WorldWideScience

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.

    2018-05-01

    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. 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.

  4. Cell-free synthesis of functional antibody fragments to provide a structural basis for antibody-antigen interaction.

    Directory of Open Access Journals (Sweden)

    Takayoshi Matsuda

    Full Text Available Growing numbers of therapeutic antibodies offer excellent treatment strategies for many diseases. Elucidation of the interaction between a potential therapeutic antibody and its target protein by structural analysis reveals the mechanism of action and offers useful information for developing rational antibody designs for improved affinity. Here, we developed a rapid, high-yield cell-free system using dialysis mode to synthesize antibody fragments for the structural analysis of antibody-antigen complexes. Optimal synthesis conditions of fragments (Fv and Fab of the anti-EGFR antibody 059-152 were rapidly determined in a day by using a 30-μl-scale unit. The concentration of supplemented disulfide isomerase, DsbC, was critical to obtaining soluble antibody fragments. The optimal conditions were directly applicable to a 9-ml-scale reaction, with linear scalable yields of more than 1 mg/ml. Analyses of purified 059-152-Fv and Fab showed that the cell-free synthesized antibody fragments were disulfide-bridged, with antigen binding activity comparable to that of clinical antibodies. Examination of the crystal structure of cell-free synthesized 059-152-Fv in complex with the extracellular domain of human EGFR revealed that the epitope of 059-152-Fv broadly covers the EGF binding surface on domain III, including residues that formed critical hydrogen bonds with EGF (Asp355EGFR, Gln384EGFR, H409EGFR, and Lys465EGFR, so that the antibody inhibited EGFR activation. We further demonstrated the application of the cell-free system to site-specific integration of non-natural amino acids for antibody engineering, which would expand the availability of therapeutic antibodies based on structural information and rational design. This cell-free system could be an ideal antibody-fragment production platform for functional and structural analysis of potential therapeutic antibodies and for engineered antibody development.

  5. Molecular aspects of antibody-antigen interactions : size reduction of a herpes simplex virus neutralizing antibody and its antigen

    NARCIS (Netherlands)

    Schellekens, Gerardus Antonius

    1996-01-01

    Antibody molecules, produced as a response against foreign substances, interact with their antigen in a very specific manner. Antibodies with a predetermined specificity (monoclonal antibodies) can be produced and are widely used in medicine and science as indicator molecules. Genetic engineering of

  6. 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.

  7. A new application of scanning electrochemical microscopy for the label-free interrogation of antibody-antigen interactions

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, Joanne L.; Davis, Frank; Collyer, Stuart D. [Cranfield Health, Cranfield University, Cranfield, MK43 0AL (United Kingdom); Higson, Seamus P.J., E-mail: s.p.j.higson@cranfield.ac.uk [Cranfield Health, Cranfield University, Cranfield, MK43 0AL (United Kingdom)

    2011-03-18

    Within this work we present a 'proof of principle' study for the use of scanning electrochemical microscopy (SECM) to detect and image biomolecular interactions in a label-free assay as a potential alternative to current fluorescence techniques. Screen-printed carbon electrodes were used as the substrate for the deposition of a dotted array, where the dots consist of biotinylated polyethyleneimine. These were then further derivatised, first with neutravidin and then with a biotinylated antibody to the protein neuron specific enolase (NSE). SECM using a ferrocene carboxylic acid mediator showed clear differences between the array and the surrounding unmodified carbon. Imaging of the arrays before and following exposure to various concentrations of the antigen showed clear evidence for specific binding of the NSE antigen to the antibody derivatised dots. Non-specific binding was quantified. Control experiments with other proteins showed only non-specific binding across the whole of the substrate, thereby confirming that specific binding does occur between the antibody and antigen at the surface of the dots. Binding of the antigen was accompanied by a measured increase in current response, which may be explained in terms of protein electrostatic interaction and hydrophobic interactions to the mediator, thereby increasing the localised mediator flux. A calibration curve was obtained between 500 fg mL{sup -1} to 200 pg mL{sup -1} NSE which demonstrated a logarithmic relationship between the current change upon binding and antigen concentration without the need for any labelling of the substrate.

  8. A theoretical interpretation of the antibody-antigen interactions between Salmonella and a thickness shear mode (TSM) quartz resonator

    Science.gov (United States)

    Bailey, Claude Albert

    This dissertation outlines the developmental procedure for a real-time food-borne pathogen detector that uses a thickness shear mode (TSM) quartz resonator. A theory is discussed which provides some understanding of the measured signals obtained from the TSM resonator-based Salmonella detector. The theory explains surface viscosity and mass effects, but has yet to be fully implemented for anomalous bacterial interactions. An equivalent circuit model for an immunochemical coating and its effect on the TSM resonator frequency is presented. The latter part of this dissertation describes immunological experiments with precoated piezoelectric quartz crystals. A highly purified immunological system was used to optimize the immobilization procedure. The use of biosensors is becoming a viable alternative to conventional analysis and promises to experience dramatic growth, especially after their true potential is realized and more cost-effective assays are developed. Concern about the safety of our food and water supplies will undoubtedly stimulate further research, and miniaturized biosensors will be developed for use by safety inspectors, and concerned personnel. A Salmonella detector has been demonstrated consisting of a TSM resonator with antibodies immobilized in a Langmuir Blodgett (LB) film on the surface [3]. Scanning Electron Microscopy (SEM) images of bound Salmonella bacteria to both polished and unpolished TSM resonators were taken to correlate the mass of the bound organism to the Sauerbrey equation. Antigen-antibody interactions change the acoustic resonant properties that are reflected in the sensor frequency response. The Salmonella detector operates in a liquid environment (Salmonella suspended in a phosphate buffered saline solution). The viscous properties of this liquid overlayer could influence the TSM resonator's response. Various liquid media (buffer solutions, chicken exudate, and varying fat contents of milk) were studied as a function of

  9. Carbon-13 NMR study of switch variant anti-dansyl antibodies: Antigen binding and domain-domain interactions

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Koichi; Matsunaga, Chigusa; Odaka, Asano; Yamato, Sumie; Takaha, Wakana; Shimada, Ichio; Arata, Yoji (Univ. of Tokyo (Japan))

    1991-07-02

    A {sup 13}C NMR study is reported of switch variant anti-dansyl antibodies, which possess the identical V{sub H}, V{sub L}, and C{sub L} domains in conjunction with highly homologous but not identical heavy-chain constant regions. Each of the antibodies has been selectively labeled with {sup 13}C at the carbonyl carbon of Trp, Tyr, His, or Cys residue by growing hybridoma cells in serum-free medium. Spectral assignments have been made by folowing the procedure described previously for the switch variant antibodies labeled with (1-{sup 13}C)Met. On the basis of the spectral data collected for the antibodies and their proteolytic fragments, the authors discuss how {sup 13}C NMR spectroscopy can be used for the structural analyses of antigen binding and also of domain-domain interactions in the antibody molecule.

  10. Carbon-13 NMR study of switch variant anti-dansyl antibodies: Antigen binding and domain-domain interactions

    International Nuclear Information System (INIS)

    Kato, Koichi; Matsunaga, Chigusa; Odaka, Asano; Yamato, Sumie; Takaha, Wakana; Shimada, Ichio; Arata, Yoji

    1991-01-01

    A 13 C NMR study is reported of switch variant anti-dansyl antibodies, which possess the identical V H , V L , and C L domains in conjunction with highly homologous but not identical heavy-chain constant regions. Each of the antibodies has been selectively labeled with 13 C at the carbonyl carbon of Trp, Tyr, His, or Cys residue by growing hybridoma cells in serum-free medium. Spectral assignments have been made by folowing the procedure described previously for the switch variant antibodies labeled with [1- 13 C]Met. On the basis of the spectral data collected for the antibodies and their proteolytic fragments, the authors discuss how 13 C NMR spectroscopy can be used for the structural analyses of antigen binding and also of domain-domain interactions in the antibody molecule

  11. 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.

  12. 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).

  13. The interfacial character of antibody paratopes: analysis of antibody-antigen structures.

    Science.gov (United States)

    Nguyen, Minh N; Pradhan, Mohan R; Verma, Chandra; Zhong, Pingyu

    2017-10-01

    In this study, computational methods are applied to investigate the general properties of antigen engaging residues of a paratope from a non-redundant dataset of 403 antibody-antigen complexes to dissect the contribution of hydrogen bonds, hydrophobic, van der Waals contacts and ionic interactions, as well as role of water molecules in the antigen-antibody interface. Consistent with previous reports using smaller datasets, we found that Tyr, Trp, Ser, Asn, Asp, Thr, Arg, Gly, His contribute substantially to the interactions between antibody and antigen. Furthermore, antibody-antigen interactions can be mediated by interfacial waters. However, there is no reported comprehensive analysis for a large number of structured waters that engage in higher ordered structures at the antibody-antigen interface. From our dataset, we have found the presence of interfacial waters in 242 complexes. We present evidence that suggests a compelling role of these interfacial waters in interactions of antibodies with a range of antigens differing in shape complementarity. Finally, we carry out 296 835 pairwise 3D structure comparisons of 771 structures of contact residues of antibodies with their interfacial water molecules from our dataset using CLICK method. A heuristic clustering algorithm is used to obtain unique structural similarities, and found to separate into 368 different clusters. These clusters are used to identify structural motifs of contact residues of antibodies for epitope binding. This clustering database of contact residues is freely accessible at http://mspc.bii.a-star.edu.sg/minhn/pclick.html. minhn@bii.a-star.edu.sg, chandra@bii.a-star.edu.sg or zhong_pingyu@immunol.a-star.edu.sg. 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. 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

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

    Science.gov (United States)

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

    2017-04-17

    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) technology, the former has four flow cells connected by serial flow configuration, whereas the latter presents 36 reaction spots in parallel through an improvised 6 x 6 crisscross microfluidic channel configuration. The IBIS MX96 also operates based on the SPR sensor technology, with an additional imaging feature that provides detection in spatial orientation. This detection technique coupled with the Continuous Flow Microspotter (CFM) expands the throughput significantly by enabling multiplex array printing and detection of 96 reaction sports simultaneously. In contrast, the Octet RED384 is based on the BioLayer Interferometry (BLI) optical principle, with fiber-optic probes acting as the biosensor to detect interference pattern changes upon binding interactions at the tip surface. Unlike the SPR-based platforms, the BLI system does not rely on continuous flow fluidics; instead, the sensor tips collect readings while they are immersed in analyte solutions of a 384-well microplate during orbital agitation. Each of these biosensor platforms has its own advantages and disadvantages. To provide a direct comparison of these instruments' ability to provide quality kinetic data, the described protocols illustrate experiments that use the same assay format and the same high-quality reagents to characterize antibody-antigen kinetics that fit the simple 1:1 molecular interaction model.

  16. 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

  17. Effect of polyethylene glycol conjugation on conformational and colloidal stability of a monoclonal antibody antigen-binding fragment (Fab').

    Science.gov (United States)

    Roque, Cristopher; Sheung, Anthony; Rahman, Nausheen; Ausar, S Fernando

    2015-02-02

    We have investigated the effects of site specific "hinge" polyethylene glycol conjugation (PEGylation) on thermal, pH, and colloidal stability of a monoclonal antibody antigen-binding fragment (Fab') using a variety of biophysical techniques. The results obtained by circular dichroism (CD), ultraviolet (UV) absorbance, and fluorescence spectroscopy suggested that the physical stability of the Fab' is maximized at pH 6-7 with no apparent differences due to PEGylation. Temperature-induced aggregation experiments revealed that PEGylation was able to increase the transition temperature, as well as prevent the formation of visible and subvisible aggregates. Statistical comparison of the three-index empirical phase diagram (EPD) revealed significant differences in thermal and pH stability signatures between Fab' and PEG-Fab'. Upon mechanical stress, micro-flow imaging (MFI) and measurement of the optical density at 360 nm showed that the PEG-Fab' had significantly higher resistance to surface-induced aggregation compared to the Fab'. Analysis of the interaction parameter, kD, indicated repulsive intermolecular forces for PEG-Fab' and attractive forces for Fab'. In conclusion, PEGylation appears to protect Fab' against thermal and mechanical stress-induced aggregation, likely due to a steric hindrance mechanism.

  18. 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.

  19. 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

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Martin Kreutz

    Full Text Available 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 paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.

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

    KAUST Repository

    Olimpieri, Pier Paolo; Chailyan, Anna; Tramontano, Anna; Marcatili, Paolo

    2013-01-01

    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

  3. Real time detection of antibody-antigen interaction using a laser scanning confocal imaging-surface plasmon resonance system

    International Nuclear Information System (INIS)

    Zhang Hong-Yan; Yang Li-Quan; Ning Ting-Yin; Liu Wei-Min; Sun Jia-Yu; Wang Peng-Fei; Meng Lan; Nie Jia-Cai

    2012-01-01

    A laser scanning confocal imaging-surface plasmon resonance (LSCI-SPR) instrument integrated with a wavelength-dependent surface plasmon resonance (SPR) sensor and a laser scanning confocal microscopy (LSCM) is built to detect the bonding process of human IgG and fluorescent-labeled affinity purified antibodies in real time. The shifts of resonant wavelength at different reaction time stages are obtained by SPR, corresponding well with the changes of the fluorescence intensity collected by using LSCM. The instrument shows the merits of the combination and complementation of the SPR and LSCM, with such advantages as quantificational analysis, high spatial resolution and real time monitor, which are of great importance for practical applications in biosensor and life science. (general)

  4. Use of thermodynamic coupling between antibody-antigen binding and phospholipid acyl chain phase transition energetics to predict immunoliposome targeting affinity.

    Science.gov (United States)

    Klegerman, Melvin E; Zou, Yuejiao; Golunski, Eva; Peng, Tao; Huang, Shao-Ling; McPherson, David D

    2014-09-01

    Thermodynamic analysis of ligand-target binding has been a useful tool for dissecting the nature of the binding mechanism and, therefore, potentially can provide valuable information regarding the utility of targeted formulations. Based on a consistent coupling of antibody-antigen binding and gel-liquid crystal transition energetics observed for antibody-phosphatidylethanolamine (Ab-PE) conjugates, we hypothesized that the thermodynamic parameters and the affinity for antigen of the Ab-PE conjugates could be effectively predicted once the corresponding information for the unconjugated antibody is determined. This hypothesis has now been tested in nine different antibody-targeted echogenic liposome (ELIP) preparations, where antibody is conjugated to dipalmitoylphosphatidylethanolamine (DPPE) head groups through a thioether linkage. Predictions were satisfactory (affinity not significantly different from the population of values found) in five cases (55.6%), but the affinity of the unconjugated antibody was not significantly different from the population of values found in six cases (66.7%), indicating that the affinities of the conjugated antibody tended not to deviate appreciably from those of the free antibody. While knowledge of the affinities of free antibodies may be sufficient to judge their suitability as targeting agents, thermodynamic analysis may still provide valuable information regarding their usefulness for specific applications.

  5. How-to-do-it: Immunological Assays for the Classroom 1. Enzyme Linked Immunosorbent Assay (ELISA): A Laboratory Tool for Demonstration of Antibody-Antigen Interaction.

    Science.gov (United States)

    Russo, A. J.; And Others

    1984-01-01

    Background information, list of required materials, and procedures are provided for an immunological assay which has been modified for use as a classroom/laboratory demonstration of antigen-antibody reaction. The assay is designed for a two and one-half hour laboratory period but may be modified for one hour laboratories. (JN)

  6. 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.

  7. 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.

  8. 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…

  9. 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.

  10. RAIN: RNA-protein Association and Interaction Networks

    DEFF Research Database (Denmark)

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

    2017-01-01

    is challenging due to data heterogeneity. Here, we present a database of ncRNA-RNA and ncRNA-protein interactions and its integration with the STRING database of protein-protein interactions. These ncRNA associations cover four organisms and have been established from curated examples, experimental data...

  11. Interaction of Caffeine Molecular Associates with Water: Theory and Experiment

    OpenAIRE

    Shestopalova, Anna V.

    1990-01-01

    Results of a Monte Carlo simulation of the association process of caffeine (1,3,7-trimethyl-2,6-dioxipurine) in water are presented. Simulation was performed in a cluster approximation ; the system contained 200 water molecules. The nature of the stabilization of caffeine stacking associates in water was considered. Hydrophobic behaviour of methyl group s during association of caffeine molecules in water is shown. The peculiarity of interaction of caffeine associates with wa...

  12. Associative Interactions in Crowded Solutions of Biopolymers Counteract Depletion Effects.

    Science.gov (United States)

    Groen, Joost; Foschepoth, David; te Brinke, Esra; Boersma, Arnold J; Imamura, Hiromi; Rivas, Germán; Heus, Hans A; Huck, Wilhelm T S

    2015-10-14

    The cytosol of Escherichia coli is an extremely crowded environment, containing high concentrations of biopolymers which occupy 20-30% of the available volume. Such conditions are expected to yield depletion forces, which strongly promote macromolecular complexation. However, crowded macromolecule solutions, like the cytosol, are very prone to nonspecific associative interactions that can potentially counteract depletion. It remains unclear how the cytosol balances these opposing interactions. We used a FRET-based probe to systematically study depletion in vitro in different crowded environments, including a cytosolic mimic, E. coli lysate. We also studied bundle formation of FtsZ protofilaments under identical crowded conditions as a probe for depletion interactions at much larger overlap volumes of the probe molecule. The FRET probe showed a more compact conformation in synthetic crowding agents, suggesting strong depletion interactions. However, depletion was completely negated in cell lysate and other protein crowding agents, where the FRET probe even occupied slightly more volume. In contrast, bundle formation of FtsZ protofilaments proceeded as readily in E. coli lysate and other protein solutions as in synthetic crowding agents. Our experimental results and model suggest that, in crowded biopolymer solutions, associative interactions counterbalance depletion forces for small macromolecules. Furthermore, the net effects of macromolecular crowding will be dependent on both the size of the macromolecule and its associative interactions with the crowded background.

  13. 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.

  14. Associated charm production in neutrino-nucleus interactions

    International Nuclear Information System (INIS)

    Kayis-Topaksu, A.; Oenenguet, G.; van Dantzig, R.; de Jong, M.; Oldeman, R.G.C.; Gueler, M.; Koese, U.; Tolun, P.; Catanesi, M.G.; Muciaccia, M.T.; Winter, K.; Van de Vyver, B.; Vilain, P.; Wilquet, G.; Saitta, B.; Di Capua, E.; Ogawa, S.; Shibuya, H.; Hristova, I.R.; Kawamura, T.; Kolev, D.; Meinhard, H.; Panman, J.; Tsenov, R.; Uiterwijk, J.W.E.; Rozanov, A.; Zucchelli, P.; Goldberg, J.; Chikawa, M.; Song, J.S.; Yoon, C.S.; Kodama, K.; Ushida, N.; Aoki, S.; Hara, T.; Delbar, T.; Favart, D.; Gregoire, G.; Kalinin, S.; Makhlioueva, I.; Artamonov, A.; Khovansky, V.; Shamanov, V.; Tsukerman, I.; Gorbunov, P.; Bruski, N.; Frekers, D.; Hoshino, K.; Kawada, J.; Komatsu, M.; Miyanishi, M.; Nakamura, M.; Nakano, T.; Narita, K.; Niu, K.; Niwa, K.; Nonaka, N.; Sato, O.; Toshito, T.; Buontempo, S.; Cocco, A.G.; D'Ambrosio, N.; De Lellis, G.; De Rosa, G.; Di Capua, F.; Fiorillo, G.; Marotta, A.; Migliozzi, P.; Scotto Lavina, L.; Strolin, P.; Tioukov, V.; Okusawa, T.; Dore, U.; Loverre, P.F.; Ludovici, L.; Rosa, G.; Santacesaria, R.; Satta, A.; Spada, F.R.; Barbuto, E.; Bozza, C.; Grella, G.; Romano, G.; Sirignano, C.; Sorrentino, S.; Sato, Y.; Tezuka, I.

    2007-01-01

    In this paper a search for associated charm production both in neutral and charged current ν-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 ν 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 ν interactions, σ(c anti cν)/σ NC DIS =(3.62 +2.95 -2.42 (stat)±0.54(syst)) x 10 -3 has been measured. One event with two charm decays has been observed in charged-current ν μ 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 σ(c anti cμ - )/σ CC -4 . (orig.)

  15. 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 ...

  16. 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…

  17. Investigating the association between social interactions and personality states dynamics.

    Science.gov (United States)

    Gundogdu, Didem; Finnerty, Ailbhe N; Staiano, Jacopo; Teso, Stefano; Passerini, Andrea; Pianesi, Fabio; Lepri, Bruno

    2017-09-01

    The recent personality psychology literature has coined the name of personality states to refer to states having the same behavioural, affective and cognitive content (described by adjectives) as the corresponding trait, but for a shorter duration. The variability in personality states may be the reaction to specific characteristics of situations. The aim of our study is to investigate whether specific situational factors, that is, different configurations of face-to-face interactions, are predictors of variability of personality states in a work environment. The obtained results provide evidence that within-person variability in personality is associated with variation in face-to-face interactions. Interestingly, the effects differ by type and level of the personality states: adaptation effects for Agreeableness and Emotional Stability, whereby the personality states of an individual trigger similar states in other people interacting with them and complementarity effects for Openness to Experience, whereby the personality states of an individual trigger opposite states in other people interacting with them. Overall, these findings encourage further research to characterize face-to-face and social interactions in terms of their relevance to personality states.

  18. Scanning probe and optical tweezer investigations of biomolecular interactions

    International Nuclear Information System (INIS)

    Rigby-Singleton, Shellie

    2002-01-01

    A complex array of intermolecular forces controls the interactions between and within biological molecules. The desire to empirically explore the fundamental forces has led to the development of several biophysical techniques. Of these, the atomic force microscope (AFM) and the optical tweezers have been employed throughout this thesis to monitor the intermolecular forces involved in biomolecular interactions. The AFM is a well-established force sensing technique capable of measuring biomolecular interactions at a single molecule level. However, its versatility has not been extrapolated to the investigation of a drug-enzyme complex. The energy landscape for the force induced dissociation of the DHFR-methotrexate complex was studied. Revealing an energy barrier to dissociation located ∼0.3 nm from the bound state. Unfortunately, the AFM has a limited range of accessible loading rates and in order to profile the complete energy landscape alternative force sensing instrumentation should be considered, for example the BFP and optical tweezers. Thus, this thesis outlines the development and construction an optical trap capable of measuring intermolecular forces between biomolecules at the single molecule level. To demonstrate the force sensing abilities of the optical set up, proof of principle measurements were performed which investigate the interactions between proteins and polymer surfaces subjected to varying degrees of argon plasma treatment. Complementary data was gained from measurements performed independently by the AFM. Changes in polymer resistance to proteins as a response to changes in polymer surface chemistry were detected utilising both AFM and optical tweezers measurements. Finally, the AFM and optical tweezers were employed as ultrasensitive biosensors. Single molecule investigations of the antibody-antigen interaction between the cardiac troponin I marker and its complementary antibody, reveals the impact therapeutic concentrations of heparin have

  19. 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.

  20. 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.

  1. 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.

  2. Instrumental biosensors: new perspectives for the analysis of biomolecular interactions.

    Science.gov (United States)

    Nice, E C; Catimel, B

    1999-04-01

    The use of instrumental biosensors in basic research to measure biomolecular interactions in real time is increasing exponentially. Applications include protein-protein, protein-peptide, DNA-protein, DNA-DNA, and lipid-protein interactions. Such techniques have been applied to, for example, antibody-antigen, receptor-ligand, signal transduction, and nuclear receptor studies. This review outlines the principles of two of the most commonly used instruments and highlights specific operating parameters that will assist in optimising experimental design, data generation, and analysis.

  3. 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

  4. Specificity of molecular interactions in transient protein-protein interaction interfaces.

    Science.gov (United States)

    Cho, Kyu-il; Lee, KiYoung; Lee, Kwang H; Kim, Dongsup; Lee, Doheon

    2006-11-15

    In this study, we investigate what types of interactions are specific to their biological function, and what types of interactions are persistent regardless of their functional category in transient protein-protein heterocomplexes. This is the first approach to analyze protein-protein interfaces systematically at the molecular interaction level in the context of protein functions. We perform systematic analysis at the molecular interaction level using classification and feature subset selection technique prevalent in the field of pattern recognition. To represent the physicochemical properties of protein-protein interfaces, we design 18 molecular interaction types using canonical and noncanonical interactions. Then, we construct input vector using the frequency of each interaction type in protein-protein interface. We analyze the 131 interfaces of transient protein-protein heterocomplexes in PDB: 33 protease-inhibitors, 52 antibody-antigens, 46 signaling proteins including 4 cyclin dependent kinase and 26 G-protein. Using kNN classification and feature subset selection technique, we show that there are specific interaction types based on their functional category, and such interaction types are conserved through the common binding mechanism, rather than through the sequence or structure conservation. The extracted interaction types are C(alpha)-- H...O==C interaction, cation...anion interaction, amine...amine interaction, and amine...cation interaction. With these four interaction types, we achieve the classification success rate up to 83.2% with leave-one-out cross-validation at k = 15. Of these four interaction types, C(alpha)--H...O==C shows binding specificity for protease-inhibitor complexes, while cation-anion interaction is predominant in signaling complexes. The amine ... amine and amine...cation interaction give a minor contribution to the classification accuracy. When combined with these two interactions, they increase the accuracy by 3.8%. In the case of

  5. 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

  6. The interaction of antibodies with lipid membranes unraveled by fluorescence methodologies

    Science.gov (United States)

    Figueira, Tiago N.; Veiga, Ana Salomé; Castanho, Miguel A. R. B.

    2014-12-01

    The interest and investment in antibody therapies has reached an overwhelming scale in the last decade. Yet, little concern has been noticed among the scientific community to unravel important interactions of antibodies with biological structures other than their respective epitopes. Lipid membranes are particularly relevant in this regard as they set the stage for protein-protein recognition, a concept potentially inclusive of antibody-antigen recognition. Fluorescence techniques allow experimental monitoring of protein partition between aqueous and lipid phases, deciphering events of adsorption, insertion and diffusion. This review focuses on the available fluorescence spectroscopy methodologies directed to the study of antibody-membrane interactions.

  7. Social interaction is associated with changes in infants’ motor activity

    Directory of Open Access Journals (Sweden)

    Céline Scola

    2015-11-01

    Full Text Available Background: In developmental research, infants are commonly assumed to be early stakeholders in interactions with their caregivers. The tools that infants can use to interact with others vary from visual contact to smiling or vocalizing, and also include motor activity. However, surprisingly few studies have explored how the nature and context of social interactions affect infants’ engagement in motor activity. Methods: We investigated the kinematic properties of foot and face movements produced by 11 infants aged between 5 and 9 months during six contrasting dyadic episodes (i.e. passive presence of a stranger or the infant's mother, weak or intense interaction with the stranger/mother as she sings a nursery play song. Results: The infants’ face and foot motor activity was significantly reduced during the interactive episodes, compared with the episodes without any interaction, in both the mother and stranger conditions. Furthermore, the level of their motor activity was significantly lower in the stranger condition than in the mother one for some parameters. Conclusion: These results are in line with those reported by previous studies and confirm the relevance of using motor activity to delineate the early forms of interactive episodes in infants.

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

    DEFF Research Database (Denmark)

    Lichota, J.; Grasser, Klaus D.

    2003-01-01

    maize HMGA and five different HMGB proteins with mononucleosomes (containing approx. 165 bp of DNA) purified from micrococcal nuclease-digested maize chromatin. The HMGB proteins interacted with the nucleosomes independent of the presence of the linker histone H1, while the binding of HMGA...

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

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research August 2017; 16 (8): 2007-2012. ISSN: 1596-5996 ... Original Research Article. Association ... affect the stability of plaques among patients with ... inflammation caused by proliferation of bacteria,.

  10. 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,...

  11. RAID: a comprehensive resource for human RNA-associated (RNA–RNA/RNA–protein) interaction

    Science.gov (United States)

    Zhang, Xiaomeng; Wu, Deng; Chen, Liqun; Li, Xiang; Yang, Jinxurong; Fan, Dandan; Dong, Tingting; Liu, Mingyue; Tan, Puwen; Xu, Jintian; Yi, Ying; Wang, Yuting; Zou, Hua; Hu, Yongfei; Fan, Kaili; Kang, Juanjuan; Huang, Yan; Miao, Zhengqiang; Bi, Miaoman; Jin, Nana; Li, Kongning; Li, Xia; Xu, Jianzhen; Wang, Dong

    2014-01-01

    Transcriptomic analyses have revealed an unexpected complexity in the eukaryote transcriptome, which includes not only protein-coding transcripts but also an expanding catalog of noncoding RNAs (ncRNAs). Diverse coding and noncoding RNAs (ncRNAs) perform functions through interaction with each other in various cellular processes. In this project, we have developed RAID (http://www.rna-society.org/raid), an RNA-associated (RNA–RNA/RNA–protein) interaction database. RAID intends to provide the scientific community with all-in-one resources for efficient browsing and extraction of the RNA-associated interactions in human. This version of RAID contains more than 6100 RNA-associated interactions obtained by manually reviewing more than 2100 published papers, including 4493 RNA–RNA interactions and 1619 RNA–protein interactions. Each entry contains detailed information on an RNA-associated interaction, including RAID ID, RNA/protein symbol, RNA/protein categories, validated method, expressing tissue, literature references (Pubmed IDs), and detailed functional description. Users can query, browse, analyze, and manipulate RNA-associated (RNA–RNA/RNA–protein) interaction. RAID provides a comprehensive resource of human RNA-associated (RNA–RNA/RNA–protein) interaction network. Furthermore, this resource will help in uncovering the generic organizing principles of cellular function network. PMID:24803509

  12. Toppar: an interactive browser for viewing association study results.

    Science.gov (United States)

    Juliusdottir, Thorhildur; Banasik, Karina; Robertson, Neil R; Mott, Richard; McCarthy, Mark I

    2018-06-01

    Data integration and visualization help geneticists make sense of large amounts of data. To help facilitate interpretation of genetic association data we developed Toppar, a customizable visualization tool that stores results from association studies and enables browsing over multiple results, by combining features from existing tools and linking to appropriate external databases. Detailed information on Toppar's features and functionality are on our website http://mccarthy.well.ox.ac.uk/toppar/docs along with instructions on how to download, install and run Toppar. Our online version of Toppar is accessible from the website and can be test-driven using Firefox, Safari or Chrome on sub-sets of publicly available genome-wide association study anthropometric waist and body mass index data (Locke et al., 2015; Shungin et al., 2015) from the Genetic Investigation of ANthropometric Traits consortium. totajuliusd@gmail.com.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Unsupportive social interactions and affective states: examining associations of two oxytocin-related polymorphisms.

    Science.gov (United States)

    McInnis, Opal A; McQuaid, Robyn J; Matheson, Kimberly; Anisman, Hymie

    2017-01-01

    Two single-nucleotide polymorphisms (SNPs) on oxytocin-related genes, specifically the oxytocin receptor (OXTR) rs53576 and the CD38 rs3796863 variants, have been associated with alterations in prosocial behaviors. A cross-sectional study was conducted among undergraduate students (N = 476) to examine associations between the OXTR and CD38 polymorphisms and unsupportive social interactions and mood states. Results revealed no association between perceived levels of unsupportive social interactions and the OXTR polymorphism. However, A carriers of the CD38 polymorphism, a variant previously associated with elevated oxytocin, reported greater perceived peer unsupportive interactions compared to CC carriers. As expected, perceived unsupportive interactions from peers was associated with greater negative affect, which was moderated by the CD38 polymorphism. Specifically, this relation was stronger among CC carriers of the CD38 polymorphism (a variant thought to be linked to lower oxytocin). When examining whether the OXTR polymorphism moderated the relation between unsupportive social interactions from peers and negative affect there was a trend toward significance, however, this did not withstand multiple testing corrections. These findings are consistent with the perspective that a variant on an oxytocin polymorphism that may be tied to lower oxytocin is related to poor mood outcomes in association with negative social interactions. At the same time, having a genetic constitution presumed to be associated with higher oxytocin was related to increased perceptions of unsupportive social interactions. These seemingly paradoxical findings could be related to previous reports in which variants associated with prosocial behaviors were also tied to relatively more effective coping styles to deal with challenges.

  1. Association between social interaction and affect in nursing home residents with dementia.

    Science.gov (United States)

    Jao, Ying-Ling; Loken, Eric; MacAndrew, Margaret; Van Haitsma, Kimberly; Kolanowski, Ann

    2018-06-01

    Social interactions that lead to positive affect are fundamental to human well-being. However, individuals with dementia are challenged to achieve positive social interaction. It is unclear how social interactions influence affect in people with dementia. This study examined the association between social interactions and affect in nursing home residents with dementia. This repeated measures study used baseline data from a clinical trial in which 126 residents from 12 nursing homes were enrolled. Participants were video recorded twice daily on five days. Ratings of social interaction and affect were taken from the videotapes using the Interacting with People subscale of the Passivity in Dementia and the Philadelphia Geriatric Center Apparent Affect Rating Scale. Linear mixed models were used for analysis. Social interaction was significantly related to higher interest and pleasure at within- and between-person levels. Social interaction significantly predicted anxiety and sadness at the between-person level only. Residents with higher cognitive function also displayed greater pleasure. Greater interest and anxiety was evident during the afternoon hours. This study supports the impact of social interactions on positive and negative affect. Findings can guide intervention development, aimed at promoting positive social interactions and improving affect for people with dementia.

