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Sample records for investigating gene-environment interactions

  1. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations.

    Science.gov (United States)

    van Os, Jim; Rutten, Bart P; Myin-Germeys, Inez; Delespaul, Philippe; Viechtbauer, Wolfgang; van Zelst, Catherine; Bruggeman, Richard; Reininghaus, Ulrich; Morgan, Craig; Murray, Robin M; Di Forti, Marta; McGuire, Philip; Valmaggia, Lucia R; Kempton, Matthew J; Gayer-Anderson, Charlotte; Hubbard, Kathryn; Beards, Stephanie; Stilo, Simona A; Onyejiaka, Adanna; Bourque, Francois; Modinos, Gemma; Tognin, Stefania; Calem, Maria; O'Donovan, Michael C; Owen, Michael J; Holmans, Peter; Williams, Nigel; Craddock, Nicholas; Richards, Alexander; Humphreys, Isla; Meyer-Lindenberg, Andreas; Leweke, F Markus; Tost, Heike; Akdeniz, Ceren; Rohleder, Cathrin; Bumb, J Malte; Schwarz, Emanuel; Alptekin, Köksal; Üçok, Alp; Saka, Meram Can; Atbaşoğlu, E Cem; Gülöksüz, Sinan; Gumus-Akay, Guvem; Cihan, Burçin; Karadağ, Hasan; Soygür, Haldan; Cankurtaran, Eylem Şahin; Ulusoy, Semra; Akdede, Berna; Binbay, Tolga; Ayer, Ahmet; Noyan, Handan; Karadayı, Gülşah; Akturan, Elçin; Ulaş, Halis; Arango, Celso; Parellada, Mara; Bernardo, Miguel; Sanjuán, Julio; Bobes, Julio; Arrojo, Manuel; Santos, Jose Luis; Cuadrado, Pedro; Rodríguez Solano, José Juan; Carracedo, Angel; García Bernardo, Enrique; Roldán, Laura; López, Gonzalo; Cabrera, Bibiana; Cruz, Sabrina; Díaz Mesa, Eva Ma; Pouso, María; Jiménez, Estela; Sánchez, Teresa; Rapado, Marta; González, Emiliano; Martínez, Covadonga; Sánchez, Emilio; Olmeda, Ma Soledad; de Haan, Lieuwe; Velthorst, Eva; van der Gaag, Mark; Selten, Jean-Paul; van Dam, Daniella; van der Ven, Elsje; van der Meer, Floor; Messchaert, Elles; Kraan, Tamar; Burger, Nadine; Leboyer, Marion; Szoke, Andrei; Schürhoff, Franck; Llorca, Pierre-Michel; Jamain, Stéphane; Tortelli, Andrea; Frijda, Flora; Vilain, Jeanne; Galliot, Anne-Marie; Baudin, Grégoire; Ferchiou, Aziz; Richard, Jean-Romain; Bulzacka, Ewa; Charpeaud, Thomas; Tronche, Anne-Marie; De Hert, Marc; van Winkel, Ruud; Decoster, Jeroen; Derom, Catherine; Thiery, Evert; Stefanis, Nikos C; Sachs, Gabriele; Aschauer, Harald; Lasser, Iris; Winklbaur, Bernadette; Schlögelhofer, Monika; Riecher-Rössler, Anita; Borgwardt, Stefan; Walter, Anna; Harrisberger, Fabienne; Smieskova, Renata; Rapp, Charlotte; Ittig, Sarah; Soguel-dit-Piquard, Fabienne; Studerus, Erich; Klosterkötter, Joachim; Ruhrmann, Stephan; Paruch, Julia; Julkowski, Dominika; Hilboll, Desiree; Sham, Pak C; Cherny, Stacey S; Chen, Eric Y H; Campbell, Desmond D; Li, Miaoxin; Romeo-Casabona, Carlos María; Emaldi Cirión, Aitziber; Urruela Mora, Asier; Jones, Peter; Kirkbride, James; Cannon, Mary; Rujescu, Dan; Tarricone, Ilaria; Berardi, Domenico; Bonora, Elena; Seri, Marco; Marcacci, Thomas; Chiri, Luigi; Chierzi, Federico; Storbini, Viviana; Braca, Mauro; Minenna, Maria Gabriella; Donegani, Ivonne; Fioritti, Angelo; La Barbera, Daniele; La Cascia, Caterina Erika; Mulè, Alice; Sideli, Lucia; Sartorio, Rachele; Ferraro, Laura; Tripoli, Giada; Seminerio, Fabio; Marinaro, Anna Maria; McGorry, Patrick; Nelson, Barnaby; Amminger, G Paul; Pantelis, Christos; Menezes, Paulo R; Del-Ben, Cristina M; Gallo Tenan, Silvia H; Shuhama, Rosana; Ruggeri, Mirella; Tosato, Sarah; Lasalvia, Antonio; Bonetto, Chiara; Ira, Elisa; Nordentoft, Merete; Krebs, Marie-Odile; Barrantes-Vidal, Neus; Cristóbal, Paula; Kwapil, Thomas R; Brietzke, Elisa; Bressan, Rodrigo A; Gadelha, Ary; Maric, Nadja P; Andric, Sanja; Mihaljevic, Marina; Mirjanic, Tijana

    2014-07-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions.

    Science.gov (United States)

    Manuguerra, M; Matullo, G; Veglia, F; Autrup, H; Dunning, A M; Garte, S; Gormally, E; Malaveille, C; Guarrera, S; Polidoro, S; Saletta, F; Peluso, M; Airoldi, L; Overvad, K; Raaschou-Nielsen, O; Clavel-Chapelon, F; Linseisen, J; Boeing, H; Trichopoulos, D; Kalandidi, A; Palli, D; Krogh, V; Tumino, R; Panico, S; Bueno-De-Mesquita, H B; Peeters, P H; Lund, E; Pera, G; Martinez, C; Amiano, P; Barricarte, A; Tormo, M J; Quiros, J R; Berglund, G; Janzon, L; Jarvholm, B; Day, N E; Allen, N E; Saracci, R; Kaaks, R; Ferrari, P; Riboli, E; Vineis, P

    2007-02-01

    It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n=124), lung cancer (n=116) and myeloid leukemia (n=169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, PT (mean prediction error of 22%, PT, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P<0.001) and a maximum CVC of 4.40 (P=0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.

  3. Power Analysis for Population-Based Longitudinal Studies Investigating Gene-Environment Interactions in Chronic Diseases: A Simulation Study.

    Directory of Open Access Journals (Sweden)

    Jinhui Ma

    was not very low (≥0.1 and the disease of interest was not rare (such as diabetes and dementia. The CLSA had enough power to detect a large effect of the gene-environment interaction only when both risk exposures had relatively high prevalence (0.2 and the disease of interest was very common (such as diabetes. The minimum detectable hazard ratios (MDHR of the CLSA for the environmental and genetic risk exposures obtained from this simulation study were larger than those calculated according to the conventional sample size calculation method. For example, the MDHR for the environmental risk exposure was 1.15 according to the conventional method if the prevalence of the risk exposure was 0.1 and the disease of interest was dementia. In contrast, the MDHR was 1.61 if the same exposure was measured every 3 years with a misclassification rate of 0.1 according to this simulation study. With a given sample size, higher statistical power could be achieved by increasing the measuring frequency in participants with high risk of declining health status or changing risk exposures, and by increasing measurement accuracy of diseases and risk exposures. A properly designed simulation-based sample size calculation is superior to conventional methods when rigorous sample size calculation is necessary.

  4. Finding gene-environment interactions for Phobias

    OpenAIRE

    Gregory, Alice M.; Lau, Jennifer Y. F.; Eley, Thalia C.

    2008-01-01

    Phobias are common disorders causing a great deal of suffering. Studies of gene-environment interaction (G × E) have revealed much about the complex processes underlying the development of various psychiatric disorders but have told us little about phobias. This article describes what is already known about genetic and environmental influences upon phobias and suggests how this information can be used to optimise the chances of discovering G × Es for phobias. In addition to the careful concep...

  5. Gene-environment interactions on growth trajectories.

    Science.gov (United States)

    Wang, Shuang; Xiong, Wei; Ma, Weiping; Chanock, Stephen; Jedrychowski, Wieslaw; Wu, Rongling; Perera, Frederica P

    2012-04-01

    It has been suggested that children with larger brains tend to perform better on IQ tests or cognitive function tests. Prenatal head growth and head growth in infancy are two crucial periods for subsequent intelligence. Studies have shown that environmental exposure to air pollutants during pregnancy is associated with fetal growth reduction, developmental delay, and reduced IQ. Meanwhile, genetic polymorphisms may modify the effect of environment on head growth. However, studies on gene-environment or gene-gene interactions on growth trajectories have been quite limited partly due to the difficulty to quantitatively measure interactions on growth trajectories. Moreover, it is known that assessing the significance of gene-environment or gene-gene interactions on cross-sectional outcomes empirically using the permutation procedures may bring substantial errors in the tests. We proposed a score that quantitatively measures interactions on growth trajectories and developed an algorithm with a parametric bootstrap procedure to empirically assess the significance of the interactions on growth trajectories under the likelihood framework. We also derived a Wald statistic to test for interactions on growth trajectories and compared it to the proposed parametric bootstrap procedure. Through extensive simulation studies, we demonstrated the feasibility and power of the proposed testing procedures. We applied our method to a real dataset with head circumference measures from birth to age 7 on a cohort currently being conducted by the Columbia Center for Children's Environmental Health (CCCEH) in Krakow, Poland, and identified several significant gene-environment interactions on head circumference growth trajectories. © 2012 Wiley Periodicals, Inc.

  6. Finding gene-environment interactions for phobias.

    Science.gov (United States)

    Gregory, Alice M; Lau, Jennifer Y F; Eley, Thalia C

    2008-03-01

    Phobias are common disorders causing a great deal of suffering. Studies of gene-environment interaction (G x E) have revealed much about the complex processes underlying the development of various psychiatric disorders but have told us little about phobias. This article describes what is already known about genetic and environmental influences upon phobias and suggests how this information can be used to optimise the chances of discovering G x Es for phobias. In addition to the careful conceptualisation of new studies, it is suggested that data already collected should be re-analysed in light of increased understanding of processes influencing phobias.

  7. Gene-environment interactions involving functional variants

    DEFF Research Database (Denmark)

    Barrdahl, Myrto; Rudolph, Anja; Hopper, John L

    2017-01-01

    epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind. Analyses were carried out separately for estrogen receptor (ER.......01. The strongest interaction result in relation to overall breast cancer risk was found between CFLAR-rs7558475 and current smoking (ORint  = 0.77, 95% CI: 0.67-0.88, pint  = 1.8 × 10(-4) ). The interaction with the strongest statistical evidence was found between 5q14-rs7707921 and alcohol consumption (ORint =1.......36, 95% CI: 1.16-1.59, pint  = 1.9 × 10(-5) ) in relation to ER- disease risk. The remaining two gene-environment interactions were also identified in relation to ER- breast cancer risk and were found between 3p21-rs6796502 and age at menarche (ORint  = 1.26, 95% CI: 1.12-1.43, pint =1.8 × 10...

  8. A flexible Bayesian model for studying gene-environment interaction.

    Directory of Open Access Journals (Sweden)

    Kai Yu

    2012-01-01

    Full Text Available An important follow-up step after genetic markers are found to be associated with a disease outcome is a more detailed analysis investigating how the implicated gene or chromosomal region and an established environment risk factor interact to influence the disease risk. The standard approach to this study of gene-environment interaction considers one genetic marker at a time and therefore could misrepresent and underestimate the genetic contribution to the joint effect when one or more functional loci, some of which might not be genotyped, exist in the region and interact with the environment risk factor in a complex way. We develop a more global approach based on a Bayesian model that uses a latent genetic profile variable to capture all of the genetic variation in the entire targeted region and allows the environment effect to vary across different genetic profile categories. We also propose a resampling-based test derived from the developed Bayesian model for the detection of gene-environment interaction. Using data collected in the Environment and Genetics in Lung Cancer Etiology (EAGLE study, we apply the Bayesian model to evaluate the joint effect of smoking intensity and genetic variants in the 15q25.1 region, which contains a cluster of nicotinic acetylcholine receptor genes and has been shown to be associated with both lung cancer and smoking behavior. We find evidence for gene-environment interaction (P-value = 0.016, with the smoking effect appearing to be stronger in subjects with a genetic profile associated with a higher lung cancer risk; the conventional test of gene-environment interaction based on the single-marker approach is far from significant.

  9. Environmental confounding in gene-environment interaction studies.

    Science.gov (United States)

    Vanderweele, Tyler J; Ko, Yi-An; Mukherjee, Bhramar

    2013-07-01

    We show that, in the presence of uncontrolled environmental confounding, joint tests for the presence of a main genetic effect and gene-environment interaction will be biased if the genetic and environmental factors are correlated, even if there is no effect of either the genetic factor or the environmental factor on the disease. When environmental confounding is ignored, such tests will in fact reject the joint null of no genetic effect with a probability that tends to 1 as the sample size increases. This problem with the joint test vanishes under gene-environment independence, but it still persists if estimating the gene-environment interaction parameter itself is of interest. Uncontrolled environmental confounding will bias estimates of gene-environment interaction parameters even under gene-environment independence, but it will not do so if the unmeasured confounding variable itself does not interact with the genetic factor. Under gene-environment independence, if the interaction parameter without controlling for the environmental confounder is nonzero, then there is gene-environment interaction either between the genetic factor and the environmental factor of interest or between the genetic factor and the unmeasured environmental confounder. We evaluate several recently proposed joint tests in a simulation study and discuss the implications of these results for the conduct of gene-environment interaction studies.

  10. A Comparison of Case-Control and Case-Only Designs to Investigate Gene-Environment Interactions Using Breast Cancer Data

    Directory of Open Access Journals (Sweden)

    Jafar Hassanzadeh

    2012-06-01

    Full Text Available Background: The traditional methods of studying the gene-environment interactions need a control group. However, the selection of an appropriate control group has been associated with problems. Therefore, new methods, such as case-only design, have been created to study such interactions. The objective of this study was to compare the case-only and case-control designs using data from patients with breast cancer.Methods: The interaction of genetic and environmental factor as well as the ratio of control to population odds ratio was calculated for case-only (300 patients with breast cancer and case-control (300 cases of breast cancer and 300 matched controls designs. Results: The confidence intervals and -2log likelihood in all variables in case-only design was smaller than those in the matched case-control design. In case-only design, the standard errors of some variables such as age at menarche, the first delivery at the age of 35 yrs and more or no delivery, the history of having live birth, use of oral contraception pills, breastfeeding history were less than those in the matched case-control design. Conclusion: The findings indicate that the case-only design is an efficient method to investigate the interaction of genetic and environmental factors.

  11. Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

    DEFF Research Database (Denmark)

    Rudolph, Anja; Milne, Roger L; Truong, Thérèse

    2015-01-01

    A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated...

  12. Animal models of gene-environment interactions in schizophrenia.

    Science.gov (United States)

    Ayhan, Yavuz; Sawa, Akira; Ross, Christopher A; Pletnikov, Mikhail V

    2009-12-07

    The pathogenesis of schizophrenia and related mental illnesses likely involves multiple interactions between susceptibility genes of small effects and environmental factors. Gene-environment interactions occur across different stages of neurodevelopment to produce heterogeneous clinical and pathological manifestations of the disease. The main obstacle for mechanistic studies of gene-environment interplay has been the paucity of appropriate experimental systems for elucidating the molecular pathways that mediate gene-environment interactions relevant to schizophrenia. Recent advances in psychiatric genetics and a plethora of experimental data from animal studies allow us to suggest a new approach to gene-environment interactions in schizophrenia. We propose that animal models based on identified genetic mutations and measurable environment factors will help advance studies of the molecular mechanisms of gene-environment interplay.

  13. Gene-Environment Interactions in Severe Mental Illness

    Directory of Open Access Journals (Sweden)

    Rudolf eUher

    2014-05-01

    Full Text Available Severe mental illness is a broad category that includes schizophrenia, bipolar disorder and severe depression. Both genetic disposition and environmental exposures play important roles in the development of severe mental illness. Multiple lines of evidence suggest that the roles of genetic and environmental depend on each other. Gene-environment interactions may underlie the paradox of strong environmental factors for highly heritable disorders, the low estimates of shared environmental influences in twin studies of severe mental illness and the heritability gap between twin and molecular heritability estimates. Sons and daughters of parents with severe mental illness are more vulnerable to the effects of prenatal and postnatal environmental exposures, suggesting that the expression of genetic liability depends on environment. In the last decade, gene-environment interactions involving specific molecular variants in candidate genes have been identified. Replicated findings include an interaction between a polymorphism in the AKT1 gene and cannabis use in the development of psychosis and an interaction between the length polymorphism of the serotonin transporter gene and childhood maltreatment in the development of persistent depressive disorder. Bipolar disorder has been underinvestigated, with only a single study showing an interaction between a functional polymorphism in BDNF and stressful life events triggering bipolar depressive episodes. The first systematic search for gene-environment interactions has found that a polymorphism in CTNNA3 may sensitise the developing brain to the pathogenic effect of cytomegalovirus in utero, leading to schizophrenia in adulthood. Strategies for genome-wide investigations will likely include coordination between epidemiological and genetic research efforts, systematic assessment of multiple environmental factors in large samples, and prioritization of genetic variants.

  14. Gene-Environment Interaction in Parkinson's Disease

    DEFF Research Database (Denmark)

    Chuang, Yu-Hsuan; Lill, Christina M; Lee, Pei-Chen

    2016-01-01

    BACKGROUND AND PURPOSE: Drinking caffeinated coffee has been reported to provide protection against Parkinson's disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2......) metabolizes caffeine; thus, gene polymorphisms in ADORA2A and CYP1A2 may influence the effect coffee consumption has on PD risk. METHODS: In a population-based case-control study (PASIDA) in Denmark (1,556 PD patients and 1,606 birth year- and gender-matched controls), we assessed interactions between...... lifetime coffee consumption and 3 polymorphisms in ADORA2A and CYP1A2 for all subjects, and incident and prevalent PD cases separately using logistic regression models. We also conducted a meta-analysis combining our results with those from previous studies. RESULTS: We estimated statistically significant...

  15. Identifying Gene-Environment Interactions in Schizophrenia

    DEFF Research Database (Denmark)

    van Os, Jim; Rutten, Bart P; Myin-Germeys, Inez

    2014-01-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual...... of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap...

  16. Gene-environment interaction and male reproductive function

    Science.gov (United States)

    Axelsson, Jonatan; Bonde, Jens Peter; Giwercman, Yvonne L.; Rylander, Lars; Giwercman, Aleksander

    2010-01-01

    As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism, but the number of studies is still limited. This type of interaction studies may improve our understanding of normal physiology and help us to identify the risk factors to male reproductive malfunction. We also shortly discuss other aspects of gene-environment interaction specifically associated with the issue of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity in the offspring. PMID:20348940

  17. Robust Tests for Additive Gene-Environment Interaction in Case-Control Studies Using Gene-Environment Independence

    DEFF Research Database (Denmark)

    Liu, Gang; Lee, Seunggeun; Lee, Alice W

    2018-01-01

    There have been recent proposals advocating the use of additive gene-environment interaction instead of the widely used multiplicative scale, as a more relevant public health measure. Using gene-environment independence enhances the power for testing multiplicative interaction in case...... in a data-adaptive way, to the additive scale. An EB estimator of Relative Excess Risk due to Interaction is derived and the corresponding Wald test is proposed with general regression setting under a retrospective likelihood framework. We study the impact of gene-environment association on the resultant...... test with case-control data. Our simulation studies suggest that the EB approach uses the gene-environment independence assumption in a data-adaptive way and provides power gain compared to the standard logistic regression analysis and better control of Type I error when compared to the analysis...

  18. Meta-analysis of gene-environment interaction exploiting gene-environment independence across multiple case-control studies.

    Science.gov (United States)

    Estes, Jason P; Rice, John D; Li, Shi; Stringham, Heather M; Boehnke, Michael; Mukherjee, Bhramar

    2017-10-30

    Multiple papers have studied the use of gene-environment (G-E) independence to enhance power for testing gene-environment interaction in case-control studies. However, studies that evaluate the role of G-E independence in a meta-analysis framework are limited. In this paper, we extend the single-study empirical Bayes type shrinkage estimators proposed by Mukherjee and Chatterjee (2008) to a meta-analysis setting that adjusts for uncertainty regarding the assumption of G-E independence across studies. We use the retrospective likelihood framework to derive an adaptive combination of estimators obtained under the constrained model (assuming G-E independence) and unconstrained model (without assumptions of G-E independence) with weights determined by measures of G-E association derived from multiple studies. Our simulation studies indicate that this newly proposed estimator has improved average performance across different simulation scenarios than the standard alternative of using inverse variance (covariance) weighted estimators that combines study-specific constrained, unconstrained, or empirical Bayes estimators. The results are illustrated by meta-analyzing 6 different studies of type 2 diabetes investigating interactions between genetic markers on the obesity related FTO gene and environmental factors body mass index and age. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Animal model for schizophrenia that reflects gene-environment interactions.

    Science.gov (United States)

    Nagai, Taku; Ibi, Daisuke; Yamada, Kiyofumi

    2011-01-01

    Schizophrenia is a devastating psychiatric disorder that impairs mental and social functioning and affects approximately 1% of the population worldwide. Genetic susceptibility factors for schizophrenia have recently been reported, some of which are known to play a role in neurodevelopment; these include neuregulin-1, dysbindin, and disrupted-in-schizophrenia 1 (DISC1). Moreover, epidemiologic studies suggest that environmental insults, such as prenatal infection and perinatal complication, are involved in the development of schizophrenia. The possible interaction between environment and genetic susceptibility factors, especially during neurodevelopment, is proposed as a promising disease etiology of schizophrenia. Polyriboinosinic-polyribocytidilic acid (polyI : C) is a synthetic analogue of double-stranded RNA that leads to the pronounced but time-limited production of pro-inflammatory cytokines. Maternal immune activation by polyI : C exposure in rodents is known to precipitate a wide spectrum of behavioral, cognitive, and pharmacological abnormalities in adult offspring. Recently, we have reported that neonatal injection of polyI : C in mice results in schizophrenia-like behavioral alterations in adulthood. In this review, we show how gene-environment interactions during neurodevelopment result in phenotypic changes in adulthood by injecting polyI : C into transgenic mice that express a dominant-negative form of human DISC1 (DN-DISC1). Our findings suggest that polyI : C-treated DN-DISC1 mice are a well-validated animal model for schizophrenia that reflects gene-environment interactions.

  20. Gene-environment interaction and male reproductive function

    DEFF Research Database (Denmark)

    Axelsson, Jonatan; Bonde, Jens Peter; Giwercman, Yvonne L

    2010-01-01

    , but the number of studies is still limited. This type of interaction studies may improve our understanding of normal physiology and help us to identify the risk factors to male reproductive malfunction. We also shortly discuss other aspects of gene-environment interaction specifically associated with the issue......As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between...... and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated...

  1. Gene-environment interactions and alcohol use and dependence: current status and future challenges

    NARCIS (Netherlands)

    Zwaluw, C.S. van der; Engels, R.C.M.E.

    2009-01-01

    To discuss the current status of gene-environment interaction research with regard to alcohol use and dependence. Further, we highlight the difficulties concerning gene-environment studies. Overview of the current evidence for gene-environment interactions in alcohol outcomes, and of the associated

  2. Sleep Duration and Depressive Symptoms: A Gene-Environment Interaction

    Science.gov (United States)

    Watson, Nathaniel F.; Harden, Kathryn Paige; Buchwald, Dedra; Vitiello, Michael V.; Pack, Allan I.; Strachan, Eric; Goldberg, Jack

    2014-01-01

    Objective: We used quantitative genetic models to assess whether sleep duration modifies genetic and environmental influences on depressive symptoms. Method: Participants were 1,788 adult twins from 894 same-sex twin pairs (192 male and 412 female monozygotic [MZ] pairs, and 81 male and 209 female dizygotic [DZ] pairs] from the University of Washington Twin Registry. Participants self-reported habitual sleep duration and depressive symptoms. Data were analyzed using quantitative genetic interaction models, which allowed the magnitude of additive genetic, shared environmental, and non-shared environmental influences on depressive symptoms to vary with sleep duration. Results: Within MZ twin pairs, the twin who reported longer sleep duration reported fewer depressive symptoms (ec = -0.17, SE = 0.06, P sleep duration interaction effect on depressive symptoms (a'c = 0.23, SE = 0.08, P sleep duration and depressive symptoms. Among individuals with sleep duration within the normal range (7-8.9 h/night), the total heritability (h2) of depressive symptoms was approximately 27%. However, among individuals with sleep duration within the low (sleep duration extremes (5 h/night: h2 = 53%; 10 h/night: h2 = 49%). Conclusion: Genetic contributions to depressive symptoms increase at both short and long sleep durations. Citation: Watson NF; Harden KP; Buchwald D; Vitiello MV; Pack AI; Stachan E; Goldberg J. Sleep duration and depressive symptoms: a gene-environment interaction. SLEEP 2014;37(2):351-358. PMID:24497663

  3. Study of oral clefts: Indication of gene-environment interaction

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, S.J.; Beaty, T.H.; Panny, S. [Johns Hopkins Univ., Baltimore, MD (United States)] [and others

    1994-09-01

    In this study of infants with isolated birth defects, 69 cleft palate-only (CPO) cases, 114 cleft lip with or without palate (CL/P), and 284 controls with non-cleft birth defects (all born in Maryland during 1984-1992) were examined to test for associations among genetic markers and different oral clefts. Modest associations were found between transforming growth factor {alpha} (TGF{alpha}) marker and CPO, as well as that between D17S579 (Mfd188) and CL/P in this study. The association between TGF{alpha} marker and CPO reflects a statistical interaction between mother`s smoking and child`s TGF{alpha} genotype. A significantly higher risk of CPO was found among those reporting maternal smoking during pregnancy and carrying less common TGF{alpha} TaqI allele (odds ratio=7.02 with 95% confidence interval 1.8-27.6). This gene-environment interaction was also found among those who reported no family history of any type of birth defect (odds ratio=5.60 with 95% confidence interval 1.4-22.9). Similar associations were seen for CL/P, but these were not statistically significant.

  4. Music training and speech perception: a gene-environment interaction.

    Science.gov (United States)

    Schellenberg, E Glenn

    2015-03-01

    Claims of beneficial side effects of music training are made for many different abilities, including verbal and visuospatial abilities, executive functions, working memory, IQ, and speech perception in particular. Such claims assume that music training causes the associations even though children who take music lessons are likely to differ from other children in music aptitude, which is associated with many aspects of speech perception. Music training in childhood is also associated with cognitive, personality, and demographic variables, and it is well established that IQ and personality are determined largely by genetics. Recent evidence also indicates that the role of genetics in music aptitude and music achievement is much larger than previously thought. In short, music training is an ideal model for the study of gene-environment interactions but far less appropriate as a model for the study of plasticity. Children seek out environments, including those with music lessons, that are consistent with their predispositions; such environments exaggerate preexisting individual differences. © 2015 New York Academy of Sciences.

  5. Eating disorders, gene-environment interactions and epigenetics.

    Science.gov (United States)

    Campbell, Iain C; Mill, Jonathan; Uher, Rudolf; Schmidt, Ulrike

    2011-01-01

    This review describes the various subtypes of eating disorders and examines factors associated with the risk of illness. It considers evidence that the development and maintenance of eating disorders is due to gene-environment interactions (GxE) that alter genetic expression via epigenetic processes. It describes how environmental factors such as those associated with nutrition and/or stress may cause epigenetic changes which have transcriptional and phenotypic effects, which, in turn, alter the long term risk of developing an eating disorder. It reviews theoretical and practical issues associated with epigenetic studies in psychiatry and how these are relevant to eating disorders. It examines the limited number of epigenetic studies which have been conducted in eating disorders and suggests directions for further research. Understanding the relationship between epigenetic processes and the risk of an eating disorder opens possibilities for preventive and/or therapeutic interventions. For example, epigenetic changes associated with diet and weight may be reversible and those associated with cognitive processes may be accessible to pharmacological interventions. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer

    National Research Council Canada - National Science Library

    Adegoke, Olufemi

    2003-01-01

    The objective of this CDA is to evaluate the gene-gene and gene-environment interactions in the etiology of breast cancer in two ongoing case-control studies, the Shanghai Breast Cancer Study (SBCS...

  7. The impact of imprecisely measured covariates on estimating gene-environment interactions

    Directory of Open Access Journals (Sweden)

    Gilthorpe Mark S

    2006-05-01

    Full Text Available Abstract Background The effects of measurement error in epidemiological exposures and confounders on estimated effects of exposure are well described, but the effects on estimates for gene-environment interactions has received rather less attention. In particular, the effects of confounder measurement error on gene-environment interactions are unknown. Methods We investigate these effects using simulated data and illustrate our results with a practical example in nutrition epidemiology. Results We show that the interaction regression coefficient is unchanged by confounder measurement error under certain conditions, but biased by exposure measurement error. We also confirm that confounder measurement error can lead to estimated effects of exposure biased either towards or away from the null, depending on the correlation structure, with associated effects on type II errors. Conclusion Whilst measurement error in confounders does not lead to bias in interaction coefficients, it may still lead to bias in the estimated effects of exposure. There may still be cost implications for epidemiological studies that need to calibrate all error-prone covariates against a valid reference, in addition to the exposure, to reduce the effects of confounder measurement error.

  8. Gene-environment interaction in the etiology of mathematical ability using SNP sets.

    Science.gov (United States)

    Docherty, Sophia J; Kovas, Yulia; Plomin, Robert

    2011-01-01

    Mathematics ability and disability is as heritable as other cognitive abilities and disabilities, however its genetic etiology has received relatively little attention. In our recent genome-wide association study of mathematical ability in 10-year-old children, 10 SNP associations were nominated from scans of pooled DNA and validated in an individually genotyped sample. In this paper, we use a 'SNP set' composite of these 10 SNPs to investigate gene-environment (GE) interaction, examining whether the association between the 10-SNP set and mathematical ability differs as a function of ten environmental measures in the home and school in a sample of 1888 children with complete data. We found two significant GE interactions for environmental measures in the home and the school both in the direction of the diathesis-stress type of GE interaction: The 10-SNP set was more strongly associated with mathematical ability in chaotic homes and when parents are negative.

  9. From 'omics' to complex disease: a systems biology approach to gene-environment interactions in cancer

    Directory of Open Access Journals (Sweden)

    Knox Sarah S

    2010-04-01

    Full Text Available Abstract Background Cancer is a complex disease that involves a sequence of gene-environment interactions in a progressive process that cannot occur without dysfunction in multiple systems, including DNA repair, apoptotic and immune functions. Epigenetic mechanisms, responding to numerous internal and external cues in a dynamic ongoing exchange, play a key role in mediating environmental influences on gene expression and tumor development. Hypothesis The hypothesis put forth in this paper addresses the limited success of treatment outcomes in clinical oncology. It states that improvement in treatment efficacy requires a new paradigm that focuses on reversing systemic dysfunction and tailoring treatments to specific stages in the process. It requires moving from a reductionist framework of seeking to destroy aberrant cells and pathways to a transdisciplinary systems biology approach aimed at reversing multiple levels of dysfunction. Conclusion Because there are many biological pathways and multiple epigenetic influences working simultaneously in the expression of cancer phenotypes, studying individual components in isolation does not allow an adequate understanding of phenotypic expression. A systems biology approach using new modeling techniques and nonlinear mathematics is needed to investigate gene-environment interactions and improve treatment efficacy. A broader array of study designs will also be required, including prospective molecular epidemiology, immune competent animal models and in vitro/in vivo translational research that more accurately reflects the complex process of tumor initiation and progression.

  10. Modelling gene-environment interaction in first episodes of psychosis.

    Science.gov (United States)

    Bernardo, Miguel; Bioque, Miquel; Cabrera, Bibiana; Lobo, Antonio; González-Pinto, Ana; Pina, Laura; Corripio, Iluminada; Sanjuán, Julio; Mané, Anna; Castro-Fornieles, Josefina; Vieta, Eduard; Arango, Celso; Mezquida, Gisela; Gassó, Patricia; Parellada, Mara; Saiz-Ruiz, Jerónimo; Cuesta, Manuel J; Mas, Sergi

    2017-11-01

    Recent research demonstrates the heterogeneous etiology of psychotic disorders, where gen-environment (GxE) interaction plays a key role. Large genetic studies have linked many genetic variants with schizophrenia, but each variant is only associated with a small effect and the GxE interaction contribution has not been evaluated. The PEPs Project was designed to carefully collect a large amount of genetic and environmental exposure data of 335 FEP patients and 253 matched healthy controls.780single-nucleotide polymorphisms (from 159 candidate genes)and 16 environmental variables previously reported as the main psychosis non-genetic risk factors were analyzed together using entropy-based measures of information gain. Our analyses identified an interaction between nine SNPs and the exposition to the environmental risk factors of psychosis, showing a clear enrichment of genes linked to serotonin neurotransmission and neurodevelopmental processes. This study has allowed the identification of several GxE-environment interactions involved in the risk of presenting a FEP. Our results highlight the importance of serotonin neurotransmission interacting with certain environmental stimuli. The serotoninergic system may be playing a key role in the regulatory network of stress and other systems implicated in the emergence and development of psychotic disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Environmental and gene-environment interactions and risk of rheumatoid arthritis

    Science.gov (United States)

    Karlson, Elizabeth W.; Deane, Kevin

    2012-01-01

    Multiple environmental factors including hormones, dietary factors, infections and exposure to tobacco smoke as well as gene-environment interactions have been associated with increased risk for rheumatoid arthritis (RA). Importantly, the growing understanding of the prolonged period prior to the first onset of symptoms of RA suggests that these environmental and genetic factors are likely acting to drive the development of RA-related autoimmunity long before the appearance of the first joint symptoms and clinical findings that are characteristic of RA. Herein we will review these factors and interactions, especially those that have been investigated in a prospective fashion prior to the symptomatic onset of RA. We will also discuss how these factors may be explored in future study to further the understanding of the pathogenesis of RA, and ultimately perhaps develop preventive measures for this disease. PMID:22819092

  12. Gene-environment interactions in sarcoidosis: challenge and opportunity

    OpenAIRE

    Culver, Daniel A.; Newman, Lee S.; Kavuru, Mani S.

    2007-01-01

    Susceptibility to most human diseases is polygenic, with complex interactions between functional polymorphisms of single genes governing disease incidence, phenotype, or both. In this context, the contribution of any discrete gene is generally modest for a single individual, but may confer substantial attributable risk on a population level. Environmental exposure can modify the effects of a polymorphism, either by providing a necessary substrate for development of human disease or because th...

  13. Gene-environment interactions in early life and adulthood : implications for cocaine intake

    NARCIS (Netherlands)

    Veen, Rixt van der

    2008-01-01

    The objective of the research described in this thesis was to demonstrate the role of gene-environment interactions in the emergence of individual differences in cocaine use. For this purpose we used two inbred mouse strains, the C57Bl/6 (C57) and DBA/2 (DBA), which are known to differ in

  14. A novel approach to simulate gene-environment interactions in complex diseases

    Directory of Open Access Journals (Sweden)

    Nicodemi Mario

    2010-01-01

    Full Text Available Abstract Background Complex diseases are multifactorial traits caused by both genetic and environmental factors. They represent the major part of human diseases and include those with largest prevalence and mortality (cancer, heart disease, obesity, etc.. Despite a large amount of information that has been collected about both genetic and environmental risk factors, there are few examples of studies on their interactions in epidemiological literature. One reason can be the incomplete knowledge of the power of statistical methods designed to search for risk factors and their interactions in these data sets. An improvement in this direction would lead to a better understanding and description of gene-environment interactions. To this aim, a possible strategy is to challenge the different statistical methods against data sets where the underlying phenomenon is completely known and fully controllable, for example simulated ones. Results We present a mathematical approach that models gene-environment interactions. By this method it is possible to generate simulated populations having gene-environment interactions of any form, involving any number of genetic and environmental factors and also allowing non-linear interactions as epistasis. In particular, we implemented a simple version of this model in a Gene-Environment iNteraction Simulator (GENS, a tool designed to simulate case-control data sets where a one gene-one environment interaction influences the disease risk. The main aim has been to allow the input of population characteristics by using standard epidemiological measures and to implement constraints to make the simulator behaviour biologically meaningful. Conclusions By the multi-logistic model implemented in GENS it is possible to simulate case-control samples of complex disease where gene-environment interactions influence the disease risk. The user has full control of the main characteristics of the simulated population and a Monte

  15. A methodology to establish a database to study gene environment interactions for childhood asthma

    Directory of Open Access Journals (Sweden)

    McCormick Jonathan

    2010-12-01

    Full Text Available Abstract Background Gene-environment interactions are likely to explain some of the heterogeneity in childhood asthma. Here, we describe the methodology and experiences in establishing a database for childhood asthma designed to study gene-environment interactions (PAGES - Paediatric Asthma Gene Environment Study. Methods Children with asthma and under the care of a respiratory paediatrician are being recruited from 15 hospitals between 2008 and 2011. An asthma questionnaire is completed and returned by post. At a routine clinic visit saliva is collected for DNA extraction. Detailed phenotyping in a proportion of children includes spirometry, bronchodilator response (BDR, skin prick reactivity, exhaled nitric oxide and salivary cotinine. Dietary and quality of life questionnaires are completed. Data are entered onto a purpose-built database. Results To date 1045 children have been invited to participate and data collected in 501 (48%. The mean age (SD of participants is 8.6 (3.9 years, 57% male. DNA has been collected in 436 children. Spirometry has been obtained in 172 children, mean % predicted (SD FEV1 97% (15 and median (IQR BDR is 5% (2, 9. There were differences in age, socioeconomic status, severity and %FEV1 between the different centres (p≤0.024. Reasons for non-participation included parents not having time to take part, children not attending clinics and, in a small proportion, refusal to take part. Conclusions It is feasible to establish a national database to study gene-environment interactions within an asthmatic paediatric population; there are barriers to participation and some different characteristics in individuals recruited from different centres. Recruitment to our study continues and is anticipated to extend current understanding of asthma heterogeneity.

  16. Gene-Environment Interactions in Stress Response Contribute Additively to a Genotype-Environment Interaction.

    Directory of Open Access Journals (Sweden)

    Takeshi Matsui

    2016-07-01

    Full Text Available How combinations of gene-environment interactions collectively give rise to genotype-environment interactions is not fully understood. To shed light on this problem, we genetically dissected an environment-specific poor growth phenotype in a cross of two budding yeast strains. This phenotype is detectable when certain segregants are grown on ethanol at 37°C ('E37', a condition that differs from the standard culturing environment in both its carbon source (ethanol as opposed to glucose and temperature (37°C as opposed to 30°C. Using recurrent backcrossing with phenotypic selection, we identified 16 contributing loci. To examine how these loci interact with each other and the environment, we focused on a subset of four loci that together can lead to poor growth in E37. We measured the growth of all 16 haploid combinations of alleles at these loci in all four possible combinations of carbon source (ethanol or glucose and temperature (30 or 37°C in a nearly isogenic population. This revealed that the four loci act in an almost entirely additive manner in E37. However, we also found that these loci have weaker effects when only carbon source or temperature is altered, suggesting that their effect magnitudes depend on the severity of environmental perturbation. Consistent with such a possibility, cloning of three causal genes identified factors that have unrelated functions in stress response. Thus, our results indicate that polymorphisms in stress response can show effects that are intensified by environmental stress, thereby resulting in major genotype-environment interactions when multiple of these variants co-occur.

  17. Gene-Environment Interactions in Stress Response Contribute Additively to a Genotype-Environment Interaction.

    Science.gov (United States)

    Matsui, Takeshi; Ehrenreich, Ian M

    2016-07-01

    How combinations of gene-environment interactions collectively give rise to genotype-environment interactions is not fully understood. To shed light on this problem, we genetically dissected an environment-specific poor growth phenotype in a cross of two budding yeast strains. This phenotype is detectable when certain segregants are grown on ethanol at 37°C ('E37'), a condition that differs from the standard culturing environment in both its carbon source (ethanol as opposed to glucose) and temperature (37°C as opposed to 30°C). Using recurrent backcrossing with phenotypic selection, we identified 16 contributing loci. To examine how these loci interact with each other and the environment, we focused on a subset of four loci that together can lead to poor growth in E37. We measured the growth of all 16 haploid combinations of alleles at these loci in all four possible combinations of carbon source (ethanol or glucose) and temperature (30 or 37°C) in a nearly isogenic population. This revealed that the four loci act in an almost entirely additive manner in E37. However, we also found that these loci have weaker effects when only carbon source or temperature is altered, suggesting that their effect magnitudes depend on the severity of environmental perturbation. Consistent with such a possibility, cloning of three causal genes identified factors that have unrelated functions in stress response. Thus, our results indicate that polymorphisms in stress response can show effects that are intensified by environmental stress, thereby resulting in major genotype-environment interactions when multiple of these variants co-occur.

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

    Science.gov (United States)

    Hambrick, David Z; Tucker-Drob, Elliot M

    2015-02-01

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

  19. Environmental factors as modulators of neurodegeneration: insights from gene-environment interactions in Huntington's disease.

    Science.gov (United States)

    Mo, Christina; Hannan, Anthony J; Renoir, Thibault

    2015-05-01

    Unlike many other neurodegenerative diseases with established gene-environment interactions, Huntington's disease (HD) is viewed as a disorder governed by genetics. The cause of the disease is a highly penetrant tandem repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. In the year 2000, a pioneering study showed that the disease could be delayed in transgenic mice by enriched housing conditions. This review describes subsequent human and preclinical studies identifying environmental modulation of motor, cognitive, affective and other symptoms found in HD. Alongside the behavioral observations we also discuss potential mechanisms and the relevance to other neurodegenerative disorders, including Alzheimer's and Parkinson's disease. In mouse models of HD, increased sensorimotor and cognitive stimulation can delay or ameliorate various endophenotypes. Potential mechanisms include increased trophic support, synaptic plasticity, adult neurogenesis, and other forms of experience-dependent cellular plasticity. Subsequent clinical investigations support a role for lifetime activity levels in modulating the onset and progression of HD. Stress can accelerate memory and olfactory deficits and exacerbate cellular dysfunctions in HD mice. In the absence of effective treatments to slow the course of HD, environmental interventions offer feasible approaches to delay the disease, however further preclinical and human studies are needed in order to generate clinical recommendations. Environmental interventions could be combined with future pharmacological therapies and stimulate the identification of enviromimetics, drugs which mimic or enhance the beneficial effects of cognitive stimulation and physical activity. Copyright © 2015. Published by Elsevier Ltd.

  20. Gene-environment interaction influences attachment-like style in mice.

    Science.gov (United States)

    Lassi, G; Tucci, V

    2017-07-01

    Attachment styles are established soon after birth and form the basis for a healthy psychological life during adulthood. Here, we investigated whether genetic background (i.e. isogenic strains: C57BL/6N and BALB/c) and parent-of-origin (i.e. reciprocal hybrids) epigenetic effects influence attachment-like styles in mice. We discovered that a specific genetic and epigenetic assortment exerts a role on the development of a secure or insecure attachment-like style. In particular, when biological mothers raise their pups, the attachment-like style is mainly secure, independently of the genetic background. However, when foster mothers raise pups, the attachment-like style can be either secure or insecure, depending on the particular genetic background, and this effect is paternally transmitted. Finally, we observed that secure attachment-like in mice leads to greater sociability during adulthood, while insecure attachment-like leads to reduced sociability. Our study sheds light on gene-environment interactions that shape the attachment-like style early in development and pave the way for a healthy psychological life. © 2017 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

  1. Cognitive endophenotypes, gene-environment interactions and experience-dependent plasticity in animal models of schizophrenia.

    Science.gov (United States)

    Burrows, Emma L; Hannan, Anthony J

    2016-04-01

    Schizophrenia is a devastating brain disorder caused by a complex and heterogeneous combination of genetic and environmental factors. In order to develop effective new strategies to prevent and treat schizophrenia, valid animal models are required which accurately model the disorder, and ideally provide construct, face and predictive validity. The cognitive deficits in schizophrenia represent some of the most debilitating symptoms and are also currently the most poorly treated. Therefore it is crucial that animal models are able to capture the cognitive dysfunction that characterizes schizophrenia, as well as the negative and psychotic symptoms. The genomes of mice have, prior to the recent gene-editing revolution, proven the most easily manipulable of mammalian laboratory species, and hence most genetic targeting has been performed using mouse models. Importantly, when key environmental factors of relevance to schizophrenia are experimentally manipulated, dramatic changes in the phenotypes of these animal models are often observed. We will review recent studies in rodent models which provide insight into gene-environment interactions in schizophrenia. We will focus specifically on environmental factors which modulate levels of experience-dependent plasticity, including environmental enrichment, cognitive stimulation, physical activity and stress. The insights provided by this research will not only help refine the establishment of optimally valid animal models which facilitate development of novel therapeutics, but will also provide insight into the pathogenesis of schizophrenia, thus identifying molecular and cellular targets for future preclinical and clinical investigations. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Shame and Guilt-Proneness in Adolescents: Gene-Environment Interactions

    Science.gov (United States)

    Szentágotai-Tătar, Aurora; Chiș, Adina; Vulturar, Romana; Dobrean, Anca; Cândea, Diana Mirela; Miu, Andrei C.

    2015-01-01

    Rooted in people’s preoccupation with how they are perceived and evaluated, shame and guilt are self-conscious emotions that play adaptive roles in social behavior, but can also contribute to psychopathology when dysregulated. Shame and guilt-proneness develop during childhood and adolescence, and are influenced by genetic and environmental factors that are little known to date. This study investigated the effects of early traumatic events and functional polymorphisms in the brain-derived neurotrophic factor (BDNF) gene and the serotonin transporter gene promoter (5-HTTLPR) on shame and guilt in adolescents. A sample of N = 271 healthy adolescents between 14 and 17 years of age filled in measures of early traumatic events and proneness to shame and guilt, and were genotyped for the BDNF Val66Met and 5-HTTLPR polymorphisms. Results of moderator analyses indicated that trauma intensity was positively associated with guilt-proneness only in carriers of the low-expressing Met allele of BDNF Val66Met. This is the first study that identifies a gene-environment interaction that significantly contributes to guilt proneness in adolescents, with potential implications for developmental psychopathology. PMID:26230319

  3. Childhood problem behavior and parental divorce: evidence for gene-environment interaction.

    Science.gov (United States)

    Robbers, Sylvana; van Oort, Floor; Huizink, Anja; Verhulst, Frank; van Beijsterveldt, Catharina; Boomsma, Dorret; Bartels, Meike

    2012-10-01

    The importance of genetic and environmental influences on children's behavioral and emotional problems may vary as a function of environmental exposure. We previously reported that 12-year-olds with divorced parents showed more internalizing and externalizing problems than children with married parents, and that externalizing problems in girls precede and predict later parental divorce. The aim of the current study was to investigate as to whether genetic and environmental influences on internalizing and externalizing problems were different for children from divorced versus non-divorced families. Maternal ratings on internalizing and externalizing problems were collected with the Child Behavior Checklist in 4,592 twin pairs at ages 3 and 12 years, of whom 367 pairs had experienced a parental divorce between these ages. Variance in internalizing and externalizing problems at ages 3 and 12 was analyzed with biometric models in which additive genetic and environmental effects were allowed to depend on parental divorce and sex. A difference in the contribution of genetic and environmental influences between divorced and non-divorced groups would constitute evidence for gene-environment interaction. For both pre- and post-divorce internalizing and externalizing problems, the total variances were larger for children from divorced families, which was mainly due to higher environmental variances. As a consequence, heritabilities were lower for children from divorced families, and the relative contributions of environmental influences were higher. Environmental influences become more important in explaining variation in children's problem behaviors in the context of parental divorce.

  4. Gene-environment interaction involving recently identified colorectal cancer susceptibility loci

    Science.gov (United States)

    Kantor, Elizabeth D.; Hutter, Carolyn M.; Minnier, Jessica; Berndt, Sonja I.; Brenner, Hermann; Caan, Bette J.; Campbell, Peter T.; Carlson, Christopher S.; Casey, Graham; Chan, Andrew T.; Chang-Claude, Jenny; Chanock, Stephen J.; Cotterchio, Michelle; Du, Mengmeng; Duggan, David; Fuchs, Charles S.; Giovannucci, Edward L.; Gong, Jian; Harrison, Tabitha A.; Hayes, Richard B.; Henderson, Brian E.; Hoffmeister, Michael; Hopper, John L.; Jenkins, Mark A.; Jiao, Shuo; Kolonel, Laurence N.; Le Marchand, Loic; Lemire, Mathieu; Ma, Jing; Newcomb, Polly A.; Ochs-Balcom, Heather M.; Pflugeisen, Bethann M.; Potter, John D.; Rudolph, Anja; Schoen, Robert E.; Seminara, Daniela; Slattery, Martha L.; Stelling, Deanna L.; Thomas, Fridtjof; Thornquist, Mark; Ulrich, Cornelia M.; Warnick, Greg S.; Zanke, Brent W.; Peters, Ulrike; Hsu, Li; White, Emily

    2014-01-01

    BACKGROUND Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are associated with risk of colorectal cancer (CRC). Prior research has evaluated the presence of gene-environment interaction involving the first 10 identified susceptibility loci, but little work has been conducted on interaction involving SNPs at recently identified susceptibility loci, including: rs10911251, rs6691170, rs6687758, rs11903757, rs10936599, rs647161, rs1321311, rs719725, rs1665650, rs3824999, rs7136702, rs11169552, rs59336, rs3217810, rs4925386, and rs2423279. METHODS Data on 9160 cases and 9280 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR) were used to evaluate the presence of interaction involving the above-listed SNPs and sex, body mass index (BMI), alcohol consumption, smoking, aspirin use, post-menopausal hormone (PMH) use, as well as intake of dietary calcium, dietary fiber, dietary folate, red meat, processed meat, fruit, and vegetables. Interaction was evaluated using a fixed-effects meta-analysis of an efficient Empirical Bayes estimator, and permutation was used to account for multiple comparisons. RESULTS None of the permutation-adjusted p-values reached statistical significance. CONCLUSIONS The associations between recently identified genetic susceptibility loci and CRC are not strongly modified by sex, BMI, alcohol, smoking, aspirin, PMH use, and various dietary factors. IMPACT Results suggest no evidence of strong gene-environment interactions involving the recently identified 16 susceptibility loci for CRC taken one at a time. PMID:24994789

  5. Gene-environment interactions of CETP gene variation in a high cardiovascular risk Mediterranean population.

    Science.gov (United States)

    Corella, Dolores; Carrasco, Paula; Fitó, Montserrat; Martínez-González, Miguel Angel; Salas-Salvadó, Jordi; Arós, Fernando; Lapetra, José; Guillén, Marisa; Ortega-Azorín, Carolina; Warnberg, Julia; Fiol, Miquel; Ruiz-Gutierrez, Valentina; Serra-Majem, Lluís; Martínez, J Alfredo; Ros, Emilio; Estruch, Ramón

    2010-09-01

    Genome-wide association studies show that cholesteryl ester transfer protein (CETP) single nucleotide polymorphisms (SNPs) are more strongly associated with HDL cholesterol (HDL-C) concentrations than any other loci across the genome. However, gene-environment interactions for clinical applications are still largely unknown. We studied gene-environment interactions between CETP SNPs and dietary fat intake, adherence to the Mediterranean diet, alcohol consumption, smoking, obesity, and diabetes on HDL-C in 4,210 high cardiovascular risk subjects from a Mediterranean population. We focused on the -4,502C>T and the TaqIB SNPs in partial linkage disequilibrium (D'= 0.88; P < 0.001). They were independently associated with higher HDL-C (P < 0.001); this clinically relevant association was greater when their diplotype was considered (14% higher in TT/B2B2 vs. CC/B1B1). No gene-gene interaction was observed. We also analyzed the association of these SNPs with blood pressure, and no clinically relevant associations were detected. No statistically significant interactions of these SNPs with obesity, diabetes, and smoking in determining HDL-C concentrations were found. Likewise, alcohol, dietary fat, and adherence to the Mediterranean diet did not statistically interact with the CETP variants (independently or as diplotype) in determining HDL-C. In conclusion, the strong association of the CETP SNPs and HDL-C was not statistically modified by diet or by the other environmental factors.

  6. Assessment of Multifactor Gene-Environment Interactions and Ovarian Cancer Risk

    DEFF Research Database (Denmark)

    Usset, Joseph L; Raghavan, Rama; Tyrer, Jonathan P

    2016-01-01

    BACKGROUND: Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure and elevated estrogen levels are associated with obesity in postmenopausal women. Therefore, we hypothesized that gene-environment interactions related to hormone-related risk factors could differ between obese......, and estrogen use) and assessed whether these interactions differed between obese and non-obese women. Interactions were assessed using logistic regression models and data from 14 case-control studies (6,247 cases; 10,379 controls). Histotype-specific analyses were also completed. RESULTS: SNPs in the following...... candidate genes showed notable interaction: IGF1R (rs41497346, estrogen plus progesterone hormone therapy, histology = all, P = 4.9 × 10(-6)) and ESR1 (rs12661437, endometriosis, histology = all, P = 1.5 × 10(-5)). The most notable obesity-gene-hormone risk factor interaction was within INSR (rs113759408...

  7. Gene-environment interactions in early life and adulthood: implications for cocaine intake

    OpenAIRE

    Veen, Rixt van der

    2008-01-01

    The objective of the research described in this thesis was to demonstrate the role of gene-environment interactions in the emergence of individual differences in cocaine use. For this purpose we used two inbred mouse strains, the C57Bl/6 (C57) and DBA/2 (DBA), which are known to differ in drug-intake and to be differentially sensitive to several stressors. We studied the impact of early life experiences (long-term influence) as well as a later life psychosocial stressor (short-term influence)...

  8. [The role of gene-environment interaction in the development of eating disorders].

    Science.gov (United States)

    Gáti, Agnes; Abrahám, Ildikó

    2009-01-01

    The biological research predominant in the last decades have not brought a solution in the discovery of risk factors contributing to the development of eating disorders, and elaborating a more effective therapy. The large amount of molecular genetic studies, however, by showing the various genetic vulnerability, contributed significantly to recognizing a more specific effect of the environmental factors. The authors evaluate the genetic studies of eating disorders and present environmental factors having a role in the development of eating disorders. They report about recently published data of gene-environment interaction and conclude from the data clinically applicable consequences.

  9. The role of gene-environment correlations and interactions in middle childhood depressive symptoms.

    Science.gov (United States)

    Wilkinson, Paul O; Trzaskowski, Maciej; Haworth, Claire M A; Eley, Thalia C

    2013-02-01

    Depression is known to be associated with a wide array of environmental factors. Such associations are due at least in part to genetic influences on both. This issue has been little explored with preadolescent children. Measures of family chaos and parenting style at age 9 and child depressive symptoms at age 12 were completed by 3,258 twin pairs from the Twins Early Development Study and their parents. Quantitative genetic modeling was used to explore common and unique genetic and environmental influences on both family environment and later depressive symptoms. Depressive symptoms at age 12 were significantly heritable. Moderate genetic effects influenced parenting style and family chaos at the age of 9, indicating gene-environment correlation. There were significant genetic correlations between family environment and depressive symptoms. There was some evidence of a Gene × Environment interaction, with stronger genetic effects on depressive symptoms for children with more suboptimal family environment. There was an Environment × Environment interaction, with effects of nonshared environment on depressive symptoms stronger for twins with more adverse parenting experiences. There is some evidence for gene-environment correlation between aspects of family environment in middle childhood and subsequent depressive symptoms. This suggests that one of the mechanisms by which genes lead to depressive symptoms may be by themselves influencing depressogenic environments.

  10. [Detecting gene-gene/environment interactions by model-based multifactor dimensionality reduction].

    Science.gov (United States)

    Fan, Wei; Shen, Chao; Guo, Zhirong

    2015-11-01

    This paper introduces a method called model-based multifactor dimensionality reduction (MB-MDR), which was firstly proposed by Calle et al., and can be applied for detecting gene-gene or gene-environment interactions in genetic studies. The basic principle and characteristics of MB-MDR as well as the operation in R program are briefly summarized. Besides, the detailed procedure of MB-MDR is illustrated by using example. Compared with classical MDR, MB-MDR has similar principle, which merges multi-locus genotypes into a one-dimensional construct and can be used in the study with small sample size. However, there is some difference between MB-MDR and classical MDR. First, it has higher statistical power than MDR and other MDR in the presence of different noises due to the different way the genotype cells merged. Second, compared with MDR, it can deal with all binary and quantitative traits, adjust marginal effects of factors and confounders. MBMDR could be a useful method in the analyses of gene-gene/environment interactions.

  11. Bisphenol-A and Female Infertility: A Possible Role of Gene-Environment Interactions

    Directory of Open Access Journals (Sweden)

    Xiaona Huo

    2015-09-01

    Full Text Available Background: Bisphenol-A (BPA is widely used and ubiquitous in the environment. Animal studies indicate that BPA affects reproduction, however, the gene-environment interaction mechanism(s involved in this association remains unclear. We performed a literature review to summarize the evidence on this topic. Methods: A comprehensive search was conducted in PubMed using as keywords BPA, gene, infertility and female reproduction. Full-text articles in both human and animals published in English prior to December 2014 were selected. Results: Evidence shows that BPA can interfere with endocrine function of hypothalamic-pituitary axis, such as by changing gonadotropin-releasing hormones (GnRH secretion in hypothalamus and promoting pituitary proliferation. Such actions affect puberty, ovulation and may even result in infertility. Ovary, uterus and other reproductive organs are also targets of BPA. BPA exposure impairs the structure and functions of female reproductive system in different times of life cycle and may contribute to infertility. Both epidemiological and experimental evidences demonstrate that BPA affects reproduction-related gene expression and epigenetic modification that are closely associated with infertility. The detrimental effects on reproduction may be lifelong and transgenerational. Conclusions: Evidence on gene-environment interactions, especially from human studies, is still limited. Further research on this topic is warranted.

  12. Leveraging gene-environment interactions and endotypes for asthma gene discovery

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Ober, Carole

    2016-01-01

    Asthma is a heterogeneous clinical syndrome that includes subtypes of disease with different underlying causes and disease mechanisms. Asthma is caused by a complex interaction between genes and environmental exposures; early-life exposures in particular play an important role. Asthma is also...... heritable, and a number of susceptibility variants have been discovered in genome-wide association studies, although the known risk alleles explain only a small proportion of the heritability. In this review, we present evidence supporting the hypothesis that focusing on more specific asthma phenotypes......, such as childhood asthma with severe exacerbations, and on relevant exposures that are involved in gene-environment interactions (GEIs), such as rhinovirus infections, will improve detection of asthma genes and our understanding of the underlying mechanisms. We will discuss the challenges of considering GEIs...

  13. Genetic risk for schizophrenia, obstetric complications, and adolescent school outcome: evidence for gene-environment interaction.

    Science.gov (United States)

    Forsyth, Jennifer K; Ellman, Lauren M; Tanskanen, Antti; Mustonen, Ulla; Huttunen, Matti O; Suvisaari, Jaana; Cannon, Tyrone D

    2013-09-01

    Low birth weight (LBW) and hypoxia are among the environmental factors most reliably associated with schizophrenia; however, the nature of this relationship is unclear and both gene-environment interaction and gene-environment covariation models have been proposed as explanations. High-risk (HR) designs that explore whether obstetric complications differentially predict outcomes in offspring at low risk (LR) vs HR for schizophrenia, while accounting for differences in rates of maternal risk factors, may shed light on this question. This study used prospectively obtained data to examine relationships between LBW and hypoxia on school outcome at age 15-16 years in a Finnish sample of 1070 offspring at LR for schizophrenia and 373 offspring at HR for schizophrenia, based on parental psychiatric history. Controlling for offspring sex, maternal smoking, social support, parity, age, and number of prenatal care visits, HR offspring performed worse than LR offspring across academic, nonacademic, and physical education domains. LBW predicted poorer academic and physical education performance in HR offspring, but not in LR offspring, and this association was similar for offspring of fathers vs mothers with schizophrenia. Hypoxia predicted poorer physical education score across risk groups. Rates of LBW and hypoxia were similar for LR and HR offspring and for offspring of fathers vs mothers with schizophrenia. Results support the hypothesis that genetic susceptibility to schizophrenia confers augmented vulnerability of the developing brain to the effects of obstetric complications, possibly via epigenetic mechanisms.

  14. From a genetic predisposition to an interactive predisposition: rethinking the ethical implications of screening for gene-environment interactions.

    Science.gov (United States)

    Tabery, James

    2009-02-01

    In a widely acclaimed study from 2002, researchers found a case of gene-environment interaction for a gene controlling neuroenzymatic activity (low vs. high), exposure to childhood maltreatment, and antisocial personality disorder (ASPD). Cases of gene-environment interaction are generally characterized as evincing a genetic predisposition; for example, individuals with low neuroenzymatic activity are generally characterized as having a genetic predisposition to ASPD. I first argue that the concept of a genetic predisposition fundamentally misconstrues these cases of gene-environment interaction. This misconstrual will be diagnosed, and then a new concept--interactive predisposition--will be introduced. I then show how this conceptual shift reconfigures old questions and raises new questions for genetic screening. Attempts to screen embryos or fetuses for the gene associated with low neuroenzymatic activity with an eye toward selecting against the low-activity variant fall prey to the myth of pre-environmental prediction; attempts to screen newborns for the gene associated with low neuroenzymatic activity with an eye toward early intervention will have to face the interventionist's dilemma.

  15. Evaluation of two methods for assessing gene-environment interactions using data from the Danish case-control study of facial clefts

    DEFF Research Database (Denmark)

    Etheredge, Analee J; Christensen, Kaare; Del Junco, Deborah

    2005-01-01

    BACKGROUND: Epidemiological investigations have begun to consider gene-environment (GE) interactions as potential risk factors for many diseases, including several different birth defects. However, traditional methodological approaches for the analysis of case-control data tend to have low power...

  16. Behavior of QQ-plots and genomic control in studies of gene-environment interaction.

    Science.gov (United States)

    Voorman, Arend; Lumley, Thomas; McKnight, Barbara; Rice, Kenneth

    2011-05-12

    Genome-wide association studies of gene-environment interaction (GxE GWAS) are becoming popular. As with main effects GWAS, quantile-quantile plots (QQ-plots) and Genomic Control are being used to assess and correct for population substructure. However, in G x E work these approaches can be seriously misleading, as we illustrate; QQ-plots may give strong indications of substructure when absolutely none is present. Using simulation and theory, we show how and why spurious QQ-plot inflation occurs in G x E GWAS, and how this differs from main-effects analyses. We also explain how simple adjustments to standard regression-based methods used in G x E GWAS can alleviate this problem.

  17. Animal models of gene-environment interaction in schizophrenia: A dimensional perspective.

    Science.gov (United States)

    Ayhan, Yavuz; McFarland, Ross; Pletnikov, Mikhail V

    2016-01-01

    Schizophrenia has long been considered as a disorder with multifactorial origins. Recent discoveries have advanced our understanding of the genetic architecture of the disease. However, even with the increase of identified risk variants, heritability estimates suggest an important contribution of non-genetic factors. Various environmental risk factors have been proposed to play a role in the etiopathogenesis of schizophrenia. These include season of birth, maternal infections, obstetric complications, adverse events at early childhood, and drug abuse. Despite the progress in identification of genetic and environmental risk factors, we still have a limited understanding of the mechanisms whereby gene-environment interactions (G × E) operate in schizophrenia and psychoses at large. In this review we provide a critical analysis of current animal models of G × E relevant to psychotic disorders and propose that dimensional perspective will advance our understanding of the complex mechanisms of these disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Behavior of QQ-plots and genomic control in studies of gene-environment interaction.

    Directory of Open Access Journals (Sweden)

    Arend Voorman

    2011-05-01

    Full Text Available Genome-wide association studies of gene-environment interaction (GxE GWAS are becoming popular. As with main effects GWAS, quantile-quantile plots (QQ-plots and Genomic Control are being used to assess and correct for population substructure. However, in G x E work these approaches can be seriously misleading, as we illustrate; QQ-plots may give strong indications of substructure when absolutely none is present. Using simulation and theory, we show how and why spurious QQ-plot inflation occurs in G x E GWAS, and how this differs from main-effects analyses. We also explain how simple adjustments to standard regression-based methods used in G x E GWAS can alleviate this problem.

  19. A combination test for detection of gene-environment interaction in cohort studies.

    Science.gov (United States)

    Coombes, Brandon; Basu, Saonli; McGue, Matt

    2017-07-01

    Identifying gene-environment (G-E) interactions can contribute to a better understanding of disease etiology, which may help researchers develop disease prevention strategies and interventions. One big criticism of studying G-E interaction is the lack of power due to sample size. Studies often restrict the interaction search to the top few hundred hits from a genome-wide association study or focus on potential candidate genes. In this paper, we test interactions between a candidate gene and an environmental factor to improve power by analyzing multiple variants within a gene. We extend recently developed score statistic based genetic association testing approaches to the G-E interaction testing problem. We also propose tests for interaction using gene-based summary measures that pool variants together. Although it has recently been shown that these summary measures can be biased and may lead to inflated type I error, we show that under several realistic scenarios, we can still provide valid tests of interaction. These tests use significantly less degrees of freedom and thus can have much higher power to detect interaction. Additionally, we demonstrate that the iSeq-aSum-min test, which combines a gene-based summary measure test, iSeq-aSum-G, and an interaction-based summary measure test, iSeq-aSum-I, provides a powerful alternative to test G-E interaction. We demonstrate the performance of these approaches using simulation studies and illustrate their performance to study interaction between the SNPs in several candidate genes and family climate environment on alcohol consumption using the Minnesota Center for Twin and Family Research dataset. © 2017 WILEY PERIODICALS, INC.

  20. Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions.

    Science.gov (United States)

    Hahn, Lance W; Ritchie, Marylyn D; Moore, Jason H

    2003-02-12

    Polymorphisms in human genes are being described in remarkable numbers. Determining which polymorphisms and which environmental factors are associated with common, complex diseases has become a daunting task. This is partly because the effect of any single genetic variation will likely be dependent on other genetic variations (gene-gene interaction or epistasis) and environmental factors (gene-environment interaction). Detecting and characterizing interactions among multiple factors is both a statistical and a computational challenge. To address this problem, we have developed a multifactor dimensionality reduction (MDR) method for collapsing high-dimensional genetic data into a single dimension thus permitting interactions to be detected in relatively small sample sizes. In this paper, we describe the MDR approach and an MDR software package. We developed a program that integrates MDR with a cross-validation strategy for estimating the classification and prediction error of multifactor models. The software can be used to analyze interactions among 2-15 genetic and/or environmental factors. The dataset may contain up to 500 total variables and a maximum of 4000 study subjects. Information on obtaining the executable code, example data, example analysis, and documentation is available upon request. All supplementary information can be found at http://phg.mc.vanderbilt.edu/Software/MDR.

  1. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

    DEFF Research Database (Denmark)

    Shungin, Dmitry; Deng, Wei Q; Varga, Tibor V

    2017-01-01

    Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (G×E) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between...... variance effects (Pv), G×E interaction effects (with smoking and physical activity), and marginal genetic effects (Pm). Correlations between Pv and Pm were stronger for SNPs with established marginal effects (Spearman's ρ = 0.401 for triglycerides, and ρ = 0.236 for BMI) compared to all SNPs. When Pv...... and Pm were compared for all pruned SNPs, only BMI was statistically significant (Spearman's ρ = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the Pv distribution (Pbinomial BMI had...

  2. CardioGxE, a catalog of gene-environment interactions for cardiometabolic traits

    Science.gov (United States)

    2014-01-01

    Background Genetic understanding of complex traits has developed immensely over the past decade but remains hampered by incomplete descriptions of contribution to phenotypic variance. Gene-environment (GxE) interactions are one of these contributors and in the guise of diet and physical activity are important modulators of cardiometabolic phenotypes and ensuing diseases. Results We mined the scientific literature to collect GxE interactions from 386 publications for blood lipids, glycemic traits, obesity anthropometrics, vascular measures, inflammation and metabolic syndrome, and introduce CardioGxE, a gene-environment interaction resource. We then analyzed the genes and SNPs supporting cardiometabolic GxEs in order to demonstrate utility of GxE SNPs and to discern characteristics of these important genetic variants. We were able to draw many observations from our extensive analysis of GxEs. 1) The CardioGxE SNPs showed little overlap with variants identified by main effect GWAS, indicating the importance of environmental interactions with genetic factors on cardiometabolic traits. 2) These GxE SNPs were enriched in adaptation to climatic and geographical features, with implications on energy homeostasis and response to physical activity. 3) Comparison to gene networks responding to plasma cholesterol-lowering or regression of atherosclerotic plaques showed that GxE genes have a greater role in those responses, particularly through high-energy diets and fat intake, than do GWAS-identified genes for the same traits. Other aspects of the CardioGxE dataset were explored. Conclusions Overall, we demonstrate that SNPs supporting cardiometabolic GxE interactions often exhibit transcriptional effects or are under positive selection. Still, not all such SNPs can be assigned potential functional or regulatory roles often because data are lacking in specific cell types or from treatments that approximate the environmental factor of the GxE. With research on metabolic related

  3. Generalized partial linear varying multi-index coefficient model for gene-environment interactions.

    Science.gov (United States)

    Liu, Xu; Gao, Bin; Cui, Yuehua

    2017-03-01

    Epidemiological studies have suggested the joint effect of simultaneous exposures to multiple environments on disease risk. However, how environmental mixtures as a whole jointly modify genetic effect on disease risk is still largely unknown. Given the importance of gene-environment (G×E) interactions on many complex diseases, rigorously assessing the interaction effect between genes and environmental mixtures as a whole could shed novel insights into the etiology of complex diseases. For this purpose, we propose a generalized partial linear varying multi-index coefficient model (GPLVMICM) to capture the genetic effect on disease risk modulated by multiple environments as a whole. GPLVMICM is semiparametric in nature which allows different index loading parameters in different index functions. We estimate the parametric parameters by a profile procedure, and the nonparametric index functions by a B-spline backfitted kernel method. Under some regularity conditions, the proposed parametric and nonparametric estimators are shown to be consistent and asymptotically normal. We propose a generalized likelihood ratio (GLR) test to rigorously assess the linearity of the interaction effect between multiple environments and a gene, while apply a parametric likelihood test to detect linear G×E interaction effect. The finite sample performance of the proposed method is examined through simulation studies and is further illustrated through a real data analysis.

