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Sample records for antibody-antigen interacting associations

  1. Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions.

    Science.gov (United States)

    Akiba, Hiroki; Tsumoto, Kouhei

    2015-07-01

    Antibodies (immunoglobulins) bind specific molecules (i.e. antigens) with high affinity and specificity. In order to understand their mechanisms of recognition, interaction analysis based on thermodynamic and kinetic parameters, as well as structure determination is crucial. In this review, we focus on mutational analysis which gives information about the role of each amino acid residue in antibody-antigen interaction. Taking anti-hen egg lysozyme antibodies and several anti-small molecule antibodies, the energetic contribution of hot-spot and non-hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics of the contribution from aromatic, charged and hydrogen bond-forming amino acids are discussed, and their different characteristics have been elucidated. The information gives fundamental understanding of the antibody-antigen interaction. Furthermore, the consequences of antibody engineering are analysed from thermodynamic viewpoints: humanization to reduce immunogenicity and rational design to improve affinity. Amino acid residues outside hot-spots in the interface play important roles in these cases, and thus thermodynamic and kinetic parameters give much information about the antigen recognition. Thermodynamic analysis of mutant antibodies thus should lead to advanced strategies to design and select antibodies with high affinity. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  2. Characterization of ELISA Antibody-Antigen Interaction using Footprinting-Mass Spectrometry and Negative Staining Transmission Electron Microscopy

    Science.gov (United States)

    Lin, Margaret; Krawitz, Denise; Callahan, Matthew D.; Deperalta, Galahad; Wecksler, Aaron T.

    2018-03-01

    We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA). Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP) indicates suppression of labeling across the antigen upon binding either of the monoclonal antibodies (mAbs) utilized in the ELISA. Combining these data with Western blot analysis enabled the identification of the putative epitopes that appeared to span regions containing N-linked glycans. An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes. Deglycosylation of the antigen resulted in loss of potency in the ELISA, supporting the FPOP and GEE labeling data by indicating N-linked glycans are necessary for antigen binding. Finally, mapping of the epitopes onto the antigen crystal structure revealed an approximate 90° relative spatial orientation, optimal for a noncompetitive binding ELISA. TEM data shows both linear and diamond antibody-antigen complexes with a similar binding orientation as predicted from the two footprinting-MS techniques. This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA. [Figure not available: see fulltext.

  3. Designing binding kinetic assay on the bio-layer interferometry (BLI) biosensor to characterize antibody-antigen interactions.

    Science.gov (United States)

    Kamat, Vishal; Rafique, Ashique

    2017-11-01

    The Octet biosensors provide a high-throughput alternative to the well-established surface plasmon resonance (SPR) and SPR imaging (SPRi) biosensors to characterize antibody-antigen interactions. However, the utility of the Octet biosensors for accurate and reproducible measurement of binding rate constants of monoclonal antibodies (mAbs) is limited due to challenges such as analyte rebinding, and mass transport limitation (MTL). This study focuses on addressing these challenges and provides experimental conditions to reliably measure kinetics of mAb-antigen interactions. The mAb capture density of less than 0.6 nm was found to be optimal to measure a wide range of binding affinities on Octet HTX biosensor. The titration kinetic and single cycle kinetic assays performed on Octet HTX generated reproducible binding kinetic parameters and correlated with the values measured on Biacore 4000 and MASS-1. Kinetic assays performed on 0.1 nm density mAb surfaces significantly reduced MTL and enabled characterization of picomolar affinity mAbs. Finally, kinetic analysis performed on 150 antibodies to 10 antigens with molecular weights ranging from 21kD to 105kD showed concordance between Octet HTX, Biacore 4000 and MASS-1 (R 2  > 0.90). The data presented in this study suggest that under optimal experimental conditions, Octet biosensor is capable of generating kinetic values comparable to SPR/SPRi biosensors. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Extending the throughput of Biacore 4000 biosensor to accelerate kinetic analysis of antibody-antigen interaction.

    Science.gov (United States)

    Kamat, Vishal; Rafique, Ashique

    2017-08-01

    The surface plasmon resonance (SPR) biosensors are being routinely used in different stages of drug discovery and development. However, the lack of high throughput SPR biosensors continues to be a primary bottleneck for the rapid kinetic screening of large panels of monoclonal antibodies (mAbs). To further increase the throughput of the Biacore 4000 biosensor, we have developed three kinetic screening assays to characterize mAb-antigen interactions - (i) 16-mAb capture kinetic, (ii) single cycle kinetic (SCK), and (iii) parallel kinetic (PK). The performance of all three kinetic assays was evaluated by characterizing the binding of kinetically diverse human mAbs to four antigens with molecular weights of 14kD, 29kD, 38kD, and 48kD and binding affinities ranging from 130pM to 200 nM. The binding rate constants measured using all three kinetic assays were reproducible across multiple experiments and correlated with the values generated using the conventional 8-mAb capture kinetic assay on the Biacore 4000 (R 2  > 0.94). Moreover, the 16-mAb capture assay decreased experiment time and analyte consumption by 35% and 50%, respectively. This work illustrates the significance of the 16-mAb capture kinetic, SCK, and PK assays to increase the throughput of Biacore 4000 and to support rapid kinetic screening of mAbs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Affinity improvement of a therapeutic antibody by structure-based computational design: generation of electrostatic interactions in the transition state stabilizes the antibody-antigen complex.

    Directory of Open Access Journals (Sweden)

    Masato Kiyoshi

    Full Text Available The optimization of antibodies is a desirable goal towards the development of better therapeutic strategies. The antibody 11K2 was previously developed as a therapeutic tool for inflammatory diseases, and displays very high affinity (4.6 pM for its antigen the chemokine MCP-1 (monocyte chemo-attractant protein-1. We have employed a virtual library of mutations of 11K2 to identify antibody variants of potentially higher affinity, and to establish benchmarks in the engineering of a mature therapeutic antibody. The most promising candidates identified in the virtual screening were examined by surface plasmon resonance to validate the computational predictions, and to characterize their binding affinity and key thermodynamic properties in detail. Only mutations in the light-chain of the antibody are effective at enhancing its affinity for the antigen in vitro, suggesting that the interaction surface of the heavy-chain (dominated by the hot-spot residue Phe101 is not amenable to optimization. The single-mutation with the highest affinity is L-N31R (4.6-fold higher affinity than wild-type antibody. Importantly, all the single-mutations showing increase affinity incorporate a charged residue (Arg, Asp, or Glu. The characterization of the relevant thermodynamic parameters clarifies the energetic mechanism. Essentially, the formation of new electrostatic interactions early in the binding reaction coordinate (transition state or earlier benefits the durability of the antibody-antigen complex. The combination of in silico calculations and thermodynamic analysis is an effective strategy to improve the affinity of a matured therapeutic antibody.

  6. Prediction of site-specific interactions in antibody-antigen complexes: the proABC method and server.

    KAUST Repository

    Olimpieri, Pier Paolo

    2013-06-26

    MOTIVATION: Antibodies or immunoglobulins are proteins of paramount importance in the immune system. They are extremely relevant as diagnostic, biotechnological and therapeutic tools. Their modular structure makes it easy to re-engineer them for specific purposes. Short of undergoing a trial and error process, these experiments, as well as others, need to rely on an understanding of the specific determinants of the antibody binding mode. RESULTS: In this article, we present a method to identify, on the basis of the antibody sequence alone, which residues of an antibody directly interact with its cognate antigen. The method, based on the random forest automatic learning techniques, reaches a recall and specificity as high as 80% and is implemented as a free and easy-to-use server, named prediction of Antibody Contacts. We believe that it can be of great help in re-design experiments as well as a guide for molecular docking experiments. The results that we obtained also allowed us to dissect which features of the antibody sequence contribute most to the involvement of specific residues in binding to the antigen. AVAILABILITY: http://www.biocomputing.it/proABC. CONTACT: anna.tramontano@uniroma1.it or paolo.marcatili@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

  7. A new technique to detect antibody-antigen reaction (biological interactions) on a localized surface plasmon resonance (LSPR) based nano ripple gold chip

    Energy Technology Data Exchange (ETDEWEB)

    Saleem, Iram, E-mail: iiram.qau@gmail.com [Department of Physics and Texas Center for Superconductivity, University of Houston, Houston, TX 77204 (United States); Widger, William, E-mail: widger@uh.edu [Department of Biology and Biochemistry and Texas Center for Superconductivity, University of Houston, Houston, TX 77204 (United States); Chu, Wei-Kan, E-mail: wkchu@uh.edu [Department of Physics and Texas Center for Superconductivity, University of Houston, Houston, TX 77204 (United States)

    2017-07-31

    Highlights: • The nano ripple LSPR chip has monolayer molecule-coating sensitivity and specific selectivity. • Gold nano-ripple sensing chip is a low cost, and a label-free method for detecting the antibody-antigen reaction. • The plasmonic resonance shift depends upon the concentration of the biomolecules attached on the surface of the nano ripple pattern. - Abstract: We demonstrate that the gold nano-ripple localized surface plasmon resonance (LSPR) chip is a low cost and a label-free method for detecting the presence of an antigen. A uniform stable layer of an antibody was coated on the surface of a nano-ripple gold pattern chip followed by the addition of different concentrations of the antigen. A red shift was observed in the LSPR spectral peak caused by the change in the local refractive index in the vicinity of the nanostructure. The LSPR chip was fabricated using oblique gas cluster ion beam (GCIB) irradiation. The plasmon-resonance intensity of the scattered light was measured by a simple optical spectroscope. The gold nano ripple chip shows monolayer scale sensitivity and high selectivity. The LSPR substrate was used to detect antibody-antigen reaction of rabbit X-DENTT antibody and DENTT blocking peptide (antigen).

  8. Rationalization and Design of the Complementarity Determining Region Sequences in an Antibody-Antigen Recognition Interface

    Science.gov (United States)

    Chen, Ing-Chien; Lee, Yu-Ching; Chen, Jun-Bo; Tsai, Keng-Chang; Chen, Ching-Tai; Chang, Jeng-Yih; Yang, Ei-Wen; Hsu, Po-Chiang; Jian, Jhih-Wei; Hsu, Hung-Ju; Chang, Hung-Ju; Hsu, Wen-Lian; Huang, Kai-Fa; Ma, Alex Che; Yang, An-Suei

    2012-01-01

    Protein-protein interactions are critical determinants in biological systems. Engineered proteins binding to specific areas on protein surfaces could lead to therapeutics or diagnostics for treating diseases in humans. But designing epitope-specific protein-protein interactions with computational atomistic interaction free energy remains a difficult challenge. Here we show that, with the antibody-VEGF (vascular endothelial growth factor) interaction as a model system, the experimentally observed amino acid preferences in the antibody-antigen interface can be rationalized with 3-dimensional distributions of interacting atoms derived from the database of protein structures. Machine learning models established on the rationalization can be generalized to design amino acid preferences in antibody-antigen interfaces, for which the experimental validations are tractable with current high throughput synthetic antibody display technologies. Leave-one-out cross validation on the benchmark system yielded the accuracy, precision, recall (sensitivity) and specificity of the overall binary predictions to be 0.69, 0.45, 0.63, and 0.71 respectively, and the overall Matthews correlation coefficient of the 20 amino acid types in the 24 interface CDR positions was 0.312. The structure-based computational antibody design methodology was further tested with other antibodies binding to VEGF. The results indicate that the methodology could provide alternatives to the current antibody technologies based on animal immune systems in engineering therapeutic and diagnostic antibodies against predetermined antigen epitopes. PMID:22457753

  9. Computational Docking of Antibody-Antigen Complexes, Opportunities and Pitfalls Illustrated by Influenza Hemagglutinin

    Directory of Open Access Journals (Sweden)

    Mattia Pedotti

    2011-01-01

    Full Text Available Antibodies play an increasingly important role in both basic research and the pharmaceutical industry. Since their efficiency depends, in ultimate analysis, on their atomic interactions with an antigen, studying such interactions is important to understand how they function and, in the long run, to design new molecules with desired properties. Computational docking, the process of predicting the conformation of a complex from its separated components, is emerging as a fast and affordable technique for the structural characterization of antibody-antigen complexes. In this manuscript, we first describe the different computational strategies for the modeling of antibodies and docking of their complexes, and then predict the binding of two antibodies to the stalk region of influenza hemagglutinin, an important pharmaceutical target. The purpose is two-fold: on a general note, we want to illustrate the advantages and pitfalls of computational docking with a practical example, using different approaches and comparing the results to known experimental structures. On a more specific note, we want to assess if docking can be successful in characterizing the binding to the same influenza epitope of other antibodies with unknown structure, which has practical relevance for pharmaceutical and biological research. The paper clearly shows that some of the computational docking predictions can be very accurate, but the algorithm often fails to discriminate them from inaccurate solutions. It is of paramount importance, therefore, to use rapidly obtained experimental data to validate the computational results.

  10. Characterisation of peptide microarrays for studying antibody-antigen binding using surface plasmon resonance imagery.

    Directory of Open Access Journals (Sweden)

    Claude Nogues

    Full Text Available BACKGROUND: Non-specific binding to biosensor surfaces is a major obstacle to quantitative analysis of selective retention of analytes at immobilized target molecules. Although a range of chemical antifouling monolayers has been developed to address this problem, many macromolecular interactions still remain refractory to analysis due to the prevalent high degree of non-specific binding. We describe how we use the dynamic process of the formation of self assembling monolayers and optimise physical and chemical properties thus reducing considerably non-specific binding and allowing analysis of specific binding of analytes to immobilized target molecules. METHODOLOGY/PRINCIPAL FINDINGS: We illustrate this approach by the production of specific protein arrays for the analysis of interactions between the 65kDa isoform of human glutamate decarboxylase (GAD65 and a human monoclonal antibody. Our data illustrate that we have effectively eliminated non-specific interactions with the surface containing the immobilised GAD65 molecules. The findings have several implications. First, this approach obviates the dubious process of background subtraction and gives access to more accurate kinetic and equilibrium values that are no longer contaminated by multiphase non-specific binding. Second, an enhanced signal to noise ratio increases not only the sensitivity but also confidence in the use of SPR to generate kinetic constants that may then be inserted into van't Hoff type analyses to provide comparative DeltaG, DeltaS and DeltaH values, making this an efficient, rapid and competitive alternative to ITC measurements used in drug and macromolecular-interaction mechanistic studies. Third, the accuracy of the measurements allows the application of more intricate interaction models than simple Langmuir monophasic binding. CONCLUSIONS: The detection and measurement of antibody binding by the type 1 diabetes autoantigen GAD65 represents an example of an antibody-antigen

  11. Direct correlation between potentiometric and impedance biosensing of antibody-antigen interactions using an integrated system

    Science.gov (United States)

    Tsai, Meng-Yen; Creedon, Niamh; Brightbill, Eleanor; Pavlidis, Spyridon; Brown, Billyde; Gray, Darren W.; Shields, Niall; Sayers, Ríona; Mooney, Mark H.; O'Riordan, Alan; Vogel, Eric M.

    2017-08-01

    A fully integrated system that combines extended gate field-effect transistor (EGFET)-based potentiometric biosensors and electrochemical impedance spectroscopy (EIS)-based biosensors has been demonstrated. This integrated configuration enables the sequential measurement of the same immunological binding event on the same sensing surface and consequently sheds light on the fundamental origins of sensing signals produced by FET and EIS biosensors, as well as the correlation between the two. Detection of both the bovine serum albumin (BSA)/anti-BSA model system in buffer solution and bovine parainfluenza antibodies in complex blood plasma samples was demonstrated using the integrated biosensors. Comparison of the EGFET and EIS sensor responses reveals similar dynamic ranges, while equivalent circuit modeling of the EIS response shows that the commonly reported total impedance change (ΔZtotal) is dominated by the change in charge transfer resistance (Rct) rather than surface capacitance (Csurface). Using electrochemical kinetics and the Butler-Volmer equation, we unveil that the surface potential and charge transfer resistance, measured by potentiometric and impedance biosensors, respectively, are, in fact, intrinsically linked. This observation suggests that there is no significant gain in using the FET/EIS integrated system and leads to the demonstration that low-cost EGFET biosensors are sufficient as a detection tool to resolve the charge information of biomolecules for practical sensing applications.

  12. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity

    NARCIS (Netherlands)

    Kreutz, M.; Giquel, B.; Hu, Q.; Abuknesha, R.; Uematsu, S.; Akira, S.; Nestle, F.O.; Diebold, S.S.

    2012-01-01

    Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is

  13. Prevalence of Helicobacter pylori and parasites in symptomatic children examined for Helicobacter pylori antibodies, antigens, and parasites in Yemen.

    Science.gov (United States)

    Bin Mohanna, Mabrook A; Al-Zubairi, Lutf M; Sallam, Abdul K

    2014-11-01

    To estimate the prevalence of Helicobacter pylori (H. pylori) and parasites in symptomatic children examined for H. pylori antibodies, antigens, and parasites in Yemen. A record-based study was carried out at Specialized Sam Pediatric Center in Sana'a, Yemen for 3 years between 2011-2013. Out of the 43,200 patients seen for different causes through that period, 1008 (2.3%) (females: 675 [67%]; males: 333 [33%]) had gastric complaints, and were subjected to an examination of blood and stool for H. pylori and parasites. Data regarding age and gender was also collected. The age of the patients ranged from 3-15 years. The prevalence of H. pylori among children examined for H. pylori was 65%, 30% of them were males, and 35% were females (chi square [I2]=142, p<0.01]). The prevalence in the 6-8 years age group was 83%, and it was 52% in the age group of 12-15 years. The prevalence of giardiasis was 10%, and amoebiasis was 25%. Prevalence of H. pylori infection among children was high, and was more prevalent in the age group of 6-8 years than in the other age groups. Females were more affected than males. Parasites (amoebiasis and giardiasis) infestation was less prevalent.

  14. Determination of High-affinity Antibody-antigen Binding Kinetics Using Four Biosensor Platforms

    OpenAIRE

    Yang, Danlin; Singh, Ajit; Wu, Helen; Kroe-Barrett, Rachel

    2017-01-01

    Label-free optical biosensors are powerful tools in drug discovery for the characterization of biomolecular interactions. In this study, we describe the use of four routinely used biosensor platforms in our laboratory to evaluate the binding affinity and kinetics of ten high-affinity monoclonal antibodies (mAbs) against human proprotein convertase subtilisin kexin type 9 (PCSK9). While both Biacore T100 and ProteOn XPR36 are derived from the well-established Surface Plasmon Resonance (SPR) te...

  15. Competitive interactions between sponge-associated bacteria.

    Science.gov (United States)

    Esteves, Ana I S; Cullen, Alescia; Thomas, Torsten

    2017-03-01

    The diversity of the microbial communities associated with marine sponges has been extensively studied, but their functioning and interactions within the sponge holobiont are only recently being appreciated. Sponge-associated microorganisms are known for the production of a range of inhibitory metabolites with biotechnological application, but the ecological role that these compounds remains elusive. In this work, we explore the competitive interactions between cultivated sponge-associated bacteria to inspect whether bacteria that produce antimicrobial activities are able to inhibit potentially pathogenic bacteria. We isolated a Bacillus sp. bacterium with sponge-degrading activity, which likely has a negative impact on the host. This bacterium, along with other sponge isolates from the same genus, was found to be inhibited by a subpopulation of closely related sponge-derived Pseudovibrio spp. In some Pseudovibrio strains, these inhibitory activities were correlated with the genetic capacity to produce polyketides, such as erythronolide. Our observations suggest that antagonistic activities likely influence the composition of the sponge microbiome, including the abundance of bacteria that can be harmful to the host. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. The Global Alzheimer's Association Interactive Network.

    Science.gov (United States)

    Toga, Arthur W; Neu, Scott C; Bhatt, Priya; Crawford, Karen L; Ashish, Naveen

    2016-01-01

    The Global Alzheimer's Association Interactive Network (GAAIN) is consolidating the efforts of independent Alzheimer's disease data repositories around the world with the goals of revealing more insights into the causes of Alzheimer's disease, improving treatments, and designing preventative measures that delay the onset of physical symptoms. We developed a system for federating these repositories that is reliant on the tenets that (1) its participants require incentives to join, (2) joining the network is not disruptive to existing repository systems, and (3) the data ownership rights of its members are protected. We are currently in various phases of recruitment with over 55 data repositories in North America, Europe, Asia, and Australia and can presently query >250,000 subjects using GAAIN's search interfaces. GAAIN's data sharing philosophy, which guided our architectural choices, is conducive to motivating membership in a voluntary data sharing network. Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  17. Microbial interactions associated with secondary cucumber fermentation.

    Science.gov (United States)

    Franco, W; Pérez-Díaz, I M

    2013-01-01

    To evaluate the interaction between selected yeasts and bacteria and associate their metabolic activity with secondary cucumber fermentation. Selected yeast and bacteria, isolated from cucumber secondary fermentations, were inoculated as single and mixed cultures in a cucumber juice model system. Our results confirmed that during storage of fermented cucumbers and in the presence of oxygen, spoilage yeasts are able to grow and utilize the lactic and acetic acids present in the medium, which results in increased brine pH and the chemical reduction in the environment. These conditions favour opportunistic bacteria that continue the degradation of lactic acid. Lactobacillus buchneri, Clostridium bifermentans and Enterobacter cloacae were able to produce acetic, butyric and propionic acids, respectively, when inoculated in the experimental medium at pH 4.6. Yeast and bacteria interactions favoured the survival of Cl. bifermentans and E. cloacae at the acidic pH typical of fermented cucumbers (3.2), but only E. cloacae was able to produce a secondary product. The methodology used in this study confirmed that a complex microbiota is responsible for the changes observed during fermented cucumber secondary fermentation and that certain microbial interactions may be essential for the production of propionic and butyric acids. Understanding the dynamics of the development of secondary cucumber fermentation aids in the identification of strategies to prevent its occurrence and economic losses for the pickling industry. © 2012 No claim to US Government works.

  18. A nanobiosensing method based on force measurement of antibody-antigen interaction for direct detection of enterovirus 71 by the chemically modified atomic force microscopic probe.

    Science.gov (United States)

    Hong, Chung-Hung; Hsieh, Chung-Fan; Tseng, Chi-Shin; Huang, Wei-Chih; Guo, Cheng-Yan; Lin, Shiming; Lee, Si-Chen

    2017-10-01

    Hand, Foot and mouth disease (HFMD) is a common disease with high infectivity for children, and enterovirus 71 (EV71) is one of the main pathogens to cause the type of illness. Therefore, the aim of this study was to propose a rapid and effective technique for detecting EV71 directly based on the mechanism of biological intermolecular force by using atomic force microscopy (AFM). At first, we coated EV71 particles on the mica surface and made the EV71 antibodies (anti-EV71) fixed on the AFM tip by means of several chemical procedures. Then, AFM chemically modified tip was applied to measure the unbinding forces between EV71 and anti-EV71 by contact mode. Finally, by using AFM imaging calculating software, the EV71 particle size (mean±SD) was 31.36±3.87 nm (n = 200) and this result was concordance with previous literature. Besides, the force (mean±SD) between EV71 antigen and antibody complex was 336.9±64.7 pN. The force (mean±SD) between anti-EV71 and non-specific specimens was 47.1±15.1 pN and was significantly smaller (P measuring the force magnitude and observing the occurrence of EV71/anti-EV71 unbinding events. Therefore, the combination of AFM system and the chemically modified tip has the potential to be a rapid and effective method for detecting EV71 directly. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Quantifying the molecular origins of opposite solvent effects on protein-protein interactions.

    Directory of Open Access Journals (Sweden)

    Vincent Vagenende

    Full Text Available Although the nature of solvent-protein interactions is generally weak and non-specific, addition of cosolvents such as denaturants and osmolytes strengthens protein-protein interactions for some proteins, whereas it weakens protein-protein interactions for others. This is exemplified by the puzzling observation that addition of glycerol oppositely affects the association constants of two antibodies, D1.3 and D44.1, with lysozyme. To resolve this conundrum, we develop a methodology based on the thermodynamic principles of preferential interaction theory and the quantitative characterization of local protein solvation from molecular dynamics simulations. We find that changes of preferential solvent interactions at the protein-protein interface quantitatively account for the opposite effects of glycerol on the antibody-antigen association constants. Detailed characterization of local protein solvation in the free and associated protein states reveals how opposite solvent effects on protein-protein interactions depend on the extent of dewetting of the protein-protein contact region and on structural changes that alter cooperative solvent-protein interactions at the periphery of the protein-protein interface. These results demonstrate the direct relationship between macroscopic solvent effects on protein-protein interactions and atom-scale solvent-protein interactions, and establish a general methodology for predicting and understanding solvent effects on protein-protein interactions in diverse biological environments.

  20. Associations of Low-Income Working Mothers' Daily Interactions with Supervisors and Mother-Child Interactions

    Science.gov (United States)

    Gassman-Pines, Anna

    2011-01-01

    This study investigated associations of low-income working mothers' daily interactions with supervisors and their interactions with children. Sixty-one mothers of preschool-aged children were asked to report on their interactions with their supervisors at work and their interactions with children for 2 weeks (N = 520 workdays). Results show…

  1. Plants and insects in interactions: multitrophic associations

    Directory of Open Access Journals (Sweden)

    Žikić, V.

    2016-12-01

    Full Text Available Studying a biological species, we are very often obliged to examine many other species which are directly or indirectly related to the particular species in order to have broader perspective of its being. Interactions between organisms can be perceived on various levels concerning biological study areas, such as ecology, physiology, morphology etc. In this place, the authors have given some peculiar examples concerning parasitism. This specific interaction is very common in the animal kingdom, having in mind that about a half of all known organisms are parasitic. The importance of this phenomenon is reflected on many aspects of life, propelling evolution and speciation of each member in the relation.

  2. Factors associated with social interaction anxiety among Chinese adolescents.

    Science.gov (United States)

    Peng, Z W; Lam, L T; Jin, J

    2011-12-01

    To investigate potential risk factors for social anxiety, particularly social interaction anxiety among the Chinese adolescents. A cross-sectional health survey was conducted in Guangzhou city of the Guangdong Province where high school students aged 13 to 18 years were recruited. The sample was selected from all high schools in the city using a 2-stage random cluster sampling technique. Social interaction anxiety was assessed using the Social Interaction Anxiety Scale. Information collected in the survey included: demographics, self-perception on school performance, relationship with teachers and peers, satisfaction with self-image, achievements, and parenting style of the mother. The parent-child relationship, specifically the relationship between respondents and their mothers, was assessed using the mother attachment subscale of the Inventory of Parent and Peer Attachment. Self-esteem was assessed using the Rosenberg Self-Esteem Scale. The multiple linear regression technique was applied to investigate associations between selected potential risk factors and social interaction anxiety, with adjustments for cluster sampling. Lower family income, lower self-esteem, and hostility were significantly associated with social interaction anxiety among adolescents. Variables identified as risk factors of anxiety disorder in the literature, such as gender, were not associated with social interaction anxiety in this sample. These results were consistent with those of other studies conducted mainly in the United States and Europe. Regarding non-significant results related to gender, they need viewing in the context of parenting styles of Chinese mothers.

  3. Associated charm production in neutrino-nucleus interactions

    Energy Technology Data Exchange (ETDEWEB)

    Kayis-Topaksu, A.; Oenenguet, G. [Cukurova University, Adana (Turkey); van Dantzig, R.; de Jong, M. [NIKHEF, Amsterdam (Netherlands); Oldeman, R.G.C. [NIKHEF, Amsterdam (Netherlands)]|[Universita di Cagliari, Cagliari (Italy); Gueler, M.; Koese, U.; Tolun, P. [Physics Department of Middle East Technical University, Ankara (Turkey); Catanesi, M.G.; Muciaccia, M.T. [Universita di Bari and INFN, Bari (Italy); Winter, K. [Humboldt Universitaet, Berlin (Germany); Van de Vyver, B. [Inter-University Institute for High Energies (ULB-VUB) Brussels, Brussels (Belgium)]|[SpinX Technologies, Geneva (Switzerland); Vilain, P.; Wilquet, G. [Inter-University Institute for High Energies (ULB-VUB) Brussels, Brussels (Belgium); Saitta, B. [Universita di Cagliari and INFN, Cagliari (Italy); Di Capua, E. [Universita di Ferrara and INFN, Ferrara (Italy); Ogawa, S.; Shibuya, H. [Toho University, Funabashi (Japan); Hristova, I.R. [CERN, Geneva (Switzerland)]|[DESY, Hamburg (Germany); Kawamura, T.; Kolev, D.; Meinhard, H.; Panman, J.; Tsenov, R.; Uiterwijk, J.W.E. [CERN, Geneva (Switzerland); Rozanov, A. [CERN, Geneva (Switzerland)]|[CPPM CNRS-IN2P3, Marseille (France); Zucchelli, P. [CERN, Geneva (Switzerland)]|[SpinX Technologies, Geneva (Switzerland); Goldberg, J. [Technion, Haifa (Israel); Chikawa, M. [Kinki University, Higashiosaka (Japan); Song, J.S.; Yoon, C.S. [Gyeongsang National Univ., Jinju (Korea); Kodama, K.; Ushida, N. [Aichi University of Education, Kariya (Japan); Aoki, S.; Hara, T. [Kobe University, Kobe (Japan); Delbar, T.; Favart, D.; Gregoire, G.; Kalinin, S.; Makhlioueva, I. [Universite Catholique de Louvain, Louvain-la-Neuve (Belgium); Artamonov, A.; Khovansky, V.; Shamanov, V.; Tsukerman, I. [Inst. for Theoretical and Experimental Physics, Moscow (Russian Federation); Gorbunov, P. [Inst. for Theoretical and Experimental Physics, Moscow (Russian Federation)]|[SpinX Technologies, Geneva (Switzerland); Bruski, N.; Frekers, D. [and others

    2007-11-15

    In this paper a search for associated charm production both in neutral and charged current {nu}-nucleus interactions is presented. The improvement of automatic scanning systems in the CHORUS experiment allows an efficient search to be performed in emulsion for short-lived particles. Hence a search for rare processes, like the associated charm production, becomes possible through the observation of the double charm-decay topology with a very low background. About 130000 {nu} interactions located in the emulsion target have been analysed. Three events with two charm decays have been observed in the neutral-current sample with an estimated background of 0.18{+-}0.05. The relative rate of the associated charm cross-section in deep inelastic {nu} interactions, {sigma}(c anti c{nu})/{sigma}{sub NC}{sup DIS}=(3.62{sup +2.95}{sub -2.42}(stat){+-}0.54(syst)) x 10{sup -3} has been measured. One event with two charm decays has been observed in charged-current {nu}{sub {mu}} interactions with an estimated background of 0.18{+-}0.06 and the upper limit on associated charm production in charged-current interactions at 90% C.L. has been found to be {sigma}(c anti c{mu}{sup -})/{sigma}{sub CC}<9.69 x 10{sup -4}. (orig.)

  4. Association between cystatin C and the interaction of pulmonary ...

    African Journals Online (AJOL)

    Purpose: To determine the association between Cystatin C (Cys C) levels and the interaction of pulmonary tuberculosis (PTB) with chronic diseases (CD). Methods: Participants (n = 356) were selected randomly from The First Affiliated Hospital of Wannan Medical College, China, and divided into 4 groups: normal control ...

  5. Association between cystatin C and the interaction of pulmonary ...

    African Journals Online (AJOL)

    Purpose: To determine the association between Cystatin C (Cys C) levels and the interaction of pulmonary tuberculosis (PTB) with chronic diseases (CD). Methods: Participants (n = 356) were selected randomly from The First Affiliated Hospital of Wannan. Medical College, China, and divided into 4 groups: normal control ...

  6. Interaction of maize chromatin-associated HMG proteins with mononucleosomes

    DEFF Research Database (Denmark)

    Lichota, J.; Grasser, Klaus D.

    2003-01-01

    Two groups of plant chromatin-associated high mobility group (HMG) proteins, namely the HMGA family, typically containing four A/T-hook DNA-binding motifs, and the HMGB family, containing a single HMG-box DNA-binding domain, have been identified. We have examined the interaction of recombinant...

  7. Increased Interhemispheric Interaction Is Associated with Decreased False Memories in a Verbal Converging Semantic Associates Paradigm

    Science.gov (United States)

    Christman, S.D.; Propper, R.E.; Dion, A.

    2004-01-01

    Recent evidence indicates that task and subject variables that are associated with increased interaction between the left and right cerebral hemispheres result in enhanced performance on tests of episodic memory. The current study looked at the effects of increased interhemispheric interaction on false memories using a verbal converging semantic…

  8. Are some parents' interaction styles associated with richer grammatical input?

    Science.gov (United States)

    Fitzgerald, Colleen E; Hadley, Pamela A; Rispoli, Matthew

    2013-08-01

    Evidence for tense marking in child-directed speech varies both across languages ( Guasti, 2002; Legate & Yang, 2007) and across speakers of a single language ( Hadley, Rispoli, Fitzgerald, & Bahnsen, 2011). The purpose of this study was to understand how parent interaction styles and register use overlap with the tense-marking properties of child-directed speech. This study investigated how parent interaction style, measured by utterance function, and parent register use when asking questions interacted with verb forms in child-directed input to identify interaction styles associated with the richest grammatical input. Participants were 15 parent-toddler dyads. The communicative function of parent utterances and the form of their questions were coded from language samples of parent-child play when children were 21 months of age. Verbs were coded for linguistic form (e.g., imperative, modal, copula). Directives and reduced questions were both negatively related to input informativeness (i.e., the proportion of unambiguous evidence for tense). Other-focused descriptives were positively related to input informativeness. Predictable overlap existed between the characteristics of parents' interaction styles and register use and their input informativeness. An other-focused descriptive style most strongly related to richer evidence for the +Tense grammar of English.

  9. Transcriptional robustness and protein interactions are associated in yeast

    Directory of Open Access Journals (Sweden)

    Conant Gavin C

    2011-05-01

    Full Text Available Abstract Background Robustness to insults, both external and internal, is a characteristic feature of life. One level of biological organization for which noise and robustness have been extensively studied is gene expression. Cells have a variety of mechanisms for buffering noise in gene expression, but it is not completely clear what rules govern whether or not a given gene uses such tools to maintain appropriate expression. Results Here, we show a general association between the degree to which yeast cells have evolved mechanisms to buffer changes in gene expression and whether they possess protein-protein interactions. We argue that this effect bears an affinity to epistasis, because yeast appears to have evolved regulatory mechanisms such that distant changes in gene copy number for a protein-protein interaction partner gene can alter a gene's expression. This association is not unexpected given recent work linking epistasis and the deleterious effects of changes in gene dosage (i.e., the dosage balance hypothesis. Using gene expression data from artificial aneuploid strains of bakers' yeast, we found that genes coding for proteins that physically interact with other proteins show less expression variation in response to aneuploidy than do other genes. This effect is even more pronounced for genes whose products interact with proteins encoded on aneuploid chromosomes. We further found that genes targeted by transcription factors encoded on aneuploid chromosomes were more likely to change in expression after aneuploidy. Conclusions We suggest that these observations can be best understood as resulting from the higher fitness cost of misexpression in epistatic genes and a commensurate greater regulatory control of them.

  10. Interacting CMEs and their associated flare and SEP activities

    Science.gov (United States)

    Shanmugaraju, A.; Prasanna Subramanian, S.

    2014-08-01

    We have analyzed a set of 25 interacting events which are associated with the DH type II bursts. These events are selected from the Coronal Mass Ejections (CMEs) observed during the period 1997-2010 in SOHO/LASCO and DH type IIs observed in Wind/WAVES. Their pre and primary CMEs from nearby active regions are identified using SOHO/LASCO and EIT images and their height-time diagrams. Their interacting time and height are obtained, and their associated activities, such as, flares and Solar Energetic Particles (>10 pfu) are also investigated. Results from the analysis are: primary CMEs are much faster than the pre-CMEs, their X-ray flares are also stronger (X- and M-class) compared to the flares (C- and M-class) of pre-CMEs. Most of the events (22/25) occurred during the period 2000-2006. From the observed width and speed of pre and primary CMEs, it is found that the pre-CMEs are found to be less energetic than the primary CMEs. While the primary CMEs are tracked up to the end of LASCO field of view (30 Rs), most of the pre-CMEs can be tracked up to <26 Rs. The SEP intensity is found to be related with the integrated flux of X-ray flares associated with the primary CMEs for nine events originating from the western region.

  11. Ceramide-Protein Interactions Modulate Ceramide-Associated Lipotoxic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Stanley M. Walls

    2018-03-01

    Full Text Available Lipotoxic cardiomyopathy (LCM is characterized by abnormal myocardial accumulation of lipids, including ceramide; however, the contribution of ceramide to the etiology of LCM is unclear. Here, we investigated the association of ceramide metabolism and ceramide-interacting proteins (CIPs in LCM in the Drosophila heart model. We find that ceramide feeding or ceramide-elevating genetic manipulations are strongly associated with cardiac dilation and defects in contractility. High ceramide-associated LCM is prevented by inhibiting ceramide synthesis, establishing a robust model of direct ceramide-associated LCM, corroborating previous indirect evidence in mammals. We identified several CIPs from mouse heart and Drosophila extracts, including caspase activator Annexin-X, myosin chaperone Unc-45, and lipogenic enzyme FASN1, and remarkably, their cardiac-specific manipulation can prevent LCM. Collectively, these data suggest that high ceramide-associated lipotoxicity is mediated, in part, through altering caspase activation, sarcomeric maintenance, and lipogenesis, thus providing evidence for conserved mechanisms in LCM pathogenesis in mammals.

  12. Anthropomorphic Robot Design and User Interaction Associated with Motion

    Science.gov (United States)

    Ellis, Stephen R.

    2016-01-01

    Though in its original concept a robot was conceived to have some human-like shape, most robots now in use have specific industrial purposes and do not closely resemble humans. Nevertheless, robots that resemble human form in some way have continued to be introduced. They are called anthropomorphic robots. The fact that the user interface to all robots is now highly mediated means that the form of the user interface is not necessarily connected to the robots form, human or otherwise. Consequently, the unique way the design of anthropomorphic robots affects their user interaction is through their general appearance and the way they move. These robots human-like appearance acts as a kind of generalized predictor that gives its operators, and those with whom they may directly work, the expectation that they will behave to some extent like a human. This expectation is especially prominent for interactions with social robots, which are built to enhance it. Often interaction with them may be mainly cognitive because they are not necessarily kinematically intricate enough for complex physical interaction. Their body movement, for example, may be limited to simple wheeled locomotion. An anthropomorphic robot with human form, however, can be kinematically complex and designed, for example, to reproduce the details of human limb, torso, and head movement. Because of the mediated nature of robot control, there remains in general no necessary connection between the specific form of user interface and the anthropomorphic form of the robot. But their anthropomorphic kinematics and dynamics imply that the impact of their design shows up in the way the robot moves. The central finding of this report is that the control of this motion is a basic design element through which the anthropomorphic form can affect user interaction. In particular, designers of anthropomorphic robots can take advantage of the inherent human-like movement to 1) improve the users direct manual control over

  13. Development and application of an interaction network ontology for literature mining of vaccine-associated gene-gene interactions.

    Science.gov (United States)

    Hur, Junguk; Özgür, Arzucan; Xiang, Zuoshuang; He, Yongqun

    2015-01-01

    Literature mining of gene-gene interactions has been enhanced by ontology-based name classifications. However, in biomedical literature mining, interaction keywords have not been carefully studied and used beyond a collection of keywords. In this study, we report the development of a new Interaction Network Ontology (INO) that classifies >800 interaction keywords and incorporates interaction terms from the PSI Molecular Interactions (PSI-MI) and Gene Ontology (GO). Using INO-based literature mining results, a modified Fisher's exact test was established to analyze significantly over- and under-represented enriched gene-gene interaction types within a specific area. Such a strategy was applied to study the vaccine-mediated gene-gene interactions using all PubMed abstracts. The Vaccine Ontology (VO) and INO were used to support the retrieval of vaccine terms and interaction keywords from the literature. INO is aligned with the Basic Formal Ontology (BFO) and imports terms from 10 other existing ontologies. Current INO includes 540 terms. In terms of interaction-related terms, INO imports and aligns PSI-MI and GO interaction terms and includes over 100 newly generated ontology terms with 'INO_' prefix. A new annotation property, 'has literature mining keywords', was generated to allow the listing of different keywords mapping to the interaction types in INO. Using all PubMed documents published as of 12/31/2013, approximately 266,000 vaccine-associated documents were identified, and a total of 6,116 gene-pairs were associated with at least one INO term. Out of 78 INO interaction terms associated with at least five gene-pairs of the vaccine-associated sub-network, 14 terms were significantly over-represented (i.e., more frequently used) and 17 under-represented based on our modified Fisher's exact test. These over-represented and under-represented terms share some common top-level terms but are distinct at the bottom levels of the INO hierarchy. The analysis of these

  14. RAIN: RNA-protein Association and Interaction Networks

    DEFF Research Database (Denmark)

    Junge, Alexander; Refsgaard, Jan Christian; Garde, Christian

    2017-01-01

    Protein association networks can be inferred from a range of resources including experimental data, literature mining and computational predictions. These types of evidence are emerging for non-coding RNAs (ncRNAs) as well. However, integration of ncRNAs into protein association networks...

  15. Minimal metabolic pathway structure is consistent with associated biomolecular interactions

    DEFF Research Database (Denmark)

    Bordbar, Aarash; Nagarajan, Harish; Lewis, Nathan E.

    2014-01-01

    Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high-throughput data generation have transformed biology, the core of our biological understanding, and hence data interpretation, is still predicated on human-defined pathways. Here, we...... suggesting a functional organization for metabolism based on parsimonious use of cellular components. We use the inherent predictive capability of these pathways to experimentally discover novel transcriptional regulatory interactions in Escherichia coli metabolism for three transcription factors...

  16. Salmonella interactions with plants and their associated microbiota.

    Science.gov (United States)

    Brandl, Maria T; Cox, Clayton E; Teplitski, Max

    2013-04-01

    The increase in the incidence of gastroenteritis outbreaks linked to the consumption of foods of plant origin has ignited public concern and scientific interest in understanding interactions of human enteric pathogens with plants. Enteric disease caused by nontyphoidal Salmonella is a major public health burden, with the number of cases of illness linked to fresh produce, spices, and nuts surpassing those linked to foods of animal origin. Mounting evidence supports the hypothesis that colonization of plants is an important part of the life cycle of this human pathogen. Although plant responses to human pathogens are distinct from the more specific responses to phytopathogens, plants appear to recognize Salmonella, likely by detecting conserved microbial patterns, which subsequently activates basal defenses. Numerous Salmonella genes have been identified as playing a role in its colonization of plant surfaces and tissues, and in its various interactions with other members of the phyto-microbial community. Importantly, Salmonella utilizes diverse and overlapping strategies to interact with plants and their microflora, and to successfully colonize its vertebrate hosts. This review provides insight into the complex behavior of Salmonella on plants and the apparent remarkable adaptation of this human pathogen to a potentially secondary host.

  17. Social Anxiety in Online and Real-Life Interaction and Their Associated Factors

    OpenAIRE

    Yen, Ju-Yu; Yen, Cheng-Fang; Chen, Cheng-Sheng; Wang, Peng-Wei; Chang, Yi-Hsin; Ko, Chih-Hung

    2012-01-01

    Social anxiety was compared between online and real-life interaction in a sample of 2,348 college students. Severity of social anxiety in both real-life and online interaction was tested for associations with depression, Internet addiction, Internet activity type (gaming versus chatting), and scores on Behavioral Inhibition System (BIS)/Behavioral Activation System (BAS) scales. The results showed that social anxiety was lower when interacting online than when interacting offline. Depression,...

  18. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions...... including puppetry and dance. However, the aesthetics of these traditions vary across cultures and carry different associative and interpretive meanings. Puppetry offers a useful frame for understanding the relationship between abstract and imitative gestures and behavior, and instantiates the complex...... interaction between a human operator and an artificial actor or agent. We can apply insights from puppetry to develop culturally-aware robots. Here we describe the development of a robotic marionette theatre wherein robotic controllers assume the role of human puppeteers. The system has been built, tested...

  19. Disease-associated mutations prevent GPR56-collagen III interaction.

    Directory of Open Access Journals (Sweden)

    Rong Luo

    Full Text Available GPR56 is a member of the adhesion G protein-coupled receptor (GPCR family. Mutations in GPR56 cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP. Using the N-terminal fragment of GPR56 (GPR56(N as a probe, we have recently demonstrated that collagen III is the ligand of GPR56 in the developing brain. In this report, we discover a new functional domain in GPR56(N, the ligand binding domain. This domain contains four disease-associated mutations and two N-glycosylation sites. Our study reveals that although glycosylation is not required for ligand binding, each of the four disease-associated mutations completely abolish the ligand binding ability of GPR56. Our data indicates that these four single missense mutations cause BFPP mostly by abolishing the ability of GPR56 to bind to its ligand, collagen III, in addition to affecting GPR56 protein surface expression as previously shown.

  20. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions...... including puppetry and dance. However, the aesthetics of these traditions vary across cultures and carry different associative and interpretive meanings. Puppetry offers a useful frame for understanding the relationship between abstract and imitative gestures and behavior, and instantiates the complex...

  1. Associative self-anchoring interacts with obtainability of chosen objects

    Directory of Open Access Journals (Sweden)

    Dean eMobbs

    2016-01-01

    Full Text Available While there is evidence that implicit self-esteem transfers to chosen objects (associative self-anchoring, it is still unknown whether this phenomenon extends to explicit self-esteem. Moreover, whether the knowledge that these objects might belong to the self in the future or not affects the evaluation of these objects has yet to be tested. Here, we demonstrate that evaluations of chosen objects are further enhanced when they are obtainable as compared to when they are not in participants with high explicit self-esteem, whereas participants with low explicit self-esteem exhibit the opposite pattern. These findings extend previous results and shed new light on the role of self-esteem in altering preferences for chosen objects depending on their obtainability.

  2. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

    DEFF Research Database (Denmark)

    Lundby, Alicia; Rossin, Elizabeth J.; Steffensen, Annette B.

    2014-01-01

    Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five gen...

  3. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

    NARCIS (Netherlands)

    Lundby, Alicia; Rossin, Elizabeth J.; Steffensen, Annette B.; Acha, Moshe Ray; Newton-Cheh, Christopher; Pfeufer, Arne; Lyneh, Stacey N.; Olesen, Soren-Peter; Brunak, Soren; Ellinor, Patrick T.; Jukema, J. Wouter; Trompet, Stella; Ford, Ian; Macfarlane, Peter W.; Krijthe, Bouwe P.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H.; Nathoe, Hendrik M.; Spiering, Wilko; Daly, Mark J.; Asselbergs, Ikea W.; van der Harst, Pim; Milan, David J.; de Bakker, Paul I. W.; Lage, Kasper; Olsen, Jesper V.

    Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes

  4. Social Anxiety in Online and Real-Life Interaction and Their Associated Factors

    Science.gov (United States)

    Yen, Ju-Yu; Yen, Cheng-Fang; Chen, Cheng-Sheng; Wang, Peng-Wei; Chang, Yi-Hsin

    2012-01-01

    Abstract Social anxiety was compared between online and real-life interaction in a sample of 2,348 college students. Severity of social anxiety in both real-life and online interaction was tested for associations with depression, Internet addiction, Internet activity type (gaming versus chatting), and scores on Behavioral Inhibition System (BIS)/Behavioral Activation System (BAS) scales. The results showed that social anxiety was lower when interacting online than when interacting offline. Depression, Internet addiction, and high BIS and BAS scores were associated with high social anxiety. The social anxiety decreased more in online interaction among subjects with high social anxiety, depression, BIS, and BAS. This result suggests that the Internet has good potential as an alternative medium for delivering interventions for social anxiety. Further, the effect of BIS on social anxiety is decreased in online interaction. More attention should be paid for BIS when the treatment for social anxiety is delivered online. PMID:22175853

  5. Social anxiety in online and real-life interaction and their associated factors.

    Science.gov (United States)

    Yen, Ju-Yu; Yen, Cheng-Fang; Chen, Cheng-Sheng; Wang, Peng-Wei; Chang, Yi-Hsin; Ko, Chih-Hung

    2012-01-01

    Social anxiety was compared between online and real-life interaction in a sample of 2,348 college students. Severity of social anxiety in both real-life and online interaction was tested for associations with depression, Internet addiction, Internet activity type (gaming versus chatting), and scores on Behavioral Inhibition System (BIS)/Behavioral Activation System (BAS) scales. The results showed that social anxiety was lower when interacting online than when interacting offline. Depression, Internet addiction, and high BIS and BAS scores were associated with high social anxiety. The social anxiety decreased more in online interaction among subjects with high social anxiety, depression, BIS, and BAS. This result suggests that the Internet has good potential as an alternative medium for delivering interventions for social anxiety. Further, the effect of BIS on social anxiety is decreased in online interaction. More attention should be paid for BIS when the treatment for social anxiety is delivered online.

  6. Gene-based testing of interactions in association studies of quantitative traits.

    Directory of Open Access Journals (Sweden)

    Li Ma

    Full Text Available Various methods have been developed for identifying gene-gene interactions in genome-wide association studies (GWAS. However, most methods focus on individual markers as the testing unit, and the large number of such tests drastically erodes statistical power. In this study, we propose novel interaction tests of quantitative traits that are gene-based and that confer advantage in both statistical power and biological interpretation. The framework of gene-based gene-gene interaction (GGG tests combine marker-based interaction tests between all pairs of markers in two genes to produce a gene-level test for interaction between the two. The tests are based on an analytical formula we derive for the correlation between marker-based interaction tests due to linkage disequilibrium. We propose four GGG tests that extend the following P value combining methods: minimum P value, extended Simes procedure, truncated tail strength, and truncated P value product. Extensive simulations point to correct type I error rates of all tests and show that the two truncated tests are more powerful than the other tests in cases of markers involved in the underlying interaction not being directly genotyped and in cases of multiple underlying interactions. We applied our tests to pairs of genes that exhibit a protein-protein interaction to test for gene-level interactions underlying lipid levels using genotype data from the Atherosclerosis Risk in Communities study. We identified five novel interactions that are not evident from marker-based interaction testing and successfully replicated one of these interactions, between SMAD3 and NEDD9, in an independent sample from the Multi-Ethnic Study of Atherosclerosis. We conclude that our GGG tests show improved power to identify gene-level interactions in existing, as well as emerging, association studies.

  7. Ontology-based literature mining of E. coli vaccine-associated gene interaction networks.

    Science.gov (United States)

    Hur, Junguk; Özgür, Arzucan; He, Yongqun

    2017-03-14

    Pathogenic Escherichia coli infections cause various diseases in humans and many animal species. However, with extensive E. coli vaccine research, we are still unable to fully protect ourselves against E. coli infections. To more rational development of effective and safe E. coli vaccine, it is important to better understand E. coli vaccine-associated gene interaction networks. In this study, we first extended the Vaccine Ontology (VO) to semantically represent various E. coli vaccines and genes used in the vaccine development. We also normalized E. coli gene names compiled from the annotations of various E. coli strains using a pan-genome-based annotation strategy. The Interaction Network Ontology (INO) includes a hierarchy of various interaction-related keywords useful for literature mining. Using VO, INO, and normalized E. coli gene names, we applied an ontology-based SciMiner literature mining strategy to mine all PubMed abstracts and retrieve E. coli vaccine-associated E. coli gene interactions. Four centrality metrics (i.e., degree, eigenvector, closeness, and betweenness) were calculated for identifying highly ranked genes and interaction types. Using vaccine-related PubMed abstracts, our study identified 11,350 sentences that contain 88 unique INO interactions types and 1,781 unique E. coli genes. Each sentence contained at least one interaction type and two unique E. coli genes. An E. coli gene interaction network of genes and INO interaction types was created. From this big network, a sub-network consisting of 5 E. coli vaccine genes, including carA, carB, fimH, fepA, and vat, and 62 other E. coli genes, and 25 INO interaction types was identified. While many interaction types represent direct interactions between two indicated genes, our study has also shown that many of these retrieved interaction types are indirect in that the two genes participated in the specified interaction process in a required but indirect process. Our centrality analysis of

  8. Serotonergic and adrenergic drug interactions associated with linezolid: a critical review and practical management approach.

    Science.gov (United States)

    Ramsey, Tasha D; Lau, Tim Ty; Ensom, Mary Hh

    2013-04-01

    To describe the evidence for serotonergic and adrenergic drug interactions with linezolid and discuss clinical management strategies. A literature search of PubMed (1947-November 2012), MEDLINE (1946-November 2012), EMBASE (1974-November 2012), and International Pharmaceutical Abstracts (1970-November 2012) was conducted using the terms linezolid, drug interaction, serotonin syndrome, serotonin toxicity, sympathomimetic, serotonergic agents, and adrenergic agents. Citations of retrieved articles were also reviewed. English-language articles describing coadministration of serotonergic or adrenergic agents with linezolid to humans were included. Studies published only in abstract form were excluded. One prospective study, 6 retrospective studies, and 24 case reports were identified describing a serotonergic or adrenergic drug interaction. Incidence of serotonin syndrome in patients on linezolid and serotonergic agents ranged between 0.24% and 4%. Serotonergic agents determined to have probable (according to the Horn Drug Interaction Probability Scale) linezolid interactions in case reports included meperidine, citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, and venlafaxine. Serotonergic agent dose and duration of coadministration with linezolid did not appear to influence the occurrence of serotonin syndrome. Adrenergic medication coadministration was associated with a possible drug interaction as determined by the Horn Drug Interaction Probability Scale but did not appear to result in clinically significant drug interactions with linezolid. Linezolid-associated serotonergic drug interactions occur more commonly than adrenergic interactions. Serotonergic interactions considered probable according to the Horn Drug Interaction Probability Scale do not appear to correlate with drug dosage; time of onset ranges from serotonergic agent cannot be avoided, clinicians should be aware of the symptoms and management of serotonergic toxicity; close

  9. Network graph analysis of gene-gene interactions in genome-wide association study data.

    Science.gov (United States)

    Lee, Sungyoung; Kwon, Min-Seok; Park, Taesung

    2012-12-01

    Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs). For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR) is one of the powerful and efficient methods for detecting high-order gene-gene (GxG) interactions. However, the biological interpretation of GxG interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified GxG interactions. The proposed network graph analysis consists of three steps. The first step is for performing GxG interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified GxG interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE) data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform GxG interaction analysis of body mass index (BMI). Our network graph analysis successfully showed that many identified GxG interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of GxG interactions.

  10. "My love-hate relationship": Ethical issues associated with nurses' interactions with industry.

    Science.gov (United States)

    Grundy, Quinn

    2014-08-01

    Ethical issues associated with nurses' interactions with industry have implications for the safety, quality, and cost of healthcare. To date, little work has explored nurse-industry interactions and their associated ethical issues empirically. A phenomenological study was conducted to explore registered nurses' interactions with industry in clinical practice. Five registered nurses working in direct patient care were recruited and individual, in-depth interviews were conducted. The University's Committee on Human Research approved the study. Nurses frequently interacted with industry in their practice and felt ambivalent about these interactions. Nurses described systemic cuts to multiple "goods" central to nursing practice, including patient support, but paradoxically relied on industry resources to deliver these "goods." They relied on a particular conception of trust to navigate these interactions but were left to do so individually on the basis of their experience. Conflicts of interest arose as a result of multiple competing interests, and were frequently mediated through nurses' superiors. Nursing as a profession requires a guiding narrative to aid nurses in interpreting and navigating interactions with industry. A conception of trust that incorporates both the work of caring and attention to social justice could form the basis of these interactions, but would require that nursing take a much more critical stance toward marketing interactions. © The Author(s) 2013.

  11. Severe potential drug-drug interactions in older adults with dementia and associated factors

    Directory of Open Access Journals (Sweden)

    Michele Bogetti-Salazar

    2016-01-01

    Full Text Available OBJECTIVE: To identify the main severe potential drug-drug interactions in older adults with dementia and to examine the factors associated with these interactions. METHOD: This was a cross-sectional study. The enrolled patients were selected from six geriatrics clinics of tertiary care hospitals across Mexico City. The patients had received a clinical diagnosis of dementia based on the current standards and were further divided into the following two groups: those with severe drug-drug interactions (contraindicated/severe (n=64 and those with non-severe drug-drug interactions (moderate/minor/absent (n=117. Additional socio-demographic, clinical and caregiver data were included. Potential drug-drug interactions were identified using Micromedex Drug Reax 2.0® database. RESULTS: A total of 181 patients were enrolled, including 57 men (31.5% and 124 women (68.5% with a mean age of 80.11±8.28 years. One hundred and seven (59.1% patients in our population had potential drug-drug interactions, of which 64 (59.81% were severe/contraindicated. The main severe potential drug-drug interactions were caused by the combinations citalopram/anti-platelet (11.6%, clopidogrel/omeprazole (6.1%, and clopidogrel/aspirin (5.5%. Depression, the use of a higher number of medications, dementia severity and caregiver burden were the most significant factors associated with severe potential drug-drug interactions. CONCLUSIONS: Older people with dementia experience many severe potential drug-drug interactions. Anti-depressants, antiplatelets, anti-psychotics and omeprazole were the drugs most commonly involved in these interactions. Despite their frequent use, anti-dementia drugs were not involved in severe potential drug-drug interactions. The number and type of medications taken, dementia severity and depression in patients in addition to caregiver burden should be considered to avoid possible drug interactions in this population.

  12. Interaction patterns of trauma providers are associated with length of stay.

    Science.gov (United States)

    Chen, You; Patel, Mayur B; McNaughton, Candace D; Malin, Bradley A

    2018-02-22

    Trauma-related hospitalizations drive a high percentage of health care expenditure and inpatient resource consumption, which is directly related to length of stay (LOS). Robust and reliable interactions among health care employees can reduce LOS. However, there is little known about whether certain patterns of interactions exist and how they relate to LOS and its variability. The objective of this study is to learn interaction patterns and quantify the relationship to LOS within a mature trauma system and long-standing electronic medical record (EMR). We adapted a spectral co-clustering methodology to infer the interaction patterns of health care employees based on the EMR of 5588 hospitalized adult trauma survivors. The relationship between interaction patterns and LOS was assessed via a negative binomial regression model. We further assessed the influence of potential confounders by age, number of health care encounters to date, number of access action types care providers committed to patient EMRs, month of admission, phenome-wide association study codes, procedure codes, and insurance status. Three types of interaction patterns were discovered. The first pattern exhibited the most collaboration between employees and was associated with the shortest LOS. Compared to this pattern, LOS for the second and third patterns was 0.61 days (P = 0.014) and 0.43 days (P = 0.037) longer, respectively. Although the 3 interaction patterns dealt with different numbers of patients in each admission month, our results suggest that care was provided for similar patients. The results of this study indicate there is an association between LOS and the extent to which health care employees interact in the care of an injured patient. The findings further suggest that there is merit in ascertaining the content of these interactions and the factors that induce these differences in interaction patterns within a trauma system.

  13. Inferring Intra-Community Microbial Interaction Patterns from Metagenomic Datasets Using Associative Rule Mining Techniques

    Science.gov (United States)

    Mande, Sharmila S.

    2016-01-01

    The nature of inter-microbial metabolic interactions defines the stability of microbial communities residing in any ecological niche. Deciphering these interaction patterns is crucial for understanding the mode/mechanism(s) through which an individual microbial community transitions from one state to another (e.g. from a healthy to a diseased state). Statistical correlation techniques have been traditionally employed for mining microbial interaction patterns from taxonomic abundance data corresponding to a given microbial community. In spite of their efficiency, these correlation techniques can capture only 'pair-wise interactions'. Moreover, their emphasis on statistical significance can potentially result in missing out on several interactions that are relevant from a biological standpoint. This study explores the applicability of one of the earliest association rule mining algorithm i.e. the 'Apriori algorithm' for deriving 'microbial association rules' from the taxonomic profile of given microbial community. The classical Apriori approach derives association rules by analysing patterns of co-occurrence/co-exclusion between various '(subsets of) features/items' across various samples. Using real-world microbiome data, the efficiency/utility of this rule mining approach in deciphering multiple (biologically meaningful) association patterns between 'subsets/subgroups' of microbes (constituting microbiome samples) is demonstrated. As an example, association rules derived from publicly available gut microbiome datasets indicate an association between a group of microbes (Faecalibacterium, Dorea, and Blautia) that are known to have mutualistic metabolic associations among themselves. Application of the rule mining approach on gut microbiomes (sourced from the Human Microbiome Project) further indicated similar microbial association patterns in gut microbiomes irrespective of the gender of the subjects. A Linux implementation of the Association Rule Mining (ARM

  14. Inferring Intra-Community Microbial Interaction Patterns from Metagenomic Datasets Using Associative Rule Mining Techniques.

    Directory of Open Access Journals (Sweden)

    Disha Tandon

    Full Text Available The nature of inter-microbial metabolic interactions defines the stability of microbial communities residing in any ecological niche. Deciphering these interaction patterns is crucial for understanding the mode/mechanism(s through which an individual microbial community transitions from one state to another (e.g. from a healthy to a diseased state. Statistical correlation techniques have been traditionally employed for mining microbial interaction patterns from taxonomic abundance data corresponding to a given microbial community. In spite of their efficiency, these correlation techniques can capture only 'pair-wise interactions'. Moreover, their emphasis on statistical significance can potentially result in missing out on several interactions that are relevant from a biological standpoint. This study explores the applicability of one of the earliest association rule mining algorithm i.e. the 'Apriori algorithm' for deriving 'microbial association rules' from the taxonomic profile of given microbial community. The classical Apriori approach derives association rules by analysing patterns of co-occurrence/co-exclusion between various '(subsets of features/items' across various samples. Using real-world microbiome data, the efficiency/utility of this rule mining approach in deciphering multiple (biologically meaningful association patterns between 'subsets/subgroups' of microbes (constituting microbiome samples is demonstrated. As an example, association rules derived from publicly available gut microbiome datasets indicate an association between a group of microbes (Faecalibacterium, Dorea, and Blautia that are known to have mutualistic metabolic associations among themselves. Application of the rule mining approach on gut microbiomes (sourced from the Human Microbiome Project further indicated similar microbial association patterns in gut microbiomes irrespective of the gender of the subjects. A Linux implementation of the Association Rule

  15. Self-care actions of chronic schizophrenics associated with meeting solitude and social interaction requisites.

    Science.gov (United States)

    Harris, J L

    1990-10-01

    Solitude becomes a way of life and social interaction a scarce commodity for many chronic schizophrenics who are in institutional settings. This article describes the self-care actions associated with meeting solitude and social interaction requisites as reported by 10 institutionalized chronic schizophrenics. Eighteen solitude self-care actions and 10 social interaction self-care actions emerged from the interview data. The solitude self-care actions clustered around two distinct categories: distancing and organizing. The social interaction self-care actions clustered around one category, managing situations. The implications of this study extend to anyone who is in the position of providing care and support to an individual diagnosed as a chronic schizophrenic. Additional research is suggested to increase the generalizability of the findings of this study and to isolate conditions related to Orem's (1985) sets of actions for maintenance of a balance between solitude and social interaction.

  16. Distinct neuronal interactions in anterior inferotemporal areas of macaque monkeys during retrieval of object association memory.

    Science.gov (United States)

    Hirabayashi, Toshiyuki; Tamura, Keita; Takeuchi, Daigo; Takeda, Masaki; Koyano, Kenji W; Miyashita, Yasushi

    2014-07-09

    In macaque monkeys, the anterior inferotemporal cortex, a region crucial for object memory processing, is composed of two adjacent, hierarchically distinct areas, TE and 36, for which different functional roles and neuronal responses in object memory tasks have been characterized. However, it remains unknown how the neuronal interactions differ between these areas during memory retrieval. Here, we conducted simultaneous recordings from multiple single-units in each of these areas while monkeys performed an object association memory task and examined the inter-area differences in neuronal interactions during the delay period. Although memory neurons showing sustained activity for the presented cue stimulus, cue-holding (CH) neurons, interacted with each other in both areas, only those neurons in area 36 interacted with another type of memory neurons coding for the to-be-recalled paired associate (pair-recall neurons) during memory retrieval. Furthermore, pairs of CH neurons in area TE showed functional coupling in response to each individual object during memory retention, whereas the same class of neuron pairs in area 36 exhibited a comparable strength of coupling in response to both associated objects. These results suggest predominant neuronal interactions in area 36 during the mnemonic processing, which may underlie the pivotal role of this brain area in both storage and retrieval of object association memory. Copyright © 2014 the authors 0270-6474/14/349377-12$15.00/0.

  17. Retrospective analysis of main and interaction effects in genetic association studies of human complex traits

    Directory of Open Access Journals (Sweden)

    Brasch-Andersen Charlotte

    2007-10-01

    Full Text Available Abstract Background The etiology of multifactorial human diseases involves complex interactions between numerous environmental factors and alleles of many genes. Efficient statistical tools are demanded in identifying the genetic and environmental variants that affect the risk of disease development. This paper introduces a retrospective polytomous logistic regression model to measure both the main and interaction effects in genetic association studies of human discrete and continuous complex traits. In this model, combinations of genotypes at two interacting loci or of environmental exposure and genotypes at one locus are treated as nominal outcomes of which the proportions are modeled as a function of the disease trait assigning both main and interaction effects and with no assumption of normality in the trait distribution. Performance of our method in detecting interaction effect is compared with that of the case-only model. Results Results from our simulation study indicate that our retrospective model exhibits high power in capturing even relatively small effect with reasonable sample sizes. Application of our method to data from an association study on the catalase -262C/T promoter polymorphism and aging phenotypes detected significant main and interaction effects for age-group and allele T on individual's cognitive functioning and produced consistent results in estimating the interaction effect as compared with the popular case-only model. Conclusion The retrospective polytomous logistic regression model can be used as a convenient tool for assessing both main and interaction effects in genetic association studies of human multifactorial diseases involving genetic and non-genetic factors as well as categorical or continuous traits.

  18. Network Graph Analysis of Gene-Gene Interactions in Genome-Wide Association Study Data

    Directory of Open Access Journals (Sweden)

    Sungyoung Lee

    2012-12-01

    Full Text Available Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs. For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR is one of the powerful and efficient methods for detecting high-order gene-gene (GxG interactions. However, the biological interpretation of GxG interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified GxG interactions. The proposed network graph analysis consists of three steps. The first step is for performing GxG interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified GxG interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform GxG interaction analysis of body mass index (BMI. Our network graph analysis successfully showed that many identified GxG interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of GxG interactions.

  19. The Self-Association of Graphane Is Driven by London Dispersion and Enhanced Orbital Interactions.

    Science.gov (United States)

    Wang, Changwei; Mo, Yirong; Wagner, J Philipp; Schreiner, Peter R; Jemmis, Eluvathingal D; Danovich, David; Shaik, Sason

    2015-04-14

    We investigated the nature of the cohesive energy between graphane sheets via multiple CH···HC interactions, using density functional theory (DFT) including dispersion correction (Grimme's D3 approach) computations of [n]graphane σ dimers (n = 6-73). For comparison, we also evaluated the binding between graphene sheets that display prototypical π/π interactions. The results were analyzed using the block-localized wave function (BLW) method, which is a variant of ab initio valence bond (VB) theory. BLW interprets the intermolecular interactions in terms of frozen interaction energy (ΔE(F)) composed of electrostatic and Pauli repulsion interactions, polarization (ΔE(pol)), charge-transfer interaction (ΔE(CT)), and dispersion effects (ΔE(disp)). The BLW analysis reveals that the cohesive energy between graphane sheets is dominated by two stabilizing effects, namely intermolecular London dispersion and two-way charge transfer energy due to the σ(CH) → σ*(HC) interactions. The shift of the electron density around the nonpolar covalent C-H bonds involved in the intermolecular interaction decreases the C-H bond lengths uniformly by 0.001 Å. The ΔE(CT) term, which accounts for ∼15% of the total binding energy, results in the accumulation of electron density in the interface area between two layers. This accumulated electron density thus acts as an electronic "glue" for the graphane layers and constitutes an important driving force in the self-association and stability of graphane under ambient conditions. Similarly, the "double faced adhesive tape" style of charge transfer interactions was also observed among graphene sheets in which it accounts for ∼18% of the total binding energy. The binding energy between graphane sheets is additive and can be expressed as a sum of CH···HC interactions, or as a function of the number of C-H bonds.

  20. Association of COMT and COMT-DRD2 interaction with creative potential

    Directory of Open Access Journals (Sweden)

    Shun eZhang

    2014-04-01

    Full Text Available Several lines of evidence suggest that genes involved in dopamine (DA transmission may contribute to creativity. Among these genes, the catechol-O-methyltransferase gene (COMT and the dopamine D2 receptor gene (DRD2 are the most promising candidates. Our previous study has revealed evidence for the involvement of DRD2 in creative potential. The present study extended our previous study by systematically exploring the association of COMT with creative potential as well as the interaction between COMT and DRD2. Twelve single nucleotide polymorphisms (SNPs covering COMT were genotyped in 543 healthy Chinese college students whose creative potentials were assessed by divergent thinking tests. Single SNP analysis showed that rs174697 was nominally associated with verbal originality, two SNPs (rs737865 and rs5993883 were nominally associated with figural fluency, and two SNPs (rs737865 and rs4680 were nominally associated with figural originality. Haplotype analysis showed that, the TCT and CCT haplotype (rs737865-rs174675-rs5993882 were nominally associated with figural originality, and the TATGCAG and CGCGGGA haplotype (rs4646312-rs6269-rs4633-rs6267-rs4818-rs4680-rs769224 were nominally associated with figural originality and verbal flexibility, respectively. However, none of these nominal findings survived correction for multiple testing. Gene-gene interaction analysis identified one significant four-way interaction of rs174675 (COMT, rs174697 (COMT, rs1076560 (DRD2 and rs4436578 (DRD2 on verbal fluency, one significant four-way interaction of rs174675 (COMT, rs4818 (COMT, rs1076560 (DRD2 and rs4648317 (DRD2 on verbal flexibility, and one significant three-way interaction of rs5993883 (COMT, rs4648319 (DRD2 and rs4648317 (DRD2 on figural flexibility. In conclusion, the present study provides nominal evidence for the involvement of COMT in creative potential and suggests that DA related genes may act in coordination to contribute to creativity.

  1. SNPs in PPARG associate with type 2 diabetes and interact with physical activity

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas; Lakka, Timo A; Laaksonen, David E

    2008-01-01

    To study the associations of seven single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor gamma (PPARG) gene with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D), and the interactions of the SNPs with physical activity (PA)....

  2. Young Children's Sibling Relationship Interactional Types: Associations with Family Characteristics, Parenting, and Child Characteristics

    Science.gov (United States)

    Gamble, Wendy C.; Yu, Jeong Jin

    2014-01-01

    Research Findings: This study examines patterns of sibling relationship qualities or interactional types and their association with family characteristics, parenting, and the characteristics of 1 of those children. Participants were 65 children (34 boys; Time 1 mean age = 51 months), their mothers, fathers, and Head Start teachers. Approximately…

  3. Using biological networks to search for interacting loci in genomewide association studies

    DEFF Research Database (Denmark)

    Emily, Mathieu; Mailund, Thomas; Hein, Jotun

    2009-01-01

    Genome-wide association studies have identified a large number of single-nucleotide polymorphisms (SNPs) that individually predispose to diseases. However, many genetic risk factors remain unaccounted for. Proteins coded by genes interact in the cell, and it is most likely that certain variants...... to Crohn's disease, bipolar disorder, hypertension and rheumatoid arthritis....

  4. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

    NARCIS (Netherlands)

    A.D. Børglum; D. Demontis; J. Grove (Jakob); J. Pallesen (J.); M.V. Hollegaard (Mads V); C.B. Pedersen (C.); A. Hedemand (A.); M. Mattheisen (Manuel); A.G. Uitterlinden (André); M. Nyegaard (M.); T.F. Orntoft (Torben); C. Wiuf (Carsten); M. Didriksen (Michael); M. Nordentoft (M.); M.M. Nö then (M.); M. Rietschel (Marcella); R.A. Ophoff (Roel); S. Cichon (Sven); R.H. Yolken (Robert); D.M. Hougaard (David); P.B. Mortensen; O. Mors

    2014-01-01

    textabstractGenetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all

  5. Associations between Observed Mother-Adolescent Interactions and Adolescent Information Management

    Science.gov (United States)

    Rote, Wendy M.; Smetana, Judith G.; Campione-Barr, Nicole; Villalobos, Myriam; Tasopoulos-Chan, Marina

    2012-01-01

    Associations between observed mother-adolescent interactions during a conflict task and adolescents' information management strategies were examined in 108 primarily middle class, European-American adolescents (M = 13.80 years, SD = 1.52) and their mothers. Teens who communicated more clearly disclosed more about personal and multifaceted…

  6. Multifactor-dimensionality reduction shows a two-locus interaction associated with Type 2 diabetes mellitus.

    Science.gov (United States)

    Cho, Y M; Ritchie, M D; Moore, J H; Park, J Y; Lee, K-U; Shin, H D; Lee, H K; Park, K S

    2004-03-01

    Type 2 diabetes mellitus is a complex genetic disease, which results from interactions between multiple genes and environmental factors without any single factor having strong independent effects. This study was done to identify gene to gene interactions which could be associated with the risk of Type 2 diabetes. We genotyped 23 different loci in the 15 candidate genes of Type 2 diabetes in 504 unrelated Type 2 diabetic patients and 133 non-diabetic control subjects. We analysed gene to gene interactions among 23 polymorphic loci using the multifactor-dimensionality reduction (MDR) method, which has been shown to be effective for detecting and characterising gene to gene interactions in case-control studies with relatively small samples. The MDR analysis showed a significant gene to gene interaction between the Ala55Val polymorphism in the uncoupling protein 2 gene ( UCP2) and the 161C>T polymorphism in the exon 6 of peroxisome proliferator-activated receptor gamma ( PPARgamma) gene. This interaction showed the maximum consistency and minimum prediction error among all gene to gene interaction models evaluated. Moreover, the combination of the UCP2 55 Ala/Val heterozygote and the PPARgamma 161 C/C homozygote was associated with a reduced risk of Type 2 diabetes (odds ratio: 0.51, 95% CI: 0.34 to 0.77, p=0.0016). Using the MDR method, we showed a two-locus interaction between the UCP2 and PPARgamma genes among 23 loci in the candidate genes of Type 2 diabetes. The determination of such genotype combinations contributing to Type 2 diabetes mellitus could provide a new tool for identifying high-risk individuals.

