The Dovyren Intrusive Complex (DIC, Northern Baikal region, 728 Ma) includes the layered dunite-troctolite-gabbronorite Yoko-Dovyren massif (YDM), associated mafic-ultramafic sills, and dykes of olivine-rich to olivine-free gabbronorite. Major rock types of the DIC are presented, including a diversity of olivine orthocumulates to olivine-plagioclase and gabbroic adcumulates, carbonate-contaminated ultramafics and Cu-Ni-PGE mineralisation. Detailed comparisons of complete cross-sections of the YDM in its centre and at the NE and SW margins demonstrate differences in the cumulate succession, mineral chemistry, and geochemical structure that likely reflect variations in parental magma compositions. Combining petrochemical reconstructions for most primitive rocks and calculations using the COMAGMAT-5 model, it is shown that the central and peripheral parts of the intrusion formed by olivine-laden parental magmas ranged in their temperatures by 100 °C, approximately from 1290 °C ( 11 wt% MgO, olivine Fo88) to 1190 °C ( 8 wt% MgO, olivine Fo86). Thermodynamic modelling suggests that the most primitive high-Mg magma was S-undersaturated, whereas its derivatives became S-saturated at T piles to generate poorly-mineralised plagiodunite. In the troctolite and gabbroic parts of the Dovyren chamber, sulphide immiscibility likely occurred at lower temperatures, producing Cu-rich sulphide precursors, which gave rise to the 'platinum group mineral' (PGM-containing) troctolite and low-mineralised PGE-rich anorthosite in the Main Reef. The geochemical structure of the YDM demonstrates C-shaped distributions of TiO2, K2O, P2O5, and incompatible trace elements, which are 3-5 fold depleted in the cumulate rocks from the inner horizons of the intrusion with respect to the relatively thin lower and upper contact zones. In addition, a marked misbalance between estimates of the average composition of the YDM and that of the proposed olivine-laden parental magmas is established. This

  2. Length Scales and Types of Heterogeneities Along the Deep Subduction Interface: Insights From an Exhumed Subduction Complex on Syros Island, Greece

    Science.gov (United States)

    Kotowski, A. J.; Behr, W. M.; Tong, X.; Lavier, L.

    2017-12-01

    The rheology of the deep subduction interface strongly influences the occurrence, recurrence, and migration of episodic tremor and slow slip (ETS) events. To better understand the environment of deep ETS, we characterize the length scales and types of rheological heterogeneities that decorate the deep interface using an exhumed subduction complex. The Cycladic Blueschist Unit on Syros, Greece, records Eocene subduction to 60 km, partial exhumation along the top of the slab, and final exhumation along Miocene detachment faults. The CBU reached 450-580˚C and 14-16 kbar, PT conditions similar to where ETS occurs in several modern subduction zones. Rheological heterogeneity is preserved in a range of rock types on Syros, with the most prominent type being brittle pods embedded within a viscous matrix. Prograde, blueschist-facies metabasalts show strong deformation fabrics characteristic of viscous flow; cm- to m-scale eclogitic lenses are embedded within them as massive, veined pods, foliated pods rotated with respect to the blueschist fabric, and attenuated, foliation-parallel lenses. Similar relationships are observed in blueschist-facies metasediments interpreted to have deformed during early exhumation. In these rocks, metabasalts form lenses ranging in size from m- to 10s of m and are distributed at the m-scale throughout the metasedimentary matrix. Several of the metamafic lenses, and the matrix rocks immediately adjacent to them, preserve multiple generations of dilational veins and shear fractures filled with quartz and high pressure minerals. These observations suggest that coupled brittle-viscous deformation under high fluid pressures may characterize the subduction interface in the deep tremor source region. To test this further, we modeled the behavior of an elasto-plastic pod in a viscous shear zone under high fluid pressures. Our models show that local stress concentrations around the pod are large enough to generate transient dilational shear at seismic

  3. Unusual Synthetic Pathway for an {Fe(NO)2}9 Dinitrosyl Iron Complex (DNIC) and Insight into DNIC Electronic Structure via Nuclear Resonance Vibrational Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Speelman, Amy L.; Zhang, Bo; Silakov, Alexey; Skodje, Kelsey M.; Alp, E. Ercan; Zhao, Jiyong; Hu, Michael Y.; Kim, Eunsuk; Krebs, Karsten; Lehnert, Nicolai

    2016-06-06

    Dinitrosyl iron complexes (DNICs) are among the most abundant NO-derived cellular species. Monomeric DNICs can exist in the {Fe(NO)2}9 or {Fe(NO)2}10 oxidation state (in the Enemark -Feltham notation). However, experimental studies of analogous DNICs in both oxidation states are rare, which prevents a thorough understanding of the di ff erences in the electronic structures of these species. Here, the {Fe(NO)2}9 DNIC [Fe(dmp)(NO)2](OTf) ( 1 ; dmp = 2,9-dimethyl-1,10- phenanthroline) is synthesized from a ferrous precursor via an unusual pathway, involving disproportionation of an {FeNO}7 complex to yield the {Fe(NO)2}9 DNIC and a ferric species, which is subsequently reduced by NO gas to generate a ferrous complex that re-enters the reaction cycle. In contrast to most {Fe(NO)2}9 DNICs with neutral N-donor ligands, 1 exhibits high solution stability and can be characterized structurally and spectroscopically. Reduction of 1 yields the corresponding {Fe(NO)2}10 DNIC [Fe(dmp)(NO)2](2). The Mo ssbauer isomer shift of 2 is 0.08 mm/s smaller than that of 1 , which indicates that the iron center is slightly more oxidized in the reduced complex. The nuclear resonance vibrational spectra (NRVS) of 1 and 2 are distinct and provide direct experimental insight into di ff erences in bonding in these complexes. In particular, the symmetric out-of-plane Fe -N - O bending mode is shifted to higher energy by 188 cm-1 in 2 in comparison to 1 . Using quantum chemistry centered normal coordinate analysis (QCC-NCA), this is shown to arise from an increase in Fe - NO bond order and a sti ff ening of the Fe(NO)2 unit upon reduction of 1 to 2 . DFT calculations demonstrate that the changes in bonding arise from an iron- centered reduction which leads to a distinct increase in Fe - NO π -back-bonding in

  4. Personality traits of Australian nurses and doctors: challenging stereotypes?

    Science.gov (United States)

    Eley, Diann S; Eley, Robert M

    2011-08-01

    This study compared temperament and character traits of Australian registered nurses and general practitioners. A cross-sectional quantitative design used the Temperament and Character Inventory. Total sample size was 426. Only main effects were detected. Nurses were higher in the temperament traits of Novelty Seeking and Reward Dependence, lower in the character traits of Self-Directedness and Cooperativeness but higher in Self-Transcendence compared with the sample of doctors. Differences in personality profiles between registered nurses and general practitioners might challenge existing stereotypes between these professions. Further exploration of traits exclusive to and shared among health professions would supplement a broad conceptualization of specialities and support the enhancement of appropriate training and career counselling. Awareness of one's temperament and character can lead to a clearer understanding of how they function in the workplace and might encourage reflection on and insight into the implications of their personality and career plans. © 2011 Blackwell Publishing Asia Pty Ltd.

  5. Disorganized Amygdala Networks in Conduct-Disordered Juvenile Offenders With Callous-Unemotional Traits.

    Science.gov (United States)

    Aghajani, Moji; Klapwijk, Eduard T; van der Wee, Nic J; Veer, Ilya M; Rombouts, Serge A R B; Boon, Albert E; van Beelen, Peter; Popma, Arne; Vermeiren, Robert R J M; Colins, Olivier F

    2017-08-15

    The developmental trajectory of psychopathy seemingly begins early in life and includes the presence of callous-unemotional (CU) traits (e.g., deficient emotional reactivity, callousness) in conduct-disordered (CD) youth. Though subregion-specific anomalies in amygdala function have been suggested in CU pathophysiology among antisocial populations, system-level studies of CU traits have typically examined the amygdala as a unitary structure. Hence, nothing is yet known of how amygdala subregional network function may contribute to callous-unemotionality in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral amygdala (BLA) and centromedial amygdala (CMA) networks across three matched groups of juveniles: CD offenders with CU traits (CD/CU+; n = 25), CD offenders without CU traits (CD/CU-; n = 25), and healthy control subjects (n = 24). We additionally examined whether perturbed amygdala subregional connectivity coincides with altered volume and shape of the amygdaloid complex. Relative to CD/CU- and healthy control youths, CD/CU+ youths showed abnormally increased BLA connectivity with a cluster that included both dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices, along with posterior cingulate, sensory associative, and striatal regions. In contrast, compared with CD/CU- and healthy control youths, CD/CU+ youths showed diminished CMA connectivity with ventromedial/orbitofrontal regions. Critically, these connectivity changes coincided with local hypotrophy of BLA and CMA subregions (without being statistically correlated) and were associated to more severe CU symptoms. These findings provide unique insights into a putative mechanism for perturbed attention-emotion interactions, which could bias salience processing and associative learning in youth with CD/CU+. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights

  6. Quantitative Trait Loci Affecting Calving Traits in Danish Holstein Cattle

    DEFF Research Database (Denmark)

    Thomasen, J R; Guldbrandtsen, B; Sørensen, P

    2008-01-01

    The objectives of this study were 1) to detect quantitative trait loci (QTL) affecting direct and maternal calving traits at first calving in the Danish Holstein population, 2) to distinguish between pleiotropic and linked QTL for chromosome regions affecting more than one trait, and 3) to detect...

  7. Quantitative trait loci for behavioural traits in chicken

    NARCIS (Netherlands)

    Buitenhuis, A.J.; Rodenburg, T.B.; Siwek, M.Z.; Cornelissen, S.J.B.; Nieuwland, M.G.B.; Crooijmans, R.P.M.A.; Groenen, M.A.M.; Koene, P.; Bovenhuis, H.; Poel, van der J.J.

    2005-01-01

    The detection of quantitative trait loci (QTL) of behavioural traits has mainly been focussed on mouse and rat. With the rapid development of molecular genetics and the statistical tools, QTL mapping for behavioural traits in farm animals is developing. In chicken, a total of 30 QTL involved in

  8. Quantifying the effects of ecological constraints on trait expression using novel trait-gradient analysis parameters.

    Science.gov (United States)

    Ottaviani, Gianluigi; Tsakalos, James L; Keppel, Gunnar; Mucina, Ladislav

    2018-01-01

    Complex processes related to biotic and abiotic forces can impose limitations to assembly and composition of plant communities. Quantifying the effects of these constraints on plant functional traits across environmental gradients, and among communities, remains challenging. We define ecological constraint ( C i ) as the combined, limiting effect of biotic interactions and environmental filtering on trait expression (i.e., the mean value and range of functional traits). Here, we propose a set of novel parameters to quantify this constraint by extending the trait-gradient analysis (TGA) methodology. The key parameter is ecological constraint, which is dimensionless and can be measured at various scales, for example, on population and community levels. It facilitates comparing the effects of ecological constraints on trait expressions across environmental gradients, as well as within and among communities. We illustrate the implementation of the proposed parameters using the bark thickness of 14 woody species along an aridity gradient on granite outcrops in southwestern Australia. We found a positive correlation between increasing environmental stress and strength of ecological constraint on bark thickness expression. Also, plants from more stressful habitats (shrublands on shallow soils and in sun-exposed locations) displayed higher ecological constraint for bark thickness than plants in more benign habitats (woodlands on deep soils and in sheltered locations). The relative ease of calculation and dimensionless nature of C i allow it to be readily implemented at various scales and make it widely applicable. It therefore has the potential to advance the mechanistic understanding of the ecological processes shaping trait expression. Some future applications of the new parameters could be investigating the patterns of ecological constraints (1) among communities from different regions, (2) on different traits across similar environmental gradients, and (3) for the same

  9. Trait Emotional Intelligence and Personality

    OpenAIRE

    Siegling, Alexander B.; Furnham, Adrian; Petrides, K. V.

    2015-01-01

    This study investigated if the linkages between trait emotional intelligence (trait EI) and the Five-Factor Model of personality were invariant between men and women. Five English-speaking samples (N = 307-685) of mostly undergraduate students each completed a different measure of the Big Five personality traits and either the full form or short form of the Trait Emotional Intelligence Questionnaire (TEIQue). Across samples, models predicting global TEIQue scores from the Big Five were invari...

  10. The politics of insight.

    Science.gov (United States)

    Salvi, Carola; Cristofori, Irene; Grafman, Jordan; Beeman, Mark

    2016-01-01

    Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insight and analytic problem-solving, are reliable and are associated with two different neural circuits. In our research we found that participants self-identifying with distinct political orientations demonstrated differences in problem-solving strategy. Liberals solved significantly more problems via insight instead of in a step-by-step analytic fashion. Our findings extend previous observations that self-identified political orientations reflect differences in cognitive styles. More specifically, we show that type of political orientation is associated with problem-solving strategy. The data converge with previous neurobehavioural and cognitive studies indicating a link between cognitive style and the psychological mechanisms that mediate political beliefs.

  11. The politics of insight

    Science.gov (United States)

    Salvi, Carola; Cristofori, Irene; Grafman, Jordan; Beeman, Mark

    2016-01-01

    Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insight and analytic problem-solving, are reliable and are associated with two different neural circuits. In our research we found that participants self-identifying with distinct political orientations demonstrated differences in problem-solving strategy. Liberals solved significantly more problems via insight instead of in a step-by-step analytic fashion. Our findings extend previous observations that self-identified political orientations reflect differences in cognitive styles. More specifically, we show that type of political orientation is associated with problem-solving strategy. The data converge with previous neurobehavioural and cognitive studies indicating a link between cognitive style and the psychological mechanisms that mediate political beliefs. PMID:26810954

  12. The Trait Lady Speaks Up

    Science.gov (United States)

    Culham, Ruth

    2006-01-01

    The acknowledged expert on the 6+1 traits of writing explains what the traits are and what they are not: The traits are not a curriculum; they are part and parcel of the writing process; they are a model, not a program; they are not a prepackaged replacement for teaching writing; and they are the language of the writing workshop. The author…

  13. Utilizing Advanced Psychometric Methods in Research on Trait Expression across Situations

    DEFF Research Database (Denmark)

    Lang, Jonas W. B.; Tackett, Jennifer; Zettler, Ingo

    2017-01-01

    Lievens emphasized the extent to which new measurement tools and additional statistics can be used to advance research on trait expression across situations. We suggest that advanced psychometric models represent additional important and complementary building blocks for progress and new insights...... in research on trait expression across situations. Here, we offer two specific examples of this: (1) Item Response Theory modelling of within-person variability simultaneous with estimation of latent trait levels and (2) estimation of latent trait and latent situation factors from a multitrait...