  2. Slow, target associated particles produced in ultrarelativistic heavy-ion interactions

    Energy Technology Data Exchange (ETDEWEB)

    Adamovich, M I; Aggarwal, M M; Alexandrov, Y A; Andreeva, N P; Anson, Z V; Arora, R; Avetyan, F A; Badyal, S K; Basova, E; Bhalla, K B; Bhasin, A; Bhatia, V S; Bogdanov, V G; Bubnov, V I; Burnett, T H; Cai, X; Chasnikov, I Y; Chernova, L P; Chernyavsky, M M; Dressel, B; Eligbaeva, G Z; Eremenko, L E; Friedlander, E M; Gaitinov, A S; Ganssauge, E R; Garpman, S; Gerassimov, S G; Grote, J; Gulamov, K G; Gupta, S K; Gupta, V; Heckman, H H; Huang, H; Jakobsson, B; Judek, B; Kachroo, S; Kadyrov, F G; Kalyachkina, G S; Kanygina, E K; Karabova, M; Kaul, G L; Kaur, M; Kharlamov, S P; Koss, Y; Krasnov,; Kumar,; Lal, P; Larionova,; Lepetan,; Lindstrom,; Liu,; Lokanathan, S; Lord, J; Lukicheva, N S; Luo, S B; Mangotra, L K; Marutyan,; Maslennikova, N V; Mittra, I S; Mookerjee, S; Mueller, C; Nasrulaeva, H; Nasyrov, S H; Navotny, V S; Orlova, G I; Otterlund, I; Palsania, H S; Peresadko, N G; Petrov, N V; Plyushchev, V A; Qian, W Y; Raniwala,; EMU01 Collaboration

    1991-06-20

    The slow, target associated particles produced in ultrarelativistic heavy-ion interactions are a quantitative probe of the cascading processes in the spectator parts of the target nucleus. These processes are directly influenced by the proper timescale for the formation of hadronic matter. In this letter we show experimental data on singly and multiply charged particles, with velocities smaller than 0.7c, produced in ultrarelativistic heavy-ion interactions in nuclear emulsion. (orig.).

  3. A novel test for gene-ancestry interactions in genome-wide association data.

    Directory of Open Access Journals (Sweden)

    Joanna L Davies

    Full Text Available Genome-wide association study (GWAS data on a disease are increasingly available from multiple related populations. In this scenario, meta-analyses can improve power to detect homogeneous genetic associations, but if there exist ancestry-specific effects, via interactions on genetic background or with a causal effect that co-varies with genetic background, then these will typically be obscured. To address this issue, we have developed a robust statistical method for detecting susceptibility gene-ancestry interactions in multi-cohort GWAS based on closely-related populations. We use the leading principal components of the empirical genotype matrix to cluster individuals into "ancestry groups" and then look for evidence of heterogeneous genetic associations with disease or other trait across these clusters. Robustness is improved when there are multiple cohorts, as the signal from true gene-ancestry interactions can then be distinguished from gene-collection artefacts by comparing the observed interaction effect sizes in collection groups relative to ancestry groups. When applied to colorectal cancer, we identified a missense polymorphism in iron-absorption gene CYBRD1 that associated with disease in individuals of English, but not Scottish, ancestry. The association replicated in two additional, independently-collected data sets. Our method can be used to detect associations between genetic variants and disease that have been obscured by population genetic heterogeneity. It can be readily extended to the identification of genetic interactions on other covariates such as measured environmental exposures. We envisage our methodology being of particular interest to researchers with existing GWAS data, as ancestry groups can be easily defined and thus tested for interactions.

  4. Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.

    Directory of Open Access Journals (Sweden)

    Ifeoma Jane Nwigwe

    Full Text Available CCCTC binding factor (CTCF is involved in organizing chromosomes into mega base-sized, topologically associated domains (TADs along with other factors that define sub-TAD organization. CTCF-Cohesin interactions have been shown to be critical for transcription insulation activity as it stabilizes long-range interactions to promote proper gene expression. Previous studies suggest that heterochromatin boundary activity of CTCF may be independent of Cohesin, and there may be additional mechanisms for defining topological domains. Here, we show that a boundary site we previously identified known as CTCF binding site 5 (CBS5 from the homeotic gene cluster A (HOXA locus exhibits robust promoter activity. This promoter activity from the CBS5 boundary element generates a long noncoding RNA that we designate as boundary associated long noncoding RNA-1 (blncRNA1. Functional characterization of this RNA suggests that the transcript stabilizes long-range interactions at the HOXA locus and promotes proper expression of HOXA genes. Additionally, our functional analysis also shows that this RNA is not needed in the stabilization of CTCF-Cohesin interactions however CTCF-Cohesin interactions are critical in the transcription of blncRNA1. Thus, the CTCF-associated boundary element, CBS5, employs both Cohesin and noncoding RNA to establish and maintain topologically associated domains at the HOXA locus.

  5. 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.

  6. 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).......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)....

  7. 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.

  8. Capturing the spectrum of interaction effects in genetic association studies by simulated evaporative cooling network analysis.

    Directory of Open Access Journals (Sweden)

    Brett A McKinney

    2009-03-01

    Full Text Available Evidence from human genetic studies of several disorders suggests that interactions between alleles at multiple genes play an important role in influencing phenotypic expression. Analytical methods for identifying Mendelian disease genes are not appropriate when applied to common multigenic diseases, because such methods investigate association with the phenotype only one genetic locus at a time. New strategies are needed that can capture the spectrum of genetic effects, from Mendelian to multifactorial epistasis. Random Forests (RF and Relief-F are two powerful machine-learning methods that have been studied as filters for genetic case-control data due to their ability to account for the context of alleles at multiple genes when scoring the relevance of individual genetic variants to the phenotype. However, when variants interact strongly, the independence assumption of RF in the tree node-splitting criterion leads to diminished importance scores for relevant variants. Relief-F, on the other hand, was designed to detect strong interactions but is sensitive to large backgrounds of variants that are irrelevant to classification of the phenotype, which is an acute problem in genome-wide association studies. To overcome the weaknesses of these data mining approaches, we develop Evaporative Cooling (EC feature selection, a flexible machine learning method that can integrate multiple importance scores while removing irrelevant genetic variants. To characterize detailed interactions, we construct a genetic-association interaction network (GAIN, whose edges quantify the synergy between variants with respect to the phenotype. We use simulation analysis to show that EC is able to identify a wide range of interaction effects in genetic association data. We apply the EC filter to a smallpox vaccine cohort study of single nucleotide polymorphisms (SNPs and infer a GAIN for a collection of SNPs associated with adverse events. Our results suggest an important

  9. 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.

  10. A new protein-protein interaction sensor based on tripartite split-GFP association.

    Science.gov (United States)

    Cabantous, Stéphanie; Nguyen, Hau B; Pedelacq, Jean-Denis; Koraïchi, Faten; Chaudhary, Anu; Ganguly, Kumkum; Lockard, Meghan A; Favre, Gilles; Terwilliger, Thomas C; Waldo, Geoffrey S

    2013-10-04

    Monitoring protein-protein interactions in living cells is key to unraveling their roles in numerous cellular processes and various diseases. Previously described split-GFP based sensors suffer from poor folding and/or self-assembly background fluorescence. Here, we have engineered a micro-tagging system to monitor protein-protein interactions in vivo and in vitro. The assay is based on tripartite association between two twenty amino-acids long GFP tags, GFP10 and GFP11, fused to interacting protein partners, and the complementary GFP1-9 detector. When proteins interact, GFP10 and GFP11 self-associate with GFP1-9 to reconstitute a functional GFP. Using coiled-coils and FRB/FKBP12 model systems we characterize the sensor in vitro and in Escherichia coli. We extend the studies to mammalian cells and examine the FK-506 inhibition of the rapamycin-induced association of FRB/FKBP12. The small size of these tags and their minimal effect on fusion protein behavior and solubility should enable new experiments for monitoring protein-protein association by fluorescence.

  11. 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...

  12. 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…

  13. 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…

  14. 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

  15. Increased frequency of social interaction is associated with enjoyment enhancement and reward system activation.

    Science.gov (United States)

    Kawamichi, Hiroaki; Sugawara, Sho K; Hamano, Yuki H; Makita, Kai; Kochiyama, Takanori; Sadato, Norihiro

    2016-04-19

    Positive social interactions contribute to the sense that one's life has meaning. Enjoyment of feelings associated through social interaction motivates humans to build social connections according to their personal preferences. Therefore, we hypothesized that social interaction itself activates the reward system in a manner that depends upon individual interaction preferences. To test this hypothesis, we conducted a functional magnetic resonance imaging (fMRI) study in which 38 participants played a virtual ball-toss game in which the number of ball tosses to the participant was either similar to (normal-frequency condition) or higher than (high-frequency condition) the number of tosses to the other players. Participants reported greater-than-anticipated enjoyment during the high-frequency condition, suggesting that receiving a social reward led to unexpected positive feelings. Consistent with this, the high-frequency condition produced stronger activation in the ventral striatum, which is part of the reward system, and the precuneus, representing positive self-image, which might be translated to social reward. Furthermore, ventral striatal activation covaried with individual participants' preference for interactions with others. These findings suggest that an elevated frequency of social interaction is represented as a social reward, which might motivate individuals to promote social interaction in a manner that is modulated by personal preference.

  16. 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.

  17. An information-gain approach to detecting three-way epistatic interactions in genetic association studies

    DEFF Research Database (Denmark)

    Hu, Ting; Chen, Yuanzhu; Kiralis, Jeff W

    2013-01-01

    Background Epistasis has been historically used to describe the phenomenon that the effect of a given gene on a phenotype can be dependent on one or more other genes, and is an essential element for understanding the association between genetic and phenotypic variations. Quantifying epistasis......-way epistasis. Methods Such a measure is based on information gain, and is able to separate all lower order effects from pure three-way epistasis. Results Our method was verified on synthetic data and applied to real data from a candidate-gene study of tuberculosis in a West African population....... In the tuberculosis data, we found a statistically significant pure three-way epistatic interaction effect that was stronger than any lower-order associations. Conclusion Our study provides a methodological basis for detecting and characterizing high-order gene-gene interactions in genetic association studies....

  18. Thioredoxin interacting protein and its association with clinical outcome in gastro-oesophageal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Caroline M. Woolston

    2013-01-01

    Full Text Available The overall prognosis for operable gastro-oesophageal adenocarcinoma remains poor and therefore neoadjuvant chemotherapy has become the standard of care, in addition to radical surgery. Certain anticancer agents (e.g. anthracyclines and cisplatin generate damaging reactive oxygen species as by-products of their mechanism of action. Drug effectiveness can therefore depend upon the presence of cellular redox buffering systems that are often deregulated in cancer. The expression of the redox protein, thioredoxin interacting protein, was assessed in gastro-oesophageal adenocarcinomas. Thioredoxin interacting protein expression was assessed using conventional immunohistochemistry on a tissue microarray of 140 adenocarcinoma patients treated by primary surgery alone and 88 operable cases treated with neoadjuvant chemotherapy. In the primary surgery cases, high thioredoxin interacting protein expression associated with a lack of lymph node involvement (p=0.005, no perineural invasion (p=0.030 and well/moderate tumour differentiation (p=0.033. In the neoadjuvant tumours, high thioredoxin interacting protein expression was an independent marker for improved disease specific survival (p=0.002 especially in cases with anthracycline-based regimes (p=0.008. This study highlights the potential of thioredoxin interacting protein as a biomarker for response in neoadjuvant treated gastro-oesophageal adenocarcinoma and may represent a useful therapeutic target due to its association with tumour progression.

  19. 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.

  20. Associations between Relational Pronoun Usage and the Quality of Early Family Interactions

    OpenAIRE

    Galdiolo, Sarah; Roskam, Isabelle; Verhofstadt, Lesley L.; De Mol, Jan; Dewinne, Laura; Vandaudenard, Sylvain

    2016-01-01

    Our study examined the relationships of relational pronouns used in parental conversation to the quality of early family interactions, as indexed by Family Alliance (FA). We hypothesized that more positive family interactions were associated with the use of more we-pronouns (e.g., we, us, our; we-ness) and fewer I- and you-pronouns (e.g., I, me, you, your; separateness) by both mothers and fathers. Our statistical model using a multilevel modeling framework and two levels of analysis (i.e., a...

  1. 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...

  2. Mining association patterns of drug-interactions using post marketing FDA's spontaneous reporting data.

    Science.gov (United States)

    Ibrahim, Heba; Saad, Amr; Abdo, Amany; Sharaf Eldin, A

    2016-04-01

    Pharmacovigilance (PhV) is an important clinical activity with strong implications for population health and clinical research. The main goal of PhV is the timely detection of adverse drug events (ADEs) that are novel in their clinical nature, severity and/or frequency. Drug interactions (DI) pose an important problem in the development of new drugs and post marketing PhV that contribute to 6-30% of all unexpected ADEs. Therefore, the early detection of DI is vital. Spontaneous reporting systems (SRS) have served as the core data collection system for post marketing PhV since the 1960s. The main objective of our study was to particularly identify signals of DI from SRS. In addition, we are presenting an optimized tailored mining algorithm called "hybrid Apriori". The proposed algorithm is based on an optimized and modified association rule mining (ARM) approach. A hybrid Apriori algorithm has been applied to the SRS of the United States Food and Drug Administration's (U.S. FDA) adverse events reporting system (FAERS) in order to extract significant association patterns of drug interaction-adverse event (DIAE). We have assessed the resulting DIAEs qualitatively and quantitatively using two different triage features: a three-element taxonomy and three performance metrics. These features were applied on two random samples of 100 interacting and 100 non-interacting DIAE patterns. Additionally, we have employed logistic regression (LR) statistic method to quantify the magnitude and direction of interactions in order to test for confounding by co-medication in unknown interacting DIAE patterns. Hybrid Apriori extracted 2933 interacting DIAE patterns (including 1256 serious ones) and 530 non-interacting DIAE patterns. Referring to the current knowledge using four different reliable resources of DI, the results showed that the proposed method can extract signals of serious interacting DIAEs. Various association patterns could be identified based on the relationships among

  3. 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.

  4. Associations between relational pronoun usage and the quality of early family interactions

    Directory of Open Access Journals (Sweden)

    Sarah Galdiolo

    2016-11-01

    Full Text Available Our study examined the relationships of relational pronouns used in parental conversation to the quality of early family interactions, as indexed by Family Alliance (FA. We hypothesized that more positive family interactions were associated with the use of more we-pronouns (e.g., we, us, our; we-ness and fewer I- and you-pronouns (e.g., I, me, you, your; separateness by both mothers and fathers. Our statistical model using a multilevel modelling framework and two levels of analysis (i.e., a couple level and an individual level was tested on 47 non-referred families (n = 31 primiparous families; child’s age, M = 15.75 months, SD = 2.73 with we-ness and separateness as outcomes and FA functions as between-dyads variables. Analyses revealed that we-ness within the parental couple was only positively associated with family affect sharing while separateness was negatively associated with different FA functions (e.g., communication mistakes. Our main finding suggested that the kinds of personal pronouns used by parental couples when discussing children’s education would be associated to the emotional quality of the family interactions.

  5. Associations between Relational Pronoun Usage and the Quality of Early Family Interactions.

    Science.gov (United States)

    Galdiolo, Sarah; Roskam, Isabelle; Verhofstadt, Lesley L; De Mol, Jan; Dewinne, Laura; Vandaudenard, Sylvain

    2016-01-01

    Our study examined the relationships of relational pronouns used in parental conversation to the quality of early family interactions, as indexed by Family Alliance (FA). We hypothesized that more positive family interactions were associated with the use of more we-pronouns (e.g., we, us, our; we-ness ) and fewer I- and you-pronouns (e.g., I, me, you, your; separateness ) by both mothers and fathers. Our statistical model using a multilevel modeling framework and two levels of analysis (i.e., a couple level and an individual level) was tested on 47 non-referred families ( n = 31 primiparous families; child's age, M = 15.75 months, SD = 2.73) with we-ness and separateness as outcomes and FA functions as between-dyads variables. Analyses revealed that we-ness within the parental couple was only positively associated with family affect sharing while separateness was negatively associated with different FA functions (e.g., communication mistakes). Our main finding suggested that the kinds of personal pronouns used by parental couples when discussing children's education would be associated to the emotional quality of the family interactions.

  6. Independent Associations and Interactions of Perceived Neighborhood and Psychosocial Constructs on Adults' Physical Activity.

    Science.gov (United States)

    Dwyer, Laura A; Patel, Minal; Nebeling, Linda C; Oh, April Y

    2018-05-01

    Neighborhood and psychosocial variables are related to physical activity (PA), yet interactions between these factors in predicting PA are infrequently studied. This analysis examines the independent associations and interactions between self-reported neighborhood and psychosocial variables in relation to moderate to vigorous PA (MVPA) among adults from a US panel sample. In adjusted models, neighborhood social capital was positively associated with meeting MVPA guidelines. Fewer barriers, greater self-efficacy, and greater autonomous motivation also corresponded with greater odds of meeting MVPA guidelines. An interaction between social capital and autonomous motivation showed that social capital was only associated with MVPA when autonomous motivation was high. Participants who reported both high autonomous motivation and high social capital were most likely to meet MVPA guidelines. Neighborhood social capital, barriers, self-efficacy, and autonomous motivation may be important correlates in promoting adults' PA. Future directions include using objective neighborhood and PA data in similar analyses and investigating associations of neighborhood and psychosocial variables with multiple PA activities. Intervention research to promote PA should also examine whether effects of interventions targeting psychosocial constructs are moderated by features of an individual's neighborhood or whether perceived social capital can be addressed in interventions in conjunction with psychosocial variables.

  7. GIMDA: Graphlet interaction-based MiRNA-disease association prediction.

    Science.gov (United States)

    Chen, Xing; Guan, Na-Na; Li, Jian-Qiang; Yan, Gui-Ying

    2018-03-01

    MicroRNAs (miRNAs) have been confirmed to be closely related to various human complex diseases by many experimental studies. It is necessary and valuable to develop powerful and effective computational models to predict potential associations between miRNAs and diseases. In this work, we presented a prediction model of Graphlet Interaction for MiRNA-Disease Association prediction (GIMDA) by integrating the disease semantic similarity, miRNA functional similarity, Gaussian interaction profile kernel similarity and the experimentally confirmed miRNA-disease associations. The related score of a miRNA to a disease was calculated by measuring the graphlet interactions between two miRNAs or two diseases. The novelty of GIMDA lies in that we used graphlet interaction to analyse the complex relationships between two nodes in a graph. The AUCs of GIMDA in global and local leave-one-out cross-validation (LOOCV) turned out to be 0.9006 and 0.8455, respectively. The average result of five-fold cross-validation reached to 0.8927 ± 0.0012. In case study for colon neoplasms, kidney neoplasms and prostate neoplasms based on the database of HMDD V2.0, 45, 45, 41 of the top 50 potential miRNAs predicted by GIMDA were validated by dbDEMC and miR2Disease. Additionally, in the case study of new diseases without any known associated miRNAs and the case study of predicting potential miRNA-disease associations using HMDD V1.0, there were also high percentages of top 50 miRNAs verified by the experimental literatures. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  8. Interactions Between Energy Drink Consumption and Sleep Problems: Associations with Alcohol Use Among Young Adolescents.

    Science.gov (United States)

    Marmorstein, Naomi R

    2017-09-01

    Background: Energy drink consumption and sleep problems are both associated with alcohol use among adolescents. In addition, caffeine consumption (including energy drinks) is associated with sleep problems. However, information about how these three constructs may interact is limited. The goal of this study was to examine potential interactions between energy drink consumption and sleep problems in the concurrent prediction of alcohol use among young adolescents. Coffee and soda consumption were also examined for comparison. Methods: Participants from the Camden Youth Development Study were included ( n  = 127; mean age = 13.1; 68% Hispanic, 29% African American) and questionnaire measures of frequency of caffeinated beverage consumption (energy drinks, coffee, and soda), sleep (initial insomnia, sleep disturbances, daytime fatigue, and sleep duration), and alcohol consumption were used. Regression analyses were conducted to examine interactions between caffeinated beverage consumption and sleep in the concurrent prediction of alcohol use. Results: Energy drink consumption interacted with initial insomnia and daytime fatigue to concurrently predict particularly frequent alcohol use among those with either of these sleep-related problems and energy drink consumption. The pattern of results for coffee consumption was similar for insomnia but reached only a trend level of significance. Results of analyses examining soda consumption were nonsignificant. Conclusions: Young adolescents who both consume energy drinks and experience initial insomnia and/or daytime fatigue are at particularly high risk for alcohol use. Coffee consumption appears to be associated with similar patterns. Longitudinal research is needed to explain the developmental pathways by which these associations emerge, as well as mediators and moderators of these associations.

  9. Dyadic variability in mother-adolescent interactions: developmental trajectories and associations with psychosocial functioning.

    Science.gov (United States)

    Van der Giessen, Daniёlle; Branje, Susan J T; Frijns, Tom; Meeus, Wim H J

    2013-01-01

    Dyadic variability is considered to be a key mechanism in the development of mother-adolescent relationships, and low levels of dyadic flexibility are thought to be associated with behavior and relationship problems. The present observational study examined heterogeneity in the development of dyadic variability in mother-adolescent interactions and associations with psychosocial functioning. Dyadic variability refers to the range of emotional states during interactions of mother-adolescent dyads. During five annual home visits, 92 mother-adolescent dyads (M age T1 = 13; 65.2 % boys) were videotaped while discussing a conflict, and they completed several questionnaires on adolescents' aggressive behavior and adolescents' and mothers' perceived relationship quality. Two types of dyads were distinguished: low variability dyads (52 %) and high decreasing variability dyads (48 %). Over time, high decreasing variability dyads were characterized by a broader emotional repertoire than low variability dyads. Moreover, these two dyad types had distinct developmental patterns of psychosocial adjustment. Over time, high decreasing variability dyads showed lower levels of adolescents' aggressive behavior, and higher levels of perceived relationship quality than low variability dyads. These findings suggest that over time more dyadic variability is associated with less adjustment problems and a more constructive development of the mother-adolescent relationship. Adaptive interactions seem to be characterized by a wider range of emotional states and mothers should guide adolescents during interactions to express both positive and negative affect. Observing the dyadic variability during mother-adolescent interactions can help clinicians to distinguish adaptive from maladaptive mother-adolescent dyads.

  10. Concentration and the second stage of labor: outcomes associated with the interactive metronome.

    Science.gov (United States)

    McGowan, Meghan L; Lin, Alexander; Ou-Yang, Robin; Zei, Markus; Grobman, William

    2012-11-01

    To analyze the association between concentration, as measured by the Interactive Metronome, and a prolonged second stage of labor in nulliparous patients. From September 2008 to November 2009, nulliparous women at ≥34 weeks' gestation who were planning to use an epidural were asked to perform a 1-minute Interactive Metronome clapping test. Scores and demographic information were recorded. Data were then abstracted regarding each patient's labor course. The main outcome measure was the frequency of the second stage of labor exceeding 2 hours. Only patients with epidural anesthesia who completed the second stage of labor and did not require operative delivery performed for fetal indications prior to 2 full hours of pushing were included. Of the patients whose Interactive Metronome test scores were in the last quartile, which we associated with poor concentration, 52.9% (18/34) had a second stage of labor exceeding 2 hours compared with only 31.7% (33/104) of patients whose scores placed them in the first three quartiles (p = 0.026). Nulliparous patients with poor concentration scores, as measured by the Interactive Metronome, were more likely to push greater than 2 hours in the second stage of labor. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  11. 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 ...

  12. Investigation of the interaction of hydroxyapatite with technetium in association with stannous pyrophosphate

    International Nuclear Information System (INIS)

    Billinghurst, M.W.; Jette, D.; Somers, E.

    1981-01-01

    The individual components of technetium-99m stannous pyrophosphate were studied with respect to their interaction with hydroxyapatite. It is demonstrated that the role of the pyrophosphate molecule is one of a solubilizing and transporting molecule to carry the technetium atom to the site of the hydroxyapatite where the chelate disassociates and both the pyrophosphate and the technetium individually bind to the hydroxyapatite. The stannous ion is shown to associate with the hydroxyapatite also and although also solubilized by the pyrophosphate appears to be less strongly associated with the pyrophosphate. (author)

  13. 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.

  14. 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

    2018-05-23

    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.

  15. Nitrogen signalling in plant interactions with associative and endophytic diazotrophic bacteria.

    Science.gov (United States)

    Carvalho, T L G; Balsemão-Pires, E; Saraiva, R M; Ferreira, P C G; Hemerly, A S

    2014-10-01

    Some beneficial plant-interacting bacteria can biologically fix N2 to plant-available ammonium. Biological nitrogen fixation (BNF) is an important source of nitrogen (N) input in agriculture and represents a promising substitute for chemical N fertilizers. Diazotrophic bacteria have the ability to develop different types of root associations with different plant species. Among the highest rates of BNF are those measured in legumes nodulated by endosymbionts, an already very well documented model of plant-diazotrophic bacterial association. However, it has also been shown that economically important crops, especially monocots, can obtain a substantial part of their N needs from BNF by interacting with associative and endophytic diazotrophic bacteria, that either live near the root surface or endophytically colonize intercellular spaces and vascular tissues of host plants. One of the best reported outcomes of this association is the promotion of plant growth by direct and indirect mechanisms. Besides fixing N, these bacteria can also produce plant growth hormones, and some species are reported to improve nutrient uptake and increase plant tolerance against biotic and abiotic stresses. Thus, this particular type of plant-bacteria association consists of a natural beneficial system to be explored; however, the regulatory mechanisms involved are still not clear. Plant N status might act as a key signal, regulating and integrating various metabolic processes that occur during association with diazotrophic bacteria. This review will focus on the recent progress in understanding plant association with associative and endophytic diazotrophic bacteria, particularly on the knowledge of the N networks involved in BNF and in the promotion of plant growth. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. 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, pfamily and marital conflict and warmth, and positive and negative mood over a two-month period. To our knowledge, these findings, although cross-sectional, represent the first 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.

  17. Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction.

    Directory of Open Access Journals (Sweden)

    Shizhong Han

    2008-03-01

    Full Text Available Osteopontin (SPP1 is an important bone matrix mediator found to have key roles in inflammation and immunity. SPP1 genetic polymorphisms and increased osteopontin protein levels have been reported to be associated with SLE in small patient collections. The present study evaluates association between SPP1 polymorphisms and SLE in a large cohort of 1141 unrelated SLE patients [707 European-American (EA and 434 African-American (AA], and 2009 unrelated controls (1309 EA and 700 AA. Population-based case-control association analyses were performed. To control for potential population stratification, admixture adjusted logistic regression, genomic control (GC, structured association (STRAT, and principal components analysis (PCA were applied. Combined analysis of 2 ethnic groups, showed the minor allele of 2 SNPs (rs1126616T and rs9138C significantly associated with higher risk of SLE in males (P = 0.0005, OR = 1.73, 95% CI = 1.28-2.33, but not in females. Indeed, significant gene-gender interactions in the 2 SNPs, rs1126772 and rs9138, were detected (P = 0.001 and P = 0.0006, respectively. Further, haplotype analysis identified rs1126616T-rs1126772A-rs9138C which demonstrated significant association with SLE in general (P = 0.02, OR = 1.30, 95%CI 1.08-1.57, especially in males (P = 0.0003, OR = 2.42, 95%CI 1.51-3.89. Subgroup analysis with single SNPs and haplotypes also identified a similar pattern of gender-specific association in AA and EA. GC, STRAT, and PCA results within each group showed consistent associations. Our data suggest SPP1 is associated with SLE, and this association is especially stronger in males. To our knowledge, this report serves as the first association of a specific autosomal gene with human male lupus.

  18. Association with humans and seasonality interact to reverse predictions for animal space use.

    Science.gov (United States)

    Laver, Peter N; Alexander, Kathleen A

    2018-01-01

    Variation in animal space use reflects fitness trade-offs associated with ecological constraints. Associated theories such as the metabolic theory of ecology and the resource dispersion hypothesis generate predictions about what drives variation in animal space use. But, metabolic theory is usually tested in macro-ecological studies and is seldom invoked explicitly in within-species studies. Full evaluation of the resource dispersion hypothesis requires testing in more species. Neither have been evaluated in the context of anthropogenic landscape change. In this study, we used data for banded mongooses ( Mungos mungo ) in northeastern Botswana, along a gradient of association with humans, to test for effects of space use drivers predicted by these theories. We used Bayesian parameter estimation and inference from linear models to test for seasonal differences in space use metrics and to model seasonal effects of space use drivers. Results suggest that space use is strongly associated with variation in the level of overlap that mongoose groups have with humans. Seasonality influences this association, reversing seasonal space use predictions historically-accepted by ecologists. We found support for predictions of the metabolic theory when moderated by seasonality, by association with humans and by their interaction. Space use of mongooses living in association with humans was more concentrated in the dry season than the wet season, when historically-accepted ecological theory predicted more dispersed space use. Resource richness factors such as building density were associated with space use only during the dry season. We found negligible support for predictions of the resource dispersion hypothesis in general or for metabolic theory where seasonality and association with humans were not included. For mongooses living in association with humans, space use was not associated with patch dispersion or group size over both seasons. In our study, living in association

  19. 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.

  20. 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.

  1. 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

  2. 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 ...

  3. 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.

  4. 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 genes...... involved in the Mendelian disorder long QT syndrome (LOTS). We integrated the LOTS network with GWAS loci from the corresponding common complex trait, QT-interval variation, to identify candidate genes that were subsequently confirmed in Xenopus laevis oocytes and zebrafish. We used the LOTS protein...... network to filter weak GWAS signals by identifying single-nucleotide polymorphisms (SNPs) in proximity to genes in the network supported by strong proteomic evidence. Three SNPs passing this filter reached genome-wide significance after replication genotyping. Overall, we present a general strategy...

  5. Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas.

    Science.gov (United States)

    Polte, T R; Hanks, S K

    1995-11-07

    The focal adhesion kinase (FAK) has been implicated in integrin-mediated signaling events and in the mechanism of cell transformation by the v-Src and v-Crk oncoproteins. To gain further insight into FAK signaling pathways, we used a two-hybrid screen to identify proteins that interact with mouse FAK. The screen identified two proteins that interact with FAK via their Src homology 3 (SH3) domains: a v-Crk-associated tyrosine kinase substrate (Cas), p130Cas, and a still uncharacterized protein, FIPSH3-2, which contains an SH3 domain closely related to that of p130Cas. These SH3 domains bind to the same proline-rich region of FAK (APPKPSR) encompassing residues 711-717. The mouse p130Cas amino acid sequence was deduced from cDNA clones, revealing an overall high degree of similarity to the recently reported rat sequence. Coimmunoprecipitation experiments confirmed that p130Cas and FAK are associated in mouse fibroblasts. The stable interaction between p130Cas and FAK emerges as a likely key element in integrin-mediated signal transduction and further represents a direct molecular link between the v-Src and v-Crk oncoproteins. The Src family kinase Fyn, whose Src homology 2 (SH2) domain binds to the major FAK autophosphorylation site (tyrosine 397), was also identified in the two-hybrid screen.

  6. 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.

  7. 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......-analyses, FTO-rs9939609 was associated with BMI (β (SE), 0.17 (0.08) kg·m(-2)/allele; P = 0.034) and WC (0.47 (0.21) cm/allele; P = 0.026) at baseline, but not with weight change (5.55 (12.5) g·year(-1)/allele; P = 0.66) during follow up. In the CNC-analysis, FTO-rs9939609 was associated with increased risk...... of being a weight-gainer (OR: 1.1; P = 0.045). We observed no interaction between FTO-rs9939609 and dietary fat, protein and carbohydrate, and GI on BMI and WC at baseline or on change in weight and WC. FTO-rs9939609 is associated with BMI and WC at baseline, but association with weight gain is weak...

  8. 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...... 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...... 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....

  9. 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

    The origin of multiple myeloma depends on interactions with stromal cells in the course of normal B-cell differentiation and evolution of immunity. The concept of the present study is that genes involved in MM pathogenesis, such as immune response genes, can be identified by screening for single......3L1 gene promoters. The occurrence of single polymorphisms, haplotypes and SNP-SNP interactions were statistically analyzed for association with disease risk and outcome following high-dose therapy. Identified genes that carried SNPs or haplotypes that were identified as risk or prognostic factors......= .005). The 'risk genes' were analyzed for expression in normal B-cell subsets (N = 6) from seven healthy donors and we found TNFA and IL-6 expressed both in naïve and in memory B cells when compared to preBI, II, immature and plasma cells. The 'prognosis genes' CHI3L1, IL-6 and IL-10 were differential...

  10. Darapladib Binds to Lipoprotein-Associated Phospholipase A2 with Meaningful Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Do, Kyungrok; Chang, Byungha; Shin, Jae Min; No, Kyoung Tai; Lee, Jeeyoung [Bioinformatics and Molecular Design Research Center, Seoul (Korea, Republic of); Kim, Chul; Yea, Sangjun; Song, Miyoung [Korea Institute of Oriental Medicine, Daejeon (Korea, Republic of)

    2014-01-15

    Lipoprotein-associated phospholipase A{sub 2} (Lp-PLA{sub 2}) is a crucial enzyme in atherosclerosis as a potential drug target. The most remarkable Lp-PLA{sub 2} inhibitory drug is Darapladib. We determined the binding pose of Darapladib to Lp-PLA{sub 2} through docking study. Darapladib formed two hydrogen bonding interactions with the side chain of Tyr160 and Gln352 and several pi-pi interactions with aromatic and aliphatic hydrophobic residues of Lp-PLA{sub 2}. It is known that the dietylpropan-amine moiety of Darapladib has influence on the improvement of its oral bioavailability and we supposed this in our docking results.