  4. Exposure enriched outcome dependent designs for longitudinal studies of gene-environment interaction.

    Science.gov (United States)

    Sun, Zhichao; Mukherjee, Bhramar; Estes, Jason P; Vokonas, Pantel S; Park, Sung Kyun

    2017-08-15

    Joint effects of genetic and environmental factors have been increasingly recognized in the development of many complex human diseases. Despite the popularity of case-control and case-only designs, longitudinal cohort studies that can capture time-varying outcome and exposure information have long been recommended for gene-environment (G × E) interactions. To date, literature on sampling designs for longitudinal studies of G × E interaction is quite limited. We therefore consider designs that can prioritize a subsample of the existing cohort for retrospective genotyping on the basis of currently available outcome, exposure, and covariate data. In this work, we propose stratified sampling based on summaries of individual exposures and outcome trajectories and develop a full conditional likelihood approach for estimation that adjusts for the biased sample. We compare the performance of our proposed design and analysis with combinations of different sampling designs and estimation approaches via simulation. We observe that the full conditional likelihood provides improved estimates for the G × E interaction and joint exposure effects over uncorrected complete-case analysis, and the exposure enriched outcome trajectory dependent design outperforms other designs in terms of estimation efficiency and power for detection of the G × E interaction. We also illustrate our design and analysis using data from the Normative Aging Study, an ongoing longitudinal cohort study initiated by the Veterans Administration in 1963. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Comparison of weighting approaches for genetic risk scores in gene-environment interaction studies.

    Science.gov (United States)

    Hüls, Anke; Krämer, Ursula; Carlsten, Christopher; Schikowski, Tamara; Ickstadt, Katja; Schwender, Holger

    2017-12-16

    Weighted genetic risk scores (GRS), defined as weighted sums of risk alleles of single nucleotide polymorphisms (SNPs), are statistically powerful for detection gene-environment (GxE) interactions. To assign weights, the gold standard is to use external weights from an independent study. However, appropriate external weights are not always available. In such situations and in the presence of predominant marginal genetic effects, we have shown in a previous study that GRS with internal weights from marginal genetic effects ("GRS-marginal-internal") are a powerful and reliable alternative to single SNP approaches or the use of unweighted GRS. However, this approach might not be appropriate for detecting predominant interactions, i.e. interactions showing an effect stronger than the marginal genetic effect. In this paper, we present a weighting approach for such predominant interactions ("GRS-interaction-training") in which parts of the data are used to estimate the weights from the interaction terms and the remaining data are used to determine the GRS. We conducted a simulation study for the detection of GxE interactions in which we evaluated power, type I error and sign-misspecification. We compared this new weighting approach to the GRS-marginal-internal approach and to GRS with external weights. Our simulation study showed that in the absence of external weights and with predominant interaction effects, the highest power was reached with the GRS-interaction-training approach. If marginal genetic effects were predominant, the GRS-marginal-internal approach was more appropriate. Furthermore, the power to detect interactions reached by the GRS-interaction-training approach was only slightly lower than the power achieved by GRS with external weights. The power of the GRS-interaction-training approach was confirmed in a real data application to the Traffic, Asthma and Genetics (TAG) Study (N = 4465 observations). When appropriate external weights are unavailable, we

  6. Identification of New Genetic Susceptibility Loci for Breast Cancer Through Consideration of Gene-Environment Interactions

    Science.gov (United States)

    Schoeps, Anja; Rudolph, Anja; Seibold, Petra; Dunning, Alison M.; Milne, Roger L.; Bojesen, Stig E.; Swerdlow, Anthony; Andrulis, Irene; Brenner, Hermann; Behrens, Sabine; Orr, Nicholas; Jones, Michael; Ashworth, Alan; Li, Jingmei; Cramp, Helen; Connley, Dan; Czene, Kamila; Darabi, Hatef; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Knight, Julia; Glendon, Gord; Mulligan, Anna M.; Dumont, Martine; Severi, Gianluca; Baglietto, Laura; Olson, Janet; Vachon, Celine; Purrington, Kristen; Moisse, Matthieu; Neven, Patrick; Wildiers, Hans; Spurdle, Amanda; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Hamann, Ute; Ko, Yon-Dschun; Dieffenbach, Aida K.; Arndt, Volker; Stegmaier, Christa; Malats, Núria; Arias Perez, JoséI.; Benítez, Javier; Flyger, Henrik; Nordestgaard, Børge G.; Truong, Théresè; Cordina-Duverger, Emilie; Menegaux, Florence; Silva, Isabel dos Santos; Fletcher, Olivia; Johnson, Nichola; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Braaf, Linde; Atsma, Femke; van den Broek, Alexandra J.; Makalic, Enes; Schmidt, Daniel F.; Southey, Melissa C.; Cox, Angela; Simard, Jacques; Giles, Graham G.; Lambrechts, Diether; Mannermaa, Arto; Brauch, Hiltrud; Guénel, Pascal; Peto, Julian; Fasching, Peter A.; Hopper, John; Flesch-Janys, Dieter; Couch, Fergus; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Schmidt, Marjanka K.; Hall, Per; Easton, Douglas F.; Chang-Claude, Jenny

    2014-01-01

    Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10−07), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m2 (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m2 or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10−05). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci. PMID:24248812

  7. Dissecting gene-environment interactions: A penalized robust approach accounting for hierarchical structures.

    Science.gov (United States)

    Wu, Cen; Jiang, Yu; Ren, Jie; Cui, Yuehua; Ma, Shuangge

    2018-02-10

    Identification of gene-environment (G × E) interactions associated with disease phenotypes has posed a great challenge in high-throughput cancer studies. The existing marginal identification methods have suffered from not being able to accommodate the joint effects of a large number of genetic variants, while some of the joint-effect methods have been limited by failing to respect the "main effects, interactions" hierarchy, by ignoring data contamination, and by using inefficient selection techniques under complex structural sparsity. In this article, we develop an effective penalization approach to identify important G × E interactions and main effects, which can account for the hierarchical structures of the 2 types of effects. Possible data contamination is accommodated by adopting the least absolute deviation loss function. The advantage of the proposed approach over the alternatives is convincingly demonstrated in both simulation and a case study on lung cancer prognosis with gene expression measurements and clinical covariates under the accelerated failure time model. Copyright © 2017 John Wiley & Sons, Ltd.

  8. Detection of gene-environment interactions in a family-based population using SCAD.

    Science.gov (United States)

    Kim, Gwangsu; Lai, Chao-Qiang; Arnett, Donna K; Parnell, Laurence D; Ordovas, Jose M; Kim, Yongdai; Kim, Joungyoun

    2017-09-30

    Gene-environment interaction (GxE) is emphasized as one potential source of missing genetic variation on disease traits, and the ultimate goal of GxE research is prediction of individual risk and prevention of complex diseases. However, there are various challenges in statistical analysis of GxE. In this paper, we focus on the three methodological challenges: (i) the high dimensions of genes; (ii) the hierarchical structure between interaction effects and their corresponding main effects; and (iii) the correlation among subjects from family-based population studies. In this paper, we propose an algorithm that approaches all three challenges simultaneously. This is the first penalized method focusing on an interaction search based on a linear mixed effect model. For verification, we compare the empirical performance of our new method with other existing methods in simulation study. The results demonstrate the superiority of our method under overall simulation setup. In particular, the outperformance obviously becomes greater as the correlation among subjects increases. In addition, the new method provides a robust estimate for the correlation among subjects. We also apply the new method on Genetics of Lipid Lowering Drugs and Diet Network study data. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  9. An Efficient Test for Gene-Environment Interaction in Generalized Linear Mixed Models with Family Data.

    Science.gov (United States)

    Mazo Lopera, Mauricio A; Coombes, Brandon J; de Andrade, Mariza

    2017-09-27

    Gene-environment (GE) interaction has important implications in the etiology of complex diseases that are caused by a combination of genetic factors and environment variables. Several authors have developed GE analysis in the context of independent subjects or longitudinal data using a gene-set. In this paper, we propose to analyze GE interaction for discrete and continuous phenotypes in family studies by incorporating the relatedness among the relatives for each family into a generalized linear mixed model (GLMM) and by using a gene-based variance component test. In addition, we deal with collinearity problems arising from linkage disequilibrium among single nucleotide polymorphisms (SNPs) by considering their coefficients as random effects under the null model estimation. We show that the best linear unbiased predictor (BLUP) of such random effects in the GLMM is equivalent to the ridge regression estimator. This equivalence provides a simple method to estimate the ridge penalty parameter in comparison to other computationally-demanding estimation approaches based on cross-validation schemes. We evaluated the proposed test using simulation studies and applied it to real data from the Baependi Heart Study consisting of 76 families. Using our approach, we identified an interaction between BMI and the Peroxisome Proliferator Activated Receptor Gamma ( PPARG ) gene associated with diabetes.

  10. An Efficient Test for Gene-Environment Interaction in Generalized Linear Mixed Models with Family Data

    Directory of Open Access Journals (Sweden)

    Mauricio A. Mazo Lopera

    2017-09-01

    Full Text Available Gene-environment (GE interaction has important implications in the etiology of complex diseases that are caused by a combination of genetic factors and environment variables. Several authors have developed GE analysis in the context of independent subjects or longitudinal data using a gene-set. In this paper, we propose to analyze GE interaction for discrete and continuous phenotypes in family studies by incorporating the relatedness among the relatives for each family into a generalized linear mixed model (GLMM and by using a gene-based variance component test. In addition, we deal with collinearity problems arising from linkage disequilibrium among single nucleotide polymorphisms (SNPs by considering their coefficients as random effects under the null model estimation. We show that the best linear unbiased predictor (BLUP of such random effects in the GLMM is equivalent to the ridge regression estimator. This equivalence provides a simple method to estimate the ridge penalty parameter in comparison to other computationally-demanding estimation approaches based on cross-validation schemes. We evaluated the proposed test using simulation studies and applied it to real data from the Baependi Heart Study consisting of 76 families. Using our approach, we identified an interaction between BMI and the Peroxisome Proliferator Activated Receptor Gamma (PPARG gene associated with diabetes.

  11. A Nonlinear Model for Gene-Based Gene-Environment Interaction

    Directory of Open Access Journals (Sweden)

    Jian Sa

    2016-06-01

    Full Text Available A vast amount of literature has confirmed the role of gene-environment (G×E interaction in the etiology of complex human diseases. Traditional methods are predominantly focused on the analysis of interaction between a single nucleotide polymorphism (SNP and an environmental variable. Given that genes are the functional units, it is crucial to understand how gene effects (rather than single SNP effects are influenced by an environmental variable to affect disease risk. Motivated by the increasing awareness of the power of gene-based association analysis over single variant based approach, in this work, we proposed a sparse principle component regression (sPCR model to understand the gene-based G×E interaction effect on complex disease. We first extracted the sparse principal components for SNPs in a gene, then the effect of each principal component was modeled by a varying-coefficient (VC model. The model can jointly model variants in a gene in which their effects are nonlinearly influenced by an environmental variable. In addition, the varying-coefficient sPCR (VC-sPCR model has nice interpretation property since the sparsity on the principal component loadings can tell the relative importance of the corresponding SNPs in each component. We applied our method to a human birth weight dataset in Thai population. We analyzed 12,005 genes across 22 chromosomes and found one significant interaction effect using the Bonferroni correction method and one suggestive interaction. The model performance was further evaluated through simulation studies. Our model provides a system approach to evaluate gene-based G×E interaction.

  12. Gene-environment Interactions in Late Life: Linking Psychosocial Stress with Brain Aging.

    Science.gov (United States)

    Zannas, Anthony S

    2018-03-05

    Gene-environment interactions (GxE) can have lasting consequences on brain structure and function, potentially contributing to diverse neuropsychiatric phenotypes. This has been extensively demonstrated by studies examining GxE in childhood and early adulthood, whereas much fewer studies have addressed this question in late life. The relative paucity of studies examining GxE in late life may stem from the working hypothesis that brains become less malleable to environmental inputs as life progresses. However, while some components of brain plasticity decline with increasing age, others are retained and may even become more pronounced in old ages. Moreover, the micro- and macro-structural brain changes that accrue as a result of aging-related morbidities are likely to accentuate the susceptibility of neural circuits to environmental stressors as life advances. Supporting this hypothesis, psychosocial stress can increase the risk for late-life neuropsychiatric syndromes, especially when afflicting genetically predisposed individuals. This article reviews evidence showing how gene-stress interactions can impact the aging brain and related phenotypes in late life, and it discusses the potential mechanisms underlying such GxE and their implications for the prevention and treatment of late-life neuropsychiatric syndromes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Normal and abnormal cerebrovascular development: gene-environment interactions during early life with later life consequences.

    Science.gov (United States)

    Scher, Mark S

    2013-01-01

    A greater understanding of cerebrovascular health and disease requires the consideration of recent neuroscience advances concerning neuroplasticity in the context of classical developmental neurology principles. Consideration of the ontogenetic interplay of nature and nurture influencing brain development during prenatal and early postnatal time periods should consider the concept of the developmental origins of neurological health and disease. Adaptive and maladaptive effects of neuroplasticity require a systems biology approach integrating molecular, receptor, cellular, neural network, and behavioral perspectives, culminating in the structural and functional cerebrovascular phenotypes that express health or disease across the lifespan. Cognizance of the interrelationships among maternal, placental, fetal, and neonatal factors requires an interdisciplinary appreciation of genetic/epigenetic forces of neuroplasticity during early life that incrementally influence cerebrovascular health or disease throughout childhood and adulthood. Knowledge of the systemic effects of multiorgan function on cerebrovascular development further broadens the systems biology approach to general plasticity of the individual as a whole organism. Short- and long-term consequences of the positive and negative effects of neuroplasticity must consider ongoing gene-environment interactions with maturation and aging, superimposed on earlier fetal/neonatal experiences that sustain neurological health or contribute to disease during childhood and adulthood. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Multifactor dimensionality reduction for detecting gene-gene and gene-environment interactions in pharmacogenomics studies.

    Science.gov (United States)

    Ritchie, Marylyn D; Motsinger, Alison A

    2005-12-01

    In the quest for discovering disease susceptibility genes, the reality of gene-gene and gene-environment interactions creates difficult challenges for many current statistical approaches. In an attempt to overcome limitations with current disease gene detection methods, the multifactor dimensionality reduction (MDR) approach was previously developed. In brief, MDR is a method that reduces the dimensionality of multilocus information to identify polymorphisms associated with an increased risk of disease. This approach takes multilocus genotypes and develops a model for defining disease risk by pooling high-risk genotype combinations into one group and low-risk combinations into another. Cross-validation and permutation testing are used to identify optimal models. While this approach was initially developed for studies of complex disease, it is also directly applicable to pharmacogenomic studies where the outcome variable is drug treatment response/nonresponse or toxicity/no toxicity. MDR is a nonparametric and model-free approach that has been shown to have reasonable power to detect epistasis in both theoretical and empirical studies. This computational technology is described in detail in this review, and its application in pharmacogenomic studies is demonstrated.

  15. Rethinking expertise: A multifactorial gene-environment interaction model of expert performance.

    Science.gov (United States)

    Ullén, Fredrik; Hambrick, David Zachary; Mosing, Miriam Anna

    2016-04-01

    Scientific interest in expertise-superior performance within a specific domain-has a long history in psychology. Although there is a broad consensus that a long period of practice is essential for expertise, a long-standing controversy in the field concerns the importance of other variables such as cognitive abilities and genetic factors. According to the influential deliberate practice theory, expert performance is essentially limited by a single variable: the amount of deliberate practice an individual has accumulated. Here, we provide a review of the literature on deliberate practice, expert performance, and its neural correlates. A particular emphasis is on recent studies indicating that expertise is related to numerous traits other than practice as well as genetic factors. We argue that deliberate practice theory is unable to account for major recent findings relating to expertise and expert performance, and propose an alternative multifactorial gene-environment interaction model of expertise, which provides an adequate explanation for the available empirical data and may serve as a useful framework for future empirical and theoretical work on expert performance. (c) 2016 APA, all rights reserved).

  16. Gene-environment interaction and covariation in schizophrenia: the role of obstetric complications.

    Science.gov (United States)

    Mittal, Vijay A; Ellman, Lauren M; Cannon, Tyrone D

    2008-11-01

    While genetic factors account for a significant proportion of liability to schizophrenia, a body of evidence attests to a significant environmental contribution. Understanding the mechanisms through which genetic and environmental factors coalesce in influencing schizophrenia is critical for elucidating the pathways underlying psychotic illness and for developing primary prevention strategies. Although obstetric complications (OCs) remain among the most well-documented environmental indicators of risk for schizophrenia, the pathogenic role they play in the etiology of schizophrenia continues to remain poorly understood. A question of major importance is do these factors result from a genetic diathesis to schizophrenia (as in gene-environment covariation), act additively or interactively with predisposing genes for the disorder in influencing disease risk, or independently cause disease onset? In this review, we evaluate 3 classes of OCs commonly related to schizophrenia including hypoxia-associated OCs, maternal infection during pregnancy, and maternal stress during pregnancy. In addition, we discuss several mechanisms by which OCs impact on genetically susceptible brain regions, increasing constitutional vulnerability to neuromaturational events and stressors later in life (ie, adolescence), which may in turn contribute to triggering psychosis.

  17. Metabolic syndrome, diabetes and atherosclerosis: Influence of gene-environment interaction

    Energy Technology Data Exchange (ETDEWEB)

    Andreassi, Maria Grazia, E-mail: andreas@ifc.cnr.it [CNR Institute of Clinical Physiology, G. Pasquinucci Hospital, Via Aurelia Sud, Massa (Italy)

    2009-07-10

    Despite remarkable progress in diagnosis and understanding of risk factors, cardiovascular disease (CVD) remains still the leading cause of morbidity and mortality in the world's developed countries. The metabolic syndrome, a cluster of risk factors (visceral obesity, insulin resistance, dyslipidaemia, and hypertension), is increasingly being recognized as a new risk factor for type 2 diabetes and atherosclerotic cardiovascular disease. Nevertheless, there is wide variation in both the occurrence of disease and age of onset, even in individuals who display very similar risk profiles. There is now compelling evidence that a complex interplay between genetic determinants and environmental factors (still largely unknown) is the reason for this large inter-individual variation in disease susceptibility. The purpose of the present review is to describe the current status of our knowledge concerning the gene-environment interactions potentially implicated in the pathogenesis of metabolic syndrome, diabetes and cardiovascular disease. It focuses predominantly on studies of genes (peroxisome proliferator-activated receptor-gamma, alcohol dehydrogenase type 1C, apolipoprotein E, glutathione S-transferases T1 and M1) that are known to be modified by dietary and lifestyle habits (fat diet, intake of alcohol and smoking habit). It also describes the limited current understanding of the role of genetic variants of xenobiotic metabolizing enzymes and their interactions with environmental toxicants. Additional studies are needed in order to clarify whether inter-individual differences in detoxification of environmental toxicants may have an essential role in the development of CVD and contribute to the emerging field of 'environmental cardiology'. Such knowledge may be particularly relevant for improving cardiovascular risk stratification and conceiving the development of 'personalized intervention program'.

  18. The complement system: a gateway to gene-environment interactions in schizophrenia pathogenesis.

    Science.gov (United States)

    Nimgaonkar, V L; Prasad, K M; Chowdari, K V; Severance, E G; Yolken, R H

    2017-11-01

    The pathogenesis of schizophrenia is considered to be multi-factorial, with likely gene-environment interactions (GEI). Genetic and environmental risk factors are being identified with increasing frequency, yet their very number vastly increases the scope of possible GEI, making it difficult to identify them with certainty. Accumulating evidence suggests a dysregulated complement pathway among the pathogenic processes of schizophrenia. The complement pathway mediates innate and acquired immunity, and its activation drives the removal of damaged cells, autoantigens and environmentally derived antigens. Abnormalities in complement functions occur in many infectious and autoimmune disorders that have been linked to schizophrenia. Many older reports indicate altered serum complement activity in schizophrenia, though the data are inconclusive. Compellingly, recent genome-wide association studies suggest repeat polymorphisms incorporating the complement 4A (C4A) and 4B (C4B) genes as risk factors for schizophrenia. The C4A/C4B genetic associations have re-ignited interest not only in inflammation-related models for schizophrenia pathogenesis, but also in neurodevelopmental theories, because rodent models indicate a role for complement proteins in synaptic pruning and neurodevelopment. Thus, the complement system could be used as one of the 'staging posts' for a variety of focused studies of schizophrenia pathogenesis. They include GEI studies of the C4A/C4B repeat polymorphisms in relation to inflammation-related or infectious processes, animal model studies and tests of hypotheses linked to autoimmune diseases that can co-segregate with schizophrenia. If they can be replicated, such studies would vastly improve our understanding of pathogenic processes in schizophrenia through GEI analyses and open new avenues for therapy.

  19. DISC1 mouse models as a tool to decipher gene-environment interactions in psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Tyler eCash-Padgett

    2013-09-01

    Full Text Available DISC1 was discovered in a Scottish pedigree in which a chromosomal translocation that breaks this gene segregates with psychiatric disorders, mainly depression and schizophrenia. Linkage and association studies in diverse populations support DISC1 as a susceptibility gene to a variety of neuropsychiatric disorders. Many Disc1 mouse models have been generated to study its neuronal functions. These mouse models display variable phenotypes, some of them relevant to schizophrenia, others to depression.The Disc1 mouse models are popular genetic models for studying gene-environment interactions in schizophrenia. Five different Disc1 models have been combined with environmental factors. The environmental stressors employed can be classified as either early immune activation or later social paradigms. These studies cover major time points along the neurodevelopmental trajectory: prenatal, early postnatal, adolescence, and adulthood. Various combinations of molecular, anatomical and behavioral methods have been used to assess the outcomes. Additionally, three of the studies sought to rescue the resulting abnormalities.Here we provide background on the environmental paradigms used, summarize the results of these studies combining Disc1 mouse models with environmental stressors and discuss what we can learn and how to proceed. A major question is how the genetic and environmental factors determine which psychiatric disorder will be clinically manifested. To address this we can take advantage of the many Disc1 models available and expose them to the same environmental stressor. The complementary experiment would be to expose the same model to different environmental stressors. DISC1 is an ideal gene for this approach, since in the Scottish pedigree the same chromosomal translocation results in different psychiatric conditions.

  20. Gene-environment interaction in skeletal maturity and body dimensions of urban Oaxaca Mestizo schoolchildren.

    Science.gov (United States)

    Little, Bertis B; Malina, Robert M

    2007-01-01

    The study analyzed the relationship between skeletal age (SA) and the difference between skeletal and chronological ages (SA-CA) and body size among growth-stunted and well-nourished children. Tanner-Whitehouse 2 (TW2) 20 bone, radius-ulna-short (RUS) bone, and carpal SAs were analyzed in three cross-sectional samples of school children aged 6-13 years: Mestizo children (n = 396) from the city of Oaxaca, southern Mexico, and American Black (n = 570) and White (n = 432) from Philadelphia. The Oaxaca children were mild-to-moderately undernourished while the Philadelphia children were well nourished. The total sample included 1398 radiographs assessed with the Tanner-Whitehouse protocol by a single, experienced rater. Maturity scores were converted to TW2 20 bone, RUS and carpal SAs. Correlations of SA and SA-CA differences with body dimensions (height, sitting height, leg length, weight, triceps skinfold, arm and estimated midarm muscle circumferences) were consistent and approximately equal in magnitude for the well-nourished samples but were different among Oaxaca children. SAs of Philadelphia children were significantly more highly correlated with body dimensions than were SA-CA differences compared to Oaxaca Mestizo children. Patterns of RUS and carpal SA correlations with body size (height, sitting height, and leg length) in Oaxaca children were different from the Philadelphia samples. Oaxaca children tended to have advanced RUS SA and delayed carpal SA. Long bone complexes mature earlier than round bone complexes in Oaxaca children compared to Philadelphia Black and White children, resulting in short stature in Oaxaca children. Results suggest a gene-environment interaction effect on the program for skeletal growth and maturation in undernourished Oaxaca children compared to well-nourished Black and White children from Philadelphia.

  1. The Association between Gene-Environment Interactions and Diseases Involving the Human GST Superfamily with SNP Variants

    Directory of Open Access Journals (Sweden)

    Antoinesha L. Hollman

    2016-03-01

    Full Text Available Exposure to environmental hazards has been associated with diseases in humans. The identification of single nucleotide polymorphisms (SNPs in human populations exposed to different environmental hazards, is vital for detecting the genetic risks of some important human diseases. Several studies in this field have been conducted on glutathione S-transferases (GSTs, a phase II detoxification superfamily, to investigate its role in the occurrence of diseases. Human GSTs consist of cytosolic and microsomal superfamilies that are further divided into subfamilies. Based on scientific search engines and a review of the literature, we have found a large amount of published articles on human GST super- and subfamilies that have greatly assisted in our efforts to examine their role in health and disease. Because of its polymorphic variations in relation to environmental hazards such as air pollutants, cigarette smoke, pesticides, heavy metals, carcinogens, pharmaceutical drugs, and xenobiotics, GST is considered as a significant biomarker. This review examines the studies on gene-environment interactions related to various diseases with respect to single nucleotide polymorphisms (SNPs found in the GST superfamily. Overall, it can be concluded that interactions between GST genes and environmental factors play an important role in human diseases.

  2. Gene-environment interaction between the brain-derived neurotrophic factor Val66Met polymorphism, psychosocial stress and dietary intake in early psychosis.

    Science.gov (United States)

    Gattere, Giulia; Stojanovic-Pérez, Alexander; Monseny, Rosa; Martorell, Lourdes; Ortega, Laura; Montalvo, Itziar; Solé, Montse; Algora, María José; Cabezas, Ángel; Reynolds, Rebecca M; Vilella, Elisabet; Labad, Javier

    2016-09-15

    The brain-derived neurotrophic factor (BDNF) is a major participant in the regulation of food intake and may play a role in the regulation of the stress response. We aimed to investigate whether there is a gene-environment interaction in the relationship between stress and BDNF Val66Met polymorphism in relation to dietary patterns in a sample of subjects with early psychosis. We studied 124 early psychotic disorder (PD) patients, 36 At-Risk Mental States (ARMS) and 62 healthy subjects (HS). Dietary patterns were examined by a dietician. Physical activity, life stress and perceived stress were assessed by validated questionnaires. BDNF Val66Met polymorphism (rs6265) was genotyped. A gene-environment interaction was tested with multiple linear regression analysis while adjusting for covariates. Perceived stress was not associated with calorie intake in HS. In ARMS subjects, Met-carriers who presented low-perceived stress were associated with increased caloric intake. Conversely, those who presented high-perceived stress were associated with reduced caloric intake. In PD, perceived stress was neither associated with increased calorie intake without an effect by BDNF genotype nor a gene-environment interaction. Perceived stress was associated with food craving in PD patients, independent of genotype, and in ARMS or HS who were Val homozygous. This study suggests that the common Val66Met polymorphism of the BDNF gene may modulate the relationship between life stress and calorie intake in subjects at risk for psychosis. © 2016 John Wiley & Sons Australia, Ltd.

  3. A model of gene-gene and gene-environment interactions and its implications for targeting environmental interventions by genotype

    OpenAIRE

    Wallace Helen M

    2006-01-01

    Abstract Background The potential public health benefits of targeting environmental interventions by genotype depend on the environmental and genetic contributions to the variance of common diseases, and the magnitude of any gene-environment interaction. In the absence of prior knowledge of all risk factors, twin, family and environmental data may help to define the potential limits of these benefits in a given population. However, a general methodology to analyze twin data is required becaus...

  4. A model of gene-gene and gene-environment interactions and its implications for targeting environmental interventions by genotype.

    Science.gov (United States)

    Wallace, Helen M

    2006-10-09

    The potential public health benefits of targeting environmental interventions by genotype depend on the environmental and genetic contributions to the variance of common diseases, and the magnitude of any gene-environment interaction. In the absence of prior knowledge of all risk factors, twin, family and environmental data may help to define the potential limits of these benefits in a given population. However, a general methodology to analyze twin data is required because of the potential importance of gene-gene interactions (epistasis), gene-environment interactions, and conditions that break the 'equal environments' assumption for monozygotic and dizygotic twins. A new model for gene-gene and gene-environment interactions is developed that abandons the assumptions of the classical twin study, including Fisher's (1918) assumption that genes act as risk factors for common traits in a manner necessarily dominated by an additive polygenic term. Provided there are no confounders, the model can be used to implement a top-down approach to quantifying the potential utility of genetic prediction and prevention, using twin, family and environmental data. The results describe a solution space for each disease or trait, which may or may not include the classical twin study result. Each point in the solution space corresponds to a different model of genotypic risk and gene-environment interaction. The results show that the potential for reducing the incidence of common diseases using environmental interventions targeted by genotype may be limited, except in special cases. The model also confirms that the importance of an individual's genotype in determining their risk of complex diseases tends to be exaggerated by the classical twin studies method, owing to the 'equal environments' assumption and the assumption of no gene-environment interaction. In addition, if phenotypes are genetically robust, because of epistasis, a largely environmental explanation for shared sibling

  5. Challenges in the use of literature-based meta-analysis to examine gene-environment interactions.

    Science.gov (United States)

    Palla, Luigi; Higgins, Julian P T; Wareham, Nicholas J; Sharp, Stephen J

    2010-06-01

    Statistical interactions between genes and environmental exposures with respect to disease outcomes may help to identify biologic mechanisms and pathways and inform behavioral interventions. The number of persons required for a single study to have sufficient statistical power to detect such interactions may be considered prohibitively large, making a meta-analysis of published literature an apparently attractive alternative. However, meta-analysis of gene-environment interactions using published literature is challenging, with the conclusions being likely to suffer from bias and lack of generalizability. The authors highlight these challenges and biases using an illustrative example: meta-analysis of interactions between the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma (PPARgamma) gene and various diet and lifestyle factors in the risk of diabetes. The authors conclude that literature-based meta-analysis conducted to examine gene-environment interactions is unlikely to provide a meaningful quantitative conclusion. Alternative strategies are required, including analyses in scientific consortia established to assess main genetic effects, where individual participant data can be shared, allowing both greater power and consistency of analysis methods. However, these consortia are likely to be limited by lack of standardization of the measures of environmental factors. This issue may ultimately only be resolvable by the de novo establishment of large single or multicenter cohorts using comparable methods.

  6. Gene-environment interactions between stress and 5-HTTLPR in depression: A meta-analytic update.

    Science.gov (United States)

    Bleys, Dries; Luyten, Patrick; Soenens, Bart; Claes, Stephan

    2018-01-15

    Meta-analyses have yielded contradictory findings concerning the role of 5-HTTLPR in interaction with stress (GxE) in depression. The current meta-analysis investigates if these contradictory findings are a result of differences between studies in methodological approaches towards the assessment of stress and depression. After performing a systematic database search (February to December 2016), first, a meta-analysis was used to investigate the total effect size and publication bias. Second, stratified meta-analyses were used to investigate the potential moderating influence of different methodological approaches on heterogeneity of study findings. Third, a meta-regression was used to investigate the combined influence of the methodological approaches on the overall effect size. Results showed a small but significant effect of 5-HTTLPR in interaction with stress in the prediction of depression (OR[95%CI] = 1.18[1.09; 1.28], n = 48 effect sizes from 51 studies, totaling 51,449 participants). There was no evidence of publication bias. Heterogeneity of effect sizes was a result of outliers and not due to different methodological approaches towards the assessment of stress and depression. Yet, there was some evidence that studies adopting a categorical and interview approach to the assessment of stress report higher GxE effects, but further replication of this finding is needed. A large amount of heterogeneity (i.e., 46%) was not explained by the methodological factors included in the study and there was a low response rate of invited studies. The current meta-analysis provides new evidence for the robustness of the interaction between stress and 5-HTTLPR in depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Gene-gene and gene-environment interactions in prostate, breast and colorectal cancer

    DEFF Research Database (Denmark)

    Kopp, Tine Iskov

    The incidence of cancer in the western world has increased steeply during the last 50 years. For three of the most prevalent cancer types in Denmark, prostate, breast and colorectal cancer (PC, BC and CRC, respectively), only a small fraction (1-15%) of the incidences are caused by highly penetrant......, such as alcohol consumption, smoking, obesity, inflammation and high meat intake; whereas other factors protect against cancer, such as high intake of dietary fibre, fruits and vegetables, and physical activity. Investigating the interactions between genetic variations and environmental factors, such as dietary...... was used to examine gene-gene and geneenvironment interactions in relation to risk of cancer (Paper I-V). A human intervention trial (Paper V) was conducted in order to directly examine the effect on concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) and alcohol consumption on circulating...

  8. Does parental divorce moderate the heritability of body dissatisfaction? An extension of previous gene-environment interaction effects.

    Science.gov (United States)

    O'Connor, Shannon M; Klump, Kelly L; VanHuysse, Jessica L; McGue, Matt; Iacono, William

    2016-02-01

    Previous research suggests that parental divorce moderates genetic influences on body dissatisfaction. Specifically, the heritability of body dissatisfaction is higher in children of divorced versus intact families, suggesting possible gene-environment interaction effects. However, prior research is limited to a single, self-reported measure of body dissatisfaction. The primary aim of this study was to examine whether these findings extend to a different dimension of body dissatisfaction: body image perceptions. Participants were 1,534 female twins from the Minnesota Twin Family Study, aged 16-20 years. The Body Rating Scale (BRS) was used to assess body image perceptions. Although BRS scores were heritable in twins from divorced and intact families, the heritability estimates in the divorced group were not significantly greater than estimates in the intact group. However, there were differences in nonshared environmental effects, where the magnitude of these environmental influences was larger in the divorced as compared with the intact families. Different dimensions of body dissatisfaction (i.e., negative self-evaluation versus body image perceptions) may interact with environmental risk, such as parental divorce, in discrete ways. Future research should examine this possibility and explore differential gene-environment interactions using diverse measures. © 2015 Wiley Periodicals, Inc.

  9. Screening for gene-environment (G×E) interaction using omics data from exposed individuals: an application to gene-arsenic interaction.

    Science.gov (United States)

    Argos, Maria; Tong, Lin; Roy, Shantanu; Sabarinathan, Mekala; Ahmed, Alauddin; Islam, Md Tariqul; Islam, Tariqul; Rakibuz-Zaman, Muhammad; Sarwar, Golam; Shahriar, Hasan; Rahman, Mahfuzar; Yunus, Md; Graziano, Joseph H; Jasmine, Farzana; Kibriya, Muhammad G; Zhou, Xiang; Ahsan, Habibul; Pierce, Brandon L

    2018-02-01

    Identifying gene-environment interactions is a central challenge in the quest to understand susceptibility to complex, multi-factorial diseases. Developing an understanding of how inter-individual variability in inherited genetic variation alters the effects of environmental exposures will enhance our knowledge of disease mechanisms and improve our ability to predict disease and target interventions to high-risk sub-populations. Limited progress has been made identifying gene-environment interactions in the epidemiological setting using existing statistical approaches for genome-wide searches for interaction. In this paper, we describe a novel two-step approach using omics data to conduct genome-wide searches for gene-environment interactions. Using existing genome-wide SNP data from a large Bangladeshi cohort study specifically designed to assess the effect of arsenic exposure on health, we evaluated gene-arsenic interactions by first conducting genome-wide searches for SNPs that modify the effect of arsenic on molecular phenotypes (gene expression and DNA methylation features). Using this set of SNPs showing evidence of interaction with arsenic in relation to molecular phenotypes, we then tested SNP-arsenic interactions in relation to skin lesions, a hallmark characteristic of arsenic toxicity. With the emergence of additional omics data in the epidemiologic setting, our approach may have the potential to boost power for genome-wide interaction research, enabling the identification of interactions that will enhance our understanding of disease etiology and our ability to develop interventions targeted at susceptible sub-populations.

  10. Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study.

    Science.gov (United States)

    Karwowski, Mateusz P; Just, Allan C; Bellinger, David C; Jim, Rebecca; Hatley, Earl L; Ettinger, Adrienne S; Hu, Howard; Wright, Robert O

    2014-10-06

    Given the relationship between iron metabolism and lead toxicokinetics, we hypothesized that polymorphisms in iron metabolism genes might modify maternal-fetal lead transfer. The objective of this study was to determine whether maternal and/or infant transferrin (TF) and hemochromatosis (HFE) gene missense variants modify the association between maternal blood lead (MBL) and umbilical cord blood lead (UCBL). We studied 476 mother-infant pairs whose archived blood specimens were genotyped for TF P570S, HFE H63D and HFE C282Y. MBL and UCBL were collected within 12 hours of delivery. Linear regression models were used to examine the association between log-transformed MBL and UCBL, examine for confounding and collinearity, and explore gene-environment interactions. The geometric mean MBL was 0.61 μg/dL (range 0.03, 3.2) and UCBL 0.42 (lead transfer among women with MBL 5 μg/dL. Maternal HFE C282Y gene variant status is associated with greater reductions in placental transfer of lead as MBL increases. The inclusion of gene-environment interaction in risk assessment models may improve efforts to safeguard vulnerable populations.

  11. On meta- and mega-analyses for gene-environment interactions.

    Science.gov (United States)

    Huang, Jing; Liu, Yulun; Vitale, Steve; Penning, Trevor M; Whitehead, Alexander S; Blair, Ian A; Vachani, Anil; Clapper, Margie L; Muscat, Joshua E; Lazarus, Philip; Scheet, Paul; Moore, Jason H; Chen, Yong

    2017-12-01

    Gene-by-environment (G × E) interactions are important in explaining the missing heritability and understanding the causation of complex diseases, but a single, moderately sized study often has limited statistical power to detect such interactions. With the increasing need for integrating data and reporting results from multiple collaborative studies or sites, debate over choice between mega- versus meta-analysis continues. In principle, data from different sites can be integrated at the individual level into a "mega" data set, which can be fit by a joint "mega-analysis." Alternatively, analyses can be done at each site, and results across sites can be combined through a "meta-analysis" procedure without integrating individual level data across sites. Although mega-analysis has been advocated in several recent initiatives, meta-analysis has the advantages of simplicity and feasibility, and has recently led to several important findings in identifying main genetic effects. In this paper, we conducted empirical and simulation studies, using data from a G × E study of lung cancer, to compare the mega- and meta-analyses in four commonly used G × E analyses under the scenario that the number of studies is small and sample sizes of individual studies are relatively large. We compared the two data integration approaches in the context of fixed effect models and random effects models separately. Our investigations provide valuable insights in understanding the differences between mega- and meta-analyses in practice of combining small number of studies in identifying G × E interactions. © 2017 WILEY PERIODICALS, INC.

  12. Gene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits.

    Science.gov (United States)

    Dashti, Hassan S; Follis, Jack L; Smith, Caren E; Tanaka, Toshiko; Garaulet, Marta; Gottlieb, Daniel J; Hruby, Adela; Jacques, Paul F; Kiefte-de Jong, Jessica C; Lamon-Fava, Stefania; Scheer, Frank A J L; Bartz, Traci M; Kovanen, Leena; Wojczynski, Mary K; Frazier-Wood, Alexis C; Ahluwalia, Tarunveer S; Perälä, Mia-Maria; Jonsson, Anna; Muka, Taulant; Kalafati, Ioanna P; Mikkilä, Vera; Ordovás, José M

    2015-08-01

    significant interactions is conducted, recommendations applicable to the general population regarding diet—specifically higher carbohydrate and lower fat composition—and normal sleep duration should continue to be emphasized among individuals with the investigated circadian-related gene variants. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Characterization of 9p24 risk locus and colorectal adenoma and cancer: gene-environment interaction and meta-analysis.

    Science.gov (United States)

    Kocarnik, Jonathan D; Hutter, Carolyn M; Slattery, Martha L; Berndt, Sonja I; Hsu, Li; Duggan, David J; Muehling, Jill; Caan, Bette J; Beresford, Shirley A A; Rajkovic, Aleksandar; Sarto, Gloria E; Marshall, James R; Hammad, Nazik; Wallace, Robert B; Makar, Karen W; Prentice, Ross L; Potter, John D; Hayes, Richard B; Peters, Ulrike

    2010-12-01

    A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive. We genotyped this locus and explored interactions with known risk factors as potential sources of heterogeneity, which may explain the previously inconsistent replication. We included Caucasians with colorectal adenoma or colorectal cancer and controls from 4 studies (total 3,891 cases, 4,490 controls): the Women's Health Initiative (WHI); the Diet, Activity and Lifestyle Study (DALS); a Minnesota population-based case-control study (MinnCCS); and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). We used logistic regression to evaluate the association and test for gene-environment interactions. SNP rs719725 was statistically significantly associated with risk of colorectal cancer in WHI (OR per A allele 1.19; 95% CI, 1.01-1.40; P(trend) = 0.04), marginally associated with adenoma risk in PLCO (OR per A allele 1.11; 95% CI, 0.99-1.25; P(trend) = 0.07), and not associated in DALS and MinnCCS. Evaluating for gene-environment interactions yielded no consistent results across the studies. A meta-analysis of 17 studies (including these 4) gave an OR per A allele of 1.07 (95% CI, 1.03-1.12; P(trend) = 0.001). Our results suggest the Aallele for SNP rs719725 at locus 9p24 is positively associated with a small increase in risk for colorectal tumors. Environmental risk factors for colorectal cancer do not appear to explain heterogeneity across studies. If this finding is supported by further replication and functional studies, it may highlight new pathways underlying colorectal neoplasia. ©2010 AACR.

  14. Degenerative periodontal-diseases and oral osteonecrosis: The role of gene-environment interactions

    International Nuclear Information System (INIS)

    Baldi, D.; Izzotti, A.; Bonica, P.; Pera, P.; Pulliero, A.

    2009-01-01

    Chronic-degenerative dentistry diseases, including periodontal diseases and oral osteonecrosis, are widespread in human populations and represent a significant problem for public health. These diseases result from pathogenic mechanisms created by the interaction between environmental genotoxic risk-factors and genetic assets conferring individual susceptibility. Osteonecrosis occurs in subjects undergoing exposure to high doses of DNA-damaging agents for chemo- and radiotherapy of neoplastic diseases. In susceptible patients, ionizing radiation and biphosphonate-chemotherapy induce severe, progressive, and irreversible degeneration of facial bones, resulting in avascular necrosis of the jaw. This may also occur in patients receiving biphosphonate for osteoporosis therapy. Periodontal diseases include chronic, aggressive, and necrotizing periodontitis, often resulting in severe alteration of periodontal tissues and tooth loss. Cigarette smoking and chronic inflammation caused by specific bacteria are the main risk factors for periodontitis. Oxidative damage plays a fundamental pathogenic role, as established by detection of mitochondrial DNA damage in the gingival tissue of patients with periodontitis. Endogenous risk factors in dental diseases include polymorphisms for metabolic enzymes such as glutathione transferases M1 and T1, N-acetyl transferase 2, and CYP 1A1. Other genetic polymorphisms that confer susceptibility to dentistry diseases affect genes encoding metalloproteases (involved in periodontal tissue remodeling and degradation), cytokines (involved in inflammation), prothrombin, and DNA repair activities. These findings provide evidence that dentistry diseases are related to risk factors associated with environmental mutagenesis. This issue warrants future investigations aimed at improving oral health and preventing oral degenerative diseases using molecular and experimental approaches currently utilized in mutagenicity studies.

  15. Degenerative periodontal-diseases and oral osteonecrosis: The role of gene-environment interactions

    Energy Technology Data Exchange (ETDEWEB)

    Baldi, D. [Department of Medical, Biophysical, and Dentistry Sciences and Technologies, University of Genoa (Italy); Izzotti, A. [Department of Health Sciences, University of Genoa, Via A. Pastore 1 (Italy); Bonica, P.; Pera, P. [Department of Medical, Biophysical, and Dentistry Sciences and Technologies, University of Genoa (Italy); Pulliero, A., E-mail: alessandra.pulliero@unige.it [Department of Health Sciences, University of Genoa, Via A. Pastore 1 (Italy)

    2009-07-10

    Chronic-degenerative dentistry diseases, including periodontal diseases and oral osteonecrosis, are widespread in human populations and represent a significant problem for public health. These diseases result from pathogenic mechanisms created by the interaction between environmental genotoxic risk-factors and genetic assets conferring individual susceptibility. Osteonecrosis occurs in subjects undergoing exposure to high doses of DNA-damaging agents for chemo- and radiotherapy of neoplastic diseases. In susceptible patients, ionizing radiation and biphosphonate-chemotherapy induce severe, progressive, and irreversible degeneration of facial bones, resulting in avascular necrosis of the jaw. This may also occur in patients receiving biphosphonate for osteoporosis therapy. Periodontal diseases include chronic, aggressive, and necrotizing periodontitis, often resulting in severe alteration of periodontal tissues and tooth loss. Cigarette smoking and chronic inflammation caused by specific bacteria are the main risk factors for periodontitis. Oxidative damage plays a fundamental pathogenic role, as established by detection of mitochondrial DNA damage in the gingival tissue of patients with periodontitis. Endogenous risk factors in dental diseases include polymorphisms for metabolic enzymes such as glutathione transferases M1 and T1, N-acetyl transferase 2, and CYP 1A1. Other genetic polymorphisms that confer susceptibility to dentistry diseases affect genes encoding metalloproteases (involved in periodontal tissue remodeling and degradation), cytokines (involved in inflammation), prothrombin, and DNA repair activities. These findings provide evidence that dentistry diseases are related to risk factors associated with environmental mutagenesis. This issue warrants future investigations aimed at improving oral health and preventing oral degenerative diseases using molecular and experimental approaches currently utilized in mutagenicity studies.

  16. Interaction between Social/Psychosocial Factors and Genetic Variants on Body Mass Index: A Gene-Environment Interaction Analysis in a Longitudinal Setting

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    2017-09-01

    Full Text Available Obesity, which develops over time, is one of the leading causes of chronic diseases such as cardiovascular disease. However, hundreds of BMI (body mass index-associated genetic loci identified through large-scale genome-wide association studies (GWAS only explain about 2.7% of BMI variation. Most common human traits are believed to be influenced by both genetic and environmental factors. Past studies suggest a variety of environmental features that are associated with obesity, including socioeconomic status and psychosocial factors. This study combines both gene/regions and environmental factors to explore whether social/psychosocial factors (childhood and adult socioeconomic status, social support, anger, chronic burden, stressful life events, and depressive symptoms modify the effect of sets of genetic variants on BMI in European American and African American participants in the Health and Retirement Study (HRS. In order to incorporate longitudinal phenotype data collected in the HRS and investigate entire sets of single nucleotide polymorphisms (SNPs within gene/region simultaneously, we applied a novel set-based test for gene-environment interaction in longitudinal studies (LGEWIS. Childhood socioeconomic status (parental education was found to modify the genetic effect in the gene/region around SNP rs9540493 on BMI in European Americans in the HRS. The most significant SNP (rs9540488 by childhood socioeconomic status interaction within the rs9540493 gene/region was suggestively replicated in the Multi-Ethnic Study of Atherosclerosis (MESA (p = 0.07.

  17. Gene Environment Interaction: A Trigger Point of Developing Polyglandular Autoimmunity in A Minor Girl from Rural India

    Directory of Open Access Journals (Sweden)

    Dastidar Rinini

    2017-05-01

    Full Text Available A six-year-old girl from rural Bengal was admitted in our hospital with complaints of thirst, frequent micturition, pain in abdomen and constipation. Polyglandular endocrinopathies were identified in the girl thorough clinical and biochemical examination. Hashimoto’s thyroiditis along with Type 1 diabetes mellitus made her a candidate of Polyglandular Autoimmune disease type IIIA. Patient’s history revealed that she was on cow milk since birth. Presence of high risk alleles for T1DM HLA DQA1*0101-DQB1*0302 and DQA1*0301-DQB1*0501 in the girl was disclosed by genetic study. The effect of environmental factors along with genetic susceptibility might contribute to the aggravation and early expression of these rare autoimmune diseases in this girl. This could be a classic example of gene environment interaction in case of unexplained endocrinopathies

  18. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors

    DEFF Research Database (Denmark)

    Nickels, Stefan; Truong, Thérèse; Hein, Rebecca

    2013-01-01

    at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood......Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer....... Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age...

  19. Conceptual shifts needed to understand the dynamic interactions of genes, environment, epigenetics, social processes, and behavioral choices.

    Science.gov (United States)

    Jackson, Fatimah L C; Niculescu, Mihai D; Jackson, Robert T

    2013-10-01

    Social and behavioral research in public health is often intimately tied to profound, but frequently neglected, biological influences from underlying genetic, environmental, and epigenetic events. The dynamic interplay between the life, social, and behavioral sciences often remains underappreciated and underutilized in addressing complex diseases and disorders and in developing effective remediation strategies. Using a case-study format, we present examples as to how the inclusion of genetic, environmental, and epigenetic data can augment social and behavioral health research by expanding the parameters of such studies, adding specificity to phenotypic assessments, and providing additional internal control in comparative studies. We highlight the important roles of gene-environment interactions and epigenetics as sources of phenotypic change and as a bridge between the life and social and behavioral sciences in the development of robust interdisciplinary analyses.

  20. Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions

    DEFF Research Database (Denmark)

    Schoeps, Anja; Rudolph, Anja; Seibold, Petra

    2014-01-01

    recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714...... in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(-07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8...... confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci....

  1. Novel Likelihood Ratio Tests for Screening Gene-Gene and Gene-Environment Interactions with Unbalanced Repeated-Measures Data

    Science.gov (United States)

    Ko, Yi-An; Saha-Chaudhuri, Paramita; Park, Sung Kyun; Vokonas, Pantel Steve; Mukherjee, Bhramar

    2013-01-01

    There has been extensive literature on modeling gene-gene interaction (GGI) and gene-environment interaction (GEI) in case-control studies with limited literature on statistical methods for GGI and GEI in longitudinal cohort studies. We borrow ideas from the classical two-way analysis of variance (ANOVA) literature to address the issue of robust modeling of interactions in repeated-measures studies. While classical interaction models proposed by Tukey and Mandel have interaction structures as a function of main effects, a newer class of models, additive main effects and multiplicative interaction (AMMI) models, do not have similar restrictive assumptions on the interaction structure. AMMI entails a singular value decomposition of the cell residual matrix after fitting the additive main effects and has been shown to perform well across various interaction structures. We consider these models for testing GGI and GEI from two perspectives: likelihood ratio test based on cell means and a regression based approach using individual observations. Simulation results indicate that both approaches for AMMI models lead to valid tests in terms of maintaining the type I error rate, with the regression approach having better power properties. The performance of these models was evaluated across different interaction structures and 12 common epistasis patterns. In summary, AMMI model is robust with respect to misspecified interaction structure and is a useful screening tool for interaction even in the absence of main effects. We use the proposed methods to examine the interplay between the hemochromatosis gene and cumulative lead exposure on pulse pressure in the Normative Aging Study. PMID:23798480

  2. Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity

    Science.gov (United States)

    Bouret, Sebastien; Levin, Barry E.; Ozanne, Susan E.

    2015-01-01

    Obesity and type 2 diabetes mellitus (T2DM) often occur together and affect a growing number of individuals in both the developed and developing worlds. Both are associated with a number of other serious illnesses that lead to increased rates of mortality. There is likely a polygenic mode of inheritance underlying both disorders, but it has become increasingly clear that the pre- and postnatal environments play critical roles in pushing predisposed individuals over the edge into a disease state. This review focuses on the many genetic and environmental variables that interact to cause predisposed individuals to become obese and diabetic. The brain and its interactions with the external and internal environment are a major focus given the prominent role these interactions play in the regulation of energy and glucose homeostasis in health and disease. PMID:25540138

  3. Blood lead levels, iron metabolism gene polymorphisms and homocysteine: a gene-environment interaction study.

    Science.gov (United States)

    Kim, Kyoung-Nam; Lee, Mee-Ri; Lim, Youn-Hee; Hong, Yun-Chul

    2017-12-01

    Homocysteine has been causally associated with various adverse health outcomes. Evidence supporting the relationship between lead and homocysteine levels has been accumulating, but most prior studies have not focused on the interaction with genetic polymorphisms. From a community-based prospective cohort, we analysed 386 participants (aged 41-71 years) with information regarding blood lead and plasma homocysteine levels. Blood lead levels were measured between 2001 and 2003, and plasma homocysteine levels were measured in 2007. Interactions of lead levels with 42 genotyped single-nucleotide polymorphisms (SNPs) in five genes ( TF , HFE , CBS , BHMT and MTR ) were assessed via a 2-degree of freedom (df) joint test and a 1-df interaction test. In secondary analyses using imputation, we further assessed 58 imputed SNPs in the TF and MTHFR genes. Blood lead concentrations were positively associated with plasma homocysteine levels (p=0.0276). Six SNPs in the TF and MTR genes were screened using the 2-df joint test, and among them, three SNPs in the TF gene showed interactions with lead with respect to homocysteine levels through the 1-df interaction test (phomocysteine levels at an α-level of 0.05, but the associations did not persist after Bonferroni correction. These SNPs did not show interactions with lead levels. Blood lead levels were positively associated with plasma homocysteine levels measured 4-6 years later, and three SNPs in the TF gene modified the association. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Evidence for plasticity genotypes in a gene-gene-environment interaction : the TRAILS study

    NARCIS (Netherlands)

    Nederhof, E; Bouma, Esther; Riese, Harriette; Laceulle, Odilia; Ormel, J.; Oldehinkel, A.J.

    2010-01-01

    The purpose was to study how functional polymorphisms in the brain derived neurotrophic factor gene (BDNF val66met) and the serotonin transporter gene linked promotor region (5-HTTLPR) interact with childhood adversities in predicting Effortful Control. Effortful Control refers to the ability to

  5. Differential susceptibility in longitudinal models of gene-environment interaction for adolescent depression.

    Science.gov (United States)

    Li, James J; Berk, Michele S; Lee, Steve S

    2013-11-01

    Although family support reliably predicts the development of adolescent depression and suicidal behaviors, relatively little is known about the interplay of family support with potential genetic factors. We tested the association of the 44 base pair polymorphism in the serotonin transporter linked promoter region gene (5-HTTLPR), family support (i.e., cohesion, communication, and warmth), and their interaction with self-reported depression symptoms and risk for suicide in 1,030 Caucasian adolescents and young adults from the National Longitudinal Study of Adolescent Health. High-quality family support predicted fewer symptoms of depression and reduced risk for suicidality. There was also a significant interaction between 5-HTTLPR and family support for boys and a marginally significant interaction for girls. Among boys with poor family support, youth with at least one short allele had more symptoms of depression and a higher risk for suicide attempts relative to boys homozygous for the long allele. However, in the presence of high family support, boys with the short allele had the fewest depression symptoms (but not suicide attempts). Results suggest that the short allele may increase reactivity to both negative and positive family influences in the development of depression. We discuss the potential role of interactive exchanges between family support and offspring genotype in the development of adolescent depression and suicidal behaviors.

  6. Gene - environment interactions determine the individual variability in cocaine self-administration.

    NARCIS (Netherlands)

    Kam, E.L. van der; Ellenbroek, B.A.; Cools, A.R.

    2005-01-01

    Research into factors that determine the propensity to self-administer cocaine has shown that stressors can determine the amount of cocaine self-administered as well as the rate of acquisition. However, the interaction between the genetic make-up of the animal and stress is unknown. This study

  7. The Behavioural Phenotype of Smith-Magenis Syndrome: Evidence for a Gene-Environment Interaction

    Science.gov (United States)

    Taylor, L.; Oliver, C.

    2008-01-01

    Background: Behaviour problems and a preference for adult contact are reported to be prominent in the phenotype of Smith-Magenis syndrome. In this study we examined the relationship between social interactions and self-injurious and aggressive/disruptive behaviour in Smith-Magenis syndrome to explore potential operant reinforcement of problem…

  8. Gene-Environment Interaction in Parkinson's Disease: Coffee, ADORA2A, and CYP1A2.

    Science.gov (United States)

    Chuang, Yu-Hsuan; Lill, Christina M; Lee, Pei-Chen; Hansen, Johnni; Lassen, Christina F; Bertram, Lars; Greene, Naomi; Sinsheimer, Janet S; Ritz, Beate

    2016-01-01

    Drinking caffeinated coffee has been reported to provide protection against Parkinson's disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2) metabolizes caffeine; thus, gene polymorphisms in ADORA2A and CYP1A2 may influence the effect coffee consumption has on PD risk. In a population-based case-control study (PASIDA) in Denmark (1,556 PD patients and 1,606 birth year- and gender-matched controls), we assessed interactions between lifetime coffee consumption and 3 polymorphisms in ADORA2A and CYP1A2 for all subjects, and incident and prevalent PD cases separately using logistic regression models. We also conducted a meta-analysis combining our results with those from previous studies. We estimated statistically significant interactions for ADORA2A rs5760423 and heavy vs. light coffee consumption in incident (OR interaction = 0.66 [95% CI 0.46-0.94], p = 0.02) but not prevalent PD. We did not observe interactions for CYP1A2 rs762551 and rs2472304 in incident or prevalent PD. In meta-analyses, PD associations with daily coffee consumption were strongest among carriers of variant alleles in both ADORA2A and CYP1A2. We corroborated results from a previous report that described interactions between ADORA2A and CYP1A2 polymorphisms and coffee consumption. Our results also suggest that survivor bias may affect results of studies that enroll prevalent PD cases. © 2017 S. Karger AG, Basel.

  9. BDNF Val66Met polymorphism, life stress and depression: A meta-analysis of gene-environment interaction.

    Science.gov (United States)

    Zhao, Mingzhe; Chen, Lu; Yang, Jiarun; Han, Dong; Fang, Deyu; Qiu, Xiaohui; Yang, Xiuxian; Qiao, Zhengxue; Ma, Jingsong; Wang, Lin; Jiang, Shixiang; Song, Xuejia; Zhou, Jiawei; Zhang, Jian; Chen, Mingqi; Qi, Dong; Yang, Yanjie; Pan, Hui

    2018-02-01

    Depression is thought to be multifactorial in etiology, including genetic and environmental components. While a number of gene-environment interaction studies have been carried out, meta-analyses are scarce. The present meta-analysis aimed to quantify evidence on the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and stress in depression. Included were 31 peer-reviewed with a pooled total of 21060 participants published before October 2016 and literature searches were conducted using PubMed, Wolters Kluwer, Web of Science, EBSCO, Elsevier Science Direct and Baidu Scholar databases. The results indicated that the Met allele of BDNF Val66Met polymorphism significantly moderated the relationship between stress and depression (Z=2.666, p = 0.003). The results of subgroup analysis concluded that stressful life events and childhood adversity separately interacted with the Met allele of BDNF Val66Met polymorphism in depression (Z = 2.552, p = 0.005; Z = 1.775, p = 0.03). The results could be affected by errors or bias in primary studies which had small sample sizes with relatively lower statistic power. We could not estimate how strong the interaction effect between gene and environment was. We found evidence that supported the hypothesis that BDNF Val66Met polymorphism moderated the relationship between stress and depression, despite the fact that many included individual studies did not show this effect. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Gene-Environment Interaction and Breast Cancer on Long Island, NY

    Science.gov (United States)

    2008-05-01

    Rossner P Jr, Terry MB, Gammon MD, Agrawal M, Zhang FF, Ferris JS, Teitelbaum SL, Eng SM, Gaudet MM, Neugut AI, Santella RM. Plasma protein carbonyl...Santella RM, Gammon MD. Interactions among GSTM1, GSTT1 and GSTP1 polymorphisms, cruciferous vegetable intake and breast cancer risk. Carcinogenesis...analytes are enzymatically hydrolyzed , and then concentrated and separated from other urine components by on-line solid phase extraction coupled to

  11. Gene-Environment Interactions in the Development of Complex Disease Phenotypes

    Directory of Open Access Journals (Sweden)

    Kenneth Olden

    2008-03-01

    Full Text Available The lack of knowledge about the earliest events in disease development is due to the multi-factorial nature of disease risk. This information gap is the consequence of the lack of appreciation for the fact that most diseases arise from the complex interactions between genes and the environment as a function of the age or stage of development of the individual. Whether an environmental exposure causes illness or not is dependent on the efficiency of the so-called “environmental response machinery” (i.e., the complex of metabolic pathways that can modulate response to environmental perturbations that one has inherited. Thus, elucidating the causes of most chronic diseases will require an understanding of both the genetic and environmental contribution to their etiology. Unfortunately, the exploration of the relationship between genes and the environment has been hampered in the past by the limited knowledge of the human genome, and by the inclination of scientists to study disease development using experimental models that consider exposure to a single environmental agent. Rarely in the past were interactions between multiple genes or between genes and environmental agents considered in studies of human disease etiology. The most critical issue is how to relate exposure-disease association studies to pathways and mechanisms. To understand how genes and environmental factors interact to perturb biological pathways to cause injury or disease, scientists will need tools with the capacity to monitor the global expression of thousands of genes, proteins and metabolites simultaneously. The generation of such data in multiple species can be used to identify conserved and functionally significant genes and pathways involved in geneenvironment interactions. Ultimately, it is this knowledge that will be used to guide agencies such as the U.S. Department of Health and Human Services in decisions regarding biomedical research funding

  12. Gene Environment Interactions and Predictors of Colorectal Cancer in Family-Based, Multi-Ethnic Groups

    Directory of Open Access Journals (Sweden)

    S. Pamela K. Shiao

    2018-02-01

    Full Text Available For the personalization of polygenic/omics-based health care, the purpose of this study was to examine the gene–environment interactions and predictors of colorectal cancer (CRC by including five key genes in the one-carbon metabolism pathways. In this proof-of-concept study, we included a total of 54 families and 108 participants, 54 CRC cases and 54 matched family friends representing four major racial ethnic groups in southern California (White, Asian, Hispanics, and Black. We used three phases of data analytics, including exploratory, family-based analyses adjusting for the dependence within the family for sharing genetic heritage, the ensemble method, and generalized regression models for predictive modeling with a machine learning validation procedure to validate the results for enhanced prediction and reproducibility. The results revealed that despite the family members sharing genetic heritage, the CRC group had greater combined gene polymorphism rates than the family controls (p < 0.05, on MTHFR C677T, MTR A2756G, MTRR A66G, and DHFR 19 bp except MTHFR A1298C. Four racial groups presented different polymorphism rates for four genes (all p < 0.05 except MTHFR A1298C. Following the ensemble method, the most influential factors were identified, and the best predictive models were generated by using the generalized regression models, with Akaike’s information criterion and leave-one-out cross validation methods. Body mass index (BMI and gender were consistent predictors of CRC for both models when individual genes versus total polymorphism counts were used, and alcohol use was interactive with BMI status. Body mass index status was also interactive with both gender and MTHFR C677T gene polymorphism, and the exposure to environmental pollutants was an additional predictor. These results point to the important roles of environmental and modifiable factors in relation to gene–environment interactions in the prevention of CRC.

  13. Sample size requirements to detect gene-environment interactions in genome-wide association studies.

    Science.gov (United States)

    Murcray, Cassandra E; Lewinger, Juan Pablo; Conti, David V; Thomas, Duncan C; Gauderman, W James

    2011-04-01

    Many complex diseases are likely to be a result of the interplay of genes and environmental exposures. The standard analysis in a genome-wide association study (GWAS) scans for main effects and ignores the potentially useful information in the available exposure data. Two recently proposed methods that exploit environmental exposure information involve a two-step analysis aimed at prioritizing the large number of SNPs tested to highlight those most likely to be involved in a GE interaction. For example, Murcray et al. ([2009] Am J Epidemiol 169:219–226) proposed screening on a test that models the G-E association induced by an interaction in the combined case-control sample. Alternatively, Kooperberg and LeBlanc ([2008] Genet Epidemiol 32:255–263) suggested screening on genetic marginal effects. In both methods, SNPs that pass the respective screening step at a pre-specified significance threshold are followed up with a formal test of interaction in the second step. We propose a hybrid method that combines these two screening approaches by allocating a proportion of the overall genomewide significance level to each test. We show that the Murcray et al. approach is often the most efficient method, but that the hybrid approach is a powerful and robust method for nearly any underlying model. As an example, for a GWAS of 1 million markers including a single true disease SNP with minor allele frequency of 0.15, and a binary exposure with prevalence 0.3, the Murcray, Kooperberg and hybrid methods are 1.90, 1.27, and 1.87 times as efficient, respectively, as the traditional case-control analysis to detect an interaction effect size of 2.0.

  14. Gene-environment interactions in cancer epidemiology: a National Cancer Institute Think Tank report.

    Science.gov (United States)

    Hutter, Carolyn M; Mechanic, Leah E; Chatterjee, Nilanjan; Kraft, Peter; Gillanders, Elizabeth M

    2013-11-01

    Cancer risk is determined by a complex interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified hundreds of common (minor allele frequency [MAF] > 0.05) and less common (0.01 Think Tank" on January 10-11, 2012. The objective of the Think Tank was to facilitate discussions on (1) the state of the science, (2) the goals of G × E interaction studies in cancer epidemiology, and (3) opportunities for developing novel study designs and analysis tools. This report summarizes the Think Tank discussion, with a focus on contemporary approaches to the analysis of G × E interactions. Selecting the appropriate methods requires first identifying the relevant scientific question and rationale, with an important distinction made between analyses aiming to characterize the joint effects of putative or established genetic and environmental factors and analyses aiming to discover novel risk factors or novel interaction effects. Other discussion items include measurement error, statistical power, significance, and replication. Additional designs, exposure assessments, and analytical approaches need to be considered as we move from the current small number of success stories to a fuller understanding of the interplay of genetic and environmental factors. © 2013 WILEY PERIODICALS, INC.

  15. Plasma selenium levels and oxidative stress biomarkers: a gene-environment interaction population-based study.

    Science.gov (United States)

    Galan-Chilet, Inmaculada; Tellez-Plaza, Maria; Guallar, Eliseo; De Marco, Griselda; Lopez-Izquierdo, Raul; Gonzalez-Manzano, Isabel; Carmen Tormos, M; Martin-Nuñez, Gracia M; Rojo-Martinez, Gemma; Saez, Guillermo T; Martín-Escudero, Juan C; Redon, Josep; Javier Chaves, F

    2014-09-01

    The role of selenium exposure in preventing chronic disease is controversial, especially in selenium-repleted populations. At high concentrations, selenium exposure may increase oxidative stress. Studies evaluating the interaction of genetic variation in genes involved in oxidative stress pathways and selenium are scarce. We evaluated the cross-sectional association of plasma selenium concentrations with oxidative stress levels, measured as oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8-oxo-7,8-dihydroguanine (8-oxo-dG) in urine, and the interacting role of genetic variation in oxidative stress candidate genes, in a representative sample of 1445 men and women aged 18-85 years from Spain. The geometric mean of plasma selenium levels in the study sample was 84.76 µg/L. In fully adjusted models the geometric mean ratios for oxidative stress biomarker levels comparing the highest to the lowest quintiles of plasma selenium levels were 0.61 (0.50-0.76) for GSSG/GSH, 0.89 (0.79-1.00) for MDA, and 1.06 (0.96-1.18) for 8-oxo-dG. We observed nonlinear dose-responses of selenium exposure and oxidative stress biomarkers, with plasma selenium concentrations above ~110 μg/L being positively associated with 8-oxo-dG, but inversely associated with GSSG/GSH and MDA. In addition, we identified potential risk genotypes associated with increased levels of oxidative stress markers with high selenium levels. Our findings support that high selenium levels increase oxidative stress in some biological processes. More studies are needed to disentangle the complexity of selenium biology and the relevance of potential gene-selenium interactions in relation to health outcomes in human populations. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Gene-environment interaction in the onset of eczema in infancy

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Simpson, Angela; Palmer, Colin N A

    2008-01-01

    = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79-32.60, p dog exposure was moderately protective (HR 0.49, 95% CI 0.24-1.01, p = 0.05), but not related to FLG genotype. In Manchester (n = 503) an independent...... of the interaction with dog ownership (HR 0.59, 95% CI 0.16-2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation. CONCLUSIONS: We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat...... ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG...

  17. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors.

    Directory of Open Access Journals (Sweden)

    Stefan Nickels

    Full Text Available Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6 and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4. Overall, the per-allele odds ratio (95% confidence interval for LSP1-rs3817198 was 1.08 (1.01-1.16 in nulliparous women and ranged from 1.03 (0.96-1.10 in parous women with one birth to 1.26 (1.16-1.37 in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98 in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85 in those who drank ≥ 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 × 10(-5, with a per-allele OR of 1.14 (1.11-1.17 in parous women and 0.98 (0.92-1.05 in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.

  18. C-reactive protein gene polymorphisms and gene-environment interactions in ischaemic stroke.

    Science.gov (United States)

    Chen, Zhongyun; Yu, Dan; Xu, Zhi-Wei; Li, Shan-Shan; Li, Xiao-Feng; Li, Jing; Yang, Xu

    2015-11-01

    Ischaemic stroke is a heterogeneous, multifactorial disease caused by the combination of certain risk factors and genetic factors. Several single nucleotide polymorphisms (SNPs) of C-reactive protein (CRP) have been reported to be associated with serum CRP levels. However, genetic association studies have produced conflicting results regarding the association between these SNPs and ischaemic stroke. In this paper, we conducted a population-based case-control study to determine whether two SNPs of CRP (rs1800947 and rs3093059) are associated with ischaemic stroke in Chinese Han population and to evaluate their interaction with environmental risk factors. We found that the rs1800947 GC genotype is significantly associated with the risk of ischaemic stroke, particularly the small-vessel disease and its subtype. Crossover analysis revealed that patients with the rs1800947 GC genotype and habits of smoking or drinking were more susceptible to ischaemic stroke. No association was found between the rs3093059 and ischaemic stroke.

  19. Measuring epigenetics as the mediator of gene/environment interactions in DOHaD.

    Science.gov (United States)

    Ong, M-L; Lin, X; Holbrook, J D

    2015-02-01

    Analysis of DNA methylation data in epigenome-wide association studies provides many bioinformatics and statistical challenges. Not least of these, are the non-independence of individual DNA methylation marks from each other, from genotype and from technical sources of variation. In this review we discuss DNA methylation data from the Infinium450K array and processing methodologies to reduce technical variation. We describe recent approaches to harness the concordance of neighbouring DNA methylation values to improve power in association studies. We also describe how the non-independence of genotype and DNA methylation has been used to infer causality (in the case of Mendelian randomization approaches); suggest the mediating effect of DNA methylation in linking intergenic single nucleotide polymorphisms, identified in genome-wide association studies, to phenotype; and to uncover the widespread influence of gene and environment interactions on methylation levels.