  14. Breeding for cuticle-associated traits in crop species: traits, targets, and strategies.

    Science.gov (United States)

    Petit, Johann; Bres, Cécile; Mauxion, Jean-Philippe; Bakan, Bénédicte; Rothan, Christophe

    2017-11-09

    Improving crop productivity and quality while promoting sustainable agriculture have become major goals in plant breeding. The cuticle is a natural film covering the aerial organs of plants and consists of lipid polyesters covered and embedded with wax. The cuticle protects plants against water loss and pathogens and affects traits with strong impacts on crop quality such as, for horticultural crops, fruit brightness, cracking, russeting, netting, and shelf life. Here we provide an overview of the most important cuticle-associated traits that can be targeted for crop improvement. To date, most studies on cuticle-associated traits aimed at crop breeding have been done on fleshy fruits. Less information is available for staple crops such as rice, wheat or maize. Here we present new insights into cuticle formation and properties resulting from the study of genetic resources available for the various crop species. Our review also covers the current strategies and tools aimed at exploiting available natural and artificially induced genetic diversity and the technologies used to transfer the beneficial alleles affecting cuticle-associated traits to commercial varieties. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. Quantitative traits and diversification.

    Science.gov (United States)

    FitzJohn, Richard G

    2010-12-01

    Quantitative traits have long been hypothesized to affect speciation and extinction rates. For example, smaller body size or increased specialization may be associated with increased rates of diversification. Here, I present a phylogenetic likelihood-based method (quantitative state speciation and extinction [QuaSSE]) that can be used to test such hypotheses using extant character distributions. This approach assumes that diversification follows a birth-death process where speciation and extinction rates may vary with one or more traits that evolve under a diffusion model. Speciation and extinction rates may be arbitrary functions of the character state, allowing much flexibility in testing models of trait-dependent diversification. I test the approach using simulated phylogenies and show that a known relationship between speciation and a quantitative character could be recovered in up to 80% of the cases on large trees (500 species). Consistent with other approaches, detecting shifts in diversification due to differences in extinction rates was harder than when due to differences in speciation rates. Finally, I demonstrate the application of QuaSSE to investigate the correlation between body size and diversification in primates, concluding that clade-specific differences in diversification may be more important than size-dependent diversification in shaping the patterns of diversity within this group.

  16. Trait Emotional Intelligence and Personality

    Science.gov (United States)

    Furnham, Adrian; Petrides, K. V.

    2015-01-01

    This study investigated if the linkages between trait emotional intelligence (trait EI) and the Five-Factor Model of personality were invariant between men and women. Five English-speaking samples (N = 307-685) of mostly undergraduate students each completed a different measure of the Big Five personality traits and either the full form or short form of the Trait Emotional Intelligence Questionnaire (TEIQue). Across samples, models predicting global TEIQue scores from the Big Five were invariant between genders, with Neuroticism and Extraversion being the strongest trait EI correlates, followed by Conscientiousness, Agreeableness, and Openness. However, there was some evidence indicating that the gender-specific contributions of the Big Five to trait EI vary depending on the personality measure used, being more consistent for women. Discussion focuses on the validity of the TEIQue as a measure of trait EI and its psychometric properties, more generally. PMID:25866439

  17. QTLs for seedling traits under salinity stress in hexaploid wheat

    OpenAIRE

    Ren, Yongzhe; Xu, Yanhua; Teng, Wan; Li, Bin; Lin, Tongbao

    2018-01-01

    ABSTRACT: Soil salinity limits agricultural production and is a major obstacle for increasing crop yield. Common wheat is one of the most important crops with allohexaploid characteristic and a highly complex genome. QTL mapping is a useful way to identify genes for quantitative traits such as salinity tolerance in hexaploid wheat. In the present study, a hydroponic trial was carried out to identify quantitative trait loci (QTLs) associated with salinity tolerance of wheat under 150mM NaCl co...

  18. Phylogeny and species traits predict bird detectability

    Science.gov (United States)

    Solymos, Peter; Matsuoka, Steven M.; Stralberg, Diana; Barker, Nicole K. S.; Bayne, Erin M.

    2018-01-01

    Avian acoustic communication has resulted from evolutionary pressures and ecological constraints. We therefore expect that auditory detectability in birds might be predictable by species traits and phylogenetic relatedness. We evaluated the relationship between phylogeny, species traits, and field‐based estimates of the two processes that determine species detectability (singing rate and detection distance) for 141 bird species breeding in boreal North America. We used phylogenetic mixed models and cross‐validation to compare the relative merits of using trait data only, phylogeny only, or the combination of both to predict detectability. We found a strong phylogenetic signal in both singing rates and detection distances; however the strength of phylogenetic effects was less than expected under Brownian motion evolution. The evolution of behavioural traits that determine singing rates was found to be more labile, leaving more room for species to evolve independently, whereas detection distance was mostly determined by anatomy (i.e. body size) and thus the laws of physics. Our findings can help in disentangling how complex ecological and evolutionary mechanisms have shaped different aspects of detectability in boreal birds. Such information can greatly inform single‐ and multi‐species models but more work is required to better understand how to best correct possible biases in phylogenetic diversity and other community metrics.

  19. Beta-thalassaemia trait: haematological parameters

    International Nuclear Information System (INIS)

    Yousafzai, Y.M.; Khan, S.; Raziq, F.

    2010-01-01

    Thalassaemia syndromes are a group of hereditary disorders characterised by a genetic deficiency in the synthesis of --globin genes. The objective of this study was to determine the haematological features -thalassaemia trait (BTT), and to determine the sensitivity of Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH) and -thalassaemia trait. Methods: A descriptive study was conducted in Hayatabad Medical Complex, Peshawar from May 2009 to May 2010 with 203 subjects having BTT. Blood samples were collected in EDTA anti-coagulated tubes. RBC indices were taken as part of complete blood count (CBC) by haematology analyser, and Haemoglobin (Hb) electrophoresis was done to determine the HbA2 percentage. The data was collected and analyzed on statistical software for demographic details, RBC indices and HBA2 levels. Results: Out of 203 patients, 92 (45%) were males and 111 (55%) were females. Most patients tested were in the 15-45 year age group. One-hundred-sixty (79%) patients had anaemia. MCV was lower than 76 fl in all the cases. Mean MCV was 59.1 fl. MCH was low, the mean MCH being 19.3 g/dl. MCH <26 gave sensitivity of 99% in detecting BTT. We calculated MI for these cases and found out that it was <12 in 75% of cases and <15 in 197 (97%). Conclusion: Beta-thalassaemia traits present with a microcytic hypochromic blood picture, detected on simple haematology analysers as low MCV and MCH and MI which provide a beta- thalassaemia trait. (author)

  20. Revisiting the Holy Grail: using plant functional traits to understand ecological processes.

    Science.gov (United States)

    Funk, Jennifer L; Larson, Julie E; Ames, Gregory M; Butterfield, Bradley J; Cavender-Bares, Jeannine; Firn, Jennifer; Laughlin, Daniel C; Sutton-Grier, Ariana E; Williams, Laura; Wright, Justin

    2017-05-01

    One of ecology's grand challenges is developing general rules to explain and predict highly complex systems. Understanding and predicting ecological processes from species' traits has been considered a 'Holy Grail' in ecology. Plant functional traits are increasingly being used to develop mechanistic models that can predict how ecological communities will respond to abiotic and biotic perturbations and how species will affect ecosystem function and services in a rapidly changing world; however, significant challenges remain. In this review, we highlight recent work and outstanding questions in three areas: (i) selecting relevant traits; (ii) describing intraspecific trait variation and incorporating this variation into models; and (iii) scaling trait data to community- and ecosystem-level processes. Over the past decade, there have been significant advances in the characterization of plant strategies based on traits and trait relationships, and the integration of traits into multivariate indices and models of community and ecosystem function. However, the utility of trait-based approaches in ecology will benefit from efforts that demonstrate how these traits and indices influence organismal, community, and ecosystem processes across vegetation types, which may be achieved through meta-analysis and enhancement of trait databases. Additionally, intraspecific trait variation and species interactions need to be incorporated into predictive models using tools such as Bayesian hierarchical modelling. Finally, existing models linking traits to community and ecosystem processes need to be empirically tested for their applicability to be realized. © 2016 Cambridge Philosophical Society.

  1. Mining Login Data for Actionable Student Insight

    Science.gov (United States)

    Agnihotri, Lalitha; Aghababyan, Ani; Mojarad, Shirin; Riedesel, Mark; Essa, Alfred

    2015-01-01

    Student login data is a key resource for gaining insight into their learning experience. However, the scale and the complexity of this data necessitate a thorough exploration to identify potential actionable insights, thus rendering it less valuable compared to student achievement data. To compensate for the underestimation of login data…

  2. Mapping genomic features to functional traits through microbial whole genome sequences.

    Science.gov (United States)

    Zhang, Wei; Zeng, Erliang; Liu, Dan; Jones, Stuart E; Emrich, Scott

    2014-01-01

    Recently, the utility of trait-based approaches for microbial communities has been identified. Increasing availability of whole genome sequences provide the opportunity to explore the genetic foundations of a variety of functional traits. We proposed a machine learning framework to quantitatively link the genomic features with functional traits. Genes from bacteria genomes belonging to different functional traits were grouped to Cluster of Orthologs (COGs), and were used as features. Then, TF-IDF technique from the text mining domain was applied to transform the data to accommodate the abundance and importance of each COG. After TF-IDF processing, COGs were ranked using feature selection methods to identify their relevance to the functional trait of interest. Extensive experimental results demonstrated that functional trait related genes can be detected using our method. Further, the method has the potential to provide novel biological insights.

  3. Heritability, covariation and natural selection on 24 traits of common evening primrose (Oenothera biennis) from a field experiment.

    Science.gov (United States)

    Johnson, M T J; Agrawal, A A; Maron, J L; Salminen, J-P

    2009-06-01

    This study explored genetic variation and co-variation in multiple functional plant traits. Our goal was to characterize selection, heritabilities and genetic correlations among different types of traits to gain insight into the evolutionary ecology of plant populations and their interactions with insect herbivores. In a field experiment, we detected significant heritable variation for each of 24 traits of Oenothera biennis and extensive genetic covariance among traits. Traits with diverse functions formed several distinct groups that exhibited positive genetic covariation with each other. Genetic variation in life-history traits and secondary chemistry together explained a large proportion of variation in herbivory (r(2) = 0.73). At the same time, selection acted on lifetime biomass, life-history traits and two secondary compounds of O. biennis, explaining over 95% of the variation in relative fitness among genotypes. The combination of genetic covariances and directional selection acting on multiple traits suggests that adaptive evolution of particular traits is constrained, and that correlated evolution of groups of traits will occur, which is expected to drive the evolution of increased herbivore susceptibility. As a whole, our study indicates that an examination of genetic variation and covariation among many different types of traits can provide greater insight into the evolutionary ecology of plant populations and plant-herbivore interactions.

  4. Managing Complex Dynamical Systems

    Science.gov (United States)

    Cox, John C.; Webster, Robert L.; Curry, Jeanie A.; Hammond, Kevin L.

    2011-01-01

    Management commonly engages in a variety of research designed to provide insight into the motivation and relationships of individuals, departments, organizations, etc. This paper demonstrates how the application of concepts associated with the analysis of complex systems applied to such data sets can yield enhanced insights for managerial action.

  5. The Longitudinal Relation between Childhood Autistic Traits and Psychosexual Problems in Early Adolescence: The Tracking Adolescents' Individual Lives Survey Study

    Science.gov (United States)

    Dekker, Linda P.; Hartman, Catharina A.; van der Vegt, Esther J. M.; Verhulst, Frank C.; van Oort, Floor V. A.; Greaves-Lord, Kirstin

    2015-01-01

    Individuals with autistic traits are considered to be prone to develop psychosexual problems due to their limited social skills and insight. This study investigated the longitudinal relation between autistic traits in childhood (T1; age 10-12 years) and parent-reported psychosexual problems in early adolescence (T2; age 12-15 years). In a general…

  6. The longitudinal relation between childhood autistic traits and psychosexual problems in early adolescence : The Tracking Adolescents' Individual Lives Survey study

    NARCIS (Netherlands)

    Dekker, Linda P.; Hartman, Catharina A.; van der Vegt, Esther J. M.; Verhulst, Frank C.; van Oort, Floor V. A.; Greaves-Lord, Kirstin

    Individuals with autistic traits are considered to be prone to develop psychosexual problems due to their limited social skills and insight. This study investigated the longitudinal relation between autistic traits in childhood (T1; age 10-12 years) and parent-reported psychosexual problems in early

  7. Leaf optical properties shed light on foliar trait variability at individual to global scales

    Science.gov (United States)

    Shiklomanov, A. N.; Serbin, S.; Dietze, M.

    2017-12-01

    Recent syntheses of large trait databases have contributed immensely to our understanding of drivers of plant function at the global scale. However, the global trade-offs revealed by such syntheses, such as the trade-off between leaf productivity and resilience (i.e. "leaf economics spectrum"), are often absent at smaller scales and fail to correlate with actual functional limitations. An improved understanding of how traits vary among communities, species, and individuals is critical to accurate representations of vegetation ecophysiology and ecological dynamics in ecosystem models. Spectral data from both field observations and remote sensing platforms present a rich and widely available source of information on plant traits. Here, we apply Bayesian inversion of the PROSPECT leaf radiative transfer model to a large global database of over 60,000 field spectra and plant traits to (1) comprehensively assess the accuracy of leaf trait estimation using PROSPECT spectral inversion; (2) investigate the correlations between optical traits estimable from PROSPECT and other important foliar traits such as nitrogen and lignin concentrations; and (3) identify dominant sources of variability and characterize trade-offs in optical and non-optical foliar traits. Our work provides a key methodological contribution by validating physically-based retrieval of plant traits from remote sensing observations, and provides insights about trait trade-offs related to plant acclimation, adaptation, and community assembly.

