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Sample records for antibody-antigen interacting associations

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

    Science.gov (United States)

    Akiba, Hiroki; Tsumoto, Kouhei

    2015-07-01

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

  2. Assessment of Solvated Interaction Energy Function for Ranking Antibody-Antigen Binding Affinities.

    Science.gov (United States)

    Sulea, Traian; Vivcharuk, Victor; Corbeil, Christopher R; Deprez, Christophe; Purisima, Enrico O

    2016-07-25

    Affinity modulation of antibodies and antibody fragments of therapeutic value is often required in order to improve their clinical efficacies. Virtual affinity maturation has the potential to quickly focus on the critical hotspot residues without the combinatorial explosion problem of conventional display and library approaches. However, this requires a binding affinity scoring function that is capable of ranking single-point mutations of a starting antibody. We focus here on assessing the solvated interaction energy (SIE) function that was originally developed for and is widely applied to scoring of protein-ligand binding affinities. To this end, we assembled a structure-function data set called Single-Point Mutant Antibody Binding (SiPMAB) comprising several antibody-antigen systems suitable for this assessment, i.e., based on high-resolution crystal structures for the parent antibodies and coupled with high-quality binding affinity measurements for sets of single-point antibody mutants in each system. Using this data set, we tested the SIE function with several mutation protocols based on the popular methods SCWRL, Rosetta, and FoldX. We found that the SIE function coupled with a protocol limited to sampling only the mutated side chain can reasonably predict relative binding affinities with a Spearman rank-order correlation coefficient of about 0.6, outperforming more aggressive sampling protocols. Importantly, this performance is maintained for each of the seven system-specific component subsets as well as for other relevant subsets including non-alanine and charge-altering mutations. The transferability and enrichment in affinity-improving mutants can be further enhanced using consensus ranking over multiple methods, including the SIE, Talaris, and FOLDEF energy functions. The knowledge gained from this study can lead to successful prospective applications of virtual affinity maturation. PMID:27367467

  3. Multiscale sensing of antibody-antigen interactions by organic transistors and single-molecule force spectroscopy.

    Science.gov (United States)

    Casalini, Stefano; Dumitru, Andra C; Leonardi, Francesca; Bortolotti, Carlo A; Herruzo, Elena T; Campana, Alessandra; de Oliveira, Rafael F; Cramer, Tobias; Garcia, Ricardo; Biscarini, Fabio

    2015-05-26

    Antibody-antigen (Ab-Ag) recognition is the primary event at the basis of many biosensing platforms. In label-free biosensors, these events occurring at solid-liquid interfaces are complex and often difficult to control technologically across the smallest length scales down to the molecular scale. Here a molecular-scale technique, such as single-molecule force spectroscopy, is performed across areas of a real electrode functionalized for the immunodetection of an inflammatory cytokine, viz. interleukin-4 (IL4). The statistical analysis of force-distance curves allows us to quantify the probability, the characteristic length scales, the adhesion energy, and the time scales of specific recognition. These results enable us to rationalize the response of an electrolyte-gated organic field-effect transistor (EGOFET) operated as an IL4 immunosensor. Two different strategies for the immobilization of IL4 antibodies on the Au gate electrode have been compared: antibodies are bound to (i) a smooth film of His-tagged protein G (PG)/Au; (ii) a 6-aminohexanethiol (HSC6NH2) self-assembled monolayer on Au through glutaraldehyde. The most sensitive EGOFET (concentration minimum detection level down to 5 nM of IL4) is obtained with the first functionalization strategy. This result is correlated to the highest probability (30%) of specific binding events detected by force spectroscopy on Ab/PG/Au electrodes, compared to 10% probability on electrodes with the second functionalization. Specifically, this demonstrates that Ab/PG/Au yields the largest areal density of oriented antibodies available for recognition. More in general, this work shows that specific recognition events in multiscale biosensors can be assessed, quantified, and optimized by means of a nanoscale technique. PMID:25868724

  4. 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

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

    Directory of Open Access Journals (Sweden)

    Masato Kiyoshi

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

  6. 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.

  7. 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.

  8. Control of antibody-antigen binding or dissociation by electric field

    Science.gov (United States)

    Oldham, Philip B.; Asanov, Alexander N.

    1999-04-01

    The development of a biosensor with adequate sensitivity generally requires a biospecific interaction with high binding affinity. The affinity constants for most antibody- antigen interactions are determined largely by the dissociation constants, kd, with little variation observed in rates of associated. additionally, surface immobilization typically results in a reduced kd. In this case, the sensor binds analyte kinetically irreversibly preventing response to changes in analytic concentration or reuse. Regeneration of the sensor surface is difficult, at best. On the other hand, a higher dissociation rate which would lend itself to a linear and reusable sensor, results in lower affinity and poor sensitivity. Consequently, most biosensors are disposable devices and quantitation is obtained using multiple single-use sensors. In this work, a new reusable biosensor platform which provides simultaneous fluorescence detection and electrochemical control of biospecific binding has been developed. Biotin was covalently attached to a transparent indium tin oxide electrode, which also served as an integral part of a total internal reflection fluorescence (TIRF) flow cell. TIRF was used to monitor biospecific interactions while electrochemical polarization was employed to control the interactions. Two possible mechanisms of the electric field effect involving interactions with induced and permanent dipoles of proteins will be discussed.

  9. 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

  10. 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

    2015-02-01

    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.

  11. PK/PD analysis of a novel pH-dependent antigen-binding antibody using a dynamic antibody-antigen binding model.

    Science.gov (United States)

    Haraya, Kenta; Tachibana, Tatsuhiko; Iwayanagi, Yuki; Maeda, Atsuhiko; Ozeki, Kazuhisa; Nezu, Junichi; Ishigai, Masaki; Igawa, Tomoyuki

    2016-04-01

    Previously, we have reported novel engineered antibody with pH-dependent antigen-binding (recycling antibody), and with both pH-dependent antigen-binding and increased FcRn-binding at neutral pH (sweeping antibody). The purpose of this study is to perform PK/PD predictions to better understand the potential applications of the antibodies as therapeutics. To demonstrate the applicability of recycling and sweeping antibodies over conventional antibodies, PK/PD analyses were performed. PK/PD parameters for antibody and antigen dynamics were estimated from the results of a pharmacokinetic study in human FcRn transgenic mice. A simulation study was performed using the estimated PK/PD parameters with various target antigen profiles. In comparison to conventional antibody, recycling antibody enhanced antibody-antigen complex clearance by 3 folds, while sweeping antibody accelerated antigen clearance by 10 folds in a pharmacokinetic study. Simulation results showed that recycling and sweeping antibodies can improve dosage frequency and reduce the required dose for target antigens with various clearances, plasma concentrations or binding kinetics. Moreover, importance of the association rate constant to enhance the beneficial effect of antibodies was shown. These results support the conclusion that recycling and sweeping antibodies can be applied to various target antigens with different profiles, and expand the number of antigens that antibodies can target. PMID:26944099

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  13. PULSED ELECTROCHEMICAL TECHNIQUE FOR MONITORING ANTIBODY-ANTIGEN REACTIONS AT INTERFACES. (R825323)

    Science.gov (United States)

    AbstractThe mechanism of pulsed potential waveform for monitoring antibody¯antigen interactions at immunosensor interfaces is discussed. Some examples of antibody¯antigen interactions at quartz crystal microbalance and polymer-modified ...

  14. Comparison of biosensor platforms in the evaluation of high affinity antibody-antigen binding kinetics.

    Science.gov (United States)

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

    2016-09-01

    The acquisition of reliable kinetic parameters for the characterization of biomolecular interactions is an important component of the drug discovery and development process. While several benchmark studies have explored the variability of kinetic rate constants obtained from multiple laboratories and biosensors, a direct comparison of these instruments' performance has not been undertaken, and systematic factors contributing to data variability from these systems have not been discussed. To address these questions, a panel of ten high-affinity monoclonal antibodies was simultaneously evaluated for their binding kinetics against the same antigen on four biosensor platforms: GE Healthcare's Biacore T100, Bio-Rad's ProteOn XPR36, ForteBio's Octet RED384, and Wasatch Microfluidics's IBIS MX96. We compared the strengths and weaknesses of these systems and found that despite certain inherent systematic limitations in instrumentation, the rank orders of both the association and dissociation rate constants were highly correlated between these instruments. Our results also revealed a trade-off between data reliability and sample throughput. Biacore T100, followed by ProteOn XPR36, exhibited excellent data quality and consistency, whereas Octet RED384 and IBIS MX96 demonstrated high flexibility and throughput with compromises in data accuracy and reproducibility. Our results support the need for a "fit-for-purpose" approach in instrument selection for biosensor studies. PMID:27365220

  15. 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.

  16. Cost Savings Associated with Testing of Antibodies, Antigens, and Nucleic Acids for Diagnosis of Acute HIV Infection

    OpenAIRE

    Karris, Maile Y.; Anderson, Christy M.; Sheldon R. Morris; Smith, Davey M.; Little, Susan J.

    2012-01-01

    Efforts to identify all persons infected with HIV in the United States are driven by the hope that early diagnosis will lower risk behaviors and decrease HIV transmission. Identification of HIV-infected people earlier in the course of their infection with HIV antigen/antibody (Ag/Ab) combination assays (4th-generation HIV assays) should help achieve this goal. We compared HIV RNA nucleic acid test (NAT) results to the results of a 4th-generation Ag/Ab assay (Architect HIV Ag/Ab Combo [HIV Com...

  17. Limitation of tuning the antibody-antigen reaction by changing the value of pH and its consequence for hyperthermia.

    Science.gov (United States)

    Mleczko, J; Defort, A; Kozioł, J J; Nguyen, T T; Mirończyk, A; Zapotoczny, B; Nowak-Jary, J; Gronczewska, E; Marć, M; Dudek, M R

    2016-04-01

    Distribution of the isoelectric point (pI) was calculated for the hypervariable regions of Fab fragments of the antibody molecules, which structure is annotated in the structural antibody database SabDab. The distribution is consistent with the universal for all organisms dividing the proteome into two sets of acidic and basic proteins. It shows the additional fine structure in a form of the narrow-sized peaks of pI values. This is an explanation why a small change of the environmental pH can have a strong effect on the antibody-antigen affinity. To show this, a typical enzyme-linked immunospecific assay experiment for testing the reaction of goat anti-human IgA antibodies with human IgA immunoglobulins of saliva as antigens was modified in such a way that Fe3O4magnetic nanoparticles were added to PBS buffer. The magnetic nanoparticles were remotely heated by the radio frequency magnetic field providing the local change of temperature and pH. It was observed that short times of the heating were significantly increasing the antibody-antigen binding strength while it was not the case for a longer time. The finding discussed in the study can be useful for biopharmaceuticals using antibodies, the immunoassay techniques as well as for control over the use of hyperthermia. PMID:26634446

  18. Fabrication of fiber-optic localized surface plasmon resonance sensor and its application to detect antibody-antigen reaction of interferon-gamma

    Science.gov (United States)

    Jeong, Hyeon-Ho; Erdene, Norov; Lee, Seung-Ki; Jeong, Dae-Hong; Park, Jae-Hyoung

    2011-12-01

    A fiber-optic localized surface plasmon (FO LSPR) sensor was fabricated by gold nanoparticles (Au NPs) immobilized on the end-face of an optical fiber. When Au NPs were formed on the end-face of an optical fiber by chemical reaction, Au NPs aggregation occurred and the Au NPs were immobilized in various forms such as monomers, dimers, trimers, etc. The component ratio of the Au NPs on the end-face of the fabricated FO LSPR sensor was slightly changed whenever the sensors were fabricated in the same condition. Including this phenomenon, the FO LSPR sensor was fabricated with high sensitivity by controlling the density of Au NPs. Also, the fabricated sensors were measured for the resonance intensity for the different optical systems and analyzed for the effect on sensitivity. Finally, for application as a biosensor, the sensor was used for detecting the antibody-antigen reaction of interferon-gamma.

  19. 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…

  20. Interactions between ectomycorrhizal associations and bacteria

    OpenAIRE

    Marupakula, Srisailam

    2016-01-01

    Boreal forest podzol soils have vertically stratified horizons with different physico-chemical characteristics and high microbial diversity. Ectomycorrhizal fungi play key roles in accessing nutrients from both organic and mineral substrates. The role of associated bacteria in these processes is still poorly understood. The aim of the studies described in this thesis was to improve understanding of the distribution, diversity and community structure of fungi and bacteria on roots and in soil ...

  1. Is social interaction associated with alcohol consumption in Uganda?

    Science.gov (United States)

    Tumwesigye, Nazarius Mbona; Kasirye, Rogers; Nansubuga, Elizabeth

    2009-07-01

    Little is documented about the association of alcohol consumption and social interaction in Uganda, a country with one of the highest per capita alcohol consumptions in the world. This paper describes the pattern of social interaction by sex and establishes the relationship between social interaction and alcohol consumption with and without the consideration of confounders. The data used had 1479 records and were collected in a survey in 2003. The study was part of a multinational study on Gender, Alcohol, and Culture International Study (GENACIS). Each question on social interaction had been pre-coded in a way that quantified the extent of social interaction. The sum of responses on interaction questions gave a summative score which was used to compute summary indices on social interaction. Principal component analysis (PCA) was used to identify the best combination of variables for a social interaction index. The index was computed by a prediction using a PCA model developed from the selected variables. The index was categorised into quintiles and used in bivariate and multivariate logistic regression analysis of alcohol consumption and social interaction. The stronger the social interaction the more the likelihood of taking alcohol frequently (chi(trend)(2)=4.72, psex, age group and education level (p=0.008). The strength of relationship between social interaction and heavy consumption of alcohol gets weak in multivariate analysis. Communication messages meant to improve health, well-being and public order need to incorporate dangers of negative influence of social interaction. PMID:19406589

  2. 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.

  3. Associated charm production in neutrino-nucleus interactions

    International Nuclear Information System (INIS)

    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)/σNCDIS=(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 νμ 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-)/σCC-4. (orig.)

  4. 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…

  5. Prospective Associations From Family-of-Origin Interactions to Adult Marital Interactions and Relationship Adjustment

    OpenAIRE

    Whitton, Sarah W.; Waldinger, Robert J.; Schulz, Marc S.; Allen, Joseph P.; Crowell, Judith A.; Hauser, Stuart T.

    2008-01-01

    To test the social learning–based hypothesis that marital conflict resolution patterns are learned in the family of origin, longitudinal, observational data were used to assess prospective associations between family conflict interaction patterns during adolescence and offspring’s later marital conflict interaction patterns. At age 14 years, 47 participants completed an observed family conflict resolution task with their parents. In a subsequent assessment 17 years later, the participants com...

  6. Methodology to study polymers interaction by surface plasmon resonance imaging ☆

    OpenAIRE

    N. Vollmer; Trombini, F.; M. Hely; Bellon, S.; Mercier, K.; Cazeneuve, C

    2014-01-01

    The surface plasmon resonance (SPR) technique has been primarily used in the field of biology, in particular for the study of antibody-antigen interactions. Recently, polymers were introduced to form inclusion complexes. We describe here, a methodology based on surface plasmon resonance imaging to study water-resistant and reversible inclusion complexes using systems which are compatible with a cosmetic use. The purpose of this study is to follow in real time the interaction between two po...

  7. Human ALKBH4 interacts with proteins associated with transcription.

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    Linn G Bjørnstad

    Full Text Available The Fe(II- and 2-oxoglutarate (2OG-dependent dioxygenase AlkB from E. coli is a demethylase which repairs alkyl lesions in DNA, as well as RNA, through a direct reversal mechanism. Humans possess nine AlkB homologs (ALKBH1-8 and FTO. ALKBH2 and ALKBH3 display demethylase activities corresponding to that of AlkB, and both ALKBH8 and FTO are RNA modification enzymes. The biochemical functions of the rest of the homologs are still unknown. To increase our knowledge on the functions of ALKBH4 and ALKBH7 we have here performed yeast two-hybrid screens to identify interaction partners of the two proteins. While no high-confidence hits were detected in the case of ALKBH7, several proteins associated with chromatin and/or involved in transcription were found to interact with ALKBH4. For all interaction partners, the regions mediating binding to ALKBH4 comprised domains previously reported to be involved in interaction with DNA or chromatin. Furthermore, some of these partners showed nuclear co-localization with ALKBH4. However, the global gene expression pattern was only marginally altered upon ALKBH4 over-expression, and larger effects were observed in the case of ALKBH7. Although the molecular function of both proteins remains to be revealed, our findings suggest a role for ALKBH4 in regulation of gene expression or chromatin state.

  8. Transcriptional robustness and protein interactions are associated in yeast

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    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.

  9. Interacting CMEs and their associated flare and SEP activities

    CERN Document Server

    Shanmugaraju, A

    2015-01-01

    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 observed during the period 1997-2010 in SOHO/LASCO and DH type IIs in Wind/WAVES. Their pre and primary CMEs from nearby active regions are identified using 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 (>10pfu) 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 occurred during the period 2000-2006. From the observed width and speed of pre and primary CMEs, 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, most of the pre-CMEs are tracked up to < 26Rs. The SEP in...

  10. Hippocampal-neocortical interaction: a hierarchy of associativity.

    Science.gov (United States)

    Lavenex, P; Amaral, D G

    2000-01-01

    The structures forming the medial temporal lobe appear to be necessary for the establishment of long-term declarative memory. In particular, they may be involved in the "consolidation" of information in higher-order associational cortices, perhaps through feedback projections. This review highlights the fact that the medial temporal lobe is organized as a hierarchy of associational networks. Indeed, associational connections within the perirhinal, parahippocampal, and entorhinal cortices enables a significant amount of integration of unimodal and polymodal inputs, so that only highly integrated information reaches the remainder of the hippocampal formation. The feedback efferent projections from the perirhinal and parahippocampal cortices to the neocortex largely reciprocate the afferent projections from the neocortex to these areas. There are, however, noticeable differences in the degree of reciprocity of connections between the perirhinal and parahippocampal cortices and certain areas of the neocortex, in particular in the frontal and temporal lobes. These observations are particularly important for models of hippocampal-neocortical interaction and long-term storage of information in the neocortex. Furthermore, recent functional studies suggest that the perirhinal and parahippocampal cortices are more than interfaces for communication between the neocortex and the hippocampal formation. These structures participate actively in memory processes, but the precise role they play in the service of memory or other cognitive functions is currently unclear. PMID:10985281

  11. Interaction of dietary resveratrol with animal-associated bacteria.

    Science.gov (United States)

    Jung, Carina M; Heinze, Thomas M; Schnackenberg, Laura K; Mullis, Lisa B; Elkins, Stephanie A; Elkins, Christopher A; Steele, Roger S; Sutherland, John B

    2009-08-01

    Resveratrol (3,5,4'-trihydroxy-trans-stilbene), an antifungal phytoalexin produced by grapes, peanuts, and Japanese knotweeds, is thought to be a beneficial dietary phytochemical in red wine and grape juice. Information on its antibacterial properties and biotransformation, however, is limited. We surveyed the interactions of resveratrol with 43 strains of bacterial species that are often animal- or human-associated. Resveratrol at 50 mg L(-1) reduced the growth rates of most of the bacteria tested, but did not totally prevent growth even at much higher levels. Eleven of the 43 bacteria were capable of transforming at least 20% of the resveratrol. Three major metabolites were identified as resveratroloside, piceid, and dihydroresveratrol, and three other metabolites were partially characterized.

  12. Suprathermal helium associated with corotating interaction regions: A case study

    Science.gov (United States)

    Yu, J.; Berger, L.; Wimmer-Schweingruber, R. F.; Hilchenbach, M.; Kallenbach, R.; Klecker, B.; Guo, J.

    2016-03-01

    Enhancements of suprathermal particles observed at 1AU often can be related to Corotating Interaction Regions (CIRs). The compression regions associated with CIRs and their driven shocks which typically form at a few AU distance to the Sun can efficiently accelerate particles. If accelerated at the trailing edge of a CIR these particles can travel sunward along the ambient magnetic field and thus enhanced fluxes can be observed even if the acceleration region has passed over the spacecraft. We have analysed a CIR that has been observed at L1 by ACE/SWICS and SOHO/CELIAS/STOF on days 207 and 208 in 2003. The combination of SWICS and STOF data allowed us to study suprathermal Helium ranging from its onset at solar wind bulk energies up to 330 keV/nuc. Here we present our results for the temporal evolution of the flux, energy spectra and the He+/He++ ratio. In particular we present observational evidence for a turnover of the energy spectra at lower energies after the CIR passage which has been theoretically predicted but never been observed so far.

  13. Scanning probe and optical tweezer investigations of biomolecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Rigby-Singleton, Shellie

    2002-07-01

    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 {approx}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

  14. Real-time association rate constant measurement using combination tapered fiber-optic biosensor (CTFOB) dip-probes

    Science.gov (United States)

    Simmonds, Boris; Wang, Chun-Wei; Kapoor, Rakesh

    2010-02-01

    This document reports a novel method of measuring association rate constant (ka) for antibody-antigen interaction using evanescent wave-based combination tapered fiber-optic biosensor (CTFOB) dip-probes. The method was demonstrated by measuring association rate constant for bovine serum albumin (BSA) and anti-BSA antibody interaction. "Direct method" was used for detection; goat anti-BSA "capture" antibodies were immobilized on the probe surfaces while the antigen (BSA) was directly labeled with Alexa 488 dye. The probes were subsequently submerged in 3nM Labeled BSA in egg albumin (1 mg/ml). The fluorescence signal recorded was proportional to BSA anti-BSA conjugates and continuous signal was acquired suing a fiber optic spectrometer (Ocean Optics, Inc.). A 476 nm diode laser was use as an excitation source. Association constant was estimated from a plot of signal as a function of time. Measured association rate constant ka for the binding of BSA with anti-BSA at room temperature is (8.33 +/- 0.01) x 104 M-1s-1.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    suggesting a functional organization for metabolism based on parsimonious use of cellular components. We use the inherent predictive capability of these pathways to experimentally discover novel transcriptional regulatory interactions in Escherichia coli metabolism for three transcription factors...

  16. DNA nanostructures interacting with lipid bilayer membranes.

    Science.gov (United States)

    Langecker, Martin; Arnaut, Vera; List, Jonathan; Simmel, Friedrich C

    2014-06-17

    membranes and can dynamically associate into higher order complexes. Hydrophobic modification of DNA nanostructures can further result in intra- or intermolecular aggregation, which can also be utilized as a structural switching mechanism. Appropriate design and chemical modification even allows insertion of DNA nanostructures into lipid bilayer membranes, resulting in artificial ion channel mimics made from DNA. Interactions of DNA nanodevices with living cells also involve interactions with membrane structures. DNA-based nanostructures can be directed to cell surfaces via antibody-antigen interactions, and their cellular uptake can be stimulated by modification with appropriate receptor ligands. In the future, membrane-embedded DNA nanostructures are expected to find application in diverse areas ranging from basic biological research over nanotechnology to synthetic biology. PMID:24828105

  17. Woody stem galls interact with foliage to affect community associations.

    Science.gov (United States)

    Cooper, W R; Rieske, L K

    2009-04-01

    Gall wasps (Hymenoptera: Cynipidae) hijack the physiology of their host plant to produce galls that house wasps throughout their immature stages. The gall-maker-host plant interaction is highly evolved, and galls represent an extended phenotype of the gall wasp. We evaluated two-way interactions between stem galls produced by Dryocosmus kuriphilus Yasumatsu on Castanea spp. (Fagales: Fagaceae) and foliage directly attached to galls (gall leaves) using gall leaf excision experiments and herbivore bioassays. Early season gall leaf excision decreased the dry weight per chamber (nutritive index) and thickness of the protective schlerenchyma layer and increased the number of empty chambers and the occurrence and size of exterior fungal lesions. Leaf excision also caused a modestly significant (alpha = 0.1) increase in the incidence of feeding chamber fungi and herbivory by Curculio sayi Gyllenhal (Coleoptera: Curculionidae), and a modest decrease in parasitoids. This study shows that gall leaves are important for stem gall development, quality, and defenses, adding support for the nutrient and enemy hypotheses. We also evaluated the effects of stem galls on the suitability of gall leaves to Lymantria dispar L. (Lepidoptera: Lymantriidae) herbivory to assess the extent of gall defenses in important source leaves. Relative growth rate of L. dispar larvae was greater on gall leaves compared with normal leaves, indicating that, despite their importance, gall leaves may be more suitable to generalist insect herbivores, suggesting limitations to the extended phenotype of the gall wasp. Our results improve our knowledge of host-cynipid interactions, gall source-sink relations, and D. kuriphilus community interactions.

  18. A novel biclustering approach to association rule mining for predicting HIV-1-human protein interactions.

    Directory of Open Access Journals (Sweden)

    Anirban Mukhopadhyay

    Full Text Available Identification of potential viral-host protein interactions is a vital and useful approach towards development of new drugs targeting those interactions. In recent days, computational tools are being utilized for predicting viral-host interactions. Recently a database containing records of experimentally validated interactions between a set of HIV-1 proteins and a set of human proteins has been published. The problem of predicting new interactions based on this database is usually posed as a classification problem. However, posing the problem as a classification one suffers from the lack of biologically validated negative interactions. Therefore it will be beneficial to use the existing database for predicting new viral-host interactions without the need of negative samples. Motivated by this, in this article, the HIV-1-human protein interaction database has been analyzed using association rule mining. The main objective is to identify a set of association rules both among the HIV-1 proteins and among the human proteins, and use these rules for predicting new interactions. In this regard, a novel association rule mining technique based on biclustering has been proposed for discovering frequent closed itemsets followed by the association rules from the adjacency matrix of the HIV-1-human interaction network. Novel HIV-1-human interactions have been predicted based on the discovered association rules and tested for biological significance. For validation of the predicted new interactions, gene ontology-based and pathway-based studies have been performed. These studies show that the human proteins which are predicted to interact with a particular viral protein share many common biological activities. Moreover, literature survey has been used for validation purpose to identify some predicted interactions that are already validated experimentally but not present in the database. Comparison with other prediction methods is also discussed.

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

    Directory of Open Access Journals (Sweden)

    Rong Luo

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

  20. 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...... in the presence of H1 differed from that observed in the absence of H1. HMGA and the HMGB proteins bound H1-containing nucleosome particles with similar affinity. The plant HMG proteins could also bind nucleosomes that were briefly treated with trypsin (removing the N-terminal domains of the core histones......), suggesting that the histone N-termini are dispensable for HMG protein binding. In the presence of untreated nucleosomes and trypsinised nucleosomes, HMGB1 could be chemically crosslinked with a core histone, which indicates that the trypsin-resistant part of the histones within the nucleosome is the main...

  1. Protein Cross-Linking Capillary Electrophoresis for Protein-Protein Interaction Analysis.

    Science.gov (United States)

    Ouimet, Claire M; Shao, Hao; Rauch, Jennifer N; Dawod, Mohamed; Nordhues, Bryce; Dickey, Chad A; Gestwicki, Jason E; Kennedy, Robert T

    2016-08-16

    Capillary electrophoresis (CE) has been identified as a useful platform for detecting, quantifying, and screening for modulators of protein-protein interactions (PPIs). In this method, one protein binding partner is labeled with a fluorophore, the protein binding partners are mixed, and then, the complex is separated from free protein to allow direct determination of bound to free ratios. Although it possesses many advantages for PPI studies, the method is limited by the need to have separation conditions that both prevent protein adsorption to capillary and maintain protein interactions during the separation. In this work, we use protein cross-linking capillary electrophoresis (PXCE) to overcome this limitation. In PXCE, the proteins are cross-linked under binding conditions and then separated. This approach eliminates the need to maintain noncovalent interactions during electrophoresis and facilitates method development. We report PXCE methods for an antibody-antigen interaction and heterodimer and homodimer heat shock protein complexes. Complexes are cross-linked by short treatments with formaldehyde after reaching binding equilibrium. Cross-linked complexes are separated by electrophoretic mobility using free solution CE or by size using sieving electrophoresis of SDS complexes. The method gives good quantitative results; e.g., a lysozyme-antibody interaction was found to have Kd = 24 ± 3 nM by PXCE and Kd = 17 ± 2 nM using isothermal calorimetry (ITC). Heat shock protein 70 (Hsp70) in complex with bcl2 associated athanogene 3 (Bag3) was found to have Kd = 25 ± 5 nM by PXCE which agrees with Kd values reported without cross-linking. Hsp70-Bag3 binding site mutants and small molecule inhibitors of Hsp70-Bag3 were characterized by PXCE with good agreement to inhibitory constants and IC50 values obtained by a bead-based flow cytometry protein interaction assay (FCPIA). PXCE allows rapid method development for quantitative analysis of PPIs. PMID:27434096

  2. 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 of...... 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....

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

    Science.gov (United States)

    Tandon, Disha; Haque, Mohammed Monzoorul; Mande, Sharmila S

    2016-01-01

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

  4. Genome-wide interaction-based association analysis identified multiple new susceptibility Loci for common diseases.

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2011-03-01

    Full Text Available Genome-wide interaction-based association (GWIBA analysis has the potential to identify novel susceptibility loci. These interaction effects could be missed with the prevailing approaches in genome-wide association studies (GWAS. However, no convincing loci have been discovered exclusively from GWIBA methods, and the intensive computation involved is a major barrier for application. Here, we developed a fast, multi-thread/parallel program named "pair-wise interaction-based association mapping" (PIAM for exhaustive two-locus searches. With this program, we performed a complete GWIBA analysis on seven diseases with stringent control for false positives, and we validated the results for three of these diseases. We identified one pair-wise interaction between a previously identified locus, C1orf106, and one new locus, TEC, that was specific for Crohn's disease, with a Bonferroni corrected P < 0.05 (P = 0.039. This interaction was replicated with a pair of proxy linked loci (P = 0.013 on an independent dataset. Five other interactions had corrected P < 0.5. We identified the allelic effect of a locus close to SLC7A13 for coronary artery disease. This was replicated with a linked locus on an independent dataset (P = 1.09 × 10⁻⁷. Through a local validation analysis that evaluated association signals, rather than locus-based associations, we found that several other regions showed association/interaction signals with nominal P < 0.05. In conclusion, this study demonstrated that the GWIBA approach was successful for identifying novel loci, and the results provide new insights into the genetic architecture of common diseases. In addition, our PIAM program was capable of handling very large GWAS datasets that are likely to be produced in the future.

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

    International Nuclear Information System (INIS)

    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.)

  6. 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.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Weak and transient protein–protein interactions underlie numerous biological processes. However, the location of the interaction sites of the specific complexes and the effect of transient, non-specific protein–protein interactions often remain elusive. We have investigated the weak selfassociation...... relaxation agent, it is shown that a distinction can be made between residues that are affected only by transient, non-specific protein–protein interactions and residues that are involved in specific protein-protein associations. Thus, the PREs of the former residues increase linearly with the h......GH concentration in the entire concentration range because of a reduction of the diffusion caused by the transient, non-specific protein-protein interactions, while the PREs of the latter residues increase only at the lower hGH concentrations but decrease at the higher concentrations because of specific protein-protein...

  8. Wave-particle interaction phenomena associated with shocks in the solar wind

    Science.gov (United States)

    Scarf, F. L.

    1977-01-01

    Microscopic wave-particle interaction phenomena must generally affect the evolution of a traveling interplanetary discontinuity such as a collisionless shock, and solar wind plasma instabilities should also be associated with interplanetary acceleration, diffusion, and dissipation. Recent local measurements from diagnostics on widely separated spacecraft illustrate some examples of these interaction phenomena, and two bounding cases are considered in detail here. It is shown that the interplanetary shock of September 14, 1974 (detected on IMP-7, 8, Hawkeye-1, and Pioneer 11) was associated with intense local electrostatic noise and ion acceleration, while the shock of January 6, 1975 (detected on IMP-7 and Helios-1) had no detectable electrostatic turbulence.

  9. 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...... to propose candidates in GWAS loci for functional studies and to systematically filter subtle association signals using tissue-specific quantitative interaction proteomics....

  10. SNP-SNP interaction network in angiogenesis genes associated with prostate cancer aggressiveness.

    Directory of Open Access Journals (Sweden)

    Hui-Yi Lin

    Full Text Available Angiogenesis has been shown to be associated with prostate cancer development. The majority of prostate cancer studies focused on individual single nucleotide polymorphisms (SNPs while SNP-SNP interactions are suggested having a great impact on unveiling the underlying mechanism of complex disease. Using 1,151 prostate cancer patients in the Cancer Genetic Markers of Susceptibility (CGEMS dataset, 2,651 SNPs in the angiogenesis genes associated with prostate cancer aggressiveness were evaluated. SNP-SNP interactions were primarily assessed using the two-stage Random Forests plus Multivariate Adaptive Regression Splines (TRM approach in the CGEMS group, and were then re-evaluated in the Moffitt group with 1,040 patients. For the identified gene pairs, cross-evaluation was applied to evaluate SNP interactions in both study groups. Five SNP-SNP interactions in three gene pairs (MMP16+ ROBO1, MMP16+ CSF1, and MMP16+ EGFR were identified to be associated with aggressive prostate cancer in both groups. Three pairs of SNPs (rs1477908+ rs1387665, rs1467251+ rs7625555, and rs1824717+ rs7625555 were in MMP16 and ROBO1, one pair (rs2176771+ rs333970 in MMP16 and CSF1, and one pair (rs1401862+ rs6964705 in MMP16 and EGFR. The results suggest that MMP16 may play an important role in prostate cancer aggressiveness. By integrating our novel findings and available biomedical literature, a hypothetical gene interaction network was proposed. This network demonstrates that our identified SNP-SNP interactions are biologically relevant and shows that EGFR may be the hub for the interactions. The findings provide valuable information to identify genotype combinations at risk of developing aggressive prostate cancer and improve understanding on the genetic etiology of angiogenesis associated with prostate cancer aggressiveness.

  11. 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

  12. Aplysia synapse associated protein (APSAP): identification, characterization, and selective interactions with Shaker-type potassium channels

    OpenAIRE

    Reissner, Kathryn J.; Boyle, Heather D.; Ye, Xiaojing; Carew, Thomas J.

    2007-01-01

    The vertebrate post-synaptic density (PSD) is a region of high molecular complexity in which dynamic protein interactions modulate receptor localization and synaptic function. Members of the membrane-associated guanylate kinase (MAGUK) family of proteins represent a major structural and functional component of the vertebrate PSD. In order to investigate the expression and significance of orthologous PSD components associated with the Aplysia sensory neuron-motor neuron synapse, we have cloned...

  13. Interactions of the HSV-1 UL25 Capsid Protein with Cellular Microtubule-associated Protein

    Institute of Scientific and Technical Information of China (English)

    Lei GUO; Ying ZHANG; Yan-chun CHE; Wen-juan WU; Wei-zhong LI; Li-chun WANG; Yun LIAO; Long-ding LIU; Qi-han LI

    2008-01-01

    An interaction between the HSV-1 UL25 capsid protein and cellular microtubule-associated protein was found using a yeast two-hybrid screen and β-D-galactosidase activity assays. Immunofluorescence microscopy of the UL25 protein demonstrated its co-localization with cellular microtubule-associated protein in the plasma membrane. Further investigations with deletion mutants suggest that UL25 is likely to have a function in the nucleus.

  14. 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.

  15. 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...

  16. The Quality of Teacher-Student Interactions: Associations with First Graders' Academic and Behavioral Outcomes

    Science.gov (United States)

    Cadima, Joana; Leal, Teresa; Burchinal, Margaret

    2010-01-01

    The associations between the quality of teacher-student interactions and first grade academic and adaptive behavior outcomes were examined in a study of 106 Portuguese students in 64 first grade classrooms. Students' vocabulary, print concepts, math, and adaptive skills were assessed both at the end of preschool and in first grade. Classrooms were…

  17. 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…

  18. The influence of third-order interactions on the density profile of associating hard spheres

    Science.gov (United States)

    Henderson, D.; Sokolowski, S.; Zagorski, R.; Trokhymchuk, A.

    Canonical ensemble Monte Carlo simulations and the non-uniform Percus-Yevick (NPY) equation for the local density are used to study the influence of surface mediated thirdorder interactions on the adsorption of associating hard spheres on a hard wall. A comparison of the NPY density profiles with the computer simulations data indicates that this approximation predicts the fluid structure reasonably well.

  19. 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)....

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

    DEFF Research Database (Denmark)

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

    1989-01-01

    A comprehensive range of chemical reagents and ribonucleases was employed to investigate the interaction of the antibiotics thiostrepton and micrococcin with the ribosomal protein L11-23S RNA complex and with the 50S subunit. Both antibiotics block processes associated with the ribosomal A-site b...

  1. 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 (M.); 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 indi

  2. Assessment of potential drug-drug interactions and its associated factors in the hospitalized cardiac patients.

    Science.gov (United States)

    Murtaza, Ghulam; Khan, Muhammad Yasir Ghani; Azhar, Saira; Khan, Shujaat Ali; Khan, Tahir M

    2016-03-01

    Drug-drug interactions (DDIs) may result in the alteration of therapeutic response. Sometimes they may increase the untoward effects of many drugs. Hospitalized cardiac patients need more attention regarding drug-drug interactions due to complexity of their disease and therapeutic regimen. This research was performed to find out types, prevalence and association between various predictors of potential drug-drug interactions (pDDIs) in the Department of Cardiology and to report common interactions. This study was performed in the hospitalized cardiac patients at Ayub Teaching Hospital, Abbottabad, Pakistan. Patient charts of 2342 patients were assessed for pDDIs using Micromedex® Drug Information. Logistic regression was applied to find predictors of pDDIs. The main outcome measure in the study was the association of the potential drug-drug interactions with various factors such as age, gender, polypharmacy, and hospital stay of the patients. We identified 53 interacting-combinations that were present in total 5109 pDDIs with median number of 02 pDDIs per patient. Overall, 91.6% patients had at least one pDDI; 86.3% were having at least one major pDDI, and 84.5% patients had at least one moderate pDDI. Among 5109 identified pDDIs, most were of moderate (55%) or major severity (45%); established (24.2%), theoretical (18.8%) or probable (57%) type of scientific evidence. Top 10 common pDDIs included 3 major and 7 moderate interactions. Results obtained by multivariate logistic regression revealed a significant association of the occurrence of pDDIs in patient with age of 60 years or more (p Older patients, patients with longer hospital stay and with elevated number of prescribed drugs were at higher risk of pDDIs. PMID:27013915

  3. Topology association analysis in weighted protein interaction network for gene prioritization

    Science.gov (United States)

    Wu, Shunyao; Shao, Fengjing; Zhang, Qi; Ji, Jun; Xu, Shaojie; Sun, Rencheng; Sun, Gengxin; Du, Xiangjun; Sui, Yi

    2016-11-01

    Although lots of algorithms for disease gene prediction have been proposed, the weights of edges are rarely taken into account. In this paper, the strengths of topology associations between disease and essential genes are analyzed in weighted protein interaction network. Empirical analysis demonstrates that compared to other genes, disease genes are weakly connected with essential genes in protein interaction network. Based on this finding, a novel global distance measurement for gene prioritization with weighted protein interaction network is proposed in this paper. Positive and negative flow is allocated to disease and essential genes, respectively. Additionally network propagation model is extended for weighted network. Experimental results on 110 diseases verify the effectiveness and potential of the proposed measurement. Moreover, weak links play more important role than strong links for gene prioritization, which is meaningful to deeply understand protein interaction network.

  4. 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.

  5. An Interactive System using Association Rule Discovery for Dyeing Processing System

    Directory of Open Access Journals (Sweden)

    Rama Sree .R.J

    2011-09-01

    Full Text Available This paper uses prior domain knowledge to guide the mining of association rules in the dyeing business process environment. This approach is used in order to overcome the drawbacks of data mining using rule induction such as loss of information, discover too many obvious patterns, and mining of overwhelmed association rules. A data mining interactive rule induction algorithm is introduced to mine rules at micro levels. The mined rules describe the impact of different shades of the colours, originator of the treatment, treatment details to improve the dyeing process quality and production growth. A system was built based on this algorithm and was tested and verified on real data set in Emerald Dyeing unit, which is the leading dyeing industry in Andhra Pradesh, India. Hence, this paper contributes more on to derive simple interactive system called process model using association rule mining algorithm for dyeing processing system.

  6. 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...

  7. Protein-protein interactions of mitochondrial-associated protein via bioluminescence resonance energy transfer

    Science.gov (United States)

    Koshiba, Takumi

    2015-01-01

    Protein-protein interactions are essential biological reactions occurring at inter- and intra-cellular levels. The analysis of their mechanism is generally required in order link to understand their various cellular functions. Bioluminescence resonance energy transfer (BRET), which is based on an enzymatic activity of luciferase, is a useful tool for investigating protein-protein interactions in live cells. The combination of the BRET system and biomolecular fluorescence complementation (BiFC) would provide us a better understanding of the hetero-oligomeric structural states of protein complexes. In this review, we discuss the application of BRET to the protein-protein interactions of mitochondrial-associated proteins and discuss its physiological relevance. PMID:27493852

  8. Distributed interacted multisensor joint probabilistic data association algorithm based on D-S theory

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to resolve the multisensor multiplied maneuvering target tracking problem, this paper presents a distributed interacted multiple model multisensor joint probabilistic data association algorithm (DIMM-MSJPDA). First of all, the interacted multiple model joint probabilistic data association algorithm is applied to each sensor, and then the state estimation, estimation covariance, model probability, combined innovation, innovation covariance are delivered to the fusion center. Then, the tracks from each sensor are correlated and the D-S evidence theory is used to gain the model probability of an identical target. Finally, the ultimate state estimation of each target is calculated according to the new model probability, and the state estimation is transmitted to each sensor. Simulations are designed to test the tracking performance of DIMM-MSJPDA algorithm. The results show that the use of DIMM-MSJPDA algorithm enables the distributed multisensor system to track multiplied maneuvering targets and its tracking performance is much better than that of IMMJPDA algorithm.

  9. Selective associations produced solely with appetitive contingencies: the stimulus-reinforcer interaction revisited.

    OpenAIRE

    Weiss, S J; Panlilio, L V; Schindler, C W

    1993-01-01

    In studies reporting stimulus-reinforcer interactions in traditional conditioning paradigms, when a tone-light compound was associated with food the light gained stimulus control, but when the compound was paired with shock avoidance the tone gained control. However, the physical nature of the reinforcer-related events (food vs. shock) presented in the presence of the tone-light compound was always confounded with the conditioned hedonic value of the compound's presence relative to its absenc...

  10. Size-invariant facial expression categorization and associated gaze allocation within social interaction space

    OpenAIRE

    Guo, Kun

    2013-01-01

    As faces often appear under very different viewing conditions (e.g., brightness, viewing angle or viewing distance), invariant facial information recognition is a key to our social interactions. Despite we would clearly benefit from differentiating different facial expressions (e.g., anger vs. happy) at a distance, there is surprisingly little research examining how expression categorization and associated gaze allocation is affected by viewing distance within the range of typical social spac...