  11. Antiparallel Self-Association of a γ,α-Hybrid Peptide: More Relevance of Weak Interactions.

    Science.gov (United States)

    Venugopalan, Paloth; Kishore, Raghuvansh

    2015-08-01

    To learn how a preorganized peptide-based molecular template, together with diverse weak non-covalent interactions, leads to an effective self-association, we investigated the conformational characteristics of a simple γ,α-hybrid model peptide, Boc-γ-Abz-Gly-OMe. The single-crystal X-ray diffraction analysis revealed the existence of a fully extended β-strand-like structure stabilized by two non-conventional C-H⋅⋅⋅O=C intramolecular H-bonds. The 2D (1) H NMR ROESY experiment led us to propose that the flat topology of the urethane-γ-Abz-amide moiety is predominantly preserved in a non-polar environment. The self-association of the energetically more favorable antiparallel β-strand-mimic in solid-state engenders an unusual 'flight of stairs' fabricated through face-to-face and edge-to-edge Ar⋅⋅⋅Ar interactions. In conjunction with FT-IR spectroscopic analysis in chloroform, we highlight that conformationally semi-rigid γ-Abz foldamer in appositely designed peptides may encourage unusual β-strand or β-sheet-like self-association and supramolecular organization stabilized via weak attractive forces. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. In Situ Tagged nsp15 Reveals Interactions with Coronavirus Replication/Transcription Complex-Associated Proteins

    Directory of Open Access Journals (Sweden)

    Jeremiah Athmer

    2017-01-01

    Full Text Available Coronavirus (CoV replication and transcription are carried out in close proximity to restructured endoplasmic reticulum (ER membranes in replication/transcription complexes (RTC. Many of the CoV nonstructural proteins (nsps are required for RTC function; however, not all of their functions are known. nsp15 contains an endoribonuclease domain that is conserved in the CoV family. While the enzymatic activity and crystal structure of nsp15 are well defined, its role in replication remains elusive. nsp15 localizes to sites of RNA replication, but whether it acts independently or requires additional interactions for its function remains unknown. To begin to address these questions, we created an in situ tagged form of nsp15 using the prototypic CoV, mouse hepatitis virus (MHV. In MHV, nsp15 contains the genomic RNA packaging signal (P/S, a 95-bp RNA stem-loop structure that is not required for viral replication or nsp15 function. Utilizing this knowledge, we constructed an internal hemagglutinin (HA tag that replaced the P/S. We found that nsp15-HA was localized to discrete perinuclear puncta and strongly colocalized with nsp8 and nsp12, both well-defined members of the RTC, but not the membrane (M protein, involved in virus assembly. Finally, we found that nsp15 interacted with RTC-associated proteins nsp8 and nsp12 during infection, and this interaction was RNA independent. From this, we conclude that nsp15 localizes and interacts with CoV proteins in the RTC, suggesting it plays a direct or indirect role in virus replication. Furthermore, the use of in situ epitope tags could be used to determine novel nsp-nsp interactions in coronaviruses.

  13. MVP-Associated Filamin A Mutations Affect FlnA-PTPN12 (PTP-PEST) Interactions.

    Science.gov (United States)

    Duval, Damien; Labbé, Pauline; Bureau, Léa; Le Tourneau, Thierry; Norris, Russell A; Markwald, Roger R; Levine, Robert; Schott, Jean-Jacques; Mérot, Jean

    2015-09-08

    Although the genetic basis of mitral valve prolapse (MVP) has now been clearly established, the molecular and cellular mechanisms involved in the pathological processes associated to a specific mutation often remain to be determined. The FLNA gene (encoding Filamin A; FlnA) was the first gene associated to non-syndromic X-linked myxomatous valvular dystrophy, but the impacts of the mutations on its function remain un-elucidated. Here, using the first repeats (1-8) of FlnA as a bait in a yeast two-hybrid screen, we identified the tyrosine phosphatase PTPN12 (PTP-PEST) as a specific binding partner of this region of FlnA protein. In addition, using yeast two-hybrid trap assay pull down and co-immunoprecipitation experiments, we showed that the MVP-associated FlnA mutations (G288R, P637Q, H743P) abolished FlnA/PTPN12 interactions. PTPN12 is a key regulator of signaling pathways involved in cell-extracellular matrix (ECM) crosstalk, cellular responses to mechanical stress that involve integrins, focal adhesion transduction pathways, and actin cytoskeleton dynamics. Interestingly, we showed that the FlnA mutations impair the activation status of two PTPN12 substrates, the focal adhesion associated kinase Src, and the RhoA specific activating protein p190RhoGAP. Together, these data point to PTPN12/FlnA interaction and its weakening by FlnA mutations as a mechanism potentially involved in the physiopathology of FlnA-associated MVP.

  14. MVP-Associated Filamin A Mutations Affect FlnA-PTPN12 (PTP-PEST Interactions

    Directory of Open Access Journals (Sweden)

    Damien Duval

    2015-09-01

    Full Text Available Although the genetic basis of mitral valve prolapse (MVP has now been clearly established, the molecular and cellular mechanisms involved in the pathological processes associated to a specific mutation often remain to be determined. The FLNA gene (encoding Filamin A; FlnA was the first gene associated to non-syndromic X-linked myxomatous valvular dystrophy, but the impacts of the mutations on its function remain un-elucidated. Here, using the first repeats (1–8 of FlnA as a bait in a yeast two-hybrid screen, we identified the tyrosine phosphatase PTPN12 (PTP-PEST as a specific binding partner of this region of FlnA protein. In addition, using yeast two-hybrid trap assay pull down and co-immunoprecipitation experiments, we showed that the MVP-associated FlnA mutations (G288R, P637Q, H743P abolished FlnA/PTPN12 interactions. PTPN12 is a key regulator of signaling pathways involved in cell-extracellular matrix (ECM crosstalk, cellular responses to mechanical stress that involve integrins, focal adhesion transduction pathways, and actin cytoskeleton dynamics. Interestingly, we showed that the FlnA mutations impair the activation status of two PTPN12 substrates, the focal adhesion associated kinase Src, and the RhoA specific activating protein p190RhoGAP. Together, these data point to PTPN12/FlnA interaction and its weakening by FlnA mutations as a mechanism potentially involved in the physiopathology of FlnA-associated MVP.

  15. 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.

  16. 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

  17. 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...

  18. 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

  19. 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......Recently, a novel protein named MBL/ficolin associated protein-1 (MAP-1) derived from the MASP1 gene through differential splicing was identified. In the present study, we established biochemical characteristics, determined the serum level and assessed the interactions between the lectin complement...... 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...

  20. 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.

  1. 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.

  2. Technical and Technological Support of Agricultural Enterprises on the Basis of Association Interaction: a Methodical Approach

    Directory of Open Access Journals (Sweden)

    Pyvovar Petro V.

    2017-12-01

    Full Text Available The aim of the research is the development of a methodical approach to justifying directions of association interaction of agricultural enterprises for the most effective technical and technological support of their economic activities. It is substantiated that the decision-making regarding the directions of group interaction in the field of forming and using the machine and tractor fleet of agricultural enterprises should be based on results of a strategic analysis of the current level of and trends in the changes in indicators of their technical support. This includes several stages: 1 determining a scenario for the development of the technical base of the economic entity (matrix methods; 2 multifactor grouping taking into account the available equipment and resource potential; 3 identification of potential sources of financing and ways of attracting necessary funds, priority partners and types of equipment and technologies; 4 estimation of a current condition of the enterprise on financial, technical, economic and market criteria; 5 substantiation of directions of group interaction of the enterprise.

  3. 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.

  4. 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

  5. Microsatellite polymorphisms associated with human behavioural and psychological phenotypes including a gene-environment interaction.

    Science.gov (United States)

    Bagshaw, Andrew T M; Horwood, L John; Fergusson, David M; Gemmell, Neil J; Kennedy, Martin A

    2017-02-03

    The genetic and environmental influences on human personality and behaviour are a complex matter of ongoing debate. Accumulating evidence indicates that short tandem repeats (STRs) in regulatory regions are good candidates to explain heritability not accessed by genome-wide association studies. We tested for associations between the genotypes of four selected repeats and 18 traits relating to personality, behaviour, cognitive ability and mental health in a well-studied longitudinal birth cohort (n = 458-589) using one way analysis of variance. The repeats were a highly conserved poly-AC microsatellite in the upstream promoter region of the T-box brain 1 (TBR1) gene and three previously studied STRs in the activating enhancer-binding protein 2-beta (AP2-β) and androgen receptor (AR) genes. Where significance was found we used multiple regression to assess the influence of confounding factors. Carriers of the shorter, most common, allele of the AR gene's GGN microsatellite polymorphism had fewer anxiety-related symptoms, which was consistent with previous studies, but in our study this was not significant following Bonferroni correction. No associations with two repeats in the AP2-β gene withstood this correction. A novel finding was that carriers of the minor allele of the TBR1 AC microsatellite were at higher risk of conduct problems in childhood at age 7-9 (p = 0.0007, which did pass Bonferroni correction). Including maternal smoking during pregnancy (MSDP) in models controlling for potentially confounding influences showed that an interaction between TBR1 genotype and MSDP was a significant predictor of conduct problems in childhood and adolescence (p behaviour up to age 25 years (p ≤ 0.02). This interaction remained significant after controlling for possible confounders including maternal age at birth, socio-economic status and education, and offspring birth weight. The potential functional importance of the TBR1 gene's promoter microsatellite

  6. 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.

  7. 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).

  8. 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.

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

    Science.gov (United States)

    Ennajdaoui, Hanane; Howard, Jonathan M; Sterne-Weiler, Timothy; Jahanbani, Fereshteh; Coyne, Doyle J; Uren, Philip J; Dargyte, Marija; Katzman, Sol; Draper, Jolene M; Wallace, Andrew; Cazarez, Oscar; Burns, Suzanne C; Qiao, Mei; Hinck, Lindsay; Smith, Andrew D; Toloue, Masoud M; Blencowe, Benjamin J; Penalva, Luiz O F; Sanford, Jeremy R

    2016-05-31

    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. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. 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.

  11. 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.

  12. iLOCi: a SNP interaction prioritization technique for detecting epistasis in genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Piriyapongsa Jittima

    2012-12-01

    Full Text Available Abstract Background Genome-wide association studies (GWAS do not provide a full account of the heritability of genetic diseases since gene-gene interactions, also known as epistasis are not considered in single locus GWAS. To address this problem, a considerable number of methods have been developed for identifying disease-associated gene-gene interactions. However, these methods typically fail to identify interacting markers explaining more of the disease heritability over single locus GWAS, since many of the interactions significant for disease are obscured by uninformative marker interactions e.g., linkage disequilibrium (LD. Results In this study, we present a novel SNP interaction prioritization algorithm, named iLOCi (Interacting Loci. This algorithm accounts for marker dependencies separately in case and control groups. Disease-associated interactions are then prioritized according to a novel ranking score calculated from the difference in marker dependencies for every possible pair between case and control groups. The analysis of a typical GWAS dataset can be completed in less than a day on a standard workstation with parallel processing capability. The proposed framework was validated using simulated data and applied to real GWAS datasets using the Wellcome Trust Case Control Consortium (WTCCC data. The results from simulated data showed the ability of iLOCi to identify various types of gene-gene interactions, especially for high-order interaction. From the WTCCC data, we found that among the top ranked interacting SNP pairs, several mapped to genes previously known to be associated with disease, and interestingly, other previously unreported genes with biologically related roles. Conclusion iLOCi is a powerful tool for uncovering true disease interacting markers and thus can provide a more complete understanding of the genetic basis underlying complex disease. The program is available for download at http://www4a.biotec.or.th/GI/tools/iloci.

  13. 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

  14. 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.

  15. Investigating the Association between Flowering Time and Defense in the Arabidopsis thaliana-Fusarium oxysporum Interaction

    Science.gov (United States)

    Lyons, Rebecca; Rusu, Anca; Stiller, Jiri; Powell, Jonathan; Manners, John M.; Kazan, Kemal

    2015-01-01

    Plants respond to pathogens either by investing more resources into immunity which is costly to development, or by accelerating reproductive processes such as flowering time to ensure reproduction occurs before the plant succumbs to disease. In this study we explored the link between flowering time and pathogen defense using the interaction between Arabidopsis thaliana and the root infecting fungal pathogen Fusarium oxysporum. We report that F. oxysporum infection accelerates flowering time and regulates transcription of a number of floral integrator genes, including FLOWERING LOCUS C (FLC), FLOWERING LOCUS T (FT) and GIGANTEA (GI). Furthermore, we observed a positive correlation between late flowering and resistance to F. oxysporum in A. thaliana natural ecotypes. Late-flowering gi and autonomous pathway mutants also exhibited enhanced resistance to F. oxysporum, supporting the association between flowering time and defense. However, epistasis analysis showed that accelerating flowering time by deletion of FLC in fve-3 or fpa-7 mutants did not alter disease resistance, suggesting that the effect of autonomous pathway on disease resistance occurs independently from flowering time. Indeed, RNA-seq analyses suggest that fve-3 mediated resistance to F. oxysporum is most likely a result of altered defense-associated gene transcription. Together, our results indicate that the association between flowering time and pathogen defense is complex and can involve both pleiotropic and direct effects. PMID:26034991

  16. 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.

  17. [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.

  18. Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions.

    Science.gov (United States)

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

    2013-12-03

    Pyrethroid insecticides are used to control 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 nonmetabolizing mosquito P450s, as well as rodent microsomes, to measure labeling specificity, plus cytochrome P450 oxidoreductase and b5 knockout mouse livers to validate P450 activation and establish the role for b5 in probe activation. Using PyABPs, we were able to profile active enzymes in rat liver microsomes and identify pyrethroid-metabolizing enzymes in the target tissue. These included P450s as well as related detoxification enzymes, notably UDP-glucuronosyltransferases, suggesting a network of associated pyrethroid-metabolizing enzymes, or "pyrethrome." Considering the central role P450s play in metabolizing insecticides, we anticipate that PyABPs will aid in 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 unique tools for disease control.

  19. 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.

  20. 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.

  1. Lipid Raft Association Restricts CD44-Ezrin Interaction and Promotion of Breast Cancer Cell Migration

    Science.gov (United States)

    Donatello, Simona; Babina, Irina S.; Hazelwood, Lee D.; Hill, Arnold D.K.; Nabi, Ivan R.; Hopkins, Ann M.

    2012-01-01

    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. PMID:23031255

  2. 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.

  3. Association of apolipoprotein e gene polymorphisms with blood lipids and their interaction with dietary factors

    DEFF Research Database (Denmark)

    Shatwan, Israa M.; Winther, Kristian Hillert; Ellahi, Basma

    2018-01-01

    of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors. Methods: The population studied for this investigation included 660 individuals from...... the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ......Background: Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association...

  4. Dynamic interactions of the asialoglycoprotein receptor subunits with coated pits. Enhanced interactions of H2 following association with H1.

    Science.gov (United States)

    Katzir, Z; Nardi, N; Geffen, I; Fuhrer, C; Henis, Y I

    1994-08-26

    Lateral mobility studies comparing native and mutated membrane proteins, combined with treatments that alter clathrin lattice structure, can measure membrane protein-coated pit interactions in intact cells (Fire, E., Zwart, D., Roth, M. G., and Henis, Y. I. (1991) J. Cell Biol. 115, 1585-1594). We applied this approach to study the interactions of the H1 and H2 human asialoglycoprotein receptor subunits with coated pits. The lateral mobilities of singly expressed and coexpressed H1 and H2B (the H2 species that reaches the cell surface) were measured by fluorescence photobleaching recovery. They were compared with mutant proteins, H1(5A) (Tyr-5 replaced by Ala) and H2(5A) (Phe-5 replaced by Ala). While the mobile fractions of H1, H2B, and their mutants were similar, the lateral diffusion rate (measured by D, the lateral diffusion coefficient) was significantly slower for H1, whether expressed alone or with H2B. Coexpression with H1 reduced D of H2B to that of H1. Disruption of the clathrin lattices by hypertonic medium elevated D of H1, H1(5A), H2B, and H2(5A) to the same final level, without affecting their mobile fractions. Cytosol acidification, which retains altered clathrin lattices attached to the membrane and prevents coated vesicle formation, immobilized part of the H1 molecules, reflecting stable entrapment in "frozen" coated pits. H1(5A), H2B, and H2(5A) were not affected; however, coexpression of H2B with H1 conferred the sensitivity to cytosol acidification on H2B. Our results suggest that H1 lateral mobility is inhibited by dynamic interactions with coated pits in which Tyr-5 is involved. H2B resembles H1(5A) rather than H1, and its interactions with coated pits are weaker; efficient interaction of H2B with coated pits depends on complex formation with H1.

  5. 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.

  6. AprioriGWAS, a new pattern mining strategy for detecting genetic variants associated with disease through interaction effects.

    Science.gov (United States)

    Zhang, Qingrun; Long, Quan; Ott, Jurg

    2014-06-01

    Identifying gene-gene interaction is a hot topic in genome wide association studies. Two fundamental challenges are: (1) how to smartly identify combinations of variants that may be associated with the trait from astronomical number of all possible combinations; and (2) how to test epistatic interaction when all potential combinations are available. We developed AprioriGWAS, which brings two innovations. (1) Based on Apriori, a successful method in field of Frequent Itemset Mining (FIM) in which a pattern growth strategy is leveraged to effectively and accurately reduce search space, AprioriGWAS can efficiently identify genetically associated genotype patterns. (2) To test the hypotheses of epistasis, we adopt a new conditional permutation procedure to obtain reliable statistical inference of Pearson's chi-square test for the [Formula: see text] contingency table generated by associated variants. By applying AprioriGWAS to age-related macular degeneration (AMD) data, we found that: (1) angiopoietin 1 (ANGPT1) and four retinal genes interact with Complement Factor H (CFH). (2) GO term "glycosaminoglycan biosynthetic process" was enriched in AMD interacting genes. The epistatic interactions newly found by AprioriGWAS on AMD data are likely true interactions, since genes interacting with CFH are retinal genes, and GO term enrichment also verified that interaction between glycosaminoglycans (GAGs) and CFH plays an important role in disease pathology of AMD. By applying AprioriGWAS on Bipolar disorder in WTCCC data, we found variants without marginal effect show significant interactions. For example, multiple-SNP genotype patterns inside gene GABRB2 and GRIA1 (AMPA subunit 1 receptor gene). AMPARs are found in many parts of the brain and are the most commonly found receptor in the nervous system. The GABRB2 mediates the fastest inhibitory synaptic transmission in the central nervous system. GRIA1 and GABRB2 are relevant to mental disorders supported by multiple

  7. Association between the physical stability of flurbiprofen suspension and the interaction of HPMC/SDS

    Directory of Open Access Journals (Sweden)

    Hongyu Wang

    2018-01-01

    Full Text Available The anionic surfactant sodium dodecylsulfate (SDS has improved the physical stability of flurbiprofen (FBP suspension, which was suspended by 0.2% (w/v hydroxypropylmethyl cellulose (HPMC, K4M. Therefore, the physical stability of FBP suspensions and the interaction of HPMC/SDS were studied, and a certain association between them was revealed. The anti-solvent precipitation method was used to prepare suspensions. The apparent drug concentration from different sites was evaluated to get the dispersion of drug actually. The process of flocculation and deflocculation with the addition of SDS was caught by analyzing the morphology of the suspended particles. The physical stability of the FBP suspensions was characterized mainly by measuring the re-dispersion time, the zeta potential and particle size. Meanwhile, conductivity measurements were carried out to obtain the characteristic concentrations of SDS in HPMC/SDS system. The viscosities, the abilities for improving the solubility and wettability of FBP in the separate and mixed HPMC/SDS solutions were also contrasted respectively. The suspensions prepared with HPMC/SDS possessed better physical stability. The suspensions were uniform when the concentration of SDS was between the critical adsorption concentration (CAC and the polymer saturation point (PSP. After PSP, the uniformity became worse and worse until the SDS was enough to form a deflocculation state. Besides, the re-dispersion time of FBP suspensions was longest when the concentration of SDS around CAC and shorter by shorter after the critical micelle concentration (CMC. The article provided a new sight on the relation between the interaction of excipient matrix and pharmaceutical preparations.

  8. 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.

  9. ER-mitochondria associations are regulated by the VAPB-PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43

    Science.gov (United States)

    Stoica, Radu; de Vos, Kurt J.; Paillusson, Sébastien; Mueller, Sarah; Sancho, Rosa M.; Lau, Kwok-Fai; Vizcay-Barrena, Gema; Lin, Wen-Lang; Xu, Ya-Fei; Lewis, Jada; Dickson, Dennis W.; Petrucelli, Leonard; Mitchell, Jacqueline C.; Shaw, Christopher E.; Miller, Christopher C. J.

    2014-06-01

    Mitochondria and the endoplasmic reticulum (ER) form tight structural associations and these facilitate a number of cellular functions. However, the mechanisms by which regions of the ER become tethered to mitochondria are not properly known. Understanding these mechanisms is not just important for comprehending fundamental physiological processes but also for understanding pathogenic processes in some disease states. In particular, disruption to ER-mitochondria associations is linked to some neurodegenerative diseases. Here we show that the ER-resident protein VAPB interacts with the mitochondrial protein tyrosine phosphatase-interacting protein-51 (PTPIP51) to regulate ER-mitochondria associations. Moreover, we demonstrate that TDP-43, a protein pathologically linked to amyotrophic lateral sclerosis and fronto-temporal dementia perturbs ER-mitochondria interactions and that this is associated with disruption to the VAPB-PTPIP51 interaction and cellular Ca2+ homeostasis. Finally, we show that overexpression of TDP-43 leads to activation of glycogen synthase kinase-3β (GSK-3β) and that GSK-3β regulates the VAPB-PTPIP51 interaction. Our results describe a new pathogenic mechanism for TDP-43.

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

    Science.gov (United States)

    Zeng, Yi; Cheng, Lingguo; Zhao, Ling; Tan, Qihua; Feng, Qiushi; Chen, Huashuai; Shen, Ke; Li, Jianxin; Zhang, Fengyu; Cao, Huiqing; Gregory, Simon G; Yang, Ze; Gu, Jun; Tao, Wei; Tian, Xiao-Li; Hauser, Elizabeth R

    2013-09-09

    Existing literature indicates that ADRB2 gene is associated with health and longevity, but none of previous studies investigated associations of carrying the ADRB2 minor alleles and interactions between ADRB2 genotypes and social/behavioral factors(GxE) with health outcomes at advanced ages. This study intends to fill in this research gap. 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 social/behavioral factors and various other potentially confounding factors, we develop and test an innovative three-step procedure which combines logistic regression and structural equation methods. Interaction between regular exercise and carrying rs1042718 minor allele is significantly 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 is significantly and positively associated with self-reported good health. Carrying rs1042718 or rs1042719 minor alleles is significantly and negatively associated with negative emotion, but the ADRB2 SNPs are not significantly associated with cognitive function and self-reported health. Our structural equation analysis found that, adjusted for the confounding effects of correlation of the ADRB2 SNPs with negative emotion, interaction between negative emotion and carrying rs1042718 or rs1042719 minor allele is significantly and negatively associated with cognitive function. The positive association of regular 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 rs

  11. Dynamics of tactical behaviour in association football when manipulating players' space of interaction.

    Directory of Open Access Journals (Sweden)

    Angel Ric

    Full Text Available The analysis of positional data in association football allows the spatial distribution of players during matches to be described in order to improve the understanding of tactical-related constraints on the behavioural dynamics of players. The aim of this study was to identify how players' spatial restrictions affected the exploratory tactical behaviour and constrained the perceptual-motor workspace of players in possession of the ball, as well as inter-player passing interactions. Nineteen professional outfield male players were divided into two teams of 10 and 9 players, respectively. The game was played under three spatial constraints: a players were not allowed to move out of their allocated zones, except for the player in possession of the ball; b players were allowed to move to an adjacent zone, and; c non-specific spatial constraints. Positional data was captured using a 5 Hz interpolated GPS tracking system and used to define the configuration states of players for each second in time. The configuration state comprised 37 categories derived from tactical actions, distance from the nearest opponent, distance from the target and movement speed. Notational analysis of players in possession of the ball allowed the mean time of ball possession and the probabilities of passing the ball between players to be calculated. The results revealed that the players' long-term exploratory behaviour decreased and their short-term exploration increased when restricting their space of interaction. Relaxing players' positional constraints seemed to increase the speed of ball flow dynamics. Allowing players to move to an adjacent sub-area increased the probabilities of interaction with the full-back during play build-up. The instability of the coordinative state defined by being free from opponents when players had the ball possession was an invariant feature under all three task constraints. By allowing players to move to adjacent sub-areas, the

  12. [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.

  13. Nuclear γ-tubulin associates with nucleoli and interacts with tumor suppressor protein C53.

    Science.gov (United States)

    Hořejší, Barbora; Vinopal, Stanislav; Sládková, Vladimíra; Dráberová, Eduarda; Sulimenko, Vadym; Sulimenko, Tetyana; Vosecká, Věra; Philimonenko, Anatoly; Hozák, Pavel; Katsetos, Christos D; Dráber, Pavel

    2012-01-01

    γ-Tubulin is assumed to be a typical cytosolic protein necessary for nucleation of microtubules from microtubule organizing centers. Using immunolocalization and cell fractionation techniques in combination with siRNAi and expression of FLAG-tagged constructs, we have obtained evidence that γ-tubulin is also present in nucleoli of mammalian interphase cells of diverse cellular origins. Immunoelectron microscopy has revealed γ-tubulin localization outside fibrillar centers where transcription of ribosomal DNA takes place. γ-Tubulin was associated with nucleolar remnants after nuclear envelope breakdown and could be translocated to nucleoli during mitosis. Pretreatment of cells with leptomycin B did not affect the distribution of nuclear γ-tubulin, making it unlikely that rapid active transport via nuclear pores participates in the transport of γ-tubulin into the nucleus. This finding was confirmed by heterokaryon assay and time-lapse imaging of photoconvertible protein Dendra2 tagged to γ-tubulin. Immunoprecipitation from nuclear extracts combined with mass spectrometry revealed an association of γ-tubulin with tumor suppressor protein C53 located at multiple subcellular compartments including nucleoli. The notion of an interaction between γ-tubulin and C53 was corroborated by pull-down and co-immunoprecipitation experiments. Overexpression of γ-tubulin antagonized the inhibitory effect of C53 on DNA damage G(2) /M checkpoint activation. The combined results indicate that aside from its known role in microtubule nucleation, γ-tubulin may also have nuclear-specific function(s). Copyright © 2011 Wiley Periodicals, Inc.

  14. Dopamine and dopamine receptor D1 associated with decreased social interaction.

    Science.gov (United States)

    Liu, Qiang; Shi, Jieyun; Lin, Rongfei; Wen, Tieqiao

    2017-05-01

    Deficits in social interaction are hallmarks of neurological and psychiatric disorders. However, its underlying mechanism is still unclear. Here, we show that the loss of dendritic cell factor 1 (Dcf1) in the nervous system of mice induces social interaction deficiency, autism-like behaviour, and influences social interaction via the dopamine system. Dopamine receptor D1 agonist rescues this social cognition phenotype, and improves short-term plasticity. Together, this study presents a new genetic mechanism that affects social interaction and may provide a new way to improve positive social interaction and treat autism spectrum disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Antenatal interpersonal sensitivity is more strongly associated than perinatal depressive symptoms with postnatal mother-infant interaction quality.

    Science.gov (United States)

    Raine, Karen; Cockshaw, Wendell; Boyce, Philip; Thorpe, Karen

    2016-10-01

    Maternal mental health has enduring effects on children's life chances and is a substantial cost driver for child health, education and social services. A key linking mechanism is the quality of mother-infant interaction. A body of work associates maternal depressive symptoms across the antenatal and postnatal (perinatal) period with less-than-optimal mother-infant interaction. Our study aims to build on previous research in the field through exploring the association of a maternal personality trait, interpersonal sensitivity, measured in early pregnancy, with subsequent mother-infant interaction quality. We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine the association between antenatal interpersonal sensitivity and postnatal mother-infant interaction quality in the context of perinatal depressive symptoms. Interpersonal sensitivity was measured during early pregnancy and depressive symptoms in the antenatal year and across the first 21 months of the postnatal period. In a subsample of the ALSPAC, mother-infant interaction was measured at 12 months postnatal through a standard observation. For the subsample that had complete data at all time points (n = 706), hierarchical regression examined the contribution of interpersonal sensitivity to variance in mother-infant interaction quality. Perinatal depressive symptoms predicted little variance in mother-infant interaction. Antenatal interpersonal sensitivity explained a greater proportion of variance in mother-infant interaction quality. The personality trait, interpersonal sensitivity, measured in early pregnancy, is a more robust indicator of subsequent mother-infant-interaction quality than perinatal depressive symptoms, thus affording enhanced opportunity to identify vulnerable mother-infant relationships for targeted early intervention.

  16. Welcome to the neighbourhood: interspecific genotype by genotype interactions in Solidago influence above- and belowground biomass and associated communities.

    Science.gov (United States)

    Genung, Mark A; Bailey, Joseph K; Schweitzer, Jennifer A

    2012-01-01

    Intra- and interspecific plant-plant interactions are fundamental to patterns of community assembly and to the mixture effects observed in biodiversity studies. Although much research has been conducted at the species level, very little is understood about how genetic variation within and among interacting species may drive these processes. Using clones of both Solidago altissima and Solidago gigantea, we found that genotypic variation in a plant's neighbours affected both above- and belowground plant traits, and that genotype by genotype interactions between neighbouring plants impacted associated pollinator communities. The traits for which focal plant genotypic variation explained the most variation varied by plant species, whereas neighbour genotypic variation explained the most variation in coarse root biomass. Our results provide new insight into genotypic and species diversity effects in plant-neighbour interactions, the extended consequences of diversity effects, and the potential for evolution in response to competitive or to facilitative plant-neighbour interactions. © 2011 Blackwell Publishing Ltd/CNRS.

  17. 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.

  18. 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.

  19. 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 social/behavioral factors and various other potentially confounding factors, we develop and test an innovative three-step procedure which combines logistic regression and structural equation methods. Results: Interaction between regular exercise and carrying rs1042718 minor allele is significantly...... analysis found that, adjusted for the confounding effects of correlation of the ADRB2 SNPs with negative emotion, interaction between negative emotion and carrying rs1042718 or rs1042719 minor allele is significantly and negatively associated with cognitive function. The positive association of regular...

  20. VARIATIONS OF THE MUON FLUX AT SEA LEVEL ASSOCIATED WITH INTERPLANETARY ICMEs AND COROTATING INTERACTION REGIONS

    Energy Technology Data Exchange (ETDEWEB)

    Augusto, C. R. A.; Kopenkin, V.; Navia, C. E.; Tsui, K. H.; Shigueoka, H. [Instituto de Fisica, Universidade Federal Fluminense, 24210-346, Niteroi, RJ (Brazil); Fauth, A. C.; Kemp, E.; Manganote, E. J. T. [Instituto de Fisica Gleb Wathagin, Universidade Estadual de Campinas, Campinas, SP (Brazil); Leigui de Oliveira, M. A. [Centro de Ciencias Naturais e Humanas da Universidade Federal do ABC, Santo Andre, SP (Brazil); Miranda, P.; Ticona, R.; Velarde, A. [Instituto de Investigaciones Fisicas, UMSA, La Paz Bolivia (United States)

    2012-11-10

    We present the results of an ongoing survey on the association between the muon flux variation at ground level (3 m above sea level) registered by the Tupi telescopes (Niteri-Brazil, 22.{sup 0}9S, 43.{sup 0}2W, 3 m) and the Earth-directed transient disturbances in the interplanetary medium propagating from the Sun (such as coronal mass ejections (CME), and corotating interaction regions (CIRs)). Their location inside the South Atlantic Anomaly region enables the muon telescopes to achieve a low rigidity of response to primary and secondary charged particles. The present study is primarily based on experimental events obtained by the Tupi telescopes in the period from 2010 August to 2011 December. This time period corresponds to the rising phase of solar cycle 24. The Tupi events are studied in correlation with data obtained by space-borne detectors (SOHO, ACE, GOES). Identification of interplanetary structures and associated solar activity was based on the nomenclature and definitions given by the satellite observations, including an incomplete list of possible interplanetary shocks observed by the CELIAS/MTOF Proton Monitor on the Solar and Heliospheric Observatory (SOHO) spacecraft. Among 29 experimental events reported in the present analysis, there are 15 possibly associated with the CMEs and sheaths, and 3 events with the CIRs (forward or reverse shocks); the origin of the remaining 11 events has not been determined by the satellite detectors. We compare the observed time (delayed or anticipated) of the muon excess (positive or negative) signal on Earth (the Tupi telescopes) with the trigger time of the interplanetary disturbances registered by the satellites located at Lagrange point L1 (SOHO and ACE). The temporal correlation of the observed ground-based events with solar transient events detected by spacecraft suggests a real physical connection between them. We found that the majority of observed events detected by the Tupi experiment were delayed in

  1. Using Media While Interacting Face-to-Face Is Associated With Psychosocial Well-Being and Personality Traits.

    Science.gov (United States)

    Lee, Mindy; Murphy, Karen; Andrews, Glenda

    2018-01-01

    Positive face-to-face human interactions are known to benefit well-being. Drawing upon previous work regarding the interference of media (via technological devices or print) in social interaction, the aim of this study was to identify whether using media during face-to-face interaction could potentially limit the positive effect of interaction on well-being. Participants were 437 university students who completed an online survey which assessed media multitasking behaviors, well-being (trait depression, trait anxiety, social anxiety, empathy, and psychological well-being), and personality traits (Big-5 and narcissism). Face-to-face interaction was positively associated with well-being. However, when media use during face-to-face interaction was considered, there was a negative relationship with well-being (more depression, more anxiety, and less psychological well-being). Those who used certain media types, such as phone or video chatting, listening to music, and gaming, while interacting with others, also had lower scores on measures of empathy. Regression analyses showed significant contributions by these media types to empathy levels, even after controlling for age, gender, and personality traits. Face-to-face media multitasking was related to higher levels of narcissism and neuroticism, and lower levels of agreeableness, conscientiousness, and openness. This study provides insight into the possible role of media multitasking during face-to-face interaction on psychosocial outcomes.