  8. Quantitative trait loci (QTL) mapping for inflorescence length traits in ...

    African Journals Online (AJOL)

    Lablab purpureus (L.) sweet is an ancient legume species whose immature pods serve as a vegetable in south and south-east Asia. The objective of this study is to identify quantitative trait loci (QTLs) associated with quantitative traits such as inflorescence length, peduncle length from branch to axil, peduncle length from ...

  9. Associations between animal traits, carcass traits and carcass ...

    African Journals Online (AJOL)

    In this study the associations between animal traits, carcass traits and carcass classification within cattle, sheep and pigs slaughtered in a high throughput abattoir were determined. Classes of carcasses from cattle, sheep and pigs delivered for slaughter at this abattoir were recorded and analysed. Significant associations ...

  10. Uncovering the genetic landscape for multiple sleep-wake traits.

    Directory of Open Access Journals (Sweden)

    Christopher J Winrow

    Full Text Available Despite decades of research in defining sleep-wake properties in mammals, little is known about the nature or identity of genes that regulate sleep, a fundamental behaviour that in humans occupies about one-third of the entire lifespan. While genome-wide association studies in humans and quantitative trait loci (QTL analyses in mice have identified candidate genes for an increasing number of complex traits and genetic diseases, the resources and time-consuming process necessary for obtaining detailed quantitative data have made sleep seemingly intractable to similar large-scale genomic approaches. Here we describe analysis of 20 sleep-wake traits from 269 mice from a genetically segregating population that reveals 52 significant QTL representing a minimum of 20 genomic loci. While many (28 QTL affected a particular sleep-wake trait (e.g., amount of wake across the full 24-hr day, other loci only affected a trait in the light or dark period while some loci had opposite effects on the trait during the light vs. dark. Analysis of a dataset for multiple sleep-wake traits led to previously undetected interactions (including the differential genetic control of number and duration of REM bouts, as well as possible shared genetic regulatory mechanisms for seemingly different unrelated sleep-wake traits (e.g., number of arousals and REM latency. Construction of a Bayesian network for sleep-wake traits and loci led to the identification of sub-networks of linkage not detectable in smaller data sets or limited single-trait analyses. For example, the network analyses revealed a novel chain of causal relationships between the chromosome 17@29cM QTL, total amount of wake, and duration of wake bouts in both light and dark periods that implies a mechanism whereby overall sleep need, mediated by this locus, in turn determines the length of each wake bout. Taken together, the present results reveal a complex genetic landscape underlying multiple sleep-wake traits

  11. A Trait-Based Approach to Advance Coral Reef Science.

    Science.gov (United States)

    Madin, Joshua S; Hoogenboom, Mia O; Connolly, Sean R; Darling, Emily S; Falster, Daniel S; Huang, Danwei; Keith, Sally A; Mizerek, Toni; Pandolfi, John M; Putnam, Hollie M; Baird, Andrew H

    2016-06-01

    Coral reefs are biologically diverse and ecologically complex ecosystems constructed by stony corals. Despite decades of research, basic coral population biology and community ecology questions remain. Quantifying trait variation among species can help resolve these questions, but progress has been hampered by a paucity of trait data for the many, often rare, species and by a reliance on nonquantitative approaches. Therefore, we propose filling data gaps by prioritizing traits that are easy to measure, estimating key traits for species with missing data, and identifying 'supertraits' that capture a large amount of variation for a range of biological and ecological processes. Such an approach can accelerate our understanding of coral ecology and our ability to protect critically threatened global ecosystems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. New insight from noble gas and stable isotopes of geothermal/hydrothermal fluids at Caviahue-Copahue Volcanic Complex: Boiling steam separation and water-rock interaction at shallow depth

    Science.gov (United States)

    Roulleau, Emilie; Tardani, Daniele; Sano, Yuji; Takahata, Naoto; Vinet, Nicolas; Bravo, Francisco; Muñoz, Carlos; Sanchez, Juan

    2016-12-01

    We measured noble gas and stable isotopes of the geothermal and hydrothermal fluids of the Caviahue-Copahue Volcanic Complex (CCVC), one of the most important geothermal systems in Argentina/Chile, in order to provide new insights into fluid circulation and origin. With the exception of Anfiteatro and Chancho-co geothermal systems, mantle-derived helium dominates in the CCVC fluids, with measured 3He/4He ratios up to 7.86Ra in 2015. Their positive δ15N is an evidence for subducted sediment-derived nitrogen, which is commonly observed in subduction settings. Both He-N2-Ar composition and positive correlation between δD-H2O and δ18O-H2O suggest that the fluids from Anfiteatro and Chancho-co (and partly from Pucon-Mahuida as well, on the southern flank of Copahue volcano) represent a meteoric water composition with a minor magmatic contribution. The Ne, Kr and Xe isotopic compositions are entirely of atmospheric origin, but processes of boiling and steam separation have led to fractionation of their elemental abundances. We modeled the CCVC fluid evolution using Rayleigh distillation curves, considering an initial air saturated geothermal water (ASGW) end-member at 250 and 300 °C, followed by boiling and steam separation at lower temperatures (from 200 °C to 150 °C). Between 2014 and 2015, the CCVC hydrogen and oxygen isotopes shifted from local meteoric water-dominated to andesitic water-dominated signature. This shift is associated with an increase of δ13C values and Stotal, HCl and He contents. These characteristics are consistent with a change in the gas ascent pathway between 2014 and 2015, which in turn induced higher magmatic-hydrothermal contribution in the fluid signature. The composition of the magmatic source of the CCVC fluids is: 3He/4He = 7.7Ra, δ15N = + 6‰, and δ13C = - 6.5‰. Mixing models between air-corrected He and N suggest the involvement of 0.5% to 5% of subducted sediments in the magmatic source. The magmatic sulfur isotopic

  13. Quantitative trait loci for fertility traits in Finnish Ayrshire cattle

    Directory of Open Access Journals (Sweden)

    Viitala Sirja M

    2008-03-01

    Full Text Available Abstract A whole genome scan was carried out to detect quantitative trait loci (QTL for fertility traits in Finnish Ayrshire cattle. The mapping population consisted of 12 bulls and 493 sons. Estimated breeding values for days open, fertility treatments, maternal calf mortality and paternal non-return rate were used as phenotypic data. In a granddaughter design, 171 markers were typed on all 29 bovine autosomes. Associations between markers and traits were analysed by multiple marker regression. Multi-trait analyses were carried out with a variance component based approach for the chromosomes and trait combinations, which were observed significant in the regression method. Twenty-two chromosome-wise significant QTL were detected. Several of the detected QTL areas were overlapping with milk production QTL previously identified in the same population. Multi-trait QTL analyses were carried out to test if these effects were due to a pleiotropic QTL affecting fertility and milk yield traits or to linked QTL causing the effects. This distinction could only be made with confidence on BTA1 where a QTL affecting milk yield is linked to a pleiotropic QTL affecting days open and fertility treatments.

  14. Genomic Regions Influencing Seminal Root Traits in Barley.

    Science.gov (United States)

    Robinson, Hannah; Hickey, Lee; Richard, Cecile; Mace, Emma; Kelly, Alison; Borrell, Andrew; Franckowiak, Jerome; Fox, Glen

    2016-03-01

    Water availability is a major limiting factor for crop production, making drought adaptation and its many component traits a desirable attribute of plant cultivars. Previous studies in cereal crops indicate that root traits expressed at early plant developmental stages, such as seminal root angle and root number, are associated with water extraction at different depths. Here, we conducted the first study to map seminal root traits in barley ( L.). Using a recently developed high-throughput phenotyping method, a panel of 30 barley genotypes and a doubled-haploid (DH) population (ND24260 × 'Flagship') comprising 330 lines genotyped with diversity array technology (DArT) markers were evaluated for seminal root angle (deviation from vertical) and root number under controlled environmental conditions. A high degree of phenotypic variation was observed in the panel of 30 genotypes: 13.5 to 82.2 and 3.6 to 6.9° for root angle and root number, respectively. A similar range was observed in the DH population: 16.4 to 70.5 and 3.6 to 6.5° for root angle and number, respectively. Seven quantitative trait loci (QTL) for seminal root traits (root angle, two QTL; root number, five QTL) were detected in the DH population. A major QTL influencing both root angle and root number (/) was positioned on chromosome 5HL. Across-species analysis identified 10 common genes underlying root trait QTL in barley, wheat ( L.), and sorghum [ (L.) Moench]. Here, we provide insight into seminal root phenotypes and provide a first look at the genetics controlling these traits in barley. Copyright © 2016 Crop Science Society of America.

  15. Genomic Regions Influencing Seminal Root Traits in Barley

    Directory of Open Access Journals (Sweden)

    Hannah Robinson

    2016-03-01

    Full Text Available Water availability is a major limiting factor for crop production, making drought adaptation and its many component traits a desirable attribute of plant cultivars. Previous studies in cereal crops indicate that root traits expressed at early plant developmental stages, such as seminal root angle and root number, are associated with water extraction at different depths. Here, we conducted the first study to map seminal root traits in barley ( L.. Using a recently developed high-throughput phenotyping method, a panel of 30 barley genotypes and a doubled-haploid (DH population (ND24260 × ‘Flagship’ comprising 330 lines genotyped with diversity array technology (DArT markers were evaluated for seminal root angle (deviation from vertical and root number under controlled environmental conditions. A high degree of phenotypic variation was observed in the panel of 30 genotypes: 13.5 to 82.2 and 3.6 to 6.9° for root angle and root number, respectively. A similar range was observed in the DH population: 16.4 to 70.5 and 3.6 to 6.5° for root angle and number, respectively. Seven quantitative trait loci (QTL for seminal root traits (root angle, two QTL; root number, five QTL were detected in the DH population. A major QTL influencing both root angle and root number (/ was positioned on chromosome 5HL. Across-species analysis identified 10 common genes underlying root trait QTL in barley, wheat ( L., and sorghum [ (L. Moench]. Here, we provide insight into seminal root phenotypes and provide a first look at the genetics controlling these traits in barley.

  16. Path analysis of the productive traits in Sorghum species

    Directory of Open Access Journals (Sweden)

    Ikanović Jela

    2011-01-01

    Full Text Available This research studied the phenotypic correlation coefficients between three Sorghum species, namely forage sorghum S. bicolor Moench. (c. NS-Džin, Sudan grass S. sudanense L. (c. Zora and interspecies hybrid S. bicolor x S. sudanense (c. Siloking. The analyses were performed on plant material samples taken from the first cutting, when plants were in the beginning phase of tasseling. The following morphologic traits were studied: plant height, number of leaves per plant, stem leaf weight and mean stem weight. Additionally, their direct and indirect effect on dependent variable green biomass yield was analyzed, for which path coefficients were calculated. This method enables more quality and full insight into relations existing among the studied traits, more precise establishment of cause-effect connections among them, as well as to separate direct from indirect effects of any particular trait on dependent variable, being biomass yield in this case. The analysis of phenotypic coefficients revealed differences in direct and indirect effect of certain traits on dependent variable. Sudan grass had the highest stem (2.281 m and most leaves per plant (7.917. Forage sorghum had the largest leaf weight per plant (49.05 g, while interspecies hybrid had the highest mean stem weight (80.798 g. Variations of these morphologic traits among species were found to be significant and very significant. Morphologic traits - stem height and weight significantly affected sorghum green biomass yield. Leaf number and leaf portion in total biomass were negatively correlated with yield. Cultivars differed significantly regarding morphologic and productive traits. Sudan grass had the lowest green biomass yield, while forage sorghum and interspecies hybrid had significant yield increase.

  17. Modeling the genealogy of a cultural trait.

    Science.gov (United States)

    Aguilar, Elliot; Ghirlanda, Stefano

    2015-05-01

    The mathematical study of genealogies has yielded important insights in population biology, such as the ability to estimate the time to the most recent common ancestor (MRCA) of a sample of genetic sequences or of a group of individuals. Here we introduce a model of cultural genealogies that is a step toward answering similar questions for cultural traits. In our model individuals can inherit from a variable, potentially large number of ancestors, rather than from a fixed, small number of ancestors (one or two) as is typical of genetic evolution. We first show that, given a sample of individuals, a cultural common ancestor does not necessarily exist. We then introduce a related concept: the most recent unique ancestor (MRUA), i.e., the most recent single individual who is the earliest cultural ancestor of the sample. We show that, under neutral evolution, the time to the MRUA can be staggeringly larger than the time to MRCA in a single ancestor model, except when the average number of learning opportunities per individuals is small. Our results point out that the properties of cultural genealogies may be very different from those of genetic genealogies, with potential implications for reconstructing the histories of cultural traits. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Application of integrative genomics and systems biology to conventional and in vitro reproductive traits in cattle

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Pedersen, Hanne S.; de Oliveira Junior, Gerson A.

    2017-01-01

    by both conventional and ARTs such as OPU-IVP. The integration of systems biology information across different biological layers generates a complete view of the different molecular networks that control complex traits and can provide a strong contribution to the understanding of traits related to ARTs....