  11. Microtubule-associated proteins and tubulin interaction by isothermal titration calorimetry.

    Science.gov (United States)

    Tsvetkov, P O; Barbier, P; Breuzard, G; Peyrot, V; Devred, F

    2013-01-01

    Microtubules play an important role in a number of vital cell processes such as cell division, intracellular transport, and cell architecture. The highly dynamic structure of microtubules is tightly regulated by a number of stabilizing and destabilizing microtubule-associated proteins (MAPs), such as tau and stathmin. Because of their importance, tubulin-MAPs interactions have been extensively studied using various methods that provide researchers with complementary but sometimes contradictory thermodynamic data. Isothermal titration calorimetry (ITC) is the only direct thermodynamic method that enables a full thermodynamic characterization (stoichiometry, enthalpy, entropy of binding, and association constant) of the interaction after a single titration experiment. This method has been recently applied to study tubulin-MAPs interactions in order to bring new insights into molecular mechanisms of tubulin regulation. In this chapter, we review the technical specificity of this method and then focus on the use of ITC in the investigation of tubulin-MAPs binding. We describe technical issues which could arise during planning and carrying out the ITC experiments, in particular with fragile proteins such as tubulin. Using examples of stathmin and tau, we demonstrate how ITC can be used to gain major insights into tubulin-MAP interaction.

  12. Comparative Analysis of Protein-Protein Interactions in Cancer-Associated Genes 25

    Institute of Scientific and Technical Information of China (English)

    Purnima Guda; Sridar V. Chittur; Chittibabu Guda

    2009-01-01

    Protein-protein interactions (PPIs) have been widely studied to understand the bi-ological processes or molecular functions associated with different disease systems like cancer. While focused studies on individual cancers have generated valuable in-formation, global and comparative analysis of datasets from different cancer types has not been done. In this work, we carried out bioinformatic analysis of PPIs corresponding to differentially expressed genes from microarrays of various tumor tissues (belonging to bladder, colon, kidney and thyroid cancers) and compared their associated biological processes and molecular functions (based on Gene On-tology terms). We identified a set of processes or functions that are common to all these cancers, as well as those that are specific to only one or partial cancer types. Similarly, protein interaction networks in nucleic acid metabolism were compared to identify the common/specific clusters of proteins across different cancer types. Our results provide a basis for further experimental investigations to study protein interaction networks associated with cancer. The methodology developed in this work can also be applied to study similar disease systems.

  13. Interpretation of Association Behavior and Molecular Interactions in Binary Mixtures from Thermoacoustics and Molecular Compression Data

    Science.gov (United States)

    Shukla, Rajeev K.; Kumar, Atul; Srivastava, Urvashi; Srivastava, Kirti; Pandey, Vivek K.

    2016-09-01

    Density and acoustic velocity were measured for binary liquid mixtures of formamide, N-methylacetamide (NMA), dimethylformamide (DMF), and dimethylacetamide (DMA) with acetonitrile at atmospheric pressure and 293.15 K, 298.15 K, 303.15 K, 308.15 K, or 313.15 K over the concentration range 0.12 to 0.97. Models assuming association and nonassociation of the components of the mixtures were used to predict the behavior of the studied liquids, which would typically show weak interactions. The measured properties were fitted to the Redlich-Kister polynomial to estimate the binary coefficients and standard errors. The data were used to study the molecular interactions in the binary mixtures. Furthermore, the McAllister multibody interaction model was used to correlate the properties of the binary liquid mixtures. Testing of the nonassociation and association models for the different systems showed that, compared with the nonassociation model theoretical results, the association model theoretical results were more consistent with the experimental results.

  14. 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

    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

  15. Assessment of potential drug–drug interactions and its associated factors in the hospitalized cardiac patients

    Directory of Open Access Journals (Sweden)

    Ghulam Murtaza

    2016-03-01

    Full Text Available Drug–drug interactions (DDIs may result in the alteration of therapeutic response. Sometimes they may increase the untoward effects of many drugs. Hospitalized cardiac patients need more attention regarding drug–drug interactions due to complexity of their disease and therapeutic regimen. This research was performed to find out types, prevalence and association between various predictors of potential drug–drug interactions (pDDIs in the Department of Cardiology and to report common interactions. This study was performed in the hospitalized cardiac patients at Ayub Teaching Hospital, Abbottabad, Pakistan. Patient charts of 2342 patients were assessed for pDDIs using Micromedex® Drug Information. Logistic regression was applied to find predictors of pDDIs. The main outcome measure in the study was the association of the potential drug–drug interactions with various factors such as age, gender, polypharmacy, and hospital stay of the patients. We identified 53 interacting-combinations that were present in total 5109 pDDIs with median number of 02 pDDIs per patient. Overall, 91.6% patients had at least one pDDI; 86.3% were having at least one major pDDI, and 84.5% patients had at least one moderate pDDI. Among 5109 identified pDDIs, most were of moderate (55% or major severity (45%; established (24.2%, theoretical (18.8% or probable (57% type of scientific evidence. Top 10 common pDDIs included 3 major and 7 moderate interactions. Results obtained by multivariate logistic regression revealed a significant association of the occurrence of pDDIs in patient with age of 60 years or more (p < 0.001, hospital stay of 7 days or longer (p < 0.001 and taking 7 or more drugs (p < 0.001. We found a high prevalence for pDDIs in the Department of Cardiology, most of which were of moderate severity. Older patients, patients with longer hospital stay and with elevated number of prescribed drugs were at higher risk of pDDIs.

  16. 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.

  17. Genotype × Environment Interactions for Agronomic Traits of Rice Revealed by Association Mapping

    Institute of Scientific and Technical Information of China (English)

    XU Fei-fei; TANG Fu-fu; SHAO Ya-fang; CHEN Ya-ling; TONG Chuan; BAO Jin-song

    2014-01-01

    Agronomic traits are important determinants to rice yield, which are controlled by complex genetic factors as well as genotype by environment (G × E) interaction effects. The G × E effects for agronomic traits of rice have been dissected with various approaches, but not with the current available approach, the association studies. In this study, a total of 32 655 single nucleotide polymorphisms were used to carry out associations with 14 agronomic traits among 20 rice accessions in two environments. The G × E interaction effects for all the agronomic traits were at highly significant levels (P<0.01), accounting for 3.4%-22.3% of the total sum of squares except for the length of brown rice. Twenty three putative quantitative trait loci (QTLs), including five previously known and several new promising associations, were identified for 10 of 14 traits. Analysis of the relationships between the traits for which QTLs and the genotype effects could be identified suggested that the higher the genotypic effect, the higher the possibility to identify QTLs for the given trait. The new QTLs detected in this study will facilitate dissection of the complex agronomic traits and may give insight into the G × E effects with association mapping.

  18. 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.

  19. 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...... 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...

  20. Association of HS6ST3 gene polymorphisms with obesity and triglycerides: gene × gender interaction

    Indian Academy of Sciences (India)

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

    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 $(P \\lt 0.05)$. SNP rs535812 revealed a stronger association with obesity in meta-analysis of these two samples $(P = 0.0105)$. The T–A haplotype from rs878950 and rs9525149 revealed significant association with obesity in the Marshfield sample $(P = 0.012)$. Moreover, nine SNPs showed associations with triglycerides in the Marshfield sample $(P \\lt 0.05)$ and the best signal was rs1927796 $(P = 0.00858)$. In addition, rs7331762 showed a strong gene × gender interaction $(P = 0.00956)$ for obesity while rs1927796 showed a strong gene × gender interaction $(P = 0.000625)$ for 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.

  1. Interactions of calmodulin with death-associated protein kinase peptides: experimental and modeling studies.

    Science.gov (United States)

    Kuczera, Krzysztof; Kursula, Petri

    2012-01-01

    We have studied the interactions between calmodulin (CaM) and three target peptides from the death-associated protein kinase (DAPK) protein family using both experimental and modeling methods, aimed at determining the details of the underlying biological regulation mechanisms. Experimentally, calorimetric binding free energies were determined for the complexes of CaM with peptides representing the DAPK2 wild-type and S308D mutant, as well as DAPK1. The observed affinity of CaM was very similar for all three studied peptides. The DAPK2 and DAPK1 peptides differ significantly in sequence and total charge, while the DAPK2 S308D mutant is designed to model the effects of DAPK2 Ser308 phosphorylation. The crystal structure of the CaM-DAPK2 S308D mutant peptide is also reported. The structures of CaM-DAPK peptide complexes present a mode of CaM-kinase interaction, in which bulky hydrophobic residues at positions 10 and 14 are both bound to the same hydrophobic cleft. To explain the microscopic effects underlying these interactions, we performed free energy calculations based on the approximate MM-PBSA approach. For these highly charged systems, standard MM-PBSA calculations did not yield satisfactory results. We proposed a rational modification of the approach which led to reasonable predictions of binding free energies. All three complexes are strongly stabilized by two effects: electrostatic interactions and buried surface area. The strong favorable interactions are to a large part compensated by unfavorable entropic terms, in which vibrational entropy is the largest contributor. The electrostatic component of the binding free energy followed the trend of the overall peptide charge, with strongest interactions for DAPK1 and weakest for the DAPK2 mutant. The electrostatics was dominated by interactions of the positively charged residues of the peptide with the negatively charged residues of CaM. The nonpolar binding free energy was comparable for all three peptides, the

  2. Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: A GWAS data analysis

    Science.gov (United States)

    Tang, Hongwei; Wei, Peng; Duell, Eric J.; Risch, Harvey A.; Olson, Sara H.; Bueno-de-Mesquita, H. Bas; Gallinger, Steven; Holly, Elizabeth A.; Petersen, Gloria M.; Bracci, Paige M.; McWilliams, Robert R.; Jenab, Mazda; Riboli, Elio; Tjønneland, Anne; Boutron-Ruault, Marie Christine; Kaaks, Rudolf; Trichopoulos, Dimitrios; Panico, Salvatore; Sund, Malin; Peeters, Petra H.M; Khaw, Kay-Tee; Amos, Christopher I; Li, Donghui

    2013-01-01

    Background Obesity and diabetes are potentially alterable risk factors for pancreatic cancer. Genetic factors that modify the associations of obesity and diabetes with pancreatic cancer have previously not been examined at the genome-wide level. Methods Using GWAS genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study of 2,028 cases and 2,109 controls to examine gene-obesity and gene-diabetes interactions in relation to pancreatic cancer risk by employing the likelihood ratio test (LRT) nested in logistic regression models and Ingenuity Pathway Analysis (IPA). Results After adjusting for multiple comparisons, a significant interaction of the chemokine signaling pathway with obesity (P = 3.29 × 10−6) and a near significant interaction of calcium signaling pathway with diabetes (P = 1.57 × 10−4) in modifying the risk of pancreatic cancer was observed. These findings were supported by results from IPA analysis of the top genes with nominal interactions. The major contributing genes to the two top pathways include GNGT2, RELA, TIAM1 and GNAS. None of the individual genes or SNPs except one SNP remained significant after adjusting for multiple testing. Notably, SNP rs10818684 of the PTGS1 gene showed an interaction with diabetes (P = 7.91 × 10−7) at a false discovery rate of 6%. Conclusions Genetic variations in inflammatory response and insulin resistance may affect the risk of obesity and diabetes-related pancreatic cancer. These observations should be replicated in additional large datasets. Impact Gene-environment interaction analysis may provide new insights into the genetic susceptibility and molecular mechanisms of obesity- and diabetes-related pancreatic cancer. PMID:24136929

  3. 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

  4. 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.

  5. 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.

  6. 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

    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......Background Identifying high-order genetics associations with non-additive (i.e. epistatic) effects in population-based studies of common human diseases is a computational challenge. Multifactor dimensionality reduction (MDR) is a machine learning method that was designed specifically for this....... This study highlights the importance of using machine learning methods that are designed to embrace, rather than ignore, the complexity of common diseases such as TB. We recommend future studies of the genetic of TB take into account the possibility that high-order epistatic interactions might play an...

  7. Interactions between hyphosphere-associated bacteria and the fungus Cladosporium herbarum on aquatic leaf litter.

    Science.gov (United States)

    Baschien, Christiane; Rode, Georg; Böckelmann, Uta; Götz, Peter; Szewzyk, Ulrich

    2009-10-01

    We investigated microbial interactions of aquatic bacteria associated with hyphae (the hyphosphere) of freshwater fungi on leaf litter. Bacteria were isolated directly from the hyphae of fungi from sedimented leaves of a small stream in the National Park "Lower Oder," Germany. To investigate interactions, bacteria and fungi were pairwise co-cultivated on leaf-extract medium and in microcosms loaded with leaves. The performance of fungi and bacteria was monitored by measuring growth, enzyme production, and respiration of mono- and co-cultures. Growth inhibition of the fungus Cladosporium herbarum by Ralstonia pickettii was detected on leaf extract agar plates. In microcosms, the presence of Chryseobacterium sp. lowered the exocellulase, endocellulase, and cellobiase activity of the fungus. Additionally, the conversion of leaf material into microbial biomass was retarded in co-cultures. The respiration of the fungus was uninfluenced by the presence of the bacterium.

  8. 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.

  9. Fragile X mental retardation protein interactions with the microtubule associated protein 1B RNA

    OpenAIRE

    Menon, Lakshmi; Mader, Samantha Ann; Mihailescu, Mihaela-Rita

    2008-01-01

    Fragile X mental retardation syndrome, the most common form of inherited mental retardation, is caused by the absence of the fragile X mental retardation protein (FMRP). FMRP has been shown to use its arginine–glycine–glycine (RGG) box to bind to a subset of RNA targets that form a G quadruplex structure. We performed a detailed analysis of the interactions between the FMRP RGG box and the microtubule associated protein 1B (MAP1B) mRNA, a relevant in vivo FMRP target. We show that MAP1B RNA f...

  10. Differential expression of immune defences is associated with specific host-parasite interactions in insects.

    Directory of Open Access Journals (Sweden)

    Carolyn Riddell

    Full Text Available Recent ecological studies in invertebrates show that the outcome of an infection is dependent on the specific pairing of host and parasite. Such specificity contrasts the long-held view that invertebrate innate immunity depends on a broad-spectrum recognition system. An important question is whether this specificity is due to the immune response rather than some other interplay between host and parasite genotypes. By measuring the expression of putative bumblebee homologues of antimicrobial peptides in response to infection by their gut trypanosome Crithidia bombi, we demonstrate that expression differences are associated with the specific interactions.

  11. Fen1 mutations that specifically disrupt its interaction with PCNA cause aneuploidy-associated cancer

    Institute of Scientific and Technical Information of China (English)

    Li Zheng; Sankar Mitra; Qin Huang; Kemp H Kernstine; Gerd P Pfeifer; Binghui Shen; Huifang Dai; Muralidhar L Hegde; Mian Zhou; Zhigang Guo; Xiwei Wu; Jun WU; Lei Su; Xueyan Zhong

    2011-01-01

    DNA replication and repair are critical processes for all living organisms to ensure faithful duplication and transmission of genetic information. Flap endonuclease 1 (Feni), a structure-specific nuclease, plays an important role in multiple DNA metabolic pathways and maintenance of genome stability. Human FEN1 mutations that impair its exonuclease activity have been linked to cancer development. FEN1 interacts with multiple proteins, including proliferation cell nuclear antigen (PCNA), to form various functional complexes. Interactions with these proteins are considered to be the key molecular mechanisms mediating FEN1's key biological functions. The current challenge is to experimentally demonstrate the biological consequence of a specific interaction without compromising other functions of a desired protein. To address this issue, we established a mutant mouse model harboring a FEN1 point mutation (F343A/F344A, FFAA), which specifically abolishes the FEN1/PCNA interaction. We show that the FFAA mutation causes defects in RNA primer removal and long-patch base excision repair, even in the heterozygous state, resulting in numerous DNA breaks. These breaks activate the G2/M checkpoint protein, Chk1, and induce neartetraploid aneuploidy, commonly observed in human cancer, consequently elevating the transformation frequency. Consistent with this, inhibition of aneupioidy formation by a Chk1 inhibitor significantly suppressed the cellular transformation. WT/FFAA FEN1 mutant mice develop aneuploidy-associated cancer at a high frequency. Thus, this study establishes an exemplary case for investigating the biological significance of protein-protein interactions by knock-in of a point mutation rather than knock-out of a whole gene.

  12. Hydrophobic Interactions Are Key To Drive the Association of Tapasin with Peptide Transporter Subunit TAP2.

    Science.gov (United States)

    Rufer, Elke; Kägebein, Danny; Leonhardt, Ralf M; Knittler, Michael R

    2015-12-01

    The transporter associated with Ag processing (TAP) translocates proteasomally derived cytosolic peptides into the endoplasmic reticulum. TAP is a central component of the peptide-loading complex (PLC), to which tapasin (TPN) recruits MHC class I (MHC I) and accessory chaperones. The PLC functions to facilitate and optimize MHC I-mediated Ag presentation. The heterodimeric peptide transporter consists of two homologous subunits, TAP1 and TAP2, each of which contains an N-terminal domain (N-domain) in addition to a conserved transmembrane (TM) core segment. Each N-domain binds to the TM region of a single TPN molecule, which recruits one MHC I molecule to TAP1 and/or TAP2. Although both N-domains act as TPN-docking sites, various studies suggest a functional asymmetry within the PLC resulting in greater significance of the TAP2/TPN interaction for MHC loading. In this study, we demonstrate that the leucine-rich hydrophobic sequence stretches (with the central leucine residues L20 and L66) in the first and second TM helix of TAP2 form a functional unit acting as a docking site for optimal TPN/MHC I recruitment, whereas three distinct highly conserved arginine and/or aspartate residues inside or flanking these TM helices are dispensable. Moreover, we show that the physical interaction between TAP2 and TPN is disrupted by benzene, a compound known to interfere with hydrophobic interactions, such as those between pairing leucine zippers. No such effects were observed for the TAP1/TAP2 interaction or the complex formation between TPN and MHC I. We propose that TAP/TPN complex formation is driven by hydrophobic interactions via leucine zipper-like motifs.

  13. 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...... positive associations of interactions between social/behavioral factors and the ADRB2 genotypes with health outcomes of cognitive function and self-reported health, and negative associations of carrying rs1042718 or rs1042719 minor alleles with negative emotion, at advanced ages in China. Our findings...... 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...

  14. 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

    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...... 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...... without the signal peptide. We found that serum MAP-1 was very stable when subjected to repeated freeze and thaw cycles. The mean serum concentration of MAP-1 was found to be 240ng/ml (range: 115-466ng/ml). MAP-1 was predominantly found in complex with Ficolin-3 and to a lesser degree with Ficolin-2...

  15. 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.

  16. 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.

  17. Drosophila PIWI associates with chromatin and interacts directly with HP1a.

    Science.gov (United States)

    Brower-Toland, Brent; Findley, Seth D; Jiang, Ling; Liu, Li; Yin, Hang; Dus, Monica; Zhou, Pei; Elgin, Sarah C R; Lin, Haifan

    2007-09-15

    The interface between cellular systems involving small noncoding RNAs and epigenetic change remains largely unexplored in metazoans. RNA-induced silencing systems have the potential to target particular regions of the genome for epigenetic change by locating specific sequences and recruiting chromatin modifiers. Noting that several genes encoding RNA silencing components have been implicated in epigenetic regulation in Drosophila, we sought a direct link between the RNA silencing system and heterochromatin components. Here we show that PIWI, an ARGONAUTE/PIWI protein family member that binds to Piwi-interacting RNAs (piRNAs), strongly and specifically interacts with heterochromatin protein 1a (HP1a), a central player in heterochromatic gene silencing. The HP1a dimer binds a PxVxL-type motif in the N-terminal domain of PIWI. This motif is required in fruit flies for normal silencing of transgenes embedded in heterochromatin. We also demonstrate that PIWI, like HP1a, is itself a chromatin-associated protein whose distribution in polytene chromosomes overlaps with HP1a and appears to be RNA dependent. These findings implicate a direct interaction between the PIWI-mediated small RNA mechanism and heterochromatin-forming pathways in determining the epigenetic state of the fly genome. PMID:17875665

  18. Study on interaction between microtubule associated protein tau and prion protein

    Institute of Scientific and Technical Information of China (English)

    HAN Jun; ZHOU Wei; DONG Xiaoping; ZHANG Jin; YAO Hailan; WANG Xiaofan; LI Feng; CHEN Lan; GAO Chen; GAO Jianmei; NIE Kai

    2006-01-01

    Microtubule-associated protein tau is considered to play roles in many neurodegenerative diseases including some transmissible spongiform encephalopathies. To address the possible molecular linkage of prion protein (PrP) and tau, a GST-fusion segment of human tau covering the three-repeat region and various PrP segments was used in the tests of GST pull-down and immunoprecipitation. We found tau protein interacted with various style prion proteins such as native prion protein (PrPC) or protease-resistant isoform (prpSc). Co-localization signals of tau and PrP were found in the CHO cell tranfected with both PrP and tau gene. The domain of interaction with tau was located at N-terminal of PrP (residues 23 to 91). The evidence of molecular interactions between PrP and tau protein highlights a potential role of tau in the biological function of PrP and the pathogenesis of TSEs.

  19. 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.

  20. 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.

  1. Molecular Markers for Biomass Traits: Association, Interaction and Genetic Divergence in Silkworm Bombyx mori

    Directory of Open Access Journals (Sweden)

    Appukuttannair R Pradeep

    2007-01-01

    Full Text Available Improvement of high yielding, disease resistant silkworm strains became imminent to increase production of silk, which is a major revenue earner for sericulturists. Since environment interacts with phenotype, conventional breeding did not result in commendable yield improvement in synthetic strains of silkworm, Bombyx mori. Identification of DNA markers associated with different economically important biomass traits and its introgression could assist molecular breeding and expression of stabilized high yielding characters, but genetic basis of most quantitative traits in silkworm is poorly understood due to its polygenic control. Correlation analysis (R = 0.9 revealed significant interrelation among biomass traits viz., larval duration (TLD, larval weight (LWT, cocoon weight (CWT, shell weight (SWT, shell ratio (SR and floss content. PCR using inter simple sequence repeat (ISSR primers revealed 92% polymorphism among 14 tropical and temperate strains of B. mori, with average diversity index of 0.747. Stepwise multiple regression analysis (MRA selected 35 ISSR markers positively or negatively correlated with different biomass traits, illustrated polygenic control. ISSR marker 830.81050bp was significantly associated with LWT, CWT, SWT, SR and fl oss content, indicated its pleiotropic role. Two ISSR markers, 835.51950bp and 825.9710bp showed significant association with floss content and TLD. These markers were segregated in F2 generation and Chi-square test confirmed (χ2 = ~45; P < 0.05 its genetic contribution to the associated biomass traits. Strains, with both positively and negatively correlated markers, had intermediate mean value for biomass traits (eg. SWT = 0.17 ± 0.014 g in GNM and Moria indicated interaction of loci in natural populations. Low yielding Indian strains grouped together by Hierarchical clustering. Chinese and Japanese strains were distributed in the periphery of ALSCAL matrix indicated convergence of genetic characters

  2. Interaction among apoptosis-associated sequence variants and joint effects on aggressive prostate cancer

    Directory of Open Access Journals (Sweden)

    Lavender Nicole A

    2012-04-01

    Full Text Available Abstract Background Molecular and epidemiological evidence demonstrate that altered gene expression and single nucleotide polymorphisms in the apoptotic pathway are linked to many cancers. Yet, few studies emphasize the interaction of variant apoptotic genes and their joint modifying effects on prostate cancer (PCA outcomes. An exhaustive assessment of all the possible two-, three- and four-way gene-gene interactions is computationally burdensome. This statistical conundrum stems from the prohibitive amount of data needed to account for multiple hypothesis testing. Methods To address this issue, we systematically prioritized and evaluated individual effects and complex interactions among 172 apoptotic SNPs in relation to PCA risk and aggressive disease (i.e., Gleason score ≥ 7 and tumor stages III/IV. Single and joint modifying effects on PCA outcomes among European-American men were analyzed using statistical epistasis networks coupled with multi-factor dimensionality reduction (SEN-guided MDR. The case-control study design included 1,175 incident PCA cases and 1,111 controls from the prostate, lung, colo-rectal, and ovarian (PLCO cancer screening trial. Moreover, a subset analysis of PCA cases consisted of 688 aggressive and 488 non-aggressive PCA cases. SNP profiles were obtained using the NCI Cancer Genetic Markers of Susceptibility (CGEMS data portal. Main effects were assessed using logistic regression (LR models. Prior to modeling interactions, SEN was used to pre-process our genetic data. SEN used network science to reduce our analysis from > 36 million to Results Following LR modeling, eleven and thirteen sequence variants were associated with PCA risk and aggressive disease, respectively. However, none of these markers remained significant after we adjusted for multiple comparisons. Nevertheless, we detected a modest synergistic interaction between AKT3 rs2125230-PRKCQ rs571715 and disease aggressiveness using SEN-guided MDR (p = 0

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

    Directory of Open Access Journals (Sweden)

    Linlin Wu

    2015-09-01

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

  4. 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.

  5. The Interactive Association of General Obesity and Central Obesity with Prevalent Hypertension in Rural Lanzhou, China

    Science.gov (United States)

    Wang, Yuhong; Wan, Liping; Wang, Zengwu; Wang, Xin; Di, Zhaoxin; Liu, Xiaoyu

    2016-01-01

    Objective To evaluate the interactive association between obesity with different anthropometry indices and prevalence of hypertension in rural Lanzhou. Methods A cross-sectional survey was conducted in rural Lanzhou from April to July in 2013. The available information of 1275 rural residents aged more than 35 years was collected with a unified questionnaire and their blood pressure and anthropometry indices were measured in the field. The male-to-female ratio was 1:1.1. A generalized estimate equation (GEE) linear model was used to determine the association between obesity with different indexes and hypertension. Results There was a moderate prevalence of general obesity (~11%) and very high prevalence of central obesity (53.2~67%) among the adults of rural Lanzhou. The prevalence of hypertension approximated 28%. GEE linear models showed that obesity with any one of anthropometry indices was associated significantly with the increased prevalence of hypertension among both males and females. In females, general obesity increased the prevalence of hypertension by 37% (0.37, 95%CI: 0.27,0.47) but in males by 23% (0.23, 95%CI: 0.12,0.35). The hypertensive effect of all central obesity was much lower than that of general obesity but approximately comparable to that of overweight. In addition, the interactions of the classified body mass index (BMI) and central obesity showed that when general obesity or overweight coexisted with any one of central obesity, the prevalence of hypertension was increased significantly, and this effect was a little higher than the corresponding main effect of general obesity or overweight in females but was much higher in males. In addition, general obesity or overweight which did not coexist with central obesity was not significantly associated with the increased prevalence of hypertension, nor were the other situations of central obesity in the normal weight or underweight except for the situation of central obesity with waist

  6. 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

    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 to dete...

  7. Physical interaction and association by contiguity in memory for the words and melodies of songs.

    Science.gov (United States)

    Crowder, R G; Serafine, M L; Repp, B

    1990-09-01

    Three experiments were designed to investigate two explanations for the integration effect in memory for songs (Serafine, Crowder, & Repp, 1984; Serafine, Davidson, Crowder, & Repp, 1986). The integration effect is the finding that recognition of the melody (or text) of a song is better in the presence of the text (or melody) with which it had been heard originally than in the presence of a different text (or melody). One explanation for this finding is the physical interaction hypothesis, which holds that one component of a song exerts subtle but memorable physical changes on the other component, making the latter different from what it would be with a different companion. In Experiments 1 and 2, we investigated the influence that words could exert on the subtle musical character of a melody. A second explanation for the integration effect is the association-by-contiguity hypothesis, which holds that any two events experienced in close temporal proximity may become connected in memory such that each acts as a recall cue for the other. In Experiment 3, we investigated the degree to which simultaneous presentations of spoken text with a hummed melody would induce an association between the two components. The results gave encouragement for both explanations and are discussed in terms of the distinction between encoding specificity and independent associative bonding. PMID:2233260

  8. 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.

  9. 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.

  10. 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

    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...... 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...

  11. Local network topology in human protein interaction data predicts functional association.

    Directory of Open Access Journals (Sweden)

    Hua Li

    Full Text Available The use of high-throughput techniques to generate large volumes of protein-protein interaction (PPI data has increased the need for methods that systematically and automatically suggest functional relationships among proteins. In a yeast PPI network, previous work has shown that the local connection topology, particularly for two proteins sharing an unusually large number of neighbors, can predict functional association. In this study we improved the prediction scheme by developing a new algorithm and applied it on a human PPI network to make a genome-wide functional inference. We used the new algorithm to measure and reduce the influence of hub proteins on detecting function-associated protein pairs. We used the annotations of the Gene Ontology (GO and the Kyoto Encyclopedia of Genes and Genomes (KEGG as benchmarks to compare and evaluate the function relevance. The application of our algorithms to human PPI data yielded 4,233 significant functional associations among 1,754 proteins. Further functional comparisons between them allowed us to assign 466 KEGG pathway annotations to 274 proteins and 123 GO annotations to 114 proteins with estimated false discovery rates of <21% for KEGG and <30% for GO. We clustered 1,729 proteins by their functional associations and made functional inferences from detailed analysis on one subcluster highly enriched in the TGF-beta signaling pathway (P<10(-50. Analysis of another four subclusters also suggested potential new players in six signaling pathways worthy of further experimental investigations. Our study gives clear insight into the common neighbor-based prediction scheme and provides a reliable method for large-scale functional annotation in this post-genomic era.

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

    Science.gov (United States)

    Hamaneh, Mehdi Bagheri; Yu, Yi-Kuo

    2014-01-01

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

  13. Huntingtin-associated protein 1 interacts with breakpoint cluster region protein to regulate neuronal differentiation.

    Directory of Open Access Journals (Sweden)

    Pai-Tsang Huang

    Full Text Available Alterations in microtubule-dependent trafficking and certain signaling pathways in neuronal cells represent critical pathogenesis in neurodegenerative diseases. Huntingtin (Htt-associated protein-1 (Hap1 is a brain-enriched protein and plays a key role in the trafficking of neuronal surviving and differentiating cargos. Lack of Hap1 reduces signaling through tropomyosin-related kinases including extracellular signal regulated kinase (ERK, resulting in inhibition of neurite outgrowth, hypothalamic dysfunction and postnatal lethality in mice. To examine how Hap1 is involved in microtubule-dependent trafficking and neuronal differentiation, we performed a proteomic analysis using taxol-precipitated microtubules from Hap1-null and wild-type mouse brains. Breakpoint cluster region protein (Bcr, a Rho GTPase regulator, was identified as a Hap1-interacting partner. Bcr was co-immunoprecipitated with Hap1 from transfected neuro-2a cells and co-localized with Hap1A isoform more in the differentiated than in the nondifferentiated cells. The Bcr downstream effectors, namely ERK and p38, were significantly less activated in Hap1-null than in wild-type mouse hypothalamus. In conclusion, Hap1 interacts with Bcr on microtubules to regulate neuronal differentiation.

  14. An Efficient Low Storage and Memory Treatment of Gridded Interaction Fields for Simulations of Macromolecular Association.

    Science.gov (United States)

    Ozboyaci, Musa; Martinez, Michael; Wade, Rebecca C

    2016-09-13

    Computer simulations of molecular systems often make use of regular rectangular grids with equidistant spacing to store information on their molecular interaction fields, e.g., electrostatic potential. These grids provide an easy way to store the data as they do not require any particular specification of the structure of the data. However, such grids may easily become large, and the storage and memory demands may become so high that calculations become infeasible. To overcome this problem, we show here how the data structure DT-Grid can be adapted and applied to efficiently represent macromolecular interaction grids by exploiting the nonuniformity of information on the grid; at the same time, this data structure ensures fast random data access. We demonstrate use of the DT-Grid data structure for potential of mean force and Brownian dynamics simulations of protein-surface binding and macromolecular association with the SDA software. We further demonstrate that the DT-Grid structure enables systems of large size, such as a viral capsid, and high resolution grids to be handled that are beyond current computational feasibility. PMID:27463233

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

    DEFF Research Database (Denmark)

    Westergaard, David; Li, Jun; Jensen, Kasper;

    2014-01-01

    Background: Epidemiological studies in the recent years have investigated the relationship between dietary habits and disease risk demonstrating that diet has a direct effect on public health. Especially plant-based diets-fruits, vegetables and herbs-are known as a source of molecules with pharma......Background: Epidemiological studies in the recent years have investigated the relationship between dietary habits and disease risk demonstrating that diet has a direct effect on public health. Especially plant-based diets-fruits, vegetables and herbs-are known as a source of molecules......-nutrient interactions. Here, we used colon cancer as a proof-of-concept for understanding key regulatory sites of diet on the disease pathway. Results: We started from a unique vantage point by having a database of 158 plants positively associated to colon cancer reduction and their molecular composition (similar to 3......,500 unique compounds). We generated a comprehensive picture of the interaction profile of these edible and non-edible plants with a predefined candidate colon cancer target space consisting of similar to 1,900 proteins. This knowledge allowed us to study systematically the key components in colon cancer...

  16. Staphylococcus via an interaction with the ELR+ CXC chemokine ENA-78 is associated with BOS.

    Science.gov (United States)

    Gregson, A L; Wang, X; Injean, P; Weigt, S S; Shino, M; Sayah, D; DerHovanessian, A; Lynch, J P; Ross, D J; Saggar, R; Ardehali, A; Li, G; Elashoff, R; Belperio, J A

    2015-03-01

    Staphylococcus aureus is the most commonly isolated gram-positive bacterium after lung transplantation (LT) and has been associated with poor posttransplant outcomes, but its effect on bronchiolitis obliterans syndrome (BOS) and death in the context of the allograft inflammatory environment has not been studied. A three-state Cox semi-Markovian model was used to determine the influence of allograft S. aureus and the ELR+ CXC chemokines on the survival rates and cause-specific hazards for movement from lung transplant (State 1) to BOS (State 2), from transplant (State 1) to death (State 3), and from BOS (State 2) to death (State 3). Acute rejection, pseudomonas pneumonia, bronchoalveolar lavage fluid (BALF) CXCL5 and its interaction with S. aureus all increased the likelihood of transition from transplant to BOS. Transition to death from transplant was facilitated by pseudomonas infection and single lung transplant. Movement from BOS to death was affected by the interaction between aspergillus, pseudomonas and CXCL5, but not S. aureus. S. aureus isolation had state specific effects after LT and only in concert with elevated BALF CXCL5 concentrations did it augment the risk of BOS. Pseudomonas and elevated BALF concentrations of CXCL5 continued as significant risk factors for BOS and death after BOS in lung transplantation.

  17. False Appearance of Gene-Environment Interactions in Genetic Association Studies.

    Science.gov (United States)

    Su, Yi-Shan; Lee, Wen-Chung

    2016-03-01

    Under the assumption of gene-environment independence, unknown/unmeasured environmental factors, irrespective of what they may be, cannot confound the genetic effects. This may lead many people to believe that genetic heterogeneity across different levels of the studied environmental exposure should only mean gene-environment interaction--even though other environmental factors are not adjusted for. However, this is not true if the odds ratio is the effect measure used for quantifying genetic effects. This is because the odds ratio is a "noncollapsible" measure--a marginal odds ratio is not a weighted average of the conditional odds ratios, but instead has a tendency toward the null. In this study, the authors derive formulae for gene-environment interaction bias due to noncollapsibility. They use computer simulation and real data example to show that the bias can be substantial for common diseases. For genetic association study of nonrare diseases, researchers are advised to use collapsible measures, such as risk ratio or peril ratio.

  18. 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.

  19. Superparamagnetic bead interactions with functionalized surfaces characterized by an immunomicroarray

    DEFF Research Database (Denmark)

    Skottrup, Peter Durand; Hansen, Mikkel Fougt; Moresco, Jacob Lange;

    2010-01-01

    Magneto-resistive sensors capable of detecting superparamagnetic micro-/nano-sized beads are promising alternatives to standard diagnostic assays based on absorbance or fluorescence and streptavidin-functionalized beads are widely used as an integral part of these sensors. Here we have developed an...... SiO2 performed better than polyethylene glycol-modified surfaces Two beads, Masterbeads and M-280 beads, were found to give superior results compared with other bead types. Antibody/ antigen interactions, Illustrated by C-reactive protein, were best performed with Masterbeads The results provide...... important information concerning the surface binding properties of streptavidin-functionalized beads and the immunomicroarray can be used when optimizing the performance of bead-based biosensors....

  20. Selective associations produced solely with appetitive contingencies: the stimulus-reinforcer interaction revisited.

    Science.gov (United States)

    Weiss, S J; Panlilio, L V; Schindler, C W

    1993-03-01

    In studies reporting stimulus-reinforcer interactions in traditional conditioning paradigms, when a tone-light compound was associated with food the light gained stimulus control, but when the compound was paired with shock avoidance the tone gained control. However, the physical nature of the reinforcer-related events (food vs. shock) presented in the presence of the tone-light compound was always confounded with the conditioned hedonic value of the compound's presence relative to its absence. When the compound was paired with shock, its presence was negative relative to its absence (which was shock-free). In contrast, when the compound was paired with food, its presence was positive relative to its absence (which was food-free). The present experiment dealt with this confounding effect by conditioning a tone-light compound to be positive or negative, relative to its absence, solely with food reinforcement. One group of rats received food for responding in the presence of the tone-light compound and no food in its absence. The other group also responded in the presence of the compound, but received food only in its absence. These rats were trained on a chained schedule in which responding in the presence of the tone-light compound produced a terminal link signaled by the absence of the compound; responding ceased in the terminal link because it delayed food delivery. In a test session to assess stimulus control by the elements of the compound, tone and light were presented separately under extinction conditions. Rats that had been exposed to a positive correlation between food and the compound emitted almost double the responses in the presence of the light as in the presence of the tone. In comparison, rats that had been exposed to a negative correlation emitted only two thirds as many responses in the presence of the light as in the presence of the tone. Because this selective association was produced using only food, it appears that the contingencies under

  1. Selective associations produced solely with appetitive contingencies: the stimulus-reinforcer interaction revisited.

    Science.gov (United States)

    Weiss, S J; Panlilio, L V; Schindler, C W

    1993-03-01

    In studies reporting stimulus-reinforcer interactions in traditional conditioning paradigms, when a tone-light compound was associated with food the light gained stimulus control, but when the compound was paired with shock avoidance the tone gained control. However, the physical nature of the reinforcer-related events (food vs. shock) presented in the presence of the tone-light compound was always confounded with the conditioned hedonic value of the compound's presence relative to its absence. When the compound was paired with shock, its presence was negative relative to its absence (which was shock-free). In contrast, when the compound was paired with food, its presence was positive relative to its absence (which was food-free). The present experiment dealt with this confounding effect by conditioning a tone-light compound to be positive or negative, relative to its absence, solely with food reinforcement. One group of rats received food for responding in the presence of the tone-light compound and no food in its absence. The other group also responded in the presence of the compound, but received food only in its absence. These rats were trained on a chained schedule in which responding in the presence of the tone-light compound produced a terminal link signaled by the absence of the compound; responding ceased in the terminal link because it delayed food delivery. In a test session to assess stimulus control by the elements of the compound, tone and light were presented separately under extinction conditions. Rats that had been exposed to a positive correlation between food and the compound emitted almost double the responses in the presence of the light as in the presence of the tone. In comparison, rats that had been exposed to a negative correlation emitted only two thirds as many responses in the presence of the light as in the presence of the tone. Because this selective association was produced using only food, it appears that the contingencies under

  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...... interaction between a human operator and an artificial actor or agent. We can apply insights from puppetry to develop culturally-aware robots. Here we describe the development of a robotic marionette theatre wherein robotic controllers assume the role of human puppeteers. The system has been built, tested......, and demonstrated in public settings. We then describe INTERACT, a proposed research project that stages the robotic marionettes in a live performance. The interdisciplinary project brings humanities research to bear on scientific and technological inquiry, and culminates in the development a live performance which...

  3. CD91 interacts with mannan-binding lectin (MBL) through the MBL-associated serine protease-binding site

    DEFF Research Database (Denmark)

    Duus, Karen; Thielens, Nicole M; Lacroix, Monique;

    2010-01-01

    CD91 plays an important role in the scavenging of apoptotic material, possibly through binding to soluble pattern-recognition molecules. In this study, we investigated the interaction of CD91 with mannan-binding lectin (MBL), ficolins and lung surfactant proteins. Both MBL and L-ficolin were found...... to bind CD91. The MBL-CD91 interaction was time- and concentration-dependent and could be inhibited by known ligands of CD91. MBL-associated serine protease 3 (MASP-3) also inhibited binding between MBL and CD91, suggesting that the site of interaction is located at or near the MASP-MBL interaction site....... This was confirmed by using MBL mutants deficient for MASP binding that were unable to interact with CD91. These findings demonstrate that MBL and L-ficolin interact with CD91, strongly suggesting that they have the potential to function as soluble recognition molecules for scavenging microbial and apoptotic...

  4. Interactions

    DEFF Research Database (Denmark)

    The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists such as ......The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists...... also key figures in the philosophical discussions of nature and science - from philosophical tendencies like logical empiricism via critical rationalism to various neo-Kantian trends....

  5. Free energetics of rigid body association of ubiquitin binding domains: a biochemical model for binding mediated by hydrophobic interaction.

    Science.gov (United States)

    Cui, Di; Ou, Shuching; Patel, Sandeep

    2014-07-01

    Weak intermolecular interactions, such as hydrophobic associations, underlie numerous biomolecular recognition processes. Ubiquitin is a small protein that represents a biochemical model for exploring thermodynamic signatures of hydrophobic association as it is widely held that a major component of ubiquitin's binding to numerous partners is mediated by hydrophobic regions on both partners. Here, we use atomistic molecular dynamics simulations in conjunction with the Adaptive Biasing Force sampling method to compute potentials of mean force (the reversible work, or free energy, associated with the binding process) to investigate the thermodynamic signature of complexation in this well-studied biochemical model of hydrophobic association. We observe that much like in the case of a purely hydrophobic solute (i.e., graphene, carbon nanotubes), association is favored by entropic contributions from release of water from the interprotein regions. Moreover, association is disfavored by loss of enthalpic interactions, but unlike in the case of purely hydrophobic solutes, in this case protein-water interactions are lost and not compensated for by additional water-water interactions generated upon release of interprotein and moreso, hydration, water. We further find that relative orientations of the proteins that mutually present hydrophobic regions of each protein to its partner are favored over those that do not. In fact, the free energy minimum as predicted by a force field based method recapitulates the experimental NMR solution structure of the complex.

  6. A neural model of hippocampal-striatal interactions in associative learning and transfer generalization in various neurological and psychiatric patients

    OpenAIRE

    Ahmed A. Moustafa; Keri, Szabolcs; Herzallah, Mohammad M.; Myers, Catherine E.; Gluck, Mark A.

    2010-01-01

    Building on our previous neurocomputational models of basal ganglia and hippocampal-region function (and their modulation by dopamine and acetylcholine, respectively), we show here how an integration of these models can inform our understanding of the interaction between the basal ganglia and hippocampal region in associative learning and transfer generalization across various patient populations. As a common test bed for exploring interactions between these brain regions and neuromodulators,...