  2. 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.

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

    International Nuclear Information System (INIS)

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

    2005-01-01

    The Nopal I uranium (U) deposit, Pena Blanca District, Mexico, largely consists of secondary U 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 ∼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 (∼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 18 O = -10.8(per t housand), whereas the uraninite within the Pozos conglomerate has a (delta) 18 O = +1.5(per t housand). If it is assumed that both uraninites precipitated from meteoric water ((delta) 18 O = -7(per t housand)), 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 temperatures for clay minerals associated with uraninite

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

    Directory of Open Access Journals (Sweden)

    Anna R Gagliardi

    Full Text Available 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

  5. 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.

  6. 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.

  7. Interaction matters: quantifying conduct problem × depressive symptoms interaction and its association with adolescent alcohol, cigarette, and marijuana use in a national sample.

    Science.gov (United States)

    Maslowsky, Julie; Schulenberg, John E

    2013-11-01

    Substance use is a major contributor to morbidity and mortality among American adolescents. Conduct problems and depressive symptoms have each been found to be associated with adolescent substance use. Although they are highly comorbid, the role of the interaction of conduct problems and depressive symptoms in substance use is not clear. In national samples of 8th-, 10th-, and 12th-grade students from the Monitoring the Future study, latent moderated structural equation modeling was used to estimate the association of conduct problems, depressive symptoms, and their interaction to the use of alcohol (including binge drinking), cigarettes, and marijuana. Moderation by age and sex was tested. The interaction of conduct problems with depressive symptoms was a strong predictor of substance use, particularly among younger adolescents. With few exceptions, adolescents with high levels of both conduct problems and depressive symptoms used substances most frequently. Conduct problems were a strong positive predictor of substance use, and depressive symptoms were a weak positive predictor. Whereas conduct problems are often thought to be a primary predictor of substance use, this study revealed that depressive symptoms potentiate the relation of conduct problems to substance use. Therefore, substance use prevention efforts should target both depressive symptoms and conduct problems.

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

    Science.gov (United States)

    Rossin, Elizabeth J.; Lage, Kasper; Raychaudhuri, Soumya; Xavier, Ramnik J.; Tatar, Diana; Benita, Yair

    2011-01-01

    Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed by these risk variants. It has previously been observed that different genes harboring causal mutations for the same Mendelian disease often physically interact. We sought to evaluate the degree to which this is true of genes within strongly associated loci in complex disease. Using sets of loci defined 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 densely connected than chance expectation. To confirm biological relevance, we show that the components of the networks tend to be expressed in similar tissues relevant to the phenotypes in question, suggesting the network indicates common underlying processes perturbed by risk loci. Furthermore, we show 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-immune traits to assess its applicability to complex traits in general. We find that genes in loci associated to height and lipid levels assemble into significantly connected networks but did not detect excess connectivity among Type 2 Diabetes (T2D) loci beyond chance. Taken together, our results constitute 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

  9. 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

  10. 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......Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact...... 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...

  11. Affiliation and control in marital interaction: interpersonal complementarity is present but is not associated with affect or relationship quality.

    Science.gov (United States)

    Cundiff, Jenny M; Smith, Timothy W; Butner, Jonathan; Critchfield, Kenneth L; Nealey-Moore, Jill

    2015-01-01

    The principle of complementarity in interpersonal theory states that an actor's behavior tends to "pull, elicit, invite, or evoke" responses from interaction partners who are similar in affiliation (i.e., warmth vs. hostility) and opposite in control (i.e., dominance vs. submissiveness). Furthermore, complementary interactions are proposed to evoke less negative affect and promote greater relationship satisfaction. These predictions were examined in two studies of married couples. Results suggest that complementarity in affiliation describes a robust general pattern of marital interaction, but complementarity in control varies across contexts. Consistent with behavioral models of marital interaction, greater levels of affiliation and lower control by partners-not complementarity in affiliation or control-were associated with less anger and anxiety and greater relationship quality. Partners' levels of affiliation and control combined in ways other than complementarity-mostly additively, but sometimes synergistically-to predict negative affect and relationship satisfaction. © 2014 by the Society for Personality and Social Psychology, Inc.

  12. Genetic variation in thioredoxin interacting protein (TXNIP) is associated with hypertriglyceridaemia and blood pressure in diabetes mellitus

    NARCIS (Netherlands)

    Greevenbroek, van M.M.J.; Vermeulen, V.; Feskens, E.J.M.; Evelo, V.T.; Kruijshoop, M.; Hoebee, B.; Kallen, van der C.J.H.; Bruin, de T.W.A.

    2007-01-01

    Aims Thioredoxin interacting protein (TXNIP) is an attractive candidate gene for diabetes or diabetic dyslipidaemia, since TXNIP is the strongest glucose-responsive gene in pancreatic B-cells, TXNIP deficiency in a mouse model is associated with hyperlipidaemia and TXNIP is located in the 1q21-1q23

  13. Brain regions associated with the acquisition of conditioned place preference for cocaine vs. social interaction.

    Science.gov (United States)

    El Rawas, Rana; Klement, Sabine; Kummer, Kai K; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

    2012-01-01

    Positive social interaction could play an essential role in switching the preference of the substance dependent individual away from drug related activities. We have previously shown that conditioned place preference (CPP) for cocaine at the dose of 15 mg/kg and CPP for four 15-min episodes of social interaction were equally strong when rats were concurrently conditioned for place preference by pairing cocaine with one compartment and social interaction with the other. The aim of the present study was to investigate the differential activation of brain regions related to the reward circuitry after acquisition/expression of cocaine CPP or social interaction CPP. Our findings indicate that cocaine CPP and social interaction CPP activated almost the same brain regions. However, the granular insular cortex and the dorsal part of the agranular insular cortex were more activated after cocaine CPP, whereas the prelimbic cortex and the core subregion of the nucleus accumbens were more activated after social interaction CPP. These results suggest that the insular cortex appears to be potently activated after drug conditioning learning while activation of the prelimbic cortex-nucleus accumbens core projection seems to be preferentially involved in the conditioning to non-drug stimuli such as social interaction.

  14. 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...

  15. Quality control of radiolabeled antibodies through simultaneous determination of antibody concentration and specific activity using time-resolved interaction analysis and reverse kinetic fit

    International Nuclear Information System (INIS)

    Andersson, K.; Mihaylova, D.; Wang, E.; Abrahamsen, L.; Buijs, J.; Bjoerkelund, H.

    2015-01-01

    Full text of publication follows. With the advent of efficient methods for producing proteins that bind to a defined target, the number of radiolabeled proteins, and in particular antibodies, used for medical imaging and cancer therapy is increasing rapidly. In line with this increase, focus should be put on methods for the quality control (QC). Proper antibody quality is of fundamental importance to guarantee safety and consistent efficacy for the patient. Adequate QC procedures exist for small radiolabeled synthetic compounds like FDG, but antibody based radiopharmaceuticals are different. Proteins are much more complex and fragile than the synthetic compounds, and hence require new methods for adequate characterization and QC. Yet another complication is the labeling where there is a risk that a subpopulation of the protein is damaged to the level that it no longer binds the target. Therefore, a new toolbox is required to fulfill the quality characterization of radiolabeled antibodies. We have developed a QC assay for the simultaneous determination of antibody function, concentration and specific activity. The assay is based on time-resolved detection of the antibody interaction with antigen-coated magnetic beads in LigandTracer instruments. The resulting binding curve is evaluated using reverse kinetic fits, where the known interaction parameters of the antibody-antigen interaction are set constant while as the concentration and signal level are fitted. The assay takes approximately 2 hours and the majority of the time constitutes automated data collection in the instrument. The QC assay has been tested on multiple antibody-antigen interactions and consistently provides repeatable results for concentration and specific activity, both with coefficient of variation (CV) less than 15%. We believe that this QC assay can improve the quality of radiolabeled therapeutic antibodies. (authors)

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

    KAUST Repository

    Chan, Tak Ming; Wong, Ka Chun; Lee, Kin Hong; Wong, Man Hon; Lau, Chi Kong; Tsui, Stephen Kwok Wing; Leung, Kwong Sak

    2010-01-01

    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

  17. Family Interaction Patterns Associated with Self-Esteem in Preadolescent Girls and Boys.

    Science.gov (United States)

    Loeb, Roger C.; And Others

    1980-01-01

    Examines four traditional explanatory models for the influence of parents on children's self-esteem. These models are directiveness, modeling, reward and punishment, and positive family interaction. (Author/DB)

  18. 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

  19. bNEAT: a Bayesian network method for detecting epistatic interactions in genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Chen Xue-wen

    2011-07-01

    Full Text Available Abstract Background Detecting epistatic interactions plays a significant role in improving pathogenesis, prevention, diagnosis and treatment of complex human diseases. A recent study in automatic detection of epistatic interactions shows that Markov Blanket-based methods are capable of finding genetic variants strongly associated with common diseases and reducing false positives when the number of instances is large. Unfortunately, a typical dataset from genome-wide association studies consists of very limited number of examples, where current methods including Markov Blanket-based method may perform poorly. Results To address small sample problems, we propose a Bayesian network-based approach (bNEAT to detect epistatic interactions. The proposed method also employs a Branch-and-Bound technique for learning. We apply the proposed method to simulated datasets based on four disease models and a real dataset. Experimental results show that our method outperforms Markov Blanket-based methods and other commonly-used methods, especially when the number of samples is small. Conclusions Our results show bNEAT can obtain a strong power regardless of the number of samples and is especially suitable for detecting epistatic interactions with slight or no marginal effects. The merits of the proposed approach lie in two aspects: a suitable score for Bayesian network structure learning that can reflect higher-order epistatic interactions and a heuristic Bayesian network structure learning method.

  20. Interaction between MAOA and FOXP2 in association with autism and verbal communication in a Korean population.

    Science.gov (United States)

    Park, YoungJoon; Won, SeongSik; Nam, Min; Chung, Joo-Ho; Kwack, KyuBum

    2014-12-01

    Expression levels of monoamine oxidase A (MAOA), the enzyme that related to monoamine neurotransmitters metabolism such as serotonin, are related to schizophrenia and autism spectrum disorder. Forkhead box protein P2 (FOXP2), a transcription factor, is associated with abnormal language development and is expressed in several areas of the central nervous system in response to serotonin. For this reason, we undertook interaction analysis between MAOA and FOXP2 in autism spectrum disorder, including testing the verbal communication score of the childhood autism rating scale. In interaction analysis, the FOXP2-TCGC (rs12531289-rs1350135-rs10230087-rs2061183) diplotype and MAOA-TCG (rs6323-rs1801291-rs3027407) haplotype were significantly associated with autism spectrum disorder in males. However, when the interaction term was omitted, neither MAOA nor FOXP2 was associated with autism spectrum disorder or verbal communication. These results indicate that language and speech ability is affected by an interaction between FOXP2 and MAOA, but not by either gene separately. © The Author(s) 2013.

  1. 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.

  2. [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.

  3. Neuropeptide Y gene-by-psychosocial stress interaction effect is associated with obesity in a Korean population.

    Science.gov (United States)

    Kim, Hyun-Jin; Min, Kyoung-Bok; Min, Jin-Young

    2016-07-01

    Chronic psychosocial stress is a crucial risk factor in the development of many diseases including obesity. Neuropeptide Y (NPY), distributed throughout the peripheral and central nervous system, is believed to pay a role in the pathophysiologic relationship between stress and obesity. Although several animal studies have investigated the impact on obesity of interactions between NPY single nucleotide polymorphisms (SNPs) and stress, the same remains to be analyzed in humans. To identify NPY gene-by-stress interaction effects on human obesity, we analyzed the interaction between four NPY SNPs and stress with obesity-related traits, including visceral adipose tissue (VAT). A total of 1468 adult subjects were included for this analysis. In a SNP-only model without interaction with stress, no significant SNPs were found (pSNP>0.05). However, NPY SNPs-by-stress interaction effects were significantly linked to body mass index (BMI), waist circumference, and VAT (pintobesity. Among the obesity traits, mean changes of VAT by increased stress levels in homozygous risk allele carriers were the greatest (range of mean increases for four SNPs (min-max)=12.57cm(2)-29.86cm(2)). This study suggests that common polymorphisms for NPY were associated with human obesity by interacting with psychosocial stress, emphasizing the need for stress management in obesity prevention. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Insights into the interaction between nucleoid-associated proteins H ha and H-NS by NMR and fluorescence anisotropy

    Energy Technology Data Exchange (ETDEWEB)

    Cordeiro, T.N.; Garcia, J. [Institut de Recerca Biomedica-Parc Cientific de (Spain). Lab. of Biomolecular NMR; Pons, M. [Universitat de Barcelona (Spain). Dept. de Quimica Organica]. E-mail: mpons@ub.edu

    2005-07-01

    NMR and fluorescence anisotropy are both valuable tools for studying bio molecular interactions. NMR can provide structural insights at atomic resolution. Still, it can be wisely complemented by lower-resolution biophysical techniques, such as fluorescence anisotropy. In this article we report the combination of NMR and fluorescence anisotropy in establishing novel structure-function insights into the interaction between two bacterial nucleoid-associated proteins, H ha and H-NS. H ha (H-NS) complexes are known to play an important role in modulating the expression of some environmentally regulated genes that confer survival advantage in a particular growth condition. (author)

  5. Insights into the interaction between nucleoid-associated proteins H ha and H-NS by NMR and fluorescence anisotropy

    International Nuclear Information System (INIS)

    Cordeiro, T.N.; Garcia, J.; Pons, M.

    2005-01-01

    NMR and fluorescence anisotropy are both valuable tools for studying bio molecular interactions. NMR can provide structural insights at atomic resolution. Still, it can be wisely complemented by lower-resolution biophysical techniques, such as fluorescence anisotropy. In this article we report the combination of NMR and fluorescence anisotropy in establishing novel structure-function insights into the interaction between two bacterial nucleoid-associated proteins, H ha and H-NS. H ha (H-NS) complexes are known to play an important role in modulating the expression of some environmentally regulated genes that confer survival advantage in a particular growth condition. (author)

  6. Brain transcriptome-wide screen for HIV-1 Nef protein interaction partners reveals various membrane-associated proteins.

    Directory of Open Access Journals (Sweden)

    Ellen C Kammula

    Full Text Available HIV-1 Nef protein contributes essentially to the pathology of AIDS by a variety of protein-protein-interactions within the host cell. The versatile functionality of Nef is partially attributed to different conformational states and posttranslational modifications, such as myristoylation. Up to now, many interaction partners of Nef have been identified using classical yeast two-hybrid screens. Such screens rely on transcriptional activation of reporter genes in the nucleus to detect interactions. Thus, the identification of Nef interaction partners that are integral membrane proteins, membrane-associated proteins or other proteins that do not translocate into the nucleus is hampered. In the present study, a split-ubiquitin based yeast two-hybrid screen was used to identify novel membrane-localized interaction partners of Nef. More than 80% of the hereby identified interaction partners of Nef are transmembrane proteins. The identified hits are GPM6B, GPM6A, BAP31, TSPAN7, CYB5B, CD320/TCblR, VSIG4, PMEPA1, OCIAD1, ITGB1, CHN1, PH4, CLDN10, HSPA9, APR-3, PEBP1 and B3GNT, which are involved in diverse cellular processes like signaling, apoptosis, neurogenesis, cell adhesion and protein trafficking or quality control. For a subfraction of the hereby identified proteins we present data supporting their direct interaction with HIV-1 Nef. We discuss the results with respect to many phenotypes observed in HIV infected cells and patients. The identified Nef interaction partners may help to further elucidate the molecular basis of HIV-related diseases.

  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. Membrane association of the Arabidopsis ARF exchange factor GNOM involves interaction of conserved domains

    DEFF Research Database (Denmark)

    Anders, Nadine; Nielsen, Michael M.; Keicher, Jutta

    2008-01-01

    vesicle formation by activating ARF GTPases on specific membranes in animals, plants, and fungi. However, apart from the catalytic exchange activity of the SEC7 domain, the functional significance of other conserved domains is virtually unknown. Here, we show that a distinct N-terminal domain of GNOM......The GNOM protein plays a fundamental role in Arabidopsis thaliana development by regulating endosome-to-plasma membrane trafficking required for polar localization of the auxin efflux carrier PIN1. GNOM is a family member of large ARF guanine nucleotide exchange factors (ARF-GEFs), which regulate...... mediates dimerization and in addition interacts heterotypically with two other conserved domains in vivo. In contrast with N-terminal dimerization, the heterotypic interaction is essential for GNOM function, as mutations abolishing this interaction inactivate the GNOM protein and compromise its membrane...

  9. A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction

    Science.gov (United States)

    Tsai, Kuang-Lei; Sato, Shigeo; Tomomori-Sato, Chieri; Conaway, Ronald C.; Conaway, Joan W.; Asturias, Francisco J.

    2013-01-01

    The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) carboxy-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a preeminent complex in eukaryotic transcription regulation. We used macromolecular electron microscopy and biochemistry to investigate the subunit organization, structure, and Mediator interaction of the Saccharomyces cerevisiae CKM. We found that interaction of the CKM with Mediator’s Middle module interferes with CTD-dependent RNAPII binding to a previously unknown Middle module CTD-binding site targeted early on in a multi-step holoenzyme formation process. Taken together, our results reveal the basis for CKM repression, clarify the origin of the connection between CKM subunits and the CTD, and suggest that a combination of competitive interactions and conformational changes that facilitate holoenzyme formation underlie the Mediator mechanism. PMID:23563140

  10. Correcting systematic inflation in genetic association tests that consider interaction effects: application to a genome-wide association study of posttraumatic stress disorder.

    Science.gov (United States)

    Almli, Lynn M; Duncan, Richard; Feng, Hao; Ghosh, Debashis; Binder, Elisabeth B; Bradley, Bekh; Ressler, Kerry J; Conneely, Karen N; Epstein, Michael P

    2014-12-01

    Genetic association studies of psychiatric outcomes often consider interactions with environmental exposures and, in particular, apply tests that jointly consider gene and gene-environment interaction effects for analysis. Using a genome-wide association study (GWAS) of posttraumatic stress disorder (PTSD), we report that heteroscedasticity (defined as variability in outcome that differs by the value of the environmental exposure) can invalidate traditional joint tests of gene and gene-environment interaction. To identify the cause of bias in traditional joint tests of gene and gene-environment interaction in a PTSD GWAS and determine whether proposed robust joint tests are insensitive to this problem. The PTSD GWAS data set consisted of 3359 individuals (978 men and 2381 women) from the Grady Trauma Project (GTP), a cohort study from Atlanta, Georgia. The GTP performed genome-wide genotyping of participants and collected environmental exposures using the Childhood Trauma Questionnaire and Trauma Experiences Inventory. We performed joint interaction testing of the Beck Depression Inventory and modified PTSD Symptom Scale in the GTP GWAS. We assessed systematic bias in our interaction analyses using quantile-quantile plots and genome-wide inflation factors. Application of the traditional joint interaction test to the GTP GWAS yielded systematic inflation across different outcomes and environmental exposures (inflation-factor estimates ranging from 1.07 to 1.21), whereas application of the robust joint test to the same data set yielded no such inflation (inflation-factor estimates ranging from 1.01 to 1.02). Simulated data further revealed that the robust joint test is valid in different heteroscedasticity models, whereas the traditional joint test is invalid. The robust joint test also has power similar to the traditional joint test when heteroscedasticity is not an issue. We believe the robust joint test should be used in candidate-gene studies and GWASs of

  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

    Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed by these r......Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed...... 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...

  12. 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.…

  13. Severe Impairments of Social Interaction and Associated Abnormalities in Children: Epidemiology and Classification.

    Science.gov (United States)

    Wing, Lorna; Gould, Judith

    1979-01-01

    The prevalence of severe impairments of social interaction, language abnormalities, and repetitive stereotyped behaviors was investigated in a group of 132 children under 15 years old, consisting of a socially impaired group (more than half of whom were severely retarded) and a comparison group of sociable severely mentally retarded. Author/DLS)

  14. Factors Associated with Social Interactions between Deaf Children and Their Hearing Peers: A Systematic Literature Review

    Science.gov (United States)

    Batten, Georgina; Oakes, Peter M.; Alexander, Tim

    2014-01-01

    Research indicates that deaf children can have marked social difficulties compared with their hearing peers. Factors that influence these social interactions need to be reviewed to inform interventions. A systematic search of 5 key databases and 3 specialized journals identified 14 papers that met the inclusion criteria. Methodological quality of…

  15. 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

  16. Gene-Environment Interactions in Genome-Wide Association Studies: Current Approaches and New Directions

    Science.gov (United States)

    Winham, Stacey J.; Biernacka, Joanna M.

    2013-01-01

    Background: Complex psychiatric traits have long been thought to be the result of a combination of genetic and environmental factors, and gene-environment interactions are thought to play a crucial role in behavioral phenotypes and the susceptibility and progression of psychiatric disorders. Candidate gene studies to investigate hypothesized…

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

    DEFF Research Database (Denmark)

    Collins, Ryan L; Hu, Ting; Wejse, Christian

    2013-01-01

    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). Results The study used a previously published data set consisting of 19 candidate single-nucleotide polymorphisms (SNPs) in 321 pulmonary TB cases...

  18. 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.

  19. 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.

  20. 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.

  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. High performance computing enabling exhaustive analysis of higher order single nucleotide polymorphism interaction in Genome Wide Association Studies.

    Science.gov (United States)

    Goudey, Benjamin; Abedini, Mani; Hopper, John L; Inouye, Michael; Makalic, Enes; Schmidt, Daniel F; Wagner, John; Zhou, Zeyu; Zobel, Justin; Reumann, Matthias

    2015-01-01

    Genome-wide association studies (GWAS) are a common approach for systematic discovery of single nucleotide polymorphisms (SNPs) which are associated with a given disease. Univariate analysis approaches commonly employed may miss important SNP associations that only appear through multivariate analysis in complex diseases. However, multivariate SNP analysis is currently limited by its inherent computational complexity. In this work, we present a computational framework that harnesses supercomputers. Based on our results, we estimate a three-way interaction analysis on 1.1 million SNP GWAS data requiring over 5.8 years on the full "Avoca" IBM Blue Gene/Q installation at the Victorian Life Sciences Computation Initiative. This is hundreds of times faster than estimates for other CPU based methods and four times faster than runtimes estimated for GPU methods, indicating how the improvement in the level of hardware applied to interaction analysis may alter the types of analysis that can be performed. Furthermore, the same analysis would take under 3 months on the currently largest IBM Blue Gene/Q supercomputer "Sequoia" at the Lawrence Livermore National Laboratory assuming linear scaling is maintained as our results suggest. Given that the implementation used in this study can be further optimised, this runtime means it is becoming feasible to carry out exhaustive analysis of higher order interaction studies on large modern GWAS.

  3. MeCP2 interacts with HP1 and modulates its heterochromatin association during myogenic differentiation

    Science.gov (United States)

    Agarwal, Noopur; Hardt, Tanja; Brero, Alessandro; Nowak, Danny; Rothbauer, Ulrich; Becker, Annette; Leonhardt, Heinrich; Cardoso, M. Cristina

    2007-01-01

    There is increasing evidence of crosstalk between epigenetic modifications such as histone and DNA methylation, recognized by HP1 and methyl CpG-binding proteins, respectively. We have previously shown that the level of methyl CpG-binding proteins increased dramatically during myogenesis leading to large-scale heterochromatin reorganization. In this work, we show that the level of HP1 isoforms did not change significantly throughout myogenic differentiation but their localization did. In particular, HP1γ relocalization to heterochromatin correlated with MeCP2 presence. Using co-immunoprecipitation assays, we found that these heterochromatic factors interact in vivo via the chromo shadow domain of HP1 and the first 55 amino acids of MeCP2. We propose that this dynamic interaction of HP1 and MeCP2 increases their concentration at heterochromatin linking two major gene silencing pathways to stabilize transcriptional repression during differentiation. PMID:17698499

  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. Interactive multimodal ambulatory monitoring to investigate the association between physical activity and affect

    Directory of Open Access Journals (Sweden)

    Ulrich W. Ebner-Priemer

    2013-01-01

    Full Text Available Although there is a wealth of evidence that physical activity has positive effects on psychological health, a large proportion of people are inactive. Data regarding counts, steps, and movement patterns are limited in their ability to explain why people remain inactive. We propose that multimodal ambulatory monitoring, which combines the assessment of physical activity with the assessment of psychological variables, helps to elucidate real world physical activity. Whereas physical activity can be monitored continuously, psychological variables can only be assessed at discrete intervals, such as every hour. Moreover, the assessment of psychological variables must be linked to the activity of interest. For example, if an inactive and overweight person is physically active once a week, psychological variables should be assessed during this episode. Linking the assessment of psychological variables to episodes of an activity of interest can be achieved with interactive monitoring. The primary aim of our interactive multimodal ambulatory monitoring approach was to intentionally increase the number of e-diary assessments during active episodes.We developed and tested an interactive monitoring algorithm that continuously monitors physical activity in everyday life. When predefined thresholds are surpassed, the algorithm triggers a signal for participants to answer questions in their electronic diary.Using data from 70 participants wearing an accelerative device for 24 hours each, we found that our algorithm quadrupled the frequency of e-diary assessments during the activity episodes of interest compared to random sampling. Multimodal interactive ambulatory monitoring appears to be a promising approach to enhancing our understanding of real world physical activity and movement.

  6. Dyadic social interaction inhibits cocaine-conditioned place preference and the associated activation of the accumbens corridor.

    Science.gov (United States)

    Zernig, Gerald; Pinheiro, Barbara S

    2015-09-01

    Impaired social interaction is a hallmark symptom of many psychiatric disorders. In substance use disorders, impaired social interaction is triply harmful (a) because addicts increasingly prefer the drug of abuse to the natural reward of drug-free social interaction, thus worsening the progression of the disease by increasing their drug consumption, (b) because treatment adherence and, consequently, treatment success itself depends on the ability of the recovering addict to maintain social interaction and adhere to treatment, and (c) because socially interacting with an individual suffering from a substance use disorder may be harmful for others. Helping the addict reorient his/her behavior away from the drug of abuse toward social interaction would therefore be of considerable therapeutic benefit. This article reviews our work on the neural basis of such a reorientation from cocaine, as a prototypical drug of abuse, toward dyadic (i.e. one-to-one) social interaction and compares our findings with the effects of other potentially beneficial interventions, that is, environmental enrichment or paired housing, on the activation of the accumbens and other brain regions involved in behavior motivated by drugs of abuse or nondrug stimuli. Our experimental models are based on the conditioned place preference paradigm. As the therapeutically most promising finding, only four 15 min episodes of dyadic social interaction were able to inhibit both the subsequent reacquisition/re-expression of preference for cocaine and the neural activation associated with this behavior, that is, an increase in the expression of the immediate early gene Early Growth Response protein 1 (EGR1, Zif268) in the nucleus accumbens, basolateral and central amygdala, and the ventral tegmental area. The time spent in the cocaine-associated conditioning compartment was correlated with the density of EGR1-activated neurons not only in the medial core (AcbCm) and medial shell (AcbShm) of the nucleus

  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. 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.

  9. 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.

  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 Negative

  11. 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.

  12. 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.

  13. 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.

  14. 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/.

  15. 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.

  16. The translation initiation factor 3 subunit eIF3K interacts with PML and associates with PML nuclear bodies

    Energy Technology Data Exchange (ETDEWEB)

    Salsman, Jayme; Pinder, Jordan; Tse, Brenda [Department of Pathology, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2 (Canada); Corkery, Dale [Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia (Canada); Dellaire, Graham, E-mail: dellaire@dal.ca [Department of Pathology, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2 (Canada); Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia (Canada)

    2013-10-15

    The promyelocytic leukemia protein (PML) is a tumor suppressor protein that regulates a variety of important cellular processes, including gene expression, DNA repair and cell fate decisions. Integral to its function is the ability of PML to form nuclear bodies (NBs) that serve as hubs for the interaction and modification of over 90 cellular proteins. There are seven canonical isoforms of PML, which encode diverse C-termini generated by alternative pre-mRNA splicing. Recruitment of specific cellular proteins to PML NBs is mediated by protein–protein interactions with individual PML isoforms. Using a yeast two-hybrid screen employing peptide sequences unique to PML isoform I (PML-I), we identified an interaction with the eukaryotic initiation factor 3 subunit K (eIF3K), and in the process identified a novel eIF3K isoform, which we term eIF3K-2. We further demonstrate that eIF3K and PML interact both in vitro via pull-down assays, as well as in vivo within human cells by co-immunoprecipitation and co-immunofluorescence. In addition, eIF3K isoform 2 (eIF3K-2) colocalizes to PML bodies, particularly those enriched in PML-I, while eIF3K isoform 1 associates poorly with PML NBs. Thus, we report eIF3K as the first known subunit of the eIF3 translation pre-initiation complex to interact directly with the PML protein, and provide data implicating alternative splicing of both PML and eIF3K as a possible regulatory mechanism for eIF3K localization at PML NBs. - Highlights: • The PML-I C-terminus, encoded by exon 9, interacts with translation factor eIF3K. • We identify a novel eIF3K isoform that excludes exon 2 (eIF3K-2). • eIF3K-2 preferentially associates with PML bodies enriched in PML-I vs. PML-IV. • Alternative splicing of eIF3K regulates association with PML bodies.

  17. 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

  18. 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.

  19. 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.

  20. The Membrane-Associated Form of αs1-Casein Interacts with Cholesterol-Rich Detergent-Resistant Microdomains

    Science.gov (United States)

    Le Parc, Annabelle; Honvo Houéto, Edith; Pigat, Natascha; Chat, Sophie; Leonil, Joëlle; Chanat, Eric

    2014-01-01

    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 αs1-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 αs1-casein in rat mammary epithelial cells. Using metabolic labelling we show that αs1-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 αs1-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 αs1-casein. These experiments reveal that the insolubility of αs1-casein reflects its partial association with a cholesterol-rich detergent-resistant microdomain. We propose that the membrane-associated form of αs1-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. PMID:25549363

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

    Science.gov (United States)

    Le Parc, Annabelle; Honvo Houéto, Edith; Pigat, Natascha; Chat, Sophie; Leonil, Joëlle; Chanat, Eric

    2014-01-01

    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.

  2. 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.

  3. Nectin-like interactions between poliovirus and its receptor trigger conformational changes associated with cell entry.