  20. Gene-environment interactions linking air pollution and inflammation in Parkinson's disease.

    Science.gov (United States)

    Lee, Pei-Chen; Raaschou-Nielsen, Ole; Lill, Christina M; Bertram, Lars; Sinsheimer, Janet S; Hansen, Johnni; Ritz, Beate

    2016-11-01

    Both air pollution exposure and systemic inflammation have been linked to Parkinson's disease (PD). In the PASIDA study, 408 incident cases of PD diagnosed in 2006-2009 and their 495 population controls were interviewed and provided DNA samples. Markers of long term traffic related air pollution measures were derived from geographic information systems (GIS)-based modeling. Furthermore, we genotyped functional polymorphisms in genes encoding proinflammatory cytokines, namely rs1800629 in TNFα (tumor necrosis factor alpha) and rs16944 in IL1B (interleukin-1β). In logistic regression models, long-term exposure to NO 2 increased PD risk overall (odds ratio (OR)=1.06 per 2.94μg/m 3 increase, 95% CI=1.00-1.13). The OR for PD in individuals with high NO 2 exposure (≧75th percentile) and the AA genotype of IL1B rs16944 was 3.10 (95% CI=1.14-8.38) compared with individuals with lower NO 2 exposure (environment interactions with TNF rs1800629. Our finds may provide suggestive evidence that a combination of traffic-related air pollution and genetic variation in the proinflammatory cytokine gene IL1B contribute to risk of developing PD. However, as statistical evidence was only modest in this large sample we cannot rule out that these results represent a chance finding, and additional replication efforts are warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. GMDR: Versatile Software for Detecting Gene-Gene and Gene-Environ- ment Interactions Underlying Complex Traits

    Science.gov (United States)

    Xu, Hai-Ming; Xu, Li-Feng; Hou, Ting-Ting; Luo, Lin-Feng; Chen, Guo-Bo; Sun, Xi-Wei; Lou, Xiang-Yang

    2016-01-01

    Identification of multifactor gene-gene (G×G) and gene-environment (G×E) interactions underlying complex traits poses one of the great challenges to today’s genetic study. Development of the generalized multifactor dimensionality reduction (GMDR) method provides a practicable solution to problems in detection of interactions. To exploit the opportunities brought by the availability of diverse data, it is in high demand to develop the corresponding GMDR software that can handle a breadth of phenotypes, such as continuous, count, dichotomous, polytomous nominal, ordinal, survival and multivariate, and various kinds of study designs, such as unrelated case-control, family-based and pooled unrelated and family samples, and also allows adjustment for covariates. We developed a versatile GMDR package to implement this serial of GMDR analyses for various scenarios (e.g., unified analysis of unrelated and family samples) and large-scale (e.g., genome-wide) data. This package includes other desirable features such as data management and preprocessing. Permutation testing strategies are also built in to evaluate the threshold or empirical p values. In addition, its performance is scalable to the computational resources. The software is available at http://www.soph.uab.edu/ssg/software or http://ibi.zju.edu.cn/software. PMID:28479868

  2. Refining the Candidate Environment: Interpersonal Stress, the Serotonin Transporter Polymorphism, and Gene-Environment Interactions in Major Depression.

    Science.gov (United States)

    Vrshek-Schallhorn, Suzanne; Mineka, Susan; Zinbarg, Richard E; Craske, Michelle G; Griffith, James W; Sutton, Jonathan; Redei, Eva E; Wolitzky-Taylor, Kate; Hammen, Constance; Adam, Emma K

    2014-05-01

    Meta-analytic evidence supports a gene-environment (G×E) interaction between life stress and the serotonin transporter polymorphism (5-HTTLPR) on depression, but few studies have examined factors that influence detection of this effect, despite years of inconsistent results. We propose that the "candidate environment" (akin to a candidate gene) is key. Theory and evidence implicate major stressful life events (SLEs)-particularly major interpersonal SLEs-as well as chronic family stress. Participants ( N = 400) from the Youth Emotion Project (which began with 627 high school juniors oversampled for high neuroticism) completed up to five annual diagnostic and life stress interviews and provided DNA samples. A significant G×E effect for major SLEs and S -carrier genotype was accounted for significantly by major interpersonal SLEs but not significantly by major non-interpersonal SLEs. S -carrier genotype and chronic family stress also significantly interacted. Identifying such candidate environments may facilitate future G×E research in depression and psychopathology more broadly.

  3. Evidence for gene-environment interaction in a genome wide study of isolated, non-syndromic cleft palate

    Science.gov (United States)

    Beaty, Terri H.; Ruczinski, Ingo; Murray, Jeffrey C.; Marazita, Mary L.; Munger, Ronald G.; Hetmanski, Jacqueline B.; Murray, Tanda; Redett, Richard J.; Fallin, M. Daniele; Liang, Kung Yee; Wu, Tao; Patel, Poorav J.; Jin, Sheng C.; Zhang, Tian Xiao; Schwender, Holger; Wu-Chou, Yah Huei; Chen, Philip K; Chong, Samuel S; Cheah, Felicia; Yeow, Vincent; Ye, Xiaoqian; Wang, Hong; Huang, Shangzhi; Jabs, Ethylin W.; Shi, Bing; Wilcox, Allen J.; Lie, Rolv T.; Jee, Sun Ha; Christensen, Kaare; Doheny, Kimberley F.; Pugh, Elizabeth W.; Ling, Hua; Scott, Alan F.

    2011-01-01

    Non-syndromic cleft palate (CP) is a common birth defect with a complex and heterogeneous etiology involving both genetic and environmental risk factors. We conducted a genome wide association study (GWAS) using 550 case-parent trios, ascertained through a CP case collected in an international consortium. Family based association tests of single nucleotide polymorphisms (SNP) and three common maternal exposures (maternal smoking, alcohol consumption and multivitamin supplementation) were used in a combined 2 df test for gene (G) and gene-environment (G×E) interaction simultaneously, plus a separate 1 df test for G×E interaction alone. Conditional logistic regression models were used to estimate effects on risk to exposed and unexposed children. While no SNP achieved genome wide significance when considered alone, markers in several genes attained or approached genome wide significance when G×E interaction was included. Among these, MLLT3 and SMC2 on chromosome 9 showed multiple SNPs resulting in increased risk if the mother consumed alcohol during the peri-conceptual period (3 months prior to conception through the first trimester). TBK1 on chr. 12 and ZNF236 on chr. 18 showed multiple SNPs associated with higher risk of CP in the presence of maternal smoking. Additional evidence of reduced risk due to G×E interaction in the presence of multivitamin supplementation was observed for SNPs in BAALC on chr. 8. These results emphasize the need to consider G×E interaction when searching for genes influencing risk to complex and heterogeneous disorders, such as non-syndromic CP. PMID:21618603

  4. Gene-Gene and Gene-Environment Interactions Involving HLA-DRB1, PTPN22, and Smoking in Two Subsets of Rheumatoid Arthritis

    Science.gov (United States)

    Källberg, Henrik; Padyukov, Leonid; Plenge, Robert M.; Rönnelid, Johan; Gregersen, Peter K.; van der Helm-van Mil, Annette H. M.; Toes, Rene E. M.; Huizinga, Tom W.; Klareskog, Lars; Alfredsson, Lars

    2007-01-01

    Gene-gene and gene-environment interactions are key features in the development of rheumatoid arthritis (RA) and other complex diseases. The aim of this study was to use and compare three different definitions of interaction between the two major genetic risk factors of RA—the HLA-DRB1 shared epitope (SE) alleles and the PTPN22 R620W allele—in three large case-control studies: the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, the North American RA Consortium (NARAC) study, and the Dutch Leiden Early Arthritis Clinic study (in total, 1,977 cases and 2,405 controls). The EIRA study was also used to analyze interactions between smoking and the two genes. “Interaction” was defined either as a departure from additivity, as interaction in a multiplicative model, or in terms of linkage disequilibrium—for example, deviation from independence of penetrance of two unlinked loci. Consistent interaction, defined as departure from additivity, between HLA-DRB1 SE alleles and the A allele of PTPN22 R620W was seen in all three studies regarding anti-CCP–positive RA. Testing for multiplicative interactions demonstrated an interaction between the two genes only when the three studies were pooled. The linkage disequilibrium approach indicated a gene-gene interaction in EIRA and NARAC, as well as in the pooled analysis. No interaction was seen between smoking and PTPN22 R620W. A new pattern of interactions is described between the two major known genetic risk factors and the major environmental risk factor concerning the risk of developing anti-CCP–positive RA. The data extend the basis for a pathogenetic hypothesis for RA involving genetic and environmental factors. The study also raises and illustrates principal questions concerning ways to define interactions in complex diseases. PMID:17436241

  5. Gene-environment interactions in multiple sclerosis: innate and adaptive immune responses to human endogenous retrovirus and herpesvirus antigens and the lectin complement activation pathway

    DEFF Research Database (Denmark)

    Christensen, Tove; Petersen, Thor; Thiel, Steffen

    2006-01-01

    Aspects of gene-environment interactions in multiple sclerosis (MS) were analysed in serum samples from 46 MS families (25 sporadic MS cases and 42 familial MS cases): antibodies to the MS-associated human endogenous retrovirus HERV-H, and levels of three components in the innate pathogen...

  6. Vulnerability or Sensitivity to the Environment? Methodological Issues, Trends, and Recommendations in Gene-Environment Interactions Research in Human Behavior.

    Science.gov (United States)

    Leighton, Caroline; Botto, Alberto; Silva, Jaime R; Jiménez, Juan Pablo; Luyten, Patrick

    2017-01-01

    Research on the potential role of gene-environment interactions (GxE) in explaining vulnerability to psychopathology in humans has witnessed a shift from a diathesis-stress perspective to differential susceptibility approaches. This paper critically reviews methodological issues and trends in this body of research. Databases were screened for studies of GxE in the prediction of personality traits, behavior, and mental health disorders in humans published between January 2002 and January 2015. In total, 315 papers were included. Results showed that 34 candidate genes have been included in GxE studies. Independent of the type of environment studied (early or recent life events, positive or negative environments), about 67-83% of studies have reported significant GxE interactions, which is consistent with a social susceptibility model. The percentage of positive results does not seem to differ depending on the gene studied, although publication bias might be involved. However, the number of positive findings differs depending on the population studied (i.e., young adults vs. older adults). Methodological considerations limit the ability to draw strong conclusions, particularly as almost 90% ( n  = 283/315) of published papers are based on samples from North America and Europe, and about 70% of published studies (219/315) are based on samples that were also used in other reports. At the same time, there are clear indications of methodological improvements over time, as is shown by a significant increase in longitudinal and experimental studies as well as in improved minimum genotyping. Recommendations for future research, such as minimum quality assessment of genes and environmental factors, specifying theoretical models guiding the study, and taking into account of cultural, ethnic, and lifetime perspectives, are formulated.

  7. Multiple Gene-Environment Interactions on the Angiogenesis Gene-Pathway Impact Rectal Cancer Risk and Survival

    Directory of Open Access Journals (Sweden)

    Noha Sharafeldin

    2017-09-01

    Full Text Available Characterization of gene-environment interactions (GEIs in cancer is limited. We aimed at identifying GEIs in rectal cancer focusing on a relevant biologic process involving the angiogenesis pathway and relevant environmental exposures: cigarette smoking, alcohol consumption, and animal protein intake. We analyzed data from 747 rectal cancer cases and 956 controls from the Diet, Activity and Lifestyle as a Risk Factor for Rectal Cancer study. We applied a 3-step analysis approach: first, we searched for interactions among single nucleotide polymorphisms on the pathway genes; second, we searched for interactions among the genes, both steps using Logic regression; third, we examined the GEIs significant at the 5% level using logistic regression for cancer risk and Cox proportional hazards models for survival. Permutation-based test was used for multiple testing adjustment. We identified 8 significant GEIs associated with risk among 6 genes adjusting for multiple testing: TNF (OR = 1.85, 95% CI: 1.10, 3.11, TLR4 (OR = 2.34, 95% CI: 1.38, 3.98, and EGR2 (OR = 2.23, 95% CI: 1.04, 4.78 with smoking; IGF1R (OR = 1.69, 95% CI: 1.04, 2.72, TLR4 (OR = 2.10, 95% CI: 1.22, 3.60 and EGR2 (OR = 2.12, 95% CI: 1.01, 4.46 with alcohol; and PDGFB (OR = 1.75, 95% CI: 1.04, 2.92 and MMP1 (OR = 2.44, 95% CI: 1.24, 4.81 with protein. Five GEIs were associated with survival at the 5% significance level but not after multiple testing adjustment: CXCR1 (HR = 2.06, 95% CI: 1.13, 3.75 with smoking; and KDR (HR = 4.36, 95% CI: 1.62, 11.73, TLR2 (HR = 9.06, 95% CI: 1.14, 72.11, EGR2 (HR = 2.45, 95% CI: 1.42, 4.22, and EGFR (HR = 6.33, 95% CI: 1.95, 20.54 with protein. GEIs between angiogenesis genes and smoking, alcohol, and animal protein impact rectal cancer risk. Our results support the importance of considering the biologic hypothesis to characterize GEIs associated with cancer outcomes.

  8. Research Review: Gene-Environment Interaction Research in Youth Depression--A Systematic Review with Recommendations for Future Research

    Science.gov (United States)

    Dunn, Erin C.; Uddin, Monica; Subramanian, S. V.; Smoller, Jordan W.; Galea, Sandro; Koenen, Karestan C.

    2011-01-01

    Background: Depression is a major public health problem among youth, currently estimated to affect as many as 9% of US children and adolescents. The recognition that both genes (nature) and environments (nurture) are important for understanding the etiology of depression has led to a rapid growth in research exploring gene-environment interactions…

  9. The Cumulative Effect of Gene-Gene and Gene-Environment Interactions on the Risk of Prostate Cancer in Chinese Men

    Directory of Open Access Journals (Sweden)

    Ming Liu

    2016-01-01

    Full Text Available Prostate cancer (PCa is a multifactorial disease involving complex genetic and environmental factors interactions. Gene-gene and gene-environment interactions associated with PCa in Chinese men are less studied. We explored the association between 36 SNPs and PCa in 574 subjects from northern China. Body mass index (BMI, smoking, and alcohol consumption were determined through self-administered questionnaires in 134 PCa patients. Then gene-gene and gene-environment interactions among the PCa-associated SNPs were analyzed using the generalized multifactor dimensionality reduction (GMDR and logistic regression methods. Allelic and genotypic association analyses showed that six variants were associated with PCa and the cumulative effect suggested men who carried any combination of 1, 2, or ≥3 risk genotypes had a gradually increased PCa risk (odds ratios (ORs = 1.79–4.41. GMDR analysis identified the best gene-gene interaction model with scores of 10 for both the cross-validation consistency and sign tests. For gene-environment interactions, rs6983561 CC and rs16901966 GG in individuals with a BMI ≥ 28 had ORs of 7.66 (p = 0.032 and 5.33 (p = 0.046, respectively. rs7679673 CC + CA and rs12653946 TT in individuals that smoked had ORs of 2.77 (p = 0.007 and 3.11 (p = 0.024, respectively. rs7679673 CC in individuals that consumed alcohol had an OR of 4.37 (p = 0.041. These results suggest that polymorphisms, either individually or by interacting with other genes or environmental factors, contribute to an increased risk of PCa.

  10. Genetic susceptibility loci, environmental exposures, and Parkinson's disease: a case-control study of gene-environment interactions.

    Science.gov (United States)

    Chung, Sun Ju; Armasu, Sebastian M; Anderson, Kari J; Biernacka, Joanna M; Lesnick, Timothy G; Rider, David N; Cunningham, Julie M; Ahlskog, J Eric; Frigerio, Roberta; Maraganore, Demetrius M

    2013-06-01

    Prior studies causally linked mutations in SNCA, MAPT, and LRRK2 genes with familial Parkinsonism. Genome-wide association studies have demonstrated association of single nucleotide polymorphisms (SNPs) in those three genes with sporadic Parkinson's disease (PD) susceptibility worldwide. Here we investigated the interactions between SNPs in those three susceptibility genes and environmental exposures (pesticides application, tobacco smoking, coffee drinking, and alcohol drinking) also associated with PD susceptibility. Pairwise interactions between environmental exposures and 18 variants (16 SNPs and two variable number tandem repeats, or "VNTRs") in SNCA, MAPT and LRRK2, were investigated using data from 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Environmental exposures were assessed using a validated telephone interview script. Five pairwise interactions had uncorrected P-values coffee drinking × MAPT H1/H2 haplotype or MAPT rs16940806, and alcohol drinking × MAPT rs2435211. None of these interactions remained significant after Bonferroni correction. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not identify significant interactions after Bonferroni correction. This study documented limited pairwise interactions between established genetic and environmental risk factors for PD; however, the associations were not significant after correction for multiple testing. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Neuregulin 1: a prime candidate for research into gene-environment interactions in schizophrenia? Insights from genetic rodent models

    Directory of Open Access Journals (Sweden)

    Tim eKarl

    2013-08-01

    Full Text Available Schizophrenia is a multi-factorial disease characterized by a high heritability and environmental risk factors. In recent years, an increasing number of researchers worldwide have started investigating the ‘two-hit hypothesis’ of schizophrenia predicting that genetic and environmental risk factors (GxE interactively cause the development of the disorder. This work is starting to produce valuable new animal models and reveal novel insights into the pathophysiology of schizophrenia. This mini review will focus on recent advancements in the field made by challenging mutant and transgenic rodent models for the schizophrenia candidate gene neuregulin 1 (NRG1 with particular environmental factors. It will outline results obtained from mouse and rat models for various Nrg1 isoforms/isoform types (e.g. transmembrane domain Nrg1, Type II Nrg1, which have been exposed to different forms of stress (acute versus chronic, restraint versus social and housing conditions (standard laboratory versus minimally enriched housing. These studies suggest Nrg1 as a prime candidate for GxE interactions in schizophrenia rodent models and that the use of rodent models will enable a better understanding of GxE interactions and the underlying mechanisms.

  12. Effect of gene-environment Interactions on mental development in African American, Dominican, and Caucasian mothers and newborns.

    Science.gov (United States)

    Wang, Shuang; Chanock, Stephen; Tang, Deliang; Li, Zhigang; Edwards, Susan; Jedrychowski, Wieslaw; Perera, Frederica P

    2010-01-01

    The health impact of environmental toxins has gained increasing recognition over the years. Polycyclic aromatic hydrocarbons (PAHs) and environmental tobacco smoke (ETS) are known to affect nervous system development in children, but no studies have investigated how polymorphisms in PAH metabolic genes affect child cognitive development following PAH exposure during pregnancy. In two parallel prospective cohort studies of non-smoking African American and Dominican mothers and children in New York City and of Caucasian mothers and children in Krakow, Poland, we explored the effect of gene-PAH interaction on child mental development index (MDI). Genes known to play important roles in the metabolic activation or detoxification of PAHs were selected. Genetic variations in these genes could influence susceptibility to adverse effects of PAHs in polluted air. We explored the effects of interactions between prenatal PAH exposure and 21 polymorphisms or haplotypes in these genes on MDI at 12, 24, and 36 months among 547 newborns and 806 mothers from three different ethnic groups. Significant interaction effects between haplotypes and PAHs were observed in mothers and their newborns in all three ethnic groups after Bonferroni correction. The strongest and most consistent effect observed was between PAH and haplotype ACCGGC of the CYP1B1 gene.

  13. The oxytocin receptor gene (OXTR) in relation to state levels of loneliness in adolescence: evidence for micro-level gene-environment interactions.

    Science.gov (United States)

    van Roekel, Eeske; Verhagen, Maaike; Scholte, Ron H J; Kleinjan, Marloes; Goossens, Luc; Engels, Rutger C M E

    2013-01-01

    Previous research has shown that the rs53576 variant of the oxytocin receptor gene (OXTR) is associated with trait levels of loneliness, but results are inconsistent. The aim of the present study is to examine micro-level effects of the OXTR rs53576 variant on state levels of loneliness in early adolescents. In addition, gene-environment interactions are examined between this OXTR variant and positive and negative perceptions of company. Data were collected in 278 adolescents (58% girls), by means of the Experience Sampling Method (ESM). Sampling periods consisted of six days with nine assessments per day. A relation was found between the OXTR rs53576 variant and state loneliness, in girls only. Girls carrying an A allele had higher levels of state loneliness than girls carrying the GG genotype. In addition, adolescents with an A allele were more affected by negative perceptions of company than GG carriers, on weekend days only. No significant gene-environment interactions were found with positive company. Adolescents carrying an A allele were more susceptible to negative environments during weekend days than GG carriers. Our findings emphasize the importance of operationalizing the phenotype and the environment accurately.

  14. Gene-environment interactions on the risk of esophageal cancer among Asian populations with the G48A polymorphism in the alcohol dehydrogenase-2 gene: a meta-analysis.

    Science.gov (United States)

    Zhang, Long; Jiang, Yingjiu; Wu, Qingcheng; Li, Qiang; Chen, Dan; Xu, Ling; Zhang, Cheng; Zhang, Min; Ye, Ling

    2014-05-01

    The aim of this study is to investigate the gene-environment interactions between the G48A polymorphism in the alcohol dehydrogenase-2 (ADH2) gene and environmental factors in determining the risk of esophageal cancer (EC). A literature search was conducted in the PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar databases to indentify eligible studies published before November 1, 2013. We performed a meta-analysis of 18 case-control studies with a total of 8,906 EC patients and 13,712 controls. The overall analysis suggested that individuals with the GG genotype were associated with a 2.77-fold increased risk of EC, compared with carriers of the GA and AA genotypes. In a stratified analysis by ethnic group, Japanese, Mainland Chinese, and Taiwan Chinese with the GG genotype had a significantly higher risk of EC, compared with Thai and Iranian populations, indicating ethnic variance in EC susceptibility. An analysis of combined effect indicated that GG genotype of ADH2 G48A was associated with the highest risk of EC in heavy drinkers and smokers. A striking difference was found to exist between males and females, showing gender variance for the association between ADH2 G48A and EC risk. This meta-analysis shows that the GG genotype of ADH2 G48A may be associated with an increased risk of EC in Asian populations. In addition, significant gene-environment interactions were found. Heavy drinkers, smokers, and males with the GG genotype may have a higher EC risk. Thus, our results shed new light on the complex gene-environment interactions that exist between environmental factors and ADH2 G48A polymorphism in EC risk.

  15. Gene-environment interactions associated with CYP1A1 MspI and GST polymorphisms and the risk of upper aerodigestive tract cancers in an Indian population.

    Science.gov (United States)

    Sam, Soya Sisy; Thomas, Vinod; Reddy, K S; Surianarayanan, Gopalakrishnan; Chandrasekaran, Adithan

    2010-06-01

    Genetic risk to tobacco related cancers are associated with polymorphisms in CYP1A1 and GST, which are involved in the metabolic activation and detoxification of carcinogens. The genetic variations in these drug-metabolizing enzymes may alter the susceptibility to UADT cancers triggered by environmental exposures. The hospital-based case-control study evaluated the impact of combined CYP1A1 MspI and GST (M1 & T1) polymorphisms among the individuals exposed to environmental risk factors as modulators in the risk of UADT cancers in Tamilians, a population of south India. The unrelated histopathologically confirmed 408 cases and 220 population-based controls matched by age and gender were genotyped for CYP1A1 MspI, GSTM1 and GSTT1 polymorphisms using PCR based methods. To investigate the potential gene-environment interactions, analyses were carried out stratifying by smoking and tobacco chewing status using SPSS software. The combination of genes and environment interactions by stratified analyses revealed significant interactions among the habitual tobacco smokers (CYP1A1 MspI & GSTM1 null: OR 14.06; 95% CI 3.90-50.68, CYP1A1 MspI & GSTT1 null: OR 33.28; 95% CI 4.24-261.19) and tobacco chewers (CYP1A1 MspI & GSTM1 null: OR 20.51; 95% CI 6.77-62.13, CYP1A1 MspI & GSTT1 null: OR 79.35; 95% CI 10.40-605.55) on the multiplicative scale. Our findings have indicated that the individuals polymorphic for CYP1A1 MspI either with GSTM1 null or with GSTT1 null genotypes revealed an increased risk for UADT cancers than that ascribed to a single susceptible gene among the tobacco users in the population [single gene risk among smokers and chewers, respectively, for CYP1A1 MspI (OR 6.43; 95% CI 3.69-11.21); (OR 10.24; 95% CI 5.95-17.60), GSTM1*0 (OR 3.77; 95% CI 1.94-7.37); (OR 7.97 95% CI 4.10-15.76) and GSTT1*0 (OR 6.95 95% CI 2.88-16.77); (OR 25.83 95% CI 7.78-85.76).

  16. Multivariate dimensionality reduction approaches to identify gene-gene and gene-environment interactions underlying multiple complex traits.

    Science.gov (United States)

    Xu, Hai-Ming; Sun, Xi-Wei; Qi, Ting; Lin, Wan-Yu; Liu, Nianjun; Lou, Xiang-Yang

    2014-01-01

    The elusive but ubiquitous multifactor interactions represent a stumbling block that urgently needs to be removed in searching for determinants involved in human complex diseases. The dimensionality reduction approaches are a promising tool for this task. Many complex diseases exhibit composite syndromes required to be measured in a cluster of clinical traits with varying correlations and/or are inherently longitudinal in nature (changing over time and measured dynamically at multiple time points). A multivariate approach for detecting interactions is thus greatly needed on the purposes of handling a multifaceted phenotype and longitudinal data, as well as improving statistical power for multiple significance testing via a two-stage testing procedure that involves a multivariate analysis for grouped phenotypes followed by univariate analysis for the phenotypes in the significant group(s). In this article, we propose a multivariate extension of generalized multifactor dimensionality reduction (GMDR) based on multivariate generalized linear, multivariate quasi-likelihood and generalized estimating equations models. Simulations and real data analysis for the cohort from the Study of Addiction: Genetics and Environment are performed to investigate the properties and performance of the proposed method, as compared with the univariate method. The results suggest that the proposed multivariate GMDR substantially boosts statistical power.

  17. Multivariate dimensionality reduction approaches to identify gene-gene and gene-environment interactions underlying multiple complex traits.

    Directory of Open Access Journals (Sweden)

    Hai-Ming Xu

    Full Text Available The elusive but ubiquitous multifactor interactions represent a stumbling block that urgently needs to be removed in searching for determinants involved in human complex diseases. The dimensionality reduction approaches are a promising tool for this task. Many complex diseases exhibit composite syndromes required to be measured in a cluster of clinical traits with varying correlations and/or are inherently longitudinal in nature (changing over time and measured dynamically at multiple time points. A multivariate approach for detecting interactions is thus greatly needed on the purposes of handling a multifaceted phenotype and longitudinal data, as well as improving statistical power for multiple significance testing via a two-stage testing procedure that involves a multivariate analysis for grouped phenotypes followed by univariate analysis for the phenotypes in the significant group(s. In this article, we propose a multivariate extension of generalized multifactor dimensionality reduction (GMDR based on multivariate generalized linear, multivariate quasi-likelihood and generalized estimating equations models. Simulations and real data analysis for the cohort from the Study of Addiction: Genetics and Environment are performed to investigate the properties and performance of the proposed method, as compared with the univariate method. The results suggest that the proposed multivariate GMDR substantially boosts statistical power.

  18. Gene-environment interaction: Does fluoride influence the reproductive hormones in male farmers modified by ERα gene polymorphisms?

    Science.gov (United States)

    Ma, Qiang; Huang, Hui; Sun, Long; Zhou, Tong; Zhu, Jingyuan; Cheng, Xuemin; Duan, Lijv; Li, Zhiyuan; Cui, Liuxin; Ba, Yue

    2017-12-01

    The occurrence of endemic fluorosis is derived from high fluoride levels in drinking water and industrial fumes or dust. Reproductive disruption is also a major harm caused by fluoride exposure besides dental and skeletal lesions. However, few studies focus on the mechanism of fluoride exposure on male reproductive function, especially the possible interaction of fluoride exposure and gene polymorphism on male reproductive hormones. Therefore, we conducted a cross-sectional study in rural areas of Henan province in China to explore the interaction between the estrogen receptor alpha (ERα) gene and fluoride exposure on reproductive hormone levels in male farmers living in the endemic fluorosis villages. The results showed that fluoride exposure significantly increased the serum level of estradiol in the hypothalamic-pituitary-testicular (HPT) axis in male farmers. Moreover, the observations indicated that fluoride exposure and genetic markers had an interaction on serum concentration of follicle-stimulating hormone and estradiol, and the interaction among different loci of the ERα gene could impact the serum testosterone level. Findings in the present work suggest that chronic fluoride exposure in drinking water could modulate the levels of reproductive hormones in males living in endemic fluorosis areas, and the interaction between fluoride exposure and ERα polymorphisms might affect the serum levels of hormones in the HPT axis in male farmers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations

    NARCIS (Netherlands)

    van Os, Jim; Rutten, Bart P.; Myin-Germeys, Inez; Delespaul, Philippe; Viechtbauer, Wolfgang; van Zelst, Catherine; Bruggeman, Richard; Reininghaus, Ulrich; Morgan, Craig; Murray, Robin M.; Di Forti, Marta; McGuire, Philip; Valmaggia, Lucia R.; Kempton, Matthew J.; Gayer-Anderson, Charlotte; Hubbard, Kathryn; Beards, Stephanie; Stilo, Simona A.; Onyejiaka, Adanna; Bourque, Francois; Modinos, Gemma; Tognin, Stefania; Calem, Maria; O'Donovan, Michael C.; Owen, Michael J.; Holmans, Peter; Williams, Nigel; Craddock, Nicholas; Richards, Alexander; Humphreys, Isla; Meyer-Lindenberg, Andreas; Leweke, F. Markus; Tost, Heike; Akdeniz, Ceren; Rohleder, Cathrin; Bumb, J. Malte; Schwarz, Emanuel; Alptekin, Köksal; Üçok, Alp; Saka, Meram Can; Atbaşoğlu, E. Cem; Gülöksüz, Sinan; Gumus-Akay, Guvem; Cihan, Burçin; Karadağ, Hasan; Soygür, Haldan; Cankurtaran, Eylem Şahin; Ulusoy, Semra; Akdede, Berna; Binbay, Tolga; Ayer, Ahmet; Noyan, Handan; Karadayı, Gülşah; Akturan, Elçin; Ulaş, Halis; Arango, Celso; Parellada, Mara; Bernardo, Miguel; Sanjuán, Julio; Bobes, Julio; Arrojo, Manuel; Santos, Jose Luis; Cuadrado, Pedro; Rodríguez Solano, José Juan; Carracedo, Angel; García Bernardo, Enrique; Roldán, Laura; López, Gonzalo; Cabrera, Bibiana; Cruz, Sabrina; Díaz Mesa, Eva Ma; Pouso, María; Jiménez, Estela; Sánchez, Teresa; Rapado, Marta; González, Emiliano; Martínez, Covadonga; Sánchez, Emilio; Olmeda, Ma Soledad; de Haan, Lieuwe; Velthorst, Eva; van der Gaag, Mark; Selten, Jean-Paul; van Dam, Daniella; van der Ven, Elsje; van der Meer, Floor; Messchaert, Elles; Kraan, Tamar; Burger, Nadine; Leboyer, Marion; Szoke, Andrei; Schürhoff, Franck; Llorca, Pierre-Michel; Jamain, Stéphane; Tortelli, Andrea; Frijda, Flora; Vilain, Jeanne; Galliot, Anne-Marie; Baudin, Grégoire; Ferchiou, Aziz; Richard, Jean-Romain; Bulzacka, Ewa; Charpeaud, Thomas; Tronche, Anne-Marie; de Hert, Marc; van Winkel, Ruud; Decoster, Jeroen; Derom, Catherine; Thiery, Evert; Stefanis, Nikos C.; Sachs, Gabriele; Aschauer, Harald; Lasser, Iris; Winklbaur, Bernadette; Schlögelhofer, Monika; Riecher-Rössler, Anita; Borgwardt, Stefan; Walter, Anna; Harrisberger, Fabienne; Smieskova, Renata; Rapp, Charlotte; Ittig, Sarah; Soguel-Dit-Piquard, Fabienne; Studerus, Erich; Klosterkötter, Joachim; Ruhrmann, Stephan; Paruch, Julia; Julkowski, Dominika; Hilboll, Desiree; Sham, Pak C.; Cherny, Stacey S.; Chen, Eric Y. H.; Campbell, Desmond D.; Li, Miaoxin; Romeo-Casabona, Carlos María; Emaldi Cirión, Aitziber; Urruela Mora, Asier; Jones, Peter; Kirkbride, James; Cannon, Mary; Rujescu, Dan; Tarricone, Ilaria; Berardi, Domenico; Bonora, Elena; Seri, Marco; Marcacci, Thomas; Chiri, Luigi; Chierzi, Federico; Storbini, Viviana; Braca, Mauro; Minenna, Maria Gabriella; Donegani, Ivonne; Fioritti, Angelo; La Barbera, Daniele; La Cascia, Caterina Erika; Mulè, Alice; Sideli, Lucia; Sartorio, Rachele; Ferraro, Laura; Tripoli, Giada; Seminerio, Fabio; Marinaro, Anna Maria; McGorry, Patrick; Nelson, Barnaby; Amminger, G. Paul; Pantelis, Christos; Menezes, Paulo R.; del-Ben, Cristina M.; Gallo Tenan, Silvia H.; Shuhama, Rosana; Ruggeri, Mirella; Tosato, Sarah; Lasalvia, Antonio; Bonetto, Chiara; Ira, Elisa; Nordentoft, Merete; Krebs, Marie-Odile; Barrantes-Vidal, Neus; Cristóbal, Paula; Kwapil, Thomas R.; Brietzke, Elisa; Bressan, Rodrigo A.; Gadelha, Ary; Maric, Nadja P.; Andric, Sanja; Mihaljevic, Marina; Mirjanic, Tijana

    2014-01-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular

  20. Identifying Gene-Environment Interactions in Schizophrenia : Contemporary Challenges for Integrated, Large-scale Investigations

    NARCIS (Netherlands)

    van Os, Jim; Rutten, Bart P.; Myin-Germeys, Inez; Delespaul, Philippe; Viechtbauer, Wolfgang; van Zelst, Catherine; Bruggeman, Richard; Reininghaus, Ulrich; Morgan, Craig; Murray, Robin M.; Di Forti, Marta; McGuire, Philip; Valmaggia, Lucia R.; Kempton, Matthew J.; Gayer-Anderson, Charlotte; Hubbard, Kathryn; Beards, Stephanie; Stilo, Simona A.; Onyejiaka, Adanna; Bourque, Francois; Modinos, Gemma; Tognin, Stefania; Calem, Maria; O'Donovan, Michael C.; Owen, Michael J.; Holmans, Peter; Williams, Nigel; Craddock, Nicholas; Richards, Alexander; Humphreys, Isla; Meyer-Lindenberg, Andreas; Leweke, F. Markus; Tost, Heike; Akdeniz, Ceren; Rohleder, Cathrin; Bumb, J. Malte; Schwarz, Emanuel; Alptekin, Koksal; Ucok, Alp; Saka, Meram Can; Atbasoglu, E. Cem; Guloksuz, Sinan; Gumus-Akay, Guvem; Cihan, Burin; Karadag, Hasan; Soygur, Haldan; Cankurtaran, Eylem Sahin; Ulusoy, Semra; Akdede, Berna; Binbay, Tolga

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular

  1. Identifying Gene-Environment interactions in schizophrenia: Contemporary challenges for integrated, large-scale investigations

    NARCIS (Netherlands)

    European Network authors, o.a.; van der Gaag, M.

    2014-01-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular

  2. Measuring the genetic influence on human life span: gene-environment interaction and sex-specific genetic effects

    DEFF Research Database (Denmark)

    Tan, Qihua; De Benedictis, G; Yashin, Annatoli

    2001-01-01

    New approaches are needed to explore the different ways in which genes affect the human life span. One needs to assess the genetic effects themselves, as well as gene–environment interactions and sex dependency. In this paper, we present a new model that combines both genotypic and demographicinf...

  3. Physical activity, diet and gene-environment interactions in relation to body mass index and waist circumference

    DEFF Research Database (Denmark)

    Karnehed, Nina; Tynelius, Per; Heitmann, Berit L

    2006-01-01

    dizygotic young adult male twin pairs. Increased knowledge about interactions between genes and environment may provide insight into why some individuals are more prone to obesity than others. DESIGN: Information about PA, BMI, dietary habits, WC and potential confounders was collected by questionnaire...

  4. Toll-like receptors and microbial exposure : gene-gene and gene-environment interaction in the development of atopy

    NARCIS (Netherlands)

    Reijmerink, N. E.; Kerkhof, M.; Bottema, R. W. B.; Gerritsen, J.; Stelma, F. F.; Thijs, C.; van Schayck, C. P.; Smit, H. A.; Brunekreef, B.; Postma, D. S.; Koppelman, G. H.

    2011-01-01

    Environmental and genetic factors contribute to atopy development. High microbial exposure may confer a protective effect on atopy. Toll-like receptors (TLRs) bind microbial products and are important in activating the immune system. To assess whether interactions between microbial exposures and

  5. Toll-like receptors and microbial exposure: gene-gene and gene-environment interaction in the development of atopy

    NARCIS (Netherlands)

    Reijmerink, N.E.; Kerkhof, M. van de; Bottema, R.W.; Gerritsen, J.; Stelma, F.F.; Thijs, C.; Schayck, C.P. van; Smit, H.A.; Brunekreef, B.; Postma, D.S.; Koppelman, G.H.

    2011-01-01

    Environmental and genetic factors contribute to atopy development. High microbial exposure may confer a protective effect on atopy. Toll-like receptors (TLRs) bind microbial products and are important in activating the immune system. To assess whether interactions between microbial exposures and

  6. Gene-environment interaction in Parkinson’s disease: coffee, ADORA2A, and CYP1A2

    Science.gov (United States)

    Chuang, Yu-Hsuan; Lill, Christina M.; Lee, Pei-Chen; Hansen, Johnni; Lassen, Christina Funch; Bertram, Lars; Greene, Naomi; Sinsheimer, Janet S.; Ritz, Beate

    2017-01-01

    Background and purpose Drinking caffeinated coffee has been reported to protect against Parkinson’s disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2) metabolizes caffeine, thus gene polymorphisms in ADORA2A and CYP1A2 may influence the effect coffee consumption has on PD risk. Methods In a population-based case control study (PASIDA) in Denmark (1,556 PD patients and 1,606 birth year- and sex- matched controls), we assessed interactions between lifetime coffee consumption and three polymorphisms in ADORA2A and CYP1A2 for all subjects and incident and prevalent PD cases separately using logistic regression models. We also conducted a meta-analysis combining our results with those from previous studies. Results We estimated statistically significant interactions for ADORA2A rs5760423 and heavy vs. light coffee consumption in incident (OR interaction=0.66 [0.46–0.94], p=0.02) but not prevalent PD. We did not observe interactions for CYP1A2 rs762551 and rs2472304 in incident or prevalent PD. In meta-analyses, PD associations with daily coffee consumption were strongest among carriers of variant alleles in both ADORA2A and CYP1A2. Conclusion We corroborated results from a previous report that described interactions between ADORA2A and CYP1A2 polymorphisms and coffee consumption. Our results also suggest that survivor bias may affect results of studies that enrol prevalent PD cases. PMID:28135712

  7. Dopamine transporter DAT and receptor DRD2 variants affect risk of lethal cocaine abuse: a gene-gene-environment interaction.

    Science.gov (United States)

    Sullivan, D; Pinsonneault, J K; Papp, A C; Zhu, H; Lemeshow, S; Mash, D C; Sadee, W

    2013-01-22

    Epistatic gene-gene interactions could contribute to the heritability of complex multigenic disorders, but few examples have been reported. Here, we focus on the role of aberrant dopaminergic signaling, involving the dopamine transporter DAT, a cocaine target, and the dopamine D2 receptor, which physically interacts with DAT. Splicing polymorphism rs2283265 of DRD2, encoding D2 receptors, were shown to confer risk of cocaine overdose/death (odds ratio ∼3) in subjects and controls from the Miami Dade County Brain Bank.(1) Risk of cocaine-related death attributable to the minor allele of rs2283265 was significantly enhanced to OR=7.5 (P=0.0008) in homozygous carriers of the main 6-repeat allele of DAT rs3836790, a regulatory VNTR in intron8 lacking significant effect itself. In contrast, carriers of the minor 5-repeat DAT allele showed no significant risk (OR=1.1, P=0.84). DAT rs3836790 and DRD2 rs2283265 also interacted by modulating DAT protein activity in the ventral putamen of cocaine abusers. In high-linkage disequilibrium with the VNTR, DAT rs6347 in exon9 yielded similar results. Assessing the impact of DAT alone, a rare DAT haplotype formed by the minor alleles of rs3836790 and rs27072, a regulatory DAT variant in the 3'-UTR, occurred in nearly one-third of the cocaine abusers but was absent in African American controls, apparently conferring strong risk. These results demonstrate gene-gene-drug interaction affecting risk of fatal cocaine intoxication.

  8. Vulnerability or Sensitivity to the Environment? Methodological Issues, Trends, and Recommendations in Gene?Environment Interactions Research in Human Behavior

    OpenAIRE

    Leighton, Caroline; Botto, Alberto; Silva, Jaime R.; Jim?nez, Juan Pablo; Luyten, Patrick

    2017-01-01

    Research on the potential role of gene–environment interactions (GxE) in explaining vulnerability to psychopathology in humans has witnessed a shift from a diathesis-stress perspective to differential susceptibility approaches. This paper critically reviews methodological issues and trends in this body of research. Databases were screened for studies of GxE in the prediction of personality traits, behavior, and mental health disorders in humans published between January 2002 and January 2015....

  9. Detection of gene-environment interactions in the presence of linkage disequilibrium and noise by using genetic risk scores with internal weights from elastic net regression.

    Science.gov (United States)

    Hüls, Anke; Ickstadt, Katja; Schikowski, Tamara; Krämer, Ursula

    2017-06-12

    For the analysis of gene-environment (GxE) interactions commonly single nucleotide polymorphisms (SNPs) are used to characterize genetic susceptibility, an approach that mostly lacks power and has poor reproducibility. One promising approach to overcome this problem might be the use of weighted genetic risk scores (GRS), which are defined as weighted sums of risk alleles of gene variants. The gold-standard is to use external weights from published meta-analyses. In this study, we used internal weights from the marginal genetic effects of the SNPs estimated by a multivariate elastic net regression and thereby provided a method that can be used if there are no external weights available. We conducted a simulation study for the detection of GxE interactions and compared power and type I error of single SNPs analyses with Bonferroni correction and corresponding analysis with unweighted and our weighted GRS approach in scenarios with six risk SNPs and an increasing number of highly correlated (up to 210) and noise SNPs (up to 840). Applying weighted GRS increased the power enormously in comparison to the common single SNPs approach (e.g. 94.2% vs. 35.4%, respectively, to detect a weak interaction with an OR ≈ 1.04 for six uncorrelated risk SNPs and n = 700 with a well-controlled type I error). Furthermore, weighted GRS outperformed the unweighted GRS, in particular in the presence of SNPs without any effect on the phenotype (e.g. 90.1% vs. 43.9%, respectively, when 20 noise SNPs were added to the six risk SNPs). This outperforming of the weighted GRS was confirmed in a real data application on lung inflammation in the SALIA cohort (n = 402). However, in scenarios with a high number of noise SNPs (>200 vs. 6 risk SNPs), larger sample sizes are needed to avoid an increased type I error, whereas a high number of correlated SNPs can be handled even in small samples (e.g. n = 400). In conclusion, weighted GRS with weights from the marginal genetic effects of the

  10. Influence of 5-HTT variation, childhood trauma and self-efficacy on anxiety traits: a gene-environment-coping interaction study.

    Science.gov (United States)

    Schiele, Miriam A; Ziegler, Christiane; Holitschke, Karoline; Schartner, Christoph; Schmidt, Brigitte; Weber, Heike; Reif, Andreas; Romanos, Marcel; Pauli, Paul; Zwanzger, Peter; Deckert, Jürgen; Domschke, Katharina

    2016-08-01

    Environmental vulnerability factors such as adverse childhood experiences in interaction with genetic risk variants, e.g., the serotonin transporter gene linked polymorphic region (5-HTTLPR), are assumed to play a role in the development of anxiety and affective disorders. However, positive influences such as general self-efficacy (GSE) may exert a compensatory effect on genetic disposition, environmental adversity, and anxiety traits. We, thus, assessed childhood trauma (Childhood Trauma Questionnaire, CTQ) and GSE in 678 adults genotyped for 5-HTTLPR/rs25531 and their interaction on agoraphobic cognitions (Agoraphobic Cognitions Questionnaire, ACQ), social anxiety (Liebowitz Social Anxiety Scale, LSAS), and trait anxiety (State-Trait Anxiety Inventory, STAI-T). The relationship between anxiety traits and childhood trauma was moderated by self-efficacy in 5-HTTLPR/rs25531 LALA genotype carriers: LALA probands maltreated as children showed high anxiety scores when self-efficacy was low, but low anxiety scores in the presence of high self-efficacy despite childhood maltreatment. Our results extend previous findings regarding anxiety-related traits showing an interactive relationship between 5-HTT genotype and adverse childhood experiences by suggesting coping-related measures to function as an additional dimension buffering the effects of a gene-environment risk constellation. Given that anxiety disorders manifest already early in childhood, this insight could contribute to the improvement of psychotherapeutic interventions by including measures strengthening self-efficacy and inform early targeted preventive interventions in at-risk populations, particularly within the crucial time window of childhood and adolescence.

  11. Gene-environment Interactions in Human Health: Case Studies and Strategies for developing new paradigms and research methodologies

    Directory of Open Access Journals (Sweden)

    Fatimah L.C. Jackson

    2014-08-01

    Full Text Available The synergistic effects of genes and the environment on health are explored in three case studies: adult lactase persistence, autism spectrum disorders, and the metabolic syndrome, providing examples of the interactive complexities underlying these phenotypes. Since the phenotypes are the initial targets of evolutionary processes, understanding the specific environmental contexts of the genetic, epigenetic, and proteomic changes associated with these phenotypes is essential in predicting their health implications. Robust databases must be developed on the local scale to deconstruct both the population substructure and the unique components of the environment that stimulate geographically-specific changes in gene expression patterns. To produce these databases and make valid predictions, new, locally-focused and information-dense models are needed that incorporate data on evolutionary ecology, environmental complexity, local geographic patterns of gene expression, and population substructure.

  12. Assessing clinical and functional outcomes in a gene-environment interaction study in first episode of psychosis (PEPs).

    Science.gov (United States)

    Bernardo, Miquel; Bioque, Miquel; Parellada, Mara; Saiz Ruiz, Jerónimo; Cuesta, Manuel J; Llerena, Adrián; Sanjuán, Julio; Castro-Fornieles, Josefina; Arango, Celso; Cabrera, Bibiana

    2013-01-01

    The PEPs study is a multicenter, naturalistic, prospective, longitudinal study designed to evaluate clinical, neuropsychological, neuroimaging, biochemical, environmental and pharmacogenetic variables in a sample of nearly 350 first episode of psychosis patients and 250 healthy controls. The PEPs project was conducted in Spain from January 2009 to December 2011. This article describes the rationale for the measurement approach adopted, providing an overview of the selected clinical and functional measures. The main objectives are: a) the thorough clinical and neurocognitive characterization of a sample of first episodes of psychosis, and b) the study of the interactions between the genetic and environmental variables selected to predict clinical and brain structural outcomes, and to determine the relationship of genetic polymorphisms involved in the pharmacokinetics and pharmacodynamics, and the responses and adverse effects of treatment. Copyright © 2012 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

  13. Urine cadmium levels and albuminuria in a general population from Spain: A gene-environment interaction analysis.

    Science.gov (United States)

    Grau-Perez, Maria; Pichler, Gernot; Galan-Chilet, Inma; Briongos-Figuero, Laisa S; Rentero-Garrido, Pilar; Lopez-Izquierdo, Raul; Navas-Acien, Ana; Weaver, Virginia; García-Barrera, Tamara; Gomez-Ariza, Jose L; Martín-Escudero, Juan C; Chaves, F Javier; Redon, Josep; Tellez-Plaza, Maria

    2017-09-01

    The interaction of cadmium with genes involved in oxidative stress, cadmium metabolism and transport pathways on albuminuria can provide biological insight on the relationship between cadmium and albuminuria at low exposure levels. We tested the hypothesis that specific genotypes in candidate genes may confer increased susceptibility to cadmium exposure. Cadmium exposure was estimated by inductively coupled plasma mass spectrometry (ICPMS) in urine from 1397 men and women aged 18-85years participating in the Hortega Study, a representative sample of a general population from Spain. Urine albumin was measured by automated nephelometric immunochemistry. Abnormal albuminuria was defined as urine albumin greater than or equal to 30mg/g. The weighted prevalence of abnormal albuminuria was 6.3%. The median level of urine cadmium was 0.39 (IQR, 0.23-0.65) μg/g creatinine. Multivariable-adjusted geometric mean ratios of albuminuria comparing the two highest to the lowest tertile of urine cadmium were 1.62 (95% CI, 1.43-1.84) and 2.94 (95% CI, 2.58-3.35), respectively. The corresponding odds ratios of abnormal albuminuria were 1.58 (0.83, 3.02) and 4.54 (2.58, 8.00). The association between urine cadmium and albuminuria was observed across all participant subgroups evaluated including participants without hypertension, diabetes or chronic kidney disease. We observed Bonferroni-corrected statistically significant interactions between urine cadmium levels and polymorphisms in gene SLC30A7 and RAC1. Increasing urine cadmium concentrations were cross-sectionally associated with increased albuminuria in a representative sample of a general population from Spain. Genetic variation in oxidative stress and cadmium metabolism and transport genes may confer differential susceptibility to potential cadmium effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Gene-environment interactions in male reproductive health: special reference to the aryl hydrocarbon receptor signaling pathway

    Directory of Open Access Journals (Sweden)

    Leon J S Brokken

    2014-02-01

    Full Text Available Over the last few decades, there have been numerous reports of adverse effects on the reproductive health of wildlife and laboratory animals caused by exposure to endocrine disrupting chemicals (EDCs. The increasing trends in human male reproductive disorders and the mounting evidence for causative environmental factors have therefore sparked growing interest in the health threat posed to humans by EDCs, which are substances in our food, environment and consumer items that interfere with hormone action, biosynthesis or metabolism, resulting in disrupted tissue homeostasis or reproductive function. The mechanisms of EDCs involve a wide array of actions and pathways. Examples include the estrogenic, androgenic, thyroid and retinoid pathways, in which the EDCs may act directly as agonists or antagonists, or indirectly via other nuclear receptors. Dioxins and dioxin-like EDCs exert their biological and toxicological actions through activation of the aryl hydrocarbon-receptor, which besides inducing transcription of detoxifying enzymes also regulates transcriptional activity of other nuclear receptors. There is increasing evidence that genetic predispositions may modify the susceptibility to adverse effects of toxic chemicals. In this review, potential consequences of hereditary predisposition and EDCs are discussed, with a special focus on the currently available publications on interactions between dioxin and androgen signaling.

  15. Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders.

    Directory of Open Access Journals (Sweden)

    Kaichi Yoshizaki

    Full Text Available Neurodevelopmental disorders such as autism spectrum disorder (ASD and attention deficit and hyperactivity disorder (ADHD have increased over the last few decades. These neurodevelopmental disorders are characterized by a complex etiology, which involves multiple genes and gene-environmental interactions. Various genes that control specific properties of neural development exert pivotal roles in the occurrence and severity of phenotypes associated with neurodevelopmental disorders. Moreover, paternal aging has been reported as one of the factors that contribute to the risk of ASD and ADHD. Here we report, for the first time, that paternal aging has profound effects on the onset of behavioral abnormalities in mice carrying a mutation of Pax6, a gene with neurodevelopmental regulatory functions. We adopted an in vitro fertilization approach to restrict the influence of additional factors. Comprehensive behavioral analyses were performed in Sey/+ mice (i.e., Pax6 mutant heterozygotes born from in vitro fertilization of sperm taken from young or aged Sey/+ fathers. No body weight changes were found in the four groups, i.e., Sey/+ and wild type (WT mice born to young or aged father. However, we found important differences in maternal separation-induced ultrasonic vocalizations of Sey/+ mice born from young father and in the level of hyperactivity of Sey/+ mice born from aged fathers in the open-field test, respectively, compared to WT littermates. Phenotypes of anxiety were observed in both genotypes born from aged fathers compared with those born from young fathers. No significant difference was found in social behavior and sensorimotor gating among the four groups. These results indicate that mice with a single genetic risk factor can develop different phenotypes depending on the paternal age. Our study advocates for serious considerations on the role of paternal aging in breeding strategies for animal studies.

  16. Genetic susceptibility to breast cancer in French-Canadians: role of carcinogen-metabolizing enzymes and gene-environment interactions.

    Science.gov (United States)

    Krajinovic, M; Ghadirian, P; Richer, C; Sinnett, H; Gandini, S; Perret, C; Lacroix, A; Labuda, D; Sinnett, D

    2001-04-15

    Breast cancer is the most frequent malignancy among women. Since genetic factors such as BRCA1 and BRCA2 as well as reproductive history constitute only 30% of the cause, environmental exposure may play a significant role in the development of breast cancer. Likewise, the relevant enzymes involved in the biotransformation of xenobiotics (from tobacco smoke, diet or other environmental sources) might play a role in breast carcinogenesis. Since individuals with modified ability to metabolize these carcinogens could have a different risk for breast cancer, we investigated the role of cytochromes P-450 (CYP1A1, CYP2D6), glutathione-S-transferases (GSTM1, GSTT1, GSTP1) and N-acetyltransferases (NAT1, NAT2) gene variants in breast carcinogenesis. A case-control study was conducted on 149 women with breast carcinoma and 207 healthy controls, both of French-Canadian origin. The CYP1A1*4 allele was found to be a significant risk determinant of breast carcinoma (OR = 3.3, 95% CI 1.1-9.7), particularly among post-menopausal women (OR = 4.0, 95% CI 1.2-13.8). The frequency of NAT2 rapid acetylators was increased among smokers (OR = 2.6, 95% CI 0.8-8.2), while the NAT1*10 allele conferred a 4-fold increase in risk among women who consumed well-done meat (OR = 4.4, 95% CI 1.0-18.9). These data suggest that CYP1A1*4, NAT1 and NAT2 variants are involved in the susceptibility to breast carcinoma by modifying the impact of exogenous and/or endogenous exposures. Copyright 2001 Wiley-Liss, Inc.

  17. The role of genes involved in neuroplasticity and neurogenesis in the observation of a gene-environment interaction (GxE) in schizophrenia.

    Science.gov (United States)

    Le Strat, Yann; Ramoz, Nicolas; Gorwood, Philip

    2009-05-01

    Schizophrenia is a multifactorial disease characterized by a high heritability. Several candidate genes have been suggested, with the strongest evidences for genes encoding dystrobrevin binding protein 1 (DTNBP1), neuregulin 1 (NRG1), neuregulin 1 receptor (ERBB4) and disrupted in schizophrenia 1 (DISC1), as well as several neurotrophic factors. These genes are involved in neuronal plasticity and play also a role in adult neurogenesis. Therefore, the genetic basis of schizophrenia could involve different factors more or less specifically required for neuroplasticity, including the synapse maturation, potentiation and plasticity as well as neurogenesis. Following the model of Knudson in tumors, we propose a two-hit hypothesis of schizophrenia. In this model of gene-environment interaction, a variant in a gene related to neurogenesis is transmitted to the descent (first hit), and, secondarily, an environmental factor occurs during the development of the central nervous system (second hit). Both of these vulnerability and trigger factors are probably necessary to generate a deficit in neurogenesis and therefore to cause schizophrenia. The literature supporting this gene x environment hypothesis is reviewed, with emphasis on some molecular pathways, raising the possibility to propose more specific molecular medicine.

  18. Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate.

    Directory of Open Access Journals (Sweden)

    Tao Wu

    Full Text Available Nonsyndromic cleft palate (CP is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester. When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10(-6interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10(-7 in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10(-7 and P = 1.98×10(-7 in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP.

  19. Does accounting for gene-environment (GxE) interaction increase the power to detect the effect of a gene in a multifactorial disease?

    Science.gov (United States)

    Selinger-Leneman, Hana; Genin, Emmanuelle; Norris, Jill M; Khlat, Myriam

    2003-04-01

    Despite tremendous efforts, few genes involved in the susceptibility for complex disorders have been identified. One explanation is that these disorders are a result of an interaction between genes and environment, and under such conditions, it may be difficult to measure the true genetic effect without accounting for the interaction. Umbach and Weinberg ([2000] Am. J. Hum. Genet. 66:251-261) proposed an association test which looks at the joint effects of genotype and environment, using case-parent trios. In this study, we explore under which conditions accounting for GxE interaction enhances one's ability to detect the role of genetic factors in complex diseases. Using asymptotic power calculations, we investigate the power to detect the gene effect over varying exposure frequencies and different scenarios of GxE interaction. We show that for a given sample size, interaction scenario, and allele frequency, the actual gain in power while accounting for the interaction depends on the magnitude of the exposure frequency: the largest gains are seen for relatively low exposure frequencies. Moreover, a loss of power can be observed when the exposure is frequent and/or the exposure effect is strong. If we consider a gene with a disease allele frequency of 0.2, with no effect in the absence of exposure, an exposure with a 10-fold increase risk and a GxE relative risk of 2, then when the exposure frequency is 0.1, accounting for GxE interaction increases the power to detect the gene effect in 200 trios by 10%; alternatively, when the exposure frequency is 0.9, it decreases the power by 15%. Copyright 2003 Wiley-Liss, Inc.

  20. Genes, Environment, and Human Behavior.

    Science.gov (United States)

    Bloom, Mark V.; Cutter, Mary Ann; Davidson, Ronald; Dougherty, Michael J.; Drexler, Edward; Gelernter, Joel; McCullough, Laurence B.; McInerney, Joseph D.; Murray, Jeffrey C.; Vogler, George P.; Zola, John

    This curriculum module explores genes, environment, and human behavior. This book provides materials to teach about the nature and methods of studying human behavior, raise some of the ethical and public policy dilemmas emerging from the Human Genome Project, and provide professional development for teachers. An extensive Teacher Background…

  1. Gene-environment interaction in the onset of eczema in infancy: filaggrin loss-of-function mutations enhanced by neonatal cat exposure.

    Directory of Open Access Journals (Sweden)

    Hans Bisgaard

    2008-06-01

    Full Text Available BACKGROUND: Loss-of-function variants in the gene encoding filaggrin (FLG are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites in relation to the development of eczema. METHODS AND FINDINGS: We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379, FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27-4.00, p = 0.005, with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79-32.60, p < 0.0001; dog exposure was moderately protective (HR 0.49, 95% CI 0.24-1.01, p = 0.05, but not related to FLG genotype. In Manchester (n = 503 an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13-3.36, p = 0.02. In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35-10.81, p = 0.01, with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16-2.20, p = 0.43. Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation. CONCLUSIONS: We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4 and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially

  2. Impact of variation in the BDNF gene on social stress sensitivity and the buffering impact of positive emotions: replication and extension of a gene-environment interaction.

    Science.gov (United States)

    van Winkel, Mark; Peeters, Frenk; van Winkel, Ruud; Kenis, Gunter; Collip, Dina; Geschwind, Nicole; Jacobs, Nele; Derom, Catherine; Thiery, Evert; van Os, Jim; Myin-Germeys, Inez; Wichers, Marieke

    2014-06-01

    A previous study reported that social stress sensitivity is moderated by the brain-derived-neurotrophic-factor(Val66Met) (BDNF rs6265) genotype. Additionally, positive emotions partially neutralize this moderating effect. The current study aimed to: (i) replicate in a new independent sample of subjects with residual depressive symptoms the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity, (ii) replicate the neutralizing impact of positive emotions, (iii) extend these analyses to other variations in the BDNF gene in the new independent sample and the original sample of non-depressed individuals. Previous findings were replicated in an experience sampling method (ESM) study. Negative Affect (NA) responses to social stress were stronger in "Val/Met" carriers of BDNF(Val66Met) compared to "Val/Val" carriers. Positive emotions neutralized the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity in a dose-response fashion. Finally, two of four additional BDNF SNPs (rs11030101, rs2049046) showed similar moderating effects on social stress-sensitivity across both samples. The neutralizing effect of positive emotions on the moderating effects of these two additional SNPs was found in one sample. In conclusion, ESM has important advantages in gene-environment (GxE) research and may attribute to more consistent findings in future GxE research. This study shows how the impact of BDNF genetic variation on depressive symptoms may be explained by its impact on subtle daily life responses to social stress. Further, it shows that the generation of positive affect (PA) can buffer social stress sensitivity and partially undo the genetic susceptibility. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  3. Genetic loci for serum magnesium among African-Americans and gene-environment interaction at MUC1 and TRPM6 in European-Americans: the Atherosclerosis Risk in Communities (ARIC) study.

    Science.gov (United States)

    Tin, Adrienne; Köttgen, Anna; Folsom, Aaron R; Maruthur, Nisa M; Tajuddin, Salman M; Nalls, Mike A; Evans, Michele K; Zonderman, Alan B; Friedrich, Christopher A; Boerwinkle, Eric; Coresh, Josef; Kao, Wen Hong Linda

    2015-05-29

    Low serum magnesium levels have been associated with multiple chronic diseases. The regulation of serum magnesium homeostasis is not well understood. A previous genome-wide association study (GWAS) of European ancestry (EA) populations identified nine loci for serum magnesium. No such study has been conducted in African-Americans, nor has there been an evaluation of the interaction of magnesium-associated SNPs with environmental factors. The goals of this study were to identify genetic loci associated with serum magnesium in an African-American (AA) population using both genome-wide and candidate region interrogation approaches and to evaluate gene-environment interaction for the magnesium-associated variants in both EA and AA populations. We conducted a GWAS of serum magnesium in 2737 AA participants of the Atherosclerosis Risk in Communities (ARIC) Study and interrogated the regions of the nine published candidate loci in these results. Literature search identified the influence of progesterone on MUC1 expression and insulin on TRPM6 expression. The GWAS approach in African-American participants identified a locus near MUC1 as genome-wide significant (rs2974937, beta=-0.013, p=6.1x10(-9)). The candidate region interrogation approach identified two of the nine loci previously discovered in EA populations as containing SNPs that were significantly associated in African-American participants (SHROOM3 and TRPM6). The index variants at these three loci together explained 2.8 % of the variance in serum magnesium concentration in ARIC African-American participants. On the test of gene-environment interaction in ARIC EA participants, the index variant at MUC1 had 2.5 times stronger association in postmenopausal women with progestin use (beta=-0.028, p=7.3x10(-5)) than in those without any hormone use (beta=-0.011, p=7.0x10(-8), p for interaction 0.03). At TRPM6, the index variant had 1.6 times stronger association in those with lower fasting insulin levels (African

  4. The influence of gene-environment interactions on GHR and IGF-1 expression and their association with growth in brook charr, Salvelinus fontinalis (Mitchill

    Directory of Open Access Journals (Sweden)

    Blier Pierre

    2007-12-01

    Full Text Available Abstract Background Quantitative reaction norm theory proposes that genotype-by-environment interaction (GxE results from inter-individual differences of expression in adaptive suites of genes in distinct environments. However, environmental norms for actual gene suites are poorly documented. In this study, we investigated the effects of GxE interactions on levels of gene transcription and growth by documenting the impact of rearing environment (freshwater vs. saltwater, sex and genotypic (low vs. high estimated breeding value EBV effects on the transcription level of insulin-like growth factor (IGF-1 and growth hormone receptor (GHR in brook charr (Salvelinus fontinalis. Results Males grew faster than females (μ♀ = 1.20 ± 0.07 g·d-1, μ♂ = 1.46 ± 0.06 g·d-1 and high-EBV fish faster than low-EBV fish (μLOW = 0.97 ± 0.05 g·d-1, μHIGH = 1.58 ± 0.07 g·d-1; p FW = 1.52 ± 0.07 g·d-1, μSW = 1.15 ± 0.06 g·d-1, yet GHR mRNA transcription level was significantly higher in saltwater than in freshwater (μSW = 0.85 ± 0.05, μFW = 0.61 ± 0.05. The ratio of actual growth to units in assayed mRNA ('individual transcript efficiency', iTE; g·d-1·u-1 also differed among EBV groups (μLOW = 2.0 ± 0.24 g·d-1·u-1; μHIGH = 3.7 ± 0.24 g·d-1·u-1 and environments (μSW = 2.0 ± 0.25 g·d-1·u-1; μFW = 3.7 ± 0.25 g·d-1·u-1 for GHR. Males had a lower iTE for GHR than females (μ♂ = 2.4 ± 0.29 g·d-1·u-1; μ♀ = 3.1 ± 0.23 g·d-1·u-1. There was no difference in IGF-1 transcription level between environments (p > 0.7 or EBV groups (p > 0.15 but the level of IGF-1 was four times higher in males than females (μ♂ = 2.4 ± 0.11, μ♀ = 0.58 ± 0.09; p ♂ = 1.3 ± 0.59 g·d-1·u-1; μ♀ = 3.9 ± 0.47 g·d-1·u-1, salinities (μSW = 2.3 ± 0.52 g·d-1·u-1; μFW = 3.7 ± 0.53 g·d-1·u-1 and EBV-groups (μLOW = 2.4 ± 0.49 g·d-1·u-1; μHIGH = 3.8 ± 0.49 g·d-1·u-1. Interaction between EBV-group and environment was detected for

  5. Gene-environment interaction affects substance P and neurokinin A in the entorhinal cortex and periaqueductal grey in a genetic animal model of depression: implications for the pathophysiology of depression

    DEFF Research Database (Denmark)

    Husum, Henriette; Wörtwein, Gitta; Andersson, Weronika

    2008-01-01

    Evidence implies a role for corticotropin-releasing hormone (CRH) and tachykinins, e.g. substance P (SP) and neurokinin A (NKA) in the pathophysiology of depression. We have previously shown that SP- and NKA-like immunoreactivity (-LI) concentrations were altered in the frontal cortex and striatum...... of the congenitally 'depressed' Flinders Sensitive Line (FSL) compared to the Flinders Resistant Line (FRL) control rats. It is also known that environmental stress may affect brain levels of tachykinins. In view of these results we decided to superimpose maternal deprivation, an early life environmental stressor......, onto the genetically predisposed 'depressed' FSL rats and the FRL control rats and use this paradigm as a model of gene-environment interaction. The adult animals were sacrificed, adrenal glands and brains dissected out and SP-, NKA- and CRH-LI levels were determined in ten discrete brain regions...

  6. Gene-Environment Interplay in Common Complex Diseases: Forging an Integrative Model—Recommendations From an NIH Workshop

    Science.gov (United States)

    Bookman, Ebony B.; McAllister, Kimberly; Gillanders, Elizabeth; Wanke, Kay; Balshaw, David; Rutter, Joni; Reedy, Jill; Shaughnessy, Daniel; Agurs-Collins, Tanya; Paltoo, Dina; Atienza, Audie; Bierut, Laura; Kraft, Peter; Fallin, M. Daniele; Perera, Frederica; Turkheimer, Eric; Boardman, Jason; Marazita, Mary L.; Rappaport, Stephen M.; Boerwinkle, Eric; Suomi, Stephen J.; Caporaso, Neil E.; Hertz-Picciotto, Irva; Jacobson, Kristen C.; Lowe, William L.; Goldman, Lynn R.; Duggal, Priya; Gunnar, Megan R.; Manolio, Teri A.; Green, Eric D.; Olster, Deborah H.; Birnbaum, Linda S.

    2011-01-01

    Although it is recognized that many common complex diseases are a result of multiple genetic and environmental risk factors, studies of gene-environment interaction remain a challenge and have had limited success to date. Given the current state-of-the-science, NIH sought input on ways to accelerate investigations of gene-environment interplay in health and disease by inviting experts from a variety of disciplines to give advice about the future direction of gene-environment interaction studies. Participants of the NIH Gene-Environment Interplay Workshop agreed that there is a need for continued emphasis on studies of the interplay between genetic and environmental factors in disease and that studies need to be designed around a multifaceted approach to reflect differences in diseases, exposure attributes, and pertinent stages of human development. The participants indicated that both targeted and agnostic approaches have strengths and weaknesses for evaluating main effects of genetic and environmental factors and their interactions. The unique perspectives represented at the workshop allowed the exploration of diverse study designs and analytical strategies, and conveyed the need for an interdisciplinary approach including data sharing, and data harmonization to fully explore gene-environment interactions. Further, participants also emphasized the continued need for high-quality measures of environmental exposures and new genomic technologies in ongoing and new studies. PMID:21308768

  7. Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee.

    OpenAIRE

    Taye H Hamza; Honglei Chen; Erin M Hill-Burns; Shannon L Rhodes; Jennifer Montimurro; Denise M Kay; Albert Tenesa; Victoria I Kusel; Patricia Sheehan; Muthukrishnan Eaaswarkhanth; Dora Yearout; Ali Samii; John W Roberts; Pinky Agarwal; Yvette Bordelon

    2011-01-01

    Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal compo...

  8. Gene-gene-environment interactions between drugs, transporters, receptors, and metabolizing enzymes: Statins, SLCO1B1, and CYP3A4 as an example.

    Science.gov (United States)

    Sadee, Wolfgang

    2013-09-01

    Pharmacogenetic biomarker tests include mostly specific single gene-drug pairs, capable of accounting for a portion of interindividual variability in drug response and toxicity. However, multiple genes are likely to contribute, either acting independently or epistatically, with the CYP2C9-VKORC1-warfarin test panel, an example of a clinically used gene-gene-dug interaction. I discuss here further instances of gene-gene-drug interactions, including a proposed dynamic effect on statin therapy by genetic variants in both a transporter (SLCO1B1) and a metabolizing enzyme (CYP3A4) in liver cells, the main target site where statins block cholesterol synthesis. These examples set a conceptual framework for developing diagnostic panels involving multiple gene-drug combinations. Copyright © 2013 Wiley Periodicals, Inc.

  9. [Application of multifactor dimensionality reduction on the interactions between gene-gene, gene-environment and the risk sporadic colorectal cancer in Chinese population].

    Science.gov (United States)

    Jin, Ming-Juan; Liu, Bing; Zhang, Shuang-Shuang; Zhang, Yong-Jing; Xu, Mei; Ma, Xin-Yuan; Yao, Kai-Yan; Chen, Kun

    2008-06-01

    To identify the association between risk of sporadic colorectal cancer and the common single nucleotide polymorphisms (SNPs) in DNA repairs genes, gene to gene interactions among them and their gene to environment interactions with common environmental factors. In this population-based case-control study, 206 primary colorectal cancer cases and 845 cancer-free healthy controls were enrolled. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, with the status of subjects case or controls unknown. Multifactor dimensionality reduction (MDR) and logistic analysis were both used for association analysis. As compared to the younger age group (> or = 42, or = 61 years) increased significantly (OR = 2.04, 95% CI: 1.49-2.80). Similar result was observed in the family cancer history (OR = 1.51, 95% CI: 1.05-2.17). However, no significant association between any single DNA repair gene SNP and colorectal cancer risk was discovered. Results from MDR analysis only showed a significant interaction among the four following factors: age, alcohol drinking, XRCC1 Arg194Trp and OGG1 Ser326Cys (the cross-validation consistency = 10/10, the average testing accuracy = 0.616, P = 0.011). Using a logistic regression model, the "high-risk" individuals had a significantly elevated risk of colorectal cancer compared to those "low- risk" individuals classified by the above MDR model (OR = 2.72, 95% CI: 1.66-4.47). The impact of polymorphisms in DNA repair genes on the risk of sporadic colorectal cancer exhibited a low-penetrance characteristics while the intricate interactions existing among them and with environmental factors.

  10. Current research trends in early life stress and depression: review of human studies on sensitive periods, gene-environment interactions, and epigenetics.