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

    Directory of Open Access Journals (Sweden)

    Sara Lindstrom

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

  8. Amplitude internal friction peaks associated with the interaction between dislocation kinks and solute atoms in aluminium

    International Nuclear Information System (INIS)

    Early in 1950, Ke observed in slightly cold-worked dilute aluminium-copper solid solutions a pronounced low-frequency internal friction peak around room temperature as a function of strain amplitude in which the high-amplitude side of the peak decreases rapidly to a very small value. This paper reviews the experimental results since the work of Ke, with emphasis on cold-worked aluminium containing Cu or Mg as substitutional solute atoms. A dislocation kink dragging and break away model is suggested. The latest results show that this internal friction peak around room temperature consists of two separate peaks. The amplitude peak accompanying the lower temperature peak shifts toward lower amplitudes and that accompanying the higher temperature peak shifts toward higher amplitudes with an increase of temperature of measurement. The former amplitude peak appears at an amplitude range lower than that of the former peak. A mechanism of the double amplitude peaks is suggested in terms of the simultaneous occurrence of longitudinal core diffusion (LCD) and transverse core diffusion (TCD) of the solute atoms during the to and fro sidewise motion of the dislocation kinks. Some conclusions concerning the mechanism of Hasiguti peaks are drawn from the comparison with studies on the internal friction peaks associated with the interaction between dislocation kinks and solute atoms. (orig.)

  9. High resolution study of hyperon-nucleon interactions by associated strangeness production in pp collisions

    Energy Technology Data Exchange (ETDEWEB)

    Siebert, R. (Inst. de Physique Nucleaire, 91 Orsay (France)); Didelez, J.P. (Inst. de Physique Nucleaire, 91 Orsay (France)); Frascaria, R. (Inst. de Physique Nucleaire, 91 Orsay (France)); Reposeur, T. (Inst. de Physique Nucleaire, 91 Orsay (France)); Warde, E. (Inst. de Physique Nucleaire, 91 Orsay (France)); Lippert, C. (Inst. fuer Strahlen- und Kernphysik der Univ. Bonn, Bonn (Germany)); Ernst, J. (Inst. fuer Strahlen- und Kernphysik der Univ. Bonn, Bonn (Germany)); Hinterberger, F. (Inst. fuer Strahlen- und Kernphysik der Univ. Bonn, Bonn (Germany)); Mayer-Kuckuk, T. (Inst. fuer Strahlen- und Kernphysik der Univ. Bonn, Bonn (Germany)); Boivin, M. (Lab. National Saturne, 91 Gif-sur-Yvette (France)); Yonnet, J. (Lab. National Saturne, 91 Gif-sur-Yvette (France)); Saghai, B. (DAPNIA-SPhN, CEA Saclay, 91 Gif-sur-Yvette (France)); Grossiord, J.Y. (Inst. de Physique Nucleaire, Univ. Claude Bernard Lyon-1, 69 Villeurbanne (France)); Bovet, E. (Inst. de Physique de l' Univ., N

    1994-01-31

    The associated strangeness production in pp collisions was studied at bombarding energies of 2.3 and 2.7 GeV by detecting the outgoing K[sup +] particles with a high resolution magnetic spectrometer at forward angles up to 23.5 laboratory angle. The kaons were separated from an immense background of protons and pions by a highly resolving TOF electronics in addition to vetoes from Cerenkov detectors utilizing either [beta] differing Cerenkov light cones in lucite or different thresholds for light production in aerogel. The hyperon-nucleon missing mass spectra obtained show strong deviations from pure phase space which is ascribed to final state interactions of the p[Lambda] and the N[Sigma] systems. The structures found are discussed and compared with results from K[sup -]d [yields] [pi][sup -]YN experiments, with theoretical calculations in the frame of OBE models, and with the prediction of sharp strange dibaryon resonances from several quark-bag models. (orig.)

  10. [Fe II] emissions associated with the young interacting binary UY Aurige

    CERN Document Server

    Pyo, Tae-Soo; Beck, Tracy; Davis, Christopher J; Takami, Michihiro

    2014-01-01

    We present high resolution 1.06 -- 1.28 micron spectra toward the interacting binary UY Aur obtained with GEMINI/NIFS and the AO system Altair. We have detected [FeII] $\\lambda$~1.257 micron and [He I] $\\lambda$~1.083 micron lines from both UY Aur A (the primary source) and UY Aur B (the secondary). In [Fe II] UY Aur A drives fast and widely opening outflows with an opening angle of ~ 90 degree along a position angle of ~40 degree, while UY Aur B is associated with a redshifted knot. The blueshifted and redshifted emissions show complicated structure between the primary and secondary. The radial velocities of the [Fe II] emission features are similar for UY Aur A and B: ~ -100 km/s for the blueshifted emission and ~ +130 km/s for the red-shifted component. The [He I] line profile observed toward UY Aur A comprises a central emission feature with deep absorptions at both blueshifted and redshifted velocities. These absorption features may be explained by stellar wind models. The [He I] line profile of UY Aur B...

  11. 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. PMID:27487250

  12. Development of interactive workplace improvement programs in collaboration with trade associations of small-scale industries.

    Science.gov (United States)

    Ito, Akiyoshi; Sakai, Kazuhiro; Kogi, Kazutaka

    2006-01-01

    Serial participatory action programs for reducing occupational safety and health risks were undertaken to know the types of support suited for small-scale industries. Working groups were formed with workplace people and occupational safety and health experts. It was agreed to develop an action-oriented strategy focusing on improving both work environment and productivity by making low-cost improvements through group work. Many workplace improvements achieved by participating enterprises and the group work procedures taken were analyzed. As supporting tools for effectively implementing the workplace improvement action programs, we developed action checklists according to industry and workplace implementation guides. Collections of local good examples also served as part of these support tools. These experiences show that keys to the sustainable action in small-scale industries are: (1) mobilization of the industry-wise network by trade associations, (2) an output-oriented strategy based on interactive group work and (3) the effective use of support tools such as low-cost action checklists and group work methods.

  13. Contact Interactions in Higgs-Vector Boson Associated Production at the ILC

    CERN Document Server

    Cohen, Jonathan; Eilam, Gad

    2016-01-01

    We explore new physics (NP) effects in Higgs-Vector boson associated production at a future International Linear Collider (ILC) via e+e- -> Zh,Zhh, using effective field theory (EFT) techniques. In particular, we focus on a certain class of dimension 6 operators, which are generated by tree-level exchanges of a new heavy vector field in the underlying theory. These operators induce new contact terms of the form \\psi\\psi\\phi D\\phi, involving the Standard Model (SM) fermions (\\psi), gauge-bosons (D is the covariant derivative) and the SM Higgs field (\\phi). We investigate the high-energy behaviour of these new effective interactions in e+e- -> Zh,Zhh, imposing bounds from electroweak precision measurements, and show that the ILC is an excellent testing ground for probing this type of NP via e+e- -> Zh,Zhh. We also address the validity of the EFT expansion and we study the correlation between the hZ and hhZ signals, which can be utilized in future searches for NP in these channels.

  14. Development of interactive workplace improvement programs in collaboration with trade associations of small-scale industries.

    Science.gov (United States)

    Ito, Akiyoshi; Sakai, Kazuhiro; Kogi, Kazutaka

    2006-01-01

    Serial participatory action programs for reducing occupational safety and health risks were undertaken to know the types of support suited for small-scale industries. Working groups were formed with workplace people and occupational safety and health experts. It was agreed to develop an action-oriented strategy focusing on improving both work environment and productivity by making low-cost improvements through group work. Many workplace improvements achieved by participating enterprises and the group work procedures taken were analyzed. As supporting tools for effectively implementing the workplace improvement action programs, we developed action checklists according to industry and workplace implementation guides. Collections of local good examples also served as part of these support tools. These experiences show that keys to the sustainable action in small-scale industries are: (1) mobilization of the industry-wise network by trade associations, (2) an output-oriented strategy based on interactive group work and (3) the effective use of support tools such as low-cost action checklists and group work methods. PMID:16610539

  15. Contact interactions in Higgs-vector boson associated production at the ILC

    Science.gov (United States)

    Cohen, Jonathan; Bar-Shalom, Shaouly; Eilam, Gad

    2016-08-01

    We explore new physics (NP) effects in Higgs-vector boson associated production at a future International Linear Collider (ILC) via e+e-→Z h ,Z h h , using effective field theory (EFT) techniques. In particular, we focus on a certain class of dimension 6 operators, which are generated by tree-level exchanges of a new heavy vector field in the underlying theory. These operators induce new contact terms of the form ψ ψ ϕ D ϕ , involving the Standard Model (SM) fermions (ψ ), gauge-bosons (D is the covariant derivative) and the SM Higgs field (ϕ ). We investigate the high-energy behavior of these new effective interactions in e+e-→Z h ,Z h h , imposing bounds from electroweak precision measurements, and show that the ILC is an excellent testing ground for probing this type of NP via e+e-→Z h ,Z h h . We also address the validity of the EFT expansion and we study the correlation between the h Z and h h Z signals, which can be utilized in future searches for NP in these channels.

  16. Association genetics in Populus reveals the interactions between Pt-miR397a and its target genes

    Science.gov (United States)

    Chen, Jinhui; Chen, Beibei; Yang, Xiaohui; Tian, Jiaxing; Du, Qingzhang; Zhang, Deqiang

    2015-01-01

    Recent studies have revealed associations between single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes and diseases. However, association studies to decipher the interactions between miRNAs and their target genes remain to be conducted. Here, we investigated the association of growth and wood traits with SNPs in Pt-miR397a and its targets, in 261 individuals from a natural population of Populus tomentosa. Of the 57 SNPs identified in Pt-miR397a, three strongly affect its secondary stability, and SNPs in target sites in Pt-LAC20 and Pt-HSP40 changed the binding affinity of Pt-miR397a. Single-SNP association analysis revealed that SNPs in Pt-miR397a significantly associated with α-cellulose content and stem volume, and SNPs in target genes also associated with growth and wood-property traits. Multi-SNP association analysis with additive and dominant models found that SNPs in six potential target genes associated with at least one trait in common with Pt-miR397a, revealing a possible genetic interaction between Pt-miR397a and its targets. Furthermore, epistasis analysis revealed epistatic interactions between SNPs in Pt-miR397a and its target genes. Thus, our study indicated that SNPs in Pt-miR397a and six target genes affect wood formation and that association studies can reveal the interactions between miRNAs and their target genes. PMID:26115173

  17. Housing system and herd size interactions in Norwegian dairy herds; associations with performance and disease incidence

    Directory of Open Access Journals (Sweden)

    Ruud Lars

    2010-02-01

    Full Text Available Abstract Background According to the Norwegian animal welfare regulations, it has been forbidden to build new tie-stall barns since the end of 2004. Previous studies have shown that cow performance and health differ between housing systems. The interaction between housing system and herd size with respect to performance and disease incidence has not been evaluated. Methods Cow performance and health in 620 herds housed in free-stall barns were compared with in 192 herds housed in tie-stall barns based on a mail survey and data from the Norwegian Dairy Herd Recording and Cattle Health Systems. The housing systems herds were comparable with respect to herd size (15-55 cows. Associations between performance/disease incidence and housing system, herd size and year of building the cow barn were tested in general linear models, and values for fixed herd size of 20 and 50 cows were calculated. On the individual cow level mixed models were run to test the effect of among others housing system and herd size on test-day milk yield, and to evaluate lactation curves in different parities. All cows were of the Norwegian Red Breed. Results Average milk production per cow-year was 134 kg lower in free-stall herd than in tie-stall herds, but in the range 27-45 cows there was no significant difference in yields between the herd categories. In herds with less than 27 cows there were increasingly lower yields in free-stalls, particularly in first parity, whereas the yields were increasingly higher in free-stalls with more than 45 cows. In free-stalls fertility was better, calving interval shorter, and the incidence rate of teat injuries, ketosis, indigestions, anoestrus and cystic ovaries was lower than in tie-stalls. All of these factors were more favourable in estimated 50-cow herds as compared to 20-cow herds. In the larger herd category, bulk milk somatic cell counts were higher, and the incidence rate of mastitis (all cases and all diseases was lower

  18. Interactions between Seagrass Complexity, Hydrodynamic Flow and Biomixing Alter Food Availability for Associated Filter-Feeding Organisms

    OpenAIRE

    Vanessa González-Ortiz; Luis G Egea; Rocio Jiménez-Ramos; Francisco Moreno-Marín; José L Pérez-Lloréns; Bouma, Tjeed J.; Brun, Fernando G.

    2014-01-01

    Seagrass shoots interact with hydrodynamic forces and thereby a positively or negatively influence the survival of associated species. The modification of these forces indirectly alters the physical transport and flux of edible particles within seagrass meadows, which will influence the growth and survivorship of associated filter-feeding organisms. The present work contributes to gaining insight into the mechanisms controlling the availability of resources for filter feeders inhabiting seagr...

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

    International Nuclear Information System (INIS)

    The Nopal I uranium (U) deposit, Pena Blanca District, Mexico, largely consists of secondary U6+ 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 18O = -10.8(perthousand), whereas the uraninite within the Pozos conglomerate has a (delta)18O = +1.5(perthousand). If it is assumed that both uraninites precipitated from meteoric water ((delta)18O = -7(perthousand)), 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

  20. Clinical pharmacokinetic drug interactions associated with artemisinin derivatives and HIV-antivirals

    OpenAIRE

    Kiang, Tony K.L.; Kyle J Wilby; Ensom, Mary H H

    2014-01-01

    Management of HIV and malaria co-infection is challenging due to potential drug-drug interactions between antimalarial and HIV-antiviral drugs. Little is known of the clinical significance of these drug interactions, and this review provides a comprehensive summary and critical evaluation of the literature. Specifically, drug interactions between WHO-recommended artemisinin combination therapies (ACT) and HIV-antivirals are discussed. An extensive literature search produced eight articles det...

  1. Literature based drug interaction prediction with clinical assessment using electronic medical records: novel myopathy associated drug interactions.

    Directory of Open Access Journals (Sweden)

    Jon D Duke

    Full Text Available Drug-drug interactions (DDIs are a common cause of adverse drug events. In this paper, we combined a literature discovery approach with analysis of a large electronic medical record database method to predict and evaluate novel DDIs. We predicted an initial set of 13197 potential DDIs based on substrates and inhibitors of cytochrome P450 (CYP metabolism enzymes identified from published in vitro pharmacology experiments. Using a clinical repository of over 800,000 patients, we narrowed this theoretical set of DDIs to 3670 drug pairs actually taken by patients. Finally, we sought to identify novel combinations that synergistically increased the risk of myopathy. Five pairs were identified with their p-values less than 1E-06: loratadine and simvastatin (relative risk or RR = 1.69; loratadine and alprazolam (RR = 1.86; loratadine and duloxetine (RR = 1.94; loratadine and ropinirole (RR = 3.21; and promethazine and tegaserod (RR = 3.00. When taken together, each drug pair showed a significantly increased risk of myopathy when compared to the expected additive myopathy risk from taking either of the drugs alone. Based on additional literature data on in vitro drug metabolism and inhibition potency, loratadine and simvastatin and tegaserod and promethazine were predicted to have a strong DDI through the CYP3A4 and CYP2D6 enzymes, respectively. This new translational biomedical informatics approach supports not only detection of new clinically significant DDI signals, but also evaluation of their potential molecular mechanisms.

  2. Dysregulated neutrophil-endothelial interaction in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides : Implications for pathogenesis and disease intervention

    NARCIS (Netherlands)

    Hu, Nan; Westra, Johanna; Kallenberg, Cees G. M.

    2011-01-01

    The interplay between neutrophils and endothelial cells allows ANCA to become pathogenic and results in uncontrolled inflammation in the vessel wall. This review presents an overall view on neutrophil-endothelial interaction during inflammation with a focus on ANCA-associated vasculitis, and summari

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  4. 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

  5. Interactions between Seagrass Complexity, Hydrodynamic Flow and Biomixing Alter Food Availability for Associated Filter-Feeding Organisms

    NARCIS (Netherlands)

    González-Ortis, V.; Egea, L.G.; Jiménez-Ramos, R.; Moreno-Marín, F.; Pérez-Llorens, J.L.; Bouma , T.J.; Brun, F.G.

    2014-01-01

    Seagrass shoots interact with hydrodynamic forces and thereby a positively or negatively influence the survival of associated species. The modification of these forces indirectly alters the physical transport and flux of edible particles within seagrass meadows, which will influence the growth and s

  6. 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, ptelomere length.

  7. Dynamic changes in host-virus interactions associated with colony founding and social environment in fire ant queens (Solenopsis invicta).

    Science.gov (United States)

    Manfredini, Fabio; Shoemaker, DeWayne; Grozinger, Christina M

    2016-01-01

    The dynamics of host-parasite interactions can change dramatically over the course of a chronic infection as the internal (physiological) and external (environmental) conditions of the host change. When queens of social insects found a colony, they experience changes in both their physiological state (they develop their ovaries and begin laying eggs) and the social environment (they suddenly stop interacting with the other members of the mother colony), making this an excellent model system for examining how these factors interact with chronic infections. We investigated the dynamics of host-viral interactions in queens of Solenopsis invicta (fire ant) as they transition from mating to colony founding/brood rearing to the emergence of the first workers. We examined these dynamics in naturally infected queens in two different social environments, where queens either founded colonies as individuals or as pairs. We hypothesized that stress associated with colony founding plays an important role in the dynamics of host-parasite interactions. We also hypothesized that different viruses have different modalities of interaction with the host that can be quantified by physiological measures and genomic analysis of gene expression in the host. We found that the two most prevalent viruses, SINV-1 and SINV-2, are associated with different fitness costs that are mirrored by different patterns of gene expression in the host. In fact SINV-2, the virus that imposes the significant reduction of a queen's reproductive output is also associated with larger changes of global gene expression in the host. These results show the complexity of interactions between S. invicta and two viral parasites. Our findings also show that chronic infections by viral parasites in insects are dynamic processes that may pose different challenges in the host, laying the groundwork for interesting ecological and evolutionary considerations. PMID:26811788

  8. 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.

  9. 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. PMID:25367005

  10. Reasons and strategies associated with positive interaction between work and home amongst managers: An exploratory study

    Directory of Open Access Journals (Sweden)

    Janet Oosthuizen

    2010-03-01

    Full Text Available Orientation: In order to facilitate positive interaction between work and home, it is necessary to understand the reasons for and strategies used by managerial employees to manage this interaction.Research purpose: The objectives of this study were to determine, (1 reasons why employees experience high or low positive work–home interaction and (2 strategies that employees with high and low positive interaction use.Motivation for the study: Positive interaction between work and home, particularly in managerial employees, is becoming increasingly more important with a view to ensuring a stable and healthy work–home life.Research design, approach and method: A random clustered sample (n = 275 was taken from managerial employees in a multinational organisation and the Survey Work–Home Interaction-Nijmegen (SWING was administered to identify participants with high and low positive interaction between work and home respectively. Thereafter, exploratory qualitative interviews were conducted with selected participants (n = 32 to deduce themes for the above-mentioned objectives. Content analysis was used to analyse, quantify and interpret the research data.Main findings: Reasons for high or low positive interaction were identified in conjunction with previous research. Ten successful strategies for positive interaction between work and home were identified and reported.Managerial/practical implications: Organisational recommendations made include changing the organisational culture to being more supportive, developing employees for future positions and creating social networks. In addition, individual strategies and recommendations for future research are identified.Contribution/value-add: This study contributes to the limited research on strategies for positive interaction between work and home among managerial employees.

  11. Genetic Interactions Explain Variance in Cingulate Amyloid Burden: An AV-45 PET Genome-Wide Association and Interaction Study in the ADNI Cohort

    Directory of Open Access Journals (Sweden)

    Jin Li

    2015-01-01

    Full Text Available Alzheimer’s disease (AD is the most common neurodegenerative disorder. Using discrete disease status as the phenotype and computing statistics at the single marker level may not be able to address the underlying biological interactions that contribute to disease mechanism and may contribute to the issue of “missing heritability.” We performed a genome-wide association study (GWAS and a genome-wide interaction study (GWIS of an amyloid imaging phenotype, using the data from Alzheimer’s Disease Neuroimaging Initiative. We investigated the genetic main effects and interaction effects on cingulate amyloid-beta (Aβ load in an effort to better understand the genetic etiology of Aβ deposition that is a widely studied AD biomarker. PLINK was used in the single marker GWAS, and INTERSNP was used to perform the two-marker GWIS, focusing only on SNPs with p≤0.01 for the GWAS analysis. Age, sex, and diagnosis were used as covariates in both analyses. Corrected p values using the Bonferroni method were reported. The GWAS analysis revealed significant hits within or proximal to APOE, APOC1, and TOMM40 genes, which were previously implicated in AD. The GWIS analysis yielded 8 novel SNP-SNP interaction findings that warrant replication and further investigation.

  12. Association of interacting genes in the toll-like receptor signaling pathway and the antibody response to pertussis vaccination.

    Directory of Open Access Journals (Sweden)

    Tjeerd G Kimman

    Full Text Available BACKGROUND: Activation of the Toll-like receptor (TLR signaling pathway through TLR4 may be important in the induction of protective immunity against Bordetella pertussis with TLR4-mediated activation of dendritic and B cells, induction of cytokine expression, and reversal of tolerance as crucial steps. We examined whether single nucleotide polymorphisms (SNPs in genes of the TLR4 pathway and their interaction are associated with the response to whole-cell vaccine (WCV pertussis vaccination in 490 one-year-old children. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed associations of 75 haplotype-tagging SNPs in genes in the TLR4 signaling pathway with pertussis toxin (PT-IgG titers. We found significant associations between the PT-IgG titer and SNPs in CD14, TLR4, TOLLIP, TIRAP, IRAK3, IRAK4, TICAM1, and TNFRSF4 in one or more of the analyses. The strongest evidence for association was found for two SNPs (rs5744034 and rs5743894 in TOLLIP that were almost completely in linkage disequilibrium, provided statistically significant associations in all tests with the lowest p-values, and displayed a dominant mode of inheritance. However, none of these single gene associations would withstand correction for multiple testing. In addition, Multifactor Dimensionality Reduction Analysis, an approach that does not need correction for multiple testing, showed significant and strong two and three locus interactions between SNPs in TOLLIP (rs4963060, TLR4 (rs6478317 and IRAK1 (rs1059703. CONCLUSIONS/SIGNIFICANCE: We have identified significant interactions between genes in the TLR pathway in the induction of vaccine-induced immunity. These interactions underline that these genes are functionally related and together form a true biological relationship in a protein-protein interaction network. Practically all our findings may be explained by genetic variation in directly or indirectly interacting proteins at the extra- and intracytoplasmic sites of the cell

  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. PMID:23015784

  14. Brain regions associated with the acquisition of conditioned place preference for cocaine versus social interaction

    Directory of Open Access Journals (Sweden)

    Rana eEl Rawas

    2012-09-01

    Full Text Available 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.

  15. 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

  16. 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. PMID:24356376

  17. The Potato Sucrose Transporter StSUT1 Interacts with a DRM-Associated Protein Disulfide Isomerase

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Environmental conditions, dispersal lags, and interactions among species are major factors structuring communities through time and across space. Ecologists have emphasized the importance of biotic interactions in determining local patterns of species association. In contrast, abiotic limits...... with significant patterns of taxon association. Most taxon pairs that exhibited co-occurrence patterns indicative of biotic interactions at one time did not exhibit significant associations at other times. Evidence for environmental filtering and dispersal limitation was weakest for aggregated pairs between 16...

  19. TP53 regulates miRNA association with AGO2 to remodel the miRNA-mRNA interaction network.

    Science.gov (United States)

    Krell, Jonathan; Stebbing, Justin; Carissimi, Claudia; Dabrowska, Aleksandra F; de Giorgio, Alexander; Frampton, Adam E; Harding, Victoria; Fulci, Valerio; Macino, Giuseppe; Colombo, Teresa; Castellano, Leandro

    2016-03-01

    DNA damage activates TP53-regulated surveillance mechanisms that are crucial in suppressing tumorigenesis. TP53 orchestrates these responses directly by transcriptionally modulating genes, including microRNAs (miRNAs), and by regulating miRNA biogenesis through interacting with the DROSHA complex. However, whether the association between miRNAs and AGO2 is regulated following DNA damage is not yet known. Here, we show that, following DNA damage, TP53 interacts with AGO2 to induce or reduce AGO2's association of a subset of miRNAs, including multiple let-7 family members. Furthermore, we show that specific mutations in TP53 decrease rather than increase the association of let-7 family miRNAs, reducing their activity without preventing TP53 from interacting with AGO2. This is consistent with the oncogenic properties of these mutants. Using AGO2 RIP-seq and PAR-CLIP-seq, we show that the DNA damage-induced increase in binding of let-7 family members to the RISC complex is functional. We unambiguously determine the global miRNA-mRNA interaction networks involved in the DNA damage response, validating them through the identification of miRNA-target chimeras formed by endogenous ligation reactions. We find that the target complementary region of the let-7 seed tends to have highly fixed positions and more variable ones. Additionally, we observe that miRNAs, whose cellular abundance or differential association with AGO2 is regulated by TP53, are involved in an intricate network of regulatory feedback and feedforward circuits. TP53-mediated regulation of AGO2-miRNA interaction represents a new mechanism of miRNA regulation in carcinogenesis. PMID:26701625

  20. MegaSNPHunter: a learning approach to detect disease predisposition SNPs and high level interactions in genome wide association study

    Directory of Open Access Journals (Sweden)

    Xue Hong

    2009-01-01

    Full Text Available Abstract Background The interactions of multiple single nucleotide polymorphisms (SNPs are highly hypothesized to affect an individual's susceptibility to complex diseases. Although many works have been done to identify and quantify the importance of multi-SNP interactions, few of them could handle the genome wide data due to the combinatorial explosive search space and the difficulty to statistically evaluate the high-order interactions given limited samples. Results Three comparative experiments are designed to evaluate the performance of MegaSNPHunter. The first experiment uses synthetic data generated on the basis of epistasis models. The second one uses a genome wide study on Parkinson disease (data acquired by using Illumina HumanHap300 SNP chips. The third one chooses the rheumatoid arthritis study from Wellcome Trust Case Control Consortium (WTCCC using Affymetrix GeneChip 500K Mapping Array Set. MegaSNPHunter outperforms the best solution in this area and reports many potential interactions for the two real studies. Conclusion The experimental results on both synthetic data and two real data sets demonstrate that our proposed approach outperforms the best solution that is currently available in handling large-scale SNP data both in terms of speed and in terms of detection of potential interactions that were not identified before. To our knowledge, MegaSNPHunter is the first approach that is capable of identifying the disease-associated SNP interactions from WTCCC studies and is promising for practical disease prognosis.

  1. A review on protein-protein interaction network of APE1/Ref-1 and its associated biological functions.

    Science.gov (United States)

    Thakur, S; Dhiman, M; Tell, G; Mantha, A K

    2015-04-01

    Apurinic/apyrimidinic endonuclease 1 (APE1) is a classic example of functionally variable protein. Besides its well-known role in (i) DNA repair of oxidative base damage, APE1 also plays a critical role in (ii) redox regulation of transcription factors controlling gene expression for cell survival pathways, for which it is also known as redox effector factor 1 (Ref-1), and recent evidences advocates for (iii) coordinated control of other non-canonical protein-protein interaction(s) responsible for significant biological functions in mammalian cells. The diverse functions of APE1 can be ascribed to its ability to interact with different protein partners, owing to the attainment of unfolded domains during evolution. Association of dysregulation of APE1 with various human pathologies, such as cancer, cardiovascular diseases and neurodegeneration, is attributable to its multifunctional nature, and this makes APE1 a potential therapeutic target. This review covers the important aspects of APE1 in terms of its significant protein-protein interaction(s), and this knowledge is required to understand the onset and development of human pathologies and to design or improve the strategies to target such interactions for treatment and management of various human diseases.

  2. 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.

  3. Association Between FTO Variant and Change in Body Weight and Its Interaction With Dietary Factors

    DEFF Research Database (Denmark)

    Vimaleswaran, Karani S; Angquist, 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....... and only observed for extreme gain. Dietary factors did not influence the associations.......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.......8 years follow-up in a large-scale prospective study and examined whether these associations were modified by dietary energy percentage from fat, protein, carbohydrate, or glycemic index (GI). This study comprised data from five countries of European Prospective Investigation into Cancer and Nutrition...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    GPCR desensitization and down-regulation are considered key molecular events underlying the development of tolerance in vivo. Among the many regulatory proteins that are involved in these complex processes, GASP-1 have been shown to participate to the sorting of several receptors toward the degra......GPCR desensitization and down-regulation are considered key molecular events underlying the development of tolerance in vivo. Among the many regulatory proteins that are involved in these complex processes, GASP-1 have been shown to participate to the sorting of several receptors toward...... the degradation pathway. This protein belongs to the recently identified GPCR-associated sorting proteins (GASPs) family that comprises ten members for which structural and functional details are poorly documented. We present here a detailed structure-function relationship analysis of the molecular interaction...... between GASPs and a panel of GPCRs. In a first step, GST-pull down experiments revealed that all the tested GASPs display significant interactions with a wide range of GPCRs. Importantly, the different GASP members exhibiting the strongest interaction properties were also characterized by the presence...

  5. 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

    Micellar Concentration is rather. improbable. The influence of the water dissolved in the-toluene has been studied but the difficulties in keeping the water concentration low hinder the discussion of the results. The calorimetry data have been treated with a simple dimer dissociation model and compared...... not associate or the dilution effect does not break the aggregates. The fluorescence spectroscopy results support the results of calorimetry with respect to the self-association at low concentrations. ITC has been applied for the first time to the study of the interaction between asphaltenes and a model resin...

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

    Directory of Open Access Journals (Sweden)

    Angel Mozo-Villarías

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

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

    Science.gov (United States)

    Mozo-Villarías, Angel; Cedano, Juan; Querol, Enrique

    2014-01-01

    The propensity of many proteins to oligomerize and associate to form complex structures from their constituent monomers, is analyzed in terms of their hydrophobic (H), and electric pseudo-dipole (D) moment vectors. In both cases these vectors are defined as the product of the distance between their positive and negative centroids, times the total hydrophobicity or total positive charge of the protein. Changes in the magnitudes and directions of H and D are studied as monomers associate to form larger complexes. We use these descriptors to study similarities and differences in two groups of associations: a) open associations such as polymers with an undefined number of monomers (i.e. actin polymerization, amyloid and HIV capsid assemblies); b) closed symmetrical associations of finite size, like spherical virus capsids and protein cages. The tendency of the hydrophobic moments of the monomers in an association is to align in parallel arrangements following a pattern similar to those of phospholipids in a membrane. Conversely, electric dipole moments of monomers tend to align in antiparallel associations. The final conformation of a given assembly is a fine-tuned combination of these forces, limited by steric constraints. This determines whether the association will be open (indetermined number of monomers) or closed (fixed number of monomers). Any kinetic, binding or molecular peculiarities that characterize a protein assembly, comply with the vector rules laid down in this paper. These findings are also independent of protein size and shape. PMID:25329830

  8. Using yeast two-hybrid system to identify ECRG2 associated proteins and their possible interactions with ECRG2 gene

    Institute of Scientific and Technical Information of China (English)

    Yong-Ping Cui; Jian-Bo Wang; Xin-Yu Zhang; Mei-Xia Bi; Li-Ping Guo; Shih-Hsin Lu

    2003-01-01

    AIM: To identify esophageal cancer related gene2 (ECRG2)associated proteins and their possible interactions withECRG2 gene.METHODS: In the yeast forward two-hybrid system, ECRG2was fused with the DNA-binding domain (DBD) of Gal4 andhuman fetal liver cDNA library was fused with thetranscriptional activation domain (AD) of Gal4. We performeda high-stringency scale procedure to screen ECRG2 againsthuman fetal liver cDNA library and characterized positivesby sequence analysis.RESULTS: We found the following 9 putatively associatedproteins. They were metallothionein2A, metallothionein1H,metallothionein1G, ferritin, erythrocyte membrane proteinband4.2, mitochondrial ribosomal protein S12, hypotheticalprotein FLJ10101, and a novel gene whose cDNA was foundto have no strong homology to any other previouslycharacterized gene whose DDBJ/EMBL/GenBank accessionnumber is AF422192 mapped to human chromosome 14q31.CONCLUSION: MT, a potential interaction partner forECRG2, might be involved in the regulation of cellproliferation and apoptosis, and in various physiologicalprocesses. Determination of a reliability score for each singleprotein-protein interaction, especially interaction of ECRG2and MT, permits the assignment of ECRG2 and unannotatedproteins to biological pathways. A further understanding ofthe association between ECRG2 and MT should facilitate the functions of ECRG2 gene.

  9. Interactive and Multimedia Contents Associated with a System for Computer-Aided Assessment

    Science.gov (United States)

    Paiva, Rui C.; Ferreira, Milton S.; Mendes, Ana G.; Eusébio, Augusto M. J.

    2015-01-01

    This article presents a research study addressing the development, implementation, evaluation, and use of Interactive Modules for Online Training (MITO) of mathematics in higher education. This work was carried out in the context of the MITO project, which combined several features of the learning and management system Moodle, the computer-aided…

  10. Are Some Parents' Interaction Styles Associated with Richer Grammatical Input?

    Science.gov (United States)

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

    2013-01-01

    Purpose: Evidence for tense marking in child-directed speech varies both across languages (Guasti, 2002; Legate & Yang, 2007) and across speakers of a single language (Hadley, Rispoli, Fitzgerald, & Bahnsen, 2011). The purpose of this study was to understand how parent interaction styles and register use overlap with the tense-marking…

  11. 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…

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

    Science.gov (United States)

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

    2016-04-01

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

  13. Interaction between obesity-related genes, FTO and MC4R, associated to an increase of breast cancer risk.

    Science.gov (United States)

    da Cunha, Patrícia Amorim; de Carlos Back, Lia Kubelka; Sereia, Aline Fernanda Rodrigues; Kubelka, Clara; Ribeiro, Maria Cecíia Menks; Fernandes, Bráulio Leal; de Souza, Ilíada Rainha

    2013-12-01

    Breast cancer (BC) is a complex disease and obesity is a well-known risk factor for its development, especially after menopause. Several studies have shown Single Nucleotide Polymorphisms (SNPs) linked to overweight and obesity, such as: rs1121980 (T/C) and rs9939609 (A/T) in Fat Mass and Obesity Associated gene (FTO) and rs17782313 (T/C) in Melanocortin 4 Receptor gene (MC4R). Thus, we aimed to investigate the association between these obesity-related SNPs and BC risk. One hundred BC patients and 148 healthy women from Santa Catarina, Brazil entered the study. SNPs were genotyped using Taqman assays. For statistical analyses SNPStats and SPSS softwares were used. Association analyses were performed by logistic regression and were adjusted for age and Body mass index (BMI). Multiple SNPs inheritance models (log-additive, dominant, recessive, codominant) were performed to determine odds ratios (ORs), assuming 95 % confidence interval (CI) and P value = 0.05 as the significance limit. When analyzed alone, FTO rs1121980 and rs9939609 did not show significant associations with BC development, however MC4R rs17782313 showed increased risk for BC even after adjustments (P-value = 0.032). Interestingly, the interaction of FTO and MC4R polymorphisms showed a powerful association with BC. We observed a 4.59-fold increased risk for woman who have the allele combination C/T/C (FTO rs1121980/FTO rs9939609/MC4R rs17782313) (P-value = 0.0011, adjusted for age and BMI). We found important and unpublished associations between these obesity-related genes and BC risk. These associations seem to be independent of their effect on BMI, indicating a direct role of the interaction between FTO and MC4R polymorphisms in BC development.

  14. Networking and interaction between a Mutual Assistance Association and other agencies (Pamplona, 1902–1919

    Directory of Open Access Journals (Sweden)

    Pilar Leon Sanz

    2009-12-01

    Full Text Available Between 1902-1919, the most important Mutual Assistance Association in the northern Spanish region of Navarre was “The Catholic Workers Protection Society La Conciliación” a private, mixed association which integrated -until 1919- employers, employees and protectors members. Its primary activities involved medical-pharmaceutical assistance, financial aid to the ill and labour mediation. La Conciliación was presided by people who were influential in the political and social life of the city, a fact which allowed the representatives of this association to belong to the Commissions set up by the city council and the regional government. Aiming to solve sanitary and social problems, it was also in contact with other government agencies and other Mutual Assistance Associations both in Spain and abroad. The article analyses the relations and the networks established by this institution, using its archives and the press, where the activities of La Conciliación were widely reflected.

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

    Science.gov (United States)

    Kieft, Thomas L.; Simmons, Karen A.

    2015-01-01

    Animals live in close association with microorganisms, mostly prokaryotes, living in or on them as commensals, mutualists or parasites, and profoundly affecting host fitness. Most animal–microbe studies focus on microbial community structure; for this project, allometry (scaling of animal attributes with animal size) was applied to animal–microbe relationships across a range of species spanning 12 orders of magnitude in animal mass, from nematodes to whales. Microbial abundances per individual animal were gleaned from published literature and also microscopically counted in three species. Abundance of prokaryotes/individual versus animal mass scales as a nearly linear power function (exponent = 1.07, R2 = 0.94). Combining this power function with allometry of animal abundance indicates that macrofauna have an outsized share of animal-associated microorganisms. The total number of animal-associated prokaryotes in Earth's land animals was calculated to be 1.3–1.4 × 1025 cells and the total of marine animal-associated microbes was calculated to be 8.6–9.0 × 1024 cells. Animal-associated microbes thus total 2.1–2.3 × 1025 of the approximately 1030 prokaryotes on the Earth. Microbes associated with humans comprise 3.3–3.5% of Earth's animal-associated microbes, and domestic animals harbour 14–20% of all animal-associated microbes, adding a new dimension to the scale of human impact on the biosphere. This novel allometric power function may reflect underlying mechanisms involving the transfer of energy and materials between microorganisms and their animal hosts. Microbial diversity indices of animal gut communities and gut microbial species richness for 60 mammals did not indicate significant scaling relationships with animal body mass; however, further research in this area is warranted. PMID:26108631

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

    Science.gov (United States)

    Kieft, Thomas L; Simmons, Karen A

    2015-07-01

    Animals live in close association with microorganisms, mostly prokaryotes, living in or on them as commensals, mutualists or parasites, and profoundly affecting host fitness. Most animal-microbe studies focus on microbial community structure; for this project, allometry (scaling of animal attributes with animal size) was applied to animal-microbe relationships across a range of species spanning 12 orders of magnitude in animal mass, from nematodes to whales. Microbial abundances per individual animal were gleaned from published literature and also microscopically counted in three species. Abundance of prokaryotes/individual versus animal mass scales as a nearly linear power function (exponent = 1.07, R(2) = 0.94). Combining this power function with allometry of animal abundance indicates that macrofauna have an outsized share of animal-associated microorganisms. The total number of animal-associated prokaryotes in Earth's land animals was calculated to be 1.3-1.4 × 10(25) cells and the total of marine animal-associated microbes was calculated to be 8.6-9.0 × 10(24) cells. Animal-associated microbes thus total 2.1-2.3 × 10(25) of the approximately 10(30) prokaryotes on the Earth. Microbes associated with humans comprise 3.3-3.5% of Earth's animal-associated microbes, and domestic animals harbour 14-20% of all animal-associated microbes, adding a new dimension to the scale of human impact on the biosphere. This novel allometric power function may reflect underlying mechanisms involving the transfer of energy and materials between microorganisms and their animal hosts. Microbial diversity indices of animal gut communities and gut microbial species richness for 60 mammals did not indicate significant scaling relationships with animal body mass; however, further research in this area is warranted. PMID:26108631

  17. 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

    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...... association. Our results suggest a general model of large ARF-GEF function in which regulated changes in protein conformation control membrane association of the exchange factor and, thus, activation of ARFs....

  18. BDNF Val66Met is Associated with Introversion and Interacts with 5-HTTLPR to Influence Neuroticism

    OpenAIRE

    Terracciano, Antonio; Tanaka, Toshiko; Sutin, Angelina R.; Deiana, Barbara; Balaci, Lenuta; Sanna, Serena; Olla, Nazario; Maschio, Andrea; Uda, Manuela; Ferrucci, Luigi; Schlessinger, David; Costa, Paul T.

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) regulates synaptic plasticity and neurotransmission, and has been linked to neuroticism, a major risk factor for psychiatric disorders. A recent genome-wide association (GWA) scan, however, found the BDNF Val66Met polymorphism (rs6265) associated with extraversion but not with neuroticism. In this study, we examine the links between BDNF and personality traits, assessed using the Revised NEO Personality Inventory (NEO-PI-R), in a sample from SardiNIA (...

  19. Identification of Significant Association and Gene-Gene Interaction of GABA Receptor Subunit Genes in Autism

    OpenAIRE

    Ma, D Q; Whitehead, P. L.; Menold, M M; Martin, E. R.; Ashley-Koch, A. E.; Mei, H; Ritchie, M. D.; Delong, G R; Abramson, R.K.; Wright, H. H.; Cuccaro, M. L.; Hussman, J. P.; Gilbert, J.R.; Pericak-Vance, M A

    2005-01-01

    Autism is a common neurodevelopmental disorder with a significant genetic component. Existing research suggests that multiple genes contribute to autism and that epigenetic effects or gene-gene interactions are likely contributors to autism risk. However, these effects have not yet been identified. Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, has been implicated in autism etiology. Fourteen known autosomal GABA receptor subunit genes were studied...

  20. Drug interactions associated with methadone, buprenorphine, cocaine, and HIV medications: implications for pregnant women

    OpenAIRE

    McCance-Katz, Elinore F.

    2010-01-01

    Pregnancy in substance-abusing women with HIV/AIDS presents a complex clinical challenge. Opioid-dependent women need treatment with opioid therapy during pregnancy to protect the health of mother and developing fetus. However, opioid therapies, methadone and buprenorphine, may have drug interactions with some HIV medications that can have adverse effects leading to suboptimal clinical outcomes. Further, many opioid-dependent individuals have problems with other forms of substance abuse, for ...

  1. Interaction of Bovine Papillomavirus E2 Protein with Brd4 Stabilizes Its Association with Chromatin

    OpenAIRE

    McPhillips, Maria G.; Ozato, Keiko; Alison A McBride

    2005-01-01

    The bovine papillomavirus E2 protein maintains and segregates the viral extrachromosomal genomes by tethering them to cellular mitotic chromosomes. E2 interacts with a cellular bromodomain protein, Brd4, to mediate the segregation of viral genomes into daughter cells. Brd4 binds acetylated histones and has been observed to diffusely coat mitotic chromosomes in several cell types. In this study, we show that in mitotic C127 cells, Brd4 diffusely coated the condensed chromosomes. However, in th...

  2. General environment for human interaction with a robot hand-arm system and associate elements

    OpenAIRE

    Fortín, José; Suárez Feijóo, Raúl

    2010-01-01

    Software development in robotics is a complex task due to the existing heterogeneity in terms of hardware, communications, and programming languages that are used in current robotic systems. In this work a general environment for the interaction between the human operator and different elements in a robotized cell is presented, such that all the involved elements can be easily managed from a unique interface. The aim of the developments is to provide a common frame that can be ported to...