  19. Genetic, Genomic, and Breeding Approaches to Further Explore Kernel Composition Traits and Grain Yield in Maize

    Science.gov (United States)

    Da Silva, Helena Sofia Pereira

    2009-01-01

    Maize ("Zea mays L.") is a model species well suited for the dissection of complex traits which are often of commercial value. The purpose of this research was to gain a deeper understanding of the genetic control of maize kernel composition traits starch, protein, and oil concentration, and also kernel weight and grain yield. Germplasm with…

  20. Quantitative Trait Loci for Fertility Traits in Finnish Ayrshire Cattle

    DEFF Research Database (Denmark)

    Schulman, Nina F; Sahana, Goutam; Lund, Mogens S

    2008-01-01

    A whole genome scan was carried out to detect quantitative trait loci (QTL) for fertility traits in Finnish Ayrshire cattle. The mapping population consisted of 12 bulls and 493 sons. Estimated breeding values for days open, fertility treatments, maternal calf mortality and paternal non-return rate...... combinations, which were observed significant in the regression method. Twenty-two chromosome-wise significant QTL were detected. Several of the detected QTL areas were overlapping with milk production QTL previously identified in the same population. Multi-trait QTL analyses were carried out to test...... if these effects were due to a pleiotropic QTL affecting fertility and milk yield traits or to linked QTL causing the effects. This distinction could only be made with confidence on BTA1 where a QTL affecting milk yield is linked to a pleiotropic QTL affecting days open and fertility treatments...

  1. Quantitative trait loci mapping for stomatal traits in interspecific ...

    Indian Academy of Sciences (India)

    M. Sumathi

    2018-02-23

    Feb 23, 2018 ... Journal of Genetics, Vol. ... QTL analysis was carried out to identify the chromosomal regions affecting ... Keywords. linkage map; quantitative trait loci; stomata; stress ..... of India for providing financial support for the project.

  2. Coping skills: role of trait sport confidence and trait anxiety.

    Science.gov (United States)

    Cresswell, Scott; Hodge, Ken

    2004-04-01

    The current research assesses relationships among coping skills, trait sport confidence, and trait anxiety. Two samples (n=47 and n=77) of international competitors from surf life saving (M=23.7 yr.) and touch rugby (M=26.2 yr.) completed the Athletic Coping Skills Inventory, Trait Sport Confidence Inventory, and Sport Anxiety Scale. Analysis yielded significant correlations amongst trait anxiety, sport confidence, and coping. Specifically confidence scores were positively associated with coping with adversity scores and anxiety scores were negatively associated. These findings support the inclusion of the personality characteristics of confidence and anxiety within the coping model presented by Hardy, Jones, and Gould, Researchers should be aware that confidence and anxiety may influence the coping processes of athletes.

  3. Phylogenetic Structure of Foliar Spectral Traits in Tropical Forest Canopies

    Directory of Open Access Journals (Sweden)

    Kelly M. McManus

    2016-02-01

    Full Text Available The Spectranomics approach to tropical forest remote sensing has established a link between foliar reflectance spectra and the phylogenetic composition of tropical canopy tree communities vis-à-vis the taxonomic organization of biochemical trait variation. However, a direct relationship between phylogenetic affiliation and foliar reflectance spectra of species has not been established. We sought to develop this relationship by quantifying the extent to which underlying patterns of phylogenetic structure drive interspecific variation among foliar reflectance spectra within three Neotropical canopy tree communities with varying levels of soil fertility. We interpreted the resulting spectral patterns of phylogenetic signal in the context of foliar biochemical traits that may contribute to the spectral-phylogenetic link. We utilized a multi-model ensemble to elucidate trait-spectral relationships, and quantified phylogenetic signal for spectral wavelengths and traits using Pagel’s lambda statistic. Foliar reflectance spectra showed evidence of phylogenetic influence primarily within the visible and shortwave infrared spectral regions. These regions were also selected by the multi-model ensemble as those most important to the quantitative prediction of several foliar biochemical traits. Patterns of phylogenetic organization of spectra and traits varied across sites and with soil fertility, indicative of the complex interactions between the environmental and phylogenetic controls underlying patterns of biodiversity.

  4. Proofs that Develop Insight

    Science.gov (United States)

    Weber, Keith

    2010-01-01

    Many mathematics educators have noted that mathematicians do not only read proofs to gain conviction but also to obtain insight. The goal of this article is to discuss what this insight is from mathematicians' perspective. Based on interviews with nine research-active mathematicians, two sources of insight are discussed. The first is reading a…

  5. Relationships between nutrient-related plant traits and combinations of soil N and P fertility measures.

    Science.gov (United States)

    Fujita, Yuki; van Bodegom, Peter M; Witte, Jan-Philip M

    2013-01-01

    Soil fertility and nutrient-related plant functional traits are in general only moderately related, hindering the progress in trait-based prediction models of vegetation patterns. Although the relationships may have been obscured by suboptimal choices in how soil fertility is expressed, there has never been a systematic investigation into the suitability of fertility measures. This study, therefore, examined the effect of different soil fertility measures on the strength of fertility-trait relationships in 134 natural plant communities. In particular, for eight plot-mean traits we examined (1) whether different elements (N or P) have contrasting or shared influences, (2) which timescale of fertility measures (e.g. mineralization rates for one or five years) has better predictive power, and (3) if integrated fertility measures explain trait variation better than individual fertility measures. Soil N and P had large mutual effects on leaf nutrient concentrations, whereas they had element-specific effects on traits related to species composition (e.g. Grime's CSR strategy). The timescale of fertility measures only had a minor impact on fertility-trait relationships. Two integrated fertility measures (one reflecting overall fertility, another relative availability of soil N and P) were related significantly to most plant traits, but were not better in explaining trait variation than individual fertility measures. Using all fertility measures together, between-site variations of plant traits were explained only moderately for some traits (e.g. 33% for leaf N concentrations) but largely for others (e.g. 66% for whole-canopy P concentration). The moderate relationships were probably due to complex regulation mechanisms of fertility on traits, rather than to a wrong choice of fertility measures. We identified both mutual (i.e. shared) and divergent (i.e. element-specific and stoichiometric) effects of soil N and P on traits, implying the importance of explicitly

  6. Personality Traits in Huntington's Disease

    DEFF Research Database (Denmark)

    Larsen, Ida Unmack; Mortensen, Erik Lykke; Vinther-Jensen, Tua

    2016-01-01

    Huntington's disease (HD) is associated with risk for developing psychiatric symptoms. Vulnerability or resilience to psychiatric symptoms may be associated with personality traits. This exploratory study, aimed to investigate personality traits in a large cohort of HD carriers and at risk gene......-expansion negative individuals (HD non-carriers), exploring whether carrying the HD gene or growing up in an HD family influences personality traits. Forty-seven HD carriers, Thirty-nine HD non-carriers, and 121 healthy controls answered the Danish version of the revised NEO personality inventory. Comparisons...... symptoms. Our findings suggest that, there is no direct effect of the HD gene on personality traits, but that personality assessment may be relevant to use when identifying individuals from HD families who are vulnerable to develop psychiatric symptoms....

  7. Authoritarian Personality Traits Among Students

    Science.gov (United States)

    Dunham, J.

    1973-01-01

    The results are reported of an investigation into the social attitudes of the total population (800) of one English university using Adorno's F scale to measure authoritarian personality traits. (Author)

  8. Highly pathogenic avian influenza virus H5N1 controls type I IFN induction in chicken macrophage HD-11 cells: a polygenic trait that involves NS1 and the polymerase complex

    Science.gov (United States)

    2012-01-01

    Background Influenza A viruses are well characterized to antagonize type I IFN induction in infected mammalian cells. However, limited information is available for avian cells. It was hypothesised that avian influenza viruses (AIV) with distinct virulence may interact differently with the avian innate immune system. Therefore, the type I IFN responses induced by highly virulent and low virulent H5N1 AIV and reassortants thereof were analysed in chicken cells. Results The highly pathogenic (HP) AIV A/chicken/Yamaguchi/7/04 (H5N1) (Yama) did not induce type I IFN in infected chicken HD-11 macrophage-like cells. This contrasted with an NS1 mutant Yama virus (Yama-NS1A144V) and with the attenuated H5N1 AIV A/duck/Hokkaido/Vac-1/04 (Vac) carrying the haemagglutinin (HA) of the Yama virus (Vac-Yama/HA), that both induced type I IFN in these cells. The substitution of the NS segment from Yama with that from Vac in the Yama backbone resulted in induction of type I IFN secretion in HD-11 cells. However, vice versa, the Yama NS segment did not prevent type I IFN induction by the Vac-Yama/HA virus. This was different with the PB1/PB2/PA segment reassortant Yama and Vac-Yama/HA viruses. Whereas the Yama virus with the Vac PB1/PB2/PA segments induced type I IFN in HD-11 cells, the Vac-Yama/HA virus with the Yama PB1/PB2/PA segments did not. As reported for mammalian cells, the expression of H5N1 PB2 inhibited the activation of the IFN-β promoter in chicken DF-1 fibroblast cells. Importantly, the Yama PB2 was more potent at inhibiting the IFN-β promoter than the Vac PB2. Conclusions The present study demonstrates that the NS1 protein and the polymerase complex of the HPAIV Yama act in concert to antagonize chicken type I IFN secretion in HD-11 cells. PB2 alone can also exert a partial inhibitory effect on type I IFN induction. In conclusion, the control of type I IFN induction by H5N1 HPAIV represents a complex phenotype that involves a particular viral gene constellation

  9. Three Nightmare Traits in Leaders

    Directory of Open Access Journals (Sweden)

    Reinout E. de Vries

    2018-06-01

    Full Text Available This review offers an integration of dark leadership styles with dark personality traits. The core of dark leadership consists of Three Nightmare Traits (TNT—leader dishonesty, leader disagreeableness, and leader carelessness—that are conceptualized as contextualized personality traits aligned with respectively (low honesty-humility, (low agreeableness, and (low conscientiousness. It is argued that the TNT, when combined with high extraversion and low emotionality, can have serious (“explosive” negative consequences for employees and their organizations. A Situation-Trait-Outcome Activation (STOA model is presented in which a description is offered of situations that are attractive to TNT leaders (situation activation, situations that activate TNT traits (trait activation, and the kinds of outcomes that may result from TNT behaviors (outcome activation. Subsequently, the TNT and STOA models are combined to offer a description of the organizational actions that may strengthen or weaken the TNT during six career stages: attraction, selection, socialization, production, promotion, and attrition. Except for mainly negative consequences of the TNT, possible positive consequences of TNT leadership are also explored, and an outline of a research program is offered that may provide answers to the most pressing questions in dark leadership research.

  10. Complexity and technological evolution: What everybody knows?

    NARCIS (Netherlands)

    Vaesen, K.; Houkes, W.N.

    2018-01-01

    The consensus among cultural evolutionists seems to be that human cultural evolution is cumulative, which is commonly understood in the specific sense that cultural traits, especially technological traits, increase in complexity over generations. Here we argue that there is insufficient credible

  11. Strategies for defining traits when calculating economic values for livestock breeding: a review.

    Science.gov (United States)

    Wolfová, M; Wolf, J

    2013-09-01

    The objective of the present review was (i) to survey different approaches for choosing the complex of traits for which economic values (EVs) are calculated, (ii) to call attention to the proper definition of traits and (iii) to discuss the manner and extent to which relationships among traits have been considered in the calculation of EVs. For this purpose, papers dealing with the estimation of EVs of traits in livestock were reviewed. The most important reasons for incompatibility of EVs for similar traits estimated in different countries and by different authors were found to be inconsistencies in trait definitions and in assumptions being made about relationships among traits. An important problem identified was how to choose the most appropriate criterion to characterise production or functional ability for a particular class of animals. Accordingly, the review covered the following three topics: (i) which trait(s) would best characterise the growth ability of an animal; (ii) how to define traits expressed repeatedly in subsequent reproductive cycles of breeding females and (iii) how to deal with traits that differ in average value between sexes or among animal groups. Various approaches that have been used to solve these problems were discussed. Furthermore, the manner in which diverse authors chose one or more traits from a group of alternatives for describing a specific biological potential were reviewed and commented on. The consequences of including or excluding relationships among economically important traits when estimating the EV for a specific trait were also examined. An important conclusion of the review is that, for a better comparability and interpretability of estimated EVs in the literature, it is desirable that clear and unique definitions of the traits, complete information on assumptions used in analytical models and details on inter-relationships between traits are documented. Furthermore, the method and the model used for the genetic

  12. Trait and state anxiety reduce the mere exposure effect

    Directory of Open Access Journals (Sweden)

    Sandra L Ladd

    2015-05-01

    Full Text Available The mere exposure effect refers to an affective preference elicited by exposure to previously unfamiliar items. Although it is a well-established finding, its mechanism remains uncertain, with some positing that it reflects affective processes and others positing that it reflects perceptual or motor fluency with repeated items. Here we examined whether individual differences in trait and state anxiety, which have been associated with the experience of emotion, influence the mere exposure effect. Participants’ trait (Study 1 and state (Study 2 anxiety were characterized with the State-Trait Anxiety Inventory. Greater trait and state anxiety correlated with greater negative affect and lesser positive affect. In both experiments, greater anxiety was associated with a reduced mere exposure effect. Measures of fluency (response times at study and test were unrelated to the mere exposure effect. These findings support the role of affective processes in the mere exposure effect, and offer a new insight into the nature of anxiety such that anxiety is associated with a reduced experience of positive affect typically associated with familiarity.

  13. Trait and state anxiety reduce the mere exposure effect.

    Science.gov (United States)

    Ladd, Sandra L; Gabrieli, John D E

    2015-01-01

    The mere exposure effect refers to an affective preference elicited by exposure to previously unfamiliar items. Although it is a well-established finding, its mechanism remains uncertain, with some positing that it reflects affective processes and others positing that it reflects perceptual or motor fluency with repeated items. Here we examined whether individual differences in trait and state anxiety, which have been associated with the experience of emotion, influence the mere exposure effect. Participants' trait (Study 1) and state (Study 2) anxiety were characterized with the State-Trait Anxiety Inventory. Greater trait and state anxiety correlated with greater negative affect and lesser positive affect. In both experiments, greater anxiety was associated with a reduced mere exposure effect. Measures of fluency (response times at study and test) were unrelated to the mere exposure effect. These findings support the role of affective processes in the mere exposure effect, and offer a new insight into the nature of anxiety such that anxiety is associated with a reduced experience of positive affect typically associated with familiarity.