    Science.gov (United States)

    Strauss, Mike; Filman, David J; Belnap, David M; Cheng, Naiqian; Noel, Roane T; Hogle, James M

    2015-04-01

    Poliovirus infection is initiated by attachment to a receptor on the cell surface called Pvr or CD155. At physiological temperatures, the receptor catalyzes an irreversible expansion of the virus to form an expanded form of the capsid called the 135S particle. This expansion results in the externalization of the myristoylated capsid protein VP4 and the N-terminal extension of the capsid protein VP1, both of which become inserted into the cell membrane. Structures of the expanded forms of poliovirus and of several related viruses have recently been reported. However, until now, it has been unclear how receptor binding triggers viral expansion at physiological temperature. Here, we report poliovirus in complex with an enzymatically partially deglycosylated form of the 3-domain ectodomain of Pvr at a 4-Å resolution, as determined by cryo-electron microscopy. The interaction of the receptor with the virus in this structure is reminiscent of the interactions of Pvr with its natural ligands. At a low temperature, the receptor induces very few changes in the structure of the virus, with the largest changes occurring within the footprint of the receptor, and in a loop of the internal protein VP4. Changes in the vicinity of the receptor include the displacement of a natural lipid ligand (called "pocket factor"), demonstrating that the loss of this ligand, alone, is not sufficient to induce particle expansion. Finally, analogies with naturally occurring ligand binding in the nectin family suggest which specific structural rearrangements in the virus-receptor complex could help to trigger the irreversible expansion of the capsid. The cell-surface receptor (Pvr) catalyzes a large structural change in the virus that exposes membrane-binding protein chains. We fitted known atomic models of the virus and Pvr into three-dimensional experimental maps of the receptor-virus complex. The molecular interactions we see between poliovirus and its receptor are reminiscent of the nectin

  4. Genetic determinants of cardiometabolic risk: a proposed model for phenotype association and interaction.

    Science.gov (United States)

    Blackett, Piers R; Sanghera, Dharambir K

    2013-01-01

    This review provides a translational and unifying summary of metabolic syndrome genetics and highlights evidence that genetic studies are starting to unravel and untangle origins of the complex and challenging cluster of disease phenotypes. The associated genes effectively express in the brain, liver, kidney, arterial endothelium, adipocytes, myocytes, and β cells. Progression of syndrome traits has been associated with ectopic lipid accumulation in the arterial wall, visceral adipocytes, myocytes, and liver. Thus, it follows that the genetics of dyslipidemia, obesity, and nonalcoholic fatty liver disease are central in triggering progression of the syndrome to overt expression of disease traits and have become a key focus of interest for early detection and for designing prevention and treatments. To support the "birds' eye view" approach, we provide a road-map depicting commonality and interrelationships between the traits and their genetic and environmental determinants based on known risk factors, metabolic pathways, pharmacologic targets, treatment responses, gene networks, pleiotropy, and association with circadian rhythm. Although only a small portion of the known heritability is accounted for and there is insufficient support for clinical application of gene-based prediction models, there is direction and encouraging progress in a rapidly moving field that is beginning to show clinical relevance. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  5. Fas-associated factor 1 interacts with protein kinase CK2 in vivo upon apoptosis induction

    DEFF Research Database (Denmark)

    Guerra, B; Boldyreff, B; Issinger, O G

    2001-01-01

    We show here that in several different cell lines protein kinase CK2 and Fas-associated factor 1 (FAF1) exist together in a complex which is stable to high monovalent salt concentration. The CK2/FAF1 complex formation is significantly increased after induction of apoptosis with various DNA damaging...

  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. 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.

  8. The Us2 gene product of herpes simplex virus 2 is a membrane-associated ubiquitin-interacting protein.

    Science.gov (United States)

    Kang, Ming-Hsi; Roy, Bibhuti B; Finnen, Renée L; Le Sage, Valerie; Johnston, Susan M; Zhang, Hui; Banfield, Bruce W

    2013-09-01

    The Us2 gene encodes a tegument protein that is conserved in most members of the Alphaherpesvirinae. Previous studies on the pseudorabies virus (PRV) Us2 ortholog indicated that it is prenylated, associates with membranes, and spatially regulates the enzymatic activity of the MAP (mitogen-activated protein) kinase ERK (extracellular signal-related kinase) through direct binding and sequestration of ERK at the cytoplasmic face of the plasma membrane. Here we present an analysis of the herpes simplex virus 2 (HSV-2) Us2 ortholog and demonstrate that, like PRV Us2, HSV-2 Us2 is a virion component and that, unlike PRV Us2, it does not interact with ERK in yeast two-hybrid assays. HSV-2 Us2 lacks prenylation signals and other canonical membrane-targeting motifs yet is tightly associated with detergent-insoluble membranes and localizes predominantly to recycling endosomes. Experiments to identify cellular proteins that facilitate HSV-2 Us2 membrane association were inconclusive; however, these studies led to the identification of HSV-2 Us2 as a ubiquitin-interacting protein, providing new insight into the functions of HSV-2 Us2.

  9. Emotional and Psychosocial Factors Associated With Drunkenness and the Use of Tobacco and Cannabis in Adolescence: Independent or Interactive Effects?

    Science.gov (United States)

    García-Moya, Irene; Ortiz Barón, María José; Moreno, Carmen

    2017-07-03

    Although previous research has examined emotional and psychosocial factors associated with substance use, there is a paucity of studies examining both at the same time, and insufficient attention has been paid to how these factors may interact. The aim of this study was to simultaneously examine the contributions from emotional (emotional control and depression) and psychosocial (peers' conventional behavior, peers' substance use and parent-child relationships) factors to drunkenness and the use of tobacco and cannabis in adolescence. Sample consisted of 1,752 adolescents aged 15 to 16 years who had participated in the 2014 edition of the WHO Health Behaviour in School-aged Children survey in Spain. Data were collected by means of anonymous online questionnaires, and hierarchical multiple regression models (with sex and age as controls and including interactions among the examined predictors) were used for statistical analysis. Emotional and psychosocial factors showed significant interactive effects on substance use. Emotional control, which tended to buffer the effects of potential risk factors, and peers' substance use were consistent predictors of substance use. In contrast, the role of other factors depended on the substance under study, with depression and peers' conventional behavior being part of interactive terms for tobacco use and cannabis use only, and the quality of parent-child relationships being absent from the final model on cannabis use. Conclusions/Importance: Exploring interactions and potential substance-specific effects is fundamental to reach a better understanding of how emotional and psychosocial factors work in concert relative to substance use in adolescence.

  10. 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

  11. 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

  12. Association of HS6ST3 gene polymorphisms with obesity and triglycerides: gene x gender interaction.

    Science.gov (United States)

    Wang, Ke-Sheng; Wang, Liang; Liu, Xuefeng; Zeng, Min

    2013-12-01

    The heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) gene is involved in heparan sulphate and heparin metabolism, and has been reported to be associated with diabetic retinopathy in type 2 diabetes.We hypothesized that HS6ST3 gene polymorphisms might play an important role in obesity and related phenotypes (such as triglycerides). We examined genetic associations of 117 single-nucleotide polymorphisms (SNPs) within the HS6ST3 gene with obesity and triglycerides using two Caucasian samples: the Marshfield sample (1442 obesity cases and 2122 controls), and the Health aging and body composition (Health ABC) sample (305 cases and 1336 controls). Logistic regression analysis of obesity as a binary trait and linear regression analysis of triglycerides as a continuous trait, adjusted for age and sex, were performed using PLINK. Single marker analysis showed that six SNPs in the Marshfield sample and one SNP in the Health ABC sample were associated with obesity (P triglycerides in the Marshfield sample (P triglycerides in the Marshfield sample. These findings contribute new insights into the pathogenesis of obesity and triglycerides and demonstrate the importance of gender differences in the aetiology.

  13. Genetic Determinants of Cardio-Metabolic Risk: A Proposed Model for Phenotype Association and Interaction

    Science.gov (United States)

    Blackett, Piers R; Sanghera, Dharambir K

    2012-01-01

    This review provides a translational and unifying summary of metabolic syndrome genetics and highlights evidence that genetic studies are starting to unravel and untangle origins of the complex and challenging cluster of disease phenotypes. The associated genes effectively express in the brain, liver, kidney, arterial endothelium, adipocytes, myocytes and β cells. Progression of syndrome traits has been associated with ectopic lipid accumulation in the arterial wall, visceral adipocytes, myocytes, and liver. Thus it follows that the genetics of dyslipidemia, obesity, and non-alcoholic fatty liver (NAFLD) disease are central in triggering progression of the syndrome to overt expression of disease traits, and have become a key focus of interest for early detection and for designing prevention and treatments. To support the “birds’ eye view” approach we provide a road-map depicting commonality and interrelationships between the traits and their genetic and environmental determinants based on known risk factors, metabolic pathways, pharmacological targets, treatment responses, gene networks, pleiotropy, and association with circadian rhythm. Although only a small portion of the known heritability is accounted for and there is insufficient support for clinical application of gene-based prediction models, there is direction and encouraging progress in a rapidly moving field that is beginning to show clinical relevance. PMID:23351585

  14. 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

  15. 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.

  16. 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.

  17. Synergistic interaction of Helichrysum pedunculatum leaf extracts with antibiotics against wound infection associated bacteria

    Directory of Open Access Journals (Sweden)

    OLAYINKA A AIYEGORO

    2009-01-01

    Full Text Available The effect of combinations of the crude methanolic extract of the leaves of Helichrysum pedunculatum and eight first-line antibiotics were investigated by time kill assays against a panel of bacterial strains that have been implicated in wound infections. The plant extract showed appreciable antibacterial activities against the test bacteria with zones of inhibition ranging between 18 and 27 mm, and minimum inhibitory concentrations (MICs varying between 0.1 and 5.0 mg/ml. The MICs of the test antibiotics range between 0.001 and 0.412 mg/ml, and combination of the plant extract and the antibiotics resulted in reduction of bacterial counts by between 0 and 6.63 Log10 cfu/ml. At V2 MIC, 56.81% synergy; 43.19% indifference and no antagonism were observed, and at MIC levels, 55.68% synergy; 44.32% indifference and no antagonism were observed when the extracts were combined with eight different antibiotics. In all, 60% of the interactions were synergistic. All combination regimes on Staphylococcus aureus ATCC 6538 yielded no synergy, neither was antagonism detected in any of the assays. We propose that extracts of the leaves of Helichrysum pedunculatum could be of relevance in combination therapy and as a source of resistance modifying principies that could be useful as treatment options for persistent wound infections.

  18. Synergistic interaction of Helichrysum pedunculatum leaf extracts with antibiotics against wound infection associated bacteria.

    Science.gov (United States)

    Aiyegoro, Olayinka A; Afolayan, Anthony J; Okoh, Anthony I

    2009-01-01

    The effect of combinations of the crude methanolic extract of the leaves of Helichrysum pedunculatum and eight first-line antibiotics were investigated by time kill assays against a panel of bacterial strains that have been implicated in wound infections. The plant extract showed appreciable antibacterial activities against the test bacteria with zones of inhibition ranging between 18 and 27 mm, and minimum inhibitory concentrations (MICs) varying between 0.1 and 5.0 mg/ml. The MICs of the test antibiotics range between 0.001 and 0.412 mg/ml, and combination of the plant extract and the antibiotics resulted in reduction of bacterial counts by between 0 and 6.63 Log10 cfu/ml. At V2 MIC, 56.81% synergy; 43.19% indifference and no antagonism were observed, and at MIC levels, 55.68% synergy; 44.32% indifference and no antagonism were observed when the extracts were combined with eight different antibiotics. In all, 60% of the interactions were synergistic. All combination regimes on Staphylococcus aureus ATCC 6538 yielded no synergy, neither was antagonism detected in any of the assays. We propose that extracts of the leaves of Helichrysum pedunculatum could be of relevance in combination therapy and as a source of resistance modifying principies that could be useful as treatment options for persistent wound infections.

  19. 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.

  20. 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...

  1. 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

  2. KIR and HLA interactions are associated with control of primary CMV infection in solid organ transplant recipients.

    Science.gov (United States)

    van Duin, D; Avery, R K; Hemachandra, S; Yen-Lieberman, B; Zhang, A; Jain, A; Butler, R S; Barnard, J; Schold, J D; Fung, J; Askar, M

    2014-01-01

    Cytomegalovirus (CMV) infection remains a major source of morbidity and mortality in solid organ transplant recipients. Killer immunoglobulin-like receptors(KIR) are genetically polymorphic natural killer(NK) cell receptors important in antiviral responses. A retrospective, single-center cohort study was performed to study the interaction of KIR genotype and primary control of CMV infection after transplantation.Time to first CMV viremia was determined for a cohort of 531 CMV serology donor positive/recipient negative solid organ transplant recipients. Of the KIR genes,KIR2DL3 and KIR2DS2 were most strongly associated with time to CMV viremia in random survival forest analysis. As KIR2DL3 and KIR2DS2 both interact with HLA-C1, these interactions were evaluated. Seventy six recipients were found to be positive for both KIR2DL3 and KIR2DS2 and expressed only HLA-C1 antigens in both recipient and donor. These patients had a substantially reduced hazard of CMV viremia in the first year after solid organ transplantation (hazard ratio 0.44, 95% CI 0.27–0.72, p=0.0012). In KIR2DL3+/KIR2DS2+/HLA-C1/1 recipients who received an organ from a non-C1/1 donor, this protective effect was not observed. These results improve our understanding of human NK cell function in primary CMV infection after transplant.

  3. 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.

  4. 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.

  5. Electron precipitation and VLF emissions associated with cyclotron resonance interactions near the plasmapause

    International Nuclear Information System (INIS)

    Foster, J.C.; Rosenberg, T.J.

    1976-01-01

    Correlated bursts of bremsstrahlung X rays and VLF emissions were recorded for approx.25 min at Siple Station, Antarctica, on January 2, 1971. The burst occurred quasi-periodically with spectral power predominantly in the period range 4--12 s. A typical VLF burst consisted of 3--5 rising elements of approx.0.1-s duration separated by approx.0.15 s and was confined to the frequency range 1.5--3.8 kHz. Evidence is presented to show that the bursts were triggered by the low-frequency tail of whistlers propagating from the northern hemisphere. The interpretation of the observations in terms of an equatorial cyclotron resonance interaction occurring at the outer edge of the plasmapause on the L=4.2 field line, offered initially by Rosenberg et al. (1971), is given further support by the more extensive analysis presented here of the electron energy-wave frequency relationship in the bursts and the propagation times for the resonant waves and electrons. It is inferred from the X ray data that the equatorial flux of trapped electrons was probably anisotropic and near the stable trapping limit at the time of this event. It is suggested that an important effect of the trigger signal is the increase of the anisotropy of the resonant electrons. Wave growth rates calculated in the random phase approximation for electron pitch angle distributions that might apply in this event can explain certain features of the VLF and precipitation data during and between the bursts

  6. 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.

  7. 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.

  8. The SEMA5A gene is associated with hippocampal volume, and their interaction is associated with performance on Raven's Progressive Matrices.

    Science.gov (United States)

    Zhu, Bi; Chen, Chuansheng; Xue, Gui; Moyzis, Robert K; Dong, Qi; Chen, Chunhui; Li, Jin; He, Qinghua; Lei, Xuemei; Wang, Yunxin; Lin, Chongde

    2014-03-01

    The Allen Brain Atlas shows that the semaphorin 5A (SEMA5A) gene, which encodes an important protein for neurogenesis and neuronal apoptosis, is predominantly expressed in the human hippocampus. Structural and functional neuroimaging studies have further shown that the hippocampus plays an important role in the performance on Raven's Progressive Matrices (RPM), a measure of reasoning ability and general fluid intelligence. Thus far, however, no study has examined the relationships between the SEMA5A gene polymorphism, hippocampal volume, and RPM performance. The current study collected both structural MRI, genetic, and behavioral data in 329 healthy Chinese adults, and examined associations between SEMA5A variants, hippocampal volume, and performance on RAPM (the advanced form of RPM). After controlling for intracranial volume (ICV), sex, and age, SEMA5A genetic polymorphism at the SNP rs42352 had the strongest association with hippocampal volume (p=0.00000552 and 0.000103 for right and left hippocampal volumes, respectively), with TT homozygotes having higher hippocampal volume than the other genotypes. Furthermore, there was a high correlation between right hippocampal volume and RAPM performance (r=0.42, p=0.0000509) for SEMA5A rs42352 TT homozygotes. This study provides the first evidence for the involvement of the SEMA5A gene in hippocampal structure and their interaction on RAPM performance. Future studies of the hippocampus-RPM associations should consider genetic factors as potential moderators. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. 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

  10. Bidirectional Associations between Bedtime Parenting and Infant Sleep: Parenting Quality, Parenting Practices, and their Interaction

    Science.gov (United States)

    Philbrook, Lauren E.; Teti, Douglas M.

    2016-01-01

    In keeping with transactional conceptualizations of infant sleep development (Sadeh et al., 2010), the present study examined longitudinal, bidirectional linkages between bedtime parenting (direct observations of parenting practices and quality) and infant sleep across the first six months postpartum. In doing so, we also drew from Darling and Steinberg's (1993) conceptual model to examine parenting quality as a moderator of linkages between specific bedtime practices and infant sleep. Multilevel model analyses revealed that the strongest increases in infant nighttime sleep across the first six months occurred among infants of mothers who engaged in low levels of nursing at bedtime. Within-person linkages between mothers' emotional availability (EA) at bedtime, infant distress, and infant sleep were found, such that at time points when mothers were more emotionally available, infants were less distressed and slept more throughout the night. Several moderating effects of maternal EA on linkages between parenting practices and infant sleep were obtained that were consistent with predictions from Darling and Steinberg (1993). Higher maternal EA in combination with less close contact at bedtime was associated with more infant sleep across the night on average, and higher EA in combination with fewer arousing bedtime activities predicted more rapid increases in infant sleep with age. Finally, there was evidence of infant-driven effects, as higher infant nighttime distress predicted lower EA at subsequent time points. Results showcased the complex, reciprocal interplay between parents and infants in the development of infant sleep patterns and parenting behavior during the first six months postpartum. PMID:27010601

  11. 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.

  12. 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 employees, higher sitting times on work days and occupational sitting were associated with decreased mental well-being (p 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.

  13. Bidirectional associations between bedtime parenting and infant sleep: Parenting quality, parenting practices, and their interaction.

    Science.gov (United States)

    Philbrook, Lauren E; Teti, Douglas M

    2016-06-01

    In keeping with transactional conceptualizations of infant sleep development (Sadeh, Tikotzky, & Scher, 2010), the present study was an examination of longitudinal, bidirectional linkages between bedtime parenting (through direct observations of parenting practices and quality) and infant sleep across the first 6 months postpartum. In doing so, we also drew from Darling and Steinberg's (1993) conceptual model to examine parenting quality as a moderator of linkages between specific bedtime practices and infant sleep. Multilevel model analyses revealed that the strongest increases in infant nighttime sleep across the first 6 months occurred among infants of mothers who engaged in low levels of nursing at bedtime. Within-person linkages between mothers' emotional availability (EA) at bedtime, infant distress, and infant sleep were found, such that at time points when mothers were more emotionally available, infants were less distressed and slept more throughout the night. Several moderating effects of maternal EA on linkages between parenting practices and infant sleep were obtained that were consistent with predictions from Darling and Steinberg (1993). Higher maternal EA in combination with less close contact at bedtime was associated with more infant sleep across the night on average, and higher EA in combination with fewer arousing bedtime activities predicted more rapid increases in infant sleep with age. Finally, there was evidence of infant-driven effects, as higher infant nighttime distress predicted lower EA at subsequent time points. Results showcased the complex, reciprocal interplay between parents and infants in the development of infant sleep patterns and parenting behavior during the first 6 months postpartum. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  14. Whole brain and brain regional coexpression network interactions associated with predisposition to alcohol consumption.

    Directory of Open Access Journals (Sweden)

    Lauren A Vanderlinden

    Full Text Available To identify brain transcriptional networks that may predispose an animal to consume alcohol, we used weighted gene coexpression network analysis (WGCNA. Candidate coexpression modules are those with an eigengene expression level that correlates significantly with the level of alcohol consumption across a panel of BXD recombinant inbred mouse strains, and that share a genomic region that regulates the module transcript expression levels (mQTL with a genomic region that regulates alcohol consumption (bQTL. To address a controversy regarding utility of gene expression profiles from whole brain, vs specific brain regions, as indicators of the relationship of gene expression to phenotype, we compared candidate coexpression modules from whole brain gene expression data (gathered with Affymetrix 430 v2 arrays in the Colorado laboratories and from gene expression data from 6 brain regions (nucleus accumbens (NA; prefrontal cortex (PFC; ventral tegmental area (VTA; striatum (ST; hippocampus (HP; cerebellum (CB available from GeneNetwork. The candidate modules were used to construct candidate eigengene networks across brain regions, resulting in three "meta-modules", composed of candidate modules from two or more brain regions (NA, PFC, ST, VTA and whole brain. To mitigate the potential influence of chromosomal location of transcripts and cis-eQTLs in linkage disequilibrium, we calculated a semi-partial correlation of the transcripts in the meta-modules with alcohol consumption conditional on the transcripts' cis-eQTLs. The function of transcripts that retained the correlation with the phenotype after correction for the strong genetic influence, implicates processes of protein metabolism in the ER and Golgi as influencing susceptibility to variation in alcohol consumption. Integration of these data with human GWAS provides further information on the function of polymorphisms associated with alcohol-related traits.

  15. 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.

  16. 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.

  17. Centrobin-centrosomal protein 4.1-associated protein (CPAP) interaction promotes CPAP localization to the centrioles during centriole duplication.

    Science.gov (United States)

    Gudi, Radhika; Zou, Chaozhong; Dhar, Jayeeta; Gao, Qingshen; Vasu, Chenthamarakshan

    2014-05-30

    Centriole duplication is the process by which two new daughter centrioles are generated from the proximal end of preexisting mother centrioles. Accurate centriole duplication is important for many cellular and physiological events, including cell division and ciliogenesis. Centrosomal protein 4.1-associated protein (CPAP), centrosomal protein of 152 kDa (CEP152), and centrobin are known to be essential for centriole duplication. However, the precise mechanism by which they contribute to centriole duplication is not known. In this study, we show that centrobin interacts with CEP152 and CPAP, and the centrobin-CPAP interaction is critical for centriole duplication. Although depletion of centrobin from cells did not have an effect on the centriolar levels of CEP152, it caused the disappearance of CPAP from both the preexisting and newly formed centrioles. Moreover, exogenous expression of the CPAP-binding fragment of centrobin also caused the disappearance of CPAP from both the preexisting and newly synthesized centrioles, possibly in a dominant negative manner, thereby inhibiting centriole duplication and the PLK4 overexpression-mediated centrosome amplification. Interestingly, exogenous overexpression of CPAP in the centrobin-depleted cells did not restore CPAP localization to the centrioles. However, restoration of centrobin expression in the centrobin-depleted cells led to the reappearance of centriolar CPAP. Hence, we conclude that centrobin-CPAP interaction is critical for the recruitment of CPAP to procentrioles to promote the elongation of daughter centrioles and for the persistence of CPAP on preexisting mother centrioles. Our study indicates that regulation of CPAP levels on the centrioles by centrobin is critical for preserving the normal size, shape, and number of centrioles in the cell. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Centrobin-Centrosomal Protein 4.1-associated Protein (CPAP) Interaction Promotes CPAP Localization to the Centrioles during Centriole Duplication*

    Science.gov (United States)

    Gudi, Radhika; Zou, Chaozhong; Dhar, Jayeeta; Gao, Qingshen; Vasu, Chenthamarakshan

    2014-01-01

    Centriole duplication is the process by which two new daughter centrioles are generated from the proximal end of preexisting mother centrioles. Accurate centriole duplication is important for many cellular and physiological events, including cell division and ciliogenesis. Centrosomal protein 4.1-associated protein (CPAP), centrosomal protein of 152 kDa (CEP152), and centrobin are known to be essential for centriole duplication. However, the precise mechanism by which they contribute to centriole duplication is not known. In this study, we show that centrobin interacts with CEP152 and CPAP, and the centrobin-CPAP interaction is critical for centriole duplication. Although depletion of centrobin from cells did not have an effect on the centriolar levels of CEP152, it caused the disappearance of CPAP from both the preexisting and newly formed centrioles. Moreover, exogenous expression of the CPAP-binding fragment of centrobin also caused the disappearance of CPAP from both the preexisting and newly synthesized centrioles, possibly in a dominant negative manner, thereby inhibiting centriole duplication and the PLK4 overexpression-mediated centrosome amplification. Interestingly, exogenous overexpression of CPAP in the centrobin-depleted cells did not restore CPAP localization to the centrioles. However, restoration of centrobin expression in the centrobin-depleted cells led to the reappearance of centriolar CPAP. Hence, we conclude that centrobin-CPAP interaction is critical for the recruitment of CPAP to procentrioles to promote the elongation of daughter centrioles and for the persistence of CPAP on preexisting mother centrioles. Our study indicates that regulation of CPAP levels on the centrioles by centrobin is critical for preserving the normal size, shape, and number of centrioles in the cell. PMID:24700465

  19. 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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Antoinesha L. Hollman

    2016-03-01

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

  2. 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.

  3. 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.

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

    Science.gov (United States)

    Cloyd, Raymond A

    2015-04-09

    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.

  5. Associative birth of the J/PSI meson and photon in the polarizing ep and pp interactions

    International Nuclear Information System (INIS)

    Temiraliev, A.T.

    2001-01-01

    Appearance of so named 'spin crisis' acutely states the problem about role of gluons and sea quacks in nucleon spin structure function. For revealing of gluons contribution the joint birth of J/PSI meson and photon with opposite transverse impulse in polarizing electron-proton and proton-proton interactions have been studied. Calculation have been carried within the framework of the theory of quantum chromodynamics collisions. Charming meson decay into either electron-positron pair or meson pair gives experimental pure finite state. Measurement of the polarizing asymmetry of associative birth of J/PSI meson and photon in the result of both experiments (ep and pp) allow to determine gluons polarization unambiguously

  6. 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.

  7. Ionic association and interspecies interactions of 1-1 electrolytes in ethyl acetate solutions at 5-45 deg C

    International Nuclear Information System (INIS)

    Kalugin, O. N.; Panchenko, V. G.; V'yunnik, I. N.

    2005-01-01

    The data of conductometric studies of LiClO 4 , NaClO 4 , NaBPh 4 , and Bu 4 NClO 4 solutions in ethylacetate in the temperature range 5 to 45 deg C are reported. The constants of ionic association resulting in formation of ion pairs and triple ions, as well as limiting molar electric conductivities of the ions and triple ions are determined. It is found that the formation of contact triple ions having mutually interpenetrated structural elements in cavities of each others is characteristic of electrolytes with bulky organic ions. Anomalous temperature dependence of dynamic sizes of the [Na 2 BPh 4 ] + and [Na(BPh 4 ) 2 ] - ions and substantial differences in energy characteristics of inter-ion interactions are revealed during formation of ion pairs and triple ions in ethylacetate solutions of NaBPh 4 [ru

  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. 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.

  10. Deceptive but Not Honest Manipulative Actions Are Associated with Increased Interaction between Middle and Inferior Frontal gyri

    Directory of Open Access Journals (Sweden)

    Maxim Kireev

    2017-08-01

    Full Text Available The prefrontal cortex is believed to be responsible for execution of deceptive behavior and its involvement is associated with greater cognitive efforts. It is also generally assumed that deception is associated with the inhibition of default honest actions. However, the precise neurophysiological mechanisms underlying this process remain largely unknown. The present study was aimed to use functional magnetic resonance imaging to reveal the underlying functional integration within the prefrontal cortex during the task which requires that subjects to deliberately mislead an opponent through the sequential execution of deceptive and honest claims. To address this issue, we performed psychophysiological interaction (PPI analysis, which allows for statistical assessment of changes in functional relationships between active brain areas in changing psychological contexts. As a result the whole brain PPI-analysis established that both manipulative honest and deceptive claiming were associated with an increase in connectivity between the left middle frontal gyrus and right temporo-parietal junction (rTPJ. Taking into account the role played by rTPJ in processes associated with the theory of mind the revealed data can reflect possible influence of socio-cognitive context on the process of selecting manipulative claiming regardless their honest or deceptive nature. Direct comparison between deceptive and honest claims revealed pattern enhancement of coupling between the left middle frontal gyrus and the left inferior frontal gyrus. This finding provided evidence that the execution of deception relies to a greater extent on higher-order hierarchically-organized brain mechanisms of executive control required to select between two competing deceptive or honest task sets.

  11. 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.

  12. 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

  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. Evidence for a new particle with naked ''beauty'' and for its associated production in high-energy (pp) interactions

    International Nuclear Information System (INIS)

    Basile, M.; Bonvicini, G.; Cara Romeo, G.; Cifarelli, L.; Contin, A.; D'Ali, G.; Di Cesare, P.; Esposito, B.; Giusti, P.; Massam, T.; Nania, R.; Palmonari, F.; Sartorelli, G.; Valenti, G.; Zichichi, A.; Bologna Univ.; Perugia Univ.

    1981-01-01

    Evidence is reported for the existence, with six standard deviations significance, of a new particle: the heaviest baryon observed so far, whose mass is measured to be m = (5,425 +- 75 175 ) MeV/c 2 . Its width is compatible with zero. It is electrically neutral and it decays into a proton, a D 0 , and a π - . This particle is produced in association with a hadronic state whose semileptonic decay contains a positive electron. The partial cross section for the observed effect is δσ = (3.8 +- 1.2) x 10 - 35 cm 2 . The interpretation of these results is in terms of the associated production of naked ''beauty'' states in (pp) interactions at √s = 62 GeV c.m. energy. The new particle is identified as the first ''beauty''-flavoured baryon with quark composition (udb), i.e. the #betta# 0 sub(b). The discrimination power of the experiment against ''known'' physics, is of the order of 10 - 10 . (author)

  16. 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.

  17. Evaluation of potential novel variations and their interactions related to bipolar disorders: analysis of genome-wide association study data.

    Science.gov (United States)

    Acikel, Cengizhan; Aydin Son, Yesim; Celik, Cemil; Gul, Husamettin

    2016-01-01

    Multifactor dimensionality reduction (MDR) is a nonparametric approach that can be used to detect relevant interactions between single-nucleotide polymorphisms (SNPs). The aim of this study was to build the best genomic model based on SNP associations and to identify candidate polymorphisms that are the underlying molecular basis of the bipolar disorders. This study was performed on Whole-Genome Association Study of Bipolar Disorder (dbGaP [database of Genotypes and Phenotypes] study accession number: phs000017.v3.p1) data. After preprocessing of the genotyping data, three classification-based data mining methods (ie, random forest, naïve Bayes, and k-nearest neighbor) were performed. Additionally, as a nonparametric, model-free approach, the MDR method was used to evaluate the SNP profiles. The validity of these methods was evaluated using true classification rate, recall (sensitivity), precision (positive predictive value), and F-measure. Random forests, naïve Bayes, and k-nearest neighbors identified 16, 13, and ten candidate SNPs, respectively. Surprisingly, the top six SNPs were reported by all three methods. Random forests and k-nearest neighbors were more successful than naïve Bayes, with recall values >0.95. On the other hand, MDR generated a model with comparable predictive performance based on five SNPs. Although different SNP profiles were identified in MDR compared to the classification-based models, all models mapped SNPs to the DOCK10 gene. Three classification-based data mining approaches, random forests, naïve Bayes, and k-nearest neighbors, have prioritized similar SNP profiles as predictors of bipolar disorders, in contrast to MDR, which has found different SNPs through analysis of two-way and three-way interactions. The reduced number of associated SNPs discovered by MDR, without loss in the classification performance, would facilitate validation studies and decision support models, and would reduce the cost to develop predictive and

  18. 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.

  19. Interactions between smoking and other exposures associated with lung cancer risk in women: diet and physical activity.

    Science.gov (United States)

    Kubík, A; Zatloukal, P; Tomásek, L; Pauk, N; Havel, L; Dolezal, J; Plesko, I

    2007-01-01

    The objective of the study is to estimate the differences in the impact of diet and physical exercise on lung cancer risk in female nonsmokers vs. smokers, and reveal interactions, if any. In a hospital based case-control study, data collected by in-person interviews from 569 female lung cancer cases and 2120 controls were analyzed using unconditional logistic regression stratifying by appropriate factors. Protective effects were observed for intake of milk/dairy products (OR=0.57, 95%CI 0.35-0.94), vegetables (OR=0.60, 95%CI 0.40-0.91), apples (OR=0.69), wine (OR=0.77), and physical exercise (OR=0.59, 95%CI 0.42-0.83) among smokers only, while no similar effects were found among nonsmokers. In contrast, the intake of black tea was associated with a protective effect (OR=0.66, 95%CI 0.47-0.94) among nonsmokers only. Comparing the effects of dietary items and physical activity on lung cancer risk among nonsmokers versus smokers, statistically significant effect modifications were found for black tea (P 0.005), and milk/dairy products (P 0.047). Borderline effect modifications emerged for physical exercise (P 0.077). These results indicate protective effects of some components of healthful diet and physical exercise among smokers, and of the intake of black tea among nonsmokers. The observed interactions of the impact of black tea, milk/dairy products and physical activity upon lung cancer risk in women at different levels of the smoking habit deserve further studies.

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

    Directory of Open Access Journals (Sweden)

    Colette Broekgaarden

    Full Text Available 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.

  1. 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

  2. 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.

  3. 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.

  4. The interactive association between heat shock factor 1 and heat shock proteins in primary myocardial cells subjected to heat stress.

    Science.gov (United States)

    Tang, Shu; Chen, Hongbo; Cheng, Yanfen; Nasir, Mohammad Abdel; Kemper, Nicole; Bao, Endong

    2016-01-01

    Heat shock factor 1 (HSF1) is a heat shock transcription factor that rapidly induces heat shock gene transcription following thermal stress. In this study, we subjected primary neonatal rat myocardial cells to heat stress in vitro to create a model system for investigating the trends in expression and association between various heat shock proteins (HSPs) and HSF1 under adverse environmental conditions. After the cells were subjected to heat stress at 42˚C for different periods of time, HSP and HSF1 mRNA and protein levels were detected by qPCR and western blot analysis in the heat-stressed cells. The HSF1 expression levels significantly increased in the cells following 120 min of exposure to heat stess compared to the levels observed at the beginning of heat stress exposure. HSP90 followed a similar trend in expression to HSF1, whereas HSP70 followed an opposite trend. However, no significant changes were observed in the crystallin, alpha B (CRYAB, also known as HSP beta-5) expression levels during the 480‑min period of exposure to heat stress. The interaction between the HSPs and HSF1 was analyzed by STRING 9.1, and it was found that HSF1 interacted with HSP90 and HSP70, and that it did not play a role in regulating CRYAB expression. Based on our findings, HSP70 may suppress HSF1 in rat myocardial cells under conditions of heat stress. Furthermore, our data demonstrate that HSF1 is not the key factor for all HSPs, and this was particularly the case for CRYAB.