    Science.gov (United States)

    Heim, Christine; Binder, Elisabeth B

    2012-01-01

    Early life stress, such as childhood abuse, neglect and loss, is a well established major risk factor for developing depressive disorders later in life. We here summarize and discuss current developments in human research regarding the link between early life stress and depression. Specifically, we review the evidence for the existence of sensitive periods for the adverse effects of early life stress in humans. We further review the current state of knowledge regarding gene×environment (G×E) interactions in the effects of early life stress. While multiple genes operate in multiple environments to induce risk for depression after early life stress, these same genes also seem to enhance the beneficial effects of a positive early environment. Also, we discuss the epigenetic mechanisms that might underlie these G×E interactions. Finally, we discuss the potential importance of identifying sensitive time periods of opportunity, as well as G×E interactions and epigenetic mechanisms, for early interventions that might prevent or reverse the detrimental outcomes of early life stress and its transmission across generations. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. SLC6A1 gene involvement in susceptibility to attention-deficit/hyperactivity disorder: A case-control study and gene-environment interaction.

    Science.gov (United States)

    Yuan, Fang-Fen; Gu, Xue; Huang, Xin; Zhong, Yan; Wu, Jing

    2017-07-03

    Attention-deficit/hyperactivity disorder (ADHD) is an early onset childhood neurodevelopmental disorder with an estimated heritability of approximately 76%. We conducted a case-control study to explore the role of the SLC6A1 gene in ADHD. The genotypes of eight variants were determined using Sequenom MassARRAY technology. The participants in the study were 302 children with ADHD and 411 controls. ADHD symptoms were assessed using the Conners Parent Symptom Questionnaire. In our study, rs2944366 was consistently shown to be associated with the ADHD risk in the dominant model (odds ratio [OR]=0.554, 95% confidence interval [CI]=0.404-0.760), and nominally associated with Hyperactive index score (P=0.027). In addition, rs1170695 has been found to be associated with the ADHD risk in the addictive model (OR=1.457, 95%CI=1.173-1.809), while rs9990174 was associated with the Hyperactive index score (P=0.010). Intriguingly, gene-environmental interactions analysis consistently revealed the potential interactions of rs1170695 with blood lead (P mul =0.044) to modify the ADHD risk. Expression quantitative trait loci analysis suggested that these positive single nucleotide polymorphisms (SNPs) may mediate SLC6A1 gene expression. Therefore, our results suggest that selected SLC6A1 gene variants may have a significant effect on the ADHD risk. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Chronic exposure of mutant DISC1 mice to lead produces sex-dependent abnormalities consistent with schizophrenia and related mental disorders: a gene-environment interaction study.

    Science.gov (United States)

    Abazyan, Bagrat; Dziedzic, Jenifer; Hua, Kegang; Abazyan, Sofya; Yang, Chunxia; Mori, Susumu; Pletnikov, Mikhail V; Guilarte, Tomas R

    2014-05-01

    The glutamatergic hypothesis of schizophrenia suggests that hypoactivity of the N-methyl-D-aspartate receptor (NMDAR) is an important factor in the pathophysiology of schizophrenia and related mental disorders. The environmental neurotoxicant, lead (Pb(2+)), is a potent and selective antagonist of the NMDAR. Recent human studies have suggested an association between prenatal Pb(2+) exposure and the increased likelihood of schizophrenia later in life, possibly via interacting with genetic risk factors. In order to test this hypothesis, we examined the neurobehavioral consequences of interaction between Pb(2+) exposure and mutant disrupted in schizophrenia 1 (mDISC1), a risk factor for major psychiatric disorders. Mutant DISC1 and control mice born by the same dams were raised and maintained on a regular diet or a diet containing moderate levels of Pb(2+). Chronic, lifelong exposure of mDISC1 mice to Pb(2+) was not associated with gross developmental abnormalities but produced sex-dependent hyperactivity, exaggerated responses to the NMDAR antagonist, MK-801, mildly impaired prepulse inhibition of the acoustic startle, and enlarged lateral ventricles. Together, these findings support the hypothesis that environmental toxins could contribute to the pathogenesis of mental disease in susceptible individuals.

  13. A proposal for a new multiaxial model of psychiatric diagnosis. A continuum-based patient model derived from evolutionary developmental gene-environment interaction.

    Science.gov (United States)

    Leigh, Hoyle

    2009-01-01

    To review recent genetic and neuroscientific research on psychiatric syndromes based on the current diagnostic scheme, and develop a better-fitting multiaxial patient-oriented diagnostic model. DSM I, published in 1952, considered psychiatric illnesses as reactions or extremes of adaptations of the patient's personality to stressful environmental demands. Personality itself was determined by constitution and psychodynamic development. In 1980, this continuum model gave way to an atheoretical categorical diagnostic scheme (DSM III), based on research diagnostic criteria for obtaining 'pure cultures' of patients for biological research. Subsequent research using the 'pure cultures' suggests that psychiatric syndromes represent a phenotypic continuum determined by genes, childhood traumas, and recent stress, mitigated by childhood nurturance, education, and current social support. Specific gene x childhood abuse x recent stress interactions have been discovered, which may serve as a model of how interacting vulnerability genes may or may not result in a psychiatric syndrome, depending on the individual's developmental history and current stress. A continuum model is proposed, with genes interacting with early experiences of stress or nurturance resulting in brain states that may evince minor but persistent symptoms (neurosis) or maladaptive patterns of behavior (personality disorder). The addition of recent or current stress may precipitate a major psychiatric syndrome. While a severe genetic predisposition, such as a mutation, may be sufficient to cause a major syndrome, major psychiatric syndromes are best conceptualized as dysregulation of evolutionarily adaptive brain functions, such as anxiety and vigilance. A new multiaxial model of psychiatric diagnosis is proposed based on this model: axis I for phenomenological diagnoses that include major psychiatric syndromes (e.g. depressive syndrome, psychosis), neuroses, personality disorders, and isolated symptoms; axis

  14. Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee.

    Science.gov (United States)

    Hamza, Taye H; Chen, Honglei; Hill-Burns, Erin M; Rhodes, Shannon L; Montimurro, Jennifer; Kay, Denise M; Tenesa, Albert; Kusel, Victoria I; Sheehan, Patricia; Eaaswarkhanth, Muthukrishnan; Yearout, Dora; Samii, Ali; Roberts, John W; Agarwal, Pinky; Bordelon, Yvette; Park, Yikyung; Wang, Liyong; Gao, Jianjun; Vance, Jeffery M; Kendler, Kenneth S; Bacanu, Silviu-Alin; Scott, William K; Ritz, Beate; Nutt, John; Factor, Stewart A; Zabetian, Cyrus P; Payami, Haydeh

    2011-08-01

    Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P(2df) = 10(-6), GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10(-7)) but not in light coffee-drinkers. The a priori Replication hypothesis that "Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers" was confirmed: OR(Replication) = 0.59, P(Replication) = 10(-3); OR(Pooled) = 0.51, P(Pooled) = 7×10(-8). Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10(-3)), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10(-13)). Imputation revealed a block of SNPs that achieved P(2df)coffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify

  15. UCP2 and UCP3 variants and gene-environment interaction associated with prediabetes and T2DM in a rural population: a case control study in China.

    Science.gov (United States)

    Su, Meifang; Chen, Xiaoying; Chen, Yue; Wang, Congyun; Li, Songtao; Ying, Xuhua; Xiao, Tian; Wang, Na; Jiang, Qingwu; Fu, Chaowei

    2018-03-12

    There are disparities for the association between uncoupling proteins (UCP) and type 2 diabetes (T2DM). The study was to examine the associations of genetic variants of UCP2 and UCP3 with prediabetes and T2DM in a rural Chinese population. A population-based case-control study of 397 adults with T2DM, 394 with prediabetes and 409 with normal glucose tolerance (NGT) was carried out in 2014 in a rural community in eastern China. Three groups were identified through a community survey and the prediabetes and NGT groups were frequently matched by age and gender with the T2DM group and they were not relatives of T2DM subjects. With r 2  ≥ 0.8 and minor allele frequency (MAF) ≥0.05 for tag single nucleotide polymorphisms (SNPs) with potential function, three (rs660339, rs45560234 and rs643064) and six (rs7930460, rs15763, rs647126, rs1800849, rs3781907 and rs1685356) SNPs were selected respectively for UCP2 and UCP3 and genotyped in real time using the MassARRAY system (Sequenom; USA). The haplotypes, gene-environmental interaction and association between genetic variants of UCP2 and UCP3 and prediabetes or T2DM were explored. There were no significant differences in age and sex among three study groups. After the adjustment for possible covariates, the A allele of rs1800849 in UCP3 was significantly associated with prediabetes (aOR AA vs GG  = 1.68, 95% CI: 1.02-2.78), and the association was also significant under the recessive model (aOR AA vs GA + GG  = 1.64, 95% CI: 1.02-2.66). Also, rs15763 was found to be marginally significantly associated with T2DM under dominant model (OR GA + AA vs GG  = 0.73, 95% CI: 0.52-1.03, P = 0.072). No haplotype was significantly associated with prediabetes or T2DM. Multiplicative interactions for rs660339-overweight on T2DM were observed. In addition, the AA genotype of rs660339 was associated with an increased risk of T2DM in overweight subjects (OR = 1.48, 95%CI: 0.87-2.52) but with a decreased

  16. Peer deviance, parental divorce, and genetic risk in the prediction of drug abuse in a nationwide Swedish sample: evidence of environment-environment and gene-environment interaction.

    Science.gov (United States)

    Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

    2014-04-01

    Peer deviance (PD) strongly predicts externalizing psychopathologic conditions but has not been previously assessable in population cohorts. We sought to develop such an index of PD and to clarify its effects on risk of drug abuse (DA). To examine how strongly PD increases the risk of DA and whether this community-level liability indicator interacts with key DA risk factors at the individual and family levels. Studies of future DA registration in 1,401,698 Swedish probands born from January 1, 1970, through December 31, 1985, and their adolescent peers in approximately 9200 small community areas. Peer deviance was defined as the proportion of individuals born within 5 years of the proband living in the same small community when the proband was 15 years old who eventually were registered for DA. Drug abuse recorded in medical, legal, or pharmacy registry records. Peer deviance was associated with future DA in the proband, with rates of DA in older and male peers more strongly predictive than in younger or female peers. The predictive power of PD was only slightly attenuated by adding measures of community deprivation, collective efficacy, or family socioeconomic status. Probands whose parents were divorced were more sensitive to the pathogenic effects of high PD environments. A robust positive interaction was also seen between genetic risk of DA (indexed by rates of DA in first-, second-, and third-degree relatives) and PD exposure. With sufficient data, PD can be measured in populations and strongly predicts DA. In a nationwide sample, risk factors at the level of the individual (genetic vulnerability), family (parental loss), and community (PD) contribute substantially to risk of DA. Individuals at elevated DA risk because of parental divorce or high genetic liability are more sensitive to the pathogenic effects of PD. Although the effect of our PD measure on DA liability cannot be explained by standard measures of community or family risk, we cannot, with

  17. Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene GRIN2A as a Parkinson's Disease Modifier Gene via Interaction with Coffee

    Science.gov (United States)

    Hamza, Taye H.; Chen, Honglei; Hill-Burns, Erin M.; Rhodes, Shannon L.; Montimurro, Jennifer; Kay, Denise M.; Tenesa, Albert; Kusel, Victoria I.; Sheehan, Patricia; Eaaswarkhanth, Muthukrishnan; Yearout, Dora; Samii, Ali; Roberts, John W.; Agarwal, Pinky; Bordelon, Yvette; Park, Yikyung; Wang, Liyong; Gao, Jianjun; Vance, Jeffery M.; Kendler, Kenneth S.; Bacanu, Silviu-Alin; Scott, William K.; Ritz, Beate; Nutt, John; Factor, Stewart A.; Zabetian, Cyrus P.; Payami, Haydeh

    2011-01-01

    Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P2df = 10−6, GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10−7) but not in light coffee-drinkers. The a priori Replication hypothesis that “Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers” was confirmed: ORReplication = 0.59, PReplication = 10−3; ORPooled = 0.51, PPooled = 7×10−8. Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10−3), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10−13). Imputation revealed a block of SNPs that achieved P2dfcoffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify genes that

  18. Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee.

    Directory of Open Access Journals (Sweden)

    Taye H Hamza

    2011-08-01

    Full Text Available Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD. We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC, and we performed a genome-wide association and interaction study (GWAIS, testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P(2df = 10(-6, GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10(-7 but not in light coffee-drinkers. The a priori Replication hypothesis that "Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers" was confirmed: OR(Replication = 0.59, P(Replication = 10(-3; OR(Pooled = 0.51, P(Pooled = 7×10(-8. Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10(-3, whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10(-13. Imputation revealed a block of SNPs that achieved P(2df<5×10(-8 in GWAIS, and OR = 0.41, P = 3×10(-8 in heavy coffee-drinkers. This study is proof of

  19. Witnessing Substance Use and Same-Day Antisocial Behavior among At-Risk Adolescents: Gene-Environment Interaction in a 30-Day Ecological Momentary Assessment Study

    Science.gov (United States)

    Russell, Michael A.; Wang, Lin; Odgers, Candice L.

    2017-01-01

    Many young adolescents are embedded in neighborhoods, schools, and homes where alcohol and drugs are frequently used. However, little is known about (a) how witnessing others’ substance use affects adolescents in their daily lives and (b) which adolescents will be most affected. The current study used ecological momentary assessment with 151 young adolescents (ages 11–15) to examine the daily association between witnessing substance use and antisocial behavior across 38 consecutive days. Results from multilevel logistic regression models indicated that adolescents were more likely to engage in antisocial behavior on days when they witnessed others using substances—an association that held both when substance use was witnessed inside the home as well as outside the home (e.g., at school or in their neighborhoods). A significant gene-by-environment interaction suggested that the same-day association between witnessing substance use and antisocial behavior was significantly stronger among adolescents with, versus without, with the DRD4-7R allele. The implications of our findings for theory and research related to adolescent antisocial behavior are discussed. PMID:26648004

  20. Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment: A Scientific Statement From the American Heart Association.

    Science.gov (United States)

    Ferguson, Jane F; Allayee, Hooman; Gerszten, Robert E; Ideraabdullah, Folami; Kris-Etherton, Penny M; Ordovás, José M; Rimm, Eric B; Wang, Thomas J; Bennett, Brian J

    2016-06-01

    Cardiometabolic diseases are the leading cause of death worldwide and are strongly linked to both genetic and nutritional factors. The field of nutrigenomics encompasses multiple approaches aimed at understanding the effects of diet on health or disease development, including nutrigenetic studies investigating the relationship between genetic variants and diet in modulating cardiometabolic risk, as well as the effects of dietary components on multiple "omic" measures, including transcriptomics, metabolomics, proteomics, lipidomics, epigenetic modifications, and the microbiome. Here, we describe the current state of the field of nutrigenomics with respect to cardiometabolic disease research and outline a direction for the integration of multiple omics techniques in future nutrigenomic studies aimed at understanding mechanisms and developing new therapeutic options for cardiometabolic disease treatment and prevention. © 2016 American Heart Association, Inc.

  1. Gene-environment effects on hippocampal neurodevelopment

    DEFF Research Database (Denmark)

    Rosenthal, Eva Helga

    factors. Hence, a deeper understanding is needed of how cortical neurodevelopmental deficiencies can arise from such gene-environment interactions. The convergence of genetic and environmental risk factors is a recent field of research. It is now clear that disease, infection and stress factors may...... disrupt the normal function of neurodevelopmental genes. Here, the transcriptional repressor Zbtb20, which we and others have shown is a master regulator of hippocampal neurodevelopment, deserves special interest. We study the possibility that environmental factors such as steroid hormones, cytokines......Mental disorders like schizophrenia and autism put a heavy load on today’s societies, creating a steady call for revealing underlying disease mechanisms and the development of effective treatments. The etiology of major psychiatric illnesses is complex involving gene by environment susceptibility...

  2. [Impact of gene-environment interaction between the C (-344) T polymorphism of CYP11B2 and drinking index on the risk of hypertension under multifactor dimensionality reduction model in Chinese Mongolian population].

    Science.gov (United States)

    Pan, Xing-qiang; Liu, Yong-yue; Zhang, Xian-yu; Zhang, Yong-hong; Xu, Qun; Qiu, Chang-chun; Tong, Wei-jun

    2009-09-01

    To explore the interaction between C (-344) T polymorphism of CYP11B2 and drinking index (DI) as well as their impact on the risk of hypertension in Chinese Mongolian population. A total of 1575 Mongolian people aged 20 and older including 562 hypertensive and 1013 normal-tensive from agricultural and pastoral areas in Tongliao city of Inner Mongolia, were included in this study. A cross-sectional survey was conducted to collect data by personal interview with local residents, using a standard questionnaire. Fasting blood samples were drawn and height, weight and blood pressure were measured. The variant genotypes of CYP11B2, ACE and eNOS were identified by PCR assays. Gene-environment interactions were analyzed, using multifactor dimensionality reduction (MDR) model. Based on the result of the best MDR model, a multiple logistic regression model was constructed as the final cause-effect interpretative model. The interaction between CYP11B2 variant genotype and drinking index appeared the best MDR model with statistical significance (chi(2) = 66.35, P or = 168), the genotype (TT) combining the drinking index (> or = 40), the genotype (TT) combining the drinking index (> or = 1) and the genotype (TC) combining the drinking index (> or = 90), were all risk factors of hypertension when comparing with genotype (CC) combining the drinking index (0), and the ORs (95%CI) appeared to be 2.07 (1.15 - 3.70), 2.35 (1.22 - 4.56), 2.05 (1.07 - 3.94) and 5.56 (2.54 - 12.18) respectively. Essential hypertension might positively be affected by the interaction of the C (-344) T polymorphism of CYP11B2 and the drinking index in Chinese Mongolian population.

  3. Gene environment interactions in bipolar disorder.

    Science.gov (United States)

    Pregelj, Peter

    2011-09-01

    It has been estimated that the heritable component of bipolar disorder ranges between 80 and 90%. However, even genome-wide association studies explain only a fraction of phenotypic variability not resolving the problem of "lost heritability". Although direct evidence for epigenetic dysfunction in bipolar disorder is still limited, methodological technologies in epigenomic profiling have advanced, offering even single cell analysing and resolving the problem of cell heterogeneity in epigenetics research. Gene overlapping with other mental disorders represents another problem in identifying potential susceptibility genes in bipolar disorder. Better understanding of the interplay between multiple environmental and genetic factors involved in the patogenesis of bipolar disorder could provide relevant information for treatment of patients with this complex disorder. Future studies on the role of these factors in psychopathological conditions, subphenotypes and endophenotypes may greatly benefit by using more precise clinical data and a combined approach with multiple research tools incorporated into a single study.

  4. Gene-environment interaction in atopic diseases

    DEFF Research Database (Denmark)

    Kahr, Niklas; Naeser, Vibeke; Stensballe, Lone Graff

    2015-01-01

    INTRODUCTION: The development of atopic diseases early in life suggests an important role of perinatal risk factors. OBJECTIVES: To study whether early-life exposures modify the genetic influence on atopic diseases in a twin population. METHODS: Questionnaire data on atopic diseases from 850....... Significant predictors of atopic diseases were identified with logistic regression and subsequently tested for genetic effect modification using variance components analysis. RESULTS: After multivariable adjustment, prematurity (gestational age below 32 weeks) [odds ratio (OR) = 1.93, confidence interval (CI...... stratified by exposure status showed no significant change in the heritability of asthma according to the identified risk factors. CONCLUSION: In this population-based study of children, there was no evidence of genetic effect modification of atopic diseases by several identified early-life risk factors...

  5. Gene-Environment Interplay between Number of Friends and Prosocial Leadership Behavior in Children

    Science.gov (United States)

    Rivizzigno, Alessandra S.; Brendgen, Mara; Feng, Bei; Vitaro, Frank; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

    2014-01-01

    Enriched environments may moderate the effect of genetic factors on prosocial leadership (gene-environment interaction, G × E). However, positive environmental experiences may also themselves be influenced by a genetic disposition for prosocial leadership (gene-environment correlation, rGE). Relating these processes to friendships, the present…

  6. [Schizophrenia: genes, environment and neurodevelopment].

    Science.gov (United States)

    Do, K Q

    2013-09-18

    Psychoses are complex diseases resulting from the interaction between genetic vulnerability factors and various environmental risk factors during the brain development and leading to the emergence of the clinical phenotype at the end of adolescence. Among the mechanisms involved, a redox imbalance plays an important role, inducing oxidative stress damaging to developing neurons. As a consequence, the excitatory/inhibitory balance in cortex and the pathways connecting brain areas are both impaired. Childhood and adolescence appear as critical periods of vulnerability for deleterious environmental insults. Antioxidants, applied during the environmental impacts, should allow preventing these impairments as well as their clinical consequences.

  7. Interactive investigations into planetary interiors

    Science.gov (United States)

    Rose, I.

    2015-12-01

    Many processes in Earth science are difficult to observe or visualize due to the large timescales and lengthscales over which they operate. The dynamics of planetary mantles are particularly challenging as we cannot even look at the rocks involved. As a result, much teaching material on mantle dynamics relies on static images and cartoons, many of which are decades old. Recent improvements in computing power and technology (largely driven by game and web development) have allowed for advances in real-time physics simulations and visualizations, but these have been slow to affect Earth science education.Here I demonstrate a teaching tool for mantle convection and seismology which solves the equations for conservation of mass, momentum, and energy in real time, allowing users make changes to the simulation and immediately see the effects. The user can ask and answer questions about what happens when they add heat in one place, or take it away from another place, or increase the temperature at the base of the mantle. They can also pause the simulation, and while it is paused, create and visualize seismic waves traveling through the mantle. These allow for investigations into and discussions about plate tectonics, earthquakes, hot spot volcanism, and planetary cooling.The simulation is rendered to the screen using OpenGL, and is cross-platform. It can be run as a native application for maximum performance, but it can also be embedded in a web browser for easy deployment and portability.

  8. Interacting With Robots to Investigate the Bases of Social Interaction.

    Science.gov (United States)

    Sciutti, Alessandra; Sandini, Giulio

    2017-12-01

    Humans show a great natural ability at interacting with each other. Such efficiency in joint actions depends on a synergy between planned collaboration and emergent coordination, a subconscious mechanism based on a tight link between action execution and perception. This link supports phenomena as mutual adaptation, synchronization, and anticipation, which cut drastically the delays in the interaction and the need of complex verbal instructions and result in the establishment of joint intentions, the backbone of social interaction. From a neurophysiological perspective, this is possible, because the same neural system supporting action execution is responsible of the understanding and the anticipation of the observed action of others. Defining which human motion features allow for such emergent coordination with another agent would be crucial to establish more natural and efficient interaction paradigms with artificial devices, ranging from assistive and rehabilitative technology to companion robots. However, investigating the behavioral and neural mechanisms supporting natural interaction poses substantial problems. In particular, the unconscious processes at the basis of emergent coordination (e.g., unintentional movements or gazing) are very difficult-if not impossible-to restrain or control in a quantitative way for a human agent. Moreover, during an interaction, participants influence each other continuously in a complex way, resulting in behaviors that go beyond experimental control. In this paper, we propose robotics technology as a potential solution to this methodological problem. Robots indeed can establish an interaction with a human partner, contingently reacting to his actions without losing the controllability of the experiment or the naturalness of the interactive scenario. A robot could represent an "interactive probe" to assess the sensory and motor mechanisms underlying human-human interaction. We discuss this proposal with examples from our

  9. A variable-number-of-tandem-repeats polymorphism in the dopamine D4 receptor gene affects social adaptation of alcohol use: investigation of a gene-environment interaction

    NARCIS (Netherlands)

    Larsen, H.; van der Zwaluw, C.S.; Overbeek, G.; Granic, I.; Franke, B.; Engels, R.C.M.E.

    2010-01-01

    Research suggests that people adapt their own drinking behavior to that of other people. According to a genetic-differences approach, some individuals may be more inclined than others to adapt their alcohol consumption level to that of other people. Using a 3 (drinking condition) × 2 (genotype)

  10. A variable-number-of-tandem-repeats polymorphism in the dopamine D4 receptor gene affects social adaptation of alcohol use: investigation of a gene-environment interaction.

    NARCIS (Netherlands)

    Larsen, H.; Zwaluw, C.S. van der; Overbeek, G.; Granic, I.; Franke, B.; Engels, R.C.M.E.

    2010-01-01

    Research suggests that people adapt their own drinking behavior to that of other people. According to a genetic-differences approach, some individuals may be more inclined than others to adapt their alcohol consumption level to that of other people. Using a 3 (drinking condition) x 2 (genotype)

  11. A Variable-Number-of-Tandem-Repeats Polymorphism in the Dopamine D4 Receptor Gene Affects Social Adaptation of Alcohol Use. Investigation of a Gene-Environment Interaction

    NARCIS (Netherlands)

    Larsen, H.; Zwaluw, C.S. van der; Overbeek, G.J.; Granic, I.; Franke, B.; Engels, R.C.M.E.

    2010-01-01

    Research suggests that people adapt their own drinking behavior to that of other people. According to a genetic-differences approach, some individuals may be more inclined than others to adapt their alcohol consumption level to that of other people. Using a 3 (drinking condition) × 2 (genotype)

  12. Experimental investigation on particle-wall interactions

    International Nuclear Information System (INIS)

    Zeisel, H.; Dorfner, V.

    1988-01-01

    There is still a lack in the knowledge about many physical processes in two-phase flows and therefore their mathematical description for the modelling of two-phase flows by computer simulations still needs some improvement. One required information is the physical procedure of the momentum transfer between the phases themselves, such as particle-particle or particle-fluid interactions, and between the phases and the flow boundaries, such as particle-wall or fluid-wall interactions. The interaction between the two phases can be either a 'long-range' interference or a direct contact between both. For the particle-fluid two-phase flow system the interaction can be devided in particle-fluid, particle-particle and particle-boundary interactions. In this investigation the attention is drawn to the special case of a particle-wall interaction and its 'long-range' interference effect between the wall and a small particle which approaches the wall in normal direction. (orig./GL)

  13. Gene-environment interplay in the context of romantic relationships.

    Science.gov (United States)

    Whisman, Mark A; South, Susan C

    2017-02-01

    A growing body of research supports an important role for genetic factors on intimate, romantic relationships. In this article, we review research that has examined the interplay between genetic and environmental influences on romantic relationships and the associations between relationship outcomes and important individual differences related to relationships. We first elaborate on how behavioral genetic and molecular genetic methods can be used to understand the etiology of relationship outcomes. We then review empirical studies that have examined gene-environment correlations and gene-by-environment interactions in predicting romantic relationship outcomes (e.g., relationship formation, relationship quality and functioning, relationship dissolution) and their association with the physical health, mental health, and well-being of relationship partners. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Gene-Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood

    DEFF Research Database (Denmark)

    Reynolds, Chandra A; Gatz, Margaret; Christensen, Kaare

    2016-01-01

    Despite emerging interest in gene-environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G×E for body m...

  15. Commentary: Gene-Environment Interplay in the Context of Genetics, Epigenetics, and Gene Expression.

    Science.gov (United States)

    Kramer, Douglas A.

    2005-01-01

    Objective: To comment on the article in this issue of the Journal by Professor Michael Rutter, "Environmentally Mediated Risks for Psychopathology: Research Strategies and Findings," in the context of current research findings on gene-environment interaction, epigenetics, and gene expression. Method: Animal and human studies are reviewed that…

  16. When chocolate seeking becomes compulsion: gene-environment interplay.

    Directory of Open Access Journals (Sweden)

    Enrico Patrono

    Full Text Available Eating disorders appear to be caused by a complex interaction between environmental and genetic factors, and compulsive eating in response to adverse circumstances characterizes many eating disorders.We compared compulsion-like eating in the form of conditioned suppression of palatable food-seeking in adverse situations in stressed C57BL/6J and DBA/2J mice, two well-characterized inbred strains, to determine the influence of gene-environment interplay on this behavioral phenotype. Moreover, we tested the hypothesis that low accumbal D2 receptor (R availability is a genetic risk factor of food compulsion-like behavior and that environmental conditions that induce compulsive eating alter D2R expression in the striatum. To this end, we measured D1R and D2R expression in the striatum and D1R, D2R and α1R levels in the medial prefrontal cortex, respectively, by western blot.Exposure to environmental conditions induces compulsion-like eating behavior, depending on genetic background. This behavioral pattern is linked to decreased availability of accumbal D2R. Moreover, exposure to certain environmental conditions upregulates D2R and downregulates α1R in the striatum and medial prefrontal cortex, respectively, of compulsive animals. These findings confirm the function of gene-environment interplay in the manifestation of compulsive eating and support the hypothesis that low accumbal D2R availability is a "constitutive" genetic risk factor for compulsion-like eating behavior. Finally, D2R upregulation and α1R downregulation in the striatum and medial prefrontal cortex, respectively, are potential neuroadaptive responses that parallel the shift from motivated to compulsive eating.

  17. When Chocolate Seeking Becomes Compulsion: Gene-Environment Interplay

    Science.gov (United States)

    Patella, Loris; Andolina, Diego; Valzania, Alessandro; Latagliata, Emanuele Claudio; Felsani, Armando; Pompili, Assunta; Gasbarri, Antonella; Puglisi-Allegra, Stefano; Ventura, Rossella

    2015-01-01

    Background Eating disorders appear to be caused by a complex interaction between environmental and genetic factors, and compulsive eating in response to adverse circumstances characterizes many eating disorders. Materials and Methods We compared compulsion-like eating in the form of conditioned suppression of palatable food-seeking in adverse situations in stressed C57BL/6J and DBA/2J mice, two well-characterized inbred strains, to determine the influence of gene-environment interplay on this behavioral phenotype. Moreover, we tested the hypothesis that low accumbal D2 receptor (R) availability is a genetic risk factor of food compulsion-like behavior and that environmental conditions that induce compulsive eating alter D2R expression in the striatum. To this end, we measured D1R and D2R expression in the striatum and D1R, D2R and α1R levels in the medial prefrontal cortex, respectively, by western blot. Results Exposure to environmental conditions induces compulsion-like eating behavior, depending on genetic background. This behavioral pattern is linked to decreased availability of accumbal D2R. Moreover, exposure to certain environmental conditions upregulates D2R and downregulates α1R in the striatum and medial prefrontal cortex, respectively, of compulsive animals. These findings confirm the function of gene-environment interplay in the manifestation of compulsive eating and support the hypothesis that low accumbal D2R availability is a “constitutive” genetic risk factor for compulsion-like eating behavior. Finally, D2R upregulation and α1R downregulation in the striatum and medial prefrontal cortex, respectively, are potential neuroadaptive responses that parallel the shift from motivated to compulsive eating. PMID:25781028

  18. Microglia Polarization, Gene-Environment Interactions and Wnt/β-Catenin Signaling: Emerging Roles of Glia-Neuron and Glia-Stem/Neuroprogenitor Crosstalk for Dopaminergic Neurorestoration in Aged Parkinsonian Brain

    Directory of Open Access Journals (Sweden)

    Francesca L'Episcopo

    2018-02-01

    recent findings unveiling major microglial inflammatory and oxidative stress pathways converging in the regulation of Wnt/β-catenin signaling, and reciprocally, the ability of Wnt signaling pathways to modulate microglial activation in PD. Unraveling the key factors and conditons promoting the switch of the proinflammatory M1 microglia status into a neuroprotective and regenerative M2 phenotype will have important consequences for neuroimmune interactions and neuronal outcome under inflammatory and/or neurodegenerative conditions.

  19. Joint testing of genotypic and gene-environment interaction identified novel association for BMP4 with non-syndromic CL/P in an Asian population using data from an International Cleft Consortium.

    Science.gov (United States)

    Chen, Qianqian; Wang, Hong; Schwender, Holger; Zhang, Tianxiao; Hetmanski, Jacqueline B; Chou, Yah-Huei Wu; Ye, Xiaoqian; Yeow, Vincent; Chong, Samuel S; Zhang, Bo; Jabs, Ethylin Wang; Parker, Margaret M; Scott, Alan F; Beaty, Terri H

    2014-01-01

    Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered. We performed the analysis considering G and interactions with multiple maternal environmental exposures using additive conditional logistic regression models in 895 Asian and 681 European complete NSCL/P trios. Single nucleotide polymorphisms (SNPs) that passed the quality control criteria among 122 genotyped and 25 imputed single nucleotide variants in and around the gene were used in analysis. Selected maternal environmental exposures during 3 months prior to and through the first trimester of pregnancy included any personal tobacco smoking, any environmental tobacco smoke in home, work place or any nearby places, any alcohol consumption and any use of multivitamin supplements. A novel significant association held for rs7156227 among Asian NSCL/P and non-syndromic cleft lip and palate (NSCLP) trios after Bonferroni correction which was not seen when G main effects alone were considered in either allelic or genotypic transmission disequilibrium tests. Odds ratios for carrying one copy of the minor allele without maternal exposure to any of the four environmental exposures were 0.58 (95%CI = 0.44, 0.75) and 0.54 (95%CI = 0.40, 0.73) for Asian NSCL/P and NSCLP trios, respectively. The Bonferroni P values corrected for the total number of 117 tested SNPs were 0.0051 (asymptotic P = 4.39*10(-5)) and 0.0065 (asymptotic P = 5.54*10(-5)), accordingly. In European trios, no significant association was seen for any SNPs after Bonferroni

  20. Investigation of nanodiamonds interactions in canine blood

    Science.gov (United States)

    WÄ sowicz, Michał; Marek, Kulka; Cićkiewicz, Maciej; Cymerman, Magdalena

    2017-02-01

    The whole blood contains red cells, white cells, and platelets suspended in plasma. In the following study we investigated an impact of nanodiamond particles on blood elements over various periods of time.The material used in the study consisted of samples taken from ten healthy canines (Canis lupus f. domestica) of various age, different blood types and both sexes. The markings were conducted by adding to the blood unmodified diamonds (SND), modified O2 (SO2) suspended in 0,9% NaCl. The blood was put under an impact of two diamond concentrations: 20μl and 100μl. The amount of abnormal cells increased with time. The percentage of echinocytes as a result of interaction with nanodiamonds in various time periods for individual specimens was scarce. In the examined microscopic image a summary was made for 100 white blood cells. Following cells were included in said group: band neutrophils, segmented neutrophils, eosinophils, basophils, lymphocytes, monocytes, lymphocytes with granulates, stimulated lymphocytes, lymphocytes with vacuoles, metamielocytes and smudge cells. The impact of the three diamond types had no clinical importance on red blood cells. After the diamonds mixed with white blood cells, atypical cells came into being, in the range of agranulocytes in stimulated form or with granulates and/or vacuoles. It is supposed that as a result of longlasting exposure a stimulation and vacuolisation takes place, because of the function of the cells.

  1. Gene-environment interaction and male reproductive function

    DEFF Research Database (Denmark)

    Axelsson, Jonatan; Bonde, Jens Peter; Giwercman, Yvonne L

    2010-01-01

    As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between...... and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated...... that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism...

  2. Gene-environment interaction and male reproductive function

    DEFF Research Database (Denmark)

    Axelsson, Jonatan; Bonde, Jens Peter; Giwercman, Yvonne L

    2010-01-01

    that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism...

  3. Quantitative investigation of intermolecular interactions in dimorphs ...

    Indian Academy of Sciences (India)

    RAHUL SHUKLA

    2018-03-23

    Mar 23, 2018 ... molecular interactions in derivatives of 1,2,4-triazoles. CrystEngComm 16 1702. 48. Shukla R, Mohan T P, Vishalakshi B and Chopra D. 2017 Synthesis, crystal structure and theoretical analysis of intermolecular interactions in two biologically active derivatives of 1,2,4-triazoles J. Mol. Struct. 1134 426. 49.

  4. Experimental investigation of shock wave - bubble interaction

    Energy Technology Data Exchange (ETDEWEB)

    Alizadeh, Mohsen

    2010-04-09

    In this work, the dynamics of laser-generated single cavitation bubbles exposed to lithotripter shock waves has been investigated experimentally. The energy of the impinging shock wave is varied in several steps. High-speed photography and pressure field measurements simultaneously with image acquisition provide the possibility of capturing the fast bubble dynamics under the effect of the shock wave impact. The pressure measurement is performed using a fiber optic probe hydrophone (FOPH) which operates based on optical diagnostics of the shock wave propagating medium. After a short introduction in chapter 1 an overview of the previous studies in chapter 2 is presented. The reported literatures include theoretical and experimental investigations of several configurations of physical problems in the field of bubble dynamics. In chapter 3 a theoretical description of propagation of a shock wave in a liquid like water has been discussed. Different kinds of reflection of a shock wave at an interface are taken into account. Undisturbed bubble dynamics as well as interaction between a planar shock wave and an initially spherical bubble are explored theoretically. Some physical parameters which are important in this issue such as the velocity of the shock-induced liquid jet, Kelvin impulse and kinetic energy are explained. The shock waves are generated in a water filled container by a focusing piezoelectric generator. The shock wave profile has a positive part with pulse duration of ∼1 μs followed by a longer tension tail (i.e. ∼3 μs). In chapter 4 high-speed images depict the propagation of a shock wave in the water filled tank. The maximum pressure is also derived for different intensity levels of the shock wave generator. The measurement is performed in the free field (i.e. in the absence of laser-generated single bubbles). In chapter 5 the interaction between lithotripter shock waves and laserinduced single cavitation bubbles is investigated experimentally. An

  5. Investigation on particle-solid interactions

    International Nuclear Information System (INIS)

    Yano, Syukuro

    1988-08-01

    Basic processes in plasma-material interactions have been surveyed and reviewed. Problems concerned with carbon materials, which have been progressively used for the first wall and limiters in Tokamaks, are mainly discussed. Recent usage of carbon materials, basic properties and characteristics of carbon/graphite materials, desorption of gasses are described. As to the interactions of incident hydrogen isotope particles with graphite surface, data of trapping, depth profile, reemission, isotope exchange, and diffusion are reviewed and discussed. (author)

  6. Investigations of interactions mediated by neutral currents

    International Nuclear Information System (INIS)

    Witek, M.

    2007-03-01

    The report is devoted to four-fermion interactions mediated by the neutral currents. The results from the second phase of LEP are presented, when the production of two massive bosons was possible with the increased energy of the e + e - collisions. It enabled for a direct test of nonabelian structure of the electroweak theory. The results concern the four-fermion production of the pairs of the ZZ bosons, single Z and Zγ * production as well as search for anomalous gauge bosons couplings. The large part of the report is devoted to experimental techniques, physics analyses and discussion of results. (author)

  7. Investigation of beryllium/steam interaction

    Energy Technology Data Exchange (ETDEWEB)

    Chekhonadskikh, A.M.; Vurim, A.D.; Vasilyev, Yu.S.; Pivovarov, O.S. [Inst. of Atomic Energy National Nuclear Center of the Republic of Kazakstan Semipalatinsk (Kazakhstan); Shestakov, V.P.; Tazhibayeva, I.L.

    1998-01-01

    In this report program on investigations of beryllium emissivity and transient processes on overheated beryllium surface attacked by water steam to be carried out in IAE NNC RK within Task S81 TT 2096-07-16 FR. The experimental facility design is elaborated in this Report. (author)

  8. Investigation of molybdenum pentachloride interaction with chlorine

    International Nuclear Information System (INIS)

    Salyulev, A.B.; Vovkotrub, Eh.G.; Strekalovskij, V.N.

    1993-01-01

    In Raman spectra of molybdenum pentachloride solutions in liquid chlorine lines were recorded in case of 397, 312, 410, 217 and 180 cm - 1 vibrations of ν 1 (A 1 '), ν 2 (A 1 '), ν 5 (E'), ν 6 (E') and ν 8 (E'') monomer (symmetry D 3h ) molecules of MoCl 5 . Interaction of molten molybdenum pentachloride with chlorine at increased (up to 6 MPa) pressures of Cl 2 was studied. In Raman spectra of its vapour distillation in liquid chlorine alongside with MoCl 5 lines appearance of new lines at 363 and 272 cm -1 , similar in their frequency to the ones calculated for the vibrations ν 1 (A 1g ) and ν 2 (E g ) of MoCl 6 molecules (symmetry O h ), was observed

  9. Gene-environment correlations in the stress-depression relationship.

    Science.gov (United States)

    Schnittker, Jason

    2010-09-01

    A critical feature of the social stress model is the apparent relationship between stress and depression. Although many studies have demonstrated a connection between the two, the relationship may be contaminated by genes affecting both stress and depression. Using a sample of identical and fraternal twins, this study explores genetic influences on depression and assorted sources of stress while explicitly estimating, and thereby controlling for, gene-environment correlations. I consider both stress and depression in a fine-grained fashion. For the former, the study explores assorted sources of stress, including health and disability, family, unemployment, discrimination, and perceived neighborhood safety, as gene-environment correlations may be stronger for some forms of stress than others. For the latter, the study explores both depressive symptoms and major depressive disorders, as each may entail a different epidemiological process, especially with respect to genes. The results reveal that most, but not all, measures of stress have moderate heritabilities, suggesting that genes influence exposure to the environment in a broad fashion. Yet, despite this, the relationship between stress and depression is generally robust to gene-environment correlations. There are some notable exceptions. For example, allowing for gene-environment correlations, marital conflict is generally unrelated to depression. Moreover, gene-environment correlations are generally stronger for major depression than for depressive symptoms, encouraging further elaboration of the distinction between the onset of depression and its recurrence, especially in the context of genes. These exceptions do not put limits on environmental influence, but do suggest that genes operate in a complex life-course fashion.

  10. Investigation of groundwater-seawater interactions: a review

    Science.gov (United States)

    Purwoarminta, A.; Moosdorf, N.; Delinom, R. M.

    2018-02-01

    This paper is to review how to investigate the interactions between groundwater and seawater. Those interactions divide into two, which are submarine groundwater discharge and seawater intrusion. This investigation is important because the interactions can give impact to coastal aquifer and marine ecosystem. On land, fresh groundwater is vulnerable to seawater disturbance. Coastal aquifer is under pressure from abstraction caused by population, industry, and agriculture. The pumping can induce seawater intrusion and land subsidence. Then in marine, seawater mixes with freshwater and it decreases salinity. Low salinity will influence marine ecosystem. The ecosystem will be disturbed by groundwater discharge if that water is contaminated. Based on the argue investigation of groundwater-seawater interactions is important and must be accurate because the results are used for coastal water management. To investigate the interactions data, i.e., lithology, pumping tests, hydrochemical data, sea level rise estimates, precipitation data, geophysics, environmental isotopes, and drilling information, should be compiled. The interaction can feed a model to determine how much groundwater extraction happening on coastal areas to prevent seawater intrusion and land subsidence. Water resources management on coasts should consider groundwater-seawater interactions.

  11. Investigating physics learning with layered student interaction networks

    DEFF Research Database (Denmark)

    Bruun, Jesper; Traxler, Adrienne

    Centrality in student interaction networks (SINs) can be linked to variables like grades [1], persistence [2], and participation [3]. Recent efforts in the field of network science have been done to investigate layered - or multiplex - networks as mathematical objects [4]. These networks can be e......, this study investigates how target entropy [5,1] and pagerank [6,7] are affected when we take time and modes of interaction into account. We present our preliminary models and results and outline our future work in this area....

  12. Diffraction stress analysis of thin films; investigating elastic grain interaction

    International Nuclear Information System (INIS)

    Kumar, A.

    2005-12-01

    This work is dedicated to the investigation of specimens exhibiting anisotropic microstructures (and thus macroscopic elastic anisotropy) and/or inhomogeneous microstructures, as met near surfaces and in textured materials. The following aspects are covered: (i) Analysis of specimens with direction-dependent (anisotropic) elastic grain-interaction. Elastic grain-interaction determines the distribution of stresses and strains over the (crystallographically) differently oriented grains of a mechanically stressed polycrystal and the mechanical and diffraction (X-ray) elastic constants (relating (diffraction) lattice strains to mechanical stresses). Grain interaction models that allow for anisotropic, direction-dependent grain interaction have been developed very recently. The notion 'direction-dependent' grain-interaction signifies that different grain-interaction constraints prevail along different directions in a specimen. Practical examples of direction-dependent grain interaction are the occurrence of surface anisotropy in thin films and the surface regions of bulk polycrystals and the occurrence of grain-shape (morphological) texture. In this work, for the first time, stress analyses of thin films have been performed on the basis of these newly developed grain-interaction models. It has also been demonstrated that the identification of the (dominant) source of direction-dependent grain interaction is possible. The results for the grain interaction have been discussed in the light of microstructural investigations of the specimens by microscopic techniques. (ii) Analysis of specimens with depth gradients: Diffraction stress analysis can be hindered if gradients of the stress state, the composition or the microstructure occur in the specimen under investigation, as the so-called information depth varies in the course of a traditional stress measurement: Ambiguous results are thus generally obtained. In this work, a strategy for stress measurements at fixed

  13. Virtual Manipulatives on the Interactive Whiteboard: A Preliminary Investigation

    Science.gov (United States)

    Mildenhall, Paula; Swan, Paul; Northcote, Maria; Marshall, Linda

    2008-01-01

    As part of the project titled "Hands-On Heads-On: The Effective Use of Manipulatives Both Virtual and Physical" being undertaken at Edith Cowan University, there was an investigation into the use of virtual manipulatives and the interactive whiteboard (IWB). Virtual manipulatives may be defined as a virtual representation of a physical…

  14. Investigating the amplitude of interactive footstep sounds and soundscape reproduction

    DEFF Research Database (Denmark)

    Turchet, Luca; Serafin, Stefania

    2013-01-01

    In this paper, we study the perception of amplitude of soundscapes and interactively generated footstep sounds provided both through headphones and a surround sound system. In particular, we investigate whether there exists a value for the amplitude of soundscapes and footstep sounds which is con...

  15. Investigating Stratification, Language Diversity and Mathematics Classroom Interaction

    Science.gov (United States)

    Barwell, Richard

    2016-01-01

    Research on the socio-political dimensions of language diversity in mathematics classrooms is under-theorised and largely focuses on language choice. These dimensions are, however, likely to influence mathematics classroom interaction in many other ways than participants' choice of language. To investigate these influences, I propose that the…

  16. A preliminary investigation into genotype x environment interaction ...

    African Journals Online (AJOL)

    The purpose of the study was to investigate a possible genotype by environment interaction in first calf South African Holstein cows for both production and reproduction traits. Data from 100 975 cows on a total mixed ration (TMR) and 22 083 pasture based cows were used. These cows were the progeny of 4 391 sires and ...

  17. Investigating the Nature of GxE Interaction under Different ...

    African Journals Online (AJOL)

    for this study were from Intermediate to Late Hybrid Trials (ILHT) conducted in ... This phenomenon, referred to as COI, introduces a degree of uncertainty into the ... Investigating the Nature of GxE Interaction under Different Management Systems [3]. Materials and Methods. Setup of the trial. The number of trial sites used for ...

  18. An Investigation of the Interaction between Resazurin and Cd 2+ ...

    African Journals Online (AJOL)

    The voltammetric behaviour of resazurin in the presence of Cd2+ and Zn2+ ions at a hanging mercury drop electrode (HMDE) was investigated by using square wave voltammetry (SWV), cyclic voltammetry (CV) and adsorptive square wave voltammetry (AdsSWV). The interaction of resazurin with Cd2+ and Zn2+ starts ...

  19. Experimental investigations and modelling of sodium-concrete interaction

    International Nuclear Information System (INIS)

    Schultheiss, G.F.; Deeg, H.J.

    1990-01-01

    The use of sodium as a coolant in liquid metal fast breeder reactors, fusion reactors, and solar plants requires special consideration of its chemical reactivity and related safety problems in the case of sodium leckage. On contact between hot sodium and concrete an interaction takes place resulting in energy release and hydrogen generation, which may contribute to containment loading by pressurization in a hypothetical accident situation. For this reason, sodium-concrete interactions were investigated experimentally and theoretically. The experiments revealed important effects of quartzitic material within the concrete and of the sodium temperature on the interaction mechanisms, the energy release and the consequent hydrogen production. The numerical model shows good agreement with the experimental results. (orig.) [de

  20. Investigation of morphological features of six interacting galaxies. I

    International Nuclear Information System (INIS)

    Koroviakovskaia, A.A.

    1984-01-01

    The morphology of six groups of interacting galaxies in Vorontsov-Vel'iaminov's atlas is investigated by digital filtering methods using large-scale photographs obtained with the 6-m telescope. It is shown that of five groups of galaxies that might appear as chains in direct photographs, only one is probably a real chain. In the group VV 551, which was previously classified as a blue nest consisting of four or five members, only two spiral galaxies have been found

  1. Investigation into complexity and interaction in supervisory control

    International Nuclear Information System (INIS)

    Tholen, N.

    1989-01-01

    Optimizing Man-Machine Systems presupposes a sound knowledge of interactions involved. Two research facilities are described which are intended as a vehicle for investigating the influences of process and controller complexity, interface design and task. The processes on which they rely have much in common, but they each have their own strong points. Together they form a good basis for human supervisory control research. (author) 12 refs

  2. Evidence of reactive gene-environment correlation in preschoolers' prosocial play with unfamiliar peers.

    Science.gov (United States)

    DiLalla, Lisabeth Fisher; Bersted, Kyle; John, Sufna Gheyara

    2015-10-01

    The development of prosocial behaviors during the preschool years is essential for children's positive interactions with peers in school and other social situations. Although there is some evidence of genetic influences on prosocial behaviors, very little is known about how genes and environment, independently and in concert, affect prosocial behaviors in young children. This study of 126 twin and sibling pairs examined 5-year-old preschool children's positive behaviors (prosocial and easy-going) while playing freely with an unfamiliar, same-age, same-sex peer. Children were randomly paired, allowing us to rule out passive (parent-influenced environment) and active (child-driven peer choices) gene-environment correlations as potential influences on the results. We found evidence of reactive gene-environment correlation, demonstrating that children who are genetically more likely to act prosocially and to be temperamentally outgoing appear to evoke more prosocial and easy-going behaviors from an unfamiliar peer. We also found that both dominant genetic and nonshared environmental factors were significant influences on preschoolers' prosocial play behaviors, but that neither genetic nor shared environmental factors were significant for easy-going play behaviors. These findings shed important light on influences of prosocial behaviors in preschoolers. Via inherited tendencies, preschool children's positive behaviors evoke similar positive behaviors from their play peers. Given that prosocial behaviors are preludes to a large range of important socially appropriate behaviors, prosocial children should be encouraged to interact with their peers to potentially create a more positive atmosphere within social contexts. (c) 2015 APA, all rights reserved).

  3. Investigations of the D-multi-ρ interactions

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, C.W. [Institut fuer Kernphysik (Theorie), Institute for Advanced Simulation, and Juelich Center for Hadron Physics, Forschungszentrum Juelich (Germany); Central South University, School of Physics and Electronics, Changsha (China)

    2017-09-15

    In the present work, which aims at searching for bound states, the interactions of the D-multi-ρ systems are investigated by means of the formalism of the fixed-center approximation to Faddeev equations. Reproducing the states of f{sub 2}(1270) and D{sub 1}(2420) dynamically in the two-body ρρ and ρD interactions, respectively, as the clusters of the fixed-center approximation, the state of D(3000){sup 0} is found as a molecule of D - f{sub 2} or ρ - D{sub 1} structures in the three-body interactions, where we determine its quantum number J{sup P} = 2{sup -} and find another possible state of D{sub 2}(3100) with isospin I = 3/2. In our results, there are some other predictions with uncertainties, a D{sub 3}(3160) state with I(J{sup P}) = (1)/(2)(3{sup +}) in the four-body interactions, a narrow D{sub 4}(3730) state with I(J{sup P}) = (1)/(2)(4{sup -}), a wide D{sub 4}(3410) state of I(J{sup P}) = (1)/(2)(4{sup -}), and another wide D{sub 4}(3770) state but with I(J{sup P}) = (3)/(2)(4{sup -}) in the five-body interactions, and a D{sub 5}(3570) state with I(J{sup P}) = (1)/(2)(5{sup +}) in the six-body interactions. (orig.)

  4. Experimental investigation of the piano hammer-string interaction.

    Science.gov (United States)

    Birkett, Stephen

    2013-04-01

    Experimental techniques for investigating the piano hammer-string interaction are described. It is argued that the accuracy, consistency, and scope of conclusions of previous studies can be compromised by limitations of the conventional methods relating to key inputs; physical distortion; numerical distortion, particularly when differentiation or integration of measured signals is used to derive primary response variables; contact identification; and synchronization issues. These problems are discussed, and experimental methods that have been devised to avoid them are described and illustrated by detailed results from a study of the hammer-string interaction in a vertical piano. High resolution displacements are obtained directly by non-contact high-speed imaging and quantitative motion tracking. The attention focused on achieving very accurate and consistent temporal and spatial alignment, including the objective procedure used for contact identification, allows meaningful comparisons of responses from separate tests. String motion at the strike point and on each side of it, as well as hammer motion, is obtained for eight dynamic levels from 1.06 to 2.98 m/s impact velocity. Detailed observations of the force-compression behavior of the hammer interacting with real strings are presented. The direct effects of hammer shank deflection and agraffe string pulses on the interaction are also highlighted.

  5. Optoelectronic investigation of nanodiamond interactions with human blood

    Science.gov (United States)

    Ficek, M.; Wróbel, M. S.; Wasowicz, M.; Jedrzejewska-Szczerska, M.

    2016-03-01

    We present optoelectronic investigation of in vitro interactions of whole human blood with different nanodiamond biomarkers. Plasmo-chemical modifications of detonation nanodiamond particles gives the possibility for controlling their surface for biological applications. Optical investigations reveal the biological activity of nanodiamonds in blood dependent on its surface termination. We compare different types of nanodiamonds: commercial non-modified detonation nanodiamonds, and nanodiamonds modified by MW PACVD method with H2-termination, and chemically modified nanodiamond with O2-termination. The absorption spectra, and optical microscope investigations were conducted. The results indicate haemocompatibility of non-modified detonation nanodiamond as well as modified nanodiamonds, which enables their application for drug delivery, as well as sensing applications.

  6. Detailed Investigations of Interactions between Ionizing Radiation and Neutral Gases

    Energy Technology Data Exchange (ETDEWEB)

    Landers, Allen L

    2014-03-31

    We are investigating phenomena that stem from the many body dynamics associated with ionization of an atom or molecule by photon or charged particle. Our program is funded through the Department of Energy EPSCoR Laboratory Partnership Award in collaboration with Lawrence Berkeley National Laboratory. We are using variations on the well established COLTRIMS technique to measure ions and electrons ejected during these interactions. Photoionization measurements take place at the Advanced Light Source at LBNL as part of the ALS-COLTRIMS collaboration with the groups of Reinhard Dörner at Frankfurt and Ali Belkacem at LBNL. Additional experiments on charged particle impact are conducted locally at Auburn University where we are studying the dissociative molecular dynamics following interactions with either ions or electrons over a velocity range of 1 to 12 atomic units.

  7. Spectroscopic investigations of pentobarbital interaction with human serum albumin

    Science.gov (United States)

    Darwish, Saqer M.; Abu sharkh, Sawsan E.; Abu Teir, Musa M.; Makharza, Sami A.; Abu-hadid, Mahmoud M.

    2010-01-01

    The interaction between pentobarbital and human serum albumin has been investigated. The basic binding interaction was studied by UV-absorption and fluorescence spectroscopy. From spectral analysis pentobarbital showed a strong ability to quench the intrinsic fluorescence of HSA through a static quenching procedure. The binding constant ( k) is estimated at 1.812 × 10 4 M -1 at 293 K. FT-IR spectroscopy with Fourier self-deconvolution technique was used to determine the protein secondary structure and drug binding mechanisms. The observed spectral changes of HSA-pentobarbital complex indicate a larger intensity decrease in the absorption band of α-helix relative to that of β-sheets. This variation in intensity is related indirectly to the formation of H-bonding in the complex molecules, which accounts for the different intrinsic propensities of α-helix and β-sheets.

  8. Investigation of the limits of nanoscale filopodial interactions

    Directory of Open Access Journals (Sweden)

    Laura E McNamara

    2014-05-01

    Full Text Available Mesenchymal stem cells are sensitive to changes in feature height, order and spacing. We had previously noted that there was an inverse relationship between osteoinductive potential and feature height on 15-, 55- and 90 nm-high titania nanopillars, with 15 nm-high pillars being the most effective substrate at inducing osteogenesis of human mesenchymal stem cells. The osteoinductive effect was somewhat diminished by decreasing the feature height to 8 nm, however, which suggested that there was a cut-off point, potentially associated with a change in cell–nanofeature interactions. To investigate this further, in this study, a scanning electron microscopy/three-dimensional scanning electron microscopy approach was used to examine the interactions between mesenchymal stem cells and the 8 and 15 nm nanopillared surfaces. As expected, the cells adopted a predominantly filopodial mode of interaction with the 15 nm-high pillars. Interestingly, fine nanoscale membrane projections, which we have termed ‘nanopodia,’ were also employed by the cells on the 8 nm pillars, and it seems that this is analogous to the cells ‘clinging on with their fingertips’ to this scale of features.

  9. Gene-Environment Interplay and Psychopathology: Multiple Varieties but Real Effects

    Science.gov (United States)

    Rutter, Michael; Moffitt, Terrie E.; Caspi, Avshalom

    2006-01-01

    Gene-environment interplay is a general term that covers several divergent concepts with different meanings and different implications. In this review, we evaluate research evidence on four varieties of gene-environment interplay. First, we consider epigenetic mechanisms by which environmental influences alter the effects of genes. Second, we…

  10. Investigation of cellular responses upon interaction with silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Subbiah R

    2015-08-01

    Full Text Available Ramesh Subbiah,1,2 Seong Beom Jeon,3,4 Kwideok Park,1,2 Sang Jung Ahn,4,5 Kyusik Yun3 1Center for Biomaterials, Korea Institute of Science and Technology, Seoul, 2Department of Biomedical Engineering, Korea University of Science and Technology, Daejon, 3Department of Bionanotechnology, Gachon University, Gyeonggi-do, 4Centre for Advanced Instrumentation, Korea Research Institute of Standard and Science, 5Major of Nano Science, Korea University of Science and Technology, Daejeon, Republic of Korea Abstract: In order for nanoparticles (NPs to be applied in the biomedical field, a thorough investigation of their interactions with biological systems is required. Although this is a growing area of research, there is a paucity of comprehensive data in cell-based studies. To address this, we analyzed the physicomechanical responses of human alveolar epithelial cells (A549, mouse fibroblasts (NIH3T3, and human bone marrow stromal cells (HS-5, following their interaction with silver nanoparticles (AgNPs. When compared with kanamycin, AgNPs exhibited moderate antibacterial activity. Cell viability ranged from ≤80% at a high AgNPs dose (40 µg/mL to >95% at a low dose (10 µg/mL. We also used atomic force microscopy-coupled force spectroscopy to evaluate the biophysical and biomechanical properties of cells. This revealed that AgNPs treatment increased the surface roughness (P<0.001 and stiffness (P<0.001 of cells. Certain cellular changes are likely due to interaction of the AgNPs with the cell surface. The degree to which cellular morphology was altered directly proportional to the level of AgNP-induced cytotoxicity. Together, these data suggest that atomic force microscopy can be used as a potential tool to develop a biomechanics-based biomarker for the evaluation of NP-dependent cytotoxicity and cytopathology. Keywords: AFM, roughness, nanoindentation, biomarker, cytotoxicity, biomechanics

  11. Investigation of syngas interactions in alcohol synthesis catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Akundi, M.A.

    1998-04-15

    The primary objectives of the project are to (a) synthesize, by controlled sequential and co-impregnation techniques, three distinct composition metal clusters (consisting of Cu-Co-Cr and Cu-Fe-Zn): rich in copper (Methanol selective), rich in ferromagnetic metal (Co or Fe-Hydrocarbon selective) and intermediate range (mixed alcohol catalysts); (b) investigate the changes in the magnetic character of the systems due to interaction with CO, through Zero-field Nuclear Magnetic Resonance (ZFNMR) study of cobalt and Magnetic character (saturation magnetization and coercive field) analysis of the composite catalyst of Vibrating Sample Magnetometry (VSM); (c) examine the changes in syngas adsorption character of the catalyst as the composition changes, by FTIR Spectroscopic analysis of CO stretching frequencies; (d) determine the nature and size of these intermetallic clusters by Scanning Electron Microscopy (SEM); and (e) perform catalytic runs on selected samples and analyze the correlations between the physical and chemical characteristics. The catalysts chosen have a greater promise for industrial application than the Rh and Mo based catalysts. Several groups preparing catalysts by synthetic routes have reported divergent results for activity and selectivity. Generally the research has followed an empirical path and less effort is devoted to analyze the mechanisms and the scientific basis. The primary intent of this study is to analyze the nature of the intermetallic and gas-metal interactions and examine the correlations to catalytic properties.

  12. Investigation on interaction of prulifloxacin with pepsin: A spectroscopic analysis

    Science.gov (United States)

    Huang, Yabei; Yan, Jie; Liu, Benzhi; Yu, Zhang; Gao, Xiaoyan; Tang, Yingcai; Zi, Yanqin

    2010-03-01

    The interaction between prulifloxacin, a kind of new oral taking antibiotic and pepsin, a kind of enzyme in the stomach has been investigated in vitro under a simulated physiological condition by different spectroscopic methods. The intrinsic fluorescence of pepsin was strongly quenched by prulifloxacin. This effect was rationalized in terms of a static quenching procedure. The binding parameters have been evaluated by fluorescence quenching methods. The negative value of Δ G0 reveals that the binding process is a spontaneous process. The binding distance R between donor (pepsin) and acceptor (prulifloxacin) was obtained according to the Förster's resonance energy transfer theory and found to be 0.95 nm. The results obtained herein will be of biological significance in pharmacology and clinical medicine.

  13. Genes, environment, and dyslexia. The 2005 Norman Geschwind Memorial Lecture.

    Science.gov (United States)

    Olson, Richard K

    2006-12-01

    This article presents an overview of some methods and results from our continuing studies of genetic and environmental influences on dyslexia, and on individual differences across the normal range that have been conducted over the past 25 years in the Colorado Learning Disabilities Research Center (CLDRC) and in related projects. CLDRC investigators compare the similarities of identical twin pairs who share all their genes and fraternal twins who share half their segregating genes to assess the balance of genetic, shared family environment, and nonshared environment influences on dyslexia and on individual differences across the normal range. We have learned that among the children we have studied in Colorado, group deficits in reading (dyslexia) and individual differences in reading across the normal range are primarily due to genetic influences, and these genetic influences are often shared with some of the same genetic influences on deficits and individual differences in language and ADHD. We have also learned from our molecular-genetic linkage studies that there are regions on several chromosomes likely to contain genes that influence dyslexia. Several specific genes within these regions have been tentatively identified through molecular-genetic association analyses, but much more research is needed to understand the pathways among specific genes, regions of noncoding DNA that regulate the activity of those genes, the brain, and dyslexia. I conclude with a discussion of our research on individual differences in early reading development, on the role of early learning constraints in dyslexia, and on how genetic influences are expressed through their interaction and correlation with the environment.

  14. Molecular genetic gene-environment studies using candidate genes in schizophrenia: a systematic review.

    Science.gov (United States)

    Modinos, Gemma; Iyegbe, Conrad; Prata, Diana; Rivera, Margarita; Kempton, Matthew J; Valmaggia, Lucia R; Sham, Pak C; van Os, Jim; McGuire, Philip

    2013-11-01

    The relatively high heritability of schizophrenia suggests that genetic factors play an important role in the etiology of the disorder. On the other hand, a number of environmental factors significantly influence its incidence. As few direct genetic effects have been demonstrated, and there is considerable inter-individual heterogeneity in the response to the known environmental factors, interactions between genetic and environmental factors may be important in determining whether an individual develops the disorder. To date, a considerable number of studies of gene-environment interactions (G×E) in schizophrenia have employed a hypothesis-based molecular genetic approach using candidate genes, which have led to a range of different findings. This systematic review aims to summarize the results from molecular genetic candidate studies and to review challenges and opportunities of this approach in psychosis research. Finally, we discuss the potential of future prospects, such as new studies that combine hypothesis-based molecular genetic candidate approaches with agnostic genome-wide association studies in determining schizophrenia risk. © 2013 Elsevier B.V. All rights reserved.

  15. An experimental and numerical investigation on wave-mud interactions

    Science.gov (United States)

    Hsu, W. Y.; Hwung, H. H.; Hsu, T. J.; Torres-Freyermuth, A.; Yang, R. Y.

    2013-03-01

    Wave attenuation over a mud (kaolinite) layer is investigated via laboratory experiments and numerical modeling. The rheological behavior of kaolinite exhibits hybrid properties of a Bingham and pseudoplastic fluid. Moreover, the measured time-dependent velocity profiles in the mud layer reveal that the shear rate under wave loading is highly phase dependent. The measured shear rate and rheological data allow us to back-calculate the time-dependent viscosity of the mud layer under various wave loadings, which is also shown to fluctuate up to 1 order of magnitude during one wave period. However, the resulting time-dependent bottom stress is shown to only fluctuate within 25% of its mean. The back-calculated wave-averaged bottom stress is well correlated with the wave damping rate in the intermediate-wave energy condition. The commonly adopted constant viscosity assumption is then evaluated via linear and nonlinear wave-mud interaction models. When driving the models with measured wave-averaged mud viscosity (forward modeling), the wave damping rate is generally overpredicted under the low wave energy condition. On the other hand, when a constant viscosity is chosen to match the observed wave damping rate (inverse modeling), the predicted velocity profiles in the mud layer are not satisfactory and the corresponding viscosity is lower than the measured value. These discrepancies are less pronounced when waves become more energetic. Differences between the linear and nonlinear model results become significant under low-energy conditions, suggesting an amplification of wave nonlinearity due to non-Newtonian rheology. In general, the constant viscosity assumption for modeling wave-mud interaction is only appropriate for more energetic wave conditions.

  16. Experimental investigation of interactions between proteins and carbon nanomaterials

    Science.gov (United States)

    Sengupta, Bishwambhar

    The global market for nanomaterials based products is forecasted to reach $1 trillion per annum per annum for 2015. Engineered nanomaterials (ENMs) exhibit unique physicochemical properties with potential to impact diverse aspects of society through applications in electronics, renewable energy, and medicine. While the research and proposed applications of ENMs continue to grow rapidly, the health and safety of ENMs still remains a major concern to the public as well as to policy makers and funding agencies. It is now widely accepted that focused efforts are needed for identifying the list of physicochemical descriptors of ENM before they can be evaluated for nanotoxicity and biological response. This task is surprisingly challenging, as many physicochemical properties of ENMs are closely inter related and cannot be varied independently (e.g. increasing the size of an ENM can introduce additional defects). For example, varying toxic response may ensue due to different methods of nanomaterial preparation, dissimilar impurities and defects. Furthermore, the inadvertent coating of proteins on ENM surface in any biological milieu results in the formation of the so-called "protein/bio-corona" which can in turn alter the fate of ENMs and their biological response. Carbon nanomaterials (CNMs) such as carbon nanotubes, graphene, and graphene oxide are widely used ENMs. It is now known that defects in CNMs play an important role not only in materials properties but also in the determination of how materials interact at the nano-bio interface. In this regard, this work investigates the influence of defect-induced hydrophilicity on the bio-corona formation using micro Raman, photoluminescence, infrared spectroscopy, electrochemistry, and molecular dynamics simulations. Our results show that the interaction of proteins (albumin and fibrinogen) with CNMs is strongly influenced by charge transfer between them, inducing protein unfolding which enhances conformational entropy and

  17. REVIEW: Genome-wide findings in schizophrenia and the role of gene-environment interplay.

    Science.gov (United States)

    Van Winkel, Ruud; Esquivel, Gabriel; Kenis, Gunter; Wichers, Marieke; Collip, Dina; Peerbooms, Odette; Rutten, Bart; Myin-Germeys, Inez; Van Os, Jim

    2010-10-01

    The recent advent of genome-wide mass-marker technology has resulted in renewed optimism to unravel the genetic architecture of psychotic disorders. Genome-wide association studies have identified a number of common polymorphisms robustly associated with schizophrenia, in ZNF804A, transcription factor 4, major histocompatibility complex, and neurogranin. In addition, copy number variants (CNVs) in 1q21.1, 2p16.3, 15q11.2, 15q13.3, 16p11.2, and 22q11.2 were convincingly implicated in schizophrenia risk. Furthermore, these studies have suggested considerable genetic overlap with bipolar disorder (particularly for common polymorphisms) and neurodevelopmental disorders such as autism (particularly for CNVs). The influence of these risk variants on relevant intermediate phenotypes needs further study. In addition, there is a need for etiological models of psychosis integrating genetic risk with environmental factors associated with the disorder, focusing specifically on environmental impact on gene expression (epigenetics) and convergence of genes and environment on common biological pathways bringing about larger effects than those of genes or environment in isolation (gene-environment interaction). Collaborative efforts that bring together expertise in statistics, genetics, epidemiology, experimental psychiatry, brain imaging, and clinical psychiatry will be required to succeed in this challenging task. © 2010 Blackwell Publishing Ltd.

  18. Modelling social interaction as perceptual crossing: an investigation into the dynamics of the interaction process

    Science.gov (United States)

    Froese, Tom; Di Paolo, Ezequiel A.

    2010-03-01

    This paper continues efforts to establish a mutually informative dialogue between psychology and evolutionary robotics in order to investigate the dynamics of social interaction. We replicate a recent simulation model of a minimalist experiment in perceptual crossing and confirm the results with significantly simpler artificial agents. A series of psycho-physical tests of their behaviour informs a hypothetical circuit model of their internal operation. However, a detailed study of the actual internal dynamics reveals this circuit model to be unfounded, thereby offering a tale of caution for those hypothesising about sub-personal processes in terms of behavioural observations. In particular, it is shown that the behaviour of the agents largely emerges out of the interaction process itself rather than being an individual achievement alone. We also extend the original simulation model in two novel directions in order to test further the extent to which perceptual crossing between agents can self-organise in a robust manner. These modelling results suggest new hypotheses that can become the basis for further psychological experiments.

  19. [Association between MAOA-u VNTR polymorphism and its interaction with stressful life events and major depressive disorder in adolescents].

    Science.gov (United States)

    Ma, Jing; Yu, Shun-Ying; Liang, Shan; Ding, Jun; Feng, Zhe; Yang, Fan; Gao, Wei-Jia; Lin, Jia-Ni; Huang, Chun-Xiang; Liu, Xue-Jun; Su, Lin-Yan

    2013-07-01

    To investigate whether the genetic polymorphism, upstream variable number of tandem repeats (uVNTR), in the monoamine oxidase A (MAOA) gene, is associated with major depressive disorder (MDD) in adolescents and to test whether there is gene-environment interaction between MAOA-uVNTR polymorphism and stressful life events (SLEs). A total of 394 Chinese Han subjects, including 187 adolescent patients with MDD and 207 normal students as a control group, were included in the study. Genotyping was performed by SNaP-shot assay. SLEs in the previous 12 months were evaluated. The groups were compared in terms of the frequency distributions of MAOA-uVNTR genotypes and alleles using statistical software. The binary logistic regression model of gene-environment interaction was established to analyze the association of the gene-environment interaction between MAOA-u VNTR genotypes and SLEs with adolescent MDD. The distribution profiles of MAOA-u VNTR genotypes and alleles were not related to the onset of MDD, severity of depression, comorbid anxiety and suicidal ideation/behavior/attempt in adolescents. The gene-environment interaction between MAOA-u VNTR genotypes and SLEs was not associated with MDD in male or female adolescents. It is not proven that MAOA-u VNTR polymorphism is associated with adolescent MDD. There is also no gene-environment interaction between MAOA-u VNTR polymorphism and SLEs that is associated with adolescent MDD.