  14. Genomic and Genetic Diversity within the Pseudomonas fluorescens Complex.

    Directory of Open Access Journals (Sweden)

    Daniel Garrido-Sanz

    Full Text Available The Pseudomonas fluorescens complex includes Pseudomonas strains that have been taxonomically assigned to more than fifty different species, many of which have been described as plant growth-promoting rhizobacteria (PGPR with potential applications in biocontrol and biofertilization. So far the phylogeny of this complex has been analyzed according to phenotypic traits, 16S rDNA, MLSA and inferred by whole-genome analysis. However, since most of the type strains have not been fully sequenced and new species are frequently described, correlation between taxonomy and phylogenomic analysis is missing. In recent years, the genomes of a large number of strains have been sequenced, showing important genomic heterogeneity and providing information suitable for genomic studies that are important to understand the genomic and genetic diversity shown by strains of this complex. Based on MLSA and several whole-genome sequence-based analyses of 93 sequenced strains, we have divided the P. fluorescens complex into eight phylogenomic groups that agree with previous works based on type strains. Digital DDH (dDDH identified 69 species and 75 subspecies within the 93 genomes. The eight groups corresponded to clustering with a threshold of 31.8% dDDH, in full agreement with our MLSA. The Average Nucleotide Identity (ANI approach showed inconsistencies regarding the assignment to species and to the eight groups. The small core genome of 1,334 CDSs and the large pan-genome of 30,848 CDSs, show the large diversity and genetic heterogeneity of the P. fluorescens complex. However, a low number of strains were enough to explain most of the CDSs diversity at core and strain-specific genomic fractions. Finally, the identification and analysis of group-specific genome and the screening for distinctive characters revealed a phylogenomic distribution of traits among the groups that provided insights into biocontrol and bioremediation applications as well as their role as

  15. Genetic basis of haloperidol resistance in Saccharomyces cerevisiae is complex and dose dependent.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2014-12-01

    Full Text Available The genetic basis of most heritable traits is complex. Inhibitory compounds and their effects in model organisms have been used in many studies to gain insights into the genetic architecture underlying quantitative traits. However, the differential effect of compound concentration has not been studied in detail. In this study, we used a large segregant panel from a cross between two genetically divergent yeast strains, BY4724 (a laboratory strain and RM11_1a (a vineyard strain, to study the genetic basis of variation in response to different doses of a drug. Linkage analysis revealed that the genetic architecture of resistance to the small-molecule therapeutic drug haloperidol is highly dose-dependent. Some of the loci identified had effects only at low doses of haloperidol, while other loci had effects primarily at higher concentrations of the drug. We show that a major QTL affecting resistance across all concentrations of haloperidol is caused by polymorphisms in SWH1, a homologue of human oxysterol binding protein. We identify a complex set of interactions among the alleles of the genes SWH1, MKT1, and IRA2 that are most pronounced at a haloperidol dose of 200 µM and are only observed when the remainder of the genome is of the RM background. Our results provide further insight into the genetic basis of drug resistance.

  16. Genetic Basis of Haloperidol Resistance in Saccharomyces cerevisiae Is Complex and Dose Dependent

    Science.gov (United States)

    Wang, Xin; Kruglyak, Leonid

    2014-01-01

    The genetic basis of most heritable traits is complex. Inhibitory compounds and their effects in model organisms have been used in many studies to gain insights into the genetic architecture underlying quantitative traits. However, the differential effect of compound concentration has not been studied in detail. In this study, we used a large segregant panel from a cross between two genetically divergent yeast strains, BY4724 (a laboratory strain) and RM11_1a (a vineyard strain), to study the genetic basis of variation in response to different doses of a drug. Linkage analysis revealed that the genetic architecture of resistance to the small-molecule therapeutic drug haloperidol is highly dose-dependent. Some of the loci identified had effects only at low doses of haloperidol, while other loci had effects primarily at higher concentrations of the drug. We show that a major QTL affecting resistance across all concentrations of haloperidol is caused by polymorphisms in SWH1, a homologue of human oxysterol binding protein. We identify a complex set of interactions among the alleles of the genes SWH1, MKT1, and IRA2 that are most pronounced at a haloperidol dose of 200 µM and are only observed when the remainder of the genome is of the RM background. Our results provide further insight into the genetic basis of drug resistance. PMID:25521586

  17. Complex bioclimatic and soil gradients shape leaf trait variation in Embothrium coccineum (Proteaceae among austral forests in Patagonia Gradientes bioclimáticos y edáficos modelan la variación en caracteres foliares de Embothrium coccineum (Proteaceae en los bosques australes de la Patagonia

    Directory of Open Access Journals (Sweden)

    CINTIA P SOUTO

    2009-06-01

    nutrient conditions are useful predictors for leaf size and structure in the widespread E. coccineum. The SLA patterns probably resulted from lower values in long lasting leaves, in addition to increasing soil nitrogen, so leaves in the south are thicker. Alternatively, it could be consequence from non-isometrical scaling of LA and DM, so larger leaves such as those under oceanic western climates have lower SLA. Patterns of multiple leaf trait variation along complex environmental gradients may become uncoupled from each other, differing from what is suggested in the literature for traits that vary along simple environmental gradients.Los patrones de variación de un rasgo pueden ser adaptativos cuando varían en relación a un gradiente ambiental. En particular, los caracteres foliares pueden afectar la productividad y la habilidad competitiva de las plantas. Identificamos patrones de variación en el tamaño y forma de la hoja con la heterogeneidad ambiental en una de las especies de más amplia distribución del bosque templado de Sudamérica: Embothrium coccineum (Proteaceae. Colectamos hojas y muestras compuestas de suelo de 35 poblaciones entre los 38° y 55° de latitud S, cubriendo un amplio rango de precipitación media anual (MAP y de temperatura media anual (MAT. En cada localidad se midieron nueve caracteres morfológicos foliares, algunos de los cuales están correlacionados entre sí, de manera que enfocaremos en algunos rasgos representativos. Predecimos que el área de la hoja (LA, el peso seco (DM, y el área foliar específica (SLA tenderán a aumentar y la forma de la hoja se alargará con el aumento de la temperatura, la precipitación y la disponibilidad de nutrientes en el suelo. También esperamos que el clima de la estación de crecimiento esté más asociado con los rasgos foliares que las métricas climáticas anuales. Utilizamos regresiones múltiples bivariadas y paso a paso reversas para analizar la dependencia de los rasgos morfológicos con

  18. Abandoned seasonal livestock migration reflected by plant functional traits: A case study in Kyrgyz rangelands

    Science.gov (United States)

    Hoppe, Franziska; Zhusui Kyzy, Taalaigul; Usupbaev, Adilet; Schickoff, Udo

    2017-04-01

    At least 30% of Kyrgyz pasture areas are considered to be subject to vegetation and soil degradation. Since animal husbandry is the economic basis to sustain people's livelihoods, rangeland degradation presents a threat for the majority of the population. Recently, the usage of plant functional traits as a powerful tool for the characterization of vegetation dynamics in response to anthropogenic and natural disturbances has been put forward. Grazing is one of the most severe disturbances on vegetation, which concerns equally the loss of area and biomass. Because grazing is both depending on and affecting plant functional traits, important insights can be generated, based on this codependency. We hypothesized that the contrasting grazing intensity of summer and winter pastures is reflected by the chosen traits. We used traits such as plant height, flowering start, growth form as well as SLA (Specific Leaf Area) and LMA (Leaf Mass per Area). Based on former phytosociological classification of the main pasture types (summer and winter pastures), community structure and the traits of dominant plant species were analyzed. Our results showed that on winter pastures grazing decreased plant height and SLA and favored plants with an earlier flowering start as well as rosette plants and ascending plants. We conclude that the study of trait composition in relation to anthropogenic disturbances can provide important insights into the mechanism of plant response to grazing in high-altitude rangelands.

  19. The effect of flower position on variation and covariation in floral traits in a wild hermaphrodite plant.

    Science.gov (United States)

    Zhao, Zhi-Gang; Du, Guo-Zhen; Huang, Shuang-Quan

    2010-05-20

    Floral traits within plants can vary with flower position or flowering time. Within an inflorescence, sexual allocation of early produced basal flowers is often female-biased while later produced distal flowers are male-biased. Such temporal adjustment of floral resource has been considered one of the potential advantages of modularity (regarding a flower as a module) in hermaphrodites. However, flowers are under constraints of independent evolution of a given trait. To understand flower diversification within inflorescences, here we examine variation and covariation in floral traits within racemes at the individual and the maternal family level respectively in an alpine herb Aconitum gymnandrum (Ranunculaceae). We found that floral traits varied significantly with flower position and among families, and position effects were family-specific. Most of the variance of floral traits was among individuals rather than among flowers within individuals or among families. Significant phenotypic correlations between traits were not affected by position, indicating trait integration under shared developmental regulation. In contrast, positive family-mean correlations in floral traits declined gradually from basal to distal flowers (nine significant correlations among floral traits in basal flowers and only three in distal flowers), showing position-specificity. Therefore, the pattern and magnitude of genetic correlations decreased with flower position. This finding on covariation pattern in floral reproductive structures within racemes has not been revealed before, providing insights into temporal variation and position effects in floral traits within plants and the potential advantages of modularity in hermaphrodites.

  20. The effect of flower position on variation and covariation in floral traits in a wild hermaphrodite plant

    Directory of Open Access Journals (Sweden)

    Du Guo-Zhen

    2010-05-01

    Full Text Available Abstract Background Floral traits within plants can vary with flower position or flowering time. Within an inflorescence, sexual allocation of early produced basal flowers is often female-biased while later produced distal flowers are male-biased. Such temporal adjustment of floral resource has been considered one of the potential advantages of modularity (regarding a flower as a module in hermaphrodites. However, flowers are under constraints of independent evolution of a given trait. To understand flower diversification within inflorescences, here we examine variation and covariation in floral traits within racemes at the individual and the maternal family level respectively in an alpine herb Aconitum gymnandrum (Ranunculaceae. Results We found that floral traits varied significantly with flower position and among families, and position effects were family-specific. Most of the variance of floral traits was among individuals rather than among flowers within individuals or among families. Significant phenotypic correlations between traits were not affected by position, indicating trait integration under shared developmental regulation. In contrast, positive family-mean correlations in floral traits declined gradually from basal to distal flowers (nine significant correlations among floral traits in basal flowers and only three in distal flowers, showing position-specificity. Therefore, the pattern and magnitude of genetic correlations decreased with flower position. Conclusions This finding on covariation pattern in floral reproductive structures within racemes has not been revealed before, providing insights into temporal variation and position effects in floral traits within plants and the potential advantages of modularity in hermaphrodites.

  1. Personality Traits and Second Language Acquisition: The Influence of the Enneagram on Adult ESOL Students

    Science.gov (United States)

    Coker, Crystal; Mihai, Florin

    2017-01-01

    In this qualitative study, researchers focused on providing explicit knowledge of personality traits via the Enneagram profile to a group of 10 adult advanced students of English for speakers of other languages. Through the Enneagram and two surveys, researchers gained insight into how students perceived the influence of their personality type on…

  2. Sexual Assault and Rape Perpetration by College Men: The Role of the Big Five Personality Traits

    Science.gov (United States)

    Voller, Emily K.; Long, Patricia J.

    2010-01-01

    A sample of 521 college men completed the Revised NEO Personality Inventory and an expanded version of the Sexual Experiences Survey to examine whether variation in the Big Five personality traits in a normal, college population provides any insight into the nature of sexual assault and rape perpetrators. Rape perpetrators reported lower levels of…

  3. Root phenotyping: from component trait in the lab to breeding.

    Science.gov (United States)

    Kuijken, René C P; van Eeuwijk, Fred A; Marcelis, Leo F M; Bouwmeester, Harro J

    2015-09-01

    In the last decade cheaper and faster sequencing methods have resulted in an enormous increase in genomic data. High throughput genotyping, genotyping by sequencing and genomic breeding are becoming a standard in plant breeding. As a result, the collection of phenotypic data is increasingly becoming a limiting factor in plant breeding. Genetic studies on root traits are being hampered by the complexity of these traits and the inaccessibility of the rhizosphere. With an increasing interest in phenotyping, breeders and scientists try to overcome these limitations, resulting in impressive developments in automated phenotyping platforms. Recently, many such platforms have been thoroughly described, yet their efficiency to increase genetic gain often remains undiscussed. This efficiency depends on the heritability of the phenotyped traits as well as the correlation of these traits with agronomically relevant breeding targets. This review provides an overview of the latest developments in root phenotyping and describes the environmental and genetic factors influencing root phenotype and heritability. It also intends to give direction to future phenotyping and breeding strategies for optimizing root system functioning. A quantitative framework to determine the efficiency of phenotyping platforms for genetic gain is described. By increasing heritability, managing effects caused by interactions between genotype and environment and by quantifying the genetic relation between traits phenotyped in platforms and ultimate breeding targets, phenotyping platforms can be utilized to their maximum potential. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  4. Selection for components of complex characteristics - indirect selection

    International Nuclear Information System (INIS)

    Haensel, H.

    1984-01-01

    A hierarchy of complexity exists in plant characteristics. The efficiency of indirect selection for a complex characteristic by a sub-trait depends on the heritability of the complex characteristic (hsub(c)), the heritability of the sub-trait (hsub(s)), and the genotypic correlation between sub-trait and complex characteristic (rsub(s.c)). In 1961 hsub(s)Xrsub(s.c)>hsub(c) was postulated, when indirect selection becomes more efficient than direct selection. Numerical examples for this relationship are given and a table for indirect selection for yield in wheat is elaborated. Efficiency ranking of sub-traits in indirect selection may change with climate, conditions of cultivation, the level of other sub-traits, the level of the complex characteristic already reached by breeding, and the breeding material. An example shows that regression analysis for different sub-traits on the same complex characteristic, and an estimation of the differences of the within - and the between - variety slopes, may help to select the more efficient sub-trait. In another example, where simultaneous selection was made for two polygenic characteristics, one directly and the other indirectly by two sub-traits, less than half the F 5 -lines had to be continued, when using the more efficient sub-trait. (author)

  5. Trait Sources of Spirituality Scale: Assessing Trait Spirituality More Inclusively

    Science.gov (United States)

    Westbrook, Charles J.; Davis, Don E.; McElroy, Stacey E.; Brubaker, Kacy; Choe, Elise; Karaga, Sara; Dooley, Matt; O'Bryant, Brittany L.; Van Tongeren, Daryl R.; Hook, Joshua

    2018-01-01

    We develop the Trait Sources of Spirituality Scale (TSSS), which assesses experiences of closeness to the sacred, within and outside a religious tradition. After using factor analysis to finalize the scale, we examine evidence of construct validity, including latent profile analysis that reveals 5 patterns of how spirituality is experienced.