  5. 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

  6. Pharmacovigilance Evaluation of the Association Between DPP-4 Inhibitors and Heart Failure: Stimulated Reporting and Moderation by Drug Interactions.

    Science.gov (United States)

    Fadini, Gian Paolo; Sarangdhar, Mayur; Avogaro, Angelo

    2018-04-01

    In the SAVOR-TIMI trial, the risk of heart failure (HF) was increased by 27% in T2D patients randomized to the dipeptidyl peptidase-4 inhibitor (DPP4i) saxagliptin. Other studies have provided inconsistent results regarding this association. Herein, we performed a pharmacovigilance analysis of the rate of HF associated with DPP4is, focusing on stimulated reporting and moderation by drug-drug interactions. We mined the FDA adverse event (AE) reporting system (FAERS) from 2004q1 to 2017q3, including a total of 9906,642 AE reports. Rates (/1000 reports) of HF within the reports for DPP4is and reports for other antidiabetic drugs were calculated for the period up to 2013q3 (date of publication of the SAVOR-TIMI trial results) and from 2013q4 to 2017q3. Analyses were refined by filtering according to therapeutic area, concomitant diseases and drugs, and competing AEs. The rate of HF among the AE reports filed for DPP4is significantly increased after 2013q3, especially for saxagliptin. When compared to non-insulin non-glitazone antidiabetic drugs, the proportional reporting ratio (PRR) of HF for DPP4is was 0.62 (95% CI 0.56-0.68) up to 2013q3 and 2.12 (95% CI 1.96-2.28) from 2013q4 to 2017q3. This stimulated reporting was consistent in subanalyses based on the presence/absence of cardiac disorders and after controlling for competing AEs. The rate of HF among AE reports for DPP4is was modestly moderated by the concomitant use of metformin (- 15%) and strongly moderated by the concomitant use of SGLT2 inhibitors (- 63%), even after excluding competing AEs. Within the FAERS, the association between HF and DPP4is was biased by stimulated reporting, implying that the publication of the SAVOR-TIMI trial and the subsequent regulatory warnings primed clinicians to report HF events in DPP4i users as drug-related AEs. The rate of HF associated with DPP4is was moderated when they were used in combination with SGLT2 inhibitors.

  7. Association and Interaction Effect of AGTR1 and AGTR2 Gene Polymorphisms with Dietary Pattern on Metabolic Risk Factors of Cardiovascular Disease in Malaysian Adults

    OpenAIRE

    Yap, Roseline Wai Kuan; Shidoji, Yoshihiro; Yap, Wai Sum; Masaki, Motofumi

    2017-01-01

    Gene-diet interaction using a multifactorial approach is preferred to study the multiple risk factors of cardiovascular disease (CVD). This study examined the association and gene-diet interaction effects of the angiotensin II type 1 receptor (AGTR1) gene (rs5186), and type 2 receptor (AGTR2) gene (rs1403543) polymorphisms on metabolic risk factors of CVD in Malaysian adults. CVD parameters (BMI, blood pressure, glycated hemoglobin, total cholesterol (TC), triglycerides, low-density lipoprote...

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Gavin R. McCormack

    2017-01-01

    Full Text Available 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.

  10. Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes.

    Science.gov (United States)

    Saad, Rama; Rizkallah, Mariam R; Aziz, Ramy K

    2012-11-30

    The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP) opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics), notably in the human gut. The HMP continues to characterize the microbial communities associated with the human gut, determine whether there is a common gut microbiome profile shared among healthy humans, and investigate the effect of its alterations on health. Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. We discuss a few examples representing how the microbiome interacts with human metabolic enzymes in the liver and intestine. In addition, we attempt to envisage a roadmap for the future implications of the HMP on therapeutics and personalized medicine.

  11. Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes

    Directory of Open Access Journals (Sweden)

    Saad Rama

    2012-11-01

    Full Text Available Abstract The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics, notably in the human gut. The HMP continues to characterize the microbial communities associated with the human gut, determine whether there is a common gut microbiome profile shared among healthy humans, and investigate the effect of its alterations on health. Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. We discuss a few examples representing how the microbiome interacts with human metabolic enzymes in the liver and intestine. In addition, we attempt to envisage a roadmap for the future implications of the HMP on therapeutics and personalized medicine.

  12. 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

  13. 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.

  14. 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 interaction between endogenous uPA and uPAR is selectively abrogated, whereas other functions of both the protease and its receptor are retained. Specifically, we introduced 4 amino acid substitutions into the growth factor domain (GFD) of uPA that abrogate uPAR binding while preserving the overall structure...... 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....

  15. 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.

  16. BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions.

    Science.gov (United States)

    Shalev, Idan; Lerer, Elad; Israel, Salomon; Uzefovsky, Florina; Gritsenko, Inga; Mankuta, David; Ebstein, Richard P; Kaitz, Marsha

    2009-04-01

    A key protein in maintaining neuronal integrity throughout the life span is brain-derived neurotrophic factor (BDNF). The BDNF gene is characterized by a functional polymorphism, which has been associated with stress-related disorders such as anxiety-related syndromes and depression, prompting us to examine individual responses by Genotype and Sex to a standardized social stress paradigm. Gender differences in BDNFxstress responses were posited because estrogen induces synthesis of BDNF in several brain regions. 97 university students (51 females and 46 males) participated in a social stress procedure (Trier Social Stress Test, TSST). Indices of stress were derived from repeated measurement of cortisol, blood pressure, and heart rate during the TSST. All subjects were genotyped for the Val66Met polymorphism. Tests of within-subject effects showed a significant three-way interaction (SPSS GLM repeated measures: Time (eight levels)xBDNF (val/val, val/met)xSex: p=0.0002), which reflects gender differences in the pattern of cortisol rise and decline during the social challenge. In male subjects, val/val homozygotes showed a greater rise in salivary cortisol than val/met heterozygotes. In female subjects, there was a trend for the opposite response, which is significant when area under the curve increase (AUCi) was calculated for the val/val homozygotes to show the lowest rise. Overall, the same pattern of results was observed for blood pressure and heart rate. These results indicate that a common, functionally significant polymorphism in the BDNF gene modulates HPA axis reactivity and regulation during the TSST differently in men and women. Findings may be related to gender differences in reactivity and vulnerability to social stress.

  17. 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.

  18. 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.

  19. Young Children's Self-Concepts: Associations with Child Temperament, Mothers' and Fathers' Parenting, and Triadic Family Interaction

    Science.gov (United States)

    Brown, Geoffrey L.; Mangelsdorf, Sarah C.; Neff, Cynthia; Schoppe-Sullivan, Sarah J.; Frosch, Cynthia A.

    2009-01-01

    This study explored how children's self-concepts were related to child temperament, dyadic parenting behavior, and triadic family interaction. At age 3, child temperament, mothers' and fathers' parenting behavior, and triadic (mother, father, and child) family interaction were observed in the homes of 50 families. At age 4, children's…

  20. 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

  1. Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review.

    Science.gov (United States)

    Tsai, H-H; Lin, H-W; Simon Pickard, A; Tsai, H-Y; Mahady, G B

    2012-11-01

    The use of herbs and dietary supplements (HDS) alone or concomitantly with medications can potentially increase the risk of adverse events experienced by the patients. This review aims to evaluate the documented HDS-drug interactions and contraindications. A structured literature review was conducted on PubMed, EMBASE, Cochrane Library, tertiary literature and Internet. While 85 primary literatures, six books and two web sites were reviewed for a total of 1,491 unique pairs of HDS-drug interactions, 213 HDS entities and 509 medications were involved. HDS products containing St. John's Wort, magnesium, calcium, iron, ginkgo had the greatest number of documented interactions with medications. Warfarin, insulin, aspirin, digoxin, and ticlopidine had the greatest number of reported interactions with HDS. Medications affecting the central nervous system or cardiovascular system had more documented interactions with HDS. Of the 882 HDS-drug interactions being described its mechanism and severity, 42.3% were due to altered pharmacokinetics and 240 were described as major interactions. Of the 152 identified HDS contraindications, the most frequent involved gastrointestinal (16.4%), neurological (14.5%), and renal/genitourinary diseases (12.5%). Flaxseed, echinacea, and yohimbe had the largest number of documented contraindications. Although HDS-drug interactions and contraindications primarily concerned a relatively small subset of commonly used medications and HDS entities, this review provides the summary to identify patients, HDS products, and medications that are more susceptible to HDS-drug interactions and contraindications. The findings would facilitate the health-care professionals to communicate these documented interactions and contraindications to their patients and/or caregivers thereby preventing serious adverse events and improving desired therapeutic outcomes. © 2012 Blackwell Publishing Ltd.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. Interactions among variants in TXA2R, P2Y12 and GPIIIa are associated with carotid plaque vulnerability in Chinese population.

    Science.gov (United States)

    Yi, Xingyang; Lin, Jing; Luo, Hua; Zhou, Ju; Zhou, Qiang; Wang, Yanfen; Wang, Chun

    2018-04-03

    The associations between variants in platelet activation-relevant genes and carotid plaque vulnerability are not fully understood. The aim of the present study was to investigate the associations of the variants in platelet activation-relevant genes and interactions among these variants with carotid plaque vulnerability. There were no significant differences in the frequencies of genotypes of the 11 variants between patients and controls. Among 396 patients, 102 patients had not carotid plaque, 106 had VP, and 188 had SP. The 11 variants were not independently associated with risk of carotid plaque vulnerability after adjusting for potential confounding variables. However, the GMDR analysis showed that there were synergistic effects of gene-gene interactions among TXA2Rr s1131882, GPIIIa rs2317676 and P2Y12 rs16863323 on carotid plaque vulnerability. The high-risk interactions among the three variants were associated with high platelet activation, and independently associated with the risk of carotid plaque vulnerability. Eleven variants in platelet activation-relevant genes were examined using mass spectrometry methods in 396 ischemic stroke patients and 291controls. Platelet-leukocyte aggregates and platelet aggregation were also measured. Carotid plaques were assessed by B-mode ultrasound. According to the results of ultrasound, the patients were stratified into three groups: non-plaque group, vulnerable plaque (VP) group and stable plaque (SP) group. Furthermore, gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) methods. The rs1131882, rs2317676, and rs16863323 three-loci interactions may confer a higher risk of carotid plaque vulnerability, and might be potential markers for plaque instability.

  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, 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

  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, 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

  10. Investigation and identification of functional post-translational modification sites associated with drug binding and protein-protein interactions.

    Science.gov (United States)

    Su, Min-Gang; Weng, Julia Tzu-Ya; Hsu, Justin Bo-Kai; Huang, Kai-Yao; Chi, Yu-Hsiang; Lee, Tzong-Yi

    2017-12-21

    Protein post-translational modification (PTM) plays an essential role in various cellular processes that modulates the physical and chemical properties, folding, conformation, stability and activity of proteins, thereby modifying the functions of proteins. The improved throughput of mass spectrometry (MS) or MS/MS technology has not only brought about a surge in proteome-scale studies, but also contributed to a fruitful list of identified PTMs. However, with the increase in the number of identified PTMs, perhaps the more crucial question is what kind of biological mechanisms these PTMs are involved in. This is particularly important in light of the fact that most protein-based pharmaceuticals deliver their therapeutic effects through some form of PTM. Yet, our understanding is still limited with respect to the local effects and frequency of PTM sites near pharmaceutical binding sites and the interfaces of protein-protein interaction (PPI). Understanding PTM's function is critical to our ability to manipulate the biological mechanisms of protein. In this study, to understand the regulation of protein functions by PTMs, we mapped 25,835 PTM sites to proteins with available three-dimensional (3D) structural information in the Protein Data Bank (PDB), including 1785 modified PTM sites on the 3D structure. Based on the acquired structural PTM sites, we proposed to use five properties for the structural characterization of PTM substrate sites: the spatial composition of amino acids, residues and side-chain orientations surrounding the PTM substrate sites, as well as the secondary structure, division of acidity and alkaline residues, and solvent-accessible surface area. We further mapped the structural PTM sites to the structures of drug binding and PPI sites, identifying a total of 1917 PTM sites that may affect PPI and 3951 PTM sites associated with drug-target binding. An integrated analytical platform (CruxPTM), with a variety of methods and online molecular docking

  11. Association of STAT4 and PTPN22 polymorphisms and their interactions with type-1 autoimmune hepatitis susceptibility in Chinese Han children.

    Science.gov (United States)

    Li, Xiaofeng; Chen, Huiqin; Cai, Yun; Zhang, Pingping; Chen, Zhuanggui

    2017-09-22

    To investigate the impact of signal transducer and activator of transcription 4 (STAT4) and the protein tyrosine phosphatase N22 (PTPN22) gene single nucleotide polymorphisms (SNPs), gene-gene interactions and haplotype on type-1 Autoimmune Hepatitis (AIH) risk. Logistic regression analysis showed that type 1 AIH was significantly higher in carriers of T allele of rs7574865 than those with GG genotype ( P - value less than 0.001), higher in carriers of C allele of rs7582694 than those with GG genotype ( P - value rs7574865-T alleles were associated with a statistically increased type 1 AIH risk ( P rs7574865 and rs7582694 in STAT4 gene minor alleles, interaction between rs7582694 and rs2476601, and haplotype containing the rs7582694-C and rs7574865-T alleles are associated with increased type 1 AIH risk, but rs2476601 in PTPN22 gene minor allele is associated with decreased type 1 AIH risk.

  12. 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.

  13. 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.

  14. Factors Associated with Potential Food-Drug Interaction in Hospitalized Patients: A Cross-Sectional Study in Northeast Iran

    Directory of Open Access Journals (Sweden)

    Mostafa Abdollahi

    2018-04-01

    Full Text Available Background: The minimization of adverse food-drug interactions will improve patient care by optimizing the therapeutic effects and maintaining proper nutritional status. Aim: The aim of the present study was to find the main factors that may place the hospitalized patients at risk of potential food-drug interactions. Method: This cross-sectional, descriptive study was conducted on 400 inpatients admitted to the Department of Internal Medicine of a teaching hospital in Mashhad, Northeast Iran, within 20 March 2013 to 20 April 2013. The potential food-drug interactions were evaluated for 19 commonly prescribed medications. The main factors (e.g., age, gender, education level, number of medications, and duration of the disease that may place the patients at risk of potential food-drug interactions were analyzed for each patient. Results: Out of the 19 commonly prescribed medications, 17 drugs (89% were not properly used with respect to meal. Furthermore, 14 commonly prescribed drugs were found to have a high frequency (≥50% of potential food-drug interactions. Most of the patients (n=359, 89.8% consumed their medicines at inappropriate time with respect to meals. The results of a multiple logistic regression after adjustment for confounders revealed that the age [β=0.005, CI: 0.0-0.01; P=033], number of medications [β=0.1, CI: 0.083-0.117; P

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

    2014-01-01

    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. PMID:24978879

  1. 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.

  2. Interaction between IL-6 and TNF-α genotypes associated with bacteremia in multiple myeloma patients submitted to autologous stem cell transplantation (ASCT).

    Science.gov (United States)

    Trigo, Fernanda M B; Luizon, Marcelo R; Dutra, Hélio S; Maiolino, Angelo; Nucci, Márcio; Simões, Belinda P

    2014-01-01

    Stem cell transplantation affects patient׳s vulnerability to infections due to immunological changes related to chemotherapy. Multiple myeloma is characterized by susceptibility to infections, and IL-6 and TNF-α increased levels affect immune response (IR). Polymorphisms in promoter region of cytokine genes may alter expression levels and affect IR. We performed interaction analysis of IL-6 (-174G/C) and TNF-α (-308G/A) polymorphisms with infection susceptibility in 148 patients classified accordingly to infection status and found an interaction when compared groups with and without bacteremia (p=0.0380). The interaction may be more important than single effects for the IR associated with the infection susceptibility in ASCT.

  3. 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

  4. Interactions between stream fungi and bacteria associated with decomposing leaf litter at different levels of nutrient availability

    Science.gov (United States)

    Vladislav Gulis; Keller Suberkropp

    2003-01-01

    We examined the potential for interactions between aquatic hyphomycetes and bacteria isolated from leaves decaying in a headwater stream. In agar plate assays, culture filtrates of each of 28 aquatic hyphomycete isolates tested (5 species) inhibited bacterial growth (16 Gram-negative bacterial isolates belonging to 6 colony morphotypes were tested). Inhibition of...

  5. The home literacy environment: exploring how media and parent-child interactions are associated with children’s language production

    NARCIS (Netherlands)

    Liebeskind, K.G.; Piotrowski, J.; Lapierre, M.A.; Linebarger, D.L.

    2014-01-01

    Children who start school with strong language skills initiate a trajectory of academic success, while children with weaker skills are likely to struggle. Research has demonstrated that media and parent-child interactions, both characteristics of the home literacy environment, influence children's

  6. 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.…

  7. 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…

  8. Maternal Depression and Mother-Child Interaction Patterns: Association with Toddler Problems and Continuity of Effects to Late Childhood

    Science.gov (United States)

    Leckman-Westin, Emily; Cohen, Patricia R.; Stueve, Ann

    2009-01-01

    Objective: Increased behavior problems have been reported in offspring of mothers with depression. In-home observations link maternal depressive symptoms (MDS) and mother-child interaction patterns with toddler behavior problems and examine their persistence into late childhood. Method: Maternal characteristics (N = 153) and behaviors of…

  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. Affordances of Interactive Whiteboards and Associated Pedagogical Practices: Perspectives of Teachers of Science with Children Aged Five to Six Years

    Science.gov (United States)

    Teck, Wong Kung

    2013-01-01

    The integration of information and communication technology into early year's classrooms is increasingly important for engaging and motivating digital learners. One of the more promising recent revolutions in educational technology that encourages learner's involvement is interactive whiteboard (IWB). Many schools have accepted IWB as core…

  11. 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.

  12. Revealing the neural networks associated with processing of natural social interaction and the related effects of actor-orientation and face-visibility.

    Science.gov (United States)

    Saggar, Manish; Shelly, Elizabeth Walter; Lepage, Jean-Francois; Hoeft, Fumiko; Reiss, Allan L

    2014-01-01

    Understanding the intentions and desires of those around us is vital for adapting to a dynamic social environment. In this paper, a novel event-related functional Magnetic Resonance Imaging (fMRI) paradigm with dynamic and natural stimuli (2s video clips) was developed to directly examine the neural networks associated with processing of gestures with social intent as compared to nonsocial intent. When comparing social to nonsocial gestures, increased activation in both the mentalizing (or theory of mind) and amygdala networks was found. As a secondary aim, a factor of actor-orientation was included in the paradigm to examine how the neural mechanisms differ with respect to personal engagement during a social interaction versus passively observing an interaction. Activity in the lateral occipital cortex and precentral gyrus was found sensitive to actor-orientation during social interactions. Lastly, by manipulating face-visibility we tested whether facial information alone is the primary driver of neural activation differences observed between social and nonsocial gestures. We discovered that activity in the posterior superior temporal sulcus (pSTS) and fusiform gyrus (FFG) was partially driven by observing facial expressions during social gestures. Altogether, using multiple factors associated with processing of natural social interaction, we conceptually advance our understanding of how social stimuli is processed in the brain and discuss the application of this paradigm to clinical populations where atypical social cognition is manifested as a key symptom. © 2013.

  13. Revealing the neural networks associated with processing of natural social interaction and the related effects of actor-orientation and face-visibility

    Science.gov (United States)

    Saggar, Manish; Shelly, Elizabeth Walter; Lepage, Jean-Francois; Hoeft, Fumiko; Reiss, Allan L.

    2013-01-01

    Understanding the intentions and desires of those around us is vital for adapting to a dynamic social environment. In this paper, a novel event-related functional Magnetic Resonance Imaging (fMRI) paradigm with dynamic and natural stimuli (2s video clips) was developed to directly examine the neural networks associated with processing of gestures with social intent as compared to nonsocial intent. When comparing social to nonsocial gestures, increased activation in both the mentalizing (or theory of mind) and amygdala networks were found. As a secondary aim, a factor of actor-orientation was included in the paradigm to examine how the neural mechanisms differ with respect to personal engagement during a social interaction versus passively observing an interaction. Activity in the lateral occipital cortex and precentral gyrus were found sensitive to actor-orientation during social interactions. Lastly, by manipulating face-visibility we tested whether facial information alone is the primary driver of neural activation differences observed between social and nonsocial gestures. We discovered that activity in the posterior superior temporal sulcus (pSTS) and fusiform gyrus (FFG) were partially driven by observing facial expressions during social gestures. Altogether, using multiple factors associated with processing of natural social interaction, we conceptually advance our understanding of how social stimuli is processed in the brain and discuss the application of this paradigm to clinical populations where atypical social cognition is manifested as a key symptom. PMID:24084068

  14. 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.

  15. Association and Interaction Effect of AGTR1 and AGTR2 Gene Polymorphisms with Dietary Pattern on Metabolic Risk Factors of Cardiovascular Disease in Malaysian Adults.

    Science.gov (United States)

    Yap, Roseline Wai Kuan; Shidoji, Yoshihiro; Yap, Wai Sum; Masaki, Motofumi

    2017-08-09

    Gene-diet interaction using a multifactorial approach is preferred to study the multiple risk factors of cardiovascular disease (CVD). This study examined the association and gene-diet interaction effects of the angiotensin II type 1 receptor ( AGTR1 ) gene (rs5186), and type 2 receptor ( AGTR2 ) gene (rs1403543) polymorphisms on metabolic risk factors of CVD in Malaysian adults. CVD parameters (BMI, blood pressure, glycated hemoglobin, total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and TC/HDL-C ratio), and constructed dietary patterns "vegetables, fruits, and soy diet" (VFSD), and "rice, egg, and fish diet" (REFD) were obtained from previous studies. Genotyping analysis was performed by real-time PCR using Taqman probes. The subjects were 507 adults (151 Malays; 179 Chinese; and 177 Indians). Significant genetic associations were obtained on blood lipids for rs5186 in Malays and Chinese, and rs1403543 in Chinese females. The significant gene-diet interaction effects after adjusting for potential confounders were: rs5186 × VFSD on blood pressure in Malays ( p = 0.016), and in Chinese on blood lipids for rs5186 × REFD ( p = 0.009-0.023), and rs1403543 × VFSD in female subjects ( p = 0.001-0.011). Malays and Chinese showed higher risk for blood pressure and/or lipids involving rs5186 and rs1403543 SNPs together with gene-diet interactions, but not Indians.

  16. 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...

  17. The role of sponge-bacteria interactions: the sponge Aplysilla rosea challenged by its associated bacterium Streptomyces ACT-52A in a controlled aquarium system.

    Science.gov (United States)

    Mehbub, Mohammad F; Tanner, Jason E; Barnett, Stephen J; Franco, Christopher M M; Zhang, Wei

    2016-12-01

    Sponge-associated bacteria play a critical role in sponge biology, metabolism and ecology, but how they interact with their host sponges and the role of these interactions are poorly understood. This study investigated the role of the interaction between the sponge Aplysilla rosea and its associated actinobacterium, Streptomyces ACT-52A, in modifying sponge microbial diversity, metabolite profile and bioactivity. A recently developed experimental approach that exposes sponges to bacteria of interest in a controlled aquarium system was improved by including the capture and analysis of secreted metabolites by the addition of an absorbent resin in the seawater. In a series of controlled aquaria, A. rosea was exposed to Streptomyces ACT-52A at 10 6  cfu/ml and monitored for up to 360 h. Shifts in microbial communities associated with the sponges occurred within 24 to 48 h after bacterial exposure and continued until 360 h, as revealed by TRFLP. The metabolite profiles of sponge tissues also changed substantially as the microbial community shifted. Control sponges (without added bacteria) and Streptomyces ACT-52A-exposed sponges released different metabolites into the seawater that was captured by the resin. The antibacterial activity of compounds collected from the seawater increased at 96 and 360 h of exposure for the treated sponges compared to the control group due to new compounds being produced and released. Increased antibacterial activity of metabolites from treated sponge tissue was observed only at 360 h, whereas that of control sponge tissue remained unchanged. The results demonstrate that the interaction between sponges and their associated bacteria plays an important role in regulating secondary metabolite production.

  18. 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...

  19. 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...

  20. In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction & stability and is associated with gigantism.

    OpenAIRE

    Salvatori, R.; Radian, S.; Diekmann, Y.; Iacovazzo, D.; David, A.; Grabovska, P.; Grassi, G.; Bussell, A-M; Stals, K.; Weber, A.; Quinton, R.; Crowne, E.; Corazzini, V.; Metherell, L. A.; Kearney, T.

    2017-01-01

    OBJECTIVE: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. DESIGN & METHODS: Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to mo...

  1. In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism

    OpenAIRE

    Salvatori, Roberto; Radian, Serban; Diekmann, Yoan; Iacovazzo, Donato; David, Alessia; Gabrovska, Plamena; Grassi, Giorgia; Bussell, Anna-Marie; Stals, Karen; Weber, Astrid; Quinton, Richard; Crowne, Elizabeth C; Corazzini, Valentina; Metherell, Lou; Kearney, Tara

    2017-01-01

    Objective Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Design and methods Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3?Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to mo...

  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. Loci Affecting Gamma-Glutamyl Transferase in Adults and Adolescents Show Age X SNP interaction and Cardiometabolic Disease Associations

    NARCIS (Netherlands)

    Middelberg, R.P.S.; Benyamin, B.; de Moor, M.H.M.; Warrington, N.M.; Gordon, S.; Henders, A.K.; Medland, S.E.; Nyholt, DR; de Geus, E.J.C.; Hottenga, J.J.; Willemsen, G.; Beilin, L.J.; Mori, T.A.; Wright, M.J.; Heath, A.C.; Madden, P.A.F.; Boomsma, D.I.; Pennell, C.E.; Montgomery, G.W.; Martin, N.G.; Whitfield, J.B.

    2012-01-01

    Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in

  4. 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

  5. Interactions between Maternal Parenting and Children's Early Disruptive Behavior: Bidirectional Associations across the Transition from Preschool to School Entry

    Science.gov (United States)

    Combs-Ronto, Lindsey A.; Olson, Sheryl L.; Lunkenheimer, Erika S.; Sameroff, Arnold J.

    2009-01-01

    This study was a prospective 2-year longitudinal investigation of associations between negative maternal parenting and disruptive child behavior across the preschool to school transition. Our main goals were to 1) determine the direction of association between early maternal negativity and child disruptive behaviors across this important…

  6. Lipid-mediated interactions tune the association of glycophorin A helix and its disruptive mutants in membranes

    NARCIS (Netherlands)

    Sengupta, Durba; Marrink, Siewert J.

    2010-01-01

    The specific and non-specific driving forces of helix association within membranes are still poorly understood. Here, we use coarse-grain molecular dynamics simulations to study the association behavior of glycophorin A and two disruptive mutants, T87F and a triple mutant of the GxxxG motif

  7. 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.

  8. 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.

  9. 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...

  10. 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.

  11. 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.

  12. Association and interaction between dietary pattern and VEGF receptor-2 (VEGFR2) gene polymorphisms on blood lipids in Chinese Malaysian and Japanese adults.

    Science.gov (United States)

    Yap, Roseline Wai Kuan; Shidoji, Yoshihiro; Hon, Wei Min; Masaki, Motofumi

    2012-01-01

    Dietary pattern and genetic predisposition of each population have different impacts on lifestyle-related chronic diseases. This study was conducted to evaluate the association and interaction between dietary patterns and VEGFR2 or KDR gene polymorphisms on physical and biochemical risk factors of cardiovascular disease in two Asian populations (179 Chinese Malaysian and 136 Japanese adults). Dietary patterns were constructed from food frequency questionnaire using factor analysis. Genotyping of rs1870377 and rs2071559 was performed by real-time PCR using TaqMan probes. Physical measurements: body mass index, systolic and diastolic blood pressures and biochemical parameters: glycated hemoglobin A1c and blood lipids (total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol and total cholesterol/HDL-C ratio) were measured. Two dietary patterns were extracted for: Japanese ('Japanese diet' and 'Western diet') and Chinese Malaysians ('Balanced diet'; and 'Meat, rice and noodles diet'). In Japanese, 'Western Diet' and rs2071559 were associated with LDL-C and HDL-C, respectively. In Chinese Malaysians, 'Meat, rice and noodles diet' was asso-ciated with triglycerides, HDL-C and total cholesterol/HDL ratio while rs1870377 and rs2071559 were associated with total cholesterol and/or LDL-C. The interaction between 'Western Diet' and rs2071559 in Japanese and 'Meat, rice and noodles diet' and rs1870377 in Malaysians had significant effects on blood lipids after adjusting for confounders. The association and interaction of dietary patterns and VEGFR2 gene polymorphisms on blood lipids differ between Chinese Malaysian and Japanese subjects by either decreasing or increasing the risk of cardiovascular disease.

  13. Investigation of attractive and repulsive interactions associated with ketones in supercritical CO2, based on Raman spectroscopy and theoretical calculations.

    Science.gov (United States)

    Kajiya, Daisuke; Saitow, Ken-ichi

    2013-08-07

    Carbonyl compounds are solutes that are highly soluble in supercritical CO2 (scCO2). Their solubility governs the efficiency of chemical reactions, and is significantly increased by changing a chromophore. To effectively use scCO2 as solvent, it is crucial to understand the high solubility of carbonyl compounds, the solvation structure, and the solute-solvent intermolecular interactions. We report Raman spectroscopic data, for three prototypical ketones dissolved in scCO2, and four theoretical analyses. The vibrational Raman spectra of the C=O stretching modes of ketones (acetone, acetophenone, and benzophenone) were measured in scCO2 along the reduced temperature Tr = T∕Tc = 1.02 isotherm as a function of the reduced density ρr = ρ∕ρc in the range 0.05-1.5. The peak frequencies of the C=O stretching modes shifted toward lower energies as the fluid density increased. The density dependence was analyzed by using perturbed hard-sphere theory, and the shift was decomposed into attractive and repulsive energy components. The attractive energy between the ketones and CO2 was up to nine times higher than the repulsive energy, and its magnitude increased in the following order: acetone attractive energy and optimized the relative configuration between each solute and CO2. According to theoretical calculations for the dispersion energy, the dipole-induced-dipole interaction energy, and the frequency shift due to their interactions, the experimentally determined attractive energy differences in the three solutes were attributed to the dispersion energies that depended on a chromophore attached to the carbonyl groups. It was found that the major intermolecular interaction with the attractive shift varied from dipole-induced dipole to dispersion depending on the chromophore in the ketones in scCO2. As the common conclusion for the Raman spectral measurements and the four theoretical calculations, solute polarizability, modified by the chromophore, was at the core of

  14. Associations between Methylated Metabolites of Arsenic and Selenium in Urine of Pregnant Bangladeshi Women and Interactions between the Main Genes Involved.

    Science.gov (United States)

    Skröder, Helena; Engström, Karin; Kuehnelt, Doris; Kippler, Maria; Francesconi, Kevin; Nermell, Barbro; Tofail, Fahmida; Broberg, Karin; Vahter, Marie

    2018-02-01

    It has been proposed that interactions between selenium and arsenic in the body may affect their kinetics and toxicity. However, it is unknown how the elements influence each other in humans. We aimed to investigate potential interactions in the methylation of selenium and arsenic. Urinary selenium (U-Se) and arsenic (U-As) were measured using inductively coupled plasma mass spectrometry (ICPMS) in samples collected from pregnant women ( n =226) in rural Bangladesh at gestational weeks (GW) 8, 14, 19, and 30. Urinary concentrations of trimethyl selenonium ion (TMSe) were measured by HPLC-vapor generation-ICPMS, as were inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA). Methylation efficiency was assessed based on relative amounts (%) of arsenic and selenium metabolites in urine. Genotyping for the main arsenite and selenium methyltransferases, AS3MT and INMT, was performed using TaqMan probes or Sequenom. Multivariable-adjusted linear regression analyses indicated that %TMSe (at GW8) was positively associated with %MMA (β=1.3, 95% CI: 0.56, 2.0) and U-As, and inversely associated with %DMA and U-Se in producers of TMSe ( INMT rs6970396 AG+AA, n =74), who had a wide range of urinary TMSe (12-42%). Also, %TMSe decreased in parallel to %MMA during pregnancy, especially in the first trimester (-0.58 %TMSe per gestational week). We found a gene-gene interaction for %MMA ( p -interaction=0.076 for haplotype 1). In analysis stratified by INMT genotype, the association between %MMA and both AS3MT haplotypes 1 and 3 was stronger in women with the INMT GG (TMSe nonproducers, 5th-95th percentile: 0.2-2%TMSe) vs. AG+AA genotype. Our findings for Bangladeshi women suggest a positive association between urinary %MMA and %TMSe. Genes involved in the methylation of selenium and arsenic may interact on associations with urinary %MMA. https://doi.org/10.1289/EHP1912.

  15. 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

  16. Analysis of SLC16A11 Variants in 12,811 American Indians: Genotype-Obesity Interaction for Type 2 Diabetes and an Association With RNASEK Expression.