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

    Directory of Open Access Journals (Sweden)

    Debasree Sarkar

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

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

    Science.gov (United States)

    Sarkar, Debasree; Patra, Piya; Ghosh, Abhirupa; Saha, Sudipto

    2016-01-01

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

  5. Mammalian splicing factor SF1 interacts with SURP domains of U2 snRNP-associated proteins.

    Science.gov (United States)

    Crisci, Angela; Raleff, Flore; Bagdiul, Ivona; Raabe, Monika; Urlaub, Henning; Rain, Jean-Christophe; Krämer, Angela

    2015-12-01

    Splicing factor 1 (SF1) recognizes the branch point sequence (BPS) at the 3' splice site during the formation of early complex E, thereby pre-bulging the BPS adenosine, thought to facilitate subsequent base-pairing of the U2 snRNA with the BPS. The 65-kDa subunit of U2 snRNP auxiliary factor (U2AF65) interacts with SF1 and was shown to recruit the U2 snRNP to the spliceosome. Co-immunoprecipitation experiments of SF1-interacting proteins from HeLa cell extracts shown here are consistent with the presence of SF1 in early splicing complexes. Surprisingly almost all U2 snRNP proteins were found associated with SF1. Yeast two-hybrid screens identified two SURP domain-containing U2 snRNP proteins as partners of SF1. A short, evolutionarily conserved region of SF1 interacts with the SURP domains, stressing their role in protein-protein interactions. A reduction of A complex formation in SF1-depleted extracts could be rescued with recombinant SF1 containing the SURP-interaction domain, but only partial rescue was observed with SF1 lacking this sequence. Thus, SF1 can initially recruit the U2 snRNP to the spliceosome during E complex formation, whereas U2AF65 may stabilize the association of the U2 snRNP with the spliceosome at later times. In addition, these findings may have implications for alternative splicing decisions. PMID:26420826

  6. 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/.

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

    International Nuclear Information System (INIS)

    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

  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. 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.

  10. Interactions of Genetic Variants with Physical Activity are Associated with Blood Pressure in Chinese: The GenSalt Study

    Science.gov (United States)

    Montasser, May E.; Gu, Donfeng; Chen, Jing; Shimmin, Lawrence C.; Gu, Charles; Kelly, Tanika N.; Jaquish, Cashell E.; Rice, Treva; Rao, DC; Cao, Jie; Chen, Jichun; Liu, De-pei; Whelton, Paul; He, Jiang; Hixson, James E.

    2016-01-01

    Background Blood pressure (BP) homeostasis involves complex interactions among genetic and non-genetic factors, providing major challenges to dissection of the genetic components that influence BP and hypertension. In this study, we examine the effects of interaction of genetic variants with physical activity on BP in a relatively genetically homogenous cohort of rural Chinese villagers. Methods Generalized estimating equations analysis was used to test for associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with variants in 24 genes in BP pathways (196 SNPs) among 3,142 Chinese participants divided according to physical activity (active versus inactive groups). Results In the physically active group, 2 SNPs in NR3C2 were significantly associated with lower SBP, and a SNP in SCNN1B was significantly associated with lower SBP and DBP. In the physically inactive group, a SNP in APLNR was associated with lower SBP, a SNP in GNB3 was associated with higher SBP and DBP, and a SNP in BDKRB2 was associated with lower DBP. Cumulative effects in carriers of minor alleles of these SNPs showed reductions of SBP and DBP as large as 8 and 5 mmHg, respectively, in the active individuals compared to inactive individuals carrying the same number of minor alleles. Conclusions We found that physical activity modifies the effects of genetic variants on BP. However, our results also show that active individuals with specific genotypes always have lower BP than inactive individuals with the same genotypes, demonstrating the overall beneficial effects of physical activity on blood pressure. PMID:21654856

  11. Association and interaction analyses of eight genes under asthma linkage peaks

    DEFF Research Database (Denmark)

    Ferreira, M.A.R.; Zhao, Z.Z.; Thomsen, S.F.;

    2009-01-01

    Background: Linkage studies have implicated the 2q33, 9p21, 11q13 and 20q13 regions in the regulation of allergic disease. The aim of this study was to test genetic variants in candidate genes from these regions for association with specific asthma traits. Methods: Ninety-five single nucleotide...... polymorphisms (SNP) located in eight genes (CD28, CTLA4, ICOS, ADAM23, ADAMTSL1, MS4A2, CDH26 and HRH3) were genotyped in > 5000 individuals from Australian (n = 1162), Dutch (n = 99) and Danish (n = 303) families. Traits tested included doctor-diagnosed asthma, atopy, airway obstruction, total serum...... immunoglobulin (Ig) E levels and eosinophilia. Association was tested using both multivariate and univariate methods, with gene-wide thresholds for significance determined through simulation. Gene-by-gene and gene-by-environment analyses were also performed. Results: There was no overall evidence for association...

  12. Association mapping for epistasis and environmental interaction of yield traits in 323 cotton cultivars under 9 different environments.

    Directory of Open Access Journals (Sweden)

    Yinhua Jia

    Full Text Available Improving yield is a major objective for cotton breeding schemes, and lint yield and its three component traits (boll number, boll weight and lint percentage are complex traits controlled by multiple genes and various environments. Association mapping was performed to detect markers associated with these four traits using 651 simple sequence repeats (SSRs. A mixed linear model including epistasis and environmental interaction was used to screen the loci associated with these four yield traits by 323 accessions of Gossypium hirsutum L. evaluated in nine different environments. 251 significant loci were detected to be associated with lint yield and its three components, including 69 loci with individual effects and all involved in epistasis interactions. These significant loci explain ∼ 62.05% of the phenotypic variance (ranging from 49.06% ∼ 72.29% for these four traits. It was indicated by high contribution of environmental interaction to the phenotypic variance for lint yield and boll numbers, that genetic effects of SSR loci were susceptible to environment factors. Shared loci were also observed among these four traits, which may be used for simultaneous improvement in cotton breeding for yield traits. Furthermore, consistent and elite loci were screened with -Log10 (P-value >8.0 based on predicted effects of loci detected in different environments. There was one locus and 6 pairs of epistasis for lint yield, 4 loci and 10 epistasis for boll number, 15 loci and 2 epistasis for boll weight, and 2 loci and 5 epistasis for lint percentage, respectively. These results provided insights into the genetic basis of lint yield and its components and may be useful for marker-assisted breeding to improve cotton production.

  13. Association Mapping for Epistasis and Environmental Interaction of Yield Traits in 323 Cotton Cultivars under 9 Different Environments

    Science.gov (United States)

    Pan, Zhaoe; Wang, Xiwen; He, Shoupu; Xiao, Songhua; Shi, Weijun; Zhou, Zhongli; Pang, Baoyin; Wang, Liru; Liu, Jianguang; Ma, Jun; Du, Xiongming; Zhu, Jun

    2014-01-01

    Improving yield is a major objective for cotton breeding schemes, and lint yield and its three component traits (boll number, boll weight and lint percentage) are complex traits controlled by multiple genes and various environments. Association mapping was performed to detect markers associated with these four traits using 651 simple sequence repeats (SSRs). A mixed linear model including epistasis and environmental interaction was used to screen the loci associated with these four yield traits by 323 accessions of Gossypium hirsutum L. evaluated in nine different environments. 251 significant loci were detected to be associated with lint yield and its three components, including 69 loci with individual effects and all involved in epistasis interactions. These significant loci explain ∼ 62.05% of the phenotypic variance (ranging from 49.06% ∼ 72.29% for these four traits). It was indicated by high contribution of environmental interaction to the phenotypic variance for lint yield and boll numbers, that genetic effects of SSR loci were susceptible to environment factors. Shared loci were also observed among these four traits, which may be used for simultaneous improvement in cotton breeding for yield traits. Furthermore, consistent and elite loci were screened with −Log10 (P-value) >8.0 based on predicted effects of loci detected in different environments. There was one locus and 6 pairs of epistasis for lint yield, 4 loci and 10 epistasis for boll number, 15 loci and 2 epistasis for boll weight, and 2 loci and 5 epistasis for lint percentage, respectively. These results provided insights into the genetic basis of lint yield and its components and may be useful for marker-assisted breeding to improve cotton production. PMID:24810754

  14. Interactions between mycoplasma lipid-associated membrane proteins and the host cells

    Institute of Scientific and Technical Information of China (English)

    YOU Xiao-xing; ZENG Yan-hua; WU Yi-mou

    2006-01-01

    Mycoplamas are a group of wall-less prokaryotes widely distributed in nature, some of which are pathogenic for humans and animals. There are many lipoproteins anchored on the outer face of the plasma membrane, called lipid-associated membrane proteins (LAMPs). LAMPs are highly antigenic and could undergo phase and size variation, and are recognized by the innate immune system through Toll-like receptors (TLR) 2 and 6. LAMPs can modulate the immune system, and could induce immune cells apoptosis or death. In addition, they may associate with malignant transformation of host cells and are also considered to be cofactors in the progression of AIDS.

  15. 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.

  16. Molecular basis of filamin A-FilGAP interaction and its impairment in congenital disorders associated with filamin A mutations.

    Directory of Open Access Journals (Sweden)

    Fumihiko Nakamura

    Full Text Available BACKGROUND: Mutations in filamin A (FLNa, an essential cytoskeletal protein with multiple binding partners, cause developmental anomalies in humans. METHODOLOGY/PRINCIPAL FINDINGS: We determined the structure of the 23rd Ig repeat of FLNa (IgFLNa23 that interacts with FilGAP, a Rac-specific GTPase-activating protein and regulator of cell polarity and movement, and the effect of the three disease-related mutations on this interaction. A combination of NMR structural analysis and in silico modeling revealed the structural interface details between the C and D beta-strands of the IgFLNa23 and the C-terminal 32 residues of FilGAP. Mutagenesis of the predicted key interface residues confirmed the binding constraints between the two proteins. Specific loss-of-function FLNa constructs were generated and used to analyze the importance of the FLNa-FilGAP interaction in vivo. Point mutagenesis revealed that disruption of the FLNa-FilGAP interface perturbs cell spreading. FilGAP does not bind FLNa homologs FLNb or FLNc establishing the importance of this interaction to the human FLNa mutations. Tight complex formation requires dimerization of both partners and the correct alignment of the binding surfaces, which is promoted by a flexible hinge domain between repeats 23 and 24 of FLNa. FLNa mutations associated with human developmental anomalies disrupt the binding interaction and weaken the elasticity of FLNa/F-actin network under high mechanical stress. CONCLUSIONS/SIGNIFICANCE: Mutational analysis informed by structure can generate reagents for probing specific cellular interactions of FLNa. Disease-related FLNa mutations have demonstrable effects on FLNa function.

  17. Antidepressant-warfarin interaction and associated gastrointestinal bleeding risk in a case-control study.

    Directory of Open Access Journals (Sweden)

    Hedi Schelleman

    Full Text Available BACKGROUND: Bleeding is the most common and worrisome adverse effect of warfarin therapy. One of the factors that might increase bleeding risk is initiation of interacting drugs that potentiate warfarin. We sought to evaluate whether initiation of an antidepressant increases the risk of hospitalization for gastrointestinal bleeding in warfarin users. METHODOLOGY/PRINCIPAL FINDINGS: Medicaid claims data (1999-2005 were used to perform an observational case-control study nested within person-time exposed to warfarin in those ≥18 years. In total, 430,455 warfarin users contributed 407,370 person-years of warfarin use. The incidence rate of hospitalization for GI bleeding among warfarin users was 4.48 per 100 person-years (95% CI, 4.42-4.55. Each gastrointestinal bleeding cases was matched to 50 controls based on index date and state. Warfarin users had an increased odds ratio of gastrointestinal bleeding upon initiation of citalopram (OR = 1.73 [95% CI, 1.25-2.38], fluoxetine (OR = 1.63 [95% CI, 1.11-2.38], paroxetine (OR = 1.64 [95% CI, 1.27-2.12], amitriptyline (OR = 1.47 [95% CI, 1.02-2.11]. Also mirtazapine, which is not believed to interact with warfarin, increased the risk of GI bleeding (OR = 1.75 [95% CI, 1.30-2.35]. CONCLUSIONS/SIGNIFICANCE: Warfarin users who initiated citalopram, fluoxetine, paroxetine, amitriptyline, or mirtazapine had an increased risk of hospitalization for gastrointestinal bleeding. However, the elevated risk with mirtazapine suggests that a drug-drug interaction may not have been responsible for all of the observed increased risk.

  18. Do Family Mealtime Interactions Mediate the Association between Asthma Symptoms and Separation Anxiety?

    Science.gov (United States)

    Fiese, Barbara H.; Winter, Marcia A.; Wamboldt, Frederick S.; Anbar, Ran D.; Wamboldt, Marianne Z.

    2010-01-01

    Background: Respiratory problems have been shown to be associated with the development of panic anxiety. Family members play an essential role for children to emotionally manage their symptoms. This study aimed to examine the relation between severity of respiratory symptoms in children with asthma and separation anxiety. Relying on direct…

  19. 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...

  20. Peax: interactive visual analysis and exploration of complex clinical phenotype and gene expression association.

    Science.gov (United States)

    Hinterberg, Michael A; Kao, David P; Bristow, Michael R; Hunter, Lawrence E; Port, J David; Görg, Carsten

    2015-01-01

    Increasing availability of high-dimensional clinical data, which improves the ability to define more specific phenotypes, as well as molecular data, which can elucidate disease mechanisms, is a driving force and at the same time a major challenge for translational and personalized medicine. Successful research in this field requires an approach that ties together specific disease and health expertise with understanding of molecular data through statistical methods. We present PEAX (Phenotype-Expression Association eXplorer), built upon open-source software, which integrates visual phenotype model definition with statistical testing of expression data presented concurrently in a web-browser. The integration of data and analysis tasks in a single tool allows clinical domain experts to obtain new insights directly through exploration of relationships between multivariate phenotype models and gene expression data, showing the effects of model definition and modification while also exploiting potential meaningful associations between phenotype and miRNA-mRNA regulatory relationships. We combine the web visualization capabilities of Shiny and D3 with the power and speed of R for backend statistical analysis, in order to abstract the scripting required for repetitive analysis of sub-phenotype association. We describe the motivation for PEAX, demonstrate its utility through a use case involving heart failure research, and discuss computational challenges and observations. We show that our visual web-based representations are well-suited for rapid exploration of phenotype and gene expression association, facilitating insight and discovery by domain experts. PMID:25592601

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

    Science.gov (United States)

    Singh, Ravindra Pal; Reddy, C R K

    2014-05-01

    Seaweed-associated bacteria play a crucial role in morphogenesis and growth of seaweeds (macroalgae) in direct and/or indirect ways. Bacterial communities belonging to the phyla Proteobacteria and Firmicutes are generally the most abundant on seaweed surfaces. Associated bacterial communities produce plant growth-promoting substances, quorum sensing signalling molecules, bioactive compounds and other effective molecules that are responsible for normal morphology, development and growth of seaweeds. Also, bioactive molecules of associated bacteria determine the presence of other bacterial strains on seaweeds and protect the host from harmful entities present in the pelagic realm. The ecological functions of cross-domain signalling between seaweeds and bacteria have been reported as liberation of carpospores in the red seaweeds and settlement of zoospores in the green seaweeds. In the present review, the role of extracellular polymeric substances in growth and settlement of seaweeds spores is also highlighted. To elucidate the functional roles of associated bacteria and the molecular mechanisms underlying reported ecological phenomena in seaweeds requires a combined ecological, microbiological and biochemical approach. PMID:24512602

  2. 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.

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Science.gov (United States)

    Cale, Jonathan A; Collignon, R Maxwell; Klutsch, Jennifer G; Kanekar, Sanat S; Hussain, Altaf; Erbilgin, Nadir

    2016-01-01

    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. PMID:27583519

  5. A neural model of hippocampal-striatal interactions in associative learning and transfer generalization in various neurological and psychiatric patients.

    Science.gov (United States)

    Moustafa, Ahmed A; Keri, Szabolcs; Herzallah, Mohammad M; Myers, Catherine E; Gluck, Mark A

    2010-11-01

    Building on our previous neurocomputational models of basal ganglia and hippocampal region function (and their modulation by dopamine and acetylcholine, respectively), we show here how an integration of these models can inform our understanding of the interaction between the basal ganglia and hippocampal region in associative learning and transfer generalization across various patient populations. As a common test bed for exploring interactions between these brain regions and neuromodulators, we focus on the acquired equivalence task, an associative learning paradigm in which stimuli that have been associated with the same outcome acquire a functional similarity such that subsequent generalization between these stimuli increases. This task has been used to test cognitive dysfunction in various patient populations with damages to the hippocampal region and basal ganglia, including studies of patients with Parkinson's disease (PD), schizophrenia, basal forebrain amnesia, and hippocampal atrophy. Simulation results show that damage to the hippocampal region-as in patients with hippocampal atrophy (HA), hypoxia, mild Alzheimer's (AD), or schizophrenia-leads to intact associative learning but impaired transfer generalization performance. Moreover, the model demonstrates how PD and anterior communicating artery (ACoA) aneurysm-two very different brain disorders that affect different neural mechanisms-can have similar effects on acquired equivalence performance. In particular, the model shows that simulating a loss of dopamine function in the basal ganglia module (as in PD) leads to slow acquisition learning but intact transfer generalization. Similarly, the model shows that simulating the loss of acetylcholine in the hippocampal region (as in ACoA aneurysm) also results in slower acquisition learning. We argue from this that changes in associative learning of stimulus-action pathways (in the basal ganglia) or changes in the learning of stimulus representations (in the

  6. The exosome associates cotranscriptionally with the nascent pre-mRNP through interactions with heterogeneous nuclear ribonucleoproteins

    DEFF Research Database (Denmark)

    Hessle, Viktoria; Björk, Petra; Sokolowski, Marcus;

    2009-01-01

    Eukaryotic cells have evolved quality control mechanisms to degrade aberrant mRNA molecules and prevent the synthesis of defective proteins that could be deleterious for the cell. The exosome, a protein complex with ribonuclease activity, is a key player in quality control. An early quality...... checkpoint takes place cotranscriptionally but little is known about the molecular mechanisms by which the exosome is recruited to the transcribed genes. Here we study the core exosome subunit Rrp4 in two insect model systems, Chironomus and Drosophila. We show that a significant fraction of Rrp4...... is associated with the nascent pre-mRNPs and that a specific mRNA-binding protein, Hrp59/hnRNP M, interacts in vivo with multiple exosome subunits. Depletion of Hrp59 by RNA interference reduces the levels of Rrp4 at transcription sites, which suggests that Hrp59 is needed for the exosome to stably interact...

  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. Gene-Gene Interaction between PPARδ and PPARγ Is Associated with Abdominal Obesity in a Chinese Population

    Institute of Scientific and Technical Information of China (English)

    Yi Ding; Zhi-Rong Guo; Ming Wu; Qiu Chen; Hao Yu; Wen-Shu Luo

    2012-01-01

    The peroxisome proliferator-activated receptors (PPARs) -α,-δ/β and -γ are the ligand-activated transcription factors that function as the master regulators of glucose,fatty acid and lipoprotein metabolism,energy balance,cell proliferation and differentiation,inflammation,and atherosclerosis.The objective of the current study was to examine the main and interactive effect of seven single nucleotide polymorphisms (SNPs) of PPARδ/γ in contribution to abdominal obesity.A total of 820 subjects were randomly selected and no individuals were related.The selected SNPs in PPARδ (rs2016520 and rs9794) and PPARγ (rs10865710,rs1805192,rs709158,rs3856806,and rs4684847) were genotyped.Mean difference and 95% confident interval were calculated.Interactions were explored by the method of generalized multifactor dimensionality reduction.After adjustment for gender,age,and smoking status,it was found that the carriers of the C allele (TC + CC) of rs2016520 were associated with a decreased risk of abdominal obesity compared to the carriers of the TT genotype (mean difference =-2.63,95% CI =-3.61--1.64,P < 0.0001).A significant two-locus model (P =0.0107) involving rs2016520 and rs10865710 and a significant three-locus model (P =0.0107) involving rs2016520,rs9794,and rs1805192 were observed.Overall,the three-locus model had the highest level of testing accuracy (59.85%) and showed a better cross-validation consistency (9/10) than two-locus model.Therefore,for abdominal obesity defined by waist circumference,we chose the three-locus model as the best interaction model.In conclusion,the C allele in rs2016520 was significantly associated with a lower abdominal obesity.Moreover,an interaction among rs2016520,rs1805192,and rs9794 on incident abdominal obesity could be demonstrated.

  9. Accounting for Population Structure in Gene-by-Environment Interactions in Genome-Wide Association Studies Using Mixed Models.

    Science.gov (United States)

    Sul, Jae Hoon; Bilow, Michael; Yang, Wen-Yun; Kostem, Emrah; Furlotte, Nick; He, Dan; Eskin, Eleazar

    2016-03-01

    Although genome-wide association studies (GWASs) have discovered numerous novel genetic variants associated with many complex traits and diseases, those genetic variants typically explain only a small fraction of phenotypic variance. Factors that account for phenotypic variance include environmental factors and gene-by-environment interactions (GEIs). Recently, several studies have conducted genome-wide gene-by-environment association analyses and demonstrated important roles of GEIs in complex traits. One of the main challenges in these association studies is to control effects of population structure that may cause spurious associations. Many studies have analyzed how population structure influences statistics of genetic variants and developed several statistical approaches to correct for population structure. However, the impact of population structure on GEI statistics in GWASs has not been extensively studied and nor have there been methods designed to correct for population structure on GEI statistics. In this paper, we show both analytically and empirically that population structure may cause spurious GEIs and use both simulation and two GWAS datasets to support our finding. We propose a statistical approach based on mixed models to account for population structure on GEI statistics. We find that our approach effectively controls population structure on statistics for GEIs as well as for genetic variants.

  10. Accounting for Population Structure in Gene-by-Environment Interactions in Genome-Wide Association Studies Using Mixed Models.

    Directory of Open Access Journals (Sweden)

    Jae Hoon Sul

    2016-03-01

    Full Text Available Although genome-wide association studies (GWASs have discovered numerous novel genetic variants associated with many complex traits and diseases, those genetic variants typically explain only a small fraction of phenotypic variance. Factors that account for phenotypic variance include environmental factors and gene-by-environment interactions (GEIs. Recently, several studies have conducted genome-wide gene-by-environment association analyses and demonstrated important roles of GEIs in complex traits. One of the main challenges in these association studies is to control effects of population structure that may cause spurious associations. Many studies have analyzed how population structure influences statistics of genetic variants and developed several statistical approaches to correct for population structure. However, the impact of population structure on GEI statistics in GWASs has not been extensively studied and nor have there been methods designed to correct for population structure on GEI statistics. In this paper, we show both analytically and empirically that population structure may cause spurious GEIs and use both simulation and two GWAS datasets to support our finding. We propose a statistical approach based on mixed models to account for population structure on GEI statistics. We find that our approach effectively controls population structure on statistics for GEIs as well as for genetic variants.

  11. Accounting for Population Structure in Gene-by-Environment Interactions in Genome-Wide Association Studies Using Mixed Models

    Science.gov (United States)

    Yang, Wen-Yun; Kostem, Emrah; Furlotte, Nick; He, Dan; Eskin, Eleazar

    2016-01-01

    Although genome-wide association studies (GWASs) have discovered numerous novel genetic variants associated with many complex traits and diseases, those genetic variants typically explain only a small fraction of phenotypic variance. Factors that account for phenotypic variance include environmental factors and gene-by-environment interactions (GEIs). Recently, several studies have conducted genome-wide gene-by-environment association analyses and demonstrated important roles of GEIs in complex traits. One of the main challenges in these association studies is to control effects of population structure that may cause spurious associations. Many studies have analyzed how population structure influences statistics of genetic variants and developed several statistical approaches to correct for population structure. However, the impact of population structure on GEI statistics in GWASs has not been extensively studied and nor have there been methods designed to correct for population structure on GEI statistics. In this paper, we show both analytically and empirically that population structure may cause spurious GEIs and use both simulation and two GWAS datasets to support our finding. We propose a statistical approach based on mixed models to account for population structure on GEI statistics. We find that our approach effectively controls population structure on statistics for GEIs as well as for genetic variants. PMID:26943367

  12. Lipid peroxidation - inhibitory effects of perioperatively used drugs associated with their membrane interactions.

    OpenAIRE

    Tsuchiya, Hironori

    2014-01-01

    Objective: Oxidative/nitrative stress, an imbalance between oxidant production and antioxidant defense in the biological system, is induced not only by various diseases but also by anesthesia and surgical trauma. Since the choice of drugs is expected to reduce oxidative/nitrative stress in the perioperative period, the lipid peroxidation inhibition by different drugs associated with surgery was studied together with investigating one of their possible mechanisms.Methods: Lipid peroxidation-in...

  13. Interaction between common variants of FTO and MC4R is associated with risk of PCOS

    OpenAIRE

    Yuan, Huiqin; Zhu, Guoping; Wang, Fang; Wang, Xiang; Guo, Huihui; Shen, Mo

    2015-01-01

    Background Polycystic ovary syndrome (PCOS) is a common and complex endocrine-metabolic disease. One of the well-documented characteristics of PCOS is obesity or overweightness. It is possible to be genetically predisposed to becoming obese or overweight, and several potentially causative single nucleotide polymorphisms (SNPs), such as rs9939609 (A/T) in the fat mass, and obesity-associated gene (FTO) and rs17782313 (T/C) in the melanocortin-4 receptor gene (MC4R), have been investigated. Fur...

  14. 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...... the view that protein kinase CK2 plays an important role in certain steps of apoptosis....

  15. Maternal oxytocin response during mother–infant interaction: Associations with adult temperament

    OpenAIRE

    Strathearn, Lane; Iyengar, Udita; Fonagy, Peter; Kim, Sohye

    2012-01-01

    Oxytocin is a neuropeptide associated with social affiliation and maternal caregiving. However, its effects appear to be moderated by various contextual factors and stable individual characteristics. The purpose of this study was to investigate the relationship of self-reported state and trait measures (such as temperament, mood and affect) with peripheral oxytocin response in mothers. Fifty-five first-time mothers participated in a semi-structured procedure, during which time repeated periph...

  16. Post genome-wide association studies of novel genes associated with type 2 diabetes show gene-gene interaction and high predictive value.

    Directory of Open Access Journals (Sweden)

    Stéphane Cauchi

    Full Text Available BACKGROUND: Recently, several Genome Wide Association (GWA studies in populations of European descent have identified and validated novel single nucleotide polymorphisms (SNPs, highly associated with type 2 diabetes (T2D. Our aims were to validate these markers in other European and non-European populations, then to assess their combined effect in a large French study comparing T2D and normal glucose tolerant (NGT individuals. METHODOLOGY/PRINCIPAL FINDINGS: In the same French population analyzed in our previous GWA study (3,295 T2D and 3,595 NGT, strong associations with T2D were found for CDKAL1 (OR(rs7756992 = 1.30[1.19-1.42], P = 2.3x10(-9, CDKN2A/2B (OR(rs10811661 = 0.74[0.66-0.82], P = 3.5x10(-8 and more modestly for IGFBP2 (OR(rs1470579 = 1.17[1.07-1.27], P = 0.0003 SNPs. These results were replicated in both Israeli Ashkenazi (577 T2D and 552 NGT and Austrian (504 T2D and 753 NGT populations (except for CDKAL1 but not in the Moroccan population (521 T2D and 423 NGT. In the overall group of French subjects (4,232 T2D and 4,595 NGT, IGFBP2 and CXCR4 synergistically interacted with (LOC38776, SLC30A8, HHEX and (NGN3, CDKN2A/2B, respectively, encoding for proteins presumably regulating pancreatic endocrine cell development and function. The T2D risk increased strongly when risk alleles, including the previously discovered T2D-associated TCF7L2 rs7903146 SNP, were combined (8.68-fold for the 14% of French individuals carrying 18 to 30 risk alleles with an allelic OR of 1.24. With an area under the ROC curve of 0.86, only 15 novel loci were necessary to discriminate French individuals susceptible to develop T2D. CONCLUSIONS/SIGNIFICANCE: In addition to TCF7L2, SLC30A8 and HHEX, initially identified by the French GWA scan, CDKAL1, IGFBP2 and CDKN2A/2B strongly associate with T2D in French individuals, and mostly in populations of Central European descent but not in Moroccan subjects. Genes expressed in the pancreas interact together and their

  17. Aromatic Interactions Promote Self-association of Collagen Triple-helical Peptides to Higher Order Structures

    OpenAIRE

    Kar, Karunakar; Ibrar, Sajjad; Nanda, Vikas; Getz, Todd M; Kunapuli, Satya P.; Brodsky, Barbara

    2009-01-01

    Aromatic residues are relatively rare within the collagen triple-helix, but they appear to play a specialized role in higher order structure and function. The role of aromatic amino acids in the self-assembly of triple-helical peptides was investigated in terms of the kinetics of self-association, the nature of aggregated species formed, and the ability of these species to activate platelet aggregation. The presence of aromatic residues on both ends of a type IV collagen model peptide is obse...

  18. Association and interaction analyses of eight genes under asthma linkage peaks

    DEFF Research Database (Denmark)

    Ferreira, M A R; Zhao, Z Z; Thomsen, S F;

    2009-01-01

    BACKGROUND: Linkage studies have implicated the 2q33, 9p21, 11q13 and 20q13 regions in the regulation of allergic disease. The aim of this study was to test genetic variants in candidate genes from these regions for association with specific asthma traits. METHODS: Ninety-five single nucleotide...... polymorphisms (SNP) located in eight genes (CD28, CTLA4, ICOS, ADAM23, ADAMTSL1, MS4A2, CDH26 and HRH3) were genotyped in >5000 individuals from Australian (n = 1162), Dutch (n = 99) and Danish (n = 303) families. Traits tested included doctor-diagnosed asthma, atopy, airway obstruction, total serum...

  19. Protein-protein interaction studies revealed genes associated with plant disease resistance and drought tolerance (abstract)

    International Nuclear Information System (INIS)

    Under natural conditions, plants are frequently subjected to biotic and abiotic constraints that cause considerable damage and limit plant productivity worldwide. Biotic and abiotic stresses results in the accumulation of Reactive Oxygen Species, ROS (H/sub 2/O/sub 2/, O/sub 2/), Nitric oxide (NO) and cytosolic calcium (Ca/sup 2), indicating that plant responses to diseases and drought may operate, at least in part, through common molecular pathways. Additionally, stress-inducible genes have been categorized in two different groups: (a) genes that directly protect against environmental stresses and (b) genes that encode protein kinases intriguingly, protein kinases are also involved in disease resistance since many resistance genes (R genes) are in fact kinases. Here, we describe an interactor hunt using the bacterial virulent gene, VirPphA as a bait to screen an Arabidopsis thaliana cDNA prey library. VirPpha shares sequence similarity with another type III effector protein. AvrPtoB. The screen, originally designed to search for key signaling components involved in disease resistance, identified several putative and promising interactors (2-cys peroxiredoxin-like protein, kinase-like protein and ER6 protein, which is a universal stress protein) that might be involved in both biotic and abiotic stress responses. Simultaneously, another screen using AvrPtoB as a bait was conducted searching the same library for common interactors. Fibrillin (Fibri, At4g04020) was identified in both screens indicating a possible involvement in plant disease resistance through its influence on the plant cytoskeleton, which has been implicated in localized defence response. Furthermore, At4g04020 is 82% similar to the Rice fibrillin, At4g22240, which was recently shown to interact the, rice SGT1 (OsSGT1). SGT1 is a gene that is required for multiple R-gene function. Using the yeast two-hybrid system, fibrillin was found to interact strongly with all VirPphA homologues identified in

  20. 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

  1. 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.

  2. Polymer gels with associating side chains and their interaction with surfactants

    Science.gov (United States)

    Gordievskaya, Yulia D.; Rumyantsev, Artem M.; Kramarenko, Elena Yu.

    2016-05-01

    Conformational behaviour of hydrophobically modified (HM) polymer gels in solutions of nonionic surfactants is studied theoretically. A HM gel contains hydrophobic side chains (stickers) grafted to its subchains. Hydrophobic stickers are capable to aggregate into joint micelles with surfactant molecules. Micelles containing more than one sticker serve as additional physical cross-links of the network, and their formation causes gel shrinking. In the proposed theoretical model, the interior of the gel/surfactant complex is treated as an array of densely packed spherical polymer brushes consisting of gel subchains tethered to the surface of the spherical sticker/surfactant micelles. Effect of stickers length and grafting density, surfactant concentration and hydrophobicity on gel swelling as well as on hydrophobic association inside it is analyzed. It is shown that increasing surfactant concentration can result in a gel collapse, which is caused by surfactant-induced hydrophobic aggregation of stickers, and a successive gel reswelling. The latter should be attributed to a growing fraction of surfactants in joint aggregates and, hence, increasing number of micelles containing only one sticker and not participating in gel physical cross-linking. In polyelectrolyte (PE) gels hydrophobic aggregation is opposed by osmotic pressure of mobile counterions, so that at some critical ionization degree hydrophobic association is completely suppressed. Hydrophobic modification of polymers is shown to open new ways for controlling gel responsiveness. In particular, it is discussed that incorporation of photosensitive groups into gel subchains and/or surfactant tail could give a possibility to vary the gel volume by light. Since hydrophobic aggregation regularities in gels and solutions are common, we hope our findings will be useful for design of polymer based self-healing materials as well.

  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. Electrostatic interaction between oxysterol-binding protein and VAMP-associated protein A revealed by NMR and mutagenesis studies.

    Science.gov (United States)

    Furuita, Kyoko; Jee, JunGoo; Fukada, Harumi; Mishima, Masaki; Kojima, Chojiro

    2010-04-23

    Oxysterol-binding protein (OSBP), a cytosolic receptor of cholesterol and oxysterols, is recruited to the endoplasmic reticulum by binding to the cytoplasmic major sperm protein (MSP) domain of integral endoplasmic reticulum protein VAMP-associated protein-A (VAP-A), a process essential for the stimulation of sphingomyelin synthesis by 25-hydroxycholesterol. To delineate the interaction mechanism between VAP-A and OSBP, we determined the complex structure between the VAP-A MSP domain (VAP-A(MSP)) and the OSBP fragment containing a VAP-A binding motif FFAT (OSBP(F)) by NMR. This solution structure explained that five of six conserved residues in the FFAT motif are required for the stable complex formation, and three of five, including three critical intermolecular electrostatic interactions, were not explained before. By combining NMR relaxation and titration, isothermal titration calorimetry, and mutagenesis experiments with structural information, we further elucidated the detailed roles of the FFAT motif and underlying motions of VAP-A(MSP), OSBP(F), and the complex. Our results show that OSBP(F) is disordered in the free state, and VAP-A(MSP) and OSBP(F) form a final complex by means of intermediates, where electrostatic interactions through acidic residues, including an acid patch preceding the FFAT motif, probably play a collective role. Additionally, we report that the mutation that causes the familial motor neuron disease decreases the stability of the MSP domain.

  5. Electrostatic Interaction between Oxysterol-binding Protein and VAMP-associated Protein A Revealed by NMR and Mutagenesis Studies*

    Science.gov (United States)

    Furuita, Kyoko; Jee, JunGoo; Fukada, Harumi; Mishima, Masaki; Kojima, Chojiro

    2010-01-01

    Oxysterol-binding protein (OSBP), a cytosolic receptor of cholesterol and oxysterols, is recruited to the endoplasmic reticulum by binding to the cytoplasmic major sperm protein (MSP) domain of integral endoplasmic reticulum protein VAMP-associated protein-A (VAP-A), a process essential for the stimulation of sphingomyelin synthesis by 25-hydroxycholesterol. To delineate the interaction mechanism between VAP-A and OSBP, we determined the complex structure between the VAP-A MSP domain (VAP-AMSP) and the OSBP fragment containing a VAP-A binding motif FFAT (OSBPF) by NMR. This solution structure explained that five of six conserved residues in the FFAT motif are required for the stable complex formation, and three of five, including three critical intermolecular electrostatic interactions, were not explained before. By combining NMR relaxation and titration, isothermal titration calorimetry, and mutagenesis experiments with structural information, we further elucidated the detailed roles of the FFAT motif and underlying motions of VAP-AMSP, OSBPF, and the complex. Our results show that OSBPF is disordered in the free state, and VAP-AMSP and OSBPF form a final complex by means of intermediates, where electrostatic interactions through acidic residues, including an acid patch preceding the FFAT motif, probably play a collective role. Additionally, we report that the mutation that causes the familial motor neuron disease decreases the stability of the MSP domain. PMID:20178991

  6. HPA regulation and dating couples' behaviors during conflict: gender-specific associations and cross-partner interactions.

    Science.gov (United States)

    Laurent, Heidemarie K; Powers, Sally I; Laws, Holly; Gunlicks-Stoessel, Meredith; Bent, Eileen; Balaban, Susan

    2013-06-13

    The way romantic partners behave during conflict is known to relate to stress responses, including activation of the hypothalamic-pituitary-adrenal (HPA) axis; however, little attention has been paid to interactive effects of partners' behaviors, or to behavior outside of marital relationships. This study examined relations between unmarried partners' negative and positive behaviors during discussion of conflict and their HPA responses, including both main effects and cross-partner interactions. Emerging adult opposite-sex couples (n=199) participated in a 15-minute conflict discussion and afterward rated their behavior on 3 dimensions: conflictual, holding back, and supportive. Seven saliva samples collected before and after the discussion were assayed for cortisol to determine HPA response. Quadratic growth models demonstrated associations between male×female partners' behaviors and cortisol trajectories. Two negative dyadic patterns-mutual conflictual behavior (negative reciprocity); female conflictual/male holding back (demand-withdraw)-and one positive pattern-mutual supportive behavior-were identified. Whereas negative patterns related to lower cortisol and impaired post-discussion recovery for women, the positive pattern related to lower cortisol and better recovery for men. Women's conflictual behavior only predicted problematic cortisol responses if their partner was highly conflictual or holding back; at lower levels of these partner behaviors, the opposite was true. This work demonstrates similar costs of negative reciprocity and demand-withdraw and benefits of supportive conflict dynamics in dating couples as found in marital research, but associations with HPA are gender-specific. Cross-partner interactions suggest that behavior during discussion of conflict should not be categorized as helpful or harmful without considering the other partner's behavior. PMID:23711564

  7. The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat.

    Directory of Open Access Journals (Sweden)

    Emanuele Miraglia del Giudice

    Full Text Available BACKGROUND AND AIMS: A polymorphism in adiponutrin/patatin-like phospholipase-3 gene (PNPLA3, rs738409 C->G, encoding for the I148M variant, is the strongest genetic determinant of liver fat and ALT levels in adulthood and childhood obesity. Aims of this study were i to analyse in a large group of obese children the role of the interaction of not-genetic factors such as BMI, waist circumference (W/Hr and insulin resistance (HOMA-IR in exposing the association between the I148M polymorphism and ALT levels and ii to stratify the individual risk of these children to have liver injury on the basis of this gene-environment interaction. METHODS: 1048 Italian obese children were investigated. Anthropometric, clinical and metabolic data were collected and the PNPLA3 I148M variant genotyped. RESULTS: Children carrying the 148M allele showed higher ALT and AST levels (p = 0.000006 and p = 0.0002, respectively. Relationships between BMI-SDS, HOMA-IR and W/Hr with ALT were analysed in function of the different PNPLA3 genotypes. Children 148M homozygous showed a stronger correlation between ALT and W/Hr than those carrying the other genotypes (p: 0.0045 and, therefore, 148M homozygotes with high extent of abdominal fat (W/Hr above 0.62 had the highest OR (4.9, 95% C. I. 3.2-7.8, p = 0.00001 to develop pathologic ALT. CONCLUSIONS: We have i showed for the first time that the magnitude of the association of PNPLA3 with liver enzymes is driven by the size of abdominal fat and ii stratified the individual risk to develop liver damage on the basis of the interaction between the PNPLA3 genotype and abdominal fat.

  8. Temperature-enhanced association of proteins due to electrostatic interaction: a coarse-grained simulation of actin-myosin binding.

    Science.gov (United States)

    Okazaki, Kei-ichi; Sato, Takato; Takano, Mitsunori

    2012-05-30

    Association of protein molecules constitutes the basis for the interaction network in a cell. Despite its fundamental importance, the thermodynamic aspect of protein-protein binding, particularly the issues relating to the entropy change upon binding, remains elusive. The binding of actin and myosin, which are vital proteins in motility, is a typical example, in which two different binding mechanisms have been argued: the binding affinity increases with increasing temperature and with decreasing salt-concentration, indicating the entropy-driven binding and the enthalpy-driven binding, respectively. How can these thermodynamically different binding mechanisms coexist? To address this question, which is of general importance in understanding protein-protein bindings, we conducted an in silico titration of the actin-myosin system by molecular dynamics simulation using a residue-level coarse-grained model, with particular focus on the role of the electrostatic interaction. We found a good agreement between in silico and in vitro experiments on the salt-concentration dependence and the temperature dependence of the binding affinity. We then figured out how the two binding mechanisms can coexist: the enthalpy (due to electrostatic interaction between actin and myosin) provides the basal binding affinity, and the entropy (due to the orientational disorder of water molecules) enhances it at higher temperatures. In addition, we analyzed the actin-myosin complex structures observed during the simulation and obtained a variety of weak-binding complex structures, among which were found an unusual binding mode suggested by an earlier experiment and precursor structures of the strong-binding complex proposed by electron microscopy. These results collectively indicate the potential capability of a residue-level coarse-grained model to simulate the association-dissociation dynamics (particularly for transient weak-bindings) exhibited by larger and more complicated systems, as in a

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

    Science.gov (United States)

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

    2015-11-01

    The proprotein convertases (PCs) furin, PC5, PACE4, and PC7 cleave secretory proteins after basic residues, including the HIV envelope glycoprotein (gp160) and Vpr. We evaluated the abundance of PC mRNAs in postmortem brains of individuals exhibiting HIV-associated neurocognitive disorder (HAND), likely driven by neuroinflammation and neurotoxic HIV proteins (e.g., envelope and Vpr). Concomitant with increased inflammation-related gene expression (interleukin-1β [IL-1β]), the mRNA levels of the above PCs are significantly increased, together with those of the proteinase-activated receptor 1 (PAR1), an inflammation-associated receptor that is cleaved by thrombin at ProArg41↓ (where the down arrow indicates the cleavage location), and potentially by PCs at Arg41XXXXArg46↓. The latter motif in PAR1, but not its R46A mutant, drives its interactions with PCs. Indeed, PAR1 upregulation leads to the inhibition of membrane-bound furin, PC5B, and PC7 and inhibits gp160 processing and HIV infectivity. Additionally, a proximity ligation assay revealed that furin and PC7 interact with PAR1. Reciprocally, increased furin expression reduces the plasma membrane abundance of PAR1 by trapping it in the trans-Golgi network. Furthermore, soluble PC5A/PACE4 can target/disarm cell surface PAR1 through cleavage at Arg46↓. PACE4/PC5A decreased calcium mobilization induced by thrombin stimulation. Our data reveal a new PC-PAR1-interaction pathway, which offsets the effects of HIV-induced neuroinflammation, viral infection, and potentially the development of HAND. PMID:26283733

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

    Science.gov (United States)

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

    2014-05-01

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

  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. 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

  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 PMID:27010601

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

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    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. Meaning-Related and Print-Related Interactions between Preschoolers and Parents during Shared Book Reading and Their Associations with Emergent Literacy Skills

    Science.gov (United States)

    Han, Jisu; Neuharth-Pritchett, Stacey

    2015-01-01

    This study examined interactions between preschool children and parents during shared book reading by analyzing parental self-report data. Using confirmatory factor analytic procedures and structural equation modeling, this study developed a scale measuring meaning-related and print-related reading interactions and examined their associations with…

  16. Associations of two common genetic variants with breast cancer risk in a chinese population: a stratified interaction analysis.