  7. Identification of fever and vaccine-associated gene interaction networks using ontology-based literature mining.

    Science.gov (United States)

    Hur, Junguk; Ozgür, Arzucan; Xiang, Zuoshuang; He, Yongqun

    2012-12-20

    Fever is one of the most common adverse events of vaccines. The detailed mechanisms of fever and vaccine-associated gene interaction networks are not fully understood. In the present study, we employed a genome-wide, Centrality and Ontology-based Network Discovery using Literature data (CONDL) approach to analyse the genes and gene interaction networks associated with fever or vaccine-related fever responses. Over 170,000 fever-related articles from PubMed abstracts and titles were retrieved and analysed at the sentence level using natural language processing techniques to identify genes and vaccines (including 186 Vaccine Ontology terms) as well as their interactions. This resulted in a generic fever network consisting of 403 genes and 577 gene interactions. A vaccine-specific fever sub-network consisting of 29 genes and 28 gene interactions was extracted from articles that are related to both fever and vaccines. In addition, gene-vaccine interactions were identified. Vaccines (including 4 specific vaccine names) were found to directly interact with 26 genes. Gene set enrichment analysis was performed using the genes in the generated interaction networks. Moreover, the genes in these networks were prioritized using network centrality metrics. Making scientific discoveries and generating new hypotheses were possible by using network centrality and gene set enrichment analyses. For example, our study found that the genes in the generic fever network were more enriched in cell death and responses to wounding, and the vaccine sub-network had more gene enrichment in leukocyte activation and phosphorylation regulation. The most central genes in the vaccine-specific fever network are predicted to be highly relevant to vaccine-induced fever, whereas genes that are central only in the generic fever network are likely to be highly relevant to generic fever responses. Interestingly, no Toll-like receptors (TLRs) were found in the gene-vaccine interaction network. Since

  8. Age, class and race discrimination: their interactions and associations with mental health among Brazilian university students

    Directory of Open Access Journals (Sweden)

    Joao Luiz Bastos

    2014-01-01

    Full Text Available Although research on discrimination and health has progressed significantly, it has tended to focus on racial discrimination and US populations. This study explored different types of discrimination, their interactions and associations with common mental disorders among Brazilian university students, in Rio de Janeiro in 2010. Associations between discrimination and common mental disorders were examined using multiple logistic regression models, adjusted for confounders. Interactions between discrimination and socio-demographics were tested. Discrimination attributed to age, class and skin color/race were the most frequently reported. In a fully adjusted model, discrimination attributed to skin color/race and class were both independently associated with increased odds of common mental disorders. The simultaneous reporting of skin color/race, class and age discrimination was associated with the highest odds ratio. No significant interactions were found. Skin color/race and class discrimination were important, but their simultaneous reporting, in conjunction with age discrimination, were associated with the highest occurrence of common mental disorders.

  9. What can we learn from the microbial ecological interactions associated with polymicrobial diseases?

    Science.gov (United States)

    Antiabong, J F; Boardman, W; Ball, A S

    2014-03-15

    Periodontal diseases in humans and animals are model polymicrobial diseases which are associated with a shift in the microbial community structure and function; there is therefore a need to investigate these diseases from a microbial ecological perspective. This review highlights three important areas of microbial ecological investigation of polymicrobial diseases and the lessons that could be learnt: (1) identification of disease-associated microbes and the implications for choice of anti-infective treatment; (2) the implications associated with vaccine design and development and (3) application of the dynamics of microbial interaction in the discovery of novel anti-infective agents. This review emphasises the need to invigorate microbial ecological approaches to the study of periodontal diseases and other polymicrobial diseases for greater understanding of the ecological interactions between and within the biotic and abiotic factors of the environment. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Screen and clean: a tool for identifying interactions in genome-wide association studies.

    Science.gov (United States)

    Wu, Jing; Devlin, Bernie; Ringquist, Steven; Trucco, Massimo; Roeder, Kathryn

    2010-04-01

    Epistasis could be an important source of risk for disease. How interacting loci might be discovered is an open question for genome-wide association studies (GWAS). Most researchers limit their statistical analyses to testing individual pairwise interactions (i.e., marginal tests for association). A more effective means of identifying important predictors is to fit models that include many predictors simultaneously (i.e., higher-dimensional models). We explore a procedure called screen and clean (SC) for identifying liability loci, including interactions, by using the lasso procedure, which is a model selection tool for high-dimensional regression. We approach the problem by using a varying dictionary consisting of terms to include in the model. In the first step the lasso dictionary includes only main effects. The most promising single-nucleotide polymorphisms (SNPs) are identified using a screening procedure. Next the lasso dictionary is adjusted to include these main effects and the corresponding interaction terms. Again, promising terms are identified using lasso screening. Then significant terms are identified through the cleaning process. Implementation of SC for GWAS requires algorithms to explore the complex model space induced by the many SNPs genotyped and their interactions. We propose and explore a set of algorithms and find that SC successfully controls Type I error while yielding good power to identify risk loci and their interactions. When the method is applied to data obtained from the Wellcome Trust Case Control Consortium study of Type 1 Diabetes it uncovers evidence supporting interaction within the HLA class II region as well as within Chromosome 12q24.

  11. Employees' negative and positive work-home interaction and their association with depressive symptoms.

    Science.gov (United States)

    Nitzsche, Anika; Jung, Julia; Pfaff, Holger; Driller, Elke

    2013-05-01

    Depression is the leading cause of disability and high costs worldwide. One possibility for preventing depression in the workplace, which has received little consideration so far, is the promotion of a successful balance between work and personal life. The aim of this study was to investigate employees' negative and positive work-home interaction and their association with depressive symptoms. A cross-sectional study was conducted in the micro- and nanotechnology sector in Germany. A stepwise multivariate logistic regression analysis was performed using data from N = 213 employees. The results suggest that while negative work-home interaction is associated with an increased risk for depressive symptoms, positive work-home interaction is correlated with a lower risk. Neither positive nor negative interaction in the home-to-work direction demonstrated a significant association with depressive symptoms. When attempting to prevent mental illnesses, such as depression, it is important to develop strategies aimed at reducing conflict between work and personal life and promoting a positive exchange between these two domains. Copyright © 2012 Wiley Periodicals, Inc.

  12. XTACC3-XMAP215 association reveals an asymmetric interaction promoting microtubule elongation

    DEFF Research Database (Denmark)

    Mortuza, Gulnahar B; Cavazza, Tommaso; Garcia-Mayoral, Maria Flor

    2014-01-01

    215 (chTOG), dissecting the mechanism by which their interaction promotes microtubule elongation during spindle assembly. Using SAXS, we show that the TACC domain (TD) is an elongated structure that mediates the interaction with the C terminus of XMAP215. Our data suggest that one TD and two XMAP215...... molecules associate to form a four-helix coiled-coil complex. A hybrid methods approach was used to define the precise regions of the TACC heptad repeat and the XMAP215 C terminus required for assembly and functioning of the complex. We show that XTACC3 can induce the recruitment of larger amounts of XMAP...

  13. Two microcephaly-associated novel missense mutations in CASK specifically disrupt the CASK-neurexin interaction.

    Science.gov (United States)

    LaConte, Leslie E W; Chavan, Vrushali; Elias, Abdallah F; Hudson, Cynthia; Schwanke, Corbin; Styren, Katie; Shoof, Jonathan; Kok, Fernando; Srivastava, Sarika; Mukherjee, Konark

    2018-03-01

    Deletion and truncation mutations in the X-linked gene CASK are associated with severe intellectual disability (ID), microcephaly and pontine and cerebellar hypoplasia in girls (MICPCH). The molecular origin of CASK-linked MICPCH is presumed to be due to disruption of the CASK-Tbr-1 interaction. This hypothesis, however, has not been directly tested. Missense variants in CASK are typically asymptomatic in girls. We report three severely affected girls with heterozygous CASK missense mutations (M519T (2), G659D (1)) who exhibit ID, microcephaly, and hindbrain hypoplasia. The mutation M519T results in the replacement of an evolutionarily invariant methionine located in the PDZ signaling domain known to be critical for the CASK-neurexin interaction. CASK M519T is incapable of binding to neurexin, suggesting a critically important role for the CASK-neurexin interaction. The mutation G659D is in the SH3 (Src homology 3) domain of CASK, replacing a semi-conserved glycine with aspartate. We demonstrate that the CASK G659D mutation affects the CASK protein in two independent ways: (1) it increases the protein's propensity to aggregate; and (2) it disrupts the interface between CASK's PDZ (PSD95, Dlg, ZO-1) and SH3 domains, inhibiting the CASK-neurexin interaction despite residing outside of the domain deemed critical for neurexin interaction. Since heterozygosity of other aggregation-inducing mutations (e.g., CASK W919R ) does not produce MICPCH, we suggest that the G659D mutation produces microcephaly by disrupting the CASK-neurexin interaction. Our results suggest that disruption of the CASK-neurexin interaction, not the CASK-Tbr-1 interaction, produces microcephaly and cerebellar hypoplasia. These findings underscore the importance of functional validation for variant classification.

  14. Efficient two-step testing of gene-gene interactions in genome-wide association studies.

    Science.gov (United States)

    Lewinger, Juan Pablo; Morrison, John L; Thomas, Duncan C; Murcray, Cassandra E; Conti, David V; Li, Dalin; Gauderman, W James

    2013-07-01

    Exhaustive testing of all possible SNP pairs in a genome-wide association study (GWAS) generally yields low power to detect gene-gene (G × G) interactions because of small effect sizes and stringent requirements for multiple-testing correction. We introduce a new two-step procedure for testing G × G interactions in case-control GWAS to detect interacting single nucleotide polymorphisms (SNPs) regardless of their marginal effects. In an initial screening step, all SNP pairs are tested for gene-gene association in the combined sample of cases and controls. In the second step, the pairs that pass the screening are followed up with a traditional test for G × G interaction. We show that the two-step method is substantially more powerful to detect G × G interactions than the exhaustive testing approach. For example, with 2,000 cases and 2,000 controls, the two-step method can have more than 90% power to detect an interaction odds ratio of 2.0 compared to less than 50% power for the exhaustive testing approach. Moreover, we show that a hybrid two-step approach that combines our newly proposed two-step test and the two-step test that screens for marginal effects retains the best power properties of both. The two-step procedures we introduce have the potential to uncover genetic signals that have not been previously identified in an initial single-SNP GWAS. We demonstrate the computational feasibility of the two-step G × G procedure by performing a G × G scan in the asthma GWAS of the University of Southern California Children's Health Study. © 2013 WILEY PERIODICALS, INC.

  15. [Gene-nutrient interaction and its association with obesity and diabetes mellitus].

    Science.gov (United States)

    Steemburgo, Thais; Azevedo, Mirela J de; Martínez, José Alfredo

    2009-07-01

    Nutritional genomics evaluates the effects of genetic variation in the interaction between diet and chronic diseases. The aim of this manuscript was to review the most important genetic polymorphisms associated with obesity, diabetes mellitus, and dietary factors. The main interactions among genetic polymorphisms and diet were: for obesity: interleukin-6 (IL-6) with daily intake; peroxisome proliferator-activated receptor gamma 2 (PPAR-gama2) and fat mass and obesity associated (FTO) with fat intake; beta-adrenergic receptor 2 (ADRB2) and melanocortin receptor 4 (MCR4) with carbohydrate intake; or reduction in body weight: uncoupling proteins (UCPs) with restriction of energy; for leptinemia: leptin receptor (LEPR) with restriction of energy; for diabetes mellitus: PPAR-gama2 with fat intake; for hypertriglyceridemia: fatty acid-binding protein 2 (FABP2) with fat intake. The data demonstrated suggest that nutritional genomics is important for the development of obesity and diabetes mellitus.

  16. Associated W±D(*) production at the LHC and prospects to observe double parton interactions

    International Nuclear Information System (INIS)

    Baranov, S.P.; Lipatov, A.V.; Malyshev, M.A.; Snigirev, A.M.; Zotov, N.P.

    2015-03-01

    Associated production of charged gauge bosons and charged charmed mesons at the LHC is considered in the framework of k t -factorization approach. Theoretical predictions are compared with ATLAS data, and reasonably good agreement is found. Predictions on the same-sign W ± D ± configurations are presented including single parton scattering and double parton scattering contributions. The latter are shown to dominate over the former, thus giving evidence that the proposed process can serve as another indicator of double parton interactions.

  17. Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses

    DEFF Research Database (Denmark)

    Christensen, Tove

    2005-01-01

    may be members of the Herpesviridae. Several herpes viruses, such as HSV-1, VZV, EBV and HHV-6, have been associated with MS pathogenesis, and retroviruses and herpes viruses have complex interactions. The current understanding of HERVs, and specifically the investigations of HERV activation...... and expression in MS are the major subjects of this review, which also proposes to synergise the herpes and HERV findings, and presents several possible pathogenic mechanisms for HERVs in MS. Copyright (c) 2005 ...

  18. Emotions and family interactions in childhood: Associations with leukocyte telomere length emotions, family interactions, and telomere length.

    Science.gov (United States)

    Robles, Theodore F; Carroll, Judith E; Bai, Sunhye; Reynolds, Bridget M; Esquivel, Stephanie; Repetti, Rena L

    2016-01-01

    Conceptualizations of links between stress and cellular aging in childhood suggest that accumulating stress predicts shorter leukocyte telomere length (LTL). At the same time, several models suggest that emotional reactivity to stressors may play a key role in predicting cellular aging. Using intensive repeated measures, we tested whether exposure or emotional "reactivity" to conflict and warmth in the family were related to LTL. Children (N=39; 30 target children and 9 siblings) between 8 and 13 years of age completed daily diary questionnaires for 56 consecutive days assessing daily warmth and conflict in the marital and the parent-child dyad, and daily positive and negative mood. To assess exposure to conflict and warmth, diary scale scores were averaged over the 56 days. Mood "reactivity" was operationalized by using multilevel modeling to generate estimates of the slope of warmth or conflict scores (marital and parent-child, separately) predicting same-day mood for each individual child. After diary collection, a blood sample was collected to determine LTL. Among children aged 8-13 years, a stronger association between negative mood and marital conflict, suggesting greater negative mood reactivity to marital conflict, was related to shorter LTL (B=-1.51, paffection, suggesting positive mood reactivity, was related to longer LTL (B=1.15, pfirst evidence showing that link between children's affective responses and daily family interactions may have implications for telomere length. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Multifactor dimensionality reduction reveals a three-locus epistatic interaction associated with susceptibility to pulmonary tuberculosis.

    Science.gov (United States)

    Collins, Ryan L; Hu, Ting; Wejse, Christian; Sirugo, Giorgio; Williams, Scott M; Moore, Jason H

    2013-02-18

    Identifying high-order genetics associations with non-additive (i.e. epistatic) effects in population-based studies of common human diseases is a computational challenge. Multifactor dimensionality reduction (MDR) is a machine learning method that was designed specifically for this problem. The goal of the present study was to apply MDR to mining high-order epistatic interactions in a population-based genetic study of tuberculosis (TB). The study used a previously published data set consisting of 19 candidate single-nucleotide polymorphisms (SNPs) in 321 pulmonary TB cases and 347 healthy controls from Guniea-Bissau in Africa. The ReliefF algorithm was applied first to generate a smaller set of the five most informative SNPs. MDR with 10-fold cross-validation was then applied to look at all possible combinations of two, three, four and five SNPs. The MDR model with the best testing accuracy (TA) consisted of SNPs rs2305619, rs187084, and rs11465421 (TA = 0.588) in PTX3, TLR9 and DC-Sign, respectively. A general 1000-fold permutation test of the null hypothesis of no association confirmed the statistical significance of the model (p = 0.008). An additional 1000-fold permutation test designed specifically to test the linear null hypothesis that the association effects are only additive confirmed the presence of non-additive (i.e. nonlinear) or epistatic effects (p = 0.013). An independent information-gain measure corroborated these results with a third-order epistatic interaction that was stronger than any lower-order associations. We have identified statistically significant evidence for a three-way epistatic interaction that is associated with susceptibility to TB. This interaction is stronger than any previously described one-way or two-way associations. This study highlights the importance of using machine learning methods that are designed to embrace, rather than ignore, the complexity of common diseases such as TB. We recommend future studies of the

  20. Parallel interactive retrieval of item and associative information from event memory.

    Science.gov (United States)

    Cox, Gregory E; Criss, Amy H

    2017-09-01

    Memory contains information about individual events (items) and combinations of events (associations). Despite the fundamental importance of this distinction, it remains unclear exactly how these two kinds of information are stored and whether different processes are used to retrieve them. We use both model-independent qualitative properties of response dynamics and quantitative modeling of individuals to address these issues. Item and associative information are not independent and they are retrieved concurrently via interacting processes. During retrieval, matching item and associative information mutually facilitate one another to yield an amplified holistic signal. Modeling of individuals suggests that this kind of facilitation between item and associative retrieval is a ubiquitous feature of human memory. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Sex-specific Profiles of Blood Metal Levels Associated with Metal–Iron Interactions

    Directory of Open Access Journals (Sweden)

    Byung-Kook Lee

    2014-09-01

    Full Text Available The mechanisms by which iron is absorbed are similar to those of divalent metals, particularly manganese, lead, and cadmium. These metals, however, show different toxicokinetics in relation to menarche or menopause, although their interaction with iron is the same. This review focuses on the kinetics of these three toxic metals (manganese, lead, and cadmium in relation to menarche, pregnancy, and menopause. The iron–manganese interaction is the major factor determining sex-specific differences in blood manganese levels throughout the whole life cycle. The effects of estrogen overshadow the association between iron deficiency and increased blood lead concentrations, explaining why women, despite having lower ferritin concentrations, have lower blood lead concentrations than men. Iron deficiency is associated with elevated cadmium levels in premenopausal women, but not in postmenopausal women or men; these findings indicate that sex-specific differences in cadmium levels at older ages are not due to iron–cadmium interactions, and that further studies are required to identify the source of these differences. In summary, the potential causes of sex-specific differences in the blood levels of manganese, lead, and cadmium differ from each other, although all these three metals are associated with iron deficiency. Therefore, other factors such as estrogen effects, or absorption rate as well as iron deficiency, should be considered when addressing environmental exposure to toxic metals and sex-specific differences in the blood levels of these metals.

  2. Caspase-2 associates with FAN through direct interaction and overlapping functionality.

    Science.gov (United States)

    Forsberg, Jeremy; Li, Xinge; Zamaraev, Aleksey V; Panaretakis, Theocharis; Zhivotovsky, Boris; Olsson, Magnus

    2018-04-06

    Caspase-2 has been implicated in diverse cellular processes, and the identification of factors with which it interacts has steadily increased. In the present study, we report a direct interaction between caspase-2 and factor associated with neutral sphingomyelinase activation (FAN) using yeast two-hybrid screening and co-immunoprecipitation. Further, stable suppression of caspase-2 expression in HEK293T and HeLa cells enabled a systematic investigation of putative novel enzyme functionalities, especially with respect to ceramide production, cell migration, IL-6 production and vesicular homeostasis, all of which have been previously reported to be associated with FAN. Lipidomics excluded the involvement of caspase-2 in the generation of ceramide species, but caspase-2-dependent deregulation of IL-6 release, vesicular size and delayed cell relocation supported an association between caspase-2 and FAN. Collectively, these data identify a novel caspase-2-interacting factor, FAN, and expand the role for the enzyme in seemingly non-apoptotic cellular mechanisms. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Interactions

    DEFF Research Database (Denmark)

    The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists such as ......The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists...... such as Lorentz and Einstein as well as mathematicians such as Poincare, Minkowski, Hilbert and Weyl contributed to this development. They created the new physical theories and the mathematical disciplines that play such paramount roles in their mathematical formulations. These physicists and mathematicians were...... also key figures in the philosophical discussions of nature and science - from philosophical tendencies like logical empiricism via critical rationalism to various neo-Kantian trends....

  4. Association mapping and gene-gene interaction for stem rust resistance in CIMMYT spring wheat germplasm.

    Science.gov (United States)

    Yu, Long-Xi; Lorenz, Aaron; Rutkoski, Jessica; Singh, Ravi P; Bhavani, Sridhar; Huerta-Espino, Julio; Sorrells, Mark E

    2011-12-01

    The recent emergence of wheat stem rust Ug99 and evolution of new races within the lineage threatens global wheat production because they overcome widely deployed stem rust resistance (Sr) genes that had been effective for many years. To identify loci conferring adult plant resistance to races of Ug99 in wheat, we employed an association mapping approach for 276 current spring wheat breeding lines from the International Maize and Wheat Improvement Center (CIMMYT). Breeding lines were genotyped with Diversity Array Technology (DArT) and microsatellite markers. Phenotypic data was collected on these lines for stem rust race Ug99 resistance at the adult plant stage in the stem rust resistance screening nursery in Njoro, Kenya in seasons 2008, 2009 and 2010. Fifteen marker loci were found to be significantly associated with stem rust resistance. Several markers appeared to be linked to known Sr genes, while other significant markers were located in chromosome regions where no Sr genes have been previously reported. Most of these new loci colocalized with QTLs identified recently in different biparental populations. Using the same data and Q + K covariate matrices, we investigated the interactions among marker loci using linear regression models to calculate P values for pairwise marker interactions. Resistance marker loci including the Sr2 locus on 3BS and the wPt1859 locus on 7DL had significant interaction effects with other loci in the same chromosome arm and with markers on chromosome 6B. Other resistance marker loci had significant pairwise interactions with markers on different chromosomes. Based on these results, we propose that a complex network of gene-gene interactions is, in part, responsible for resistance to Ug99. Further investigation may provide insight for understanding mechanisms that contribute to this resistance gene network.

  5. Proteomic analysis of FOXP proteins reveals interactions between cortical transcription factors associated with neurodevelopmental disorders.

    Science.gov (United States)

    Estruch, Sara B; Graham, Sarah A; Quevedo, Martí; Vino, Arianna; Dekkers, Dick H W; Deriziotis, Pelagia; Sollis, Elliot; Demmers, Jeroen; Poot, Raymond A; Fisher, Simon E

    2018-04-01

    FOXP transcription factors play important roles in neurodevelopment, but little is known about how their transcriptional activity is regulated. FOXP proteins cooperatively regulate gene expression by forming homo- and hetero-dimers with each other. Physical associations with other transcription factors might also modulate the functions of FOXP proteins. However, few FOXP-interacting transcription factors have been identified so far. Therefore, we sought to discover additional transcription factors that interact with the brain-expressed FOXP proteins, FOXP1, FOXP2 and FOXP4, through affinity-purifications of protein complexes followed by mass spectrometry. We identified seven novel FOXP-interacting transcription factors (NR2F1, NR2F2, SATB1, SATB2, SOX5, YY1 and ZMYM2), five of which have well-estabslished roles in cortical development. Accordingly, we found that these transcription factors are co-expressed with FoxP2 in the deep layers of the cerebral cortex and also in the Purkinje cells of the cerebellum, suggesting that they may cooperate with the FoxPs to regulate neural gene expression in vivo. Moreover, we demonstrated that etiological mutations of FOXP1 and FOXP2, known to cause neurodevelopmental disorders, severely disrupted the interactions with FOXP-interacting transcription factors. Additionally, we pinpointed specific regions within FOXP2 sequence involved in mediating these interactions. Thus, by expanding the FOXP interactome we have uncovered part of a broader neural transcription factor network involved in cortical development, providing novel molecular insights into the transcriptional architecture underlying brain development and neurodevelopmental disorders.

  6. iHAT: interactive Hierarchical Aggregation Table for Genetic Association Data

    Directory of Open Access Journals (Sweden)

    Heinrich Julian

    2012-05-01

    Full Text Available Abstract In the search for single-nucleotide polymorphisms which influence the observable phenotype, genome wide association studies have become an important technique for the identification of associations between genotype and phenotype of a diverse set of sequence-based data. We present a methodology for the visual assessment of single-nucleotide polymorphisms using interactive hierarchical aggregation techniques combined with methods known from traditional sequence browsers and cluster heatmaps. Our tool, the interactive Hierarchical Aggregation Table (iHAT, facilitates the visualization of multiple sequence alignments, associated metadata, and hierarchical clusterings. Different color maps and aggregation strategies as well as filtering options support the user in finding correlations between sequences and metadata. Similar to other visualizations such as parallel coordinates or heatmaps, iHAT relies on the human pattern-recognition ability for spotting patterns that might indicate correlation or anticorrelation. We demonstrate iHAT using artificial and real-world datasets for DNA and protein association studies as well as expression Quantitative Trait Locus data.

  7. The Effect of Attractive Interactions and Macromolecular Crowding on Crystallins Association.

    Directory of Open Access Journals (Sweden)

    Jiachen Wei

    Full Text Available In living systems proteins are typically found in crowded environments where their effective interactions strongly depend on the surrounding medium. Yet, their association and dissociation needs to be robustly controlled in order to enable biological function. Uncontrolled protein aggregation often causes disease. For instance, cataract is caused by the clustering of lens proteins, i.e., crystallins, resulting in enhanced light scattering and impaired vision or blindness. To investigate the molecular origins of cataract formation and to design efficient treatments, a better understanding of crystallin association in macromolecular crowded environment is needed. Here we present a theoretical study of simple coarse grained colloidal models to characterize the general features of how the association equilibrium of proteins depends on the magnitude of intermolecular attraction. By comparing the analytic results to the available experimental data on the osmotic pressure in crystallin solutions, we identify the effective parameters regimes applicable to crystallins. Moreover, the combination of two models allows us to predict that the number of binding sites on crystallin is small, i.e. one to three per protein, which is different from previous estimates. We further observe that the crowding factor is sensitive to the size asymmetry between the reactants and crowding agents, the shape of the protein clusters, and to small variations of intermolecular attraction. Our work may provide general guidelines on how to steer the protein interactions in order to control their association.

  8. Impact of Microalgae-Bacteria Interactions on the Production of Algal Biomass and Associated Compounds.

    Science.gov (United States)

    Fuentes, Juan Luis; Garbayo, Inés; Cuaresma, María; Montero, Zaida; González-Del-Valle, Manuel; Vílchez, Carlos

    2016-05-19

    A greater insight on the control of the interactions between microalgae and other microorganisms, particularly bacteria, should be useful for enhancing the efficiency of microalgal biomass production and associated valuable compounds. Little attention has been paid to the controlled utilization of microalgae-bacteria consortia. However, the studies of microalgal-bacterial interactions have revealed a significant impact of the mutualistic or parasitic relationships on algal growth. The algal growth, for instance, has been shown to be enhanced by growth promoting factors produced by bacteria, such as indole-3-acetic acid. Vitamin B12 produced by bacteria in algal cultures and bacterial siderophores are also known to be involved in promoting faster microalgal growth. More interestingly, enhancement in the intracellular levels of carbohydrates, lipids and pigments of microalgae coupled with algal growth stimulation has also been reported. In this sense, massive algal production might occur in the presence of bacteria, and microalgae-bacteria interactions can be beneficial to the massive production of microalgae and algal products. This manuscript reviews the recent knowledge on the impact of the microalgae-bacteria interactions on the production of microalgae and accumulation of valuable compounds, with an emphasis on algal species having application in aquaculture.

  9. Interaction of c-Cbl with myosin IIA regulates Bleb associated macropinocytosis of Kaposi's sarcoma-associated herpesvirus.

    Science.gov (United States)

    Valiya Veettil, Mohanan; Sadagopan, Sathish; Kerur, Nagaraj; Chakraborty, Sayan; Chandran, Bala

    2010-12-23

    KSHV is etiologically associated with Kaposi's sarcoma (KS), an angioproliferative endothelial cell malignancy. Macropinocytosis is the predominant mode of in vitro entry of KSHV into its natural target cells, human dermal microvascular endothelial (HMVEC-d) cells. Although macropinocytosis is known to be a major route of entry for many viruses, the molecule(s) involved in the recruitment and integration of signaling early during macropinosome formation is less well studied. Here we demonstrate that tyrosine phosphorylation of the adaptor protein c-Cbl is required for KSHV induced membrane blebbing and macropinocytosis. KSHV induced the tyrosine phosphorylation of c-Cbl as early as 1 min post-infection and was recruited to the sites of bleb formation. Infection also led to an increase in the interaction of c-Cbl with PI3-K p85 in a time dependent manner. c-Cbl shRNA decreased the formation of KSHV induced membrane blebs and macropinocytosis as well as virus entry. Immunoprecipitation of c-Cbl followed by mass spectrometry identified the interaction of c-Cbl with a novel molecular partner, non-muscle myosin heavy chain IIA (myosin IIA), in bleb associated macropinocytosis. Phosphorylated c-Cbl colocalized with phospho-myosin light chain II in the interior of blebs of infected cells and this interaction was abolished by c-Cbl shRNA. Studies with the myosin II inhibitor blebbistatin demonstrated that myosin IIA is a biologically significant component of the c-Cbl signaling pathway and c-Cbl plays a new role in the recruitment of myosin IIA to the blebs during KSHV infection. Myosin II associates with actin in KSHV induced blebs and the absence of actin and myosin ubiquitination in c-Cbl ShRNA cells suggested that c-Cbl is also responsible for the ubiquitination of these proteins in the infected cells. This is the first study demonstrating the role of c-Cbl in viral entry as well as macropinocytosis, and provides the evidence that a signaling complex containing c

  10. Interaction of c-Cbl with myosin IIA regulates Bleb associated macropinocytosis of Kaposi's sarcoma-associated herpesvirus.

    Directory of Open Access Journals (Sweden)

    Mohanan Valiya Veettil

    2010-12-01

    Full Text Available KSHV is etiologically associated with Kaposi's sarcoma (KS, an angioproliferative endothelial cell malignancy. Macropinocytosis is the predominant mode of in vitro entry of KSHV into its natural target cells, human dermal microvascular endothelial (HMVEC-d cells. Although macropinocytosis is known to be a major route of entry for many viruses, the molecule(s involved in the recruitment and integration of signaling early during macropinosome formation is less well studied. Here we demonstrate that tyrosine phosphorylation of the adaptor protein c-Cbl is required for KSHV induced membrane blebbing and macropinocytosis. KSHV induced the tyrosine phosphorylation of c-Cbl as early as 1 min post-infection and was recruited to the sites of bleb formation. Infection also led to an increase in the interaction of c-Cbl with PI3-K p85 in a time dependent manner. c-Cbl shRNA decreased the formation of KSHV induced membrane blebs and macropinocytosis as well as virus entry. Immunoprecipitation of c-Cbl followed by mass spectrometry identified the interaction of c-Cbl with a novel molecular partner, non-muscle myosin heavy chain IIA (myosin IIA, in bleb associated macropinocytosis. Phosphorylated c-Cbl colocalized with phospho-myosin light chain II in the interior of blebs of infected cells and this interaction was abolished by c-Cbl shRNA. Studies with the myosin II inhibitor blebbistatin demonstrated that myosin IIA is a biologically significant component of the c-Cbl signaling pathway and c-Cbl plays a new role in the recruitment of myosin IIA to the blebs during KSHV infection. Myosin II associates with actin in KSHV induced blebs and the absence of actin and myosin ubiquitination in c-Cbl ShRNA cells suggested that c-Cbl is also responsible for the ubiquitination of these proteins in the infected cells. This is the first study demonstrating the role of c-Cbl in viral entry as well as macropinocytosis, and provides the evidence that a signaling complex

  11. Mother's marital satisfaction associated with the quality of mother-father-child triadic interaction.

    Science.gov (United States)

    Korja, Riikka; Piha, Jorma; Otava, Riia; Lavanchy-Scaiola, Chloe; Ahlqvist-Björkroth, Sari; Aromaa, Minna; Räihä, Hannele

    2016-08-01

    Low marital satisfaction has been shown to be a risk factor for early parenthood and parent-child relationship problems (Erel & Burman, ; McHale, ). The aim of this study was to assess how parental reports of marital satisfaction related to family alliance and coordination in the observed triadic interaction. The study group included 120 families. Marital satisfaction was evaluated during pregnancy, at 4 months, and at 18 months using the Revised Dyadic Adjustment Scale (RDAS; Busby, Christensen, Crane & Larsson, ) for both parents. Mother-father-child interaction was analyzed in the Lausanne Triadic Play setting and coded using the Family Alliance Assessment Scale (Favez, Lavanchy Scaiola, Tissot, Darwiche & Frascarolo, ) when the child reached 18 months of age. The mother's higher marital satisfaction at every measuring point was associated with a cooperative family alliance and/or higher family coordination at 18 months. The father's experience of marital satisfaction was not related to family interaction at any assessment point. Our study suggests that a mother's experience of lower marital satisfaction during pregnancy may be an early sign of later problems in family relationships. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  12. Interactions between SNPs affecting inflammatory response genes are associated with multiple myeloma disease risk and survival

    DEFF Research Database (Denmark)

    Nielsen, Kaspar René; Rodrigo-Domingo, Maria; Steffensen, Rudi

    2017-01-01

    -nucleotide polymorphisms (SNPs) involved in the immune response and a subsequent statistical analysis that focusses on the association of SNPs, certain haplotypes or SNP-SNP interactions with MM risk and prognosis. We genotyped 348 Danish patients and 355 controls for 13 SNPs located in the TNFA, IL-4, IL-6, IL-10 and CHI...... were studied for expression in normal B-cell subsets and myeloma plasma cells. We observed a significantly reduced risk when harboring the TNFA-238A allele (OR = 0.51 (0.29-0.86)) and interactions between the TNFA-1031T/C * and IL-10 -3575T/A (p = .007) as well as the TNFA-308G/A * and IL-10-1082G/A (p...... = .008) allels. By statistical approaches, we observed association between prognosis and the TNFA-857CC genotype (HR = 2.80 (1.29-6.10)) and IL-10-1082GG + GA genotypes (HR = 1.93 (1.07-3.49)) and interactions between IL-6-174G/C and IL-10-3575T/A (p = .001) and between TNFA-308G/A and IL-4-1098T/G (p...

  13. Robust Gene-Gene Interaction Analysis in Genome Wide Association Studies.

    Directory of Open Access Journals (Sweden)

    Yongkang Kim

    Full Text Available Genome-wide association studies (GWAS have successfully discovered hundreds of associations between genetic variants and complex traits. Most GWAS have focused on the identification of single variants. It has been shown that most of the variants that were discovered by GWAS could only partially explain disease heritability. The explanation for this missing heritability is generally believed to be gene-gene (GG or gene-environment (GE interactions and other structural variants. Generalized multifactor dimensionality reduction (GMDR has been proven to be reasonably powerful in detecting GG and GE interactions; however, its performance has been found to decline when outlying quantitative traits are present. This paper proposes a robust GMDR estimation method (based on the L-estimator and M-estimator estimation methods in an attempt to reduce the effects caused by outlying traits. A comparison of robust GMDR with the original MDR based on simulation studies showed the former method to outperform the latter. The performance of robust GMDR is illustrated through a real GWA example consisting of 8,577 samples from the Korean population using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR level as a phenotype. Robust GMDR identified the KCNH1 gene to have strong interaction effects with other genes on the function of insulin secretion.

  14. Discovering disease-associated genes in weighted protein-protein interaction networks

    Science.gov (United States)

    Cui, Ying; Cai, Meng; Stanley, H. Eugene

    2018-04-01

    Although there have been many network-based attempts to discover disease-associated genes, most of them have not taken edge weight - which quantifies their relative strength - into consideration. We use connection weights in a protein-protein interaction (PPI) network to locate disease-related genes. We analyze the topological properties of both weighted and unweighted PPI networks and design an improved random forest classifier to distinguish disease genes from non-disease genes. We use a cross-validation test to confirm that weighted networks are better able to discover disease-associated genes than unweighted networks, which indicates that including link weight in the analysis of network properties provides a better model of complex genotype-phenotype associations.

  15. Cognitive ability and psychopathic traits: independent and interactive associations with youth conduct problems.

    Science.gov (United States)

    McKenzie, Meghan E; Lee, Steve S

    2015-05-01

    Although average or high IQ was central to initial conceptualizations of psychopathy, IQ is typically negatively associated with oppositional defiant disorder (ODD) and conduct disorder (CD). Few studies have simultaneously considered narcissism and callous-unemotional (CU) traits with respect to ODD and CD symptoms, including potential interactive associations with IQ. Participants were 221 ethnically-diverse (45 % non-White) 6-9 year-old children with (n = 114) and without (n = 107) attention-deficit/hyperactivity disorder (ADHD) with separate parent and teacher ratings of narcissism, CU traits, ODD, and CD. To minimize shared method variance, we conservatively examined the association of parent-rated psychopathic traits with teacher-rated ODD and CD as well as the association of teacher-rated psychopathic traits with parent-rated ODD and CD. Controlling for age, sex, and the number of child ADHD symptoms, narcissism, but not CU traits, uniquely and positively predicted parent- and teacher-rated ODD and CD symptoms. We also observed a significant IQ × narcissism interaction where narcissism was more strongly associated with ODD and CD among children with high IQ relative to average and low IQ youth. Whereas studies of youth psychopathic traits focus almost exclusively on CU traits, narcissism independently predicted separate parent and teacher ratings of ODD and CD, particularly among children with high IQ. These preliminary data persuasively suggest that early narcissism is a critical facet of psychopathy and in conjunction with IQ, may suggest a unique profile associated with emergent conduct problems.

  16. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

    DEFF Research Database (Denmark)

    Børglum, A D; Demontis, D; Grove, J

    2014-01-01

    Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals...... was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies....... born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases...

  17. Effect of temperature on the association step in thrombin-fibrinogen interaction.

    Science.gov (United States)

    Picozzi, M; De Cristofaro, R

    1993-01-01

    Kinetics of fibrinopeptide A release by human alpha-thrombin at low fibrinogen concentration allowed us to measure the specificity constant, i.e. kcat/Km, for the interaction between the enzyme and human fibrinogen. A study of the dependence of the ratio kcat/Km upon the viscosity of the medium revealed that fibrinogen acts as a 'sticky' substrate, or, in other words, as a substrate that dissociates from the Michaelis complex with a rate comparable with that for acylation of the active site. These experiments allowed us also to compute for the first time the second-order rate constant for thrombin-fibrinogen association. A study of the temperature-dependence of the association rate, carried out over the temperature range spanning from 10 degrees C to 37 degrees C (pH 7.50; I0.15) permitted the estimation of the enthalpy and entropy of activation, delta H++ and delta S++, which were found to be equal to 5.69 +/- 0.77 kJ.mol-1 and -80.25 +/- 1.79 kJ.K-1.mol-1 respectively. In addition, the values of Km for thrombin-fibrinogen reaction were measured at different solution viscosities in order to derive the equilibrium dissociation constant, Ks, of this interaction. These experiments showed that the Ks values for thrombin-fibrinogen binding was equal to 1.8 microM at 25 degrees C. Altogether these results indicated that fibrinogen, though interacting with both the catalytic pocket and the fibrinogen recognition site on the thrombin molecule, dissociates from Michaelis complex with a rate comparable with that shown by amide substrates, which interact only with the catalytic site. PMID:8373370

  18. 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.

  19. Mapping substrate interactions of the human membrane-associated neuraminidase, NEU3, using STD NMR.

    Science.gov (United States)

    Albohy, Amgad; Richards, Michele R; Cairo, Christopher W

    2015-03-01

    Saturation transfer difference (STD) nuclear magnetic resonance (NMR) is a powerful technique which can be used to investigate interactions between proteins and their substrates. The method identifies specific sites of interaction found on a small molecule ligand when in complex with a protein. The ability of STD NMR to provide specific insight into binding interactions in the absence of other structural data is an attractive feature for its use with membrane proteins. We chose to employ STD NMR in our ongoing investigations of the human membrane-associated neuraminidase NEU3 and its interaction with glycolipid substrates (e.g., GM3). In order to identify critical substrate-enzyme interactions, we performed STD NMR with a catalytically inactive form of the enzyme, NEU3(Y370F), containing an N-terminal maltose-binding protein (MBP)-affinity tag. In the absence of crystallographic data on the enzyme, these data represent a critical experimental test of proposed homology models, as well as valuable new structural data. To aid interpretation of the STD NMR data, we compared the results with molecular dynamics (MD) simulations of the enzyme-substrate complexes. We find that the homology model is able to predict essential features of the experimental data, including close contact of the hydrophobic aglycone and the Neu5Ac residue with the enzyme. Additionally, the model and STD NMR data agree on the facial recognition of the galactose and glucose residues of the GM3-analog studied. We conclude that the homology model of NEU3 can be used to predict substrate recognition, but our data indicate that unstructured portions of the NEU3 model may require further refinement. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

    Science.gov (United States)

    Børglum, A D; Demontis, D; Grove, J; Pallesen, J; Hollegaard, M V; Pedersen, C B; Hedemand, A; Mattheisen, M; Uitterlinden, A; Nyegaard, M; Ørntoft, T; Wiuf, C; Didriksen, M; Nordentoft, M; Nöthen, M M; Rietschel, M; Ophoff, R A; Cichon, S; Yolken, R H; Hougaard, D M; Mortensen, P B; Mors, O

    2014-03-01

    Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies.

  1. Cellular and molecular-genetic mechanisms of symbiosis and associative interaction of microorganisms with plants in rhizosphere

    Directory of Open Access Journals (Sweden)

    Lioshina L. G.

    2009-02-01

    Full Text Available The review contains the results of research on symbiotic and associative interaction of microorganisms and plants in rhizosphere. A special attention is given to the process of contact association of microorganisms and plants tissues including the concrete molecular structures and dominant role pertaining to protein-carbohydrate interaction. There are common features and distinctions at formation of arbuscular mycorhiza, rhizobia– legume symbiosis and association of non-leguminous plants with Azospirillum

  2. Cellular and molecular-genetic mechanisms of symbiosis and associative interaction of microorganisms with plants in rhizosphere

    OpenAIRE

    Lioshina L. G.

    2009-01-01

    The review contains the results of research on symbiotic and associative interaction of microorganisms and plants in rhizosphere. A special attention is given to the process of contact association of microorganisms and plants tissues including the concrete molecular structures and dominant role pertaining to protein-carbohydrate interaction. There are common features and distinctions at formation of arbuscular mycorhiza, rhizobia– legume symbiosis and association of non-leguminous plants with...

  3. Antibiotic interactions at the GTPase-associated centre within Escherichia coli 23S rRNA

    DEFF Research Database (Denmark)

    Egebjerg, J; Douthwaite, S; Garrett, R A

    1989-01-01

    A comprehensive range of chemical reagents and ribonucleases was employed to investigate the interaction of the antibiotics thiostrepton and micrococcin with the ribosomal protein L11-23S RNA complex and with the 50S subunit. Both antibiotics block processes associated with the ribosomal A-site b...... important exception, however, occurred at nucleotide A1067 within a terminal loop where thiostrepton protected the N-1 position while micrococcin rendered it more reactive. This difference correlates with the opposite effects of the two antibiotics on GTPase activity....

  4. Statin-associated rhabdomyolysis triggered by drug-drug interaction with itraconazole

    DEFF Research Database (Denmark)

    Dybro, Anne Mette; Damkier, Per; Rasmussen, Torsten Bloch

    2016-01-01

    -associated rhabdomyolysis, probably caused by a drug-drug interaction between simvastatin and itraconazole. The patient made full recovery. Three commonly used statins-simvastatin, atorvastatin and lovastatin-are metabolised by the liver enzyme CYP3A4. Several potent inhibitors of this enzyme are known, for example, azole...... antifungal agents such as itraconazole and posaconazole. If antifungal treatment is indicated in a patient using a CYP3A4-metabolised statin, we recommend (1) topical administration of the antifungal agent if possible, (2) the use of a non-CYP3A4-inhibiting antifungal drug such as terbinafine or (3...

  5. Adverse effects and Drug Interactions Associated with Inhaled Recreational and Medical Marijuana

    Directory of Open Access Journals (Sweden)

    Maisha Kelly Freeman

    2016-06-01

    those studies were included in this review. Several studies were located that evaluated the safety of medical marijuana; however, much of the review focused on inhaled, recreational marijuana use due to the paucity of information on inhaled medical marijuana. Since marijuana is a Schedule1 product, few clinical studies have been conducted to determine the adverse event profile of the product. As a result, several articles that characterized recreational inhaled marijuana were included. Recreational inhaled marijuana use may be associated with an increase in cardiovascular (CV/ cerebrovascular effects (CVA; however, conflicting information exists in the literature. Recreational marijuana use may also increase risky behaviors that increase the transmission of infectious diseases and respiratory diseases. Many of the studies were retrospective in nature; therefore, it was difficult to determine a cause and effect relationship between inhaled marijuana use and the development of adverse reactions or drug-drug interactions. Conclusions: There is a paucity of information related to the use of inhaled medical marijuana. Recreational marijuana use is associated with several adverse events including CV/CVA, respiratory, and transmission of infectious diseases. Theoretical literature indicates that medical marijuana may be associated with significant drug-drug interactions and adverse drug reactions. Legalization of medical marijuana may be associated with an increase in abuse/dependence and accidental exposures in children. Pharmacists need to be educated regarding the appropriate use of medical marijuana to avoid adverse reactions and potential drug-drug interactions between medical marijuana and other products.   Type: Original Research

  6. HiTAD: detecting the structural and functional hierarchies of topologically associating domains from chromatin interactions.

    Science.gov (United States)

    Wang, Xiao-Tao; Cui, Wang; Peng, Cheng

    2017-11-02

    A current question in the high-order organization of chromatin is whether topologically associating domains (TADs) are distinct from other hierarchical chromatin domains. However, due to the unclear TAD definition in tradition, the structural and functional uniqueness of TAD is not well studied. In this work, we refined TAD definition by further constraining TADs to the optimal separation on global intra-chromosomal interactions. Inspired by this constraint, we developed a novel method, called HiTAD, to detect hierarchical TADs from Hi-C chromatin interactions. HiTAD performs well in domain sensitivity, replicate reproducibility and inter cell-type conservation. With a novel domain-based alignment proposed by us, we defined several types of hierarchical TAD changes which were not systematically studied previously, and subsequently used them to reveal that TADs and sub-TADs differed statistically in correlating chromosomal compartment, replication timing and gene transcription. Finally, our work also has the implication that the refinement of TAD definition could be achieved by only utilizing chromatin interactions, at least in part. HiTAD is freely available online. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. Lipid raft association restricts CD44-ezrin interaction and promotion of breast cancer cell migration.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2012-12-01

    Cancer cell migration is an early event in metastasis, the main cause of breast cancer-related deaths. Cholesterol-enriched membrane domains called lipid rafts influence the function of many molecules, including the raft-associated protein CD44. We describe a novel mechanism whereby rafts regulate interactions between CD44 and its binding partner ezrin in migrating breast cancer cells. Specifically, in nonmigrating cells, CD44 and ezrin localized to different membranous compartments: CD44 predominantly in rafts, and ezrin in nonraft compartments. After the induction of migration (either nonspecific or CD44-driven), CD44 affiliation with lipid rafts was decreased. This was accompanied by increased coprecipitation of CD44 and active (threonine-phosphorylated) ezrin-radixin-moesin (ERM) proteins in nonraft compartments and increased colocalization of CD44 with the nonraft protein, transferrin receptor. Pharmacological raft disruption using methyl-β-cyclodextrin also increased CD44-ezrin coprecipitation and colocalization, further suggesting that CD44 interacts with ezrin outside rafts during migration. Conversely, promoting CD44 retention inside lipid rafts by pharmacological inhibition of depalmitoylation virtually abolished CD44-ezrin interactions. However, transient single or double knockdown of flotillin-1 or caveolin-1 was not sufficient to increase cell migration over a short time course, suggesting complex crosstalk mechanisms. We propose a new model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration. This could have implications for rafts as pharmacological targets to down-regulate cancer cell migration.

  8. Interaction of Two Filaments in a Long Filament Channel Associated with Twin Coronal Mass Ejections

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Ruisheng; Chen, Yao; Wang, Bing; Du, Guohui; Li, Chuanyang [Shandong Provincial Key Laboratory of Optical Astronomy and Solar-Terrestrial Environment, and Institute of Space Sciences, Shandong University, 264209 Weihai (China); Zhang, Qingmin [Key Laboratory for Dark Matter and Space Science, Purple Mountain Observatory, CAS, Nanjing 210008 (China); Yang, Kai, E-mail: ruishengzheng@sdu.edu.cn [School of Astronomy and Space Science, Nanjing University, 210023 Nanjing (China)

    2017-02-20

    Using the high-quality observations of the Solar Dynamics Observatory , we present the interaction of two filaments (F1 and F2) in a long filament channel associated with twin coronal mass ejections (CMEs) on 2016 January 26. Before the eruption, a sequence of rapid cancellation and emergence of the magnetic flux has been observed, which likely triggered the ascending of the west filament (F1). The east footpoints of rising F1 moved toward the east far end of the filament channel, accompanied by post-eruption loops and flare ribbons. This likely indicated a large-scale eruption involving the long filament channel, which resulted from the interaction between F1 and the east filament (F2). Some bright plasma flew over F2, and F2 stayed at rest during the eruption, likely due to the confinement of its overlying lower magnetic field. Interestingly, the impulsive F1 pushed its overlying magnetic arcades to form the first CME, and F1 finally evolved into the second CME after the collision with the nearby coronal hole. We suggest that the interaction of F1 and the overlying magnetic field of F2 led to the merging reconnection that forms a longer eruptive filament loop. Our results also provide a possible picture of the origin of twin CMEs and show that the large-scale magnetic topology of the coronal hole is important for the eventual propagation direction of CMEs.

  9. Association testing to detect gene-gene interactions on sex chromosomes in trio data

    Directory of Open Access Journals (Sweden)

    Yeonok eLee

    2013-11-01

    Full Text Available Autism Spectrum Disorder (ASD occurs more often among males than females in a 4:1 ratio. Among theories used to explain the causes of ASD, the X chromosome and the Y chromosome theories attribute ASD to X-linked mutation and the male-limited gene expressions on the Y chromosome, respectively. Despite the rationale of the theory, studies have failed to attribute the sex-biased ratio to the significant linkage or association on the regions of interest on X chromosome. We further study the gender biased ratio by examining the possible interaction effects between two genes in the sex chromosomes. We propose a logistic regression model with mixed effects to detect gene-gene interactions on sex chromosomes. We investigated the power and type I error rates of the approach for a range of minor allele frequencies and varying linkage disequilibrium between markers and QTLs. We also evaluated the robustness of the model to population stratification. We applied the model to a trio-family data set with an ASD affected male child to study gene-gene interactions on sex chromosomes.

  10. Child, family, and neighborhood associations with parent and peer interactive play during early childhood.

    Science.gov (United States)

    Kenney, Mary Kay

    2012-04-01

    To examine national patterns of peer and parent interactive play opportunities that enhance early learning/socialization. Bivariate and multivariable analyses of cross-sectional data on 22,797 children aged 1-5 years from the National Survey of Children's Health 2007 were performed to determine the child, family, and neighborhood factors associated with four parent-initiated activities. Outcomes measures included time (days/week) children spent: participating in peer play; being read to; sung to/told stories; and taken on family outings. Covariates included race/ethnicity, poverty, TV watching, childcare, child and maternal physical and mental health, family factors (structure, size, language, stress, education), and neighborhood factors (amenities, support, physical condition, safety). According to adjusted regression models, minority children from lower income, non-English-speaking households with limited education, poorer maternal health and greater parenting stress were read to/told stories less than children without these characteristics, while neighborhood factors exerted less influence. In contrast, significant reductions in days/week of peer play were associated with unsupportive neighborhoods and those with the poorest physical conditions and limited amenities. Likewise, reductions in outings were associated with fewer neighborhood amenities. The findings of this study indicate that a variety of child, family, and neighborhood factors are associated with parent-initiated behaviors such as reading, storytelling, peer interactive play, and family outings. Appropriate evidence-based home visiting interventions targeting child health, parenting skills, early childhood education, and social services in at-risk communities would appear to be appropriate vehicles for addressing such parent-initiated play activities that have the potential to enhance development.

  11. Atypical energetic particle events observed prior energetic particle enhancements associated with corotating interaction regions

    Science.gov (United States)

    Khabarova, Olga; Malandraki, Olga; Zank, Gary; Jackson, Bernard; Bisi, Mario; Desai, Mihir; Li, Gang; le Roux, Jakobus; Yu, Hsiu-Shan

    2017-04-01

    Recent studies of mechanisms of particle acceleration in the heliosphere have revealed the importance of the comprehensive analysis of stream-stream interactions as well as the heliospheric current sheet (HCS) - stream interactions that often occur in the solar wind, producing huge magnetic cavities bounded by strong current sheets. Such cavities are usually filled with small-scale magnetic islands that trap and re-accelerate energetic particles (Zank et al. ApJ, 2014, 2015; le Roux et al. ApJ, 2015, 2016; Khabarova et al. ApJ, 2015, 2016). Crossings of these regions are associated with unusual variations in the energetic particle flux up to several MeV/nuc near the Earth's orbit. These energetic particle flux enhancements called "atypical energetic particle events" (AEPEs) are not associated with standard mechanisms of particle acceleration. The analysis of multi-spacecraft measurements of energetic particle flux, plasma and the interplanetary magnetic field shows that AEPEs have a local origin as they are observed by different spacecraft with a time delay corresponding to the solar wind propagation from one spacecraft to another, which is a signature of local particle acceleration in the region embedded in expanding and rotating background solar wind. AEPEs are often observed before the arrival of corotating interaction regions (CIRs) or stream interaction regions (SIRs) to the Earth's orbit. When fast solar wind streams catch up with slow solar wind, SIRs of compressed heated plasma or more regular CIRs are created at the leading edge of the high-speed stream. Since coronal holes are often long-lived structures, the same CIR re-appears often for several consecutive solar rotations. At low heliographic latitudes, such CIRs are typically bounded by forward and reverse waves on their leading and trailing edges, respectively, that steepen into shocks at heliocentric distances beyond 1 AU. Energetic ion increases have been frequently observed in association with CIR

  12. Association Between Parental Social Interaction and Behavior Problems in Offspring: a Population-Based Study in Japan.

    Science.gov (United States)

    Ochi, Manami; Fujiwara, Takeo

    2016-08-01

    Research in parental social support has chiefly examined received social support. Studies have suggested that provided social support may also be protective for child mental health problems. We aim to investigate the association between parental social interaction (both received and provided social support) and offspring behavior problems. We analyzed the data of 982 households, including 1538 children aged 4 to 16 years, from the Japanese Study of Stratification, Health, Income, and Neighborhood (J-SHINE) survey conducted over 2010-2011. We used a 5-point Likert scale to assess social interaction including parental emotional and instrumental support received from and provided to the spouse, other co-residing family members, non-co-residing family members or relatives, neighbors, and friends. Behavior problems in offspring were assessed using parental responses to the Strengths and Difficulties Questionnaire. Associations between parental social interaction and behavior problems were analyzed using ordered logistic regression. We found that higher maternal social interaction is significantly associated with lower odds of both difficult and prosocial behavior problems, while the same associations were not found for paternal social interaction. Further, maternal provided social support showed an independent negative association with prosocial behavior problems in offspring, even when adjusted for received maternal social support and paternal social interaction. This study showed that maternal social interaction, but not paternal social interaction, might have a protective effect on offspring behavior problems. Further study is required to investigate the effect of the intervention to increase social participation among mothers whose children have behavior problems.

  13. IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC

    Directory of Open Access Journals (Sweden)

    Hanane Ennajdaoui

    2016-05-01

    Full Text Available Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3 expression correlates with malignancy, but its role(s in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation, and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual nucleotide resolution crosslinking immunoprecipitation (iCLIP revealed significant overlap of IGF2BP3 and microRNA (miRNA binding sites. IGF2BP3 promotes association of the RNA-induced silencing complex (RISC with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions.

  14. Multifactor dimensionality reduction reveals gene–gene interactions associated with multiple sclerosis susceptibility in African Americans

    Science.gov (United States)

    Brassat, D; Motsinger, AA; Caillier, SJ; Erlich, HA; Walker, K; Steiner, LL; Cree, BAC; Barcellos, LF; Pericak-Vance, MA; Schmidt, S; Gregory, S; Hauser, SL; Haines, JL; Oksenberg, JR; Ritchie, MD

    2015-01-01

    Multiple sclerosis (MS) is a common disease of the central nervous system characterized by inflammation, myelin loss, gliosis, varying degrees of axonal pathology, and progressive neurological dysfunction. Multiple sclerosis exhibits many of the characteristics that distinguish complex genetic disorders including polygenic inheritance and environmental exposure risks. Here, we used a highly efficient multilocus genotyping assay representing variation in 34 genes associated with inflammatory pathways to explore gene–gene interactions and disease susceptibility in a well-characterized African-American case–control MS data set. We applied the multifactor dimensionality reduction (MDR) test to detect epistasis, and identified single-IL4R(Q576R)- and three-IL4R(Q576R), IL5RA(-80), CD14(-260)- locus association models that predict MS risk with 75–76% accuracy (P < 0.01). These results demonstrate the importance of exploring both main effects and gene–gene interactions in the study of complex diseases. PMID:16625214

  15. Multifactor dimensionality reduction reveals gene-gene interactions associated with multiple sclerosis susceptibility in African Americans.

    Science.gov (United States)

    Brassat, D; Motsinger, A A; Caillier, S J; Erlich, H A; Walker, K; Steiner, L L; Cree, B A C; Barcellos, L F; Pericak-Vance, M A; Schmidt, S; Gregory, S; Hauser, S L; Haines, J L; Oksenberg, J R; Ritchie, M D

    2006-06-01

    Multiple sclerosis (MS) is a common disease of the central nervous system characterized by inflammation, myelin loss, gliosis, varying degrees of axonal pathology, and progressive neurological dysfunction. Multiple sclerosis exhibits many of the characteristics that distinguish complex genetic disorders including polygenic inheritance and environmental exposure risks. Here, we used a highly efficient multilocus genotyping assay representing variation in 34 genes associated with inflammatory pathways to explore gene-gene interactions and disease susceptibility in a well-characterized African-American case-control MS data set. We applied the multifactor dimensionality reduction (MDR) test to detect epistasis, and identified single-IL4R(Q576R)- and three-IL4R(Q576R), IL5RA(-80), CD14(-260)- locus association models that predict MS risk with 75-76% accuracy (P<0.01). These results demonstrate the importance of exploring both main effects and gene-gene interactions in the study of complex diseases.

  16. Daily interactions with aging parents and adult children: Associations with negative affect and diurnal cortisol.

    Science.gov (United States)

    Birditt, Kira S; Manalel, Jasmine A; Kim, Kyungmin; Zarit, Steven H; Fingerman, Karen L

    2017-09-01

    Midlife adults report greater investment in their children than in their parents, and these ties have important implications for well-being. To date, little research has addressed daily experiences in these ties. The present study examines daily experiences (negative and positive) with aging parents and adult children and their associations with daily negative affect and diurnal cortisol rhythms. Participants were middle-aged adults (N = 156; 56% women) from Wave 2 of the Family Exchanges Study, conducted in 2013, who completed a 7-day daily diary study, which included assessments of daily negative and positive social encounters and negative affect, and 4 days of saliva collection, which was collected 3 times a day (upon waking, 30 min after waking, and at bedtime) and assayed for cortisol. Multilevel models revealed that individuals were more likely to have contact with adult children than with parents but more likely to have negative experiences (negative interactions, avoidance, negative thoughts) with parents than with adult children. Nevertheless, contact and negative experiences with adult children were more consistently associated with negative affect and daily cortisol patterns than were interactions with parents. Findings are consistent with the intergenerational stake hypothesis, which suggests that individuals have a greater stake in their children than in their parents. Indeed, negative experiences with adult children may be more salient because tensions with adult children occur less frequently than do tensions with parents. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  17. ABOVE AND BELOW GROUND INTERACTIONS IN THE AGROFORESTAL ASSOCIATION 'RED CEDAR-PERSIAN LIME-CHAYA'

    Directory of Open Access Journals (Sweden)

    Jesús Mao Estanislao Aguilar-Luna

    2011-05-01

    Full Text Available Above and below ground interactions were analyzed in the agroforestal association 'red cedar-Persian lime-chaya', to know the initial optimum planting density (PD, in Quintana Roo, Mexico. Red cedar and Persian lime were placed in a 'Nelder' circle of 3154 m2 which consisted of 20 concentric circles alternating red cedars and Persian limes to 1.50 m apart and 10 plants per circle; chaya rectangular frame was set at 1.50 x 3.00 m, superimposed on the 'Nelder' circle. Defined eight PD 2602 to 3772 pl·ha-1 with 10 repetitions, to evaluate the length of main root (LMR, radical exploration range (RER, below ground interaction (BGI, plant height (PH, crown diameter (CD, above ground interaction (AGI and soil fertility (SF. The growth intraspecific he present statistical difference (P≤0.05 when moving from one PD to another PD, while the growth interespecific manifested different growth habit. The agroforestal association propitious in soil decreased phosphorous ±2 %, and increases organic matter ±14 % and nitrogen ±10 % on all PD. The BGI was increased in direct relation with the PD, reaching its highest value (64±5.8 % to 3772 pl·ha-1; the AGI also increased in direct relation with the PD, its highest value (52±3.1 % went to 3772 pl·ha-1; therefore, to higher PD increased BGI and AGI, at 20 months after planting.

  18. Discovering approximate-associated sequence patterns for protein-DNA interactions

    KAUST Repository

    Chan, Tak Ming

    2010-12-30

    Motivation: The bindings between transcription factors (TFs) and transcription factor binding sites (TFBSs) are fundamental protein-DNA interactions in transcriptional regulation. Extensive efforts have been made to better understand the protein-DNA interactions. Recent mining on exact TF-TFBS-associated sequence patterns (rules) has shown great potentials and achieved very promising results. However, exact rules cannot handle variations in real data, resulting in limited informative rules. In this article, we generalize the exact rules to approximate ones for both TFs and TFBSs, which are essential for biological variations. Results: A progressive approach is proposed to address the approximation to alleviate the computational requirements. Firstly, similar TFBSs are grouped from the available TF-TFBS data (TRANSFAC database). Secondly, approximate and highly conserved binding cores are discovered from TF sequences corresponding to each TFBS group. A customized algorithm is developed for the specific objective. We discover the approximate TF-TFBS rules by associating the grouped TFBS consensuses and TF cores. The rules discovered are evaluated by matching (verifying with) the actual protein-DNA binding pairs from Protein Data Bank (PDB) 3D structures. The approximate results exhibit many more verified rules and up to 300% better verification ratios than the exact ones. The customized algorithm achieves over 73% better verification ratios than traditional methods. Approximate rules (64-79%) are shown statistically significant. Detailed variation analysis and conservation verification on NCBI records demonstrate that the approximate rules reveal both the flexible and specific protein-DNA interactions accurately. The approximate TF-TFBS rules discovered show great generalized capability of exploring more informative binding rules. © The Author 2010. Published by Oxford University Press. All rights reserved.

  19. Understanding trophic interactions in host-parasite associations using stable isotopes of carbon and nitrogen.

    Science.gov (United States)

    Nachev, Milen; Jochmann, Maik A; Walter, Friederike; Wolbert, J Benjamin; Schulte, S Marcel; Schmidt, Torsten C; Sures, Bernd

    2017-02-17

    Stable isotope analysis of carbon and nitrogen can deliver insights into trophic interactions between organisms. While many studies on free-living organisms are available, the number of those focusing on trophic interactions between hosts and their associated parasites still remains scarce. In some cases information about taxa (e.g. acanthocephalans) is completely missing. Additionally, available data revealed different and occasionally contrasting patterns, depending on the parasite's taxonomic position and its degree of development, which is most probably determined by its feeding strategy (absorption of nutrients through the tegument versus active feeding) and its localization in the host. Using stable isotope analysis of carbon and nitrogen we provided first data on the trophic position of an acanthocephalan species with respect to its fish host. Barbels (Barbus barbus) infected only with adult acanthocephalans Pomphorhynchus laevis as well as fish co-infected with the larval (L4) nematodes Eustrongylides sp. from host body cavity were investigated in order to determine the factors shaping host-parasite trophic interactions. Fish were collected in different seasons, to study also potential isotopic shifts over time, whereas barbels with single infection were obtained in summer and co-infected ones in autumn. Acanthocephalans as absorptive feeders showed lower isotope discrimination values of δ 15 N than the fish host. Results obtained for the acanthocephalans were in line with other parasitic taxa (e.g. cestodes), which exhibit a similar feeding strategy. We assumed that they feed mainly on metabolites, which were reprocessed by the host and are therefore isotopically lighter. In contrast, the nematodes were enriched in the heavier isotope δ 15 N with respect to their host and the acanthocephalans, respectively. As active feeders they feed on tissues and blood in the body cavity of the host and thus showed isotope discrimination patterns resembling those of

  20. An association study of NRAMP1, VDR, MBL and their interaction with the susceptibility to tuberculosis in a Chinese population

    Directory of Open Access Journals (Sweden)

    Linlin Wu

    2015-09-01

    Conclusions: Our study suggests that genotypes of many polymorphic genes are associated with TB, it is necessary to further explore the mechanism of genotypes and gene-gene interaction in susceptibility to tuberculosis.

  1. Word learning emerges from the interaction of online referent selection and slow associative learning

    Science.gov (United States)

    McMurray, Bob; Horst, Jessica S.; Samuelson, Larissa K.

    2013-01-01

    Classic approaches to word learning emphasize the problem of referential ambiguity: in any naming situation the referent of a novel word must be selected from many possible objects, properties, actions, etc. To solve this problem, researchers have posited numerous constraints, and inference strategies, but assume that determining the referent of a novel word is isomorphic to learning. We present an alternative model in which referent selection is an online process that is independent of long-term learning. This two timescale approach creates significant power in the developing system. We illustrate this with a dynamic associative model in which referent selection is simulated as dynamic competition between competing referents, and learning is simulated using associative (Hebbian) learning. This model can account for a range of findings including the delay in expressive vocabulary relative to receptive vocabulary, learning under high degrees of referential ambiguity using cross-situational statistics, accelerating (vocabulary explosion) and decelerating (power-law) learning rates, fast-mapping by mutual exclusivity (and differences in bilinguals), improvements in familiar word recognition with development, and correlations between individual differences in speed of processing and learning. Five theoretical points are illustrated. 1) Word learning does not require specialized processes – general association learning buttressed by dynamic competition can account for much of the literature. 2) The processes of recognizing familiar words are not different than those that support novel words (e.g., fast-mapping). 3) Online competition may allow the network (or child) to leverage information available in the task to augment performance or behavior despite what might be relatively slow learning or poor representations. 4) Even associative learning is more complex than previously thought – a major contributor to performance is the pruning of incorrect associations

  2. Identification of a novel protein-protein interaction motif mediating interaction of GPCR-associated sorting proteins with G protein-coupled receptors

    DEFF Research Database (Denmark)

    Bornert, Olivier; Møller, Thor Christian; Boeuf, Julien

    2013-01-01

    the degradation pathway. This protein belongs to the recently identified GPCR-associated sorting proteins (GASPs) family that comprises ten members for which structural and functional details are poorly documented. We present here a detailed structure-function relationship analysis of the molecular interaction...

  3. Inference of gene-phenotype associations via protein-protein interaction and orthology.

    Directory of Open Access Journals (Sweden)

    Panwen Wang

    Full Text Available One of the fundamental goals of genetics is to understand gene functions and their associated phenotypes. To achieve this goal, in this study we developed a computational algorithm that uses orthology and protein-protein interaction information to infer gene-phenotype associations for multiple species. Furthermore, we developed a web server that provides genome-wide phenotype inference for six species: fly, human, mouse, worm, yeast, and zebrafish. We evaluated our inference method by comparing the inferred results with known gene-phenotype associations. The high Area Under the Curve values suggest a significant performance of our method. By applying our method to two human representative diseases, Type 2 Diabetes and Breast Cancer, we demonstrated that our method is able to identify related Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. The web server can be used to infer functions and putative phenotypes of a gene along with the candidate genes of a phenotype, and thus aids in disease candidate gene discovery. Our web server is available at http://jjwanglab.org/PhenoPPIOrth.

  4. Pyrethroid Activity-Based Probes for Profiling Cytochrome P450 Activities Associated with Insecticide Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Ismail, Hanafy M.; O' Neill, Paul M.; Hong, David; Finn, Robert; Henderson, Colin; Wright, Aaron T.; Cravatt, Benjamin; Hemingway, Janet; Paine, Mark J.

    2014-01-18

    Pyrethroid insecticides are used to control a diverse spectrum of diseases spread by arthropods. We have developed a suite of pyrethroid mimetic activity based probes (PyABPs) to selectively label and identify P450s associated with pyrethroid metabolism. The probes were screened against pyrethroid metabolizing and non-metabolizing mosquito P450s, as well as rodent microsomes to measure labeling specificity, plus CPR and b5 knockout mouse livers to validate P450 activation and establish the role for b5 in probe activation. Using a deltamethrin mimetic PyABP we were able to profile active enzymes in rat liver microsomes and identify pyrethroid metabolizing enzymes in the target tissue. The most reactive enzyme was a P450, CYP2C11, which is known to metabolize deltamethrin. Furthermore, several other pyrethroid metabolizers were identified (CYPs 2C6, 3A4, 2C13 and 2D1) along with related detoxification enzymes, notably UDP-g’s 2B1 - 5, suggesting a network of associated pyrethroid metabolizing enzymes, or ‘pyrethrome’. Considering the central role that P450s play in metabolizing insecticides, we anticipate that PyABPs will aid the identification and profiling of P450s associated with insecticide pharmacology in a wide range of species, improving understanding of P450-insecticide interactions and aiding the development of new tools for disease control.

  5. [Childhood obesity is associated to the interaction between firmicutes and high energy food consumption].

    Science.gov (United States)

    Estrada-Velasco, Barbara Ixchel; Cruz, Miguel; Garcia-Mena, Jaime; Valladares Salgado, Adan; Peralta Romero, Jesus; Guna Serrano, Maria de Los Remedios; Madrid-Marina, Vicente; Orbe Orihuela, Citlalli; López Islas, Claudia; Burguete-García, Ana Isabel

    2014-12-16

    INTRODUCTIÓN: Obesity is a serious public health problem in Mexico, the National Health and Nutrition Survey (ENSANUT 2012) reported a 34.4% prevalence of overweight, and obesity in children aged 5-11. Recent research has suggested that the gut microbiota may be a risk factor of obesity through its influence on human metabolism. To evaluate association between the intestinal microbiota profile and obesity among children and whether this association is modified depending on the feeding pattern of a sample of schoolchildren from Mexico City. METODOLOGY AND RESULTS: Cross-sectional study on 1042 children aged 6-14 years; physical activity questionnaire, personal medical history and heredofamilial of obesity and type 2 diabetes were administered to all the children. Eating patterns was performed by principal component analysis (PCA). The association between intestinal microbiota and overweight / obesity depending on diet was assessed with logistic regression models. Our results shows that the interaction between the intestinal microbiota and diet, particularly high in fats and simple carbohydrates increases the chance of developing obesity. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  6. DO COROTATING INTERACTION REGION ASSOCIATED SHOCKS SURVIVE WHEN THEY PROPAGATE INTO THE HELIOSHEATH?

    International Nuclear Information System (INIS)

    Provornikova, E.; Opher, M.; Izmodenov, V.; Toth, G.

    2012-01-01

    During the solar minimum at the distance of 42-52 AU from the Sun, Voyager 2 observed recurrent sharp, shock-like increases in the solar wind speed that look very much like forward shocks (Lazarus et al.). The shocks were produced by corotating interaction regions (CIRs) that originated near the Sun. After the termination shock (TS) crossing in 2007, Voyager 2 entered the heliosheath and has been observing the plasma emanated during the recent solar minima. Measurements show high variable flow, but there were no shocks detected in the heliosheath. When CIR-driven shocks propagate to the outer heliosphere, their structure changes due to collision and merging processes of CIRs. In this Letter, we explore an effect of the merging of CIRs on the structure of CIR-associated shocks. We use a three-dimensional MHD model to study the outward propagation of the shocks with characteristics similar to those observed by Voyager 2 at ∼45 AU (Lazarus et al. 1999). We show that due to merging of CIRs (1) reverse shocks disappear, (2) forward shocks become weaker due to interaction with rarefaction regions from preceding CIRs, and (3) forward shocks significantly weaken in the heliosheath. Merged CIRs produce compression regions in the heliosheath with small fluctuations of plasma parameters. Amplitudes of the fluctuations diminish as they propagate deeper in the sheath. We conclude that interaction of shocks and rarefaction regions could be one of the explanations, why shocks produced by CIRs are not observed in the heliosheath by Voyager 2 while they were frequently observed upstream the TS.

  7. Mathematical modeling of tumor-associated macrophage interactions with the cancer microenvironment.

    Science.gov (United States)

    Mahlbacher, Grace; Curtis, Louis T; Lowengrub, John; Frieboes, Hermann B

    2018-01-30

    Immuno-oncotherapy has emerged as a promising means to target cancer. In particular, therapeutic manipulation of tumor-associated macrophages holds promise due to their various and sometimes opposing roles in tumor progression. It is established that M1-type macrophages suppress tumor progression while M2-types support it. Recently, Tie2-expressing macrophages (TEM) have been identified as a distinct sub-population influencing tumor angiogenesis and vascular remodeling as well as monocyte differentiation. This study develops a modeling framework to evaluate macrophage interactions with the tumor microenvironment, enabling assessment of how these interactions may affect tumor progression. M1, M2, and Tie2 expressing variants are integrated into a model of tumor growth representing a metastatic lesion in a highly vascularized organ, such as the liver. Behaviors simulated include M1 release of nitric oxide (NO), M2 release of growth-promoting factors, and TEM facilitation of angiogenesis via Angiopoietin-2 and promotion of monocyte differentiation into M2 via IL-10. The results show that M2 presence leads to larger tumor growth regardless of TEM effects, implying that immunotherapeutic strategies that lead to TEM ablation may fail to restrain growth when the M2 represents a sizeable population. As TEM pro-tumor effects are less pronounced and on a longer time scale than M1-driven tumor inhibition, a more nuanced approach to influence monocyte differentiation taking into account the tumor state (e.g., under chemotherapy) may be desirable. The results highlight the dynamic interaction of macrophages within a growing tumor, and, further, establish the initial feasibility of a mathematical framework that could longer term help to optimize cancer immunotherapy.