  20. Electrochemical Investigation of the Interaction between Catecholamines and ATP.

    Science.gov (United States)

    Taleat, Zahra; Estévez-Herrera, Judith; Machado, José D; Dunevall, Johan; Ewing, Andrew G; Borges, Ricardo

    2018-02-06

    The study of the colligative properties of adenosine 5'-triphosphate (ATP) and catecholamines has received the attention of scientists for decades, as they could explain the capabilities of secretory vesicles (SVs) to accumulate neurotransmitters. In this Article, we have applied electrochemical methods to detect such interactions in vitro, at the acidic pH of SVs (pH 5.5) and examined the effect of compounds having structural similarities that correlate with functional groups of ATP (adenosine, phosphoric acid and sodium phosphate salts) and catecholamines (catechol). Chronoamperometry and fast scan cyclic voltammetry (FSCV) provide evidence compatible with an interaction of the catechol and adenine rings. This interaction is also reinforced by an electrostatic interaction between the phosphate group of ATP and the protonated ammonium group of catecholamines. Furthermore, chronoamperometry data suggest that the presence of ATP subtlety reduces the apparent diffusion coefficient of epinephrine in aqueous media that adds an additional factor leading to a slower rate of catecholamine exocytosis. This adds another plausible mechanism to regulate individual exocytosis events to alter communication.

  1. A preliminary investigation into genotype x environment interaction ...

    African Journals Online (AJOL)

    uvp

    2014-08-24

    Aug 24, 2014 ... 1 Department of Animal, Wildlife and Grassland Sciences, UFS, P.O. Box 339, Bloemfontein, 9300, South Africa;. 2INRA ... Bivariate analyses, fitting an animal model using the ASREML software, were used to obtain genetic correlations .... Genotype x environment interactions in conventional versus.

  2. Investigating the interactions of the enantiomers of phenylglycine ...

    Indian Academy of Sciences (India)

    So, movement, radius of gyration and angle of orientation of S-isomers inside nanopores are decreased, while R-isomers interact more strongly with each other. ... BC, Canada; School of Chemical Engineering- University College of Engineering-University of Tehran, Tehran, Iran; School of Chemistry- University College of ...

  3. The interaction between cannabis use and the Val158Met polymorphism of the COMT gene in psychosis: A transdiagnostic meta - analysis

    NARCIS (Netherlands)

    Vaessen, Thomas Stephanus Johannes; de Jong, Lea; Schäfer, Annika Theresia; Damen, Thomas; Uittenboogaard, Aniek; Krolinski, Pauline; Nwosu, Chinyere Vicky; Pinckaers, Florentina Maria Egidius; Rotee, Iris Leah Marije; Smeets, Antonius Petrus Wilhelmus; Ermiş, Ayşegül; Kennedy, James L.; Nieman, Dorien H.; Tiwari, Arun; van Os, Jim; Drukker, Marjan

    2018-01-01

    Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive. A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl

  4. Investigation of sodium - carbon dioxide interactions with calorimetric studies

    International Nuclear Information System (INIS)

    Simon, N.; Latge, C.; Gicquel, L.

    2007-01-01

    The supercritical CO 2 Brayton cycle could be a promising option to enhance the competitiveness of future Sodium fast reactors but it is highly necessary to get thermodynamic and kinetics information on potential sodium-CO 2 chemical reactions and their consequences. We have studied the interaction between Na and CO 2 via calorimetric methods. These methods are able to point out exothermic/endothermic phenomena and to measure heat of chemical reactions. The main feature of the Na/CO 2 interaction seems to be its sharp dependence on temperature. At low temperature, below 500 C degrees, CO 2 and sodium react and exhibit an induction time which decreases when temperature increases. Above 500 C degrees, we observe a global phenomenon with a fast and instantaneous chemical reaction which may be understood as an auto-combustion of CO 2 in sodium. We clearly demonstrated that Na/CO 2 interaction does not proceed as an auto-catalytic process and is more satisfactorily explained by the occurring of an auto-combustion phenomenon

  5. Gene-air pollution interaction and cardiovascular disease: a review.

    Science.gov (United States)

    Zanobetti, Antonella; Baccarelli, Andrea; Schwartz, Joel

    2011-01-01

    Genetic susceptibility is likely to play a role in response to air pollution. Hence, gene-environment interaction studies can be a tool for exploring the mechanisms and the importance of the pathway in the association between air pollution and a cardiovascular outcome. In this article, we present a systematic review of the studies that have examined gene-environment interactions in relation to the cardiovascular health effects of air pollutants. We identified 16 articles meeting our search criteria. Of these studies, most have focused on individual functional polymorphisms or individual candidate genes. Moreover, they were all based on 3 study populations that have been extensively investigated in relation to air pollution effects: the Normative Aging Study, Air Pollution and Inflammatory Response in Myocardial Infarction Survivors: Gene-Environment Interaction in a High Risk Group, and Multiethnic Study of Atherosclerosis. In conclusions, the studies differed substantially in both the cardiovascular outcomes examined and the polymorphisms examined, so there is little confirmation of results across cohorts. Gene-environment interaction studies can help explore the mechanisms and the potential pathway in the association between air pollution and a cardiovascular outcome; replication of findings and studies involving multiple cohorts would be needed to draw stronger conclusions. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Effect of paternal alcohol and drug dependence on offspring conduct disorder: gene-environment interplay.

    Science.gov (United States)

    Haber, Jon Randolph; Bucholz, Kathleen K; Jacob, Theodore; Grant, Julia D; Scherrer, Jeffrey F; Sartor, Carolyn E; Duncan, Alexis E; Heath, Andrew

    2010-09-01

    Not only are substance-use disorders and externalizing disorders frequently comorbid, they often co-occur in families across generations. The current study examined the role of genetic and environmental influences in the relationship between paternal histories of drug dependence or alcohol dependence and offspring conduct disorder using an offspring-of-twins design. Participants were male twins (n = 1,774) from the Vietnam Era Twin Registry, their offspring (n = 1,917), and mothers of the offspring (n = 1,202). Twins had a history of drug dependence, alcohol dependence, or neither. Based on the father's and his co-twin's drug-dependence or alcohol-dependence history and zygosity, risk groups were constructed to reflect different levels of genetic and environmental risk that were then used to predict offspring conduct disorder. After controlling for potentially confounding variables, the offspring of men with a history of drug dependence or alcohol dependence had significantly higher rates of conduct disorder, compared with offspring of men without this history. Offspring at higher genetic risk had higher rates of conduct disorder. High-risk offspring at lower environmental risk had lower rates of conduct disorder but only in the case of paternal drug-dependence risk. Lower environmental risk did not influence rates of offspring conduct disorder when the father had an alcohol-dependence history. Genetic risk associated with both paternal drug-dependence and paternal alcohol-dependence histories predicted offspring conduct-disorder risk, but only risk associated with paternal drug-dependence history was mitigated by having a low-risk environment. These results demonstrated a significant gene-environment interaction effect.

  7. Further investigations of the NN interaction in the Skyrme model

    International Nuclear Information System (INIS)

    Kaelbermann, G.; Eisenberg, J.M.

    1989-01-01

    We examine the influence of the coupling to NΔ and ΔΔ degrees of freedom for the NN interaction as derived in the Skyrme model, carrying out an extensive search for parameters in the basic Lagrangian that will yield both reasonable single-baryon results and appreciable attraction. Separately the free one-body skyrmeon solution and an improved two-body solution are inserted in the product ansatz for the two-body system both with and without time-dependent dynamical terms. No appreciable central attraction between nucleons is found with either of these approaches. (author)

  8. Microscopic investigation of the 12C + 12C interaction

    International Nuclear Information System (INIS)

    Baye, D.; Pecher, N.; Brussels Univ.

    1982-01-01

    The 12 C + 12 C system is studied in the framework of the generator coordinate method. Each 12 C nucleus is described by a closed psub(3/2) subshell. Phase shifts and resonances are determined for several effective two-body interactions involving a spin-orbit term. The existence and properties of simple local equivalent potentials for the 12 C + 12 C collision are discussed. The 12 C + 12 C system is too light to be well described by potentials independent of the angular momentum or weakly dependent on it. (orig.)

  9. Investigating Conversational Dynamics: Interactive Alignment, Interpersonal Synergy, and Collective Task Performance

    Science.gov (United States)

    Fusaroli, Riccardo; Tylén, Kristian

    2016-01-01

    This study investigates interpersonal processes underlying dialog by comparing two approaches, "interactive alignment" and "interpersonal synergy", and assesses how they predict collective performance in a joint task. While the interactive alignment approach highlights imitative patterns between interlocutors, the synergy…

  10. A preliminary investigation of affective interaction in chronic pain couples.

    Science.gov (United States)

    Johansen, Ayna Beate; Cano, Annmarie

    2007-11-01

    The objective of this preliminary study was to examine the extent to which affective marital interaction related to depressive symptoms in persons with chronic pain and their spouses and to pain severity in persons with pain. Couples from the community completed self-report surveys and engaged in a videotaped conversation on a topic of mutual disagreement that was coded for three affect types (i.e., anger/contempt, sadness, humor). Humor was positively related to marital satisfaction in both partners. Spouse anger/contempt and sadness were positively related to depressive symptoms in spouses. Several significant interaction effects between couple pain status (i.e., whether one or both partners reported pain) and affect also emerged. Specifically, sadness in the participant designated as the person with pain was associated with greater depressive symptoms and pain severity when only he or she reported pain whereas sadness was related to fewer depressive symptoms and less pain severity when both partners reported pain. The relationships between spouse anger and spouse depressive symptoms and between spouse humor and pain severity in the person with pain were also moderated by couple pain status. These exploratory findings can be interpreted in light of emotion regulation and pain empathy theories. For example, partners who have not experienced pain themselves may fail to empathize with persons in pain, thus preventing effective emotion regulation. When both spouses report chronic pain, expressions of negative affect may instead promote emotion regulation because the affect is experienced with a spouse who may be more empathetic.

  11. Satiety and the self-regulation of food take in children: A potential role for gene-environment interplay

    Science.gov (United States)

    Hughes, Sheryl O.

    2016-01-01

    Child eating self-regulation refers to behaviors that enable children to start and stop eating in a manner consistent with maintaining energy balance. Perturbations in these behaviors, manifesting as poorer child eating self-regulation, are associated with higher child weight status. Initial research into child eating self-regulation focused on the role of parent feeding styles and behaviors. However, we argue that child eating self-regulation is better understood as arising from a complex interplay between the child and their feeding environment, and highlight newer research into the heritable child characteristics, such as cognitive ability, that play an important role in this dynamic. Therefore, child eating self-regulation arises from gene-environment interactions. Identifying the genes and environmental influences contributing to these will help us tailor our parental feeding advice to the unique nature of the child. In this way, we will devise more effective advice for preventing childhood obesity. PMID:26847550

  12. Experimental Investigation of Hypersonic Flow and Plasma Aerodynamic Actuation Interaction

    International Nuclear Information System (INIS)

    Sun Quan; Cheng Bangqin; Li Yinghong; Cui Wei; Yu Yonggui; Jie Junhun

    2013-01-01

    For hypersonic flow, it was found that the most effective plasma actuator is derived from an electromagnetic perturbation. An experimental study was performed between hypersonic flow and plasma aerodynamic actuation interaction in a hypersonic shock tunnel, in which a Mach number of 7 was reached. The plasma discharging characteristic was acquired in static flows. In a hypersonic flow, the flow field can affect the plasma discharging characteristics. DC discharging without magnetic force is unstable, and the discharge channel cannot be maintained. When there is a magnetic field, the energy consumption of the plasma source is approximately three to four times larger than that without a magnetic field, and at the same time plasma discharge can also affect the hypersonic flow field. Through schlieren pictures and pressure measurement, it was found that plasma discharging could induce shockwaves and change the total pressure and wall pressure of the flow field

  13. Gene-Environment Interplay in Internalizing Disorders: Consistent Findings across Six Environmental Risk Factors

    Science.gov (United States)

    Hicks, Brian M.; Dirago, Ana C.; Iacono, William G.; McGue, Matt

    2009-01-01

    Background: Behavior genetic methods can help to elucidate gene-environment (G-E) interplay in the development of internalizing (INT) disorders (i.e., major depression and anxiety disorders). To date, however, no study has conducted a comprehensive analysis examining multiple environmental risk factors with the purpose of delineating general…

  14. AESOP: A Python Library for Investigating Electrostatics in Protein Interactions.

    Science.gov (United States)

    Harrison, Reed E S; Mohan, Rohith R; Gorham, Ronald D; Kieslich, Chris A; Morikis, Dimitrios

    2017-05-09

    Electric fields often play a role in guiding the association of protein complexes. Such interactions can be further engineered to accelerate complex association, resulting in protein systems with increased productivity. This is especially true for enzymes where reaction rates are typically diffusion limited. To facilitate quantitative comparisons of electrostatics in protein families and to describe electrostatic contributions of individual amino acids, we previously developed a computational framework called AESOP. We now implement this computational tool in Python with increased usability and the capability of performing calculations in parallel. AESOP utilizes PDB2PQR and Adaptive Poisson-Boltzmann Solver to generate grid-based electrostatic potential files for protein structures provided by the end user. There are methods within AESOP for quantitatively comparing sets of grid-based electrostatic potentials in terms of similarity or generating ensembles of electrostatic potential files for a library of mutants to quantify the effects of perturbations in protein structure and protein-protein association. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  15. Antiretroviral Drug Interactions: Overview of Interactions Involving New and Investigational Agents and the Role of Therapeutic Drug Monitoring for Management

    Directory of Open Access Journals (Sweden)

    R. Chris Rathbun

    2011-10-01

    Full Text Available Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. Interactions between antiretrovirals and medications for other diseases are common due to shared metabolism through cytochrome P450 (CYP450 and uridine diphosphate glucuronosyltransferase (UGT enzymes and transport by membrane proteins (e.g., p-glycoprotein, organic anion-transporting polypeptide. The clinical significance of antiretroviral drug interactions is reviewed, with a focus on new and investigational agents. An overview of the mechanistic basis for drug interactions and the effect of individual antiretrovirals on CYP450 and UGT isoforms are provided. Interactions between antiretrovirals and medications for other co-morbidities are summarized. The role of therapeutic drug monitoring in the detection and management of antiretroviral drug interactions is also briefly discussed.

  16. Final Report on Investigation of the Electron Interactions in Graphene

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Philip [Columbia University

    2015-02-14

    In graphene, combined with the real spin degree of freedom, which exhibits SU(2) symmetry, the total internal degrees of freedom of graphene carriers is thus described by a larger SU(4) symmetry, which produces a richer space for potential phenomena of emergent correlated electron phenomena. The major part of this proposal is exploring this unique multicomponent correlated system in the quantum limit. In the current period of DOE BES support we have made several key advances that will serve as a foundation for the new studies in this proposal. Employing the high-mobility encapsulated graphene heterostructures developed during the current phase of research, we have investigated spin and valley quantum Hall ferromagnetism in graphene and discovered a spin phase transition leading to a quantum spin Hall analogue. We have also observed the fractal quantum Hall effect arising from the Hofstadter’s butterfly energy spectrum. In addition, we have discovered multiband transport phenomena in bilayer graphene at high carrier densities.

  17. Theoretical investigation of electron-positive ion/atom interactions

    International Nuclear Information System (INIS)

    Msezane, A.Z.

    1992-01-01

    Very brief summaries are given on three research topics. Electron impact elastic, excitation, and total cross sections for K were investigated by using elaborate Cl target wave functions in the close-coupling approximation. Photoionization cross sections from ground-state Na were calculated near the 2s 2 2p 5 3s and 2s2p 6 3s inner-shell thresholds; also, the photoionization cross sections of excited 3p 2 P o and 3d 2 D states were calculated with the R-matrix methodology near the 2s2p 6 3s thresholds. A numerical approach was developed to calculate the charge transfer matrix elements for ion-atom(ion) collisions; this was used for the proton-hydrogen collision problem as an illustration

  18. Investigation of electron heating in laser-plasma interaction

    Directory of Open Access Journals (Sweden)

    A Parvazian

    2013-03-01

    Full Text Available  In this paper, stimulated Raman scattering (SRS and electron heating in laser plasma propagating along the plasma fusion is investigated by particle-in cell simulation. Applying an external magnetic field to plasma, production of whistler waves and electron heating associated with whistler waves in the direction perpendicular to external magnetic field was observed in this simulation. The plasma waves with low phase velocities, generated in backward-SRS and dominateing initially in time and space, accelerated the backward electrons by trapping them. Then these electrons promoted to higher energies by the forward-SRS plasma waves with high phase velocities. This tow-stage electron acceleration is more efficient due to the coexistence of these two instabilities.

  19. Landscape genomics in Atlantic salmon (Salmo salar): searching for gene-environment interactions driving local adaptation.

    Science.gov (United States)

    Vincent, Bourret; Dionne, Mélanie; Kent, Matthew P; Lien, Sigbjørn; Bernatchez, Louis

    2013-12-01

    A growing number of studies are examining the factors driving historical and contemporary evolution in wild populations. By combining surveys of genomic variation with a comprehensive assessment of environmental parameters, such studies can increase our understanding of the genomic and geographical extent of local adaptation in wild populations. We used a large-scale landscape genomics approach to examine adaptive and neutral differentiation across 54 North American populations of Atlantic salmon representing seven previously defined genetically distinct regional groups. Over 5500 genome-wide single nucleotide polymorphisms were genotyped in 641 individuals and 28 bulk assays of 25 pooled individuals each. Genome scans, linkage map, and 49 environmental variables were combined to conduct an innovative landscape genomic analysis. Our results provide valuable insight into the links between environmental variation and both neutral and potentially adaptive genetic divergence. In particular, we identified markers potentially under divergent selection, as well as associated selective environmental factors and biological functions with the observed adaptive divergence. Multivariate landscape genetic analysis revealed strong associations of both genetic and environmental structures. We found an enrichment of growth-related functions among outlier markers. Climate (temperature-precipitation) and geological characteristics were significantly associated with both potentially adaptive and neutral genetic divergence and should be considered as candidate loci involved in adaptation at the regional scale in Atlantic salmon. Hence, this study significantly contributes to the improvement of tools used in modern conservation and management schemes of Atlantic salmon wild populations. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  20. The clinical application of UGT1A1 pharmacogenetic testing: Gene-environment interactions

    Directory of Open Access Journals (Sweden)

    Marques Sara

    2010-04-01

    Full Text Available Abstract Over the past decade, the number of pharmacogenetic tests has increased considerably, allowing for the development of our knowledge of their clinical application. The uridine diphosphate glucuronosyltransferase 1A1 gene (UGT1A1 assay is an example of a pharmacogenetic test. Numerous variants have been found in UGT1A1, the main conjugating enzyme of bilirubin and drugs such as the anticancer drug irinotecan. Recently, the US Food and Drug Administration (FDA recommended testing for the presence of UGT1A1*28, an allele correlated with decreased transcriptional activity, to predict patients at risk of irinotecan toxicity. The administration of other drugs -- such as inhibitors of the UGT1A1 enzyme -- can clinically mimic the *28 phenotype, whereas inducers of UGT1A1 can increase the glucuronidation rate of the enzyme. The *28 polymorphism is not present in all ethnicities at a similar frequency, which suggests that it is important to study different populations to determine the clinical relevance of testing for UGT1A1*28 and to identify other clinically relevant UGT1A1 variants. Environmental factors such as lifestyle can also affect UGT1A1 activity. This review is a critical analysis of studies on drugs that can be affected by the presence of UGT1A1*28, the distribution of this polymorphism around the globe, distinct variants that may be clinically significant in African and Asian populations and how lifestyle can affect treatment outcomes that depend on UGT1A1 activity.

  1. The role of epigenetics in depression and suicide: A platform for gene-environment interactions.

    Science.gov (United States)

    Lockwood, Laura E; Su, Shaoyong; Youssef, Nagy A

    2015-08-30

    Epigenetics involves functional modifications of genes. The aim of this paper is to explore if an association exists between epigenetics and depression and/or suicide. MedLine/PubMed searches were performed using both Medical Subject Heading (MeSH) and Non-MeSH terms. Based on pre-specified terms and inclusion criteria, sixteen studies met inclusion criteria by the 3 independent reviewers. Epigenetic changes seem to be important in both depression and suicide. All of the studies reviewed herein found significant epigenetic changes associated with depression and suicide except for two. Several studies showed that hypermethylation of BDNF is involved in suicide. TrkB hypermethylation was also shown to be associated with suicide by several studies, specifically in Brodmann's Areas (BA) 8 and 9. Future research is needed in a larger sample to further characterize these changes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Gene-environment interactions in considering physical activity for the prevention of dementia

    Directory of Open Access Journals (Sweden)

    Kristyn Alissa Bates

    2015-09-01

    Full Text Available Alzheimer's disease (AD, the most common neurodegenerative disease worldwide, ranks as one of the most feared diseases in the world. Similarly, recent studies suggest that AD may be the third leading cause of death in the United States, behind heart disease and cancer. In the absence of a cure or effective treatment, strategies to prevent or delay the onset and progression of the disease are desperately needed. Decades of research have identified key risk and protective factors including genetic polymorphism in the APOE gene, age and lifestyle factors. Physical activity (PA is emerging as an attractive primary prevention strategy. This review will summarise the latest findings supporting the role of physical activity in the prevention of AD, including possible mechanisms and the influence of genetics on disease prevention. Given that AD and other dementias are recognised as a world health priority, public health strategies are needed to incorporate promoting the health benefits of physical activity across the lifespan.

  3. Childhood problem behavior and parental divorce: evidence for gene-environment interaction

    NARCIS (Netherlands)

    S.C.C. Robbers (Sylvana); F.V.A. van Oort (Floor); A.C. Huizink (Anja); F.C. Verhulst (Frank); C.E.M. van Beijsterveldt (Toos); D.I. Boomsma (Dorret); M. Bartels (Meike)

    2012-01-01

    textabstractObjective: The importance of genetic and environmental influences on children's behavioral and emotional problems may vary as a function of environmental exposure. We previously reported that 12-year-olds with divorced parents showed more internalizing and externalizing problems than

  4. Challenges of Analysing Gene-Environment Interactions in Mouse Models of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Peter L. Oliver

    2011-01-01

    Full Text Available The modelling of neuropsychiatric disease using the mouse has provided a wealth of information regarding the relationship between specific genetic lesions and behavioural endophenotypes. However, it is becoming increasingly apparent that synergy between genetic and nongenetic factors is a key feature of these disorders that must also be taken into account. With the inherent limitations of retrospective human studies, experiments in mice have begun to tackle this complex association, combining well-established behavioural paradigms and quantitative neuropathology with a range of environmental insults. The conclusions from this work have been varied, due in part to a lack of standardised methodology, although most have illustrated that phenotypes related to disorders such as schizophrenia are consistently modified. Far fewer studies, however, have attempted to generate a “two-hit” model, whereby the consequences of a pathogenic mutation are analysed in combination with environmental manipulation such as prenatal stress. This significant, yet relatively new, approach is beginning to produce valuable new models of neuropsychiatric disease. Focussing on prenatal and perinatal stress models of schizophrenia, this review discusses the current progress in this field, and highlights important issues regarding the interpretation and comparative analysis of such complex behavioural data.

  5. Gene-environment interactions of circadian-related genes for cardiometabolic traits

    Science.gov (United States)

    Objective: Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs1387153,...

  6. Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer

    Science.gov (United States)

    2007-06-01

    and redissolving in a methanol acetate buffer mixture. Liquid chromatography photo diode array multiple generation mass spectrometry (LC/PDA/MS...delivery liquid chromatography system with multiple channel diode-array detection and a quadrupole ion trap mass spectrometer model ’Advantage...flour) 1 2 3 4 5 120. Elubo lafu 1 2 3 4 5 121. Kpokpo gari 1 2 3 4 5 122. Cassava /Yuka boiled 1 2 3 4 5 123. Fufu 1 2 3 4 5 124. Starch

  7. Gene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits

    DEFF Research Database (Denmark)

    Dashti, Hassan S; Follis, Jack L; Smith, Caren E

    2015-01-01

    OBJECTIVE: Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs13871...

  8. Epigenetic understanding of gene-environment interactions in psychiatric disorders: a new concept of clinical genetics

    OpenAIRE

    Kubota, Takeo; Miyake, Kunio; Hirasawa, Takae

    2012-01-01

    Abstract Epigenetics is a mechanism that regulates gene expression independently of the underlying DNA sequence, relying instead on the chemical modification of DNA and histone proteins. Although environmental and genetic factors were thought to be independently associated with disorders, several recent lines of evidence suggest that epigenetics bridges these two factors. Epigenetic gene regulation is essential for normal development, thus defects in epigenetics cause various rare congenital ...

  9. Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate

    DEFF Research Database (Denmark)

    Beaty, Terri H; Ruczinski, Ingo; Murray, Jeffrey C

    2011-01-01

    Nonsyndromic cleft palate (CP) is a common birth defect with a complex and heterogeneous etiology involving both genetic and environmental risk factors. We conducted a genome-wide association study (GWAS) using 550 case-parent trios, ascertained through a CP case collected in an international...

  10. Eating disorders, gene-environment interactions and the epigenome: Roles of stress exposures and nutritional status.

    Science.gov (United States)

    Steiger, Howard; Thaler, Lea

    2016-08-01

    Epigenetic mechanisms are believed to link environmental exposures to gene expression, and in so doing, to provide a physical basis for the activation, by life experiences, of mental-health problems. This paper provides a background to the hypothesis that epigenetic mechanisms link life stresses (perinatal, childhood and adult) and effects of malnutrition to the eating disorders (EDs). The paper reviews literature bearing upon the putative link between epigenetic factors and ED development, and examines ways in which epigenetic alterations could account for risk of eating disturbances and commonly associated behavioral and emotional problems. Ultimately, we propose that epigenetic processes provide an intriguing (although hypothetical) biological "platform" upon which ED-relevant effects of perinatal insults, life stresses, and consequences of malnutrition may be registered, and argue that an epigenetically informed understanding may explain why EDs are triggered and maintained by excessive caloric restraint, why they coincide so frequently with mood- and impulse-regulation problems, and why they tend to become increasingly entrenched over time. Finally, we comment on the clinical relevance and implications of an epigenetically informed model of ED etiology. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Coronary heart disease risk : family history and gene-environment interaction

    NARCIS (Netherlands)

    Boer, J.M.A.

    1999-01-01

    The first part of this thesis describes research into lifestyle, genetic, and biological factors that may underlie the increased risk for coronary heart disease (CHD) in individuals with a family history of this disorder. The second part of this thesis describes whether levels of plasma

  12. Investigating hadronic resonances in pp interactions with HADES

    Directory of Open Access Journals (Sweden)

    Przygoda Witold

    2015-01-01

    Full Text Available In this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e− were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232 and N(1440 (1.25 GeV as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232P33. In the case of 3.5 GeV data, the study of the ppe+e− channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.

  13. Investigation of interactions between dendrimer-coated magnetite nanoparticles and bovine serum albumin

    International Nuclear Information System (INIS)

    Pan Bifeng; Gao Feng; Ao Limei

    2005-01-01

    We investigated the interactions between dendrimer-coated magnetite nanoparticles (MNPs) and the protein serum albumin. The investigation was based on the fluorescence quenching of tryptophan residue of serum albumin after binding with the dendrimer-coated magnetite nanoparticles. The extent of the interactions between bovine serum albumin and dendrimer-coated MNPs strongly depends on their surface groups and pH value

  14. Using Language Games as a Way to Investigate Interactional Engagement in Human-Robot Interaction

    DEFF Research Database (Denmark)

    Jensen, L. C.

    2016-01-01

    Social robots are employed in many classrooms and have been shown to aid learning. However, studies show that while schools intend for these robots to be social actors, they are not treated as such by the students. As the social factor is crucial for interactional engagement, this paper discusses...

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

    Science.gov (United States)

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

    2013-07-01

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

  16. Assessing the Effectiveness of Parent-Child Interaction Therapy with Language Delayed Children: A Clinical Investigation

    Science.gov (United States)

    Falkus, Gila; Tilley, Ciara; Thomas, Catherine; Hockey, Hannah; Kennedy, Anna; Arnold, Tina; Thorburn, Blair; Jones, Katie; Patel, Bhavika; Pimenta, Claire; Shah, Rena; Tweedie, Fiona; O'Brien, Felicity; Leahy, Ruth; Pring, Tim

    2016-01-01

    Parent-child interaction therapy (PCIT) is widely used by speech and language therapists to improve the interactions between children with delayed language development and their parents/carers. Despite favourable reports of the therapy from clinicians, little evidence of its effectiveness is available. We investigated the effects of PCIT as…

  17. An Investigation of Human-Computer Interaction Approaches Beneficial to Weak Learners in Complex Animation Learning

    Science.gov (United States)

    Yeh, Yu-Fang

    2016-01-01

    Animation is one of the useful contemporary educational technologies in teaching complex subjects. There is a growing interest in proper use of learner-technology interaction to promote learning quality for different groups of learner needs. The purpose of this study is to investigate if an interaction approach supports weak learners, who have…

  18. Investigating Pedagogical Techniques in Classroom Interactions at a CELTA Training Programme

    Science.gov (United States)

    Rahman, Md Shidur

    2016-01-01

    The study investigated the similarities and dissimilarities of using pedagogical techniques in classroom interactions, taken place whilst teaching a known language and an unknown language in a CELTA training classroom context. For this purpose, the classroom interactions in unknown and known languages were analysed according to the qualitative…

  19. A differential vapor-pressure equipment for investigations of biopolymer interactions

    DEFF Research Database (Denmark)

    Andersen, Kim B; Koga, Y.; Westh, Peter

    2002-01-01

    , particularly a "gas-phase titration" routine for changing the cell composition, makes it effective for the investigations of several types of biopolymer interactions. These include isothermal studies of net affinities such as the adsorption of water to proteins or membranes, the preferential interaction...

  20. Investigating Cross-Device Interaction between a Handheld Device and a Large Display

    DEFF Research Database (Denmark)

    Paay, Jeni; Raptis, Dimitrios; Kjeldskov, Jesper

    2017-01-01

    There is a growing interest in HCI research to explore cross-device interaction, giving rise to an interest in different approaches facilitating interaction between handheld devices and large displays. Contributing to this, we have investigated the use of four existing approaches combining touch...

  1. Interactivity effects in social media marketing on brand engagement: an investigation of underlying mechanisms

    NARCIS (Netherlands)

    Antheunis, M.L.; van Noort, G.; Eisend, M.; Langner, T.

    2011-01-01

    Although, SNS advertising spending increases, research on SNS campaigning is still underexposed. First, this study aims to investigate the effect of SNS campaign interactivity on the receivers brand engagement, taking four underlying mechanisms into account (brand identification, campaign

  2. Electrochemical and calorimetric investigation of interaction of novel biscationic anticancer agents with DNA

    OpenAIRE

    Silva, Láuris Lucia da; Donnici, Claudio Luis; Lopes, Júlio César Dias; Goulart, Marília Oliveira Fonseca; Abreu, Fabiane Caxico de; Paula, Francine Santos de; Bravo, Carlos E. Salas; Santoro, Marcelo Matos; Denadai, Ângelo Márcio Leite; Santos, Alexandre Martins Costa; Montanari, Carlos Alberto

    2012-01-01

    ELECTROCHEMICAL AND CALORIMETRIC INVESTIGATION OF INTERACTION OF NOVEL BISCATIONIC ANTICANCER AGENTS WITH DNA. Biscationic amidines bind in the DNA minor groove and present biological activity against a range of infectious diseases. Two new biscationic compounds (bis-alpha,omega-S-thioureido, amino and sulfide analogues) were synthesized in good yields and fully characterized, and their interaction with DNA was also investigated. Isothermal titration calorimetry (ITC) was used to measure the ...

  3. Investigating conversational dynamics: Interactive alignment, Interpersonal synergy, and collective task performance

    DEFF Research Database (Denmark)

    Fusaroli, Riccardo; Tylén, Kristian

    2016-01-01

    This study investigates interpersonal processes underlying dialog by comparing two approaches, interactive alignment and interpersonal synergy, and assesses how they predict collective performance in a joint task. While the interactive alignment approach highlights imitative patterns between...... interlocutors, the synergy approach points to structural organization at the level of the interaction - such as complementary patterns straddling speech-turns and interlocutors. We develop a general, quantitative method to assess lexical, prosodic and speech/pause patterns related to the two approaches...... does not improve the model. This suggests that structural organization at the level of the interaction plays a crucial role in task-oriented conversations, possibly constraining and integrating processes related to alignment....

  4. Investigation of atomic level patterns in protein--small ligand interactions.

    Directory of Open Access Journals (Sweden)

    Ke Chen

    Full Text Available BACKGROUND: Shape complementarity and non-covalent interactions are believed to drive protein-ligand interaction. To date protein-protein, protein-DNA, and protein-RNA interactions were systematically investigated, which is in contrast to interactions with small ligands. We investigate the role of covalent and non-covalent bonds in protein-small ligand interactions using a comprehensive dataset of 2,320 complexes. METHODOLOGY AND PRINCIPAL FINDINGS: We show that protein-ligand interactions are governed by different forces for different ligand types, i.e., protein-organic compound interactions are governed by hydrogen bonds, van der Waals contacts, and covalent bonds; protein-metal ion interactions are dominated by electrostatic force and coordination bonds; protein-anion interactions are established with electrostatic force, hydrogen bonds, and van der Waals contacts; and protein-inorganic cluster interactions are driven by coordination bonds. We extracted several frequently occurring atomic-level patterns concerning these interactions. For instance, 73% of investigated covalent bonds were summarized with just three patterns in which bonds are formed between thiol of Cys and carbon or sulfur atoms of ligands, and nitrogen of Lys and carbon of ligands. Similar patterns were found for the coordination bonds. Hydrogen bonds occur in 67% of protein-organic compound complexes and 66% of them are formed between NH- group of protein residues and oxygen atom of ligands. We quantify relative abundance of specific interaction types and discuss their characteristic features. The extracted protein-organic compound patterns are shown to complement and improve a geometric approach for prediction of binding sites. CONCLUSIONS AND SIGNIFICANCE: We show that for a given type (group of ligands and type of the interaction force, majority of protein-ligand interactions are repetitive and could be summarized with several simple atomic-level patterns. We summarize

  5. Investigation of Family Learned Behavior as Related to Personal Interactions Outside of the Family. Final Report.

    Science.gov (United States)

    Mueller, William J.

    The purpose of the study was to investigate the proposition that subjects under stress will, in their behavioral interaction with significant persons, recapitulate the behaviors learned by the subject within the family constellation. The counseling interview was the model used to investigate the relationship between family learned behavior and…

  6. Exploring Interactions in L2 Blogging: Metadiscourse in Philippine Investigative Journalism Blogs

    Directory of Open Access Journals (Sweden)

    Veronico Nogales Tarrayo

    2014-09-01

    Full Text Available Although metadiscourse has been examined in different genres, such as academic papers, newspaper editorials, school textbooks, and the like, still relatively little attention has been given to the discourse of cyber-genres, particularly blogs or weblogs. Using Hyland’s (2005 model, this paper examined the interactive and the interactional metadiscourse in Philippine investigative journalism blogs where English is used as a second language or L2. The corpus analyzed was taken from 20 investigative journalism blogs published in http://pcij.org/blog/, the official website of the Philippine Center for Investigative Journalism (PCIJ blogs. Based on the findings of the study, it can be inferred that there is much evidence in the use of metadiscourse in Philippine investigative journalism blogs; thus, the use of metadiscourse as an appropriate linguistic resource is supplemental and essential. The data revealed that the investigative journalism blogs have a higher frequency of use of interactive resources, allowing writers to organize and structure their propositions so that the text becomes more coherent to the readers. Among the five categories of interactive resources, the use of evidentials has the highest frequency. As regards the use of interactional resources, hedges are the most frequent. The findings of the study likewise provide pedagogical implications for ESL writing.

  7. Exploring Interactions in L2 Blogging: Metadiscourse in Philippine Investigative Journalism Blogs

    OpenAIRE

    Veronico Nogales Tarrayo

    2014-01-01

    Although metadiscourse has been examined in different genres, such as academic papers, newspaper editorials, school textbooks, and the like, still relatively little attention has been given to the discourse of cyber-genres, particularly blogs or weblogs. Using Hyland’s (2005) model, this paper examined the interactive and the interactional metadiscourse in Philippine investigative journalism blogs where English is used as a second language or L2. The corpus analyzed was taken from 20 invest...

  8. Investigating the Effects of Encumbrance on One-and Two-handed Interactions with Mobile Devices

    OpenAIRE

    Ng, Alexander; Brewster, Stephen; Williamson, John

    2014-01-01

    In this paper, we investigate the effects of encumbrance (carrying typical objects such as shopping bags during interaction) and walking on target acquisition on a touchscreen mobile phone. Users often hold objects and use mobile devices at the same time and we examined the impact encumbrance has on one- and two- handed interactions. Three common input postures were evaluated: two-handed index finger, one-handed preferred thumb and two-handed both thumbs, to assess the effects on performance ...

  9. Expanding Interaction Potentials within Virtual Environments: Investigating the Usability of Speech and Manual Input Modes for Decoupled Interaction

    Directory of Open Access Journals (Sweden)

    Alex Stedmon

    2011-01-01

    Full Text Available Distributed technologies and ubiquitous computing now support users who may be detached or decoupled from traditional interactions. In order to investigate the potential usability of speech and manual input devices, an evaluation of speech input across different user groups and a usability assessment of independent-user and collaborative-user interactions was conducted. Whilst the primary focus was on a formative usability evaluation, the user group evaluation provided a formal basis to underpin the academic rigor of the exercise. The results illustrate that using a speech interface is important in understanding user acceptance of such technologies. From the usability assessment it was possible to translate interactions and make them compatible with innovative input devices. This approach to interaction is still at an early stage of development, and the potential or validity of this interfacing concept is still under evaluation; however, as a concept demonstrator, the results of these initial evaluations demonstrate the potential usability issues of both input devices as well as highlighting their suitability for advanced virtual applications.

  10. Evolutionary Influenced Interaction Pattern as Indicator for the Investigation of Natural Variants Causing Nephrogenic Diabetes Insipidus

    Science.gov (United States)

    Labudde, Dirk

    2015-01-01

    The importance of short membrane sequence motifs has been shown in many works and emphasizes the related sequence motif analysis. Together with specific transmembrane helix-helix interactions, the analysis of interacting sequence parts is helpful for understanding the process during membrane protein folding and in retaining the three-dimensional fold. Here we present a simple high-throughput analysis method for deriving mutational information of interacting sequence parts. Applied on aquaporin water channel proteins, our approach supports the analysis of mutational variants within different interacting subsequences and finally the investigation of natural variants which cause diseases like, for example, nephrogenic diabetes insipidus. In this work we demonstrate a simple method for massive membrane protein data analysis. As shown, the presented in silico analyses provide information about interacting sequence parts which are constrained by protein evolution. We present a simple graphical visualization medium for the representation of evolutionary influenced interaction pattern pairs (EIPPs) adapted to mutagen investigations of aquaporin-2, a protein whose mutants are involved in the rare endocrine disorder known as nephrogenic diabetes insipidus, and membrane proteins in general. Furthermore, we present a new method to derive new evolutionary variations within EIPPs which can be used for further mutagen laboratory investigations. PMID:26180540

  11. Does action planning moderate the intention-habit interaction in the exercise domain? A three-way interaction analysis investigation.

    Science.gov (United States)

    de Bruijn, Gert-Jan; Rhodes, Ryan E; van Osch, Liesbeth

    2012-10-01

    Both habit strength and action planning have been found to moderate the intention-exercise behaviour relationship, but no research exists that has investigated how habit strength and action planning simultaneously influence this relationship. The present study was designed to explore this issue in a prospective sample of undergraduate students (N = 415): action planning, habit strength, intention, attitudes, subjective norms and perceived behavioural control were assessed at baseline and exercise behaviour was assessed 2 weeks later. Both habit strength and action planning moderated the intention-exercise relationship, with stronger relationship at higher levels of planning or habit strength. Decomposing a significant action planning × habit strength × intention interaction showed that the strength of the intention-exercise relationship progressed linearly through levels of action planning and habit strength. These novel results show that action planning strengthens the intention-habit strength interaction in the exercise domain: exercise interventions should therefore focus on simultaneously bolstering action planning and habit strength.

  12. Polymorphisms in ATP-binding cassette transporter genes and interaction with diet and life style factors in relation to colorectal cancer in a Danish prospective case-cohort study

    DEFF Research Database (Denmark)

    Kopp, Tine Iskov; Andersen, Vibeke; Tjonneland, Anne

    2015-01-01

    to assess whether polymorphisms in ABCB1, ABCC2 and ABCG2 were associated with risk of colorectal cancer (CRC) and to investigate gene-environment (dietary factors, smoking and use of non-steroidal anti-inflammatory drugs) and gene-gene interactions between previously studied polymorphisms in IL1B and IL10...

  13. Numerical Investigation of Ultrafast interaction between THz Fields and Crystalline Materials

    DEFF Research Database (Denmark)

    Pedersen, Pernille Klarskov; Clark, Stewart J.; Jepsen, Peter Uhd

    2014-01-01

    We present a quantum - mechanical molecular dynamics investigation of the interaction between strong single - cyc le THz pulses and ionic crystals . We find nonlinearities in the response of the CsI crystals at field strengths higher than 10 MV/cm.......We present a quantum - mechanical molecular dynamics investigation of the interaction between strong single - cyc le THz pulses and ionic crystals . We find nonlinearities in the response of the CsI crystals at field strengths higher than 10 MV/cm....

  14. Video elicitation interviews: a qualitative research method for investigating physician-patient interactions.

    Science.gov (United States)

    Henry, Stephen G; Fetters, Michael D

    2012-01-01

    We describe the concept and method of video elicitation interviews and provide practical guidance for primary care researchers who want to use this qualitative method to investigate physician-patient interactions. During video elicitation interviews, researchers interview patients or physicians about a recent clinical interaction using a video recording of that interaction as an elicitation tool. Video elicitation is useful because it allows researchers to integrate data about the content of physician-patient interactions gained from video recordings with data about participants' associated thoughts, beliefs, and emotions gained from elicitation interviews. This method also facilitates investigation of specific events or moments during interactions. Video elicitation interviews are logistically demanding and time consuming, and they should be reserved for research questions that cannot be fully addressed using either standard interviews or video recordings in isolation. As many components of primary care fall into this category, high-quality video elicitation interviews can be an important method for understanding and improving physician-patient interactions in primary care.

  15. Investigating Cross-Device Interaction between a Handheld Device and a Large Display

    DEFF Research Database (Denmark)

    Paay, Jeni; Raptis, Dimitrios; Kjeldskov, Jesper

    2017-01-01

    and mid-air gestures, pinching, swiping, swinging and flicking. We look specifically at their relative efficiency, effectiveness and accuracy in bi-directional interaction between a smartphone and large display in a point-click context. We report findings from two user studies, which show that swiping......There is a growing interest in HCI research to explore cross-device interaction, giving rise to an interest in different approaches facilitating interaction between handheld devices and large displays. Contributing to this, we have investigated the use of four existing approaches combining touch...... is both most effective, fastest and most accurate, closely followed by swinging. What these two approaches have in common is the ability to keep the pointer steady on the large display, unaffected by concurrent gestures or body movements used to complete the interaction, suggesting...

  16. Estimating Risks and Relative Risks in Case-Base Studies under the Assumptions of Gene-Environment Independence and Hardy-Weinberg Equilibrium

    Science.gov (United States)

    Chui, Tina Tsz-Ting; Lee, Wen-Chung

    2014-01-01

    Many diseases result from the interactions between genes and the environment. An efficient method has been proposed for a case-control study to estimate the genetic and environmental main effects and their interactions, which exploits the assumptions of gene-environment independence and Hardy-Weinberg equilibrium. To estimate the absolute and relative risks, one needs to resort to an alternative design: the case-base study. In this paper, the authors show how to analyze a case-base study under the above dual assumptions. This approach is based on a conditional logistic regression of case-counterfactual controls matched data. It can be easily fitted with readily available statistical packages. When the dual assumptions are met, the method is approximately unbiased and has adequate coverage probabilities for confidence intervals. It also results in smaller variances and shorter confidence intervals as compared with a previous method for a case-base study which imposes neither assumption. PMID:25137392

  17. Guess who? An interactive and entertaining game-like platform for investigating human emotions

    NARCIS (Netherlands)

    Ahmad, M.I.; Tariq, H.; Saeed, M.; Shahid, S.; Krahmer, E.J.

    2011-01-01

    In this paper, we discuss the design and the development of a highly customizable interactive platform ‘Guess Who’, which was designed as a tool for investigating human emotions in a variety of experimental setups. In its essence, ‘Guess Who?’ is actually a game, which includes typical game elements

  18. Bridge-in-a-Backpack(TM) task 3.1: investigating soil - structure interaction - experimental design.

    Science.gov (United States)

    2015-07-01

    This report includes fulfillment of Task 3.1 of a multi-task contract to further enhance concrete filled FRP tubes, or : the Bridge in a Backpack. Task 3 is an investigation of soil-structure interaction for the FRP tubes. Task 3.1 is the : design of...

  19. Subspace in Linear Algebra: Investigating Students' Concept Images and Interactions with the Formal Definition

    Science.gov (United States)

    Wawro, Megan; Sweeney, George F.; Rabin, Jeffrey M.

    2011-01-01

    This paper reports on a study investigating students' ways of conceptualizing key ideas in linear algebra, with the particular results presented here focusing on student interactions with the notion of subspace. In interviews conducted with eight undergraduates, we found students' initial descriptions of subspace often varied substantially from…

  20. An Investigation of Interactive, Dialogue-Based Instruction for Undergraduate Art History

    Science.gov (United States)

    Gioffre, Penelope

    2012-01-01

    This paper explores the feasibility and efficacy of incorporating an interactive, discussion-based instructional approach into an undergraduate art history survey course and investigates effects of the new pedagogic strategy on students' demonstrated comprehension and retention of required content. The action research project follows a systematic…

  1. An Investigation of the Interaction between Resazurin and Cd2+ and ...

    African Journals Online (AJOL)

    NICO

    The voltammetric behaviour of resazurin in the presence of Cd2+ and Zn2+ ions at a hanging mercury drop electrode (HMDE) was investigated by using square wave voltammetry (SWV), cyclic voltammetry (CV) and adsorptive square wave voltammetry. (AdsSWV). The interaction of resazurin with Cd2+ and Zn2+ starts ...

  2. Predicting wind farm wake interaction with RANS: an investigation of the Coriolis force

    DEFF Research Database (Denmark)

    van der Laan, Paul; Hansen, Kurt Schaldemose; Sørensen, Niels N.

    2015-01-01

    A Reynolds-averaged Navier-Stokes code is used to simulate the interaction of two neighboring wind farms. The influence of the Coriolis force is investigated by modeling the atmospheric surface/boundary layer with three different methodologies. The results show that the Coriolis force is negligible...

  3. Forms of memory: Investigating the computational basis of semantic-episodic memory interactions

    NARCIS (Netherlands)

    Neville, D.A.

    2015-01-01

    The present thesis investigated how the memory systems related to the processing of semantic and episodic information combine to generate behavioural performance as measured in standard laboratory tasks. Across a series of behavioural experiment I looked at different types of interactions between

  4. Adolescent peer choice and cigarette smoking: evidence of active gene-environment correlation?

    Science.gov (United States)

    Wills, Amanda G; Carey, Gregory

    2013-10-01

    Both peer groups and genetics have been associated with adolescent smoking behavior. Recently, Loehlin (Loehlin, J. C. (2010). Is there an active gene-environment correlation in adolescent drinking behavior? Behavior Genetics, 40, 447-451) reported that twin differences in alcohol use were associated with differences in the number of common friends. Twins with more common friends were more similar in drinking, but only for dizygotic pairs. Using the same sample as Loehlin's (the National Merit twins), we replicated all of these findings for a composite cigarette smoking measure and for smoking initiation, but not persistence. The pattern of results is most consistent with homophily, or the tendency to associate with individuals that are like oneself. If peer influence occurs in the presence of homophily, then active genotype-environment correlation will be induced.

  5. An investigation of chitosan and sodium dodecyl sulfate interactions in acetic media

    Directory of Open Access Journals (Sweden)

    Petrović Lidija B.

    2016-01-01

    Full Text Available Polymer/surfactant association is a cooperative phenomenon where surfactant binds to the polymer in the form of aggregates, usually through electrostatic or hydrophobic forces. As already known, polyelectrolytes may interact with oppositely charged surfactants through electrostatic attraction that results in polymer/surfactant complex formation. This behavior could be desirable in wide range of application of polymer/surfactant mixtures, such as improving colloid stability, gelling, emulsification and microencapsulation. In the present study surface tension, turbidity, viscosity and electrophoretic mobility measurements were used to investigate interactions of cationic polyelectrolyte chitosan (Ch and oppositely charged anionic surfactant, sodium dodecyl sulfate (SDS, in buffered water. Obtained results show the presence of interactions that lead to Ch/SDS complexes formation at all investigated pH and for all investigated polymer concentrations. Mechanisms of interaction, as well as characteristics of formed Ch/SDS complexes, are highly dependent on their mass ratio in the mixtures, while pH has no significant influence. [Projekat Ministarstva nauke Republike Srbije, br. II46010

  6. Investigation of magnetic interactions in sulfides by means of magnetic resonance

    International Nuclear Information System (INIS)

    Veen, G. van.

    1978-01-01

    Investigations have been designed to gather more information about magnetic pair interactions in sulfides by isomorphic substitution of the magnetic ions in suitable chosen diamagnetic host lattices and measurement of electron spin resonance of coupled pairs and of electron spin resonance or electron nuclear double resonance of the hyperfine interaction due to the nuclei of diamagnetic cations. The greater part of this thesis is devoted to preliminaries of magnetic resonance interpretation and sample selection and preparation. The measurements on the magnetically diluted compounds, which are described, only have an exploratory nature. (Auth.)

  7. Numerical investigations on interactions between tangles of quantized vortices and second sound

    International Nuclear Information System (INIS)

    Penz, H.; Aarts, R.; de Waele, F.

    1995-01-01

    The reconnecting vortex-tangle model is used to investigate the interaction of tangles of quantized vortices with second sound. This interaction can be expressed in terms of an effective line-length density, which depends on the direction of the second-sound wave. By comparing the effective line-length densities in various directions the tangle structure can be examined. Simulations were done for flow channels with square and circular cross sections as well as for slits. The results show that in all these cases the tangles are inhomogeneous in direction as well as in space. The calculated inhomogeneities are in agreement with experiment

  8. Can machines think? Interaction and perspective taking with robots investigated via fMRI.

    Directory of Open Access Journals (Sweden)

    Sören Krach

    Full Text Available BACKGROUND: When our PC goes on strike again we tend to curse it as if it were a human being. Why and under which circumstances do we attribute human-like properties to machines? Although humans increasingly interact directly with machines it remains unclear whether humans implicitly attribute intentions to them and, if so, whether such interactions resemble human-human interactions on a neural level. In social cognitive neuroscience the ability to attribute intentions and desires to others is being referred to as having a Theory of Mind (ToM. With the present study we investigated whether an increase of human-likeness of interaction partners modulates the participants' ToM associated cortical activity. METHODOLOGY/PRINCIPAL FINDINGS: By means of functional magnetic resonance imaging (subjects n = 20 we investigated cortical activity modulation during highly interactive human-robot game. Increasing degrees of human-likeness for the game partner were introduced by means of a computer partner, a functional robot, an anthropomorphic robot and a human partner. The classical iterated prisoner's dilemma game was applied as experimental task which allowed for an implicit detection of ToM associated cortical activity. During the experiment participants always played against a random sequence unknowingly to them. Irrespective of the surmised interaction partners' responses participants indicated having experienced more fun and competition in the interaction with increasing human-like features of their partners. Parametric modulation of the functional imaging data revealed a highly significant linear increase of cortical activity in the medial frontal cortex as well as in the right temporo-parietal junction in correspondence with the increase of human-likeness of the interaction partner (computer

  9. Can machines think? Interaction and perspective taking with robots investigated via fMRI.

    Science.gov (United States)

    Krach, Sören; Hegel, Frank; Wrede, Britta; Sagerer, Gerhard; Binkofski, Ferdinand; Kircher, Tilo

    2008-07-09

    When our PC goes on strike again we tend to curse it as if it were a human being. Why and under which circumstances do we attribute human-like properties to machines? Although humans increasingly interact directly with machines it remains unclear whether humans implicitly attribute intentions to them and, if so, whether such interactions resemble human-human interactions on a neural level. In social cognitive neuroscience the ability to attribute intentions and desires to others is being referred to as having a Theory of Mind (ToM). With the present study we investigated whether an increase of human-likeness of interaction partners modulates the participants' ToM associated cortical activity. By means of functional magnetic resonance imaging (subjects n = 20) we investigated cortical activity modulation during highly interactive human-robot game. Increasing degrees of human-likeness for the game partner were introduced by means of a computer partner, a functional robot, an anthropomorphic robot and a human partner. The classical iterated prisoner's dilemma game was applied as experimental task which allowed for an implicit detection of ToM associated cortical activity. During the experiment participants always played against a random sequence unknowingly to them. Irrespective of the surmised interaction partners' responses participants indicated having experienced more fun and competition in the interaction with increasing human-like features of their partners. Parametric modulation of the functional imaging data revealed a highly significant linear increase of cortical activity in the medial frontal cortex as well as in the right temporo-parietal junction in correspondence with the increase of human-likeness of the interaction partner (computer

  10. Numerical investigation of the wake interaction between two model wind turbines with span-wise offset

    DEFF Research Database (Denmark)

    Sarmast, Sasan; Chivaee, Hamid Sarlak; Ivanell, Stefan

    2014-01-01

    Wake interaction between two model scale wind turbines with span-wise offset is investigated numerically using Large Eddy Simulation (LES) and the results are validated against the experimental data. An actuator line technique is used for modeling the rotor. The investigated setup refers...... to a series of experimental measurements of two model scale turbines conducted by NTNU in low speed wind tunnel in which the two wind turbines are aligned with a span-wise offset resulting in half wake interaction. Two levels of free-stream turbulence are tested, the minimum undisturbed level of about Ti ≈ 0.......23% and a high level of about Ti ≈ 10% using a passive upstream grid. The results show that the rotor characteristics for both rotors are well captured numerically even if the downstream rotor operates into stall regimes. There are however some difficulties in correct prediction of the thrust level...

  11. Finite Element Investigations on the Interaction between a Pile and Swelling Clay

    DEFF Research Database (Denmark)

    Kaufmann, Kristine Lee; Nielsen, Benjaminn Nordahl; Augustesen, Anders Hust

    of Little Belt Clay. The case study involves a circular concrete pile installed in clay immediately after an excavation. The influence of the swelling soil on the soil–pile interaction and the internal pile forces are analysed by solely observing the upper pile part positioned in the swelling zone......This paper aims to investigate the interaction between a pile and a swelling soil modelled as a cohesive soil subjected to unloading. The investigations include analyses of the heave of the excavation level, shear stresses at the soil–pile interface and internal pile forces based on a case study...... of the surrounding soil implies upward shear stresses at the soil–pile interface leading to tensile vertical stresses in the pile. In the current case, they exceed the tensile strength of concrete. The tensile vertical stresses peak after 35-50 years. However, the heave of the soil continues for additional 300 years...

  12. The influence of the magnetoelastic interaction on the magnetocaloric effect in ferrimagnetic systems: a theoretical investigation

    Energy Technology Data Exchange (ETDEWEB)

    Alho, B P; De Oliveira, N A; De Sousa, V S R; Von Ranke, P J [Instituto de Fisica ' Armando Dias Tavares' , Universidade do Estado do Rio de Janeiro-UERJ, Rua Sao Francisco Xavier 524, 20550-013, RJ (Brazil); Plaza, E J R [Departamento de Fisica, Universidade Federal de Sergipe, 49100-000, Sao Cristovao, Sergipe (Brazil); Magnus G Carvalho, A, E-mail: brunoalho@gmail.co [Divisao de Metrologia de Materiais, Instituto Nacional de Metrologia, Normalizacao e Qualidade Industrial (INMETRO), 25250-020, Duque de Caxias, RJ (Brazil)

    2010-12-08

    In this work the magnetocaloric effect is theoretically investigated considering a microscopic model Hamiltonian, which describes a magnetic system formed by two sublattices of different magnetic ions coupled by exchange and magnetoelastic interactions. We analyze systematically several profiles of the ferrimagnetic arrangements that were studied earlier without the magnetoelastic interaction. The influence of changing the magnetoelastic parameters on the magnetization, isothermal entropy change and adiabatic temperature change curves are investigated. Depending on the model parameters, the magnetic system shows a first-order magnetic phase transition leading to high direct and inverse magnetocaloric effect, besides two simultaneous first-order magnetic phase transitions which were predicted. A constant {Delta}S{sub T} = 0.4 J mol{sup -1} K{sup -1} is obtained in the simulated system in a temperature interval of 50 K, around 110 K.

  13. Effect modification, interaction and mediation: an overview of theoretical insights for clinical investigators

    Directory of Open Access Journals (Sweden)

    Corraini P

    2017-06-01

    Full Text Available Priscila Corraini,1 Morten Olsen,1 Lars Pedersen,1 Olaf M Dekkers,1,2 Jan P Vandenbroucke1–3 1Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; 2Leiden University Medical Center, Leiden, the Netherlands; 3Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK Abstract: We revisited the three interrelated epidemiological concepts of effect modification, interaction and mediation for clinical investigators and examined their applicability when using research databases. The standard methods that are available to assess interaction, effect modification and mediation are explained and exemplified. For each concept, we first give a simple “best-case” example from a randomized controlled trial, followed by a structurally similar example from an observational study using research databases. Our explanation of the examples is based on recent theoretical developments and insights in the context of large health care databases. Terminology is sometimes ambiguous for what constitutes effect modification and interaction. The strong assumptions underlying the assessment of interaction, and particularly mediation, require clinicians and epidemiologists to take extra care when conducting observational studies in the context of health care databases. These strong assumptions may limit the applicability of interaction and mediation assessments, at least until the biases and limitations of these assessments when using large research databases are clarified. Keywords: methods, epidemiology, effect modifiers, stratified analyses, health care administrative claims

  14. Investigate Global Chromosomal Interaction by Hi-C in Human Naive CD4 T Cells.

    Science.gov (United States)

    Meng, Xiangzhi; Riley, Nicole; Thompson, Ryan; Sharma, Siddhartha

    2018-01-01

    Hi-C is a methodology developed to reveal chromosomal interactions from a genome-wide perspective. Here, we described a protocol for generating Hi-C sequencing libraries in resting and activated human naive CD4 T cells to investigate activation-induced chromatin structure re-arrangement in T cell activation followed by a section reviewing the general concepts of Hi-C data analysis.

  15. Investigation of the interaction of 85Kr with plants in model experiments

    International Nuclear Information System (INIS)

    Butkus, D.V.; Morkunas, G.S.; Bluvshtejn, D.Yu.; Styro, B.I.

    1988-01-01

    The method of investigation of the interaction of 85 Kr with plants is described using model experiments and data analysis. The dependencies of the coefficient of 85 Kr absorption by plants on the biological structure of the plant, the concentration of krypton-85 in the environment, the method of plant exposition in the environment with the 85 Kr admixture are provided. The time dependencies of 85 Kr desorption from plants are given. 4 refs.; 7 figs.; 3 tabs

  16. Investigation of the interaction of sertraline with calf thymus DNA by spectroscopic methods

    OpenAIRE

    Dorraji,Parisa S.; Jalali,Fahimeh

    2013-01-01

    The interaction of the antidepressant drug, sertraline, with calf thymus double stranded DNA (dsDNA) in physiological buffer (pH 7.4) was investigated by UV-Vis spectrophotometry, spectrofluorimetry, circular dichroism, Fourier transform infrared spectroscopy (FTIR), viscosity measurements and DNA melting studies. The absorption spectra of the drug with DNA showed a hyperchromic effect. Using Hoechst reagent as a fluorescence probe, quenching of the emission peak occurred in the DNA-Hoechst m...

  17. Spectrophotometric investigation of uranyl interaction with orthosilicic acid and polymeric silicon acids in aqueous solutions

    International Nuclear Information System (INIS)

    Yusov, A.B.; Fedoseev, A.M.

    2005-01-01

    Interaction of uranyl ion with orthosilicic acid and polymeric silicic acids is investigated using spectrophotometry. Equilibrium constant of UO 2 2+ + Si(OH) 4 = UO 2 OSi(OH) 3 + + H + reaction is lg K=-2.56±0.09 in solutions with ionic strength I=0.1-0.2. Stability constant of UO 2 OSi(OH) 3 + complex is determined [ru

  18. Intermolecular interactions in binary system of 1-methylimidazole with methanol: A volumetric and theoretical investigation

    Science.gov (United States)

    Guo, Chang; Fang, Hui; Huang, Rong-Yi; Xu, Heng; Wu, Gen-Hua; Ye, Shi-Yong

    2013-11-01

    The Letter demonstrates an experimental and computational investigation of intermolecular interactions in binary system of 1-methylimidazole (MeIm) with methanol. The densities of binary system were measured at T = 288.15-323.15 K, and the values of excess molar volumes were obtained as a function of composition at each temperature. The experimental results indicate the formation of strong cross-associated complex in the binary system. Meanwhile, the nature of hydrogen bond of the associated complexes was explored based on theoretical calculations. In addition, the changes of thermodynamic properties from the monomers to cross-associated complex were also investigated.

  19. Ageing, genes, environment and epigenetics: what twin studies tell us now, and in the future.

    Science.gov (United States)

    Steves, Claire Joanne; Spector, Timothy D; Jackson, Stephen H D

    2012-09-01

    Compared with younger people, older people are much more variable in their organ function, and these large individual differences contribute to the complexity of geriatric medicine. What determines this variability? Is it due to the accumulation of different life experiences, or because of the variation in the genes we are born with, or an interaction of both? This paper reviews key findings from ageing twin cohorts probing these questions. Twin studies are the perfect natural experiment to dissect out genes and life experiences. We discuss the paradox that ageing is strongly determined by heritable factors (an influence that often gets stronger with time), yet longevity and lifespan seem not to be so heritable. We then focus on the intriguing question of why DNA sequence-identical twins might age differently. Animal studies are increasingly showing that epigenetic modifications occurring in early development and adulthood, might be key to ageing phenomena but this is difficult to investigate longitudinally in human populations, due to ethical problems of intervention and long lifespan. We propose that identical twin studies using new and existing cohorts may be useful human models in which to investigate the interaction between the environment and genetics, mediated by epigenetic modifications.

  20. Interaction of von Willebrand factor domains with collagen investigated by single molecule force spectroscopy

    Science.gov (United States)

    Posch, Sandra; Obser, Tobias; König, Gesa; Schneppenheim, Reinhard; Tampé, Robert; Hinterdorfer, Peter

    2018-03-01

    von Willebrand factor (VWF) is a huge multimeric protein that plays a key role in primary hemostasis. Sites for collagen binding, an initial event of hemostasis, are located in the VWF-domains A1 and A3. In this study, we investigated single molecule interactions between collagen surfaces and wild type VWF A1A2A3 domain constructs, as well as clinically relevant VWF A3 domain point mutations, such as p.Ser1731Thr, p.Gln1734His, and p.His1786Arg. For this, we utilized atomic force microscopy based single molecular force spectroscopy. The p.Ser1731Thr mutant had no impact on the VWF-collagen type III and VI interactions, while the p.Gln1734His and p.His1786Arg mutants showed a slight increase in bond stability to collagen type III. This effect probably arises from additional hydrogen bonds that come along with the introduction of these mutations. Using the same mutants, but collagen type VI as a binding partner, resulted in a significant increase in bond stability. VWF domain A1 was reported to be essential for the interaction with collagen type VI and thus our findings strengthen the hypothesis that the VWF A1 domain can compensate for mutations in the VWF A3 domain. Additionally, our data suggest that the mutations could even stabilize the interaction between VWF and collagen without shear. VWF-collagen interactions seem to be an important system in which defective interactions between one VWF domain and one type of collagen can be compensated by alternative binding events.

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

    Science.gov (United States)

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

    2016-01-01

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

  2. Investigating interactional competence using video recordings in ESL classrooms to enhance communication

    Science.gov (United States)

    Krishnasamy, Hariharan N.

    2016-08-01

    Interactional competence, or knowing and using the appropriate skills for interaction in various communication situations within a given speech community and culture is important in the field of business and professional communication [1], [2]. Similar to many developing countries in the world, Malaysia is a growing economy and undergraduates will have to acquire appropriate communication skills. In this study, two aspects of the interactional communicative competence were investigated, that is the linguistic and paralinguistic behaviors in small group communication as well as conflict management in small group communication. Two groups of student participants were given a problem-solving task based on a letter of complaint. The two groups of students were video recorded during class hours for 40 minutes. The videos and transcription of the group discussions were analyzed to examine the use of language and interaction in small groups. The analysis, findings and interpretations were verified with three lecturers in the field of communication. The results showed that students were able to accomplish the given task using verbal and nonverbal communication. However, participation was unevenly distributed with two students talking for less than a minute. Negotiation was based more on alternative views and consensus was easily achieved. In concluding, suggestions are given on ways to improve English language communication.

  3. Investigation of the interaction of deltamethrin (DM) with human serum albumin by multi-spectroscopic method

    Science.gov (United States)

    Wang, Jiaman; Ma, Liang; Zhang, Yuhao; Jiang, Tao

    2017-02-01

    The interaction of Deltamethrin (DM) with human serum albumin (HSA) under the condition of simulating human blood pH environment (pH = 7.4) was investigated by fluorescence, UV-Vis absorbance and circular dichroism (CD) spectroscopy. It was shown that DM was a static quencher of HSA. The binding constants (Ka) are 3.598 × 104 L mol-1 (25 °C); the thermodynamic parameters (ΔH = -3.269 × 104 kJ mol-1, ΔS = -22.81 kJ mol-1 k-1, ΔG = -25889.8 kJ mol-1) obtained with the thermodynamic equation. The hydrogen bond and Vander Waals were the main driving force. The effect of DM on the conformation of HSA was observed by three-dimensional (3D) fluorescence and circular dichroism spectra, indicating that the interaction between DM and HSA was achieved through the binding of DM with the tryptophan and tyrosine residues of HSA. The study on the interaction of DM and Bovine Serum Albumin (BSA) was researched and compared. Difference exists in the interactions of with each of the serum albumins. We will verify and supplement that DM residue in animals and human metabolism, toxicology and other mechanisms are different.

  4. A method for investigating protein-protein interactions related to Salmonella typhimurium pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chowdhury, Saiful M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Shi, Liang [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Yoon, Hyunjin [Dartmouth College, Hanover, NH (United States); Ansong, Charles [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Rommereim, Leah M. [Dartmouth College, Hanover, NH (United States); Norbeck, Angela D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Auberry, Kenneth J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Moore, R. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Adkins, Joshua N. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Heffron, Fred [Oregon Health and Science Univ., Portland, OR (United States); Smith, Richard D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2009-02-10

    We successfully modified an existing method to investigate protein-protein interactions in the pathogenic bacterium Salmonella typhimurium (STM). This method includes i) addition of a histidine-biotin-histidine tag to the bait proteins via recombinant DNA techniques; ii) in vivo cross-linking with formaldehyde; iii) tandem affinity purification of bait proteins under fully denaturing conditions; and iv) identification of the proteins cross-linked to the bait proteins by liquid-chromatography in conjunction with tandem mass-spectrometry. In vivo cross-linking stabilized protein interactions permitted the subsequent two-step purification step conducted under denaturing conditions. The two-step purification greatly reduced nonspecific binding of non-cross-linked proteins to bait proteins. Two different negative controls were employed to reduce false-positive identification. In an initial demonstration of this approach, we tagged three selected STM proteins- HimD, PduB and PhoP- with known binding partners that ranged from stable (e.g., HimD) to transient (i.e., PhoP). Distinct sets of interacting proteins were identified with each bait protein, including the known binding partners such as HimA for HimD, as well as anticipated and unexpected binding partners. Our results suggest that novel protein-protein interactions may be critical to pathogenesis by Salmonella typhimurium. .

  5. Diabetes, markers of brain pathology and cognitive function: the Age, Gene/Environment Susceptibility-Reykjavik Study.

    Science.gov (United States)

    Qiu, Chengxuan; Sigurdsson, Sigurdur; Zhang, Qian; Jonsdottir, Maria K; Kjartansson, Olafur; Eiriksdottir, Gudny; Garcia, Melissa E; Harris, Tamara B; van Buchem, Mark A; Gudnason, Vilmundur; Launer, Lenore J

    2014-01-01

    We investigated whether, and the extent to which, vascular and degenerative lesions in the brain mediate the association of diabetes with poor cognitive performance. This cross-sectional study included 4,206 participants (age > 65 years; 57.8% women) of the Age, Gene/Environment Susceptibility-Reykjavik Study. Data were collected through interview, clinical examination, psychological testing, and laboratory tests. The composite scores on memory, information-processing speed, and executive function were derived from a cognitive test battery. Markers of cerebral macrovascular (cortical infarcts), microvascular (subcortical infarcts, cerebral microbleeds, and higher white matter lesion volume), and neurodegenerative (lower gray matter, normal white matter, and total brain tissue volumes) processes were assessed on magnetic resonance images. Mediation models were employed to test the mediating effect of brain lesions on the association of diabetes with cognitive performance controlling for potential confounders. There were 462 (11.0%) persons with diabetes. Diabetes was significantly associated with lower scores on processing speed and executive function, but not with memory function. Diabetes was significantly associated with all markers of brain pathology. All of these markers were significantly associated with lower scores on memory, processing speed, and executive function. Formal mediation tests suggested that markers of cerebrovascular and degenerative pathology significantly mediated the associations of diabetes with processing speed and executive function. Diabetes is associated with poor performance on cognitive tests of information-processing speed and executive function. The association is largely mediated by markers of both neurodegeneration and cerebrovascular disease. Older people with diabetes should be monitored for cognitive problems and brain lesions. © 2013 American Neurological Association.

  6. Theoretical investigation of interaction between the set of ligands and α7 nicotinic acetylcholine receptor

    Science.gov (United States)

    Glukhova, O. E.; Prytkova, T. R.; Shmygin, D. S.

    2016-03-01

    Nicotinic acetylcholine receptors (nAChRs) are neuron receptor proteins that provide a transmission of nerve impulse through the synapses. They are composed of a pentametric assembly of five homologous subunits (5 α7 subunits for α7nAChR, for example), oriented around the central pore. These receptors might be found in the chemical synapses of central and peripheral nervous system, and also in the neuromuscular synapses. Transmembrane domain of the one of such receptors constitutes ion channel. The conductive properties of ion channel strongly depend on the receptor conformation changes in the response of binding with some molecule, f.e. acetylcholine. Investigation of interaction between ligands and acetylcholine receptor is important for drug design. In this work we investigate theoretically the interaction between the set of different ligands (such as vanillin, thymoquinone, etc.) and the nicotinic acetylcholine receptor (primarily with subunit of the α7nAChR) by different methods and packages (AutodockVina, GROMACS, KVAZAR, HARLEM, VMD). We calculate interaction energy between different ligands in the subunit using molecular dynamics. On the base of obtained calculation results and using molecular docking we found an optimal location of different ligands in the subunit.