    Directory of Open Access Journals (Sweden)

    Yuxiang Lin

    Full Text Available Recent genome-wide association studies (GWAS have identified a series of new genetic susceptibility loci for breast cancer (BC. However, the correlations between these variants and breast cancer are still not clear. In order to explore the role of breast cancer susceptibility variants in a Southeast Chinese population, we genotyped two common SNPs at chromosome 6q25 (rs2046210 and in TOX3 (rs4784227 in a case-control study with a total of 702 breast cancer cases and 794 healthy-controls. In addition, we also evaluated the multiple interactions among genetic variants, risk factors, and tumor subtypes. Associations of genotypes with breast cancer risk was evaluated using multivariate logistic regression to estimate odds ratios (OR and their 95% confidence intervals (95% CI. The results indicated that both polymorphisms were significantly associated with the risk of breast cancer, with per allele OR = 1.35, (95%CI = 1.17-1.57 for rs2046210 and per allele OR = 1.24 (95%CI = 1.06-1.45 for rs4784227. Furthermore, in subgroup stratified analyses, we observed that the T allele of rs4784227 was significantly associated with elevated OR among postmenopausal populations (OR = 1.44, 95%CI 1.11-1.87 but not in premenopausal populations, with the heterogeneity P value of P = 0.064. These findings suggest that the genetic variants at chromosome 6q25 and in the TOX3 gene may play important roles in breast cancer development in a Chinese population and the underlying biological mechanisms need to be further elucidated.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    -proximal part of the NR3A C-terminus. MAP1S belongs to the same family as MAP1A and MAP1B, and was found to be abundant in both postnatal and adult rat brain. In hippocampal neurons the distribution-pattern of MAP1S resembled that of beta-tubulin III, but a fraction of the protein colocalized with synaptic......When screening a brain cDNA library, we found that the N-methyl-D-aspartate receptor subunit NR3A binds to microtubule-associated protein (MAP) 1S/chromosome 19 open reading frame 5 (C19ORF5). The interaction was confirmed in vitro and in vivo, and binding of MAP1S was localized to the membrane...

  18. 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.

  19. 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

    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...... stronger among those who carry 2 copies of the FOXO1A minor allele than those who carry 1 copy. Based on previously reported experiments on human cell models concerning FOXO1A-by-tea-compounds interactions, we speculate that results in the present study indicate that tea drinking may inhibit FOXO1A-209...... gene expression and its biological functions, which reduces the negative impacts of FOXO1A-209 gene on longevity (as reported in the literature) and offers protection against mortality risk at oldest-old ages. Our empirical findings imply that the health outcomes of particular nutritional interventions...

  20. Rule based classifier for the analysis of gene-gene and gene-environment interactions in genetic association studies

    Directory of Open Access Journals (Sweden)

    Lehr Thorsten

    2011-03-01

    Full Text Available Abstract Background Several methods have been presented for the analysis of complex interactions between genetic polymorphisms and/or environmental factors. Despite the available methods, there is still a need for alternative methods, because no single method will perform well in all scenarios. The aim of this work was to evaluate the performance of three selected rule based classifier algorithms, RIPPER, RIDOR and PART, for the analysis of genetic association studies. Methods Overall, 42 datasets were simulated with three different case-control models, a varying number of subjects (300, 600, SNPs (500, 1500, 3000 and noise (5%, 10%, 20%. The algorithms were applied to each of the datasets with a set of algorithm-specific settings. Results were further investigated with respect to a the Model, b the Rules, and c the Attribute level. Data analysis was performed using WEKA, SAS and PERL. Results The RIPPER algorithm discovered the true case-control model at least once in >33% of the datasets. The RIDOR and PART algorithm performed poorly for model detection. The RIPPER, RIDOR and PART algorithm discovered the true case-control rules in more than 83%, 83% and 44% of the datasets, respectively. All three algorithms were able to detect the attributes utilized in the respective case-control models in most datasets. Conclusions The current analyses substantiate the utility of rule based classifiers such as RIPPER, RIDOR and PART for the detection of gene-gene/gene-environment interactions in genetic association studies. These classifiers could provide a valuable new method, complementing existing approaches, in the analysis of genetic association studies. The methods provide an advantage in being able to handle both categorical and continuous variable types. Further, because the outputs of the analyses are easy to interpret, the rule based classifier approach could quickly generate testable hypotheses for additional evaluation. Since the algorithms are

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Antoinesha L. Hollman

    2016-03-01

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

  3. 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.

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

    Science.gov (United States)

    Hollman, Antoinesha L; Tchounwou, Paul B; Huang, Hung-Chung

    2016-04-01

    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. PMID:27043589

  5. "You can't kid a kidder": association between production and detection of deception in an interactive deception task.

    Science.gov (United States)

    Wright, Gordon R T; Berry, Christopher J; Bird, Geoffrey

    2012-01-01

    Both the ability to deceive others, and the ability to detect deception, has 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 (DeceIT). For the first time, signal detection theory (SDT) 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. PMID:22529790

  6. Translation initiation factor (iso) 4E interacts with BTF3, the beta subunit of the nascent polypeptide-associated complex.

    Science.gov (United States)

    Freire, Miguel Angel

    2005-01-31

    A two-hybrid screen with the translation initiation factor, eIF(iso)4E from Arabidopsis, identified a clone encoding a lipoxygenase type 2 [Freire, M.A., et al., 2000. Plant lipoxygenase 2 is a translation initiation factor-4E-binding protein. Plant Molecular Biology 44, 129-140], and three cDNA clones encoding the homologue of the mammalian BTF3 factor, the beta subunit of the nascent polypeptide-associated complex (NAC). Here we report on the interaction between the translation initiation factor eIF(iso)4E and AtBTF3. AtBTF3 protein is able to interact with the wheat initiation factors eIF4E and eIF(iso)4E. AtBTF3 contains a sequence related to the prototypic motif found on most of the 4E-binding proteins, and competes with the translation initiation factor eIF(iso)4G for eIF4(iso)4E binding, in a two hybrid interference assay. These findings provide a molecular link between the translation initiation mechanism and the emergence of the nascent polypeptide chains.

  7. 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

  8. FGFR2 intronic SNPs and breast cancer risk; associations with tumor characteristics and interactions with exogenous exposures and other known breast cancer risk factors

    OpenAIRE

    Marian, Catalin; Ochs-Balcom, Heather M; Nie, Jing; Kallakury, Bhaskar V.; Ambrosone, Christine B; Trevisan, Maurizio; Edge, Stephen; Shields, Peter G.; Freudenheim, Jo L.

    2010-01-01

    Recent genome-wide association studies have revealed several new candidate genes for breast cancer, including FGFR2. The associations were also replicated in several other independent studies. The next important step is to study whether these common variants interact with known breast cancer risk factors, exogenous exposures, and tumor characteristics. In a population-based case-control study of 1170 breast cancer cases and 2115 controls, we examined genetic associations of four intronic FGFR...

  9. Genetic association of APOA5 and APOE with metabolic syndrome and their interaction with health-related behavior in Korean men

    OpenAIRE

    Son, Ki Young; Son, Ho-Young; Chae, Jeesoo; Hwang, Jinha; Jang, SeSong; Yun, Jae Moon; Cho, Belong; Park, Jin Ho; Kim, Jong-Il

    2015-01-01

    Background Genome-wide association studies have been used extensively to identify genetic variants linked to metabolic syndrome (MetS), but most of them have been conducted in non-Asian populations. This study aimed to evaluate the association between MetS and previously studied single nucleotide polymorphisms (SNPs), and their interaction with health-related behavior in Korean men. Methods Seventeen SNPs were genotyped and their association with MetS and its components was tested in 1193 men...

  10. Comparison of the power of haplotype-based versus single- and multilocus association methods for gene × environment (gene × sex) interactions and application to gene × smoking and gene × sex interactions in rheumatoid arthritis

    OpenAIRE

    Dempfle Astrid; Hein Rebecca; Beckmann Lars; Scherag André; Van, Nguyen Thuy; Schäfer Helmut; Chang-Claude Jenny

    2007-01-01

    Abstract Accounting for interactions with environmental factors in association studies may improve the power to detect genetic effects and may help identifying important environmental effect modifiers. The power of unphased genotype-versus haplotype-based methods in regions with high linkage disequilibrium (LD), as measured by D', for analyzing gene × environment (gene × sex) interactions was compared using the Genetic Analysis Workshop 15 (GAW15) simulated data on rheumatoid arthritis with p...

  11. 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

  12. 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.

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

    Science.gov (United States)

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

    2012-07-01

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

  14. Interactive association of five candidate polymorphisms in Apelin/APJ pathway with coronary artery disease among Chinese hypertensive patients.

    Directory of Open Access Journals (Sweden)

    Wei Jin

    Full Text Available BACKGROUND: Via sequencing the genes of apelin/angiotensin receptor-like 1 (apelin/APJ pathway, we have recently identified and validated four common polymorphisms (rs3761581, rs56204867, rs7119375, and rs10501367 implicated in the development of hypertension. Extending these findings, we, in Chinese hypertensive patients, sought to investigate the association of these four polymorphisms and one additional promising candidate (rs9943582 from this pathway with the risk of developing coronary artery disease (CAD. METHODOLOGY/PRINCIPAL FINDINGS: Genotypes were obtained from 994 sporadic CAD patients and 708 age- and sex-matched controls. All participants were hypertensives and angiographically-confirmed. Data were analyzed by Haplo.Stats and multifactor dimensionality reduction (MDR softwares. Genotype distributions of five examined polymorphisms satisfied Hardy-Weinberg equilibrium in controls of both genders. Single-locus analyses exhibited no significant differences in the genotype/allele frequencies of examined polymorphisms between CAD patients and controls (P>0.05, even after controlling traditional cardiovascular confounders. In haplotype analyses, low-penetrance haplotype G-A (in order of rs56204867 and rs3761581 from apelin gene was significantly overrepresented in controls (1.73% relative to in CAD patients (0.4% in males (P = 0.047. Further interaction analyses suggested an overall best MDR model including rs3761581 in males (P = 0.0408 and including rs7119375 and rs9943582 in females (P<0.0001, which were further substantiated in the classical logistical regression model. CONCLUSIONS: Our findings demonstrated a contributive role of low-penetrance haplotype in apelin gene on CAD in males, and more importantly, interactive effects of genetic defects in apelin/APJ pathway might confer a potential risk in Chinese hypertensive patients.

  15. Transcriptional Responses Associated with Virulence and Defence in the Interaction between Heterobasidion annosum s.s. and Norway Spruce.

    Directory of Open Access Journals (Sweden)

    Karl Lundén

    Full Text Available Heterobasidion annosum sensu lato is a serious pathogen causing root and stem rot to conifers in the northern hemisphere and rendering the timber defective for sawing and pulping. In this study we applied next-generation sequencing to i identify transcriptional responses unique to Heterobasidion-inoculated Norway spruce and ii investigate the H. annosum transcripts to identify putative virulence factors. To address these objectives we wounded or inoculated 30-year-old Norway spruce clones with H. annosum and 454-sequenced the transcriptome of the interaction at 0, 5 and 15 days post inoculation. The 491,860 high-quality reads were de novo assembled and the relative expression was analysed. Overall, very few H. annosum transcripts were represented in our dataset. Three delta-12 fatty acid desaturase transcripts and one Clavaminate synthase-like transcript, both associated with virulence in other pathosystems, were found among the significantly induced transcripts. The analysis of the Norway spruce transcriptional responses produced a handful of differentially expressed transcripts. Most of these transcripts originated from genes known to respond to H. annosum. However, three genes that had not previously been reported to respond to H. annosum showed specific induction to inoculation: an oxophytodienoic acid-reductase (OPR, a beta-glucosidase and a germin-like protein (GLP2 gene. Even in a small data set like ours, five novel highly expressed Norway spruce transcripts without significant alignment to any previously annotated protein in Genbank but present in the P. abies (v1.0 gene catalogue were identified. Their expression pattern suggests a role in defence. Therefore a more complete survey of the transcriptional responses in the interactions between Norway spruce and its major pathogen H. annosum would probably provide a better understanding of gymnosperm defence than accumulated until now.

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

    Science.gov (United States)

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

    2016-01-01

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

  17. LRRTM3 interacts with APP and BACE1 and has variants associating with late-onset Alzheimer's disease (LOAD.

    Directory of Open Access Journals (Sweden)

    Sarah Lincoln

    Full Text Available Leucine rich repeat transmembrane protein 3 (LRRTM3 is member of a synaptic protein family. LRRTM3 is a nested gene within α-T catenin (CTNNA3 and resides at the linkage peak for late-onset Alzheimer's disease (LOAD risk and plasma amyloid β (Aβ levels. In-vitro knock-down of LRRTM3 was previously shown to decrease secreted Aβ, although the mechanism of this is unclear. In SH-SY5Y cells overexpressing APP and transiently transfected with LRRTM3 alone or with BACE1, we showed that LRRTM3 co-localizes with both APP and BACE1 in early endosomes, where BACE1 processing of APP occurs. Additionally, LRRTM3 co-localizes with APP in primary neuronal cultures from Tg2576 mice transduced with LRRTM3-expressing adeno-associated virus. Moreover, LRRTM3 co-immunoprecipitates with both endogenous APP and overexpressed BACE1, in HEK293T cells transfected with LRRTM3. SH-SY5Y cells with knock-down of LRRTM3 had lower BACE1 and higher CTNNA3 mRNA levels, but no change in APP. Brain mRNA levels of LRRTM3 showed significant correlations with BACE1, CTNNA3 and APP in ∼400 humans, but not in LRRTM3 knock-out mice. Finally, we assessed 69 single nucleotide polymorphisms (SNPs within and flanking LRRTM3 in 1,567 LOADs and 2,082 controls and identified 8 SNPs within a linkage disequilibrium block encompassing 5'UTR-Intron 1 of LRRTM3 that formed multilocus genotypes (MLG with suggestive global association with LOAD risk (p = 0.06, and significant individual MLGs. These 8 SNPs were genotyped in an independent series (1,258 LOADs and 718 controls and had significant global and individual MLG associations in the combined dataset (p = 0.02-0.05. Collectively, these results suggest that protein interactions between LRRTM3, APP and BACE1, as well as complex associations between mRNA levels of LRRTM3, CTNNA3, APP and BACE1 in humans might influence APP metabolism and ultimately risk of AD.

  18. 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. PMID:26187685

  19. A cautionary note on the impact of protocol changes for Genome-Wide Association SNP x SNP Interaction studies: an example on ankylosing spondylitis

    OpenAIRE

    Bessonov, Kyrylo; Gusareva, Elena; Van Steen, Kristel

    2015-01-01

    Genome-wide association interaction (GWAI) studies have increased in popularity. Yet to date, no standard protocol exists. In practice, any GWAI workflow involves making choices about quality control strategy, SNP filtering, linkage disequilibrium (LD) pruning, analytic tool to model or to test for genetic interactions. Each of these can have an impact on the final epistasis findings and may affect their reproducibility in follow-up analyses. Choosing an analytic tool is not st...

  20. A novel method to identify high order gene-gene interactions in genome-wide association studies: Gene-based MDR

    OpenAIRE

    Oh Sohee; Lee Jaehoon; Kwon Min-Seok; Weir Bruce; Ha Kyooseob; Park Taesung

    2012-01-01

    Abstract Background Because common complex diseases are affected by multiple genes and environmental factors, it is essential to investigate gene-gene and/or gene-environment interactions to understand genetic architecture of complex diseases. After the great success of large scale genome-wide association (GWA) studies using the high density single nucleotide polymorphism (SNP) chips, the study of gene-gene interaction becomes a next challenge. Multifactor dimensionality reduction (MDR) analy...

  1. QCD prediction of jet structure in 2D trigger-associated momentum correlations and implications for multiple parton interactions

    CERN Document Server

    Trainor, Thomas A

    2014-01-01

    The expression "multiple parton interactions" (MPI) denotes a conjectured QCD mechanism representing contributions from secondary (semi)hard 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 $n_{ch}$ or $p_t$ yields relative to a trigger condition (leading hadron or jet $p_t$). An alternative approach is 2D trigger-associated (TA) correlations on hadron transverse momentum $p_t$ or rapidity $y_t$ 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-\\=p fragmentation functions and a minimum-bias jet spectrum from 200 GeV p-\\=p collisions are convoluted to predict the 2D ha...

  2. Scale interaction between typhoons and the North Pacific subtropical high and associated remote effects during the Baiu/Meiyu season

    Science.gov (United States)

    Hirata, Hidetaka; Kawamura, Ryuichi

    2014-05-01

    The interaction between typhoons and the North Pacific subtropical high and the associated remote impact on East Asian and North Pacific anomalous weather during the Baiu/Meiyu season have been investigated using the Japanese long-term Reanalysis project data aided by the Japan Meteorological Agency Climate Data Assimilation System. The typhoons that appeared in July have been categorized into two primary tracks, the Hainan Island course (HC) and the Okinawa Island course (OC). A typhoon gives rise to negative absolute vorticity advection along its eastern periphery, which locally reinforces the western ridge of the North Pacific subtropical high, whereas the resultant anomalous high stimulates the westward (northward) migration of the HC (OC) typhoon through its combination with the background flow. A combined effect of the typhoon and its induced anomalous anticyclonic circulation increases the transportation of moisture into the Baiu/Meiyu frontal zone in the vicinity of Japan. Over the East China Sea and the Sea of Japan, northward or northeastward moisture flux is pronounced along the western periphery of the typhoon-induced anticyclonic circulation anomaly in the HC category, triggering heavy rainfall on central Japan's Sea of Japan coast. Similar remote effects also operate in the OC category, which is responsible for the occurrence of extremely heavy rainfall along the Pacific coast of western Japan. When an OC typhoon approaches the Asian jet, it is capable of giving rise to anticyclonic vorticity within the jet, leading to the downstream development of stationary Rossby wave packets via the North Pacific waveguide.

  3. Genetic variants associated with circulating MMP1 levels near matrix metalloproteinase genes on chromosome 11q21-22 in Taiwanese: interaction with obesity

    Science.gov (United States)

    2013-01-01

    Background MMP1 is implicated in the pathogenesis of atherothrombotic cardiovascular disease. We aimed to elucidate genetic determinants of inflammatory marker levels, including circulating MMP1, in Taiwanese, and their association with obesity. Methods Five genetic polymorphisms around matrix metalloproteinase genes on chromosome 11q21-22 region were genotyped in 519 subjects. Results After adjusting for clinical covariates, two polymorphisms were significantly associated with MMP1 levels, rs1799750 and rs495366, using an additive inheritance model (P = 1.5x10-4 and P = 2.57x10-5, respectively). Using dominant model, minor alleles of rs1799750 and rs495366 were associated with higher MMP1 levels (P = 1.3x10-4 and P = 1.95x10-5, respectively). In haplotype analysis, two haplotypes inferred from five SNPs (A2GATA and A1GATG) were associated with MMP1 levels (P = 5x10-4 and P = 8.47x10-5, respectively). Subgroup and interaction analysis revealed an association of rs1799750 and rs495366 with MMP1 levels only in non-obese subjects (P = 6.66x10-6 and P = 4.38x10-5, respectively, and interaction P = 0.008 for rs1799750). Haplotype interaction analysis also showed significant interaction for haplotype A1GATG (interaction P = 0.003). Conclusions Genotypes/haplotypes around MMP1 locus are associated with MMP1 levels in Taiwanese. Further, since genotypes/haplotypes near MMP1 locus interact with obesity to set MMP1 levels, genetic determinants for MMP1 level may be different between obese and non-obese individuals. PMID:23497408

  4. The Association between Parental Interaction Style and Children's Joint Engagement in Families with Toddlers with Autism

    Science.gov (United States)

    Patterson, Stephanie Y.; Elder, Lauren; Gulsrud, Amanda; Kasari, Connie

    2014-01-01

    Purpose: This study examines the relationship between parental interaction style (responsive vs directive) and child-initiated joint engagement within caregiver-child interactions with toddlers diagnosed with autism spectrum disorders. Method: Videotaped interactions of 85 toddler-caregiver dyads were coded for child engagement and both parental…

  5. 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

    overall structure of the domain. Analysis of Plau(GFDhu/GFDhu) mice revealed an unanticipated role of the uPA-uPAR interaction in suppressing inflammation secondary to fibrin deposition. In contrast, leukocyte recruitment and tissue regeneration were unaffected by the loss of uPA binding to uPAR. This...... study identifies a principal in vivo role of the uPA-uPAR interaction in cell-associated fibrinolysis critical for suppression of fibrin accumulation and fibrin-associated inflammation and provides a valuable model for further exploration of this multifunctional receptor....

  6. Haemophilus haemolyticus interaction with host cells is different to nontypeable Haemophilus influenzae and prevents NTHi association with epithelial cells

    Directory of Open Access Journals (Sweden)

    Janessa Lea Pickering

    2016-05-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-02-18

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

  8. Individual Differences in Response Speed and Accuracy are Associated to Specific Brain Activities of two Interacting Systems

    Directory of Open Access Journals (Sweden)

    Rinaldo Livio ePerri

    2014-07-01

    Full Text Available The study investigates the neurocognitive stages involved in the speed-accuracy trade-off (SAT. Contrary to previous approach, we did not manipulate speed and accuracy instructions: participants were required to be fast and accurate in a go/no-go task, and we selected post-hoc the groups based on the subjects’ spontaneous behavioral tendency. Based on the reaction times, we selected the fast and slow groups (Speed-groups, and based on the percentage of false alarms, we selected the accurate and inaccurate groups (Accuracy-groups. The two Speed-groups were accuracy-matched, and the two Accuracy-groups were speed-matched. High density EEG and stimulus-locked analyses allowed us to observe group differences both before and after the stimulus onset. Long before the stimulus appearance, the two Speed-groups showed different amplitude of the Bereitschaftspotential (BP, reflecting the activity of the supplementary motor area (SMA; by contrast, the two Accuracy-groups showed different amplitude of the prefrontal negativity (pN, reflecting the activity of the right prefrontal cortex (rPFC. In addition, the post-stimulus event-related potential (ERP components showed differences between groups: the P1 component was larger in accurate than inaccurate group; the N1 and N2 components were larger in the fast than slow group; the P3 component started earlier and was larger in the fast than slow group. The go minus no-go subtractive wave enhancing go-related processing revealed a differential prefrontal positivity (dpP that peaked at about 330 ms; the latency and the amplitude of this peak were associated with the speed of the decision process and the efficiency of the stimulus-response mapping, respectively. Overall, data are consistent with the view that speed and accuracy are processed by two interacting but separate neurocognitive systems, with different features in both the anticipation and the response execution phases.

  9. A kinetic analysis of the tumor-associated galactopyranosyl-(1→3)-2-acetamido-2-deoxy--D-galactopyranoside antigen-lectin interaction

    Indian Academy of Sciences (India)

    Bandaru Narasimha Murthy; Narayanaswamy Jayaraman

    2008-01-01

    A kinetic study of the tumor-associated galactopyranosyl-(1→3)-2-acetamido-2-deoxy--Dgalactopyranoside (T-antigen) with lectin peanut agglutinin is described. The disaccharide antigen was synthesized by chemical methods and was functionalized suitably for immobilization onto a carboxymethylated sensor chip. The ligand immobilized surface was allowed interaction with the lectin peanut agglutinin, which acted as the analyte and the interaction was studied by the surface plasmon resonance method. The ligand-lectin interaction was characterized by the kinetic on-off rates and a bivalent analyte binding model was found to describe the observed kinetic constants. It was identified that the antigen-lectin interaction had a faster association rate constant (a1) and a slower dissociation rate constant (d1) in the initial binding step. The subsequent binding step showed much reduced kinetic rates. The antigen-lectin interaction was compared with the kinetic rates of the interaction of a galactopyranosyl-(1→ 4)--D-galactopyranoside derivative and a mannopyranoside derivative with the lectin.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    Science.gov (United States)

    Andreou, Eleni; Didaskalou, Eleni; Vlachou, Anastasia

    2015-01-01

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

  12. A Quantitative Genetic Analysis of the Associations among Language Skills, Peer Interactions, and Behavioral Problems in Childhood: Results from a Sample of Twins

    Science.gov (United States)

    Beaver, Kevin M.; Boutwell, Brian B.; Barnes, J. C.; Schwartz, Joseph A.; Connolly, Eric J.

    2014-01-01

    A body of empirical research has revealed that there are associations among language skills, peer interactions, and behavioral problems in childhood. At the same time, however, there has been comparatively less research devoted to exploring the mutual unfolding of these factors over the first few years of life. The current study is designed to…

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

    Directory of Open Access Journals (Sweden)

    Joseph Ahlander

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

  14. It's Not Just Your Goal, but Also Who You Know: How the Cognitive Associations among Goals and Relationships Influence Goal Detection in Social Interaction

    Science.gov (United States)

    Palomares, Nicholas A.

    2009-01-01

    An experiment tested a theoretical framework for goal detection in dyadic interactions of close friends and unacquainted strangers wherein one conversationalist pursued a goal unbeknownst to a detector. The extent to which pursuers' conversation goal was cognitively associated with the dyad's relational type was manipulated. As hypothesized,…

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

    DEFF Research Database (Denmark)

    Plantard, Laure; Huber, Marcel; Macari, Francoise;

    2003-01-01

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

  16. The Association of Peroxisome Proliferator-Activated Receptor δ and Additional Gene-Gene Interaction with C-Reactive Protein in Chinese Population

    Directory of Open Access Journals (Sweden)

    Xiao-Ying Ding

    2016-01-01

    Full Text Available Aims. To examine the association between 4 single nucleotide polymorphisms (SNPs of peroxisome proliferator-activated receptors δ (PPARδ polymorphisms and C-reactive protein (CRP level and additional gene-gene interaction. Methods. Line regression analysis was performed to verify polymorphism association between SNP and CRP levels. Generalized multifactor dimensionality reduction (GMDR was employed to analyze the interaction. Results. A total of 1028 subjects (538 men, 490 women were selected. The carriers of the C allele (TC or CC of rs2016520 were associated with a significant decreased level of CRP, regression coefficients was −0.338, and standard error was 0.104 (p=0.001. The carriers of the G allele (CG or GG of rs9794 were also significantly associated with decreased level of CRP, regression coefficients was −0.219, and standard error was 0.114 (p=0.012. We also found a potential gene-gene interaction between rs2016520 and rs9794. Subjects with rs2016520-TC or CC, rs9794-CG or GG genotypes have lowest CRP level, difference (95% CI = −0.50 (−0.69 to −0.21 (p<0.001, compared to subjects with rs2016520-TT and rs9794-CC genotypes. Conclusions. rs2016520 and rs9794 minor allele of PPARδ and combined effect between the two SNP were associated with decreased CRP level.

  17. 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

    Science.gov (United States)

    Kukielka, Esther A.; Jori, Ferran; Martínez-López, Beatriz; Chenais, Erika; Masembe, Charles; Chavernac, David; Ståhl, Karl

    2016-01-01

    Bushpigs (BPs) (Potamochoerus larvatus) and warthogs (WHs) (Phacochoerus africanus), which are widely distributed in Eastern Africa, are likely to cohabitate in the same environment with domestic pigs (DPs), facilitating the transmission of shared pathogens. However, potential interactions between BP, WH, and DP, 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 DP interactions, non-linear 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 African swine fever (ASF) outbreaks. No direct interactions between wild pigs (WPs) and DP 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 DP to raw hunting leftovers of WPs. 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 WH burrow less than 3 km from the household. Our study was useful to gather local knowledge and to identify knowledge gaps about potential interactions between wild and DP 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 DPs. PMID:27148545

  18. 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

  19. 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.

    Science.gov (United States)

    Kukielka, Esther A; Jori, Ferran; Martínez-López, Beatriz; Chenais, Erika; Masembe, Charles; Chavernac, David; Ståhl, Karl

    2016-01-01

    Bushpigs (BPs) (Potamochoerus larvatus) and warthogs (WHs) (Phacochoerus africanus), which are widely distributed in Eastern Africa, are likely to cohabitate in the same environment with domestic pigs (DPs), facilitating the transmission of shared pathogens. However, potential interactions between BP, WH, and DP, 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 DP interactions, non-linear 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 African swine fever (ASF) outbreaks. No direct interactions between wild pigs (WPs) and DP 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 DP to raw hunting leftovers of WPs. 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 WH burrow less than 3 km from the household. Our study was useful to gather local knowledge and to identify knowledge gaps about potential interactions between wild and DP 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 DPs. PMID:27148545

  20. Correcting for the study bias associated with protein-protein interaction measurements reveals differences between protein degree distributions from different cancer types.

    Science.gov (United States)

    Schaefer, Martin H; Serrano, Luis; Andrade-Navarro, Miguel A

    2015-01-01

    Protein-protein interaction (PPI) networks are associated with multiple types of biases partly rooted in technical limitations of the experimental techniques. Another source of bias are the different frequencies with which proteins have been studied for interaction partners. It is generally believed that proteins with a large number of interaction partners tend to be essential, evolutionarily conserved, and involved in disease. It has been repeatedly reported that proteins driving tumor formation have a higher number of PPI partners. However, it has been noticed before that the degree distribution of PPI networks is biased toward disease proteins, which tend to have been studied more often than non-disease proteins. At the same time, for many poorly characterized proteins no interactions have been reported yet. It is unclear to which extent this study bias affects the observation that cancer proteins tend to have more PPI partners. Here, we show that the degree of a protein is a function of the number of times it has been screened for interaction partners. We present a randomization-based method that controls for this bias to decide whether a group of proteins is associated with significantly more PPI partners than the proteomic background. We apply our method to cancer proteins and observe, in contrast to previous studies, no conclusive evidence for a significantly higher degree distribution associated with cancer proteins as compared to non-cancer proteins when we compare them to proteins that have been equally often studied as bait proteins. Comparing proteins from different tumor types, a more complex picture emerges in which proteins of certain cancer classes have significantly more interaction partners while others are associated with a smaller degree. For example, proteins of several hematological cancers tend to be associated with a higher number of interaction partners as expected by chance. Solid tumors, in contrast, are usually associated with a degree

  1. Supramolecular association via Sb...S and C-H...S interactions in dimeric tris(N,N-dimethyldithiocarbamato-S,S')antimony(III): an approach to overcome the concept of steric bulk on such interactions.

    Science.gov (United States)

    Chauhan, H P S; Carpenter, Jaswant

    2013-12-01

    Tris(N,N-dimethyldithiocarbamato-S,S')antimony(III) has been isolated as a dimer in acetonitrile. Single-crystal X-ray analysis shows that the molecule possesses both Sb···S and C-H···S interactions, which results in a supramolecular association in the absence of hydrogen-bonding functionality on the R group. The co-existence in the title compound of such interactions is a unique character of known dimeric antimony(III) alkyl and/or aryl dithiocarbamate complexes. The literature reveals that the species where the alkyl and/or aryl dithiocarbamates carry the following groups: R = methyl (chloroform solvated), ethyl, n-propyl, pyrrolidine, morpholine, piperidine, azepane, benzyl, methylphenyl, are not capable of forming significant hydrogen-bonding interactions. However, either Sb···S or C-H···S intermolecular interactions dominate between two centrosymmetrically related molecules leading to a supramolecular aggregation. In the species where the R group carries hydrogen-bonding functionality, i.e. 2-hydroxylethyl, the C-H···S interactions are subverted by O-H···O hydrogen bonding. In addition, the title compound does not have steric hindrance or any hydrogen-bonding group but is stabilized with the co-existence of Sb···S and C-H···S interactions. Analysis of the secondary interactions of a series of analogues previously reported reveals that steric bulk is unnecessary for the mitigation of Sb···S interactions and for the establishment of C-H···S secondary bonding. PMID:24253087

  2. High Order Gene-Gene Interactions in Eight Single Nucleotide Polymorphisms of Renin-Angiotensin System Genes for Hypertension Association Study

    Directory of Open Access Journals (Sweden)

    Cheng-Hong Yang

    2015-01-01

    Full Text Available Several single nucleotide polymorphisms (SNPs of renin-angiotensin system (RAS genes are associated with hypertension (HT but most of them are focusing on single locus effects. Here, we introduce an unbalanced function based on multifactor dimensionality reduction (MDR for multiloci genotypes to detect high order gene-gene (SNP-SNP interaction in unbalanced cases and controls of HT data. Eight SNPs of three RAS genes (angiotensinogen, AGT; angiotensin-converting enzyme, ACE; angiotensin II type 1 receptor, AT1R in HT and non-HT subjects were included that showed no significant genotype differences. In 2- to 6-locus models of the SNP-SNP interaction, the SNPs of AGT and ACE genes were associated with hypertension (bootstrapping odds ratio [Boot-OR] = 1.972~3.785; 95%, confidence interval (CI 1.26~6.21; P<0.005. In 7- and 8-locus model, SNP A1166C of AT1R gene is joined to improve the maximum Boot-OR values of 4.050 to 4.483; CI = 2.49 to 7.29; P<1.63E−08. In conclusion, the epistasis networks are identified by eight SNP-SNP interaction models. AGT, ACE, and AT1R genes have overall effects with susceptibility to hypertension, where the SNPs of ACE have a mainly hypertension-associated effect and show an interacting effect to SNPs of AGT and AT1R genes.

  3. 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 wave

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    The urokinase plasminogen activator receptor-associated protein/Endo180 (uPARAP/Endo180) is a newly discovered member of the macrophage mannose receptor family that was reported to interact with ligand-bound urokinase plasminogen activator receptor (uPAR), matrix metalloprotease-13 (MMP-13), and ......, uPARAP/Endo180 expression was detected only in a mesenchymal condensation of the midbrain and in the developing lungs. The data suggest a function of this novel protease receptor in bone development, possibly mediated through its interactions with uPAR, MMP-13, or collagen V....

  5. 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 BACKGROUND: 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. METHODS AND FINDINGS: 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

  6. 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.

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

    Science.gov (United States)

    Miwa, Naofumi

    2015-05-22

    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.

  8. Metagenome Survey of a Multispecies and Alga-Associated Biofilm Revealed Key Elements of Bacterial-Algal Interactions in Photobioreactors

    OpenAIRE

    Krohn-Molt, Ines; Wemheuer, Bernd; Alawi, Malik; Poehlein, Anja; Güllert, Simon; Schmeisser, Christel; Pommerening-Röser, Andreas; Grundhoff, Adam; Daniel, Rolf; Hanelt, Dieter; Wolfgang R Streit

    2013-01-01

    Photobioreactors (PBRs) are very attractive for sunlight-driven production of biofuels and capturing of anthropogenic CO2. One major problem associated with PBRs however, is that the bacteria usually associated with microalgae in nonaxenic cultures can lead to biofouling and thereby affect algal productivity. Here, we report on a phylogenetic, metagenome, and functional analysis of a mixed-species bacterial biofilm associated with the microalgae Chlorella vulgaris and Scenedesmus obliquus in ...

  9. Nucleotide excision repair is associated with the replisome and its efficiency depends on a direct interaction between XPA and PCNA.

    Directory of Open Access Journals (Sweden)

    Karin M Gilljam

    Full Text Available Proliferating cell nuclear antigen (PCNA is an essential protein for DNA replication, DNA repair, cell cycle regulation, chromatin remodeling, and epigenetics. Many proteins interact with PCNA through the PCNA interacting peptide (PIP-box or the newly identified AlkB homolog 2 PCNA interacting motif (APIM. The xeroderma pigmentosum group A (XPA protein, with a central but somewhat elusive role in nucleotide excision repair (NER, contains the APIM sequence suggesting an interaction with PCNA. With an in vivo based approach, using modern techniques in live human cells, we show that APIM in XPA is a functional PCNA interacting motif and that efficient NER of UV lesions is dependent on an intact APIM sequence in XPA. We show that XPA(-/- cells complemented with XPA containing a mutated APIM sequence have increased UV sensitivity, reduced repair of cyclobutane pyrimidine dimers and (6-4 photoproducts, and are consequently more arrested in S phase as compared to XPA(-/- cells complemented with wild type XPA. Notably, XPA colocalizes with PCNA in replication foci and is loaded on newly synthesized DNA in undamaged cells. In addition, the TFIIH subunit XPD, as well as XPF are loaded on DNA together with XPA, and XPC and XPG colocalize with PCNA in replication foci. Altogether, our results suggest a presence of the NER complex in the vicinity of the replisome and a novel role of NER in post-replicative repair.

  10. Stromal response to prostate cancer: nanotechnology-based detection of thioredoxin-interacting protein partners distinguishes prostate cancer associated stroma from that of benign prostatic hyperplasia.

    Directory of Open Access Journals (Sweden)

    Elizabeth Singer

    Full Text Available Histological staining of reactive stroma has been shown to be a predictor of biochemical recurrence in prostate cancer, however, molecular markers of the stromal response to prostate cancer have not yet been fully delineated. The objective of this study was to determine whether or not the stromal biomarkers detected with a thioredoxin-targeted nanodevice could be used to distinguish the stroma associated with benign prostatic hyperplasia from that associated with PCA. In this regard, we recently demonstrated that a thioredoxin-targeted nanodevice selectively binds to reactive stroma in frozen prostate tumor tissue sections. To accomplish this, random frozen prostate tissue sections from each of 35 patients who underwent resection were incubated with the nanodevice and graded for fluorescent intensity. An adjacent section from each case was stained with Hematoxylin & Eosin to confirm the diagnosis. Select cases were stained with Masson's Trichrome or immunohistochemically using antibodies to thioredoxin reductase 1, thioredoxin reductase 2 or peroxiredoxin 1. Our results demonstrate that the graded intensity of nanodevice binding to the stroma associated with PCA was significantly higher (p = 0.0127 than that of benign prostatic hyperplasia using the t-test. Immunohistochemical staining of adjacent sections in representative cases showed that none of the two commonly studied thioredoxin interacting protein partners mirrored the fluorescence pattern seen with the nanodevice. However, thioredoxin reductase 2 protein was clearly shown to be a biomarker of prostate cancer-associated reactive stroma whose presence distinguishes the stroma associated with benign prostatic hyperplasia from that associated with prostate cancer. We conclude that the signal detected by the nanodevice, in contrast to individual targets detected with antibodies used in this study, originates from multiple thioredoxin interacting protein partners that distinguish the M2

  11. 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

    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......(nominal) ¿=¿0.0008). Significant interaction between maternal HSV-2 seropositivity and GRIN2B genetic variation in the offspring were observed for seven SNPs and two remained significant after Bonferroni correction (rs1805539, P(nominal) ¿=¿0.0001 and rs1806205, P(nominal) ¿=¿0.0008). The significant...... associations and interactions were located at the 3' region of GRIN2B suggesting that genetic variation in this part of the gene may be involved in the pathophysiology of schizophrenia. © 2011 Wiley Periodicals, Inc....

  12. Large Deviations for Finite State Markov Jump Processes with Mean-Field Interaction Via the Comparison Principle for an Associated Hamilton-Jacobi Equation

    Science.gov (United States)

    Kraaij, Richard

    2016-07-01

    We prove the large deviation principle (LDP) for the trajectory of a broad class of finite state mean-field interacting Markov jump processes via a general analytic approach based on viscosity solutions. Examples include generalized Ehrenfest models as well as Curie-Weiss spin flip dynamics with singular jump rates. The main step in the proof of the LDP, which is of independent interest, is the proof of the comparison principle for an associated collection of Hamilton-Jacobi equations. Additionally, we show that the LDP provides a general method to identify a Lyapunov function for the associated McKean-Vlasov equation.

  13. Identification of CXCL5/ENA-78 as a factor involved in the interaction between cholangiocarcinoma cells and cancer-associated fibroblasts.

    Science.gov (United States)

    Okabe, Hirohisa; Beppu, Toru; Ueda, Mitsuharu; Hayashi, Hiromitsu; Ishiko, Takatoshi; Masuda, Toshiro; Otao, Ryu; Horlad, Hasita; Mima, Kosuke; Miyake, Keisuke; Iwatsuki, Masaaki; Baba, Yoshifumi; Takamori, Hiroshi; Jono, Hirofumi; Shinriki, Satoru; Ando, Yukio; Baba, Hideo

    2012-11-15

    Knowledge of tumor-stromal interactions is essential for understanding tumor development. We focused on the interaction between cholangiocarcinoma and cancer-associated fibroblasts (CAFs) in intrahepatic cholangiocarcinoma and reported their positive interaction in vitro and in vivo. The aim of this study is to identify the key protein involved in the interaction between cholangiocarcinoma cells and CAFs and its role on cholangiocarcinoma progression. Using the conditioning medium from cholangiocarcinoma cells, hepatic stellate cells and coculture of them, Protein-Chip analysis with SELDI-TOF-MS showed that the peak of an 8,360-Da protein remarkably increased in the coculture medium. This protein was identified as CXCL5/ENA78, epithelial cell-derived neutrophil-activating peptide-78, by q-TOF/MS/MS analysis. Two cholangiocarcinoma cell lines, HuCCT1 and RBE, produced CXCL5 that promoted their invasion and migration in an autocrine fashion. These effects of CXCL5 significantly decreased by inhibition of CXC-receptor 2, which is the receptor for CXCL5. In addition, IL-1β produced by hepatic stellate cells induced the expression of CXCL5 in cholangiocarcinoma cells. In human tissue samples, a significant correlation was observed between CAFs and CXCL5 produced by cholangiocarcinoma cells in intrahepatic cholangiocarcinoma (p = 0.0044). Furthermore, the high-CXCL5-expression group exhibited poor overall survival after curative hepatic resection (p = 0.027). The presence of tumor-infiltrating neutrophils expressing CD66b was associated with CXCL5 expression in tumor cells (p < 0.0001). These data suggest that CXCL5 is important for the interaction between cholangiocarcinoma and CAFs, and inhibition of tumor-stromal interactions may be a useful therapeutic approach for cholangiocarcinoma.

  14. 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...

  15. Extent of poly-pharmacy, occurrence and associated factors of drug-drug interaction and potential adverse drug reactions in Gondar Teaching Referral Hospital, North West Ethiopia

    OpenAIRE

    Endalkachew Admassie; Tesfahun Melese; Woldeselassie Mequanent; Wubshet Hailu; B Akshaya Srikanth

    2013-01-01

    The aim of this study was to assess the extent of poly-pharmacy, occurrence, and associated factors for the occurrence of drug–drug interaction (DDI) and potential adverse drug reaction (ADR) in Gondar University Teaching Referral Hospital. Institutional-based retrospective cross-sectional study. This study was conducted on prescriptions of both in and out-patients for a period of 3 months at Gondar University Hospital. Both bivariate analysis and multivariate logistic regression were used to...

  16. Critical Temperature Associated to Symmetry Breaking of Klein--Gordon fields versus Condensation Temperature in a Weakly interacting Bose--Einstein Gas

    CERN Document Server

    Castellanos, Elias

    2012-01-01

    We deduce the relation between the critical temperature associated to the U(1) symmetry breaking of scalar fields with one--loop correction potential immersed in a thermal bath, and the condensation temperature of the aforementioned system in the thermodynamic limit, within the semiclassical approximation for a weakly interacting bosonic gas with a positive coupling constant. Additionally, we show that the shift in the condensation temperature caused by the coupling constant is independent of the thermal bath.