  8. Dairy Product Consumption Interacts with Glucokinase (GCK Gene Polymorphisms Associated with Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Marine S. Da Silva

    2017-08-01

    Full Text Available Dairy product intake and a person’s genetic background have been reported to be associated with the risk of type 2 diabetes (T2D. The objective of this study was to examine the interaction between dairy products and genes related to T2D on glucose-insulin homeostasis parameters. A validated food frequency questionnaire, fasting blood samples, and glucokinase (GCK genotypes were analyzed in 210 healthy participants. An interaction between rs1799884 in GCK and dairy intake on the homeostasis model assessment of insulin resistance was identified. Secondly, human hepatocellular carcinoma cells (HepG2 were grown in a high-glucose medium and incubated with either 1-dairy proteins: whey, caseins, and a mixture of whey and casein; and 2-four amino acids (AA or mixtures of AA. The expression of GCK-related genes insulin receptor substrate-1 (IRS-1 and fatty acid synthase (FASN was increased with whey protein isolate or hydrolysate. Individually, leucine increased IRS-1 expression, whereas isoleucine and valine decreased FASN expression. A branched-chain AA mixture decreased IRS-1 and FASN expression. In conclusion, carriers of the A allele for rs1799884 in the GCK gene may benefit from a higher intake of dairy products to maintain optimal insulin sensitivity. Moreover, the results show that whey proteins affect the expression of genes related to glucose metabolism.

  9. Analysis of genotype × environment interactions for polyphenols and antioxidant capacity of rice by association mapping.

    Science.gov (United States)

    Shao, Yafang; Tang, Fufu; Huang, Yan; Xu, Feifei; Chen, Yaling; Tong, Chuan; Chen, Hao; Bao, Jinsong

    2014-06-11

    Uncovering the genetic basis of polyphenol content and antioxidant activity traits in rice accessions is important to improve the nutritional quality of whole grain rice and to ameliorate the increasing nutrition problem of the rice-eating population. In this study, 20 diverse rice accessions were planted in Hainan province, China, for 2 years to investigate the effects of genotype, environment, and their interactions on total phenolic (TPC), flavonoid (TFC), proanthocyanidins content (TPAC), ABTS, and DPPH radical scavenging activity by association mapping. Analyses of variance (ANOVA) showed that TPC, TFC, TPAC, ABTS, and DPPH were mainly affected by genetic variance, accounting for >94% of the total variance. The interaction between genotype × environment (G × E) was also highly significant (P 0.96; P < 0.001). Twenty-three putative unique loci were identified by association mapping. Five loci were close to previously identified genes or quantitative trait loci (QTLs). Among them, qPAC7-3 identified for TPAC in 2011 was near to the brown pericarp and seed coat (Rc) gene, and the locus at the qPC4/qFC4/qPAC4/qACA4/qACD4 cluster on chromosome 4 detected in two environments was near to a transcriptional activator A (Ra) gene. Some loci were identified in only one environment, indicating that these QTLs were sensitive to environment. This study provides a primary SNP-resource for further identification of genes responsible for polyhenol contents and antioxidant activity in rice whole grains.

  10. Relating diseases by integrating gene associations and information flow through protein interaction network.

    Science.gov (United States)

    Hamaneh, Mehdi Bagheri; Yu, Yi-Kuo

    2014-01-01

    Identifying similar diseases could potentially provide deeper understanding of their underlying causes, and may even hint at possible treatments. For this purpose, it is necessary to have a similarity measure that reflects the underpinning molecular interactions and biological pathways. We have thus devised a network-based measure that can partially fulfill this goal. Our method assigns weights to all proteins (and consequently their encoding genes) by using information flow from a disease to the protein interaction network and back. Similarity between two diseases is then defined as the cosine of the angle between their corresponding weight vectors. The proposed method also provides a way to suggest disease-pathway associations by using the weights assigned to the genes to perform enrichment analysis for each disease. By calculating pairwise similarities between 2534 diseases, we show that our disease similarity measure is strongly correlated with the probability of finding the diseases in the same disease family and, more importantly, sharing biological pathways. We have also compared our results to those of MimMiner, a text-mining method that assigns pairwise similarity scores to diseases. We find the results of the two methods to be complementary. It is also shown that clustering diseases based on their similarities and performing enrichment analysis for the cluster centers significantly increases the term association rate, suggesting that the cluster centers are better representatives for biological pathways than the diseases themselves. This lends support to the view that our similarity measure is a good indicator of relatedness of biological processes involved in causing the diseases. Although not needed for understanding this paper, the raw results are available for download for further study at ftp://ftp.ncbi.nlm.nih.gov/pub/qmbpmn/DiseaseRelations/.

  11. Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology

    DEFF Research Database (Denmark)

    Rossin, Elizabeth J.; Hansen, Kasper Lage; Raychaudhuri, Soumya

    2011-01-01

    in rheumatoid arthritis (RA) and Crohn's disease (CD) GWAS, we build protein-protein interaction (PPI) networks for genes within associated loci and find abundant physical interactions between protein products of associated genes. We apply multiple permutation approaches to show that these networks are more...... that the RA and CD networks have predictive power by demonstrating that proteins in these networks, not encoded in the confirmed list of disease associated loci, are significantly enriched for association to the phenotypes in question in extended GWAS analysis. Finally, we test our method in 3 non...... evidence that, for many of the complex diseases studied here, common genetic associations implicate regions encoding proteins that physically interact in a preferential manner, in line with observations in Mendelian disease....

  12. Identifying gene-gene interactions that are highly associated with Body Mass Index using Quantitative Multifactor Dimensionality Reduction (QMDR).

    Science.gov (United States)

    De, Rishika; Verma, Shefali S; Drenos, Fotios; Holzinger, Emily R; Holmes, Michael V; Hall, Molly A; Crosslin, David R; Carrell, David S; Hakonarson, Hakon; Jarvik, Gail; Larson, Eric; Pacheco, Jennifer A; Rasmussen-Torvik, Laura J; Moore, Carrie B; Asselbergs, Folkert W; Moore, Jason H; Ritchie, Marylyn D; Keating, Brendan J; Gilbert-Diamond, Diane

    2015-01-01

    Despite heritability estimates of 40-70 % for obesity, less than 2 % of its variation is explained by Body Mass Index (BMI) associated loci that have been identified so far. Epistasis, or gene-gene interactions are a plausible source to explain portions of the missing heritability of BMI. Using genotypic data from 18,686 individuals across five study cohorts - ARIC, CARDIA, FHS, CHS, MESA - we filtered SNPs (Single Nucleotide Polymorphisms) using two parallel approaches. SNPs were filtered either on the strength of their main effects of association with BMI, or on the number of knowledge sources supporting a specific SNP-SNP interaction in the context of BMI. Filtered SNPs were specifically analyzed for interactions that are highly associated with BMI using QMDR (Quantitative Multifactor Dimensionality Reduction). QMDR is a nonparametric, genetic model-free method that detects non-linear interactions associated with a quantitative trait. We identified seven novel, epistatic models with a Bonferroni corrected p-value of association < 0.1. Prior experimental evidence helps explain the plausible biological interactions highlighted within our results and their relationship with obesity. We identified interactions between genes involved in mitochondrial dysfunction (POLG2), cholesterol metabolism (SOAT2), lipid metabolism (CYP11B2), cell adhesion (EZR), cell proliferation (MAP2K5), and insulin resistance (IGF1R). Moreover, we found an 8.8 % increase in the variance in BMI explained by these seven SNP-SNP interactions, beyond what is explained by the main effects of an index FTO SNP and the SNPs within these interactions. We also replicated one of these interactions and 58 proxy SNP-SNP models representing it in an independent dataset from the eMERGE study. This study highlights a novel approach for discovering gene-gene interactions by combining methods such as QMDR with traditional statistics.

  13. CMDR based differential evolution identifies the epistatic interaction in genome-wide association studies.

    Science.gov (United States)

    Yang, Cheng-Hong; Chuang, Li-Yeh; Lin, Yu-Da

    2017-08-01

    Detecting epistatic interactions in genome-wide association studies (GWAS) is a computational challenge. Such huge numbers of single-nucleotide polymorphism (SNP) combinations limit the some of the powerful algorithms to be applied to detect the potential epistasis in large-scale SNP datasets. We propose a new algorithm which combines the differential evolution (DE) algorithm with a classification based multifactor-dimensionality reduction (CMDR), termed DECMDR. DECMDR uses the CMDR as a fitness measure to evaluate values of solutions in DE process for scanning the potential statistical epistasis in GWAS. The results indicated that DECMDR outperforms the existing algorithms in terms of detection success rate by the large simulation and real data obtained from the Wellcome Trust Case Control Consortium. For running time comparison, DECMDR can efficient to apply the CMDR to detect the significant association between cases and controls amongst all possible SNP combinations in GWAS. DECMDR is freely available at https://goo.gl/p9sLuJ . chuang@isu.edu.tw or e0955767257@yahoo.com.tw. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  14. Interaction between Ester-Type Tea Catechins and Neutrophil Gelatinase-Associated Lipocalin: Inhibitory Mechanism.

    Science.gov (United States)

    Zhang, Wei; Li, Xiao; Hua, Fang; Chen, Wei; Wang, Wei; Chu, Gang-Xiu; Bao, Guan-Hu

    2018-02-07

    Tea is thought to alleviate neurotoxicity due to the antioxidative effect of ester-type tea catechins (ETC). Neutrophil gelatinase-associated lipocalin (NGAL) can sensitize β-amyloid (Aβ) induced neurotoxicity, and inhibitors of NGAL may relieve associated symptoms. As such, the interactions of ETC with NGAL were investigated by fluorescence spectrometry and molecular simulation. NGAL fluorescence is quenched regularly when being added with six processing types of tea infusion (SPTT) and ETC. Thermodynamic analyses suggest that ETC with more catechol moieties has a stronger binding capacity with NGAL especially in the presence of Fe 3+ . (-)-Epicatechin 3-O-caffeoate (ECC), a natural product isolated from Zijuan green tea, shows the strongest binding ability with NGAL (K d = 15.21 ± 8.68 nM in the presence of Fe 3+ ). All ETC are effective in protecting nerve cells against H 2 O 2 or Aβ 1-42 induced injury. The inhibitory mechanism of ETC against NGAL supports its potential use in attenuation of neurotoxicity.

  15. Orlistat-associated adverse effects and drug interactions: a critical review.

    Science.gov (United States)

    Filippatos, Theodosios D; Derdemezis, Christos S; Gazi, Irene F; Nakou, Eleni S; Mikhailidis, Dimitri P; Elisaf, Moses S

    2008-01-01

    Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. In light of the recent US FDA approval of the over-the-counter sale of orlistat (60 mg three times daily), clinicians need to be aware that its use may be associated with less well known, but sometimes clinically relevant, adverse effects. More specifically, the use of orlistat has been associated with several mild-to-moderate gastrointestinal adverse effects, such as oily stools, diarrhoea, abdominal pain and faecal spotting. A few cases of serious hepatic adverse effects (cholelithiasis, cholostatic hepatitis and subacute liver failure) have been reported. However, the effects of orlistat on non-alcoholic fatty liver disease are beneficial. Orlistat-induced weight loss seems to have beneficial effects on blood pressure. No effect has been observed on calcium, phosphorus, magnesium, iron, copper or zinc balance or on bone biomarkers. Interestingly, the use of orlistat has been associated with rare cases of acute kidney injury, possibly due to the increased fat malabsorption resulting from the inhibition of pancreatic and gastric lipase by orlistat, leading to the formation of soaps with calcium and resulting in increased free oxalate absorption and enteric hyperoxaluria. Orlistat has a beneficial effect on carbohydrate metabolism. No significant effect on cancer risk has been reported with orlistat.Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness. This review considers orlistat-related adverse effects and drug interactions. The clinical relevance and pathogenesis of these effects is also discussed.

  16. Interactions between Social/ behavioral factors and ADRB2 genotypes may be associated with health at advanced ages in China

    DEFF Research Database (Denmark)

    Zeng, Y.; Cheng, L. G.; Zhao, L.

    2013-01-01

    ages. This study intends to fill in this research gap. Method: We conducted an exploratory analysis, using longitudinal survey phenotype/genotype data from 877 oldest-old aged 90+. To estimate association of GxE interactions with health outcome, adjusted for the potential correlation between genotypes...... and positively associated with good cognitive function; interaction between regular exercise and carrying rs1042718 or rs1042719 minor allele is significantly and positively associated with self-reported good health; and interaction between social-leisure activities and carrying rs1042719 minor allele...... exercise and social-leisure activities with cognitive function and self-reported health, and negative association of negative emotion with cognitive function, were much stronger among carriers of rs1042718 or rs1042719 alleles, compared to the non-carriers. Conclusions: The results indicate significant...

  17. Wnt/Yes-Associated Protein Interactions During Neural Tissue Patterning of Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Bejoy, Julie; Song, Liqing; Zhou, Yi; Li, Yan

    2018-04-01

    Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain-like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests. However, the interactions between Wnt and YAP expression for neural lineage commitment of hiPSCs remain poorly explored. The objective of this study is to investigate the effects of Wnt signaling and YAP expression on the cellular population in three-dimensional (3D) neural spheroids derived from hiPSCs. In this study, Wnt signaling was activated using CHIR99021 for 3D neural spheroids derived from human iPSK3 cells through embryoid body formation. Our results indicate that Wnt activation induces nuclear localization of YAP and upregulates the expression of HOXB4, the marker for hindbrain/spinal cord. By contrast, the cells exhibit more rostral forebrain neural identity (expression of TBR1) without Wnt activation. Cytochalasin D was then used to induce cytoplasmic YAP and the results showed the decreased HOXB4 expression. In addition, the incorporation of microparticles in the neural spheroids was investigated for the perturbation of neural patterning. This study may indicate the bidirectional interactions of Wnt signaling and YAP expression during neural tissue patterning, which have the significance in neurological disease modeling, drug screening, and neural tissue regeneration.

  18. Exploring mechanisms of diet-colon cancer associations through candidate molecular interaction networks.

    Science.gov (United States)

    Westergaard, David; Li, Jun; Jensen, Kasper; Kouskoumvekaki, Irene; Panagiotou, Gianni

    2014-05-17

    Epidemiological studies in the recent years have investigated the relationship between dietary habits and disease risk demonstrating that diet has a direct effect on public health. Especially plant-based diets -fruits, vegetables and herbs- are known as a source of molecules with pharmacological properties for treatment of several malignancies. Unquestionably, for developing specific intervention strategies to reduce cancer risk there is a need for a more extensive and holistic examination of the dietary components for exploring the mechanisms of action and understanding the nutrient-nutrient interactions. Here, we used colon cancer as a proof-of-concept for understanding key regulatory sites of diet on the disease pathway. We started from a unique vantage point by having a database of 158 plants positively associated to colon cancer reduction and their molecular composition (~3,500 unique compounds). We generated a comprehensive picture of the interaction profile of these edible and non-edible plants with a predefined candidate colon cancer target space consisting of ~1,900 proteins. This knowledge allowed us to study systematically the key components in colon cancer that are targeted synergistically by phytochemicals and identify statistically significant and highly correlated protein networks that could be perturbed by dietary habits. We propose here a framework for interrogating the critical targets in colon cancer processes and identifying plant-based dietary interventions as important modifiers using a systems chemical biology approach. Our methodology for better delineating prevention of colon cancer by nutritional interventions relies heavily on the availability of information about the small molecule constituents of our diet and it can be expanded to any other disease class that previous evidence has linked to lifestyle.

  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. Metabolite transport and associated sugar signalling systems underpinning source/sink interactions.

    Science.gov (United States)

    Griffiths, Cara A; Paul, Matthew J; Foyer, Christine H

    2016-10-01

    Metabolite transport between organelles, cells and source and sink tissues not only enables pathway co-ordination but it also facilitates whole plant communication, particularly in the transmission of information concerning resource availability. Carbon assimilation is co-ordinated with nitrogen assimilation to ensure that the building blocks of biomass production, amino acids and carbon skeletons, are available at the required amounts and stoichiometry, with associated transport processes making certain that these essential resources are transported from their sites of synthesis to those of utilisation. Of the many possible posttranslational mechanisms that might participate in efficient co-ordination of metabolism and transport only reversible thiol-disulphide exchange mechanisms have been described in detail. Sucrose and trehalose metabolism are intertwined in the signalling hub that ensures appropriate resource allocation to drive growth and development under optimal and stress conditions, with trehalose-6-phosphate acting as an important signal for sucrose availability. The formidable suite of plant metabolite transporters provides enormous flexibility and adaptability in inter-pathway coordination and source-sink interactions. Focussing on the carbon metabolism network, we highlight the functions of different transporter families, and the important of thioredoxins in the metabolic dialogue between source and sink tissues. In addition, we address how these systems can be tailored for crop improvement. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Molecular characterization of Salmonella enterica isolates associated with starling-livestock interactions.

    Science.gov (United States)

    Carlson, James C; Hyatt, Doreene R; Bentler, Kevin; Mangan, Anna M; Russell, Michael; Piaggio, Antoinette J; Linz, George M

    2015-08-31

    Bird-livestock interactions have been implicated as potential sources for bacteria within concentrated animal feeding operations (CAFO). In this study we characterized XbaI-digested genomic DNA from Salmonella enterica using pulsed-field gel electrophoresis (PFGE). The PFGE analysis was conducted using 182 S. enterica isolates collected from a single CAFO between 2009 and 2012. Samples collected in 2012 were subjected to antimicrobial susceptibility testing. The analysis was limited to S. enterica serotypes, with at least 10 isolates, known to occur in both European starlings (Sturnus vulgaris) and cattle (Bos taurus) within this CAFO. A total of five different serotypes were screened; S. Anatum, S. Kentucky, S. Meleagridis, S. Montevideo, S. Muenchen. These samples were recovered from five different sample types; starling gastrointestinal tracts (GI), starling external wash, cattle feces, cattle feed and cattle water troughs. Indistinguishable S. enterica PFGE profiles were recovered from isolates originating in all sample types. Antimicrobial resistance (AMR) was also associated with indistinguishable S. enterica isolates recovered from all samples types. These data suggests that AMR S. enterica is transmitted between cattle and starlings and that shared feed sources are likely contributing to infections within both species. Moreover we isolated indistinguishable PFGE profiles across all years of data collection, suggesting long-term environmental persistence may be mediated by starling visits to CAFO. Published by Elsevier B.V.

  2. Associative memory based on synchronized firing of spiking neurons with time-delayed interactions

    Science.gov (United States)

    Yoshioka, Masahiko; Shiino, Masatoshi

    1998-09-01

    We study associative memory of a neural network of spiking neurons with time-delayed synaptic interactions incorporating the time taken by an action potential to propagate along the axon. Individual spiking neurons are described by a set of nonlinear differential equations capable of exhibiting excitability such as that of Hodgkin-Huxley and FitzHugh neurons. When a simple learning rule of the autocorrelation type based on random patterns is assumed, memory retrieval is shown to be accompanied by synchronized firing of neurons. The reduced dynamics with a few degrees of freedom of the network with a finite number of stored patterns is analytically derived in the limit of infinitely many neurons. The dependence of the appearance of retrieval states on the distribution of time delay and on the size of refractory period given implicitly in the model is obtained, showing good agreement between the result of numerical simulations and that obtained from the reduced dynamics. The behavior of the network with an extensive number of patterns is also investigated and an approximate analysis is presented to discuss the storage capacity.

  3. Specific and nonspecific interactions in ultraweak protein−protein associations revealed by solvent paramagnetic relaxation enhancements

    DEFF Research Database (Denmark)

    Johansson, Helle; Jensen, Malene Ringkjøbing; Gesmar, Henrik

    2014-01-01

    of human growth hormone (hGH, KD = 0.90 ± 0.03 mM) at neutral pH by the paramagnetic relaxation enhancement (PRE) of the amide protons induced by the soluble paramagnetic relaxation agent, gadodiamide (Gd(DTPA-BMA)). Primarily, it was found that the PREs are in agreement with the general Hwang-Freed model...... for relaxation by translational diffusion (J. Chem. Phys. 1975, 63, 4017–4025), only if crowding effects on the diffusion in the protein solution are taken into account. Secondly, by measuring the PREs of the hGH amide protons at increasing hGH concentrations and a constant concentration of the relaxation agent......, it is shown that a distinction can be made between residues that are affected only by transient, non-specific protein–protein interactions and residues that are involved in specific protein-protein associations. Thus, the PREs of the former residues increase linearly with the hGH concentration in the entire...

  4. Two-way plant mediated interactions between root-associated microbes and insects: from ecology to mechanisms

    Directory of Open Access Journals (Sweden)

    Nurmi ePangesti

    2013-10-01

    Full Text Available Plants are members of complex communities and function as a link between above- and below-ground organisms. Associations between plants and soil-borne microbes commonly occur and have often been found beneficial for plant fitness. Root-associated microbes may trigger physiological changes in the host plant that influence interactions between plants and aboveground insects at several trophic levels. Aboveground, plants are under continuous attack by insect herbivores and mount multiple responses that also have systemic effects on belowground microbes. Until recently, both ecological and mechanistic studies have mostly focused on exploring these below- and above-ground interactions using simplified systems involving both single microbe and herbivore species, which is far from the naturally occurring interactions. Increasing the complexity of the systems studied is required to increase our understanding of microbe - plant - insect interactions and to gain more benefit from the use of non-pathogenic microbes in agriculture. In this review, we explore how colonization by either single non-pathogenic microbe species or a community of such microbes belowground affects plant growth and defense and how this affects the interactions of plants with aboveground insects at different trophic levels. Moreover, we review how plant responses to foliar herbivory by insects belonging to different feeding guilds affect interactions of plants with non-pathogenic soil-borne microbes. The role of phytohormones in coordinating plant growth, plant defenses against foliar herbivores while simultaneously establishing associations with non-pathogenic soil microbes is discussed.

  5. Genetic and Physical Interaction of the B-Cell SLE-Associated Genes BANK1 and BLK

    Science.gov (United States)

    Castillejo-López, Casimiro; Delgado-Vega, Angélica M.; Wojcik, Jerome; Kozyrev, Sergey V.; Thavathiru, Elangovan; Wu, Ying-Yu; Sánchez, Elena; Pöllmann, David; López-Egido, Juan R.; Fineschi, Serena; Domínguez, Nicolás; Lu, Rufei; James, Judith A.; Merrill, Joan T.; Kelly, Jennifer A.; Kaufman, Kenneth M.; Moser, Kathy; Gilkeson, Gary; Frostegård, Johan; Pons-Estel, Bernardo A.; D’Alfonso, Sandra; Witte, Torsten; Callejas, José Luis; Harley, John B.; Gaffney, Patrick; Martin, Javier; Guthridge, Joel M.; Alarcón-Riquelme, Marta E.

    2012-01-01

    Objectives Altered signaling in B-cells is a predominant feature of systemic lupus erythematosus (SLE). The genes BANK1 and BLK were recently described as associated with SLE. BANK1 codes for a B-cell-specific cytoplasmic protein involved in B-cell receptor signaling and BLK codes for an Src tyrosine kinase with important roles in B-cell development. To characterize the role of BANK1 and BLK in SLE, we performed a genetic interaction analysis hypothesizing that genetic interactions could reveal functional pathways relevant to disease pathogenesis. Methods We Used the method GPAT16 to analyze the gene-gene interactions of BANK1 and BLK. Confocal microscopy was used to investigate co-localization, and immunoprecipitation was used to verify the physical interaction of BANK1 and BLK. Results Epistatic interactions between BANK1 and BLK polymorphisms associated with SLE were observed in a discovery set of 279 patients and 515 controls from Northern Europe. A meta-analysis with 4399 European individuals confirmed the genetic interactions between BANK1 and BLK. As BANK1 was identified as a binding partner of the Src tyrosine kinase LYN, we tested the possibility that BANK1 and BLK could also show a protein-protein interaction. We demonstrated co-immunoprecipitation and co-localization of BLK and BANK1. In a Daudi cell line and primary naïve B-cells the endogenous binding was enhanced upon B-cell receptor stimulation using anti-IgM antibodies. Conclusions Here, we show a genetic interaction between BANK1 and BLK, and demonstrate that these molecules interact physically. Our results have important consequences for the understanding of SLE and other autoimmune diseases and identify a potential new signaling pathway. PMID:21978998

  6. Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK.

    Science.gov (United States)

    Castillejo-López, Casimiro; Delgado-Vega, Angélica M; Wojcik, Jerome; Kozyrev, Sergey V; Thavathiru, Elangovan; Wu, Ying-Yu; Sánchez, Elena; Pöllmann, David; López-Egido, Juan R; Fineschi, Serena; Domínguez, Nicolás; Lu, Rufei; James, Judith A; Merrill, Joan T; Kelly, Jennifer A; Kaufman, Kenneth M; Moser, Kathy L; Gilkeson, Gary; Frostegård, Johan; Pons-Estel, Bernardo A; D'Alfonso, Sandra; Witte, Torsten; Callejas, José Luis; Harley, John B; Gaffney, Patrick M; Martin, Javier; Guthridge, Joel M; Alarcón-Riquelme, Marta E

    2012-01-01

    Altered signalling in B cells is a predominant feature of systemic lupus erythematosus (SLE). The genes BANK1 and BLK were recently described as associated with SLE. BANK1 codes for a B-cell-specific cytoplasmic protein involved in B-cell receptor signalling and BLK codes for an Src tyrosine kinase with important roles in B-cell development. To characterise the role of BANK1 and BLK in SLE, a genetic interaction analysis was performed hypothesising that genetic interactions could reveal functional pathways relevant to disease pathogenesis. The GPAT16 method was used to analyse the gene-gene interactions of BANK1 and BLK. Confocal microscopy was used to investigate co-localisation, and immunoprecipitation was used to verify the physical interaction of BANK1 and BLK. Epistatic interactions between BANK1 and BLK polymorphisms associated with SLE were observed in a discovery set of 279 patients and 515 controls from northern Europe. A meta-analysis with 4399 European individuals confirmed the genetic interactions between BANK1 and BLK. As BANK1 was identified as a binding partner of the Src tyrosine kinase LYN, the possibility that BANK1 and BLK could also show a protein-protein interaction was tested. The co-immunoprecipitation and co-localisation of BLK and BANK1 were demonstrated. In a Daudi cell line and primary naive B cells endogenous binding was enhanced upon B-cell receptor stimulation using anti-IgM antibodies. This study shows a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically. The results have important consequences for the understanding of SLE and other autoimmune diseases and identify a potential new signalling pathway.

  7. Characterizing associations and SNP-environment interactions for GWAS-identified prostate cancer risk markers--results from BPC3.

    Directory of Open Access Journals (Sweden)

    Sara Lindstrom

    2011-02-01

    Full Text Available Genome-wide association studies (GWAS have identified multiple single nucleotide polymorphisms (SNPs associated with prostate cancer risk. However, whether these associations can be consistently replicated, vary with disease aggressiveness (tumor stage and grade and/or interact with non-genetic potential risk factors or other SNPs is unknown. We therefore genotyped 39 SNPs from regions identified by several prostate cancer GWAS in 10,501 prostate cancer cases and 10,831 controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3. We replicated 36 out of 39 SNPs (P-values ranging from 0.01 to 10⁻²⁸. Two SNPs located near KLK3 associated with PSA levels showed differential association with Gleason grade (rs2735839, P = 0.0001 and rs266849, P = 0.0004; case-only test, where the alleles associated with decreasing PSA levels were inversely associated with low-grade (as defined by Gleason grade < 8 tumors but positively associated with high-grade tumors. No other SNP showed differential associations according to disease stage or grade. We observed no effect modification by SNP for association with age at diagnosis, family history of prostate cancer, diabetes, BMI, height, smoking or alcohol intake. Moreover, we found no evidence of pair-wise SNP-SNP interactions. While these SNPs represent new independent risk factors for prostate cancer, we saw little evidence for effect modification by other SNPs or by the environmental factors examined.

  8. Multiple interacting factors influence adherence, and outcomes associated with surgical safety checklists: a qualitative study.

    Science.gov (United States)

    Gagliardi, Anna R; Straus, Sharon E; Shojania, Kaveh G; Urbach, David R

    2014-01-01

    The surgical safety checklist (SSC) is meant to enhance patient safety but studies of its impact conflict. This study explored factors that influenced SSC adherence to suggest how its impact could be optimized. Participants were recruited purposively by profession, region, hospital type and time using the SSC. They were asked to describe how the SSC was adopted, associated challenges, perceived impact, and suggestions for improving its use. Grounded theory and thematic analysis were used to collect and analyse data. Findings were interpreted using an implementation fidelity conceptual framework. Fifty-one participants were interviewed (29 nurses, 13 surgeons, 9 anaesthetists; 18 small, 14 large and 19 teaching hospitals; 8 regions; 31 had used the SC for ≤12 months, 20 for 13+ months). The SSC was inconsistently reviewed, and often inaccurately documented as complete. Adherence was influenced by multiple issues. Extensive modification to accommodate existing practice patterns eliminated essential interaction at key time points to discuss patient management. Staff were often absent or not paying attention. They did not feel it was relevant to their work given limited evidence of its effectiveness, and because they were not engaged in its implementation. Organizations provided little support for implementation, training, monitoring and feedback, which are needed to overcome these, and other individual and team factors that challenged SSC adherence. Responses were similar across participants with different characteristics. Multiple processes and factors influenced SSC adherence. This may explain why, in studies evaluating SSC impact, outcomes were variable. Recommendations included continuing education, time for pilot-testing, and engaging all staff in SSC review. Others may use the implementation fidelity framework to plan SSC implementation or evaluate SSC adherence. Further research is needed to establish which SSC components can be modified without compromising

  9. Radar tracking with an interacting multiple model and probabilistic data association filter for civil aviation applications.

    Science.gov (United States)

    Jan, Shau-Shiun; Kao, Yu-Chun

    2013-05-17

    The current trend of the civil aviation technology is to modernize the legacy air traffic control (ATC) system that is mainly supported by many ground based navigation aids to be the new air traffic management (ATM) system that is enabled by global positioning system (GPS) technology. Due to the low receiving power of GPS signal, it is a major concern to aviation authorities that the operation of the ATM system might experience service interruption when the GPS signal is jammed by either intentional or unintentional radio-frequency interference. To maintain the normal operation of the ATM system during the period of GPS outage, the use of the current radar system is proposed in this paper. However, the tracking performance of the current radar system could not meet the required performance of the ATM system, and an enhanced tracking algorithm, the interacting multiple model and probabilistic data association filter (IMMPDAF), is therefore developed to support the navigation and surveillance services of the ATM system. The conventional radar tracking algorithm, the nearest neighbor Kalman filter (NNKF), is used as the baseline to evaluate the proposed radar tracking algorithm, and the real flight data is used to validate the IMMPDAF algorithm. As shown in the results, the proposed IMMPDAF algorithm could enhance the tracking performance of the current aviation radar system and meets the required performance of the new ATM system. Thus, the current radar system with the IMMPDAF algorithm could be used as an alternative system to continue aviation navigation and surveillance services of the ATM system during GPS outage periods.

  10. Radar Tracking with an Interacting Multiple Model and Probabilistic Data Association Filter for Civil Aviation Applications

    Directory of Open Access Journals (Sweden)

    Shau-Shiun Jan

    2013-05-01

    Full Text Available The current trend of the civil aviation technology is to modernize the legacy air traffic control (ATC system that is mainly supported by many ground based navigation aids to be the new air traffic management (ATM system that is enabled by global positioning system (GPS technology. Due to the low receiving power of GPS signal, it is a major concern to aviation authorities that the operation of the ATM system might experience service interruption when the GPS signal is jammed by either intentional or unintentional radio-frequency interference. To maintain the normal operation of the ATM system during the period of GPS outage, the use of the current radar system is proposed in this paper. However, the tracking performance of the current radar system could not meet the required performance of the ATM system, and an enhanced tracking algorithm, the interacting multiple model and probabilistic data association filter (IMMPDAF, is therefore developed to support the navigation and surveillance services of the ATM system. The conventional radar tracking algorithm, the nearest neighbor Kalman filter (NNKF, is used as the baseline to evaluate the proposed radar tracking algorithm, and the real flight data is used to validate the IMMPDAF algorithm. As shown in the results, the proposed IMMPDAF algorithm could enhance the tracking performance of the current aviation radar system and meets the required performance of the new ATM system. Thus, the current radar system with the IMMPDAF algorithm could be used as an alternative system to continue aviation navigation and surveillance services of the ATM system during GPS outage periods.

  11. Cryptic effects of habitat declines: coral-associated fishes avoid coral-seaweed interactions due to visual and chemical cues.

    Science.gov (United States)

    Brooker, Rohan M; Brandl, Simon J; Dixson, Danielle L

    2016-01-04

    Seaweed-dominated coral reefs are becoming increasingly common as environmental conditions shift away from those required by corals and toward those ideal for rampant seaweed growth. How coral-associated organisms respond to seaweed will not only impact their fate following environmental change but potentially also the trajectories of the coral communities on which they rely. However, behavioral responses by coral-associated organisms to seaweeds are poorly understood. This study examined interactions between a guild of obligate and opportunistic coral-feeding butterflyfishes (Chaetodontidae) and scleractinian corals to determine whether fishes continue to interact with corals in contact with seaweed or if they are avoided. Under natural conditions, all species interacted almost exclusively with seaweed-free corals. In a controlled patch reef experiment, fishes avoided corals in physical contact with seaweed, irrespective of dietary preferences. When visual seaweed cues were removed, butterflyfish continued to avoid corals that had been in contact with the allelopathic Galaxaura filamentosa, suggesting that chemical cues produced by coral-seaweed interactions are repellent. These findings suggest that, due to deleterious visual and chemical cues produced by coral-seaweed interactions, coral-associated organisms may struggle to locate resources as seaweed-free corals decline in abundance.

  12. The potato sucrose transporter StSUT1 interacts with a DRM-associated protein disulfide isomerase.

    Science.gov (United States)

    Krügel, Undine; He, Hong-Xia; Gier, Konstanze; Reins, Jana; Chincinska, Izabela; Grimm, Bernhard; Schulze, Waltraud X; Kühn, Christina

    2012-01-01

    Organization of proteins into complexes is crucial for many cellular functions. Recently, the SUT1 protein was shown to form homodimeric complexes, to be associated with lipid raft-like microdomains in yeast as well as in plants and to undergo endocytosis in response to brefeldin A. We therefore aimed to identify SUT1-interacting proteins that might be involved in dimerization, endocytosis, or targeting of SUT1 to raft-like microdomains. Therefore, we identified potato membrane proteins, which are associated with the detergent-resistant membrane (DRM) fraction. Among the proteins identified, we clearly confirmed StSUT1 as part of DRM in potato source leaves. We used the yeast two-hybrid split ubiquitin system (SUS) to systematically screen for interaction between the sucrose transporter StSUT1 and other membrane-associated or soluble proteins in vivo. The SUS screen was followed by immunoprecipitation using affinity-purified StSUT1-specific peptide antibodies and mass spectrometric analysis of co-precipitated proteins. A large overlap was observed between the StSUT1-interacting proteins identified in the co-immunoprecipitation and the detergent-resistant membrane fraction. One of the SUT1-interacting proteins, a protein disulfide isomerase (PDI), interacts also with other sucrose transporter proteins. A potential role of the PDI as escort protein is discussed.

  13. Association between physicians' interaction with pharmaceutical companies and their clinical practices: A systematic review and meta-analysis.

    Science.gov (United States)

    Brax, Hneine; Fadlallah, Racha; Al-Khaled, Lina; Kahale, Lara A; Nas, Hala; El-Jardali, Fadi; Akl, Elie A

    2017-01-01

    Pharmaceutical company representatives likely influence the prescribing habits and professional behaviors of physicians. The objective of this study was to systematically review the association between physicians' interactions with pharmaceutical companies and their clinical practices. We used the standard systematic review methodology. Observational and experimental study designs examining any type of targeted interaction between practicing physicians and pharmaceutical companies were eligible. The search strategy included a search of MEDLINE and EMBASE databases up to July 2016. Two reviewers selected studies, abstracted data, and assessed risk of bias in duplicate and independently. We assessed the quality of evidence using the GRADE approach. Twenty articles reporting on 19 studies met our inclusion criteria. All of these studies were conducted in high-income countries and examined different types of interactions, including detailing, industry-funded continuing medical education, and receiving free gifts. While all included studies assessed prescribing behaviors, four studies also assessed financial outcomes, one assessed physicians' knowledge, and one assessed their beliefs. None of the studies assessed clinical outcomes. Out of the 19 studies, 15 found a consistent association between interactions promoting a medication, and inappropriately increased prescribing rates, lower prescribing quality, and/or increased prescribing costs. The remaining four studies found both associations and lack of significant associations for the different types of exposures and drugs examined in the studies. A meta-analysis of six of these studies found a statistically significant association between exposure and physicians' prescribing behaviors (OR = 2.52; 95% CI 1.82-3.50). The quality of evidence was downgraded to moderate for risk of bias and inconsistency. Sensitivity analysis excluding studies at high risk of bias did not substantially change these results. A subgroup

  14. Integrating genome-wide association study summaries and element-gene interaction datasets identified multiple associations between elements and complex diseases.

    Science.gov (United States)

    He, Awen; Wang, Wenyu; Prakash, N Tejo; Tinkov, Alexey A; Skalny, Anatoly V; Wen, Yan; Hao, Jingcan; Guo, Xiong; Zhang, Feng

    2018-03-01

    Chemical elements are closely related to human health. Extensive genomic profile data of complex diseases offer us a good opportunity to systemically investigate the relationships between elements and complex diseases/traits. In this study, we applied gene set enrichment analysis (GSEA) approach to detect the associations between elements and complex diseases/traits though integrating element-gene interaction datasets and genome-wide association study (GWAS) data of complex diseases/traits. To illustrate the performance of GSEA, the element-gene interaction datasets of 24 elements were extracted from the comparative toxicogenomics database (CTD). GWAS summary datasets of 24 complex diseases or traits were downloaded from the dbGaP or GEFOS websites. We observed significant associations between 7 elements and 13 complex diseases or traits (all false discovery rate (FDR) elements and complex diseases. © 2017 WILEY PERIODICALS, INC.

  15. Functional contributions and interactions between the human hippocampus and subregions of the striatum during arbitrary associative learning and memory

    Science.gov (United States)

    Mattfeld, Aaron T.; Stark, Craig E. L.

    2015-01-01

    The hippocampus and striatum are thought to have different functional roles in learning and memory. It is unknown under what experimental conditions their contributions are dissimilar or converge, and the extent to which they interact over the course of learning. In order to evaluate both the functional contributions of as well as the interactions between the human hippocampus and striatum, the present study used high-resolution functional magnetic resonance imaging (fMRI) and variations of a conditional visuomotor associative learning task that either taxed arbitrary associative learning (Experiment 1) or stimulus-response learning (Experiment 2). In the first experiment we observed changes in activity in the hippocampus and anterior caudate that reflect differences between the two regions consistent with distinct computational principles. In the second experiment we observed activity in the putamen that reflected content specific representations during the learning of arbitrary conditional visuomotor associations. In both experiments the hippocampus and ventral striatum demonstrated dynamic functional coupling during the learning of new arbitrary associations, but not during retrieval of well-learned arbitrary associations using control variants of the tasks that did not preferentially tax one system versus the other. These findings suggest that both the hippocampus and subregions of the dorsal striatum contribute uniquely to the learning of arbitrary associations while the hippocampus and ventral striatum interact over the course of learning. PMID:25560298

  16. A case-only genome-wide association study for assessing gene-sex interaction in Allergic rhinitis

    DEFF Research Database (Denmark)

    Mohammadnejad, Afsaneh; Brasch-Andersen, Charlotte; Haagerup, Annette

    Background: Allergic rhinitis (AR) is a complex disorder with important sex dependency in its prevalence. In this regard, genotype-by-sex interaction is one of the important phenomena in understanding the genetic basis of the disease. We aimed to apply a case-only genome-wide association study...

  17. Identifying gene-gene interactions that are highly associated with Body Mass Index using Quantitative Multifactor Dimensionality Reduction (QMDR)

    NARCIS (Netherlands)

    De, Rishika; Verma, Shefali S; Drenos, Fotios; Holzinger, Emily R; Holmes, Michael V; Hall, Molly A; Crosslin, David R; Carrell, David S; Hakonarson, Hakon; Jarvik, Gail; Larson, Eric; Pacheco, Jennifer A; Rasmussen-Torvik, Laura J; Moore, Carrie B; Asselbergs, Folkert W; Moore, Jason H; Ritchie, Marylyn D; Keating, Brendan J; Gilbert-Diamond, Diane

    2015-01-01

    BACKGROUND: Despite heritability estimates of 40-70 % for obesity, less than 2 % of its variation is explained by Body Mass Index (BMI) associated loci that have been identified so far. Epistasis, or gene-gene interactions are a plausible source to explain portions of the missing heritability of

  18. A framework for evaluating the influence of climate, dispersal limitation, and biotic interactions using fossil pollen associations across the late Quaternary

    DEFF Research Database (Denmark)

    Blois, Jessica L.; Gotelli, Nicholas J.; Behrensmeyer, Anna K.

    2014-01-01

    Environmental conditions, dispersal lags, and interactions among species are major factors structuring communities through time and across space. Ecologists have emphasized the importance of biotic interactions in determining local patterns of species association. In contrast, abiotic limits, dis...

  19. Social interaction associated with visual art discussions: a controlled intervention study.

    Science.gov (United States)

    Wikström, B-M

    2002-02-01

    The investigation was aimed to assess the link between visual art discussions and social interaction. The study was designed as a controlled intervention study. Participants were older women living in a block of specially designed older persons' flats in Sweden. Reproductions of well-known artists' works of art were used as an intervention instrument. Measurements were older women's self-reported social interaction. The results show significant improvement in the visual art group compared to the matched control group. The differences in ratings between the groups indicated increased social interaction in the visual art group, which continued to exist four months after the intervention. Visual art discussions encouraged reminiscence and stimulated the older women to be more socially active. The study is an example of how visual art could be used in order to stimulate older women to interact in a social network in order to remain in contact with the world instead of retreating from it.

  20. Sex-specific Profiles of Blood Metal Levels Associated with Metal–Iron Interactions

    OpenAIRE

    Lee, Byung-Kook; Kim, Yangho

    2014-01-01

    The mechanisms by which iron is absorbed are similar to those of divalent metals, particularly manganese, lead, and cadmium. These metals, however, show different toxicokinetics in relation to menarche or menopause, although their interaction with iron is the same. This review focuses on the kinetics of these three toxic metals (manganese, lead, and cadmium) in relation to menarche, pregnancy, and menopause. The iron–manganese interaction is the major factor determining sex-specific differenc...

  1. TATA binding protein associated factor 3 (TAF3 interacts with p53 and inhibits its function

    Directory of Open Access Journals (Sweden)

    Tora Laszlo

    2008-06-01

    Full Text Available Abstract Background The tumour suppressor protein p53 is a sequence specific DNA-binding transcription regulator, which exerts its versatile roles in genome protection and apoptosis by affecting the expression of a large number of genes. In an attempt to obtain a better understanding of the mechanisms by which p53 transcription function is regulated, we studied p53 interactions. Results We identified BIP2 (Bric-à-brac interacting protein 2, the fly homolog of TAF3, a histone fold and a plant homeodomain containing subunit of TFIID, as an interacting partner of Drosophila melanogaster p53 (Dmp53. We detected physical interaction between the C terminus of Dmp53 and the central region of TAF3 both in yeast two hybrid assays and in vitro. Interestingly, DmTAF3 can also interact with human p53, and mammalian TAF3 can bind to both Dmp53 and human p53. This evolutionarily conserved interaction is functionally significant, since elevated TAF3 expression severely and selectively inhibits transcription activation by p53 in human cell lines, and it decreases the level of the p53 protein as well. Conclusion We identified TAF3 as an evolutionarily conserved negative regulator of p53 transcription activation function.

  2. Geochronology and Fluid-Rock Interaction Associated with the Nopal I Uranium Deposit, Pena Blanca, Mexico

    Energy Technology Data Exchange (ETDEWEB)

    M. Fayek; P. Goodell; M. Ren; A. Simmons

    2005-07-11

    The Nopal I uranium (U) deposit, Pena Blanca District, Mexico, largely consists of secondary U{sup 6+} minerals, which occur within a breccia pipe mainly hosted by the 44 Ma Nopal and Colorados volcanic formations. These two units overly the Pozos conglomerate formation and Cretaceous limestone. Three new vertical diamond drill holes (DDHs) were recently drilled at Nopal I. DDH-PB1 with continuous core was drilled through the Nopal I deposit and two additional DDHs were drilled {approx}50 m on either side of the cored hole. These DDHs terminate 20 m below the current water table, thus allowing the detection of possible gradients in radionuclide contents resulting from transport from the overlying uranium deposit. Primary uraninite within the main ore body is rare and fine-grained ({approx}50 micrometers), thus making geochronology of the Nopal I deposit very difficult. Uranium, lead and oxygen isotopes can be used to study fluid-uraninite interaction, provided that the analyses are obtained on the micro-scale. Secondary ionization mass spectrometry (SIMS) permits in situ measurement of isotopic ratios with a spatial resolution on the scale of a few {micro}m. Preliminary U-Pb results show that uraninite from the main ore body gives an age of 32 {+-} 8 Ma, whereas uraninite from the uraniferous Pozos conglomerate that lies nearly 100 m below the main ore body and 25 meters above the water table, gives a U-Pb age that is <1 Ma. Oxygen isotopic analyses show that uraninite from the ore body has a {delta}{sup 18}O = -10.8{per_thousand}, whereas the uraninite within the Pozos conglomerate has a {delta}{sup 18}O = +1.5{per_thousand}. If it is assumed that both uraninites precipitated from meteoric water ({delta}{sup 18}O = -7{per_thousand}), then calculated precipitation temperatures are 55 C for the uraninite from the ore body and 20 C for uraninite hosted by the Pozos conglomerate. These temperatures are consistent with previous studies that calculated precipitation

  3. No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels

    DEFF Research Database (Denmark)

    Scott, Robert A; Chu, Audrey Y; Grarup, Niels

    2012-01-01

    to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were...... dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (ß = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were...... associated with 2-h glucose (ß = 0.06-0.12 mmol/allele, P = 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P = 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated...

  4. Siderophore biosynthesis coordinately modulated the virulence-associated interactive metabolome of uropathogenic Escherichia coli and human urine.

    Science.gov (United States)

    Su, Qiao; Guan, Tianbing; Lv, Haitao

    2016-04-14

    Uropathogenic Escherichia coli (UPEC) growth in women's bladders during urinary tract infection (UTI) incurs substantial chemical exchange, termed the "interactive metabolome", which primarily accounts for the metabolic costs (utilized metabolome) and metabolic donations (excreted metabolome) between UPEC and human urine. Here, we attempted to identify the individualized interactive metabolome between UPEC and human urine. We were able to distinguish UPEC from non-UPEC by employing a combination of metabolomics and genetics. Our results revealed that the interactive metabolome between UPEC and human urine was markedly different from that between non-UPEC and human urine, and that UPEC triggered much stronger perturbations in the interactive metabolome in human urine. Furthermore, siderophore biosynthesis coordinately modulated the individualized interactive metabolome, which we found to be a critical component of UPEC virulence. The individualized virulence-associated interactive metabolome contained 31 different metabolites and 17 central metabolic pathways that were annotated to host these different metabolites, including energetic metabolism, amino acid metabolism, and gut microbe metabolism. Changes in the activities of these pathways mechanistically pinpointed the virulent capability of siderophore biosynthesis. Together, our findings provide novel insights into UPEC virulence, and we propose that siderophores are potential targets for further discovery of drugs to treat UPEC-induced UTI.

  5. Interactions between the breast cancer-associated MUC1 mucins and C-type lectin characterized by optical tweezers.

    Directory of Open Access Journals (Sweden)

    Soosan Hadjialirezaei

    Full Text Available Carbohydrate-protein interactions govern many crucial processes in biological systems including cell recognition events. We have used the sensitive force probe optical tweezers to quantify the interactions occurring between MGL lectins and MUC1 carrying the cancer-associated glycan antigens mucins Tn and STn. Unbinding forces of 7.6 pN and 7.1 pN were determined for the MUC1(Tn-MGL and MUC1(STn-MGL interactions, at a force loading rate of ~40 pN/s. The interaction strength increased with increasing force loading rate, to 27 and 37 pN at a force loading rate of ~ 310 pN/s. No interactions were detected between MGL and MUC1(ST, a glycoform of MUC1 also expressed by breast carcinoma cells. Interestingly, this glycan (ST can be found on proteins expressed by normal cells, although in this case not on MUC1. Additionally, GalNAc decorated polyethylene glycol displayed similar rupture forces as observed for MUC1(Tn and MUC1(STn when forced to unbind from MGL, indicating that GalNAc is an essential group in these interactions. Since the STn glycan decoration is more frequently found on the surface of carcinomas than the Tn glycan, the binding of MUC1 carrying STn to MGL may be more physiologically relevant and may be in part responsible for some of the characteristics of STn expressing tumours.

  6. [Internet addiction disorder and social networks: statistical analysis of correlation and study of the association with social interaction anxiousness].

    Science.gov (United States)

    Rusconi, Anna Carlotta; Valeriani, Giuseppe; Carlone, Cristiano; Raimondo, Pasquale; Quartini, Adele; Coccanari de' Fornari, Maria Antonietta; Biondi, Massimo

    2012-01-01

    Internet Addiction Disorder (IAD) is an emerging psychiatric disorder, assimilable to impulse control problems and related to maladaptive use of new networks and social and virtual technologies. Our study aims to analyze the presence of IAD among adolescents and to study the correlation with social interaction anxiousness. We investigated also the possibility that the Social Network (SN) represent a source of risk for the development of IAD. The test group was composed of 250 subjects, aged between 14 and 18 years. They were administered: Young's IAT; IAS (Interaction Anxiousness Scale), AAS (Audience Anxiousness Scale) and SISST (Social Interaction Self-Statement Test) to analyze the dimension of social interaction anxiousness. We found a rate of 2% of the IAD. The SN are the most common use of the Net in our sample, but not the most clicked sites by subjects with IAD. It should be noted, finally, a correlation between social interaction anxiety and IAD, but not a significant difference in scores of social anxiousness scales based on the SN use/non-use. The use of SN intended as single variable doesn't correlate with increased risk for IAD, or for increased social interaction anxiousness. However, if associated with prolonged use of the net for 5-6 hours or more, or concomitant use of chat rooms and/or net gambling, we find a more significant risk of psychopathology. The data presented require further investigations, in order to guide new pathogenetic models and appropriate intervention strategies.

  7. Association between PTGS1 polymorphisms and functional outcomes in Chinese patients with stroke during aspirin therapy: Interaction with smoking.

    Science.gov (United States)

    Cai, Huan; Cai, Biyang; Sun, Lingli; Zhang, Hao; Zhou, Shuyu; Cao, Liping; Guo, Hongquan; Sun, Wen; Yan, Bernard; Davis, Stephen M; Zhang, Zhizhong; Liu, Xinfeng

    2017-05-15

    Prostaglandin-Endoperoxide Synthase 1 (PTGS1) and smoking may play important roles in aspirin nonresponsiveness, but the effect of their interaction on stroke outcomes remains largely unknown. We examined the effects of PTGS1 polymorphisms, smoking status, and their interaction on functional outcomes in a cohort of Chinese Han patients with stroke during aspirin therapy. A total of 617 ischemic stroke patients taking aspirin were enrolled. Three single nucleotide polymorphisms (SNPs) rs1330344, rs3842788, and rs5788 in PTGS1 were determined for genotyping. Poor functional outcomes were defined as a modified Rankin Scale (mRS) of 3-6 at 90-day follow-up. The influence of PTGS1 gene-smoking interaction on functional outcomes was examined. Poor functional outcomes occurred in 145 (23.5%) patients. When adjusting multiple factors by logistic regression, CC genotype of rs1330344 was associated with poor functional outcomes (risk ratio [RR]=1.73; 95% confidence interval [CI]: 1.17-2.37). A similar connection was found in the CGC haplotype (RR=1.40; 95% CI: 1.08-1.77). Furthermore, we found a significant interaction between rs1330344 and smoking status (P interaction =0.018); the interaction effect between the PTGS1 haplotype and smoking also showed statistical significance (P interaction =0.040). In Chinese Han stroke patients with aspirin therapy, the adverse effect of PTGS1 polymorphisms on functional outcomes may be modulated by the smoking status. PTGS1 gene-smoking interaction might in part reflect the heterogeneity in the prognosis of patients treated with aspirin. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Investigating the separate and interactive associations of trauma and depression on brain structure: implications for cognition and aging.

    Science.gov (United States)

    Karstens, Aimee J; Ajilore, Olusola; Rubin, Leah H; Yang, Shaolin; Zhang, Aifeng; Leow, Alex; Kumar, Anand; Lamar, Melissa

    2017-11-01

    Trauma and depression are associated with brain structural alterations; their combined effects on these outcomes are unclear. We previously reported a negative effect of trauma, independent of depression, on verbal learning and memory; less is known about underlying structural associates. We investigated separate and interactive associations of trauma and depression on brain structure. Adults aged 30-89 (N = 203) evaluated for depression (D+) and trauma history (T+) using structured clinical interviews were divided into 53 D+T+, 42 D+T-, 50 D-T+, and 58 D-T-. Multivariable linear regressions examined the separate and interactive associations of depression and trauma with prefrontal and temporal lobe cortical thickness composites and hippocampal volumes adjusting for age, sex, predicted verbal IQ, comorbid anxiety, and vascular risk. Significant results informed analyses of tract-based structural connectomic measures of efficiency and centrality. Trauma, independent of depression, was associated with greater left prefrontal cortex (PFC) thickness, in particular the medial orbitofrontal cortex and pars orbitalis. A trauma × depression interaction was observed for the right PFC in age-stratified analyses: Older D + T+ had reduced PFC thickness compared with older D - T+ individuals. Regardless of age, trauma was associated with more left medial orbitofrontal cortex efficiency and less pars orbitalis centrality. In the T+ group, left pars orbitalis cortical thickness and centrality negatively correlated with verbal learning. Trauma, independent of depression, associated with altered PFC characteristics, morphologically and in terms of structural network communication and influence. Additionally, findings suggest that there may be a combined effect of trauma and depression in older adults. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Affective and Behavioral Features of Jealousy Protest: Associations with Child Temperament, Maternal Interaction Style, and Attachment

    Science.gov (United States)

    Hart, Sybil L.; Behrens, Kazuko Y.

    2013-01-01

    This study explored variation in affective and behavioral components of infants' jealousy protests during an eliciting condition in which mother and an experimenter directed differential attention exclusively toward a rival. Variation was examined in relation to child temperamental emotionality, maternal interaction style, and attachment security.…

  10. Children's observed interactions with best friends : Associations with friendship jealousy and satisfaction

    NARCIS (Netherlands)

    Deutz, Marike H F; Lansu, Tessa A M; Cillessen, Antonius H N

    2015-01-01

    This study examined the role of friendship jealousy and satisfaction in nine-year-old children's observed interactions with their best friends. One hundred five dyads (51 female, 54 male) participated in a 30-min closed-field observational setting and reported their jealousy and satisfaction within

  11. Demographic and Instructor-Student Interaction Factors Associated with Community College Students' Intent to Persist

    Science.gov (United States)

    Mitchell, Yolanda F.; Hughes, Gail D.

    2014-01-01

    The classroom is the main point of contact for community college students due to their part-time status, employment, family responsibilities, and limited campus involvement. To examine the relationship between community college students' demographics and instructor interactions as they relate to intention to persist in college, researchers…

  12. A Characteristic Destabilization Profile in Parent-Child Interactions Associated with Treatment Efficacy for Aggressive Children

    NARCIS (Netherlands)

    Lichtwarck-Aschoff, Anna; Hasselman, Fred; Cox, Ralf; Pepler, Debra; Granic, Isabela

    This study examined profiles of change in repeated mother-child interactions over the course of a 12 week treatment period for childhood aggression. The aim of this study was to investigate whether it was possible to detect the characteristic profile of change, typical for phase transitions, over

  13. A characteristic destabilization profile in parent-child interactions associated with treatment efficacy for aggressive children

    NARCIS (Netherlands)

    Lichtwarck-Aschoff, A.; Hasselman, F.W.; Cox, R.F.A.; Pepler, D.; Granic, I.

    2012-01-01

    This study examined profiles of change in repeated mother-child interactions over the course of a 12 week treatment period for childhood aggression. The aim of this study was to investigate whether it was possible to detect the characteristic profile of change, typical for phase transitions, over

  14. LRP4 association to bone properties and fracture and interaction with genes in the Wnt- and BMP signaling pathways.

    Science.gov (United States)

    Kumar, Jitender; Swanberg, Maria; McGuigan, Fiona; Callreus, Mattias; Gerdhem, Paul; Akesson, Kristina

    2011-09-01

    Osteoporosis is a common complex disorder in postmenopausal women leading to changes in the micro-architecture of bone and increased risk of fracture. Members of the low-density lipoprotein receptor-related protein (LRP) gene family regulates the development and physiology of bone through the Wnt/β-catenin (Wnt) pathway that in turn cross-talks with the bone morphogenetic protein (BMP) pathway. In two cohorts of Swedish women: OPRA (n=1002; age 75 years) and PEAK-25 (n=1005; age 25 years), eleven single nucleotide polymorphisms (SNPs) from Wnt pathway genes (LRP4; LRP5; G protein-coupled receptor 177, GPR177) were analyzed for association with Bone Mineral Density (BMD), rate of bone loss, hip geometry, quantitative ultrasound and fracture. Additionally, interaction of LRP4 with LRP5, GPR177 and BMP2 were analyzed. LRP4 (rs6485702) was associated with higher total body (TB) and lumbar spine (LS) BMD in the PEAK-25 cohort (p=0.006 and 0.005 respectively), and interaction was observed with LRP5 (p=0.007) and BMP2 (p=0.004) for TB BMD. LRP4 also showed significant interaction with LRP5 for femoral neck (FN) and LS BMD in this cohort. In the OPRA cohort, LRP4 polymorphisms were associated with significantly lower fracture incidence overall (p=0.008-0.001) and fewer hip fractures (rs3816614, p=0.006). Significant interaction in the OPRA cohort was observed for LRP4 with BMP2 and GPR177 for FN BMD as well as for rate of bone loss at TB and FN (p=0.007-0.0001). In conclusion, LRP4 and interaction between LRP4 and genes in the Wnt and BMP signaling pathways modulate bone phenotypes including peak bone mass and fracture, the clinical endpoint of osteoporosis. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Turbulence-wave interactions associated to drainage flows observed during the BLLAST field campaign

    Science.gov (United States)

    Yagüe, Carlos; Sun, Jielun; Román-Cascón, Carlos; Sastre, Mariano; Arrillaga, Jon A.

    2016-04-01

    Gravity waves are often observed in the Nocturnal Stable Atmospheric Boundary Layer (SBL). One of the main topics in SBL studies, which is still far from being well understood, is the interaction between these waves and the turbulence present at the lower troposphere [1]. However it is not easy to establish the origin of these waves and how they interact with turbulence. Following the case study occurred along the evening transition of 2nd July 2011 over the area of Lannemezan (France) during the Boundary Layer Late Afternoon and Sunset Turbulence (BLLAST) field campaign [2], in the present work we have extended the study to all the cases found along the campaign, where the evening transition of the Atmospheric Boundary Layer was followed by the formation of drainage flows. Different multiscale techniques (Wavelet Transform -WT- and MultiResolution Flux Decomposition -MRFD-) have been applied to the extensive records of instrumentation deployed at BLLAST. In this way, we can underline the different features related to surface turbulent parameters in the SBL, where several of the studied processes showed an interaction, producing important variations in turbulence with height and between sites along the steep terrain. [1] Sun, J., C. J. Nappo, L. Mahrt, D. Belusic, B. Grisogono, D. R. Stauffer, M. Pulido, C. Staquet, Q. Jiang, A. Pouquet, C. Yagüe, B. Galperin, R. B. Smith, J. J. Finnigan, S.D. Mayor, G. Svensson, A. A. Grachev, and W.D.Neff. (2015): Review of wave-turbulence interactions in the stable atmospheric boundary layer, Rev. Geophys., 53, 956-993, doi:10.1002/2015RG000487. [2] Román-Cascón, C., Yagüe, C., Mahrt, L., Sastre, M., Steeneveld, G.-J., Pardyjak, E., van de Boer, A., and Hartogensis, O (2015).: Interactions among drainage flows, gravity waves and turbulence: a BLLAST case study, Atmos. Chem. Phys., 15, 9031-9047, doi:10.5194/acp-15-9031-2015.

  16. Association mapping of loci controlling genetic and environmental interaction of soybean flowering time under various photo-thermal conditions.

    Science.gov (United States)

    Mao, Tingting; Li, Jinyu; Wen, Zixiang; Wu, Tingting; Wu, Cunxiang; Sun, Shi; Jiang, Bingjun; Hou, Wensheng; Li, Wenbin; Song, Qijian; Wang, Dechun; Han, Tianfu

    2017-05-26

    Soybean (Glycine max (L.) Merr.) is a short day plant. Its flowering and maturity time are controlled by genetic and environmental factors, as well the interaction between the two factors. Previous studies have shown that both genetic and environmental factors, mainly photoperiod and temperature, control flowering time of soybean. Additionally, these studies have reported gene × gene and gene × environment interactions on flowering time. However, the effects of quantitative trait loci (QTL) in response to photoperiod and temperature have not been well evaluated. The objectives of the current study were to identify the effects of loci associated with flowering time under different photo-thermal conditions and to understand the effects of interaction between loci and environment on soybean flowering. Different photoperiod and temperature combinations were obtained by adjusting sowing dates (spring sowing and summer sowing) or day-length (12 h, 16 h). Association mapping was performed on 91 soybean cultivars from different maturity groups (MG000-VIII) using 172 SSR markers and 5107 SNPs from the Illumina SoySNP6K iSelectBeadChip. The effects of the interaction between QTL and environments on flowering time were also analysed using the QTXNetwork. Large-effect loci were detected on Gm 11, Gm 16 and Gm 20 as in previous reports. Most loci associated with flowering time are sensitive to photo-thermal conditions. Number of loci associated with flowering time was more under the long day (LD) than under the short day (SD) condition. The variation of flowering time among the soybean cultivars mostly resulted from the epistasis × environment and additive × environment interactions. Among the three candidate loci, i.e. Gm04_4497001 (near GmCOL3a), Gm16_30766209 (near GmFT2a and GmFT2b) and Gm19_47514601 (E3 or GmPhyA3), the Gm04_4497001 may be the key locus interacting with other loci for controlling soybean flowering time. The effects of loci associated

  17. Dog Owners' Interaction Styles: Their Components and Associations with Reactions of Pet Dogs to a Social Threat.

    Science.gov (United States)

    Cimarelli, Giulia; Turcsán, Borbála; Bánlaki, Zsófia; Range, Friederike; Virányi, Zsófia

    2016-01-01

    The bond dogs develop with their owner received increased attention in the last years but no study aimed at characterizing the way in which owners interact with their dogs in their daily life and how this might influence dog behavior. In order to examine how dog owners interact with their dogs, we first analyzed the behavior of 220 dog owners in 8 different standardized situations involving the owner-dog dyad. We extracted 3 behavioral factors related to " Owner Warmth ," " Owner Social Support ," and " Owner Control ." Further, we investigated whether owner personality, gender and age are associated with these three factors. Results indicated that older owners scored lower in " Owner Warmth " and in " Owner Social Support " and higher in " Owner Control " than younger owners. Furthermore, owners scoring high in " Owner Control " scored lower in the personality trait Openness and owners scoring high in " Owner Social Support " scored lower in the personality trait Conscientiousness. Finally, we also analyzed whether the dogs' reaction to an unfamiliar woman's threatening approach was associated with the owners' interaction styles. Results showed that dogs that searched for proximity of their owners during the threatening situation had owners scoring higher in " Owner Warmth ," as compared to dogs that reacted more autonomously, approaching the unfamiliar experimenter. Analogies between dog-owner interaction styles and human parenting styles are discussed considering the implications of the present findings for human social psychology as well as the practical relevance for dog welfare and human safety.

  18. Dog Owners' Interaction Styles: their Components and Associations with Reactions of Pet Dogs to a Social Threat

    Directory of Open Access Journals (Sweden)

    Giulia Cimarelli

    2016-12-01

    Full Text Available The bond dogs develop with their owner received increased attention in the last years but no study aimed at characterizing the way in which owners interact with their dogs in their daily life and how this might influence dog behavior. In order to examine how dog owners interact with their dogs, we first analyzed the behavior of 220 dog owners in 8 different standardized situations involving the owner-dog dyad. We extracted 3 behavioral factors related to Owner Warmth, Owner Social Support and Owner Control. Further, we investigated whether owner personality, gender and age are associated with these three factors. Results indicated that older owners scored lower in Owner Warmth and in Owner Social Support and higher in Owner Control than younger owners. Furthermore, owners scoring high in Owner Control scored lower in the personality trait Openness and owners scoring high in Owner Social Support scored lower in the personality trait Conscientiousness. Finally, we also analyzed whether the dogs´ reaction to an unfamiliar woman’s threatening approach was associated with the owners’ interaction styles. Results showed that dogs that searched for proximity of their owners during the threatening situation had owners scoring higher in Owner Warmth, as compared to dogs that reacted more autonomously, approaching the unfamiliar experimenter. Analogies between dog-owner interaction styles and human parenting styles are discussed considering the implications of the present findings for human social psychology as well as the practical relevance for dog welfare and human safety.

  19. Medical Schools' Industry Interaction Policies Not Associated With Trainees' Self-Reported Behavior as Residents: Results of a National Survey

    Science.gov (United States)

    Yeh, James S.; Austad, Kirsten E.; Franklin, Jessica M.; Chimonas, Susan; Campbell, Eric G.; Avorn, Jerry; Kesselheim, Aaron S.

    2015-01-01

    Background Medical students attending schools with policies limiting industry/student interactions report fewer relationships with pharmaceutical representatives. Objective To investigate whether associations between students' medical school policies and their more limited industry interaction behaviors persist into residency. Methods We randomly sampled 1800 third-year residents who graduated from 120 allopathic US-based medical schools, using the American Medical Association Physician Masterfile. We surveyed them in 2011 to determine self-reported behavior and preferences for brand-name prescriptions, and we calculated the strength of their medical schools' industry interaction policies using the 2008 American Medical Student Association and Institute on Medicine as a Profession databases. We used logistic regression to estimate the association between strength of school policies and residents' behaviors with adjustments for class size, postresidency career plan, and concern about medical school debt. Results We achieved a 44% survey response rate (n = 739). Residents who graduated from schools with restrictive policies were no more or less likely to accept industry gifts or industry-sponsored meals, speak with marketing representative about drug products, attend industry-sponsored lectures, or prefer brand-name medications than residents who graduated from schools with less restrictive policies. Residents who correctly answered evidence-based prescription questions were about 30% less likely to have attended industry-sponsored lectures (OR = 0.72, 95% CI 0.56–0.98). Conclusions Any effect that medical school industry interaction policies had on insulating students from pharmaceutical marketing did not persist in the behavior of residents in our sample. This suggests that residency training environments are important in influencing behavior. PMID:26692972

  20. Association of fat mass and obesity-associated and retinitis pigmentosa guanosine triphosphatase (GTPase) regulator-interacting protein-1 like polymorphisms with body mass index in Chinese women.

    Science.gov (United States)

    Chen, Boyu; Li, Zhiqiang; Chen, Jianhua; Ji, Jue; Shen, Jingyi; Xu, Yufeng; Zhao, Yingying; Liu, Danping; Shen, Yinhuan; Zhang, Weijie; Shen, Jiawei; Wang, Yonggang; Shi, Yongyong

    2018-04-14

    Body mass index (BMI) is the most commonly used quantitative measure of adiposity. It is a kind of complex genetic diseases which are caused by multiple susceptibility genes. The first intron of fat mass and obesity-associated (FTO) has been widely discovered to be associated with BMI. Retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L) is located in the upstream region of FTO and has been proved to be linked with obesity through functional tests. We carried out a genetic association analysis to figure out the role of the FTO gene and the RPGRIP1L gene in BMI. A quantitative traits study with 6,102 Chinese female samples, adjusted for age, was performed during our project. Among the twelve SNPs, rs1421085, rs1558902, rs17817449, rs8050136, rs9939609, rs7202296, rs56137030, rs9930506 and rs12149832 in the FTO gene were significantly associated with BMI after Bonferroni correction. Meanwhile, rs9934800 in the RPGRIP1L gene showed significance with BMI before Bonferroni correction, but this association was eliminated after Bonferroni correction. Our results suggested that genetic variants in the FTO gene were strongly associated with BMI in Chinese women, which may serve as targets of pharmaceutical research and development concerning BMI. Meanwhile, we didn't found the significant association between RPGRIP1L and BMI in Chinese women.

  1. Interaction between FOXO1A-209 Genotype and Tea Drinking is Significantly Associated with Reduced Mortality at Advanced Ages

    DEFF Research Database (Denmark)

    Zeng, Yi; Chen, Huashuai; Ni, Ting

    2016-01-01

    Based on the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality...... at advanced ages. Such significant association is replicated in two independent Han Chinese CLHLS cohorts (p =0.028-0.048 in the discovery and replication cohorts, and p =0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers...... of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably...

  2. A model of protein association based on their hydrophobic and electric interactions.

    Directory of Open Access Journals (Sweden)

    Angel Mozo-Villarías

    Full Text Available The propensity of many proteins to oligomerize and associate to form complex structures from their constituent monomers, is analyzed in terms of their hydrophobic (H, and electric pseudo-dipole (D moment vectors. In both cases these vectors are defined as the product of the distance between their positive and negative centroids, times the total hydrophobicity or total positive charge of the protein. Changes in the magnitudes and directions of H and D are studied as monomers associate to form larger complexes. We use these descriptors to study similarities and differences in two groups of associations: a open associations such as polymers with an undefined number of monomers (i.e. actin polymerization, amyloid and HIV capsid assemblies; b closed symmetrical associations of finite size, like spherical virus capsids and protein cages. The tendency of the hydrophobic moments of the monomers in an association is to align in parallel arrangements following a pattern similar to those of phospholipids in a membrane. Conversely, electric dipole moments of monomers tend to align in antiparallel associations. The final conformation of a given assembly is a fine-tuned combination of these forces, limited by steric constraints. This determines whether the association will be open (indetermined number of monomers or closed (fixed number of monomers. Any kinetic, binding or molecular peculiarities that characterize a protein assembly, comply with the vector rules laid down in this paper. These findings are also independent of protein size and shape.

  3. Association between FTO variant and change in body weight and its interaction with dietary factors

    DEFF Research Database (Denmark)

    Vimaleswaran, Karani S; Ängquist, Lars; Hansen, Rikke D

    2012-01-01

    Although FTO is an established obesity-susceptibility locus, it remains unknown whether it influences weight change in adult life and whether diet attenuates this association. Therefore, we investigated the association of FTO-rs9939609 with changes in weight and waist circumference (WC) during 6....

  4. Adverse effects and Drug Interactions Associated with Inhaled Recreational and Medical Marijuana

    OpenAIRE

    Maisha Kelly Freeman; Pilar Z Murphy

    2016-01-01

    Objectives: To provide an overview of the addiction potential; adverse effects (e.g., cardiovascular, immune dysfunction, respiratory system, mental health disorders); drug interactions; effects of accidental exposure; crime statistics; and pharmacist’s considerations for the use of inhaled medical marijuana. Methods: A PubMed search was conducted from 1966 to March 2016 to identify articles in which the safety of inhaled medical marijuana was assessed. Key MeSH search terms included med...

  5. Iron and aluminum interaction with amyloid-beta peptides associated with Alzheimer’s disease

    Energy Technology Data Exchange (ETDEWEB)

    Drochioiu, Gabi; Ion, Laura [Alexandru Ioan Cuza University of Iasi, 11 Carol I, Iasi 700506 (Romania); Murariu, Manuela; Habasescu, Laura [Petru Poni Institute of Macromolecular Chemistry, 41A Grigore Ghica Voda Alley, Iasi 700487 (Romania)

    2014-10-06

    An elevation in the concentration of heavy metal ions in Alzheimer’s disease (AD) brain has been demonstrated in many studies. Aβ precipitation and toxicity in AD brains seem to be caused by abnormal interactions with neocortical metal ions, especially iron, copper, zinc, and aluminum [1–3]. There is increasing evidence that iron and aluminum ions are involved in the mechanisms that underlie the neurodegenerative diseases [4,5]. However, evidence was brought to demonstrate that some Aβ fragments, at physiological pH, are not able to form binary complexes with Fe(III) ions of sufficient stability to compete with metal hydroxide precipitation [6]. On the contrary, multiple metal ions are known to interact with Aβ peptides [7]. Consequently, we investigated here the interaction of Fe(II/III) and Al(III) ions with some amyloid-β peptides and fragments that results in peptide aggregation and fibrillation [8,9]. Infrared spectroscopy, atomic force microscopy, scanning electron microscopy, electrophoresis and mass spectrometry demonstrated conformational changes of peptides in the presence of such metals.