    Science.gov (United States)

    Traurig, Michael; Hanson, Robert L; Marinelarena, Alejandra; Kobes, Sayuko; Piaggi, Paolo; Cole, Shelley; Curran, Joanne E; Blangero, John; Göring, Harald; Kumar, Satish; Nelson, Robert G; Howard, Barbara V; Knowler, William C; Baier, Leslie J; Bogardus, Clifton

    2016-02-01

    Genetic variants in SLC16A11 were recently reported to be associated with type 2 diabetes in Mexican and other Latin American populations. The diabetes risk haplotype had a frequency of 50% in Native Americans from Mexico but was rare in Europeans and Africans. In the current study, we analyzed SLC16A11 in 12,811 North American Indians and found that the diabetes risk haplotype, tagged by the rs75493593 A allele, was nominally associated with type 2 diabetes (P = 0.001, odds ratio 1.11). However, there was a strong interaction with BMI (P = 5.1 × 10(-7)) such that the diabetes association was stronger in leaner individuals. rs75493593 was also strongly associated with BMI in individuals with type 2 diabetes (P = 3.4 × 10(-15)) but not in individuals without diabetes (P = 0.77). Longitudinal analyses suggest that this is due, in part, to an association of the A allele with greater weight loss following diabetes onset (P = 0.02). Analyses of global gene expression data from adipose tissue, skeletal muscle, and whole blood provide evidence that rs75493593 is associated with expression of the nearby RNASEK gene, suggesting that RNASEK expression may mediate the effect of genotype on diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  17. Using imputed genotype data in the joint score tests for genetic association and gene-environment interactions in case-control studies.

    Science.gov (United States)

    Song, Minsun; Wheeler, William; Caporaso, Neil E; Landi, Maria Teresa; Chatterjee, Nilanjan

    2018-03-01

    Genome-wide association studies (GWAS) are now routinely imputed for untyped single nucleotide polymorphisms (SNPs) based on various powerful statistical algorithms for imputation trained on reference datasets. The use of predicted allele counts for imputed SNPs as the dosage variable is known to produce valid score test for genetic association. In this paper, we investigate how to best handle imputed SNPs in various modern complex tests for genetic associations incorporating gene-environment interactions. We focus on case-control association studies where inference for an underlying logistic regression model can be performed using alternative methods that rely on varying degree on an assumption of gene-environment independence in the underlying population. As increasingly large-scale GWAS are being performed through consortia effort where it is preferable to share only summary-level information across studies, we also describe simple mechanisms for implementing score tests based on standard meta-analysis of "one-step" maximum-likelihood estimates across studies. Applications of the methods in simulation studies and a dataset from GWAS of lung cancer illustrate ability of the proposed methods to maintain type-I error rates for the underlying testing procedures. For analysis of imputed SNPs, similar to typed SNPs, the retrospective methods can lead to considerable efficiency gain for modeling of gene-environment interactions under the assumption of gene-environment independence. Methods are made available for public use through CGEN R software package. © 2017 WILEY PERIODICALS, INC.

  18. 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.

  19. 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.

  20. Investigation of the network of preferred interactions in an artificial coiled-coil association using the peptide array technique

    Directory of Open Access Journals (Sweden)

    Raheleh Rezaei Araghi

    2012-04-01

    Full Text Available We screened a randomized library and identified natural peptides that bound selectively to a chimeric peptide containing α-, β- and γ-amino acids. The SPOT arrays provide a means for the systematic study of the possible interaction space accessible to the αβγ-chimera. The mutational analysis reveals the dependence of the binding affinities of α-peptides to the αβγ-chimera, on the hydrophobicity and bulkiness of the side chains at the corresponding hydrophobic interface. The stability of the resulting heteroassemblies was further confirmed in solution by CD and thermal denaturation.

  1. 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.

  2. Association and interaction between triglyceride-glucose index and obesity on risk of hypertension in middle-aged and elderly adults.

    Science.gov (United States)

    Jian, Song; Su-Mei, Nie; Xue, Chen; Jie, Zhang; Xue-Sen, Wu

    2017-01-01

    To investigate the association between triglyceride-glucose(TyG) index and the risk of hypertension. A cross-sectional study was conducted in Bengbu, China. The participants received relevant questionnaire survey, anthropometric tests, and laboratory examination. Multivariate logistic regression analysis was performed to estimate the possible association between TyG index and hypertension risk. The additive interaction evaluated by the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index(SI) was calculated. A total of 1777 participants (748 men and 1029 women) were investigated. There was a significant increase in the risk of hypertension and isolated systolic hypertension (ISH) when comparing the highest TyG index (the fourth quartile) to the lowest TyG index (the first quartile) and corresponding ORs were 2.446 (95% CI: 1.746-3.426) and 2.621(95%CI: 1.627-4.224), respectively. However, no significant relationship was observed between TyG index and isolated diastolic hypertension (IDH). In males, significant interactions between TyG index and WHtR (RERI:1.978, 95%CI: 0.162-3.792; AP: 0.359, 0.113-0.605; SI:1.782, 1.017-3.122), smoking (AP: 0.437, 95%CI: 0.048-0.825), family history of hypertension (AP:0.433, 95%CI: 0.203-0.662; SI:2.248, 95%CI: 1.333-3.791) were observed. As for females, there were also significant interactions between TyG index and WHtR (RERI:1.415, 95%CI: 0.693-2.136; AP: 0.198, 95%CI: 0.104-0.291; SI:1.298, 95%CI:1.101-1.530), family history of hypertension (RERI:1.744, 95%CI: 0.221-3.267; AP:0.405, 95%CI: 0.113-0.697) on risk of hypertension. Increased TyG index was significantly associated with higher risk of hypertension and ISH, but not for IDH in middle-aged and elderly adults. Our results also demonstrated interactions of TyG index and abdominal obesity and family history of hypertension on hypertension risk.

  3. Interaction of Cefpiramide sodium with bovine hemoglobin and effect of the coexistent metal ion on the protein-drug association

    International Nuclear Information System (INIS)

    Yan, Xiaona; Liu, Baosheng; Chong, Baohong; Cao, Shina

    2013-01-01

    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 2+ , Zn 2+ , Cu 2+ , Co 2+ , Fe 3+ , Ni 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 a ) was 10 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

  4. Rab11-family of interacting protein 2 associates with chlamydial inclusions through its Rab-binding domain and promotes bacterial multiplication.

    Science.gov (United States)

    Leiva, Natalia; Capmany, Anahí; Damiani, María Teresa

    2013-01-01

    Chlamydia trachomatis, an obligate intracellular pathogen, survives within host cells in a special compartment named 'inclusion' and takes advantage of host vesicular transport pathways for its growth and replication. Rab GTPases are key regulatory proteins of intracellular trafficking. Several Rabs, among them Rab11 and Rab14, are implicated in chlamydial development. FIP2, a member of the Rab11-Family of Interacting Proteins, presents at the C-terminus a Rab-binding domain that interacts with both Rab11 and Rab14. In this study, we determined and characterized the recruitment of endogenous and GFP-tagged FIP2 to the chlamydial inclusions. The recruitment of FIP2 is specific since other members of the Rab11-Family of Interacting Proteins do not associate with the chlamydial inclusions. The Rab-binding domain of FIP2 is essential for its association. Our results indicate that FIP2 binds to Rab11 at the chlamydial inclusion membrane through its Rab-binding domain. The presence of FIP2 at the chlamydial inclusion favours the recruitment of Rab14. Furthermore, our results show that FIP2 promotes inclusion development and bacterial replication. In agreement, the silencing of FIP2 decreases the bacterial progeny. C. trachomatis likely recruits FIP2 to hijack host intracellular trafficking to redirect vesicles full of nutrients towards the inclusion. © 2012 Blackwell Publishing Ltd.

  5. An unusual mode of DNA duplex association: Watson-Crick interaction of all-purine deoxyribonucleic acids.

    Science.gov (United States)

    Battersby, Thomas R; Albalos, Maria; Friesenhahn, Michel J

    2007-05-01

    Nucleic acid duplexes associating through purine-purine base pairing have been constructed and characterized in a remarkable demonstration of nucleic acids with mixed sequence and a natural backbone in an alternative duplex structure. The antiparallel deoxyribose all-purine duplexes associate specifically through Watson-Crick pairing, violating the nucleobase size-complementarity pairing convention found in Nature. Sequence-specific recognition displayed by these structures makes the duplexes suitable, in principle, for information storage and replication fundamental to molecular evolution in all living organisms. All-purine duplexes can be formed through association of purines found in natural ribonucleosides. Key to the formation of these duplexes is the N(3)-H tautomer of isoguanine, preferred in the duplex, but not in aqueous solution. The duplexes have relevance to evolution of the modern genetic code and can be used for molecular recognition of natural nucleic acids.

  6. 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

  7. 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.

  8. 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

  9. Integrin cytoplasmic domain-associated protein-1 (ICAP-1) interacts with the ROCK-I kinase at the plasma membrane

    NARCIS (Netherlands)

    Stroeken, Peter J. M.; Alvarez, Belén; van Rheenen, Jacco; Wijnands, Yvonne M.; Geerts, Dirk; Jalink, Kees; Roos, Ed

    2006-01-01

    The integrin cytoplasmic domain-associated protein-1 (ICAP-1) binds via its C-terminal PTB (phosphotyrosine-binding) domain to the cytoplasmic tails of beta1 but not other integrins. Using the yeast two-hybrid assay, we found that ICAP-1 binds the ROCK-I kinase, an effector of the RhoA GTPase. By

  10. 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...

  11. Analysis of SLC16A11 Variants in 12,811 American Indians: Genotype-Obesity Interaction for Type 2 Diabetes and an Association With RNASEK Expression

    Science.gov (United States)

    Traurig, Michael; Hanson, Robert L.; Marinelarena, Alejandra; Kobes, Sayuko; Piaggi, Paolo; Cole, Shelley; Curran, Joanne E.; Blangero, John; Göring, Harald; Kumar, Satish; Nelson, Robert G.; Howard, Barbara V.; Knowler, William C.; Baier, Leslie J.

    2016-01-01

    Genetic variants in SLC16A11 were recently reported to be associated with type 2 diabetes in Mexican and other Latin American populations. The diabetes risk haplotype had a frequency of 50% in Native Americans from Mexico but was rare in Europeans and Africans. In the current study, we analyzed SLC16A11 in 12,811 North American Indians and found that the diabetes risk haplotype, tagged by the rs75493593 A allele, was nominally associated with type 2 diabetes (P = 0.001, odds ratio 1.11). However, there was a strong interaction with BMI (P = 5.1 × 10−7) such that the diabetes association was stronger in leaner individuals. rs75493593 was also strongly associated with BMI in individuals with type 2 diabetes (P = 3.4 × 10−15) but not in individuals without diabetes (P = 0.77). Longitudinal analyses suggest that this is due, in part, to an association of the A allele with greater weight loss following diabetes onset (P = 0.02). Analyses of global gene expression data from adipose tissue, skeletal muscle, and whole blood provide evidence that rs75493593 is associated with expression of the nearby RNASEK gene, suggesting that RNASEK expression may mediate the effect of genotype on diabetes. PMID:26487785

  12. 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...

  13. 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...

  14. 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

    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......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...

  15. 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

    2018-07-01

    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.

  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

    -value = 2.8 × 10−5) sits in C5orf66 gene on 5q31. Poster abstract 2 Discussion: Our study was able to detect a significant SNP rs4251459 mapping to IRAK4 gene on 12q12 locus which appeared to increase the risk of AR in females than males. This gene has previously been reported to have a sex dependent effect...... on AR. C5orf66 loci might also be an interesting candidate for AR, but its role warrants further validations. Additionally, pathway analysis from GSEA identified a pathway related to immune system which is biologically meaningful and supportive. In conclusion, our study revealed the gene-sex interaction...

  17. 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.

  18. Genetic interactions between the chromosome axis-associated protein Hop1 and homologous recombination determinants in Schizosaccharomyces pombe.

    Science.gov (United States)

    Brown, Simon David; Jarosinska, Olga Dorota; Lorenz, Alexander

    2018-03-17

    Hop1 is a component of the meiosis-specific chromosome axis and belongs to the evolutionarily conserved family of HORMA domain proteins. Hop1 and its orthologs in higher eukaryotes are a major factor in promoting double-strand DNA break formation and inter-homolog recombination. In budding yeast and mammals, they are also involved in a meiotic checkpoint kinase cascade monitoring the completion of double-strand DNA break repair. We used the fission yeast, Schizosaccharomyces pombe, which lacks a canonical synaptonemal complex to test whether Hop1 has a role beyond supporting the generation of double-strand DNA breaks and facilitating inter-homolog recombination events. We determined how mutants of homologous recombination factors genetically interact with hop1, studied the role(s) of the HORMA domain of Hop1, and characterized a bio-informatically predicted interactor of Hop1, Aho1 (SPAC688.03c). Our observations indicate that in fission yeast, Hop1 does require its HORMA domain to support wild-type levels of meiotic recombination and localization to meiotic chromatin. Furthermore, we show that hop1∆ only weakly interacts genetically with mutants of homologous recombination factors, and in fission yeast likely has no major role beyond break formation and promoting inter-homolog events. We speculate that after the evolutionary loss of the synaptonemal complex, Hop1 likely has become less important for modulating recombination outcome during meiosis in fission yeast, and that this led to a concurrent rewiring of genetic pathways controlling meiotic recombination.

  19. 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.

  20. 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

  1. 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.

  2. Protein phosphatase 2A interacts with the Na,K-ATPase and modulates its trafficking by inhibition of its association with arrestin.

    Directory of Open Access Journals (Sweden)

    Toru Kimura

    Full Text Available The P-type ATPase family constitutes a collection of ion pumps that form phosphorylated intermediates during ion transport. One of the best known members of this family is the Na⁺,K⁺-ATPase. The catalytic subunit of the Na⁺,K⁺-ATPase includes several functional domains that determine its enzymatic and trafficking properties.Using the yeast two-hybrid system we found that protein phosphatase 2A (PP2A catalytic C-subunit is a specific Na⁺,K⁺-ATPase interacting protein. PP-2A C-subunit interacted with the Na⁺,K⁺-ATPase, but not with the homologous sequences of the H⁺,K⁺-ATPase. We confirmed that the Na⁺,K⁺-ATPase interacts with a complex of A- and C-subunits in native rat kidney. Arrestins and G-protein coupled receptor kinases (GRKs are important regulators of G-protein coupled receptor (GPCR signaling, and they also regulate Na⁺,K⁺-ATPase trafficking through direct association. PP2A inhibits association between the Na⁺,K⁺-ATPase and arrestin, and diminishes the effect of arrestin on Na⁺,K⁺-ATPase trafficking. GRK phosphorylates the Na⁺,K⁺-ATPase and PP2A can at least partially reverse this phosphorylation.Taken together, these data demonstrate that the sodium pump belongs to a growing list of ion transport proteins that are regulated through direct interactions with the catalytic subunit of a protein phosphatase.

  3. 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.

  4. Native Hydrophobic Binding Interactions at the Transition State for Association between the TAZ1 Domain of CBP and the Disordered TAD-STAT2 Are Not a Requirement.

    Science.gov (United States)

    Lindström, Ida; Dogan, Jakob

    2017-08-15

    A significant fraction of the eukaryotic proteome consists of proteins that are either partially or completely disordered under native-like conditions. Intrinsically disordered proteins (IDPs) are common in protein-protein interactions and are involved in numerous cellular processes. Although many proteins have been identified as disordered, much less is known about the binding mechanisms of the coupled binding and folding reactions involving IDPs. Here we have analyzed the rate-limiting transition state for binding between the TAZ1 domain of CREB binding protein and the intrinsically disordered transactivation domain of STAT2 (TAD-STAT2) by site-directed mutagenesis and kinetic experiments (Φ-value analysis) and found that the native protein-protein binding interface is not formed at the transition state for binding. Instead, native hydrophobic binding interactions form late, after the rate-limiting barrier has been crossed. The association rate constant in the absence of electrostatic enhancement was determined to be rather high. This is consistent with the Φ-value analysis, which showed that there are few or no obligatory native contacts. Also, linear free energy relationships clearly demonstrate that native interactions are cooperatively formed, a scenario that has usually been observed for proteins that fold according to the so-called nucleation-condensation mechanism. Thus, native hydrophobic binding interactions at the rate-limiting transition state for association between TAD-STAT2 and TAZ1 are not a requirement, which is generally in agreement with previous findings on other IDP systems and might be a common mechanism for IDPs.

  5. 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

  6. 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

  7. 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.

  8. Aging and sarcopenia associate with specific interactions between gut microbes, serum biomarkers and host physiology in rats.

    Science.gov (United States)

    Siddharth, Jay; Chakrabarti, Anirikh; Pannérec, Alice; Karaz, Sonia; Morin-Rivron, Delphine; Masoodi, Mojgan; Feige, Jerome N; Parkinson, Scott James

    2017-07-17

    The microbiome has been demonstrated to play an integral role in the maintenance of many aspects of health that are also associated with aging. In order to identify areas of potential exploration and intervention, we simultaneously characterized age-related alterations in gut microbiome, muscle physiology and serum proteomic and lipidomic profiles in aged rats to define an integrated signature of the aging phenotype. We demonstrate that aging skews the composition of the gut microbiome, in particular by altering the Sutterella to Barneseilla ratio, and alters the metabolic potential of intestinal bacteria. Age-related changes of the gut microbiome were associated with the physiological decline of musculoskeletal function, and with molecular markers of nutrient processing/availability, and inflammatory/immune status in aged versus adult rats. Altogether, our study highlights that aging leads to a complex interplay between the microbiome and host physiology, and provides candidate microbial species to target physical and metabolic decline during aging by modulating gut microbial ecology.

  9. 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.

  10. 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.

  11. 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.

  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

    2014-01-01

    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

  13. 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

    . The GTPase-activating proteins AGAP1 and AGAP3 were also enriched in the CLASP2 interactome, although subsequent AGAP3 and CLIP2 interactome analysis suggests a preference of AGAP3 for CLIP2. Follow-up MARK2 interactome analysis confirmed reciprocal co-IP of CLASP2 and also revealed MARK2 can co-IP SOGA1......, 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....... These results introduce the metabolic function of these proposed novel protein networks and their relationship with microtubules as new fields of cytoskeleton-associated protein biology....

  14. Emory University: High-Throughput Protein-Protein Interaction Dataset for Lung Cancer-Associated Genes | Office of Cancer Genomics

    Science.gov (United States)

    To discover novel PPI signaling hubs for lung cancer, CTD2 Center at Emory utilized large-scale genomics datasets and literature to compile a set of lung cancer-associated genes. A library of expression vectors were generated for these genes and utilized for detecting pairwise PPIs with cell lysate-based TR-FRET assays in high-throughput screening format. Read the abstract.

  15. 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.

  16. 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.

  17. Phosphorylation and interactions associated with the control of the Leishmania Poly-A Binding Protein 1 (PABP1) function during translation initiation.

    Science.gov (United States)

    de Melo Neto, Osvaldo P; da Costa Lima, Tamara D C; Merlo, Kleison C; Romão, Tatiany P; Rocha, Pollyanna O; Assis, Ludmila A; Nascimento, Larissa M; Xavier, Camila C; Rezende, Antonio M; Reis, Christian R S; Papadopoulou, Barbara

    2018-03-23

    The Poly-A Binding Protein (PABP) is a conserved eukaryotic polypeptide involved in many aspects of mRNA metabolism. During translation initiation, PABP interacts with the translation initiation complex eIF4F and enhances the translation of polyadenylated mRNAs. Schematically, most PABPs can be divided into an N-terminal RNA-binding region, a non-conserved linker segment and the C-terminal MLLE domain. In pathogenic Leishmania protozoans, three PABP homologues have been identified, with the first one (PABP1) targeted by phosphorylation and shown to co-immunoprecipitate with an eIF4F-like complex (EIF4E4/EIF4G3) implicated in translation initiation. Here, PABP1 phosphorylation was shown to be linked to logarithmic cell growth, reminiscent of EIF4E4 phosphorylation, and coincides with polysomal association. Phosphorylation targets multiple serine-proline (SP) or threonine-proline (TP) residues within the PABP1 linker region. This is an essential protein, but phosphorylation is not needed for its association with polysomes or cell viability. Mutations which do impair PABP1 polysomal association and are required for viability do not prevent phosphorylation, although further mutations lead to a presumed inactive protein largely lacking phosphorylated isoforms. Co-immunoprecipitation experiments were carried out to investigate PABP1 function further, identifying several novel protein partners and the EIF4E4/EIF4G3 complex, but no other eIF4F-like complex or subunit. A novel, direct interaction between PABP1 and EIF4E4 was also investigated and found to be mediated by the PABP1 MLLE binding to PABP Interacting Motifs (PAM2) within the EIF4E4 N-terminus. The results shown here are consistent with phosphorylation of PABP1 being part of a novel pathway controlling its function and possibly translation in Leishmania.

  18. Association of peroxisome proliferator-activated receptor single-nucleotide polymorphisms and gene-gene interactions with the lipoprotein(a)

    Institute of Scientific and Technical Information of China (English)

    解惠坚

    2014-01-01

    Objective To examine the associations of 10 singlenucleotide polymorphisms(SNPs)in peroxisome proliferator-activated receptor(PPARs)gene with lipoprotein(a)level,and to investigate if there is gene-gene interaction among the SNPs on lipoprotein(a)level.Methods Totally 644 subjects(234 men and 410 women)were enrolled from Prevention of Multiple Metabolic Disorders and Metabolic Syndrome Study Cohort,which was an urban community survey study conducted in Jiangsu province.Ten SNPs in PPARα(rs135539,rs4253778,

  19. Recognition of abstract objects via neural oscillators: interaction among topological organization, associative memory and gamma band synchronization.

    Science.gov (United States)

    Ursino, Mauro; Magosso, Elisa; Cuppini, Cristiano

    2009-02-01

    Synchronization of neural activity in the gamma band is assumed to play a significant role not only in perceptual processing, but also in higher cognitive functions. Here, we propose a neural network of Wilson-Cowan oscillators to simulate recognition of abstract objects, each represented as a collection of four features. Features are ordered in topological maps of oscillators connected via excitatory lateral synapses, to implement a similarity principle. Experience on previous objects is stored in long-range synapses connecting the different topological maps, and trained via timing dependent Hebbian learning (previous knowledge principle). Finally, a downstream decision network detects the presence of a reliable object representation, when all features are oscillating in synchrony. Simulations performed giving various simultaneous objects to the network (from 1 to 4), with some missing and/or modified properties suggest that the network can reconstruct objects, and segment them from the other simultaneously present objects, even in case of deteriorated information, noise, and moderate correlation among the inputs (one common feature). The balance between sensitivity and specificity depends on the strength of the Hebbian learning. Achieving a correct reconstruction in all cases, however, requires ad hoc selection of the oscillation frequency. The model represents an attempt to investigate the interactions among topological maps, autoassociative memory, and gamma-band synchronization, for recognition of abstract objects.

  20. The growth, properties and interactions of yeasts and bacteria associated with the maturation of Camembert and blue-veined cheeses.

    Science.gov (United States)

    Addis, E; Fleet, G H; Cox, J M; Kolak, D; Leung, T

    2001-09-19

    The growth of yeasts and bacteria were monitored during the maturation of Camembert and blue-veined cheese produced in Australia. Yeasts were prominent throughout maturation, growing to 10(5)-10(9)/g, depending on the manufacturer. Debaryomyces hansenii predominated, but there were lesser, inconsistent contributions from Yarrowia lipolytica. Of the non-lactic acid bacteria, Acinetobacter species were significant during the maturation of Camembert but not blue-veined cheeses, and grew to 10(6)-10(8) cfu/g. Staphylococcus and Micrococcus species were consistently isolated from the cheeses with Staphylococcus xylosus growing to 10(5)-10(9) cfu/g, depending on the product. Lactic acid bacteria (10(7)-10(9) cfu/g) were present throughout maturation but were not identified. Interactions between the various yeasts and bacterial isolates were examined. Several strains of D. hansenii exhibited killer activity but not against Y. lipolytica. None of the yeasts were antagonistic towards the bacteria but some strains of D. hansenii enhanced the growth of Y. lipolytica and S. xylosus. The yeast and bacterial isolates exhibited various degrees of extracellular proteolytic and lipolytic activities.

  1. 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

    OBJECTIVE: To investigate the association between the behaviour of health professionals as reported by patients, the quality of communication, patients' communication about their disease, and non-adherence to Directly Observed Tuberculosis Treatment Short-course, DOTS. METHODS: This study...... was designed as a case-control study based on 50 cases (non-adherents) and 100 controls (adherents), conducted in a hilly western district in Nepal. The participation rate was 80% for 50 cases and 95% for 100 controls. All covariates with p-value

  2. Essential Aspects in Assessing the Safety Impact of Interactions between a Drug Product and Its Associated Manufacturing System.

    Science.gov (United States)

    Jenke, Dennis

    2012-01-01

    An emerging trend in the biotechnology industry is the utilization of plastic components in manufacturing systems for the production of an active pharmaceutical ingredient (API) or a finished drug product (FDP). If the API, the FDP, or any solution used to generate them (for example, process streams such as media, buffers, and the like) come in contact with a plastic at any time during the manufacturing process, there is the potential that substances leached from the plastic may accumulate in the API or FDP, affecting safety and/or efficacy. In this article the author develops a terminology that addresses process streams associated with the manufacturing process. Additionally, the article outlines the safety assessment process for manufacturing systems, specifically addressing the topics of risk management and the role of compendial testing. Finally, the proper use of vendor-supplied extractables information is considered. Manufacturing suites used to produce biopharmaceuticals can include components that are made out of plastics. Thus it is possible that substances could leach out of the plastics and into manufacturing solutions, and it is further possible that such leachables could accumulate in the pharmaceutical product. In this article, the author develops a terminology that addresses process streams associated with the manufacturing process. Additionally, the author proposes a process by which the impact on product safety of such leached substances can be assessed.

  3. Extracellular Vesicle-Associated Transitory Cell Wall Components and Their Impact on the Interaction of Fungi with Host Cells.

    Science.gov (United States)

    Nimrichter, Leonardo; de Souza, Marcio M; Del Poeta, Maurizio; Nosanchuk, Joshua D; Joffe, Luna; Tavares, Patricia de M; Rodrigues, Marcio L

    2016-01-01

    Classic cell wall components of fungi comprise the polysaccharides glucans and chitin, in association with glycoproteins and pigments. During the last decade, however, system biology approaches clearly demonstrated that the composition of fungal cell walls include atypical molecules historically associated with intracellular or membrane locations. Elucidation of mechanisms by which many fungal molecules are exported to the extracellular space suggested that these atypical components are transitorily located to the cell wall. The presence of extracellular vesicles (EVs) at the fungal cell wall and in culture supernatants of distinct pathogenic species suggested a highly functional mechanism of molecular export in these organisms. Thus, the passage of EVs through fungal cell walls suggests remarkable molecular diversity and, consequently, a potentially variable influence on the host antifungal response. On the basis of information derived from the proteomic characterization of fungal EVs from the yeasts Cryptoccocus neoformans and Candida albicans and the dimorphic fungi Histoplasma capsulatum and Paracoccidioides brasiliensis, our manuscript is focused on the clear view that the fungal cell wall is much more complex than previously thought.

  4. 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.

  5. 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...... the NMDA receptors are therefore likely to influence the risk of schizophrenia. The aim of this study was to determine (1) whether SNP variation in the genes (GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D) encoding the NMDA receptor were associated with schizophrenia; (2) whether GRIN gene variation...... 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...

  6. Germinal Center Kinases SmKIN3 and SmKIN24 Are Associated with the Sordaria macrospora Striatin-Interacting Phosphatase and Kinase (STRIPAK) Complex.

    Science.gov (United States)

    Frey, Stefan; Reschka, Eva J; Pöggeler, Stefanie

    2015-01-01

    The striatin-interacting phosphatase and kinase (STRIPAK) complex is composed of striatin, protein phosphatase PP2A and protein kinases that regulate development in animals and fungi. In the filamentous ascomycete Sordaria macrospora, it is required for fruiting-body development and cell fusion. Here, we report on the presence and function of STRIPAK-associated kinases in ascomycetes. Using the mammalian germinal center kinases (GCKs) MST4, STK24, STK25 and MINK1 as query, we identified the two putative homologs SmKIN3 and SmKIN24 in S. macrospora. A BLASTP search revealed that both kinases are conserved among filamentous ascomycetes. The physical interaction of the striatin homolog PRO11 with SmKIN3 and SmKIN24 were verified by yeast two-hybrid (Y2H) interaction studies and for SmKIN3 by co-Immunoprecipitation (co-IP). In vivo localization found that both kinases were present at the septa and deletion of both Smkin3 and Smkin24 led to abnormal septum distribution. While deletion of Smkin3 caused larger distances between adjacent septa and increased aerial hyphae, deletion of Smkin24 led to closer spacing of septa and to sterility. Although phenotypically distinct, both kinases appear to function independently because the double-knockout strain ΔSmkin3/ΔSmkin24 displayed the combined phenotypes of each single-deletion strain.

  7. Germinal Center Kinases SmKIN3 and SmKIN24 Are Associated with the Sordaria macrospora Striatin-Interacting Phosphatase and Kinase (STRIPAK Complex.

    Directory of Open Access Journals (Sweden)

    Stefan Frey

    Full Text Available The striatin-interacting phosphatase and kinase (STRIPAK complex is composed of striatin, protein phosphatase PP2A and protein kinases that regulate development in animals and fungi. In the filamentous ascomycete Sordaria macrospora, it is required for fruiting-body development and cell fusion. Here, we report on the presence and function of STRIPAK-associated kinases in ascomycetes. Using the mammalian germinal center kinases (GCKs MST4, STK24, STK25 and MINK1 as query, we identified the two putative homologs SmKIN3 and SmKIN24 in S. macrospora. A BLASTP search revealed that both kinases are conserved among filamentous ascomycetes. The physical interaction of the striatin homolog PRO11 with SmKIN3 and SmKIN24 were verified by yeast two-hybrid (Y2H interaction studies and for SmKIN3 by co-Immunoprecipitation (co-IP. In vivo localization found that both kinases were present at the septa and deletion of both Smkin3 and Smkin24 led to abnormal septum distribution. While deletion of Smkin3 caused larger distances between adjacent septa and increased aerial hyphae, deletion of Smkin24 led to closer spacing of septa and to sterility. Although phenotypically distinct, both kinases appear to function independently because the double-knockout strain ΔSmkin3/ΔSmkin24 displayed the combined phenotypes of each single-deletion strain.

  8. No Association between HMOX1 and Risk of Colorectal Cancer and No Interaction with Diet and Lifestyle Factors in a Prospective Danish Case-Cohort Study

    DEFF Research Database (Denmark)

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

    2015-01-01

    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......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...... 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...

  9. A cancer-associated RING finger protein, RNF43, is a ubiquitin ligase that interacts with a nuclear protein, HAP95

    International Nuclear Information System (INIS)

    Sugiura, Takeyuki; Yamaguchi, Aya; Miyamoto, Kentaro

    2008-01-01

    RNF43 is a recently discovered RING finger protein that is implicated in colon cancer pathogenesis. This protein possesses growth-promoting activity but its mechanism remains unknown. In this study, to gain insight into the biological action of RNF43 we characterized it biochemically and intracellularly. A combination of indirect immunofluorescence analysis and biochemical fractionation experiments suggests that RNF43 resides in the endoplasmic reticulum (ER) as well as in the nuclear envelope. Sucrose density gradient fractionation demonstrates that RNF43 co-exists with emerin, a representative inner nuclear membrane protein in the nuclear subcompartment. The cell-free system with pure components reveals that recombinant RNF43 fused with maltose-binding protein has autoubiquitylation activity. By the yeast two-hybrid screening we identified HAP95, a chromatin-associated protein interfacing the nuclear envelope, as an RNF43-interacting protein and substantiated this interaction in intact cells by the co-immunoprecipitation experiments. HAP95 is ubiquitylated and subjected to a proteasome-dependent degradation pathway, however, the experiments in which 293 cells expressing both RNF43 and HAP95 were treated with a proteasome inhibitor, MG132, show that HAP95 is unlikely to serve as a substrate of RNF43 ubiquitin ligase. These results infer that RNF43 is a resident protein of the ER and, at least partially, the nuclear membrane, with ubiquitin ligase activity and may be involved in cell growth control potentially through the interaction with HAP95

  10. 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.

  11. 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.

  12. 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

  13. 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.

    Science.gov (United States)

    Pérez-Lachaud, Gabriela; Lachaud, Jean-Paul

    2014-01-01

    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. 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. 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. 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 programs.

  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

    Science.gov (United States)

    Pérez-Lachaud, Gabriela; Lachaud, Jean-Paul

    2014-01-01

    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 programs. PMID:24941047

  15. Coactivator-associated arginine methyltransferase 1 enhances transcriptional activity of the human T-cell lymphotropic virus type 1 long terminal repeat through direct interaction with Tax.