  6. Quantitative trait loci mapping for stomatal traits in interspecific ...

    Indian Academy of Sciences (India)

    Dr.YASODHA

    seedling raising, field planting and maintenance of the mapping population. ... tereticornis and production of interspecific hybrids displaying hybrid vigour in terms of .... A total of 114, 115 and 129 SSR, ISSR and SRAP markers were generated .... stomatal traits with yield and adaptability would help to improve productivity of ...

  7. Quantitative trait loci (QTL) mapping for inflorescence length traits in ...

    African Journals Online (AJOL)

    User

    2011-05-02

    May 2, 2011 ... character affected by ecological surroundings, growth ... developed from each F2 by bud self-pollination for QTL analysis. ... Quantitative traits measured for the each individual plant in F2 the population and F3 families ..... sex and parental interactions (Liu et al., 1996). ... evolution of solanaceous species.

  8. In Search of Insight.

    Science.gov (United States)

    Kaplan, Craig A.; Simon, Herbert A.

    1990-01-01

    Attaining the insight needed to solve the Mutilated Checkerboard problem, which requires discovery of an effective problem representation (EPR), is described. Performance on insight problems can be predicted from the availability of generators and constraints in the search for an EPR. Data for 23 undergraduates were analyzed. (TJH)

  9. Quantitative genetic methods depending on the nature of the phenotypic trait.

    Science.gov (United States)

    de Villemereuil, Pierre

    2018-01-24

    A consequence of the assumptions of the infinitesimal model, one of the most important theoretical foundations of quantitative genetics, is that phenotypic traits are predicted to be most often normally distributed (so-called Gaussian traits). But phenotypic traits, especially those interesting for evolutionary biology, might be shaped according to very diverse distributions. Here, I show how quantitative genetics tools have been extended to account for a wider diversity of phenotypic traits using first the threshold model and then more recently using generalized linear mixed models. I explore the assumptions behind these models and how they can be used to study the genetics of non-Gaussian complex traits. I also comment on three recent methodological advances in quantitative genetics that widen our ability to study new kinds of traits: the use of "modular" hierarchical modeling (e.g., to study survival in the context of capture-recapture approaches for wild populations); the use of aster models to study a set of traits with conditional relationships (e.g., life-history traits); and, finally, the study of high-dimensional traits, such as gene expression. © 2018 New York Academy of Sciences.

  10. Use of genetic data to infer population-specific ecological and phenotypic traits from mixed aggregations.

    Directory of Open Access Journals (Sweden)

    Paul Moran

    Full Text Available Many applications in ecological genetics involve sampling individuals from a mixture of multiple biological populations and subsequently associating those individuals with the populations from which they arose. Analytical methods that assign individuals to their putative population of origin have utility in both basic and applied research, providing information about population-specific life history and habitat use, ecotoxins, pathogen and parasite loads, and many other non-genetic ecological, or phenotypic traits. Although the question is initially directed at the origin of individuals, in most cases the ultimate desire is to investigate the distribution of some trait among populations. Current practice is to assign individuals to a population of origin and study properties of the trait among individuals within population strata as if they constituted independent samples. It seemed that approach might bias population-specific trait inference. In this study we made trait inferences directly through modeling, bypassing individual assignment. We extended a Bayesian model for population mixture analysis to incorporate parameters for the phenotypic trait and compared its performance to that of individual assignment with a minimum probability threshold for assignment. The Bayesian mixture model outperformed individual assignment under some trait inference conditions. However, by discarding individuals whose origins are most uncertain, the individual assignment method provided a less complex analytical technique whose performance may be adequate for some common trait inference problems. Our results provide specific guidance for method selection under various genetic relationships among populations with different trait distributions.

  11. Use of genetic data to infer population-specific ecological and phenotypic traits from mixed aggregations

    Science.gov (United States)

    Moran, Paul; Bromaghin, Jeffrey F.; Masuda, Michele

    2014-01-01

    Many applications in ecological genetics involve sampling individuals from a mixture of multiple biological populations and subsequently associating those individuals with the populations from which they arose. Analytical methods that assign individuals to their putative population of origin have utility in both basic and applied research, providing information about population-specific life history and habitat use, ecotoxins, pathogen and parasite loads, and many other non-genetic ecological, or phenotypic traits. Although the question is initially directed at the origin of individuals, in most cases the ultimate desire is to investigate the distribution of some trait among populations. Current practice is to assign individuals to a population of origin and study properties of the trait among individuals within population strata as if they constituted independent samples. It seemed that approach might bias population-specific trait inference. In this study we made trait inferences directly through modeling, bypassing individual assignment. We extended a Bayesian model for population mixture analysis to incorporate parameters for the phenotypic trait and compared its performance to that of individual assignment with a minimum probability threshold for assignment. The Bayesian mixture model outperformed individual assignment under some trait inference conditions. However, by discarding individuals whose origins are most uncertain, the individual assignment method provided a less complex analytical technique whose performance may be adequate for some common trait inference problems. Our results provide specific guidance for method selection under various genetic relationships among populations with different trait distributions.

  12. Trait Emotional Intelligence Is Related to Risk Taking when Adolescents Make Deliberative Decisions

    Directory of Open Access Journals (Sweden)

    Angelo Panno

    2016-08-01

    Full Text Available Most forms of risky behavior reach their peak during adolescence. A prominent line of research is exploring the relationship between people’s emotional self-efficacy and risk taking, but little is known about this relationship in the cognitive-deliberative domain among adolescents. The main aim of the present study consists in investigating whether trait EI (Emotional Intelligence is positively related to risk taking under predominantly cognitive-deliberative conditions among adolescents. Ninety-four adolescents played the cold version of the Columbia Card Task one month following an assessment of their trait EI. Results showed that trait EI is associated with risk taking under cognitive-deliberative conditions among adolescents. Moreover, the present research showed that trait EI is related to risk taking through the decision makers’ self-motivation. These results provide novel insights into research investigating the connections between emotional intelligence, decision science and adolescence research.

  13. Identifying plant traits: a key aspect for suitable species selection in ecological restoration of semiarid slopes

    Science.gov (United States)

    Bochet, Esther; García-Fayos, Patricio

    2017-04-01

    In the context of ecological restoration, one of the greatest challenges for practitioners and scientists is to select suitable species for revegetation purposes. In semiarid environments where restoration projects often fail, little attention has been paid so far to the contribution of plant traits to species success. The objective of this study was to (1) identify plant traits associated with species success on four roadside situations along an erosion-productivity gradient, and (2) to provide an ecological framework for selecting suitable species on the basis of their morphological and functional traits, applied to semiarid environments. We analyzed the association of 10 different plant traits with species success of 296 species surveyed on the four roadside situations in a semiarid region (Valencia, Spain). Plant traits included general plant traits (longevity, woodiness) and more specific root-, seed- and leaf-related traits (root type, sprouting ability, seed mucilage, seed mass, seed susceptibility to removal, specific leaf area and leaf dry matter content). All of them were selected according to the prevailing limiting ecogeomorphological processes acting along the erosion-productivity gradient. We observed strong shifts along the erosion-productivity gradient in the traits associated to species success. At the harshest end of the gradient, the most intensely eroded and driest one, species success was mainly associated to seed resistance to removal by runoff and to resistance to drought. At the opposite end of the gradient, the most productive one, species success was associated to a competitive-ruderal plant strategy (herbaceous successful species with high specific leaf area and low leaf dry matter content). Our study provides an ecologically-based approach for selecting suitable native species on the basis or their morphological and functional traits and supports a differential trait-based selection of species as regards roadslope type and aspect. In

  14. Ecological interactions drive evolutionary loss of traits.

    Science.gov (United States)

    Ellers, Jacintha; Kiers, E Toby; Currie, Cameron R; McDonald, Bradon R; Visser, Bertanne

    2012-10-01

    Loss of traits can dramatically alter the fate of species. Evidence is rapidly accumulating that the prevalence of trait loss is grossly underestimated. New findings demonstrate that traits can be lost without affecting the external phenotype, provided the lost function is compensated for by species interactions. This is important because trait loss can tighten the ecological relationship between partners, affecting the maintenance of species interactions. Here, we develop a new perspective on so-called `compensated trait loss' and how this type of trait loss may affect the evolutionary dynamics between interacting organisms. We argue that: (1) the frequency of compensated trait loss is currently underestimated because it can go unnoticed as long as ecological interactions are maintained; (2) by analysing known cases of trait loss, specific factors promoting compensated trait loss can be identified and (3) genomic sequencing is a key way forwards in detecting compensated trait loss. We present a comprehensive literature survey showing that compensated trait loss is taxonomically widespread, can involve essential traits, and often occurs as replicated evolutionary events. Despite its hidden nature, compensated trait loss is important in directing evolutionary dynamics of ecological relationships and has the potential to change facultative ecological interactions into obligatory ones. © 2012 Blackwell Publishing Ltd/CNRS.

  15. Assessing the Impact of Transgenerational Epigenetic Variation on Complex Traits

    NARCIS (Netherlands)

    Johannes, Frank; Porcher, Emmanuelle; Teixeira, Felipe K.; Saliba-Colombani, Vera; Simon, Matthieu; Agier, Nicolas; Bulski, Agnes; Albuisson, Juliette; Heredia, Fabiana; Audigier, Pascal; Bouchez, David; Dillmann, Christine; Guerche, Philippe; Hospital, Frederic; Colot, Vincent

    Loss or gain of DNA methylation can affect gene expression and is sometimes transmitted across generations. Such epigenetic alterations are thus a possible source of heritable phenotypic variation in the absence of DNA sequence change. However, attempts to assess the prevalence of stable epigenetic

  16. Accounting for genetic architecture improves sequence based genomic prediction for a Drosophila fitness trait.

    Science.gov (United States)

    Ober, Ulrike; Huang, Wen; Magwire, Michael; Schlather, Martin; Simianer, Henner; Mackay, Trudy F C

    2015-01-01

    The ability to predict quantitative trait phenotypes from molecular polymorphism data will revolutionize evolutionary biology, medicine and human biology, and animal and plant breeding. Efforts to map quantitative trait loci have yielded novel insights into the biology of quantitative traits, but the combination of individually significant quantitative trait loci typically has low predictive ability. Utilizing all segregating variants can give good predictive ability in plant and animal breeding populations, but gives little insight into trait biology. Here, we used the Drosophila Genetic Reference Panel to perform both a genome wide association analysis and genomic prediction for the fitness-related trait chill coma recovery time. We found substantial total genetic variation for chill coma recovery time, with a genetic architecture that differs between males and females, a small number of molecular variants with large main effects, and evidence for epistasis. Although the top additive variants explained 36% (17%) of the genetic variance among lines in females (males), the predictive ability using genomic best linear unbiased prediction and a relationship matrix using all common segregating variants was very low for females and zero for males. We hypothesized that the low predictive ability was due to the mismatch between the infinitesimal genetic architecture assumed by the genomic best linear unbiased prediction model and the true genetic architecture of chill coma recovery time. Indeed, we found that the predictive ability of the genomic best linear unbiased prediction model is markedly improved when we combine quantitative trait locus mapping with genomic prediction by only including the top variants associated with main and epistatic effects in the relationship matrix. This trait-associated prediction approach has the advantage that it yields biologically interpretable prediction models.

  17. Accounting for genetic architecture improves sequence based genomic prediction for a Drosophila fitness trait.

    Directory of Open Access Journals (Sweden)

    Ulrike Ober

    Full Text Available The ability to predict quantitative trait phenotypes from molecular polymorphism data will revolutionize evolutionary biology, medicine and human biology, and animal and plant breeding. Efforts to map quantitative trait loci have yielded novel insights into the biology of quantitative traits, but the combination of individually significant quantitative trait loci typically has low predictive ability. Utilizing all segregating variants can give good predictive ability in plant and animal breeding populations, but gives little insight into trait biology. Here, we used the Drosophila Genetic Reference Panel to perform both a genome wide association analysis and genomic prediction for the fitness-related trait chill coma recovery time. We found substantial total genetic variation for chill coma recovery time, with a genetic architecture that differs between males and females, a small number of molecular variants with large main effects, and evidence for epistasis. Although the top additive variants explained 36% (17% of the genetic variance among lines in females (males, the predictive ability using genomic best linear unbiased prediction and a relationship matrix using all common segregating variants was very low for females and zero for males. We hypothesized that the low predictive ability was due to the mismatch between the infinitesimal genetic architecture assumed by the genomic best linear unbiased prediction model and the true genetic architecture of chill coma recovery time. Indeed, we found that the predictive ability of the genomic best linear unbiased prediction model is markedly improved when we combine quantitative trait locus mapping with genomic prediction by only including the top variants associated with main and epistatic effects in the relationship matrix. This trait-associated prediction approach has the advantage that it yields biologically interpretable prediction models.

  18. Phenotypic Characterization and Genetic Dissection of Growth Period Traits in Soybean (Glycine max Using Association Mapping.