  7. Investigation of Interactions between DNA and Nuclear Receptors: A Review of the Most Used Methods

    Directory of Open Access Journals (Sweden)

    Juliana Fattori

    2014-10-01

    Full Text Available Nuclear receptors (NRs comprise a superfamily of proteins modulated by ligands that regulate the expression of target genes. These proteins share a multidomain structure harboring an N-terminal domain, a highly conserved DNA binding domain, and a ligand binding domain, which has ligand dependent activation function. They play key roles in development, metabolism, and physiology being closely related to diseases. Most of the knowledge about this superfamily emerges from investigations on new ligands and are mostly centered in the ligand binding domain. However, more investigation focusing on interactions between DNA and DNA binding domain is necessary to shed light on important roles of NRs' participation in transcriptional mechanisms and in specific genes network. Here, our goal is to discuss some nuances of NRs-DNA interaction, describing details of the most used techniques in this sort of study, such as gel shift (EMSA, DNA footprinting, reporter gene assay, ChIP-Seq, 3C, and fluorescence anisotropy. Additionally, we aim to provide tools, presenting advantages and disadvantages of these common methods, when choosing the most suitable one to study NRs-DNA interactions to answer specific questions.

  8. Well-Controlled Cell-Trapping Systems for Investigating Heterogeneous Cell-Cell Interactions.

    Science.gov (United States)

    Kamiya, Koki; Abe, Yuta; Inoue, Kosuke; Osaki, Toshihisa; Kawano, Ryuji; Miki, Norihisa; Takeuchi, Shoji

    2018-03-01

    Microfluidic systems have been developed for patterning single cells to study cell-cell interactions. However, patterning multiple types of cells to understand heterogeneous cell-cell interactions remains difficult. Here, it is aimed to develop a cell-trapping device to assemble multiple types of cells in the well-controlled order and morphology. This device mainly comprises a parylene sheet for assembling cells and a microcomb for controlling the cell-trapping area. The cell-trapping area is controlled by moving the parylene sheet on an SU-8 microcomb using tweezers. Gentle downward flow is used as a driving force for the cell-trapping. The assembly of cells on a parylene sheet with round and line-shaped apertures is demonstrated. The cell-cell contacts of the trapped cells are then investigated by direct cell-cell transfer of calcein via connexin nanopores. Finally, using the device with a system for controlling the cell-trapping area, three different types of cells in the well-controlled order are assembled. The correct cell order rate obtained using the device is 27.9%, which is higher than that obtained without the sliding parylene system (0.74%). Furthermore, the occurrence of cell-cell contact between the three cell types assembled is verified. This cell-patterning device will be a useful tool for investigating heterogeneous cell-cell interactions. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Unsteady Aerodynamic Investigation of the Propeller-Wing Interaction for a Rocket Launched Unmanned Air Vehicle

    Directory of Open Access Journals (Sweden)

    G. Q. Zhang

    2013-01-01

    Full Text Available The aerodynamic characteristics of propeller-wing interaction for the rocket launched UAV have been investigated numerically by means of sliding mesh technology. The corresponding forces and moments have been collected for axial wing placements ranging from 0.056 to 0.5D and varied rotating speeds. The slipstream generated by the rotating propeller has little effects on the lift characteristics of the whole UAV. The drag can be seen to remain unchanged as the wing's location moves progressively closer to the propeller until 0.056D away from the propeller, where a nearly 20% increase occurred sharply. The propeller position has a negligible effect on the overall thrust and torque of the propeller. The efficiency affected by the installation angle of the propeller blade has also been analyzed. Based on the pressure cloud and streamlines, the vortices generated by propeller, propeller-wing interaction, and wing tip have also been captured and analyzed.

  10. Geomechanical analyses to investigate wellbore/mine interactions in the Potash Enclave of Southeastern New Mexico.

    Energy Technology Data Exchange (ETDEWEB)

    Ehgartner, Brian L.; Bean, James E. (Sandia Staffing Alliance, LLC, Albuquerque, NM); Arguello, Jose Guadalupe, Jr.; Stone, Charles Michael

    2010-04-01

    Geomechanical analyses have been performed to investigate potential mine interactions with wellbores that could occur in the Potash Enclave of Southeastern New Mexico. Two basic models were used in the study; (1) a global model that simulates the mechanics associated with mining and subsidence and (2) a wellbore model that examines the resulting interaction impacts on the wellbore casing. The first model is a 2D approximation of a potash mine using a plane strain idealization for mine depths of 304.8 m (1000 ft) and 609.6 m (2000 ft). A 3D wellbore model then considers the impact of bedding plane slippage across single and double cased wells cemented through the Salado formation. The wellbore model establishes allowable slippage to prevent casing yield.

  11. Spectroscopic investigation of the interactions of carbofuran and amitrol herbicides with human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Tunç, Sibel, E-mail: stunc@akdeniz.edu.tr; Duman, Osman, E-mail: osmanduman@akdeniz.edu.tr; Soylu, İnanç; Kancı Bozoğlan, Bahar

    2014-07-01

    In this study, various spectroscopic techniques including UV absorption, fluorescence and synchronous fluorescence spectroscopy were used to examine the interactions of carbofuran (CF) and amitrol (AMT) herbicides with human serum albumin (HSA). The results of spectroscopic experiments illustrated that CF was bound by HSA, on the other hand there was no interaction between HSA and AMT molecules. In HSA–CF system, static quenching mechanism was responsible for the fluorescence quenching of HSA. The Stern–Volmer constant and binding constant decreased with increasing temperature. This means that an increase in temperature reduces the stability of HSA–CF complex. In HSA–CF system, the number of binding site on protein was found to be one. From the thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS) were calculated as −22.30 kJ mol{sup −1} and −10.70 J mol{sup −1} K{sup −1}, respectively, which indicated that the interaction forces between HSA and CF molecules were mainly hydrogen bonding and van der Waals forces. The conformational change in the protein structure was investigated by synchronous fluorescence spectroscopy. According to the results of synchronous fluorescence analysis, there was a change in the protein structure owing to the interaction of CF with HSA. - Highlights: • UV absorption, fluorescence and synchronous fluorescence measurements confirm the formation of HSA–CF complex. • The formation of HSA–CF complex involves both hydrogen bonding and van der Waals forces. • There is no interaction between HSA and AMT molecules. • Binding constants, numbers of binding sites and thermodynamic parameters have been calculated. • The binding of CF to HSA changes the conformational structure of protein.

  12. Investigating the context-dependency of plant-soil-AMF-microbe interactions along a pollution gradient

    Science.gov (United States)

    Glassman, S. I.; Casper, B. B.

    2010-12-01

    Background/Question/Methods Investigating how arbuscular mycorrhizal fungi (AMF)-plant interactions vary with edaphic conditions provides an opportunity to test the context-dependency of interspecific interactions, which is currently recognized as a major avenue of future research. We study plant-mycorrhiza symbiotic relationships along a gradient of heavy metal contamination at a recently revegetated “Superfund” site on Blue Mountain, in Palmerton, Pennsylvania. We investigated the interactions involving the native mycorrhizal fungi, non-mycorrhizal soil microbes, soil, and two plant species (a C3 and C4 grass) along the contamination gradient. The native C3 study species Deschampsia flexuosa, is dominant along the gradient and established naturally; the C4 Sorghastrum nutans, is native to Pennsylvania but not to the site and was introduced during restoration. Because C4 grasses are obligate mycotrophs, we expected S. nutans to have a different effect on and response to the soil symbiont community than the C3 grass. We carried out a full factorial greenhouse experiment using field-collected seeds of D. flexuosa and S. nutans, soil, AMF spores, and non-mycorrhizal microbes from both high and low contaminated ends of the gradient. After 11 weeks of growth in the greenhouses, we harvested above and belowground plant biomass, and quantified AMF root colonization and AMF sporulation. Results/Conclusions Our results indicate that context-dependent function is an important factor driving specific ecological interactions between plants and soil microbes. We found that soil origin significantly affected plant growth. Plants from both species grew much larger in soil from low contaminated (LC) origin than high contaminated (HC) origin. Furthermore, we found that the efficacy of AMF in promoting plant growth depended on AMF origin. Specifically, AMF from LC improved growth of D. flexuosa best in either soil background and improved survivorship of S. nutans in HC soil

  13. Experimental Investigation of the Interaction of Blast Waves Generated by Exploding Wires using Background Oriented Schlieren

    Science.gov (United States)

    Gross, Jonathan; Eliasson, Veronica

    2015-11-01

    Work has been performed to experimentally characterize the interaction of a multiple blast waves. The blast waves were generated using an exploding wire system. This system can store up to 400 J of energy in a high voltage capacitor bank. By discharging the capacitors through wires of a diameter of 150 μm it was possible to produce blast waves with Mach numbers as high as 2.3 at a distance of 40 mm from the center of the blast. A parametric study was performed to measure the behavior of the shocks for a variety of wire thicknesses, voltages, and separation distances. Additionally a background oriented schlieren system was used to quantify the flowfield behind the shocks. The interaction of the shocks featured expected nonlinear phenomena such as the presence of Mach stems, and showed good agreement with results in the shock wave literature. This investigation lays the groundwork for subsequent research that will use exploding wires to experimentally reproduce conditions investigated numerically, in which the effects of multiple converging blast waves on a central target were investigated.

  14. Molecular dynamics investigation of nanoscale substrate topography and its interaction with liquids

    Science.gov (United States)

    Cordeiro Rodrigues, Jhonatam

    Nanotechnology has been presenting successful applications in several areas. However, experimentation with nanoscale materials is costly and limited in analysis capability. This research investigates the use of molecular dynamics (MD) simulations to model and study nanomaterials and manufacturing processes. MD simulations are employed to reduce cost, optimize design, increase productivity and allow for the investigation of material interactions not yet observable through experimentation. This work investigates the interaction of water with substrates at the nanoscale. The effect of temperature, droplet impingement velocities and size, as well as substrate material, are investigated at the nanoscale. Several substrate topography designs were modeled to reveal their influence on the wettability of the substrate. Nanoscale gold and silicon substrates are more hydrophilic at higher temperatures than at room temperature. The reduction in droplet diameter increases its wettability. High impingement velocity of droplets does not influence final wettability of substrates but induces higher diffusion rates of droplets in a heated environment. Droplets deposited over a gradient of surface exposure presents spontaneous movement. The Leidenfrost effect was investigated at the nanoscale. Droplets of 4 and 10nm in diameter presented behaviors pertinent to the Leidenfrost effect at 373K, significantly lower than at micro scale and of potential impact to the field. Topographical features were manipulated using superhydrophobic coating resulting in micro whiskers. Nanoimprint lithography (NIL) was used to manufacture substrate topographies at the nanoscale. Water droplets were deposited on the substrates and their wettability was measured using droplet contact angles. Lower surface area exposure resulted in higher contact angles. The experimental relationships between surface topography and substrate wettability were used to validate the insights gained from MD simulations for

  15. Investigation of Anti-Icing Chemicals and Their Interactions with Pavement Concretes

    OpenAIRE

    Olek, Jan; Janusz, Anna; Jain, Jitendra; Ashraf, Warda

    2013-01-01

    The interactions of concrete specimens (both plain and with fly ash addition) with six different deicers was investigated by exposing them to solutions of sodium chloride (NaCl), magnesium chloride (MgCl2), calcium chloride (CaCl2), and the combinations of: sodium chloride with magnesium chloride (NaCl + MgCl2), sodium chloride with calcium chloride (NaCl + CaCl2), sodium chloride with agricultural by product – Ice Ban® (NaCl + Ice Ban®). In addition, control group of specimens was exposed to...

  16. Investigation of sodium concrete interaction and the effect of different by-products

    International Nuclear Information System (INIS)

    Schultheiss, G.F.; Fritzke, H.W.

    1983-01-01

    For heat transfer at temperatures of more than 770 K sodium or sodium-potassium alloy is used in fast breeder reactors or solar power plants. In case of leakage of hot liquid metal concrete is loaded thermally and chemically. The interaction of sodium with several concretes of different composition has been investigated experimentally and theoretically. Especially the quartz content of concrete has a significant influence on reaction behavior. Quartz-containing concrete specimens were severely damaged at temperatures of more than 600 0 C. Computer code modelling shows good agreement with experiments. (orig.) [de

  17. Investigation of the molecular level interactions between mucins and food proteins: Spectroscopic, tribological and rheological studies

    DEFF Research Database (Denmark)

    Celebioglu, Hilal Yilmaz

    The thesis investigated the structure and molecular-level interaction of β-lactoglobulin (BLG) and mucins, representing major components of the dairy products and saliva/digestion systems, respectively. Mucins are long glycoprotein molecules responsible for the gel nature of the mucous layer covers...... submaxillary mucin (BSM), a major salivary protein, were studied using high and low field Nuclear Magnetic Resonance (NMR), Dynamic Light Scattering (DLS), and Circular Dichroism (CD) spectroscopy. The zeta potentials of the proteins were also measured to provide information on the role of electrostatic forces...

  18. Investigation of the proton-neutron interaction by high-precision nuclear mass measurements

    CERN Multimedia

    Savreux, R P; Akkus, B

    2007-01-01

    We propose to measure the atomic masses of a series of short-lived nuclides, including $^{70}$Ni, $^{122-130}$Cd, $^{134}$Sn, $^{138,140}$Xe, $^{207-210}$Hg, and $^{223-225}$Rn, that contribute to the investigation of the proton-neutron interaction and its role in nuclear structure. The high-precision mass measurements are planned for the Penning trap mass spectrometer ISOLTRAP that reaches the required precision of 10 keV in the nuclear mass determination.

  19. Investigation on the toxic interaction of typical plasticizers with calf thymus DNA

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xiaojing [School of Environmental Science and Engineering, China–America CRC for Environment & Health, Shandong University, 27# Shanda South Road, Jinan 250100, Shandong Province (China); Zong, Wansong, E-mail: gaocz@sdu.edu.cn [College of Population, Resources and Environment, Shandong Normal University, 88# East Wenhua Road, Jinan 250014 (China); Liu, Chunguang; Liu, Yang [School of Environmental Science and Engineering, China–America CRC for Environment & Health, Shandong University, 27# Shanda South Road, Jinan 250100, Shandong Province (China); Gao, Canzhu, E-mail: rutaoliu@sdu.edu.cn [School of Environmental Science and Engineering, China–America CRC for Environment & Health, Shandong University, 27# Shanda South Road, Jinan 250100, Shandong Province (China); Liu, Rutao [School of Environmental Science and Engineering, China–America CRC for Environment & Health, Shandong University, 27# Shanda South Road, Jinan 250100, Shandong Province (China)

    2015-05-15

    The interactions of typical plasticizers dimethyl phthalate (DMP), diethyl phthalate (DEP) and dibutyl phthalate (DBP) with calf thymus DNA (ctDNA) were investigated by fluorescence spectroscopic techniques and molecular modeling. Experimental results indicated that the characteristic fluorescence intensity of phthalic acid rose with the increase of DNA concentration; while the characteristic fluorescence intensities of plasticizers decreased with the increase of DNA concentration. Experiments on native and denatured DNA determined that plasticizers interacted with DNA both in groove and electrostatic binding mode. The molecular modeling results further illustrated that there is groove binding between them; hydrogen bonding and Van der Waals interactions were the main forces. With the extension of branched-chains, the binding effects between plasticizers and DNA were weakened, which could be related to the increased steric hindrance. - Highlights: • This work established the binding mode of plasticizers with DNA on molecular level. • The mechanism was explored by fluorescence spectroscopic and molecular docking methods. • There are two kinds of binding mode between DMP, DEP, DBP and DNA, electrostatic and groove. • With the branched chain extension, the binding effect of plasticizers and DNA has been weakened.

  20. The interactions between lipase and pyridinium ligands investigated by electrochemical and spectrophotometric methods

    Directory of Open Access Journals (Sweden)

    Simona Patriche

    2016-04-01

    Full Text Available The interaction between pyridinium ligands derived from 4,4’-bipyridine (N,N’-bis(p-bromophenacyl-4,4’-bipyridinium dibromide – Lr and (N,N’-bis(p-bromophenacyl-1,2-bis (4-pyridyl ethane dibromide – Lm with lipase enzyme was evaluated. The stability of the pyridinium ligands, having an essential role in biological systems, in 0.1 M KNO3 as supporting electrolyte is influenced by the lipase concentration added. The pH and conductometry measurements in aqueous solution suggest a rapid ionic exchange process. The behavior of pyridinium ligands in the presence of lipase is investigated by cyclic voltammetry and UV/Vis spectroscopy, which indicated bindings and changes from the interaction between them. The voltammograms recorded on the glassy carbon electrode showed a more intense electronic transfer for the Lr interaction with lipase compared to Lm, which is due to the absence of mobile ethylene groups from Lr structure.

  1. Interaction of ZnS nanoparticles with flavins and glucose oxidase: A fluorimetric investigation

    International Nuclear Information System (INIS)

    Chatterjee, Anindita; Priyam, Amiya; Ghosh, Debasmita; Mondal, Somrita; Bhattacharya, Subhash C.; Saha, Abhijit

    2012-01-01

    Interactions of luminescence, water soluble ZnS nanoparticles (NPs) with flavins and glucose oxidase have been thoroughly investigated through optical spectroscopy. The photoluminescence of ZnS nanoparticles was quenched severely (∼60%) by riboflavin while other flavins such as flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) show quenching to different extents under analogous conditions. However, interestingly no effect in luminescence intensity of ZnS NPs was observed with protein bound flavins such as in glucose oxidase. Fluorescence lifetime measurement confirmed the quenching to be static in nature. Scavenging of photo-generated electron of ZnS nanoparticles by the flavin molecules may be attributed to the decrease in luminescence intensity. Quenching of ZnS nanoparticles with flavins follows the linear Stern–Volmer plot. The Stern–Volmer constants decreased in the following order: K S−V (Riboflavin)> K S−V (FAD)> K S−V (FMN). This interaction study could generate useful protocol for the fluorimetric determination of riboflavin (vitamin B 2 ) content and also riboflavin status in biological systems. - Highlights: ► Unique interaction specificity of ZnS nanoparticles with flavins has been explored. ► Unlike protein-bound flavin, fluorescence of free flavins was quenched by ZnS nanoparticles. ► FMN and FAD show quenching to different extents under analogous conditions. ► Fluorescence lifetime measurement confirmed the quenching to be static in nature. ► This study is useful for probing riboflavin in biological systems.

  2. Investigation of the pH-dependence of dye-doped protein-protein interactions.

    Science.gov (United States)

    Nudelman, Roman; Gloukhikh, Ekaterina; Rekun, Antonina; Richter, Shachar

    2016-11-01

    Proteins can dramatically change their conformation under environmental conditions such as temperature and pH. In this context, Glycoprotein's conformational determination is challenging. This is due to the variety of domains which contain rich chemical characters existing within this complex. Here we demonstrate a new, straightforward and efficient technique that uses the pH-dependent properties of dyes-doped Pig Gastric Mucin (PGM) for predicting and controlling protein-protein interaction and conformation. We utilize the PGM as natural host matrix which is capable of dynamically changing its conformational shape and adsorbing hydrophobic and hydrophilic dyes under different pH conditions and investigate and control the fluorescent properties of these composites in solution. It is shown at various pH conditions, a large variety of light emission from these complexes such as red, green and white is obtained. This phenomenon is explained by pH-dependent protein folding and protein-protein interactions that induce different emission spectra which are mediated and controlled by means of dye-dye interactions and surrounding environment. This process is used to form the technologically challenging white light-emitting liquid or solid coating for LED devices. © 2016 The Protein Society.

  3. Integration of statistical modeling and high-content microscopy to systematically investigate cell-substrate interactions.

    Science.gov (United States)

    Chen, Wen Li Kelly; Likhitpanichkul, Morakot; Ho, Anthony; Simmons, Craig A

    2010-03-01

    Cell-substrate interactions are multifaceted, involving the integration of various physical and biochemical signals. The interactions among these microenvironmental factors cannot be facilely elucidated and quantified by conventional experimentation, and necessitate multifactorial strategies. Here we describe an approach that integrates statistical design and analysis of experiments with automated microscopy to systematically investigate the combinatorial effects of substrate-derived stimuli (substrate stiffness and matrix protein concentration) on mesenchymal stem cell (MSC) spreading, proliferation and osteogenic differentiation. C3H10T1/2 cells were grown on type I collagen- or fibronectin-coated polyacrylamide hydrogels with tunable mechanical properties. Experimental conditions, which were defined according to central composite design, consisted of specific permutations of substrate stiffness (3-144 kPa) and adhesion protein concentration (7-520 microg/mL). Spreading area, BrdU incorporation and Runx2 nuclear translocation were quantified using high-content microscopy and modeled as mathematical functions of substrate stiffness and protein concentration. The resulting response surfaces revealed distinct patterns of protein-specific, substrate stiffness-dependent modulation of MSC proliferation and differentiation, demonstrating the advantage of statistical modeling in the detection and description of higher-order cellular responses. In a broader context, this approach can be adapted to study other types of cell-material interactions and can facilitate the efficient screening and optimization of substrate properties for applications involving cell-material interfaces. Copyright 2009 Elsevier Ltd. All rights reserved.

  4. Polyphilic Interactions as Structural Driving Force Investigated by Molecular Dynamics Simulation (Project 7

    Directory of Open Access Journals (Sweden)

    Christopher Peschel

    2017-09-01

    Full Text Available We investigated the effect of fluorinated molecules on dipalmitoylphosphatidylcholine (DPPC bilayers by force-field molecular dynamics simulations. In the first step, we developed all-atom force-field parameters for additive molecules in membranes to enable an accurate description of those systems. On the basis of this force field, we performed extensive simulations of various bilayer systems containing different additives. The additive molecules were chosen to be of different size and shape, and they included small molecules such as perfluorinated alcohols, but also more complex molecules. From these simulations, we investigated the structural and dynamic effects of the additives on the membrane properties, as well as the behavior of the additive molecules themselves. Our results are in good agreement with other theoretical and experimental studies, and they contribute to a microscopic understanding of interactions, which might be used to specifically tune membrane properties by additives in the future.

  5. Investigation of a mutual interaction force at different pressure amplitudes in sulfuric acid

    International Nuclear Information System (INIS)

    Rezaee, Nastaran; Sadighi-Bonabi, Rasoul; Mirheydari, Mona; Ebrahimi, Homa

    2011-01-01

    This paper investigates the secondary Bjerknes force for two oscillating bubbles in various pressure amplitudes in a concentration of 95% sulfuric acid. The equilibrium radii of the bubbles are assumed to be smaller than 10 μm at a frequency of 37 kHz in various strong driving acoustical fields around 2.0 bars (1 bar=10 5 Pa). The secondary Bjerknes force is investigated in uncoupled and coupled states between the bubbles, with regard to the quasi-adiabatic model for the bubble interior. It finds that the value of the secondary Bjerknes force depends on the driven pressure of sulfuric acid and its amount would be increased by liquid pressure amplitude enhancement. The results show that the repulsion area of the interaction force would be increased by increasing the driven pressure because of nonlinear oscillation of bubbles. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  6. Investigation Of Interaction Between Nitinol Stent And A Vascular Plaque Using Finite Element Method

    Directory of Open Access Journals (Sweden)

    Recep Güneş

    2012-06-01

    Full Text Available In this study, the interaction between the Nitinol stent and the artery with plaque was investigated using finite element method. The occurring pressure values during the cardiac contraction (systolic and loosening (diastolic were applied as loading to the modeled system with Nitinol stent. In the light of the stress values, the suitability of the Nitinol stent in an artery with plaque was investigated. In the analysis, Nitinol stent was assumed to be shape memory alloy, and artery and plaque were assumed to behave linearly elastic. As a result, the stress and deformations in the plaque and artery due to the interference of Nitinol stent were discussed and concluded that the structure of artery with plaque can be expanded in accordance with Nitinol stent.

  7. Investigation of ion acceleration mechanism through laser-matter interaction in femtosecond domain

    Energy Technology Data Exchange (ETDEWEB)

    Altana, C., E-mail: altana@lns.infn.it [Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Sud, Via S. Sofia 62, 95123 Catania (Italy); Dipartimento di Fisica e Astronomia, Università degli Studi di Catania, Via S. Sofia 64, 95123 Catania (Italy); Muoio, A. [Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Sud, Via S. Sofia 62, 95123 Catania (Italy); Dipartimento di Fisica e Scienze della Terra, Università degli Studi di Messina, Viale F.S. D’Alcontres 31, 98166 Messina (Italy); Lanzalone, G. [Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Sud, Via S. Sofia 62, 95123 Catania (Italy); Università degli Studi di Enna “Kore”, Via delle Olimpiadi, 94100 Enna (Italy); Tudisco, S. [Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Sud, Via S. Sofia 62, 95123 Catania (Italy); Brandi, F. [CNR, Intense Laser Irradiation Laboratory, Via G. Moruzzi 1, 56124 Pisa (Italy); Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova (Italy); Cirrone, G.A.P. [Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Sud, Via S. Sofia 62, 95123 Catania (Italy); Cristoforetti, G. [CNR, Intense Laser Irradiation Laboratory, Via G. Moruzzi 1, 56124 Pisa (Italy); Fazzi, A. [Energy Department, Polytechnic of Milan and INFN, Milan (Italy); Ferrara, P.; Fulgentini, L. [CNR, Intense Laser Irradiation Laboratory, Via G. Moruzzi 1, 56124 Pisa (Italy); Giove, D. [Energy Department, Polytechnic of Milan and INFN, Milan (Italy); Koester, P. [CNR, Intense Laser Irradiation Laboratory, Via G. Moruzzi 1, 56124 Pisa (Italy); Labate, L. [CNR, Intense Laser Irradiation Laboratory, Via G. Moruzzi 1, 56124 Pisa (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); and others

    2016-09-01

    An experimental campaign aiming to investigate the ion acceleration mechanisms through laser-matter interaction in the femtosecond domain has been carried out at the ILIL facility at a laser intensity of up to 2×10{sup 19} W/cm{sup 2}. A Thomson Parabola Spectrometer was used to identify different ion species and measure the energy spectra and the corresponding temperature parameters. We discuss the dependence of the protons spectra upon the structural characteristics of the targets (thickness and atomic mass) and the role of surface versus target bulk during acceleration process. - Highlights: • Ion acceleration mechanism in TNSA regime was investigated. • The energy spectra and the corresponding temperature parameters were measured. • Dependence of the spectra upon the target structural characteristics was discussed.

  8. Smoking interacts with HLA-DRB1 shared epitope in the development of anti-citrullinated protein antibody-positive rheumatoid arthritis: results from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA).

    Science.gov (United States)

    Too, Chun Lai; Yahya, Abqariyah; Murad, Shahnaz; Dhaliwal, Jasbir Singh; Larsson, Per Tobias; Muhamad, Nor Asiah; Abdullah, Nor Aini; Mustafa, Amal Nasir; Klareskog, Lars; Alfredsson, Lars; Padyukov, Leonid; Bengtsson, Camilla

    2012-04-26

    associated with a strong gene-environment interaction between smoking and HLA-DRB1 SE alleles in a Malaysian multiethnic population of Asian descent. This interaction seems to apply also between smoking and the specific HLA-DRB1*04:05 SE allele, which is common in Asian populations but not in Caucasians.

  9. An experimental investigation of high-temperature interactions between seawater and rhyolite, andesite, basalt and peridotite

    Science.gov (United States)

    Hajash, Andrew; Chandler, Gary W.

    1982-01-01

    Natural seawater was allowed to react with rhyolite, andesite, basalt, and peridotite at 200° 500° C, and 1,000 bars at water/rock mass ratios of 5 and 50 in order to investigate the effects of rock type, water/rock ratio, and temperature on solution chemistry and alteration mineralogy. The results indicate that interactions of seawater with various igneous rocks are similar in the production of a hydrous Mg-silicate and anhydrite as major alteration products. Fluids involved in the interactions lose Mg to alteration phases while leaching Fe, Mn, and Si from the rocks. The pH of the solutions is primarily controlled by Mg-OH-silicate formation and therefore varies with Mg and Si concentration of the system. Other reactions which involve Mg (such as Mg-Ca exchange) or which produce free H+, cause major differences in fluid chemistry between different seawater/ rock systems. High water/rock ratio systems (50/1) are generally more acidic and more efficient in leaching than low ratio systems (5/1), due to relatively more seawater Mg available for Mgsilicate production. The experiments show that large-scale seawater/rock interaction could exert considerable control on the chemistry of seawater, as well as producing large bodies of altered rock with associated ore-deposits. Active plate margins of convergence or divergence are suitable environments for hydrothermal systems due to the concurrence of igneous activity, tectonism, and a nearby water reservoir (seawater or connate water). The experimental data indicate that seawater interactions with igneous host rocks could generate many of the features of ore-deposits such as the Kuroko deposits of Japan, the Raul Mine of Peru, the Bleida deposit of Morocco, and deposits associated with ophiolites. Serpentinization of peridotite and alteration of igneous complexes associated with plate margins can also be explained by seawater interaction with the cooling rock. Geothermal energy production could benefit from experimental

  10. Investigation of the interaction of naringin palmitate with bovine serum albumin: spectroscopic analysis and molecular docking.

    Directory of Open Access Journals (Sweden)

    Xia Zhang

    Full Text Available BACKGROUND: Bovine serum albumin (BSA contains high affinity binding sites for several endogenous and exogenous compounds and has been used to replace human serum albumin (HSA, as these two compounds share a similar structure. Naringin palmitate is a modified product of naringin that is produced by an acylation reaction with palmitic acid, which is considered to be an effective substance for enhancing naringin lipophilicity. In this study, the interaction of naringin palmitate with BSA was characterised by spectroscopic and molecular docking techniques. METHODOLOGY/PRINCIPAL FINDINGS: The goal of this study was to investigate the interactions between naringin palmitate and BSA under physiological conditions, and differences in naringin and naringin palmitate affinities for BSA were further compared and analysed. The formation of naringin palmitate-BSA was revealed by fluorescence quenching, and the Stern-Volmer quenching constant (KSV was found to decrease with increasing temperature, suggesting that a static quenching mechanism was involved. The changes in enthalpy (ΔH and entropy (ΔS for the interaction were detected at -4.11 ± 0.18 kJ·mol(-1 and -76.59 ± 0.32 J·mol(-1·K(-1, respectively, which indicated that the naringin palmitate-BSA interaction occurred mainly through van der Waals forces and hydrogen bond formation. The negative free energy change (ΔG values of naringin palmitate at different temperatures suggested a spontaneous interaction. Circular dichroism studies revealed that the α-helical content of BSA decreased after interacting with naringin palmitate. Displacement studies suggested that naringin palmitate was partially bound to site I (subdomain IIA of the BSA, which was also substantiated by the molecular docking studies. CONCLUSIONS/SIGNIFICANCE: In conclusion, naringin palmitate was transported by BSA and was easily removed afterwards. As a consequence, an extension of naringin applications for use in food, cosmetic

  11. Understanding the interactions of neptunium and plutonium ions with graphene oxide: scalar-relativistic DFT investigations.

    Science.gov (United States)

    Wu, Qun-Yan; Lan, Jian-Hui; Wang, Cong-Zhi; Zhao, Yu-Liang; Chai, Zhi-Fang; Shi, Wei-Qun

    2014-11-06

    Due to the vast application potential of graphene oxide (GO)-based materials in nuclear waste processing, it is of pivotal importance to investigate the interaction mechanisms between actinide cations such as Np(V) and Pu(IV, VI) ions and GO. In this work, we have considered four types of GOs modified by hydroxyl, carboxyl, and carbonyl groups at the edge and epoxy group on the surface, respectively. The structures, bonding nature, and binding energies of Np(V) and Pu(IV, VI) complexes with GOs have been investigated systematically using scalar-relativistic density functional theory (DFT). Geometries and harmonic frequencies suggest that Pu(IV) ions coordinate more easily with GOs compared to Np(V) and Pu(VI) ions. NBO and electron density analyses reveal that the coordination bond between Pu(IV) ions and GO possesses more covalency, whereas for Np(V) and Pu(VI) ions electrostatic interaction dominates the An-OG bond. The binding energies in aqueous solution reveal that the adsorption abilities of all GOs for actinide ions follow the order of Pu(IV) > Pu(VI) > Np(V), which is in excellent agreement with experimental observations. It is expected that this study can provide useful information for developing more efficient GO-based materials for radioactive wastewater treatment.

  12. Investigation of the interaction of β-methylamino-L-alanine with eukaryotic and prokaryotic proteins.

    Science.gov (United States)

    Main, Brendan J; Italiano, Carly J; Rodgers, Kenneth J

    2017-12-12

    There is a strong body of evidence linking the non-protein amino acid (NPAA) β-methylamino-L-alanine (BMAA) to the development of a number of neurodegenerative diseases. BMAA has been found globally, is produced by a number of organisms including cyanobacteria, diatoms, and dinoflagellates; and has been shown to biomagnify through trophic levels. The role of BMAA in neurodegenerative disease is highlighted by its presence in the brains of a number of neurodegenerative disease patients, where it was found in a protein-bound form. We have previously shown that BMAA is bound to cell proteins, and results in the upregulation of the unfolded protein response, an endoplasmic reticulum stress response activated by the presence of misfolded proteins within the cell. Structurally aberrant proteins are features of a number of neurodegenerative diseases, and further investigation of how BMAA interacts with proteins is crucial to our understanding of its toxicity. Here we use radiolabelled BMAA to investigate the interaction and binding of BMAA to eukaryotic and prokaryotic proteins. We found differences in the presence and distribution of protein-bound BMAA between E. coli and neuroblastoma cells, with an increase in binding over time only seen in the eukaryotic cells. We also found that BMAA was unable to bind to pure proteins, or cell lysate in native or denaturing conditions, indicating that biological processing is required for BMAA to bind to proteins.

  13. Investigation of structural responses of breakwaters for green water based on fluid-structure interaction analysis

    Directory of Open Access Journals (Sweden)

    Chi-Seung Lee

    2012-06-01

    Full Text Available In the present study, the structural response of breakwaters installed on container carriers against green water impact loads was numerically investigated on the basis of the fluid-structure interaction analysis. A series of numerical studies is carried out to induce breakwater collapse under such conditions, whereby a widely accepted fluid-structure interaction analysis technique is adopted to realistically consider the phenomenon of green water impact loads. In addition, the structural behaviour of these breakwaters under green water impact loads is investigated simultaneously throughout the transient analysis. A verification study of the numerical results is performed using data from actual collapse incidents of breakwaters on container carriers. On the basis of the results of a series of numerical analyses, the pressure distribution of green water was accurately predicted with respect to wave mass and velocity. It is expected that the proposed analytical methodology and predicted pressure distribution could be used as a practical guideline for the design of breakwaters on container carriers.

  14. Investigation of Interactions between Embodiment and its Controller Using a Passive Dynamic Walking Robot

    Science.gov (United States)

    Kawasumi, Kenta; Fujii, Akinobu; Ishiguro, Akio

    Over the past decade it has been widely recognized that not only the controllers implemented but also their embodiment, such as robots’ body, significantly influence the emergence of intelligence. In spite of its importance, still few studies have explicitly investigated this mutual interaction. In light of these facts, in this article, the interaction between controllers and their embodiments is investigated. To do so, a synthetic approach is employed. More specifically, construction of a locomotion controller that enables a passive dynamic walking (PDW) robot to walk on a flat terrain is taken as a practical example. In this study, so-called staged evolution is conducted for this purpose. First, body parameters (e.g. mass, length) of a biped robot are evolved in order to elicit PDW. After obtaining acceptable embodiments, their CPG (Central Pattern Generator)-based controllers are evolved. Simulations have been carried out and the results have shown that “appropriate” embodiments allow us to significantly increase the efficiency of developing their controllers.

  15. Spectroscopic investigations of novel pharmaceuticals: Stability and resonant interaction with laser beam

    Science.gov (United States)

    Smarandache, Adriana; Boni, Mihai; Andrei, Ionut Relu; Handzlik, Jadwiga; Kiec-Kononowicz, Katarzyna; Staicu, Angela; Pascu, Mihail-Lucian

    2017-09-01

    This paper presents data about photophysics of two novel thio-hydantoins that exhibit promising pharmaceutical properties in multidrug resistance control. Time stability studies are necessary to establish the proper use of these compounds in different applications. As for their administration as drugs, it is imperative to know their shelf life, as well as storage conditions. At the same time, laser induced modified properties of the two new compounds are valuable to further investigate their specific interactions with other materials, including biological targets. The two new thio-hydantoins under generic names SZ-2 and SZ-7 were prepared as solutions in dimethyl sulfoxide at different concentrations, as well as in deionised water. For the stability assay they were kept in various light/temperature conditions up to 60 days. The stability was estimates based on UV-vis absorption measurements. The samples in bulk shape were exposed different time intervals to laser radiation emitted at 266 nm as the fourth harmonic of a Nd:YAG laser. The resonant interaction of the studied compounds with laser beams was analysed through spectroscopic methods UV-vis and FTIR absorption, as well as laser induced fluorescence spectroscopy. As for stability assay, only solutions kept in dark at 4 °C have preserved the absorption characteristics, considering the cumulated measuring errors, less than one week. The vibrational changes that occur in their FTIR and modified fluorescence spectra upon laser beam exposure are also discussed. A result of the experimental analysis is that modifications are induced in molecular structures of the investigated compounds by resonant interaction with laser radiation. This fact evidences that the molecules are photoreactive and their characteristics might be shaped through controlled laser radiation exposure using appropriate protocols. This conclusion opens many opportunities both in the biomedical field, but also in other industrial activities

  16. Spectroscopic investigation of Bovine Liver Catalase interactions with a novel phen-imidazole derivative of platinum.

    Science.gov (United States)

    Ghobadi, Roohollah; Divsalar, Adeleh; Harifi-Mood, Ali Reza; Saboury, Ali Akbar

    2018-02-01

    Successful clinical experience of using cisplatin and its derivatives in cancer therapy has encouraged scientists to synthesize new metal complexes with the aim of interacting with special targets such as proteins In this regard, biological effects of [Pt(FIP)(Phen)](NO 3 ) 2 compound which contains a novel phen-imidazole ligand, FIP, was investigated on bovine liver catalase (BLC) structure and function. Various spectroscopic methods such as UV-visible, fluorescence, and circular dichroism (CD) were applied at two temperatures 25 and 37°C for kinetics and structural studies. As a consequence, the enzymatic activity decreased slightly with increasing the platinum compound's concentration up to 30 μM and then remained constant at near 80% after this concentration. On the other hand, the fluorescence quenching measurements revealed that despite slight changes in activity, catalase experiences notable alterations in three-dimensional environment around the chromophores of the enzyme structure with increasing platinum complex concentration. Moreover, quenching data showed that BLC has two binding sites for Pt complex and hydrogen bonding interactions play a major role in the binding process. Furthermore, CD spectroscopy data showed that Pt(II) complex induces significant decrease in α-helix content of the secondary structure of BLC, but notable increase in random coil proportion accompanying a slight decrease in β-sheet content. All in all, hydrogen bonding interactions which are mainly involved in the binding process of the novel phen-imidazole compound to BLC significantly alter the protein structure but slightly change its function. This might be a promising outcome for chemotherapists and medicinal chemists to investigate in vivo properties of this novel metal complex with significant binding tendency to a macromolecule in the low concentrations without decreasing its intrinsic function.

  17. Investigation on the toxic interaction of superparamagnetic iron oxide nanoparticles with catalase

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Zehua [Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, China–America CRC for Environment and Health, Shandong Province, Shandong University, 27# Shanda South Road, Jinan 250100 (China); Liu, Hongwei [Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, China–America CRC for Environment and Health, Shandong Province, Shandong University, 27# Shanda South Road, Jinan 250100 (China); Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Hu, Xinxin; Song, Wei [Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, China–America CRC for Environment and Health, Shandong Province, Shandong University, 27# Shanda South Road, Jinan 250100 (China); Liu, Rutao, E-mail: rutaoliu@sdu.edu.cn [Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, China–America CRC for Environment and Health, Shandong Province, Shandong University, 27# Shanda South Road, Jinan 250100 (China)

    2015-03-15

    Superparamagnetic iron oxide nanoparticles (SPIONs) have been investigated for various applications in targeted drug delivery and magnetic resonance imaging. Given their clinical relevance, there is a need to understand these particles' potential cytotoxic effects and possible mechanisms of cytotoxicity. Using a variety of spectroscopic techniques, we investigated the interaction of SPIONs with catalase (CAT) in an aqueous environment. Catalase is an important enzyme that protects cells and tissues from oxidative damage by reactive oxygen species (ROS). Therefore, in this work, CAT served as a model protein for examining the physiological effects of SPIONs due to is function in eliminating H{sub 2}O{sub 2}. Synchronous fluorescence spectroscopy results showed that SPIONs have little effect on tryptophan residues in CAT. Data from circular dichroism (CD) and UV–vis spectroscopies showed that CAT α-helical content decreased from 32.4% to 29.1% in the presence of SPIONs. Moreover, a ca. 10% decrease in CAT activity was observed in the presence of SPIONs at a 20:1 particle:protein ratio. These results show that SPIONs can interact with proteins to alter both their structure and function. Further studies with CAT or other toxicologically relevant enzymes may be used for elucidating the mechanisms of SPION cytotoxicity. - Highlights: • This work established the binding mode of SPIONs with CAT on molecular level. • The interaction mechanism was explored by multiple spectroscopic techniques. • SPIONs can loosen the skeleton of protein and increase the exposure of amide moieties in the hydrophobic pocket. • SPIONs can inhibit CAT activity and trigger conformational changes in CAT.

  18. Investigation on the toxic interaction of superparamagnetic iron oxide nanoparticles with catalase

    International Nuclear Information System (INIS)

    Yu, Zehua; Liu, Hongwei; Hu, Xinxin; Song, Wei; Liu, Rutao

    2015-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) have been investigated for various applications in targeted drug delivery and magnetic resonance imaging. Given their clinical relevance, there is a need to understand these particles' potential cytotoxic effects and possible mechanisms of cytotoxicity. Using a variety of spectroscopic techniques, we investigated the interaction of SPIONs with catalase (CAT) in an aqueous environment. Catalase is an important enzyme that protects cells and tissues from oxidative damage by reactive oxygen species (ROS). Therefore, in this work, CAT served as a model protein for examining the physiological effects of SPIONs due to is function in eliminating H 2 O 2 . Synchronous fluorescence spectroscopy results showed that SPIONs have little effect on tryptophan residues in CAT. Data from circular dichroism (CD) and UV–vis spectroscopies showed that CAT α-helical content decreased from 32.4% to 29.1% in the presence of SPIONs. Moreover, a ca. 10% decrease in CAT activity was observed in the presence of SPIONs at a 20:1 particle:protein ratio. These results show that SPIONs can interact with proteins to alter both their structure and function. Further studies with CAT or other toxicologically relevant enzymes may be used for elucidating the mechanisms of SPION cytotoxicity. - Highlights: • This work established the binding mode of SPIONs with CAT on molecular level. • The interaction mechanism was explored by multiple spectroscopic techniques. • SPIONs can loosen the skeleton of protein and increase the exposure of amide moieties in the hydrophobic pocket. • SPIONs can inhibit CAT activity and trigger conformational changes in CAT

  19. Investigation of fault interaction and growth in Mygdonia basin (Greece) fault system

    Science.gov (United States)

    Gkarlaouni, Charikleia; Kilias, Adamantios; Papadimitriou, Eleftheria; Lasocki, Stanislaw; Karakostas, Vasileios

    2013-04-01

    Nowadays there is a scientific debate upon the strong correlation that exists between the earthquake clusters and the active seismogenic fault systems since they both constitute populations that participate in processes that include different states of initiation, interaction and coalescence. Since faults grow by the increase in their displacement and their length, the degree of fault interaction between two neighbour segments is expressed by scaling laws describing the fault dimensions, such as the displacement and the length. The distribution of the displacement along the fault trace, follows a bell-shaped pattern according to Dugdale model and is often a key to quantify the degree of interaction between two different fault segments since it gives an insight to the stage of growth and linkage between faults. In our case the fault attributes of Mygdonia basin that is located in the northern part of the Greek mainland are investigated under the prism of the scaling properties of its major active faults. Important seismogenic fault segments such as Lagina - Agios Vasilios, Gerakarou - Stivos and Sohos fault that define the boundaries of the basin and have generated important earthquakes in the past are investigated. Displacement - length profiles were constrained for the major fault segments, using digital elevation models (DEMs) since intense tectonics is etched upon the topography of the area such as to provide valuable seismotectonic information. In our case scarp heights are used for the approximation of fault displacement. Structural information, concerning displacement measurements on active fault scarps, and slip lineaments onto fault expressions are collected in-situ from field surveys. The information based on the field observations, justify the results coming out from the D.E.M. analysis. The final results are compared to conclusions derived from the investigation of different fault systems and the influence on the hazard assessment is discussed. This work

  20. Investigating the Neural Correlates of Emotion-Cognition Interaction Using an Affective Stroop Task.

    Science.gov (United States)

    Raschle, Nora M; Fehlbaum, Lynn V; Menks, Willeke M; Euler, Felix; Sterzer, Philipp; Stadler, Christina

    2017-01-01

    The human brain has the capacity to integrate various sources of information and continuously adapts our behavior according to situational needs in order to allow a healthy functioning. Emotion-cognition interactions are a key example for such integrative processing. However, the neuronal correlates investigating the effects of emotion on cognition remain to be explored and replication studies are needed. Previous neuroimaging studies have indicated an involvement of emotion and cognition related brain structures including parietal and prefrontal cortices and limbic brain regions. Here, we employed whole brain event-related functional magnetic resonance imaging (fMRI) during an affective number Stroop task and aimed at replicating previous findings using an adaptation of an existing task design in 30 healthy young adults. The Stroop task is an indicator of cognitive control and enables the quantification of interference in relation to variations in cognitive load. By the use of emotional primes (negative/neutral) prior to Stroop task performance, an emotional variation is added as well. Behavioral in-scanner data showed that negative primes delayed and disrupted cognitive processing. Trials with high cognitive demand furthermore negatively influenced cognitive control mechanisms. Neuronally, the emotional primes consistently activated emotion-related brain regions (e.g., amygdala, insula, and prefrontal brain regions) while Stroop task performance lead to activations in cognition networks of the brain (prefrontal cortices, superior temporal lobe, and insula). When assessing the effect of emotion on cognition, increased cognitive demand led to decreases in neural activation in response to emotional stimuli (negative > neutral) within prefrontal cortex, amygdala, and insular cortex. Overall, these results suggest that emotional primes significantly impact cognitive performance and increasing cognitive demand leads to reduced neuronal activation in emotion related

  1. Investigating the Neural Correlates of Emotion–Cognition Interaction Using an Affective Stroop Task

    Directory of Open Access Journals (Sweden)

    Nora M. Raschle

    2017-09-01

    Full Text Available The human brain has the capacity to integrate various sources of information and continuously adapts our behavior according to situational needs in order to allow a healthy functioning. Emotion–cognition interactions are a key example for such integrative processing. However, the neuronal correlates investigating the effects of emotion on cognition remain to be explored and replication studies are needed. Previous neuroimaging studies have indicated an involvement of emotion and cognition related brain structures including parietal and prefrontal cortices and limbic brain regions. Here, we employed whole brain event-related functional magnetic resonance imaging (fMRI during an affective number Stroop task and aimed at replicating previous findings using an adaptation of an existing task design in 30 healthy young adults. The Stroop task is an indicator of cognitive control and enables the quantification of interference in relation to variations in cognitive load. By the use of emotional primes (negative/neutral prior to Stroop task performance, an emotional variation is added as well. Behavioral in-scanner data showed that negative primes delayed and disrupted cognitive processing. Trials with high cognitive demand furthermore negatively influenced cognitive control mechanisms. Neuronally, the emotional primes consistently activated emotion-related brain regions (e.g., amygdala, insula, and prefrontal brain regions while Stroop task performance lead to activations in cognition networks of the brain (prefrontal cortices, superior temporal lobe, and insula. When assessing the effect of emotion on cognition, increased cognitive demand led to decreases in neural activation in response to emotional stimuli (negative > neutral within prefrontal cortex, amygdala, and insular cortex. Overall, these results suggest that emotional primes significantly impact cognitive performance and increasing cognitive demand leads to reduced neuronal activation in

  2. Investigating the Neural Correlates of Emotion–Cognition Interaction Using an Affective Stroop Task

    Science.gov (United States)

    Raschle, Nora M.; Fehlbaum, Lynn V.; Menks, Willeke M.; Euler, Felix; Sterzer, Philipp; Stadler, Christina

    2017-01-01

    The human brain has the capacity to integrate various sources of information and continuously adapts our behavior according to situational needs in order to allow a healthy functioning. Emotion–cognition interactions are a key example for such integrative processing. However, the neuronal correlates investigating the effects of emotion on cognition remain to be explored and replication studies are needed. Previous neuroimaging studies have indicated an involvement of emotion and cognition related brain structures including parietal and prefrontal cortices and limbic brain regions. Here, we employed whole brain event-related functional magnetic resonance imaging (fMRI) during an affective number Stroop task and aimed at replicating previous findings using an adaptation of an existing task design in 30 healthy young adults. The Stroop task is an indicator of cognitive control and enables the quantification of interference in relation to variations in cognitive load. By the use of emotional primes (negative/neutral) prior to Stroop task performance, an emotional variation is added as well. Behavioral in-scanner data showed that negative primes delayed and disrupted cognitive processing. Trials with high cognitive demand furthermore negatively influenced cognitive control mechanisms. Neuronally, the emotional primes consistently activated emotion-related brain regions (e.g., amygdala, insula, and prefrontal brain regions) while Stroop task performance lead to activations in cognition networks of the brain (prefrontal cortices, superior temporal lobe, and insula). When assessing the effect of emotion on cognition, increased cognitive demand led to decreases in neural activation in response to emotional stimuli (negative > neutral) within prefrontal cortex, amygdala, and insular cortex. Overall, these results suggest that emotional primes significantly impact cognitive performance and increasing cognitive demand leads to reduced neuronal activation in emotion related

  3. Investigation on Melt-Structure-Water Interactions (MSWI) during severe accidents

    International Nuclear Information System (INIS)

    Sehgal, B.R.; Yang, Z.L.; Dinh, T.N.; Nourgaliev, R.R.; Bui, V.A.; Haraldsson, H.O.; Li, H.X.; Konovakhin, M.; Paladino, D.; Leung, W.H

    1999-08-01

    This report is the final report for the work performed in 1998 in the research project Melt Structure Water Interactions (MSWI), under the auspices of the APRI Project, jointly funded by SKI, HSK, USNRC and the Swedish and Finnish power companies. The present report describes results of advanced analytical and experimental studies concerning melt-water-structure interactions during the course of a hypothetical severe core meltdown accident in a light water reactor (LWR). Emphasis has been placed on phenomena and properties which govern the fragmentation and breakup of melt jets and droplets, melt spreading and coolability, and thermal and mechanical loadings of a pressure vessel during melt-vessel interaction. Many of the investigations performed in support of this project have produced papers which have been published in the proceedings of technical meetings. A short summary of the results achieved in these papers is provided in this overview. Both experimental and analytical studies were performed to improve knowledge about phenomena of melt-structure-water interactions. We believe that significant technical advances have been achieved during the course of these studies. It was found that: the solidification has a strong effect on the drop deformation and breakup. Initially appearing at the drop surface and, later, thickening inwards, the solid crust layer dampens the instability waves on the drop surface and, therefore, hinders drop deformation and breakup. The drop thermal properties also affect the thermal behavior of the drop and, therefore, have impact on its deformation behavior. The jet fragmentation process is a function of many related phenomena. The fragmentation rate depends not only on the traditional parameters, e.g. the Weber number, but also on the melt physical properties, which change as the melt cools down from the liquidus to the solidus temperature. Additionally, the crust formed on the surface of the melt jet will also reduce the propensity

  4. Investigation on Melt-Structure-Water Interactions (MSWI) during severe accidents

    Energy Technology Data Exchange (ETDEWEB)

    Sehgal, B.R.; Yang, Z.L.; Dinh, T.N.; Nourgaliev, R.R.; Bui, V.A.; Haraldsson, H.O.; Li, H.X.; Konovakhin, M.; Paladino, D.; Leung, W.H [Royal Inst. of Tech., Stockholm (Sweden). Div. of Nuclear Power Safety

    1999-08-01

    This report is the final report for the work performed in 1998 in the research project Melt Structure Water Interactions (MSWI), under the auspices of the APRI Project, jointly funded by SKI, HSK, USNRC and the Swedish and Finnish power companies. The present report describes results of advanced analytical and experimental studies concerning melt-water-structure interactions during the course of a hypothetical severe core meltdown accident in a light water reactor (LWR). Emphasis has been placed on phenomena and properties which govern the fragmentation and breakup of melt jets and droplets, melt spreading and coolability, and thermal and mechanical loadings of a pressure vessel during melt-vessel interaction. Many of the investigations performed in support of this project have produced papers which have been published in the proceedings of technical meetings. A short summary of the results achieved in these papers is provided in this overview. Both experimental and analytical studies were performed to improve knowledge about phenomena of melt-structure-water interactions. We believe that significant technical advances have been achieved during the course of these studies. It was found that: the solidification has a strong effect on the drop deformation and breakup. Initially appearing at the drop surface and, later, thickening inwards, the solid crust layer dampens the instability waves on the drop surface and, therefore, hinders drop deformation and breakup. The drop thermal properties also affect the thermal behavior of the drop and, therefore, have impact on its deformation behavior. The jet fragmentation process is a function of many related phenomena. The fragmentation rate depends not only on the traditional parameters, e.g. the Weber number, but also on the melt physical properties, which change as the melt cools down from the liquidus to the solidus temperature. Additionally, the crust formed on the surface of the melt jet will also reduce the propensity

  5. Investigating the Interaction of Fe Nanoparticles with Lysozyme by Biophysical and Molecular Docking Studies.

    Directory of Open Access Journals (Sweden)

    Zahra Aghili

    Full Text Available Herein, the interaction of hen egg white lysozyme (HEWL with iron nanoparticle (Fe NP was investigated by spectroscopic and docking studies. The zeta potential analysis revealed that addition of Fe NP (6.45±1.03 mV to HEWL (8.57±0.54 mV can cause to greater charge distribution of nanoparticle-protein system (17.33±1.84 mV. In addition, dynamic light scattering (DLS study revealed that addition of Fe NP (92.95±6.11 nm to HEWL (2.68±0.37 nm increases suspension potential of protein/nanoparticle system (51.17±3.19 nm. Fluorescence quenching studies reveled that both static and dynamic quenching mechanism occur and hydrogen bond and van der Waals interaction give rise to protein-NP system. Synchronous fluorescence spectroscopy of HEWL in the presence of Fe NP showed that the emission maximum wavelength of tryptophan (Trp residues undergoes a red-shift. ANS fluorescence data indicated a dramatic exposure of hydrophobic residues to the solvent. The considerable reduction in melting temperature (T(m of HEWL after addition of Fe NP determines an unfavorable interaction system. Furthermore circular dichoroism (CD experiments demonstrated that, the secondary structure of HEWL has not changed with increasing Fe NP concentrations; however, some conformational changes occur in tertiary structure of HEWL. Moreover, protein-ligand docking study confirmed that the Fe NP forms hydrogen bond contacts with HEWL.

  6. Interaction of ZnS nanoparticles with flavins and glucose oxidase: A fluorimetric investigation

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Anindita; Priyam, Amiya; Ghosh, Debasmita; Mondal, Somrita [UGC-DAE Consortium for Scientific Research, Kolkata Centre, III/LB-8, Bidhannagar, Kolkata 700098 (India); Bhattacharya, Subhash C. [Department of Chemistry, Jadavpur University, Kolkata 700032 (India); Saha, Abhijit, E-mail: abhijit@alpha.iuc.res.in [UGC-DAE Consortium for Scientific Research, Kolkata Centre, III/LB-8, Bidhannagar, Kolkata 700098 (India)

    2012-03-15

    Interactions of luminescence, water soluble ZnS nanoparticles (NPs) with flavins and glucose oxidase have been thoroughly investigated through optical spectroscopy. The photoluminescence of ZnS nanoparticles was quenched severely ({approx}60%) by riboflavin while other flavins such as flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) show quenching to different extents under analogous conditions. However, interestingly no effect in luminescence intensity of ZnS NPs was observed with protein bound flavins such as in glucose oxidase. Fluorescence lifetime measurement confirmed the quenching to be static in nature. Scavenging of photo-generated electron of ZnS nanoparticles by the flavin molecules may be attributed to the decrease in luminescence intensity. Quenching of ZnS nanoparticles with flavins follows the linear Stern-Volmer plot. The Stern-Volmer constants decreased in the following order: K{sub S-V} (Riboflavin)> K{sub S-V} (FAD)> K{sub S-V} (FMN). This interaction study could generate useful protocol for the fluorimetric determination of riboflavin (vitamin B{sub 2}) content and also riboflavin status in biological systems. - Highlights: Black-Right-Pointing-Pointer Unique interaction specificity of ZnS nanoparticles with flavins has been explored. Black-Right-Pointing-Pointer Unlike protein-bound flavin, fluorescence of free flavins was quenched by ZnS nanoparticles. Black-Right-Pointing-Pointer FMN and FAD show quenching to different extents under analogous conditions. Black-Right-Pointing-Pointer Fluorescence lifetime measurement confirmed the quenching to be static in nature. Black-Right-Pointing-Pointer This study is useful for probing riboflavin in biological systems.

  7. Two-dimensional numerical investigation of a normal shock wave boundary layer interaction

    Science.gov (United States)

    Turlin, Miranda P.

    Shock wave boundary layer interactions (SWBLIs) occur when a shock wave meets a boundary layer. This study aims to isolate the interaction through numerical investigation of a normal SWBLI and build knowledge of the computational fluid dynamics software, Wind-US 3.0. The test geometry, based on the experimental work of Bruce et al [16], contains a two-dimensional duct split into upper and lower channels by a shock holding plate. The boundary conditions were based on experimental conditions, and include: an inlet Mach number of 1.6; inlet total pressure and temperature of 62.5 psi and 522 degrees R, respectively; and viscous walls on all physical surfaces. Downstream boundary conditions are varied in attempts to produce a correct shock structure throughout the domain. This study uses two-dimensional structured grids containing approximately 832,000 elements. Wind-US solves the Reynolds-Averaged Navier-Stokes equations using Roe's second-order upwind-biased flux-difference splitting algorithm with a total variation diminishing (TVD) limiting parameter. The turbulence model selected for this study was the Menter SST k-o model. Attempts to produce the correct shock structure have included varying the downstream boundary conditions, changing the number of cycles and associated Courant-Friedrichs-Lewy, TVD, and grid sequencing parameters. This study used several tutorial files available through the NPARC Alliance to establish the analysis settings needed to produce a shock wave in the lower channel. This enables progress to be made on the next step of this project which is to simulate and analyze the interaction of a normal SWBLI in two dimensions. Results illustrate the correct combination of boundary conditions necessary to generate a shock in the expected location. In addition, an appropriate zonal configuration has been determined to eliminate the horizontal zone interfaces which can cause non-physical behavior in those locations.

  8. Investigations of Memory, Entanglement, and Long-Range Interactions Using Ultra-Cold Atoms

    Science.gov (United States)

    Dudin, Yaroslav

    2013-05-01

    Long-term storage of quantum information has diverse applications in quantum information science. I have employed ultra-cold rubidium atoms confined in one-dimensional optical lattices to demonstrate entanglement between a light field and a long-lived spin wave, to develop light-shift compensated quantum memories, to create entanglement between a telecom-band light field and a light-shift compensated memory qubit of a 0.1 s lifetime, and to store coherent light pulses with 1/e lifetime of 16 s in a magnetically-compensated lattice augmented by dynamic decoupling. Highly excited Rydberg atoms offer a unique platform for study of strongly correlated systems and quantum information, because of their enormous dipole moments and consequent strong, long-range interactions. I will present experimental studies of single collective Rydberg excitations created in a cold atomic gas including first realization of a Rydberg-atom-based single photon source, measurement of entanglement between a Rydberg spin wave and light, investigations of long-range correlations of strongly interacting Rydberg spin waves, and initial observations of coherent many-body Rabi oscillations between the ground level and a Rydberg level using several hundred cold rubidium atoms.

  9. An investigation into the interaction of closely-spaced starting jets

    Energy Technology Data Exchange (ETDEWEB)

    Rival, D.; Ciccarelli, G. [Department of Mechanical and Materials Engineering, Queen' s University, Kingston (Canada)

    2007-08-15

    The transient, three-dimensional scavenging flow inside a novel two-stroke engine has been investigated both experimentally in a scaled water model as well as numerically using a commercial CFD code incorporating an unsteady Reynolds averaged Navier-Stokes (URANS) formulation. The scavenging flow consists of 16 round jets in close proximity of each other and the cylinder wall, developing from the top of the combustion chamber down towards the exhaust ports located along the wall at the bottom of the cylinder. Flow visualization of the scavenging flow was performed using a scaled fixed-piston water model and was used as a means of validating the URANS simulations themselves. The flow visualization experiments provided insight into the complex jet-jet and jet-wall interactions within the engine cylinder. These interactions were not as well predicted by the CFD simulations. In fact, the CFD simulations were found to significantly under-predict the turbulent mixing between the jets. This suggests that unsteady-RANS formulations are incapable of reproducing the large-scale and unsteady mixing structures associated with the vortex shedding between the closely-spaced jets. (author)

  10. Diagnostic setup for investigation of plasma wall interactions at Wendelstein 7-X

    Energy Technology Data Exchange (ETDEWEB)

    Neubauer, Olaf, E-mail: o.neubauer@fz-juelich.de [Institute of Energy and Climate Research, Forschungszentrum Jülich GmbH, D-52425 Jülich (Germany); Biel, Wolfgang; Czymek, Guntram; Denner, Peter [Institute of Energy and Climate Research, Forschungszentrum Jülich GmbH, D-52425 Jülich (Germany); Effenberg, Florian [University Wisconsin–Madison, Madison, WI (United States); Krämer-Flecken, Andreas; Liang, Yunfeng; Marchuk, Oleksandr; Offermanns, Guido; Rack, Michael; Samm, Ulrich [Institute of Energy and Climate Research, Forschungszentrum Jülich GmbH, D-52425 Jülich (Germany); Schmitz, Oliver [University Wisconsin–Madison, Madison, WI (United States); Schweer, Bernd [Laboratoire de Physique des Plasmas – Laboratorium voor Plasmafysica, ERM/KMS, 1000 Brussels (Belgium); Terra, Alexis [Institute of Energy and Climate Research, Forschungszentrum Jülich GmbH, D-52425 Jülich (Germany)

    2015-10-15

    Graphical abstract: - Highlights: • We are investigating plasma wall interactions at Wendelstein 7-X stellarator. • Steady state operation and island divertor are unique. • We are developing diagnostics for divertor plasma and plasma facing surfaces. • A multi-purpose fast manipulator allows for exposure of probes and samples. • Versatile endoscopes allow for local divertor spectroscopy from IR to UV. - Abstract: Wendelstein 7-X being the most advanced stellarator is currently prepared for commissioning at Greifswald. Forschungszentrum Jülich is preparing a research programme in the field of plasma wall interactions (PWI) by developing a dedicated set of diagnostic systems. The specific interest at Wendelstein 7-X is to understand PWI processes in presence of a 3D plasma boundary of an island divertor. Furthermore, for the first time steady state plasma at high density and low temperature in the divertor region will be available. Since PWI only could be understood in conjunction with the edge plasma properties the aim of the setup is to observe both the edge plasma as well as surface processes. For optimum combination of different diagnostic methods the edge diagnostic systems are aligned toroidally along one out of five magnetic islands. Main systems are a multipurpose fast probe manipulator, two gas boxes in opposite divertor modules together with two endoscopes each observing the divertor regions, a poloidal correlation reflectometer, a dispersion interferometer in the divertor, and VUV and X-ray spectroscopy in the plasma core. The concept of the diagnostic setup is presented in this paper.

  11. Investigation of the Josephin Domain protein-protein interaction by molecular dynamics.

    Directory of Open Access Journals (Sweden)

    Marco A Deriu

    Full Text Available Spinocerebellar ataxia (SCA 3, the most common form of SCA, is a neurodegenerative rare disease characterized by polyglutamine tract expansion and self-assembly of Ataxin3 (At3 misfolded proteins into highly organized fibrillar aggregates. The At3 N-terminal Josephin Domain (JD has been suggested as being responsible for mediating the initial phase of the At3 double-step fibrillogenesis. Several issues concerning the residues involved in the JD's aggregation and, more generally, the JD clumping mechanism have not been clarified yet. In this paper we present an investigation focusing on the JD protein-protein interaction by means of molecular modeling. Our results suggest possible aminoacids involved in JD contact together with local and non-local effects following JD dimerization. Surprisingly, JD conformational changes following the binding may involve ubiquitin binding sites and hairpin region even though they do not pertain to the JD interaction surfaces. Moreover, the JD binding event has been found to alter the hairpin open-like conformation toward a closed-like arrangement over the simulated timescale. Finally, our results suggest that the JD aggregation might be a multi-step process, with an initial fast JD-JD binding mainly driven by Arg101, followed by slower structural global rearrangements involving the exposure to the solvent of Leu84-Trp87, which might play a role in a second step of JD aggregation.

  12. FT-IR and X-ray spectroscopic investigations of Na-diclofenac-cyclodextrins interactions

    Science.gov (United States)

    Bratu, I.; Astilean, S.; Ionesc, Corina; Indrea, E.; Huvenne, J. P.; Legrand, P.

    1998-01-01

    The association of DCF-Na (the salt of the 2-[(2,6-dichlorophenyl)amino]-phenyl-acetic acid) with β-CD (cyclodextrin) in some therapeutic formulas can contribute to the optimisation of the physico-chemical and pharmaceutical properties of the parent drug. The understanding of the interaction between DCF with β-CD represents the objective of this study. FT-IR spectroscopy is one of the methods which clarify the nature of these interactions in complexes of such type. Therefore the changes in FT-IR spectra of binary dispersed systems DCF/ β-CD in physical mixture and coprecipitate from methanol (molar ratios: 1/1, 1/2, 2/3, 3/4, 7/4) were analysed. The analysis of the broadening of the X-ray powder diffraction line has been applied to investigate the average effective crystallite size, the mean square of the microstrain caused by distortions within β-CD crystallite and the fault probability in the binary dispersed DCF/ β-CD coprecipitate system.

  13. Investigation of prescribed movement in fluid–structure interaction simulation for the human phonation process☆

    Science.gov (United States)

    Zörner, S.; Kaltenbacher, M.; Döllinger, M.

    2013-01-01

    In a partitioned approach for computational fluid–structure interaction (FSI) the coupling between fluid and structure causes substantial computational resources. Therefore, a convenient alternative is to reduce the problem to a pure flow simulation with preset movement and applying appropriate boundary conditions. This work investigates the impact of replacing the fully-coupled interface condition with a one-way coupling. To continue to capture structural movement and its effect onto the flow field, prescribed wall movements from separate simulations and/or measurements are used. As an appropriate test case, we apply the different coupling strategies to the human phonation process, which is a highly complex interaction of airflow through the larynx and structural vibration of the vocal folds (VF). We obtain vocal fold vibrations from a fully-coupled simulation and use them as input data for the simplified simulation, i.e. just solving the fluid flow. All computations are performed with our research code CFS++, which is based on the finite element (FE) method. The presented results show that a pure fluid simulation with prescribed structural movement can substitute the fully-coupled approach. However, caution must be used to ensure accurate boundary conditions on the interface, and we found that only a pressure driven flow correctly responds to the physical effects when using specified motion. PMID:24204083

  14. Investigation of hydrogen isotopes interaction processes with lithium under neutron irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Zaurbekova, Zhanna, E-mail: zaurbekova@nnc.kz [Institute of Atomic Energy, National Nuclear Center of RK, Kurchatov (Kazakhstan); Skakov, Mazhyn; Ponkratov, Yuriy; Kulsartov, Timur; Gordienko, Yuriy; Tazhibayeva, Irina; Baklanov, Viktor; Barsukov, Nikolay [Institute of Atomic Energy, National Nuclear Center of RK, Kurchatov (Kazakhstan); Chikhray, Yevgen [Institute of Experimental and Theoretical Physics of Kazakh National University, Almaty (Kazakhstan)

    2016-11-01

    Highlights: • The experiments on study of helium and tritium generation and release processes under neutron irradiation from lithium saturated with deuterium are described in paper. ​ • The values of relative tritium and helium yield from lithium sample at different levels of neutron irradiation is calculated. • It was concluded that the main affecting process on tritium release from lithium is its interaction with lithium atoms with formation of lithium tritide. - Abstract: The paper describes the experiments on study of helium and tritium generation and release processes from lithium saturated with deuterium under neutron irradiation (in temperature range from 473 to 773 K). The diagrams of two reactor experiments show the time dependences of helium, DT, T{sub 2}, and tritium water partial pressures changes in experimental chamber with investigated lithium sample. According to experimental results, the values of relative tritium and helium yield from lithium sample at different levels of neutron irradiation were calculated. The time dependences of relative tritium and helium yield from lithium sample were plotted. It was concluded that the main affecting process on tritium release from lithium is its interaction with lithium atoms with formation of lithium tritide.

  15. Investigation of Dispersion, Interaction and Superstructure Formation in PTMEG/MWCNT Nanocomposites

    Directory of Open Access Journals (Sweden)

    Atefeh Pishdad

    2012-12-01

    Full Text Available Formation of polymer/CNT nanocomposites enhances the physical and mechanical properties of polymer matrices. Basically, the mechanical properties are investigated by means of polymer/filler interactions. The other properties such as the rheological and electrical properties are examined by particle distribution and dispersion in the polymer matrices. Due to the variety of industrial applications of polyurethane and the need to improve their properties, in the current work, the improvements of PTMEG with carbon nanotubes have been studied. The particles were acid treated in a mixture of sulfuric/nitric acid, providing uniform dispersion of the nanotubes in the polymer matrix. The rheological measurements have been used to obtain the optimum degree of MWCNT dispersion, and the formation of nanoparticles superstructure were quantified by two percolation thresholds (Ф*,Ф** at low deformation rates. The critical percolation for PTMEG/MWCNT was estimated at 0.25-0.5 wt%. A significant improvement in the rheological characteristics was observed due to the agglomeration of particles at Ф* and continuous network of clusters at Ф**. The interfacial interaction of composites was also measured by means of relaxation time spectra and showed high improvement at Ф** (0.5 wt%. Considering the FE-SEM images of specimens, it was found that there is a nanotube network or cluster agglomeration at the concentration 0.75 wt% of MWCNT in the polymeric matrix.