  6. Interaction of nucleosome assembly proteins abolishes nuclear localization of DGKζ by attenuating its association with importins

    International Nuclear Information System (INIS)

    Okada, Masashi; Hozumi, Yasukazu; Ichimura, Tohru; Tanaka, Toshiaki; Hasegawa, Hiroshi; Yamamoto, Masakazu; Takahashi, Nobuya; Iseki, Ken; Yagisawa, Hitoshi; Shinkawa, Takashi; Isobe, Toshiaki; Goto, Kaoru

    2011-01-01

    Diacylglycerol kinase (DGK) is involved in the regulation of lipid-mediated signal transduction through the metabolism of a second messenger diacylglycerol. Of the DGK family, DGKζ, which contains a nuclear localization signal, localizes mainly to the nucleus but translocates to the cytoplasm under pathological conditions. However, the detailed mechanism of translocation and its functional significance remain unclear. To elucidate these issues, we used a proteomic approach to search for protein targets that interact with DGKζ. Results show that nucleosome assembly protein (NAP) 1-like 1 (NAP1L1) and NAP1-like 4 (NAP1L4) are identified as novel DGKζ binding partners. NAP1Ls constitutively shuttle between the nucleus and the cytoplasm in transfected HEK293 cells. The molecular interaction of DGKζ and NAP1Ls prohibits nuclear import of DGKζ because binding of NAP1Ls to DGKζ blocks import carrier proteins, Qip1 and NPI1, to interact with DGKζ, leading to cytoplasmic tethering of DGKζ. In addition, overexpression of NAP1Ls exerts a protective effect against doxorubicin-induced cytotoxicity. These findings suggest that NAP1Ls are involved in a novel molecular basis for the regulation of nucleocytoplasmic shuttling of DGKζ and provide a clue to examine functional significance of its translocation under pathological conditions.

  7. Paracrine interactions of cancer-associated fibroblasts, macrophages and endothelial cells: tumor allies and foes.

    Science.gov (United States)

    Ronca, Roberto; Van Ginderachter, Jo A; Turtoi, Andrei

    2018-01-01

    Tumor stroma is composed of many cellular subtypes, of which the most abundant are fibroblasts, macrophages and endothelial cells. During the process of tissue injury, these three cellular subtypes must coordinate their activity to efficiently contribute to tissue regeneration. In tumor, this mechanism is hijacked by cancer cells, which rewire the interaction of stromal cells to benefit tumor development. The present review aims at summarizing most relevant information concerning both pro-tumorigenic and anti-tumorigenic actions implicating the three stromal cell subtypes as well as their mutual interactions. Although stromal cells are generally regarded as tumor-supportive and at will manipulated by cancer cells, several novel studies point at many defaults in cancer cell-mediated stromal reprograming. Indeed, parts of initial tissue-protective and homeostatic functions of the stromal cells remain in place even after tumor development. Both tumor-supportive and tumor-suppressive functions have been well described for macrophages, whereas similar results are emerging for fibroblasts and endothelial cells. Recent success of immunotherapies have finally brought the long awaited proof that stroma is key for efficient tumor targeting. However, a better understanding of paracrine stromal interactions is needed in order to encourage drug development not only aiming at disruption of tumor-supportive communication but also re-enforcing, existing, tumor-suppressive mechanisms.

  8. Physical interaction between the strawberry allergen Fra a 1 and an associated partner FaAP: Interaction of Fra a 1 proteins and FaAP.

    Science.gov (United States)

    Franz-Oberdorf, Katrin; Langer, Andreas; Strasser, Ralf; Isono, Erika; Ranftl, Quirin L; Wunschel, Christian; Schwab, Wilfried

    2017-10-01

    The strawberry fruit allergens Fra a 1.01E, Fra a 1.02 and Fra a 1.03 belong to the group of pathogenesis-related 10 (PR-10) proteins and are homologs of the major birch pollen Bet v 1 and apple allergen Mal d 1. Bet v 1 related proteins are the most extensively studied allergens but their physiological function in planta remains elusive. Since Mal d 1-Associated Protein has been previously identified as interaction partner of Mal d 1 we studied the binding of the orthologous Fra a 1-Associated Protein (FaAP) to Fra a 1.01E/1.02/1.03. As the C-terminal sequence of FaAP showed strong auto-activation activity in yeast 2-hybrid analysis a novel time resolved DNA-switching system was successfully applied. Fra a 1.01E, Fra a 1.02, and Fra a 1.03 bind to FaAP with K D of 4.5 ± 1.1, 15 ± 3, and 11 ± 2 nM, respectively. Fra a 1.01E forms a dimer, whereas Fra a 1.02 and Fra a 1.03 bind as monomer. The results imply that PR-10 proteins might be integrated into a protein-interaction network and FaAP binding appears to be essential for the physiological function of the Fra a 1 proteins. © 2017 Wiley Periodicals, Inc.

  9. Drug-Drug Interaction Associated with Mold-Active Triazoles among Hospitalized Patients.

    Science.gov (United States)

    Andes, David; Azie, Nkechi; Yang, Hongbo; Harrington, Rachel; Kelley, Caroline; Tan, Ruo-Ding; Wu, Eric Q; Franks, Billy; Kristy, Rita; Lee, Edward; Khandelwal, Nikhil; Spalding, James

    2016-06-01

    The majority of hospitalized patients receiving mold-active triazoles are at risk of drug-drug interactions (DDIs). Efforts are needed to increase awareness of DDIs that pose a serious risk of adverse events. Triazoles remain the most commonly utilized antifungals. Recent developments have included the mold-active triazoles (MATs) itraconazole, voriconazole, and posaconazole, which are first-line agents for the treatment of filamentous fungal infections but have the potential for DDIs. This objective of this study was to evaluate the prevalence of triazole DDIs. Hospitalized U.S. adults with MAT use were identified in the Cerner HealthFacts database, which contained data from over 150 hospitals (2005 to 2013). The severities of DDIs with MATs were categorized, using drug labels and the drug information from the Drugdex system (Thompson Micromedex), into four groups (contraindicated, major, moderate, and minor severity). DDIs of minor severity were not counted. A DDI event was considered to have occurred if the following two conditions were met: (i) the patient used at least one drug with a classification of at least a moderate interaction with the MAT during the hospitalization and (ii) there was a period of overlap between the administration of the MAT and that of the interacting drug of at least 1 day. A total of 6,962 hospitalizations with MAT use were identified. Among them, 88% of hospitalizations with voriconazole use, 86% of hospitalizations with itraconazole use, and 93% of hospitalizations with posaconazole use included the use of a concomitant interacting drug. A total of 68% of hospitalizations with posaconazole use, 34% of hospitalizations with itraconazole use, and 20% of hospitalizations with voriconazole use included the use of at least one drug with a DDI of contraindicated severity. A total of 83% of hospitalizations with posaconazole use, 61% of hospitalizations with itraconazole use, and 82% of hospitalizations with voriconazole use included the

  10. Association of the Interaction Between Smoking and Depressive Symptom Clusters With Coronary Artery Calcification: The CARDIA Study.

    Science.gov (United States)

    Carroll, Allison J; Auer, Reto; Colangelo, Laura A; Carnethon, Mercedes R; Jacobs, David R; Stewart, Jesse C; Widome, Rachel; Carr, John Jeffrey; Liu, Kiang; Hitsman, Brian

    2017-01-01

    Depressive symptom clusters are differentially associated with prognosis among patients with cardiovascular disease (CVD). Few studies have prospectively evaluated the association between depressive symptom clusters and risk of CVD. Previously, we observed that smoking and global depressive symptoms were synergistically associated with coronary artery calcification (CAC). The purpose of this study was to determine whether the smoking by depressive symptoms interaction, measured cumulatively over 25 years, differed by depressive symptom cluster (negative affect, anhedonia, and somatic symptoms) in association with CAC. Participants (N = 3,189: 54.5% female; 51.5% Black; average age = 50.1 years) were followed from 1985-1986 through 2010-2011 in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Smoking exposure was measured by cumulative cigarette pack-years (cigarette packs smoked per day × number of years smoking; year 0 through year 25). Depressive symptoms were measured using a 14-item, 3-factor (negative affect, anhedonia, somatic symptoms) model of the Center for Epidemiologic Studies Depression (CES-D) Scale (years 5, 10, 15, 20, and 25). CAC was assessed at year 25. Logistic regression models were used to evaluate the association between the smoking by depressive symptom clusters interactions with CAC ( = 0 vs. > 0), adjusted for CVD-related sociodemographic, behavioral, and clinical covariates. 907 participants (28% of the sample) had CAC > 0 at year 25. The depressive symptom clusters did not differ significantly between the two groups. Only the cumulative somatic symptom cluster by cumulative smoking exposure interaction was significantly associated with CAC > 0 at year 25 (p = .028). Specifically, adults with elevated somatic symptoms (score 9 out of 18) who had 10, 20, or 30 pack-years of smoking exposure had respective odds ratios (95% confidence intervals) of 2.06 [1.08, 3.93], 3.71 [1.81, 7.57], and 6.68 [2.87, 15.53], ps affect

  11. Interactive associations of physical activity, adiposity, and oral contraceptive use on C-reactive protein levels in young women.

    Science.gov (United States)

    Fedewa, Michael V; Hathaway, Elizabeth D; Higgins, Simon; Das, Bhibha M; Forehand, Ronald L; Schmidt, Michael D; Evans, Ellen M

    2018-02-01

    Oral contraceptives (OCs) are the most frequently used type of birth control among young women. OC-users have higher C-reactive protein (CRP) values, an indicator of systemic inflammation, than do non-OC-users. In addition, adiposity (percent fat) is positively associated with CRP, and physical activity (PA) is inversely associated with CRP. The present study determined the interactive associations of PA, percent fat, and OC-use with CRP. Data were collected during 2012-2015 at the University of Georgia. Objective PA was measured via pedometers. Percent fat was measured via dual X-ray absorptiometry. The current OC-use was self-reported. High-sensitivity (hs) CRP was determined using venipuncture. Multivariate linear regression determined the interactive associations of percent fat, OC-use, and PA with hs-CRP. Participants (n = 247; mean age 18.9 ± 1.4 years, 60.7 percent white) accumulated a mean of 10,075.7 ± 3,593.4 steps/day. One-third of participants were categorized as overweight/obese by BMI (mean = 24.5 ± 4.8 kg/m 2 , mean percent fat = 35.2 ± 6.8). The current OC-use was reported by 26.2 percent of the sample (n = 61). A significant three-way interaction (β = 0.01, p = .03) indicated that higher PA was associated with lower hs-CRP in non-OC-users with higher percent fat, but not among OC-users with higher percent fat. These results highlight the need to measure and account for the current OC-use in studies examining the relationship between PA and CRP.

  12. Older age and steroid use are associated with increasing polypharmacy and potential medication interactions among patients with inflammatory bowel disease.

    Science.gov (United States)

    Parian, Alyssa; Ha, Christina Y

    2015-06-01

    Comorbidity and polypharmacy, more prevalent among older persons, may impact the treatment of patients with inflammatory bowel disease (IBD). The aims of this study were to assess the frequency of polypharmacy and medication interactions within a cohort of older patients with IBD and describe IBD treatment patterns. Cohort study of 190 patients with IBD 65 years or older followed at a tertiary IBD referral center from 2006 to 2012. Data collected included demographics, IBD-specific characteristics including disease activity, and comorbidity. Medication histories were extracted from medical records, and data were used to classify polypharmacy, frequency, and severity of potential medication interactions and inappropriate medication use. Older patients with IBD were prescribed an average of 9 routine medications. Severe polypharmacy (≥10 routine medications) was present in 43.2% of studied patients and associated with increasing age, greater comorbidity, and steroid use. Overall, 73.7% of patients had at least 1 potential medication interaction, including 40% of patients with potential IBD medication-associated interactions. Chronic steroids were prescribed to 40% of the older patients including 24% who were in remission or with mild disease activity. Only 39.5% of patients were on immunomodulators and 21.1% on biologics. Approximately, 35% of patients were given at least 1 Beers inappropriate medication and almost 10% were receiving chronic narcotics. Older patients with IBD are at increased risk for severe polypharmacy and potential major medication interactions especially with increasing comorbidity and chronic steroid use. Steroid-maintenance therapies are prevalent among the older patients with IBD with lower utilization of steroid-sparing regimens.

  13. GENIE: a software package for gene-gene interaction analysis in genetic association studies using multiple GPU or CPU cores

    Directory of Open Access Journals (Sweden)

    Wang Kai

    2011-05-01

    Full Text Available Abstract Background Gene-gene interaction in genetic association studies is computationally intensive when a large number of SNPs are involved. Most of the latest Central Processing Units (CPUs have multiple cores, whereas Graphics Processing Units (GPUs also have hundreds of cores and have been recently used to implement faster scientific software. However, currently there are no genetic analysis software packages that allow users to fully utilize the computing power of these multi-core devices for genetic interaction analysis for binary traits. Findings Here we present a novel software package GENIE, which utilizes the power of multiple GPU or CPU processor cores to parallelize the interaction analysis. GENIE reads an entire genetic association study dataset into memory and partitions the dataset into fragments with non-overlapping sets of SNPs. For each fragment, GENIE analyzes: 1 the interaction of SNPs within it in parallel, and 2 the interaction between the SNPs of the current fragment and other fragments in parallel. We tested GENIE on a large-scale candidate gene study on high-density lipoprotein cholesterol. Using an NVIDIA Tesla C1060 graphics card, the GPU mode of GENIE achieves a speedup of 27 times over its single-core CPU mode run. Conclusions GENIE is open-source, economical, user-friendly, and scalable. Since the computing power and memory capacity of graphics cards are increasing rapidly while their cost is going down, we anticipate that GENIE will achieve greater speedups with faster GPU cards. Documentation, source code, and precompiled binaries can be downloaded from http://www.cceb.upenn.edu/~mli/software/GENIE/.

  14. Maternal Time Use and Nurturing: Analysis of the Association Between Breastfeeding Practice and Time Spent Interacting with Baby.

    Science.gov (United States)

    Smith, Julie P; Forrester, Robert

    2017-06-01

    Breastfeeding supports child development through complex mechanisms that are not well understood. Numerous studies have compared how well breastfeeding and nonbreastfeeding mothers interact with their child, but few examine how much interaction occurs. Our study of weekly time use among 156 mothers of infants aged 3-9 months investigated whether lactating mothers spend more time providing emotional support or cognitive stimulation of their infants than nonbreastfeeding mothers, and whether the amount of such interactive time is associated with breastfeeding intensity. Mothers were recruited via mother's and baby groups, infant health clinics, and childcare services, and used an electronic device to record their 24-hour time use for 7 days. Sociodemographic and feeding status data were collected by questionnaire. Statistical analysis using linear mixed modeling and residual maximum likelihood analysis compared maternal time use for those giving "some breastfeeding" and those "not breastfeeding." Analysis was also conducted for more detailed feeding subgroups. Breastfeeding and nonbreastfeeding mothers had broadly similar socioeconomic and demographic characteristics. Breastfeeding was found to be associated with more mother-child interaction time, a difference only partially explained by weekly maternal employment hours or other interactive care activities such as play or reading. This study presents data suggesting that lactating mothers spent significantly more hours weekly on milk feeding and on carrying, holding, or soothing their infant than nonlactating mothers; and on providing childcare. Understanding the mechanisms by which child mental health and development benefits from breastfeeding may have important implications for policies and intervention strategies, and could be usefully informed by suitably designed time use studies.

  15. Huntingtin-associated protein-1 (HAP1) regulates endocytosis and interacts with multiple trafficking-related proteins.

    Science.gov (United States)

    Mackenzie, Kimberly D; Lim, Yoon; Duffield, Michael D; Chataway, Timothy; Zhou, Xin-Fu; Keating, Damien J

    2017-07-01

    Huntingtin-associated protein 1 (HAP1) was initially identified as a binding partner of huntingtin, mutations in which underlie Huntington's disease. Subcellular localization and protein interaction data indicate that HAP1 may be important in vesicle trafficking, cell signalling and receptor internalization. In this study, a proteomics approach was used for the identification of novel HAP1-interacting partners to attempt to shed light on the physiological function of HAP1. Using affinity chromatography with HAP1-GST protein fragments bound to Sepharose columns, this study identified a number of trafficking-related proteins that bind to HAP1. Interestingly, many of the proteins that were identified by mass spectrometry have trafficking-related functions and include the clathrin light chain B and Sec23A, an ER to Golgi trafficking vesicle coat component. Using co-immunoprecipitation and GST-binding assays the association between HAP1 and clathrin light chain B has been validated in vitro. This study also finds that HAP1 co-localizes with clathrin light chain B. In line with a physiological function of the HAP1-clathrin interaction this study detected a dramatic reduction in vesicle retrieval and endocytosis in adrenal chromaffin cells. Furthermore, through examination of transferrin endocytosis in HAP1 -/- cortical neurons, this study has determined that HAP1 regulates neuronal endocytosis. In this study, the interaction between HAP1 and Sec23A was also validated through endogenous co-immunoprecipitation in rat brain homogenate. Through the identification of novel HAP1 binding partners, many of which have putative trafficking roles, this study provides us with new insights into the mechanisms underlying the important physiological function of HAP1 as an intracellular trafficking protein through its protein-protein interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Computational Framework for Prediction of Peptide Sequences That May Mediate Multiple Protein Interactions in Cancer-Associated Hub Proteins.

    Directory of Open Access Journals (Sweden)

    Debasree Sarkar

    Full Text Available A considerable proportion of protein-protein interactions (PPIs in the cell are estimated to be mediated by very short peptide segments that approximately conform to specific sequence patterns known as linear motifs (LMs, often present in the disordered regions in the eukaryotic proteins. These peptides have been found to interact with low affinity and are able bind to multiple interactors, thus playing an important role in the PPI networks involving date hubs. In this work, PPI data and de novo motif identification based method (MEME were used to identify such peptides in three cancer-associated hub proteins-MYC, APC and MDM2. The peptides corresponding to the significant LMs identified for each hub protein were aligned, the overlapping regions across these peptides being termed as overlapping linear peptides (OLPs. These OLPs were thus predicted to be responsible for multiple PPIs of the corresponding hub proteins and a scoring system was developed to rank them. We predicted six OLPs in MYC and five OLPs in MDM2 that scored higher than OLP predictions from randomly generated protein sets. Two OLP sequences from the C-terminal of MYC were predicted to bind with FBXW7, component of an E3 ubiquitin-protein ligase complex involved in proteasomal degradation of MYC. Similarly, we identified peptides in the C-terminal of MDM2 interacting with FKBP3, which has a specific role in auto-ubiquitinylation of MDM2. The peptide sequences predicted in MYC and MDM2 look promising for designing orthosteric inhibitors against possible disease-associated PPIs. Since these OLPs can interact with other proteins as well, these inhibitors should be specific to the targeted interactor to prevent undesired side-effects. This computational framework has been designed to predict and rank the peptide regions that may mediate multiple PPIs and can be applied to other disease-associated date hub proteins for prediction of novel therapeutic targets of small molecule PPI

  17. Cortico-hippocampal interaction and adaptive stimulus representation: A neurocomputational theory of associative learning and memory.

    NARCIS (Netherlands)

    Gluck, M.A.; Myers, C.E; Meeter, M.

    2005-01-01

    Computational models of the hippocampal region link psychological theories of associative learning with their underlying physiological and anatomical substrates. Our approach to theory development began with a broad description of the computations that depend on the hippocampal region in classical

  18. Allometry of animal-microbe interactions and global census of animal-associated microbes.

    Science.gov (United States)

    Kieft, Thomas L; Simmons, Karen A

    2015-07-07

    Animals live in close association with microorganisms, mostly prokaryotes, living in or on them as commensals, mutualists or parasites, and profoundly affecting host fitness. Most animal-microbe studies focus on microbial community structure; for this project, allometry (scaling of animal attributes with animal size) was applied to animal-microbe relationships across a range of species spanning 12 orders of magnitude in animal mass, from nematodes to whales. Microbial abundances per individual animal were gleaned from published literature and also microscopically counted in three species. Abundance of prokaryotes/individual versus animal mass scales as a nearly linear power function (exponent = 1.07, R(2) = 0.94). Combining this power function with allometry of animal abundance indicates that macrofauna have an outsized share of animal-associated microorganisms. The total number of animal-associated prokaryotes in Earth's land animals was calculated to be 1.3-1.4 × 10(25) cells and the total of marine animal-associated microbes was calculated to be 8.6-9.0 × 10(24) cells. Animal-associated microbes thus total 2.1-2.3 × 10(25) of the approximately 10(30) prokaryotes on the Earth. Microbes associated with humans comprise 3.3-3.5% of Earth's animal-associated microbes, and domestic animals harbour 14-20% of all animal-associated microbes, adding a new dimension to the scale of human impact on the biosphere. This novel allometric power function may reflect underlying mechanisms involving the transfer of energy and materials between microorganisms and their animal hosts. Microbial diversity indices of animal gut communities and gut microbial species richness for 60 mammals did not indicate significant scaling relationships with animal body mass; however, further research in this area is warranted. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  19. Recurrent variations of anomalous oxygen in association with a corotating interaction region

    Directory of Open Access Journals (Sweden)

    M. K. Reuss

    Full Text Available The fluxes of anomalous oxygen (E ranging from 3.5-6.8 MeV/amu, as measured by the EPAC instrument on ULYSSES, show a recurrent variation with the solar rotation period, which is anticorrelated with the fluxes of particles accelerated at the shocks of a corotating interaction region (CIR, and correlated with the fluxes of galactic cosmic rays known to be modulated by the CIR. The amplitude of this variation is much higher than expected for galactic cosmic rays of the same rigidity.

  20. Genome-wide gene-asbestos exposure interaction association study identifies a common susceptibility variant on 22q13.31 associated with lung cancer risk

    Science.gov (United States)

    Liu, Chen-yu; Stücker, Isabelle; Chen, Chu; Goodman, Gary; McHugh, Michelle K.; D’Amelio, Anthony M.; Etzel, Carol J.; Li, Su; Lin, Xihong; Christiani, David C.

    2015-01-01

    Background Occupational asbestos exposure has been found to increase lung cancer risk in epidemiological studies. Methods We conducted an asbestos exposure-gene interaction analyses among several Caucasian populations who were current or ex-smokers. The discovery phase included 833 Caucasian cases and 739 Caucasian controls, and used a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) with gene-asbestos interaction effects. The top ranked SNPs from the discovery phase were replicated within the International Lung and Cancer Consortium (ILCCO). First, in silico replication was conducted in those groups that had GWAS and asbestos exposure data, including 1,548 cases and 1,527 controls. This step was followed by de novo genotyping to replicate the results from the in silico replication, and included 1,539 cases and 1,761 controls. Multiple logistic regression was used to assess the SNP-asbestos exposure interaction effects on lung cancer risk. Results We observed significantly increased lung cancer risk among MIRLET7BHG (MIRLET7B host gene located at 22q13.31) polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325 heterozygous and homozygous variant allele(s) carriers [pasbestos exposure score was associated with age-, sex-, smoking status- and center-adjusted ORs of 1.34 (95%CI=1.18–1.51), 1.24 (95%CI=1.14–1.35), 1.28 (95%CI=1.17–1.40), and 1.26 (95%CI=1.15–1.38), respectively for lung cancer risk. Conclusion Our findings suggest that MIRLET7BHG polymorphisms may be important predictive markers for asbestos exposure-related lung cancer. Impact To our knowledge, our study is the first report using a systematic genome-wide analysis in combination with detailed asbestos exposure data and replication to evaluate asbestos-associated lung cancer risk. PMID:26199339

  1. Fungal Volatiles Can Act as Carbon Sources and Semiochemicals to Mediate Interspecific Interactions Among Bark Beetle-Associated Fungal Symbionts.

    Directory of Open Access Journals (Sweden)

    Jonathan A Cale

    Full Text Available Mountain pine beetle (Dendroctonus ponderosae has killed millions of hectares of pine forests in western North America. Beetle success is dependent upon a community of symbiotic fungi comprised of Grosmannia clavigera, Ophiostoma montium, and Leptographium longiclavatum. Factors regulating the dynamics of this community during pine infection are largely unknown. However, fungal volatile organic compounds (FVOCs help shape fungal interactions in model and agricultural systems and thus may be important drivers of interactions among bark beetle-associated fungi. We investigated whether FVOCs can mediate interspecific interactions among mountain pine beetle's fungal symbionts by affecting fungal growth and reproduction. Headspace volatiles were collected and identified to determine species-specific volatile profiles. Interspecific effects of volatiles on fungal growth and conidia production were assessed by pairing physically-separated fungal cultures grown either on a carbon-poor or -rich substrate, inside a shared-headspace environment. Fungal VOC profiles differed by species and influenced the growth and/or conidia production of the other species. Further, our results showed that FVOCs can be used as carbon sources for fungi developing on carbon-poor substrates. This is the first report demonstrating that FVOCs can drive interactions among bark beetle fungal symbionts, and thus are important factors in beetle attack success.

  2. Review on Microwave-Matter Interaction Fundamentals and Efficient Microwave-Associated Heating Strategies

    Science.gov (United States)

    Sun, Jing; Wang, Wenlong; Yue, Qinyan

    2016-01-01

    Microwave heating is rapidly emerging as an effective and efficient tool in various technological and scientific fields. A comprehensive understanding of the fundamentals of microwave–matter interactions is the precondition for better utilization of microwave technology. However, microwave heating is usually only known as dielectric heating, and the contribution of the magnetic field component of microwaves is often ignored, which, in fact, contributes greatly to microwave heating of some aqueous electrolyte solutions, magnetic dielectric materials and certain conductive powder materials, etc. This paper focuses on this point and presents a careful review of microwave heating mechanisms in a comprehensive manner. Moreover, in addition to the acknowledged conventional microwave heating mechanisms, the special interaction mechanisms between microwave and metal-based materials are attracting increasing interest for a variety of metallurgical, plasma and discharge applications, and therefore are reviewed particularly regarding the aspects of the reflection, heating and discharge effects. Finally, several distinct strategies to improve microwave energy utilization efficiencies are proposed and discussed with the aim of tackling the energy-efficiency-related issues arising from the application of microwave heating. This work can present a strategic guideline for the developed understanding and utilization of the microwave heating technology. PMID:28773355

  3. Pax6 interacts with Iba1 and shows age-associated alterations in brain of aging mice.

    Science.gov (United States)

    Maurya, Shashank Kumar; Mishra, Rajnikant

    2017-07-01

    The Pax6, a transcriptional regulator and multifunctional protein, has been found critical for neurogenesis, neuro-degeneration, mental retardation, neuroendocrine tumors, glioblastoma and astrocytomas. The age-associated alteration in the expression of Pax6 in neuron and glia has also been observed in the immunologically privileged brain. Therefore, it is presumed that Pax6 may modulate brain immunity by activation of microglia either directly interacting with genes or proteins of microglia or indirectly though inflammation associated with neurodegeneration. This report describes evaluation of expression, co-localization and interactions of Pax6 with Ionized binding protein1 (Iba1) in brain of aging mice by Immunohistochemistry, Chromatin Immuno-precipitation (ChIP) and Co-immunoprecipitation (Co-IP), respectively. The co-localization of Pax6 with Iba1 was observed in the cerebellum, cerebral cortex, hippocampus, midbrain and olfactory lobe. The Pax6 and Iba1 also interact physically. The age-dependent alteration in their expression and co-localization were also observed in mice. Results indicate Pax6-dependent activities of Iba1 in the remodelling of microglia during immunological surveillance of the brain. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. The membrane-associated form of α(s1-casein interacts with cholesterol-rich detergent-resistant microdomains.

    Directory of Open Access Journals (Sweden)

    Annabelle Le Parc

    Full Text Available Caseins, the main milk proteins, interact with colloidal calcium phosphate to form the casein micelle. The mesostructure of this supramolecular assembly markedly influences its nutritional and technological functionalities. However, its detailed molecular organization and the cellular mechanisms involved in its biogenesis have been only partially established. There is a growing body of evidence to support the concept that α(s1-casein takes center stage in casein micelle building and transport in the secretory pathway of mammary epithelial cells. Here we have investigated the membrane-associated form of α(s1-casein in rat mammary epithelial cells. Using metabolic labelling we show that α(s1-casein becomes associated with membranes at the level of the endoplasmic reticulum, with no subsequent increase at the level of the Golgi apparatus. From morphological and biochemical data, it appears that caseins are in a tight relationship with membranes throughout the secretory pathway. On the other hand, we have observed that the membrane-associated form of α(s1-casein co-purified with detergent-resistant membranes. It was poorly solubilised by Tween 20, partially insoluble in Lubrol WX, and substantially insoluble in Triton X-100. Finally, we found that cholesterol depletion results in the release of the membrane-associated form of α(s1-casein. These experiments reveal that the insolubility of α(s1-casein reflects its partial association with a cholesterol-rich detergent-resistant microdomain. We propose that the membrane-associated form of α(s1-casein interacts with the lipid microdomain, or lipid raft, that forms within the membranes of the endoplasmic reticulum, for efficient forward transport and sorting in the secretory pathway of mammary epithelial cells.

  5. Reliability associated with the Roter Interaction Analysis System (RIAS) adapted for the telemedicine context.

    Science.gov (United States)

    Nelson, Eve-Lynn; Miller, Edward Alan; Larson, Kiley A

    2010-01-01

    This study's purpose was to adapt the Roter Interaction Analysis System (RIAS) for telemedicine clinics and to investigate the adapted measure's reliability. The study also sought to better understand the volume of technology-related utterance in established telemedicine clinics and the feasibility of using the measure within the telemedicine setting. This initial evaluation is a first step before broadly using the adapted measure across technologies and raters. An expert panel adapted the RIAS for the telemedicine context. This involved accounting for all consultation participants (patient, provider, presenter, family) and adding technology-specific subcategories. Ten new and 36 follow-up telemedicine encounters were videotaped and double coded using the adapted RIAS. These consisted primarily of follow-up visits (78.0%) involving patients, providers, presenters, and other parties. Reliability was calculated for those categories with 15 or more utterances. Traditional RIAS categories related to socioemotional and task-focused clusters had fair to excellent levels of reliability in the telemedicine setting. Although there were too few utterances to calculate the reliability of the specific technology-related subcategories, the summary technology-related category proved reliable for patients, providers, and presenters. Overall patterns seen in traditional patient-provider interactions were observed, with the number of provider utterances far exceeding patient, presenter, and family utterances, and few technology-specific utterances. The traditional RIAS is reliable when applied across multiple participants in the telemedicine context. Reliability of technology-related subcategories could not be evaluated; however, the aggregate technology-related cluster was found to be reliable and may be especially relevant in understanding communication patterns with patients new to the telemedicine setting. Use of the RIAS instrument is encouraged to facilitate comparison

  6. Retrospective analysis of main and interaction effects in genetic association studies of human complex traits

    DEFF Research Database (Denmark)

    Tan, Qihua; Christiansen, Lene; Brasch-Andersen, Charlotte

    2007-01-01

    with that of the case-only model. RESULTS: Results from our simulation study indicate that our retrospective model exhibits high power in capturing even relatively small effect with reasonable sample sizes. Application of our method to data from an association study on the catalase -262C/T promoter polymorphism...

  7. The Blues of Adolescent Romance: Observed Affective Interactions in Adolescent Romantic Relationships Associated with Depressive Symptoms

    NARCIS (Netherlands)

    Ha, P.T.; Dishion, T.J.; Overbeek, G.J.; Burk, W.J.; Engels, R.C.M.E.

    2014-01-01

    We examined the associations between observed expressions of positive and negative emotions during conflict discussions and depressive symptoms during a 2-year period in a sample of 160 adolescents in 80 romantic relationships (M age = 15.48, SD = 1.16). Conflict discussions were coded using the

  8. The blues of adolescent romance: Observed affective interactions in adolescent romantic relationships associated with depressive symptoms

    NARCIS (Netherlands)

    Ha, T.; Dishion, T.J.; Overbeek, G.; Burk, W.J.; Engels, R.C.M.E.

    2014-01-01

    We examined the associations between observed expressions of positive and negative emotions during conflict discussions and depressive symptoms during a 2-year period in a sample of 160 adolescents in 80 romantic relationships (M age = 15.48, SD = 1.16). Conflict discussions were coded using the

  9. Multifactor dimensionality reduction reveals gene–gene interactions associated with multiple sclerosis susceptibility in African Americans

    OpenAIRE

    Brassat, D; Motsinger, AA; Caillier, SJ; Erlich, HA; Walker, K; Steiner, LL; Cree, BAC; Barcellos, LF; Pericak-Vance, MA; Schmidt, S; Gregory, S; Hauser, SL; Haines, JL; Oksenberg, JR; Ritchie, MD

    2006-01-01

    Multiple sclerosis (MS) is a common disease of the central nervous system characterized by inflammation, myelin loss, gliosis, varying degrees of axonal pathology, and progressive neurological dysfunction. Multiple sclerosis exhibits many of the characteristics that distinguish complex genetic disorders including polygenic inheritance and environmental exposure risks. Here, we used a highly efficient multilocus genotyping assay representing variation in 34 genes associated with inflammatory p...

  10. Seaweed-microbial interactions: key functions of seaweed-associated bacteria.

    Science.gov (United States)

    Singh, Ravindra Pal; Reddy, C R K

    2014-05-01

    Seaweed-associated bacteria play a crucial role in morphogenesis and growth of seaweeds (macroalgae) in direct and/or indirect ways. Bacterial communities belonging to the phyla Proteobacteria and Firmicutes are generally the most abundant on seaweed surfaces. Associated bacterial communities produce plant growth-promoting substances, quorum sensing signalling molecules, bioactive compounds and other effective molecules that are responsible for normal morphology, development and growth of seaweeds. Also, bioactive molecules of associated bacteria determine the presence of other bacterial strains on seaweeds and protect the host from harmful entities present in the pelagic realm. The ecological functions of cross-domain signalling between seaweeds and bacteria have been reported as liberation of carpospores in the red seaweeds and settlement of zoospores in the green seaweeds. In the present review, the role of extracellular polymeric substances in growth and settlement of seaweeds spores is also highlighted. To elucidate the functional roles of associated bacteria and the molecular mechanisms underlying reported ecological phenomena in seaweeds requires a combined ecological, microbiological and biochemical approach. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  11. How do associative and phonemic overlap interact to boost illusory recollection?

    Science.gov (United States)

    Hutchison, Keith A; Meade, Michelle L; Williams, Nikolas S; Manley, Krista D; McNabb, Jaimie C

    2017-10-24

    This project investigated the underlying mechanisms that boost false remember responses when participants receive study words that are both semantically and phonologically similar to a critical lure. Participants completed a memory task in which they were presented with a list of words all associated with a critical lure. Included within the list of semantic associates was a target that was either semantically associated (e.g., yawn) to the critical lure (e.g., sleep) or shared the initial (e.g., slam) or final (e.g., beep) phoneme(s) with the critical lure. After hearing the list, participants recalled each list item and indicated whether they just knew it was on the list or if they instead recollected specific contextual details of that item's presentation. We found that inserting an initial phonemic overlap target boosted experiences of recollection, but only when semantically related associates were presented beforehand. The results are consistent with models of spoken word recognition and show that established semantic context plus initial phonemic overlap play important roles in boosting false recollection.

  12. The role of migraine headache severity, associated features and interactions with overweight/obesity in inhibitory control.

    Science.gov (United States)

    Galioto, Rachel; O'Leary, Kevin C; Gunstad, John; Thomas, J Graham; Lipton, Richard B; Pavlović, Jelena M; Roth, Julie; Rathier, Lucille; Bond, Dale S

    2018-01-01

    While migraine and obesity are related and both conditions are associated with reduced executive functioning, no study has examined whether obesity exacerbates executive dysfunction in migraine. This cross-sectional study examined whether overweight/obesity moderated associations of migraine severity and associated features with inhibitory control, one aspect of executive function. Women (n = 124) aged 18-50 years old with overweight/obesity body mass index (BMI) = 35.1 ± 6.4 kg/m 2 and migraine completed a 28-day smartphone-based headache diary assessing migraine headache severity (attack frequency, pain intensity) and frequency of associated features (aura, photophobia, phonophobia, nausea). They then completed computerized measures of inhibitory control during an interictal (headache-free) period. Participants with higher migraine attack frequency performed worse on the Flanker test (accuracy and reaction time; p < .05). Migraine attack frequency and pain intensity interacted with BMI to predict slower Stroop and/or Flanker Reaction Time (RT; p < .05). More frequent photophobia, phonophobia and aura were independently related to slower RT on the Stroop and/or Flanker tests (p < .05), and BMI moderated the relationship between the occurrence of aura and Stroop RT (p = .03). Associations of migraine severity and presence of associated features with inhibitory control varied by BMI in overweight/obese women with migraine. These findings warrant consideration of weight status in clarifying the role of migraine in executive functioning.

  13. Microbial interactions with naturally occurring hydrophobic sediments: Influence on sediment and associated contaminant mobility.

    Science.gov (United States)

    Droppo, I G; Krishnappan, B G; Lawrence, J R

    2016-04-01

    The erosion, transport and fate of sediments and associated contaminants are known to be influenced by both particle characteristics and the flow dynamics imparted onto the sediment. The influential role of bitumen containing hydrophobic sediments and the microbial community on sediment dynamics are however less understood. This study links an experimental evaluation of sediment erosion with measured sediment-associated contaminant concentrations and microbial community analysis to provide an estimate of the potential for sediment to control the erosion, transport and fate of contaminants. Specifically the paper addresses the unique behaviour of hydrophobic sediments and the role that the microbial community associated with hydrophobic sediment may play in the transport of contaminated sediment. Results demonstrate that the hydrophobic cohesive sediment demonstrates unique transport and particle characteristics (poor settling and small floc size). Biofilms were observed to increase with consolidation/biostabilization times and generated a unique microbial consortium relative to the eroded flocs. Natural oil associated with the flocs appeared to be preferentially associated with microbial derived extracellular polymeric substances. While PAHs and naphthenic acid increased with increasing shear (indicative of increasing loads), they tended to decrease with consolidation/biostabilization (CB) time at similar shears suggesting a chemical and/or biological degradation. PAH and napthenic acid degrading microbes decreased with time as well, which may suggest that there was a reduced pool of PAHs and naphthenic acids available resulting in their die off. This study emphasizes the importance that any management strategies and operational assessments for the protection of human and aquatic health incorporate the sediment (suspended and bed sediment) and biological (biofilm) compartments and the energy dynamics within the system in order to better predict contaminant

  14. Hsp90 interacts specifically with viral RNA and differentially regulates replication initiation of Bamboo mosaic virus and associated satellite RNA.

    Directory of Open Access Journals (Sweden)

    Ying Wen Huang

    Full Text Available Host factors play crucial roles in the replication of plus-strand RNA viruses. In this report, a heat shock protein 90 homologue of Nicotiana benthamiana, NbHsp90, was identified in association with partially purified replicase complexes from BaMV-infected tissue, and shown to specifically interact with the 3' untranslated region (3' UTR of BaMV genomic RNA, but not with the 3' UTR of BaMV-associated satellite RNA (satBaMV RNA or that of genomic RNA of other viruses, such as Potato virus X (PVX or Cucumber mosaic virus (CMV. Mutational analyses revealed that the interaction occurs between the middle domain of NbHsp90 and domain E of the BaMV 3' UTR. The knockdown or inhibition of NbHsp90 suppressed BaMV infectivity, but not that of satBaMV RNA, PVX, or CMV in N. benthamiana. Time-course analysis further revealed that the inhibitory effect of 17-AAG is significant only during the immediate early stages of BaMV replication. Moreover, yeast two-hybrid and GST pull-down assays demonstrated the existence of an interaction between NbHsp90 and the BaMV RNA-dependent RNA polymerase. These results reveal a novel role for NbHsp90 in the selective enhancement of BaMV replication, most likely through direct interaction with the 3' UTR of BaMV RNA during the initiation of BaMV RNA replication.

  15. Modeling liquid-vapor equilibria with an equation of state taking into account dipolar interactions and association by hydrogen bonding

    International Nuclear Information System (INIS)

    Perfetti, E.

    2006-11-01

    Modelling fluid-rock interactions as well as mixing and unmixing phenomena in geological processes requires robust equations of state (EOS) which must be applicable to systems containing water, gases over a broad range of temperatures and pressures. Cubic equations of state based on the Van der Waals theory (e. g. Soave-Redlich-Kwong or Peng-Robinson) allow simple modelling from the critical parameters of the studied fluid components. However, the accuracy of such equations becomes poor when water is a major component of the fluid since neither association trough hydrogen bonding nor dipolar interactions are accounted for. The Helmholtz energy of a fluid may be written as the sum of different energetic contributions by factorization of partition function. The model developed in this thesis for the pure H 2 O and H 2 S considers three contributions. The first contribution represents the reference Van der Waals fluid which is modelled by the SRK cubic EOS. The second contribution accounts for association through hydrogen bonding and is modelled by a term derived from Cubic Plus Association (CPA) theory. The third contribution corresponds to the dipolar interactions and is modelled by the Mean Spherical Approximation (MSA) theory. The resulting CPAMSA equation has six adjustable parameters, which three represent physical terms whose values are close to their experimental counterpart. This equation results in a better reproduction of the thermodynamic properties of pure water than obtained using the classical CPA equation along the vapour-liquid equilibrium. In addition, extrapolation to higher temperatures and pressure is satisfactory. Similarly, taking into account dipolar interactions together with the SRK cubic equation of state for calculating molar volume of H 2 S as a function of pressure and temperature results in a significant improvement compared to the SRK equation alone. Simple mixing rules between dipolar molecules are proposed to model the H 2 O-H 2 S

  16. An environmental analysis of genes associated with schizophrenia: hypoxia and vascular factors as interacting elements in the neurodevelopmental model.

    Science.gov (United States)

    Schmidt-Kastner, R; van Os, J; Esquivel, G; Steinbusch, H W M; Rutten, B P F

    2012-12-01

    Investigating and understanding gene-environment interaction (G × E) in a neurodevelopmentally and biologically plausible manner is a major challenge for schizophrenia research. Hypoxia during neurodevelopment is one of several environmental factors related to the risk of schizophrenia, and links between schizophrenia candidate genes and hypoxia regulation or vascular expression have been proposed. Given the availability of a wealth of complex genetic information on schizophrenia in the literature without knowledge on the connections to environmental factors, we now systematically collected genes from candidate studies (using SzGene), genome-wide association studies (GWAS) and copy number variation (CNV) analyses, and then applied four criteria to test for a (theoretical) link to ischemia-hypoxia and/or vascular factors. In all, 55% of the schizophrenia candidate genes (n=42 genes) met the criteria for a link to ischemia-hypoxia and/or vascular factors. Genes associated with schizophrenia showed a significant, threefold enrichment among genes that were derived from microarray studies of the ischemia-hypoxia response (IHR) in the brain. Thus, the finding of a considerable match between genes associated with the risk of schizophrenia and IHR and/or vascular factors is reproducible. An additional survey of genes identified by GWAS and CNV analyses suggested novel genes that match the criteria. Findings for interactions between specific variants of genes proposed to be IHR and/or vascular factors with obstetric complications in patients with schizophrenia have been reported in the literature. Therefore, the extended gene set defined here may form a reasonable and evidence-based starting point for hypothesis-based testing of G × E interactions in clinical genetic and translational neuroscience studies.

  17. Phytophthora capsici-tomato interaction features dramatic shifts in gene expression associated with a hemi-biotrophic lifestyle

    Science.gov (United States)

    2013-01-01

    Background Plant-microbe interactions feature complex signal interplay between pathogens and their hosts. Phytophthora species comprise a destructive group of fungus-like plant pathogens, collectively affecting a wide range of plants important to agriculture and natural ecosystems. Despite the availability of genome sequences of both hosts and microbes, little is known about the signal interplay between them during infection. In particular, accurate descriptions of coordinate relationships between host and microbe transcriptional programs are lacking. Results Here, we explore the molecular interaction between the hemi-biotrophic broad host range pathogen Phytophthora capsici and tomato. Infection assays and use of a composite microarray allowed us to unveil distinct changes in both P. capsici and tomato transcriptomes, associated with biotrophy and the subsequent switch to necrotrophy. These included two distinct transcriptional changes associated with early infection and the biotrophy to necrotrophy transition that may contribute to infection and completion of the P. capsici lifecycle Conclusions Our results suggest dynamic but highly regulated transcriptional programming in both host and pathogen that underpin P. capsici disease and hemi-biotrophy. Dynamic expression changes of both effector-coding genes and host factors involved in immunity, suggests modulation of host immune signaling by both host and pathogen. With new unprecedented detail on transcriptional reprogramming, we can now explore the coordinate relationships that drive host-microbe interactions and the basic processes that underpin pathogen lifestyles. Deliberate alteration of lifestyle-associated transcriptional changes may allow prevention or perhaps disruption of hemi-biotrophic disease cycles and limit damage caused by epidemics. PMID:23799990

  18. Bone marrow lesions on magnetic resonance imaging in hand osteoarthritis are associated with pain and interact with synovitis.

    Science.gov (United States)

    Liu, R; Damman, W; Reijnierse, M; Bloem, J L; Rosendaal, F R; Kloppenburg, M

    2017-07-01

    To determine the association between bone marrow lesions (BMLs) and (teno)synovitis as assessed on magnetic resonance (MR) imaging in patients with pain in hand osteoarthritis (OA). In 105 consecutive primary hand OA patients (83% women, mean age 59 years), who were diagnosed by rheumatologists and included in the HOSTAS (Hand OSTeoArthritis in Secondary care) cohort, contrast enhanced MR imaging of right distal and proximal interphalangeal joints were obtained. In 92 patients joint site specific pain upon palpation was assessed within 3 weeks of magnetic resonance imaging (MRI) examination. MR features were scored (0-3) following the Oslo hand OA score: BMLs, synovitis, cysts, flexor tenosynovitis (FTS). Additionally, extensor tendon inflammation (ETI) (0-3) was scored. Odds ratios (OR, 95% confidence interval (CI)) were calculated using generalized estimating equations for MR features with joint pain, adjusted for putative confounders. Stratified analyses were performed to investigate interaction. BMLs, synovitis, cysts, FTS and ETI were demonstrated in 56%, 90%, 22%, 16% and 30% of patients, respectively. BMLs (grade 2/3 vs 0: 3.5 (1.6-7.7)) and synovitis (3 vs 0: OR 3.6 (95% CI 1.9-6.6)) were severity-dependent associated with joint pain, but FTS and ETI were not. Stratified analyses showed that BMLs did not associate with pain in the absence of synovitis, whereas synovitis was associated with pain in the absence of BMLs. Interaction was seen between BMLs and synovitis grade 2 or 3. In hand OA patients severe synovitis is associated with joint pain, which is worsened when BMLs co-occur, suggesting synovitis as primary target of treatment. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  19. Associated average charged particle multiplicities in K+p interactions at 32GeV/c

    International Nuclear Information System (INIS)

    Ajinenko, I.V.; Chliapnikov, P.V.; Gerdyukov, L.N.; Kubic, V.M.; Manyukov, B.A.; Minaev, N.G.; Rubin, A.M.; Ryadovikov, V.N.; Beer, M. de; Loret, M.; Saudraix, J.

    1975-01-01

    The average charged particle multiplicities, in the reactions K + p→K 0 X, K + p→π - X, K + p→pX and K + p→Δ ++ (1236)X at 32GeV/c are studied as functions of the mass squared Msub(X)sup(2) of the associated system X. A comparison with the corresponding results obtained at lower incident momenta and with other incident particles is presented [fr

  20. BDNF val66met genotype and schizotypal personality traits interact to influence probabilistic association learning.

    Science.gov (United States)

    Skilleter, Ashley Jayne; Weickert, Cynthia Shannon; Moustafa, Ahmed Abdelhalim; Gendy, Rasha; Chan, Mico; Arifin, Nur; Mitchell, Philip Bowden; Weickert, Thomas Wesley

    2014-11-01

    The brain derived neurotrophic factor (BDNF) val66met polymorphism rs6265 influences learning and may represent a risk factor for schizophrenia. Healthy people with high schizotypal personality traits display cognitive deficits that are similar to but not as severe as those observed in schizophrenia and they can be studied without confounds of antipsychotics or chronic illness. How genetic variation in BDNF may impact learning in individuals falling along the schizophrenia spectrum is unknown. We predicted that schizotypal personality traits would influence learning and that schizotypal personality-based differences in learning would vary depending on the BDNF val66met genotype. Eighty-nine healthy adults completed the Schizotypal Personality Questionnaire (SPQ) and a probabilistic association learning test. Blood samples were genotyped for the BDNF val66met polymorphism. An ANOVA was performed with BDNF genotype (val homozygotes and met-carriers) and SPQ score (high/low) as grouping variables and probabilistic association learning as the dependent variable. Participants with low SPQ scores (fewer schizotypal personality traits) showed significantly better learning than those with high SPQ scores. BDNF met-carriers displaying few schizotypal personality traits performed best, whereas BDNF met-carriers displaying high schizotypal personality traits performed worst. Thus, the BDNF val66met polymorphism appears to influence probabilistic association learning differently depending on the extent of schizotypal personality traits displayed. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  1. Expression of Interactive Genes Associated with Apoptosis and Their Prognostic Value for Ovarian Serous Adenocarcinoma.

    Science.gov (United States)

    Shin, Kyusik; Kim, Ki Hyung; Yoon, Man Soo; Suh, Dong Soo; Lee, Ji Young; Kim, Ari; Eo, Wankyu

    2016-01-01

    Malignant ovarian tumor is one of the leading causes of worldwide cancer death. It is usually characterized by insidious onset and late diagnosis because of the absence of symptoms, allowing ovarian cancer cases to progress rapidly and become unresectable. The tumor suppressor, p53, plays an important role in regulating cell cycles and apoptosis. p53 is regulated by several molecules, and it interacts with other apoptotic proteins. To compare the prognosis of ovarian serous carcinoma and evaluate the expression of DNA-PKcs, Akt3, GSK-3β, and p53 in cancerous cells. DNA-PKcs, Akt3, GSK-3β, and p53 expression levels were scored using immunohistochemistry staining of tissue samples from 132 women with ovarian serous adenocarcinoma. Expression was confirmed by real-time RT-PCR. Analyses were stratified by age, tumor grades, cancer stages and serum CA 125 levels. Significant differences in DNA-PKcs, Akt3, and p53 expression were observed between participants with different stages and tumor grades of ovarian serous adenocarcinoma. DNA-PKcs and p53 expression increased along with increasing tumor grade. Meanwhile, DNA-PKcs, Akt3, and p53 expression increased along with increasing cancer stage, and with a decrease in 5-year overall survival rate. This study shows that elevated expression of DNA-PKcs, Akt3, and p53 in ovarian serous adenocarcinoma tissues are an indication of more advanced disease and worse prognosis.

  2. Alzheimer's associated β-amyloid protein inhibits influenza A virus and modulates viral interactions with phagocytes.

    Directory of Open Access Journals (Sweden)

    Mitchell R White

    Full Text Available Accumulation of β-Amyloid (βA is a key pathogenetic factor in Alzheimer's disease; however, the normal function of βA is unknown. Recent studies have shown that βA can inhibit growth of bacteria and fungi. In this paper we show that βA also inhibits replication of seasonal and pandemic strains of H3N2 and H1N1 influenza A virus (IAV in vitro. The 42 amino acid fragment of βA (βA42 had greater activity than the 40 amino acid fragment. Direct incubation of the virus with βA42 was needed to achieve optimal inhibition. Using quantitative PCR assays βA42 was shown to reduce viral uptake by epithelial cells after 45 minutes and to reduce supernatant virus at 24 hours post infection. βA42 caused aggregation of IAV particles as detected by light transmission assays and electron and confocal microscopy. βA42 did not stimulate neutrophil H2O2 production or extracellular trap formation on its own, but it increased both responses stimulated by IAV. In addition, βA42 increased uptake of IAV by neutrophils. βA42 reduced viral protein synthesis in monocytes and reduced IAV-induced interleukin-6 production by these cells. Hence, we demonstrate for the first time that βA has antiviral activity and modulates viral interactions with phagocytes.

  3. Gene-nutrient interaction and its association with obesity and diabetes mellitus

    OpenAIRE

    Steemburgo, Thais; Azevedo, Mirela Jobim de; Martínez, José Alfredo

    2009-01-01

    A genômica nutricional avalia o efeito da variação genética na interação entre dieta e doenças crônicas. O objetivo deste manuscrito foi revisar os principais polimorfismos associados à obesidade, ao diabetes melito e também aos fatores da dieta. As principais interações entre polimorfismos genéticos e dieta foram: para obesidade: interleucina-6 (IL-6) com consumo energético; receptor ativado por proliferador de peroxissoma gama 2 (PPAR-gama2) e fat mass and obesity associated (FTO) com consu...

  4. Interactions between host metabolism, immune regulation, and the gut microbiota in diet-associated obesity and metabolic dysfunction

    DEFF Research Database (Denmark)

    Andersen, Daniel

    The increase in the prevalence of obesity and obesity-associated complications such as the metabolic syndrome is becoming a global challenge. Dietary habits and nutrient consumption modulates host homeostasis, which manifests in various diet-induced complications marked by changes in host...... metabolism and immune regulation, which are intricately linked. In addition, diet effectively shapes the gut microbiota composition and activity, which in turn interacts with the host to modulate host metabolism and immune regulation. In the three studies included in this PhD thesis, we have explored...... the impact of specific dietary components on host metabolic function, immune regulation and gut microbiota composition and activity. In the first study, we have characterized the effect of a combined high-fat and gliadin-rich diet, since dietary gliadin has been reported to be associated with intestinal...

  5. Interactive associations of parental support, demands, and psychological control, over adolescents' beliefs about the legitimacy of parental authority.

    Science.gov (United States)

    Mellado, Carlos; Cumsille, Patricio; Martínez, M Loreto

    2018-04-01

    The present study examined the relationship between parental support, demand, psychological control and adolescents' beliefs about the legitimacy of parental authority for personal and multifaceted issues in a sample of 1342 Chilean adolescents (M = 16.38, SD = 1.24, age range 14-20). Results from multiple regression analyses separated by age indicated that demand was positively associated with adolescents' beliefs about the legitimacy of parental authority for personal and multifaceted issues and that psychological control was negatively associated with adolescents' legitimacy beliefs concerning personal issues. Furthermore, parental support moderated the relationship between parental demand and adolescents' beliefs about parental legitimacy for personal and multifaceted issues: those who display high levels of demand showed stronger beliefs about parental legitimacy at high level of support. These results support the interactive effect of parental support and demand on adolescent development. Copyright © 2018. Published by Elsevier Ltd.

  6. GPCR-drug interactions prediction using random forest with drug-association-matrix-based post-processing procedure.

    Science.gov (United States)

    Hu, Jun; Li, Yang; Yang, Jing-Yu; Shen, Hong-Bin; Yu, Dong-Jun

    2016-02-01

    G-protein-coupled receptors (GPCRs) are important targets of modern medicinal drugs. The accurate identification of interactions between GPCRs and drugs is of significant importance for both protein function annotations and drug discovery. In this paper, a new sequence-based predictor called TargetGDrug is designed and implemented for predicting GPCR-drug interactions. In TargetGDrug, the evolutionary feature of GPCR sequence and the wavelet-based molecular fingerprint feature of drug are integrated to form the combined feature of a GPCR-drug pair; then, the combined feature is fed to a trained random forest (RF) classifier to perform initial prediction; finally, a novel drug-association-matrix-based post-processing procedure is applied to reduce potential false positive or false negative of the initial prediction. Experimental results on benchmark datasets demonstrate the efficacy of the proposed method, and an improvement of 15% in the Matthews correlation coefficient (MCC) was observed over independent validation tests when compared with the most recently released sequence-based GPCR-drug interactions predictor. The implemented webserver, together with the datasets used in this study, is freely available for academic use at http://csbio.njust.edu.cn/bioinf/TargetGDrug. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Gene expression profiles and protein–protein interaction network analysis in AIDS patients with HIV-associated encephalitis and dementia

    Directory of Open Access Journals (Sweden)

    Shityakov S

    2015-11-01

    Full Text Available Sergey Shityakov,1 Thomas Dandekar,2 Carola Förster1 1Department of Anesthesia and Critical Care, 2Department of Bioinformatics, University of Würzburg, Würzburg, Germany Abstract: Central nervous system dysfunction is an important cause of morbidity and mortality in patients with human immunodeficiency virus type 1 (HIV-1 infection and acquired immunodeficiency virus syndrome (AIDS. Patients with AIDS are usually affected by HIV-associated encephalitis (HIVE with viral replication limited to cells of monocyte origin. To examine the molecular mechanisms underlying HIVE-induced dementia, the GSE4755 Affymetrix data were obtained from the Gene Expression Omnibus database and the differentially expressed genes (DEGs between the samples from AIDS patients with and without apparent features of HIVE-induced dementia were identified. In addition, protein–protein interaction networks were constructed by mapping DEGs into protein–protein interaction data to identify the pathways that these DEGs are involved in. The results revealed that the expression of 1,528 DEGs is mainly involved in the immune response, regulation of cell proliferation, cellular response to inflammation, signal transduction, and viral replication cycle. Heat-shock protein alpha, class A member 1 (HSP90AA1, and fibronectin 1 were detected as hub nodes with degree values >130. In conclusion, the results indicate that HSP90A and fibronectin 1 play important roles in HIVE pathogenesis.Keywords: microarray, human immunodeficiency virus, differentially expressed genes, protein–protein interaction network, gene ontology, encephalitis, dementia

  8. Identification of novel NPRAP/δ-catenin-interacting proteins and the direct association of NPRAP with dynamin 2.

    Directory of Open Access Journals (Sweden)

    Carolina Koutras

    Full Text Available Neural plakophilin-related armadillo protein (NPRAP or δ-catenin is a neuronal-specific protein that is best known for its interaction with presenilin 1 (PS1. Interestingly, the hemizygous loss of NPRAP is associated with severe mental retardation in cri du chat syndrome (CDCS, and mutations in PS1 cause an aggressive, early-onset form of Alzheimer's disease. Until recently, studies on the function of NPRAP have focused on its ability to modulate dendritic protrusion elaboration through its binding to cell adhesion and scaffolding molecules. However, mounting evidence indicates that NPRAP participates in intracellular signaling and exists in the nucleus, where it modulates gene expression. This apparent bifunctional nature suggests an elaborate neuronal role, but how NPRAP came to participate in such distinct subcellular events remains a mystery. To gain insight into this pathway, we immunoprecipitated NPRAP from human SH SY5Y cells and identified several novel interacting proteins by mass spectrometry. These included neurofilament alpha-internexin, interferon regulatory protein 2 binding factors, and dynamins 1 and 2. We further validated dynamin 2/NPRAP colocalization and direct interaction in vivo, confirming their bona fide partnership. Interestingly, dynamin 2 has established roles in endocytosis and actin assembly, and both of these processes have the potential to interface with the cell adhesion and intracellular signaling processes that involve NPRAP. Our data provide new avenues for approaching NPRAP biology and suggest a broader role for this protein than previously thought.

  9. Biology and interactions of two distinct monopartite begomoviruses and betasatellites associated with radish leaf curl disease in India

    Directory of Open Access Journals (Sweden)

    Singh AK

    2012-02-01

    Full Text Available Abstract Background Emerging whitefly transmitted begomoviruses are major pathogens of vegetable and fibre crops throughout the world, particularly in tropical and sub-tropical regions. Mutation, pseudorecombination and recombination are driving forces for the emergence and evolution of new crop-infecting begomoviruses. Leaf curl disease of field grown radish plants was noticed in Varanasi and Pataudi region of northern India. We have identified and characterized two distinct monopartite begomoviruses and associated beta satellite DNA causing leaf curl disease of radish (Raphanus sativus in India. Results We demonstrate that RaLCD is caused by a complex of two Old World begomoviruses and their associated betasatellites. Radish leaf curl virus-Varanasi is identified as a new recombinant species, Radish leaf curl virus (RaLCV sharing maximum nucleotide identity of 87.7% with Tomato leaf curl Bangladesh virus-[Bangladesh:2] (Accession number AF188481 while the virus causing radish leaf curl disease-Pataudi is an isolate of Croton yellow vein mosaic virus-[India] (CYVMV-IN (Accession number AJ507777 sharing 95.8% nucleotide identity. Further, RDP analysis revealed that the RaLCV has a hybrid genome, a putative recombinant between Euphorbia leaf curl virus and Papaya leaf curl virus. Cloned DNA of either RaLCV or CYVMV induced mild leaf curl symptoms in radish plants. However, when these clones (RaLCV or CYVMV were individually co-inoculated with their associated cloned DNA betasatellite, symptom severity and viral DNA levels were increased in radish plants and induced typical RaLCD symptoms. To further extend these studies, we carried out an investigation of the interaction of these radish-infecting begomoviruses and their associated satellite, with two tomato infecting begomoviruses (Tomato leaf curl Gujarat virus and Tomato leaf curl New Delhi virus. Both of the tomato-infecting begomoviruses showed a contrasting and differential interaction with

  10. Brown bear-human interactions associated with deer hunting on Kodiak Island

    Science.gov (United States)

    Barnes, Victor G.

    1994-01-01

    I compared distribution and range of brown bears (Ursus arctos middendorffi) with temporal and spatial distribution of Sitka black-tailed deer (Odocoileus hemionus sitkensis) hunting activity on westside Kodiak Island, Alaska, to examine impacts of deer hunting on bears. Mean number of bears that annually ranged ≤5 km from the coast, >5 km inland from the coast, or in both areas was 10, 8, and 11, respectively. Bears that exclusively or seasonally occupied the coast zone were usually classed as having moderate or high potential to interact with hunters because most hunter access and effort (>95%) was via the coast. Bears that ranged exclusively inland were considered unlikely to encounter hunters. Animals that ranged in both zones often (39%) moved inland during fall (Oct-Dec) and most bears (70%) denned in the inland zone. Females that denned near the coast entered dens later (x̄ = 22 Nov) than females that denned inland (x̄ = 12 Nov). Two radio-collared bears were known to raid deer-hunting camps and 9 other marked bears were observed by hunters or were located bear during their hunt. Seven to 21% of the respondents reported having a threatening encounter with a bear and 5-26% reported losing deer meat to bears. Human-induced mortality to radio-collared bears occurred more often near the coast (5) than inland (3); 7 bears were harvested by sport hunters and 1 was killed (nonsport) in a Native village. Deer hunters killed 2 unmarked females in defense of life or property situations in the study area. High bear densities and concentrated deer-hunting activity combine to make conflicts unavoidable. Adverse impacts to bears can be minimized by maintaining low levels of human activity in inland areas and improving hunter awareness of bear ecology and behavior.

  11. Mechanisms of antimicrobial resistant Salmonella enterica transmission associated with starling-livestock interactions.

    Science.gov (United States)

    Carlson, James C; Hyatt, Doreene R; Ellis, Jeremy W; Pipkin, David R; Mangan, Anna M; Russell, Michael; Bolte, Denise S; Engeman, Richard M; DeLiberto, Thomas J; Linz, George M

    2015-08-31

    Bird-livestock interactions have been implicated as potential sources for bacteria within concentrated animal feeding operations (CAFO). European starlings (Sturnus vulgaris) in particular are known to contaminate cattle feed and water with Salmonella enterica through their fecal waste. We propose that fecal waste is not the only mechanisms through which starlings introduce S. enterica to CAFO. The goal of this study was to assess if starlings can mechanically move S. enterica. We define mechanical movement as the transportation of media containing S. enterica, on the exterior of starlings within CAFO. We collected 100 starlings and obtained external wash and gastrointestinal tract (GI) samples. We also collected 100 samples from animal pens. Within each pen we collected one cattle fecal, feed, and water trough sample. Isolates from all S. enterica positive samples were subjected to antimicrobial susceptibility testing. All sample types, including 17% of external starling wash samples, contained S. enterica. All sample types had at least one antimicrobial resistant (AMR) isolate and starling GI samples harbored multidrug resistant S. enterica. The serotypes isolated from the starling external wash samples were all found in the farm environment and 11.8% (2/17) of isolates from positive starling external wash samples were resistant to at least one class of antibiotics. This study provides evidence of a potential mechanism of wildlife introduced microbial contamination in CAFO. Mechanical movement of microbiological hazards, by starlings, should be considered a potential source of bacteria that is of concern to veterinary, environmental and public health. Published by Elsevier B.V.

  12. Association of Human Papillomavirus 16 E2 with Rad50-Interacting Protein 1 Enhances Viral DNA Replication.

    Science.gov (United States)

    Campos-León, Karen; Wijendra, Kalpanee; Siddiqa, Abida; Pentland, Ieisha; Feeney, Katherine M; Knapman, Alison; Davies, Rachel; Androphy, Elliot J; Parish, Joanna L

    2017-03-01

    Rad50-interacting protein 1 (Rint1) associates with the DNA damage response protein Rad50 during the transition from the S phase to the G 2 /M phase and functions in radiation-induced G 2 checkpoint control. It has also been demonstrated that Rint1 is essential in vesicle trafficking from the Golgi apparatus to the endoplasmic reticulum (ER) through an interaction with Zeste-White 10 (ZW10). We have isolated a novel interaction between Rint1 and the human papillomavirus 16 (HPV16) transcription and replication factor E2. E2 binds to Rint1 within its ZW10 interaction domain, and we show that in the absence of E2, Rint1 is localized to the ER and associates with ZW10. E2 expression results in a disruption of the Rint1-ZW10 interaction and an accumulation of nuclear Rint1, coincident with a significant reduction in vesicle movement from the ER to the Golgi apparatus. Interestingly, nuclear Rint1 and members of the Mre11/Rad50/Nbs1 (MRN) complex were found in distinct E2 nuclear foci, which peaked during mid-S phase, indicating that the recruitment of Rint1 to E2 foci within the nucleus may also result in the recruitment of this DNA damage-sensing protein complex. We show that exogenous Rint1 expression enhances E2-dependent virus replication. Conversely, the overexpression of a truncated Rint1 protein that retains the E2 binding domain but not the Rad50 binding domain acts as a dominant negative inhibitor of E2-dependent HPV replication. Put together, these experiments demonstrate that the interaction between Rint1 and E2 has an important function in HPV replication. IMPORTANCE HPV infections are an important driver of many epithelial cancers, including those within the anogenital and oropharyngeal tracts. The HPV life cycle is tightly regulated and intimately linked to the differentiation of the epithelial cells that it infects. HPV replication factories formed in the nucleus are locations where viral DNA is copied to support virus persistence and amplification of

  13. Differential hydrogen/deuterium exchange mass spectrometry analysis of protein-ligand interactions.

    Science.gov (United States)

    Chalmers, Michael J; Busby, Scott A; Pascal, Bruce D; West, Graham M; Griffin, Patrick R

    2011-02-01

    Functional regulation of ligand-activated receptors is driven by alterations in the conformational dynamics of the protein upon ligand binding. Differential hydrogen/deuterium exchange (HDX) coupled with mass spectrometry has emerged as a rapid and sensitive approach for characterization of perturbations in conformational dynamics of proteins following ligand binding. While this technique is sensitive to detecting ligand interactions and alterations in receptor dynamics, it also can provide important mechanistic insights into ligand regulation. For example, HDX has been used to determine a novel mechanism of ligand activation of the nuclear receptor peroxisome proliferator activated receptor-γ, perform detailed analyses of binding modes of ligands within the ligand-binding pocket of two estrogen receptor isoforms, providing insight into selectivity, and helped classify different types of estrogen receptor-α ligands by correlating their pharmacology with the way they interact with the receptor based solely on hierarchical clustering of receptor HDX signatures. Beyond small-molecule-receptor interactions, this technique has also been applied to study protein-protein complexes, such as mapping antibody-antigen interactions. In this article, we summarize the current state of the differential HDX approaches and the future outlook. We summarize how HDX analysis of protein-ligand interactions has had an impact on biology and drug discovery.

  14. A New Search Method Using Association Rule Mining for Drug-Drug Interaction Based on Spontaneous Report System.

    Science.gov (United States)

    Noguchi, Yoshihiro; Ueno, Anri; Otsubo, Manami; Katsuno, Hayato; Sugita, Ikuto; Kanematsu, Yuta; Yoshida, Aki; Esaki, Hiroki; Tachi, Tomoya; Teramachi, Hitomi

    2018-01-01

    Background: Adverse events (AEs) can be caused not only by one drug but also by the interaction between two or more drugs. Therefore, clarifying whether an AE is due to a specific suspect drug or drug-drug interaction (DDI) is useful information for proper use of drugs. Whereas previous reports on the search for drug-induced AEs with signal detection using spontaneous reporting systems (SRSs) are numerous, reports on drug interactions are limited. This is because in methods that use "a safety signal indicator" (signal), which is frequently used in pharmacovigilance, a huge number of combinations must be prepared when signal detection is performed, and each risk index must be calculated, which makes interaction search appear unrealistic. Objective: In this paper, we propose association rule mining (AR) using large dataset analysis as an alternative to the conventional methods (additive interaction model (AI) and multiplicative interaction model (MI)). Methods: The data source used was the Japanese Adverse Drug Event Report database. The combination of drugs for which the risk index is detected by the "combination risk ratio (CR)" as the target was assumed to be true data, and the accuracy of signal detection using the AR methods was evaluated in terms of sensitivity, specificity, Youden's index, F -score. Results: Our experimental results targeting Stevens-Johnson syndrome indicate that AR has a sensitivity of 99.05%, specificity of 92.60%, Youden's index of 0.917, F -score of 0.876, AI has a sensitivity of 95.62%, specificity of 96.92%, Youden's index of 0.925, and F -score of 0.924, and MI has a sensitivity of 65.46%, specificity of 98.78%, Youden's index of 0.642, and F -score of 0.771. This result was about the same level as or higher than the conventional method. Conclusions: If you use similar calculation methods to create combinations from the database, not only for SJS, but for all AEs, the number of combinations would be so enormous that it would be

  15. Serum concentration and interaction properties of MBL/ficolin associated protein-1

    DEFF Research Database (Denmark)

    Skjoedt, Mikkel-ole; Hummelshoj, Tina; Palarasah, Yaseelan

    2011-01-01

    pathway (LCP) recognition molecules and MAP-1. We expressed recombinant MAP-1 in CHO DG44 cells, developed a quantitative ELISA assay based on a MAP-1 specific monoclonal capture antibody and measured the serum levels in 100 Danish blood donors. In addition we assessed the association properties between...... MAP-1 and Ficolin-2, -3 and MBL in serum using ELISA and density gradient ultra centrifugation. When recombinant MAP-1 was subjected to N-glycosidase F treatment the molecular mass decreased from ~45kDa to ~40kDa equivalent with the calculated molecular mass from the deduced amino acid sequence...... and MBL and by use of density gradient ultra centrifugation we could show that the major part of serum MAP-1 circulates in complex with the LCP molecules. In conclusion, these results show that MAP-1 is a highly stable glycosylated human serum protein found in complex with Ficolin-3, Ficolin-2 and MBL....

  16. Specific chlamydial inclusion membrane proteins associate with active Src family kinases in microdomains that interact with the host microtubule network.

    Science.gov (United States)

    Mital, Jeffrey; Miller, Natalie J; Fischer, Elizabeth R; Hackstadt, Ted

    2010-09-01

    Chlamydiae are Gram-negative obligate intracellular bacteria that cause diseases with significant medical and economic impact. Chlamydia trachomatis replicates within a vacuole termed an inclusion, which is extensively modified by the insertion of a number of bacterial effector proteins known as inclusion membrane proteins (Incs). Once modified, the inclusion is trafficked in a dynein-dependent manner to the microtubule-organizing centre (MTOC), where it associates with host centrosomes. Here we describe a novel structure on the inclusion membrane comprised of both host and bacterial proteins. Members of the Src family of kinases are recruited to the chlamydial inclusion in an active form. These kinases display a distinct, localized punctate microdomain-like staining pattern on the inclusion membrane that colocalizes with four chlamydial inclusion membrane proteins (Incs) and is enriched in cholesterol. Biochemical studies show that at least two of these Incs stably interact with one another. Furthermore, host centrosomes associate with these microdomain proteins in C. trachomatis-infected cells and in uninfected cells exogenously expressing one of the chlamydial effectors. Together, the data suggest that a specific structure on the C. trachomatis inclusion membrane may be responsible for the known interactions of chlamydiae with the microtubule network and resultant effects on centrosome stability.

  17. Mapping QTL associated with photoperiod sensitivity and assessing the importance of QTL×environment interaction for flowering time in maize.

    Directory of Open Access Journals (Sweden)

    Cuiling Wang

    2010-11-01

    Full Text Available An understanding of the genetic determinism of photoperiod response of flowering is a prerequisite for the successful exchange of germplasm across different latitudes. In order to contribute to resolve the genetic basis of photoperiod sensitivity in maize, a set of 201 recombinant inbred lines (RIL, derived from a temperate and tropical inbred line cross were evaluated in 5 field trials spread in short- and long-day environments.Firstly, QTL analyses for flowering time and photoperiod sensitivity in maize were conducted in individual photoperiod environments separately, and then, the total genetic effect was partitioned into additive effect (A and additive-by-environment interaction effect (AE by using a mixed-model-based composite interval mapping (MCIM method.Seven putative QTL were found associated with DPS thermal time based on the data estimated in individual environments. Nine putative QTL were found associated with DPS thermal time across environments and six of them showed significant QTL×enviroment (QE interactions. Three QTL for photoperiod sensitivity were identified on chromosome 4, 9 and 10, which had the similar position to QTL for DPS thermal time in the two long-day environment. The major photoperiod sensitive loci qDPS10 responded to both short and long-day photoperiod environments and had opposite effects in different photoperiod environment. The QTL qDPS3, which had the greatest additive effect exclusively in the short-day environment, were photoperiod independent and should be classified in autonomous promotion pathway.

  18. Association of interactions between dietary salt consumption and hypertension-susceptibility genetic polymorphisms with blood pressure among Japanese male workers.