    Directory of Open Access Journals (Sweden)

    Zhangxiong Liu

    Full Text Available The growth period traits are important traits that affect soybean yield. The insights into the genetic basis of growth period traits can provide theoretical basis for cultivated area division, rational distribution, and molecular breeding for soybean varieties. In this study, genome-wide association analysis (GWAS was exploited to detect the quantitative trait loci (QTL for number of days to flowering (ETF, number of days from flowering to maturity (FTM, and number of days to maturity (ETM using 4032 single nucleotide polymorphism (SNP markers with 146 cultivars mainly from Northeast China. Results showed that abundant phenotypic variation was presented in the population, and variation explained by genotype, environment, and genotype by environment interaction were all significant for each trait. The whole accessions could be clearly clustered into two subpopulations based on their genetic relatedness, and accessions in the same group were almost from the same province. GWAS based on the unified mixed model identified 19 significant SNPs distributed on 11 soybean chromosomes, 12 of which can be consistently detected in both planting densities, and 5 of which were pleotropic QTL. Of 19 SNPs, 7 SNPs located in or close to the previously reported QTL or genes controlling growth period traits. The QTL identified with high resolution in this study will enrich our genomic understanding of growth period traits and could then be explored as genetic markers to be used in genomic applications in soybean breeding.

  19. Leaf optical properties shed light on foliar trait variability at individual to global scales

    Science.gov (United States)

    Shiklomanov, A. N.; Serbin, S.; Dietze, M.

    2016-12-01

    Recent syntheses of large trait databases have contributed immensely to our understanding of drivers of plant function at the global scale. However, the global trade-offs revealed by such syntheses, such as the trade-off between leaf productivity and resilience (i.e. "leaf economics spectrum"), are often absent at smaller scales and fail to correlate with actual functional limitations. An improved understanding of how traits vary within communities, species, and individuals is critical to accurate representations of vegetation ecophysiology and ecological dynamics in ecosystem models. Spectral data from both field observations and remote sensing platforms present a potentially rich and widely available source of information on plant traits. In particular, the inversion of physically-based radiative transfer models (RTMs) is an effective and general method for estimating plant traits from spectral measurements. Here, we apply Bayesian inversion of the PROSPECT leaf RTM to a large database of field spectra and plant traits spanning tropical, temperate, and boreal forests, agricultural plots, arid shrublands, and tundra to identify dominant sources of variability and characterize trade-offs in plant functional traits. By leveraging such a large and diverse dataset, we re-calibrate the empirical absorption coefficients underlying the PROSPECT model and expand its scope to include additional leaf biochemical components, namely leaf nitrogen content. Our work provides a key methodological contribution as a physically-based retrieval of leaf nitrogen from remote sensing observations, and provides substantial insights about trait trade-offs related to plant acclimation, adaptation, and community assembly.

  20. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

    DEFF Research Database (Denmark)

    Mahajan, Anubha; Go, Min Jin; Zhang, Weihua

    2014-01-01

    To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We obs...... and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry....... observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls...

  1. Quantitative trait loci analysis of swine meat quality traits

    DEFF Research Database (Denmark)

    Li, H D; Lund, M S; Christensen, O F

    2010-01-01

    loss, and the Minolta color measurements L*, a*, and b* representing meat lightness, redness, and yellowness, respectively. The families consist of 3,883 progenies of 12 Duroc boars that were evaluated to identify the QTL. The linkage map consists of 462 SNP markers on 18 porcine autosomes...... were estimated from a posterior distribution of the QTL position. In total, 31 QTL for the 6 meat quality traits were found to be significant at the 5% chromosome-wide level, among which 11 QTL were significant at the 5% genome-wide level and 5 of these were significant at the 0.1% genome-wide level...... will be helpful for fine mapping and identifying genes affecting meat quality traits, and tightly linked markers may be incorporated into marker-assisted selection programs...

  2. Insight in schizophrenia: involvement of self-reflection networks?

    Science.gov (United States)

    van der Meer, Lisette; de Vos, Annerieke E; Stiekema, Annemarie P M; Pijnenborg, Gerdina H M; van Tol, Marie-José; Nolen, Willem A; David, Anthony S; Aleman, André

    2013-11-01

    Impaired insight is a common feature in psychosis and an important predictor of variables such as functional outcome, prognosis, and treatment adherence. A cognitive process that may underlie insight in psychosis is self-reflection, or the conscious evaluation of one's traits and characteristics. The current study aims to investigate the neural correlates of self-reflective processing and its relationship with insight in schizophrenia. Forty-seven schizophrenia patients and 21 healthy controls performed a self-reflection task in a functional magnetic resonance imaging (fMRI) scanner. The tasks comprised a self-reflection, close other-reflection, and a semantic (baseline) condition. Insight scores were obtained with the Schedule of Assessment of Insight Expanded. In addition, cognitive insight scores were obtained (Beck Cognitive Insight Scale [BCIS]). Schizophrenia patients demonstrated less activation in the posterior cingulate cortex in the self- and other-reflection conditions and less activation in the precuneus in the other-reflection condition compared with healthy controls. Better insight was associated with greater response in the inferior frontal gyrus, anterior insula, and inferior parietal lobule during self-reflection. In addition, better cognitive insight was associated with higher activation in ventromedial prefrontal cortex during self-reflection. In the current study, evidence for a relationship between self-reflection and insight in patients with schizophrenia was found in brain areas related to self-reflection, self/other distinction and source attribution. The findings support the rationale for a treatment that is currently under evaluation, which attempts to increase insight by enhancing self-reflection.

  3. Insight in Schizophrenia: Involvement of Self-Reflection Networks?

    Science.gov (United States)

    de Vos, Annerieke E.

    2013-01-01

    Background: Impaired insight is a common feature in psychosis and an important predictor of variables such as functional outcome, prognosis, and treatment adherence. A cognitive process that may underlie insight in psychosis is self-reflection, or the conscious evaluation of one’s traits and characteristics. The current study aims to investigate the neural correlates of self-reflective processing and its relationship with insight in schizophrenia. Methods: Forty-seven schizophrenia patients and 21 healthy controls performed a self-reflection task in a functional magnetic resonance imaging (fMRI) scanner. The tasks comprised a self-reflection, close other-reflection, and a semantic (baseline) condition. Insight scores were obtained with the Schedule of Assessment of Insight Expanded. In addition, cognitive insight scores were obtained (Beck Cognitive Insight Scale [BCIS]). Results: Schizophrenia patients demonstrated less activation in the posterior cingulate cortex in the self- and other-reflection conditions and less activation in the precuneus in the other-reflection condition compared with healthy controls. Better insight was associated with greater response in the inferior frontal gyrus, anterior insula, and inferior parietal lobule during self-reflection. In addition, better cognitive insight was associated with higher activation in ventromedial prefrontal cortex during self-reflection. Conclusion: In the current study, evidence for a relationship between self-reflection and insight in patients with schizophrenia was found in brain areas related to self-reflection, self/other distinction and source attribution. The findings support the rationale for a treatment that is currently under evaluation, which attempts to increase insight by enhancing self-reflection. PMID:23104865

  4. Tectono-metamorphic evolution of high-P/T and low-P/T metamorphic rocks in the Tia Complex, southern New England Fold Belt, eastern Australia: Insights from K-Ar chronology

    Science.gov (United States)

    Fukui, Shiro; Tsujimori, Tatsuki; Watanabe, Teruo; Itaya, Tetsumaru

    2012-10-01

    The Tia Complex in the southern New England Fold Belt is a poly-metamorphosed Late Paleozoic accretionary complex. It consists mainly of high-P/low-T type pumpellyite-actinolite facies (rare blueschist facies) schists, phyllite and serpentinite (T = 300 °C and P = 5 kbar), and low-P/high-T type amphibolite facies schist and gneiss (T = 600 °C and P Tia granodiorite). White mica and biotite K-Ar ages distinguish Carboniferous subduction zone metamorphism and Permian granitic intrusions, respectively. The systematic K-Ar age mapping along a N-S traverse of the Tia Complex exhibits a gradual change. The white mica ages become younger from the lowest-grade zone (339 Ma) to the highest-grade zone (259 Ma). In contrast, Si content of muscovite changes drastically only in the highest-grade zone. The regional changes of white mica K-Ar ages and chemical compositions of micas indicate argon depletion from precursor high-P/low-T type phengitic white mica during the thermal overprinting and recrystallization by granitoids intrusions. Our new K-Ar ages and available geological data postulate a model of the eastward rollback of a subduction zone in Early Permian. The eastward shift of a subduction zone system and subsequent magmatic activities of high-Mg andesite and adakite might explain formation of S-type granitoids (Hillgrove suite) and coeval low-P/high-T type metamorphism in the Tia Complex.

  5. Structural insights into the T6SS effector protein Tse3 and the Tse3-Tsi3 complex from Pseudomonas aeruginosa reveal a calcium-dependent membrane-binding mechanism.

    Science.gov (United States)

    Lu, Defen; Shang, Guijun; Zhang, Heqiao; Yu, Qian; Cong, Xiaoyan; Yuan, Jupeng; He, Fengjuan; Zhu, Chunyuan; Zhao, Yanyu; Yin, Kun; Chen, Yuanyuan; Hu, Junqiang; Zhang, Xiaodan; Yuan, Zenglin; Xu, Sujuan; Hu, Wei; Cang, Huaixing; Gu, Lichuan

    2014-06-01

    The opportunistic pathogen Pseudomonas aeruginosa uses the type VI secretion system (T6SS) to deliver the muramidase Tse3 into the periplasm of rival bacteria to degrade their peptidoglycan (PG). Concomitantly, P. aeruginosa uses the periplasm-localized immunity protein Tsi3 to prevent potential self-intoxication caused by Tse3, and thus gains an edge over rival bacteria in fierce niche competition. Here, we report the crystal structures of Tse3 and the Tse3-Tsi3 complex. Tse3 contains an annexin repeat-like fold at the N-terminus and a G-type lysozyme fold at the C-terminus. One loop in the N-terminal domain (Loop 12) and one helix (α9) from the C-terminal domain together anchor Tse3 and the Tse3-Tsi3 complex to membrane in a calcium-dependent manner in vitro, and this membrane-binding ability is essential for Tse3's activity. In the C-terminal domain, a Y-shaped groove present on the surface likely serves as the PG binding site. Two calcium-binding motifs are also observed in the groove and these are necessary for Tse3 activity. In the Tse3-Tsi3 structure, three loops of Tsi3 insert into the substrate-binding groove of Tse3, and three calcium ions present at the interface of the complex are indispensable for the formation of the Tse3-Tsi3 complex. © 2014 John Wiley & Sons Ltd.

  6. Personality Traits, Learning and Academic Achievements

    Science.gov (United States)

    Jensen, Mikael

    2015-01-01

    There has been an increased interest in personality traits (especially the five-factor model) in relation to education and learning over the last decade. Previous studies have shown a relation between personality traits and learning, and between personality traits and academic achievement. The latter is typically described in terms of Grade Point…

  7. Ecological interactions drive evolutionary loss of traits.

    NARCIS (Netherlands)

    Ellers, J.; Kiers, E.T.; Currie, C.R.; McDonald, B.R.; Visser, B.

    2012-01-01

    Loss of traits can dramatically alter the fate of species. Evidence is rapidly accumulating that the prevalence of trait loss is grossly underestimated. New findings demonstrate that traits can be lost without affecting the external phenotype, provided the lost function is compensated for by species

  8. Functional mapping imprinted quantitative trait loci underlying developmental characteristics

    Directory of Open Access Journals (Sweden)

    Li Gengxin

    2008-03-01

    Full Text Available Abstract Background Genomic imprinting, a phenomenon referring to nonequivalent expression of alleles depending on their parental origins, has been widely observed in nature. It has been shown recently that the epigenetic modification of an imprinted gene can be detected through a genetic mapping approach. Such an approach is developed based on traditional quantitative trait loci (QTL mapping focusing on single trait analysis. Recent studies have shown that most imprinted genes in mammals play an important role in controlling embryonic growth and post-natal development. For a developmental character such as growth, current approach is less efficient in dissecting the dynamic genetic effect of imprinted genes during individual ontology. Results Functional mapping has been emerging as a powerful framework for mapping quantitative trait loci underlying complex traits showing developmental characteristics. To understand the genetic architecture of dynamic imprinted traits, we propose a mapping strategy by integrating the functional mapping approach with genomic imprinting. We demonstrate the approach through mapping imprinted QTL controlling growth trajectories in an inbred F2 population. The statistical behavior of the approach is shown through simulation studies, in which the parameters can be estimated with reasonable precision under different simulation scenarios. The utility of the approach is illustrated through real data analysis in an F2 family derived from LG/J and SM/J mouse stains. Three maternally imprinted QTLs are identified as regulating the growth trajectory of mouse body weight. Conclusion The functional iQTL mapping approach developed here provides a quantitative and testable framework for assessing the interplay between imprinted genes and a developmental process, and will have important implications for elucidating the genetic architecture of imprinted traits.

  9. A trait-based approach to advance coral reef science

    DEFF Research Database (Denmark)

    Madin, Joshua S.; Hoogenboom, Mia O.; Connolly, Sean R.

    2016-01-01

    Coral reefs are biologically diverse and ecologically complex ecosystems constructed by stony corals. Despite decades of research, basic coral population biology and community ecology questions remain. Quantifying trait variation among species can help resolve these questions, but progress has been...... a large amount of variation for a range of biological and ecological processes. Such an approach can accelerate our understanding of coral ecology and our ability to protect critically threatened global ecosystems....

  10. Exploring the genetic architecture and improving genomic prediction accuracy for mastitis and milk production traits in dairy cattle by mapping variants to hepatic transcriptomic regions responsive to intra-mammary infection.