  16. Microfluidic synthesis of composite cross-gradient materials for investigating cell-biomaterial interactions.

    Science.gov (United States)

    He, Jiankang; Du, Yanan; Guo, Yuqi; Hancock, Matthew J; Wang, Ben; Shin, Hyeongho; Wu, Jinhui; Li, Dichen; Khademhosseini, Ali

    2011-01-01

    Combinatorial material synthesis is a powerful approach for creating composite material libraries for the high-throughput screening of cell-material interactions. Although current combinatorial screening platforms have been tremendously successful in identifying target (termed "hit") materials from composite material libraries, new material synthesis approaches are needed to further optimize the concentrations and blending ratios of the component materials. Here we employed a microfluidic platform to rapidly synthesize composite materials containing cross-gradients of gelatin and chitosan for investigating cell-biomaterial interactions. The microfluidic synthesis of the cross-gradient was optimized experimentally and theoretically to produce quantitatively controllable variations in the concentrations and blending ratios of the two components. The anisotropic chemical compositions of the gelatin/chitosan cross-gradients were characterized by Fourier transform infrared spectrometry and X-ray photoelectron spectrometry. The three-dimensional (3D) porous gelatin/chitosan cross-gradient materials were shown to regulate the cellular morphology and proliferation of smooth muscle cells (SMCs) in a gradient-dependent manner. We envision that our microfluidic cross-gradient platform may accelerate the material development processes involved in a wide range of biomedical applications. © 2010 Wiley Periodicals, Inc.

  17. Investigation on interaction between Ligupurpuroside A and pepsin by spectroscopic and docking methods

    Science.gov (United States)

    Shen, Liangliang; Xu, Hong; Huang, Fengwen; Li, Yi; Xiao, Huafeng; Yang, Zhen; Hu, Zhangli; He, Zhendan; Zeng, Zheling; Li, Yinong

    2015-01-01

    Ligupurpuroside A is one of the major glycoside in Ku-Din-Cha, a type of Chinese functional tea. In order to better understand its digestion and metabolism in humans, the interaction between Ligupurpuroside A and pepsin has been investigated by fluorescence spectra, UV-vis absorption spectra and synchronous fluorescence spectra along with molecular docking method. The fluorescence experiments indicate that Ligupurpuroside A can effectively quench the intrinsic fluorescence of pepsin through a combined quenching way at the low concentration of Ligupurpuroside A, and a static quenching procedure at the high concentration. The binding constant, binding sites of Ligupurpuroside A with pepsin have been calculated. The thermodynamic analysis suggests that non-covalent reactions, including electrostatic force, hydrophobic interaction and hydrogen bond are the main forces stabilizing the complex. According to the Förster's non-radiation energy transfer theory, the binding distance between pepsin and Ligupurpuroside A was calculated to be 3.15 nm, which implies that energy transfer occurs between pepsin and Ligupurpuroside A. Conformation change of pepsin was observed from UV-vis absorption spectra and synchronous fluorescence spectra under experimental conditions. In addition, all these experimental results have been validated by the protein-ligand docking studies which show that Ligupurpuroside A is located in the cleft between the domains of pepsin.

  18. Investigation on the interactions of clenbuterol to bovine serum albumin and lysozyme by molecular fluorescence technique.

    Science.gov (United States)

    Bi, Shuyun; Pang, Bo; Wang, Tianjiao; Zhao, Tingting; Yu, Wang

    2014-01-01

    Clenbuterol interacting with bovine serum albumin (BSA) or lysozyme (LYS) in physiological buffer (pH 7.4) was investigated by the fluorescence spectroscopy and UV-vis absorption spectroscopy. The results indicated that clenbuterol quenched the intrinsic fluorescence of BSA and LYS via a static quenching procedure. The binding constants of clenbuterol with BSA and LYS were 1.16×10(3) and 1.49×10(3) L mol(-1) at 291 K. The values of ΔH and ΔS implied that hydrophobic and electrostatic interaction played a major role in stabilizing the complex (clenbuterol-BSA or clenbuterol-LYS). In the presence of Fe2+, Fe3+, Cu2+, Mg2+, Ca2+, or Zn2+, the binding constants of clenbuterol to BSA or LYS had no significant differences. The distances between the donor (BSA or LYS) and acceptor (clenbuterol) were 2.61 and 2.19 nm for clenbuterol-BSA and clenbuterol-LYS respectively. Furthermore, synchronous fluorescence spectrometry was used to analyze the conformational changes of BSA and LYS. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Investigation of thermo-optical characteristics of the interaction processes of laser radiation with silver nanoparticles

    International Nuclear Information System (INIS)

    Pustovalov, V K; Astafyeva, L G

    2013-01-01

    Metallic nanoparticles have been actively investigated in recent years by different optical and laser methods with the purpose of their applications in optoelectronics and photonics, chemistry, laser nanobiomedicine, optical diagnostics, and other fields. A major role among metallic nanoparticles is played by nanoparticles from the noble metals (silver, gold, etc). These particles have unique plasmonic properties (resonances in the range of wavelength 400–540 nm), which can be used for the absorption, scattering and transformation of laser energy. Analysis of the thermo-optical characteristics of the interaction processes of laser radiation with silver nanoparticles is carried out, taking into account absorption, scattering and extinction of laser radiation by nanoparticles, as well as the thermo-optical and other properties of nanoparticles. Estimations are made of the influence of these nanoparticle properties on the possible results of laser radiation interaction with silver nanoparticles, including heating, heat exchange, possible melting and evaporation, and processes in the ambient media. These results can be used in laser processing of silver nanoparticles and their applications in laser nanomedicine. (paper)

  20. Investigation of the flat-beam model of the beam-beam interaction

    Directory of Open Access Journals (Sweden)

    Bjoern S. Schmekel

    2003-10-01

    Full Text Available At the interaction point of a storage ring collider each beam is subject to perturbations due to the electromagnetic field of the counterrotating beam. For flat beams, a well-known approximation models the beam by a current sheet which is uniform in the horizontal plane, restricting the particle motion to the vertical direction. In this classical model a water-bag beam distribution has been used to find working points and beam-beam tune shift parameters which lead to a stable beam distribution. We investigate the stability of a more realistic Gaussian equilibrium distribution. A linearized Vlasov equation written in action-angle variables is used to compute the radial and angular modes of a perturbation in two-dimensional phase space to first order in the displacement from the design trajectory. We find that the radial modes, which are often neglected, can have a stabilizing effect on the beam motion.

  1. The interaction between 4-aminoantipyrine and bovine serum albumin: Multiple spectroscopic and molecular docking investigations

    International Nuclear Information System (INIS)

    Teng Yue; Liu Rutao; Li Chao; Xia Qing; Zhang Pengjun

    2011-01-01

    4-Aminoantipyrine (AAP) is widely used in the pharmaceutical industry, in biochemical experiments and in environmental monitoring. AAP as an aromatic pollutant in the environment poses a great threat to human health. To evaluate the toxicity of AAP at the protein level, the effects of AAP on bovine serum albumin (BSA) were investigated by multiple spectroscopic techniques and molecular modeling. After the inner filter effect was eliminated, the experimental results showed that AAP effectively quenched the intrinsic fluorescence of BSA via static quenching. The number of binding sites, the binding constant, the thermodynamic parameters and binding subdomain were measured, and indicated that AAP could spontaneously bind with BSA on subdomain IIIA through electrostatic forces. Molecular docking results revealed that AAP interacted with the Glu 488 and Glu 502 residues of BSA. Furthermore, the conformation of BSA was demonstrably changed in the presence of AAP. The skeletal structure of BSA loosened, exposing internal hydrophobic aromatic ring amino acids and peptide strands to the solution.

  2. Microscopic and Spectroscopic Investigation of Poly(3-hexylthiophene Interaction with Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Maurizio De Crescenzi

    2011-08-01

    Full Text Available The inclusion of carbon nanotubes in polymer matrix has been proposed to enhance the polymer’s physical and electrical properties. In this study, microscopic and spectroscopic techniques are used to investigate the interaction between poly(3-hexylthiophene (P3HT and nanotubes and the reciprocal modification of physical properties. The presence of P3HT-covered nanotubes dispersed in the polymer matrix has been observed by atomic force microscopy and transmission electron microscopy. Then, the modification of P3HT optical properties due to nanotube inclusion has been evidenced with spectroscopic techniques like absorption and Raman spectroscopy. The study is completed with detailed nanoscale analysis by scanning probe techniques. The ordered self assembly of polymer adhering on the nanotube is unveiled by showing an example of helical wrapping of P3HT. Scanning tunneling spectroscopy study provides information on the electronic structure of nanotube-polymer assembly, revealing the charge transfer from P3HT to the nanotube.

  3. Investigation of the Interaction between Mucins and β-Lactoglobulin under Tribological Stress

    DEFF Research Database (Denmark)

    Celebioglu, Hilal Yilmaz; Guðjónsdóttir, María; Chronakis, Ioannis S.

    2016-01-01

    The interaction characteristics between mucins and beta-lactoglobulin (BLG) under tribological stress were investigated by comparing the lubricity of mixed solutions of mucineBLG with that of neat protein solutions at compliant hydrophobic interfaces. Surface adsorption properties of the proteins......BSM and BLGePGM, reduced significantly, and BLG appeared to dominate the surface adsorption event, presumably due to the reduced concentration of mucins and the Vroman effect. While pin-on-disk tribometry and mini-traction machine (MTM) were employed to provide the tribological contacts with varying contact...... acidic pH, such as at pH 3.5. More importantly, pH dependent lubricating properties of BLGeBSM mixed solutions appeared to be determined by competitive adsorption of the two proteins onto the substrates, which suggests that they do not form as strong aggregates as BLGesaliva, especially under...

  4. Multi-spectroscopic methods investigation on the interaction of tenoxicam with DNA.

    Science.gov (United States)

    Liu, Bing-Mi; Zhang, Jun; Liu, Yang; Zhang, Li-Ping; Ma, Ping; Wang, Xin; Liu, Bin

    2015-12-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) show chemopreventive and chemosuppressive effects on various cancer cell lines. They exert anticancer activities by inhibiting both at the protein level and/or at the transcription level. Thus, in this paper, the interaction between tenoxicam (TXM) and calf thymus DNA (ct-DNA) was investigated by UV-visible light, fluorescence, viscosity experiments and DNA melting studies. The results showed that TXM could bind to ct-DNA in the groove binding mode. The binding constants were 7.67 × 10(3) and 5.48 × 10(3) M(-1) at 293 and 300 K, respectively. Furthermore, the calculated thermodynamic parameters suggested that hydrogen bonds or van der Waals force might play an important role in the binding of TXM to ct-DNA. The obtained results should give new insight into the pharmacological activity of TXM. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Investigation of the interaction between indigotin and two serum albumins by spectroscopic approaches

    Directory of Open Access Journals (Sweden)

    Zheng-Jun Cheng

    2013-08-01

    Full Text Available The binding characteristics of indigotin with human serum albumin (HSA and bovine serum albumin (BSA have been investigated by various spectroscopic techniques. Spectroscopic analysis revealed that the quenching mechanism between indigotin and HSA/BSA belonged to the static quenching. The displacement experiments suggested that indigotin primarily bound to tryptophan residues on proteins within site I. The thermodynamic parameters indicated that the binding of indigotin–HSA/BSA mainly depended on the hydrophobic interaction. The binding distance of indigotin to HSA/BSA was evaluated. The results by synchronous fluorescence, three-dimensional fluorescence, Fourier Transform Infrared spectroscopy (FT-IR and circular dichroism (CD spectra showed that the conformation of proteins altered in the presence of indigotin. Keywords: Human serum albumin, Bovine serum albumin, Indigotin, Fluorescence spectroscopy, Binding constants

  6. Investigation of fracture-matrix interaction: Preliminary experiments in a simple system

    International Nuclear Information System (INIS)

    Foltz, S.D.; Tidwell, V.C.; Glass, R.J.; Sobolik, S.R.

    1993-01-01

    Paramount to the modeling of unsaturated flow and transport through fractured porous media is a clear understanding of the processes controlling fracture-matrix interaction. As a first step toward such an understanding, two preliminary experiments have been performed to investigate the influence of matrix imbibition on water percolation through unsaturated fractures in the plane normal to the fracture. Test systems consisted of thin slabs of either tuff or an analog material cut by a single vertical fracture into which a constant fluid flux was introduced. Transient moisture content and solute concentration fields were imaged by means of x-ray absorption. Flow fields associated with the two different media were significantly different owing to differences in material properties relative to the imposed flux. Richards' equation was found to be a valid means of modeling the imbibition of water into the tuff matrix from a saturated fracture for the current experiment

  7. Numerical investigation of convection-induced MHD waves interacting with a null point in 2D

    Science.gov (United States)

    Tarr, Lucas A.; Linton, Mark G.; Leake, James

    2015-04-01

    We use the LaRe2D MHD code to investigate the propagation of waves in a 2D geometry that includes a quadrupolar magnetic field with a single nullpoint. The simulation box spans the upper convection zone to the corona (y=[-3Mm,35.4Mm] ) and includes a stratified atmosphere. We model the upper convection zone by introducing an energy flux at the lower boundary, an ad-hoc Newton-cooling term to simulate the effect of radiation at the photosphere (y=0), and an initial condition that includes density and internal energy perturbations throughout the convection zone. This sets up the superadiabatic temperature gradient necessary to sustain convection and generate waves. We discuss the dynamic properties of these waves as they propagate through the atmosphere and interact at topologically important features of the magnetic field. This work is funded by the Chief of Naval Research.

  8. Investigation on the interaction of pyrene with bovine serum albumin using spectroscopic methods.

    Science.gov (United States)

    Xu, Chengbin; Gu, Jiali; Ma, Xiping; Dong, Tian; Meng, Xuelian

    2014-05-05

    This paper was designed to investigate the interaction of pyrene with bovine serum albumin (BSA) under physiological condition by spectroscopic methods. Spectroscopic analysis of the emission quenching revealed that the quenching mechanism of BSA by pyrene was static. The binding sites and constants of pyrene-BSA complex were observed to be 1.20 and 2.63×10(6) L mol(-1) at 298 K, respectively. The enthalpy change (ΔH) and entropy change (ΔS) revealed that van der Waals forces and hydrogen bonds stabilized the pyrene-BSA complex. Energy transfer from tryptophan to pyrene occurred by a FRET (fluorescence resonance energy transfer) mechanism, and the distance (r=2.72 nm) had been determined. The results of synchronous, three-dimensional fluorescence, and circular dichroism spectra showed that the pyrene induced conformational changes of BSA. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Aircraft-based investigation of Dynamics-Aerosol-Chemistry-Cloud Interactions in Southern West Africa

    Science.gov (United States)

    Flamant, Cyrille

    2017-04-01

    The EU-funded project DACCIWA (Dynamics-Aerosol-Chemistry-Cloud Interactions in West Africa, http://www.dacciwa.eu) is investigating the relationship between weather, climate and air pollution in southern West Africa. The air over the coastal region of West Africa is a unique mixture of natural and anthropogenic gases, liquids and particles, emitted in an environment, in which multi-layer cloud decks frequently form. These exert a large influence on the local weather and climate, mainly due to their impact on radiation, the surface energy balance and thus the diurnal cycle of the atmospheric boundary layer. The main objective for the aircraft detachment was to build robust statistics of cloud properties in southern West Africa in different chemical landscapes to investigate the physical processes involved in their life cycle in such a complex chemical environment. As part of the DACCIWA field campaigns, three European aircraft (the German DLR Falcon 20, the French SAFIRE ATR 42 and the British BAS Twin Otter) conducted a total of 50 research flights across Ivory Coast, Ghana, Togo, and Benin from 27 June to 16 July 2016 for a total of 155 flight hours, including hours sponsored through 3 EUFAR projects. The aircraft were used in different ways based on their strengths, but all three had comparable instrumentation with the the capability to do gas-phase chemistry, aerosol and clouds, thereby generating a rich dataset of atmospheric conditions across the region. Eight types of flight objectives were conducted to achieve the goals of the DACCIWA: (i) Stratus clouds, (ii) Land-sea breeze clouds, (iii) Mid-level clouds, (iv) Biogenic emission, (v) City emissions, (vi) Flaring and ship emissions, (vii) Dust and biomass burning aerosols, and (viii) air-sea interactions. An overview of the DACCIWA aircraft campaign as well as first highlights from the airborne observations will be presented.

  10. Angiotensin converting enzyme insertion/deletion genotype, exercise and physical decline: evidence of a gene-environment interaction

    NARCIS (Netherlands)

    Kritchevsky, S.B.; Nicklas, B.J.; Visser, M.; Simonsick, E.M.; Newman, A.B.; Harris, T.B.; Lange, E.M.; Penninx, B.W.J.H.; Goodpaster, B.H.; Satterfield, S.; Colbert, L.; Rubin, S; Pahor, M.

    2005-01-01

    Context: Physical performance in response to exercise appears to be influenced by the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) genotype in young adults, but whether this relationship could help explain variation in older individuals' response to exercise has not been well

  11. Gene/Environment Interaction in Atherosclerosis: An Example of Clinical Medicine as Seen from the Evolutionary Perspective

    Directory of Open Access Journals (Sweden)

    Gerhard Mertens

    2010-01-01

    The chronic multifactorial disease of atherosclerosis clearly illustrates the Darwinian paradigm. Recent research, combining the effects of genes and environment, has provided surprising clues to the pathogenesis of this major public health problem. This example makes a strong case for recognizing evolution biology as a basic science for medicine.

  12. Underlying Mechanisms of Gene-Environment Interactions in Externalizing Behavior: A Systematic Review and Search for Theoretical Mechanisms

    NARCIS (Netherlands)

    Weeland, J.; Overbeek, G.; Orobio de Castro, B.; Matthys, W.

    2015-01-01

    Over the last decade, several candidate genes (i.e., MAOA, DRD4, DRD2, DAT1, 5-HTTLPR, and COMT) have been extensively studied as potential moderators of the detrimental effects of postnatal family adversity on child externalizing behaviors, such as aggression and conduct disorder. Many studies on

  13. Underlying Mechanisms of Gene-Environment Interactions in Externalizing Behavior : A Systematic Review and Search for Theoretical Mechanisms

    NARCIS (Netherlands)

    Weeland, Joyce|info:eu-repo/dai/nl/328240583; Overbeek, Geertjan|info:eu-repo/dai/nl/25233602X; de Castro, Bram Orobio|info:eu-repo/dai/nl/166985422; Matthys, Walter|info:eu-repo/dai/nl/074826484

    2015-01-01

    Over the last decade, several candidate genes (i.e., MAOA, DRD4, DRD2, DAT1, 5-HTTLPR, and COMT) have been extensively studied as potential moderators of the detrimental effects of postnatal family adversity on child externalizing behaviors, such as aggression and conduct disorder. Many studies on

  14. The Dopamine D2 Receptor Gene, Perceived Parental Support, and Adolescent Loneliness: Longitudinal Evidence for Gene-Environment Interactions

    Science.gov (United States)

    van Roekel, Eeske; Goossens, Luc; Scholte, Ron H. J.; Engels, Rutger C. M. E.; Verhagen, Maaike

    2011-01-01

    Background: Loneliness is a common problem in adolescence. Earlier research focused on genes within the serotonin and oxytocin systems, but no studies have examined the role of dopamine-related genes in loneliness. In the present study, we focused on the dopamine D2 receptor gene (DRD2). Methods: Associations among the DRD2, sex, parental support,…

  15. Chronic and Acute Stress, Gender, and Serotonin Transporter Gene-Environment Interactions Predicting Depression Symptoms in Youth

    Science.gov (United States)

    Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Hazel, Nicholas A.; Najman, Jake M.

    2010-01-01

    Background: Many recent studies of serotonin transporter gene by environment effects predicting depression have used stress assessments with undefined or poor psychometric methods, possibly contributing to wide variation in findings. The present study attempted to distinguish between effects of acute and chronic stress to predict depressive…

  16. The dopamine D2 receptor gene, perceived parental support, and adolescent loneliness : longitudinal evidence for gene-environment interactions

    NARCIS (Netherlands)

    van Roekel, Eeske; Goossens, Luc; Scholte, Ron H. J.; Engels, Rutger C. M. E.; Verhagen, Maaike

    2011-01-01

    Background: Loneliness is a common problem in adolescence. Earlier research focused on genes within the serotonin and oxytocin systems, but no studies have examined the role of dopamine-related genes in loneliness. In the present study, we focused on the dopamine D2 receptor gene (DRD2). Methods:

  17. Evidence for gene-environment interaction in a genome wide study of isolated, non-syndromic cleft palate

    OpenAIRE

    Beaty, Terri H.; Ruczinski, Ingo; Murray, Jeffrey C.; Marazita, Mary L.; Munger, Ronald G.; Hetmanski, Jacqueline B.; Murray, Tanda; Redett, Richard J.; Fallin, M. Daniele; Liang, Kung Yee; Wu, Tao; Patel, Poorav J.; Jin, Sheng C.; Zhang, Tian Xiao; Schwender, Holger

    2011-01-01

    Non-syndromic cleft palate (CP) is a common birth defect with a complex and heterogeneous etiology involving both genetic and environmental risk factors. We conducted a genome wide association study (GWAS) using 550 case-parent trios, ascertained through a CP case collected in an international consortium. Family based association tests of single nucleotide polymorphisms (SNP) and three common maternal exposures (maternal smoking, alcohol consumption and multivitamin supplementation) were used...

  18. Interactions of Mono- and Divalent Metal Ions with Aspartic and Glutamic Acid Investigated with IR Photodissociation Spectroscopy and Theory

    NARCIS (Netherlands)

    O' Brien, J. T.; Prell, J. S.; Steill, J. D.; Oomens, J.; Williams, E. R.

    2008-01-01

    The interaction of metal ions with aspartic (Asp) and glutamic (Glu) acid and the role of gas-phase acidity on zwitterionic stability were investigated using infrared photodissociation spectroscopy in the spectral range 950-1900 cm(-1) and by hybrid density functional theory. Lithium ions interact

  19. Investigation on the interaction between bovine serum albumin and 2,2-diphenyl-1-picrylhydrazyl

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiangrong [Department of Chemistry, School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003 (China); Chen, Dejun; Wang, Gongke [School of Chemistry and Chemical Engineering, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, 46 Jian-she Road, Mu Ye District, Xinxiang, Henan 453007 (China); Lu, Yan, E-mail: 1842457577@qq.com [School of Chemistry and Chemical Engineering, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, 46 Jian-she Road, Mu Ye District, Xinxiang, Henan 453007 (China)

    2014-12-15

    Albumin represents a very abundant and important circulating antioxidant in plasma. In this paper, the ability of bovine serum albumin (BSA) to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical has been investigated using UV–vis absorption spectra. The result shows that the antioxidant activity of BSA against DPPH radical is similar to glutathione and the value of IC{sub 50} is 5.153×10{sup −5} mol L{sup −1}. The interaction between BSA and DPPH has been investigated without or with the eight popular antioxidants (L-ascorbic acid, α-tocopherol, glutathione, melatonin, (+)-catechin hydrate, procyanidine B3, β-carotene and astaxanthin) by means of fluorescence spectroscopy and circular dichroism (CD) spectroscopy. The fluorescence experiments show that DPPH quenches the fluorescence intensity of BSA through a static mechanism. The quenching process of DPPH with BSA is easily affected by the eight antioxidants, however, they cannot change the quenching mechanism of DPPH with BSA. Additionally, as shown by synchronous fluorescence spectroscopy and CD, DPPH may induce conformational and microenvironmental changes of BSA. - Highlights: • The antioxidant activity of BSA against DPPH is similar to glutathione. • DPPH can quench the fluorescence of BSA through a static quenching. • One molecule of DPPH radical reduced by one molecule of BSA. • The eight antioxidants cannot change the quenching mechanism of DPPH with BSA. • The binding parameters are decreased by the introduction of the eight antioxidants.

  20. Interaction of DNA with Cationic Lipid Mixtures-Investigation at Langmuir Lipid Monolayers.

    Science.gov (United States)

    Janich, Christopher; Hädicke, André; Bakowsky, Udo; Brezesinski, Gerald; Wölk, Christian

    2017-10-03

    Four different binary lipid mixtures composed of a cationic lipid and the zwitterionic colipids DOPE or DPPC, which show different DNA transfer activities in cell culture models, were investigated at the soft air/water interface to identify transfection efficiency determining characteristics. Langmuir films are useful models to investigate the interaction between DNA and lipid mixtures in a two-dimensional model system by using different surface sensitive techniques, namely, epifluorescence microscopy and infrared reflection-absorption spectroscopy. Especially, the effect of adsorbed DNA on the properties of the lipid mixtures has been examined. Distinct differences between the lipid composites were found which are caused by the different colipids of the mixtures. DOPE containing lipid mixtures form fluid monolayers with a uniform distribution of the fluorescent probe in the presence and absence of DNA at physiologically relevant surface pressures. Only at high nonphysiological pressures, the lipid monolayer collapses and phase separation was observed if DNA was present in the subphase. In contrast, DPPC containing lipid mixtures show domains in the liquid condensed phase state in the presence and absence of DNA in the subphase. The adsorption of DNA at the positively charged mixed lipid monolayer induces phase separation which is expressed in the morphology and the point of appearance of these domains.

  1. Experimental investigation of wavy leading edges on rod-aerofoil interaction noise

    Science.gov (United States)

    Chen, Weijie; Qiao, Weiyang; Tong, Fan; Wang, Liangfeng; Wang, Xunnian

    2018-05-01

    Experimental studies are performed to investigate the effect of wavy leading edges on rod-aerofoil interaction noise in an open-jet anechoic wind tunnel. NACA 0012 aerofoils with straight and wavy leading edges (denoted by SLE and WLE, respectively) are embedded in the wake of a circular rod. The WLEs are in the form of sinusoidal profiles of amplitude, A, and wavelength, W. Parametric studies of the amplitude and wavelength characteristics are conducted to understand the effect of WLEs on noise reduction. It is observed that the sound power reduction level is sensitive to both the amplitude and wavelength of the WLEs. The WLE with the largest amplitude and smallest wavelength can achieve the most considerable noise reduction effect of up to 4 dB. The influences of rod diameter, d, and free-stream velocity, U0, on the noise reduction effect of the WLEs are also investigated. In addition, a parametric study of the influence of separating rod-aerofoil distance on the acoustic radiation of the SLE case and on the sound power reduction level of the WLE cases is performed. It is found that a critical spacing exists where the acoustic radiation and noise reduction can be divided into two different "modes".

  2. Numerical investigation of interactions of multiple spherical shock waves between themselves and with the underlying surface

    Science.gov (United States)

    Andrushchenko, V. A.; Murashkin, I. V.; Shevelev, Yu. D.

    2016-06-01

    Within the investigation of various aspects of asteroid and comet danger and, in particular, the explosion of several fragments of meteoroids in the atmosphere above the Earth surface, the toy problem about four point explosions in the case of their special arrangement above the underlying surface is numerically solved. Complex interactions of primary and secondary shock waves between themselves, with the hard surface, and with tangential discontinuities are examined. The structure of flow inside gas regions disturbed by the explosions—the occurrence of eddy structures in them and the influence of reflected shocks waves on them—are investigated. The tendency of the external wave fronts of each explosion to form a unified front and the tendency of their internal hot domains to merge into a joined configuration (where the second process proceeds a little later than the first one) is revealed. This unified front and joined configuration are qualitatively identical to the external internal structure for the solitary explosion. The specially arranged explosions are chosen because the effects of multiple diffraction, interference, and, the main thing, cumulation of spherical waves are manifested more clearly in this caseTwo variants with different altitude of the explosions above the surface are calculated.

  3. Field Investigation of Stream-Aquifer Interactions: A Case Study in Coastal California

    Science.gov (United States)

    Pritchard-Peterson, D.; Malama, B.

    2017-12-01

    We report here results of a detailed investigation of the dynamic interaction between a stream and an alluvial aquifer at Swanton Pacific Ranch in the Scotts Creek watershed, Santa Cruz County, California. The aquifer is an important source of groundwater for cropland irrigation and for aquatic ecosystem support. Low summer base flows in Scotts Creek are a source of serious concern for land managers, fisheries biologists, and regulatory agencies due to the presence of federally protected steelhead trout and coho salmon. An understanding of the interaction between the stream and pumped aquifer will allow for assessment of the impacts of groundwater extraction on stream flows and is essential to establishing minimum flow requirements. This will aid in the development of sustainable riparian groundwater pumping practices that meet agricultural and ecological needs. Results of extensive direct-push sampling of the subsurface, laboratory falling-head permeameter tests and particle size analysis of aquifer sediments, multi-day pumping tests, long-term passive monitoring of aquifer hydraulic heads and stream stage and discharge, and electrical resistivity interrogation of the subsurface are reported here. Findings indicate that the permeable subsurface formation tapped by irrigation wells is a leaky semi-confined aquifer, overlain by a thin low permeability layer of silt and clay above which lies Scotts Creek. These results are particularly useful to land managers responsible for groundwater abstraction from wells that tap into the aquifer. Additionally, an index of stream-aquifer connectivity is proposed that would allow land managers to conveniently modify groundwater abstraction practices, minimizing concerns of stream depletion.

  4. Experimental Investigation of Mechanical Properties of Black Shales after CO2-Water-Rock Interaction

    Directory of Open Access Journals (Sweden)

    Qiao Lyu

    2016-08-01

    Full Text Available The effects of CO2-water-rock interactions on the mechanical properties of shale are essential for estimating the possibility of sequestrating CO2 in shale reservoirs. In this study, uniaxial compressive strength (UCS tests together with an acoustic emission (AE system and SEM and EDS analysis were performed to investigate the mechanical properties and microstructural changes of black shales with different saturation times (10 days, 20 days and 30 days in water dissoluted with gaseous/super-critical CO2. According to the experimental results, the values of UCS, Young’s modulus and brittleness index decrease gradually with increasing saturation time in water with gaseous/super-critical CO2. Compared to samples without saturation, 30-day saturation causes reductions of 56.43% in UCS and 54.21% in Young’s modulus for gaseous saturated samples, and 66.05% in UCS and 56.32% in Young’s modulus for super-critical saturated samples, respectively. The brittleness index also decreases drastically from 84.3% for samples without saturation to 50.9% for samples saturated in water with gaseous CO2, to 47.9% for samples saturated in water with super-critical carbon dioxide (SC-CO2. SC-CO2 causes a greater reduction of shale’s mechanical properties. The crack propagation results obtained from the AE system show that longer saturation time produces higher peak cumulative AE energy. SEM images show that many pores occur when shale samples are saturated in water with gaseous/super-critical CO2. The EDS results show that CO2-water-rock interactions increase the percentages of C and Fe and decrease the percentages of Al and K on the surface of saturated samples when compared to samples without saturation.

  5. Investigations of the structure and electromagnetic interactions of few-body systems

    International Nuclear Information System (INIS)

    Lehman, D.R.; Haberzettl, H.; Maximon, L.C.; Parke, W.C.

    1992-07-01

    In order to make it easy for the reader to see the specific research carried out and the progress made, the following report of progress is done by topic. Each item has a format layout of Topic, Investigators, Objective, Significance, and Description of Progress, followed at the end by the relevant references. As is clear from the topics listed, the emphasis of the George Washington University (GWU) theory group has been on the structure and electromagnetic interactions of few-body nuclei. Both low- and intermediate-energy electromagnetic disintegration of these nuclei is considered. When the excitation energy of the target nucleus is low, the aim has been to handle the continuum part of the theoretical work numerically with no approximations, that is, by means of full three- or four-body dynamics. When structure questions axe the issue, numerically accurate calculations axe always carried through, limited only by the underlying two-body or three-body interactions used as input. Implicit in our work is the question of how far one can go within the traditional nuclear physics framework, i.e., nucleons and mesons in a nonrelativistic setting. Our central goal is to carry through state-of-the-art fewbody calculations that wig serve as a means of determining at what point standard nuclear physics requires quark degrees of freedom in order to understand the phenomena in question. So far, in the problems considered, there has been no evidence of the necessity to go beyond the traditional approach, though we always keep in mind that possibility. As our work is involved with questions in the intermediate-energy realm, moving from a nonrelativistic framework to a relativistic one is always a consideration. Currently, for the problems that have been pursued in this domain of energy, the issues concern far more the mechanisms of the reactions and structural questions than the need to move to relativistic dynamics

  6. Theoretical investigation of interaction between a rectangular plate and fractional viscoelastic foundation

    Directory of Open Access Journals (Sweden)

    Chengcheng Zhang

    2014-08-01

    Full Text Available The interaction between plates and foundations is a typical problem encountered in geotechnical engineering. The long-term plate performance is highly dependent on the rheological characteristics of ground soil. Compared with conventional linear rheology, the fractional calculus-based theory is a more powerful mathematical tool that can address this issue. This paper proposes a fractional Merchant model (FMM to investigate the time-dependent behavior of a simply supported rectangular plate on viscoelastic foundation. The correspondence principle involving Laplace transforms was employed to derive the closed-form solutions of plate response under uniformly distributed load. The plate deflection, bending moment, and foundation reaction calculated using the FMM were compared with the results obtained from the analogous elastic model (EM and the standard Merchant model (SMM. It is shown that the upper and lower bound solutions of the FMM can be determined using the EM. In addition, a parametric study was performed to examine the influences of the model parameters on the time-dependent behavior of the plate–foundation interaction problem. The results indicate that a small fractional differential order corresponds to a plate resting on a sandy soil foundation, while the fractional differential order value should be increased for a clayey soil foundation. The long-term performance of a foundation plate can be accurately simulated by varying the values of the fractional differential order and the viscosity coefficient. The observations from this study reveal that the proposed fractional model has the capability to capture the variation of plate deflection over many decades of time.

  7. Microfluidic biofunctionalisation protocols to form multi-valent interactions for cell rolling and phenotype modification investigations

    KAUST Repository

    Perozziello, Gerardo

    2013-07-01

    In this study, we propose a fast, simple method to biofunctionalise microfluidic systems for cellomic investigations based on micro-fluidic protocols. Many available processes either require expensive and time-consuming protocols or are incompatible with the fabrication of microfluidic systems. Our method differs from the existing since it is applicable to an assembled system, uses few microlitres of reagents and it is based on the use of microbeads. The microbeads have specific surface moieties to link the biomolecules and couple cell receptors. Furthermore, the microbeads serve as arm spacer and offer the benefit of the multi-valent interaction. Microfluidics was adapted together with topology and biochemistry surface modifications to offer the microenvironment for cellomic studies. Based on this principle, we exploit the streptavidin-biotin interaction to couple antibodies to the biofunctionalised microfluidic environment within 5 h using 200 μL of reagents and biomolecules. We selected the antibodies able to form complexes with the MHC class I (MHC-I) molecules present on the cell membrane and involved in the immune surveillance. To test the microfluidic system, tumour cell lines (RMA) were rolled across the coupled antibodies to recognise and strip MHC-I molecules. As result, we show that cell rolling performed inside a microfluidic chamber functionalised with beads and the opportune antibody facilitate the removal of MHC class I molecules. We showed that the level of median fluorescent intensity of the MHC-I molecules is 300 for cells treated in a not biofunctionalised surface. It decreased to 275 for cells treated in a flat biofunctionalised surface and to 250 for cells treated on a surface where biofunctionalised microbeads were immobilised. The cells with reduced expression of MHC-I molecules showed, after cytotoxicity tests, susceptibility 3.5 times higher than normal cells. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Investigating lava-substrate interactions through flow experiments with syrup, wax, and molten basalt

    Science.gov (United States)

    Rumpf, M. E.; Lev, E.

    2015-12-01

    Among the many factors influencing the complex process of lava flow emplacement, the interaction with the substrate onto which flow is emplaced plays a central role. Lava flows are rarely emplaced onto smooth or regular surfaces. For example, at Kīlauea Volcano, Hawai'i, lava flows regularly flow over solid rock, vegetation, basaltic or silica sand, and man-made materials, including asphalt and concrete. In situ studies of lava-substrate interactions are inherently difficult, and often dangerous, to carry-out, requiring the design of controllable laboratory experiments. We investigate the effects of substrate grain size, cohesion, and roughness on flow mobility and morphology through a series of flow experiments using analog materials and molten basalt. We have developed a series of experiments that allow for adjustable substrate parameters and analyze their effects on lava flow emplacement. The first set of experiments are performed at the Fluids Mechanics Laboratory at the Lamont-Doherty Earth Observatory and focus on two analog materials: polyethylene glycol (PEG), a commercially available wax, and corn syrup. The fluids were each extruded onto a series of scaled substrate beds to replicate the emplacement of lava in a natural environment. Preliminary experiments demonstrated that irregular topography, particularly topography with a height amplitude similar to that of the flow itself, can affect flow morphology, width, and velocity by acting as local barriers or culverts to the fluid. This is expected from observations of fluid flow in natural environments. A follow-up set of experiments will be conducted in Fall 2015 at the Syracuse University (SU) Lava Project Lab. In this set, we will pour molten basalt directly onto a series of substrates representing natural environments found on the Earth and other rocky bodies in the Solar System. These experiments will allow for analysis of the effects of basaltic composition and high temperatures on lava-substrate heat

  9. Investigating the effect of surface water - groundwater interactions on stream temperature using Distributed temperature sensing and instream temperature model

    DEFF Research Database (Denmark)

    Karthikeyan, Matheswaran; Blemmer, Morten; Mortensen, Julie Flor

    2011-01-01

    Surface water–groundwater interactions at the stream interface influences, and at times controls the stream temperature, a critical water property driving biogeochemical processes. This study investigates the effects of these interactions on temperature of Stream Elverdamsåen in Denmark using...... the Distributed Temperature Sensing (DTS) system and instream temperature modelling. Locations of surface water–groundwater interactions were identified from the temperature data collected over a 2-km stream reach using a DTS system with 1-m spatial and 5-min temporal resolution. The stream under consideration...... surface water–groundwater interactions on heterogeneous behaviour of stream temperature....

  10. Investigation the interaction between the pulsed ultraviolet laser beams and PEDOT:PSS/graphene composite films

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, Shih-Feng, E-mail: tsengsf@itrc.narl.org.tw [Instrument Technology Research Center, National Applied Research Laboratories, Hsinchu 30076, Taiwan (China); Hsiao, Wen-Tse; Chung, Chien-Kai [Instrument Technology Research Center, National Applied Research Laboratories, Hsinchu 30076, Taiwan (China); Chang, Tien-Li [Department of Mechatronic Engineering, National Taiwan Normal University, Taipei 10610, Taiwan (China)

    2015-11-30

    Highlights: • This research aims to investigate the interaction between pulsed ultraviolet laser beams and transparent PEDOT:PSS/graphene composite films. • The laser ablated microstructure on film surfaces provides the electrical isolation. • The surface roughness, microhardness, spectrum and cross-sectional view of PEDOT:PSS/graphene composite film were measured and analyzed. • The focused UV laser beam was irradiated along line patterns with an overlapping rate of 60%. • The applied laser fluences much over the ablation thresholds of 1.27 J/cm{sup 2} to 3.82 J/cm{sup 2}. - Abstract: This research aims to investigate the interaction between pulsed ultraviolet (UV) laser beams and transparent PEDOT:PSS/graphene composite films. The laser ablated microstructure on film surfaces provides the electrical isolation and prevents the electrical contact from each location for the projected capacitive touch screen. Before the laser processing, the surface roughness, microhardness, spectrum and cross-sectional view of PEDOT:PSS/graphene composite film were measured by an atomic force microscope, a nanoindenter, a spectrometer and a scanning electron microscope, respectively. The focused UV laser beam was irradiated along line patterns with an overlapping rate of 60% and the applied laser fluences much over the ablation thresholds of 1.27 J/cm{sup 2} to 3.82 J/cm{sup 2}. The surface morphology, three-dimensional topography, and cross-sectional profile of isolated lines and electrode structures after laser microstructuring were measured by a confocal laser scanning microscope. By increasing the laser fluence from 1.27 J/cm{sup 2} to 3.82 J/cm{sup 2}, the ablated line widths and depths increased from 12.17 ± 0.24 μm to 21 ± 0.37 μm and from 190 ± 9 nm to 227 ± 15 nm, respectively. Moreover, the ablated lines of microstructuring electrodes had a clear and regular ablated edge quality.

  11. Interactions between {beta}-carboline alkaloids and bovine serum albumin: Investigation by spectroscopic approach

    Energy Technology Data Exchange (ETDEWEB)

    Nafisi, Shohreh, E-mail: drshnafisi@gmail.com [Department of Chemistry, Islamic Azad University, Central Tehran Branch (IAUCTB), Tehran (Iran, Islamic Republic of); Panahyab, Ataollah [Department of Chemistry, Islamic Azad University, Central Tehran Branch (IAUCTB), Tehran (Iran, Islamic Republic of); Bagheri Sadeghi, Golshan [Department of Biology, Islamic Azad University, Science and Research Branch, Tehran (Iran, Islamic Republic of)

    2012-09-15

    {beta}-Carboline alkaloids are present in medicinal plants such as Peganum harmala L. that have been used as folk medicine in anticancer therapy. BSA is the major soluble protein constituent of the circulatory system, and has many physiological functions including the transport of a variety of compounds. This study is the first attempt to investigate the binding of {beta}-carboline alkaloids to BSA by using a constant protein concentration and varying drug concentrations at pH 7.2. FTIR and UV-Vis spectroscopic methods were used to analyze the binding modes of {beta}-carboline alkaloids, the binding constants and the effects of drug complexation on BSA stability and conformation. Spectroscopic evidence showed that {beta}-carboline alkaloids bind BSA via hydrophobic interaction and van der Waals contacts along with H-bonding with the -NH groups, with overall binding constants of K{sub harmine-BSA}=2.04 Multiplication-Sign 10{sup 4} M{sup -1}, K{sub tryptoline-BSA}=1.2 Multiplication-Sign 10{sup 4} M{sup -1}, K{sub harmaline-BSA}=5.04 Multiplication-Sign 10{sup 3} M{sup -1}, K{sub harmane-BSA}=1.41 Multiplication-Sign 10{sup 3} M{sup -1} and K{sub harmalol-BSA}=1.01 Multiplication-Sign 10{sup 3} M{sup -1}, assuming that there is one drug molecule per protein. The BSA secondary structure was altered with a major decrease of {alpha}-helix from 64% (free protein) to 59% (BSA-harmane), 56% (BSA-harmaline and BSA-harmine), 55% (BSA-tryptoline), 54% (BSA-harmalol) and {beta}-sheet from 15% (free protein) to 6-8% upon {beta}-carboline alkaloids complexation, inducing a partial protein destabilization. - Highlights: Black-Right-Pointing-Pointer We model the binding of {beta}-carboline alkaloids to BSA by using the spectroscopic methods. Black-Right-Pointing-Pointer We investigate the effects of drug complexation on BSA stability and conformation. Black-Right-Pointing-Pointer A partial protein destabilization occurred at high alkaloids concentration. Black

  12. Low-temperature nuclear magnetic resonance investigation of systems frustrated by competing exchange interactions

    Science.gov (United States)

    Roy, Beas

    This doctoral thesis emphasizes on the study of frustrated systems which form a very interesting class of compounds in physics. The technique used for the investigation of the magnetic properties of the frustrated materials is Nuclear Magnetic Resonance (NMR). NMR is a very novel tool for the microscopic study of the spin systems. NMR enables us to investigate the local magnetic properties of any system exclusively. The NMR experiments on the different systems yield us knowledge of the static as well as the dynamic behavior of the electronic spins. Frustrated systems bear great possibilities of revelation of new physics through the new ground states they exhibit. The vandates AA'VO(PO4)2 [AA' ≡ Zn2 and BaCd] are great prototypes of the J1-J2 model which consists of magnetic ions sitting on the corners of a square lattice. Frustration is caused by the competing nearest-neighbor (NN) and next-nearest neighbor (NNN) exchange interactions. The NMR investigation concludes a columnar antiferromagnetic (AFM) state for both the compounds from the sharp peak of the nuclear spin-lattice relaxation rate (1/T1) and a sudden broadening of the 31P-NMR spectrum. The important conclusion from our study is the establishment of the first H-P-T phase diagram of BaCdVO(PO4)2. Application of high pressure reduces the saturation field (HS) in BaCdVO(PO4)2 and decreases the ratio J2/J1, pushing the system more towards a questionable boundary (a disordered ground state) between the columnar AFM and a ferromagnetic ground state. A pressure up to 2.4 GPa will completely suppress HS. The Fe ions in the `122' iron-arsenide superconductors also sit on a square lattice thus closely resembling the J1-J2 model. The 75As-NMR and Nuclear Quadrupole Resonance (NQR) experiments are conducted in the compound CaFe2As2 prepared by two different heat treatment methods (`as-grown' and `annealed'). Interestingly the two samples show two different ground states. While the ground state of the `as

  13. Investigating the effects of nitrous oxide sedation on frontal-parietal interactions.

    Science.gov (United States)

    Ryu, Ji-Ho; Kim, Pil-Jong; Kim, Hong-Gee; Koo, Yong-Seo; Shin, Teo Jeon

    2017-06-09

    Although functional connectivity has received considerable attention in the study of consciousness, few studies have investigated functional connectivity limited to the sedated state where consciousness is maintained but impaired. The aim of the present study was to investigate changes in functional connectivity of the parietal-frontal network resulting from nitrous oxide-induced sedation, and to determine the neural correlates of cognitive impairment during consciousness transition states. Electroencephalography was acquired from healthy adult patients who underwent nitrous oxide inhalation to induce cognitive impairment, and was analyzed using Granger causality (GC). Periods of awake, sedation and recovery for GC between frontal and parietal areas in the delta, theta, alpha, beta, gamma and total frequency bands were obtained. The Friedman test with post-hoc analysis was conducted for GC values of each period for comparison. As a sedated state was induced by nitrous oxide inhalation, power in the low frequency band showed increased activity in frontal regions that was reversed with discontinuation of nitrous oxide. Feedback and feedforward connections analyzed in spectral GC were changed differently in accordance with EEG frequency bands in the sedated state by nitrous oxide administration. Calculated spectral GC of the theta, alpha, and beta frequency regions in the parietal-to-frontal direction was significantly decreased in the sedated state while spectral GC in the reverse direction did not show significant change. Frontal-parietal functional connectivity is significantly affected by nitrous oxide inhalation. Significantly decreased parietal-to-frontal interaction may induce a sedated state. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. An Investigation to Resolve the Interaction Between Fuel Cell, Power Conditioning System and Application Loads

    Energy Technology Data Exchange (ETDEWEB)

    Sudip K. Mazumder

    2005-12-31

    Development of high-performance and durable solidoxide fuel cells (SOFCs) and a SOFC power-generating system requires knowledge of the feedback effects from the power-conditioning electronics and from application-electrical-power circuits that may pass through or excite the power-electronics subsystem (PES). Therefore, it is important to develop analytical models and methodologies, which can be used to investigate and mitigate the effects of the electrical feedbacks from the PES and the application loads (ALs) on the reliability and performance of SOFC systems for stationary and non-stationary applications. However, any such attempt to resolve the electrical impacts of the PES on the SOFC would be incomplete unless one utilizes a comprehensive analysis, which takes into account the interactions of SOFC, PES, balance-of-plant system (BOPS), and ALs as a whole. SOFCs respond quickly to changes in load and exhibit high part- and full-load efficiencies due to its rapid electrochemistry, which is not true for the thermal and mechanical time constants of the BOPS, where load-following time constants are, typically, several orders of magnitude higher. This dichotomy can affect the lifetime and durability of the SOFCSs and limit the applicability of SOFC systems for load-varying stationary and transportation applications. Furthermore, without validated analytical models and investigative design and optimization methodologies, realizations of cost-effective, reliable, and optimal PESs (and power-management controls), in particular, and SOFC systems, in general, are difficult. On the whole, the research effort can lead to (a) cost-constrained optimal PES design for high-performance SOFCS and high energy efficiency and power density, (b) effective SOFC power-system design, analyses, and optimization, and (c) controllers and modulation schemes for mitigation of electrical impacts and wider-stability margin and enhanced system efficiency.

  15. Setting the Time Frame - Investigating Culture-Environment Interactions in the Late Quaternary

    Science.gov (United States)

    Klasen, N.; Just, J.; Rethemeyer, J.

    2015-12-01

    We present a status update of luminescence age estimates of sediments from Ethiopia and the Iberian Peninsula that are related to human occupation and are currently being investigated in the interdisciplinary Collaborative Research Center "Our way to Europe - Culture-Environment Interaction and Human Mobility in the Late Quaternary" (CRC806). The aim of the project is to investigate the dispersal of anatomically modern humans from Africa to Europe, and a robust chronology is essential. In the CRC806, dating is provided by luminescence, palaeomagnetic and radiocarbon techniques. A key site of the CRC806 is Chew Bahir in Ethiopia. This lake basin is located in the source area of the emergence of anatomically modern humans. Radiocarbon, luminescence and palaeomagnetic dating have been used to develop an age-depth model for drill core sediments that date back to 115 ka over 42 m depth. The model is independent of palaeoclimatic proxy interpretation. On the Iberian Peninsula cave deposits have been dated with luminescence techniques and compared to radiocarbon ages wherever applicable. Recently, existing radiocarbon chronologies on the Iberian Peninsula have been revised in light of methodological developments. Robust luminescence dating is therefore especially important in this region, where the stratigraphy is difficult to constrain. We aim to improve the precision of luminescence age estimates by comparing different measurement techniques for equivalent dose and dose-rate determinations, and by using Bayesian statistics to develop age-depth models. Combining different chronological techniques has enabled the development of accurate and precise chronologies, which will allow a better understanding of the emergence of modern humans.

  16. The acid-catalyzed interaction of melanin with nitrite ions. An EPR investigation

    Directory of Open Access Journals (Sweden)

    Matuszak Zenon

    2015-07-01

    Full Text Available The interaction of synthetic dihydroxyphenylalanine (DOPA melanin (DM with nitrite ions, NO2−, in the pH 3.6–7.0 range, has been investigated using electron paramagnetic resonance (EPR. We found that especially at pH <5.5 (from ca. 5.5 to 3.6 the reaction of DM with nitrite generated large quantities of new melanin radicals, which implies the involvement of nitrous acid, HNO2, in the radical formation process. Measurements carried out at constant pH of 3.6 showed that the melanin signal increased together with nitrite concentration, reaching a plateau level which was more than fourfold larger compared to the initial signal amplitude observed in a nitrite-free buffer of the same pH. The effects of nitrite and DM concentrations on the melanin-free radical content were also investigated. It is proposed that the radicals are generated by one electron oxidation of melanin ortho-hydroquinone groups to ortho-semiquinones by HNO2 or related nitrogen oxides such as NO2• radicals. The possible involvement of nitric oxide (•NO and peroxynitrite (ONOO− in DM oxidation was also examined. In air-free solutions, nitric oxide per se did not generate melanin radicals; however, in the presence of oxygen a marked increase in the melanin EPR signal intensity was observed. This result is interpreted in terms of the generation of radicals via the oxidation of DM by peroxynitrite. Our findings suggest that melanin can function as a natural scavenger of nitrous acid and some nitrous acid-derived species. This property may be relevant to physiological functions of melanin pigments in vivo.

  17. Applying Geospatial Techniques to Investigate Boundary Layer Land-Atmosphere Interactions Involved in Tornadogensis

    Science.gov (United States)

    Weigel, A. M.; Griffin, R.; Knupp, K. R.; Molthan, A.; Coleman, T.

    2017-12-01

    Northern Alabama is among the most tornado-prone regions in the United States. This region has a higher degree of spatial variability in both terrain and land cover than the more frequently studied North American Great Plains region due to its proximity to the southern Appalachian Mountains and Cumberland Plateau. More research is needed to understand North Alabama's high tornado frequency and how land surface heterogeneity influences tornadogenesis in the boundary layer. Several modeling and simulation studies stretching back to the 1970's have found that variations in the land surface induce tornadic-like flow near the surface, illustrating a need for further investigation. This presentation introduces research investigating the hypothesis that horizontal gradients in land surface roughness, normal to the direction of flow in the boundary layer, induce vertically oriented vorticity at the surface that can potentially aid in tornadogenesis. A novel approach was implemented to test this hypothesis using a GIS-based quadrant pattern analysis method. This method was developed to quantify spatial relationships and patterns between horizontal variations in land surface roughness and locations of tornadogenesis. Land surface roughness was modeled using the Noah land surface model parameterization scheme which, was applied to MODIS 500 m and Landsat 30 m data in order to compare the relationship between tornadogenesis locations and roughness gradients at different spatial scales. This analysis found a statistical relationship between areas of higher roughness located normal to flow surrounding tornadogenesis locations that supports the tested hypothesis. In this presentation, the innovative use of satellite remote sensing data and GIS technologies to address interactions between the land and atmosphere will be highlighted.

  18. Investigation of molten corium-concrete interaction phenomena and aerosol release

    International Nuclear Information System (INIS)

    Spencer, B.W.; Thompson, D.H.; Armstrong, D.R.; Fink, J.K.; Gunther, W.H.; Kilsdonk, D.J.; Sehgal, B.R.

    1987-01-01

    The Electric Power Research Institute is sponsoring a program of laboratory investigations at Argonne National Laboratory to study the interaction between molten core materials and reactor concrete basemats during postulated severe reactor accidents, with particular emphasis on measurements of the magnitude and chemical species present in the aerosol releases. The approach in this program is to sustain internal heat generation in reactor-material corium using direct electrical heating and to develop test operating and diagnostics capabilities with a series of small- and intermediate-scale scoping tests followed by fully instrumented large-scale testing. Real reactor materials (UO 2 , ZrO 2 , oxides of stainless steel, plus metallics) are used, with small amounts of La 2 O 3 , BaO, and SrO added to simulate nonvolatile fission products. In intermediate-scale scoping tests completed to date, corium inventories of up to 29 kg have been heated with power inputs in excess of 1 kW/kg melt. The measured concrete ablation rates have ranged from 0.9 to 3.9 mm/minute. Aerosol samples have been examined using a scanning electron microscope and show submicron particles, 2-6 micrometer spheres, and agglomerates that range from a few micrometers to string 13 micrometers in length

  19. Use of a Rabbit Soft Tissue Chamber Model to Investigate Campylobacter jejuni - Host Interactions

    Directory of Open Access Journals (Sweden)

    Annika eFlint

    2010-11-01

    Full Text Available Despite the prevalence of C. jejuni as an important food borne pathogen, the microbial factors governing its infection process are poorly characterized. In this study, we developed a novel rabbit soft tissue chamber model to investigate C. jejuni interactions with its host. The in vivo transcriptome profile of C. jejuni was monitored as a function of time post-infection by competitive microarray hybridization with cDNA obtained from C. jejuni grown in vitro. Genome-wide expression analysis identified 449 genes expressed at significantly different levels in vivo. Genes implicated to play important roles in early colonization of C. jejuni within the tissue chamber include up-regulation of genes involved in ribosomal protein synthesis and modification, heat shock response, and primary adaptation to the host environment (DccSR regulon. Genes encoding proteins involved in the TCA cycle and flagella related components were found to be significantly down regulated during early colonization. Oxidative stress defense and stringent response genes were found to be maximally induced during the acute infectious phase. Overall, these findings reveal possible mechanisms involved in adaptation of Campylobacter to the host.

  20. Investigating Power System Primary and Secondary Reserve Interaction under High Wind Power Penetration

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yingchen [National Renewable Energy Lab. (NREL), Golden, CO (United States); Tan, Jin [National Renewable Energy Lab. (NREL), Golden, CO (United States); Krad, Ibrahim [National Renewable Energy Lab. (NREL), Golden, CO (United States); Yang, Rui [National Renewable Energy Lab. (NREL), Golden, CO (United States); Gevorgian, Vahan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Ela, Erik [Electric Power Research Inst. (EPRI), Knoxville, TN (United States)

    2016-12-01

    Power system frequency needs to be maintained close to its nominal value at all times to successfully balance load and generation and maintain system reliability. Adequate primary frequency response and secondary frequency response are the primary forces to correct an energy imbalance at the second-to-minute level. As wind energy becomes a larger portion of the world's energy portfolio, there is an increased need for wind to provide frequency response. This paper addresses one of the major concerns about using wind for frequency regulation: the unknown factor of the interaction between primary and secondary reserves. The lack of a commercially available tool to model this has limited the energy industry's understanding of when the depletion of primary reserves will impact the performance of secondary response or vice versa. This paper investigates the issue by developing a multi-area frequency response integration tool with combined primary and secondary capabilities. The simulation is conducted in close coordination with economical energy scheduling scenarios to ensure credible simulation results.

  1. Investigation of Interaction Between Ozagrel and Human Serum Albumin by Spectroscopic and Electrochemical Methods

    Science.gov (United States)

    Li, S.; Wang, Li; Hao, J.; Wang, L.; Tong, Y.-J.; Fu, Z.-Q.; Zhang, A.-P.

    2017-01-01

    The interaction between ozagrel and human serum albumin (HSA) was investigated by fl uorescence spectroscopy, UV-Vis absorption spectroscopy, cyclic voltammetry (CV), differential pulse voltammetry (DPV), and Fourier transform infrared spectroscopy (FTIR) under simulative physiological conditions. The results of CV, DPV and fl uorescence titration revealed that ozagrel bound to HSA. The enthalpy change (ΔH) and the entropy change (ΔS) were derived to be positive values, indicating that the hydrophobic force played the main role in the binding of ozagrel with HSA. The binding distance between ozagrel and HSA was 1.75 nm. Upon binding with ozagrel, the conformation and the secondary structure of HSA molecules were changed. The percentage of α-helix and β-sheet structures decreased by 7.25% and 4.58%, respectively, while the percentage of a β-turn structure increased by 2.67%. The effect of common ions on the binding of ozagrel with HSA was also examined. This study will give an insight into the evaluation of the drug's stabi-lity during transport and its releasing effi ciency at the target site under simulative physiological conditions.

  2. The continuing need to investigate the nature and content of teleconsultation communication using interaction analysis techniques.

    Science.gov (United States)

    Miller, Edward Alan

    2011-01-01

    The lack of systematically collected and analysed data about the effect of telemedicine on patient-provider communication is a frequently cited barrier for why video communication has yet to reach its full potential. Existing research provides little information about the subtle and detailed changes in communication that take place over video. Comprehensive investigations of actual medical encounter behaviour are therefore required, including verbal content analysis, which uses interaction analysis systems (IAS) to describe and categorize the communication that has taken place. Ten IAS studies were identified in the literature. Although it is difficult to generalize due to differences in methodology and context, some tentative conclusions can be drawn. First, on-site providers tend to be substantially less active than off-site providers, suggesting that the former typically serve as facilitators and observers, rather than active participants. Second, just as in the conventional face-to-face setting, providers' utterances tend to predominate in telemedicine. Third, conventional patterns of more task-focused than socio-emotional utterances tend to persist in telemedicine. However, some studies found telemedicine to be more patient-centred than conventional medicine, and others found it less so. We do not yet have a full understanding of the subtractive and enhancing effects of telemedicine on provider-patient relations and outcomes.

  3. Multi-spectroscopic investigation of the binding interaction of fosfomycin with bovine serum albumin

    Directory of Open Access Journals (Sweden)

    Manjunath D. Meti

    2015-08-01

    Full Text Available The interaction between fosfomycin (FOS and bovine serum albumin (BSA has been investigated effectively by multi-spectroscopic techniques under physiological pH 7.4. FOS quenched the intrinsic fluorescence of BSA via static quenching. The number of binding sites n and observed binding constant KA were measured by the fluorescence quenching method. The thermodynamic parameters ΔG0, ΔH0 and ΔS0 were calculated at different temperatures according to the van’t Hoff equation. The site of binding of FOS in the protein was proposed to be Sudlow’s site I based on displacement experiments using site markers viz. warfarin, ibuprofen and digitoxin. The distance r between the donor (BSA and acceptor (FOS molecules was obtained according to the Förster theory. The effect of FOS on the conformation of BSA was analyzed using synchronous fluorescence spectra (SFS, circular dichroism (CD and 3D fluorescence spectra. A molecular modeling study further confirmed the binding mode obtained by the experimental studies. Keywords: Fosfomycin, Serum albumin, Spectroscopic methods, Synchronous fluorescence, 3D spectra

  4. Experimental Investigation of the Interaction between Rising Bubbles and Swirling Water Flow

    Directory of Open Access Journals (Sweden)

    Tomomi Uchiyama

    2014-01-01

    Full Text Available This study experimentally investigates the interaction between rising bubbles and swirling water flow imposed around the central (vertical axis of a bubble plume in a cylindrical water tank. Small air bubbles are successively released from the bottom of the tank to generate a bubble plume, and a stirring disc at the bottom of the tank is rotated to impose a swirling water flow around the central axis of the bubble plume. The bubbles disperse further with the increasing rotational speed ω of the stirring disc. Some bubbles shift toward the central axis of the swirling flow when ω is high. The nondimensional swirling velocity of water reduces with increasing bubble flow rate when ω is lower than a certain value. However, it is less affected by the bubbles when ω is higher. The precessional amplitude for the upper end of the vortex core increases due to the presence of the bubbles. With increasing ω, the nondimensional precessional velocity decreases, and the bubble effect also reduces.

  5. Investigation of antioxidant interactions between Radix Astragali and Cimicifuga foetida and identification of synergistic antioxidant compounds.

    Directory of Open Access Journals (Sweden)

    Fei Wang

    Full Text Available The medicinal plants of Huang-qi (Radix Astragali and Sheng-ma (Cimicifuga foetida demonstrate significantly better antioxidant effects when used in combination than when used alone. However, the bioactive components and interactional mechanism underlying this synergistic action are still not well understood. In the present study, 2,2-diphenyl-1-picrylhydrazyl (DPPH radical scavenging assay was employed to investigate the antioxidant capacity of single herbs and their combination with the purpose of screening synergistic antioxidant compounds from them. Chromatographic isolation was performed on silica gel, Sephadex LH-20 columns and HPLC, and consequently to yield formononetin, calycosin, ferulic acid and isoferulic acid, which were identified by their retention time, UV λmax, MS and MS/MS data. The combination of isoferulic acid and calycosin at a dose ratio of 1∶1 resulted in significant synergy in scavenging DPPH radicals and ferric reducing antioxidant power (FRAP assay. Furthermore, the protective effects of these four potential synergistic compounds were examined using H2O2-induced HepG2 Cells bioassay. Results revealed that the similar synergy was observed in the combination of isoferulic acid and calycosin. These findings might provide some theoretical basis for the purported synergistic efficiency of Huang-qi and Sheng-ma as functional foods, dietary supplements and medicinal drugs.

  6. Investigation of antioxidant interactions between Radix Astragali and Cimicifuga foetida and identification of synergistic antioxidant compounds.

    Science.gov (United States)

    Wang, Fei; Zhao, Shancang; Li, Feng; Zhang, Bo; Qu, Yi; Sun, Tianlei; Luo, Ting; Li, Dapeng

    2014-01-01

    The medicinal plants of Huang-qi (Radix Astragali) and Sheng-ma (Cimicifuga foetida) demonstrate significantly better antioxidant effects when used in combination than when used alone. However, the bioactive components and interactional mechanism underlying this synergistic action are still not well understood. In the present study, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was employed to investigate the antioxidant capacity of single herbs and their combination with the purpose of screening synergistic antioxidant compounds from them. Chromatographic isolation was performed on silica gel, Sephadex LH-20 columns and HPLC, and consequently to yield formononetin, calycosin, ferulic acid and isoferulic acid, which were identified by their retention time, UV λmax, MS and MS/MS data. The combination of isoferulic acid and calycosin at a dose ratio of 1∶1 resulted in significant synergy in scavenging DPPH radicals and ferric reducing antioxidant power (FRAP) assay. Furthermore, the protective effects of these four potential synergistic compounds were examined using H2O2-induced HepG2 Cells bioassay. Results revealed that the similar synergy was observed in the combination of isoferulic acid and calycosin. These findings might provide some theoretical basis for the purported synergistic efficiency of Huang-qi and Sheng-ma as functional foods, dietary supplements and medicinal drugs.

  7. Thermodynamics of the interaction of the food additive tartrazine with serum albumins: a microcalorimetric investigation.

    Science.gov (United States)

    Basu, Anirban; Kumar, Gopinatha Suresh

    2015-05-15

    The thermodynamics of the interaction of the food colourant tartrazine with two homologous serum proteins, HSA and BSA, were investigated, employing microcalorimetric techniques. At T=298.15K the equilibrium constants for the tartrazine-BSA and HSA complexation process were evaluated to be (1.92 ± 0.05) × 10(5)M(-1) and (1.04 ± 0.05) × 10(5)M(-1), respectively. The binding was driven by a large negative standard molar enthalpic contribution. The binding was dominated essentially by non-polyelectrolytic forces which remained largely invariant at all salt concentrations. The polyelectrolytic contribution was weak at all salt concentrations and accounted for only 6-18% of the total standard molar Gibbs energy change in the salt concentration range 10-50mM. The negative standard molar heat capacity values, in conjunction with the enthalpy-entropy compensation phenomenon observed, established the involvement of dominant hydrophobic forces in the complexation process. Tartrazine enhanced the stability of both serum albumins against thermal denaturation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Does action planning moderate the intention-habit interaction in the exercise domain? A three-way interaction analysis investigation

    NARCIS (Netherlands)

    de Bruijn, G.-J.; Rhodes, R.E.; van Osch, L.

    2012-01-01

    Both habit strength and action planning have been found to moderate the intention-exercise behaviour relationship, but no research exists that has investigated how habit strength and action planning simultaneously influence this relationship. The present study was designed to explore this issue in a

  9. EXPERIMENTAL INVESTIGATIONS OF INTERACTION OF TRACK AND ROLLING STOCK ON CROSSOVERS

    Directory of Open Access Journals (Sweden)

    M. A. Arbuzov

    2016-10-01

    Full Text Available Purpose. Recently on the Ukrainian railways network more attention is paid to the cases of violations in the maintenance of crossovers, which may lead to deterioration of the train traffic safety conditions. As a rule, such violations occur as a result of inaccuracies during crossover pegging and laying, as well as are the consequence of impact of rolling stock and thermal forces. The appearance of geometrical irregularities can also be triggered by violation of the scheme of layout of concrete sleepers in the crossover turnout curve with intertrack spaces of less than 5.3 m. Therefore, we have decided to analyze the impact of the presence of deviations from the layout scheme of the sleepers and geometric irregularities on the conditions of track and rolling stock interaction based on the results of experimental investigations. It was also decided to establish a connection between the stress-strain states of the track and the presence of short sleepers. Methodology. The effect of deviations from the layout scheme of the sleepers and geometric irregularities on the interaction conditions of track and rolling stock was studied by means of theoretical calculations and experimental research. The experimental research covered the area on the non-public railway tracks that meets the required conditions for scientific and research work on the territory of «Transinvestservice» company. Findings. The distribution of stresses and forces acting on a railway track depending on speed movement of experienced rolling stock was obtained. In addition we obtained the data on the influence of the sleeper geometric parameters on its stress-strain state. Originality. For the first time the paper assessed the impact of rolling stock in the presence of geometrical irregularities and asymmetrically truncated sleepers within the crossover connection part on the stress-strain state of track in this zone. In addition, we compared the results for the area with common and

  10. Numerical investigation of particle-blast interaction during explosive dispersal of liquids and granular materials

    Science.gov (United States)

    Pontalier, Q.; Lhoumeau, M.; Milne, A. M.; Longbottom, A. W.; Frost, D. L.

    2018-04-01

    Experiments show that when a high-explosive charge with embedded particles or a charge surrounded by a layer of liquid or granular material is detonated, the flow generated is perturbed by the motion of the particles and the blast wave profile differs from that of an ideal Friedlander form. Initially, the blast wave overpressure is reduced due to the energy dissipation resulting from compaction, fragmentation, and heating of the particle bed, and acceleration of the material. However, as the blast wave propagates, particle-flow interactions collectively serve to reduce the rate of decay of the peak blast wave overpressure. Computations carried out with a multiphase hydrocode reproduce the general trends observed experimentally and highlight the transition between the particle acceleration/deceleration phases, which is not accessible experimentally, since the particles are obscured by the detonation products. The dependence of the particle-blast interaction and the blast mitigation effectiveness on the mitigant to explosive mass ratio, the particle size, and the initial solid volume fraction is investigated systematically. The reduction in peak blast overpressure is, as in experiments, primarily dependent on the mass ratio of material to explosive, with the particle size, density, and initial porosity of the particle bed playing secondary roles. In the near field, the blast overpressure decreases sharply with distance as the particles are accelerated by the flow. When the particles decelerate due to drag, energy is returned to the flow and the peak blast overpressure recovers and reaches values similar to that of a bare explosive charge for low mass ratios. Time-distance trajectory plots of the particle and blast wave motion with the pressure field superimposed, illustrate the weak pressure waves generated by the motion of the particle layer which travel upstream and perturb the blast wave motion. Computation of the particle and gas momentum flux in the multiphase

  11. Significance of investigating allelopathic interactions of marine organisms in the discovery and development of cytotoxic compounds

    Digital Repository Service at National Institute of Oceanography (India)

    Singh, A.; Thakur, N.L.

    ]. In well illuminated regions, the sponge Verongia arrophoha which contained symbiotic cyanobacteria showed a higher growth rate and production of allelochemical as compared that in darker areas where it lacked the ability of producing...-mediated interactions are well documented in literature [9-11] whereas chemically-mediated interactions have not received enough attention. These chemically-mediated interactions are the source of novel bioactive metabolites [12]. A wide range of natural products...

  12. INTERACTION OF LASER RADIATION WITH MATTER: Investigation of the interaction of laser radiation with composite materials by infrared spectroscopy methods

    Science.gov (United States)

    Eremin, V. I.; Kovalenko, I. P.; Levashenko, G. I.; Mazaev, N. V.; Sokol'nikov, A. S.; Shuralev, S. L.

    1990-10-01

    A description is given of the method and apparatus for determination of the effective temperature and composition of a jet of products of the interaction of laser radiation with a glass-fiber-reinforced plastic and an organic plastic. Measurements are also possible of the temperature and emissivity of a target when it is exposed in atmospheric air to cw CO2 laser radiation with a flux density of 3 × 102 — 103 W/cm2. The products of damage to the glass-fiber-reinforced plastic consisted of particles of metal oxides with a diameter d32 = 2.3-3.5 μm and a volume concentration Cv = (0.06-0.25) × 10 - 4, and of molecular gases CO2, H2O, and HCl; the damage products of the organic plastic were conglomerates of soot particles with the diameter d32 = 1-1.8 μm and a volume concentration Cv = (0.4-0.9) × 10 - 4, and the same molecular gases. The target emissivity increased with time and reached 0.8-0.9.

  13. From bulk soil to intracrystalline investigation of plant-mineral interaction

    Science.gov (United States)

    Lemarchand, D.; Voinot, A.; Chabaux, F.; Turpault, M.