    Science.gov (United States)

    Imaizumi, Takahiro; Ando, Masahiko; Nakatochi, Masahiro; Maruyama, Shoichi; Yasuda, Yoshinari; Honda, Hiroyuki; Kuwatsuka, Yachiyo; Kato, Sawako; Kondo, Takaaki; Iwata, Masamitsu; Nakashima, Toru; Yasui, Hiroshi; Takamatsu, Hideki; Okajima, Hiroshi; Yoshida, Yasuko; Matsuo, Seiichi

    2017-06-01

    Blood pressure is influenced by hereditary factors and dietary habits. The objective of this study was to examine the effect of dietary salt consumption and single-nucleotide polymorphisms (SNPs) on blood pressure (BP). This was a cross-sectional analysis of 2728 male participants who participated in a health examination in 2009. Average dietary salt consumption was estimated using electronically collected meal purchase data from cafeteria. A multivariate analysis, adjusting for clinically relevant factors, was conducted to examine whether the effect on BP of salt consumption, SNPs, and interaction between salt consumption and each SNP. This study examined the SNPs AGT rs699 (Met235Thr), ADD1 rs4961 (Gly460Trp), NPPA rs5063 (Val32Met), GPX1 rs1050450 (Pro198Leu), and AGTR1 rs5186 (A1166C) in relation to hypertension and salt sensitivity. BP was not significantly associated with SNPs or salt consumption. The interaction between salt consumption and SNPs with systolic BP showed a significant association in NPPA rs5063 (Val32Met) (P = 0.023) and a marginal trend toward significance in rs4961 and rs1050450 (P = 0.060 and 0.067, respectively). The effect of salt consumption on BP differed by genotype. Dietary salt consumption and genetic variation can predict a high risk of hypertension.

  19. Evaluation of Drug-Disease Interactions and Their Association with Unplanned Hospital Readmission Utilizing STOPP Version 2 Criteria

    Directory of Open Access Journals (Sweden)

    Mandy Hau Man Lau

    2017-11-01

    Full Text Available Early hospital readmission is a common problem among geriatric patients, as they are more susceptible to adverse drug events, which are associated with increased hospital admission. The objective is to examine the association between exposure to potentially inappropriate medications under selected STOPP version 2 criteria related to drug-disease interactions and unplanned early hospitalization within 28 days of index admission in elderly patients prescribed a potentially inappropriate medication. This retrospective single-center study reviewed patients 75 years of age or older that were discharged with 5 or more medications, including at least one selected medication listed in the STOPP version 2 criteria relating to drug-disease interactions. 182 patients, with a mean age of 83.5 years, were included in the study, with anticholinergics being the most common potentially inappropriate medications (22.4%. Potentially inappropriate medications (57.1% vs. 17.1%, p < 0.001, gout (31% vs. 11.5%, p = 0.003, and gastrointestinal disease (11.9% vs. 2.5%, p = 0.026 were shown to increase risk of 28-day readmission, whereas no other factors assessed correlated with readmission. A rapid evaluation of elderly patient discharge medications and concomitant disease states with the aid of the STOPP version 2 criteria could potentially reduce hospital readmissions or emergency department visits.

  20. Interaction of Pb(II) and biofilm associated extracellular polymeric substances of a marine bacterium Pseudomonas pseudoalcaligenes NP103

    Science.gov (United States)

    Kumari, Supriya; Mangwani, Neelam; Das, Surajit

    2017-02-01

    Three-dimensional excitation-emission matrix (3D EEM) fluorescence spectroscopy and attenuated total reflectance fourier-transformed infrared spectroscopy (ATR-FTIR) was used to evaluate the interaction of biofilm associated extracellular polymeric substances (EPS) of a marine bacterium Pseudomonas pseudoalcaligenes NP103 with lead [Pb(II)]. EEM fluorescence spectroscopic analysis revealed the presence of one protein-like fluorophore in the EPS of P. pseudoalcaligenes NP103. Stern-Volmer equation indicated the existence of only one binding site (n = 0.789) in the EPS of P. pseudoalcaligenes NP103. The interaction of Pb(II) with EPS was spontaneous at room temperature (Δ G = - 2.78 kJ/K/mol) having binding constant (Kb) of 2.59 M- 1. ATR-FTIR analysis asserted the involvement of various functional groups such as sulphydryl, phosphate and hydroxyl and amide groups of protein in Pb(II) binding. Scanning electron microscopy (SEM) and fluorescence microscopy analysis displayed reduced growth of biofilm with altered surface topology in Pb(II) supplemented medium. Energy dispersive X-ray spectroscopy (EDX) analysis revealed the entrapment of Pb in the EPS. Uronic acid, a characteristic functional group of biofilm, was observed in 1H NMR spectroscopy. The findings suggest that biofilm associated EPS are perfect organic ligands for Pb(II) complexation and may significantly augment the bioavailability of Pb(II) in the metal contaminated environment for subsequent sequestration.

  1. Neuroinflammation-Induced Interactions between Protease-Activated Receptor 1 and Proprotein Convertases in HIV-Associated Neurocognitive Disorder.

    Science.gov (United States)

    Kim, WooJin; Zekas, Erin; Lodge, Robert; Susan-Resiga, Delia; Marcinkiewicz, Edwidge; Essalmani, Rachid; Mihara, Koichiro; Ramachandran, Rithwik; Asahchop, Eugene; Gelman, Benjamin; Cohen, Éric A; Power, Christopher; Hollenberg, Morley D; Seidah, Nabil G

    2015-11-01

    The proprotein convertases (PCs) furin, PC5, PACE4, and PC7 cleave secretory proteins after basic residues, including the HIV envelope glycoprotein (gp160) and Vpr. We evaluated the abundance of PC mRNAs in postmortem brains of individuals exhibiting HIV-associated neurocognitive disorder (HAND), likely driven by neuroinflammation and neurotoxic HIV proteins (e.g., envelope and Vpr). Concomitant with increased inflammation-related gene expression (interleukin-1β [IL-1β]), the mRNA levels of the above PCs are significantly increased, together with those of the proteinase-activated receptor 1 (PAR1), an inflammation-associated receptor that is cleaved by thrombin at ProArg41↓ (where the down arrow indicates the cleavage location), and potentially by PCs at Arg41XXXXArg46↓. The latter motif in PAR1, but not its R46A mutant, drives its interactions with PCs. Indeed, PAR1 upregulation leads to the inhibition of membrane-bound furin, PC5B, and PC7 and inhibits gp160 processing and HIV infectivity. Additionally, a proximity ligation assay revealed that furin and PC7 interact with PAR1. Reciprocally, increased furin expression reduces the plasma membrane abundance of PAR1 by trapping it in the trans-Golgi network. Furthermore, soluble PC5A/PACE4 can target/disarm cell surface PAR1 through cleavage at Arg46↓. PACE4/PC5A decreased calcium mobilization induced by thrombin stimulation. Our data reveal a new PC-PAR1-interaction pathway, which offsets the effects of HIV-induced neuroinflammation, viral infection, and potentially the development of HAND. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. Modeling Change in Watershed Streamflow, Groundwater Recharge and Surface Water - Groundwater Interactions Due to Irrigation and Associated Diversions and Pumping

    Science.gov (United States)

    Essaid, H.; Caldwell, R. R.

    2015-12-01

    The impacts of irrigation and associated surface water (SW) diversions and groundwater (GW) pumping on instream flows, groundwater recharge and SW-GW interactions are being examined using a watershed-scale coupled SW-GW flow model. The U.S. Geological Survey (USGS) model GSFLOW (Markstrom et al., 2008), an integration of the USGS Precipitation-Runoff Modeling System (PRMS) and the Modular Ground-Water Flow Model (MODFLOW), is being utilized for this effort. Processes represented in this model include daily rain, snowfall, snowmelt, streamflow, surface runoff, interflow, infiltration, soil-zone evapotranspiration, and subsurface unsaturated and groundwater flow and evapotranspiration. The Upper Smith River watershed, an important agricultural and recreational area in west-central Montana, is being used as the basis for watershed climate, topography, hydrography, vegetation, soil properties as well as scenarios of irrigation and associated practices. The 640 square kilometer watershed area has been discretized into coincident 200 m by 200 m hydrologic response units (for climate and soil zone flow processes) and grid blocks (for unsaturated zone and GW flow processes). The subsurface GW system is discretized into 6 layers representing Quaternary alluvium, Tertiary sediments and bedrock. The model is being used to recreate natural, pre-development streamflows and GW conditions in the watershed. The results of this simulation are then compared to a simulation with flood and sprinkler irrigation supplied by SW diversion and GW pumping to examine the magnitude and timing of changes in streamflow, groundwater recharge and SW-GW interactions. Model results reproduce observed hydrologic responses to both natural climate variability and irrigation practices. Periodic irrigation creates increased evapotranspiration and GW recharge in cultivated areas of the watershed as well as SW-GW interactions that are more dynamic than under natural conditions.

  3. An analysis of interactions and outcomes associated with an online professional development course for science teachers

    Science.gov (United States)

    Randle, David Edward

    This mixed-methods study examined the interactions and learning outcomes of science teachers in an online graduate-level course on evolutionary biology intended to improve their content knowledge and science lesson planning. Discussion posts made by the teachers in this seven-week course were analyzed for cognitive presence using the Community of Inquiry framework. Compared to other studies examining cognitive presence, high levels of Integration level cognitive activity were observed (47% of total posts). This was most likely due to the design of the discussion prompts and expectations used to frame student participation. The questions were open-ended, and students were expected to use reference materials to construct their responses. During the course, 395 student posts contained statements that could be coded for scientific accuracy. Of these, 85% were coded as scientifically accurate. This reinforces reports from previous literature that the online environment is conducive to reflective and careful contributions by participants. As the course progressed, the number of faculty posts per discussion declined, while the number of student posts remained relatively constant. Student-to-student posts increased in frequency as faculty participation dropped. The number of student posts increased towards the end of each two-week discussion period, however the frequencies of posts with scientifically accurate statements and Integration level cognitive activity remained relatively constant over this same period. The increase in total posts was due to the increase in other types of communication in the discussions. Case study analysis was used to examine patterns of online behavior in three participants who achieved different course grades. A low-performing student had a pattern of intermittent activity, made low numbers of posts in each discussion, and had low percentages of posts that contained scientific statements or indicators of Integration level cognitive activity

  4. Polymorphisms in mismatch repair genes are associated with risk and microsatellite instability of gastric cancer, and interact with life exposures.

    Science.gov (United States)

    Zhu, Haifeng; Li, Xiaoqin; Zhang, Xiaomei; Chen, Deyu; Li, Dan; Ren, Jin; Gu, Hangang; Shu, Yongqian; Wang, Deqiang

    2016-03-15

    Epigenetic alterations of DNA mismatch repair (MMR) genes are associated with risk of gastric cancer (GC) by causing microsatellite instability (MSI). Less understood is the association of common polymorphisms in MMR genes with the risk and MSI phenotype of GC. A hospital-based study was conducted in China with 423 cases and 454 matched controls. Four potentially functional polymorphisms were selected and analyzed: rs1800734 in MLH1, rs2303428 in MSH2, rs735943 in EXO1, and rs11797 in TREX1. The rs1800734 G-allele was associated with decreased risk of GC (GA or GG vs AA, OR=0.72; 95% CI: 0.50-1.05; Ptrend=0.029). For combined effects, a dose-response manner was observed in which GC risk was increased with increasing number of at-risk genotypes (Ptrend=0.039); this manner mainly existed in MSI GC (Ptrend=0.047) rather than in microsatellite stability GC, though neither single polymorphism was linked with MSI. For exposures, modified effects were observed from green tea drinking and soy foods intake on rs11797 (P for interaction=0.007 and 0.016, respectively). The MLH1 rs1800734 polymorphism is associated with GC risk. Those at-risk genotypes have a joint effect on GC risk, which contributes to the MSI phenotype of GC. Life exposures modify GC risk, stratified by MMR genotypes. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Interactions Between Alcohol Metabolism Genes and Religious Involvement in Association With Maximum Drinks and Alcohol Dependence Symptoms.

    Science.gov (United States)

    Chartier, Karen G; Dick, Danielle M; Almasy, Laura; Chan, Grace; Aliev, Fazil; Schuckit, Marc A; Scott, Denise M; Kramer, John; Bucholz, Kathleen K; Bierut, Laura J; Nurnberger, John; Porjesz, Bernice; Hesselbrock, Victor M

    2016-05-01

    Variations in the genes encoding alcohol dehydrogenase (ADH) enzymes are associated with both alcohol consumption and dependence in multiple populations. Additionally, some environmental factors have been recognized as modifiers of these relationships. This study examined the modifying effect of religious involvement on relationships between ADH gene variants and alcohol consumption-related phenotypes. Subjects were African American, European American, and Hispanic American adults with lifetime exposure to alcohol (N = 7,716; 53% female) from the Collaborative Study on the Genetics of Alcoholism. Genetic markers included ADH1Brs1229984, ADH1B-rs2066702, ADH1C-rs698, ADH4-rs1042364, and ADH4-rs1800759. Phenotypes were maximum drinks consumed in a 24-hour period and total number of alcohol dependence symptoms according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Religious involvement was defined by self-reported religious services attendance. Both religious involvement and ADH1B-rs1229984 were negatively associated with the number of maximum drinks consumed and the number of lifetime alcohol dependence symptoms endorsed. The interactions of religious involvement with ADH1B-rs2066702, ADH1C-rs698, and ADH4-rs1042364 were significantly associated with maximum drinks and alcohol dependence symptoms. Risk variants had weaker associations with maximum drinks and alcohol dependence symptoms as a function of increasing religious involvement. This study provided initial evidence of a modifying effect for religious involvement on relationships between ADH variants and maximum drinks and alcohol dependence symptoms.

  6. The blues of adolescent romance: observed affective interactions in adolescent romantic relationships associated with depressive symptoms.

    Science.gov (United States)

    Ha, Thao; Dishion, Thomas J; Overbeek, Geertjan; Burk, William J; Engels, Rutger C M E

    2014-05-01

    We examined the associations between observed expressions of positive and negative emotions during conflict discussions and depressive symptoms during a 2-year period in a sample of 160 adolescents in 80 romantic relationships (M age = 15.48, SD = 1.16). Conflict discussions were coded using the 10-code Specific Affect Coding System. Depressive symptoms were assessed at the time of the observed conflict discussions (Time 1) and 2 years later (Time 2). Data were analyzed using actor-partner interdependence models. Girls' expression of both positive and negative emotions at T1 was related to their own depressive symptoms at T2 (actor effect). Boys' positive emotions and negative emotions (actor effect) and girls' negative emotions (partner effect) were related to boys' depressive symptoms at T2. Contrary to expectation, relationship break-up and relationship satisfaction were unrelated to changes in depressive symptoms or expression of negative or positive emotion during conflict discussion. These findings underscore the unique quality of adolescent romantic relationships and suggest new directions in the study of the link between mental health and romantic involvement in adolescence.

  7. How the immune and nervous systems interact during disease-associated anorexia.

    Science.gov (United States)

    Konsman, J P; Dantzer, R

    2001-01-01

    Anorexia is one of the most common symptoms associated with illness and constitutes an adaptive strategy in fighting acute infectious diseases. However, prolonged reduction in food intake and an increase in metabolic rate, as seen in the anorexia-cachexia syndrome, lead to depletion of body fat and protein reserves, thus worsening the organism's condition. Because the central nervous system controls many aspects of food intake, soluble factors known as cytokines that are secreted by immune cells might act on the brain to induce anorexia during disease. This review focuses on the communication pathways from the immune system to the brain that might mediate anorexia during disease. The vagus nerve is a rapid route of communication from the immune system to the brain, as subdiaphragmatic vagotomy attenuates the decrease in food-motivated behavior and c-Fos expression in the central nervous system in response to peripheral administration of the proinflammatory cytokine, interleukin-1beta, or bacterial lipopolysaccharide. At later time points after peripheral lipopolysaccharide administration, interleukin-1 itself acts in the brain to mediate anorexia and is found in the arcuate nucleus of the hypothalamus. The mechanisms by which interleukin-1beta gains access to the brain and the potential role of neuropeptide-Y-containing neurons in the arcuate hypothalamus in mediating anorexia during disease are discussed.

  8. Interactive Effects of Morphine on HIV Infection: Role in HIV-Associated Neurocognitive Disorder

    Directory of Open Access Journals (Sweden)

    Pichili Vijaya Bhaskar Reddy

    2012-01-01

    Full Text Available HIV epidemic continues to be a severe public health problem and concern within USA and across the globe with about 33 million people infected with HIV. The frequency of drug abuse among HIV infected patients is rapidly increasing and is another major issue since injection drug users are at a greater risk of developing HIV associated neurocognitive dysfunctions compared to non-drug users infected with HIV. Brain is a major target for many of the recreational drugs and HIV. Evidences suggest that opiate drug abuse is a risk factor in HIV infection, neural dysfunction and progression to AIDS. The information available on the role of morphine as a cofactor in the neuropathogenesis of HIV is scanty. This review summarizes the results that help in understanding the role of morphine use in HIV infection and neural dysfunction. Studies show that morphine enhances HIV-1 infection by suppressing IL-8, downregulating chemokines with reciprocal upregulation of HIV coreceptors. Morphine also activates MAPK signaling and downregulates cAMP response element-binding protein (CREB. Better understanding on the role of morphine in HIV infection and mechanisms through which morphine mediates its effects may help in devising novel therapeutic strategies against HIV-1 infection in opiate using HIV-infected population.

  9. Self-reported sitting time and physical activity: interactive associations with mental well-being and productivity in office employees.

    Science.gov (United States)

    Puig-Ribera, Anna; Martínez-Lemos, Iván; Giné-Garriga, Maria; González-Suárez, Ángel Manuel; Bort-Roig, Judit; Fortuño, Jesús; Muñoz-Ortiz, Laura; McKenna, Jim; Gilson, Nicholas D

    2015-01-31

    Little is known about how sitting time, alone or in combination with markers of physical activity (PA), influences mental well-being and work productivity. Given the need to develop workplace PA interventions that target employees' health related efficiency outcomes; this study examined the associations between self-reported sitting time, PA, mental well-being and work productivity in office employees. Descriptive cross-sectional study. Spanish university office employees (n = 557) completed a survey measuring socio-demographics, total and domain specific (work and travel) self-reported sitting time, PA (International Physical Activity Questionnaire short version), mental well-being (Warwick-Edinburg Mental Well-Being Scale) and work productivity (Work Limitations Questionnaire). Multivariate linear regression analyses determined associations between the main variables adjusted for gender, age, body mass index and occupation. PA levels (low, moderate and high) were introduced into the model to examine interactive associations. Higher volumes of PA were related to higher mental well-being, work productivity and spending less time sitting at work, throughout the working day and travelling during the week, including the weekends (p active employees, higher sitting times on work days and occupational sitting were associated with decreased mental well-being (p active (p active employees. Employees' PA levels exerts different influences on the associations between sitting time, mental well-being and work productivity. The specific associations and the broad sweep of evidence in the current study suggest that workplace PA strategies to improve the mental well-being and productivity of all employees should focus on reducing sitting time alongside efforts to increase PA.

  10. Analyzing the pathways enriched in genes associated with nicotine dependence in the context of human protein-protein interaction network.

    Science.gov (United States)

    Hu, Ying; Fang, Zhonghai; Yang, Yichen; Fan, Ting; Wang, Ju

    2018-03-16

    Nicotine dependence is the primary addictive stage of cigarette smoking. Although a lot of studies have been performed to explore the molecular mechanism underlying nicotine dependence, our understanding on this disorder is still far from complete. Over the past decades, an increasing number of candidate genes involved in nicotine dependence have been identified by different technical approaches, including the genetic association analysis. In this study, we performed a comprehensive collection of candidate genes reported to be genetically associated with nicotine dependence. Then, the biochemical pathways enriched in these genes were identified by considering the gene's propensity to be related to nicotine dependence. One of the most widely used pathway enrichment analysis approach, over-representation analysis, ignores the function non-equivalence of genes in candidate gene set and may have low discriminative power in identifying some dysfunctional pathways. To overcome such drawbacks, we constructed a comprehensive human protein-protein interaction network, and then assigned a function weighting score to each candidate gene based on their network topological features. Evaluation indicated the function weighting score scheme was consistent with available evidence. Finally, the function weighting scores of the candidate genes were incorporated into pathway analysis to identify the dysfunctional pathways involved in nicotine dependence, and the interactions between pathways was detected by pathway crosstalk analysis. Compared to conventional over-representation based pathway analysis tool, the modified method exhibited improved discriminative power and detected some novel pathways potentially underlying nicotine dependence. In summary, we conducted a comprehensive collection of genes associated with nicotine dependence and then detected the biochemical pathways enriched in these genes using a modified pathway enrichment analysis approach with function weighting

  11. Kaposi's sarcoma-associated herpesvirus ORF45 interacts with kinesin-2 transporting viral capsid-tegument complexes along microtubules.

    Directory of Open Access Journals (Sweden)

    Narayanan Sathish

    2009-03-01

    Full Text Available Open reading frame (ORF 45 of Kaposi's sarcoma-associated herpesvirus (KSHV is a tegument protein. A genetic analysis with a null mutant suggested a possible role for this protein in the events leading to viral egress. In this study, ORF45 was found to interact with KIF3A, a kinesin-2 motor protein that transports cargoes along microtubules to cell periphery in a yeast two-hybrid screen. The association was confirmed by both co-immunoprecipitation and immunoflorescence approaches in primary effusion lymphoma cells following virus reactivation. ORF45 principally mediated the docking of entire viral capsid-tegument complexes onto the cargo-binding domain of KIF3A. Microtubules served as the major highways for transportation of these complexes as evidenced by drastically reduced viral titers upon treatment of cells with a microtubule depolymerizer, nocodazole. Confocal microscopic images further revealed close association of viral particles with microtubules. Inhibition of KIF3A-ORF45 interaction either by the use of a headless dominant negative (DN mutant of KIF3A or through shRNA-mediated silencing of endogenous KIF3A expression noticeably decreased KSHV egress reflecting as appreciable reductions in the release of extracellular virions. Both these approaches, however, failed to impact HSV-1 egress, demonstrating the specificity of KIF3A in KSHV transportation. This study thus reports on transportation of KSHV viral complexes on microtubules by KIF3A, a kinesin motor thus far not implicated in virus transportation. All these findings shed light on the understudied but significant events in the KSHV life cycle, delineating a crucial role of a KSHV tegument protein in cellular transport of viral particles.

  12. A harsh parenting team? Maternal reports of coparenting and coercive parenting interact in association with children's disruptive behaviour.

    Science.gov (United States)

    Latham, Rachel M; Mark, Katharine M; Oliver, Bonamy R

    2017-05-01

    Parenting and coparenting are both important for children's adjustment, but their interaction has been little explored. Using a longitudinal design and considering two children per family, we investigated mothers' and fathers' perceptions of coparenting as moderators of associations between their coercive parenting and children's disruptive behaviour. Mothers and fathers from 106 'intact' families were included from the Twins, Family and Behaviour study. At Time 1 (M child age  = 3 years 11 months, SD child age  = 4.44 months) parents reported on their coercive parenting and children's disruptive behaviour via questionnaire; at Time 2 (M child age  = 4 years 8 months, SD child age  = 4.44 months) perceptions of coparenting and the marital relationship were collected by telephone interview. Questionnaire-based reports of children's disruptive behaviour were collected at follow-up (M child age  = 5 years 11 months, SD child age  = 5.52 months). Multilevel modelling was used to examine child-specific and family-wide effects. Conservative multilevel models including both maternal and paternal perceptions demonstrated that maternal perceptions of coparenting and overall coercive parenting interacted in their prediction of parent-reported child disruptive behaviour. Specifically, accounting for perceived marital quality, behavioural stability, and fathers' perceptions, only in the context of perceived higher quality coparenting was there a positive association between mother-reported overall coercive parenting and children's disruptive behaviour at follow-up. When combined with highly coercive parenting, maternal perceptions of high quality coparenting may be detrimental for children's adjustment. © 2016 Association for Child and Adolescent Mental Health.

  13. Placental genome and maternal-placental genetic interactions: a genome-wide and candidate gene association study of placental abruption.

    Directory of Open Access Journals (Sweden)

    Marie Denis

    Full Text Available While available evidence supports the role of genetics in the pathogenesis of placental abruption (PA, PA-related placental genome variations and maternal-placental genetic interactions have not been investigated. Maternal blood and placental samples collected from participants in the Peruvian Abruptio Placentae Epidemiology study were genotyped using Illumina's Cardio-Metabochip platform. We examined 118,782 genome-wide SNPs and 333 SNPs in 32 candidate genes from mitochondrial biogenesis and oxidative phosphorylation pathways in placental DNA from 280 PA cases and 244 controls. We assessed maternal-placental interactions in the candidate gene SNPS and two imprinted regions (IGF2/H19 and C19MC. Univariate and penalized logistic regression models were fit to estimate odds ratios. We examined the combined effect of multiple SNPs on PA risk using weighted genetic risk scores (WGRS with repeated ten-fold cross-validations. A multinomial model was used to investigate maternal-placental genetic interactions. In placental genome-wide and candidate gene analyses, no SNP was significant after false discovery rate correction. The top genome-wide association study (GWAS hits were rs544201, rs1484464 (CTNNA2, rs4149570 (TNFRSF1A and rs13055470 (ZNRF3 (p-values: 1.11e-05 to 3.54e-05. The top 200 SNPs of the GWAS overrepresented genes involved in cell cycle, growth and proliferation. The top candidate gene hits were rs16949118 (COX10 and rs7609948 (THRB (p-values: 6.00e-03 and 8.19e-03. Participants in the highest quartile of WGRS based on cross-validations using SNPs selected from the GWAS and candidate gene analyses had a 8.40-fold (95% CI: 5.8-12.56 and a 4.46-fold (95% CI: 2.94-6.72 higher odds of PA compared to participants in the lowest quartile. We found maternal-placental genetic interactions on PA risk for two SNPs in PPARG (chr3:12313450 and chr3:12412978 and maternal imprinting effects for multiple SNPs in the C19MC and IGF2/H19 regions

  14. CXCL1-Mediated Interaction of Cancer Cells with Tumor-Associated Macrophages and Cancer-Associated Fibroblasts Promotes Tumor Progression in Human Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Makito Miyake

    2016-10-01

    Full Text Available Tumor-associated macrophages (TAMs and cancer-associated fibroblasts (CAFs are reported to be associated with poor prognosis, depending on their pro-tumoral roles. Current knowledge of TAMs and CAFs in the tumor microenvironment of urothelial cancer of the bladder (UCB is limited. Therefore, we investigated the paracrine effect induced by TAMs and CAFs in the tumor microenvironment of human UCB. For this, we first carried out immunohistochemical analysis for CXCL1, CD204 (TAM marker, αSMA (CAF marker, E-cadherin, and MMP2 using 155 UBC tissue samples. Next, CXCL1-overexpressing clones of THP-1-derived TAMs and NIH3T3-derived CAFs were developed by lentiviral vector infection. The immunohistochemical study showed high CXCL1 levels in UCB cells to be associated with enhanced recruitment of TAMs/CAFs, higher metastatic potential, and poor prognosis. Three-dimensional (3D co-culture of UCB cells and TAMs/CAFs suggested that CXCL1 production in TAMs/CAFs play an important role in cell-to-cell adhesion and interaction among cancer cells and these stromal cells. CXCL1-expressing TAMs/CAFs enhanced tumor growth of subcutaneous UCB tumors in nude mice when injected together. In addition, an experiment using the orthotopic bladder cancer model revealed that CXCL1 production in TAMs/CAFs supported tumor implantation into the murine bladder wall and UCB growth when injected together, which was confirmed by clinical data of patients with bladder cancer. Thus, CXCL1 signaling in the tumor microenvironment is highly responsible for repeated intravesical recurrence, disease progression, and drug resistance through enhanced invasion ability. In conclusion, disrupting CXCL1 signaling to dysregulate this chemokine is a promising therapeutic approach for human UCB.

  15. A Study of Oceans and Atmospheric Interactions Associated with Tropical Cyclone Activity using Earth Observing Technology

    Science.gov (United States)

    Abdullah, Warith; Reddy, Remata

    computations for atmospheric interface suggests unusual warmth associated with Gulf Stream current, such that it provided Sandy with enough kinetic energy to intensify at high latitude. The study further suggests that energy gained from Caribbean TCHP and Gulf Stream SST’s were largely retained by Sandy upon losing tropical-cyclone characteristics and merging with strong cold front and polar jet stream. Storms of Sandy’s magnitude and unusual source of energy resulting from Gulf Stream may indicate a building average for tropical cyclone development and intensity for North Atlantic, particularly as the GOM waters continue to warm on seasonal averages.

  16. The Influence of Social Interaction and Physical Health on the Association Between Hearing and Depression With Age and Gender.

    Science.gov (United States)

    Keidser, Gitte; Seeto, Mark

    2017-01-01

    Recent epidemiological data suggest the relation between hearing difficulty and depression is more evident in younger and middle-aged populations than in older adults. There are also suggestions that the relation may be more evident in specific subgroups; that is, other factors may influence a relationship between hearing and depression in different subgroups. Using cross-sectional data from the UK Biobank on 134,357 community-dwelling people and structural equation modelling, this study examined the potential mediating influence of social isolation and unemployment and the confounding influence of physical illness and cardiovascular conditions on the relation between a latent hearing variable and both a latent depressive episodes variable and a latent depressive symptoms variable. The models were stratified by age (40s, 50s, and 60s) and gender and further controlled for physical illness and professional support in associations involving social isolation and unemployment. The latent hearing variable was primarily defined by reported hearing difficulty in noise. For all subgroups, poor hearing was significantly related to both more depressive episodes and more depressive symptoms. In all models, the direct and generally small association exceeded the indirect associations via physical health and social interaction. Significant (depressive episodes) and near significant (depressive symptoms) higher direct associations were estimated for males in their 40s and 50s than for males in their 60s. There was at each age-group no significant difference in estimated associations across gender. Irrespective of the temporal order of variables, findings suggest that audiological services should facilitate psychosocial counselling.

  17. Parent- and teacher-child relationships and engagement at school entry: Mediating, interactive, and transactional associations across contexts.

    Science.gov (United States)

    Heatly, Melissa Castle; Votruba-Drzal, Elizabeth

    2017-06-01

    Early school engagement patterns set the stage for short- and long-term academic behaviors and progress, and low engagement at school entry can give rise to dysfunctional school behavior and underachievement in later years. Relationships with parents and teachers provide a foundation upon which children develop the skills and behaviors that are critical for engagement in early elementary school. However, the cross-contextual and transactional processes by which these relationships are associated with engagement in early elementary school remain unclear. This investigation therefore considers how children's relationships with parents prior to school entry are indirectly and interactively associated with 1st grade engagement through teacher-child relationships. It also considers how early cognitive, self-regulatory, and behavioral skills and competencies elicit these relational responses. This investigation drew upon multimethod data from triangulated sources (parents, teachers, and direct observation) available within a large longitudinal study, the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development. Results indicate that neither 54-month or 1st grade parent-child relationships were directly associated with children's engagement in early elementary school. However, 1st grade teacher conflict was problematic for children's developing engagement. In turn, teacher conflict partially mediated linkages between maternal sensitivity and conflict prior to school entry and engagement in 1st grade. Parental closeness and sensitivity also buffered children against negative associations between teacher conflict and engagement. Finally, children's early skills and competencies at 36 months elicited relational processes that were indirectly associated with engagement. Conceptual, theoretical, and methodological challenges are also discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. I.4 Screening Experimental Designs for Quantitative Trait Loci, Association Mapping, Genotype-by Environment Interaction, and Other Investigations.

    Science.gov (United States)

    Federer, Walter T; Crossa, José

    2012-01-01

    Crop breeding programs using conventional approaches, as well as new biotechnological tools, rely heavily on data resulting from the evaluation of genotypes in different environmental conditions (agronomic practices, locations, and years). Statistical methods used for designing field and laboratory trials and for analyzing the data originating from those trials need to be accurate and efficient. The statistical analysis of multi-environment trails (MET) is useful for assessing genotype × environment interaction (GEI), mapping quantitative trait loci (QTLs), and studying QTL × environment interaction (QEI). Large populations are required for scientific study of QEI, and for determining the association between molecular markers and quantitative trait variability. Therefore, appropriate control of local variability through efficient experimental design is of key importance. In this chapter we present and explain several classes of augmented designs useful for achieving control of variability and assessing genotype effects in a practical and efficient manner. A popular procedure for unreplicated designs is the one known as "systematically spaced checks." Augmented designs contain "c" check or standard treatments replicated "r" times, and "n" new treatments or genotypes included once (usually) in the experiment.

  19. Antisense RNA controls LRP1 Sense transcript expression through interaction with a chromatin-associated protein, HMGB2.

    Science.gov (United States)

    Yamanaka, Yasunari; Faghihi, Mohammad Ali; Magistri, Marco; Alvarez-Garcia, Oscar; Lotz, Martin; Wahlestedt, Claes

    2015-05-12

    Long non-coding RNAs (lncRNAs), including natural antisense transcripts (NATs), are expressed more extensively than previously anticipated and have widespread roles in regulating gene expression. Nevertheless, the molecular mechanisms of action of the majority of NATs remain largely unknown. Here, we identify a NAT of low-density lipoprotein receptor-related protein 1 (Lrp1), referred to as Lrp1-AS, that negatively regulates Lrp1 expression. We show that Lrp1-AS directly binds to high-mobility group box 2 (Hmgb2) and inhibits the activity of Hmgb2 to enhance Srebp1a-dependent transcription of Lrp1. Short oligonucleotides targeting Lrp1-AS inhibit the interaction of antisense transcript and Hmgb2 protein and increase Lrp1 expression by enhancing Hmgb2 activity. Quantitative RT-PCR analysis of brain tissue samples from Alzheimer's disease patients and aged-matched controls revealed upregulation of LRP1-AS and downregulation of LRP1. Our data suggest a regulatory mechanism whereby a NAT interacts with a ubiquitous chromatin-associated protein to modulate its activity in a locus-specific fashion. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Antisense RNA Controls LRP1 Sense Transcript Expression through Interaction with a Chromatin-Associated Protein, HMGB2

    Directory of Open Access Journals (Sweden)

    Yasunari Yamanaka

    2015-05-01

    Full Text Available Long non-coding RNAs (lncRNAs, including natural antisense transcripts (NATs, are expressed more extensively than previously anticipated and have widespread roles in regulating gene expression. Nevertheless, the molecular mechanisms of action of the majority of NATs remain largely unknown. Here, we identify a NAT of low-density lipoprotein receptor-related protein 1 (Lrp1, referred to as Lrp1-AS, that negatively regulates Lrp1 expression. We show that Lrp1-AS directly binds to high-mobility group box 2 (Hmgb2 and inhibits the activity of Hmgb2 to enhance Srebp1a-dependent transcription of Lrp1. Short oligonucleotides targeting Lrp1-AS inhibit the interaction of antisense transcript and Hmgb2 protein and increase Lrp1 expression by enhancing Hmgb2 activity. Quantitative RT-PCR analysis of brain tissue samples from Alzheimer’s disease patients and aged-matched controls revealed upregulation of LRP1-AS and downregulation of LRP1. Our data suggest a regulatory mechanism whereby a NAT interacts with a ubiquitous chromatin-associated protein to modulate its activity in a locus-specific fashion.

  1. Remote sensing evidence of lava-ground ice interactions associated with the Lost Jim Lava Flow, Seward Peninsula, Alaska

    Science.gov (United States)

    Marcucci, Emma C.; Hamilton, Christopher W.; Herrick, Robert R.

    2017-12-01

    Thermokarst terrains develop when ice-bearing permafrost melts and causes the overlying surface to subside or collapse. This process occurs widely throughout Arctic regions due to environmental and climatological factors, but can also be induced by localized melting of ground ice by active lava flows. The Lost Jim Lava Flow (LJLF) on the Seward Peninsula of Alaska provides evidence of former lava-ground ice interactions. Associated geomorphic features, on the scale of meters to tens of meters, were identified using satellite orthoimages and stereo-derived digital terrain models. The flow exhibits positive- and mixed-relief features, including tumuli ( N = 26) and shatter rings ( N = 4), as well as negative-relief features, such as lava tube skylights ( N = 100) and irregularly shaped topographic depressions ( N = 1188) that are interpreted to include lava-rise pits and lava-induced thermokarst terrain. Along the margins of the flow, there are also clusters of small peripheral pits that may be the products of meltwater or steam escape. On Mars, we observed morphologically similar pits near lava flow margins in northeastern Elysium Planitia, which suggests a common formation mechanism. Investigating the LJLF may therefore help to elucidate processes of lava-ground ice interaction on both Earth and Mars.

  2. 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.

  3. Marine Microscale Interactions: Exploring the Ecological Relationships Between a Cosmopolitan Eukaryotic Diatom Thalassiosira rotula and its Associated Heterotrophic Bacterial Assemblage

    Science.gov (United States)

    Ahern, O. M.; Williams, T.; Whittaker, K. A.; Hunt, D.; Rynearson, T. A.

    2016-02-01

    Interspecies microscale interactions between eukaryotic marine diatoms and heterotrophic bacteria play a role in global oceanic biogeochemical cycling by influencing nutrient and carbon cycling, rates of primary production, and phytoplankton community structure. Studies have shown that marine diatoms carry a specific bacterial assemblage in their phycosphere, but little research has been done to identify these bacterial species and to characterize their ecological relationships despite their strong potential to regulate diatom growth and production. In order to further explore ecological interactions between bacteria and diatoms, we are characterizing the taxonomic composition of phycosphere communities from isolates of the cosmopolitan marine diatom Thalassiosira rotula collected from around the globe and identifying whether environmental factors, different host T. rotula strains, space or season correlate with different phycosphere communities. For our initial analyses, we amplified and sequenced the 16S rDNA v34 region of the phycosphere assemblage of 53 T. rotula isolates from eight locations around the globe and obtained > 420,000 paired-end sequences. We identified > 250 different bacterial operational taxonomic units (OTUs). Although many OTUs were shared across populations which identified to members of Alphaproteobacteria and Gammaproteobacteria, we identified distinct bacterial assemblages associated with different locations. The presence of distinct phycosphere bacterial communities may regulate diatom growth which potentially affects rates of primary production, nutrient bioavailablity, and, ultimately, energy transfer to higher trophic levels.

  4. You can’t kid a kidder: Association between production and detection of deception in an interactive deception task

    Directory of Open Access Journals (Sweden)

    Gordon R.T. Wright

    2012-04-01

    Full Text Available Both the ability to deceive others, and the ability to detect deception, have long been proposed to confer an evolutionary advantage. Deception detection has been studied extensively, and the finding that typical individuals fare little better than chance in detecting deception is one of the more robust in the behavioral sciences. Surprisingly, little research has examined individual differences in lie-production ability. As a consequence, as far as we are aware, no previous study has investigated whether there exists an association between the ability to lie successfully and the ability to detect lies. Furthermore, only a minority of studies have examined deception as it naturally occurs; in a social, interactive setting. The present study therefore explored the relationship between these two facets of deceptive behavior by employing a novel competitive interactive deception task. For the first time, signal-detection theory was used to measure performance in both the detection and production of deception. A significant relationship was found between the deception-related abilities; those who could accurately detect a lie were able to produce statements that others found difficult to classify as deceptive or truthful. Furthermore, neither ability was related to measures of intelligence or emotional ability. We therefore suggest the existence of an underlying deception-general ability that varies across individuals.

  5. Functional neuroanatomy associated with the interaction between emotion and cognition in explicit memory tasks in patients with generalized anxiety disorder.

    Science.gov (United States)

    Moon, Chung-Man; Yang, Jong-Chul; Jeong, Gwang-Woo

    2017-01-01

    The functional neuroanatomy for explicit memory in conjunction with the major anxiety symptoms in patients with generalized anxiety disorder (GAD) has not yet been clearly identified. To investigate the brain activation patterns on the interaction between emotional and cognitive function during the explicit memory tasks, as well as its correlation with clinical characteristics in GAD. The participants comprised GAD patients and age-matched healthy controls. The fMR images were obtained while the participants performed an explicit memory task with neutral and anxiety-inducing words. Patients showed significantly decreased functional activities in the putamen, head of the caudate nucleus, hippocampus, and middle cingulate gyrus during the memory tasks with the neutral and anxiety-inducing words, whereas the precentral gyrus and ventrolateral prefrontal cortex were significantly increased only in the memory tasks with the anxiety-inducing words. Also, the blood oxygenation level-dependent (BOLD) signal changes in the hippocampus were positively correlated with the recognition accuracy for both neutral and anxiety-inducing words. This study identified the brain areas associated with the interaction between emotional regulation and cognitive function in the explicit memory tasks in patients with GAD. These findings would be helpful to understand the neural mechanism on the explicit memory-related cognitive deficits and emotional dysfunction with GAD symptoms. © The Foundation Acta Radiologica 2016.

  6. Observation of prompt single muons and of missing energy associated with $\\mu^{+}\\mu^{-}$ pairs produced in hadronic interactions

    CERN Document Server

    Bodek, A.; Bartlett, J.F.; Brown, K.W.; Shaevitz, M.H.; Siskind, E.J.; Diamant-Berger, A.; Dishaw, J.P.; Faessler, M.; Liu, J.K.; Merritt, F.S.; Wojcicki, S.G.

    1979-01-01

    In a study of interactions of 400 GeV protons in a totally absorbing iron calorimeter the authors report two observations indicating the hadronic production of heavy short-lived weakly decaying particles. First they have observed a prompt muon signal in the region .8

    associated with a significant amount of missing energy indicative of final state neutrinos. Interpreting these data as production of DD pairs followed by single or double muonic decays leads to a model dependent estimate of total production cross-section of order 15 mu b. (14 refs).

  7. Ecology of Fungus Gnats (Bradysia spp. in Greenhouse Production Systems Associated with Disease-Interactions and Alternative Management Strategies

    Directory of Open Access Journals (Sweden)

    Raymond A. Cloyd

    2015-04-01

    Full Text Available Fungus gnats (Bradysia spp. are major insect pests of greenhouse-grown horticultural crops mainly due to the direct feeding damage caused by the larvae, and the ability of larvae to transmit certain soil-borne plant pathogens. Currently, insecticides and biological control agents are being used successively to deal with fungus gnat populations in greenhouse production systems. However, these strategies may only be effective as long as greenhouse producers also implement alternative management strategies such as cultural, physical, and sanitation. This includes elimination of algae, and plant and growing medium debris; placing physical barriers onto the growing medium surface; and using materials that repel fungus gnat adults. This article describes the disease-interactions associated with fungus gnats and foliar and soil-borne diseases, and the alternative management strategies that should be considered by greenhouse producers in order to alleviate problems with fungus gnats in greenhouse production systems.

  8. Toponomics analysis of functional interactions of the ubiquitin ligase PAM (Protein Associated with Myc) during spinal nociceptive processing.

    Science.gov (United States)

    Pierre, Sandra; Maeurer, Christian; Coste, Ovidiu; Becker, Wiebke; Schmidtko, Achim; Holland, Sabrina; Wittpoth, Claus; Geisslinger, Gerd; Scholich, Klaus

    2008-12-01

    Protein associated with Myc (PAM) is a giant E3 ubiquitin ligase of 510 kDa. Although the role of PAM during neuronal development is well established, very little is known about its function in the regulation of synaptic strength. Here we used multiepitope ligand cartography (MELC) to study protein network profiles associated with PAM during the modulation of synaptic strength. MELC is a novel imaging technology that utilizes biomathematical tools to describe protein networks after consecutive immunohistochemical visualization of up to 100 proteins on the same sample. As an in vivo model to modulate synaptic strength we used the formalin test, a common model for acute and inflammatory pain. MELC analysis was performed with 37 different antibodies or fluorescence tags on spinal cord slices and led to the identification of 1390 PAM-related motifs that distinguish untreated and formalin-treated spinal cords. The majority of these motifs related to ubiquitin-dependent processes and/or the actin cytoskeleton. We detected an intermittent colocalization of PAM and ubiquitin with TSC2, a known substrate of PAM, and the glutamate receptors mGluR5 and GLUR1. Importantly these complexes were detected exclusively in the presence of F-actin. A direct PAM/F-actin interaction was confirmed by colocalization and cosedimentation. The binding of PAM toward F-actin varied strongly between the PAM splice forms found in rat spinal cords. PAM did not ubiquitylate actin or alter actin polymerization and depolymerization. However, F-actin decreased the ubiquitin ligase activity of purified PAM. Because PAM activation is known to involve its translocation, the binding of PAM to F-actin may serve to control its subcellular localization as well as its activity. Taken together we show that defining protein network profiles by topological proteomics analysis is a useful tool to identify previously unknown protein/protein interactions that underlie synaptic processes.

  9. GPR68, a proton-sensing GPCR, mediates interaction of cancer-associated fibroblasts and cancer cells.

    Science.gov (United States)

    Wiley, Shu Z; Sriram, Krishna; Liang, Wenjing; Chang, Sarah E; French, Randall; McCann, Thalia; Sicklick, Jason; Nishihara, Hiroshi; Lowy, Andrew M; Insel, Paul A

    2018-03-01

    The microenvironment of pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense fibrotic stroma (desmoplasia) generated by pancreatic cancer-associated fibroblasts (CAFs) derived from pancreatic stellate cells (PSCs) and pancreatic fibroblasts (PFs). Using an unbiased GPCRomic array approach, we identified 82 G-protein-coupled receptors (GPCRs) commonly expressed by CAFs derived from 5 primary PDAC tumors. Compared with PSCs and PFs, CAFs have increased expression of GPR68 (a proton-sensing GPCR), with the results confirmed by immunoblotting, The Cancer Genome Atlas data, and immunohistochemistry of PDAC tumors. Co-culture of PSCs with PDAC cells, or incubation with TNF-α, induced GPR68 expression. GPR68 activation (by decreasing the extracellular pH) enhanced IL-6 expression via a cAMP/PKA/cAMP response element binding protein signaling pathway. Knockdown of GPR68 by short interfering RNA diminished low pH-induced production of IL-6 and enhancement of PDAC cell proliferation by CAF conditioned media. CAFs from other gastrointestinal cancers also express GPR68. PDAC cells thus induce expression by CAFs of GPR68, which senses the acidic microenvironment, thereby increasing production of fibrotic markers and IL-6 and promoting PDAC cell proliferation. CAF-expressed GPR68 is a mediator of low-pH-promoted regulation of the tumor microenvironments, in particular to PDAC cell-CAF interaction and may be a novel therapeutic target for pancreatic and perhaps other types of cancers.-Wiley, S. Z., Sriram, K., Liang, W., Chang, S. E., French, R., McCann, T., Sicklick, J., Nishihara, H., Lowy, A. M., Insel, P. A. GPR68, a proton-sensing GPCR, mediates interaction of cancer-associated fibroblasts and cancer cells.

  10. A study for association and interaction analysis to metabolic syndrome and the ESR1 gene on cardiovascular autonomic neuropathy in a Chinese Han population.

    Science.gov (United States)

    Zeng, Fangfang; Zhou, Linuo; Tang, Zihui

    2016-01-01

    The aim of this study was to investigate the association and interaction of metabolic syndrome (MetS) and estrogen receptor alpha 1 (ESR1) gene polymorphisms on cardiovascular autonomic neuropathy (CAN). A large-scale, population-based study was conducted to analyze the interaction of MetS and ESR1 gene polymorphisms to CAN, including a total of 1977 Chinese subjects. The most common studied single nucleotide polymorphism of ESR1 gene-rs9340799, was genotyped. Multiple logistic regression (MLR) was performed to evaluate the interaction effect of environmental variables and gene polymorphisms. Interaction on an additive scale can be calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). After controlling potential confounders, MLR showed that significant association between MetS and CAN (p interaction was estimated by using RETI = 0.396 (95 % CI 0.262 to 0.598), AP = 0.216 (95 % CI -0.784 to 1.216) and S = 1.906 (95 % CI 0.905 to 4.015). The present findings suggest that MetS is significantly associated with CAN and provide evidence for the hypothesis that MetS and ESR1 gene polymorphism (rs9340799) have interactive effects on CAN. ClinicalTrials gov Identifier NCT02461342.

  11. Genome-wide association study for the interaction between BMR and BMI in obese Korean women including overweight.

    Science.gov (United States)

    Lee, Myoungsook; Kwon, Dae Young; Kim, Myung-Sunny; Choi, Chong Ran; Park, Mi-Young; Kim, Ae-Jung

    2016-02-01

    This is the first study to identify common genetic factors associated with the basal metabolic rate (BMR) and body mass index (BMI) in obese Korean women including overweight. This will be a basic study for future research of obese gene-BMR interaction. The experimental design was 2 by 2 with variables of BMR and BMI. A genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) was conducted in the overweight and obesity (BMI > 23 kg/m(2)) compared to the normality, and in women with low BMR (BMR. A total of 140 SNPs reached formal genome-wide statistical significance in this study (P BMR (rs10786764; P = 8.0 × 10(-7), rs1040675; 2.3 × 10(-6)) and BMI (rs10786764; P = 2.5 × 10(-5), rs10786764; 6.57 × 10(-5)). The other genes related to BMI (HSD52, TMA16, MARCH1, NRG1, NRXN3, and STK4) yielded P BMR and BMI, including NRG3, OR8U8, BCL2L2-PABPN1, PABPN1, and SLC22A17 were identified in obese Korean women (P BMR- and BMI-related genes using GWAS. Although most of these newly established loci were not previously associated with obesity, they may provide new insights into body weight regulation. Our findings of five common genes associated with BMR and BMI in Koreans will serve as a reference for replication and validation of future studies on the metabolic rate.

  12. Air pollution and markers of coagulation, inflammation, and endothelial function: associations and epigene-environment interactions in an elderly cohort.

    Science.gov (United States)

    Bind, Marie-Abele; Baccarelli, Andrea; Zanobetti, Antonella; Tarantini, Letizia; Suh, Helen; Vokonas, Pantel; Schwartz, Joel

    2012-03-01

    Previous studies suggest that air pollution is related to thrombosis, inflammation, and endothelial dysfunction. Mechanisms and sources of susceptibility are still unclear. One possibility is that these associations can be modified by DNA methylation states. We conducted a cohort study with repeated measurements of fibrinogen, C-reactive protein, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in 704 elderly men participating in the Veterans Administration Normative Aging Study (2000-2009). We investigated short- and intermediate-term air pollution effects on these blood markers, and epigene-environment interactions by DNA methylation of Alu, LINE-1, tissue factor (F3), Toll-like receptor 2 (TLR-2), and ICAM-1. We found effects of particle number, black carbon, nitrogen dioxide (NO(2)), and carbon monoxide (CO) on fibrinogen. Ozone was a predictor of C-reactive protein and ICAM-1. Particle number, black carbon, NO(2), CO, PM(2.5), and sulfates were associated with ICAM-1 and VCAM-1. An interquartile range increase in 24-hour exposure for NO(2) was associated with a 1.7% (95% confidence interval = 0.2%-3.3%) increase in fibrinogen for ozone; a 10.8% (2.2%-20.0%) increase in C-reactive protein for particle number; a 5.9% (3.6%-8.3%) increase in ICAM-1; and for PM(2.5), a 3.7% (1.7%-5.8%) increase in VCAM-1. The air pollution effect was stronger among subjects having higher Alu, lower LINE-1, tissue factor, or TLR-2 methylation status. We observed associations of traffic-related pollutants on fibrinogen, and both traffic and secondary particles on C-reactive protein, ICAM-1, and VCAM-1. There was effect modification by DNA methylation status, indicating that epigenetic states can convey susceptibility to air pollution.

  13. SAP-like domain in nucleolar spindle associated protein mediates mitotic chromosome loading as well as interphase chromatin interaction

    Energy Technology Data Exchange (ETDEWEB)

    Verbakel, Werner, E-mail: werner.verbakel@chem.kuleuven.be [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium); Carmeliet, Geert, E-mail: geert.carmeliet@med.kuleuven.be [Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Herestraat 49, Bus 902, 3000 Leuven (Belgium); Engelborghs, Yves, E-mail: yves.engelborghs@fys.kuleuven.be [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium)

    2011-08-12

    Highlights: {yields} The SAP-like domain in NuSAP is a functional DNA-binding domain with preference for dsDNA. {yields} This SAP-like domain is essential for chromosome loading during early mitosis. {yields} NuSAP is highly dynamic on mitotic chromatin, as evident from photobleaching experiments. {yields} The SAP-like domain also mediates NuSAP-chromatin interaction in interphase nucleoplasm. -- Abstract: Nucleolar spindle associated protein (NuSAP) is a microtubule-stabilizing protein that localizes to chromosome arms and chromosome-proximal microtubules during mitosis and to the nucleus, with enrichment in the nucleoli, during interphase. The critical function of NuSAP is underscored by the finding that its depletion in HeLa cells results in various mitotic defects. Moreover, NuSAP is found overexpressed in multiple cancers and its expression levels often correlate with the aggressiveness of cancer. Due to its localization on chromosome arms and combination of microtubule-stabilizing and DNA-binding properties, NuSAP takes a special place within the extensive group of spindle assembly factors. In this study, we identify a SAP-like domain that shows DNA binding in vitro with a preference for dsDNA. Deletion of the SAP-like domain abolishes chromosome arm binding of NuSAP during mitosis, but is not sufficient to abrogate its chromosome-proximal localization after anaphase onset. Fluorescence recovery after photobleaching experiments revealed the highly dynamic nature of this NuSAP-chromatin interaction during mitosis. In interphase cells, NuSAP also interacts with chromatin through its SAP-like domain, as evident from its enrichment on dense chromatin regions and intranuclear mobility, measured by fluorescence correlation spectroscopy. The obtained results are in agreement with a model where NuSAP dynamically stabilizes newly formed microtubules on mitotic chromosomes to enhance chromosome positioning without immobilizing these microtubules. Interphase Nu

  14. SAP-like domain in nucleolar spindle associated protein mediates mitotic chromosome loading as well as interphase chromatin interaction

    International Nuclear Information System (INIS)

    Verbakel, Werner; Carmeliet, Geert; Engelborghs, Yves

    2011-01-01

    Highlights: → The SAP-like domain in NuSAP is a functional DNA-binding domain with preference for dsDNA. → This SAP-like domain is essential for chromosome loading during early mitosis. → NuSAP is highly dynamic on mitotic chromatin, as evident from photobleaching experiments. → The SAP-like domain also mediates NuSAP-chromatin interaction in interphase nucleoplasm. -- Abstract: Nucleolar spindle associated protein (NuSAP) is a microtubule-stabilizing protein that localizes to chromosome arms and chromosome-proximal microtubules during mitosis and to the nucleus, with enrichment in the nucleoli, during interphase. The critical function of NuSAP is underscored by the finding that its depletion in HeLa cells results in various mitotic defects. Moreover, NuSAP is found overexpressed in multiple cancers and its expression levels often correlate with the aggressiveness of cancer. Due to its localization on chromosome arms and combination of microtubule-stabilizing and DNA-binding properties, NuSAP takes a special place within the extensive group of spindle assembly factors. In this study, we identify a SAP-like domain that shows DNA binding in vitro with a preference for dsDNA. Deletion of the SAP-like domain abolishes chromosome arm binding of NuSAP during mitosis, but is not sufficient to abrogate its chromosome-proximal localization after anaphase onset. Fluorescence recovery after photobleaching experiments revealed the highly dynamic nature of this NuSAP-chromatin interaction during mitosis. In interphase cells, NuSAP also interacts with chromatin through its SAP-like domain, as evident from its enrichment on dense chromatin regions and intranuclear mobility, measured by fluorescence correlation spectroscopy. The obtained results are in agreement with a model where NuSAP dynamically stabilizes newly formed microtubules on mitotic chromosomes to enhance chromosome positioning without immobilizing these microtubules. Interphase NuSAP-chromatin interaction

  15. Origins of two types of serpentinites from the Qinling orogenic belt, central China and associated fluid/melt-rock interactions

    Science.gov (United States)

    Wu, Kai; Ding, Xing; Ling, Ming-Xing; Sun, Wei-dong; Zhang, Li-Peng; Hu, Yong-Bin; Huang, Rui-Fang

    2018-03-01

    Serpentinites are important volatile and fluid mobile element repositories in oceanic lithosphere and subduction zones, and thus provide significant constraints on global geochemical cycles and tectonic evolution at convergent margins. In this contribution, two types of serpentinites from the Mianlue suture zone in the Qinling orogenic belt, central China, are identified on the basis of detailed mineralogical and geochemical study. Serpentinites from the Jianchaling region (Group 1) are composed of lizardite/chrysotile + magnesite + magnetite. Most of these serpentinites (Group 1a), consist of pseudomorphic orthopyroxene and olivine, and are characterized by low Al2O3/SiO2, high MgO/SiO2 and Ir-type PGEs to Pt ratios, suggesting a residual mantle origin. Meanwhile, the U-shape REE pattern and positive Eu, Sr and Ba anomalies of these serpentinites indicate that serpentinization fluids have interacted with gabbroic cumulates at moderately high temperatures or associate with the chlorinity and redox conditions of the fluid. Considering the limited mobility of U in the hydrating fluids for the Group 1a serpentinites, hydrating fluids for these serpentinites are most likely derived from the dehydrated slab, and have been in equilibrium with subducting sediments. There are also some serpentinites with low-grade metamorphic recrystallization from the Jianchaling region (Group 1b), represented by recrystallized serpentine minerals (antigorite). The trace element compositions of these Group 1b serpentinites suggest that partial dehydration of serpentinites associated with the transformation from lizardite to antigorite in subduction zone is also likely to affect the geochemistry of serpentinites. Serpentinites from the Liangyazi region (Group 2) are composed of antigorite + dolomite + spinel + magnetite. The high Cr number (0.65-0.80) and low Ti concentrations of spinels in Group 2 serpentinites indicate a refractory mantle wedge origin. Fertile major element compositions

  16. Aberrant trafficking of NSCLC-associated EGFR mutants through the endocytic recycling pathway promotes interaction with Src@

    Directory of Open Access Journals (Sweden)

    Band Vimla

    2009-11-01

    Full Text Available Abstract Background Epidermal growth factor receptor (EGFR controls a wide range of cellular processes, and altered EGFR signaling contributes to human cancer. EGFR kinase domain mutants found in non-small cell lung cancer (NSCLC are constitutively active, a trait critical for cell transformation through activation of downstream pathways. Endocytic trafficking of EGFR is a major regulatory mechanism as ligand-induced lysosomal degradation results in termination of signaling. While numerous studies have examined mutant EGFR signaling, the endocytic traffic of mutant EGFR within the NSCLC milieu remains less clear. Results This study shows that mutant EGFRs in NSCLC cell lines are constitutively endocytosed as shown by their colocalization with the early/recycling endosomal marker transferrin and the late endosomal/lysosomal marker LAMP1. Notably, mutant EGFRs, but not the wild-type EGFR, show a perinuclear accumulation and colocalization with recycling endosomal markers such as Rab11 and EHD1 upon treatment of cells with endocytic recycling inhibitor monensin, suggesting that mutant EGFRs preferentially traffic through the endocytic recycling compartments. Importantly, monensin treatment enhanced the mutant EGFR association and colocalization with Src, indicating that aberrant transit through the endocytic recycling compartment promotes mutant EGFR-Src association. Conclusion The findings presented in this study show that mutant EGFRs undergo aberrant traffic into the endocytic recycling compartment which allows mutant EGFRs to engage in a preferential interaction with Src, a critical partner for EGFR-mediated oncogenesis.

  17. Prioritizing disease candidate proteins in cardiomyopathy-specific protein-protein interaction networks based on "guilt by association" analysis.

    Directory of Open Access Journals (Sweden)

    Wan Li

    Full Text Available The cardiomyopathies are a group of heart muscle diseases which can be inherited (familial. Identifying potential disease-related proteins is important to understand mechanisms of cardiomyopathies. Experimental identification of cardiomyophthies is costly and labour-intensive. In contrast, bioinformatics approach has a competitive advantage over experimental method. Based on "guilt by association" analysis, we prioritized candidate proteins involving in human cardiomyopathies. We first built weighted human cardiomyopathy-specific protein-protein interaction networks for three subtypes of cardiomyopathies using the known disease proteins from Online Mendelian Inheritance in Man as seeds. We then developed a method in prioritizing disease candidate proteins to rank candidate proteins in the network based on "guilt by association" analysis. It was found that most candidate proteins with high scores shared disease-related pathways with disease seed proteins. These top ranked candidate proteins were related with the corresponding disease subtypes, and were potential disease-related proteins. Cross-validation and comparison with other methods indicated that our approach could be used for the identification of potentially novel disease proteins, which may provide insights into cardiomyopathy-related mechanisms in a more comprehensive and integrated way.

  18. IGFBP-3 Interacts with the Vitamin D Receptor in Insulin Signaling Associated with Obesity in Visceral Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Inmaculada Moreno-Santos

    2017-11-01

    Full Text Available Adipose tissue has traditionally only been considered as an energy storage organ. Nevertheless, the importance of this tissue in systemic physiology and, especially, in systemic inflammation has been highlighted in recent years. Adipose tissue expresses proteins related to vitamin D (VD metabolism, and it has been proposed that it can act as a VD storage tissue. The active form of VD, 1,25-dihydroxyvitamin D3 (1,25(OH2D3, is able to modify adipocyte and adipose tissue physiology via the VD receptor (VDR, decreasing the expression of pro-inflammatory cytokines in adipose tissue. Moreover, VD deficiency and VDR has been reported to be associated with obesity and diabetes. However, the results of the different studies are not conclusive. Insulin growth binding proteins (IGFBPs have been identified in adipose tissue, but their roles are poorly understood. Therefore, the objective of this study was to analyze the plasma levels of VD and the gene expression of VDR in the adipose tissue of subjects with morbid obesity (MO and with different degrees of insulin resistance (IR, as well as the functionality of direct interaction between IGFBP-3 and VDR, which could explain its inhibitory role in adipogenesis. Our results show a novel role of the VD system in the regulation and activation of IGFBP-3 in visceral adipose tissue (VAT of patients with MO, as a new and alternative mechanism proposed in the insulin signaling associated with obesity.

  19. Alcohol consumption and its interaction with adiposity-associated genetic variants in relation to subsequent changes in waist circumference and body weight

    DEFF Research Database (Denmark)

    Rohde, Jeanett F.; Ängquist, Lars; Larsen, Sofus C.

    2017-01-01

    the association between alcohol intake recorded at baseline and subsequent annual changes in body weight (∆BW), waist circumference (ΔWC) and WC adjusted for BMI (ΔWCBMI), and to test for interaction with genetic predisposition scores based on single nucleotide polymorphisms (SNPs) associated with various forms...... interaction was observed among the men. CONCLUSION: Alcohol intake was associated with a decrease in BW and WC among men and women, and an increase in WCBMI among women only. We found no strong indication that these associations depend on a genetic predisposition to adiposity. TRIAL REGISTRATION: Registry......BACKGROUND: Studies have suggested a link between alcohol intake and adiposity. However, results from longitudinal studies have been inconsistent, and a possible interaction with genetic predisposition to adiposity measures has often not been taken into account. OBJECTIVE: To examine...

  20. INTERACTIVE SEMINARS IN BIOCHEMISTRY DISCIPLINE FOR UNDERGRADUATE DEGREE IN BIOMEDICINE: BENEFITS AND PROBLEMS OF CARBOHYDRATES ASSOCIATED WITH MODERN LIFE

    Directory of Open Access Journals (Sweden)

    R. G.G. Pessoa et al

    2015-08-01

    Full Text Available The present project is part of the course in biochemistry for biomedical undergraduate students of the Federal University of Pernambuco - UFPE, which comprises theoretical and practical classes and interactive seminars prepared by students on studied topics to supplement learning. The aim of this research was to encourage students to innovate their search for knowledge, presenting an interactive strategy to demonstrate the importance of carbohydrates, as well as other energy fuels, for undergraduates students attending classes of biochemistry at the first semester at the university, in order to clarify the importance of maintaining a healthy way of life. The methodology used was a field research, documented in videos in which the opinions of a few people were registered in different places, such as in a fast-food restaurant, on the importance of carbohydrates. Records acquired were associated with a slide presentation on the subject, based on scientific books and articles, which were presented to the students of the discipline. It was also developed a dynamic to illustrate the consumption of carbohydrates in daily life and in different situations. After the project exhibition, a review of the research was conducted to the audience to express innovations or additions to their pre-existing concepts, on consumption of carbohydrates. The results of our work were very promising and the main goal of the project was achieved, since 88.2% of the respondents said there was an improvement in their knowledge, both theoretical and practical, on the subject, while only 11.8% reported no improvement at all. In conclusion, there was a greater involvement of students during the presentation of the subject and a higher participation during the group dynamic on the consumption of carbohydrates.

  1. Interaction between Serotonin Transporter and Serotonin Receptor 1 B genes polymorphisms may be associated with antisocial alcoholism

    Directory of Open Access Journals (Sweden)

    Wang Tzu-Yun

    2012-07-01

    Full Text Available Abstract Background Several studies have hypothesized that genes regulating the components of the serotonin system, including serotonin transporter (5-HTTLPR and serotonin 1 B receptor (5-HT1B, may be associated with alcoholism, but their results are contradictory because of alcoholism’s heterogeneity. Therefore, we examined whether the 5-HTTLPR gene and 5-HT1B gene G861C polymorphism are susceptibility factors for a specific subtype of alcoholism, antisocial alcoholism in Han Chinese in Taiwan. Methods We recruited 273 Han Chinese male inmates with antisocial personality disorder (ASPD [antisocial alcoholism (AS-ALC group (n = 120 and antisocial non-alcoholism (AS-N-ALC group (n = 153] and 191 healthy male controls from the community. Genotyping was done using PCR-RFLP. Results There were no significant differences in the genotypic frequency of the 5-HT1B G861C polymorphism between the 3 groups. Although AS-ALC group members more frequently carried the 5-HTTLPR S/S, S/LG, and LG/LG genotypes than controls, the difference became non-significant after controlling for the covarying effects of age. However, the 5-HTTLPR S/S, S/LG, and LG/LG genotypes may have interacted with the 5-HT1B G861C C/C polymorphism and increased the risk of becoming antisocial alcoholism. Conclusion Our study suggests that neither the 5-HTTLPR gene nor the 5-HT1B G861C polymorphism alone is a risk factor for antisocial alcoholism in Taiwan’s Han Chinese population, but that the interaction between both genes may increase susceptibility to antisocial alcoholism.

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

    Directory of Open Access Journals (Sweden)

    Joyce E Loper

    2012-07-01

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

  3. Haemophilus haemolyticus Interaction with Host Cells Is Different to Nontypeable Haemophilus influenzae and Prevents NTHi Association with Epithelial Cells.

    Science.gov (United States)

    Pickering, Janessa L; Prosser, Amy; Corscadden, Karli J; de Gier, Camilla; Richmond, Peter C; Zhang, Guicheng; Thornton, Ruth B; Kirkham, Lea-Ann S

    2016-01-01

    Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that resides in the upper respiratory tract and contributes to a significant burden of respiratory related diseases in children and adults. Haemophilus haemolyticus is a respiratory tract commensal that can be misidentified as NTHi due to high levels of genetic relatedness. There are reports of invasive disease from H. haemolyticus, which further blurs the species boundary with NTHi. To investigate differences in pathogenicity between these species, we optimized an in vitro epithelial cell model to compare the interaction of 10 H. haemolyticus strains with 4 NTHi and 4 H. influenzae-like haemophili. There was inter- and intra-species variability but overall, H. haemolyticus had reduced capacity to attach to and invade nasopharyngeal and bronchoalveolar epithelial cell lines (D562 and A549) within 3 h when compared with NTHi. H. haemolyticus was cytotoxic to both cell lines at 24 h, whereas NTHi was not. Nasopharyngeal epithelium challenged with some H. haemolyticus strains released high levels of inflammatory mediators IL-6 and IL-8, whereas NTHi did not elicit an inflammatory response despite higher levels of cell association and invasion. Furthermore, peripheral blood mononuclear cells stimulated with H. haemolyticus or NTHi released similar and high levels of IL-6, IL-8, IL-10, IL-1β, and TNFα when compared with unstimulated cells but only NTHi elicited an IFNγ response. Due to the relatedness of H. haemolyticus and NTHi, we hypothesized that H. haemolyticus may compete with NTHi for colonization of the respiratory tract. We observed that in vitro pre-treatment of epithelial cells with H. haemolyticus significantly reduced NTHi attachment, suggesting interference or competition between the two species is possible and warrants further investigation. In conclusion, H. haemolyticus interacts differently with host cells compared to NTHi, with different immunostimulatory and cytotoxic

  4. Novel Genes Affecting the Interaction between the Cabbage Whitefly and Arabidopsis Uncovered by Genome-Wide Association Mapping.

    Science.gov (United States)

    Broekgaarden, Colette; Bucher, Johan; Bac-Molenaar, Johanna; Keurentjes, Joost J B; Kruijer, Willem; Voorrips, Roeland E; Vosman, Ben

    2015-01-01

    Plants have evolved a variety of ways to defend themselves against biotic attackers. This has resulted in the presence of substantial variation in defense mechanisms among plants, even within a species. Genome-wide association (GWA) mapping is a useful tool to study the genetic architecture of traits, but has so far only had limited exploitation in studies of plant defense. Here, we study the genetic architecture of defense against the phloem-feeding insect cabbage whitefly (Aleyrodes proletella) in Arabidopsis thaliana. We determined whitefly performance, i.e. the survival and reproduction of whitefly females, on 360 worldwide selected natural accessions and subsequently performed GWA mapping using 214,051 SNPs. Substantial variation for whitefly adult survival and oviposition rate (number of eggs laid per female per day) was observed between the accessions. We identified 39 candidate SNPs for either whitefly adult survival or oviposition rate, all with relatively small effects, underpinning the complex architecture of defense traits. Among the corresponding candidate genes, i.e. genes in linkage disequilibrium (LD) with candidate SNPs, none have previously been identified as a gene playing a role in the interaction between plants and phloem-feeding insects. Whitefly performance on knock-out mutants of a number of candidate genes was significantly affected, validating the potential of GWA mapping for novel gene discovery in plant-insect interactions. Our results show that GWA analysis is a very useful tool to gain insight into the genetic architecture of plant defense against herbivorous insects, i.e. we identified and validated several genes affecting whitefly performance that have not previously been related to plant defense against herbivorous insects.

  5. Comparative Genomics of Plant-Associated Pseudomonas spp.: Insights into Diversity and Inheritance of Traits Involved in Multitrophic Interactions

    Science.gov (United States)

    Loper, Joyce E.; Hassan, Karl A.; Mavrodi, Dmitri V.; Davis, Edward W.; Lim, Chee Kent; Shaffer, Brenda T.; Elbourne, Liam D. H.; Stockwell, Virginia O.; Hartney, Sierra L.; Breakwell, Katy; Henkels, Marcella D.; Tetu, Sasha G.; Rangel, Lorena I.; Kidarsa, Teresa A.; Wilson, Neil L.; van de Mortel, Judith E.; Song, Chunxu; Blumhagen, Rachel; Radune, Diana; Hostetler, Jessica B.; Brinkac, Lauren M.; Durkin, A. Scott; Kluepfel, Daniel A.; Wechter, W. Patrick; Anderson, Anne J.; Kim, Young Cheol; Pierson, Leland S.; Pierson, Elizabeth A.; Lindow, Steven E.; Kobayashi, Donald Y.; Raaijmakers, Jos M.; Weller, David M.; Thomashow, Linda S.; Allen, Andrew E.; Paulsen, Ian T.

    2012-01-01

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

  6. Interaction between serotonin transporter and serotonin receptor 1 B genes polymorphisms may be associated with antisocial alcoholism.

    Science.gov (United States)

    Wang, Tzu-Yun; Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsien; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Chen-Lin; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru-Band

    2012-07-11

    Several studies have hypothesized that genes regulating the components of the serotonin system, including serotonin transporter (5-HTTLPR) and serotonin 1 B receptor (5-HT1B), may be associated with alcoholism, but their results are contradictory because of alcoholism's heterogeneity. Therefore, we examined whether the 5-HTTLPR gene and 5-HT1B gene G861C polymorphism are susceptibility factors for a specific subtype of alcoholism, antisocial alcoholism in Han Chinese in Taiwan. We recruited 273 Han Chinese male inmates with antisocial personality disorder (ASPD) [antisocial alcoholism (AS-ALC) group (n=120) and antisocial non-alcoholism (AS-N-ALC) group (n=153)] and 191 healthy male controls from the community. Genotyping was done using PCR-RFLP. There were no significant differences in the genotypic frequency of the 5-HT1B G861C polymorphism between the 3 groups. Although AS-ALC group members more frequently carried the 5-HTTLPR S/S, S/LG, and LG/LG genotypes than controls, the difference became non-significant after controlling for the covarying effects of age. However, the 5-HTTLPR S/S, S/LG, and LG/LG genotypes may have interacted with the 5-HT1B G861C C/C polymorphism and increased the risk of becoming antisocial alcoholism. Our study suggests that neither the 5-HTTLPR gene nor the 5-HT1B G861C polymorphism alone is a risk factor for antisocial alcoholism in Taiwan's Han Chinese population, but that the interaction between both genes may increase susceptibility to antisocial alcoholism.

  7. Signature of intermittent behavior in the emission spectra of target associated particles from 84Kr-AgBr interactions at 0.95 GeV/A

    International Nuclear Information System (INIS)

    Bhattacharjee, B.

    2005-01-01

    Intermittency and fractal behavior have been studied for emission spectra of target associated fast and slow particles from 84 Kr-AgBr interactions at 0.95 GeV/A. Intermittent behavior is observed for both knocked out and slow target fragments. In both the cases anomalous dimensions are seen to increase with the order of moments thereby indicating the association of multifractility with production mechanism of both fast and slow target associated particles

  8. Bcl-2 antagonists interact synergistically with bortezomib in DLBCL cells in association with JNK activation and induction of ER stress.