    Science.gov (United States)

    Jeong, Soo-Jin; Lu, Hanxin; Cho, Won-Kyung; Park, Hyeon Ung; Pise-Masison, Cynthia; Brady, John N

    2006-10-01

    In this study, we demonstrate that the coactivator-associated arginine methyltransferase 1 (CARM1), which methylates histone H3 and other proteins such as p300/CBP, is positively involved in the regulation of Tax transactivation. First, transfection studies demonstrated that overexpression of CARM1 wild-type protein resulted in increased Tax transactivation of the human T-cell lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR). In contrast, transfection of a catalytically inactive CARM1 methyltransferase mutant did not enhance Tax transactivation. CARM1 facilitated Tax transactivation of the CREB-dependent cellular GEM promoter. A direct physical interaction between HTLV-1 Tax and CARM1 was demonstrated using in vitro glutathione S-transferase-Tax binding assays, in vivo coimmunoprecipitation, and confocal microscopy experiments. Finally, chromatin immunoprecipitation analysis of the activated HTLV-1 LTR promoter showed the association of CARM1 and methylated histone H3 with the template DNA. In vitro, Tax facilitates the binding of CARM1 to the transcription complex. Together, our data provide evidence that CARM1 enhances Tax transactivation of the HTLV-1 LTR through a direct interaction between CARM1 and Tax and this binding promotes methylation of histone H3 (R2, R17, and R26).

  16. 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

  17. In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism.

    Science.gov (United States)

    Salvatori, Roberto; Radian, Serban; Diekmann, Yoan; Iacovazzo, Donato; David, Alessia; Gabrovska, Plamena; Grassi, Giorgia; Bussell, Anna-Marie; Stals, Karen; Weber, Astrid; Quinton, Richard; Crowne, Elizabeth C; Corazzini, Valentina; Metherell, Lou; Kearney, Tara; Du Plessis, Daniel; Sinha, Ajay Kumar; Baborie, Atik; Lecoq, Anne-Lise; Chanson, Philippe; Ansorge, Olaf; Ellard, Sian; Trainer, Peter J; Balding, David; Thomas, Mark G; Korbonits, Márta

    2017-09-01

    Mutations in the aryl hydrocarbon receptor-interacting protein ( AIP ) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP -region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the 'English founder', with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9-113 generations, equivalent to 225-2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein-protein interactions and AIP protein stability. © 2017 The authors.

  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. Charge-mediated Fab-Fc interactions in an IgG1 antibody induce reversible self-association, cluster formation, and elevated viscosity.

    Science.gov (United States)

    Arora, Jayant; Hu, Yue; Esfandiary, Reza; Sathish, Hasige A; Bishop, Steven M; Joshi, Sangeeta B; Middaugh, C Russell; Volkin, David B; Weis, David D

    Concentration-dependent reversible self-association (RSA) of monoclonal antibodies (mAbs) poses a challenge to their pharmaceutical development as viable candidates for subcutaneous delivery. While the role of the antigen-binding fragment (Fab) in initiating RSA is well-established, little evidence supports the involvement of the crystallizable fragment (Fc). In this report, a variety of biophysical tools, including hydrogen exchange mass spectrometry, are used to elucidate the protein interface of such non-covalent protein-protein interactions. Using dynamic and static light scattering combined with viscosity measurements, we find that an IgG1 mAb (mAb-J) undergoes RSA primarily through electrostatic interactions and forms a monomer-dimer-tetramer equilibrium. We provide the first direct experimental mapping of the interface formed between the Fab and Fc domains of an antibody at high protein concentrations. Charge distribution heterogeneity between the positively charged interface spanning complementarity-determining regions CDR3H and CDR2L in the Fab and a negatively charged region in C H 3/Fc domain mediates the RSA of mAb-J. When arginine and NaCl are added, they disrupt RSA of mAb-J and decrease the solution viscosity. Fab-Fc domain interactions between mAb monomers may promote the formation of large transient antibody complexes that ultimately cause increases in solution viscosity. Our findings illustrate how limited specific arrangements of amino-acid residues can cause mAbs to undergo RSA at high protein concentrations and how conserved regions in the Fc portion of the antibody can also play an important role in initiating weak and transient protein-protein interactions.

  20. Interactions between Glu-1 and Glu-3 loci and associations of selected molecular markers with quality traits in winter wheat (Triticum aestivum L.) DH lines.

    Science.gov (United States)

    Krystkowiak, Karolina; Langner, Monika; Adamski, Tadeusz; Salmanowicz, Bolesław P; Kaczmarek, Zygmunt; Krajewski, Paweł; Surma, Maria

    2017-02-01

    The quality of wheat depends on a large complex of genes and environmental factors. The objective of this study was to identify quantitative trait loci controlling technological quality traits and their stability across environments, and to assess the impact of interaction between alleles at loci Glu-1 and Glu-3 on grain quality. DH lines were evaluated in field experiments over a period of 4 years, and genotyped using simple sequence repeat markers. Lines were analysed for grain yield (GY), thousand grain weight (TGW), protein content (PC), starch content (SC), wet gluten content (WG), Zeleny sedimentation value (ZS), alveograph parameter W (APW), hectolitre weight (HW), and grain hardness (GH). A number of QTLs for these traits were identified in all chromosome groups. The Glu-D1 locus influenced TGW, PC, SC, WG, ZS, APW, GH, while locus Glu-B1 affected only PC, ZS, and WG. Most important marker-trait associations were found on chromosomes 1D and 5D. Significant effects of interaction between Glu-1 and Glu-3 loci on technological properties were recorded, and in all types of this interaction positive effects of Glu-D1 locus on grain quality were observed, whereas effects of Glu-B1 locus depended on alleles at Glu-3 loci. Effects of Glu-A3 and Glu-D3 loci per se were not significant, while their interaction with alleles present at other loci encoding HMW and LMW were important. These results indicate that selection of wheat genotypes with predicted good bread-making properties should be based on the allelic composition both in Glu-1 and Glu-3 loci, and confirm the predominant effect of Glu-D1d allele on technological properties of wheat grains.

  1. Modeling polymer-induced interactions between two grafted surfaces: comparison between interfacial statistical associating fluid theory and self-consistent field theory.

    Science.gov (United States)

    Jain, Shekhar; Ginzburg, Valeriy V; Jog, Prasanna; Weinhold, Jeffrey; Srivastava, Rakesh; Chapman, Walter G

    2009-07-28

    The interaction between two polymer grafted surfaces is important in many applications, such as nanocomposites, colloid stabilization, and polymer alloys. In our previous work [Jain et al., J. Chem. Phys. 128, 154910 (2008)], we showed that interfacial statistical associating fluid density theory (iSAFT) successfully calculates the structure of grafted polymer chains in the absence/presence of a free polymer. In the current work, we have applied this density functional theory to calculate the force of interaction between two such grafted monolayers in implicit good solvent conditions. In particular, we have considered the case where the segment sizes of the free (sigma(f)) and grafted (sigma(g)) polymers are different. The interactions between the two monolayers in the absence of the free polymer are always repulsive. However, in the presence of the free polymer, the force either can be purely repulsive or can have an attractive minimum depending upon the relative chain lengths of the free (N(f)) and grafted polymers (N(g)). The attractive minimum is observed only when the ratio alpha = N(f)/N(g) is greater than a critical value. We find that these critical values of alpha satisfy the following scaling relation: rho(g) square root(N(g)) beta(3) proportional to alpha(-lambda), where beta = sigma(f)/sigma(g) and lambda is the scaling exponent. For beta = 1 or the same segment sizes of the free and grafted polymers, this scaling relation is in agreement with those from previous theoretical studies using self-consistent field theory (SCFT). Detailed comparisons between iSAFT and SCFT are made for the structures of the monolayers and their forces of interaction. These comparisons lead to interesting implications for the modeling of nanocomposite thermodynamics.

  2. Genome-Wide Association Study (GWAS) and Genome-Wide Environment Interaction Study (GWEIS) of Depressive Symptoms in African American and Hispanic/Latina Women

    Science.gov (United States)

    Dunn, Erin C.; Wiste, Anna; Radmanesh, Farid; Almli, Lynn M.; Gogarten, Stephanie M.; Sofer, Tamar; Faul, Jessica D.; Kardia, Sharon L.R.; Smith, Jennifer A.; Weir, David R.; Zhao, Wei; Soare, Thomas W.; Mirza, Saira S.; Hek, Karin; Tiemeier, Henning W.; Goveas, Joseph S.; Sarto, Gloria E.; Snively, Beverly M.; Cornelis, Marilyn; Koenen, Karestan C.; Kraft, Peter; Purcell, Shaun; Ressler, Kerry J.; Rosand, Jonathan; Wassertheil-Smoller, Sylvia; Smoller, Jordan W.

    2016-01-01

    Background Genome-wide association studies (GWAS) have been unable to identify variants linked to depression. We hypothesized that examining depressive symptoms and considering gene-environment interaction (G×E) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome-wide environment interaction study (GWEIS) of depressive symptoms. Methods Using data from the SHARe cohort of the Women’s Health Initiative, comprising African Americans (n=7179) and Hispanics/Latinas (n=3138), we examined genetic main effects and G×E with stressful life events and social support. We also conducted a heritability analysis using genome-wide complex trait analysis (GCTA). Replication was attempted in four independent cohorts. Results No SNPs achieved genome-wide significance for main effects in either discovery sample. The top signals in African Americans were rs73531535 (located 20kb from GPR139, p=5.75×10−8) and rs75407252 (intronic to CACNA2D3, p=6.99×10−7). In Hispanics/Latinas, the top signals were rs2532087 (located 27kb from CD38, p=2.44×10−7) and rs4542757 (intronic to DCC, p=7.31×10−7). In the GWEIS with stressful life events, one interaction signal was genome-wide significant in African Americans (rs4652467; p=4.10×10−10; located 14kb from CEP350). This interaction was not observed in a smaller replication cohort. Although heritability estimates for depressive symptoms and stressful life events were each less than 10%, they were strongly genetically correlated (rG=0.95), suggesting that common variation underlying depressive symptoms and stressful life event exposure, though modest on their own, were highly overlapping in this sample. Conclusions Our results underscore the need for larger samples, more GWEIS, and greater investigation into genetic and environmental determinants of depressive symptoms in minorities. PMID:27038408

  3. 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...

  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 of meat-associated bacteriocin-producing Lactobacilli with Listeria innocua under stringent sausage fermentation conditions.

    Science.gov (United States)

    Leroy, Frédéric; Lievens, Kristoff; De Vuyst, Luc

    2005-10-01

    The kinetics of the antilisterial effect of meat-associated lactobacilli on Listeria innocua LMG 13568 were investigated during laboratory batch fermentations. During these fermentations, which were performed in a liquid meat simulation medium, a combination of process factors typical for European-style sausage fermentations was applied, such as a temperature of 20 degrees C and a representative pH and salting profile. Two bacteriocin-producing sausage isolates (Lactobacillus sakei CTC 494 and Lactobacillus curvatus LTH 1174), which have already proven efficacy in sausage trials, and one nonbacteriocinogenic, industrial strain (Lactobacillus sakei I), were evaluated. Staphylococcus carnosus 833 was included in the experiment because of its role in flavor and color development. When grown as a monoculture or upon cocultivation with L. sakei I and S. carnosus 833, L. innocua LMG 13568 developed slightly, despite the stress of low temperature, pH, lactic acid, salt, and nitrite. In contrast, when either of the bacteriocin producers was used, the L. innocua LMG 13568 population was rapidly inactivated with more than 3 log CFU ml(-1) after 2 days of fermentation. A bacteriocin-tolerant L. innocua LMG 13568 subpopulation (4 X 10(-4)) remained after bacteriocin inactivation. Thus, when the initial level of L. innocua LMG 13568 equaled 3 log CFU ml(-1), all cells were inactivated and no bacteriocin-tolerant cells were detected, even after 7 days of incubation. S. carnosus was not inactivated by the Lactobacillus bacteriocins and displayed slight growth.

  6. Molecular Architecture of Contactin-associated Protein-like 2 (CNTNAP2) and Its Interaction with Contactin 2 (CNTN2)*

    Science.gov (United States)

    Lu, Zhuoyang; Reddy, M. V. V. V. Sekhar; Liu, Jianfang; Kalichava, Ana; Liu, Jiankang; Zhang, Lei; Chen, Fang; Wang, Yun; Holthauzen, Luis Marcelo F.; White, Mark A.; Seshadrinathan, Suchithra; Zhong, Xiaoying; Ren, Gang; Rudenko, Gabby

    2016-01-01

    Contactin-associated protein-like 2 (CNTNAP2) is a large multidomain neuronal adhesion molecule implicated in a number of neurological disorders, including epilepsy, schizophrenia, autism spectrum disorder, intellectual disability, and language delay. We reveal here by electron microscopy that the architecture of CNTNAP2 is composed of a large, medium, and small lobe that flex with respect to each other. Using epitope labeling and fragments, we assign the F58C, L1, and L2 domains to the large lobe, the FBG and L3 domains to the middle lobe, and the L4 domain to the small lobe of the CNTNAP2 molecular envelope. Our data reveal that CNTNAP2 has a very different architecture compared with neurexin 1α, a fellow member of the neurexin superfamily and a prototype, suggesting that CNTNAP2 uses a different strategy to integrate into the synaptic protein network. We show that the ectodomains of CNTNAP2 and contactin 2 (CNTN2) bind directly and specifically, with low nanomolar affinity. We show further that mutations in CNTNAP2 implicated in autism spectrum disorder are not segregated but are distributed over the whole ectodomain. The molecular shape and dimensions of CNTNAP2 place constraints on how CNTNAP2 integrates in the cleft of axo-glial and neuronal contact sites and how it functions as an organizing and adhesive molecule. PMID:27621318

  7. 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.

  8. Interactions between BMP-7 and USAG-1 (uterine sensitization-associated gene-1 regulate supernumerary organ formations.

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

  10. 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

  11. Interactive Effects of Cocaine on HIV Infection: Implication in HIV-Associated Neurocognitive Disorder and NeuroAIDS

    Directory of Open Access Journals (Sweden)

    Santosh eDahal

    2015-09-01

    Full Text Available Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV, but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine in the brain, by blocking the dopamine transporters (DAT which is critical for dopamine homeostasis and neurocognitive function. Tat protein of HIV acts as an allosteric modulator of DAT, where as cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to dopamine, their number increases. These macrophages release inflammatory mediators and neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs, which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND. HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration. Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND. Tat-induced inflammation provokes permeability of the Blood Brain Barrier (BBB in the platelet dependent manner, which can potentially be the reason for progression to HAND during HIV infection. A better understanding on the role of cocaine in HIV infection can give a clue in developing novel therapeutic strategies

  12. Making large class basic histology lectures more interactive: The use of draw-along mapping techniques and associated educational activities.

    Science.gov (United States)

    Kotzé, Sanet Henriët; Mole, Calvin Gerald

    2015-01-01

    At Stellenbosch University, South Africa, basic histology is taught to a combination class of almost 400 first-year medical, physiotherapy, and dietetic students. Many students often find the amount of work in basic histology lectures overwhelming and consequently loose interest. The aim was to determine if a draw-along mapping activity would focus students during large class lectures. After each lecture on three basic histology tissues, a guided draw-along mapping session covering the work from the lecture was introduced in the form of a click-advance PowerPoint presentation which was used to demonstrate the unfolding of an "ideal" map. The lecturer simultaneously drew a similar map using an overhead projector allowing the students to draw their own maps on blank sheets of paper along with the lecturer. Students remained attentive during the activity and many participated in answering informal questions posed by the lecturer as the map-making session progressed. After the last session, students completed an anonymous, voluntary questionnaire (response rate of 78%). The majority of students found the draw-along maps useful (94%) and believed that its use should be continued in the future (93%). A significant increase (P < 0.001) was found in the test results of student cohorts who were given the current intervention compared to cohorts from previous years who were given mind maps as handouts only or had no intervention. The use of the draw-along mapping sessions were successful in focusing students during large class lectures while also providing them with a useful tool for their studies. © 2015 American Association of Anatomists.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. Construction of the model for the Genetic Analysis Workshop 14 simulated data: genotype-phenotype relationships, gene interaction, linkage, association, disequilibrium, and ascertainment effects for a complex phenotype.

    Science.gov (United States)

    Greenberg, David A; Zhang, Junying; Shmulewitz, Dvora; Strug, Lisa J; Zimmerman, Regina; Singh, Veena; Marathe, Sudhir

    2005-12-30

    The Genetic Analysis Workshop 14 simulated dataset was designed 1) To test the ability to find genes related to a complex disease (such as alcoholism). Such a disease may be given a variety of definitions by different investigators, have associated endophenotypes that are common in the general population, and is likely to be not one disease but a heterogeneous collection of clinically similar, but genetically distinct, entities. 2) To observe the effect on genetic analysis and gene discovery of a complex set of gene x gene interactions. 3) To allow comparison of microsatellite vs. large-scale single-nucleotide polymorphism (SNP) data. 4) To allow testing of association to identify the disease gene and the effect of moderate marker x marker linkage disequilibrium. 5) To observe the effect of different ascertainment/disease definition schemes on the analysis. Data was distributed in two forms. Data distributed to participants contained about 1,000 SNPs and 400 microsatellite markers. Internet-obtainable data consisted of a finer 10,000 SNP map, which also contained data on controls. While disease characteristics and parameters were constant, four "studies" used varying ascertainment schemes based on differing beliefs about disease characteristics. One of the studies contained multiplex two- and three-generation pedigrees with at least four affected members. The simulated disease was a psychiatric condition with many associated behaviors (endophenotypes), almost all of which were genetic in origin. The underlying disease model contained four major genes and two modifier genes. The four major genes interacted with each other to produce three different phenotypes, which were themselves heterogeneous. The population parameters were calibrated so that the major genes could be discovered by linkage analysis in most datasets. The association evidence was more difficult to calibrate but was designed to find statistically significant association in 50% of datasets. We also

  19. A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order.

    Science.gov (United States)

    Ramasamy, Adaikalavan; Curjuric, Ivan; Coin, Lachlan J; Kumar, Ashish; McArdle, Wendy L; Imboden, Medea; Leynaert, Benedicte; Kogevinas, Manolis; Schmid-Grendelmeier, Peter; Pekkanen, Juha; Wjst, Matthias; Bircher, Andreas J; Sovio, Ulla; Rochat, Thierry; Hartikainen, Anna-Liisa; Balding, David J; Jarvelin, Marjo-Riitta; Probst-Hensch, Nicole; Strachan, David P; Jarvis, Deborah L

    2011-11-01

    that modified the effect of birth order on either phenotype. This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  20. 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.

  1. Association of a missense mutation in the positional candidate gene glutamate receptor-interacting protein 1 with backfat thickness traits in pigs

    Directory of Open Access Journals (Sweden)

    Jae-Bong Lee

    2017-08-01

    Full Text Available Objective Previously, we reported quantitative trait loci (QTLs affecting backfat thickness (BFT traits on pig chromosome 5 (SW1482–SW963 in an F2 intercross population between Landrace and Korean native pigs. The aim of this study was to evaluate glutamate receptor-interacting protein 1 (GRIP1 as a positional candidate gene underlying the QTL affecting BFT traits. Methods Genotype and phenotype analyses were performed using the 1,105 F2 progeny. A mixed-effect linear model was used to access association between these single nucleotide polymorphism (SNP markers and the BFT traits in the F2 intercross population. Results Highly significant associations of two informative SNPs (c.2442 T>C, c.3316 C>G [R1106G] in GRIP1 with BFT traits were detected. In addition, the two SNPs were used to construct haplotypes that were also highly associated with the BFT traits. Conclusion The SNPs and haplotypes of the GRIP1 gene determined in this study can contribute to understand the genetic structure of BFT traits in pigs.

  2. 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.

  3. Identification of distinctive interdomain interactions among ZP-N, ZP-C and other domains of zona pellucida glycoproteins underlying association of chicken egg-coat matrix.

    Science.gov (United States)

    Okumura, Hiroki; Sato, Takahiro; Sakuma, Rio; Fukushima, Hideaki; Matsuda, Tsukasa; Ujita, Minoru

    2015-01-01

    The vertebrate egg coat, including mammalian zona pellucida, is an oocyte-specific extracellular matrix comprising two to six zona pellucida (ZP) glycoproteins. The egg coat plays important roles in fertilization, especially in species-specific interactions with sperm to induce the sperm acrosome reaction and to form the block to polyspermy. It is suggested that the physiological functions of the egg coat are mediated and/or regulated coordinately by peptide and carbohydrate moieties of the ZP glycoproteins that are spatially arranged in the egg coat, whereas a comprehensive understanding of the architecture of vertebrate egg-coat matrix remains elusive. Here, we deduced the orientations and/or distributions of chicken ZP glycoproteins, ZP1, ZP3 and ZPD, in the egg-coat matrix by confocal immunofluorescent microscopy, and in the ZP1-ZP3 complexes generated in vitro by co-immunoprecipitation assays. We further confirmed interdomain interactions of the ZP glycoproteins by far-Western blot analyses of the egg-coat proteins and pull-down assays of ZP1 in the serum, using recombinant domains of ZP glycoproteins as probes. Our results suggest that the ZP1 and ZP3 bind through their ZP-C domains to form the ZP1-ZP3 complexes and fibrils, which are assembled into bundles through interactions between the repeat domains of ZP1 to form the ZP1-ZP3 matrix, and that the ZPD molecules self-associate and bind to the ZP1-ZP3 matrix through its ZP-N and ZP-C domains to form the egg-coat matrix. Based on these results, we propose a tentative model for the architecture of the chicken egg-coat matrix that might be applicable to other vertebrate ones.

  4. Interactive and independent associations between the socioeconomic and objective built environment on the neighbourhood level and individual health: a systematic review of multilevel studies.

    Science.gov (United States)

    Schüle, Steffen Andreas; Bolte, Gabriele

    2015-01-01

    The research question how contextual factors of neighbourhood environments influence individual health has gained increasing attention in public health research. Both socioeconomic neighbourhood characteristics and factors of the built environment play an important role for health and health-related behaviours. However, their reciprocal relationships have not been systematically reviewed so far. This systematic review aims to identify studies applying a multilevel modelling approach which consider both neighbourhood socioeconomic position (SEP) and factors of the objective built environment simultaneously in order to disentangle their independent and interactive effects on individual health. The three databases PubMed, PsycINFO, and Web of Science were systematically searched with terms for title and abstract screening. Grey literature was not included. Observational studies from USA, Canada, Australia, New Zealand, and Western European countries were considered which analysed simultaneously factors of neighbourhood SEP and the objective built environment with a multilevel modelling approach. Adjustment for individual SEP was a further inclusion criterion. Thirty-three studies were included in qualitative synthesis. Twenty-two studies showed an independent association between characteristics of neighbourhood SEP or the built environment and individual health outcomes or health-related behaviours. Twenty-one studies found cross-level or within-level interactions either between neighbourhood SEP and the built environment, or between neighbourhood SEP or the built environment and individual characteristics, such as sex, individual SEP or ethnicity. Due to the large variation of study design and heterogeneous reporting of results the identification of consistent findings was problematic and made quantitative analysis not possible. There is a need for studies considering multiple neighbourhood dimensions and applying multilevel modelling in order to clarify their causal

  5. TRPV1 Gene Polymorphisms Are Associated with Type 2 Diabetes by Their Interaction with Fat Consumption in the Korean Genome Epidemiology Study.

    Science.gov (United States)

    Park, Sunmin; Zhang, Xin; Lee, Na Ra; Jin, Hyun-Seok

    2016-01-01

    Different transient receptor potential vanilloid 1 (TRPV1) variants may be differently activated by noxious stimuli. We investigated how TRPV1 variants modulated the prevalence of type 2 diabetes and specific gene-nutrient interactions. Among 8,842 adults aged 40-69 years in the Korean Genome Epidemiology Study, the associations between TRPV1 genotypes and the prevalence of type 2 diabetes as well as their gene-nutrient interactions were investigated after adjusting for the covariates of age, gender, residence area, body mass index, daily energy intake, and total activity. The TRPV1 rs161364 and rs8065080 minor alleles lowered HOMA-IR and the risk of type 2 diabetes after adjusting for covariates. There were gene-nutrient interactions between TRPV1 variants rs161364 and rs8065080 and preference for oily taste, intake of oily foods, and fat intake after adjusting for covariates. Among subjects with the minor alleles of TRPV1 rs161364 and rs8065080, the group with a high preference for oily foods had a lower odds ratio for type 2 diabetes. Consistent with the preference for taste, among subjects with the minor alleles, the group with high fat intake from oily foods also exhibited a lower risk of type 2 diabetes than subjects with the major alleles. People with the minor alleles of the TRPV1 single nucleotide polymorphisms rs161364 and rs8065080 have a lower risk of diabetes with a high-fat diet, but people with the major alleles are at a higher risk of type 2 diabetes when consuming high-fat diets. The majority of people should be careful about a high fat intake. © 2016 S. Karger AG, Basel.

  6. Shrimp hemocyte homeostasis-associated protein (PmHHAP) interacts with WSSV134 to control apoptosis in white spot syndrome virus infection.

    Science.gov (United States)

    Apitanyasai, Kantamas; Amparyup, Piti; Charoensapsri, Walaiporn; Sangsuriya, Pakkakul; Tassanakajon, Anchalee

    2018-05-01

    Hemocyte homeostasis-associated protein (PmHHAP) was first identified as a viral-responsive gene, due to a high upregulation in transcription following white spot syndrome virus (WSSV) infection. Functional studies using RNA interference have suggested that PmHHAP is involved in hemocyte homeostasis by controlling apoptosis during WSSV infection. In this study, the role of PmHHAP in host-viral interactions was further investigated. Yeast two-hybrid assay and co-immunoprecipitation revealed that PmHHAP binds to an anti-apoptosis protein, WSSV134. The viral protein WSSV134 is a late protein of WSSV, expressed 24 h post infection (hpi). Gene silencing of WSSV134 in WSSV-infected shrimp resulted in a reduction of the expression level of the viral replication marker genes VP28, wsv477, and ie-1, which suggests that WSSV134 is likely involved in viral propagation. However, co-silencing of PmHHAP and WSSV134 counteracted the effects on WSSV infection, which implies the importance of the host-pathogen interaction between PmHHAP and WSSV134 in WSSV infection. In addition, caspase 3/7 activity was noticeably induced in the PmHHAP and WSSV134 co-silenced shrimp upon WSSV infection. Moreover, PmHHAP and WSSV134 inhibited caspase-induced activation of PmCasp in vitro in a non-competitive manner. Taken together, these results suggest that PmHHAP and WSSV134 play a role in the host-pathogen interaction and work concordantly to control apoptosis in WSSV infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Data in support of intermolecular interactions at early stage of protein/detergent particle association induced by salt/polyethylene glycol mixtures

    Directory of Open Access Journals (Sweden)

    Takayuki Odahara

    2016-06-01

    Full Text Available The data provide information in support of the research article, “Intermolecular interactions at early stage of protein/detergent particle association induced by salt/polyethylene glycol mixtures” [1]. The data regarding variation of absorption spectra is used as an indicator of the duration of Rp. viridis PRU and RC, Rb. sphaeroides RC and LH2, and Rb. capsulatus LH2 in the native state in the presence of NaCl/polyethylene glycol (PEG mixture. The data about minimum concentrations of salt and PEG whose aqueous phases are mutually separated presents information on additional influence of Tris buffer and N-octyl-β-d-glucoside on the salt–PEG phase separation.

  8. 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...... stress reactivity in individuals at high familial risk for mood disorders might enhance the effect of neuroticism in shaping the impact of potential environmental stress and thereby influence serotonergic neurotransmission....... and is positively correlated to frontolimbic serotonin 2A (5-HT(2A)) receptor binding. Here, we investigate whether neuroticism interacts with familial risk in relation to frontolimbic 5-HT(2A) receptor binding. Twenty-one healthy twins with a co-twin history of mood disorder and 16 healthy twins without a co...

  9. 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......The reduced folate carrier (RFC) is involved in the transport of methotrexate (MTX) across the cell membrane. The RFC gene (SLC19A1) is located on chromosome 21, and we hypothesized that the RFC80 G>A polymorphism would affect outcome and toxicity in childhood leukemia and that this could interact...... variants (P = .046). Increased copy numbers of chromosome 21 appear to improve outcome also in children with GA or GG variant. In a subset of 182 children receiving 608 high-dose MTX courses, we observed higher degree of bone marrow toxicity in patients with the RFC AA variant compared with GA/GG variants...

  10. 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...

  11. Membrane interactions of a self-assembling model peptide that mimics the self-association, structure and toxicity of Aβ(1-40)

    Science.gov (United States)

    Salay, Luiz C.; Qi, Wei; Keshet, Ben; Tamm, Lukas K.; Fernandez, Erik J.

    2013-01-01

    β-amyloid peptide (Aβ) is a primary protein component of senile plaques in Alzheimer’s disease (AD) and plays an important, but not fully understood role in neurotoxicity. Model peptides with the demonstrated ability to mimic the structural and toxicity behavior of Aβ could provide a means to evaluate the contributions to toxicity that are common to self–associating peptides from many disease states. In this work, we have studied the peptide-membrane interactions of a model β-sheet peptide, P11-2 (CH3CO-Gln-Gln-Arg-Phe-Gln-Trp-Gln-Phe-Glu-Gln-Gln-NH2), by fluorescence, infrared spectroscopy, and hydrogen-deuterium exchange. Like Aβ(1-40), the peptide is toxic, and conditions which produce intermediate oligomers show higher toxicity against cells than either monomeric forms or higher aggregates of the peptide. Further, P11-2 also binds to both zwitterionic (POPC) and negatively charged (POPC:POPG) liposomes, acquires a partial β-sheet conformation in presence of lipid, and is protected against deuterium exchange in the presence of lipids. The results show that a simple rationally designed model β-sheet peptide recapitulates many important features of Aβ peptide structure and function, reinforcing the idea that toxicity arises, at least in part, from a common mode of action on membranes that is independent of specific aspects of the amino acid sequence. Further studies of such well-behaved model peptide systems will facilitate the investigation of the general principles that govern the molecular interactions of aggregation-prone disease-associated peptides with cell and/or membrane surfaces. PMID:19393615

  12. Interactions between microfinance programmes and non-economic empowerment of women associated with intimate partner violence in Bangladesh: a cross-sectional study

    Science.gov (United States)

    Dalal, Koustuv; Dahlström, Örjan; Timpka, Toomas

    2013-01-01

    Objective This study aims to examine the associations between microfinance programme membership and intimate partner violence (IPV) in different socioeconomic strata of a nationally representative sample of women in Bangladesh. Methods The cross-sectional study was based on a nationally representative interview survey of 11 178 ever-married women of reproductive age (15–49 years). A total of 4465 women who answered the IPV-related questions were analysed separately using χ2 tests and Cramer's V as a measure of effect size to identify the differences in proportions of exposure to IPV with regard to microfinance programme membership, and demographic variables and interactions between microfinance programme membership and factors related to non-economic empowerment were considered. Results Only 39% of women were members of microfinance programmes. The prevalence of a history of IPV was 48% for moderate physical violence, 16% for severe physical violence and 16% for sexual violence. For women with secondary or higher education, and women at the two wealthiest levels of the wealth index, microfinance programme membership increased the exposure to IPV two and three times, respectively. The least educated and poorest groups showed no change in exposure to IPV associated with microfinance programmes. The educated women who were more equal with their spouses in their family relationships by participating in decision-making increased their exposure to IPV by membership in microfinance programmes. Conclusions Microfinance plans are associated with an increased exposure to IPV among educated and empowered women in Bangladesh. Microfinance firms should consider providing information about the associations between microfinance and IPV to the women belonging to the risk groups. PMID:24319278

  13. 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

  14. COROTATING INTERACTION REGION ASSOCIATED SUPRATHERMAL HELIUM ION ENHANCEMENTS AT 1 AU: EVIDENCE FOR LOCAL ACCELERATION AT THE COMPRESSION REGION TRAILING EDGE

    International Nuclear Information System (INIS)

    Ebert, R. W.; Dayeh, M. A.; Desai, M. I.; Mason, G. M.

    2012-01-01

    We examined the temporal profiles and peak intensities for 73 corotating interaction region (CIR)-associated suprathermal (∼0.1-8 MeV nucleon –1 ) helium (He) ion enhancements identified at STEREO-A, STEREO-B, and/or Advanced Composition Explorer between 2007 and 2010. We found that in most events the peak He intensity times were well organized by the CIR compression region trailing edge, regardless of whether or not a reverse shock was present. Out of these events, 19% had their 0.193 MeV nucleon –1 He intensities peak within 1 hr and 50% within 4.75 hr of the CIR trailing edge, the distribution having a 1σ value of 7.3 hr. Events with a 0.193 MeV nucleon –1 He intensity peak time within 1σ of the CIR trailing edge showed a positive correlation between the ∼0.1 and 0.8 MeV nucleon –1 He peak intensities and magnetic compression ratios in events both with and without a reverse shock. The peak intensities in all other events showed little to moderate correlation between these parameters. Our results provide evidence that some fraction of the CIR-associated –1 He intensity enhancements observed at 1 AU are locally driven. We suggest an extended source for the CIR-associated energetic particles observed at 1 AU where the –1 ions are accelerated locally at or near the CIR trailing edge, the intensities being proportional to the local compression ratio strength, while the >MeV particles are likely accelerated at CIR-driven shocks beyond Earth orbit.

  15. Modeling liquid-vapor equilibria with an equation of state taking into account dipolar interactions and association by hydrogen bonding; Modelisation des proprietes PVTX des fluides du systeme H{sub 2}O-gaz prenant en compte l'association par liaisons hydrogenes et les interactions dipolaires

    Energy Technology Data Exchange (ETDEWEB)

    Perfetti, E

    2006-11-15

    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{sub 2}O and H{sub 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 adju