    2011-12-01

    Understanding the controls and feedbacks regulating the flux of matter between bio-geochemical reservoirs in forest ecosystems receives a fast growing interest for the last decades. A complex question is to understand how minerals and vegetation interact in soils to sustain life and, to a broader scope, how forest ecosystems may respond to human activity (acid rain, harvesting,...) and climate perturbations (temperature, precipitation,...). Many mineralogical and biogeochemical approaches have longtime been developed, and occasionally coupled, in order to investigate the mechanisms by which chemical elements either are exchanged between soil particles and solutions, or are transferred to plants or to deeper soil layers and finally leave the system. But the characterization of particular processes like the contribution of minor reactive minerals to plant nutrition and global fluxes or the mechanisms by which biology can modify reaction rates and balance the bioavailability of nutrients in response to environmental perturbation sometimes fails because of the lack of suitable tracers. Recent analytical and conceptual advances have opened new perspectives for the use of light "non traditional" stable isotopes. Showing a wild range of concentrations and isotopic compositions between biogeochemical reservoirs in forest ecosystem, boron has physico-chemical properties particularly relevant to the investigation of water/rock interactions even when evolving biologically-mediated reactions. In this study, we focused on the distribution of boron isotopes from intracrystalline to bulk soil scales. An overview of the boron distribution and annual fluxes in the soil-plant system clearly indicates that the vegetation cycling largely controls the mobility of boron. We also observe that the mineral and biological B pools have drastically different isotopic signature that makes the transfer of B between them very easy to follow. In particular, the podzol soil we analyzed shows a

  14. A structural investigation of the interaction of oxalic acid with Cu(110)

    Science.gov (United States)

    White, T. W.; Duncan, D. A.; Fortuna, S.; Wang, Y.-L.; Moreton, B.; Lee, T.-L.; Blowey, P.; Costantini, G.; Woodruff, D. P.

    2018-02-01

    The interaction of oxalic acid with the Cu(110) surface has been investigated by a combination of scanning tunnelling microscopy (STM), low energy electron diffraction (LEED), soft X-ray photoelectron spectroscopy (SXPS), near-edge X-ray absorption fine structure (NEXAFS) and scanned-energy mode photoelectron diffraction (PhD), and density functional theory (DFT). O 1s SXPS and O K-edge NEXAFS show that at high coverages a singly deprotonated monooxalate is formed with its molecular plane perpendicular to the surface and lying in the [ 1 1 bar 0 ] azimuth, while at low coverage a doubly-deprotonated dioxalate is formed with its molecular plane parallel to the surface. STM, LEED and SXPS show the dioxalate to form a (3 × 2) ordered phase with a coverage of 1/6 ML. O 1s PhD modulation spectra for the monooxalate phase are found to be simulated by a geometry in which the carboxylate O atoms occupy near-atop sites on nearest-neighbour surface Cu atoms in [ 1 1 bar 0 ] rows, with a Cusbnd O bondlength of 2.00 ± 0.04 Å. STM images of the (3 × 2) phase show some centred molecules attributed to adsorption on second-layer Cu atoms below missing [001] rows of surface Cu atoms, while DFT calculations show adsorption on a (3 × 2) missing row surface (with every third [001] Cu surface row removed) is favoured over adsorption on the unreconstructed surface. O 1s PhD data from dioxalate is best fitted by a structure similar to that found by DFT to have the lowest energy, although there are some significant differences in intramolecular bondlengths.

  15. Investigation on oxidative stress of nitric oxide synthase interacting protein from Clonorchis sinensis.

    Science.gov (United States)

    Bian, Meng; Xu, Qingxia; Xu, Yanquan; Li, Shan; Wang, Xiaoyun; Sheng, Jiahe; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

    2016-01-01

    Numerous evidences indicate that excretory-secretory products (ESPs) from liver flukes trigger the generation of free radicals that are associated with the initial pathophysiological responses in host cells. In this study, we first constructed a Clonorchis sinensis (C. sinensis, Cs)-infected BALB/c mouse model and examined relative results respectively at 3, 5, 7, and 9 weeks postinfection (p.i.). Quantitative reverse transcription (RT)-PCR indicated that the transcriptional level of both endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) gradually decreased with lastingness of infection, while the transcriptional level of inducible NOS (iNOS) significantly increased. The level of malondialdehyde (MDA) in sera of infected mouse significantly increased versus the healthy control group. These results showed that the liver of C. sinensis-infected mouse was in a state with elevated levels of oxidation stress. Previously, C. sinensis NOS interacting protein coding gene (named CsNOSIP) has been isolated and recombinant CsNOSIP (rCsNOSIP) has been expressed in Escherichia coli, which has been confirmed to be a component present in CsESPs and confirmed to play important roles in immune regulation of the host. In the present paper, we investigated the effects of rCsNOSIP on the lipopolysaccharide (LPS)-induced activated RAW264.7, a murine macrophage cell line. We found that endotoxin-free rCsNOSIP significantly promoted the levels of nitric oxide (NO) and reactive oxygen species (ROS) after pretreated with rCsNOSIP, while the level of SOD decreased. Furthermore, rCsNOSIP could also increase the level of lipid peroxidation MDA. Taken together, these results suggested that CsNOSIP was a key molecule which was involved in the production of nitric oxide (NO) and its reactive intermediates, and played an important role in oxidative stress during C. sinensis infection.

  16. Detailed NMR investigation of cyclodextrin-perfluorinated surfactant interactions in aqueous media

    Energy Technology Data Exchange (ETDEWEB)

    Weiss-Errico, Mary Jo; O’Shea, Kevin E., E-mail: osheak@fiu.edu

    2017-05-05

    Highlights: • Perfluorochemicals (PFCs) are strongly encapsulated by cyclodextrins (CDs). • Competition studies confirm strong CD:PFC host-guest interactions. • {sup 19}F NMR Spectroscopy demonstrates association constants up to 10{sup 5} M{sup −1}. • Position of CD along PFC chain is elucidated from NMR results. • CD:PFC complex is not disturbed under a variety of water quality conditions. - Abstract: Perfluorochemicals (PFCs) are contaminants of serious concern because of their toxicological properties, widespread presence in drinking water sources, and incredible stability in the environment. To assess the potential application of α-, β-, and γ-cyclodextrins for PFC remediation, we investigated their complexation with linear fluorinated carboxylic acids, sulfonates, and a sulfonamide with carbon backbones ranging from C4-C9. {sup 19}F Nuclear Magnetic Resonance (NMR) spectroscopy studies demonstrated β-CD formed the strongest complexes with these PFCs. The polar head group had a modest influence, but for PFCs with backbones longer than six carbons, strong association constants are observed for 1:1 (K{sub 1:1} ∼ 10{sup 5} M{sup −1}) and 2:1 (K{sub 2:1} ∼ 10{sup 3} M{sup −1}) β-CD:PFC complexes. Excess β-CD can be used to complex 99.5% of the longer chain PFCs. Competition studies with adamantane-carboxylic acid and phenol confirmed the nature and persistence of the β-CD:PFC complex. Detailed analyses of the individual NMR chemical shifts and Job plots indicate the favored positions of the β-CD along the PFC chain. Solution pH, ionic strength, and the presence of humic acid have modest influence on the β-CD:PFC complexes. The strong encapsulation of PFCs by β-CD under a variety of water quality conditions demonstrates the tremendous potential of CD-based materials for the environmental remediation of PFCs.

  17. Investigating the potassium interactions with the palytoxin induced channels in Na+/K+ pump.

    Science.gov (United States)

    Rodrigues, Antônio M; Almeida, Antônio-Carlos G; Infantosi, Antonio F C; Teixeira, Hewerson Z; Duarte, Mário A

    2009-02-01

    K(+) has been appointed as the main physiological inhibitor of the palytoxin (PTX) effect on the Na(+)/K(+) pump. This toxin acts opening monovalent cationic channels through the Na(+)/K(+) pump. We investigate, by means of computational modeling, the kinetic mechanisms related with K(+) interacting with the complex PTX-Na(+)/K(+) pump. First, a reaction model, with structure similar to Albers-Post model, describing the functional cycle of the pump, was proposed for describing K(+) interference on the complex PTX-Na(+)/K(+) pump in the presence of intracellular ATP. A mathematic model was derived from the reaction model and it was possible to solve numerically the associated differential equations and to simulate experimental maneuvers about the PTX induced currents in the presence of K(+) in the intra- and extracellular space as well as ATP in the intracellular. After the model adjusting to the experimental data, a Monte Carlo method for sensitivity analysis was used to analyze how each reaction parameter acts during each experimental maneuver involving PTX. For ATP and K(+) concentrations conditions, the simulations suggest that the enzyme substate with ATP bound to its high-affinity sites is the main substate for the PTX binding. The activation rate of the induced current is limited by the K(+) deocclusion from the PTX-Na(+)/K(+) pump complex. The K(+) occlusion in the PTX induced channels in the enzymes with ATP bound to its low-affinity sites is the main mechanism responsible for the reduction of the enzyme affinity to PTX.

  18. [Investigation on the interaction between pentadecafluorooctanoic acid and human serum albumin by capillary electrophoresis].

    Science.gov (United States)

    Gu, Yi; Guo, Ming; Lü, Da; Hou, Ping; Yin, Xinxin

    2018-01-08

    Capillary electrophoresis (CE) has been used to establish the analytical method of interaction between pentadecafluorooctanoic acid (PFOA) and human serum albumin (HSA). Under the physiological conditions, the interaction model of PFOA and HSA were constructed. Mobility method, plug-plug kinetic (PPK) method and simplified Hummel-Dreyer method were used to determine the interaction between derivatives and HSA. Non-linear regression, Scatchard equation and Klotz equation were adopted to obtain the interaction parameters. The results showed that all the three methods can be used to analyze the interaction of PFOA-HSA system. According to the interaction parameters, the most suitable CE method is simplified Hummel-Dreyer method while the most suitable theoretical equation is non-linear regression. The binding parameters indicated that the interaction of PFOA-HSA system has only one type of binding sites and the binding is stable. The research results have illustrated the interaction between HSA and PFOA, and provided a beneficial reference for in-depth research of the toxic mechanism of PFOA.

  19. Investigating Visual-Tactile Interactions over Time and Space in Adults with Autism

    Science.gov (United States)

    Poole, Daniel; Gowen, Emma; Warren, Paul A.; Poliakoff, Ellen

    2015-01-01

    It has been suggested that the sensory symptoms which affect many people with autism spectrum conditions (ASC) may be related to alterations in multisensory processing. Typically, the likelihood of interactions between the senses increases when information is temporally and spatially coincident. We explored visual-tactile interactions in adults…

  20. Investigating Learning with an Interactive Tutorial: A Mixed-Methods Strategy

    Science.gov (United States)

    de Villiers, M. R.; Becker, Daphne

    2017-01-01

    From the perspective of parallel mixed-methods research, this paper describes interactivity research that employed usability-testing technology to analyse cognitive learning processes; personal learning styles and times; and errors-and-recovery of learners using an interactive e-learning tutorial called "Relations." "Relations"…

  1. Investigating the effect of surface water - groundwater interactions on stream temperature using Distributed temperature sensing and instream temperature model

    DEFF Research Database (Denmark)

    Karthikeyan, Matheswaran; Blemmer, Morten; Mortensen, Julie Flor

    2011-01-01

    Surface water–groundwater interactions at the stream interface influences, and at times controls the stream temperature, a critical water property driving biogeochemical processes. This study investigates the effects of these interactions on temperature of Stream Elverdamsåen in Denmark using...... the Distributed Temperature Sensing (DTS) system and instream temperature modelling. Locations of surface water–groundwater interactions were identified from the temperature data collected over a 2-km stream reach using a DTS system with 1-m spatial and 5-min temporal resolution. The stream under consideration...... exhibits three distinct thermal regimes within a 2 km reach length due to two major interactions. An energy balance model is used to simulate the instream temperature and to quantify the effect of these interactions on the stream temperature. This research demonstrates the effect of reach level small scale...

  2. Investigating direct interaction between Escherichia coli topoisomerase I and RecA

    Science.gov (United States)

    Darici, Yesim; Tse-Dinh, Yuk-Ching

    2016-01-01

    Protein-protein interactions are of special importance in cellular processes, including replication, transcription, recombination, and repair. Escherichia coli topoisomerase I (EcTOP1) is primarily involved in the relaxation of negative DNA supercoiling. E. coli RecA, the key protein for homologous recombination and SOS DNA-damage response, has been shown to stimulate the relaxation activity of EcTOP1. The evidence for their direct protein-protein interaction has not been previously established. We report here the direct physical interaction between E. coli RecA and topoisomerase I. We demonstrated the RecA-topoisomerase I interaction via pull-down assays, and surface plasmon resonance measurements. Molecular docking supports the observation that the interaction involves the topoisomerase I N-terminal domains that form the active site. Our results from pull-down assays showed that ATP, although not required, enhances the RecA-EcTOP1 interaction. We propose that E. coli RecA physically interacts with topoisomerase I to modulate the chromosomal DNA supercoiling. PMID:27001450

  3. Numerical Investigation of Compressor Non-Synchronous Vibration with Full Annulus Rotor-Stator Interaction

    Science.gov (United States)

    Espinal, Daniel

    The objective of this research is to investigate and confirm the periodicity of the Non-Synchronous Vibration (NSV) mechanism of a GE axial compressor with a full-annulus simulation. A second objective is to develop a high fidelity single-passage tool with time-accurate unsteady capabilities able to capture rotor-stator interactions and NSV excitation response. A high fidelity methodology for axial turbomachinery simulation is developed using the low diffusion shock-capturing Riemann solver with high order schemes, the Spalart-Allmaras turbulence closure model, the fully conservative unsteady sliding BC for rotor-stator interaction with extension to full-annulus and single-passage configurations, and the phase lag boundary conditions applied to rotor-stator interface and circumferential BC. A URANS solver is used and captures the NSV flow excitation frequency of 2439 Hz, which agrees reasonably well with the measured NSV frequency of 2600 Hz from strain gage test data. It is observed that the circumferentially traveling vortex formed in the vicinity of the rotor tip propagates at the speed of a non-engine order frequency and causes the NSV. The vortex travels along the suction surface of the blade and crosses the passage outlet near blade trailing edge. Such a vortex motion trajectory repeats in each blade passage and generates two low pressure regions due to the vortex core positions, one at the leading edge and one at the trailing edge, both are oscillating due to the vortex coming and leaving. These two low pressure regions create a pair of coupling forces that generates a torsion moment causing NSV. The full-annulus simulation shows that the circumferentially traveling vortex has fairly periodical behavior and is a full annulus structure. Also, frequencies below the NSV excitation frequency of 2439 Hz with large amplitudes in response to flow-separation related phenomena are present. This behavior is consistent with experimental measurements. For

  4. The application of inelastic neutron scattering to investigate the interaction of methyl propanoate with silica.

    Science.gov (United States)

    McFarlane, Andrew R; Geller, Hannah; Silverwood, Ian P; Cooper, Richard I; Watkin, David J; Parker, Stewart F; Winfield, John M; Lennon, David

    2016-06-29

    A modern industrial route for the manufacture of methyl methacrylate involves the reaction of methyl propanoate and formaldehyde over a silica-supported Cs catalyst. Although the process has been successfully commercialised, little is known about the surface interactions responsible for the forward chemistry. This work concentrates upon the interaction of methyl propanoate over a representative silica. A combination of infrared spectroscopy, inelastic neutron scattering, DFT calculations, X-ray diffraction and temperature-programmed desorption is used to deduce how the ester interacts with the silica surface.

  5. The investigation of the interaction between Oxymetazoline hydrochloride and mucin by spectroscopic approaches

    Science.gov (United States)

    Yu, Xianyong; Liu, Heting; Yang, Ying; Lu, Shiyu; Yao, Qin; Yi, Pinggui

    2013-02-01

    The fluorescence and ultraviolet spectroscopy were explored to study the interaction between Oxymetazoline hydrochloride (OMZH) and mucin under imitated physiological condition. The results demonstrated that the fluorescence quenching mechanism between OMZH and mucin is a combined quenching process. The binding constants (Ka), binding sites (n) and the corresponding thermodynamic parameters (ΔG, ΔH, and ΔS) of the interaction system were calculated at different temperatures. The hydrogen bonds and van der Waals forces play a major role in the interaction between OMZH and mucin. According to Förster non-radiation energy transfer theory, the binding distance between OMZH and mucin was calculated.

  6. Electron spin interactions in chemistry and biology fundamentals, methods, reactions mechanisms, magnetic phenomena, structure investigation

    CERN Document Server

    Likhtenshtein, Gertz

    2016-01-01

    This book presents the versatile and pivotal role of electron spin interactions in nature. It provides the background, methodologies and tools for basic areas related to spin interactions, such as spin chemistry and biology, electron transfer, light energy conversion, photochemistry, radical reactions, magneto-chemistry and magneto-biology. The book also includes an overview of designing advanced magnetic materials, optical and spintronic devices and photo catalysts. This monograph appeals to scientists and graduate students working in the areas related to spin interactions physics, biophysics, chemistry and chemical engineering.

  7. Vectors for multi-color bimolecular fluorescence complementation to investigate protein-protein interactions in living plant cells

    Directory of Open Access Journals (Sweden)

    Kuang Lin-Yun

    2008-10-01

    Full Text Available Abstract Background The investigation of protein-protein interactions is important for characterizing protein function. Bimolecular fluorescence complementation (BiFC has recently gained interest as a relatively easy and inexpensive method to visualize protein-protein interactions in living cells. BiFC uses "split YFP" tags on proteins to detect interactions: If the tagged proteins interact, they may bring the two split fluorophore components together such that they can fold and reconstitute fluorescence. The sites of interaction can be monitored using epifluorescence or confocal microscopy. However, "conventional" BiFC can investigate interactions only between two proteins at a time. There are instances when one may wish to offer a particular "bait" protein to several "prey" proteins simultaneously. Preferential interaction of the bait protein with one of the prey proteins, or different sites of interaction between the bait protein and multiple prey proteins, may thus be observed. Results We have constructed a series of gene expression vectors, based upon the pSAT series of vectors, to facilitate the practice of multi-color BiFC. The bait protein is tagged with the C-terminal portion of CFP (cCFP, and prey proteins are tagged with the N-terminal portions of either Venus (nVenus or Cerulean (nCerulean. Interaction of cCFP-tagged proteins with nVenus-tagged proteins generates yellow fluorescence, whereas interaction of cCFP-tagged proteins with nCerulean-tagged proteins generates blue fluorescence. Additional expression of mCherry indicates transfected cells and sub-cellular structures. Using this system, we have determined in both tobacco BY-2 protoplasts and in onion epidermal cells that Agrobacterium VirE2 protein interacts with the Arabidopsis nuclear transport adapter protein importin α-1 in the cytoplasm, whereas interaction of VirE2 with a different importin α isoform, importin α-4, occurs predominantly in the nucleus. Conclusion Multi

  8. Ozone-surface interactions: Investigations of mechanisms, kinetics, mass transport, and implications for indoor air quality

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, Glenn Charles [Univ. of California, Berkeley, CA (United States)

    1999-12-01

    In this dissertation, results are presented of laboratory investigations and mathematical modeling efforts designed to better understand the interactions of ozone with surfaces. In the laboratory, carpet and duct materials were exposed to ozone and measured ozone uptake kinetics and the ozone induced emissions of volatile organic compounds. To understand the results of the experiments, mathematical methods were developed to describe dynamic indoor aldehyde concentrations, mass transport of reactive species to smooth surfaces, the equivalent reaction probability of whole carpet due to the surface reactivity of fibers and carpet backing, and ozone aging of surfaces. Carpets, separated carpet fibers, and separated carpet backing all tended to release aldehydes when exposed to ozone. Secondary emissions were mostly n-nonanal and several other smaller aldehydes. The pattern of emissions suggested that vegetable oils may be precursors for these oxidized emissions. Several possible precursors and experiments in which linseed and tung oils were tested for their secondary emission potential were discussed. Dynamic emission rates of 2-nonenal from a residential carpet may indicate that intermediate species in the oxidation of conjugated olefins can significantly delay aldehyde emissions and act as reservoir for these compounds. The ozone induced emission rate of 2-nonenal, a very odorous compound, can result in odorous indoor concentrations for several years. Surface ozone reactivity is a key parameter in determining the flux of ozone to a surface, is parameterized by the reaction probability, which is simply the probability that an ozone molecule will be irreversibly consumed when it strikes a surface. In laboratory studies of two residential and two commercial carpets, the ozone reaction probability for carpet fibers, carpet backing and the equivalent reaction probability for whole carpet were determined. Typically reaction probability values for these materials were 10

  9. Investigating “Locality” of Intra-Urban Spatial Interactions in New York City Using Foursquare Data

    Directory of Open Access Journals (Sweden)

    Yeran Sun

    2016-03-01

    Full Text Available Thanks to the increasing popularity of location-based social networks, a large amount of user-generated geo-referenced check-in data is now available, and such check-in data is becoming a new data source in the study of mobility and travel. Conventionally, spatial interactions between places were measured based on the trips made between them. This paper empirically investigates the use of social media data (i.e., Foursquare data to study the “locality” of such intra-urban spatial interactions in New York City, and specifically: (i the level of “locality” of spatial interactions; (ii the impacts of personal characteristics on “locality” of spatial interaction and finally; (iii the heterogeneity in spatial distribution of “local” interactions. The results of this study indicate that: (1 spatial interactions show a high degree of locality; (2 gender does not have a considerable impact on the locality of spatial interactions and finally; (3 “local” interactions likely cluster in some places within the research city.

  10. A DFT investigation on interactions between asymmetric derivatives of cisplatin and nucleobase guanine

    Science.gov (United States)

    Tai, Truong Ba; Nhat, Pham Vu

    2017-07-01

    The interactions of hydrolysis products of cisplatin and its asymmetric derivatives cis- and trans-[PtCl2(iPram)(Mepz)] with guanine were studied using DFT methods. These interactions are dominated by electrostatic effects, namely hydrogen bond contributions and there exists a charge flow from H-atoms of ligands to the O-atoms of guanine. The replacement of NH3 moieties by larger functional groups accompanies with a moderate reaction between PtII and guanine molecule, diminishing the cytotoxicity of the drug. The asymmetric and symmetric NH2 stretching modes of complexes having strong hydrogen bond interactions are red shifted importantly as compared to complexes without presence of hydrogen bond interactions.

  11. Investigation of the interaction between modified ISCOMs and stratum corneum lipid model systems

    DEFF Research Database (Denmark)

    Madsen, Henriette Baun; Arboe-Andersen, Helle M.; Rozlosnik, Noemi

    2010-01-01

    Titration Calorimetry (ITC) confirmed existence of an enthalpically unfavorable reaction. All these methods demonstrated that the strength of electrostatic repulsion between the negatively charged SCL and the nanoparticles affected their interaction, as decreasing the negative charge of the Posintro (TM...

  12. The application of inelastic neutron scattering to investigate the interaction of methyl propanoate with silica

    OpenAIRE

    Lennon, David; McFarlane, Andrew; Geller, Hannah; Silverwood, Ian P.; Cooper, Richard I.; Watkin, David J.; Parker, Stewart F.; Winfield, John M.

    2016-01-01

    A modern industrial route for the manufacture of methyl methacrylate involves the reaction of methyl propanoate and formaldehyde over a silica-supported Cs catalyst. Although the process has been successfully commercialised, little is known about the surface interactions responsible for the forward chemistry. This work concentrates upon the interaction of methyl propanoate over a representative silica. A combination of infrared spectroscopy, inelastic neutron scattering, DFT calculations, X-r...

  13. Investigations on Fuel-Coolant Interaction with the RCN code VS-4

    International Nuclear Information System (INIS)

    Van der Putten, A.P.W.M.; Koning, H.; Van den Bogaard, J.P.A.

    1976-01-01

    Fuel-coolant interaction (FCI) processes may take place more or less coherent all along the whole coolant channel during a fast reactor accident. In order to understand the FCI phenomenon and to study its consequences for LMFBR safety, it is considered to be of great importance to take into account the axial dependency of the thermo and hydrodynamics in the computational model. To this end the programme VS-4 is being developed at RCN. This code will also be used to evaluate FCI aspects of the loss-of-cooling experiments being performed at RCN. VS-4 solves a set of partial differential equations describing the equations of conservation of mass, energy and momentum in the coolant channel as a function of the axial coordinate and time, using the method of characteristics. Notably the pressure, temperature, velocity and void fraction are calculated as functions of time and of axial coordinate. Both the all-liquid phase A and the two-phase B parts of the FCI process are described, in principle, by the same equations. It was therefore not necessary to make the so-called acoustic approximation for describing phase A. The VS-4 programme further includes: pressure losses due to friction and models describing: a. the heat transport from fuel particles into the sodium, and b. the fragmentation process. Calculations on the so-called Ispra test case have been performed giving special emphasis to the switch-over from the single phase to the two-phase part of the process. In conclusion: The method of characteristics is proved to be applicable not only for the one-phase, but also for the description of the homogeneous equilibrium two-phase part of a thermohydraulic process. To investigate the reactor safety aspects of FCI processes and to evaluate experimental research on FCI, it is indispensable to take the axial dependency effects into account. To this end the axial dependent code VS 4 based on the method of characteristics is available. At present the thermodynamic properties

  14. Interactions between geomorphology and vegetation in the Western Swiss Alps: first investigations

    Science.gov (United States)

    Giaccone, Elisa; Mariéthoz, Grégoire; Lambiel, Christophe

    2017-04-01

    The influence of earth surface processes can modify the microhabitat conditions and the species richness, composition and distribution patterns of plant communities. It is therefore important to understand how geomorphology affects the distribution of plant species to predict future vegetation evolution in a context of climate change. To better analyse the influence of geomorphology on vegetation growth in the alpine periglacial belt, we are studying various geomorphological processes (e.g. cryoturbation and solifluction), permafrost, nivation and ground surface characteristics at three focus sites of the Vaud Alps (Western Swiss Alps). The sites are located at an altitude range comprised between 2000 and 2600 m a.s.l. The geomorphology is characterized mainly by the presence of small glaciers, large moraine deposits, rock glaciers and debris slopes. Monitoring of the ground surface temperatures, permafrost mapping, vegetation survey and drone flights have been carried out to investigate in detail the environmental variables. Initial results show a heterogeneous vegetation cover depending on time since deglaciation, debris size, ground stability and soil age. Debris pioneer species are present on moraines, rock glaciers and debris slope; grassland are developed in zones not affected by LIA glacier advances or other interfering processes such as avalanches. The high-resolution images obtained from drone flights (5 cm/pixel) allow a detailed study of the granulometry. In order to use such geomorphological information on a wider area of interest, the local data acquired on focus sites have to be spatialized to a regional scale. This is accomplished by developing an approach based on remote sensing and multiple-point geostatistics that performs a semi-automated geomorphological mapping (SAGM). The SAGM is based on a training image composed by a geomorphological map yet existent, an orthophoto, the slope, the aspect, the curvature, the granulometry classification and

  15. Synthesis, Characterization and Functionalization of Polymeric Nanoparticles and Investigation of the Interaction with Biological Systems

    International Nuclear Information System (INIS)

    Bleul, Regina

    2015-01-01

    One of the main goals of nanomedicine is to improve the treatment of hazardous diseases whose conventional therapy often has serious side effects. The vision is to create a theranostic drug delivery system which is capable of safely transporting therapeutic cargo through the body to a targeted site of disease at which point the drug is released. Furthermore, it is desirable to track the carrier in real time which would allow for a personal adjustment of the therapy. Studies on the behavior of nanoparticulate substances in a physiological environment form the basis for the possibility to successfully develop a drug carrier system. In the present work, polymeric nanoparticles with different morphologies were prepared by the controlled self-assembly of amphiphilic block copolymers. The nanoparticles were subsequently characterized and their interactions with human cells and serum proteins investigated. A cytotoxicity study with spherical and cylindrical micelles as well as vesicular structures was carried out and showed a dependency of cytotoxic effects on the geometry and size of the nanoparticles. The agglomeration behavior of various polymeric nanoparticles in the presence of serum proteins was also studied. Highly uniform polymeric vesicles were continuously manufactured in a micromixer based device and in situ loading with different components was performed. In this way, dual loaded vesicles with the anticancer drug camptothecin and a high amount of hydrophobic iron oxide nanoparticles were produced. When tested in vitro, these drug-loaded vesicles showed an increased cytotoxic activity against the cancer cell line PC-3 when compared to the free drug. Specific cellular uptake in PC-3 cancer cells was demonstrated with flow cytometry and confocal laser scanning microscopy after functionalization with a cancer cell specific targeting peptide and an additional fluorescent label. Magnetic characterization of the iron oxide-loaded vesicles also confirmed the potential

  16. Prescribers' interactions with medication alerts at the point of prescribing: A multi-method, in situ investigation of the human-computer interaction.

    Science.gov (United States)

    Russ, Alissa L; Zillich, Alan J; McManus, M Sue; Doebbeling, Bradley N; Saleem, Jason J

    2012-04-01

    Few studies have examined prescribers' interactions with medication alerts at the point of prescribing. We conducted an in situ, human factors investigation of outpatient prescribing to uncover factors that influence the prescriber-alert interaction and identify strategies to improve alert design. Field observations and interviews were conducted with outpatient prescribers at a major Veterans Affairs Medical Center. Physicians, clinical pharmacists, and nurse practitioners were recruited across five primary care clinics and eight specialty clinics. Prescribers were observed in situ as they ordered medications for patients and resolved alerts. Researchers collected 351 pages of typed notes across 102 hours of observations and interviews. An interdisciplinary team identified emergent themes via inductive qualitative analysis. Altogether, 320 alerts were observed among 30 prescribers and their interactions with 146 patients. Qualitative analysis uncovered 44 emergent themes and 9 overarching factors, which were organized into a framework that describes the prescriber-alert interaction. Prescribers' ability to act on alerts was impeded by the alert interface, which did not adequately support all prescriber types. This empiric study produced a novel framework for understanding the prescriber-alert interaction. Results revealed key components of the alert interface that influence prescribers and indicate a need for more universal design. Actionable design recommendations are presented and may be used to enhance alert design and patient safety. Published by Elsevier Ireland Ltd.

  17. Genes, environment and sport performance: why the nature-nurture dualism is no longer relevant.

    Science.gov (United States)

    Davids, Keith; Baker, Joseph

    2007-01-01

    The historical debate on the relative influences of genes (i.e. nature) and environment (i.e. nurture) on human behaviour has been characterised by extreme positions leading to reductionist and polemic conclusions. Our analysis of research on sport and exercise behaviours shows that currently there is little support for either biologically or environmentally deterministic perspectives on elite athletic performance. In sports medicine, recent molecular biological advances in genomic studies have been over-interpreted, leading to a questionable 'single-gene-as-magic-bullet' philosophy adopted by some practitioners. Similarly, although extensive involvement in training and practice is needed at elite levels, it has become apparent that the acquisition of expertise is not merely about amassing a requisite number of practice hours. Although an interactionist perspective has been mooted over the years, a powerful explanatory framework has been lacking. In this article, we propose how the complementary nature of degenerate neurobiological systems might provide the theoretical basis for explaining the interactive influence of genetic and environmental constraints on elite athletic performance. We argue that, due to inherent human degeneracy, there are many different trajectories to achieving elite athletic performance. While the greatest training responses may be theoretically associated with the most favourable genotypes being exposed to highly specialised training environments, this is a rare and complex outcome. The concept of degeneracy provides us with a basis for understanding why each of the major interacting constraints might act in a compensatory manner on the acquisition of elite athletic performance.

  18. Experimental Investigation of the Wake-Mediated Interaction Forces Between Dust Particles in a Flowing Plasma

    Science.gov (United States)

    Petrov, Oleg; Lisin, Evgeny; Statsenko, Konstantin; Hyde, Truell; Carmona, Jorge

    2015-11-01

    An anisotropic spatial dependence of the wake-mediated interaction forces between dust particles in a plasma flow was studied experimentally. The measurements were performed at CASPER for the vertically aligned chain self-organized from 11 microparticles inside a glass box placed on the lower electrode of a RF gas discharge chamber. The experiment was conducted in argon plasma at 137 mTorr and monodisperse MF particles having diameters of 8.93 microns were used. To recover the wake-mediated interaction forces we improved the method based on solving the inverse Langevin problem of the dynamics of many interacting particles. To determine 3D trajectories of the particles we used a stereoscopic video surveillance system. Spatial profiles of the forces with which upstream particles act on downstream ones and vice versa were obtained. The difference between the interparticle interaction forces in the opposite directions indicates its non-reciprocal nature and can be associated with the wake. The peak position of the wake-field and the space charge concentrated in it were evaluated by the force profile analysis. The data analysis and interaction force recovering in this work was supported by the Russian Science Foundation (O.F. Petrov, K.B. Stacenko, E.?.Lisin) through Grant No. 14-12-01440).

  19. Investigation on molecular interactions of antibiotics in alcohols using volumetric and acoustic studies at different temperatures

    International Nuclear Information System (INIS)

    Naseem, Bushra; Iftikhar, Madeeha

    2017-01-01

    Highlights: • Antibiotics in different alcohols are used to study their interactions in solutions. • Density and sound velocity for antibiotic solutions are measured at different temperatures. • Apparent molar volume and isentropic compressibility are used to calculate partial molar quantities. • Acoustical parameters are calculated and discussed in terms of solute–solute and solute–solvent interactions. - Abstract: The density and sound velocity for pure alcohols (methanol, ethanol, iso-propanol and n-butanol) and molal solutions of nitroimidazoles (metronidazole (MNZ) and dimetridazole (DMZ) have been measured at different temperatures (293.15–313.15 K). Different volumetric and acoustical parameters like apparent molar volume (V ϕ ), partial molar volume (VЛљ ϕ ), apparent molar isentropic compressibility (K ϕ ), partial molar isentropic compressibility (KЛљ ϕ ), hydration number (n H ), acoustic impedance (Z) and intermolecular free length (L f ) of antibiotic solutions were calculated from the experimental values of density and sound velocity. The derived values have been used to explore the solute–solute and solute–solvent interactions. The V ϕ values are positive and K ϕ values are negative in both antibiotics, indicative of strong solute–solvent interactions and closely packed structure of antibiotics in alcohols. The decreasing trend of L f with increasing antibiotic concentration shows the presence of strong intermolecular interactions in solutions.

  20. Titin Based Viscosity in Ventricular Physiology: An Integrative Investigation of PEVK-Actin Interactions

    Science.gov (United States)

    Chung, Charles S; Methawasin, Methajit; Nelson, O Lynne; Radke, Michael H; Hidalgo, Carlos G; Gotthardt, Michael; Granzier, Henk L

    2011-01-01

    Viscosity is proposed to modulate diastolic function, but only limited understanding of the source(s) of viscosity exists. In-vitro experiments have shown that the proline-glutamic acid-valine-lysine (PEVK) rich element of titin interacts with actin, causing a viscous force in the sarcomere. It is unknown whether this mechanism contributes to viscosity in-vivo. We tested the hypothesis that PEVK-actin interaction causes cardiac viscosity and is important in-vivo via an integrative physiological study on a unique PEVK-knockout (KO) model. Both skinned cardiomyocytes and papillary muscle fibers were isolated from wildtype (WT) and PEVK KO mice and passive viscosity was examined using stretch-hold-release and sinusoidal analysis. Viscosity was reduced by ~60% in KO myocytes and ~50% in muscle fibers at room temperature. The PEVK-actin interaction was not modulated by temperature or diastolic calcium, but was increased by lattice compression. Stretch-hold and sinusoidal frequency protocols on intact isolated mouse hearts showed a smaller, 30–40% reduction in viscosity, possibly due to actomyosin interactions, and showed that microtubules did not contribute to viscosity. Transmitral Doppler echocardiography similarly revealed a 40% decrease in LV chamber viscosity in the PEVK KO in-vivo. This integrative study is the first to quantify the influence of a specific molecular (PEVK-actin) viscosity in-vivo and shows that PEVK-actin interactions are an important physiological source of viscosity. PMID:21708170

  1. Investigating multiple dysregulated pathways in rheumatoid arthritis based on pathway interaction network.

    Science.gov (United States)

    Song, Xian-Dong; Song, Xian-Xu; Liu, Gui-Bo; Ren, Chun-Hui; Sun, Yuan-Bo; Liu, Ke-Xin; Liu, Bo; Liang, Shuang; Zhu, Zhu

    2018-03-01

    The traditional methods of identifying biomarkers in rheumatoid arthritis (RA) have focussed on the differentially expressed pathways or individual pathways, which however, neglect the interactions between pathways. To better understand the pathogenesis of RA, we aimed to identify dysregulated pathway sets using a pathway interaction network (PIN), which considered interactions among pathways. Firstly, RA-related gene expression profile data, protein-protein interactions (PPI) data and pathway data were taken up from the corresponding databases. Secondly, principal component analysis method was used to calculate the pathway activity of each of the pathway, and then a seed pathway was identified using data gleaned from the pathway activity. A PIN was then constructed based on the gene expression profile, pathway data, and PPI information. Finally, the dysregulated pathways were extracted from the PIN based on the seed pathway using the method of support vector machines and an area under the curve (AUC) index. The PIN comprised of a total of 854 pathways and 1064 pathway interactions. The greatest change in the activity score between RA and control samples was observed in the pathway of epigenetic regulation of gene expression, which was extracted and regarded as the seed pathway. Starting with this seed pathway, one maximum pathway set containing 10 dysregulated pathways was extracted from the PIN, having an AUC of 0.8249, and the result indicated that this pathway set could distinguish RA from the controls. These 10 dysregulated pathways might be potential biomarkers for RA diagnosis and treatment in the future.

  2. Additivity vs Synergism: Investigation of the Additive Interaction of Cinnamon Bark Oil and Meropenem in Combinatory Therapy.

    Science.gov (United States)

    Yang, Shun-Kai; Yusoff, Khatijah; Mai, Chun-Wai; Lim, Wei-Meng; Yap, Wai-Sum; Lim, Swee-Hua Erin; Lai, Kok-Song

    2017-11-04

    Combinatory therapies have been commonly applied in the clinical setting to tackle multi-drug resistant bacterial infections and these have frequently proven to be effective. Specifically, combinatory therapies resulting in synergistic interactions between antibiotics and adjuvant have been the main focus due to their effectiveness, sidelining the effects of additivity, which also lowers the minimal effective dosage of either antimicrobial agent. Thus, this study was undertaken to look at the effects of additivity between essential oils and antibiotic, via the use of cinnamon bark essential oil (CBO) and meropenem as a model for additivity. Comparisons between synergistic and additive interaction of CBO were performed in terms of the ability of CBO to disrupt bacterial membrane, via zeta potential measurement, outer membrane permeability assay and scanning electron microscopy. It has been found that the additivity interaction between CBO and meropenem showed similar membrane disruption ability when compared to those synergistic combinations which was previously reported. Hence, results based on our studies strongly suggest that additive interaction acts on a par with synergistic interaction. Therefore, further investigation in additive interaction between antibiotics and adjuvant should be performed for a more in depth understanding of the mechanism and the impacts of such interaction.

  3. Experimental Investigation of the Vehicle–Ground Interaction – Experiment Preparation and Preliminary Results

    Directory of Open Access Journals (Sweden)

    Valašková Veronika

    2017-12-01

    Full Text Available Interaction of the moving vehicle and the ground represents the actual engineering, environmental and economic problem. Due to the complexity of the problem, a combination of the experimental measurement and the computational simulation to understand the interaction mechanism is the most beneficial approach. Results of the in-situ observation serve as an input for the numerical analysis and also as a background for the calibration of the model. Presented paper brings the summary of the experiment preparation and preliminary results which are necessary for further analyses and numerical models. Computational simulations will be helpful for understanding the vehicle-ground interaction when inputs will be verified by the experimental way at known boundary conditions.

  4. Structural study and investigation of NMR tensors in interaction of dopamine with Adenine and guanine

    Directory of Open Access Journals (Sweden)

    Lingjia Xu

    2007-04-01

    Full Text Available The interaction of dopamine with adenine and guanine were studied at the Hartree-Fock level theory. The structural and vibrational properties of dopamine-4-N7GUA and dopamine-4-N3ADE were studied at level of HF/6-31G*. Interaction energies (ΔE were calculated to be -11.49 and -11.92 kcal/mol, respectively. Some of bond lengths, angels and tortions are compared. NBO studies were performed to the second-order and perturbative estimates of donor-acceptor interaction have been done. The procedures of gauge-invariant atomic orbital (GIAO and continuous-set-of-gauge-transformation (CSGT were employed to calculate isotropic shielding, chemical shifts anisotropy and chemical shifts anisotropy asymmetry and effective anisotropy using 6-31G* basis set. These calculations yielded molecular geometries in good agreement with available experimental data.

  5. Investigating the Interaction of Graphic Organizers and Seductive Details: Can a Graphic Organizer Mitigate the Seductive-Details Effect?

    Science.gov (United States)

    Rowland-Bryant, Emily; Skinner, Christopher H.; Skinner, Amy L.; Saudargas, Richard; Robinson, Daniel H.; Kirk, Emily R.

    2009-01-01

    The interaction between seductive details (SD) and a graphic organizer (GO) was investigated. Undergraduate students (n = 207) read a target-material passage about Freud's psychosexual stages. Depending on condition, the participants also read a biographical paragraph (SD-only), viewed a graphic organizer that linked the seductive details to the…

  6. A Culturally-Adaptive Iranian Version of the Questionnaire on Teacher Interaction to Investigate English Teachers' Interpersonal Behaviour

    Science.gov (United States)

    Ahmadi Safa, Mohammad; Doosti, Mehdi

    2017-01-01

    We investigated Iranian secondary-school English teachers' interpersonal behaviour with a validated culturally-adaptive Iranian version of the Questionnaire on Teacher Interaction. Data were collected from 971 Iranian secondary-school students (398 students participated in the pilot study and 573 students in the main study) and 55 Iranian…

  7. Fundamental investigation on interaction forces in bubble swarms and its application to the design of centrifugal separators

    International Nuclear Information System (INIS)

    Wisman, R.

    1979-01-01

    The present investigation deals with two aspects of gas-liquid flows, viz. interaction forces between the phases in bubble swarms and numerical description of rotating gas-liquid flows. The insight obtained was applied to the development of axial gas-liquid cyclones, as used i.a. as primary separators in nuclear boiling water reactors. (Auth.)

  8. Investigation of syngas interaction in alcohol synthesis catalysts. Quartery technical progress report, July 1, 1995--September 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Akundi, M.A.

    1996-02-01

    This report presents the work done on {open_quotes}Investigation of Syngas Interaction in Alcohol Synthesis Catalysts{close_quotes} during the last three months. In this report the results of the work done on the effect of CO adsorption on the magnetic character of cobalt in the Cu/Co/Cr catalysts is discussed.

  9. Developing an Interactive Non-Formal Chemistry Setting and Investigating Its Effectiveness on High School Students' Attitudes towards Chemistry

    Science.gov (United States)

    Demircioglu, Gökhan

    2016-01-01

    The main purpose of this study is to design an interactive non-formal chemistry environment and investigate its effectiveness on high school students' attitudes towards chemistry. Besides that, it is tried to determine to what extent students correlate these concepts with daily life. 14 voluntary students (5 female, 9 male) from different levels…

  10. Investigation of interaction of cadmium nitrate with sodium hydroxide in aqueous solutions

    International Nuclear Information System (INIS)

    Gyunner, Eh.A.; Mel'nichenko, L.M.; Yakhkind, N.D.; Vel'mozhnyj, I.S.

    1984-01-01

    The methods of physiochemical analysis (measurement of Cd 2+ and OH - residual concentrations, refraction index and liquid phase density) as well as X-ray phase analysis of precipitations have been used to study the interaction of Cd(NO 3 ) 2 with NaOH in isomolar series of mixtures of reagent solutions and in mixtures with constant content of Cd 2+ ions at variable OH - ion concentration. It has been found that depending on reagents relations weakly-soluble interaction products are Cd 3 (OH) 5 NO 3 or Cd(OH) 2

  11. Site investigation SFR. Water-rock interaction and mixing modelling in the SFR

    International Nuclear Information System (INIS)

    Gimeno, Maria J.; Auque, Luis F.; Gomez, Javier B.; Acero, Patricia

    2011-10-01

    During 2008, the Swedish Nuclear Fuel and Waste Management Company (SKB) initiated an investigation programme for a future expansion of the final repository for low and medium level radioactive operational waste, SFR, located about 150 km north of Stockholm. The purpose of the investigations was to define and characterise a bedrock volume large enough to allow further storage of operational waste from existing Swedish nuclear power plants and future waste from the decommissioning and dismantling of nuclear power plant reactors (SKB 2008). Of several alternatives, a selected location was investigated southwest of the present SFR tunnel system. As part of the SFR Site Descriptive Model, the objective of the hydrogeochemical site description is to describe the chemistry, origin and distribution of groundwaters in the bedrock and the hydrogeochemical processes involved in their evolution. Hydrogeochemical information (salinity distribution, groundwater residence time, palaeohydrogeochemical input, etc.) are also of importance to help constrain the hydrogeological descriptive model. The hydrogeochemical modelling work has been performed in three steps, resulting in three model versions (0.1, 0.2 and 1.0). In versions 0.1 and 0.2, explorative analyses using traditional geochemical approaches (trend plots, x-y scatter plots, 3D visualisations, etc.) were performed to describe the data and to provide an early insight and understanding of the site. The final hydrogeochemical site description version 1.0 (Nilsson et al. 2011) includes data from the previous versions, as well as subsequent complementary data from the SFR extension project, and all these data are further evaluated using additional modelling approaches and techniques. In this context, the present report gives a more detailed analysis of the available data for some hydrogeochemical systems and a detailed description of the results of the geochemical and statistical modelling. One of the main aims is to establish

  12. Site investigation SFR. Water-rock interaction and mixing modelling in the SFR

    Energy Technology Data Exchange (ETDEWEB)

    Gimeno, Maria J.; Auque, Luis F.; Gomez, Javier B.; Acero, Patricia (University of Zaragoza (Spain))

    2011-10-15

    During 2008, the Swedish Nuclear Fuel and Waste Management Company (SKB) initiated an investigation programme for a future expansion of the final repository for low and medium level radioactive operational waste, SFR, located about 150 km north of Stockholm. The purpose of the investigations was to define and characterise a bedrock volume large enough to allow further storage of operational waste from existing Swedish nuclear power plants and future waste from the decommissioning and dismantling of nuclear power plant reactors (SKB 2008). Of several alternatives, a selected location was investigated southwest of the present SFR tunnel system. As part of the SFR Site Descriptive Model, the objective of the hydrogeochemical site description is to describe the chemistry, origin and distribution of groundwaters in the bedrock and the hydrogeochemical processes involved in their evolution. Hydrogeochemical information (salinity distribution, groundwater residence time, palaeohydrogeochemical input, etc.) are also of importance to help constrain the hydrogeological descriptive model. The hydrogeochemical modelling work has been performed in three steps, resulting in three model versions (0.1, 0.2 and 1.0). In versions 0.1 and 0.2, explorative analyses using traditional geochemical approaches (trend plots, x-y scatter plots, 3D visualisations, etc.) were performed to describe the data and to provide an early insight and understanding of the site. The final hydrogeochemical site description version 1.0 (Nilsson et al. 2011) includes data from the previous versions, as well as subsequent complementary data from the SFR extension project, and all these data are further evaluated using additional modelling approaches and techniques. In this context, the present report gives a more detailed analysis of the available data for some hydrogeochemical systems and a detailed description of the results of the geochemical and statistical modelling. One of the main aims is to establish

  13. Numerical investigation of gas-particle interaction in polydisperse volcanic jets

    Science.gov (United States)

    Carcano, Susanna; Esposti Ongaro, Tomaso; Bonaventura, Luca; Neri, Augusto

    2014-05-01

    We investigate the problem of underexpanded jet decompression when the injected fluid is a mixture of a gaseous phase and different classes of solid particles. The underexpanded multiphase jet problem is representative of phenomena that can be observed in the first stages of explosive volcanic eruptions. Whereas the case of homogeneous jets has been studied deeply in the literature, both experimentally, theoretically and numerically, the case of multiphase gas--particle jets still presents some open issues. It has been proven theoretically and experimentally that vents with supersonic or sonic velocity and gas pressure greater than the atmospheric one result in a rapid expansion and acceleration of the fluid to high Mach number. A series of expansion waves form and are reflected as compression waves at the flow boundary. The compression waves coealesce to form a standing normal shock wave (Mach disk), across which the fluid is rapidly compressed and decelerated to subsonic speeds. When solid particles are added to the gas flow, new phenomena associated to kinetic and thermal non-equilibrium between gas and particulate phases arise. Such effects are controlled by drag and heat exchange terms in the momentum and energy equations. In the present work we carry out two- and three-dimensional numerical simulations with the multiphase flow model PDAC (Neri et al., J. Geophys. Res, 2003; Carcano et al., Geosci. Mod. Dev., 2013), to identify and quantify non-equilibrium effects related to the interaction between the jet decompression structure and solid particles. We quantify, on a theoretical basis, the expected non-equilibrium effects between the gas and the solid phase in terms of the particle Stokes numer (St), i.e. the ratio between the particle relaxation time and a characteristic time scale of the jet (taken as the formation time of the Mach disk shock), for two sample grain-size distributions of natural events (Mount St. Helens, 1980; Vesuvius, aD 79). The Stokes

  14. Communication in the Total Institution: An Investigation of Prisoner-Guard Interaction in a State Penitentiary.

    Science.gov (United States)

    Leonard, Rebecca

    This study was concerned with determining the attitudes that prisoners and guards at Indiana State Prison hold toward one another, and with examining the interactions between prisoners and guards. Data were collected by means of structured interviews with 25 prisoners and 25 guards. Perceptions of each group were reported for the following areas:…

  15. Analytical investigation of pile-soil interaction in sand under axial and lateral loads

    Science.gov (United States)

    Abdel-Mohti, Ahmed; Khodair, Yasser

    2014-03-01

    This paper presents a numerical study of pile-soil interaction due to application of axial and lateral loads to piles in sand. The pile-soil interaction was analyzed using the finite difference (FD) software LPILE and two finite element (FE) software. The three-dimensional (3D) FE models of pile-soil interaction have been created using Abaqus/Cae and SAP2000. Various types of soft soil were studied, such as loose, medium, and dense sand. A lateral displacement of 2 cm was applied to the top of the pile while maintaining a zero slope in a guided fixation. A combined lateral and axial load of 300 kN was also studied. The paper compared between the bending moments and lateral displacements along the depth of the pile obtained from the FD solutions and FE analyses. A parametric study was conducted to study the effect of crucial design parameters such as the modulus of elasticity of soil and the number of nonlinear soil springs that can be used to model the soil. A good agreement between the results obtained by the FE models and the FD solution was observed. Also, the FE models were capable of predicting the pile-soil interaction for all types of soft soil.

  16. Investigating the Added Value of Interactivity and Serious Gaming for Educational TV

    Science.gov (United States)

    Bellotti, F.; Berta, R.; De Gloria, A.; Ozolina, A.

    2011-01-01

    TV is a medium with high penetration rates and has been suited to deliver informal education in several aspects since years. Thus, interactive TV may play a significant role in the current Life-Long Learning challenges, provided that meaningful applications are implemented. In this research work, we have explored the added value of interactivity…

  17. Affinity Capillary Electrophoresis – A Powerful Tool to Investigate Biomolecular Interactions

    Czech Academy of Sciences Publication Activity Database

    Kašička, Václav

    2017-01-01

    Roč. 30, č. 5 (2017), s. 248 ISSN 1471-6577 Institutional support: RVO:61388963 Keywords : capillary affinity electrophoresis * biomolecular interactions * binding constants Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 0.663, year: 2016

  18. Explaining Student Interaction and Satisfaction: An Empirical Investigation of Delivery Mode Influence

    Science.gov (United States)

    Johnson, Zachary S.; Cascio, Robert; Massiah, Carolyn A.

    2014-01-01

    How interpersonal interactions within a course affect student satisfaction differently between face-to-face and online modes is an important research question to answer with confidence. Using students from a marketing course delivered face-to-face and online concurrently, our first study demonstrates that student-to-professor and…

  19. INVESTIGATING THE ROLE OF PDZ-DOMAIN INTERACTIONS FOR DOPAMINE TRANSPORTER FUNCTION

    DEFF Research Database (Denmark)

    Fog, Jacob; Vægter, Christian Bjerggaard; Gether, Ulrik

    PICK1 has been shown to interact with the distal dopamine transporter (DAT) C-terminus via its PDZ domain. Although we recently have shown that ER export and targeting of the DAT to the cell surface is critically dependent on discrete epitopes in the distal C-terminus, these events do not require...

  20. A Spectroscopic and Electrochemical Investigation of Interactions of Anticancer Uracil Derivatives with Cationic and Anionic Surfactants

    International Nuclear Information System (INIS)

    Zafar, F.; Shah, A.; Ahmad, Z.; Siddiq, M.; Ali, S.; Asad Muhammad Khan, A. M.; Rana, U. A.

    2015-01-01

    Interactions of 5-fluorouracil (5-FU), a commercially available anti-cancer drug and two other possibly anti-cancer actives, 2-thiouracil (2-TU) and 2,4-dithiouracil (DTU), with anionic sodium dodecyl sulphate (SDS) and cationic cetlytrimethyl ammonium bromide (CTAB) surfactants were studied using cyclic voltammetry and UV-Visible spectroscopic techniques. The results from both techniques asserted the formation of complex between the drugs and surfactants. In the pre-micellar concentrations, the binding was mainly due to the interactions between the surfactants monomers (electrostatic) and the drug molecules, while in the post-micellar region, drug was encapsulated within the micelle due to electrostatic as well as hydrophobic interactions. The UV-Visible spectroscopic data of the interaction between 5-fluorouracil and the surfactants exhibited an isobestic point which indicated the presence of equilibrium species in bulk and the micellar phase. Binding constant, partition coefficient between bulk and miceller phase, and the number of drug molecules incorporated per micelle were calculated. (author)

  1. An Essay on Interactive Investigations of the Zeeman Effect in the Interstellar Medium

    Science.gov (United States)

    Woolsey, Lauren

    2015-01-01

    The paper presents an interactive module created through the Wolfram Demonstrations Project that visualizes the Zeeman effect for the small magnetic field strengths present in the interstellar medium. The paper provides an overview of spectral lines and a few examples of strong and weak Zeeman splitting before discussing the module in depth.…

  2. Investigating the relationship among transformational leadership, interpersonal interaction and mentoring functions.

    Science.gov (United States)

    Huang, Ching-Yuan; Weng, Rhay-Hung; Chen, Yi-Ting

    2016-08-01

    This study aims to ascertain the relationship between transformational leadership, interpersonal interaction and mentoring functions among new staff nurses. Mentoring functions could improve the job performance of new nurses, provide them with support and thus reduce their turnover rate. A cross-sectional study was employed. A questionnaire survey was carried out to collect data among a sample of new nurses from three hospitals in Taiwan. After gathering a total of 306 valid surveys, multiple regression analysis was applied to test the hypothesis. Inspirational motivation, idealised influence and individualised consideration had positive correlations with the overall mentoring function, but intellectual stimulation showed a positive association only with career development function. Perceived similarity and interaction frequency also had positive correlations with mentoring functions. When the shift overlap rate exceeded 80%, mentoring function showed a negative result. The transformational leadership of mentors would improve the mentoring functions among new staff nurses. Perceived similarity and interaction frequency between mentees and mentors also had positive correlations with mentoring functions. It is crucial for hospitals to redesign their leadership training and motivation programmes to enhance the transformational leadership of mentors. Furthermore, nursing managers should promote interaction between new staff nurses and their mentors; however, the shift overlap rate should not be too high. © 2016 John Wiley & Sons Ltd.

  3. Numerical investigation into strong axis bending shear interaction in rolled I-shaped steel sections

    NARCIS (Netherlands)

    Dekker, R.W.A.; Snijder, B.H.; Maljaars, J.

    2016-01-01

    Clause 6.2.8 of EN 1993-1-1 covers the design rules on bending-shear resistance, taking presence of shear into account by a reduced yield stress for the shear area. Numerical research on bending-shear interaction by means of the Abaqus Finite Element modelling soft-ware is presented. The numerical

  4. The investigation of the interaction between edaravone and bovine serum albumin by spectroscopic approaches

    Energy Technology Data Exchange (ETDEWEB)

    Yu Xianyong; Yang Ying; Liu Ronghua; Huang Haowen; Chen Jian; Ji Danhong [Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan Province College Key Laboratory of QSAR/QSPR, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201 (China); Li Xiaofang, E-mail: fine_chem@163.co [Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan Province College Key Laboratory of QSAR/QSPR, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201 (China); Yang Fengxian [Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan Province College Key Laboratory of QSAR/QSPR, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201 (China); Yi Pinggui, E-mail: pgyi@hnust.c [Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan Province College Key Laboratory of QSAR/QSPR, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201 (China)

    2011-07-15

    The fluorescence and ultraviolet spectroscopies were explored to study the interaction between edaravone (EDA) and bovine serum albumin (BSA) under imitated physiological condition. The experimental results show that the fluorescence quenching mechanism between EDA and BSA is a combined quenching (dynamic and static quenching). The binding constants, binding sites, and the corresponding thermodynamic parameters ({Delta}G, {Delta}H, and {Delta}S) of the interaction system were calculated at different temperatures. According to Foerster non-radiation energy transfer theory, the binding distance between EDA and BSA was calculated to be 3.10 nm. The effect of EDA on the conformation of BSA was analyzed using synchronous fluorescence spectroscopy. In addition, the effects of some common metal ions Mg{sup 2+}, Ca{sup 2+}, Cu{sup 2+}, and Ni{sup 2+} on the binding constant between EDA and BSA were examined. - Highlights: {yields} We explored the interaction of BSA and EDA using spectroscopic methods. {yields} The fluorescence quenching mechanism is combined quenching. {yields} Hydrophobic interaction force plays a major role in stabilizing the complex. {yields} The binding constants, binding sites, and thermodynamic parameters were calculated. {yields} EDA affects the conformation of tryptophan residue's microregion.

  5. A multispectroscopic and molecular docking investigation of the binding interaction between serum albumins and acid orange dye

    Science.gov (United States)

    Naveenraj, Selvaraj; Solomon, Rajadurai Vijay; Mangalaraja, Ramalinga Viswanathan; Venuvanalingam, Ponnambalam; Asiri, Abdullah M.; Anandan, Sambandam

    2018-03-01

    The interaction of Acid Orange 10 (AO10) with bovine serum albumin (BSA) was investigated comparatively with that of human serum albumin (HSA) using multispectroscopic techniques for understanding their toxic mechanism. Further, density functional theory calculations and docking studies have been carried out to gain more insights into the nature of interactions existing between AO10 and serum albumins. The fluorescence results suggest that AO10 quenched the fluorescence of BSA through the combination of static and dynamic quenching mechanism. The same trend was followed in the interaction of AO10 with HSA. In addition to the type of quenching mechanism, the fluorescence spectroscopic results suggest that the binding occurs near the tryptophan moiety of serum albumins and the binding. AO10 has more binding affinity towards BSA than HSA. An AO10-Trp model has been created to explicitly understand the Csbnd Htbnd π interactions from Bader's quantum theory of atoms in molecules analysis which confirmed that AO10 bind more strongly with BSA than that of HSA due to the formation of three hydrogen bonds with BSA whereas it forms two hydrogen bonds in the case of HSA. These obtained results provide an in-depth understanding of the interaction of the acid azo dye AO10 with serum albumins. This interaction study provides insights into the underlying reasons for toxicity of AO10 relevant to understand its effect on bovids and humans during the blood transportation process.

  6. Investigation of pajama properties on skin under mild cold conditions: the interaction between skin and clothing.

    Science.gov (United States)

    Yao, Lei; Gohel, Mayur D I; Li, Yi; Chung, Waiyee J

    2011-07-01

    Clothing is considered the second skin of the human body. The aim of this study was to determine clothing-wearer interaction on skin physiology under mild cold conditions. Skin physiological parameters, subjective sensory response, stress level, and physical properties of clothing fabric from two longitude parallel-designed wear trials were studied. The wear trials involved four kinds of pajamas made from cotton or polyester material that had hydrophilic or hydrophobic treatment, conducted for three weeks under mild cold conditions. Statistical tools, factor analysis, hierarchical linear regression, and logistic regression were applied to analyze the strong predictors of skin physiological parameters, stress level, and sensory response. A framework was established to illustrate clothing-wearer interactions with clothing fabric properties, skin physiology, stress level, and sensory response under mild cold conditions. Fabric has various effects on the human body under mild cold conditions. A fabric's properties influence skin physiology, sensation, and psychological response. © 2011 The International Society of Dermatology.

  7. Investigations of the structure and electromagnetic interactions of few-body systems

    International Nuclear Information System (INIS)

    Lehman, D.R.; Haberzettl, H.; Maximon, L.C.; Parke, W.C.; Bennhold, C.; Ito, Hiroshi; Pratt, R.K.; Najmeddine, M.; Rakei, A.

    1993-07-01

    The emphasis of the nuclear theory group has been on the structure and electromagnetic interactions of few-body nuclei. Both low- and intermediate-energy electromagnetic disintegration of these nuclei is considered, including coherent photoproduction of π mesons. When the excitation energy of the target nucleus is low, the aim is to handle the continuum part of the theoretical work numerically with no approximations, that is, by means of full three- or four-body dynamics. When structure questions are the issue, numerically accurate calculations are always carried through, limited only by the underlying two-body or three-body interactions used as input. A central goal is to carry through state-of-the-art few-body calculations that will serve as a means of determining at what point standard nuclear physics requires introduction of relativity and/or quark degrees of freedom in order to understand the phenomena in question

  8. Investigation of the spatial structure and interactions of the genome at sub-kilobase-pair resolution using T2C

    DEFF Research Database (Denmark)

    Kolovos, Petros; Brouwer, Rutger W W; Kockx, Christel E M

    2018-01-01

    -to-noise ratio. Its resolution is determined by the resulting fragment size of the chosen restriction enzyme, which can lead to sub-kilobase-pair resolution. T2C's high coverage allows the identification of the interactome of each individual DNA fragment, which makes binning of reads (often used in other methods......-domain interactions, as well as the composition of aggregated loops, interactions between nucleosomes, individual transcription factor binding sites, and promoters and enhancers. T2C can be performed by any investigator with basic skills in molecular biology techniques in ∼7-8 d. Data analysis requires basic...

  9. Synchrotron X-ray Investigations of Mineral-Microbe-Metal Interactions

    International Nuclear Information System (INIS)

    Kemner, Kenneth M.; O'Loughlin, Edward J.; Kelly, Shelly D.; Boyanov, Maxim I.

    2005-01-01

    Interactions between microbes and minerals can play an important role in metal transformations (i.e. changes to an element's valence state, coordination chemistry, or both), which can ultimately affect that element's mobility. Mineralogy affects microbial metabolism and ecology in a system; microbes, in turn, can affect the system's mineralogy. Increasingly, synchrotron-based X-ray experiments are in routine use for determining an element's valence state and coordination chemistry, as well as for examining the role of microbes in metal transformations.

  10. Investigation of mode interaction on planar dielectric waveguides with loss and gain

    Science.gov (United States)

    Hanson, George W.; Yakovlev, Alexander B.

    1999-11-01

    On lossless isotropic planar waveguides the discrete proper modes of propagation form independent transverse electric and transverse magnetic sets such that there is no mode coupling or interaction between modes. In the event of material loss or gain, mode interactions are possible, leading to a complicated spectrum and apparent nonuniqueness of the modes. In this paper we analyze for the first time the cause of these modal interactions by studying the simplest canonical planar waveguide which exhibits these effects, the symmetric-slab waveguide. We show that mode interactions are due to the migration of complex-frequency-plane branch points associated with specific wave phenomena, with varying loss or gain. As these singularities move near the real-frequency axis they influence the modal behavior for time-harmonic (real-valued) frequencies, crossing the real axis at some critical value of loss or gain. It is shown that as time-harmonic frequency varies, passing above, below, or through these branch points results in different modal behavior. Passing above or below, and near to, the branch point yields mode coupling behavior, while passing through the branch point results in modal degeneracy. The result of this branch point migration is that the association of a particular mode with a certain branch of the dispersion function depends not only on the value of material loss or gain, but also on the order in which physical parameters of the problem are varied. Three different branch point types are identified and discussed, which leads to an understanding of the relevant wave phenomena and to a method for organizing the mode spectrum in a consistent and unique manner. While many of the observations described here are based on careful numerical analysis of the transverse magnetic modes existing on a certain symmetric-slab waveguide, the described phenomena are reasonably expected to be generally found in other open dielectric waveguiding structures.

  11. Investigation of the pH‐dependence of dye‐doped protein–protein interactions

    OpenAIRE

    Nudelman, Roman; Gloukhikh, Ekaterina; Rekun, Antonina; Richter, Shachar

    2016-01-01

    Proteins can dramatically change their conformation under environmental conditions such as temperature and pH. In this context, Glycoprotein's conformational determination is challenging. This is due to the variety of domains which contain rich chemical characters existing within this complex. Here we demonstrate a new, straightforward and efficient technique that uses the pH‐dependent properties of dyes‐doped Pig Gastric Mucin (PGM) for predicting and controlling protein–protein interaction ...

  12. MRIVIEW: An interactive computational tool for investigation of brain structure and function

    International Nuclear Information System (INIS)

    Ranken, D.; George, J.

    1993-01-01

    MRIVIEW is a software system which uses image processing and visualization to provide neuroscience researchers with an integrated environment for combining functional and anatomical information. Key features of the software include semi-automated segmentation of volumetric head data and an interactive coordinate reconciliation method which utilizes surface visualization. The current system is a precursor to a computational brain atlas. We describe features this atlas will incorporate, including methods under development for visualizing brain functional data obtained from several different research modalities

  13. Spectroscopic investigation on the interaction of ruthenium complexes with tumor specific lectin, jacalin.

    Science.gov (United States)

    Ayaz Ahmed, Khan Behlol; Reshma, Elamvazhuthi; Mariappan, Mariappan; Anbazhagan, Veerappan

    2015-02-25

    Several ruthenium complexes are regarded as anticancer agents and considered as an alternative to the widely used platinum complexes. Owing to the preferential interaction of jacalin with tumor-associated T-antigen, we report the interaction of jacalin with four ruthenium complex namely, tris(1,10-phenanthroline)ruthenium(II)chloride, bis(1,10-phenanthroline)(N-[1,10]phenanthrolin-5-yl-pyrenylmethanimine)ruthenium(II)chloride, bis(1,10-phenanthroline)(dipyrido[3,2-a:2',3'-c]-phenazine)ruthenium(II)chloride, bis(1,10-phenanthroline)(11-(9-acridinyl)dipyrido[3,2-a:2',3'-c]phenazine)ruthenium(II) chloride. Fluorescence spectroscopic analysis revealed that the ruthenium complexes strongly quenched the intrinsic fluorescence of jacalin through a static quenching procedure, and a non-radiative energy transfer occurred within the molecules. Association constants obtained for the interaction of different ruthenium complexes with jacalin are in the order of 10(5) M(-1), which is in the same range as those obtained for the interaction of lectin with carbohydrate and hydrophobic ligand. Each subunit of the tetrameric jacalin binds one ruthenium complex, and the stoichiometry is found to be unaffected by the presence of the specific sugar, galactose. In addition, agglutination activity of jacalin is largely unaffected by the presence of the ruthenium complexes, indicating that the binding sites for the carbohydrate and the ruthenium complexes are different. These results suggest that the development of lectin-ruthenium complex conjugate would be feasible to target malignant cells in chemo-therapeutics. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. An Empirical Investigation of the Effect of Interaction Justice Perception on Consumer Intentions after Complaining

    OpenAIRE

    Mahesh S. Bhandari; Michael J. Polonsky

    2014-01-01

    This study examined how apology as interaction justice impacts on consumer perceptions of service recovery attempt. Data was collected using hypothetical scenarios. Two types of service failures were proposed and the impact of recovery action on each failure type was compared. Findings include that there is direct effect of recovery action on consumer future intentions in both type of failures. Implications and direction to the future research were proposed.

  15. Interactions of helquats with chiral acidic aromatic analytes investigated by partial-filling affinity capillary electrophoresis

    Czech Academy of Sciences Publication Activity Database

    Růžička, Martin; Koval, Dušan; Vávra, Jan; Reyes Gutierrez, Paul Eduardo; Teplý, Filip; Kašička, Václav

    2016-01-01

    Roč. 1467, Oct 7 (2016), s. 417-426 ISSN 0021-9673 R&D Projects: GA ČR(CZ) GA15-01948S; GA ČR GA13-32974S; GA ČR GA13-19213S Institutional support: RVO:61388963 Keywords : affinity capillary electrophoresis * binding constant * chiral separation * helquats * noncovalent interactions * partial filling Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.981, year: 2016

  16. Interaction of human chymase with ginkgolides, terpene trilactones of Ginkgo biloba investigated by molecular docking simulations.

    Science.gov (United States)

    Dubey, Amit; Marabotti, Anna; Ramteke, Pramod W; Facchiano, Angelo

    2016-04-29

    The search for natural chymase inhibitors has a good potential to provide a novel therapeutic approach against the cardiovascular diseases and other heart ailments. We selected from literature 20 promising Ginkgo biloba compounds, and tested them for their potential ability to bind chymase enzyme using docking and a deep analysis of surface pocket features. Docking results indicated that the compounds may interact with the active site of human chymase, with favorable distinct interactions with important residues Lys40, His57, Lys192, Phe191, Val146, Ser218, Gly216, and Ser195. In particular, proanthocyanidin is the one with the best-predicted binding energy, with seven hydrogen bonds. Interestingly, all active G. biloba compounds have formed the hydrogen bond interactions with the positively charged Lys192 residue at the active site, involved in the mechanism of pH enhancement for the cleavage of angiotensin I site. Ginkgolic acid and proanthocyanidin have better predicted binding energy towards chymase than other serine proteases, i.e kallikrein, tryptase and elastase, suggesting specificity for chymase inhibition. Our study suggests these G. biloba compounds are a promising starting point for developing chymase inhibitors for the potential development of future drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Investigation of natural lipid-phenolic interactions on biological properties of virgin olive oil.

    Science.gov (United States)

    Alu'datt, Muhammad H; Rababah, Taha; Ereifej, Khalil; Gammoh, Sana; Alhamad, Mohammad N; Mhaidat, Nizar; Kubow, Stan; Johargy, Ayman; Alnaiemi, Ola J

    2014-12-10

    There is limited knowledge regarding the impact of naturally occurring lipid-phenolic interactions on the biological properties of phenolics in virgin olive oil. Free and bound phenolics were isolated via sequential methanolic extraction at 30 and 60 °C, and were identified and quantified using reversed phase high performance liquid chromatography, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), and gas chromatography. Decreased oleic acid concentrations and increased concentrations of palmitoleic acid, stearic, linoleic, and linolenic acids were observed in virgin olive oil after removal of free and bound lipid phenolic compounds. The presence of p-hydroxybenzoic acid and tyrosol bound to glycerides was determined via LC-MS/MS, which indicates natural lipid-phenolic interactions in virgin olive oil. Both free and lipid bound phenolic extracts exerted antiproliferative activities against the CRC1 and CRC5 colorectal cancer cell lines. The present work indicates that naturally occurring lipid-phenolic interactions can affect the biological properties of phenolics in virgin olive oil.

  18. Inve