    Science.gov (United States)

    Dasmahapatra, Girija; Lembersky, Dmitry; Rahmani, Mohamed; Kramer, Lora; Friedberg, Jonathan; Fisher, Richard I; Dent, Paul; Grant, Steven

    2009-05-01

    Mechanisms underlying interactions between the proteasome inhibitor bortezomib and small molecule Bcl-2 antagonists were examined in GC- and ABC-type human DLBCL (diffuse lymphocytic B-cell lymphoma) cells. Concomitant or sequential exposure to non- or minimally toxic concentrations of bortezomib or other proteasome inhibitors and either HA14-1 or gossypol resulted in a striking increase in Bax/Bak conformational change/translocation, cytochrome c release, caspase activation and synergistic induction of apoptosis in both GC- and ABC-type cells. These events were associated with a sharp increase in activation of the stress kinase JNK and evidence of ER stress induction (e.g., eIF2alpha phosphorylation, activation of caspases-2 and -4, and Grp78 upregulation). Pharmacologic or genetic (e.g., shRNA knockdown) interruption of JNK signaling attenuated HA14-1/bortezomib lethality and ER stress induction. Genetic disruption of the ER stress pathway (e.g., in cells expressing caspase-4 shRNA or DN-eIF2alpha) significantly attenuated lethality. The toxicity of this regimen was independent of ROS generation. Finally, HA14-1 significantly increased bortezomib-mediated JNK activation, ER stress induction, and lethality in bortezomib-resistant cells. Collectively these findings indicate that small molecule Bcl-2 antagonists promote bortezomib-mediated mitochondrial injury and lethality in DLBCL cells in association with enhanced JNK activation and ER stress induction. They also raise the possibility that such a strategy may be effective in different DLBCL sub-types (e.g., GC- or ABC), and in bortezomib-resistant disease.

  9. Interactions between Neighbourhood Urban Form and Socioeconomic Status and Their Associations with Anthropometric Measurements in Canadian Adults

    Science.gov (United States)

    Friedenreich, Christine; McLaren, Lindsay; Potestio, Melissa; Sandalack, Beverly; Csizmadi, Ilona

    2017-01-01

    Neighbourhood-level socioeconomic composition and built context are correlates of weight-related behaviours. We investigated the relations between objective measures of neighbourhood design and socioeconomic status (SES) and their interaction, in relation to self-reported waist circumference (WC), waist-to-hip ratio, and body mass index (BMI) in a sample of Canadian adults (n = 851 from 12 Calgary neighbourhoods). WC and BMI were higher among residents of disadvantaged neighbourhoods, independent of neighbourhood design (grid, warped grid, and curvilinear street patterns) and individual-level characteristics (sex, age, education, income, dog ownership, marital status, number of dependents, motor vehicle access, smoking, sleep, mental health, physical health, and past attempts to modify bodyweight). The association between neighbourhood-level SES and WC was modified by neighbourhood design; WC was higher in disadvantaged-curvilinear neighbourhoods and lower in advantaged-grid neighbourhoods. Policies making less obesogenic neighbourhoods affordable to low socioeconomic households and that improve the supportiveness for behaviours leading to healthy weight in low socioeconomic neighbourhoods are necessary. PMID:29056976

  10. Ergonomic guidelines for using notebook personal computers. Technical Committee on Human-Computer Interaction, International Ergonomics Association.

    Science.gov (United States)

    Saito, S; Piccoli, B; Smith, M J; Sotoyama, M; Sweitzer, G; Villanueva, M B; Yoshitake, R

    2000-10-01

    In the 1980's, the visual display terminal (VDT) was introduced in workplaces of many countries. Soon thereafter, an upsurge in reported cases of related health problems, such as musculoskeletal disorders and eyestrain, was seen. Recently, the flat panel display or notebook personal computer (PC) became the most remarkable feature in modern workplaces with VDTs and even in homes. A proactive approach must be taken to avert foreseeable ergonomic and occupational health problems from the use of this new technology. Because of its distinct physical and optical characteristics, the ergonomic requirements for notebook PCs in terms of machine layout, workstation design, lighting conditions, among others, should be different from the CRT-based computers. The Japan Ergonomics Society (JES) technical committee came up with a set of guidelines for notebook PC use following exploratory discussions that dwelt on its ergonomic aspects. To keep in stride with this development, the Technical Committee on Human-Computer Interaction under the auspices of the International Ergonomics Association worked towards the international issuance of the guidelines. This paper unveils the result of this collaborative effort.

  11. The NMDAR subunit NR3A interacts with microtubule-associated protein 1S in the brain

    DEFF Research Database (Denmark)

    Eriksson, Maria; Samuelsson, Helena; Samuelsson, Eva-Britt

    2007-01-01

    When screening a brain cDNA library, we found that the N-methyl-D-aspartate receptor subunit NR3A binds to microtubule-associated protein (MAP) 1S/chromosome 19 open reading frame 5 (C19ORF5). The interaction was confirmed in vitro and in vivo, and binding of MAP1S was localized to the membrane......-proximal part of the NR3A C-terminus. MAP1S belongs to the same family as MAP1A and MAP1B, and was found to be abundant in both postnatal and adult rat brain. In hippocampal neurons the distribution-pattern of MAP1S resembled that of beta-tubulin III, but a fraction of the protein colocalized with synaptic...... markers synapsin and postsynaptic density protein 95 (PSD95), in beta-tubulin III-negative filopodia-like protrusions. There was coexistance between MAP1S and NR3A immunoreactivity in neurite shafts and occasionally in filopodia-like processes. MAP1S potentially links NR3A to the cytoskeleton, and may...

  12. Behavior problems of children in foster care: Associations with foster mothers' representations, commitment, and the quality of mother-child interaction.

    Science.gov (United States)

    Dubois-Comtois, Karine; Bernier, Annie; Tarabulsy, George M; Cyr, Chantal; St-Laurent, Diane; Lanctôt, Anne-Sophie; St-Onge, Janie; Moss, Ellen; Béliveau, Marie-Julie

    2015-10-01

    This study investigated different environmental and contextual factors associated with maltreated children's adjustment in foster care. Participants included 83 children (52 boys), ages 1-7 years, and their foster caregivers. Quality of interaction with the foster caregiver was assessed from direct observation of a free-play situation; foster caregiver attachment state of mind and commitment toward the child were assessed using two interviews; disruptive behavior symptoms were reported by foster caregivers. Results showed that quality of interaction between foster caregivers and children were associated with behavior problems, such that higher-quality interactions were related to fewer externalizing and internalizing problems. Foster caregivers' state of mind and commitment were interrelated but not directly associated with behavior problems of foster children. Type of placement moderated the association between foster caregiver commitment and foster child behavior problems. Whereas greater foster caregiver commitment was associated with higher levels of adjustment for children in foster families (kin and non-kin), this was not the case in foster-to-adopt families. Finally, the associations between foster child behavior problems and history of maltreatment and placement related-risk conditions fell below significance after considering child age and quality of interaction with the foster caregiver. Findings underscore the crucial contribution of the foster caregiver-child relationship to fostering child adjustment and, thereby, have important implications for clinical services offered to this population. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Gender differences in the associations between age trends of social media interaction and well-being among 10-15 year olds in the UK.

    Science.gov (United States)

    Booker, Cara L; Kelly, Yvonne J; Sacker, Amanda

    2018-03-20

    Adolescents are among the highest consumers of social media while research has shown that their well-being decreases with age. The temporal relationship between social media interaction and well-being is not well established. The aim of this study was to examine whether the changes in social media interaction and two well-being measures are related across ages using parallel growth models. Data come from five waves of the youth questionnaire, 10-15 years, of the Understanding Society, the UK Household Longitudinal Study (pooled n = 9859). Social media interaction was assessed through daily frequency of chatting on social websites. Well-being was measured by happiness with six domains of life and the Strengths and Difficulties Questionnaire. Findings suggest gender differences in the relationship between interacting on social media and well-being. There were significant correlations between interacting on social media and well-being intercepts and between social media interaction and well-being slopes among females. Additionally higher social media interaction at age 10 was associated with declines in well-being thereafter for females, but not for males. Results were similar for both measures of well-being. High levels of social media interaction in early adolescence have implications for well-being in later adolescence, particularly for females. The lack of an association among males suggests other factors might be associated with their reduction in well-being with age. These findings contribute to the debate on causality and may inform future policy and interventions.

  14. Interactive effects of ethanol on ulcerative colitis and its associated testicular dysfunction in pubertal BALB/c mice.

    Science.gov (United States)

    Adedara, Isaac A; Ajayi, Babajide O; Awogbindin, Ifeoluwa O; Farombi, Ebenezer O

    2017-11-01

    Available epidemiological reports have indicated an increase in the incidence of ulcerative colitis, as well as alcohol consumption, globally. The present study investigated the possible interactive effects of ethanol consumption on ulcerative colitis and its associated testicular dysfunction using six groups of 12 pubertal mice each. Group I (Control) mice received drinking water alone. Group II mice received ethanol alone at 5 g/kg body weight. Group III mice received 2.5% dextran sulphate sodium (DSS) in drinking water followed by normal drinking water. Groups IV, V, and VI mice received DSS followed by ethanol at 1.25, 2.5, and 5 g/kg, respectively. Administration of ethanol to mice with ulcerative colitis intensified the disease-activity index with marked reduction in colon length, colon mass index, body weight gain, and organo-somatic indices of testes and epididymis when compared with the DSS-alone group. Moreover, ethanol exacerbated colitis-mediated decrease in enzymatic and non-enzymatic antioxidants but increased the oxidative stress and inflammatory biomarkers in the testes and epididymis. The diminution in luteinizing hormone, follicle stimulating hormone, and testosterone levels was intensified following administration of ethanol to mice with ulcerative colitis that were administered 5 g/kg ethanol alone. The decrease in sperm functional parameters and testicular spermatogenic indices as well as histopathological damage in colon, testes, and epididymis was aggravated following administration of ethanol to mice with ulcerative colitis. In conclusion, the exacerbating effects of ethanol on ulcerative colitis-induced testicular dysfunction are related to increased oxidative stress and inflammation in the treated mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Novel secreted isoform of adhesion molecule ICAM-4: Potential regulator of membrane-associated ICAM-4 interactions

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Gloria; Spring, Frances A.; Parons, Stephen F.; Mankelow, Tosti J.; Peters, Luanne L.; Koury, Mark J.; Mohandas, Narla; Anstee, David J.; Chasis, Joel Anne

    2003-02-18

    ICAM-4, a newly characterized adhesion molecule, is expressed early in human erythropoiesis and functions as a ligand for binding a4b1 and aV integrin-expressing cells. Within the bone marrow, erythroblasts surround central macrophages forming erythroblastic islands. Evidence suggests that these islands are highly specialized subcompartments where cell adhesion events, in concert with cytokines, play critical roles in regulating erythropoiesis and apoptosis. Since erythroblasts express a4b1 and ICAM-4 and macrophages exhibit aV, ICAM-4 is an attractive candidate for mediating cellular interactions within erythroblastic islands. To determine whether ICAM-4 binding properties are conserved across species, we first cloned and sequenced the murine homologue. The translated amino acid sequence showed 68 percent overall identity with human ICAM-4. Using recombinant murine ICAM-4 extracellular domains, we discovered that hematopoietic a4b1-expressing HEL cells and non-hematopoietic aV-expressing FLY cells adhered to mouse ICAM-4. Cell adhesion studies showed that FLY and HEL cells bound to mouse and human proteins with similar avidity. These data strongly suggest conservation of integrin-binding properties across species. Importantly, we characterized a novel second splice cDNA that would be predicted to encode an ICAM-4 isoform, lacking the membrane-spanning domain. Erythroblasts express both isoforms of ICAM-4. COS-7 cells transfected with GFP constructs of prototypic or novel ICAM-4 cDNA showed different cellular localization patterns. Moreover, analysis of tissue culture medium revealed that the novel ICAM-4 cDNA encodes a secreted protein. We postulate that secretion of this newly described isoform, ICAM-4S, may modulate binding of membrane-associated ICAM-4 and could thus play a critical regulatory role in erythroblast molecular attachments.

  16. In Silico Identification of Proteins Associated with Drug-induced Liver Injury Based on the Prediction of Drug-target Interactions.

    Science.gov (United States)

    Ivanov, Sergey; Semin, Maxim; Lagunin, Alexey; Filimonov, Dmitry; Poroikov, Vladimir

    2017-07-01

    Drug-induced liver injury (DILI) is the leading cause of acute liver failure as well as one of the major reasons for drug withdrawal from clinical trials and the market. Elucidation of molecular interactions associated with DILI may help to detect potentially hazardous pharmacological agents at the early stages of drug development. The purpose of our study is to investigate which interactions with specific human protein targets may cause DILI. Prediction of interactions with 1534 human proteins was performed for the dataset with information about 699 drugs, which were divided into three categories of DILI: severe (178 drugs), moderate (310 drugs) and without DILI (211 drugs). Based on the comparison of drug-target interactions predicted for different drugs' categories and interpretation of those results using clustering, Gene Ontology, pathway and gene expression analysis, we identified 61 protein targets associated with DILI. Most of the revealed proteins were linked with hepatocytes' death caused by disruption of vital cellular processes, as well as the emergence of inflammation in the liver. It was found that interaction of a drug with the identified targets is the essential molecular mechanism of the severe DILI for the most of the considered pharmaceuticals. Thus, pharmaceutical agents interacting with many of the identified targets may be considered as candidates for filtering out at the early stages of drug research. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Magma-carbonate interaction processes and associated CO2 release at Merapi volcano, Indonesia: insights from experimental petrology

    NARCIS (Netherlands)

    Deegan, F.M.; Troll, V.R.; Freda, C.; Misti, V.; Chadwick, J.P.

    2010-01-01

    There is considerable evidence for continuing, late-stage interaction between the magmatic system at Merapi volcano, Indonesia, and local crustal carbonate (limestone). Calc-silicate xenoliths within Merapi basaltic-andesite eruptive rocks display textures indicative of intense interaction between

  18. Molecular interaction of connexin 30.3 and connexin 31 suggests a dominant-negative mechanism associated with erythrokeratodermia variabilis

    DEFF Research Database (Denmark)

    Plantard, Laure; Huber, Marcel; Macari, Francoise

    2003-01-01

    to a gigantic increase of stabilized heteromeric gap junctions. Furthermore, co-expressed wild-type Cx30.3 and Cx31 coprecipitate, which demonstrates a physical interaction. Inhibitor experiments revealed that this interaction begins in the endoplasmic reticulum. These results not only provide new insights...

  19. Associated heavy quarks pair production with Higgs as a tool for a search for non-perturbative effects of the electroweak interaction at the LHC

    Directory of Open Access Journals (Sweden)

    B.A. Arbuzov

    2017-09-01

    Full Text Available Assuming an existence of the anomalous triple electro-weak bosons interaction being defined by coupling constant λ we calculate its contribution to interactions of the Higgs with pairs of heavy particles. Bearing in mind experimental restrictions −0.011<λ<0.011 we present results for possible effects in processes pp→W+W−H,pp→W+ZH,pp→W−ZH,pp→t¯tH, pp→b¯bH. Effects could be significant with negative sign of λ in associated heavy quarks t,b pairs production with the Higgs. In calculations we rely on results of the non-perturbative approach to a spontaneous generation of effective interactions, which defines the form-factor of the three-boson anomalous interaction.

  20. Intermittent fasting promotes prolonged associative interactions during synaptic tagging/capture by altering the metaplastic properties of the CA1 hippocampal neurons.

    Science.gov (United States)

    Dasgupta, Ananya; Kim, Joonki; Manakkadan, Anoop; Arumugam, Thiruma V; Sajikumar, Sreedharan

    2017-12-19

    Metaplasticity is the inherent property of a neuron or neuronal population to undergo activity-dependent changes in neural function that modulate subsequent synaptic plasticity. Here we studied the effect of intermittent fasting (IF) in governing the interactions of associative plasticity mechanisms in the pyramidal neurons of rat hippocampal area CA1. Late long-term potentiation and its associative mechanisms such as synaptic tagging and capture at an interval of 120 min were evaluated in four groups of animals, AL (Ad libitum), IF12 (daily IF for 12 h), IF16 (daily IF for 16 h) and EOD (every other day IF for 24 h). IF had no visible effect on the early or late plasticity but it manifested a critical role in prolonging the associative interactions between weak and strong synapses at an interval of 120 min in IF16 and EOD animals. However, both IF12 and AL did not show associativity at 120 min. Plasticity genes such as Bdnf and Prkcz, which are well known for their expressions in late plasticity and synaptic tagging and capture, were significantly upregulated in IF16 and EOD in comparison to AL. Specific inhibition of brain derived neurotropic factor (BDNF) prevented the prolonged associativity expressed in EOD. Thus, daily IF for 16 h or more can be considered to enhance the metaplastic properties of synapses by improving their associative interactions that might translate into animprovedmemoryformation. Copyright © 2017. Published by Elsevier Inc.

  1. Bully/Victim Problems among Greek Pupils with Special Educational Needs: Associations with Loneliness and Self-Efficacy for Peer Interactions

    Science.gov (United States)

    Andreou, Eleni; Didaskalou, Eleni; Vlachou, Anastasia

    2015-01-01

    This study explores the prevalence of different types of bullying and victimisation among Greek pupils receiving special education support provision. Associations of these types with feelings of loneliness and perceived social efficacy for peer interactions are also examined. The sample consisted of 178 students of fifth and sixth primary school…

  2. Signature of intermittent behavior in the emission spectra of target associated particles from 84Kr-AgBr interactions at 0.95 GeV/A

    International Nuclear Information System (INIS)

    Bhattacharjee, B.; Sengupta, S.; Mukhopadhyay, A.; Singh, V.

    2004-01-01

    In this report an attempt has been made to study, by studying the fluctuation in spatial distribution in χ(cosθ) space, the intermittent behaviour and fractal properties of emission spectra of fast and slow target associated particles from 84 Kr-AgBr interactions at 0.95 GeV/A

  3. The N-terminal domain of the Drosophila retinoblastoma protein Rbf1 interacts with ORC and associates with chromatin in an E2F independent manner.

    Directory of Open Access Journals (Sweden)

    Joseph Ahlander

    2008-07-01

    Full Text Available The retinoblastoma (Rb tumor suppressor protein can function as a DNA replication inhibitor as well as a transcription factor. Regulation of DNA replication may occur through interaction of Rb with the origin recognition complex (ORC.We characterized the interaction of Drosophila Rb, Rbf1, with ORC. Using expression of proteins in Drosophila S2 cells, we found that an N-terminal Rbf1 fragment (amino acids 1-345 is sufficient for Rbf1 association with ORC but does not bind to dE2F1. We also found that the C-terminal half of Rbf1 (amino acids 345-845 interacts with ORC. We observed that the amino-terminal domain of Rbf1 localizes to chromatin in vivo and associates with chromosomal regions implicated in replication initiation, including colocalization with Orc2 and acetylated histone H4.Our results suggest that Rbf1 can associate with ORC and chromatin through domains independent of the E2F binding site. We infer that Rbf1 may play a role in regulating replication directly through its association with ORC and/or chromatin factors other than E2F. Our data suggest an important role for retinoblastoma family proteins in cell proliferation and tumor suppression through interaction with the replication initiation machinery.

  4. The urokinase plasminogen activator receptor-associated protein/endo180 is coexpressed with its interaction partners urokinase plasminogen activator receptor and matrix metalloprotease-13 during osteogenesis

    DEFF Research Database (Denmark)

    Engelholm, L H; Nielsen, B S; Netzel-Arnett, Sarah

    2001-01-01

    The urokinase plasminogen activator receptor-associated protein/Endo180 (uPARAP/Endo180) is a newly discovered member of the macrophage mannose receptor family that was reported to interact with ligand-bound urokinase plasminogen activator receptor (uPAR), matrix metalloprotease-13 (MMP-13), and ...

  5. Abnormal interaction of motor neuropathy-associated mutant HspB8 (Hsp22) forms with the RNA helicase Ddx20 (gemin3)

    NARCIS (Netherlands)

    Sun, Xiankui; Fontaine, Jean-Marc; Hoppe, Adam D.; Carra, Serena; DeGuzman, Cheryl; Martin, Jody L.; Simon, Stephanie; Vicart, Patrick; Welsh, Michael J.; Landry, Jacques; Benndorf, Rainer

    A number of missense mutations in the two related small heat shock proteins HspB8 (Hsp22) and HspB1 (Hsp27) have been associated with the inherited motor neuron diseases (MND) distal hereditary motor neuropathy and Charcot-Marie-Tooth disease. HspB8 and HspB1 interact with each other, suggesting

  6. Filamin A Modulates Store-Operated Ca2+ Entry by Regulating STIM1 (Stromal Interaction Molecule 1)-Orai1 Association in Human Platelets.

    Science.gov (United States)

    Lopez, Jose J; Albarrán, Letizia; Jardín, Isaac; Sanchez-Collado, Jose; Redondo, Pedro C; Bermejo, Nuria; Bobe, Regis; Smani, Tarik; Rosado, Juan A

    2018-02-01

    Here, we provide evidence for the role of FLNA (filamin A) in the modulation of store-operated calcium entry (SOCE). SOCE is a major mechanism for calcium influx controlled by the intracellular Ca 2+ stores. On store depletion, the endoplasmic reticulum calcium sensor STIM1 (stromal interaction molecule 1) redistributes into puncta at endoplasmic reticulum/plasma membrane junctions, a process supported by the cytoskeleton, where it interacts with the calcium channels; however, the mechanism for fine-tuning SOCE is not completely understood. Our results demonstrate that STIM1 interacts with FLNA on calcium store depletion in human platelets. The interaction is dependent on the phosphorylation of FLNA at Ser 2152 by the cAMP-dependent protein kinase. Impairment of FLNA phosphorylation and knockdown of FLNA expression using siRNA increased SOCE in platelets. Similarly, SOCE was significantly greater in FLNA-deficient melanoma M2 cells than in the FLNA-expressing M2 subclone A7. Expression of FLNA in M2 cells attenuated SOCE, an effect prevented when the cells were transfected with the nonphosphorylatable FLNA S2152A mutant. Transfection of M2 cells with the STIM1(K684,685E) mutant reduced the STIM1-FLNA interaction. In platelets, attenuation of FLNA expression using siRNA resulted in enhanced association of STIM1 with the cytoskeleton, greater STIM1-Orai1 interaction, and SOCE. Introduction of an anti-FLNA (2597-2647) antibody attenuated the STIM1-FLNA interaction and enhanced thrombin-induced platelet aggregation. Our results indicate that FLNA modulates SOCE and then the correct platelet function, by fine-tuning the distribution of STIM1 in the cytoskeleton and the interaction with Orai1 channels. © 2017 American Heart Association, Inc.

  7. Wild and domestic pig interactions at the wildlife-livestock interface of Murchison Falls National Park, Uganda, and the potential association with African Swine Fever outbreaks

    Directory of Open Access Journals (Sweden)

    Esther eKukielka

    2016-04-01

    Full Text Available Bushpigs (Potamochoerus larvatus and warthogs (Phacochoerus africanus, which are widely distributed in Eastern Africa, are likely to cohabitate in the same environment with domestic pigs, facilitating the transmission of shared pathogens. However, potential interactions between bushpig, warthog and domestic pig and the resulting potential circulation of infectious diseases have rarely been investigated in Africa to date. In order to understand the dynamics of such interactions and the potential influence of human behavior and husbandry practices on them, individual interviews (n=233 and participatory rural appraisals (n=11 were carried out among Ugandan pig farmers at the edge of Murchison Falls National Park, northern Uganda. In addition, as an example of possible implications of wild and domestic pig interactions, nonlinear multivariate analysis (multiple correspondence analyses was used to investigate the potential association between the aforementioned factors (interactions and human behavior and practices and farmer reported ASF outbreaks. No direct interactions between wild pigs and domestic pig were reported in our study area. However, indirect interactions were described by 83 (35.6 % of the participants and were identified to be more common at water sources during the dry season. Equally, eight (3.4% farmers declared exposing their domestic pig to raw hunting leftovers of wild pigs. The exploratory analysis performed suggested possible associations between the farmer reported ASF outbreaks and indirect interactions, free-range housing systems, dry season, and having a warthog burrow less than 3km from the household. Our study was useful to gather local knowledge and to identify knowledge gaps about potential interactions between wild and domestic pig in this area. This information could be useful to facilitate the design of future observational studies to better understand the potential transmission of pathogens between wild and

  8. Associations between young adult romantic relationship quality and problem behaviors : An examination of personality-environment interactions

    NARCIS (Netherlands)

    Yu, Rongqin; Branje, Susan; Keijsers, Loes; Meeus, W.H.J.

    This longitudinal study examined person–environment interplay by testing interaction effects between adolescent personality type (i.e., overcontrollers, undercontrollers, and resilients) and young adult romantic relationship quality on young adult delinquency and anxiety. The study employed six

  9. Associations between Young Adult Romantic Relationship Quality and Problem Behaviors: An Examination of Personality-Environment Interactions

    NARCIS (Netherlands)

    Yu, Rongqin; Branje, Susan; Keijsers, Loes; Meeus, Wim

    2015-01-01

    This longitudinal study examined person-environment interplay by testing interaction effects between adolescent personality type (i.e., overcontrollers, undercontrollers, and resilients) and young adult romantic relationship quality on young adult delinquency and anxiety. The study employed six

  10. Effects of fractal roughness of membrane surfaces on interfacial interactions associated with membrane fouling in a membrane bioreactor.

    Science.gov (United States)

    Feng, Shushu; Yu, Genying; Cai, Xiang; Eulade, Mahoro; Lin, Hongjun; Chen, Jianrong; Liu, Yong; Liao, Bao-Qiang

    2017-11-01

    Fractal roughness is one of the most important properties of a fractal surface. In this study, it was found that, randomly rough membrane surface was a fractal surface, which could be digitally modeled by a modified two-variable Weierstrass-Mandelbrot (WM) function. Fractal roughness of membrane surfaces has a typical power function relation with the statistical roughness of the modeled surface. Assessment of interfacial interactions showed that an increase in fractal roughness of membrane surfaces will strengthen and prolong the interfacial interactions between membranes and foulants, and under conditions in this study, will significantly increase the adhesion propensity of a foulant particle on membrane surface. This interesting result can be attributed to that increase in fractal roughness simultaneously improves separation distance and interaction surface area for adhesion of a foulant particle. This study gives deep insights into interfacial interactions and membrane fouling in MBRs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Interactions of maize bushy stunt phytoplasma with the leafhopper vector, Dalbulus maidis (Delong and Wolcott) (Hemiptera: Cicadellidae) and associated microbiota

    OpenAIRE

    Javier Garcia Gonzalez

    2016-01-01

    Phytoplasmas are bacteria with a persistent propagative transmission by insect vectors that generates direct and indirect interactions among them. In order to understand these interactions for maize bushy stunt phytoplasma (MBSP) and the leafhopper vector Dalbulus maidis (Hemiptera: Cicadellidae), two research lines were addressed. The first one aimed to determine the indirect effects of maize infection by MBSP on some biological and behavioral parameters of the vector, whereas a second line ...

  12. A Comparison of Multifactor Dimensionality Reduction and L1-Penalized Regression to Identify Gene-Gene Interactions in Genetic Association Studies*

    Science.gov (United States)

    Winham, Stacey; Wang, Chong; Motsinger-Reif, Alison A

    2011-01-01

    Recently, the amount of high-dimensional data has exploded, creating new analytical challenges for human genetics. Furthermore, much evidence suggests that common complex diseases may be due to complex etiologies such as gene-gene interactions, which are difficult to identify in high-dimensional data using traditional statistical approaches. Data-mining approaches are gaining popularity for variable selection in association studies, and one of the most commonly used methods to evaluate potential gene-gene interactions is Multifactor Dimensionality Reduction (MDR). Additionally, a number of penalized regression techniques, such as Lasso, are gaining popularity within the statistical community and are now being applied to association studies, including extensions for interactions. In this study, we compare the performance of MDR, the traditional lasso with L1 penalty (TL1), and the group lasso for categorical data with group-wise L1 penalty (GL1) to detect gene-gene interactions through a broad range of simulations. We find that each method has both advantages and disadvantages, and relative performance is context dependent. TL1 frequently over-fits, identifying false positive as well as true positive loci. MDR has higher power for epistatic models that exhibit independent main effects; for both Lasso methods, main effects tend to dominate. For purely epistatic models, GL1 has the best performance for lower minor allele frequencies, but MDR performs best for higher frequencies. These results provide guidance of when each approach might be best suited for detecting and characterizing interactions with different mechanisms. PMID:21291414

  13. A comparison of multifactor dimensionality reduction and L1-penalized regression to identify gene-gene interactions in genetic association studies.

    Science.gov (United States)

    Winham, Stacey; Wang, Chong; Motsinger-Reif, Alison A

    2011-01-01

    Recently, the amount of high-dimensional data has exploded, creating new analytical challenges for human genetics. Furthermore, much evidence suggests that common complex diseases may be due to complex etiologies such as gene-gene interactions, which are difficult to identify in high-dimensional data using traditional statistical approaches. Data-mining approaches are gaining popularity for variable selection in association studies, and one of the most commonly used methods to evaluate potential gene-gene interactions is Multifactor Dimensionality Reduction (MDR). Additionally, a number of penalized regression techniques, such as Lasso, are gaining popularity within the statistical community and are now being applied to association studies, including extensions for interactions. In this study, we compare the performance of MDR, the traditional lasso with L1 penalty (TL1), and the group lasso for categorical data with group-wise L1 penalty (GL1) to detect gene-gene interactions through a broad range of simulations. We find that each method has both advantages and disadvantages, and relative performance is context dependent. TL1 frequently over-fits, identifying false positive as well as true positive loci. MDR has higher power for epistatic models that exhibit independent main effects; for both Lasso methods, main effects tend to dominate. For purely epistatic models, GL1 has the best performance for lower minor allele frequencies, but MDR performs best for higher frequencies. These results provide guidance of when each approach might be best suited for detecting and characterizing interactions with different mechanisms.

  14. Pelota interacts with HAX1, EIF3G and SRPX and the resulting protein complexes are associated with the actin cytoskeleton

    Directory of Open Access Journals (Sweden)

    Hoyer-Fender Sigrid

    2010-04-01

    Full Text Available Abstract Background Pelota (PELO is an evolutionary conserved protein, which has been reported to be involved in the regulation of cell proliferation and stem cell self-renewal. Recent studies revealed the essential role of PELO in the No-Go mRNA decay, by which mRNA with translational stall are endonucleotically cleaved and degraded. Further, PELO-deficient mice die early during gastrulation due to defects in cell proliferation and/or differentiation. Results We show here that PELO is associated with actin microfilaments of mammalian cells. Overexpression of human PELO in Hep2G cells had prominent effect on cell growth, cytoskeleton organization and cell spreading. To find proteins interacting with PELO, full-length human PELO cDNA was used as a bait in a yeast two-hybrid screening assay. Partial sequences of HAX1, EIF3G and SRPX protein were identified as PELO-interacting partners from the screening. The interactions between PELO and HAX1, EIF3G and SRPX were confirmed in vitro by GST pull-down assays and in vivo by co-immunoprecipitation. Furthermore, the PELO interaction domain was mapped to residues 268-385 containing the c-terminal and acidic tail domain. By bimolecular fluorescence complementation assay (BiFC, we found that protein complexes resulting from the interactions between PELO and either HAX1, EIF3G or SRPX were mainly localized to cytoskeletal filaments. Conclusion We could show that PELO is subcellularly localized at the actin cytoskeleton, interacts with HAX1, EIF3G and SRPX proteins and that this interaction occurs at the cytoskeleton. Binding of PELO to cytoskeleton-associated proteins may facilitate PELO to detect and degrade aberrant mRNAs, at which the ribosome is stalled during translation.

  15. Interactive lecturing.

    Science.gov (United States)

    White, Geoff

    2011-12-01

    Lectures can vary from being entirely teacher-centred through to those that value learner-teacher and learner-learner interaction. Advocates of the exclusively didactic (teacher-centred) lecture aim to maximise the amount of lecture time available to their delivery of content, and regard other activities as 'lost' lecture time. Educational research has, however, identified the potential benefit of interactivity that promotes mentally active learning and improved learning outcomes. This article reviews the notion of 'active learning', outlines how active learning is promoted by interactivity and concludes with strategies for including interactivity within lectures. Narrative review and discussion. The article begins with a summary of the purposes of lecturing, and the distinctions between mentally active and passive learning. The associations between interactivity, cognitively active learning and improved learning outcomes are considered, and strategies for promoting interactivity and active learning are explored. Three student-student interaction strategies are discussed, and an exemplar of each of these strategies in action is provided. The exemplar addresses the 'lost time' concern of some advocates of the exclusively didactic lecture. Interactivity can be readily introduced to lectures without a significant reduction in the amount of time available for didactic lecturing. This paper challenges the view that the inclusion of interactivity equates to a loss of learning time, by showing that students' achievement of learning outcomes is enhanced by planned and structured engagement with others. The paper concludes with an example of how interactivity can be incorporated within the traditional lecture format. © Blackwell Publishing Ltd 2011.

  16. Protein-Carbohydrate Interaction between Sperm and the Egg-Coating Envelope and Its Regulation by Dicalcin, a Xenopus laevis Zona Pellucida Protein-Associated Protein

    Directory of Open Access Journals (Sweden)

    Naofumi Miwa

    2015-05-01

    Full Text Available Protein-carbohydrate interaction regulates multiple important processes during fertilization, an essential biological event where individual gametes undergo intercellular recognition to fuse and generate a zygote. In the mammalian female reproductive tract, sperm temporarily adhere to the oviductal epithelium via the complementary interaction between carbohydrate-binding proteins on the sperm membrane and carbohydrates on the oviductal cells. After detachment from the oviductal epithelium at the appropriate time point following ovulation, sperm migrate and occasionally bind to the extracellular matrix, called the zona pellucida (ZP, which surrounds the egg, thereafter undergoing the exocytotic acrosomal reaction to penetrate the envelope and to reach the egg plasma membrane. This sperm-ZP interaction also involves the direct interaction between sperm carbohydrate-binding proteins and carbohydrates within the ZP, most of which have been conserved across divergent species from mammals to amphibians and echinoderms. This review focuses on the carbohydrate-mediated interaction of sperm with the female reproductive tract, mainly the interaction between sperm and the ZP, and introduces the fertilization-suppressive action of dicalcin, a Xenopus laevis ZP protein-associated protein. The action of dicalcin correlates significantly with a dicalcin-dependent change in the lectin-staining pattern within the ZP, suggesting a unique role of dicalcin as an inherent protein that is capable of regulating the affinity between the lectin and oligosaccharides attached on its target glycoprotein.

  17. The Use of an Interactive Videodisc and Associated Instructional Materials To Teach Selected Routine and Emergency Phrases in Signed English to the Deaf and Their Hearing Associates. Final Report.

    Science.gov (United States)

    Gentry, Cass; And Others

    This final report documents a project which developed and investigated the use of interactive videodisc technology to assist in the instruction of signing with deaf children and their associates (such as parents, teachers, peers). The project first identified words and phrases considered essential for interpersonal communications. A videodisc…

  18. Social reward: interactions with social status, social communication, aggression, and associated neural activation in the ventral tegmental area.

    Science.gov (United States)

    Gil, Mario; Nguyen, Ngoc-Thao; McDonald, Mark; Albers, H Elliott

    2013-07-01

    Nearly all species engage in a variety of intraspecific social interactions, and there is evidence that these interactions are rewarding. Less is known, however, about the factors that influence social reward. Using the conditioned place preference paradigm, we tested whether social interactions are rewarding for male Syrian hamsters. We also tested whether social stimuli increase neural activation in the ventral tegmental area (VTA), a component of the mesolimbic reward system, and how individual differences in social behavior and experience influence neural activation. In the present study, we found that hamsters developed a conditioned place preference for social interactions, but the effects were significantly stronger in dominant animals compared with subordinates. The number of Fos-immunoreactive cells in the VTA was significantly higher in hamsters that had engaged in a direct social encounter compared with hamsters exposed to a caged stimulus hamster or controls. Interestingly, socially experienced males had more Fos-immunoreactive cells in the VTA than socially naive males after exposure to a social stimulus. Surprisingly, the amount of Fos immunoreactivity in the VTA induced by a social stimulus was correlated with the amount of aggressive/dominance behaviors that had been observed during interactions that had occurred 2 months earlier. Our results indicate that social interactions between males are rewarding, and that social dominance increases the reward value. Social interactions stimulate the mesolimbic reward system, and social experience enhances its response to novel social stimuli and may produce long-term changes in the neural mechanisms that mediate the maintenance of dominance over long periods of time. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. Interactions between genetic variants associated with adiposity traits and soft drinks in relation to longitudinal changes in body weight and waist circumference.

    Science.gov (United States)

    Olsen, Nanna J; Ängquist, Lars; Larsen, Sofus C; Linneberg, Allan; Skaaby, Tea; Husemoen, Lise Lotte N; Toft, Ulla; Tjønneland, Anne; Halkjær, Jytte; Hansen, Torben; Pedersen, Oluf; Overvad, Kim; Ahluwalia, Tarunveer S; Sørensen, Thorkild Ia; Heitmann, Berit L

    2016-09-01

    Intake of sugar-sweetened beverages is associated with obesity, and this association may be modified by a genetic predisposition to obesity. We examined the interactions between a molecular genetic predisposition to various aspects of obesity and the consumption of soft drinks, which are a major part of sugar-sweetened beverages, in relation to changes in adiposity measures. A total of 4765 individuals were included in the study. On the basis of 50 obesity-associated single nucleotide polymorphisms that are associated with body mass index (BMI), waist circumference (WC), or the waist-to-hip ratio adjusted for BMI (WHRBMI), the following 4 genetic predisposition scores (GRSs) were constructed: a complete genetic predisposition score including all 50 single nucleotide polymorphisms (GRSComplete), a genetic predisposition score including BMI-associated single nucleotide polymorphisms (GRSBMI), a genetic predisposition score including waist circumference-associated single nucleotide polymorphisms (GRSWC), and a genetic predisposition score including the waist-to-hip ratio adjusted for BMI-associated single nucleotide polymorphisms (GRSWHR). Associations between soft drink intake and the annual change (Δ) in body weight (BW), WC, or waist circumference adjusted for BMI (WCBMI) and possible interactions with the GRSs were examined with the use of linear regression analyses and meta-analyses. For each soft drink serving per day, soft drink consumption was significantly associated with a higher ΔBW of 0.07 kg/y (95% CI: 0.01, 0.13 kg/y; P = 0.020) but not with the ΔWC or ΔWCBMI In analyses of the ΔBW, we showed an interaction only with the GRSWC (per risk allele for each soft drink serving per day: -0.06 kg/y; 95% CI: -0.10, -0.02 kg/y; P = 0.006). In analyses of the ΔWC, we showed interactions only with the GRSBMI and GRSComplete [per risk allele for each soft drink serving per day: 0.05 cm/y (95% CI: 0.02, 0.09 cm/y; P = 0.001) and 0.05 cm/y (95% CI: 0.02, 0.07 cm

  20. Potentially severe drug-drug interactions among older people and associations in assisted living facilities in Finland: a cross-sectional study.

    Science.gov (United States)

    Teramura-Grönblad, Mariko; Raivio, Minna; Savikko, Niina; Muurinen, Seija; Soini, Helena; Suominen, Merja; Pitkälä, Kaisu

    2016-09-01

    This study aims to assess potentially severe class D drug-drug interactions (DDDIs) in residents 65 years or older in assisted living facilities with the use of a Swedish and Finnish drug-drug interaction database (SFINX). A cross-sectional study of residents in assisted living facilities in Helsinki, Finland. A total of 1327 residents were assessed in this study. Drugs were classified according to the Anatomical Therapeutic Chemical (ATC) classification system and DDDIs were coded according to the SFINX. Prevalence of DDDIs, associated factors and 3-year mortality among residents. Of the participants (mean age was 82.7 years, 78.3% were females), 5.9% (N = 78) are at risk for DDDIs, with a total of 86 interactions. Participants with DDDIs had been prescribed a higher number of drugs (10.8 (SD 3.8) vs. 7.9 (SD 3.7), p assisted living, 5.9% were exposed to DDDIs associated with the use of a higher number of drugs. Physicians should be trained to find safer alternatives to drugs associated with DDDIs. KEY POINTS   Potentially severe, class D drug-drug interactions (DDDIs) have been defined in the SFINX database as clinically relevant drug interactions that should be avoided.  • Of the residents in assisted living, 5.9% were exposed to DDDIs that were associated with the use of a higher number of drugs.  • The most frequent DDDIs were related to the concomitant use of potassium with amiloride or spironolactone. Carbamazepine and methotrexate were also linked to DDDIs.  • No difference in mortality was observed between residents exposed to DDDIs and residents not exposed to DDDIs.

  1. Interactions between genetic variants associated with adiposity traits and soft drinks in relation to longitudinal changes in body weight and waist circumference

    DEFF Research Database (Denmark)

    Olsen, Nanna J; Ängquist, Lars; Larsen, Sofus C

    2016-01-01

    Background: Intake of sugar-sweetened beverages is associated with obesity, and this association may be modified by a genetic predisposition to obesity. Objective: We examined the interactions between a molecular genetic predisposition to various aspects of obesity and the consumption of soft...... drinks, which are a major part of sugar-sweetened beverages, in relation to changes in adiposity measures. Design: A total of 4765 individuals were included in the study. On the basis of 50 obesity- Associated single nucleotide polymorphisms that are associated with body mass index (BMI), waist...... circumference (WC), or the waist- To-hip ratio adjusted for BMI (WHRBMI), the following 4 genetic predisposition scores (GRSs) were constructed: A complete genetic predisposition score including all 50 single nucleotide polymorphisms (GRSComplete), a genetic predisposition score including BMI- Associated single...

  2. Association of Maternal Interaction with Emotional Regulation in 4 and 9 Month Infants During the Still Face Paradigm

    Science.gov (United States)

    Lowe, Jean R.; MacLean, Peggy C.; Duncan, Andrea F.; Aragón, Crystal; Schrader, Ronald M.; Caprihan, Arvind; Phillips, John P.

    2013-01-01

    This study used the Still Face Paradigm to investigate the relationship of maternal interaction on infants’ emotion regulation responses. Seventy infant-mother dyads were seen at 4 months and 25 of these same dyads were re-evaluated at 9 months. Maternal interactions were coded for attention seeking and contingent responding. Emotional regulation was described by infant stress reaction and overall positive affect. Results indicated that at both 4 and 9 months mothers who used more contingent responding interactions had infants who showed more positive affect. In contrast, mothers who used more attention seeking play had infants who showed less positive affect after the Still Face Paradigm. Patterns of stress reaction were reversed, as mothers who used more attention seeking play had infants with less negative affect. Implications for intervention and emotional regulation patterns over time are discussed. PMID:22217393

  3. Association of medical students' reports of interactions with the pharmaceutical and medical device industries and medical school policies and characteristics: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    James S Yeh

    2014-10-01

    Full Text Available Professional societies use metrics to evaluate medical schools' policies regarding interactions of students and faculty with the pharmaceutical and medical device industries. We compared these metrics and determined which US medical schools' industry interaction policies were associated with student behaviors.Using survey responses from a national sample of 1,610 US medical students, we compared their reported industry interactions with their schools' American Medical Student Association (AMSA PharmFree Scorecard and average Institute on Medicine as a Profession (IMAP Conflicts of Interest Policy Database score. We used hierarchical logistic regression models to determine the association between policies and students' gift acceptance, interactions with marketing representatives, and perceived adequacy of faculty-industry separation. We adjusted for year in training, medical school size, and level of US National Institutes of Health (NIH funding. We used LASSO regression models to identify specific policies associated with the outcomes. We found that IMAP and AMSA scores had similar median values (1.75 [interquartile range 1.50-2.00] versus 1.77 [1.50-2.18], adjusted to compare scores on the same scale. Scores on AMSA and IMAP shared policy dimensions were not closely correlated (gift policies, r = 0.28, 95% CI 0.11-0.44; marketing representative access policies, r = 0.51, 95% CI 0.36-0.63. Students from schools with the most stringent industry interaction policies were less likely to report receiving gifts (AMSA score, odds ratio [OR]: 0.37, 95% CI 0.19-0.72; IMAP score, OR 0.45, 95% CI 0.19-1.04 and less likely to interact with marketing representatives (AMSA score, OR 0.33, 95% CI 0.15-0.69; IMAP score, OR 0.37, 95% CI 0.14-0.95 than students from schools with the lowest ranked policy scores. The association became nonsignificant when fully adjusted for NIH funding level, whereas adjusting for year of education, size of school, and publicly

  4. Association of medical students' reports of interactions with the pharmaceutical and medical device industries and medical school policies and characteristics: a cross-sectional study.

    Science.gov (United States)

    Yeh, James S; Austad, Kirsten E; Franklin, Jessica M; Chimonas, Susan; Campbell, Eric G; Avorn, Jerry; Kesselheim, Aaron S

    2014-10-01

    Professional societies use metrics to evaluate medical schools' policies regarding interactions of students and faculty with the pharmaceutical and medical device industries. We compared these metrics and determined which US medical schools' industry interaction policies were associated with student behaviors. Using survey responses from a national sample of 1,610 US medical students, we compared their reported industry interactions with their schools' American Medical Student Association (AMSA) PharmFree Scorecard and average Institute on Medicine as a Profession (IMAP) Conflicts of Interest Policy Database score. We used hierarchical logistic regression models to determine the association between policies and students' gift acceptance, interactions with marketing representatives, and perceived adequacy of faculty-industry separation. We adjusted for year in training, medical school size, and level of US National Institutes of Health (NIH) funding. We used LASSO regression models to identify specific policies associated with the outcomes. We found that IMAP and AMSA scores had similar median values (1.75 [interquartile range 1.50-2.00] versus 1.77 [1.50-2.18], adjusted to compare scores on the same scale). Scores on AMSA and IMAP shared policy dimensions were not closely correlated (gift policies, r = 0.28, 95% CI 0.11-0.44; marketing representative access policies, r = 0.51, 95% CI 0.36-0.63). Students from schools with the most stringent industry interaction policies were less likely to report receiving gifts (AMSA score, odds ratio [OR]: 0.37, 95% CI 0.19-0.72; IMAP score, OR 0.45, 95% CI 0.19-1.04) and less likely to interact with marketing representatives (AMSA score, OR 0.33, 95% CI 0.15-0.69; IMAP score, OR 0.37, 95% CI 0.14-0.95) than students from schools with the lowest ranked policy scores. The association became nonsignificant when fully adjusted for NIH funding level, whereas adjusting for year of education, size of school, and publicly versus

  5. Search for Screened Interactions Associated with Dark Energy below the 100 μm Length Scale.

    Science.gov (United States)

    Rider, Alexander D; Moore, David C; Blakemore, Charles P; Louis, Maxime; Lu, Marie; Gratta, Giorgio

    2016-09-02

    We present the results of a search for unknown interactions that couple to mass between an optically levitated microsphere and a gold-coated silicon cantilever. The scale and geometry of the apparatus enable a search for new forces that appear at distances below 100  μm and which would have evaded previous searches due to screening mechanisms. The data are consistent with electrostatic backgrounds and place upper limits on the strength of new interactions at 5.6×10^{4} in the region of parameter space where the self-coupling Λ≳5  meV and the microspheres are not fully screened.

  6. Association between Urine Phthalate Levels and Poor Attentional Performance in Children with Attention-Deficit Hyperactivity Disorder with Evidence of Dopamine Gene-Phthalate Interaction

    Directory of Open Access Journals (Sweden)

    Subin Park

    2014-06-01

    Full Text Available Although there is some evidence supporting the existence of an association between prenatal maternal or postnatal child’s urine phthalate metabolite concentrations and poor attentional performances, the interaction between urine phthalate metabolite levels and genetic variation for neuropsychological deficit of attention-deficit hyperactivity disorder (ADHD has not been examined. The aim of this study was to determine whether phthalate metabolites in urine are associated with poor neuropsychological performance in children with ADHD, and whether such association is affected by genotype-phthalate interaction. A cross-sectional examination of urine phthalate metabolite concentrations and the continuous performance test (CPT were performed in 179 Korean children with ADHD recruited from department of psychiatry of university hospital. Correlations between urine phthalate metabolite concentrations and the CPT scores were investigated, and the interaction of phthalate metabolite levels with the selected polymorphisms at major candidate genes for ADHD, namely dopamine receptor D4 (DRD4, dopamine transporter, α-2A-adrenergic receptor, and norepinephrine transporter genes. For the subjects with the DRD4 4/4 genotype, there were significant associations of the urine phthalate metabolite concentrations with the number of omission errors, the number of commission errors, and the response time variability scores on the CPT. However, for the subjects without the DRD4 4/4 genotype, no significant associations were found. The results of this study suggest a possible association between phthalate metabolite concentrations and poor attentional performances of ADHD as well as a genetic influence on this association. Further prospective and epigenetic studies are needed to investigate causality and pathophysiological mechanisms.

  7. Association between urine phthalate levels and poor attentional performance in children with attention-deficit hyperactivity disorder with evidence of dopamine gene-phthalate interaction.

    Science.gov (United States)

    Park, Subin; Kim, Bung-Nyun; Cho, Soo-Churl; Kim, Yeni; Kim, Jae-Won; Lee, Ju-Young; Hong, Soon-Beom; Shin, Min-Sup; Yoo, Hee Jeong; Im, Hosub; Cheong, Jae Hoon; Han, Doug Hyun

    2014-06-27

    Although there is some evidence supporting the existence of an association between prenatal maternal or postnatal child's urine phthalate metabolite concentrations and poor attentional performances, the interaction between urine phthalate metabolite levels and genetic variation for neuropsychological deficit of attention-deficit hyperactivity disorder (ADHD) has not been examined. The aim of this study was to determine whether phthalate metabolites in urine are associated with poor neuropsychological performance in children with ADHD, and whether such association is affected by genotype-phthalate interaction. A cross-sectional examination of urine phthalate metabolite concentrations and the continuous performance test (CPT) were performed in 179 Korean children with ADHD recruited from department of psychiatry of university hospital. Correlations between urine phthalate metabolite concentrations and the CPT scores were investigated, and the interaction of phthalate metabolite levels with the selected polymorphisms at major candidate genes for ADHD, namely dopamine receptor D4 (DRD4), dopamine transporter, α-2A-adrenergic receptor, and norepinephrine transporter genes. For the subjects with the DRD4 4/4 genotype, there were significant associations of the urine phthalate metabolite concentrations with the number of omission errors, the number of commission errors, and the response time variability scores on the CPT. However, for the subjects without the DRD4 4/4 genotype, no significant associations were found. The results of this study suggest a possible association between phthalate metabolite concentrations and poor attentional performances of ADHD as well as a genetic influence on this association. Further prospective and epigenetic studies are needed to investigate causality and pathophysiological mechanisms.

  8. Autism and Intellectual Disability-Associated KIRREL3 Interacts with Neuronal Proteins MAP1B and MYO16 with Potential Roles in Neurodevelopment.

    Directory of Open Access Journals (Sweden)

    Ying F Liu

    Full Text Available Cell-adhesion molecules of the immunoglobulin superfamily play critical roles in brain development, as well as in maintaining synaptic plasticity, the dysfunction of which is known to cause cognitive impairment. Recently dysfunction of KIRREL3, a synaptic molecule of the immunoglobulin superfamily, has been implicated in several neurodevelopmental conditions including intellectual disability, autism spectrum disorder, and in the neurocognitive delay associated with Jacobsen syndrome. However, the molecular mechanisms of its physiological actions remain largely unknown. Using a yeast two-hybrid screen, we found that the KIRREL3 extracellular domain interacts with brain expressed proteins MAP1B and MYO16 and its intracellular domain can potentially interact with ATP1B1, UFC1, and SHMT2. The interactions were confirmed by co-immunoprecipitation and colocalization analyses of proteins expressed in human embryonic kidney cells, mouse neuronal cells, and rat primary neuronal cells. Furthermore, we show KIRREL3 colocalization with the marker for the Golgi apparatus and synaptic vesicles. Previously, we have shown that KIRREL3 interacts with the X-linked intellectual disability associated synaptic scaffolding protein CASK through its cytoplasmic domain. In addition, we found a genomic deletion encompassing MAP1B in one patient with intellectual disability, microcephaly and seizures and deletions encompassing MYO16 in two unrelated patients with intellectual disability, autism and microcephaly. MAP1B has been previously implicated in synaptogenesis and is involved in the development of the actin-based membrane skeleton. MYO16 is expressed in hippocampal neurons and also indirectly affects actin cytoskeleton through its interaction with WAVE1 complex. We speculate KIRREL3 interacting proteins are potential candidates for intellectual disability and autism spectrum disorder. Moreover, our findings provide further insight into understanding the molecular

  9. Chemical-Gene Interactions from ToxCast Bioactivity Data Expands Universe of Literature Network-Based Associations (SOT)

    Science.gov (United States)

    Characterizing the effects of chemicals in biological systems is often summarized by chemical-gene interactions, which have sparse coverage in the literature. The ToxCast chemical screening program has produced bioactivity data for nearly 2000 chemicals and over 450 gene targets....

  10. Low-Income Mothers' Nighttime and Weekend Work: Daily Associations with Child Behavior, Mother-Child Interactions, and Mood

    Science.gov (United States)

    Gassman-Pines, Anna

    2011-01-01

    This study investigated low-income mothers' daily nighttime and weekend work and family outcomes. Sixty-one mothers of preschool-aged children reported daily on work hours, mood, mother-child interaction, and child behavior for two weeks (N = 724 person-days). Although nighttime and weekend work are both nonstandard schedules, results showed…

  11. CD91 interacts with mannan-binding lectin (MBL) through the MBL-associated serine protease-binding site

    DEFF Research Database (Denmark)

    Duus, Karen; Thielens, Nicole M; Lacroix, Monique

    2010-01-01

    CD91 plays an important role in the scavenging of apoptotic material, possibly through binding to soluble pattern-recognition molecules. In this study, we investigated the interaction of CD91 with mannan-binding lectin (MBL), ficolins and lung surfactant proteins. Both MBL and L-ficolin were foun...

  12. The multitrophic consequences of concurrent insect invasions: a range-expanding herbivore and its associated parasitoid affect native tritrophic interactions

    Science.gov (United States)

    Global climatic changes may lead to the arrival of range-expanding species into new environments. Species from different trophic levels sharing the same climatic niche may invade new habitats simultaneously or in quick succession, causing the formation of multiple novel interactions into native food...

  13. Dopaminergic, Serotonergic, and Oxytonergic Candidate Genes Associated with Infant Attachment Security and Disorganization? In Search of Main and Interaction Effects

    Science.gov (United States)

    Luijk, Maartje P. C. M.; Roisman, Glenn I.; Haltigan, John D.; Tiemeier, Henning; Booth-LaForce, Cathryn; van IJzendoorn, Marinus H.; Belsky, Jay; Uitterlinden, Andre G.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; Tharner, Anne; Bakermans-Kranenburg, Marian J.

    2011-01-01

    Background and methods: In two birth cohort studies with genetic, sensitive parenting, and attachment data of more than 1,000 infants in total, we tested main and interaction effects of candidate genes involved in the dopamine, serotonin, and oxytocin systems ("DRD4", "DRD2", "COMT", "5-HTT", "OXTR") on attachment security and disorganization.…

  14. Characterization of the interaction between Actinin-Associated LIM Protein (ALP) and the rod domain of α-actinin

    Science.gov (United States)

    Klaavuniemi, Tuula; Alho, Nanna; Hotulainen, Pirta; Kelloniemi, Annina; Havukainen, Heli; Permi, Perttu; Mattila, Sampo; Ylänne, Jari

    2009-01-01

    Background The PDZ-LIM proteins are a family of signalling adaptors that interact with the actin cross-linking protein, α-actinin, via their PDZ domains or via internal regions between the PDZ and LIM domains. Three of the PDZ-LIM proteins have a conserved 26-residue ZM motif in the internal region, but the structure of the internal region is unknown. Results In this study, using circular dichroism and nuclear magnetic resonance (NMR), we showed that the ALP internal region (residues 107–273) was largely unfolded in solution, but was able to interact with the α-actinin rod domain in vitro, and to co-localize with α-actinin on stress fibres in vivo. NMR analysis revealed that the titration of ALP with the α-actinin rod domain induces stabilization of ALP. A synthetic peptide (residues 175–196) that contained the N-terminal half of the ZM motif was found to interact directly with the α-actinin rod domain in surface plasmon resonance (SPR) measurements. Short deletions at or before the ZM motif abrogated the localization of ALP to actin stress fibres. Conclusion The internal region of ALP appeared to be largely unstructured but functional. The ZM motif defined part of the interaction surface between ALP and the α-actinin rod domain. PMID:19327143

  15. Mitochondria-associated Endoplasmic Reticulum Membrane (MAM) Regulates Steroidogenic Activity via Steroidogenic Acute Regulatory Protein (StAR)-Voltage-dependent Anion Channel 2 (VDAC2) Interaction*

    Science.gov (United States)

    Prasad, Manoj; Kaur, Jasmeet; Pawlak, Kevin J.; Bose, Mahuya; Whittal, Randy M.; Bose, Himangshu S.

    2015-01-01

    Steroid hormones are essential for carbohydrate metabolism, stress management, and reproduction and are synthesized from cholesterol in mitochondria of adrenal glands and gonads/ovaries. In acute stress or hormonal stimulation, steroidogenic acute regulatory protein (StAR) transports substrate cholesterol into the mitochondria for steroidogenesis by an unknown mechanism. Here, we report for the first time that StAR interacts with voltage-dependent anion channel 2 (VDAC2) at the mitochondria-associated endoplasmic reticulum membrane (MAM) prior to its translocation to the mitochondrial matrix. In the MAM, StAR interacts with mitochondrial proteins Tom22 and VDAC2. However, Tom22 knockdown by siRNA had no effect on pregnenolone synthesis. In the absence of VDAC2, StAR was expressed but not processed into the mitochondria as a mature 30-kDa protein. VDAC2 interacted with StAR via its C-terminal 20 amino acids and N-terminal amino acids 221–229, regulating the mitochondrial processing of StAR into the mature protein. In the absence of VDAC2, StAR could not enter the mitochondria or interact with MAM-associated proteins, and therefore steroidogenesis was inhibited. Furthermore, the N terminus was not essential for StAR activity, and the N-terminal deletion mutant continued to interact with VDAC2. The endoplasmic reticulum-targeting prolactin signal sequence did not affect StAR association with the MAM and thus its mitochondrial targeting. Therefore, VDAC2 controls StAR processing and activity, and MAM is thus a central location for initiating mitochondrial steroidogenesis. PMID:25505173

  16. Mitochondria-associated endoplasmic reticulum membrane (MAM) regulates steroidogenic activity via steroidogenic acute regulatory protein (StAR)-voltage-dependent anion channel 2 (VDAC2) interaction.

    Science.gov (United States)

    Prasad, Manoj; Kaur, Jasmeet; Pawlak, Kevin J; Bose, Mahuya; Whittal, Randy M; Bose, Himangshu S

    2015-01-30

    Steroid hormones are essential for carbohydrate metabolism, stress management, and reproduction and are synthesized from cholesterol in mitochondria of adrenal glands and gonads/ovaries. In acute stress or hormonal stimulation, steroidogenic acute regulatory protein (StAR) transports substrate cholesterol into the mitochondria for steroidogenesis by an unknown mechanism. Here, we report for the first time that StAR interacts with voltage-dependent anion channel 2 (VDAC2) at the mitochondria-associated endoplasmic reticulum membrane (MAM) prior to its translocation to the mitochondrial matrix. In the MAM, StAR interacts with mitochondrial proteins Tom22 and VDAC2. However, Tom22 knockdown by siRNA had no effect on pregnenolone synthesis. In the absence of VDAC2, StAR was expressed but not processed into the mitochondria as a mature 30-kDa protein. VDAC2 interacted with StAR via its C-terminal 20 amino acids and N-terminal amino acids 221-229, regulating the mitochondrial processing of StAR into the mature protein. In the absence of VDAC2, StAR could not enter the mitochondria or interact with MAM-associated proteins, and therefore steroidogenesis was inhibited. Furthermore, the N terminus was not essential for StAR activity, and the N-terminal deletion mutant continued to interact with VDAC2. The endoplasmic reticulum-targeting prolactin signal sequence did not affect StAR association with the MAM and thus its mitochondrial targeting. Therefore, VDAC2 controls StAR processing and activity, and MAM is thus a central location for initiating mitochondrial steroidogenesis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. The association of peroxisome proliferator-activated receptor α with diabetic retinopathy, and additional gene-obesity interaction in Chinese type 2 diabetes mellitus patients.

    Science.gov (United States)

    Qi, Shounan; Wang, Chenguang; Zhang, Yan; Cheng, Yan; Wang, Shurong; Zhao, Yixuan

    2016-09-01

    To investigate the impact of peroxisome proliferator-activated receptor α (PPAR α) SNPs and gene-obesity interaction on diabetic retinopathy (DR) susceptibility in a Chinese Han population. A total of 812 patients (373men, 439 women) with type 2 diabetes mellitus (T2DM), with a mean age of 53.3±14.0 years old, were selected, including 402 diabetic retinopathy patients and 410 controls. Three single nucleotide polymorphisms (SNPs) were selected for genotyping in the case-control study: rs4253778, rs135539 and rs1800206. Generalised multifactor dimensionality reduction (GMDR) and logistic regression model was used to examine the association and interaction between SNP and obesity on DR, odds ratio (OR) and 95% confident interval (95%CI) were calculated. The carriers of homozygous mutant of rs1800206 SNP revealed decreased DR risk than those with wild-type homozygotes, OR (95%CI) was 0.78 (0.66-0.94). GMDR analysis indicated a significant two-locus model (p=0.0107) involving rs1800206 and abdominal obesity, indicating a potential interaction among rs1800206 and abdominal obesity. Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 60.72%. We also found that subjects with abdominal obesity and LV or VV genotype have lowest DR risk, compared to subjects with normal WC and LL genotype, OR (95%CI) was 0.39 (0.30-0.74), after covariates adjustment. Our results support an important association between rs1800206 minor allele of PPAR α and DR, and the interaction analysis also shown a combined effect of Leu162 allele-abdominal obesity interaction on DR. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  18. A Typology of Interactional Patterns Between Youth and Their Stepfathers: Associations with Family Relationship Quality and Youth Well-Being.

    Science.gov (United States)

    Jensen, Todd M

    2018-03-09

    Stepfamilies are an increasingly common family form, many of which are headed by a resident mother and stepfather. Stepfather-child relationships exert notable influence on stepfamily stability and individual well-being. Although various stepfather roles have been observed, more research is warranted by which stepfather-child interactions are explored holistically and across a variety of life domains (e.g., recreational, personal, academic, and disciplinary). Thus, the primary purpose of the current study is to explore varying interactional patterns between youth and their stepfathers. A latent class analysis is conducted using a representative sample of 1,183 youth (53% female; mean age = 15.64 years, SD = 1.70 years; 62% non-Hispanic White) residing in mother-stepfather families from Wave I of the National Longitudinal Study of Adolescent to Adult Health. Latent-class enumeration processes support a four-class solution, with latent classes representing inactive, academically oriented, casually connected, and versatile and involved patterns of youth-stepparent interaction. Notable differences and similarities are evident across patterns with respect to family relationship quality, youth well-being, and socio-demographic characteristics. Differences are most stark between the inactive and versatile and involved patterns. Ultimately, the results showcase notable variation in youth-stepparent interactional patterns, and one size does not necessarily fit all stepfamilies. Family practitioners should be mindful of variation in youth-stepparent interactional patterns and assist stepfamilies in seeking out stepparent-child dynamics that are most compatible with the needs and dynamics of the larger family system. © 2018 Family Process Institute.

  19. No Association between HMOX1 and Risk of Colorectal Cancer and No Interaction with Diet and Lifestyle Factors in a Prospective Danish Case-Cohort Study

    Directory of Open Access Journals (Sweden)

    Vibeke Andersen

    2015-01-01

    Full Text Available Red meat is a risk factor for colorectal cancer (CRC. We wanted to evaluate whether a functional polymorphism in the HMOX1 gene encoding heme oxygenase modifies risk of CRC or interacts with diet or lifestyle factors because this would identify heme or heme iron as a risk factor of CRC. The HMOX1 A-413T (rs2071746 was assessed in relation to risk of colorectal cancer (CRC and interactions with diet (red meat, fish, fiber, cereals, fruit and vegetables and lifestyle (use of non-steroidal anti-inflammatory drug and smoking status were assessed in a case-cohort study of 928 CRC cases and a comparison group of 1726 randomly selected participants from a prospective study of 57,053 persons. No association between HMOX1 A-413T and CRC risk was found (TT vs. AA + TA; IRR = 1.15, 95% CI: 0.98–1.36, p = 0.10 for the adjusted estimate. No interactions were found between diet or lifestyle and HMOX1 A-413T. HMOX1 A-413T was not associated with CRC risk and no interactions with diet or lifestyle were identified in this large, prospective cohort with high meat intake. The results reproduced the previous findings from the same cohort and did not support a link between heme or heme iron and colorectal cancer. These results should be sought and replicated in other well-characterized cohorts with high meat intake.

  20. Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation

    DEFF Research Database (Denmark)

    Connolly, Brian M; Choi, Eun Young; Gårdsvoll, Henrik

    2010-01-01

    The urokinase plasminogen activator receptor (uPAR) has emerged as a potential regulator of cell adhesion, cell migration, proliferation, differentiation, and cell survival in multiple physiologic and pathologic contexts. The urokinase plasminogen activator (uPA) was the first identified ligand...... of the domain. Analysis of Plau(GFDhu/GFDhu) mice revealed an unanticipated role of the uPA-uPAR interaction in suppressing inflammation secondary to fibrin deposition. In contrast, leukocyte recruitment and tissue regeneration were unaffected by the loss of uPA binding to uPAR. This study identifies...... a principal in vivo role of the uPA-uPAR interaction in cell-associated fibrinolysis critical for suppression of fibrin accumulation and fibrin-associated inflammation and provides a valuable model for further exploration of this multifunctional receptor....

  1. Metagenome Survey of a Multispecies and Alga-Associated Biofilm Revealed Key Elements of Bacterial-Algal Interactions in Photobioreactors

    OpenAIRE

    Krohn-Molt, Ines; Wemheuer, Bernd; Alawi, Malik; Poehlein, Anja; Güllert, Simon; Schmeisser, Christel; Pommerening-Röser, Andreas; Grundhoff, Adam; Daniel, Rolf; Hanelt, Dieter; Streit, Wolfgang R.

    2013-01-01

    Photobioreactors (PBRs) are very attractive for sunlight-driven production of biofuels and capturing of anthropogenic CO2. One major problem associated with PBRs however, is that the bacteria usually associated with microalgae in nonaxenic cultures can lead to biofouling and thereby affect algal productivity. Here, we report on a phylogenetic, metagenome, and functional analysis of a mixed-species bacterial biofilm associated with the microalgae Chlorella vulgaris and Scenedesmus obliquus in ...

  2. Structural Basis for the Interaction of the Golgi-Associated Retrograde Protein (GARP) Complex with the t-SNARE Syntaxin 6

    Science.gov (United States)

    Abascal-Palacios, Guillermo; Schindler, Christina; Rojas, Adriana L; Bonifacino, Juan S.; Hierro, Aitor

    2016-01-01

    Summary The Golgi-Associated Retrograde Protein (GARP) is a tethering complex involved in the fusion of endosome-derived transport vesicles to the trans-Golgi network through interaction with components of the Syntaxin 6/Syntaxin 16/Vti1a/VAMP4 SNARE complex. The mechanisms by which GARP and other tethering factors engage the SNARE fusion machinery are poorly understood. Herein we report the structural basis for the interaction of the human Ang2 subunit of GARP with Syntaxin 6 and the closely related Syntaxin 10. The crystal structure of Syntaxin 6 Habc domain in complex with a peptide from the N terminus of Ang2 shows a novel binding mode in which a di-tyrosine motif of Ang2 interacts with a highly conserved groove in Syntaxin 6. Structure-based mutational analyses validate the crystal structure and support the phylogenetic conservation of this interaction. The same binding determinants are found in other tethering proteins and syntaxins, suggesting a general interaction mechanism. PMID:23932592

  3. Isothermal Titration Calorimetry and Fluorescence Spectroscopy Study Of Asphaltene Self-Association In Toluene And Interaction With A Model Resin

    DEFF Research Database (Denmark)

    Garcia, Daniel Merino; Andersen, Simon Ivar

    2002-01-01

    This article collects the work performed by Isothermal Titration Caloritnetry (ITC) in the study of the self-association of asphaltenes in toluene solutions. Calorimetric experiments show that asphaltenes, start self-associating at very low concentrations and that the existence of a Critical...... with the results of the titration of three model molecules: nonylphenol, which associates by means of hydrogen bond formation, and coronene and pyrene, which associates by stacking. The results obtained leave open the question about the model-stacking molecules, as it was not possible to elucidate whether they do...

  4. Work stress, worries, and pain interact synergistically with modelled traffic noise on cross-sectional associations with self-reported sleep problems

    OpenAIRE

    Kristiansen, Jesper; Persson, Roger; Björk, Jonas; Albin, Maria; Jakobsson, Kristina; Östergren, Per-Olof; Ardö, Jonas

    2011-01-01

    To examine the risk of sleep problems associated with work stress (job strain, job demands, and decision authority), worries and pain and to investigate the synergistic interaction between these factors and traffic noise. Sleep problems and predictor variables were assessed in a cross-sectional public health survey with 12,093 respondents. Traffic noise levels were assessed using modelled A-weighted energy equivalent traffic sound levels at the residence. The risk of sleep problems was modell...

  5. Intraplaque hemorrhage is associated with higher structural stresses in human atherosclerotic plaques: an in vivo MRI-based 3d fluid-structure interaction study

    OpenAIRE

    Huang, Xueying; Teng, Zhongzhao; Canton, Gador; Ferguson, Marina; Yuan, Chun; Tang, Dalin

    2010-01-01

    Abstract Background Studies using medical images have shown that intraplaque hemorrhage may accelerate plaque progression and may produce a stimulus for atherosclerosis development by increasing lipid core and plaque volume and creating new destabilizing factors. Image-based 3D computational models with fluid-structure interactions (FSI) will be used to perform plaque mechanical analysis and investigate possible associations between intraplaque hemorrhage and both plaque wall stress (PWS) and...

  6. Identification of a two-loci epistatic interaction associated with susceptibility to rheumatoid arthritis through reverse engineering and multifactor dimensionality reduction.

    Science.gov (United States)

    Julià, Antonio; Moore, Jason; Miquel, Laia; Alegre, Cayetano; Barceló, Pere; Ritchie, Marylyn; Marsal, Sara

    2007-07-01

    Altered synovial fibroblast (SF) transcriptional activity is a key factor in the disease progression of rheumatoid arthritis (RA). To determine the transcriptional regulatory network associated with SF response to an RA proinflammatory stimulus we applied a CARRIE reverse engineering approach to microarray gene expression data from SFs treated with RA synovial fluid. The association of the inferred gene network with RA susceptibility was further analyzed by a case-control study of promoter single-nucleotide polymorphisms, and the presence of epistatic interactions was determined using the multifactor dimensionality reduction methodology. Our findings suggest that a specific NF-kappaB transcriptional regulatory network of 13 genes is associated with SF response to RA proinflammatory stimulus and identify a significant epistatic association of two of its genes, IL6 and IL4I1, with RA susceptibility.

  7. Interaction between BDNF rs6265 Met allele and low family cohesion is associated with smaller left hippocampal volume in pediatric bipolar disorder.

    Science.gov (United States)

    Zeni, Cristian Patrick; Mwangi, Benson; Cao, Bo; Hasan, Khader M; Walss-Bass, Consuelo; Zunta-Soares, Giovana; Soares, Jair C

    2016-01-01

    Genetic and environmental factors are implicated in the onset and evolution of pediatric bipolar disorder, and may be associated to structural brain abnormalities. The aim of our study was to assess the impact of the interaction between the Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism and family functioning on hippocampal volumes of children and adolescents with bipolar disorder, and typically-developing controls. We evaluated the family functioning cohesion subscale using the Family Environment Scale-Revised, genotyped the BDNF rs6265 polymorphism, and performed structural brain imaging in 29 children and adolescents with bipolar disorder, and 22 healthy controls. We did not find significant differences between patients with BD or controls in left or right hippocampus volume (p=0.44, and p=0.71, respectively). However, we detected a significant interaction between low scores on the cohesion subscale and the presence of the Met allele at BNDF on left hippocampal volume of patients with bipolar disorder (F=3.4, p=0.043). None of the factors independently (BDNF Val66Met, cohesion scores) was significantly associated with hippocampal volume differences. small sample size, cross-sectional study. These results may lead to a better understanding of the impact of the interaction between genes and environment factors on brain structures associated to bipolar disorder and its manifestations. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Construct validity of the parent-child sleep interactions scale (PSIS): associations with parenting, family stress, and maternal and child psychopathology.

    Science.gov (United States)

    Smith, Victoria C; Leppert, Katherine A; Alfano, Candice A; Dougherty, Lea R

    2014-08-01

    Using a multi-method design, this study examined the construct validity of the Parent-Child Sleep Interactions Scale (PSIS; Alfano et al., 2013), which measures sleep-related parenting behaviors and interactions that contribute to preschoolers' sleep problems. Participants included a community sample of 155 preschoolers (ages 3-5years; 51.6% female). Primary caregivers completed the PSIS. Parenting styles and behaviors were assessed with laboratory observations and parent reports. Parent and child psychopathology and family life stress were assessed with clinical interviews and parent reports. Bivariate correlations revealed significant associations between the PSIS and a number of variables, including lower observed parental support and quality of instruction; higher observed parental intrusiveness; authoritative, authoritarian, and permissive parenting styles; current maternal depressive and/or anxiety disorders and depressive symptomatology; increased stressful life events; lower marital satisfaction; and higher child depressive, anxiety, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD) symptoms. The patterns of association varied based on the specific PSIS scale. The PSIS demonstrates meaningful associations with parenting, maternal psychopathology, family stress, and child psychopathology and functioning. Findings suggest that the PSIS is a valid measure for assessing sleep-related parent/child behaviors and interactions among preschoolers, suited to real-world settings. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Associations of changes in psychosocial factors and their interactions with diabetes distress in patients with type 2 diabetes: a longitudinal study.