  17. Maternal Literacy Beliefs and the Quality of Mother-Child Book-Reading Interactions: Associations with Children's Early Literacy Development

    Science.gov (United States)

    Bingham, Gary E.

    2007-01-01

    This study examined the relation among mothers' literacy-related beliefs, the home literacy environment, the quality of mother-child book-reading interactions, and children's development of early literacy skills. The participants of this study were 60 mothers and their 4-year-old children. After controlling for mothers' educational attainment,…

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

    NARCIS (Netherlands)

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

    2013-01-01

    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 l

  19. 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…

  20. 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.…

  1. Interaction of structural core protein of Classical Swine Fever Virus with endoplasmic reticulum-associated degradation pathway protein OS9

    Science.gov (United States)

    Classical Swine Fever Virus (CSFV) Core protein is involved in virus RNA protection, transcription regulation and virus virulence. To discover additional Core protein functions a yeast two-hybrid system was used to identify host proteins that interact with Core. Among the identified host proteins, t...

  2. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the Breast Cancer Association Consortium: a combined case-control study.

    OpenAIRE

    Milne, Roger L.; Gaudet, Mia M.; Spurdle, Amanda B.; Fasching, Peter A.; Couch, Fergus J.; Benitez, Javier; Arias Perez, Jose Ignacio; Zamora, Maria Pilar; Malats, Nuria; dos Santos Silva, Isabel; Gibson, Lorna J.; Fletcher, Olivia; Johnson, Nichola; Anton-Culver, Hoda; Ziogas, Argyrios

    2010-01-01

    Abstract Introduction Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. Methods We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of liv...

  3. Thioflavin S (NSC71948) interferes with Bcl-2-associated athanogene (BAG-1)-mediated protein-protein interactions.

    Science.gov (United States)

    Sharp, Adam; Crabb, Simon J; Johnson, Peter W M; Hague, Angela; Cutress, Ramsey; Townsend, Paul A; Ganesan, A; Packham, Graham

    2009-11-01

    The C-terminal BAG domain is thought to play a key role in BAG-1-induced survival and proliferation by mediating protein-protein interactions, for example, with heat shock proteins HSC70 and HSP70, and with RAF-1 kinase. Here, we have identified thioflavin S (NSC71948) as a potential small-molecule chemical inhibitor of these interactions. NSC71948 inhibited the interaction of BAG-1 and HSC70 in vitro and decreased BAG-1:HSC70 and BAG-1:HSP70 binding in intact cells. NSC71948 also reduced binding between BAG-1 and RAF-1, but had no effect on the interaction between two unrelated proteins, BIM and MCL-1. NSC71948 functionally reversed the ability of BAG-1 to promote vitamin D3 receptor-mediated transactivation, an activity of BAG-1 that depends on HSC70/HSP70 binding, and reduced phosphorylation of p44/42 mitogen-activate protein kinase. NSC71948 can be used to stain amyloid fibrils; however, structurally related compounds, thioflavin T and BTA-1, had no effect on BAG-1:HSC70 binding, suggesting that structural features important for amyloid fibril binding and inhibition of BAG-1:HSC70 binding may be separable. We demonstrated that NSC71948 inhibited the growth of BAG-1 expressing human ZR-75-1 breast cancer cells and wild-type, but not BAG-1-deficient, mouse embryo fibroblasts. Taken together, these data suggest that NSC71948 may be a useful molecule to investigate the functional significance of BAG-1 C-terminal protein interactions. However, it is important to recognize that NSC71948 may exert additional "off-target" effects. Inhibition of BAG-1 function may be an attractive strategy to inhibit the growth of BAG-1-overexpressing cancers, and further screens of additional compound collections may be warranted.

  4. FRET based quantification and screening technology platform for the interactions of leukocyte function-associated antigen-1 (LFA-1 with intercellular adhesion molecule-1 (ICAM-1.

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    Sandeep Chakraborty

    Full Text Available The interaction between leukocyte function-associated antigen-1(LFA-1 and intercellular adhesion molecule-1 (ICAM-1 plays a pivotal role in cellular adhesion including the extravasation and inflammatory response of leukocytes, and also in the formation of immunological synapse. However, irregular expressions of LFA-1 or ICAM-1 or both may lead to autoimmune diseases, metastasis cancer, etc. Thus, the LFA-1/ICAM-1 interaction may serve as a potential therapeutic target for the treatment of these diseases. Here, we developed one simple 'in solution' steady state fluorescence resonance energy transfer (FRET technique to obtain the dissociation constant (Kd of the interaction between LFA-1 and ICAM-1. Moreover, we developed the assay into a screening platform to identify peptides and small molecules that inhibit the LFA-1/ICAM-1 interaction. For the FRET pair, we used Alexa Fluor 488-LFA-1 conjugate as donor and Alexa Fluor 555-human recombinant ICAM-1 (D1-D2-Fc as acceptor. From our quantitative FRET analysis, the Kd between LFA-1 and D1-D2-Fc was determined to be 17.93±1.34 nM. Both the Kd determination and screening assay were performed in a 96-well plate platform, providing the opportunity to develop it into a high-throughput assay. This is the first reported work which applies FRET based technique to determine Kd as well as classifying inhibitors of the LFA-1/ICAM-1 interaction.

  5. Genetic Association and Gene-gene interaction of HAS2, HABP1 and HYAL3 Implicate Hyaluronan Metabolic Genes in Glaucomatous Neurodegeneration

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    Kaustuv Basu

    2012-01-01

    Full Text Available Hyaluronan (HA plays a significant role in maintaining aqueous humor outflow in trabecular meshwork, the primary ocular tissue involved in glaucoma. We examined potential association of the single nucleotide polymorphisms (SNPs of the HA synthesizing gene – hyaluronan synthase 2 (HAS2, hyaluronan binding protein 1 (HABP1 and HA catabolic gene hyaluronidase 3 (HYAL3 in the primary open angle glaucoma (POAG patients in the Indian population. Thirteen tagged SNPs (6 for HAS2, 3 for HABP1 and 4 for HYAL3 were genotyped in 116 high tension (HTG, 321 non-high tension glaucoma (NHTG samples and 96 unrelated, age-matched, glaucoma-negative, control samples. Allelic and genotypic association were analyzed by PLINK v1.04; haplotypes were identified using PHASE v2.1 and gene-gene interaction was analyzed using multifactor dimensionality reduction (MDR v2.0. An allelic association (rs6651224; p = 0.03; OR: 0.49; 95% CI: 0.25–0.94 was observed at the second intron (C>G of HAS2 both for NHTG and HTG. rs1057308 revealed a genotypic association (p = 0.03 at the 5’ UTR of HAS2 with only HTG. TCT haplotype (rs1805429 – rs2472614 – rs8072363 in HABP1 and TTAG and TTGA (rs2285044 – rs3774753 – rs1310073 – rs1076872 in HYAL3 were found to be significantly high (p < 0.05 both for HTG and NHTG compared to controls. Gene-gene interaction revealed HABP1 predominantly interacts with HAS2 in HTG while it associates with both HYAL3 and HAS2 in NHTG. This is the first genetic evidence, albeit from a smaller study, that the natural polymorphisms in the genes involved in hyaluronan metabolism are potentially involved in glaucomatous neurodegeneration.

  6. Adherence is associated with the quality of professional-patient interaction in Directly Observed Treatment Short-course, DOTS

    DEFF Research Database (Denmark)

    Mishra, Pranaya; Hansen, Ebba Holme; Sabroe, Svend;

    2006-01-01

    : Better communication between health professionals, particularly dispensers, and patients is essential for improving treatment adherence in TB treatment, even under DOTS. PRACTICE IMPLICATIONS: Drug dispensers should be trained to develop their communication skills about the use of medications, associated...

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

    OpenAIRE

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

    2016-01-01

    Seaweed-dominated coral reefs are becoming increasingly common as environmental conditions shift away from those required by corals and toward those ideal for rampant seaweed growth. How coral-associated organisms respond to seaweed will not only impact their fate following environmental change but potentially also the trajectories of the coral communities on which they rely. However, behavioral responses by coral-associated organisms to seaweeds are poorly understood. This study examined int...

  8. Ancient interaction between the teneurin C-terminal associated peptides (TCAP and latrophilin ligand-receptor coupling: A role in behaviour

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    Rebecca eWoelfle

    2015-04-01

    Full Text Available Teneurins are multifunctional transmembrane proteins that are found in all multicellular animals and exist as four paralogous forms in vertebrates. They are highly expressed in the central nervous system, where they exert their effects, in part, by high-affinity binding to latrophilin (LPHN, a G-protein coupled receptor (GPCR related to the adhesion and secretin GPCR families. The teneurin C-terminal associated peptides (TCAPs are encoded by the terminal exon of all four teneurins, where TCAPs 1 and 3 are independently transcribed as soluble peptides, and TCAPs 2 and 4 remain tethered to their teneurin proprotein. Synthetic TCAP-1 interacts with LPHN, with an association with β-dystroglycan to induce a tissue-dependent signal cascade to modulate cytoskeletal dynamics. TCAP-1 reduces stress-induced behaviours associated with anxiety, addiction and depression in a variety of models, in part, by regulating synaptic plasticity. Therefore, the TCAP-1-teneurin-LPHN interaction represents a novel receptor-ligand model and may represent a key mechanism underlying the association of behaviour and neurological conditions.

  9. 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

    2016-09-01

    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. PMID:27636465

  10. Older Age and Steroid Use Are Associated with Increasing Polypharmacy and Potential Medication Interactions Among Patients with Inflammatory Bowel Disease

    OpenAIRE

    Parian, Alyssa; Ha, Christina Y.

    2015-01-01

    Background: Comorbidity and polypharmacy, more prevalent among older persons, may impact the treatment of patients with inflammatory bowel disease (IBD). The aims of this study were to assess the frequency of polypharmacy and medication interactions within a cohort of older patients with IBD and describe IBD treatment patterns. Methods: Cohort study of 190 patients with IBD 65 years or older followed at a tertiary IBD referral center from 2006 to 2012. Data collected included demographics, IB...

  11. 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.

  12. 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.

  13. 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.

  14. 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. PMID:26487785

  15. Bacterial- and plant-type phosphoenolpyruvate carboxylase isozymes from developing castor oil seeds interact in vivo and associate with the surface of mitochondria.

    Science.gov (United States)

    Park, Joonho; Khuu, Nicholas; Howard, Alexander S M; Mullen, Robert T; Plaxton, William C

    2012-07-01

    Phosphoenolpyruvate carboxylase (PEPC) from developing castor oil seeds (COS) exists as two distinct oligomeric isoforms. The typical class-1 PEPC homotetramer consists of 107-kDa plant-type PEPC (PTPC) subunits, whereas the allosterically desensitized 910-kDa class-2 PEPC hetero-octamer arises from the association of class-1 PEPC with 118-kDa bacterial-type PEPC (BTPC) subunits. The in vivo interaction and subcellular location of COS BTPC and PTPC were assessed by imaging fluorescent protein (FP)-tagged PEPCs in tobacco suspension-cultured cells. The BTPC-FP mainly localized to cytoplasmic punctate/globular structures, identified as mitochondria by co-immunostaining of endogenous cytochrome oxidase. Inhibition of respiration with KCN resulted in proportional decreases and increases in mitochondrial versus cytosolic BTPC-FP, respectively. The FP-PTPC and NLS-FP-PTPC (containing an appended nuclear localization signal, NLS) localized to the cytosol and nucleus, respectively, but both co-localized with mitochondrial-associated BTPC when co-expressed with BTPC-FP. Transmission electron microscopy of immunogold-labeled developing COS revealed that BTPC and PTPC are localized at the mitochondrial (outer) envelope, as well as the cytosol. Moreover, thermolysin-sensitive BTPC and PTPC polypeptides were detected on immunoblots of purified COS mitochondria. Overall, our results demonstrate that: (i) COS BTPC and PTPC interact in vivo as a class-2 PEPC complex that associates with the surface of mitochondria, (ii) BTPC's unique and divergent intrinsically disordered region mediates its interaction with PTPC, whereas (iii) the PTPC-containing class-1 PEPC is entirely cytosolic. We hypothesize that mitochondrial-associated class-2 PEPC facilitates rapid refixation of respiratory CO(2) while sustaining a large anaplerotic flux to replenish tricarboxylic acid cycle C-skeletons withdrawn for biosynthesis.

  16. Breast cancer-associated high-order SNP-SNP interaction of CXCL12/CXCR4-related genes by an improved multifactor dimensionality reduction (MDR-ER).

    Science.gov (United States)

    Fu, Ou-Yang; Chang, Hsueh-Wei; Lin, Yu-Da; Chuang, Li-Yeh; Hou, Ming-Feng; Yang, Cheng-Hong

    2016-09-01

    In association studies, the combined effects of single nucleotide polymorphism (SNP)-SNP interactions and the problem of imbalanced data between cases and controls are frequently ignored. In the present study, we used an improved multifactor dimensionality reduction (MDR) approach namely MDR-ER to detect the high order SNP‑SNP interaction in an imbalanced breast cancer data set containing seven SNPs of chemokine CXCL12/CXCR4 pathway genes. Most individual SNPs were not significantly associated with breast cancer. After MDR‑ER analysis, six significant SNP‑SNP interaction models with seven genes (highest cross‑validation consistency, 10; classification error rates, 41.3‑21.0; and prediction error rates, 47.4‑55.3) were identified. CD4 and VEGFA genes were associated in a 2‑loci interaction model (classification error rate, 41.3; prediction error rate, 47.5; odds ratio (OR), 2.069; 95% bootstrap CI, 1.40‑2.90; P=1.71E‑04) and it also appeared in all the best 2‑7‑loci models. When the loci number increased, the classification error rates and P‑values decreased. The powers in 2‑7‑loci in all models were >0.9. The minimum classification error rate of the MDR‑ER‑generated model was shown with the 7‑loci interaction model (classification error rate, 21.0; OR=15.282; 95% bootstrap CI, 9.54‑23.87; P=4.03E‑31). In the epistasis network analysis, the overall effect with breast cancer susceptibility was identified and the SNP order of impact on breast cancer was identified as follows: CD4 = VEGFA > KITLG > CXCL12 > CCR7 = MMP2 > CXCR4. In conclusion, the MDR‑ER can effectively and correctly identify the best SNP‑SNP interaction models in an imbalanced data set for breast cancer cases. PMID:27461876

  17. A raft-associated species of phosphatidylethanolamine interacts with cholesterol comparably to sphingomyelin. A Langmuir-Blodgett monolayer study.

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    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.

  18. Association, Haplotype, and Gene-Gene Interactions of the HPA Axis Genes with Suicidal Behaviour in Affective Disorders

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    Anna Leszczyńska-Rodziewicz

    2013-01-01

    Full Text Available Family twin and adoption studies have noted the heritability of specific biological factors that influence suicidal behaviour. Exposure to stress is one of the factors that strongly contribute to suicide attempts. The biological response to stress involves the hypothalamic-pituitary-adrenal axis (HPA. Therefore, we found it interesting to study polymorphisms of genes involved in the HPA axis (CRHR1, NR3C1, and AVPBR1. The study was performed on 597 patients, 225 of whom had a history of suicide attempts. We did not observe any significant differences in the studied polymorphisms between the group of patients with a history of suicide attempts and the control subjects. Our haplotype analysis of the AVPR1b gene revealed an association between the GCA haplotype and suicide attempts; however, this association was not significant after correcting for multiple testing. We did not observe any other association in haplotype and MDR analysis. We report here a comprehensive analysis of the HPA axis genes and a lack of association for genetic variations regarding the risk of suicide attempts in affective disorder patients. Nonetheless, the inconsistencies with the previously published results indicate the importance of the further investigation of these polymorphisms with respect to the risk of suicide attempts.

  19. Association, haplotype, and gene-gene interactions of the HPA axis genes with suicidal behaviour in affective disorders.

    Science.gov (United States)

    Leszczyńska-Rodziewicz, Anna; Szczepankiewicz, Aleksandra; Pawlak, Joanna; Dmitrzak-Weglarz, Monika; Hauser, Joanna

    2013-01-01

    Family twin and adoption studies have noted the heritability of specific biological factors that influence suicidal behaviour. Exposure to stress is one of the factors that strongly contribute to suicide attempts. The biological response to stress involves the hypothalamic-pituitary-adrenal axis (HPA). Therefore, we found it interesting to study polymorphisms of genes involved in the HPA axis (CRHR1, NR3C1, and AVPBR1). The study was performed on 597 patients, 225 of whom had a history of suicide attempts. We did not observe any significant differences in the studied polymorphisms between the group of patients with a history of suicide attempts and the control subjects. Our haplotype analysis of the AVPR1b gene revealed an association between the GCA haplotype and suicide attempts; however, this association was not significant after correcting for multiple testing. We did not observe any other association in haplotype and MDR analysis. We report here a comprehensive analysis of the HPA axis genes and a lack of association for genetic variations regarding the risk of suicide attempts in affective disorder patients. Nonetheless, the inconsistencies with the previously published results indicate the importance of the further investigation of these polymorphisms with respect to the risk of suicide attempts.

  20. The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton

    OpenAIRE

    Gallagher, Anna Rachel; Cedzich, Anna; Gretz, Norbert; Somlo, Stefan; Witzgall, Ralph

    2000-01-01

    Despite the recent positional cloning of the PKD1 and PKD2 genes, which are mutated in the great majority of patients with autosomal-dominant polycystic kidney disease (PKD), the pathogenic mechanism for cyst formation is still unclear. The finding, that the PKD1 and PKD2 proteins interact with each other through their COOH termini, suggests that both proteins are part of the same protein complex or signal transduction pathway. Using a yeast two-hybrid screen with the PKD2 protein, we isolate...

  1. Association between the Interaction of Key Genes Involved in Effector T-Cell Pathways and Susceptibility to Develop allergic Rhinitis: A Population-Based Case-Control Association Study.

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    Full Text Available Evidence suggests that interaction between key genes mediating signaling and transcriptional networks involving effector T-cell responses may influence an individual's susceptibility to develop allergic rhinitis(AR.The aim of this study was todetermine whether specific interactions between key genes involved in effector T-cell pathways are associated with an individual's susceptibility to develop AR in Han Chinese subjects.A cohort of 489 patients with AR and 421 healthy controls was enrolled from the Han Chinese population in Beijing, China. AR was established by questionnaire and clinical examination, and peripheral blood was drawn from all subjects for DNA extraction. A total of 96 single nucleotide polymorphisms (SNPs in 26 reprehensive candidate genes involved in T helper 1 (Th1, Th2, Th17, Th9 and T regulatory cell pathways were selected from the International Haplotype Mappingdatabase for Han Chinese in Beijing (CHB population, and IlluminaGoldenGate assay was conducted for SNP genotyping. The PLINK software package was used to perform statistical analyses.Simple SNP-phenotype association analysis using logistic regression showed SNP rs8193036 in IL17A gene, rs2569254 in IL-12 and rs1898413 in RORα weresignificantlyassociatedwith AR.Simple SNP-phenotype association analysis with genetic models demonstrated thatrs2569254 in IL-12, rs1031508 in STAT4, and rs3741809 in IL-26 were likely to be recessive, rs8193036 in IL17A allelic, rs897200in STAT4 genotypic, and rs1898413 in RORα dominant. Epistasis analyses exhibited that 83 SNPs in 23 genes were significantly interactive; of which 59 interactions/SNP pairs demonstrated OR values higher than 2 or lower than 0.5, and 12 interactions/SNP pairs OR values higher than 4 or lower than 0.25. STAT3, RORα and IL-26, involved in Th17 pathway,were the mostfrequentlyinteractive genes.This study suggests that interactions between several SNPs in key genes involved in effector T-cell pathways are

  2. Interaction pattern of Arg 62 in the A-pocket of differentially disease-associated HLA-B27 subtypes suggests distinct TCR binding modes.

    Directory of Open Access Journals (Sweden)

    Elisa Nurzia

    Full Text Available 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.

  3. Interaction between PLA2R1 and HLA-DQA1 variants associates with anti-PLA2R antibodies and membranous nephropathy.

    Science.gov (United States)

    Lv, Jicheng; Hou, Wanyin; Zhou, Xujie; Liu, Gang; Zhou, Fude; Zhao, Na; Hou, Ping; Zhao, Minghui; Zhang, Hong

    2013-07-01

    Risk alleles at genome loci containing phospholipase A2 receptor 1 (PLA2R1) and HLA-DQA1 closely associate with idiopathic membranous nephropathy (IMN) in the European population, but it is unknown whether a similar association exists in the Chinese population and whether high-risk alleles promote the development of anti-PLA2R antibodies. Here, we genotyped 2132 Chinese individuals, including 1112 patients with IMN and 1020 healthy controls, for three single nucleotide polymorphisms (SNPs) within PLA2R1 and three SNPs within HLA genes. We also selected 71 patients, with varying genotypes, to assess for circulating anti-PLA2R antibody and for PLA2R expression in glomeruli. Three SNPs within PLA2R1 and one SNP within HLA-DQA1 strongly associated with IMN, and we noted gene-gene interactions involving these SNPs. Furthermore, these risk alleles strongly associated with the presence of anti-PLA2R antibodies and glomerular PLA2R expression. Among individuals who carried risk alleles for both genes, 73% had anti-PLA2R antibodies and 75% expressed PLA2R in glomeruli. In contrast, among individuals who carried protective genotypes of both genes, none had anti-PLA2R antibodies and glomerular expression of PLA2R was weak or absent. In conclusion, the interaction between PLA2R1 and HLA-DQA1 risk alleles associates with the development of IMN in the Chinese population. Individuals carrying risk alleles are predisposed to the generation of circulating anti-PLA2R autoantibodies, which may contribute to the development of IMN.

  4. 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

    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...

  5. Low level of LAT-PLC-γ1 interaction is associated with Th2 polarized differentiation: a contributing factor to the etiology of asthma.

    Science.gov (United States)

    Peng, Xiaohua; Cui, Zhilei; Gu, Wen; Xu, Weiguo; Guo, Xuejun

    2014-07-01

    Linker for activation of T cells (LAT) is a key adaptor in the T cell receptor (TCR) signaling pathway. The expression of LAT is lower in asthmatic patients than that in healthy people, but there is little knowledge about the mechanism underlying this phenomenon. This study was aimed to determine whether LAT-PLC-γ1 interaction was involved in the development of asthma. It was shown that the phosphorylation of PLC-γ1 decreased in the asthmatic mouse model and Th2 cell differentiated CD4(+) T cells. In addition, depleted endogenous PLC-γ1 promoted CD4(+) T cells to differentiate into IL-4-Productor. It was therefore concluded that the low level of LAT-PLC-γ1 interaction was associated with Th2 polarized differentiation, and this may contribute to the etiology of asthma.

  6. 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.

  7. Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1.

    Science.gov (United States)

    Garapaty, Shivani; Mahajan, Muktar A; Samuels, Herbert H

    2008-03-14

    CCR4-NOT is an evolutionarily conserved, multicomponent complex known to be involved in transcription as well as mRNA degradation. Various subunits (e.g. CNOT1 and CNOT7/CAF1) have been reported to be involved in influencing nuclear hormone receptor activities. Here, we show that CCR4/CNOT6 and RCD1/CNOT9, members of the CCR4-NOT complex, potentiate nuclear receptor activity. RCD1 interacts in vivo and in vitro with NIF-1 (NRC-interacting factor), a previously characterized nuclear receptor cotransducer that activates nuclear receptors via its interaction with NRC. As with NIF-1, RCD1 and CCR4 do not directly associate with nuclear receptors; however, they enhance ligand-dependent transcriptional activation by nuclear hormone receptors. CCR4 mediates its effect through the ligand binding domain of nuclear receptors and small interference RNA-mediated silencing of endogenous CCR4 results in a marked decrease in nuclear receptor activation. Furthermore, knockdown of CCR4 results in an attenuated stimulation of RARalpha target genes (e.g. Sox9 and HoxA1) as shown by quantitative PCR assays. The silencing of endogenous NIF-1 also resulted in a comparable decrease in the RAR-mediated induction of both Sox9 and HoxA1. Furthermore, CCR4 associates in vivo with NIF-1. In addition, the CCR4-enhanced transcriptional activation by nuclear receptors is dependent on NIF-1. The small interference RNA-mediated knockdown of NIF-1 blocks the ligand-dependent potentiating effect of CCR4. Our results suggest that CCR4 plays a role in the regulation of certain endogenous RARalpha target genes and that RCD1 and CCR4 might mediate their function through their interaction with NIF-1.

  8. Interaction 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.

  9. Interaction between Smoking and HLA-DRB1*04 Gene Is Associated with a High Cardiovascular Risk in Brazilian Amazon Patients with Rheumatoid Arthritis

    Science.gov (United States)

    Boechat, Narjara de Oliveira; Ogusku, Mauricio Morish; Boechat, Antonio Luiz; Sadahiro, Aya

    2012-01-01

    Background Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints that affects approximately 1% of the population worldwide. The HLA-DRB1 gene locus plays a major role in genetic susceptibility to RA, a condition that has been associated with a high cardiovascular morbidity and mortality in many studies. Methodology/Principal Findings The aim of this work was to investigate which types of HLA class II genes are associated with RA in patients from the Brazilian Amazon and their influence on high cardiovascular risk status in this population. For this purpose, a case-control study was carried out with a total of 350 non-Indian individuals made up of a cohort of 132 consecutive RA sufferers and 218 healthy controls. A χ2 test showed that HLADRB1*04 (p<0.0016; OR = 1.89; 95% CI = 1.29–2.79) and HLADRB1*10 (p = 0.0377; OR = 3.81; 95% CI = 1.16–12.50) are the major HLA genes associated with susceptibility to RA. A logistic regression model also showed that the interaction between HLADRB1*04 (p = 0.027; OR = 6.02; 95% CI = 1.21–29.7), age (p = 0.0001; OR = 1.26; 95% CI = 1.13–1.39) and smoking (p = 0.0001; OR = 23.6; 95% CI = 4.25–32.1) is associated with a probability of a high cardiovascular risk status at an early age. Conclusions/Significance The results of this study show for the first time that HLA class II type is associated with RA in Brazilian Amazon populations and that a specific interaction between the HLA-DRB1*04 gene and smoking is associated with a high cardiovascular risk status, as initially reported in the European population. This study therefore contributes to an understanding of gene-environment interactions in RA patients. PMID:22912672

  10. The microtubule-associated Rho activating factor GEF-H1 interacts with exocyst complex to regulate vesicle traffic.

    Science.gov (United States)

    Pathak, Ritu; Delorme-Walker, Violaine D; Howell, Michael C; Anselmo, Anthony N; White, Michael A; Bokoch, Gary M; Dermardirossian, Céline

    2012-08-14

    The exocyst complex plays a critical role in targeting and tethering vesicles to specific sites of the plasma membrane. These events are crucial for polarized delivery of membrane components to the cell surface, which is critical for cell motility and division. Though Rho GTPases are involved in regulating actin dynamics and membrane trafficking, their role in exocyst-mediated vesicle targeting is not very clear. Herein, we present evidence that depletion of GEF-H1, a guanine nucleotide exchange factor for Rho proteins, affects vesicle trafficking. Interestingly, we found that GEF-H1 directly binds to exocyst component Sec5 in a Ral GTPase-dependent manner. This interaction promotes RhoA activation, which then regulates exocyst assembly/localization and exocytosis. Taken together, our work defines a mechanism for RhoA activation in response to RalA-Sec5 signaling and involvement of GEF-H1/RhoA pathway in the regulation of vesicle trafficking.

  11. 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,

  12. Association of Angiotensin Converting Enzyme Insertion-Deletion Polymorphism with Hypertension in Emiratis with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status

    Directory of Open Access Journals (Sweden)

    Habiba Alsafar

    2015-01-01

    Full Text Available The association of Angiotensin Converting Enzyme (ACE insertion-deletion (I/D polymorphism with Type 2 Diabetes Mellitus (T2DM and hypertension has been extensively studied throughout various ethnic populations but largely with inconsistent findings. We investigated these associations in Emirati population and their interaction with obesity status. Saliva samples were collected from a total of 564 Emiratis (277 T2DM and 297 healthy. DNA was extracted and the samples were genotyped for ACE I/D polymorphism by a PCR based method followed by gel electrophoresis. Upon evaluation of the ACE I/D polymorphism amongst all T2DM, hypertensive patients, and respective controls regardless of obesity status, ACE DD genotype was not found to be associated with either T2DM [odds ratio (OR = 1.34, p=0.086] or hypertension [odd ratio (OR = 1.02, p=0.93]. When the genetic variants amongst the nonobese and obese population were analyzed separately, the risk genotype ACE DD conferred significantly increased risk of hypertension in nonobese population [odds ratio (OR = 1.80, p=0.02] but was found to be protective against the hypertension in the obese group ((OR = 0.54, p=0.01. However, there was no effect of obesity status on the association of ACE genotypes with T2DM. The risk of hypertension associated with ACE DD is modulated by obesity status and hence future genetic association studies should take obesity into account for the interpretation of data. We also confirmed that ACE I/D polymorphism is not associated with T2DM risk in Emirati population.

  13. Association of Angiotensin Converting Enzyme Insertion-Deletion Polymorphism with Hypertension in Emiratis with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status.

    Science.gov (United States)

    Alsafar, Habiba; Hassoun, Ahmed; Almazrouei, Shaikha; Kamal, Wala; Almaini, Mustafa; Odama, Unini; Rais, Naushad

    2015-01-01

    The association of Angiotensin Converting Enzyme (ACE) insertion-deletion (I/D) polymorphism with Type 2 Diabetes Mellitus (T2DM) and hypertension has been extensively studied throughout various ethnic populations but largely with inconsistent findings. We investigated these associations in Emirati population and their interaction with obesity status. Saliva samples were collected from a total of 564 Emiratis (277 T2DM and 297 healthy). DNA was extracted and the samples were genotyped for ACE I/D polymorphism by a PCR based method followed by gel electrophoresis. Upon evaluation of the ACE I/D polymorphism amongst all T2DM, hypertensive patients, and respective controls regardless of obesity status, ACE DD genotype was not found to be associated with either T2DM [odds ratio (OR) = 1.34, p = 0.086] or hypertension [odd ratio (OR) = 1.02, p = 0.93]. When the genetic variants amongst the nonobese and obese population were analyzed separately, the risk genotype ACE DD conferred significantly increased risk of hypertension in nonobese population [odds ratio (OR) = 1.80, p = 0.02] but was found to be protective against the hypertension in the obese group ((OR) = 0.54, p = 0.01). However, there was no effect of obesity status on the association of ACE genotypes with T2DM. The risk of hypertension associated with ACE DD is modulated by obesity status and hence future genetic association studies should take obesity into account for the interpretation of data. We also confirmed that ACE I/D polymorphism is not associated with T2DM risk in Emirati population.

  14. Functional Interaction of the Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 1 Polymorphism and HLA-B27 in Vivo*

    OpenAIRE

    García-Medel, Noel; Sanz-Bravo, Alejandro; Nguyen, Dung; Galocha, Begoña; Gómez-Molina, Patricia; Martín-Esteban, Adrián; Alvarez-Navarro, Carlos; de Castro, José A. López

    2012-01-01

    The association of ERAP1 with ankylosing spondylitis (AS)1 among HLA-B27-positive individuals suggests that ERAP1 polymorphism may affect pathogenesis by altering peptide-dependent features of the HLA-B27 molecule. Comparisons of HLA-B*27:04-bound peptidomes from cells expressing different natural variants of ERAP1 revealed significant differences in the size, length, and amount of many ligands, as well as in HLA-B27 stability. Peptide analyses suggested that the mechanism of ERAP1/HLA-B27 in...

  15. Identify Interaction Genes in Genome-Wide Association Studies Using a Model-Based Two-Stage Approach

    OpenAIRE

    Zhang, Zhaogong; Niu, Adan; Sha, Qiuying

    2010-01-01

    In this paper, we propose a two-stage approach based on seventeen biological plausible models to search for two-locus combinations that have significant joint effects on the disease status in genome-wide association (GWA) studies. In the two-stage analyses, we only test two-locus joint effects of SNPs that show modest marginal effects. We use simulation studies to compare the power of our two-stage analysis with a single-marker analysis and a two-stage analysis by using a full model. We find ...

  16. Marker-assisted assessment of genotype by environment interaction: a case study of single nucleotide polymorphism-mortality association in broilers in two hygiene environments.

    Science.gov (United States)

    Long, N; Gianola, D; Rosa, G J M; Weigel, K A; Avendaño, S

    2008-12-01

    Interplay between genetic and environmental factors, genotype x environment interactions (G x E), affect phenotypes of complex traits. A methodology for assessing G x E was investigated by detecting hygiene (low and high) environment-specific SNP subsets associated with broiler chicken mortality, followed by an examination of consistency between SNP subsets selected from the 2 environments. The trait was mean progeny mortality rate in 253 sire families, after adjusting records for nuisance effects affecting mortality at the individual bird level. Over 5,000 whole-genome SNP were narrowed down via a machine-learning (filter-wrapper) feature selection procedure applied to mortality rates in each of the 2 environments. For both early and late mortality, it was found that the selected SNP subsets differed across hygiene environments, in terms of either across-environment predictive ability or extent of linkage disequilibrium between the subsets. Reduction in predictive ability due to G x E was assessed by the ratio of 2 predicted residual sum of squares statistics, one associated with SNP selected from the same hygiene environment and the other associated with the SNP subset from a different environment. Reduction was 30 and 20% for early and late mortality, respectively. An extremely low level of linkage disequilibrium between SNP subsets selected under low and high hygiene also indicated G x E. Findings suggest that there may not be a universally optimal SNP subset for predicting mortality and that interactions between genome and environmental factors need to be considered in association analysis of complex traits. PMID:18765852

  17. 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

  18. Interactions between Lactobacillus crispatus and Bacterial Vaginosis (BV-Associated Bacterial Species in Initial Attachment and Biofilm Formation

    Directory of Open Access Journals (Sweden)

    Kimberly Kay Jefferson

    2013-06-01

    Full Text Available Certain anaerobic bacterial species tend to predominate the vaginal flora during bacterial vaginosis (BV, with Gardnerella vaginalis being the most common. However, the exact role of G. vaginalis in BV has not yet been determined. The main goal of this study was to test the hypothesis that G. vaginalis is an early colonizer, paving the way for intermediate (e.g., Fusobacterium nucleatum and late colonizers (e.g., Prevotella bivia. Theoretically, in order to function as an early colonizer, species would need to be able to adhere to vaginal epithelium, even in the presence of vaginal lactobacilli. Therefore, we quantified adherence of G. vaginalis and other BV-associated bacteria to an inert surface pre-coated with Lactobacillus crispatus using a new Peptide Nucleic Acid (PNA Fluorescence In Situ Hybridization (FISH methodology. We found that G. vaginalis had the greatest capacity to adhere in the presence of L. crispatus. Theoretically, an early colonizer would contribute to the adherence and/or growth of additional species, so we next quantified the effect of G. vaginalis biofilms on the adherence and growth of other BV-associated species by quantitative Polymerase Chain Reaction (qPCR technique. Interestingly, G. vaginalis derived a growth benefit from the addition of a second species, regardless of the species. Conversely, G. vaginalis biofilms enhanced the growth of P. bivia, and to a minor extent of F. nucleatum. These results contribute to our understanding of BV biofilm formation and the progression of the disorder.

  19. 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. PMID:27458437

  20. 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. PMID:27458437

  1. Study of the geoeffectiveness of coronal mass ejections, corotating interaction regions and their associated structures observed during Solar Cycle 23

    Science.gov (United States)

    Badruddin, A.; Falak, Z.

    2016-08-01

    The interplanetary coronal mass ejections (ICMEs) and the corotating interaction regions (CIRs) are the two most important structures of the interplanetary medium affecting the Earth and the near-Earth space environment. We study the solar wind-magnetosphere coupling during the passage of ICMEs and CIRs, in the Solar Cycle 23 (Jan. 1995-Dec. 2009), and their relative geoeffectiveness. We utilize the timings of different features of these structures, their arrival and duration. As geomagnetic parameter, we utilize high time resolution data of Dst and AE indices. In addition to these geomagnetic indices, we utilize the simultaneous and similar time resolution data of interplanetary plasma and field, namely, solar wind velocity, interplanetary magnetic field, its north-south component and dawn-dusk electric field. We apply the method of superposed epoch analysis. Utilizing the properties of various structures during the passage of ICMEs and CIRs, and variations observed in plasma and field parameters during their passage along with the simultaneous changes observed in geomagnetic parameters, we identify the interplanetary conditions, plasma/field parameters and their relative importance in solar wind-magnetosphere coupling. Geospace consequences of ICMEs and CIRs, and the implications of these results for solar wind-magnetosphere coupling are discussed.

  2. Genetic Interactions Reveal that Specific Defects of Chloroplast Translation are Associated with the Suppression of var2-Mediated Leaf Variegation

    Institute of Scientific and Technical Information of China (English)

    Xiayan Liu; Mengdi Zheng; Rui Wang; Ruijuan Wang; Lijun An; Steve R. Rodermel; Fei Yu

    2013-01-01

    Arabidopsis thaliana L. yellow variegated (var2) mutant is defective in a chloroplast FtsH family metalloprotease, AtFtsH2/VAR2, and displays an intriguing green and white leaf variegation. This unique var2-mediated leaf variegation offers a simple yet powerful tool for dissecting the genetic regulation of chloroplast development. Here, we report the isolation and characterization of a new var2 suppressor gene, SUPPRESSOR OF VARIEGATION8 (SVR8), which encodes a putative chloroplast ribosomal large subunit protein, L24. Mutations in SVR8 suppress var2 leaf variegation at ambient temperature and partially suppress the cold-induced chlorosis phenotype of var2. Loss of SVR8 causes unique chloroplast rRNA processing defects, particularly the 23S-4.5S dicistronic precursor. The recovery of the major abnormal processing site in svr8 23S-4.5S precursor indicate that it does not lie in the same position where SVR8/L24 binds on the ribosome. Surprisingly, we found that the loss of a chloroplast ribosomal small subunit protein, S21, results in aberrant chloroplast rRNA processing but not suppression of var2 variegation. These findings suggest that the disruption of specific aspects of chloroplast translation, rather than a general impairment in chloroplast translation, suppress var2 variegation and the existence of complex genetic interactions in chloroplast development.

  3. Genetic interactions reveal that specific defects of chloroplast translation are associated with the suppression of var2-mediated leaf variegation.

    Science.gov (United States)

    Liu, Xiayan; Zheng, Mengdi; Wang, Rui; Wang, Ruijuan; An, Lijun; Rodermel, Steve R; Yu, Fei

    2013-10-01

    Arabidopsis thaliana L. yellow variegated (var2) mutant is defective in a chloroplast FtsH family metalloprotease, AtFtsH2/VAR2, and displays an intriguing green and white leaf variegation. This unique var2-mediated leaf variegation offers a simple yet powerful tool for dissecting the genetic regulation of chloroplast development. Here, we report the isolation and characterization of a new var2 suppressor gene, SUPPRESSOR OF VARIEGATION8 (SVR8), which encodes a putative chloroplast ribosomal large subunit protein, L24. Mutations in SVR8 suppress var2 leaf variegation at ambient temperature and partially suppress the cold-induced chlorosis phenotype of var2. Loss of SVR8 causes unique chloroplast rRNA processing defects, particularly the 23S-4.5S dicistronic precursor. The recovery of the major abnormal processing site in svr8 23S-4.5S precursor indicate that it does not lie in the same position where SVR8/L24 binds on the ribosome. Surprisingly, we found that the loss of a chloroplast ribosomal small subunit protein, S21, results in aberrant chloroplast rRNA processing but not suppression of var2 variegation. These findings suggest that the disruption of specific aspects of chloroplast translation, rather than a general impairment in chloroplast translation, suppress var2 variegation and the existence of complex genetic interactions in chloroplast development. PMID:23721655

  4. [Dynamic model of protein behavior in water. Possible mechanism of association and dissociation of specific complexes].

    Science.gov (United States)

    Kiaiviariainen, A I

    1979-01-01

    The proposed mechanism of association and dissociation of specific protein complex with ligands is based on the assumption that thermal fluctuations in the non-polar cavities of protein are interrelated due to the co-operative properties of macromolecules. The non-polar cavities, representing the active centres and clefts in the globule jump from the "open" state to the "closed" one with a certain amount of water being removed to the external medium. It is assumed that the association of ligand with the active centre is accompanied by stabilization of the chest state and destibilization of the open one, dissociation being a reverse process. A rapid change in the state of the active centre under the influence of ligand induces a slow relaxation process resulting in similar alterations in the state of the auxiliary non-polar cavities of protein. As a result, the binding constant of ligand increases, while the free energy of protein decreases. Expressions have been obtained which relate the rate constants of association, dissociation and the binding constant to the rate-constant of the nonpolar cavities transitions from the closed state to the open one, and vice versa. They gave a possibility for a qualitative interpretation of the effect of some specific and non-specific agents upon the stability of immunoglobulins, on the influence of salts upon the association and dissociation of antibody-antigene complexes and on the increase in the constant of binding between antibodies and haptens in the course of prolonged immunisation.

  5. Plant-hummingbird interactions in the West Indies: floral specialisation gradients associated with environment and hummingbird size.

    Science.gov (United States)

    Dalsgaard, Bo; Martín González, Ana M; Olesen, Jens M; Ollerton, Jeff; Timmermann, Allan; Andersen, Laila H; Tossas, Adrianne G

    2009-04-01

    Floral phenotype and pollination system of a plant may be influenced by the abiotic environment and the local pollinator assemblage. This was investigated in seven plant-hummingbird assemblages on the West Indian islands of Grenada, Dominica and Puerto Rico. We report all hummingbird and insect pollinators of 49 hummingbird-pollinated plant species, as well as six quantitative and semi-quantitative floral characters that determine visitor restriction, attraction and reward. Using nonmetric multidimensional scaling analysis, we show that hummingbird-pollinated plants in the West Indies separate in floral phenotypic space into two gradients-one associated with the abiotic environment and another with hummingbird size. Plants pollinated by large, long-billed hummingbirds had flowers with long corolla tube, large amounts of nectar and showy orange-red colouration. These attracted few or no insect species, whereas plants pollinated by small, short-billed hummingbirds were frequently pollinated by insects, particularly lepidopterans. The separation of plants related to environmental factors showed that species in the wet and cold highlands produced large amounts of dilute nectar, possessed no or a weak odour, and were associated with few insects, particularly few hymenopterans, compared to plants in the dry and warm lowlands. The most specialised hummingbird-pollinated plants are found in the West Indian highlands where they are pollinated by mainly large, long-billed hummingbirds. At the other extreme, highly generalised plants growing in the dry and warm lowlands are pollinated by small, short-billed hummingbirds and numerous insect species. This illustrates that, even within the hummingbird-pollinated flora, pollination syndrome and the degree of specialisation may vary tremendously depending on pollinator morphology and environment.

  6. Plant-hummingbird interactions in the West Indies: floral specialisation gradients associated with environment and hummingbird size.