    Science.gov (United States)

    Fang, Lingzhao; Sahana, Goutam; Ma, Peipei; Su, Guosheng; Yu, Ying; Zhang, Shengli; Lund, Mogens Sandø; Sørensen, Peter

    2017-05-12

    A better understanding of the genetic architecture of complex traits can contribute to improve genomic prediction. We hypothesized that genomic variants associated with mastitis and milk production traits in dairy cattle are enriched in hepatic transcriptomic regions that are responsive to intra-mammary infection (IMI). Genomic markers [e.g. single nucleotide polymorphisms (SNPs)] from those regions, if included, may improve the predictive ability of a genomic model. We applied a genomic feature best linear unbiased prediction model (GFBLUP) to implement the above strategy by considering the hepatic transcriptomic regions responsive to IMI as genomic features. GFBLUP, an extension of GBLUP, includes a separate genomic effect of SNPs within a genomic feature, and allows differential weighting of the individual marker relationships in the prediction equation. Since GFBLUP is computationally intensive, we investigated whether a SNP set test could be a computationally fast way to preselect predictive genomic features. The SNP set test assesses the association between a genomic feature and a trait based on single-SNP genome-wide association studies. We applied these two approaches to mastitis and milk production traits (milk, fat and protein yield) in Holstein (HOL, n = 5056) and Jersey (JER, n = 1231) cattle. We observed that a majority of genomic features were enriched in genomic variants that were associated with mastitis and milk production traits. Compared to GBLUP, the accuracy of genomic prediction with GFBLUP was marginally improved (3.2 to 3.9%) in within-breed prediction. The highest increase (164.4%) in prediction accuracy was observed in across-breed prediction. The significance of genomic features based on the SNP set test were correlated with changes in prediction accuracy of GFBLUP (P layers of biological knowledge to provide novel insights into the biological basis of complex traits, and to improve the accuracy of genomic prediction. The SNP set

  11. Association genetics of growth and adaptive traits in loblolly pine (Pinus taeda L.) using whole-exome-discovered polymorphisms

    Science.gov (United States)

    Mengmeng Lu; Konstantin V. Krutovsky; C. Dana Nelson; Jason B. West; Nathalie A. Reilly; Carol A. Loopstra

    2017-01-01

    In the USA, forest genetics research began over 100 years ago and loblolly pine breeding programs were established in the 1950s. However, the genetics underlying complex traits of loblolly pine remains to be discovered. To address this, adaptive and growth traits were measured and analyzed in a clonally tested loblolly pine (Pinus taeda L.) population. Over 2.8 million...

  12. CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

    NARCIS (Netherlands)

    Macé, Aurélien; Tuke, Marcus A; Deelen, Patrick; Kristiansson, Kati; Mattsson, Hannele; Nõukas, Margit; Sapkota, Yadav; Schick, Ursula; Porcu, Eleonora; Rüeger, Sina; McDaid, Aaron F; Porteous, David; Winkler, Thomas W; Salvi, Erika; Shrine, Nick; Liu, Xueping; Ang, Wei Q; Zhang, Weihua; Feitosa, Mary F; Venturini, Cristina; van der Most, Peter J; Rosengren, Anders; Wood, Andrew R; Beaumont, Robin N; Jones, Samuel E; Ruth, Katherine S; Yaghootkar, Hanieh; Tyrrell, Jessica; Havulinna, Aki S; Boers, Harmen; Mägi, Reedik; Kriebel, Jennifer; Müller-Nurasyid, Martina; Perola, Markus; Nieminen, Markku; Lokki, Marja-Liisa; Kähönen, Mika; Viikari, Jorma S; Geller, Frank; Lahti, Jari; Palotie, Aarno; Koponen, Päivikki; Lundqvist, Annamari; Rissanen, Harri; Bottinger, Erwin P; Afaq, Saima; Wojczynski, Mary K; Lenzini, Petra; Nolte, Ilja M; Sparsø, Thomas; Schupf, Nicole; Christensen, Kaare; Perls, Thomas T; Newman, Anne B; Werge, Thomas; Snieder, Harold; Spector, Timothy D; Chambers, John C; Koskinen, Seppo; Melbye, Mads; Raitakari, Olli T; Lehtimäki, Terho; Tobin, Martin D; Wain, Louise V; Sinisalo, Juha; Peters, Annette; Meitinger, Thomas; Martin, Nicholas G; Wray, Naomi R; Montgomery, Grant W; Medland, Sarah E; Swertz, Morris A; Vartiainen, Erkki; Borodulin, Katja; Männistö, Satu; Murray, Anna; Bochud, Murielle; Jacquemont, Sébastien; Rivadeneira, Fernando; Hansen, Thomas F; Oldehinkel, Albertine J; Mangino, Massimo; Province, Michael A; Deloukas, Panos; Kooner, Jaspal S; Freathy, Rachel M; Pennell, Craig; Feenstra, Bjarke; Strachan, David P; Lettre, Guillaume; Hirschhorn, Joel; Cusi, Daniele; Heid, Iris M; Hayward, Caroline; Männik, Katrin; Beckmann, Jacques S; Loos, Ruth J F; Nyholt, Dale R; Metspalu, Andres; Eriksson, Johan G; Weedon, Michael N; Salomaa, Veikko; Franke, Lude; Reymond, Alexandre; Frayling, Timothy M; Kutalik, Zoltán

    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 at

  13. Quantitative genetics of disease traits.

    Science.gov (United States)

    Wray, N R; Visscher, P M

    2015-04-01

    John James authored two key papers on the theory of risk to relatives for binary disease traits and the relationship between parameters on the observed binary scale and an unobserved scale of liability (James Annals of Human Genetics, 1971; 35: 47; Reich, James and Morris Annals of Human Genetics, 1972; 36: 163). These two papers are John James' most cited papers (198 and 328 citations, November 2014). They have been influential in human genetics and have recently gained renewed popularity because of their relevance to the estimation of quantitative genetics parameters for disease traits using SNP data. In this review, we summarize the two early papers and put them into context. We show recent extensions of the theory for ascertained case-control data and review recent applications in human genetics. © 2015 Blackwell Verlag GmbH.

  14. A trait database for marine copepods

    DEFF Research Database (Denmark)

    Brun, Philipp Georg; Payne, Mark R.; Kiørboe, Thomas

    2016-01-01

    was more limited for quantitative traits related to reproduction and physiology. The database may be used to investigate relationships between traits, to produce trait biogeographies, or to inform and validate trait-based marine ecosystem models. The data can be downloaded from PANGAEA, doi:10.1594/PANGAEA......, and organised the data into a structured database. We collected 9345 records for 14 functional traits. Particular attention was given to body size, feeding mode, egg size, spawning strategy, respiration rate and myelination (presence of nerve sheathing). Most records were reported on the species level, but some...

  15. A trait database for marine copepods

    DEFF Research Database (Denmark)

    Brun, Philipp Georg; Payne, Mark; Kiørboe, Thomas

    2017-01-01

    , while information was more limited for quantitative traits related to reproduction and physiology. The database may be used to investigate relationships between traits, to produce trait biogeographies, or to inform and validate trait-based marine ecosystem models. The data can be downloaded from PANGAEA...... and organized the data into a structured database. We collected 9306 records for 14 functional traits. Particular attention was given to body size, feeding mode, egg size, spawning strategy, respiration rate, and myelination (presence of nerve sheathing). Most records were reported at the species level...

  16. Cultural effects on the association between election outcomes and face-based trait inferences.

    Directory of Open Access Journals (Sweden)

    Chujun Lin

    Full Text Available How competent a politician looks, as assessed in the laboratory, is correlated with whether the politician wins in real elections. This finding has led many to investigate whether the association between candidate appearances and election outcomes transcends cultures. However, these studies have largely focused on European countries and Caucasian candidates. To the best of our knowledge, there are only four cross-cultural studies that have directly investigated how face-based trait inferences correlate with election outcomes across Caucasian and Asian cultures. These prior studies have provided some initial evidence regarding cultural differences, but methodological problems and inconsistent findings have complicated our understanding of how culture mediates the effects of candidate appearances on election outcomes. Additionally, these four past studies have focused on positive traits, with a relative neglect of negative traits, resulting in an incomplete picture of how culture may impact a broader range of trait inferences. To study Caucasian-Asian cultural effects with a more balanced experimental design, and to explore a more complete profile of traits, here we compared how Caucasian and Korean participants' inferences of positive and negative traits correlated with U.S. and Korean election outcomes. Contrary to previous reports, we found that inferences of competence (made by participants from both cultures correlated with both U.S. and Korean election outcomes. Inferences of open-mindedness and threat, two traits neglected in previous cross-cultural studies, were correlated with Korean but not U.S. election outcomes. This differential effect was found in trait judgments made by both Caucasian and Korean participants. Interestingly, the faster the participants made face-based trait inferences, the more strongly those inferences were correlated with real election outcomes. These findings provide new insights into cultural effects and the

  17. Cultural effects on the association between election outcomes and face-based trait inferences.

    Science.gov (United States)

    Lin, Chujun; Adolphs, Ralph; Alvarez, R Michael

    2017-01-01

    How competent a politician looks, as assessed in the laboratory, is correlated with whether the politician wins in real elections. This finding has led many to investigate whether the association between candidate appearances and election outcomes transcends cultures. However, these studies have largely focused on European countries and Caucasian candidates. To the best of our knowledge, there are only four cross-cultural studies that have directly investigated how face-based trait inferences correlate with election outcomes across Caucasian and Asian cultures. These prior studies have provided some initial evidence regarding cultural differences, but methodological problems and inconsistent findings have complicated our understanding of how culture mediates the effects of candidate appearances on election outcomes. Additionally, these four past studies have focused on positive traits, with a relative neglect of negative traits, resulting in an incomplete picture of how culture may impact a broader range of trait inferences. To study Caucasian-Asian cultural effects with a more balanced experimental design, and to explore a more complete profile of traits, here we compared how Caucasian and Korean participants' inferences of positive and negative traits correlated with U.S. and Korean election outcomes. Contrary to previous reports, we found that inferences of competence (made by participants from both cultures) correlated with both U.S. and Korean election outcomes. Inferences of open-mindedness and threat, two traits neglected in previous cross-cultural studies, were correlated with Korean but not U.S. election outcomes. This differential effect was found in trait judgments made by both Caucasian and Korean participants. Interestingly, the faster the participants made face-based trait inferences, the more strongly those inferences were correlated with real election outcomes. These findings provide new insights into cultural effects and the difficult question of

  18. Cultural effects on the association between election outcomes and face-based trait inferences

    Science.gov (United States)

    Adolphs, Ralph; Alvarez, R. Michael

    2017-01-01

    How competent a politician looks, as assessed in the laboratory, is correlated with whether the politician wins in real elections. This finding has led many to investigate whether the association between candidate appearances and election outcomes transcends cultures. However, these studies have largely focused on European countries and Caucasian candidates. To the best of our knowledge, there are only four cross-cultural studies that have directly investigated how face-based trait inferences correlate with election outcomes across Caucasian and Asian cultures. These prior studies have provided some initial evidence regarding cultural differences, but methodological problems and inconsistent findings have complicated our understanding of how culture mediates the effects of candidate appearances on election outcomes. Additionally, these four past studies have focused on positive traits, with a relative neglect of negative traits, resulting in an incomplete picture of how culture may impact a broader range of trait inferences. To study Caucasian-Asian cultural effects with a more balanced experimental design, and to explore a more complete profile of traits, here we compared how Caucasian and Korean participants’ inferences of positive and negative traits correlated with U.S. and Korean election outcomes. Contrary to previous reports, we found that inferences of competence (made by participants from both cultures) correlated with both U.S. and Korean election outcomes. Inferences of open-mindedness and threat, two traits neglected in previous cross-cultural studies, were correlated with Korean but not U.S. election outcomes. This differential effect was found in trait judgments made by both Caucasian and Korean participants. Interestingly, the faster the participants made face-based trait inferences, the more strongly those inferences were correlated with real election outcomes. These findings provide new insights into cultural effects and the difficult question of

  19. Too much of a good thing: curvilinear relationships between personality traits and job performance.

    Science.gov (United States)

    Le, Huy; Oh, In-Sue; Robbins, Steven B; Ilies, Remus; Holland, Ed; Westrick, Paul

    2011-01-01

    The relationships between personality traits and performance are often assumed to be linear. This assumption has been challenged conceptually and empirically, but results to date have been inconclusive. In the current study, we took a theory-driven approach in systematically addressing this issue. Results based on two different samples generally supported our expectations of the curvilinear relationships between personality traits, including Conscientiousness and Emotional Stability, and job performance dimensions, including task performance, organizational citizenship behavior, and counterproductive work behaviors. We also hypothesized and found that job complexity moderated the curvilinear personality–performance relationships such that the inflection points after which the relationships disappear were lower for low-complexity jobs than they were for high-complexity jobs. This finding suggests that high levels of the two personality traits examined are more beneficial for performance in high- than low-complexity jobs. We conclude by discussing the implications of these findings for the use of personality in personnel selection.

  20. Enhanced leaf photosynthesis as a target to increase grain yield: insights from transgenic rice lines with variable Rieske FeS protein content in the cytochrome b6 /f complex.

    Science.gov (United States)

    Yamori, Wataru; Kondo, Eri; Sugiura, Daisuke; Terashima, Ichiro; Suzuki, Yuji; Makino, Amane

    2016-01-01

    Although photosynthesis is the most important source for biomass and grain yield, a lack of correlation between photosynthesis and plant yield among different genotypes of various crop species has been frequently observed. Such observations contribute to the ongoing debate whether enhancing leaf photosynthesis can improve yield potential. Here, transgenic rice plants that contain variable amounts of the Rieske FeS protein in the cytochrome (cyt) b6 /f complex between 10 and 100% of wild-type levels have been used to investigate the effect of reductions of these proteins on photosynthesis, plant growth and yield. Reductions of the cyt b6 /f complex did not affect the electron transport rates through photosystem I but decreased electron transport rates through photosystem II, leading to concomitant decreases in CO2 assimilation rates. There was a strong control of plant growth and grain yield by the rate of leaf photosynthesis, leading to the conclusion that enhancing photosynthesis at the single-leaf level would be a useful target for improving crop productivity and yield both via conventional breeding and biotechnology. The data here also suggest that changing photosynthetic electron transport rates via manipulation of the cyt b6 /f complex could be a potential target for enhancing photosynthetic capacity in higher plants. © 2015 John Wiley & Sons Ltd.

  1. Choosing and using diversity indices: insights for ecological applications from the German Biodiversity Exploratories.

    Science.gov (United States)

    Morris, E Kathryn; Caruso, Tancredi; Buscot, François; Fischer, Markus; Hancock, Christine; Maier, Tanja S; Meiners, Torsten; Müller, Caroline; Obermaier, Elisabeth; Prati, Daniel; Socher, Stephanie A; Sonnemann, Ilja; Wäschke, Nicole; Wubet, Tesfaye; Wurst, Susanne; Rillig, Matthias C