    Science.gov (United States)

    Wang, Ruey-Hsia; Hsu, Hui-Chun; Kao, Chia-Chan; Yang, Yung-Mei; Lee, Yau-Jiunn; Shin, Shyi-Jang

    2017-05-01

    To assess the associations of changes in self-management behaviours, diabetes self-efficacy, resilience, social support, patient empowerment and their interactions with changes in diabetes distress in patients with type 2 diabetes mellitus. Many patients with type 2 diabetes mellitus experience diabetes distress. Few longitudinal studies have investigated the associations of changes in various psychosocial factors with changes in diabetes distress in patients with type 2 diabetes mellitus. This study adopted a longitudinal design. Data were collected at baseline and 12 months later. Overall, 304 patients with type 2 diabetes were recruited from four hospitals in southern Taiwan by convenience sampling. A self-report questionnaire and medical record were used to collect demographic data, clinical indicators, self-management behaviours, diabetes self-efficacy, resilience, social support, patient empowerment, and diabetes distress. Data were collected from February 2014-March 2015. An increase in resilience or diabetes self-efficacy significantly associated with a decrease in diabetes distress, whereas an increase in patient empowerment significantly associated with an increase in diabetes distress. The interactions between increase in patient empowerment and increase in self-management behaviours significantly associated with decrease in diabetes distress. Nurses could endeavour to improve the diabetes self-efficacy and resilience to reducing diabetes distress. Arbitrarily empowering patients may increase diabetes distress. Increasing self-care management behaviours and patient empowerment might need to be simultaneously addressed to reduce the diabetes distress in patients with type 2 diabetes. © 2016 John Wiley & Sons Ltd.

  10. Two-way plant mediated interactions between root-associated microbes and insects: from ecology to mechanisms

    NARCIS (Netherlands)

    Pangesti, N.P.D.; Pineda Gomez, A.M.; Pieterse, C.M.J.; Dicke, M.; Loon, van J.J.A.

    2013-01-01

    Plants are members of complex communities and function as a link between above- and below-ground organisms. Associations between plants and soil-borne microbes commonly occur and have often been found beneficial for plant fitness. Root-associated microbes may trigger physiological changes in the

  11. 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...

  12. Stromal response to prostate cancer: nanotechnology-based detection of thioredoxin-interacting protein partners distinguishes prostate cancer associated stroma from that of benign prostatic hyperplasia.

    Directory of Open Access Journals (Sweden)

    Elizabeth Singer

    Full Text Available Histological staining of reactive stroma has been shown to be a predictor of biochemical recurrence in prostate cancer, however, molecular markers of the stromal response to prostate cancer have not yet been fully delineated. The objective of this study was to determine whether or not the stromal biomarkers detected with a thioredoxin-targeted nanodevice could be used to distinguish the stroma associated with benign prostatic hyperplasia from that associated with PCA. In this regard, we recently demonstrated that a thioredoxin-targeted nanodevice selectively binds to reactive stroma in frozen prostate tumor tissue sections. To accomplish this, random frozen prostate tissue sections from each of 35 patients who underwent resection were incubated with the nanodevice and graded for fluorescent intensity. An adjacent section from each case was stained with Hematoxylin & Eosin to confirm the diagnosis. Select cases were stained with Masson's Trichrome or immunohistochemically using antibodies to thioredoxin reductase 1, thioredoxin reductase 2 or peroxiredoxin 1. Our results demonstrate that the graded intensity of nanodevice binding to the stroma associated with PCA was significantly higher (p = 0.0127 than that of benign prostatic hyperplasia using the t-test. Immunohistochemical staining of adjacent sections in representative cases showed that none of the two commonly studied thioredoxin interacting protein partners mirrored the fluorescence pattern seen with the nanodevice. However, thioredoxin reductase 2 protein was clearly shown to be a biomarker of prostate cancer-associated reactive stroma whose presence distinguishes the stroma associated with benign prostatic hyperplasia from that associated with prostate cancer. We conclude that the signal detected by the nanodevice, in contrast to individual targets detected with antibodies used in this study, originates from multiple thioredoxin interacting protein partners that distinguish the M2

  13. Stromal response to prostate cancer: nanotechnology-based detection of thioredoxin-interacting protein partners distinguishes prostate cancer associated stroma from that of benign prostatic hyperplasia.

    Science.gov (United States)

    Singer, Elizabeth; Linehan, Jennifer; Babilonia, Gail; Imam, S Ashraf; Smith, David; Loera, Sofia; Wilson, Timothy; Smith, Steven

    2013-01-01

    Histological staining of reactive stroma has been shown to be a predictor of biochemical recurrence in prostate cancer, however, molecular markers of the stromal response to prostate cancer have not yet been fully delineated. The objective of this study was to determine whether or not the stromal biomarkers detected with a thioredoxin-targeted nanodevice could be used to distinguish the stroma associated with benign prostatic hyperplasia from that associated with PCA. In this regard, we recently demonstrated that a thioredoxin-targeted nanodevice selectively binds to reactive stroma in frozen prostate tumor tissue sections. To accomplish this, random frozen prostate tissue sections from each of 35 patients who underwent resection were incubated with the nanodevice and graded for fluorescent intensity. An adjacent section from each case was stained with Hematoxylin & Eosin to confirm the diagnosis. Select cases were stained with Masson's Trichrome or immunohistochemically using antibodies to thioredoxin reductase 1, thioredoxin reductase 2 or peroxiredoxin 1. Our results demonstrate that the graded intensity of nanodevice binding to the stroma associated with PCA was significantly higher (p = 0.0127) than that of benign prostatic hyperplasia using the t-test. Immunohistochemical staining of adjacent sections in representative cases showed that none of the two commonly studied thioredoxin interacting protein partners mirrored the fluorescence pattern seen with the nanodevice. However, thioredoxin reductase 2 protein was clearly shown to be a biomarker of prostate cancer-associated reactive stroma whose presence distinguishes the stroma associated with benign prostatic hyperplasia from that associated with prostate cancer. We conclude that the signal detected by the nanodevice, in contrast to individual targets detected with antibodies used in this study, originates from multiple thioredoxin interacting protein partners that distinguish the M2 neutrophil and

  14. Travel for the 2004 American Statistical Association Biannual Radiation Meeting: "Radiation in Realistic Environments: Interactions Between Radiation and Other Factors

    Energy Technology Data Exchange (ETDEWEB)

    Brenner, David J.

    2009-07-21

    The 16th ASA Conference on Radiation and Health, held June 27-30, 2004 in Beaver Creek, CO, offered a unique forum for discussing research related to the effects of radiation exposures on human health in a multidisciplinary setting. The Conference furnishes investigators in health related disciplines the opportunity to learn about new quantitative approaches to their problems and furnishes statisticians the opportunity to learn about new applications for their discipline. The Conference was attended by about 60 scientists including statisticians, epidemiologists, biologists and physicists interested in radiation research. For the first time, ten recipients of Young Investigator Awards participated in the conference. The Conference began with a debate on the question: “Do radiation doses below 1 cGy increase cancer risks?” The keynote speaker was Dr. Martin Lavin, who gave a banquet presentation on the timely topic “How important is ATM?” The focus of the 2004 Conference on Radiation and Health was Radiation in Realistic Environments: Interactions Between Radiation and Other Risk Modifiers. The sessions of the conference included: Radiation, Smoking, and Lung Cancer Interactions of Radiation with Genetic Factors: ATM Radiation, Genetics, and Epigenetics Radiotherapeutic Interactions The Conference on Radiation and Health is held bi-annually, and participants are looking forward to the 17th conference to be held in 2006.

  15. Interaction of nucleosome assembly proteins abolishes nuclear localization of DGK{zeta} by attenuating its association with importins

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Masashi; Hozumi, Yasukazu [Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585 (Japan); Ichimura, Tohru [Department of Chemistry, Graduate School of Sciences and Engineering, Tokyo Metropolitan University, Hachioji 192-0397 (Japan); Tanaka, Toshiaki; Hasegawa, Hiroshi; Yamamoto, Masakazu; Takahashi, Nobuya [Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585 (Japan); Iseki, Ken [Department of Emergency and Critical Care Medicine, Yamagata University School of Medicine, Yamagata 990-9585 (Japan); Yagisawa, Hitoshi [Laboratory of Biological Signaling, Graduate School of Life Science, University of Hyogo, Hyogo 678-1297 (Japan); Shinkawa, Takashi; Isobe, Toshiaki [Department of Chemistry, Graduate School of Sciences and Engineering, Tokyo Metropolitan University, Hachioji 192-0397 (Japan); Goto, Kaoru, E-mail: kgoto@med.id.yamagata-u.ac.jp [Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585 (Japan)

    2011-12-10

    Diacylglycerol kinase (DGK) is involved in the regulation of lipid-mediated signal transduction through the metabolism of a second messenger diacylglycerol. Of the DGK family, DGK{zeta}, which contains a nuclear localization signal, localizes mainly to the nucleus but translocates to the cytoplasm under pathological conditions. However, the detailed mechanism of translocation and its functional significance remain unclear. To elucidate these issues, we used a proteomic approach to search for protein targets that interact with DGK{zeta}. Results show that nucleosome assembly protein (NAP) 1-like 1 (NAP1L1) and NAP1-like 4 (NAP1L4) are identified as novel DGK{zeta} binding partners. NAP1Ls constitutively shuttle between the nucleus and the cytoplasm in transfected HEK293 cells. The molecular interaction of DGK{zeta} and NAP1Ls prohibits nuclear import of DGK{zeta} because binding of NAP1Ls to DGK{zeta} blocks import carrier proteins, Qip1 and NPI1, to interact with DGK{zeta}, leading to cytoplasmic tethering of DGK{zeta}. In addition, overexpression of NAP1Ls exerts a protective effect against doxorubicin-induced cytotoxicity. These findings suggest that NAP1Ls are involved in a novel molecular basis for the regulation of nucleocytoplasmic shuttling of DGK{zeta} and provide a clue to examine functional significance of its translocation under pathological conditions.

  16. Infant Massage and Quality of Early Mother–Infant Interactions: Are There Associations with Maternal Psychological Wellbeing, Marital Quality, and Social Support?

    Science.gov (United States)

    Porreca, Alessio; Parolin, Micol; Bozza, Giusy; Freato, Susanna; Simonelli, Alessandra

    2017-01-01

    Infant massage programs have proved to be effective in enhancing post-natal development of highly risk infants, such as preterm newborns and drug or HIV exposed children. Less studies have focused on the role of infant massage in supporting the co-construction of early adult–child relationships. In line with this lack of literature, the present paper reports on a pilot study aimed at investigating longitudinally the quality of mother–child interactions, with specific reference to emotional availability (EA), in a group of mother–child pairs involved in infant massage classes. Moreover, associations between mother–child EA, maternal wellbeing, marital adjustment, and social support were also investigated, with the hypothesis to find a link between low maternal distress, high couple satisfaction and high perceived support and interactions of better quality in the dyads. The study involved 20 mothers and their children, aged between 2 and 7 months, who participated to infant massage classes. The assessment took place at three stages: at the beginning of massage course, at the end of it and at 1-month follow-up. At the first stage of assessment self-report questionnaires were administered to examine the presence of maternal psychiatric symptoms (SCL-90-R), perceived social support (MSPSS), and marital adjustment (Dyadic Adjustment Scale); dyadic interactions were observed and rated with the Emotional Availability Scales (Biringen, 2008) at each stage of data collection. The results showed a significant improvement in the quality of mother–child interactions, between the first and the last evaluation, parallel to the unfolding of the massage program, highlighting a general increase in maternal and child’s EA. The presence of maternal psychological distress resulted associated with less optimal mother–child emotional exchanges, while the hypothesis regarding couple satisfaction and social support influence were not confirmed. These preliminary results, if

  17. Infant Massage and Quality of Early Mother-Infant Interactions: Are There Associations with Maternal Psychological Wellbeing, Marital Quality, and Social Support?

    Science.gov (United States)

    Porreca, Alessio; Parolin, Micol; Bozza, Giusy; Freato, Susanna; Simonelli, Alessandra

    2016-01-01

    Infant massage programs have proved to be effective in enhancing post-natal development of highly risk infants, such as preterm newborns and drug or HIV exposed children. Less studies have focused on the role of infant massage in supporting the co-construction of early adult-child relationships. In line with this lack of literature, the present paper reports on a pilot study aimed at investigating longitudinally the quality of mother-child interactions, with specific reference to emotional availability (EA), in a group of mother-child pairs involved in infant massage classes. Moreover, associations between mother-child EA, maternal wellbeing, marital adjustment, and social support were also investigated, with the hypothesis to find a link between low maternal distress, high couple satisfaction and high perceived support and interactions of better quality in the dyads. The study involved 20 mothers and their children, aged between 2 and 7 months, who participated to infant massage classes. The assessment took place at three stages: at the beginning of massage course, at the end of it and at 1-month follow-up. At the first stage of assessment self-report questionnaires were administered to examine the presence of maternal psychiatric symptoms (SCL-90-R), perceived social support (MSPSS), and marital adjustment (Dyadic Adjustment Scale); dyadic interactions were observed and rated with the Emotional Availability Scales (Biringen, 2008) at each stage of data collection. The results showed a significant improvement in the quality of mother-child interactions, between the first and the last evaluation, parallel to the unfolding of the massage program, highlighting a general increase in maternal and child's EA. The presence of maternal psychological distress resulted associated with less optimal mother-child emotional exchanges, while the hypothesis regarding couple satisfaction and social support influence were not confirmed. These preliminary results, if replicated

  18. Adherence is associated with the quality of professional-patient interaction in Directly Observed Treatment Short-course, DOTS

    DEFF Research Database (Denmark)

    Mishra, Pranaya; Hansen, Ebba Holme; Sabroe, Svend

    2006-01-01

    : Better communication between health professionals, particularly dispensers, and patients is essential for improving treatment adherence in TB treatment, even under DOTS. PRACTICE IMPLICATIONS: Drug dispensers should be trained to develop their communication skills about the use of medications, associated...

  19. Structure-function analysis of RBP-J-interacting and tubulin-associated (RITA) reveals regions critical for repression of Notch target genes.

    Science.gov (United States)

    Tabaja, Nassif; Yuan, Zhenyu; Oswald, Franz; Kovall, Rhett A

    2017-06-23

    The Notch pathway is a cell-to-cell signaling mechanism that is essential for tissue development and maintenance, and aberrant Notch signaling has been implicated in various cancers, congenital defects, and cardiovascular diseases. Notch signaling activates the expression of target genes, which are regulated by the transcription factor CSL (CBF1/RBP-J, Su(H), Lag-1). CSL interacts with both transcriptional corepressor and coactivator proteins, functioning as both a repressor and activator, respectively. Although Notch activation complexes are relatively well understood at the structural level, less is known about how CSL interacts with corepressors. Recently, a new RBP-J (mammalian CSL ortholog)-interacting protein termed RITA has been identified and shown to export RBP-J out of the nucleus, thereby leading to the down-regulation of Notch target gene expression. However, the molecular details of RBP-J/RITA interactions are unclear. Here, using a combination of biochemical/cellular, structural, and biophysical techniques, we demonstrate that endogenous RBP-J and RITA proteins interact in cells, map the binding regions necessary for RBP-J·RITA complex formation, and determine the X-ray structure of the RBP-J·RITA complex bound to DNA. To validate the structure and glean more insights into function, we tested structure-based RBP-J and RITA mutants with biochemical/cellular assays and isothermal titration calorimetry. Whereas our structural and biophysical studies demonstrate that RITA binds RBP-J similarly to the RAM (RBP-J-associated molecule) domain of Notch, our biochemical and cellular assays suggest that RITA interacts with additional regions in RBP-J. Taken together, these results provide molecular insights into the mechanism of RITA-mediated regulation of Notch signaling, contributing to our understanding of how CSL functions as a transcriptional repressor of Notch target genes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. A raft-associated species of phosphatidylethanolamine interacts with cholesterol comparably to sphingomyelin. A Langmuir-Blodgett monolayer study.

    Directory of Open Access Journals (Sweden)

    Michal Grzybek

    Full Text Available BACKGROUND: Specific interactions between sphingomyelin (SM and cholesterol (Ch are commonly believed to play a key role in the formation of rafts in the biological membranes. A weakness of this model is the implication that these microdomains are confined to the outer bilayer leaflet. The cytoplasmic leaflet, which contains the bulk of phosphatidylethanolamine (PE, phosphatidylserine (PS and phosphatidylinositol (PI, is thought also to harbour half of the membrane cholesterol. Moreover, SLPE (1-stearoyl-2-linoleoyl-sn-glycero-3-phosphatidyl-ethanolamine has recently been shown to be enriched in isolated detergent-resistant membranes (DRM, and this enrichment was independent of the method of isolation of DRM. METHODOLOGY/PRINCIPAL FINDINGS: Here we present quantitative evidence coming from Langmuir-Blodgett monolayer experiments that SLPE forms complex with Ch similar to that between SM and Ch. The energies of these interactions as calculated form the monolayer studies are highly negative. FRAP analysis showed that NBD-Ch recovery was similar in liposomes composed of DOPC/Ch SM or SLPE but not DPPE, providing further evidence that SLPE may form an l(o phase in the presence of high Ch concentration. Experiments on the solubility of DOPC liposomes containing DPPE/Ch (1ratio1, SM/Ch (1ratio1 or SLPE/Ch (1ratio1 showed the presence of Triton X-100 insoluble floating fraction (TIFF in the case of SM/Ch or SLPE/Ch but not in DPPE/Ch containing liposomes. Quantitative determination of particular lipid species in the TIFF fraction confirms the conclusion that SLPE (or similar PE species could be an important constituent of the inner leaflet raft. CONCLUSION: Such interactions suggest a possible existence of inner-leaflet nanoscale assemblies composed of cholesterol complexes with SLPE or similar unsaturated PE species.

  1. Data on interaction between adeno-associated virus and U87 cell via cRGD chemical modification

    Directory of Open Access Journals (Sweden)

    Chuanling Zhang

    2016-06-01

    Full Text Available RGD tripeptide is a specific, high-affinity ligand for integrin, which is highly expressed in cancer cells. We previously reported that cRGD chemically modified AAV2 (AAV2N587+1/azido+RGD showed significantly enhanced infectivity compared to RGD genetically inserted AAV2 (AAV2N587+RGD (10.1016/j.biomaterials.2015.11.066 [1]. Herein we provide the binding ability analysis of RGD modified AAV2 and U87 cell by flow cytometry and the theoretical working model of RGD–αvβ3 integrin interaction.

  2. Association and interaction analyses of 5-HT3 receptor and serotonin transporter genes with alcohol, cocaine, and nicotine dependence using the SAGE data.

    Science.gov (United States)

    Yang, Jiekun; Li, Ming D

    2014-07-01

    Previous studies have implicated genes encoding the 5-HT3AB receptors (HTR3A and HTR3B) and the serotonin transporter (SLC6A4), both independently and interactively, in alcohol (AD), cocaine (CD), and nicotine dependence (ND). However, whether these genetic effects also exist in subjects with comorbidities remains largely unknown. We used 1,136 African-American (AA) and 2,428 European-American (EA) subjects from the Study of Addiction: Genetics and Environment (SAGE) to determine associations between 88 genotyped or imputed variants within HTR3A, HTR3B, and SLC6A4 and three types of addictions, which were measured by DSM-IV diagnoses of AD, CD, and ND and the Fagerström Test for Nicotine Dependence (FTND), an independent measure of ND commonly used in tobacco research. Individual SNP-based association analysis revealed a significant association of rs2066713 in SLC6A4 with FTND in AA (β = -1.39; P = 1.6E - 04). Haplotype-based association analysis found one major haplotype formed by SNPs rs3891484 and rs3758987 in HTR3B that was significantly associated with AD in the AA sample, and another major haplotype T-T-G, formed by SNPs rs7118530, rs12221649, and rs2085421 in HTR3A, which showed significant association with FTND in the EA sample. Considering the biologic roles of the three genes and their functional relations, we used the GPU-based Generalized Multifactor Dimensionality Reduction (GMDR-GPU) program to test SNP-by-SNP interactions within the three genes and discovered two- to five-variant models that have significant impacts on AD, CD, ND, or FTND. Interestingly, most of the SNPs included in the genetic interaction model(s) for each addictive phenotype are either overlapped or in high linkage disequilibrium for both AA and EA samples, suggesting these detected variants in HTR3A, HTR3B, and SLC6A4 are interactively contributing to etiology of the three addictive phenotypes examined in this study.

  3. Breast cancer-associated high-order SNP-SNP interaction of CXCL12/CXCR4-related genes by an improved multifactor dimensionality reduction (MDR-ER).

    Science.gov (United States)

    Fu, Ou-Yang; Chang, Hsueh-Wei; Lin, Yu-Da; Chuang, Li-Yeh; Hou, Ming-Feng; Yang, Cheng-Hong

    2016-09-01

    In association studies, the combined effects of single nucleotide polymorphism (SNP)-SNP interactions and the problem of imbalanced data between cases and controls are frequently ignored. In the present study, we used an improved multifactor dimensionality reduction (MDR) approach namely MDR-ER to detect the high order SNP‑SNP interaction in an imbalanced breast cancer data set containing seven SNPs of chemokine CXCL12/CXCR4 pathway genes. Most individual SNPs were not significantly associated with breast cancer. After MDR‑ER analysis, six significant SNP‑SNP interaction models with seven genes (highest cross‑validation consistency, 10; classification error rates, 41.3‑21.0; and prediction error rates, 47.4‑55.3) were identified. CD4 and VEGFA genes were associated in a 2‑loci interaction model (classification error rate, 41.3; prediction error rate, 47.5; odds ratio (OR), 2.069; 95% bootstrap CI, 1.40‑2.90; P=1.71E‑04) and it also appeared in all the best 2‑7‑loci models. When the loci number increased, the classification error rates and P‑values decreased. The powers in 2‑7‑loci in all models were >0.9. The minimum classification error rate of the MDR‑ER‑generated model was shown with the 7‑loci interaction model (classification error rate, 21.0; OR=15.282; 95% bootstrap CI, 9.54‑23.87; P=4.03E‑31). In the epistasis network analysis, the overall effect with breast cancer susceptibility was identified and the SNP order of impact on breast cancer was identified as follows: CD4 = VEGFA > KITLG > CXCL12 > CCR7 = MMP2 > CXCR4. In conclusion, the MDR‑ER can effectively and correctly identify the best SNP‑SNP interaction models in an imbalanced data set for breast cancer cases.

  4. Metagenome survey of a multispecies and alga-associated biofilm revealed key elements of bacterial-algal interactions in photobioreactors.

    Science.gov (United States)

    Krohn-Molt, Ines; Wemheuer, Bernd; Alawi, Malik; Poehlein, Anja; Güllert, Simon; Schmeisser, Christel; Pommerening-Röser, Andreas; Grundhoff, Adam; Daniel, Rolf; Hanelt, Dieter; Streit, Wolfgang R

    2013-10-01

    Photobioreactors (PBRs) are very attractive for sunlight-driven production of biofuels and capturing of anthropogenic CO2. One major problem associated with PBRs however, is that the bacteria usually associated with microalgae in nonaxenic cultures can lead to biofouling and thereby affect algal productivity. Here, we report on a phylogenetic, metagenome, and functional analysis of a mixed-species bacterial biofilm associated with the microalgae Chlorella vulgaris and Scenedesmus obliquus in a PBR. The biofilm diversity and population dynamics were examined through 16S rRNA phylogeny. Overall, the diversity was rather limited, with approximately 30 bacterial species associated with the algae. The majority of the observed microorganisms were affiliated with Alphaproteobacteria, Betaproteobacteria, and Bacteroidetes. A combined approach of sequencing via GS FLX Titanium from Roche and HiSeq 2000 from Illumina resulted in the overall production of 350 Mbp of sequenced DNA, 165 Mbp of which was assembled in larger contigs with a maximum size of 0.2 Mbp. A KEGG pathway analysis suggested high metabolic diversity with respect to the use of polymers and aromatic and nonaromatic compounds. Genes associated with the biosynthesis of essential B vitamins were highly redundant and functional. Moreover, a relatively high number of predicted and functional lipase and esterase genes indicated that the alga-associated bacteria are possibly a major sink for lipids and fatty acids produced by the microalgae. This is the first metagenome study of microalga- and PBR-associated biofilm bacteria, and it gives new clues for improved biofuel production in PBRs.

  5. Importance of electrostatic interactions in the association of intrinsically disordered histone chaperone Chz1 and histone H2A.Z-H2B.

    Directory of Open Access Journals (Sweden)

    Xiakun Chu

    Full Text Available Histone chaperones facilitate assembly and disassembly of nucleosomes. Understanding the process of how histone chaperones associate and dissociate from the histones can help clarify their roles in chromosome metabolism. Some histone chaperones are intrinsically disordered proteins (IDPs. Recent studies of IDPs revealed that the recognition of the biomolecules is realized by the flexibility and dynamics, challenging the century-old structure-function paradigm. Here we investigate the binding between intrinsically disordered chaperone Chz1 and histone variant H2A.Z-H2B by developing a structure-based coarse-grained model, in which Debye-Hückel model is implemented for describing electrostatic interactions due to highly charged characteristic of Chz1 and H2A.Z-H2B. We find that major structural changes of Chz1 only occur after the rate-limiting electrostatic dominant transition state and Chz1 undergoes folding coupled binding through two parallel pathways. Interestingly, although the electrostatic interactions stabilize bound complex and facilitate the recognition at first stage, the rate for formation of the complex is not always accelerated due to slow escape of conformations with non-native electrostatic interactions at low salt concentrations. Our studies provide an ionic-strength-controlled binding/folding mechanism, leading to a cooperative mechanism of "local collapse or trapping" and "fly-casting" together and a new understanding of the roles of electrostatic interactions in IDPs' binding.

  6. Trophic Interactions Between Insects and Stream-Associated Amphibians in Steep, Cobble-Bottom Streams of the Pacific Coast of North America

    Directory of Open Access Journals (Sweden)

    Trisha Atwood

    2012-04-01

    Full Text Available Two native, stream-associated amphibians are found in coastal streams of the west coast of North America, the tailed frog and the coastal giant salamander, and each interacts with stream insects in contrasting ways. For tailed frogs, their tadpoles are the primary life stage found in steep streams and they consume biofilm from rock surfaces, which can have trophic and non-trophic effects on stream insects. By virtue of their size the tadpoles are relatively insensitive to stream insect larvae, and tadpoles are capable of depleting biofilm levels directly (exploitative competition, and may also “bulldoze” insect larvae from the surfaces of stones (interference competition. Coastal giant salamander larvae, and sometimes adults, are found in small streams where they prey primarily on stream insects, as well as other small prey. This predator-prey interaction with stream insects does not appear to result in differences in the stream invertebrate community between streams with and without salamander larvae. These two examples illustrate the potential for trophic and non-trophic interactions between stream-associated amphibians and stream insects, and also highlights the need for further research in these systems.

  7. Trophic Interactions Between Insects and Stream-Associated Amphibians in Steep, Cobble-Bottom Streams of the Pacific Coast of North America.

    Science.gov (United States)

    Atwood, Trisha; Richardson, John S

    2012-04-10

    Two native, stream-associated amphibians are found in coastal streams of the west coast of North America, the tailed frog and the coastal giant salamander, and each interacts with stream insects in contrasting ways. For tailed frogs, their tadpoles are the primary life stage found in steep streams and they consume biofilm from rock surfaces, which can have trophic and non-trophic effects on stream insects. By virtue of their size the tadpoles are relatively insensitive to stream insect larvae, and tadpoles are capable of depleting biofilm levels directly (exploitative competition), and may also "bulldoze" insect larvae from the surfaces of stones (interference competition). Coastal giant salamander larvae, and sometimes adults, are found in small streams where they prey primarily on stream insects, as well as other small prey. This predator-prey interaction with stream insects does not appear to result in differences in the stream invertebrate community between streams with and without salamander larvae. These two examples illustrate the potential for trophic and non-trophic interactions between stream-associated amphibians and stream insects, and also highlights the need for further research in these systems.

  8. The N400 as a snapshot of interactive processing: evidence from regression analyses of orthographic neighbor and lexical associate effects

    Science.gov (United States)

    Laszlo, Sarah; Federmeier, Kara D.

    2010-01-01

    Linking print with meaning tends to be divided into subprocesses, such as recognition of an input's lexical entry and subsequent access of semantics. However, recent results suggest that the set of semantic features activated by an input is broader than implied by a view wherein access serially follows recognition. EEG was collected from participants who viewed items varying in number and frequency of both orthographic neighbors and lexical associates. Regression analysis of single item ERPs replicated past findings, showing that N400 amplitudes are greater for items with more neighbors, and further revealed that N400 amplitudes increase for items with more lexical associates and with higher frequency neighbors or associates. Together, the data suggest that in the N400 time window semantic features of items broadly related to inputs are active, consistent with models in which semantic access takes place in parallel with stimulus recognition. PMID:20624252

  9. Mutations Phe785Leu and Thr618Met in Na+, K+-ATPase, Associated with Familial Rapid-Onset Dystonia Parkinsonism, Interfere with Na+ Interaction by Distinct Mechanisms

    DEFF Research Database (Denmark)

    Schack, Vivien Rodacker; Toustrup-Jensen, Mads Schak; Vilsen, Bente

    The Na+, K+-ATPase plays key roles in brain function. Recently, missense mutations in the Na+, K+-ATPase were found associated with familial rapid-onset dystonia parkinsonism (FRDP). Here, we have characterized the functional consequences of FRDP mutations Phe785Leu and Thr618Met. Both mutations...... lead to functionally altered, but active, Na+, K+-pumps that display reduced apparent affinity for cytoplasmic Na+, but the underlying mechanism differs between the mutants. In Phe785Leu, the interaction of the E1 form with Na+ is defective, and the E1-E2 equilibrium is not displaced. In Thr618Met......, the Na+ affinity is reduced because of displacement of the conformational equilibrium in favor of the K+-occluded E2(K2) form. In both mutants, K+ interaction at the external activating sites of the E2P phosphoenzyme is normal. The change of cellular Na+ homeostasis is likely a major factor contributing...

  10. Mutations Phe785Leu and Thr618Met in Na+, K+-ATPase, Associated with Familial Rapid-Onset Dystonia Parkinsonism, Interfere with Na+ Interaction by Distinct Mechanisms

    DEFF Research Database (Denmark)

    Schack, Vivien Rodacker; Toustrup-Jensen, Mads Schak; Vilsen, Bente

    The Na+, K+-ATPase plays key roles in brain function. Recently, missense mutations in the Na+, K+-ATPase were found associated with familial rapid-onset dystonia parkinsonism (FRDP). We have characterized the functional consequences of FRDP mutations Phe785Leu and Thr618Met. Both mutations lead...... to functionally altered, but active, Na+, K+-pumps that display reduced apparent affinity for cytoplasmic Na+, but the underlying mechanism differs between the mutants. In Phe785Leu, the interaction of the E1 form with Na+ is defective, and the E1-E2 equilibrium is not displaced. In Thr618Met, the Na+ affinity...... is reduced because of displacement of the conformational equilibrium in favor of the K+-occluded E2(K2) form. In both mutants, K+ interaction at the external activating sites of the E2P phosphoenzyme is normal. The change of cellular Na+ homeostasis is likely a major factor contributing to the development...

  11. The chaperone and potential mannan-binding lectin (MBL) co-receptor calreticulin interacts with MBL through the binding site for MBL-associated serine proteases

    DEFF Research Database (Denmark)

    Pagh, Rasmus; Duus, Karen; Laursen, Inga

    2008-01-01

    was immobilized on a solid surface or bound to mannan on a surface. The binding was non-covalent and biphasic with an initial salt-sensitive phase followed by a more stable salt-insensitive interaction. For plasma-derived MBL, known to be complexed with MBL-associated serine proteases (MASPs), no binding...... with calreticulin. Comparative analysis of MBL with complement component C1q, its counterpart of the classical pathway, revealed that they display similar binding characteristics for calreticulin, providing further indication that calreticulin is a common co-receptor/chaperone for both proteins. In conclusion......The chaperone calreticulin has been suggested to function as a C1q and collectin receptor. The interaction of calreticulin with mannan-binding lectin (MBL) was investigated by solid-phase binding assays. Calreticulin showed saturable and time-dependent binding to recombinant MBL, provided that MBL...

  12. Novel Genes Affecting the Interaction between the Cabbage Whitefly and Arabidopsis Uncovered by Genome-Wide Association Mapping

    NARCIS (Netherlands)

    Broekgaarden, Colette; Bucher, Johan; Bac-Molenaar, Johanna; Keurentjes, Joost J.B.; Kruijer, Willem; Voorrips, Roeland E.; Vosman, Ben

    2015-01-01

    Plants have evolved a variety of ways to defend themselves against biotic attackers. This has resulted in the presence of substantial variation in defense mechanisms among plants, even within a species. Genome-wide association (GWA) mapping is a useful tool to study the genetic architecture of

  13. Exposure to mixtures of organohalogen contaminants and associative interactions with thyroid hormones in East Greenland polar bears (Ursus maritimus)

    DEFF Research Database (Denmark)

    Villanger, Gro D.; Jenssen, Bjørn M.; Fjeldberg, Rita R.

    2011-01-01

    associations are not evidence per se of biological cause– effect relationships. Still, the results of the present study indicate that OHCs may affect circulating TH levels in East Greenland polar bears, adding to the “weight of evidence” suggesting that OHCs might interfere with thyroid homeostasis in polar...

  14. Associative Ionization of Excited Sodium Species with Various Ligands: Assessing Relative Bonding Strengths of Ion-ligand Interactions

    Czech Academy of Sciences Publication Activity Database

    Gilligan, J. J.; McCunn, L. R.; Leskiw, B. D.; Herman, Zdeněk; Castleman Jr., A. W.

    2001-01-01

    Roč. 204, 1/3 (2001), s. 247-253 ISSN 1387-3806 Institutional research plan: CEZ:AV0Z4040901 Keywords : associative ionization * cluster ions * sodium bonding energies Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.176, year: 2001

  15. Deciphering the mechanisms for targeting and interaction of Arabidopsis Lipid Droplet Associated Protein (LDAP) to the lipid droplet surface

    Science.gov (United States)

    We recently identified a new class of lipid-droplet associated proteins (LDAPs) in plants that share extensive sequence similarity with abundant structural proteins that coat rubber particles in rubber-producing plants. A majority of higher plants, however, including those that do not produce rubber...

  16. Interaction between a novel TGFB1 haplotype and CFTR genotype is associated with improved lung function in cystic fibrosis.

    Science.gov (United States)

    Bremer, Lindsay A; Blackman, Scott M; Vanscoy, Lori L; McDougal, Kathryn E; Bowers, Amanda; Naughton, Kathleen M; Cutler, David J; Cutting, Garry R

    2008-07-15

    Cystic fibrosis (CF), the most common lethal single gene disorder in Caucasians, is due to mutations in the CFTR gene. Twin and sibling analysis indicates that modifier genes, rather than allelic variation in CFTR, are responsible for most of the variability in severity of lung disease, the major cause of mortality in CF patients. We used a family-based approach to test for association between lung function and two functional SNPs (rs1800469, '-509' and rs1982073, 'codon 10') in the 5' region of transforming growth factor-beta1 (TGFB1), a putative CF modifier gene. Quantitative transmission disequilibrium testing of 472 CF patient-parent-parent trios revealed that both TGFB1 SNPs showed significant transmission distortion when patients were stratified by CFTR genotype. Although lung function and nutritional status are correlated in CF patients, there was no evidence of association between the TGFB1 SNPs and variation in nutritional status. Additional tagging SNPs (rs8179181, rs2278422, rs8110090, rs4803455 and rs1982072) that capture most of the diversity in TGFB1 were also typed but none showed association with variation in lung function. However, a haplotype composed of the -509 C and codon 10 T alleles along with the C allele of the 3' SNP rs8179181 was highly associated with increased lung function in patients grouped by CFTR genotype. These results demonstrate that TGFB1 is a modifier of CF lung disease and reveal a previously unrecognized beneficial effect of TGFB1 variants upon the pulmonary phenotype.

  17. Structural map of Kaposi sarcoma-associated herpesvirus RNA provides clues to molecular interactions | Center for Cancer Research

    Science.gov (United States)

    Scientists from CCR have generated a comprehensive structural map of Kaposi sarcoma-associated herpesvirus polyadenylated nuclear (PAN) RNA, a long non-coding RNA that helps the virus evade detection by its host’s immune system. The findings open new oppportunites to study the life cycle of this cancer-causing virus.  Learn more...

  18. Functional Characteristics of Tumor Associated Protein Spot14 and Interacting Proteins in Mouse Mammary Epithelial and Breast Cancer Cell Lines

    Science.gov (United States)

    2012-03-01

    a rat model of postmenopausal obesity and is associated with tumor glucose metabolism.” Gordon Research Conference on Mammary Gland Biology, 2011...expression profiling of multiple leiomyomata uteri and matched normal tissue from a single patient. 2009 Fertility and Sterility, Vol. 91, No. 6

  19. A Comparison of Reinforcement Sensitivity Theory Measures: Unique Associations With Social Interaction Anxiety and Social Observation Anxiety.

    Science.gov (United States)

    Kramer, Sam L; Rodriguez, Benjamin F

    2016-06-24

    Evidence suggests that the behavior inhibition system (BIS) and fight-flight-freeze system play a role in the individual differences seen in social anxiety disorder; however, findings concerning the role of the behavior approach system (BAS) have been mixed. To date, the role of revised reinforcement sensitivity theory (RST) subsystems underlying social anxiety has been measured with scales designed for the original RST. This study examined how the BIS, BAS, and fight, flight, freeze components of the fight-flight-freeze system uniquely relate to social interaction anxiety and social observation anxiety using both a measure specifically designed for the revised RST and a commonly used original RST measure. Comparison of regression analyses with the Jackson-5 and the commonly used BIS/BAS Scales revealed important differences in the relationships between RST subsystems and social anxiety depending on how RST was assessed. Limitations and future directions for revised RST measurement are discussed. © The Author(s) 2016.

  20. Guiding transcranial brain stimulation by EEG/MEG to interact with ongoing brain activity and associated functions

    DEFF Research Database (Denmark)

    Thut, Gregor; Bergmann, Til Ole; Fröhlich, Flavio

    2017-01-01

    Non-invasive transcranial brain stimulation (NTBS) techniques have a wide range of applications but also suffer from a number of limitations mainly related to poor specificity of intervention and variable effect size. These limitations motivated recent efforts to focus on the temporal dimension...... of NTBS with respect to the ongoing brain activity. Temporal patterns of ongoing neuronal activity, in particular brain oscillations and their fluctuations, can be traced with electro- or magnetoencephalography (EEG/MEG), to guide the timing as well as the stimulation settings of NTBS. These novel, online...... and offline EEG/MEG-guided NTBS-approaches are tailored to specifically interact with the underlying brain activity. Online EEG/MEG has been used to guide the timing of NTBS (i.e., when to stimulate): by taking into account instantaneous phase or power of oscillatory brain activity, NTBS can be aligned...

  1. Concurrence of Danish dementia and cataract: insights from the interactions of dementia associated peptides with eye lens alpha-crystallin.

    Science.gov (United States)

    Surolia, Ira; Sinha, Sharmistha; Sarkar, Debi Prasad; Reddy, P Yadagiri; Reddy, G Bhanuprakash; Surolia, Avadhesha

    2008-08-13

    Familial Danish Dementia (FDD) is an autosomal disease, which is distinguished by gradual loss of vision, deafness, progressive ataxia and dementia. Cataract is the first manifestation of the disease. In this article, we demonstrate a specific correlation between the poisoning of the chaperone activity of the rat eye lens alpha-crystallins, loss of lens transparency in organ culture by the pathogenic form of the Danish dementia peptide, i.e. the reduced Danish dementia peptide (redADan peptide), by a combination of ex vivo, in vitro, biophysical and biochemical techniques. The interaction of redADan peptide and lens crystallins are very specific when compared with another chaperone, HSP-70, underscoring the specificity of the pathogenic form of Danish dementia peptide, redADan, for the early onset of cataract in this disease.

  2. Concurrence of Danish dementia and cataract: insights from the interactions of dementia associated peptides with eye lens alpha-crystallin.

    Directory of Open Access Journals (Sweden)

    Ira Surolia

    Full Text Available Familial Danish Dementia (FDD is an autosomal disease, which is distinguished by gradual loss of vision, deafness, progressive ataxia and dementia. Cataract is the first manifestation of the disease. In this article, we demonstrate a specific correlation between the poisoning of the chaperone activity of the rat eye lens alpha-crystallins, loss of lens transparency in organ culture by the pathogenic form of the Danish dementia peptide, i.e. the reduced Danish dementia peptide (redADan peptide, by a combination of ex vivo, in vitro, biophysical and biochemical techniques. The interaction of redADan peptide and lens crystallins are very specific when compared with another chaperone, HSP-70, underscoring the specificity of the pathogenic form of Danish dementia peptide, redADan, for the early onset of cataract in this disease.

  3. Ecological responses to UV radiation: interactions between the biological effects of UV on plants and on associated organisms.

    Science.gov (United States)

    Paul, Nigel D; Moore, Jason P; McPherson, Martin; Lambourne, Cathryn; Croft, Patricia; Heaton, Joanna C; Wargent, Jason J

    2012-08-01

    Solar ultraviolet (UV)-B radiation (280-315 nm) has a wide range of effects on terrestrial ecosystems, yet our understanding of how UV-B influences the complex interactions of plants with pest, pathogen and related microorganisms remains limited. Here, we report the results of a series of experiments in Lactuca sativa which aimed to characterize not only key plant responses to UV radiation in a field environment but also consequential effects for plant interactions with a sap-feeding insect, two model plant pathogens and phylloplane microorganism populations. Three spectrally modifying filters with contrasting UV transmissions were used to filter ambient sunlight, and when compared with our UV-inclusive filter, L. sativa plants grown in a zero UV-B environment showed significantly increased shoot fresh weight, reduced foliar pigment concentrations and suppressed population growth of green peach aphid (Myzus persicae). Plants grown under a filter which allowed partial transmission of UV-A radiation and negligible UV-B transmission showed increased density of leaf surface phylloplane microbes compared with the UV-inclusive treatment. Effects of UV treatment on the severity of two plant pathogens, Bremia lactucae and Botrytis cinerea, were complex as both the UV-inclusive and zero UV-B filters reduced the severity of pathogen persistence. These results are discussed with reference to known spectral responses of plants, insects and microorganisms, and contrasted with established fundamental responses of plants and other organisms to solar UV radiation, with particular emphasis on the need for future integration between different experimental approaches when investigating the effects of solar UV radiation. Copyright © Physiologia Plantarum 2011.

  4. Interaction of Cefpiramide sodium with bovine hemoglobin and effect of the coexistent metal ion on the protein-drug association

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Xiaona; Liu, Baosheng, E-mail: lbs@hbu.edu.cn; Chong, Baohong; Cao, Shina

    2013-10-15

    The interaction between bovine hemoglobin (BHb) and cefpiramide sodium (CPMS) was investigated at different temperatures by fluorescence, UV absorption, and CD spectroscopy, as well as the effect of common metal ions (Mg{sup 2+}, Zn{sup 2+}, Cu{sup 2+}, Co{sup 2+}, Fe{sup 3+}, Ni{sup 2+}) on the BHb–CPMS system. Results showed that CPMS could quench the intrinsic fluorescence of BHb strongly, and the quenching mechanism was a static quenching process. The electrostatic force played an important role on the conjugation reaction between BHb and CPMS. The order of magnitude of binding constants (K{sub a}) was 10{sup 4}, the number of binding site (n) in the binary system was approximately equal to 1 and the binding distance (r) was about 3.08 nm. Besides, the values of Hill's coefficients were approximately equal to 1, which indicated there was almost no cooperativity in CPMS's binding with BHb. Synchronous spectra and CD spectra revealed that the microenvironment and the conformation of BHb were changed during the binding reaction. Studies on the interaction between BHb and drug will facilitate interpretation of the drug's metabolism and transporting process in the blood, and will help to explain the relationship between structures and functions of BHb. -- Highlights: • CPMS could quench the intrinsic fluorescence of BHb strongly through a static quenching process. • Electrostatic force played an important role on the conjugation reaction between BHb and CPMS. • The microenvironment and conformation of BHb were changed during the binding reaction.

  5. Work stress, worries, and pain interact synergistically with modelled traffic noise on cross-sectional associations with self-reported sleep problems.

    Science.gov (United States)

    Kristiansen, Jesper; Persson, Roger; Björk, Jonas; Albin, Maria; Jakobsson, Kristina; Ostergren, Per-Olof; Ardö, Jonas

    2011-02-01

    To examine the risk of sleep problems associated with work stress (job strain, job demands, and decision authority), worries and pain and to investigate the synergistic interaction between these factors and traffic noise. Sleep problems and predictor variables were assessed in a cross-sectional public health survey with 12,093 respondents. Traffic noise levels were assessed using modelled A-weighted energy equivalent traffic sound levels at the residence. The risk of sleep problems was modelled using multiple logistic regression analysis. With regard to sleep problems not attributed to any external source (general sleep problems), independent main effects were found for traffic noise (women), decision authority (women), job strain, job demands, suffering from pain or other afflictions, worries about losing the job, experiencing bullying at work, having troubles paying the bills, and having a sick, disabled, or old relative to take care of (women). Significant synergistic effects were found for traffic noise and experiencing bullying at work in women. With regard to sleep problems attributed to traffic noise, strong synergistic interactions were found between traffic noise and, respectively, job demands (men), having pain or other afflictions, taking care of a sick, old, or disabled relative, and having troubles paying the bills. Main effects were found for worries about losing the job, experiencing bullying at work, job strain (men), and decision authority (men). Synergistic interactions could potentially contribute with 10-20% of the sleep problems attributed to traffic noise in the population. Work stress, pain, and different worries were independently associated with general sleep problems and showed in general no synergistic interaction with traffic noise. In contrast, synergistic effects between traffic noise and psychological factors were found with regard to sleep problems attributed to traffic noise. The synergy may contribute significantly to sleep

  6. Interaction between oxytocin receptor DNA methylation and genotype is associated with risk of postpartum depression in women without depression in pregnancy

    Directory of Open Access Journals (Sweden)

    Aleeca F. Bell

    2015-07-01

    Full Text Available Postpartum depression (PPD affects up to 19% of women, negatively impacting maternal and infant health. Reductions in plasma oxytocin levels have been associated with PPD and heritability studies have established a genetic contribution. Epigenetic regulation of the oxytocin receptor gene (OXTR has been demonstrated and we hypothesized that individual epigenetic variability at OXTR may impact the development of PPD and that such variability may be central to predicting risk. This case-control study is nested within the Avon Longitudinal Study of Parents and Children and included 269 cases with PPD and 276 controls matched on age group, parity, and presence or absence of depressive symptoms in pregnancy as assessed by the Edinburgh Postnatal Depression Scale. OXTR DNA methylation (CpG site -934 and genotype (rs53576 and rs2254298 were assayed from DNA extracted from blood collected during pregnancy. Conditional logistic regression was used to estimate odds ratios (OR and 95% confidence intervals (CI for the association of elevated symptoms of PPD with genotype, methylation, and their interaction adjusted for psychosocial factors (n=500. There was evidence of an interaction between rs53576 and methylation in the OXTR gene amongst women who did not have depression prenatally but developed PPD (p interaction=0.026, adjusted for covariates, n=257. Those women with GG genotype showed 2.63 greater odds of PPD for every 10% increase in methylation level (95% CI: 1.37, 5.03, whereas methylation was unrelated to PPD amongst A carriers (OR=1.00, 95%CI: 0.58, 1.73. There was no such interaction among women with PPD and prenatal depression. These data indicate that epigenetic variation that decreases expression of OXTR in a susceptible genotype may play a contributory role in the etiology of postpartum depression.

  7. Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1.

    Science.gov (United States)

    Garapaty, Shivani; Mahajan, Muktar A; Samuels, Herbert H

    2008-03-14

    CCR4-NOT is an evolutionarily conserved, multicomponent complex known to be involved in transcription as well as mRNA degradation. Various subunits (e.g. CNOT1 and CNOT7/CAF1) have been reported to be involved in influencing nuclear hormone receptor activities. Here, we show that CCR4/CNOT6 and RCD1/CNOT9, members of the CCR4-NOT complex, potentiate nuclear receptor activity. RCD1 interacts in vivo and in vitro with NIF-1 (NRC-interacting factor), a previously characterized nuclear receptor cotransducer that activates nuclear receptors via its interaction with NRC. As with NIF-1, RCD1 and CCR4 do not directly associate with nuclear receptors; however, they enhance ligand-dependent transcriptional activation by nuclear hormone receptors. CCR4 mediates its effect through the ligand binding domain of nuclear receptors and small interference RNA-mediated silencing of endogenous CCR4 results in a marked decrease in nuclear receptor activation. Furthermore, knockdown of CCR4 results in an attenuated stimulation of RARalpha target genes (e.g. Sox9 and HoxA1) as shown by quantitative PCR assays. The silencing of endogenous NIF-1 also resulted in a comparable decrease in the RAR-mediated induction of both Sox9 and HoxA1. Furthermore, CCR4 associates in vivo with NIF-1. In addition, the CCR4-enhanced transcriptional activation by nuclear receptors is dependent on NIF-1. The small interference RNA-mediated knockdown of NIF-1 blocks the ligand-dependent potentiating effect of CCR4. Our results suggest that CCR4 plays a role in the regulation of certain endogenous RARalpha target genes and that RCD1 and CCR4 might mediate their function through their interaction with NIF-1.

  8. Interaction Pattern of Arg 62 in the A-Pocket of Differentially Disease-Associated HLA-B27 Subtypes Suggests Distinct TCR Binding Modes

    Science.gov (United States)

    Cauli, Alberto; Mathieu, Alessandro; Tedeschi, Valentina; Caristi, Silvana; Sorrentino, Rosa; Böckmann, Rainer A.; Fiorillo, Maria Teresa

    2012-01-01

    The single amino acid replacement Asp116His distinguishes the two subtypes HLA-B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason for this differential association is so far poorly understood and might be related to subtype-specific HLA:peptide conformations as well as to subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine functional experiments with extensive molecular dynamics simulations to investigate the molecular dynamics and function of the conserved Arg62 of the α1-helix for both B27 subtypes in complex with the self-peptides pVIPR (RRKWRRWHL) and TIS (RRLPIFSRL), and the viral peptides pLMP2 (RRRWRRLTV) and NPflu (SRYWAIRTR). Simulations of HLA:peptide systems suggest that peptide-stabilizing interactions of the Arg62 residue observed in crystal structures are metastable for both B27 subtypes under physiological conditions, rendering this arginine solvent-exposed and, probably, a key residue for TCR interaction more than peptide-binding. This view is supported by functional experiments with conservative (R62K) and non-conservative (R62A) B*2705 and B*2709 mutants that showed an overall reduction in their capability to present peptides to CD8+ T cells. Moreover, major subtype-dependent differences in the peptide recognition suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype. PMID:22403718

  9. Effects of circadian clock genes and health-related behavior on metabolic syndrome in a Taiwanese population: Evidence from association and interaction analysis.

    Directory of Open Access Journals (Sweden)

    Eugene Lin

    Full Text Available Increased risk of developing metabolic syndrome (MetS has been associated with the circadian clock genes. In this study, we assessed whether 29 circadian clock-related genes (including ADCYAP1, ARNTL, ARNTL2, BHLHE40, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, GSK3B, HCRTR2, KLF10, NFIL3, NPAS2, NR1D1, NR1D2, PER1, PER2, PER3, REV1, RORA, RORB, RORC, SENP3, SERPINE1, TIMELESS, TIPIN, VIP, and VIPR2 are associated with MetS and its individual components independently and/or through complex interactions in a Taiwanese population. We also analyzed the interactions between environmental factors and these genes in influencing MetS and its individual components. A total of 3,000 Taiwanese subjects from the Taiwan Biobank were assessed in this study. Metabolic traits such as waist circumference, triglyceride, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and fasting glucose were measured. Our data showed a nominal association of MetS with several single nucleotide polymorphisms (SNPs in five key circadian clock genes including ARNTL, GSK3B, PER3, RORA, and RORB; but none of these SNPs persisted significantly after performing Bonferroni correction. Moreover, we identified the effect of GSK3B rs2199503 on high fasting glucose (P = 0.0002. Additionally, we found interactions among the ARNTL rs10832020, GSK3B rs2199503, PER3 rs10746473, RORA rs8034880, and RORB rs972902 SNPs influenced MetS (P < 0.001 ~ P = 0.002. Finally, we investigated the influence of interactions between ARNTL rs10832020, GSK3B rs2199503, PER3 rs10746473, and RORB rs972902 with environmental factors such as alcohol consumption, smoking status, and physical activity on MetS and its individual components (P < 0.001 ~ P = 0.002. Our study indicates that circadian clock genes such as ARNTL, GSK3B, PER3, RORA, and RORB genes may contribute to the risk of MetS independently as well as through gene-gene and gene-environment interactions.

  10. 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

  11. Association between the Interaction of Key Genes Involved in Effector T-Cell Pathways and Susceptibility to Develop allergic Rhinitis: A Population-Based Case-Control Association Study.

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    Full Text Available Evidence suggests that interaction between key genes mediating signaling and transcriptional networks involving effector T-cell responses may influence an individual's susceptibility to develop allergic rhinitis(AR.The aim of this study was todetermine whether specific interactions between key genes involved in effector T-cell pathways are associated with an individual's susceptibility to develop AR in Han Chinese subjects.A cohort of 489 patients with AR and 421 healthy controls was enrolled from the Han Chinese population in Beijing, China. AR was established by questionnaire and clinical examination, and peripheral blood was drawn from all subjects for DNA extraction. A total of 96 single nucleotide polymorphisms (SNPs in 26 reprehensive candidate genes involved in T helper 1 (Th1, Th2, Th17, Th9 and T regulatory cell pathways were selected from the International Haplotype Mappingdatabase for Han Chinese in Beijing (CHB population, and IlluminaGoldenGate assay was conducted for SNP genotyping. The PLINK software package was used to perform statistical analyses.Simple SNP-phenotype association analysis using logistic regression showed SNP rs8193036 in IL17A gene, rs2569254 in IL-12 and rs1898413 in RORα weresignificantlyassociatedwith AR.Simple SNP-phenotype association analysis with genetic models demonstrated thatrs2569254 in IL-12, rs1031508 in STAT4, and rs3741809 in IL-26 were likely to be recessive, rs8193036 in IL17A allelic, rs897200in STAT4 genotypic, and rs1898413 in RORα dominant. Epistasis analyses exhibited that 83 SNPs in 23 genes were significantly interactive; of which 59 interactions/SNP pairs demonstrated OR values higher than 2 or lower than 0.5, and 12 interactions/SNP pairs OR values higher than 4 or lower than 0.25. STAT3, RORα and IL-26, involved in Th17 pathway,were the mostfrequentlyinteractive genes.This study suggests that interactions between several SNPs in key genes involved in effector T-cell pathways are

  12. Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues.

    Science.gov (United States)

    Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

    2014-12-01

    Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj-a gene encoding a transcription factor implicated in Notch signaling-in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE. © 2014 The Authors.

  13. Epithelial–stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues

    Science.gov (United States)

    Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

    2014-01-01

    Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj—a gene encoding a transcription factor implicated in Notch signaling—in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE. Subject Categories Development & Differentiation; Immunology; Signal Transduction PMID:25378482

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

    Science.gov (United States)

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

    2011-05-01

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

  15. Adhesion of Human Probiotic Lactobacillus rhamnosus to Cervical and Vaginal Cells and Interaction with Vaginosis-Associated Pathogens

    Directory of Open Access Journals (Sweden)

    Sophie Coudeyras

    2008-01-01

    Full Text Available Objectives. The ability of a probiotic Lactobacillus rhamnosus strain (Lcr35 to adhere to cervical and vaginal cells and to affect the viability of two main vaginosis-associated pathogens, Prevotella bivia, Gardnerella vaginalis, as well as Candida albicans was investigated. Methods. Adhesion ability was determined in vitro with immortalized epithelial cells from the endocervix, ectocervix, and vagina. Coculture experiments were performed to count viable pathogens cells in the presence of Lcr35. Results. Lcr35 was able to specifically and rapidly adhere to the three cell lines. In coculture assays, a decrease in pathogen cell division rate was observed as from 4 hours of incubation and bactericidal activity after a longer period of incubation, mostly with P. bivia. Conclusion. The ability of Lcr35 to adhere to cervicovaginal cells and its antagonist activities against vaginosis-associated pathogens suggest that this probiotic strain is a promising candidate for use in therapy.

  16. The association of proopiomelanocortin polymorphisms with the risk of major depressive disorder and the response to antidepressants via interactions with stressful life events.

    Science.gov (United States)

    Chang, Hun Soo; Won, Eun Soo; Lee, Hwa-Young; Ham, Byung-Joo; Kim, Yong-Gu; Lee, Min-Soo

    2015-01-01

    Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is among the most consistent neuroendocrine abnormalities in major depressive disorder (MDD). The peptide adrenocorticotropin hormone (ACTH) mediates HPA axis function during stress and is encoded by the proopiomelanocortin (POMC) gene polycistronically. After screening 39 POMC polymorphisms, we evaluated the association of polymorphisms with susceptibility to MDD in 145 MDD patients and 193 normal subjects; in patients, we also evaluated the response to treatment with antidepressants. Additionally, we investigated the role of gene-environment interaction between POMC haplotypes and stressful life events (SLE) in the treatment response. Although genotypes and haplotypes were not significantly associated with the risk of MDD, non-remitters were more likely to carry haplotype 1 (ht1) and to have no ht2 than were remitters (corrected P = 0.010-0.035). Although observations were limited in patients without SLE, a significant haplotype-SLE interaction was observed (P = 0.020). Additionally, at 1, 2, and 8 weeks of treatment, the 21-item Hamilton Depression Rating scores of MDD subjects with POMC ht2 were significantly (P = 0.003-0.044) lower than those of patients with ht1 in subjects those did not experience SLE. MDD subjects possessing POMC ht2 achieved remission significantly (P = 0.013; survival analysis) faster than patients with ht1. This study suggests that POMC haplotypes, via an interaction with SLE, are associated with antidepressant treatment outcomes in MDD patients. Regarding SLE, haplotypes of the POMC gene could be useful markers for predicting the response to antidepressant treatment in MDD patients.

  17. Old age and the associated impairment of bones' adaptation to loading are associated with transcriptomic changes in cellular metabolism, cell-matrix interactions and the cell cycle.

    Science.gov (United States)

    Galea, Gabriel L; Meakin, Lee B; Harris, Marie A; Delisser, Peter J; Lanyon, Lance E; Harris, Stephen E; Price, Joanna S

    2017-01-30

    In old animals, bone's ability to adapt its mass and architecture to functional load-bearing requirements is diminished, resulting in bone loss characteristic of osteoporosis. Here we investigate transcriptomic changes associated with this impaired adaptive response. Young adult (19-week-old) and aged (19-month-old) female mice were subjected to unilateral axial tibial loading and their cortical shells harvested for microarray analysis between 1h and 24h following loading (36 mice per age group, 6 mice per loading group at 6 time points). In non-loaded aged bones, down-regulated genes are enriched for MAPK, Wnt and cell cycle components, including E2F1. E2F1 is the transcription factor most closely associated with genes down-regulated by ageing and is down-regulated at the protein level in osteocytes. Genes up-regulated in aged bone are enriched for carbohydrate metabolism, TNFα and TGFβ superfamily components. Loading stimulates rapid and sustained transcriptional responses in both age groups. However, genes related to proliferation are predominantly up-regulated in the young and down-regulated in the aged following loading, whereas those implicated in bioenergetics are down-regulated in the young and up-regulated in the aged. Networks of inter-related transcription factors regulated by E2F1 are loading-responsive in both age groups. Loading regulates genes involved in similar signalling cascades in both age groups, but these responses are more sustained in the young than aged. From this we conclude that cells in aged bone retain the capability to sense and transduce loading-related stimuli, but their ability to translate acute responses into functionally relevant outcomes is diminished. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Gaze-Following and Reaction to an Aversive Social Interaction Have Corresponding Associations with Variation in the OXTR Gene in Dogs but Not in Human Infants.

    Science.gov (United States)

    Oláh, Katalin; Topál, József; Kovács, Krisztina; Kis, Anna; Koller, Dóra; Young Park, Soon; Virányi, Zsófia

    2017-01-01

    It has been suggested that dogs' remarkable capacity to use human communicative signals lies in their comparable social cognitive skills; however, this view has been questioned recently. The present study investigated associations between oxytocin receptor gene (OXTR) polymorphisms and social behavior in human infants and dogs with the aim to unravel potentially differential mechanisms behind their responsiveness to human gaze. Sixteen-month-old human infants ( N = 99) and adult Border Collie dogs ( N = 71) participated in two tasks designed to test (1) their use of gaze-direction as a cue to locate a hidden object, and (2) their reactions to an aversive social interaction (using the still face task for children and a threatening approach task for dogs). Moreover, we obtained DNA samples to analyze associations between single nucleotide polymorphisms (SNP) in the OXTR (dogs: -213AG, -94TC, -74CG, rs8679682, children: rs53576, rs1042778, rs2254298) and behavior. We found that OXTR genotype was significantly associated with reactions to an aversive social interaction both in dogs and children, confirming the anxiolytic effect of oxytocin in both species. In dogs, the genotypes linked to less fearful behavior were associated also with a higher willingness to follow gaze whereas in children, OXTR gene polymorphisms did not affect gaze following success. This pattern of gene-behavior associations suggests that for dogs the two situations are more alike (potentially fear-inducing or competitive) than for human children. This raises the possibility that, in contrast to former studies proposing human-like cooperativeness in dogs, dogs may perceive human gaze in an object-choice task in a more antagonistic manner than children.

  19. Gaze-Following and Reaction to an Aversive Social Interaction Have Corresponding Associations with Variation in the OXTR Gene in Dogs but Not in Human Infants

    Directory of Open Access Journals (Sweden)

    Katalin Oláh

    2017-12-01

    Full Text Available It has been suggested that dogs' remarkable capacity to use human communicative signals lies in their comparable social cognitive skills; however, this view has been questioned recently. The present study investigated associations between oxytocin receptor gene (OXTR polymorphisms and social behavior in human infants and dogs with the aim to unravel potentially differential mechanisms behind their responsiveness to human gaze. Sixteen-month-old human infants (N = 99 and adult Border Collie dogs (N = 71 participated in two tasks designed to test (1 their use of gaze-direction as a cue to locate a hidden object, and (2 their reactions to an aversive social interaction (using the still face task for children and a threatening approach task for dogs. Moreover, we obtained DNA samples to analyze associations between single nucleotide polymorphisms (SNP in the OXTR (dogs: −213AG, −94TC, −74CG, rs8679682, children: rs53576, rs1042778, rs2254298 and behavior. We found that OXTR genotype was significantly associated with reactions to an aversive social interaction both in dogs and children, confirming the anxiolytic effect of oxytocin in both species. In dogs, the genotypes linked to less fearful behavior were associated also with a higher willingness to follow gaze whereas in children, OXTR gene polymorphisms did not affect gaze following success. This pattern of gene-behavior associations suggests that for dogs the two situations are more alike (potentially fear-inducing or competitive than for human children. This raises the possibility that, in contrast to former studies proposing human-like cooperativeness in dogs, dogs may perceive human gaze in an object-choice task in a more antagonistic manner than children.

  20. Interaction between PLA2R1 and HLA-DQA1 variants associates with anti-PLA2R antibodies and membranous nephropathy.

    Science.gov (United States)

    Lv, Jicheng; Hou, Wanyin; Zhou, Xujie; Liu, Gang; Zhou, Fude; Zhao, Na; Hou, Ping; Zhao, Minghui; Zhang, Hong

    2013-07-01

    Risk alleles at genome loci containing phospholipase A2 receptor 1 (PLA2R1) and HLA-DQA1 closely associate with idiopathic membranous nephropathy (IMN) in the European population, but it is unknown whether a similar association exists in the Chinese population and whether high-risk alleles promote the development of anti-PLA2R antibodies. Here, we genotyped 2132 Chinese individuals, including 1112 patients with IMN and 1020 healthy controls, for three single nucleotide polymorphisms (SNPs) within PLA2R1 and three SNPs within HLA genes. We also selected 71 patients, with varying genotypes, to assess for circulating anti-PLA2R antibody and for PLA2R expression in glomeruli. Three SNPs within PLA2R1 and one SNP within HLA-DQA1 strongly associated with IMN, and we noted gene-gene interactions involving these SNPs. Furthermore, these risk alleles strongly associated with the presence of anti-PLA2R antibodies and glomerular PLA2R expression. Among individuals who carried risk alleles for both genes, 73% had anti-PLA2R antibodies and 75% expressed PLA2R in glomeruli. In contrast, among individuals who carried protective genotypes of both genes, none had anti-PLA2R antibodies and glomerular expression of PLA2R was weak or absent. In conclusion, the interaction between PLA2R1 and HLA-DQA1 risk alleles associates with the development of IMN in the Chinese population. Individuals carrying risk alleles are predisposed to the generation of circulating anti-PLA2R autoantibodies, which may contribute to the development of IMN.

  1. Identification of host-microbe interaction factors in the genomes of soft rot-associated pathogens Dickeya dadantii 3937 and Pectobacterium carotovorum WPP14 with supervised machine learning.

    Science.gov (United States)

    Ma, Bing; Charkowski, Amy O; Glasner, Jeremy D; Perna, Nicole T

    2014-06-21

    A wealth of genome sequences has provided thousands of genes of unknown function, but identification of functions for the large numbers of hypothetical genes in phytopathogens remains a challenge that impacts all research on plant-microbe interactions. Decades of research on the molecular basis of pathogenesis focused on a limited number of factors associated with long-known host-microbe interaction systems, providing limited direction into this challenge. Computational approaches to identify virulence genes often rely on two strategies: searching for sequence similarity to known host-microbe interaction factors from other organisms, and identifying islands of genes that discriminate between pathogens of one type and closely related non-pathogens or pathogens of a different type. The former is limited to known genes, excluding vast collections of genes of unknown function found in every genome. The latter lacks specificity, since many genes in genomic islands have little to do with host-interaction. In this study, we developed a supervised machine learning approach that was designed to recognize patterns from large and disparate data types, in order to identify candidate host-microbe interaction factors. The soft rot Enterobacteriaceae strains Dickeya dadantii 3937 and Pectobacterium carotovorum WPP14 were used for development of this tool, because these pathogens are important on multiple high value crops in agriculture worldwide and more genomic and functional data is available for the Enterobacteriaceae than any other microbial family. Our approach achieved greater than 90% precision and a recall rate over 80% in 10-fold cross validation tests. Application of the learning scheme to the complete genome of these two organisms generated a list of roughly 200 candidates, many of which were previously not implicated in plant-microbe interaction and many of which are of completely unknown function. These lists provide new targets for experimental validation and

  2. Interaction between Smoking and HLA-DRB1*04 Gene Is Associated with a High Cardiovascular Risk in Brazilian Amazon Patients with Rheumatoid Arthritis

    Science.gov (United States)

    Boechat, Narjara de Oliveira; Ogusku, Mauricio Morish; Boechat, Antonio Luiz; Sadahiro, Aya

    2012-01-01

    Background Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints that affects approximately 1% of the population worldwide. The HLA-DRB1 gene locus plays a major role in genetic susceptibility to RA, a condition that has been associated with a high cardiovascular morbidity and mortality in many studies. Methodology/Principal Findings The aim of this work was to investigate which types of HLA class II genes are associated with RA in patients from the Brazilian Amazon and their influence on high cardiovascular risk status in this population. For this purpose, a case-control study was carried out with a total of 350 non-Indian individuals made up of a cohort of 132 consecutive RA sufferers and 218 healthy controls. A χ2 test showed that HLADRB1*04 (p<0.0016; OR = 1.89; 95% CI = 1.29–2.79) and HLADRB1*10 (p = 0.0377; OR = 3.81; 95% CI = 1.16–12.50) are the major HLA genes associated with susceptibility to RA. A logistic regression model also showed that the interaction between HLADRB1*04 (p = 0.027; OR = 6.02; 95% CI = 1.21–29.7), age (p = 0.0001; OR = 1.26; 95% CI = 1.13–1.39) and smoking (p = 0.0001; OR = 23.6; 95% CI = 4.25–32.1) is associated with a probability of a high cardiovascular risk status at an early age. Conclusions/Significance The results of this study show for the first time that HLA class II type is associated with RA in Brazilian Amazon populations and that a specific interaction between the HLA-DRB1*04 gene and smoking is associated with a high cardiovascular risk status, as initially reported in the European population. This study therefore contributes to an understanding of gene-environment interactions in RA patients. PMID:22912672

  3. Interaction between Cucumber mosaic virus 2b protein and plant catalase induces a specific necrosis in association with proteasome activity.

    Science.gov (United States)

    Murota, Katsunori; Shimura, Hanako; Takeshita, Minoru; Masuta, Chikara

    2017-01-01

    Cucumber mosaic virus (CMV) can induce a specific necrosis on Arabidopsis through the interaction between the CMV 2b protein and host catalase, in which the ubiquitin-proteasome pathway may be involved. We previously reported that the CMV 2b protein, the viral RNA silencing suppressor, interacted with the H 2 O 2 scavenger catalase (CAT3), leading to necrosis on CMV-inoculated Arabidopsis leaves. We here confirmed that CMV could more abundantly accumulate in the CAT3-knockout mutant (cat3), and that CAT3 makes host plants a little more tolerant to CMV. We also found that the necrosis severity is not simply explained by a high level of H 2 O 2 given by the lack of CAT3, because the recombinant CMV, CMV-N, induced much milder necrosis in cat3 than in the wild type, suggesting some specific mechanism for the necrosis induction. To further characterize the 2b-inducing necrosis in relation to its binding to CAT3, we conducted the agroinfiltration experiments to overexpress CAT3 and 2b in N. benthamiana leaves. The accumulation levels of CAT3 were higher when co-expressed with the CMV-N 2b (N2b) than with CMV-Y 2b (Y2b). We infer that N2b made a more stable complex with CAT3 than Y2b did, and the longevity of the 2b-CAT3 complex seemed to be important to induce necrosis. By immunoprecipitation (IP) with an anti-ubiquitin antibody followed by the detection with anti-CAT3 antibodies, we detected a higher molecular-weight smear and several breakdown products of CAT3 among the IP-proteins. In addition, the proteasome inhibitor MG132 treatment could actually increase the accumulation levels of CAT3. This study suggests that the host proteasome pathway is, at least partially, responsible for the degradation of CAT3, which is manifested in CMV-infected tissues.

  4. Association of GRIN1 and GRIN2A-D With schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk

    DEFF Research Database (Denmark)

    Demontis, Ditte; Nyegaard, Mette; Buttenschøn, Henriette Nørmølle

    2011-01-01

    in the offspring interacted with maternal herpes simplex virus-2 (HSV-2) seropositivity during pregnancy influencing the risk of schizophrenia later in life. Individuals from three independently collected Danish case control samples were genotyped for 81 tagSNPs (in total 984 individuals diagnosed...... with schizophrenia and 1,500 control persons) and antibodies against maternal HSV-2 infection were measured in one of the samples (365 cases and 365 controls). Nine SNPs out of 30 in GRIN2B were significantly associated with schizophrenia. One SNP remained significant after Bonferroni correction (rs1806194, P...

  5. NCAM-associated polysialic acid on ciliary ganglion neurons is regulated by polysialytransferase levels and interaction with muscle.

    Science.gov (United States)

    Brusés, J L; Oka, S; Rutishauser, U

    1995-12-01

    NCAM in its high polysialic acid (PSA) form is expressed on chick hindlimb motoneurons during their growth, and then decreases at about the time that synaptogenesis is completed. In order to characterize this regulation at the cell and molecular level, the present studies use the chick ciliary ganglion (CG) system, which constitutes a homogeneous and developmentally synchronized population of motoneurons that can be used for in vitro studies. Levels of PSA in the CG were evaluated both by SDS-PAGE immunoblot analysis of total NCAM and by pulse radiolabeling of newly synthesized NCAM. Up- and downregulation of PSA expression on newly synthesized NCAM in the CG was found to be closely correlated with in vivo innervation and synaptogenesis, respectively. Moreover, the downregulation observed at synaptogenesis was prevented by in vivo blockade of neuromuscular activity with alpha-bungarotoxin. The developmental regulation of PSA expression was found to coincide precisely with an increase and decrease in levels of specific polysialyltransferase activity. By contrast, the expression of the VASE exon in NCAM, which in CNS is temporally correlated with PSA downregulation, was not expressed in the CG. Cocultures of CG neurons with myotubes were used to provide direct evidence that neuron-muscle interaction can cause a specific downregulation of both neuronal PSA and polysialyltransferase activity.

  6. Characterization of the CLASP2 Protein Interaction Network Identifies SOGA1 as a Microtubule-Associated Protein

    DEFF Research Database (Denmark)

    Sørensen, Rikke Kruse; Krantz, James; Barker, Natalie

    2017-01-01

    and built a CLASP2 protein network in 3T3-L1 adipocytes. Using two different commercially available antibodies for CLASP2 and an antibody for epitope-tagged, overexpressed CLASP2, we performed multiple affinity purification coupled with mass spectrometry (AP-MS) experiments in combination with label-free......, glycogen synthase, and glycogenin. Investigating the SOGA1 interactome confirmed SOGA1 can reciprocal co-IP both CLASP2 and MARK2 as well as glycogen synthase and glycogenin. SOGA1 was confirmed to colocalize with CLASP2 and also with tubulin, which identifies SOGA1 as a new microtubule-associated protein...

  7. Imaging mass spectrometry and MS/MS molecular networking reveals chemical interactions among cuticular bacteria and pathogenic fungi associated with fungus-growing ants.