    Science.gov (United States)

    Dalsgaard, Bo; Martín González, Ana M; Olesen, Jens M; Ollerton, Jeff; Timmermann, Allan; Andersen, Laila H; Tossas, Adrianne G

    2009-04-01

    Floral phenotype and pollination system of a plant may be influenced by the abiotic environment and the local pollinator assemblage. This was investigated in seven plant-hummingbird assemblages on the West Indian islands of Grenada, Dominica and Puerto Rico. We report all hummingbird and insect pollinators of 49 hummingbird-pollinated plant species, as well as six quantitative and semi-quantitative floral characters that determine visitor restriction, attraction and reward. Using nonmetric multidimensional scaling analysis, we show that hummingbird-pollinated plants in the West Indies separate in floral phenotypic space into two gradients-one associated with the abiotic environment and another with hummingbird size. Plants pollinated by large, long-billed hummingbirds had flowers with long corolla tube, large amounts of nectar and showy orange-red colouration. These attracted few or no insect species, whereas plants pollinated by small, short-billed hummingbirds were frequently pollinated by insects, particularly lepidopterans. The separation of plants related to environmental factors showed that species in the wet and cold highlands produced large amounts of dilute nectar, possessed no or a weak odour, and were associated with few insects, particularly few hymenopterans, compared to plants in the dry and warm lowlands. The most specialised hummingbird-pollinated plants are found in the West Indian highlands where they are pollinated by mainly large, long-billed hummingbirds. At the other extreme, highly generalised plants growing in the dry and warm lowlands are pollinated by small, short-billed hummingbirds and numerous insect species. This illustrates that, even within the hummingbird-pollinated flora, pollination syndrome and the degree of specialisation may vary tremendously depending on pollinator morphology and environment. PMID:19132403

  7. Interactions between genetic variants associated with adiposity traits and soft drinks in relation to longitudinal changes in body weight and waist circumference

    DEFF Research Database (Denmark)

    Olsen, Nanna J; Ängquist, Lars; Larsen, Sofus C;

    2016-01-01

    soft drink intake and the annual change (Δ) in body weight (BW), WC, or waist circumference adjusted for BMI (WCBMI) and possible interactions with the GRSs were examined with the use of linear regression analyses and meta-analyses. RESULTS: For each soft drink serving per day, soft drink consumption...... was significantly associated with a higher ΔBW of 0.07 kg/y (95% CI: 0.01, 0.13 kg/y; P = 0.020) but not with the ΔWC or ΔWCBMI In analyses of the ΔBW, we showed an interaction only with the GRSWC (per risk allele for each soft drink serving per day: -0.06 kg/y; 95% CI: -0.10, -0.02 kg/y; P = 0.006). In analyses...... of the ΔWC, we showed interactions only with the GRSBMI and GRSComplete [per risk allele for each soft drink serving per day: 0.05 cm/y (95% CI: 0.02, 0.09 cm/y; P = 0.001) and 0.05 cm/y (95% CI: 0.02, 0.07 cm/y; P = 0.001), respectively]. Nearly identical results were observed in analyses of the ΔWCBMI...

  8. The pro-apoptotic protein death-associated protein 3 (DAP3) interacts with the glucocorticoid receptor and affects the receptor function.

    Science.gov (United States)

    Hulkko, S M; Wakui, H; Zilliacus, J

    2000-08-01

    The yeast two-hybrid system was used to isolate cDNAs encoding proteins that interact with the glucocorticoid receptor (GR) ligand-binding domain in a ligand-dependent manner. One isolated cDNA encoded a fragment of death-associated protein 3 (DAP3), which has been implicated as a positive mediator of apoptosis. In vitro experiments showed that the full-length DAP3 also interacted with GR. The main interaction domain was mapped to the N-terminal region of DAP3 that had previously been shown to function in a dominant-negative fashion, protecting cells from apoptosis. Co-transfection experiments in COS-7 cells showed that DAP3 had a stimulatory effect on the ligand-induced transcriptional activation by GR and also increased the steroid-sensitivity. Furthermore, DAP3 formed a complex with several other nuclear receptors and some basic helix-loop-helix/Per-Arnt-Sim proteins, as well as with heat-shock protein 90 (hsp90) (Arnt is the aryl-hydrocarbon-receptor nuclear translocator, and Per and Sim are the Drosophila proteins Period and Single-minded). The results suggest that DAP3 could have an important role in GR action, possibly by modulating the cytoplasmic GR-hsp90 complex. Since glucocorticoids can induce apoptosis, the pro-apoptotic DAP3 protein may be involved in this function of GR. PMID:10903152

  9. Role of interspecies interactions in dual-species biofilms developed in vitro by uropathogens isolated from polymicrobial urinary catheter-associated bacteriuria.

    Science.gov (United States)

    Galván, E M; Mateyca, C; Ielpi, L

    2016-10-01

    Most catheter-associated urinary tract infections are polymicrobial. Here, uropathogen interactions in dual-species biofilms were studied. The dual-species associations selected based on their prevalence in clinical settings were Klebsiella pneumoniae-Escherichia coli, E. coli-Enterococcus faecalis, K. pneumoniae-E. faecalis, and K. pneumoniae-Proteus mirabilis. All species developed single-species biofilms in artificial urine. The ability of K. pneumoniae to form biofilms was not affected by E. coli or E. faecalis co-inoculation, but was impaired by P. mirabilis. Conversely, P. mirabilis established a biofilm when co-inoculated with K. pneumoniae. Additionally, E. coli persistence in biofilms was hampered by K. pneumoniae but not by E. faecalis. Interestingly, E. coli, but not K. pneumoniae, partially inhibited E. faecalis attachment to the surface and retarded biofilm development. The findings reveal bacterial interactions between uropathogens in dual-species biofilms ranged from affecting initial adhesion to outcompeting one bacterial species, depending on the identity of the partners involved.

  10. Membrane proteins associated with sperm-oocyte interaction: A proteomic comparison between Kedah Kelantan (Bos indicus) and Mafriwal (Bos taurus × Bos indicus) sperm

    Science.gov (United States)

    Ashrafzadeh, Ali; Nathan, Sheila; Othman, Iekhsan; Yee, Tee Ting; Karsani, Saiful Anuar

    2013-11-01

    Production performance of European cattle breeds has significantly improved through various breeding programs. However, European breeds are more susceptible to heat stress compared to zebu cattle (Bos indicus) as their conception rate can range between 20 to 30% in hot seasons compared to winter. To identify cattle sperm proteins associated with zebu cattle higher fertility and heat tolerance in tropical environments, we utilised a proteomics-based approach to compare sperm from the highly fertile Malaysian indigenous breed, Kedah Kelantan (Bos indicus), with sperm from the sub-fertile crossbreed, Mafriwal (Bos taurus × Bos indicus). Frozen semen of three high performance bulls from each breed was processed to obtain live and pure sperm. Proteins were separated and gel bands were processed by in-gel tryptic digestion. For each breed, mass spectrometry data was acquired over 11 replicates. The analyzed data identified peptides with different expression levels (99% confidence level) and protein identification was determined by targeted MS/MS. Among the identified proteins associated with sperm-oocyte interaction, two proteins were up-regulated in Kedah Kelantan sperm and 7 proteins were up-regulated in or specific to Mafriwal. Our results suggest that the higher fertility of zebu cattle in tropical areas may not be related to more efficient sperm-oocyte interaction. Further analysis of the other regulated proteins in these two breeds may contribute further knowledge on the physiological reason/s for higher fertility and heat tolerance of Zebu cattle in tropical areas.

  11. Role of interspecies interactions in dual-species biofilms developed in vitro by uropathogens isolated from polymicrobial urinary catheter-associated bacteriuria.

    Science.gov (United States)

    Galván, E M; Mateyca, C; Ielpi, L

    2016-10-01

    Most catheter-associated urinary tract infections are polymicrobial. Here, uropathogen interactions in dual-species biofilms were studied. The dual-species associations selected based on their prevalence in clinical settings were Klebsiella pneumoniae-Escherichia coli, E. coli-Enterococcus faecalis, K. pneumoniae-E. faecalis, and K. pneumoniae-Proteus mirabilis. All species developed single-species biofilms in artificial urine. The ability of K. pneumoniae to form biofilms was not affected by E. coli or E. faecalis co-inoculation, but was impaired by P. mirabilis. Conversely, P. mirabilis established a biofilm when co-inoculated with K. pneumoniae. Additionally, E. coli persistence in biofilms was hampered by K. pneumoniae but not by E. faecalis. Interestingly, E. coli, but not K. pneumoniae, partially inhibited E. faecalis attachment to the surface and retarded biofilm development. The findings reveal bacterial interactions between uropathogens in dual-species biofilms ranged from affecting initial adhesion to outcompeting one bacterial species, depending on the identity of the partners involved. PMID:27642801

  12. Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication

    Directory of Open Access Journals (Sweden)

    Bozdagi Ozlem

    2010-12-01

    , induced either with θ-burst pairing (TBP or high-frequency stimulation, was impaired in Shank3 heterozygous mice, with no significant change in long-term depression (LTD. In concordance with the LTP results, persistent expansion of spines was observed in control mice after TBP-induced LTP; however, only transient spine expansion was observed in Shank3 heterozygous mice. Male Shank3 heterozygotes displayed less social sniffing and emitted fewer ultrasonic vocalizations during interactions with estrus female mice, as compared to wild-type littermate controls. Conclusions We documented specific deficits in synaptic function and plasticity, along with reduced reciprocal social interactions in Shank3 heterozygous mice. Our results are consistent with altered synaptic development and function in Shank3 haploinsufficiency, highlighting the importance of Shank3 in synaptic function and supporting a link between deficits in synapse function and neurodevelopmental disorders. The reduced glutamatergic transmission that we observed in the Shank3 heterozygous mice represents an interesting therapeutic target in Shank3-haploinsufficiency syndromes.

  13. De novo Transcriptome Sequencing to Dissect Candidate Genes Associated with Pearl Millet-Downy Mildew (Sclerospora graminicola Sacc.) Interaction

    Science.gov (United States)

    Kulkarni, Kalyani S.; Zala, Harshvardhan N.; Bosamia, Tejas C.; Shukla, Yogesh M.; Kumar, Sushil; Fougat, Ranbir S.; Patel, Mruduka S.; Narayanan, Subhash; Joshi, Chaitanya G.

    2016-01-01

    Understanding the plant-pathogen interactions is of utmost importance to design strategies for minimizing the economic deficits caused by pathogens in crops. With an aim to identify genes underlying resistance to downy mildew, a major disease responsible for productivity loss in pearl millet, transcriptome analysis was performed in downy mildew resistant and susceptible genotypes upon infection and control on 454 Roche NGS platform. A total of ~685 Mb data was obtained with 1 575 290 raw reads. The raw reads were pre-processed into high-quality (HQ) reads making to ~82% with an average of 427 bases. The assembly was optimized using four assemblers viz. Newbler, MIRA, CLC and Trinity, out of which MIRA with a total of 14.10 Mb and 90118 transcripts proved to be the best for assembling reads. Differential expression analysis depicted 1396 and 936 and 1000 and 1591 transcripts up and down regulated in resistant inoculated/resistant control and susceptible inoculated/susceptible control respectively with a common of 3644 transcripts. The pathways for secondary metabolism, specifically the phenylpropanoid pathway was up-regulated in resistant genotype. Transcripts up-regulated as a part of defense response included classes of R genes, PR proteins, HR induced proteins and plant hormonal signaling transduction proteins. The transcripts for skp1 protein, purothionin, V type proton ATPase were found to have the highest expression in resistant genotype. Ten transcripts, selected on the basis of their involvement in defense mechanism were validated with qRT-PCR and showed positive co-relation with transcriptome data. Transcriptome analysis evoked potentials of hypersensitive response and systemic acquired resistance as possible mechanism operating in defense mechanism in pearl millet against downy mildew infection.

  14. De novo Transcriptome Sequencing to Dissect Candidate Genes Associated with Pearl Millet-Downy Mildew (Sclerospora graminicola Sacc.) Interaction.

    Science.gov (United States)

    Kulkarni, Kalyani S; Zala, Harshvardhan N; Bosamia, Tejas C; Shukla, Yogesh M; Kumar, Sushil; Fougat, Ranbir S; Patel, Mruduka S; Narayanan, Subhash; Joshi, Chaitanya G

    2016-01-01

    Understanding the plant-pathogen interactions is of utmost importance to design strategies for minimizing the economic deficits caused by pathogens in crops. With an aim to identify genes underlying resistance to downy mildew, a major disease responsible for productivity loss in pearl millet, transcriptome analysis was performed in downy mildew resistant and susceptible genotypes upon infection and control on 454 Roche NGS platform. A total of ~685 Mb data was obtained with 1 575 290 raw reads. The raw reads were pre-processed into high-quality (HQ) reads making to ~82% with an average of 427 bases. The assembly was optimized using four assemblers viz. Newbler, MIRA, CLC and Trinity, out of which MIRA with a total of 14.10 Mb and 90118 transcripts proved to be the best for assembling reads. Differential expression analysis depicted 1396 and 936 and 1000 and 1591 transcripts up and down regulated in resistant inoculated/resistant control and susceptible inoculated/susceptible control respectively with a common of 3644 transcripts. The pathways for secondary metabolism, specifically the phenylpropanoid pathway was up-regulated in resistant genotype. Transcripts up-regulated as a part of defense response included classes of R genes, PR proteins, HR induced proteins and plant hormonal signaling transduction proteins. The transcripts for skp1 protein, purothionin, V type proton ATPase were found to have the highest expression in resistant genotype. Ten transcripts, selected on the basis of their involvement in defense mechanism were validated with qRT-PCR and showed positive co-relation with transcriptome data. Transcriptome analysis evoked potentials of hypersensitive response and systemic acquired resistance as possible mechanism operating in defense mechanism in pearl millet against downy mildew infection. PMID:27446100

  15. 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.

  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)

    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. 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

  18. Intracellular clusterin interacts with brain isoforms of the bridging integrator 1 and with the microtubule-associated protein Tau in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Yuan Zhou

    Full Text Available Sporadic or late-onset Alzheimer's disease (AD is expected to affect 50% of individuals reaching 85 years of age. The most significant genetic risk factor for late-onset AD is the e4 allele of APOE gene encoding apolipoprotein E, a lipid carrier shown to modulate brain amyloid burden. Recent genome-wide association studies have uncovered additional single nucleotide polymorphisms (SNPs linked to AD susceptibility, including those in the CLU and BIN1 genes encoding for clusterin (CLU and the bridging integrator 1 (BIN1 proteins, respectively. Because CLU has been implicated in brain amyloid-β (Aβ clearance in mouse models of amyloid deposition, we sought to investigate whether an AD-linked SNP in the CLU gene altered Aβ42 biomarker levels in the cerebrospinal fluid (CSF. Instead, we found that the CLU rs11136000 SNP modified CSF levels of the microtubule-associated protein Tau in AD patients. We also found that an intracellular form of CLU (iCLU was upregulated in the brain of Tau overexpressing Tg4510 mice, but not in Tg2576 amyloid mouse model. By overexpressing iCLU and Tau in cell culture systems we discovered that iCLU was a Tau-interacting protein and that iCLU associated with brain-specific isoforms of BIN1, also recently identified as a Tau-binding protein. Through expression analysis of CLU and BIN1 variants, we found that CLU and BIN1 interacted via their coiled-coil motifs. In co-immunoprecipitation studies using human brain tissue, we showed that iCLU and the major BIN1 isoform expressed in neurons were associated with modified Tau species found in AD. Finally, we showed that expression of certain coding CLU variants linked to AD risk led to increased levels of iCLU. Together, our findings suggest that iCLU and BIN1 interaction might impact Tau function in neurons and uncover potential new mechanisms underlying the etiology of Tau pathology in AD.

  19. 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.

  20. 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.

  1. Interactive effects of cocaine on HIV infection: implication in HIV-associated neurocognitive disorder and neuroAIDS.

    Science.gov (United States)

    Dahal, Santosh; Chitti, Sai V P; Nair, Madhavan P N; Saxena, Shailendra K

    2015-01-01

    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 (DA) in the brain, by blocking the dopamine transporters (DAT) which is critical for DA 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 DA, 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 against HIV-1 infection

  2. 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

  3. 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 the

  4. Diversity of Cultivated Fungi Associated with Conventional and Transgenic Sugarcane and the Interaction between Endophytic Trichoderma virens and the Host Plant.

    Directory of Open Access Journals (Sweden)

    Aline Silva Romão-Dumaresq

    Full Text Available Plant-associated fungi are considered a vast source for biotechnological processes whose potential has been poorly explored. The interactions and diversity of sugarcane, one of the most important crops in Brazil, have been rarely studied, mainly concerning fungal communities and their interactions with transgenic plants. Taking this into consideration, the purpose of this study was, based on culture dependent strategy, to determine the structure and diversity of the fungal community (root endophytes and rhizosphere associated with two varieties of sugarcane, a non-genetically modified (SP80-1842 variety and its genetically modified counterpart (IMI-1, expressing imazapyr herbicide resistance. For this, the sugarcane varieties were evaluated in three sampling times (3, 10 and 17 months after planting under two crop management (weeding and herbicide treatments. In addition, a strain of Trichoderma virens, an endophyte isolated from sugarcane with great potential as a biological control, growth promotion and enzyme production agent, was selected for the fungal-plant interaction assays. The results of the isolation, characterization and evaluation of fungal community changes showed that the sugarcane fungal community is composed of at least 35 different genera, mostly in the phylum Ascomycota. Many genera are observed at very low frequencies among a few most abundant genera, some of which were isolated from specific plant sites (e.g., the roots or the rhizosphere. An assessment of the possible effects upon the fungal community showed that the plant growth stage was the only factor that significantly affected the community's structure. Moreover, if transgenic effects are present, they may be minor compared to other natural sources of variation. The results of interaction studies using the Green fluorescent protein (GFP-expressing T. virens strain T.v.223 revealed that this fungus did not promote any phenotypic changes in the host plant and was found

  5. 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

  6. Education is associated with lower levels of abdominal obesity in women with a non-agricultural occupation: an interaction study using China’s four provinces survey

    Science.gov (United States)

    2013-01-01

    Background The prevalence of obesity is increasing rapidly in low- and middle-income countries (LMICs) as their populations become exposed to obesogenic environments. The transition from an agrarian to an industrial and service-based economy results in important lifestyle changes. Yet different socioeconomic groups may experience and respond to these changes differently. Investigating the socioeconomic distribution of obesity in LMICs is key to understanding the causes of obesity but the field is limited by the scarcity of data and a uni-dimensional approach to socioeconomic status (SES). This study splits socioeconomic status into two dimensions to investigate how educated women may have lower levels of obesity in a context where labour market opportunities have shifted away from agriculture to other forms of employment. Methods The Four Provinces Study in China 2008/09 is a household-based community survey of 4,314 people aged ≥60  years (2,465 women). It was used to investigate an interaction between education (none/any) and occupation (agricultural/non-agricultural) on high-risk central obesity defined as a waist circumference ≥80 cm. An interaction term between education and occupation was incorporated in a multivariate logistic regression model, and the estimates adjusted for age, parity, urban/rural residence and health behaviours (smoking, alcohol, meat and fruit & vegetable consumption). Complete case analyses were undertaken and results confirmed using multiple imputation to impute missing data. Results An interaction between occupation and education was present (P = 0.02). In the group with no education, the odds of central obesity in the sedentary occupation group were more than double those of the agricultural occupation group even after taking age group and parity into account (OR; 95%CI: 2.21; 1.52, 3.21), while in the group with any education there was no evidence of such a relationship (OR; 95%CI: 1.25; 0.92, 1.70). Health behaviours

  7. Interaction of DRD2TaqI, COMT, and ALDH2 genes associated with bipolar II disorder comorbid with anxiety disorders in Han Chinese in Taiwan.

    Science.gov (United States)

    Hu, Ming-Chuan; Lee, Sheng-Yu; Wang, Tzu-Yun; Chang, Yun-Hsuan; Chen, Shiou-Lan; Chen, Shih-Heng; Chu, Chun-Hsien; Wang, Chen-Lin; Lee, I Hui; Chen, Po See; Yang, Yen Kuang; Lu, Ru-Band

    2015-06-01

    It is hypothesized that dopaminergic genes-dopamine type-2 receptor (DRD2), aldehyde dehydrogenase 2 (ALDH2), and catechol-O-methyltransferase (COMT)-are associated with bipolar disorder (BP) and anxiety disorder (AD). Bipolar II (BP-II) is reported to be highly comorbid with AD. We examined whether interactions among these three genes are susceptibility factors in BP-II with AD (BP-II(+AD)) and without AD (BP-II(-AD)). In this study, we hypothesize that the interaction of the dopaminergic genes between BP-II(+AD) and BP-II(-AD) is significant different. We recruited 1260 participants: 495 with BP-II(-AD), 170 with BP-II(+AD), and 595 healthy controls without BP-II or AD. Genotyping was done using polymerase chain reactions plus restriction fragment length polymorphism analysis. Genotypic frequencies of the DRD2TaqIA, COMT, and ALDH2 polymorphisms between the two BP-II groups were nonsignificant. In logistic regression, the ALDH2 and DRD2TaqIA genes showed a main effect that was protective against BP-II(-AD) (odds ratio [OR] = 0.497, p = 0.010, and OR = 0.415, p = 0.017, respectively). The interaction of DRD2TaqIA A1/A1 and ALDH2*1/*1 had a significant risk effect on the BP-II(-AD) group (OR = 7.177, p II(-AD) (OR = 0.205, p = 0.047). All of the significant results described above are found only in BP-II(-AD). This study supports the hypothesis the interaction of the dopaminergic genes between BP-II(+AD) and BP-II(-AD) is significant different,, and provides additional evidence that the DRD2TaqIA A1/A1, ALDH2*1/*1 and COMT genes interact in BP-II(-AD) but not in BP-II(+AD). PMID:25430946

  8. 大学生交往焦虑状况及其影响因素%Interaction anxiousness and associated factors among college students

    Institute of Scientific and Technical Information of China (English)

    李丹枫; 陈昕昱; 段添翼; 余真真; 杨智辉

    2013-01-01

    目的 了解大学生交往焦虑状况的特点及影响因素,为有针对性地开展干预活动提供有益参考.方法 采用交往焦虑量表、自尊量表、对不确定性忍受力问卷和元担忧问卷,对随机抽取的北京市17所高校905名大学生进行调查.结果 不同性别、不同家庭经济状况、不同生源地的大学生交往焦虑总分差异均有统计学意义(P值均<0.05);相关分析表明,自尊与交往焦虑呈负相关,不确定性忍受力和元担忧与交往焦虑呈正相关(P值均<0.05).路径分析表明,自尊、不确定性忍受力、元担忧对交往焦虑总分有直接效应,自尊还会通过不确定性忍受力、元担忧对交往焦虑总分起间接效应.结论 大学生交往焦虑水平较高,不确定性忍受力对交往焦虑起着最为重要的直接作用,自尊通过不确定性忍受力和元担忧对交往焦虑起间接作用.应关注大学生不确定性忍受力、自尊及元担忧,并及时采取干预措施.%Objective To explore epidemiology of anxiety among college students and to explore possible risk factors.Methods The Interaction Anxiousness Scale,Self-Esteem Scale,Intolerance of Uncertainty Questionnaire,Meta-Worry Questionnaire were used to investigate the Interaction Anxiousness and associated psychological information in 905 undergraduates.Results There were significant differences of Interaction Anxiousness scores in genders,family economic status and prior residence place.Analysis showed that Interaction Anxiousness was significantly negatively correlated with parental educational level and self-esteem and positively related to intolerance of uncertainty and meta-worry.Path analysis showed that self-esteem had the important direct effect on the Interaction Anxiousness,and also had indirect effects on it through the effects of intolerance of uncertainty and metaworry.The intolerance of uncertainty had the most impact on Interaction Anxiousness

  9. 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; Vinberg, Maj; Erritzøe, David;

    2010-01-01

    -twin history of mood disorder were included. They answered self-report personality questionnaires and underwent [(18)F]altanserin positron emission tomography. We found a significant interaction between neuroticism and familial risk in predicting the frontolimbic 5-HT(2A) receptor binding (p=0......Life stress is a robust risk factor for later development of mood disorders, particularly for individuals at familial risk. Likewise, scoring high on the personality trait neuroticism is associated with an increased risk for mood disorders. Neuroticism partly reflects stress vulnerability...... binding. These findings point at a plausible neurobiological link between genetic and personality risk factors and vulnerability to developing mood disorders. It contributes to our understanding of why some people at high risk develop mood disorders while others do not. We speculate that an increased...

  10. Interaction between serotonin transporter and dopamine D2/D3 receptor radioligand measures is associated with harm avoidant symptoms in anorexia and bulimia nervosa.

    Science.gov (United States)

    Bailer, Ursula F; Frank, Guido K; Price, Julie C; Meltzer, Carolyn C; Becker, Carl; Mathis, Chester A; Wagner, Angela; Barbarich-Marsteller, Nicole C; Bloss, Cinnamon S; Putnam, Karen; Schork, Nicholas J; Gamst, Anthony; Kaye, Walter H

    2013-02-28

    Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) have alterations of measures of serotonin (5-HT) and dopamine (DA) function, which persist after long-term recovery and are associated with elevated harm avoidance (HA), a measure of anxiety and behavioral inhibition. Based on theories that 5-HT is an aversive motivational system that may oppose a DA-related appetitive system, we explored interactions of positron emission tomography (PET) radioligand measures that reflect portions of these systems. Twenty-seven individuals recovered (REC) from eating disorders (EDs) (7 AN-BN, 11 AN, 9 BN) and nine control women (CW) were analyzed for correlations between [(11)C]McN5652 and [(11)C]raclopride binding. There was a significant positive correlation between [(11)C]McN5652 binding potential (BP(non displaceable(ND))) and [(11)C]Raclopride BP(ND) for the dorsal caudate, antero-ventral striatum (AVS), middle caudate, and ventral and dorsal putamen. No significant correlations were found in CW. [(11)C]Raclopride BP(ND), but not [(11)C]McN5652 BP(ND), was significantly related to HA in REC EDs. A linear regression analysis showed that the interaction between [(11)C]McN5652 BP(ND) and [(11)C]raclopride BP(ND) in the dorsal putamen significantly predicted HA. This is the first study using PET and the radioligands [(11)C]McN5652 and [(11)C]raclopride to show a direct relationship between 5-HT transporter and striatal DA D2/D3 receptor binding in humans, supporting the possibility that 5-HT and DA interactions contribute to HA behaviors in EDs.

  11. Interactive effects of supplemental UV-B and temperature in European aspen seedlings: Implications for growth, leaf traits, phenolic defense and associated organisms.

    Science.gov (United States)

    Randriamanana, Tendry R; Lavola, Anu; Julkunen-Tiitto, Riitta

    2015-08-01

    Past studies reveal opposite effects of elevated UV-B and temperature on plant growth and concentrations of UV-B absorbing compounds, yet few studies have dealt with the combined and interactive effects of these two climate change factors on woody dioecious plants. We investigated the interactive effects of UV-B and temperature treatments on growth, leaf traits and phenolic concentrations in Populus tremula L. (European aspen) seedlings. We also considered the consequences of these effects on their associated organisms: herbivorous insects, rust pathogens, the presence of endophytic fungi and whether or not the responses differ between genders and genotypes. Supplemental temperature and UV-B were modulated to +2 °C and +30.77% above ambient conditions, respectively. Warming increased growth, photosynthesis and foliar nitrogen concentration but reduced leaf thickness and phenolic concentrations. On the other hand, supplemental UV-B increased total phenolic glycosides, mainly flavonols and phenolic acids, and partially counteracted the positive effects of warming on growth. Fast growing genotypes were less susceptible to the growth-reducing effect of combined UVB + T, less infected with rust disease and less prone to insect damage probably due to their higher salicylate and lower nitrogen concentrations. Under ambient temperature, the males of European aspen were taller and had bigger leaves than the females, while under elevated temperature, females grew bigger and, under UV-B, had more tremulacin than males. The multiple interactive effects of UV-B and temperature on growth, leaf traits and phenolic compounds, highlight the importance of multifactor experiments as a realistic predictor of plant responses to climate change.

  12. Proteomic Analysis of Wild-type and Mutant Huntingtin-associated Proteins in Mouse Brains Identifies Unique Interactions and Involvement in Protein Synthesis*

    Science.gov (United States)

    Culver, Brady P.; Savas, Jeffrey N.; Park, Sung K.; Choi, Jeong H.; Zheng, Shuqiu; Zeitlin, Scott O.; Yates, John R.; Tanese, Naoko

    2012-01-01

    Huntington disease is a neurodegenerative disorder caused by a CAG repeat amplification in the gene huntingtin (HTT) that is reflected by a polyglutamine expansion in the Htt protein. Nearly 20 years of research have uncovered roles for Htt in a wide range of cellular processes, and many of these discoveries stemmed from the identification of Htt-interacting proteins. However, no study has employed an impartial and comprehensive strategy to identify proteins that differentially associate with full-length wild-type and mutant Htt in brain tissue, the most relevant sample source to the disease condition. We analyzed Htt affinity-purified complexes from wild-type and HTT mutant juvenile mouse brain from two different biochemical fractions by tandem mass spectrometry. We compared variations in protein spectral counts relative to Htt to identify those proteins that are the most significantly contrasted between wild-type and mutant Htt purifications. Previously unreported Htt interactions with Myo5a, Prkra (PACT), Gnb2l1 (RACK1), Rps6, and Syt2 were confirmed by Western blot analysis. Gene Ontology analysis of these and other Htt-associated proteins revealed a statistically significant enrichment for proteins involved in translation among other categories. Furthermore, Htt co-sedimentation with polysomes in cytoplasmic mouse brain extracts is dependent upon the presence of intact ribosomes. Finally, wild-type or mutant Htt overexpression inhibits cap-dependent translation of a reporter mRNA in an in vitro system. Cumulatively, these data support a new role for Htt in translation and provide impetus for further study into the link between protein synthesis and Huntington disease pathogenesis. PMID:22556411

  13. Interactions between Inhibitory Interneurons and Excitatory Associational Circuitry in Determining Spatio-Temporal Dynamics of Hippocampal Dentate Granule Cells: A Large-Scale Computational Study

    Directory of Open Access Journals (Sweden)

    Phillip eHendrickson

    2015-11-01

    Full Text Available This paper reports on findings from a million-cell granule cell model of the rat dentate gyrus that was used to explore the contributions of local interneuronal and associational circuits to network-level activity. The model contains experimentally derived morphological parameters for granule cells, which each contain approximately 200 compartments, and biophysical parameters for granule cells, basket cells and mossy cells that were based both on electrophysiological data and previously published models. Synaptic input to cells in the model consisted of glutamatergic AMPA-like EPSPs and GABAergic-like IPSPs from excitatory and inhibitory neurons, respectively. The main source of input to the model was from layer II entorhinal cortical neurons. Network connectivity was constrained by the topography of the system, and was derived from axonal transport studies, which provided details about the spatial spread of axonal terminal fields, as well as how subregions of the medial and lateral entorhinal cortices project to subregions of the dentate gyrus. Results of this study show that strong feedback inhibition from the basket cell population can cause high-frequency rhythmicity in granule cells, while the strength of feedforward inhibition serves to scale the total amount of granule cell activity. Results furthermore show that the topography of local interneuronal circuits can have just as strong an impact on the development of spatio-temporal clusters in the granule cell population as the perforant path topography does, both sharpening existing clusters and introducing new ones with a greater spatial extent. Finally, results show that the interactions between the inhibitory and associational loops can cause high frequency oscillations that are modulated by a low-frequency oscillatory signal. These results serve to further illustrate the importance of topographical constraints on a global signal processing feature of a neural network, while also

  14. A cautionary note on the impact of protocol changes for genome-wide association SNP × SNP interaction studies: an example on ankylosing spondylitis.

    Science.gov (United States)

    Bessonov, Kyrylo; Gusareva, Elena S; Van Steen, Kristel

    2015-07-01

    Genome-wide association interaction (GWAI) studies have increased in popularity. Yet to date, no standard protocol exists. In practice, any GWAI workflow involves making choices about quality control strategy, SNP filtering, linkage disequilibrium (LD) pruning, analytic tool to model or to test for genetic interactions. Each of these can have an impact on the final epistasis findings and may affect their reproducibility in follow-up analyses. Choosing an analytic tool is not straightforward, as different tools exist and current understanding about their performance is based on often very particular simulation settings. In the present study, we wish to create awareness for the impact of (minor) changes in a GWAI analysis protocol can have on final epistasis findings. In particular, we investigate the influence of marker selection and marker prioritization strategies, LD pruning and the choice of epistasis detection analytics on study results, giving rise to 8 GWAI protocols. Discussions are made in the context of the ankylosing spondylitis (AS) data obtained via the Wellcome Trust Case Control Consortium (WTCCC2). As expected, the largest impact on AS epistasis findings is caused by the choice of marker selection criterion, followed by marker coding and LD pruning. In MB-MDR, co-dominant coding of main effects is more robust to the effects of LD pruning than additive coding. We were able to reproduce previously reported epistasis involvement of HLA-B and ERAP1 in AS pathology. In addition, our results suggest involvement of MAGI3 and PARK2, responsible for cell adhesion and cellular trafficking. Gene ontology biological function enrichment analysis across the 8 considered GWAI protocols also suggested that AS could be associated to the central nervous system malfunctions, specifically, in nerve impulse propagation and in neurotransmitters metabolic processes. PMID:25939665

  15. PolyC-binding protein 1 interacts with 5'-untranslated region of enterovirus 71 RNA in membrane-associated complex to facilitate viral replication.

    Directory of Open Access Journals (Sweden)

    Zhen Luo

    Full Text Available Enterovirus 71 (EV71 is one causative agent of hand, foot, and mouth disease (HFMD, which may lead to severe neurological disorders and mortality in children. EV71 genome is a positive single-stranded RNA containing a single open reading frame (ORF flanked by 5'-untranslated region (5'UTR and 3'UTR. The 5'UTR is fundamentally important for virus replication by interacting with cellular proteins. Here, we revealed that poly(C-binding protein 1 (PCBP1 specifically binds to the 5'UTR of EV71. Detailed studies indicated that the RNA-binding K-homologous 1 (KH1 domain of PCBP1 is responsible for its binding to the stem-loop I and IV of EV71 5'UTR. Interestingly, we revealed that PCBP1 is distributed in the nucleus and cytoplasm of uninfected cells, but mainly localized in the cytoplasm of EV71-infected cells due to interaction and co-localization with the viral RNA. Furthermore, sub-cellular distribution analysis showed that PCBP1 is located in ER-derived membrane, in where virus replication occurred in the cytoplasm of EV71-infected cells, suggesting PCBP1 is recruited in a membrane-associated replication complex. In addition, we found that the binding of PCBP1 to 5'UTR resulted in enhancing EV71 viral protein expression and virus production so as to facilitate viral replication. Thus, we revealed a novel mechanism in which PCBP1 as a positive regulator involved in regulation of EV71 replication in the host specialized membrane-associated replication complex, which provides an insight into cellular factors involved in EV71 replication.

  16. Expression of a gibberellin-induced leucine-rich repeat receptor-like protein kinase in deepwater rice and its interaction with kinase-associated protein phosphatase

    Energy Technology Data Exchange (ETDEWEB)

    Knaap, E. van der; Sauter, M.; Kende, H. (Michigan State Univ., East Lansing, MI (United States). DOE Plant Research Lab.); Song, W.Y.; Ruan, D.L.; Ronald, P.C. (Univ. of California, Davis, CA (United States). Dept. of Plant Pathology)

    1999-06-01

    The authors identified in deepwater rice (Oryza sativa L.) a gene encoding a leucine-rich repeat receptor-like transmembrane protein kinase, OsTMK (O. sativa transmembrane kinase). The transcript levels of OsTMK increased in the rice internode in response to gibberellin. Expression of OsTMK was especially high in regions undergoing cell division and elongation. The kinase domain of OsTMK was enzymatically active autophosphorylating on serine and threonine residues. A cDNA encoding a rice ortholog of a kinase-associated type 2C protein phosphatase (OsKAPP) was cloned. KAPPs are putative downstream components in kinase-mediated signal transduction pathways. The kinase interaction domain of OsKAPP was phosphorylated in vitro by the kinase domain of OsTMK. RNA gel-blot analysis indicated that the expression of OsTMK and OsKAPP was similar in different tissues of the rice plant. In protein-binding assays, OsKAPP interacted with a receptor-like protein kinase, RLK5 of Arabidopsis, but not with the protein kinase domains of the rice and maize receptor-like protein kinases Xa21 and ZmPK1, respectively.

  17. BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized α helix of BCL2) not always convinces BAX (BCL-2-associated X protein) for apoptosis.

    Science.gov (United States)

    Verma, Sharad; Goyal, Sukriti; Tyagi, Chetna; Jamal, Salma; Singh, Aditi; Grover, Abhinav

    2016-06-01

    The interaction of BAX (BCL-2-associated X protein) with BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized α helix of BCL2) directly initiates BAX-mediated mitochondrial apoptosis. This molecular dynamics study reveals that BIM SAHB forms a stable complex with BAX but it remains in a non-functional conformation. N terminal of BAX folds towards the core which has been reported exposed in the functional monomer. The α1-α2 loop, which has been reported in open conformation in functional BAX, acquires a closed conformation during the simulation. BH3/α2 remains less exposed as compared to initial structure. The hydrophobic residues of BIM accommodates in the rear pocket of BAX during the simulation. A steep decrease in radius of gyration and solvent accessible surface area (SASA) indicates the complex folding to acquire a more stable but inactive conformation. Further the covariance matrix reveals that the backbone atoms' motions favour the inactive conformation of the complex. This is the first report on the non-functional BAX-BIM SAHB complex by molecular dynamics simulation in the best of our knowledge. PMID:27262527

  18. Amikacin-fosfomycin at a five-to-two ratio: characterization of mutation rates in microbial strains causing ventilator-associated pneumonia and interactions with commonly used antibiotics.

    Science.gov (United States)

    Montgomery, A Bruce; Rhomberg, Paul R; Abuan, Tammy; Walters, Kathie-Anne; Flamm, Robert K

    2014-07-01

    The amikacin-fosfomycin inhalation system (AFIS), a combination of antibiotics administered with an in-line nebulizer delivery system, is being developed for adjunctive treatment of ventilator-associated pneumonia (VAP). The in vitro characterization of amikacin-fosfomycin (at a 5:2 ratio) described here included determining resistance selection rates for pathogens that are representative of those commonly associated with VAP (including multidrug-resistant strains) and evaluating interactions with antibiotics commonly used intravenously to treat VAP. Spontaneous resistance to amikacin-fosfomycin (5:2) was not observed for most strains tested (n, 10/14). Four strains had spontaneously resistant colonies (frequencies, 4.25 × 10(-8) to 3.47 × 10(-10)), for which amikacin-fosfomycin (5:2) MICs were 2- to 8-fold higher than those for the original strains. After 7 days of serial passage, resistance (>4-fold increase over the baseline MIC) occurred in fewer strains (n, 4/14) passaged in the presence of amikacin-fosfomycin (5:2) than with either amikacin (n, 7/14) or fosfomycin (n, 12/14) alone. Interactions between amikacin-fosfomycin (5:2) and 10 comparator antibiotics in checkerboard testing against 30 different Gram-positive or Gram-negative bacterial strains were synergistic (fractional inhibitory concentration [FIC] index, ≤ 0.5) for 6.7% (n, 10/150) of combinations tested. No antagonism was observed. Synergy was confirmed by time-kill methodology for amikacin-fosfomycin (5:2) plus cefepime (against Escherichia coli), aztreonam (against Pseudomonas aeruginosa), daptomycin (against Enterococcus faecalis), and azithromycin (against Staphylococcus aureus). Amikacin-fosfomycin (5:2) was bactericidal at 4-fold the MIC for 7 strains tested. The reduced incidence of development of resistance to amikacin-fosfomycin (5:2) compared with that for amikacin or fosfomycin alone, and the lack of negative interactions with commonly used intravenous antibiotics, further supports

  19. Identification of clathrin heavy chain as a direct interaction partner for the gamma-aminobutyric acid type A receptor associated protein.

    Science.gov (United States)

    Mohrlüder, Jeannine; Hoffmann, Yvonne; Stangler, Thomas; Hänel, Karen; Willbold, Dieter

    2007-12-18

    Gamma-aminobutyric acid type A receptors (GABAA receptors) are the major sites of GABA-mediated fast synaptic inhibition in the central nervous system. Variation of the cell surface receptor count is postulated to be of importance in modulating inhibitory synaptic transmission. The GABAA receptor associated protein (GABARAP) is a ubiquitin-like modifier, implicated in GABAA receptor clustering, trafficking, and turnover. GABARAP pull-down experiments with brain lysate identified clathrin heavy chain to be GABARAP-associated. Phage display screening of a randomized peptide library for GABARAP ligands yielded a sequence motif which characterizes the peptide binding specificity of GABARAP. Sequence database searches with this motif revealed clathrin heavy chain as a protein containing the identified sequence motif within its residues 510-522, supporting the result of the pull-down experiments. Calreticulin, which was identified recently as a GABARAP ligand, contains a very similar sequence motif. We demonstrate that calreticulin indeed competes with clathrin heavy chain for GABARAP binding. Finally, employing nuclear magnetic resonance spectroscopy, we mapped the GABARAP residues responsible for binding to clathrin. The hereby mapped GABARAP regions overlap very well with the homologue residues in yeast Atg8 that were recently shown to be important for autophagy. Together with the knowledge that GABARAP and clathrin are known to be involved in GABAA receptor trafficking within the cell, this strongly suggests a clear physiological relevance of the direct interaction of GABARAP with clathrin heavy chain. PMID:18027972

  20. 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 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{sub 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

  1. Anesthetic effects changeable in habitual drinkers: Mechanistic drug interactions with neuro-active indoleamine-aldehyde condensation products associated with alcoholic beverage consumption.

    Science.gov (United States)

    Tsuchiya, Hironori

    2016-07-01

    Clinicians often experience the reduced efficacy of general and local anesthetics and anesthesia-related drugs in habitual drinkers and chronic alcoholics. However, the mechanistic background underlying such anesthetic tolerance remains unclear. Biogenic indoleamines condense with alcohol-derived aldehydes during fermentation processes and under physiological conditions to produce neuro-active tetrahydro-β-carbolines and β-carbolines, many of which are contained not only in various alcoholic beverages but also in human tissues and body fluids. These indoleamine-aldehyde condensation products are increased in the human body because of their exogenous and endogenous supply enhanced by alcoholic beverage consumption. Since tetrahydro-β-carbolines and β-carbolines target receptors, ion channels and neuronal membranes which are common to anesthetic agents, we propose a hypothesis that they may pharmacodynamically interact at GABAA receptors, NMDA receptors, voltage-gated Na(+) channels and membrane lipid bilayers to attenuate anesthetics-induced positive allosteric GABAA receptor modulation, NMDA receptor antagonism, ion channel blockade and neuronal membrane modification, thereby affecting anesthetic efficacy. The condensation products may also cooperatively interact with ethanol that induces adaptive changes and cross-tolerance to anesthetics and with dopamine-aldehyde adducts that act on GABAA receptors and membrane lipids. Because tetrahydro-β-carbolines and β-carbolines are metabolized to lose or decrease their neuro-activities, induction of the relevant enzymes by habitual drinking could produce an inter-individual difference of drinkers in susceptibility to anesthetic agents. The present hypothesis would also provide a unified framework for different modes of anesthetic action, which are inhibited by neuro-active indoleamine-aldehyde condensation products associated with alcoholic beverage consumption. PMID:27241259

  2. KIR3DL1 interaction with HLA-B27 is altered by ankylosing spondylitis associated ERAP1 and enhanced by MHC class I cross-linking.