    Science.gov (United States)

    Boya P, Cristopher A; Fernández-Marín, Hermógenes; Mejía, Luis C; Spadafora, Carmenza; Dorrestein, Pieter C; Gutiérrez, Marcelino

    2017-07-17

    The fungus-growing ant-microbe symbiosis is an ideal system to study chemistry-based microbial interactions due to the wealth of microbial interactions described, and the lack of information on the molecules involved therein. In this study, we employed a combination of MALDI imaging mass spectrometry (MALDI-IMS) and MS/MS molecular networking to study chemistry-based microbial interactions in this system. MALDI IMS was used to visualize the distribution of antimicrobials at the inhibition zone between bacteria associated to the ant Acromyrmex echinatior and the fungal pathogen Escovopsis sp. MS/MS molecular networking was used for the dereplication of compounds found at the inhibition zones. We identified the antibiotics actinomycins D, X2 and X 0β , produced by the bacterium Streptomyces CBR38; and the macrolides elaiophylin, efomycin A and efomycin G, produced by the bacterium Streptomyces CBR53.These metabolites were found at the inhibition zones using MALDI IMS and were identified using MS/MS molecular networking. Additionally, three shearinines D, F, and J produced by the fungal pathogen Escovopsis TZ49 were detected. This is the first report of elaiophylins, actinomycin X 0β and shearinines in the fungus-growing ant symbiotic system. These results suggest a secondary prophylactic use of these antibiotics by A. echinatior because of their permanent production by the bacteria.

  8. Interactive effects of ATOH7 and RFTN1 in association with juvenile primary open-angle glaucoma

    Directory of Open Access Journals (Sweden)

    De-Gui Wang

    2017-03-01

    Full Text Available AIM:To study ATOH7 and RFTN1 sequence variations in patients with juvenile primary open-angle glaucoma(JOAG. METHODS: In 298 controls(age≥60yand 52 JOAG(ageATOH7 was sequenced by direct sequencing. Additional single nucleotide polymorphisms the RFTN1 SNP(rs690037and at upstream ATOH7(rs1900004 and rs3858145were genotyped by Taqman assay. RESULTS: No any coding mutation was detected in JOAG. There were no significance in allele frequencies and haplotypes between JOAG and control group of rs7916697, rs61854782, rs1900004、rs3858145 and rs690037, so no SNP was associated with JOAG(P>0.05. CONCLUSION: Although preliminary study has showed combination of ATOH7 and RFTN1 SNPs could increase the risk of getting adult-onset primary open angle glaucoma, ATOH7 and RFTN1 are not associated with juvenile primary open-angle glaucoma in this study, so different types of open-angle glaucoma may be differences in genetic mechanism and be worthy of further study.

  9. HLA class II SNP interactions and the association with type 1 diabetes mellitus in Bengali speaking patients of Eastern India

    Science.gov (United States)

    2013-01-01

    Background Several studies have demonstrated a fundamental role for the HLA in the susceptibility of, or protection to, type 1 diabetes mellitus (T1DM). However, this has not been adequately studied in Asian Indian populations. To assess the frequency of HLA class II (DPA1, DPB1, DQA1, DQB1 and DRB1) associated to susceptibility or protection toT1DM in a Bengali population of India with diabetes. Results Single nucleotide polymorphism study. The HLA genotyping was performed by a polymerase chain reaction followed by their HLA-DP, DQ, and DRB1 genotypes and haplotypes by sequencing method. The results are studied by Plink software. The χ2 tests were used for the inferential statistics. To our knowledge, this study is the first of a kind which has attempted to check the HLA association with T1DM by SNPs analysis. The study recruited 151 patients with T1DM and same number of ethno-linguistic, sex matched non-diabetic controls. The present study found a significant SNP rs7990 of HLA-DQA1 (p = 0.009) negative correlation, again indicating that risk from HLA is considerably more with T1DM. Conclusions This study demonstrates that the HLA class-II alleles play a major role in genetic basis of T1DM. PMID:23441825

  10. Interaction of C1q and mannan-binding lectin (MBL) with C1r, C1s, MBL-associated serine proteases 1 and 2, and the MBL-associated protein MAp19

    DEFF Research Database (Denmark)

    Thiel, S; Petersen, Steen Vang; Vorup-Jensen, T

    2000-01-01

    Mannan-binding lectin (MBL) and C1q activate the complement cascade via attached serine proteases. The proteases C1r and C1s were initially discovered in a complex with C1q, whereas the MBL-associated serine proteases 1 and 2 (MASP-1 and -2) were discovered in a complex with MBL. There is controv......Mannan-binding lectin (MBL) and C1q activate the complement cascade via attached serine proteases. The proteases C1r and C1s were initially discovered in a complex with C1q, whereas the MBL-associated serine proteases 1 and 2 (MASP-1 and -2) were discovered in a complex with MBL......, whereas MASP-1, MASP-2, and a third protein, MAp19 (19-kDa MBL-associated protein), were found to be associated only with MBL. The bulk of MASP-1 and MAp19 was found in association with each other and was not bound to MBL or MASP-2. The interactions of MASP-1, MASP-2, and MAp19 with MBL differ from those...... of C1r and C1s with C1q in that both high salt concentrations and calcium chelation (EDTA) are required to fully dissociate the MASPs or MAp19 from MBL. In the presence of calcium, most of the MASP-1, MASP-2, and MAp19 emerged on gel-permeation chromatography as large complexes that were not associated...

  11. Random walks on mutual microRNA-target gene interaction network improve the prediction of disease-associated microRNAs.

    Science.gov (United States)

    Le, Duc-Hau; Verbeke, Lieven; Son, Le Hoang; Chu, Dinh-Toi; Pham, Van-Huy

    2017-11-14

    MicroRNAs (miRNAs) have been shown to play an important role in pathological initiation, progression and maintenance. Because identification in the laboratory of disease-related miRNAs is not straightforward, numerous network-based methods have been developed to predict novel miRNAs in silico. Homogeneous networks (in which every node is a miRNA) based on the targets shared between miRNAs have been widely used to predict their role in disease phenotypes. Although such homogeneous networks can predict potential disease-associated miRNAs, they do not consider the roles of the target genes of the miRNAs. Here, we introduce a novel method based on a heterogeneous network that not only considers miRNAs but also the corresponding target genes in the network model. Instead of constructing homogeneous miRNA networks, we built heterogeneous miRNA networks consisting of both miRNAs and their target genes, using databases of known miRNA-target gene interactions. In addition, as recent studies demonstrated reciprocal regulatory relations between miRNAs and their target genes, we considered these heterogeneous miRNA networks to be undirected, assuming mutual miRNA-target interactions. Next, we introduced a novel method (RWRMTN) operating on these mutual heterogeneous miRNA networks to rank candidate disease-related miRNAs using a random walk with restart (RWR) based algorithm. Using both known disease-associated miRNAs and their target genes as seed nodes, the method can identify additional miRNAs involved in the disease phenotype. Experiments indicated that RWRMTN outperformed two existing state-of-the-art methods: RWRMDA, a network-based method that also uses a RWR on homogeneous (rather than heterogeneous) miRNA networks, and RLSMDA, a machine learning-based method. Interestingly, we could relate this performance gain to the emergence of "disease modules" in the heterogeneous miRNA networks used as input for the algorithm. Moreover, we could demonstrate that RWRMTN is stable

  12. Accumulation of gentisic acid as associated with systemic infections but not with the hypersensitive response in plant-pathogen interactions.

    Science.gov (United States)

    Bellés, José M; Garro, Rafael; Pallás, Vicente; Fayos, Joaquín; Rodrigo, Ismael; Conejero, Vicente

    2006-02-01

    In the present work we have studied the accumulation of gentisic acid (2,5-dihydroxybenzoic acid, a metabolic derivative of salicylic acid, SA) in the plant-pathogen systems, Cucumis sativus and Gynura aurantiaca, infected with either prunus necrotic ringspot virus (PNRSV) or the exocortis viroid (CEVd), respectively. Both pathogens produced systemic infections and accumulated large amounts of the intermediary signal molecule gentisic acid as ascertained by electrospray ionization mass spectrometry (ESI-MS) coupled on line with high performance liquid chromatography (HPLC). The compound was found mostly in a conjugated (beta-glucoside) form. Gentisic acid has also been found to accumulate (although at lower levels) in cucumber inoculated with low doses of Pseudomonas syringae pv. tomato, producing a nonnecrotic reaction. In contrast, when cucumber was inoculated with high doses of this pathogen, a hypersensitive reaction occurred, but no gentisic-acid signal was induced. This is consistent with our results supporting the idea that gentisic-acid signaling may be restricted to nonnecrotizing reactions of the host plant (Bellés et al. in Mol Plant-Microbe Interact 12:227-235, 1999). In cucumber and Gynura plants, the activity of gentisic acid as inducing signal was different to that of SA, thus confirming the data found for tomato. Exogenously supplied gentisic acid was able to induce peroxidase activity in both Gynura and cucumber plants in a similar way as SA or pathogens. However, gentisic-acid treatments strongly induced polyphenol oxidase activity in cucumber, whereas pathogen infection or SA treatment resulted in a lower induction of this enzyme. Nevertheless, gentisic acid did not induce other defensive proteins which are induced by SA in these plants. This indicates that gentisic acid could act as an additional signal to SA for the activation of plant defenses in cucumber and Gynura plants.

  13. Alteration of host-pathogen interactions in the wake of climate change - Increasing risk for shellfish associated infections?

    Science.gov (United States)

    Hernroth, Bodil E; Baden, Susanne P

    2018-02-01

    The potential for climate-related spread of infectious diseases through marine systems has been highlighted in several reports. With this review we want to draw attention to less recognized mechanisms behind vector-borne transmission pathways to humans. We have focused on how the immune systems of edible marine shellfish, the blue mussels and Norway lobsters, are affected by climate related environmental stressors. Future ocean acidification (OA) and warming due to climate change constitute a gradually increasing persistent stress with negative trade-off for many organisms. In addition, the stress of recurrent hypoxia, inducing high levels of bioavailable manganese (Mn) is likely to increase in line with climate change. We summarized that OA, hypoxia and elevated levels of Mn did have an overall negative effect on immunity, in some cases also with synergistic effects. On the other hand, moderate increase in temperature seems to have a stimulating effect on antimicrobial activity and may in a future warming scenario counteract the negative effects. However, rising sea surface temperature and climate events causing high land run-off promote the abundance of naturally occurring pathogenic Vibrio and will in addition, bring enteric pathogens which are circulating in society into coastal waters. Moreover, the observed impairments of the immune defense enhance the persistence and occurrence of pathogens in shellfish. This may increase the risk for direct transmission of pathogens to consumers. It is thus essential that in the wake of climate change, sanitary control of coastal waters and seafood must recognize and adapt to the expected alteration of host-pathogen interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Arboreal ant colonies as 'hot-points' of cryptic diversity for myrmecophiles: the weaver ant Camponotus sp. aff. textor and its interaction network with its associates.

    Directory of Open Access Journals (Sweden)

    Gabriela Pérez-Lachaud

    Full Text Available INTRODUCTION: Systematic surveys of macrofaunal diversity within ant colonies are lacking, particularly for ants nesting in microhabitats that are difficult to sample. Species associated with ants are generally small and rarely collected organisms, which makes them more likely to be unnoticed. We assumed that this tendency is greater for arthropod communities in microhabitats with low accessibility, such as those found in the nests of arboreal ants that may constitute a source of cryptic biodiversity. MATERIALS AND METHODS: We investigated the invertebrate diversity associated with an undescribed, but already threatened, Neotropical Camponotus weaver ant. As most of the common sampling methods used in studies of ant diversity are not suited for evaluating myrmecophile diversity within ant nests, we evaluated the macrofauna within ant nests through exhaustive colony sampling of three nests and examination of more than 80,000 individuals. RESULTS: We identified invertebrates from three classes belonging to 18 taxa, some of which were new to science, and recorded the first instance of the co-occurrence of two brood parasitoid wasp families attacking the same ant host colony. This diversity of ant associates corresponded to a highly complex interaction network. Agonistic interactions prevailed, but the prevalence of myrmecophiles was remarkably low. CONCLUSIONS: Our data support the hypothesis of the evolution of low virulence in a variety of symbionts associated with large insect societies. Because most myrmecophiles found in this work are rare, strictly specific, and exhibit highly specialized biology, the risk of extinction for these hitherto unknown invertebrates and their natural enemies is high. The cryptic, far unappreciated diversity within arboreal ant nests in areas at high risk of habitat loss qualifies these nests as 'hot-points' of biodiversity that urgently require special attention as a component of conservation and management

  15. The diversity of ant-associated black yeasts: insights into a newly discovered world of symbiotic interactions.

    Science.gov (United States)

    Voglmayr, Hermann; Mayer, Veronika; Maschwitz, Ulrich; Moog, Joachim; Djieto-Lordon, Champlain; Blatrix, Rumsaïs

    2011-10-01

    Based on pure culture studies and DNA phylogenetic analyses, black yeasts (Chaetothyriales, Ascomycota) are shown to be widely distributed and important components of numerous plant-ant-fungus networks, independently acquired by several ant lineages in the Old and New World. Data from ITS and LSU nu rDNA demonstrate that a high biodiversity of fungal species is involved. There are two common ant-fungus symbioses involving black yeasts: (1) on the carton walls of ant nests and galleries, and (2) the fungal mats growing within non-pathogenic naturally hollow structures (so-called domatia) provided by myrmecophytic plants as nesting space for ants (ant-plant symbiosis). Most carton- and domatia-inhabiting fungi stem from different phylogenetic lineages within Chaetothyriales, and almost all of the fungi isolated are still undescribed. Despite being closely related, carton and domatia fungi are shown to differ markedly in their morphology and ecology, indicating that they play different roles in these associations. The carton fungi appear to improve the stability of the carton, and several species are commonly observed to co-occur on the same carton. Carton fungi commonly have dark-walled monilioid hyphae, colouring the carton blackish and apparently preventing other fungi from invading the carton. Despite the simultaneous presence of usually several species of fungi, forming complex associations on the carton, little overlap is observed between carton fungi from different ant species, even those that co-occur in nature, indicating at least some host specificity of fungi. Most fungi present on carton belong to Chaetothyriales, but in a few samples, Capnodiales are also an important component. Carton fungi are difficult to assign to anamorph genera, as most lack conidiation. The domatia fungi are more specific. In domatia, usually only one or two fungal species co-occur, producing a dense layer on living host plant tissue in domatia. They have hyaline or light brown

  16. Metabolic Interaction between Anthocyanin and Lignin Biosynthesis Is Associated with Peroxidase FaPRX27 in Strawberry Fruit1[W

    Science.gov (United States)

    Ring, Ludwig; Yeh, Su-Ying; Hücherig, Stephanie; Hoffmann, Thomas; Blanco-Portales, Rosario; Fouche, Mathieu; Villatoro, Carmen; Denoyes, Béatrice; Monfort, Amparo; Caballero, José Luis; Muñoz-Blanco, Juan; Gershenson, Jonathan; Schwab, Wilfried

    2013-01-01

    Plant phenolics have drawn increasing attention due to their potential nutritional benefits. Although the basic reactions of the phenolics biosynthetic pathways in plants have been intensively analyzed, the regulation of their accumulation and flux through the pathway is not that well established. The aim of this study was to use a strawberry (Fragaria × ananassa) microarray to investigate gene expression patterns associated with the accumulation of phenylpropanoids, flavonoids, and anthocyanins in strawberry fruit. An examination of the transcriptome, coupled with metabolite profiling data from different commercial varieties, was undertaken to identify genes whose expression correlated with altered phenolics composition. Seventeen comparative microarray analyses revealed 15 genes that were differentially (more than 200-fold) expressed in phenolics-rich versus phenolics-poor varieties. The results were validated by heterologous expression of the peroxidase FaPRX27 gene, which showed the highest altered expression level (more than 900-fold). The encoded protein was functionally characterized and is assumed to be involved in lignin formation during strawberry fruit ripening. Quantitative trait locus analysis indicated that the genomic region of FaPRX27 is associated with the fruit color trait. Down-regulation of the CHALCONE SYNTHASE gene and concomitant induction of FaPRX27 expression diverted the flux from anthocyanins to lignin. The results highlight the competition of the different phenolics pathways for their common precursors. The list of the 15 candidates provides new genes that are likely to impact polyphenol accumulation in strawberry fruit and could be used to develop molecular markers to select phenolics-rich germplasm. PMID:23835409

  17. Interactive effects of C-reactive protein levels on the association between APOE variants and triglyceride levels in a Taiwanese population.

    Science.gov (United States)

    Wu, Semon; Hsu, Lung-An; Teng, Ming-Sheng; Lin, Jeng-Feng; Chou, Hsin-Hua; Lee, Ming-Cheng; Wu, Yi-Ming; Su, Cheng-Wen; Ko, Yu-Lin

    2016-05-13

    Apolipoprotein E (APOE) plays a major role in lipid metabolism and inflammation. However, the association between APOE gene polymorphisms and serum triglyceride levels remains controversial. We tested the effects of APOE variants on triglyceride levels and their interactions with the inflammatory marker C-reactive protein (CRP) in a Taiwanese population. Two APOE single nucleotide polymorphisms (SNPs) rs429358 and rs7412 were genotyped by TaqMan Assay using real time PCR in 595 healthy subjects attending the clinic for routine visits. After adjustment for clinical covariates, subjects carrying the rs429358-TT genotype and non-ε4 alleles were found to have higher CRP levels, whereas those with rs7412-CC genotype and non-ε2 alleles had significantly higher total and low-density lipoprotein cholesterol levels (all P interaction analyses, we observed significantly lower triglyceride levels in subjects carrying the rs429358-TT genotype and non-ε4 alleles in the low CRP group (P = 2.71 × 10(-4) and P = 4.32 × 10(-4), respectively), but not in those in the high CRP group (interaction P = 0.013 and 0.045, respectively). In addition, multivariate stepwise linear regression analysis showed that subjects carrying the rs429358-TT genotype and non-ε4 alleles with low CRP levels had significantly lower triglyceride levels (P combined with the risk alleles of GCKR, APOA5 and LPL gene variants, we observed that triglyceride levels increased significantly with the number of risk alleles (P = 2.9 × 10(-12)). The combination of SNPs and ε alleles at the APOE locus is involved in managing lipid and CRP levels in the Taiwanese population. APOE polymorphisms interact with CRP to regulate triglyceride levels, thus triglyceride concentration is influenced by both the genetic background of the APOE locus and the inflammatory status of a subject.

  18. OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Wenbin [Department of Biotechnology, Jinan University, Guangzhou 510632 (China); Zhou, You [Minerva Foundation Institute for Medical Research, Helsinki (Finland); Li, Jiwei [Department of Biotechnology, Jinan University, Guangzhou 510632 (China); Mysore, Raghavendra [Minerva Foundation Institute for Medical Research, Helsinki (Finland); Luo, Wei; Li, Shiqian [Department of Biotechnology, Jinan University, Guangzhou 510632 (China); Chang, Mau-Sun [Institute of Biochemical Sciences, National Taiwan University, No. 1, Taipei, Taiwan (China); Olkkonen, Vesa M. [Minerva Foundation Institute for Medical Research, Helsinki (Finland); Yan, Daoguang, E-mail: tydg@jnu.edu.cn [Department of Biotechnology, Jinan University, Guangzhou 510632 (China)

    2014-04-01

    We earlier identified OSBP-related protein 8 (ORP8) as an endoplasmic reticulum/nuclear envelope oxysterol-binding protein implicated in cellular lipid homeostasis, migration, and organization of the microtubule cytoskeleton. Here, a yeast two-hybrid screen identified Homo sapiens sperm associated antigen 5 (SPAG5)/Astrin as interaction partner of ORP8. The putative interaction was further confirmed by pull-down and co-immunoprecipitation assays. ORP8 did not colocalize with kinetochore-associated SPAG5 in mitotic HepG2 or HuH7 cells, but overexpressed ORP8 was capable of recruiting SPAG5 onto endoplasmic reticulum membranes in interphase cells. In our experiments, 25-hydroxycholesterol (25OHC) retarded the HepG2 cell cycle, causing accumulation in G2/M phase; ORP8 overexpression resulted in the same phenotype. Importantly, ORP8 knock-down dramatically inhibited the oxysterol effect on HepG2 cell cycle, suggesting a mediating role of ORP8. Furthermore, knock-down of SPAG5 significantly reduced the effects of both ORP8 overexpression and 25OHC on the cell cycle, placing SPAG5 downstream of the two cell-cycle interfering factors. Taken together, the present results suggest that ORP8 may via SPAG5 mediate oxysterol interference of the HepG2 cell cycle. - Highlights: • The oxysterol-binding protein ORP8 was found to interact with the mitotic regulator SPAG5/Astrin. • Treatment of HepG2 cells with 25-hydroxycholesterol caused cell cycle retardation in G2/M. • ORP8 overexpression caused a similar G2/M accumulation, and ORP8 knock-down reversed the 25-hydroxycholesterol effect. • Reduction of cellular of SPAG5/Astrin reversed the cell cycle effects of both 25-hydroxycholesterol and ORP8 overexpression. • Our results suggest that ORP8 mediates via SPAG5/Astrin the oxysterol interference of HepG2 cell cycle.

  19. OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle

    International Nuclear Information System (INIS)

    Zhong, Wenbin; Zhou, You; Li, Jiwei; Mysore, Raghavendra; Luo, Wei; Li, Shiqian; Chang, Mau-Sun; Olkkonen, Vesa M.; Yan, Daoguang

    2014-01-01

    We earlier identified OSBP-related protein 8 (ORP8) as an endoplasmic reticulum/nuclear envelope oxysterol-binding protein implicated in cellular lipid homeostasis, migration, and organization of the microtubule cytoskeleton. Here, a yeast two-hybrid screen identified Homo sapiens sperm associated antigen 5 (SPAG5)/Astrin as interaction partner of ORP8. The putative interaction was further confirmed by pull-down and co-immunoprecipitation assays. ORP8 did not colocalize with kinetochore-associated SPAG5 in mitotic HepG2 or HuH7 cells, but overexpressed ORP8 was capable of recruiting SPAG5 onto endoplasmic reticulum membranes in interphase cells. In our experiments, 25-hydroxycholesterol (25OHC) retarded the HepG2 cell cycle, causing accumulation in G2/M phase; ORP8 overexpression resulted in the same phenotype. Importantly, ORP8 knock-down dramatically inhibited the oxysterol effect on HepG2 cell cycle, suggesting a mediating role of ORP8. Furthermore, knock-down of SPAG5 significantly reduced the effects of both ORP8 overexpression and 25OHC on the cell cycle, placing SPAG5 downstream of the two cell-cycle interfering factors. Taken together, the present results suggest that ORP8 may via SPAG5 mediate oxysterol interference of the HepG2 cell cycle. - Highlights: • The oxysterol-binding protein ORP8 was found to interact with the mitotic regulator SPAG5/Astrin. • Treatment of HepG2 cells with 25-hydroxycholesterol caused cell cycle retardation in G2/M. • ORP8 overexpression caused a similar G2/M accumulation, and ORP8 knock-down reversed the 25-hydroxycholesterol effect. • Reduction of cellular of SPAG5/Astrin reversed the cell cycle effects of both 25-hydroxycholesterol and ORP8 overexpression. • Our results suggest that ORP8 mediates via SPAG5/Astrin the oxysterol interference of HepG2 cell cycle

  20. The interaction with H-2Dd in cis is associated with a conformational change in the Ly49A NK cell receptor

    Directory of Open Access Journals (Sweden)

    Jonathan eBack

    2011-10-01

    Full Text Available Mouse Natural killer (NK cells express Ly49 family receptors that recognize major histocompatibility complex class I (MHC-I molecules. By interacting with MHC-I molecules expressed on other cells (in trans, inhibitory Ly49 receptors prevent the NK cell-mediated killing of normal cells. In addition, some Ly49 receptors have the unusual property to also interact with MHC-I molecules expressed by the NK cell itself (in cis. Cis binding sequesters a significant fraction of the NK cells' Ly49 receptors, reducing the number of receptors available for trans binding. This lowers the threshold at which NK cell activation exceeds inhibition rendering NK cells more sensitive. It is unclear how Ly49 receptors can bind MHC-I in trans and in cis using the same binding site. We have proposed that this is mediated by two distinct conformations of Ly49 receptors. Here we have tested this model by inferring the distance between the ligand-binding domain of Ly49A and the cell membrane using fluorescence resonance energy transfer (FRET. Consistent with the concept, reducing the distance between the ligand-binding domain of Ly49A and the cell membrane, by shortening the Ly49A stalk, resulted in a substantially increased FRET. The co-expression of cognate MHC-I ligand reduced FRET derived from Ly49A variants with a shortened stalk, indicating that cis association alters FRET. Indeed, FRET improved when cis complexes were disrupted using acid-mediated destruction of MHC-I complexes. These data provide direct evidence that the interaction with MHC-I in cis is associated with a conformational change in the Ly49A receptor on the surface of live cells. The novel FRET based approach may be generally applicable to study conformational changes in cell surface receptors.

  1. Identification of novel type 1 diabetes candidate genes by integrating genome-wide association data, protein-protein interactions, and human pancreatic islet gene expression

    DEFF Research Database (Denmark)

    Bergholdt, Regine; Brorsson, Caroline; Palleja, Albert

    2012-01-01

    Genome-wide association studies (GWAS) have heralded a new era in susceptibility locus discovery in complex diseases. For type 1 diabetes, >40 susceptibility loci have been discovered. However, GWAS do not inevitably lead to identification of the gene or genes in a given locus associated with dis......-cells. Our results provide novel insight to the mechanisms behind type 1 diabetes pathogenesis and, thus, may provide the basis for the design of novel treatment strategies.......Genome-wide association studies (GWAS) have heralded a new era in susceptibility locus discovery in complex diseases. For type 1 diabetes, >40 susceptibility loci have been discovered. However, GWAS do not inevitably lead to identification of the gene or genes in a given locus associated...... with disease, and they do not typically inform the broader context in which the disease genes operate. Here, we integrated type 1 diabetes GWAS data with protein-protein interactions to construct biological networks of relevance for disease. A total of 17 networks were identified. To prioritize...

  2. Comparison of Two Cellulomonas Strains and Their Interaction with Azospirillum brasilense in Degradation of Wheat Straw and Associated Nitrogen Fixation

    Science.gov (United States)

    Halsall, Dorothy M.; Gibson, Alan H.

    1986-01-01

    A mutant strain of Cellulomonas sp. CS1-17 was compared with Cellulomonas gelida 2480 as the cellulolytic component of a mixed culture which was responsible for the breakdown of wheat straw to support asymbiotic nitrogen fixation by Azospirillum brasilense Sp7 (ATCC 29145). Cellulomonas sp. strain CSI-17 was more efficient than was C. gelida in cellulose breakdown at lower oxygen concentrations and, in mixed culture with A. brasilense, it supported higher nitrogenase activity (C2H2 reduction) and nitrogen fixation with straw as the carbon source. Based on gravimetric determinations of straw breakdown and total N determinations, the efficiency of nitrogen fixation was 72 and 63 mg of N per g of straw utilized for the mixtures containing Cellulomonas sp. and C. gelida, respectively. Both Cellulomonas spp. and Azospirillum spp. exhibited a wide range of pH tolerance. When introduced into sterilized soil, the Cellulomonas sp.-Azospirillum brasilense association was more effective in nitrogen fixation at a pH of 7.0 than at the native soil pH (5.6). This was also true of the indigenous diazotrophic microflora of this soil. The potential implications of this work to the field situation are discussed. PMID:16347043

  3. Comparison of two Cellulomonas strains and their interaction with Azospirillum brasilense in degradation of wheat straw and associated nitrogen fixation

    Energy Technology Data Exchange (ETDEWEB)

    Halsall, D.M.; Gibson, A.H.

    1986-04-01

    A mutant strain of Cellulomonas sp. CS1-17 was compared with Cellulomonas gelida 2480 as the cellulolytic component of a mixed culture which was responsible for the breakdown of wheat straw to support asymbiotic nitrogen fixation by Azospirillum brasilense Sp7 (ATCC 29145). Cellulomonas sp. strain CS1-17 was more efficient than was C. gelida in cellulose breakdown at lower oxygen concentrations and, in mixed culture with A. brasilense, it supported higher nitrogenase activity(C/sub 2/H/sub 2/ reduction) and nitrogen fixation with straw as the carbon source. Based on gravimetric determinations of straw breakdown and total N determinations, the efficiency of nitrogen fixation was 72 and 63 mg of N per g of straw utilized for the mixtures containing Cellulomonas sp. and C. gelida, respectively. Both Cellulomonas spp. and Azospirillum spp. exhibited a wide range of pH tolerance. When introduced into sterilized soil, the Cellulomonas sp.-Azospirillum brasilense association was more effective in nitrogen fixation at a pH of 7.0 than at the native soil pH (5.6). This was also true of the indigenous diazotrophic microflora of this soil. The potential implications of this work to the field situation are discussed. 16 references.

  4. QCD prediction of jet structure in 2D trigger-associated momentum correlations and implications for multiple parton interactions

    Directory of Open Access Journals (Sweden)

    Trainor Thomas A.

    2015-01-01

    Full Text Available The expression “multiple parton interactions” (MPI denotes a conjectured QCD mechanism representing contributions from secondary (semihard parton scattering to the transverse azimuth region (TR of jet-triggered p-p collisions. MPI is an object of underlying-event (UE studies that consider variation of TR nch or pt yields relative to a trigger condition (leading hadron or jet pt. An alternative approach is 2D trigger-associated (TA correlations on hadron transverse momentum pt or rapidity yt in which all hadrons from all p-p events are included. Based on a two-component (soft+hard model (TCM of TA correlations a jet-related TA hard component is isolated. Contributions to the hard component from the triggered dijet and from secondary dijets (MPI can be distinguished, including their azimuth dependence relative to the trigger direction. Measured e+-e− and p-p̄ fragmentation functions and a minimum-bias jet spectrum from 200 GeV p-p̄ collisions are convoluted to predict the 2D hard component of TA correlations as a function of p-p collision multiplicity. The agreement between QCD predictions and TA correlation data is quantitative, confirming a dijet interpretation for the TCM hard component. The TA azimuth dependence is inconsistent with conventional UE assumptions.

  5. Interactions between BMP-7 and USAG-1 (uterine sensitization-associated gene-1 regulate supernumerary organ formations.

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    Honoka Kiso

    Full Text Available Bone morphogenetic proteins (BMPs are highly conserved signaling molecules that are part of the transforming growth factor (TGF-beta superfamily, and function in the patterning and morphogenesis of many organs including development of the dentition. The functions of the BMPs are controlled by certain classes of molecules that are recognized as BMP antagonists that inhibit BMP binding to their cognate receptors. In this study we tested the hypothesis that USAG-1 (uterine sensitization-associated gene-1 suppresses deciduous incisors by inhibition of BMP-7 function. We learned that USAG-1 and BMP-7 were expressed within odontogenic epithelium as well as mesenchyme during the late bud and early cap stages of tooth development. USAG-1 is a BMP antagonist, and also modulates Wnt signaling. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced. Using explant culture and subsequent subrenal capsule transplantation of E15 USAG-1 mutant maxillary incisor tooth primordia supplemented with BMP-7 demonstrated in USAG-1+/- as well as USAG-1-/- rescue and supernumerary tooth development. Based upon these results, we conclude that USAG-1 functions as an antagonist of BMP-7 in this model system. These results further suggest that the phenotypes of USAG-1 and BMP-7 mutant mice reported provide opportunities for regenerative medicine and dentistry.

  6. A Functional Toll-Interacting Protein Variant Is Associated with Bacillus Calmette-Guérin-Specific Immune Responses and Tuberculosis.

    Science.gov (United States)

    Shah, Javeed A; Musvosvi, Munyaradzi; Shey, Muki; Horne, David J; Wells, Richard D; Peterson, Glenna J; Cox, Jeffery S; Daya, Michelle; Hoal, Eileen G; Lin, Lin; Gottardo, Raphael; Hanekom, Willem A; Scriba, Thomas J; Hatherill, Mark; Hawn, Thomas R

    2017-08-15

    The molecular mechanisms that regulate tuberculosis susceptibility and bacillus Calmette-Guérin (BCG)-induced immunity are mostly unknown. However, induction of the adaptive immune response is a critical step in host control of Mycobacterium tuberculosis. Toll-interacting protein (TOLLIP) is a ubiquitin-binding protein that regulates innate immune responses, including Toll-like receptor signaling, which initiate adaptive immunity. TOLLIP variation is associated with susceptibility to tuberculosis, but the mechanism by which it regulates tuberculosis immunity is poorly understood. To identify functional TOLLIP variants and evaluate the role of TOLLIP variation on innate and adaptive immune responses to mycobacteria and susceptibility to tuberculosis. We used human cellular immunology approaches to characterize the role of a functional TOLLIP variant on monocyte mRNA expression and M. tuberculosis-induced monocyte immune functions. We also examined the association of TOLLIP variation with BCG-induced T-cell responses and susceptibility to latent tuberculosis infection. We identified a functional TOLLIP promoter region single-nucleotide polymorphism, rs5743854, which was associated with decreased TOLLIP mRNA expression in infant monocytes. After M. tuberculosis infection, TOLLIP-deficient monocytes demonstrated increased IL-6, increased nitrite, and decreased bacterial replication. The TOLLIP-deficiency G/G genotype was associated with decreased BCG-specific IL-2 + CD4 + T-cell frequency and proliferation. This genotype was also associated with increased susceptibility to latent tuberculosis infection. TOLLIP deficiency is associated with decreased BCG-specific T-cell responses and increased susceptibility to tuberculosis. We hypothesize that the heightened antibacterial monocyte responses after vaccination of TOLLIP-deficient infants are responsible for decreased BCG-specific T-cell responses. Activating TOLLIP may provide a novel adjuvant strategy for BCG

  7. Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment

    Directory of Open Access Journals (Sweden)

    Boscarino JA

    2012-03-01

    Full Text Available Joseph A Boscarino1,2, Porat M Erlich1,3, Stuart N Hoffman4, Xiaopeng Zhang51Center for Health Research, Geisinger Clinic, Danville, PA, 2Department of Psychiatry, 3Department of Medicine, Temple University School of Medicine, Philadelphia, PA, 4Department of Neurology, 5Department of Anesthesiology, Geisinger Clinic, Danville, PA, USAObjective: The study aim was to assess the cumulative burden of polymorphisms located within four genetic loci previously associated with posttraumatic stress disorder (PTSD among outpatients at risk for PTSD.Methods: Diagnostic interviews were completed and DNA samples collected among 412 pain patients to determine if FKBP5 (rs9470080, COMT (rs4680, CHRNA5 (rs16969968, and CRHR1 (rs110402 single nucleotide polymorphisms were cumulatively associated with increased risk for PTSD.Results: In bivariate analyses, it was found that a count of specific PTSD risk alleles located within FKBP5, COMT, CHRNA5, and CRHR1 genetic loci (allele range = 0–6, mean count = 2.92, standard deviation = 1.36 was associated with lifetime (t [409] = 3.430, P = 0.001 and early onset PTSD (t [409] = 4.239, P = 0.000028. In logistic regression, controlling for demographic factors, personality traits, and trauma exposures, this risk allele count remained associated with both lifetime (odds ratio = 1.49, P = 0.00158 and early onset PTSD (odds ratio = 2.36, P = 0.000093. Interaction effects were also detected, whereby individuals with higher risk allele counts and higher trauma exposures had an increased risk of lifetime PTSD (allele count × high trauma, P = 0.026 and early onset PTSD (allele count × high trauma, P = 0.016 in these logistic regressions. Those with no or few risk alleles appeared resilient to PTSD, regardless of exposure history.Conclusion: A cumulative risk allele count involving four single nucleotide polymorphisms located within the FKBP5, COMT, CHRNA5, and CRHR1 genes are associated with PTSD. Level of trauma exposure

  8. Arabidopsis lipid droplet-associated protein (LDAP) - interacting protein (LDIP) influences lipid droplet size and neutral lipid homeostasis in both leaves and seeds.

    Science.gov (United States)

    Pyc, Michal; Cai, Yingqi; Gidda, Satinder K; Yurchenko, Olga; Park, Sunjung; Kretzschmar, Franziska K; Ischebeck, Till; Valerius, Oliver; Braus, Gerhard H; Chapman, Kent D; Dyer, John M; Mullen, Robert T

    2017-12-01

    Cytoplasmic lipid droplets (LDs) are found in all types of plant cells; they are derived from the endoplasmic reticulum and function as a repository for neutral lipids, as well as serving in lipid remodelling and signalling. However, the mechanisms underlying the formation, steady-state maintenance and turnover of plant LDs, particularly in non-seed tissues, are relatively unknown. Previously, we showed that the LD-associated proteins (LDAPs) are a family of plant-specific, LD surface-associated coat proteins that are required for proper biogenesis of LDs and neutral lipid homeostasis in vegetative tissues. Here, we screened a yeast two-hybrid library using the Arabidopsis LDAP3 isoform as 'bait' in an effort to identify other novel LD protein constituents. One of the candidate LDAP3-interacting proteins was Arabidopsis At5g16550, which is a plant-specific protein of unknown function that we termed LDIP (LDAP-interacting protein). Using a combination of biochemical and cellular approaches, we show that LDIP targets specifically to the LD surface, contains a discrete amphipathic α-helical targeting sequence, and participates in both homotypic and heterotypic associations with itself and LDAP3, respectively. Analysis of LDIP T-DNA knockdown and knockout mutants showed a decrease in LD abundance and an increase in variability of LD size in leaves, with concomitant increases in total neutral lipid content. Similar phenotypes were observed in plant seeds, which showed enlarged LDs and increases in total amounts of seed oil. Collectively, these data identify LDIP as a new player in LD biology that modulates both LD size and cellular neutral lipid homeostasis in both leaves and seeds. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  9. Mucosal-Associated Invariant T Cell Interactions with Commensal and Pathogenic Bacteria: Potential Role in Antimicrobial Immunity in the Child

    Directory of Open Access Journals (Sweden)

    Liana Ghazarian

    2017-12-01

    Full Text Available Mucosal-associated invariant T (MAIT cells are unconventional CD3+CD161high T lymphocytes that recognize vitamin B2 (riboflavin biosynthesis precursor derivatives presented by the MHC-I related protein, MR1. In humans, their T cell receptor is composed of a Vα7.2-Jα33/20/12 chain, combined with a restricted set of Vβ chains. MAIT cells are very abundant in the liver (up to 40% of resident T cells and in mucosal tissues, such as the lung and gut. In adult peripheral blood, they represent up to 10% of circulating T cells, whereas they are very few in cord blood. This large number of MAIT cells in the adult likely results from their gradual expansion with age following repeated encounters with riboflavin-producing microbes. Upon recognition of MR1 ligands, MAIT cells have the capacity to rapidly eliminate bacterially infected cells through the production of inflammatory cytokines (IFNγ, TNFα, and IL-17 and cytotoxic effector molecules (perforin and granzyme B. Thus, MAIT cells may play a crucial role in antimicrobial defense, in particular at mucosal sites. In addition, MAIT cells have been implicated in diseases of non-microbial etiology, including autoimmunity and other inflammatory diseases. Although their participation in various clinical settings has received increased attention in adults, data in children are scarce. Due to their innate-like characteristics, MAIT cells might be particularly important to control microbial infections in the young age, when long-term protective adaptive immunity is not fully developed. Herein, we review the data showing how MAIT cells may control microbial infections and how they discriminate pathogens from commensals, with a focus on models relevant for childhood infections.

  10. Diversity of Cultivated Fungi Associated with Conventional and Transgenic Sugarcane and the Interaction between Endophytic Trichoderma virens and the Host Plant.

    Directory of Open Access Journals (Sweden)

    Aline Silva Romão-Dumaresq

    Full Text Available Plant-associated fungi are considered a vast source for biotechnological processes whose potential has been poorly explored. The interactions and diversity of sugarcane, one of the most important crops in Brazil, have been rarely studied, mainly concerning fungal communities and their interactions with transgenic plants. Taking this into consideration, the purpose of this study was, based on culture dependent strategy, to determine the structure and diversity of the fungal community (root endophytes and rhizosphere associated with two varieties of sugarcane, a non-genetically modified (SP80-1842 variety and its genetically modified counterpart (IMI-1, expressing imazapyr herbicide resistance. For this, the sugarcane varieties were evaluated in three sampling times (3, 10 and 17 months after planting under two crop management (weeding and herbicide treatments. In addition, a strain of Trichoderma virens, an endophyte isolated from sugarcane with great potential as a biological control, growth promotion and enzyme production agent, was selected for the fungal-plant interaction assays. The results of the isolation, characterization and evaluation of fungal community changes showed that the sugarcane fungal community is composed of at least 35 different genera, mostly in the phylum Ascomycota. Many genera are observed at very low frequencies among a few most abundant genera, some of which were isolated from specific plant sites (e.g., the roots or the rhizosphere. An assessment of the possible effects upon the fungal community showed that the plant growth stage was the only factor that significantly affected the community's structure. Moreover, if transgenic effects are present, they may be minor compared to other natural sources of variation. The results of interaction studies using the Green fluorescent protein (GFP-expressing T. virens strain T.v.223 revealed that this fungus did not promote any phenotypic changes in the host plant and was found

  11. Diversity of Cultivated Fungi Associated with Conventional and Transgenic Sugarcane and the Interaction between Endophytic Trichoderma virens and the Host Plant

    Science.gov (United States)

    Romão-Dumaresq, Aline Silva; Dourado, Manuella Nóbrega; Fávaro, Léia Cecilia de Lima; Mendes, Rodrigo; Ferreira, Anderson; Araújo, Welington Luiz

    2016-01-01

    Plant-associated fungi are considered a vast source for biotechnological processes whose potential has been poorly explored. The interactions and diversity of sugarcane, one of the most important crops in Brazil, have been rarely studied, mainly concerning fungal communities and their interactions with transgenic plants. Taking this into consideration, the purpose of this study was, based on culture dependent strategy, to determine the structure and diversity of the fungal community (root endophytes and rhizosphere) associated with two varieties of sugarcane, a non-genetically modified (SP80-1842) variety and its genetically modified counterpart (IMI-1, expressing imazapyr herbicide resistance). For this, the sugarcane varieties were evaluated in three sampling times (3, 10 and 17 months after planting) under two crop management (weeding and herbicide treatments). In addition, a strain of Trichoderma virens, an endophyte isolated from sugarcane with great potential as a biological control, growth promotion and enzyme production agent, was selected for the fungal-plant interaction assays. The results of the isolation, characterization and evaluation of fungal community changes showed that the sugarcane fungal community is composed of at least 35 different genera, mostly in the phylum Ascomycota. Many genera are observed at very low frequencies among a few most abundant genera, some of which were isolated from specific plant sites (e.g., the roots or the rhizosphere). An assessment of the possible effects upon the fungal community showed that the plant growth stage was the only factor that significantly affected the community’s structure. Moreover, if transgenic effects are present, they may be minor compared to other natural sources of variation. The results of interaction studies using the Green fluorescent protein (GFP)-expressing T. virens strain T.v.223 revealed that this fungus did not promote any phenotypic changes in the host plant and was found mostly in

  12. Intracellular Distribution of Capsid-Associated pUL77 of Human Cytomegalovirus and Interactions with Packaging Proteins and pUL93.

    Science.gov (United States)

    Köppen-Rung, Pánja; Dittmer, Alexandra; Bogner, Elke

    2016-07-01

    DNA packaging into procapsids is a common multistep process during viral maturation in herpesviruses. In human cytomegalovirus (HCMV), the proteins involved in this process are terminase subunits pUL56 and pUL89, which are responsible for site-specific cleavage and insertion of the DNA into the procapsid via portal protein pUL104. However, additional viral proteins are required for the DNA packaging process. We have shown previously that the plasmid that encodes capsid-associated pUL77 encodes another potential player during capsid maturation. Pulse-chase experiments revealed that pUL77 is stably expressed during HCMV infection. Time course analysis demonstrated that pUL77 is expressed in the early late part of the infectious cycle. The sequence of pUL77 was analyzed to find nuclear localization sequences (NLSs), revealing monopartite NLSm at the N terminus and bipartite NLSb in the middle of pUL77. The potential NLSs were inserted into plasmid pHM829, which encodes a chimeric protein with β-galactosidase and green fluorescent protein. In contrast to pUL56, neither NLSm nor NLSb was sufficient for nuclear import. Furthermore, we investigated by coimmunoprecipitation whether packaging proteins, as well as pUL93, the homologue protein of herpes simplex virus 1 pUL17, are interaction partners of pUL77. The interactions between pUL77 and packaging proteins, as well as pUL93, were verified. We showed that the capsid-associated pUL77 is another potential player during capsid maturation of HCMV. Protein UL77 (pUL77) is a conserved core protein of HCMV. This study demonstrates for the first time that pUL77 has early-late expression kinetics during the infectious cycle and an intrinsic potential for nuclear translocation. According to its proposed functions in stabilization of the capsid and anchoring of the encapsidated DNA during packaging, interaction with further DNA packaging proteins is required. We identified physical interactions with terminase subunits pUL56 and p

  13. A hypertension-associated mitochondrial DNA mutation alters the tertiary interaction and function of tRNALeu(UUR).

    Science.gov (United States)

    Zhou, Mi; Wang, Meng; Xue, Ling; Lin, Zhi; He, Qiufen; Shi, Wenwen; Chen, Yaru; Jin, Xiaofen; Li, Haiying; Jiang, Pingping; Guan, Min-Xin

    2017-08-25

    Several mitochondrial tRNA mutations have been associated with hypertension, but their pathophysiology remains poorly understood. In this report, we identified a novel homoplasmic 3253T→C mutation in the mitochondrial tRNA Leu(UUR) gene in a Han Chinese family with maternally inherited hypertension. The m.3253T→C mutation affected a highly conserved uridine at position 22 at the D-stem of tRNA Leu(UUR) , introducing a G-C base pairing (G13-C22) at the D-stem and a tertiary base pairing (C22-G46) between the D-stem and the variable loop. We therefore hypothesized that the m.3253T→C mutation altered both the structure and function of tRNA Leu(UUR) Using cytoplasmic hybrid (cybrid) cell lines derived from this Chinese family, we demonstrated that the m.3253T→C mutation perturbed the conformation and stability of tRNA Leu(UUR) , as suggested by faster electrophoretic mobility of mutated tRNA relative to the wild-type molecule. Northern blot analysis revealed an ∼45% decrease in the steady-state level of tRNA Leu(UUR) in the mutant cell lines carrying the m.3253T→C mutation, as compared with control cell lines. Moreover, an ∼35% reduction in aminoacylation efficiency of tRNA Leu(UUR) was observed in the m.3253T→C mutant cells. These alterations in tRNA Leu(UUR) metabolism impaired mitochondrial translation, especially for those polypeptides with a high proportion of Leu(UUR) codons, such as ND6. Furthermore, we demonstrated that the m.3253T→C mutation decreased the activities of mitochondrial complexes I and V, markedly diminished mitochondrial ATP levels and membrane potential, and increased the production of reactive oxygen species in the cells. In conclusion, our findings may provide new insights into the pathophysiology of maternally inherited hypertension. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Exposure to mixtures of organohalogen contaminants and associative interactions with thyroid hormones in East Greenland polar bears (Ursus maritimus).

    Science.gov (United States)

    Villanger, Gro D; Jenssen, Bjørn M; Fjeldberg, Rita R; Letcher, Robert J; Muir, Derek C G; Kirkegaard, Maja; Sonne, Christian; Dietz, Rune

    2011-05-01

    We investigated the multivariate relationships between adipose tissue residue levels of 48 individual organohalogen contaminants (OHCs) and circulating thyroid hormone (TH) levels in polar bears (Ursus maritimus) from East Greenland (1999-2001, n=62), using projection to latent structure (PLS) regression for four groupings of polar bears; subadults (SubA), adult females with cubs (AdF_N), adult females without cubs (AdF_S) and adult males (AdM). In the resulting significant PLS models for SubA, AdF_N and AdF_S, some OHCs were especially important in explaining variations in circulating TH levels: polybrominated diphenylether (PBDE)-99, PBDE-100, PBDE-153, polychlorinated biphenyl (PCB)-52, PCB-118, cis-nonachlor, trans-nonachlor, trichlorobenzene (TCB) and pentachlorobenzene (QCB), and both negative and positive relationships with THs were found. In addition, the models revealed that DDTs had a positive influence on total 3,5,3'-triiodothyronine (TT3) in AdF_S, and that a group of 17 higher chlorinated ortho-PCBs had a positive influence on total 3,5,3',5'-tetraiodothyronine (thyroxine, TT4) in AdF_N. TH levels in AdM seemed less influenced by OHCs because of non-significant PLS models. TH levels were also influenced by biological factors such as age, sex, body size, lipid content of adipose tissue and sampling date. When controlling for biological variables, the major relationships from the PLS models for SubA, AdF_N and AdF_S were found significant in partial correlations. The most important OHCs that influenced TH levels in the significant PLS models may potentially act through similar mechanisms on the hypothalamic-pituitary-thyroid (HPT) axis, suggesting that both combined effects by dose and response addition and perhaps synergistic potentiation may be a possibility in these polar bears. Statistical associations are not evidence per se of biological cause-effect relationships. Still, the results of the present study indicate that OHCs may affect circulating

  15. Patients' perceptions of interactions with hospital staff are associated with hospital readmissions: a national survey of 4535 hospitals.

    Science.gov (United States)

    Yang, Lianping; Liu, Chaojie; Huang, Cunrui; Mukamel, Dana B

    2018-01-29

    Reducing 30-day hospital readmissions has become a focus of the current national payment policies. Medicare requires that hospitals collect and report patients' experience with their care as a condition of payment. However, the extent to which patients' experience with hospital care is related to hospital readmission is unknown. We established multivariate regression models in which 30-day risk-adjusted readmission rates were the dependent variables and patients' perceptions of the responsiveness of the hospital staff and communication (as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores) were the independent variables of interest. We selected six different clinical conditions for analyses, including acute myocardial infarction (AMI), chronic obstructive pulmonary disease (COPD), heart failure, hip/knee surgery, pneumonia, and stroke. Data included all acute care hospitals reporting in Hospital Compare in 2014. The number of hospitals with reported readmissions ranged from 2234 hospitals for AMI to 3758 hospitals for pneumonia. The average 30-day readmission rates ranged from 5.19% for knee/hip surgery to 22.7% for COPD. Patient experience of hospital-staff responsiveness as "top-box" ranged from 64% to 67% across the six clinical conditions, communication with nurses ranged from 77% to 79% and communication with doctors ranged from 80% to 81% (higher numbers are better). Our finding suggests that hospitals with better staff responsiveness were significantly more likely to have lower 30-day readmissions for all conditions. The effect size depended on the baseline readmission rates, with the largest effect on hospitals in the upper 75th quartile. A ten-percentage-point increase in staff responsiveness led to a 0.03-0.18 percentage point decrease in readmission rates. We found that neither communication with physicians nor communication with nurses was significantly associated with hospital readmissions. Our findings

  16. Set-Based Joint Test of Interaction Between SNPs in the VEGF Pathway and Exogenous Estrogen Finds Association With Age-Related Macular Degeneration

    Science.gov (United States)

    Courtenay, Monique D.; Cade, William H.; Schwartz, Stephen G.; Kovach, Jaclyn L.; Agarwal, Anita; Wang, Gaofeng; Haines, Jonathan L.; Pericak-Vance, Margaret A.; Scott, William K.

    2014-01-01

    Purpose. Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in developed countries. Its etiology includes genetic and environmental factors. Although VEGFA variants are associated with AMD, the joint action of variants within the VEGF pathway and their interaction with nongenetic factors have not been investigated. Methods. Affymetrix 6.0 chipsets were used to genotype 668,238 single nucleotide polymorphisms (SNPs) in 1207 AMD cases and 686 controls. Environmental exposures were collected by questionnaire. A set-based test was conducted using the χ2 statistic at each SNP derived from Kraft's two degree of freedom (2df) joint test. Pathway- and gene-based test statistics were calculated as the mean of all independent SNP statistics. Phenotype labels were permuted 10,000 times to generate an empirical P value. Results. While a main effect of the VEGF pathway was not identified, the pathway was associated with neovascular AMD in women when accounting for birth control pill (BCP) use (P = 0.017). Analysis of VEGF's subpathways showed that SNPs in the proliferation subpathway were associated with neovascular AMD (P = 0.029) when accounting for BCP use. Nominally significant genes within this subpathway were also observed. Stratification by BCP use revealed novel significant genetic effects in women who had taken BCPs. Conclusions. These results illustrate that some AMD genetic risk factors may be revealed only when complex relationships among risk factors are considered. This shows the utility of exploring pathways of previously associated genes to find novel effects. It also demonstrates the importance of incorporating environmental exposures in tests of genetic association at the SNP, gene, or pathway level. PMID:25015356

  17. The mechanism by which TATA-box polymorphisms associated with human hereditary diseases influence interactions with the TATA-binding protein.

    Science.gov (United States)

    Drachkova, Irina; Savinkova, Ludmila; Arshinova, Tatyana; Ponomarenko, Mikhail; Peltek, Sergey; Kolchanov, Nikolay

    2014-05-01

    SNPs in ТАТА boxes are the cause of monogenic diseases, contribute to a large number of complex diseases, and have implications for human sensitivity to external and internal environmental signals. The aim of this work was to explore the kinetic characteristics of the formation of human ТВР complexes with ТАТА boxes, in which the SNPs are associated with β-thalassemias of diverse severity, immunosuppression, neurological disorders, and so on. It has for the first time been demonstrated, using an electrophoretic mobility shift assay, that TBP interacts with SNP-containing ТАТА boxes with a significant (8-36-fold) decrease in TBP/ТАТА association rate constant (ka ) as compared with that in healthy people, a smaller decrease in dissociation rate constant (kd ) and changes in the half-lives of TBP/ТАТА complexes. Carriers of the -24G allele (rs 1800202T>G) in the TATA box of the triosephosphate isomerase gene promoter, associated with neurological and muscular disorders, were observed to have a 36-fold decrease in TBP/TATA association rate constant that are consistent with TPI deficiency shown for patients who carry this defective allele. The kinetic characteristics of TBP/ТАТА complexes obtained suggest that, at a molecular level, hereditary diseases are largely caused by changes in TBP/ТАТА association rates and these changes have a bearing on disease severity. © 2014 WILEY PERIODICALS, INC.

  18. Characterization of iron and manganese minerals and their associated microbiota in different mine sites to reveal the potential interactions of microbiota with mineral formation.

    Science.gov (United States)

    Park, Jin Hee; Kim, Bong-Soo; Chon, Chul-Min

    2018-01-01

    Different environmental conditions such as pH and dissolved elements of mine stream induce precipitation of different minerals and their associated microbial community may vary. Therefore, mine precipitates from various environmental conditions were collected and their associated microbiota were analyzed through metagenomic DNA sequencing. Various Fe and Mn minerals including ferrihydrite, schwertmannite, goethite, birnessite, and Mn-substituted δ-FeOOH (δ-(Fe 1-x , Mn x )OOH) were found in the different environmental conditions. The Fe and Mn minerals were enriched with toxic metal(loid)s including As, Cd, Ni and Zn, indicating they can act as scavengers of toxic metal(loid)s in mine streams. Under acidic conditions, Acidobacteria was dominant phylum and Gallionella (Fe oxidizing bacteria) was the predominant genus in these Fe rich environments. Manganese oxidizing bacteria, Hyphomicrobium, was found in birnessite forming environments. Leptolyngbya within Cyanobacteria was found in Fe and Mn oxidizing environments, and might contribute to Fe and Mn oxidation through the production of molecular oxygen. The potential interaction of microbial community with minerals in mine sites can be traced by analysis of microbial community in different Fe and Mn mineral forming environments. Iron and Mn minerals contribute to the removal of toxic metal(loid)s from mine water. Therefore, the understanding characteristics of mine precipitates and their associated microbes helps to develop strategies for the management of contaminated mine water. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Nematode-trapping fungi and fungus-associated bacteria interactions: the role of bacterial diketopiperazines and biofilms on Arthrobotrys oligospora surface in hyphal morphogenesis.

    Science.gov (United States)

    Li, Lei; Yang, Min; Luo, Jun; Qu, Qing; Chen, Ying; Liang, Lianming; Zhang, Keqin

    2016-11-01

    In soil, nematode-trapping fungi and bacteria often share microhabitats and interact with each other, but effects of fungus-associated bacteria on its trap formation are underestimated. We have ascertained the presence of Stenotrophomonas and Rhizobium genera associated with A. oligospora GJ-1. After A. oligospora GJ-1 without associated bacteria (cured Arthrobotrys) was co-cultivated with Stenotrophomonas and its supernatant extract, microscopic study of hyphae from co-cultivation indicated that bacterial biofilm formation on hyphae was related to trap formation in fungi and Stenotrophomonas supernatant extract. Four diketopiperazines (DKPs) were purified from Stenotrophomonas supernatant extract that could not induce traps in the cured Arthrobotrys. When cured Arthrobotrys was cultured with Stenotrophomonas and one of DKPs, polar attachment, bacterial biofilms on hyphae and trap formation in fungi were observed. After cured Arthrobotrys with bacterial biofilms was consecutively transferred several times on nutrient poor medium, trap formation disappeared with the disappearance of bacterial biofilms on hyphae. DKPs could facilitate chemotaxis of Stenotrophomonas towards fungal extract which was suggested to contribute to bacterial biofilms on hyphae. Furthermore, when cured Arthrobotrys was cultured with Stenotrophomonas and DKPs in soil, trap formation in fungi and bacterial biofilms on hyphae were also observed, and the fungal activity against nematode was enhanced. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  20. Structural and thermodynamic characterization of the interaction between two periplasmic Treponema pallidum lipoproteins that are components of a TPR-protein-associated TRAP transporter (TPAT).

    Science.gov (United States)

    Brautigam, Chad A; Deka, Ranjit K; Schuck, Peter; Tomchick, Diana R; Norgard, Michael V

    2012-06-29

    Tripartite ATP-independent periplasmic transporters (TRAP-Ts) are bacterial transport systems that have been implicated in the import of small molecules into the cytoplasm. A newly discovered subfamily of TRAP-Ts [tetratricopeptide repeat-protein associated TRAP transporters (TPATs)] has four components. Three are common to both TRAP-Ts and TPATs: the P component, a ligand-binding protein, and a transmembrane symporter apparatus comprising the M and Q components (M and Q are sometimes fused to form a single polypeptide). TPATs are distinguished from TRAP-Ts by the presence of a unique protein called the "T component". In Treponema pallidum, this protein (TatT) is a water-soluble trimer whose protomers are each perforated by a pore. Its respective P component (TatP(T)) interacts with the TatT in vitro and in vivo. In this work, we further characterized this interaction. Co-crystal structures of two complexes between the two proteins confirm that up to three monomers of TatP(T) can bind to the TatT trimer. A putative ligand-binding cleft of TatP(T) aligns with the pore of TatT, strongly suggesting ligand transfer between T and P(T). We used a combination of site-directed mutagenesis and analytical ultracentrifugation to derive thermodynamic parameters for the interactions. These observations confirm that the observed crystallographic interface is recapitulated in solution. These results prompt a hypothesis of the molecular mechanism(s) of hydrophobic ligand transport by the TPATs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. IL-1 receptor accessory protein-like 1 associated with mental retardation and autism mediates synapse formation by trans-synaptic interaction with protein tyrosine phosphatase δ.

    Science.gov (United States)

    Yoshida, Tomoyuki; Yasumura, Misato; Uemura, Takeshi; Lee, Sung-Jin; Ra, Moonjin; Taguchi, Ryo; Iwakura, Yoichiro; Mishina, Masayoshi

    2011-09-21

    Mental retardation (MR) and autism are highly heterogeneous neurodevelopmental disorders. IL-1-receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic MR and is associated with autism. Thus, the elucidation of the functional role of IL1RAPL1 will contribute to our understanding of the pathogenesis of these mental disorders. Here, we showed that knockdown of endogenous IL1RAPL1 in cultured cortical neurons suppressed the accumulation of punctate staining signals for active zone protein Bassoon and decreased the number of dendritic protrusions. Consistently, the expression of IL1RAPL1 in cultured neurons stimulated the accumulation of Bassoon and spinogenesis. The extracellular domain (ECD) of IL1RAPL1 was required and sufficient for the presynaptic differentiation-inducing activity, while both the ECD and cytoplasmic domain were essential for the spinogenic activity. Notably, the synaptogenic activity of IL1RAPL1 was specific for excitatory synapses. Furthermore, we identified presynaptic protein tyrosine phosphatase (PTP) δ as a major IL1RAPL1-ECD interacting protein by affinity chromatography. IL1RAPL1 interacted selectively with certain forms of PTPδ splice variants carrying mini-exon peptides in Ig-like domains. The synaptogenic activity of IL1RAPL1 was abolished in primary neurons from PTPδ knock-out mice. IL1RAPL1 showed robust synaptogenic activity in vivo when transfected into the cortical neurons of wild-type mice but not in PTPδ knock-out mice. These results suggest that IL1RAPL1 mediates synapse formation through trans-synaptic interaction with PTPδ. Our findings raise an intriguing possibility that the impairment of synapse formation may underlie certain forms of MR and autism as a common pathogenic pathway shared by these mental disorders.

  2. Distinct Network Interactions in Particle-Associated and Free-Living Bacterial Communities during a Microcystis aeruginosa Bloom in a Plateau Lake

    Directory of Open Access Journals (Sweden)

    Caiyun Yang

    2017-06-01

    Full Text Available Particle-associated bacteria (PAB and free-living bacteria (FLB from aquatic environments during phytoplankton blooms differ in their physical distance from algae. Both the interactions within PAB and FLB community fractions and their relationship with the surrounding environmental properties are largely unknown. Here, by using high-throughput sequencing and network-based analyses, we compared the community and network characteristics of PAB and FLB from a plateau lake during a Microcystis aeruginosa bloom. Results showed that PAB and FLB differed significantly in diversity, structure and microbial connecting network. PAB communities were characterized by highly similar bacterial community structure in different sites, tighter network connections, important topological roles for the bloom-causing M. aeruginosa and Alphaproteobacteria, especially for the potentially nitrogen-fixing (Pleomorphomonas and algicidal bacteria (Brevundimonas sp.. FLB communities were sensitive to the detected environmental factors and were characterized by significantly higher bacterial diversity, less connectivity, larger network size and marginal role of M. aeruginosa. In both networks, covariation among bacterial taxa was extensive (>88% positive connections, and bacteria potentially affiliated with biogeochemical cycling of nitrogen (i.e., denitrification, nitrogen-fixation and nitrite-oxidization were important in occupying module hubs, such as Meganema, Pleomorphomonas, and Nitrospira. These findings highlight the importance of considering microbial network interactions for the understanding of blooms.

  3. A Perspective on Brain-Gut Communication: The American Gastroenterology Association and American Psychosomatic Society Joint Symposium on Brain-Gut Interactions and the Intestinal Microenvironment.

    Science.gov (United States)

    Aroniadis, Olga C; Drossman, Douglas A; Simrén, Magnus

    2017-10-01

    Alterations in brain-gut communication and the intestinal microenvironment have been implicated in a variety of medical and neuropsychiatric diseases. Three central areas require basic and clinical research: (1) how the intestinal microenvironment interacts with the host immune system, central nervous system, and enteric nervous system; (2) the role of the intestinal microenvironment in the pathogenesis of medical and neuropsychiatric disease; and (3) the effects of diet, prebiotics, probiotics, and fecal microbiota transplantation on the intestinal microenvironment and the treatment of disease. This review article is based on a symposium convened by the American Gastroenterology Association and the American Psychosomatic Society to foster interest in the role of the intestinal microenvironment in brain-gut communication and pathogenesis of neuropsychiatric and biopsychosocial disorders. The aims were to define the state of the art of the current scientific knowledge base and to identify guidelines and future directions for new research in this area. This review provides a characterization of the intestinal microbial composition and function. We also provide evidence for the interactions between the intestinal microbiome, the host, and the environment. The role of the intestinal microbiome in medical and neuropsychiatric diseases is reviewed as well as the treatment effects of manipulation of the intestinal microbiome. Based on this review, opportunities and challenges for conducting research in the field are described, leading to potential avenues for future research.

  4. The association of reduced folate carrier 80G>A polymorphism to outcome in childhood acute lymphoblastic leukemia interacts with chromosome 21 copy number

    DEFF Research Database (Denmark)

    Gregers, Jannie; Christensen, Ib Jarle; Dalhoff, Kim

    2010-01-01

    with chromosome 21 copy number in the leukemic clone. A total of 500 children with acute lymphoblastic leukemia treated according to the common Nordic treatment protocols were included, and we found that the RFC AA variant was associated with a 50% better chance of staying in remission compared with GG or GA...... (platelet 73 vs 99/105 x 10(9)/L, P = .004, hemoglobin 5.6 vs 5.9/6.0 mmol/L, P = .004) and a higher degree of liver toxicity in patients with RFC GG variant (alanine aminotransferase 167 vs 127/124 U/L, P = .05). In conclusion, the RFC 80G>A polymorphism interacts with chromosome 21 copy numbers...

  5. Familial risk for mood disorder and the personality risk factor, neuroticism, interact in their association with frontolimbic serotonin 2A receptor binding

    DEFF Research Database (Denmark)

    Frøkjær, Vibe Gedsø; Vinberg, Maj; Erritzoe, David

    2010-01-01

    Life stress is a robust risk factor for later development of mood disorders, particularly for individuals at familial risk. Likewise, scoring high on the personality trait neuroticism is associated with an increased risk for mood disorders. Neuroticism partly reflects stress vulnerability...... binding. These findings point at a plausible neurobiological link between genetic and personality risk factors and vulnerability to developing mood disorders. It contributes to our understanding of why some people at high risk develop mood disorders while others do not. We speculate that an increased......-twin history of mood disorder were included. They answered self-report personality questionnaires and underwent [(18)F]altanserin positron emission tomography. We found a significant interaction between neuroticism and familial risk in predicting the frontolimbic 5-HT(2A) receptor binding (p=0...

  6. Pulmonary expression of CYP2A13 and ABCB1 is regulated by FOXA2, and their genetic interaction is associated with lung cancer.

    Science.gov (United States)

    Xiang, Chan; Wang, Jiucun; Kou, Xiaochen; Chen, Xiabin; Qin, Zhaoyu; Jiang, Yan; Sun, Chang; Xu, Jibin; Tan, Wen; Jin, Li; Lin, Dongxin; He, Fuchu; Wang, Haijian

    2015-05-01

    Inhaled xenobiotics such as tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone are mainly metabolized by phase I oxidase cytochrome P450, family 2, subfamily A, polypeptide 13 (CYP2A13), phase II conjugate UDP glucuronosyltransferase 2 family, polypeptide B17 (UGT2B17), and phase III transporter ATP-binding cassette, subfamily B (MDR/TAP), member 1 (ABCB1), with genetic polymorphisms implicated in lung cancer. Their genetic interaction and pulmonary expression regulation are largely unknown. We analyzed joint association for CYP2A13 and ABCB1 polymorphisms in 2 independent lung cancer case populations (669 and 566 patients) and 1 common control population (749 subjects), and characterized the trans-acting function of the lung development-related transcription factor forkhead box A2 (FOXA2). We undertook FOXA2 overexpression and down-regulation in lung epithelial cell lines, analyzed functional impact on the transactivation of CYP2A13, UGT2B17, and ABCB1, and measured correlation for their expressions in lung tissues. We found a substantial reduction in cancer risk (OR 0.39; 95% CI 0.25-0.61; Pinteraction = 0.029) associated with combined genotypes for CYP2A13 R257C and a functionary regulatory variant in the cis element of ABCB1 synergistically targeted by GATA binding protein 6 and FOXA2. Genetic manipulation of FOXA2 consistently influenced its binding to and transactivation of the promoters of CYP2A13, UGT2B17, and ABCB1, whose mRNA and protein expressions were all consistently correlated with those of FOXA2 in both tumorous and normal lung tissues. We therefore establish FOXA2 as a core transcriptional modulator for pulmonary xenobiotic metabolic pathways and uncover an etiologically relevant interaction between CYP2A13 and ABCB1, furthering our understanding of expression and function of the xenobiotic metabolism system. © FASEB.

  7. PolyC-binding protein 1 interacts with 5'-untranslated region of enterovirus 71 RNA in membrane-associated complex to facilitate viral replication.

    Directory of Open Access Journals (Sweden)

    Zhen Luo

    Full Text Available Enterovirus 71 (EV71 is one causative agent of hand, foot, and mouth disease (HFMD, which may lead to severe neurological disorders and mortality in children. EV71 genome is a positive single-stranded RNA containing a single open reading frame (ORF flanked by 5'-untranslated region (5'UTR and 3'UTR. The 5'UTR is fundamentally important for virus replication by interacting with cellular proteins. Here, we revealed that poly(C-binding protein 1 (PCBP1 specifically binds to the 5'UTR of EV71. Detailed studies indicated that the RNA-binding K-homologous 1 (KH1 domain of PCBP1 is responsible for its binding to the stem-loop I and IV of EV71 5'UTR. Interestingly, we revealed that PCBP1 is distributed in the nucleus and cytoplasm of uninfected cells, but mainly localized in the cytoplasm of EV71-infected cells due to interaction and co-localization with the viral RNA. Furthermore, sub-cellular distribution analysis showed that PCBP1 is located in ER-derived membrane, in where virus replication occurred in the cytoplasm of EV71-infected cells, suggesting PCBP1 is recruited in a membrane-associated replication complex. In addition, we found that the binding of PCBP1 to 5'UTR resulted in enhancing EV71 viral protein expression and virus production so as to facilitate viral replication. Thus, we revealed a novel mechanism in which PCBP1 as a positive regulator involved in regulation of EV71 replication in the host specialized membrane-associated replication complex, which provides an insight into cellular factors involved in EV71 replication.

  8. Synthetic peptides from two Pf sporozoite invasion-associated proteins specifically interact with HeLa and HepG2 cells.

    Science.gov (United States)

    Arévalo-Pinzón, Gabriela; Curtidor, Hernando; Muñoz, Marina; Patarroyo, Manuel A; Patarroyo, Manuel E

    2011-09-01

    Two recently described molecules have been associated with sporozoite traversal ability and hepatocyte entry: sporozoite invasion-associated proteins (SIAP)-1 and -2. The HeLa and HepG2 cell binding ability of synthetic peptides spanning the whole SIAP-1 and -2 sequences has been studied in the search for identifying these proteins' functionally active specific regions. Twelve HepG-2 and seventeen HeLa cell high-activity binding peptides (HABPs) have been identified in SIAP-1, 8 of them having high specific binding affinity for both cell lines. Four HepG2 HABPs and two HeLa HABPs have been identified in SIAP-2, one of them interacting with both HeLa and HepG2 cells. SIAP-1 and SIAP-2 HABPs bound specifically and saturably to heparin sulfate and chondroitin sulfate-type membrane receptors on host cells. Circular dichroism assays have shown high α-helix content in SIAP-1 and SIAP-2 HABP secondary structure. Immunofluorescence analysis has revealed that specific peptides against SIAP proteins are highly immunogenic in mice and that anti-SIAP-1 and -2 antibodies recognize the native protein in Plasmodium falciparum sporozoites. Polymorphism studies have shown that a most SIAP-1 and -2 HABPs are conserved among P. falciparum strains. Our results have suggested that SIAP-1 and -2 participate in host-pathogen interactions during cell-traversal and hepatocyte invasion and highlighted the relevance of the ongoing identification and study of potentially new molecules when designing a fully protective antimalarial vaccine. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Divergent cloacal gland photo-responsiveness in male Japanese quail exposed to short days and associated differences in social interactions and reproduction.

    Science.gov (United States)

    Dominchin, M F; Busso, J M; Kembro, J M; Marin, R H; Guzman, D A

    2017-01-01

    an indicator of a reduced reproductive dependence on seasonal photoperiod cues. Differences in the expression of aggressions between NR-SD and C-LD males may underlie the observed NR-SD improved copulatory efficiency when interacting with females. © 2016 Poultry Science Association Inc.

  10. Simultaneous profiling of seed-associated bacteria and fungi reveals antagonistic interactions between microorganisms within a shared epiphytic microbiome on Triticum and Brassica seeds

    Science.gov (United States)

    Links, Matthew G; Demeke, Tigst; Gräfenhan, Tom; Hill, Janet E; Hemmingsen, Sean M; Dumonceaux, Tim J

    2014-01-01

    In order to address the hypothesis that seeds from ecologically and geographically diverse plants harbor characteristic epiphytic microbiota, we characterized the bacterial and fungal microbiota associated with Triticum and Brassica seed surfaces. The total microbial complement was determined by amplification and sequencing of a fragment of chaperonin 60 (cpn60). Specific microorganisms were quantified by qPCR. Bacteria and fungi corresponding to operational taxonomic units (OTU) that were identified in the sequencing study were isolated and their interactions examined. A total of 5477 OTU were observed from seed washes. Neither total epiphytic bacterial load nor community richness/evenness was significantly different between the seed types; 578 OTU were shared among all samples at a variety of abundances. Hierarchical clustering revealed that 203 were significantly different in abundance on Triticum seeds compared with Brassica. Microorganisms isolated from seeds showed 99–100% identity between the cpn60 sequences of the isolates and the OTU sequences from this shared microbiome. Bacterial strains identified as Pantoea agglomerans had antagonistic properties toward one of the fungal isolates (Alternaria sp.), providing a possible explanation for their reciprocal abundances on both Triticum and Brassica seeds. cpn60 enabled the simultaneous profiling of bacterial and fungal microbiota and revealed a core seed-associated microbiota shared between diverse plant genera. PMID:24444052

  11. Simultaneous profiling of seed-associated bacteria and fungi reveals antagonistic interactions between microorganisms within a shared epiphytic microbiome on Triticum and Brassica seeds.

    Science.gov (United States)

    Links, Matthew G; Demeke, Tigst; Gräfenhan, Tom; Hill, Janet E; Hemmingsen, Sean M; Dumonceaux, Tim J

    2014-04-01

    In order to address the hypothesis that seeds from ecologically and geographically diverse plants harbor characteristic epiphytic microbiota, we characterized the bacterial and fungal microbiota associated with Triticum and Brassica seed surfaces. The total microbial complement was determined by amplification and sequencing of a fragment of chaperonin 60 (cpn60). Specific microor