    Science.gov (United States)

    Abdullah, Hasan; Zhang, Zhenbo; Yee, Kirby; Haroon, Nigil

    2015-01-01

    Ankylosing spondylitis (AS) is a chronic, inflammatory arthritis of the spine and peripheral joints linked to the antigen presenting molecule HLA-B27. The risk of AS is increased in patients possessing endoplasmic reticulum aminopeptidase-1 (ERAP1) polymorphisms rs30187 and rs27044 encoding amino acid changes K528R and Q730E, respectively. Dysfunction of ERAP1 is hypothesized to cause changes in expression of HLA-B27 classical (pHLA) and non-classical (FHC) conformers on antigen presenting cells (APCs), which interact with the natural killer (NK) cell receptor KIR3DL1. Dysregulation of this pathway may be pathogenic in AS. APC cell lines expressing HLA-B27 were found to inhibit cytokine production in KIR3DL1+ NK cells due to decreased APC-NK cell adhesion, and possibly activation of receptor down-regulation. Blocking pHLA and FHC reveals that both conformers inhibit cytokine production through KIR3DL1. KIR3DL1 affinity and HLA-B27 surface expression studies suggest that ERAP1 R528 and E730 expression protects from AS by generating sub-optimal pHLA, causing reduced KIR3DL1 affinity and weaker cytokine inhibition. Secondarily we observed that KIR3DL1 binding to C1R-B27 APCs is enhanced by blocking pHLA, but not FHC, raising the possibility that antibody mediated HLA-B27 cross-linking may be important in enhancing KIR3DL1+ NK cell function. This study establishes the role of both FHC and pHLA in modulating NK cell cytokine secretion and adhesion functions by interacting with KIR3DL1. This interaction varies depending on the AS association status of the ERAP1 variant expressed in APCs. Additionally antibody cross-linking of HLA-B27 enhances KIR3DL1 binding and as such could be an important pathogenic mechanism in AS. PMID:26321090

  3. Molecular cloning, expression and functional characterization of tumor necrosis factor (TNF) receptor-associated factor (TRAF)-interacting protein (TRIP) in grass carp, Ctenopharyngodon idella.

    Science.gov (United States)

    Lu, R-H; Chang, Z-G; Sun, J; Yang, F; Nie, G-X; Ji, H

    2016-10-01

    TRIP (Tumor Necrosis Factor (TNF) Receptor-Associated Factor (TRAF)-Interacting Protein), a member of the TNF superfamily, plays a crucial role in the modulation of inflammation in vertebrates. However, no information about TRIP is available in teleosts. In this study, the full-length cDNA of TRIP, containing a 5'UTR of 112 bp, an ORF of 1359 bp, and a 3'UTR of 29 bp before the poly (A) tail, was cloned from grass carp, Ctenopharyngodon idella. The TRIP gene encoded a protein of 452 amino acids with an estimated molecular mass of 51.06 KD and a predicted theoretical isoelectric point (pI) of 9.11. Quantitative real-time PCR analysis revealed that TRIP mRNA was expressed in all the tissues examined in grass carp, with the highest expression in the kidney, followed by the intestine and thymus. However, lower levels of expression were also detected in fat, spleen, liver, gonad and heart. Subcellular localization and two-hybrid analysis revealed that TRIP was located in the nucleus and that it interacted with TRAF1 and TRAF2 in HEK293T cells. Furthermore, similar to TNF-α, IL-10 and TRIP mRNA expression was upregulated in the spleen of fish fed high-fat or high-carbohydrate diets, suggesting that TRIP might be associated with the response to excessive energy intake. The mRNA relative expression of TRIP was significantly reduced (P < 0.05) after hepatocyte of C. idella was treated with 2 μg/mL lipopolysaccharide (LPS) for 4 h, while the expression levels of inflammatory cytokines TNF-α and IL-10 were significantly increased (P < 0.05). Taken together, these results indicate that TRIP might play important roles in immune defense and has the potential to be used as a anti-inflammation target in grass carp. PMID:27546552

  4. The regulation of tooth morphogenesis is associated with epithelial cell proliferation and the expression of Sonic hedgehog through epithelial-mesenchymal interactions

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Kentaro; Murofushi, Mayumi [Faculty of Industrial Science and Technology, Tokyo University of Science, Chiba 278-8510 (Japan); Nakao, Kazuhisa; Morita, Ritsuko [Research Institute for Science and Technology, Tokyo University of Science, Chiba 278-8510 (Japan); Ogawa, Miho [Research Institute for Science and Technology, Tokyo University of Science, Chiba 278-8510 (Japan); Organ Technologies Inc., Tokyo 101-0048 (Japan); Tsuji, Takashi, E-mail: t-tsuji@rs.noda.tus.ac.jp [Faculty of Industrial Science and Technology, Tokyo University of Science, Chiba 278-8510 (Japan); Research Institute for Science and Technology, Tokyo University of Science, Chiba 278-8510 (Japan); Organ Technologies Inc., Tokyo 101-0048 (Japan)

    2011-02-18

    Research highlights: {yields} Bioengineered teeth regulated the contact area of epithelium and mesenchyme. {yields} The crown width is regulated by the contact area of the epithelium and mesenchyme. {yields} This regulation is associated with cell proliferation and Sonic hedgehog expression. {yields} The cusp number is correlated with the crown width of the bioengineered tooth. {yields} Cell proliferation and Shh expression areas regulate the tooth morphogenesis. -- Abstract: Ectodermal organs, such as the tooth, salivary gland, hair, and mammary gland, develop through reciprocal epithelial-mesenchymal interactions. Tooth morphologies are defined by the crown width and tooth length (macro-morphologies), and by the number and locations of the cusp and roots (micro-morphologies). In our current study, we report that the crown width of a bioengineered molar tooth, which was reconstructed using dissociated epithelial and mesenchymal cells via an organ germ method, can be regulated by the contact area between epithelial and mesenchymal cell layers. We further show that this is associated with cell proliferation and Sonic hedgehog (Shh) expression in the inner enamel epithelium after the germ stage has formed a secondary enamel knot. We also demonstrate that the cusp number is significantly correlated with the crown width of the bioengineered tooth. These findings suggest that the tooth micro-morphology, i.e. the cusp formation, is regulated after the tooth width, or macro-morphology, is determined. These findings also suggest that the spatiotemporal patterning of cell proliferation and the Shh expression areas in the epithelium regulate the crown width and cusp formation of the developing tooth.

  5. The Use of Protein-Protein Interactions for the Analysis of the Associations between PM2.5 and Some Diseases.

    Science.gov (United States)

    Zhang, Qing; Zhang, Pei-Wei; Cai, Yu-Dong

    2016-01-01

    Nowadays, pollution levels are rapidly increasing all over the world. One of the most important pollutants is PM2.5. It is known that the pollution environment may cause several problems, such as greenhouse effect and acid rain. Among them, the most important problem is that pollutants can induce a number of serious diseases. Some studies have reported that PM2.5 is an important etiologic factor for lung cancer. In this study, we extensively investigate the associations between PM2.5 and 22 disease classes recommended by Goh et al., such as respiratory diseases, cardiovascular diseases, and gastrointestinal diseases. The protein-protein interactions were used to measure the linkage between disease genes and genes that have been reported to be modulated by PM2.5. The results suggest that some diseases, such as diseases related to ear, nose, and throat and gastrointestinal, nutritional, renal, and cardiovascular diseases, are influenced by PM2.5 and some evidences were provided to confirm our results. For example, a total of 18 genes related to cardiovascular diseases are identified to be closely related to PM2.5, and cardiovascular disease relevant gene DSP is significantly related to PM2.5 gene JUP. PMID:27243032

  6. X-rays associated with the jet-cloud-interacting radio galaxy 3C 277.3 (Coma A): implications for energy deposition

    Science.gov (United States)

    Worrall, D. M.; Birkinshaw, M.; Young, A. J.

    2016-05-01

    We report the discovery with Chandra of X-ray-emitting gas associated with the jet-cloud interaction in the radio galaxy 3C 277.3 (Coma A), a source that falls in the most important power range for radio-mode feedback in the Universe. This hot gas, heated by the jet, dominates the mass of the cloud which is responsible for an extreme projected deflection of the kpc-scale radio jet. Highly absorbed X-ray emission from the nucleus of 3C 277.3 confirms that the jet lies close to the plane of the sky and so has a large intrinsic deflection. We detect group gas on the scale of the radio lobes, and see X-ray cavities coincident with the brightest radio emission, with the lobes embraced by X-ray enhancements that we argue are the result of shocks. The anti-correlation between the locations of X-ray arms and H α-emitting filaments that are believed to have originated from a merger with one or more gas-rich galaxies suggests that shocks advancing around the lobe are inhibited by the dense colder material. Synchrotron X-ray emission is detected from the upstream edge of a second bright radio knot. X-rays are also detected from the location where an undetected counterjet enters the northern radio hotspot. We suggest that these X-rays are synchrotron radiation from a shock in a small-scale sub-structure.

  7. Adolescent Internet addiction: testing the association between self-esteem, the perception of Internet attributes, and preference for online social interactions.

    Science.gov (United States)

    Fioravanti, Giulia; Dèttore, Davide; Casale, Silvia

    2012-06-01

    There is a general consensus that Internet addiction (IA) is mainly related to social aspects of the Web, especially among adolescents. The empirical link between poor social skills and IA is well documented; however, theoretical explanations for this relationship are less developed. One possibility is that people with poor social skills are especially prone to develop a preference for online social interaction (POSI), which, in turn, predicts problematic usage. This hypothesis has been tested for loneliness and social anxiety, but not for self-esteem (SE; one of the main antecedents of IA). Furthermore, the mediating role of the perceived relevance of some Internet features (e.g., anonymity) in the relationship between SE and POSI has never been investigated. A cross-sectional study was conducted with 257 adolescents. Using mediation analyses, we found evidence among females for the mediating role of (a) POSI in the relationship between SE and IA, and (b) the subjective relevance of some Internet features in the association between SE and POSI. No significant effects were found for males. PMID:22703038

  8. X-rays associated with the jet-cloud interacting radio galaxy 3C 277.3 (Coma A): implications for energy deposition

    CERN Document Server

    Worrall, D M; Young, A J

    2016-01-01

    We report the discovery with Chandra of X-ray-emitting gas associated with the jet-cloud interaction in the radio galaxy 3C 277.3 (Coma A), a source that falls in the most important power range for radio-mode feedback in the Universe. This hot gas, heated by the jet, dominates the mass of the cloud which is responsible for an extreme projected deflection of the kpc-scale radio jet. Highly absorbed X-ray emission from the nucleus of 3C 277.3 confirms that the jet lies close to the plane of the sky and so has a large intrinsic deflection. We detect group gas on the scale of the radio lobes, and see X-ray cavities coincident with the brightest radio emission, with the lobes embraced by X-ray enhancements that we argue are the result of shocks. The anti-correlation between the locations of X-ray arms and H$\\alpha$-emitting filaments that are believed to have originated from a merger with one or more gas-rich galaxies suggests that shocks advancing around the lobe are inhibited by the dense colder material. Synchr...

  9. SENESCENCE-SUPPRESSED PROTEIN PHOSPHATASE Directly Interacts with the Cytoplasmic Domain of SENESCENCE-ASSOCIATED RECEPTOR-LIKE KINASE and Negatively Regulates Leaf Senescence in Arabidopsis.

    Science.gov (United States)

    Xiao, Dong; Cui, Yanjiao; Xu, Fan; Xu, Xinxin; Gao, Guanxiao; Wang, Yaxin; Guo, Zhaoxia; Wang, Dan; Wang, Ning Ning

    2015-10-01

    Reversible protein phosphorylation mediated by protein kinases and phosphatases plays an important role in the regulation of leaf senescence. We previously reported that the leucine-rich repeat receptor-like kinase SENESCENCE-ASSOCIATED RECEPTOR-LIKE KINASE (AtSARK) positively regulates leaf senescence in Arabidopsis (Arabidopsis thaliana). Here, we report the involvement of a protein serine/threonine phosphatase 2C-type protein phosphatase, SENESCENCE-SUPPRESSED PROTEIN PHOSPHATASE (SSPP), in the negative regulation of Arabidopsis leaf senescence. SSPP transcript levels decreased greatly during both natural senescence and SARK-induced precocious senescence. Overexpression of SSPP significantly delayed leaf senescence in Arabidopsis. Protein pull-down and bimolecular fluorescence complementation assays demonstrated that the cytosol-localized SSPP could interact with the cytoplasmic domain of the plasma membrane-localized AtSARK. In vitro assays showed that SSPP has protein phosphatase function and can dephosphorylate the cytosolic domain of AtSARK. Consistent with these observations, overexpression of SSPP effectively rescued AtSARK-induced precocious leaf senescence and changes in hormonal responses. All our results suggested that SSPP functions in sustaining proper leaf longevity and preventing early senescence by suppressing or perturbing SARK-mediated senescence signal transduction.

  10. SPARC (secreted protein acidic and rich in cysteine) of the intestinal nematode Strongyloides ratti is involved in mucosa-associated parasite-host interaction.

    Science.gov (United States)

    Anandarajah, Emmanuela M; Ditgen, Dana; Hansmann, Jan; Erttmann, Klaus D; Liebau, Eva; Brattig, Norbert W

    2016-06-01

    The secreted protein acidic and rich in cysteine (SPARC), found in the excretory/secretory products of Strongyloides ratti, is most strongly expressed in parasitic females. Since SPARC proteins are involved in the modulation of cell-matrix interactions, a role of the secreted S. ratti SPARC (Sr-SPARC) in the manifestation of the parasite in the host's intestine is postulated. The full-length cDNA of Sr-SPARC was identified and the protein was recombinantly expressed. The purified protein was biologically active, able to bind calcium, and to attach to mucosa-associated human cells. Addition of Sr-SPARC to an in vitro mucosal three-dimensional-cell culture model led to a time-dependent release of the cytokines TNF-α, IL-22, IL-10 and TSLP. Of importance, exposure with Sr-SPARC fostered wound closure in an intestinal epithelial cell model. Here, we demonstrate for the first time that SPARC released from the nematode is a multifunctional protein affecting the mucosal immune system. PMID:27268729

  11. Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE Consortium Studies.

    Science.gov (United States)

    Hruby, Adela; Ngwa, Julius S; Renström, Frida; Wojczynski, Mary K; Ganna, Andrea; Hallmans, Göran; Houston, Denise K; Jacques, Paul F; Kanoni, Stavroula; Lehtimäki, Terho; Lemaitre, Rozenn N; Manichaikul, Ani; North, Kari E; Ntalla, Ioanna; Sonestedt, Emily; Tanaka, Toshiko; van Rooij, Frank J A; Bandinelli, Stefania; Djoussé, Luc; Grigoriou, Efi; Johansson, Ingegerd; Lohman, Kurt K; Pankow, James S; Raitakari, Olli T; Riserus, Ulf; Yannakoulia, Mary; Zillikens, M Carola; Hassanali, Neelam; Liu, Yongmei; Mozaffarian, Dariush; Papoutsakis, Constantina; Syvänen, Ann-Christine; Uitterlinden, André G; Viikari, Jorma; Groves, Christopher J; Hofman, Albert; Lind, Lars; McCarthy, Mark I; Mikkilä, Vera; Mukamal, Kenneth; Franco, Oscar H; Borecki, Ingrid B; Cupples, L Adrienne; Dedoussis, George V; Ferrucci, Luigi; Hu, Frank B; Ingelsson, Erik; Kähönen, Mika; Kao, W H Linda; Kritchevsky, Stephen B; Orho-Melander, Marju; Prokopenko, Inga; Rotter, Jerome I; Siscovick, David S; Witteman, Jacqueline C M; Franks, Paul W; Meigs, James B; McKeown, Nicola M; Nettleton, Jennifer A

    2013-03-01

    Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = -0.009 mmol/L (95% CI: -0.013, -0.005), P magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.

  12. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

    Directory of Open Access Journals (Sweden)

    Thomas W Winkler

    2015-10-01

    Full Text Available Genome-wide association studies (GWAS have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI, a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE, sex-specific effects (G x SEX or age-specific effects that differed between men and women (G x AGE x SEX. For BMI, we identified 15 loci (11 previously established for main effects, four novel that showed significant (FDR<5% age-specific effects, of which 11 had larger effects in younger (<50y than in older adults (≥50y. No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

  13. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

    Science.gov (United States)

    Feitosa, Mary F.; Chu, Su; Czajkowski, Jacek; Esko, Tõnu; Fall, Tove; Kilpeläinen, Tuomas O.; Lu, Yingchang; Mägi, Reedik; Mihailov, Evelin; Pers, Tune H.; Rüeger, Sina; Teumer, Alexander; Ehret, Georg B.; Ferreira, Teresa; Heard-Costa, Nancy L.; Karjalainen, Juha; Lagou, Vasiliki; Mahajan, Anubha; Neinast, Michael D.; Prokopenko, Inga; Simino, Jeannette; Teslovich, Tanya M.; Jansen, Rick; Westra, Harm-Jan; White, Charles C.; Absher, Devin; Ahluwalia, Tarunveer S.; Ahmad, Shafqat; Albrecht, Eva; Alves, Alexessander Couto; Bragg-Gresham, Jennifer L.; de Craen, Anton J. M.; Bis, Joshua C.; Bonnefond, Amélie; Boucher, Gabrielle; Cadby, Gemma; Cheng, Yu-Ching; Chiang, Charleston W. K.; Delgado, Graciela; Demirkan, Ayse; Dueker, Nicole; Eklund, Niina; Eiriksdottir, Gudny; Eriksson, Joel; Feenstra, Bjarke; Fischer, Krista; Frau, Francesca; Galesloot, Tessel E.; Geller, Frank; Goel, Anuj; Gorski, Mathias; Grammer, Tanja B.; Gustafsson, Stefan; Haitjema, Saskia; Hottenga, Jouke-Jan; Huffman, Jennifer E.; Jackson, Anne U.; Jacobs, Kevin B.; Johansson, Åsa; Kaakinen, Marika; Kleber, Marcus E.; Lahti, Jari; Leach, Irene Mateo; Lehne, Benjamin; Liu, Youfang; Lo, Ken Sin; Lorentzon, Mattias; Luan, Jian'an; Madden, Pamela A. F.; Mangino, Massimo; McKnight, Barbara; Medina-Gomez, Carolina; Monda, Keri L.; Montasser, May E.; Müller, Gabriele; Müller-Nurasyid, Martina; Nolte, Ilja M.; Panoutsopoulou, Kalliope; Pascoe, Laura; Paternoster, Lavinia; Rayner, Nigel W.; Renström, Frida; Rizzi, Federica; Rose, Lynda M.; Ryan, Kathy A.; Salo, Perttu; Sanna, Serena; Scharnagl, Hubert; Shi, Jianxin; Smith, Albert Vernon; Southam, Lorraine; Stančáková, Alena; Steinthorsdottir, Valgerdur; Strawbridge, Rona J.; Sung, Yun Ju; Tachmazidou, Ioanna; Tanaka, Toshiko; Thorleifsson, Gudmar; Trompet, Stella; Pervjakova, Natalia; Tyrer, Jonathan P.; Vandenput, Liesbeth; van der Laan, Sander W; van der Velde, Nathalie; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Vlachopoulou, Efthymia; Waite, Lindsay L.; Wang, Sophie R.; Wang, Zhaoming; Wild, Sarah H.; Willenborg, Christina; Wilson, James F.; Wong, Andrew; Yang, Jian; Yengo, Loïc; Yerges-Armstrong, Laura M.; Yu, Lei; Zhang, Weihua; Zhao, Jing Hua; Andersson, Ehm A.; Bakker, Stephan J. L.; Baldassarre, Damiano; Banasik, Karina; Barcella, Matteo; Barlassina, Cristina; Bellis, Claire; Benaglio, Paola; Blangero, John; Blüher, Matthias; Bonnet, Fabrice; Bonnycastle, Lori L.; Boyd, Heather A.; Bruinenberg, Marcel; Buchman, Aron S; Campbell, Harry; Chen, Yii-Der Ida; Chines, Peter S.; Claudi-Boehm, Simone; Cole, John; Collins, Francis S.; de Geus, Eco J. C.; de Groot, Lisette C. P. G. M.; Dimitriou, Maria; Duan, Jubao; Enroth, Stefan; Eury, Elodie; Farmaki, Aliki-Eleni; Forouhi, Nita G.; Friedrich, Nele; Gejman, Pablo V.; Gigante, Bruna; Glorioso, Nicola; Go, Alan S.; Gottesman, Omri; Gräßler, Jürgen; Grallert, Harald; Grarup, Niels; Gu, Yu-Mei; Broer, Linda; Ham, Annelies C.; Hansen, Torben; Harris, Tamara B.; Hartman, Catharina A.; Hassinen, Maija; Hastie, Nicholas; Hattersley, Andrew T.; Heath, Andrew C.; Henders, Anjali K.; Hernandez, Dena; Hillege, Hans; Holmen, Oddgeir; Hovingh, Kees G; Hui, Jennie; Husemoen, Lise L.; Hutri-Kähönen, Nina; Hysi, Pirro G.; Illig, Thomas; De Jager, Philip L.; Jalilzadeh, Shapour; Jørgensen, Torben; Jukema, J. Wouter; Juonala, Markus; Kanoni, Stavroula; Karaleftheri, Maria; Khaw, Kay Tee; Kinnunen, Leena; Kittner, Steven J.; Koenig, Wolfgang; Kolcic, Ivana; Kovacs, Peter; Krarup, Nikolaj T.; Kratzer, Wolfgang; Krüger, Janine; Kuh, Diana; Kumari, Meena; Kyriakou, Theodosios; Langenberg, Claudia; Lannfelt, Lars; Lanzani, Chiara; Lotay, Vaneet; Launer, Lenore J.; Leander, Karin; Lindström, Jaana; Linneberg, Allan; Liu, Yan-Ping; Lobbens, Stéphane; Luben, Robert; Lyssenko, Valeriya; Männistö, Satu; Magnusson, Patrik K.; McArdle, Wendy L.; Menni, Cristina; Merger, Sigrun; Milani, Lili; Montgomery, Grant W.; Morris, Andrew P.; Narisu, Narisu; Nelis, Mari; Ong, Ken K.; Palotie, Aarno; Pérusse, Louis; Pichler, Irene; Pilia, Maria G.; Pouta, Anneli; Rheinberger, Myriam; Ribel-Madsen, Rasmus; Richards, Marcus; Rice, Kenneth M.; Rice, Treva K.; Rivolta, Carlo; Salomaa, Veikko; Sanders, Alan R.; Sarzynski, Mark A.; Scholtens, Salome; Scott, Robert A.; Scott, William R.; Sebert, Sylvain; Sengupta, Sebanti; Sennblad, Bengt; Seufferlein, Thomas; Silveira, Angela; Slagboom, P. Eline; Smit, Jan H.; Sparsø, Thomas H.; Stirrups, Kathleen; Stolk, Ronald P.; Stringham, Heather M.; Swertz, Morris A; Swift, Amy J.; Syvänen, Ann-Christine

    2015-01-01

    Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape. PMID:26426971

  14. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

    Science.gov (United States)

    Winkler, Thomas W; Justice, Anne E; Graff, Mariaelisa; Barata, Llilda; Feitosa, Mary F; Chu, Su; Czajkowski, Jacek; Esko, Tõnu; Fall, Tove; Kilpeläinen, Tuomas O; Lu, Yingchang; Mägi, Reedik; Mihailov, Evelin; Pers, Tune H; Rüeger, Sina; Teumer, Alexander; Ehret, Georg B; Ferreira, Teresa; Heard-Costa, Nancy L; Karjalainen, Juha; Lagou, Vasiliki; Mahajan, Anubha; Neinast, Michael D; Prokopenko, Inga; Simino, Jeannette; Teslovich, Tanya M; Jansen, Rick; Westra, Harm-Jan; White, Charles C; Absher, Devin; Ahluwalia, Tarunveer S; Ahmad, Shafqat; Albrecht, Eva; Alves, Alexessander Couto; Bragg-Gresham, Jennifer L; de Craen, Anton J M; Bis, Joshua C; Bonnefond, Amélie; Boucher, Gabrielle; Cadby, Gemma; Cheng, Yu-Ching; Chiang, Charleston W K; Delgado, Graciela; Demirkan, Ayse; Dueker, Nicole; Eklund, Niina; Eiriksdottir, Gudny; Eriksson, Joel; Feenstra, Bjarke; Fischer, Krista; Frau, Francesca; Galesloot, Tessel E; Geller, Frank; Goel, Anuj; Gorski, Mathias; Grammer, Tanja B; Gustafsson, Stefan; Haitjema, Saskia; Hottenga, Jouke-Jan; Huffman, Jennifer E; Jackson, Anne U; Jacobs, Kevin B; Johansson, Åsa; Kaakinen, Marika; Kleber, Marcus E; Lahti, Jari; Mateo Leach, Irene; Lehne, Benjamin; Liu, Youfang; Lo, Ken Sin; Lorentzon, Mattias; Luan, Jian'an; Madden, Pamela A F; Mangino, Massimo; McKnight, Barbara; Medina-Gomez, Carolina; Monda, Keri L; Montasser, May E; Müller, Gabriele; Müller-Nurasyid, Martina; Nolte, Ilja M; Panoutsopoulou, Kalliope; Pascoe, Laura; Paternoster, Lavinia; Rayner, Nigel W; Renström, Frida; Rizzi, Federica; Rose, Lynda M; Ryan, Kathy A; Salo, Perttu; Sanna, Serena; Scharnagl, Hubert; Shi, Jianxin; Smith, Albert Vernon; Southam, Lorraine; Stančáková, Alena; Steinthorsdottir, Valgerdur; Strawbridge, Rona J; Sung, Yun Ju; Tachmazidou, Ioanna; Tanaka, Toshiko; Thorleifsson, Gudmar; Trompet, Stella; Pervjakova, Natalia; Tyrer, Jonathan P; Vandenput, Liesbeth; van der Laan, Sander W; van der Velde, Nathalie; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V; Verweij, Niek; Vlachopoulou, Efthymia; Waite, Lindsay L; Wang, Sophie R; Wang, Zhaoming; Wild, Sarah H; Willenborg, Christina; Wilson, James F; Wong, Andrew; Yang, Jian; Yengo, Loïc; Yerges-Armstrong, Laura M; Yu, Lei; Zhang, Weihua; Zhao, Jing Hua; Andersson, Ehm A; Bakker, Stephan J L; Baldassarre, Damiano; Banasik, Karina; Barcella, Matteo; Barlassina, Cristina; Bellis, Claire; Benaglio, Paola; Blangero, John; Blüher, Matthias; Bonnet, Fabrice; Bonnycastle, Lori L; Boyd, Heather A; Bruinenberg, Marcel; Buchman, Aron S; Campbell, Harry; Chen, Yii-Der Ida; Chines, Peter S; Claudi-Boehm, Simone; Cole, John; Collins, Francis S; de Geus, Eco J C; de Groot, Lisette C P G M; Dimitriou, Maria; Duan, Jubao; Enroth, Stefan; Eury, Elodie; Farmaki, Aliki-Eleni; Forouhi, Nita G; Friedrich, Nele; Gejman, Pablo V; Gigante, Bruna; Glorioso, Nicola; Go, Alan S; Gottesman, Omri; Gräßler, Jürgen; Grallert, Harald; Grarup, Niels; Gu, Yu-Mei; Broer, Linda; Ham, Annelies C; Hansen, Torben; Harris, Tamara B; Hartman, Catharina A; Hassinen, Maija; Hastie, Nicholas; Hattersley, Andrew T; Heath, Andrew C; Henders, Anjali K; Hernandez, Dena; Hillege, Hans; Holmen, Oddgeir; Hovingh, Kees G; Hui, Jennie; Husemoen, Lise L; Hutri-Kähönen, Nina; Hysi, Pirro G; Illig, Thomas; De Jager, Philip L; Jalilzadeh, Shapour; Jørgensen, Torben; Jukema, J Wouter; Juonala, Markus; Kanoni, Stavroula; Karaleftheri, Maria; Khaw, Kay Tee; Kinnunen, Leena; Kittner, Steven J; Koenig, Wolfgang; Kolcic, Ivana; Kovacs, Peter; Krarup, Nikolaj T; Kratzer, Wolfgang; Krüger, Janine; Kuh, Diana; Kumari, Meena; Kyriakou, Theodosios; Langenberg, Claudia; Lannfelt, Lars; Lanzani, Chiara; Lotay, Vaneet; Launer, Lenore J; Leander, Karin; Lindström, Jaana; Linneberg, Allan; Liu, Yan-Ping; Lobbens, Stéphane; Luben, Robert; Lyssenko, Valeriya; Männistö, Satu; Magnusson, Patrik K; McArdle, Wendy L; Menni, Cristina; Merger, Sigrun; Milani, Lili; Montgomery, Grant W; Morris, Andrew P; Narisu, Narisu; Nelis, Mari; Ong, Ken K; Palotie, Aarno; Pérusse, Louis; Pichler, Irene; Pilia, Maria G; Pouta, Anneli; Rheinberger, Myriam; Ribel-Madsen, Rasmus; Richards, Marcus; Rice, Kenneth M; Rice, Treva K; Rivolta, Carlo; Salomaa, Veikko; Sanders, Alan R; Sarzynski, Mark A; Scholtens, Salome; Scott, Robert A; Scott, William R; Sebert, Sylvain; Sengupta, Sebanti; Sennblad, Bengt; Seufferlein, Thomas; Silveira, Angela; Slagboom, P Eline; Smit, Jan H; Sparsø, Thomas H; Stirrups, Kathleen; Stolk, Ronald P; Stringham, Heather M; Swertz, Morris A; Swift, Amy J; Syvänen, Ann-Christine; Tan, Sian-Tsung; Thorand, Barbara; Tönjes, Anke; Tremblay, Angelo; Tsafantakis, Emmanouil; van der Most, Peter J; Völker, Uwe; Vohl, Marie-Claude; Vonk, Judith M; Waldenberger, Melanie; Walker, Ryan W; Wennauer, Roman; Widén, Elisabeth; Willemsen, Gonneke; Wilsgaard, Tom; Wright, Alan F; Zillikens, M Carola; van Dijk, Suzanne C; van Schoor, Natasja M; Asselbergs, Folkert W; de Bakker, Paul I W; Beckmann, Jacques S; Beilby, John; Bennett, David A; Bergman, Richard N; Bergmann, Sven; Böger, Carsten A; Boehm, Bernhard O; Boerwinkle, Eric; Boomsma, Dorret I; Bornstein, Stefan R; Bottinger, Erwin P; Bouchard, Claude; Chambers, John C; Chanock, Stephen J; Chasman, Daniel I; Cucca, Francesco; Cusi, Daniele; Dedoussis, George; Erdmann, Jeanette; Eriksson, Johan G; Evans, Denis A; de Faire, Ulf; Farrall, Martin; Ferrucci, Luigi; Ford, Ian; Franke, Lude; Franks, Paul W; Froguel, Philippe; Gansevoort, Ron T; Gieger, Christian; Grönberg, Henrik; Gudnason, Vilmundur; Gyllensten, Ulf; Hall, Per; Hamsten, Anders; van der Harst, Pim; Hayward, Caroline; Heliövaara, Markku; Hengstenberg, Christian; Hicks, Andrew A; Hingorani, Aroon; Hofman, Albert; Hu, Frank; Huikuri, Heikki V; Hveem, Kristian; James, Alan L; Jordan, Joanne M; Jula, Antti; Kähönen, Mika; Kajantie, Eero; Kathiresan, Sekar; Kiemeney, Lambertus A L M; Kivimaki, Mika; Knekt, Paul B; Koistinen, Heikki A; Kooner, Jaspal S; Koskinen, Seppo; Kuusisto, Johanna; Maerz, Winfried; Martin, Nicholas G; Laakso, Markku; Lakka, Timo A; Lehtimäki, Terho; Lettre, Guillaume; Levinson, Douglas F; Lind, Lars; Lokki, Marja-Liisa; Mäntyselkä, Pekka; Melbye, Mads; Metspalu, Andres; Mitchell, Braxton D; Moll, Frans L; Murray, Jeffrey C; Musk, Arthur W; Nieminen, Markku S; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J; Oostra, Ben A; Palmer, Lyle J; Pankow, James S; Pasterkamp, Gerard; Pedersen, Nancy L; Pedersen, Oluf; Penninx, Brenda W; Perola, Markus; Peters, Annette; Polašek, Ozren; Pramstaller, Peter P; Psaty, Bruce M; Qi, Lu; Quertermous, Thomas; Raitakari, Olli T; Rankinen, Tuomo; Rauramaa, Rainer; Ridker, Paul M; Rioux, John D; Rivadeneira, Fernando; Rotter, Jerome I; Rudan, Igor; den Ruijter, Hester M; Saltevo, Juha; Sattar, Naveed; Schunkert, Heribert; Schwarz, Peter E H; Shuldiner, Alan R; Sinisalo, Juha; Snieder, Harold; Sørensen, Thorkild I A; Spector, Tim D; Staessen, Jan A; Stefania, Bandinelli; Thorsteinsdottir, Unnur; Stumvoll, Michael; Tardif, Jean-Claude; Tremoli, Elena; Tuomilehto, Jaakko; Uitterlinden, André G; Uusitupa, Matti; Verbeek, André L M; Vermeulen, Sita H; Viikari, Jorma S; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Waeber, Gérard; Walker, Mark; Wallaschofski, Henri; Wareham, Nicholas J; Watkins, Hugh; Zeggini, Eleftheria; Chakravarti, Aravinda; Clegg, Deborah J; Cupples, L Adrienne; Gordon-Larsen, Penny; Jaquish, Cashell E; Rao, D C; Abecasis, Goncalo R; Assimes, Themistocles L; Barroso, Inês; Berndt, Sonja I; Boehnke, Michael; Deloukas, Panos; Fox, Caroline S; Groop, Leif C; Hunter, David J; Ingelsson, Erik; Kaplan, Robert C; McCarthy, Mark I; Mohlke, Karen L; O'Connell, Jeffrey R; Schlessinger, David; Strachan, David P; Stefansson, Kari; van Duijn, Cornelia M; Hirschhorn, Joel N; Lindgren, Cecilia M; Heid, Iris M; North, Kari E; Borecki, Ingrid B; Kutalik, Zoltán; Loos, Ruth J F

    2015-10-01

    Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape. PMID:26426971

  15. Age and haplotype variations within FADS1 interact and associate with alterations in fatty acid composition in human male cortical brain tissue.

    Directory of Open Access Journals (Sweden)

    Erika Freemantle

    Full Text Available UNLABELLED: Fatty acids (FA play an integral role in brain function and alterations have been implicated in a variety of complex neurological disorders. Several recent genomic studies have highlighted genetic variability in the fatty acid desaturase (FADS1/2/3 gene cluster as an important contributor to FA alterations in serum lipids as well as measures of FA desaturase index estimated by ratios of relevant FAs. The contribution to alterations of FAs within the brain by local synthesis is still a matter of debate. Thus, the impact of genetic variants in FADS genes on gene expression and brain FA levels is an important avenue to investigate. METHODS: Analyses were performed on brain tissue from prefrontal cortex Brodmann area 47 (BA47 of 61 male subjects of French Canadian ancestry ranging in age from young adulthood to middle age (18-58 years old, with the exception of one teenager (15 years old. Haplotype tagging SNPs were selected using the publicly available HapMap genotyping dataset in conjunction with Haploview. DNA sequencing was performed by the Sanger method and gene expression was measured by quantitative real-time PCR. FAs in brain tissue were analysed by gas chromatography. Variants in the FADS1 gene region were sequenced and analyzed for their influence on both FADS gene expression and FAs in brain tissue. RESULTS: Our results suggest an association of the minor haplotype with alteration in estimated fatty acid desaturase activity. Analysis of the impact of DNA variants on expression and alternative transcripts of FADS1 and FADS2, however, showed no differences. Furthermore, there was a significant interaction between haplotype and age on certain brain FA levels. DISCUSSION: This study suggests that genetic variability in the FADS genes cluster, previously shown to be implicated in alterations in peripheral FA levels, may also affect FA composition in brain tissue, but not likely by local synthesis.

  16. Extent of poly-pharmacy, occurrence and associated factors of drug-drug interaction and potential adverse drug reactions in Gondar Teaching Referral Hospital, North West Ethiopia

    Directory of Open Access Journals (Sweden)

    Endalkachew Admassie

    2013-01-01

    Full Text Available The aim of this study was to assess the extent of poly-pharmacy, occurrence, and associated factors for the occurrence of drug-drug interaction (DDI and potential adverse drug reaction (ADR in Gondar University Teaching Referral Hospital. Institutional-based retrospective cross-sectional study. This study was conducted on prescriptions of both in and out-patients for a period of 3 months at Gondar University Hospital. Both bivariate analysis and multivariate logistic regression were used to identify risk factors for the occurrence of DDI and possible ADRs. All the statistical calculations were performed using SPSS; software. A total of 12,334 prescriptions were dispensed during the study period of which, 2,180 prescriptions were containing two or more drugs per prescription. A total of 21,210 drugs were prescribed and the average number of drugs per prescription was 1.72. Occurrences of DDI of all categories (Major, Moderate, and Minor were analyzed and DDI were detected in 711 (32.6% prescriptions. Sex was not found to be a risk factor for the occurrence of DDI and ADR, while age and number of medications per prescription were found to be significant risk factors for the occurrence of DDI and ADR. The mean number of drugs per prescription was 1.72 and hence with regard to the WHO limit of drugs per prescription, Gondar hospital was able to maintain the limit and prescriptions containing multiple drugs supposed to be taken systemically. Numbers of drugs per prescription as well as older age were found to be predisposing factors for the occurrence of DDI and potential ADRs while sex was not a risk factor.

  17. Modeling bispecific monoclonal antibody interaction with two cell membrane targets indicates the importance of surface diffusion.

    Science.gov (United States)

    Sengers, Bram G; McGinty, Sean; Nouri, Fatma Z; Argungu, Maryam; Hawkins, Emma; Hadji, Aymen; Weber, Andrew; Taylor, Adam; Sepp, Armin

    2016-07-01

    We have developed a mathematical framework for describing a bispecific monoclonal antibody interaction with two independent membrane-bound targets that are expressed on the same cell surface. The bispecific antibody in solution binds either of the two targets first, and then cross-links with the second one while on the cell surface, subject to rate-limiting lateral diffusion step within the lifetime of the monovalently engaged antibody-antigen complex. At experimental densities, only a small fraction of the free targets is expected to lie within the reach of the antibody binding sites at any time. Using ordinary differential equation and Monte Carlo simulation-based models, we validated this approach against an independently published anti-CD4/CD70 DuetMab experimental data set. As a result of dimensional reduction, the cell surface reaction is expected to be so rapid that, in agreement with the experimental data, no monovalently bound bispecific antibody binary complexes accumulate until cross-linking is complete. The dissociation of the bispecific antibody from the ternary cross-linked complex is expected to be significantly slower than that from either of the monovalently bound variants. We estimate that the effective affinity of the bivalently bound bispecific antibody is enhanced for about 4 orders of magnitude over that of the monovalently bound species. This avidity enhancement allows for the highly specific binding of anti-CD4/CD70 DuetMab to the cells that are positive for both target antigens over those that express only one or the other We suggest that the lateral diffusion of target antigens in the cell membrane also plays a key role in the avidity effect of natural antibodies and other bivalent ligands in their interactions with their respective cell surface receptors. PMID:27097222

  18. Narrative Structure and Emotional References in Parent-Child Reminiscing: Associations with Child Gender, Temperament, and the Quality of Parent-Child Interactions

    Science.gov (United States)

    Bost, Kelly K.; Choi, Eunsil; Wong, Maria S.

    2010-01-01

    The present research examined child gender, temperament, and the quality of parent-child interactions as predictors of narrative style and references to emotion during mother-child and father-child reminiscing. Although models predicting parents' narrative styles were non-significant, results revealed significant interactions between parental…

  19. Origin of the late Early Cretaceous granodiorite and associated dioritic dikes in the Hongqilafu pluton, northwestern Tibetan Plateau: A case for crust-mantle interaction

    Science.gov (United States)

    Li, Jiyong; Niu, Yaoling; Hu, Yan; Chen, Shuo; Zhang, Yu; Duan, Meng; Sun, Pu

    2016-09-01

    We present a detailed study of geochronology, mineral chemistries, bulk-rock major and trace element abundances, and Sr-Nd-Hf isotope compositions of the granodiorite and associated dioritic dikes in the Hongqilafu pluton at the northwestern margin of the Tibetan Plateau. The granodiorite and dioritic dikes yielded zircon U-Pb ages of ~ 104 Ma and ~ 100 Ma, respectively. The dioritic dikes comprise varying lithologies of gabbroic diorite, diorite porphyry and granodiorite porphyry, exhibiting a compositional spectrum from intermediate to felsic rocks. Their mineral compositions display disequilibrium features such as large major element compositional variations of plagioclase, clinopyroxene and amphibole crystals. These dioritic dikes are enriched in incompatible elements (Ba, Rb, Th, U, K) and Sr-Nd-Hf isotopes (87Sr/86Sri: 0.7066 to 0.7071, εNd(t): - 5.3 to - 7.4, εHf(t): - 3.6 to - 6.2). We suggest that the dioritic dikes were most likely derived from partial melting of mantle wedge metasomatized by the subducted/subducting seafloor with a sediment component, followed by AFC processes with fractional crystallization of clinopyroxene, amphibole and plagioclase and assimilation of lower continental crust. The mantle-wedge derived magma parental to the dioritic dikes underplated and induced the lower continental crust to melt, forming the felsic crustal magma parental to the granodiorite with mantle melt signatures and having more enriched isotope compositions (87Sr/86Sri: 0.7087 to 0.7125, εNd(t): - 9.5 to - 11.6, εHf(t): - 10.3 to - 14.1) than those of the dioritic dikes. The Hongqilafu pluton is thus the product of mantle-crust interaction at an active continental margin subduction setting over the period of several million years. This understanding further indicates that the closure timing of the Shyok back-arc basin and the collision between the Kohistan-Ladakh Arc and the Karakoram Terrane may have taken place later than ~ 100 Ma.

  20. Management of opioid-dependent patients: comparison of the cost associated with use of buprenorphine/naloxone or methadone, and their interactions with concomitant treatments for infectious or psychiatric comorbidities.

    Science.gov (United States)

    Roncero, Carlos; Domínguez-Hernández, Raquel; Díaz, Tomás; Fernández, José Manuel; Forcada, Rafael; Martínez, José Manuel; Seijo, Pedro; Terán, Antonio; Oyagüez, Itziar

    2015-01-01

    The objective was to estimate the annual interaction management cost of agonist opioid treatment (AOT) for opioid-dependent (OD) patients with buprenorphine-naloxone (Suboxone®) (B/N) or methadone associated with concomitant treatments for infectious (HIV) or psychiatric comorbidities. A costs analysis model was developed to calculate the associated cost of AOT and interaction management. The AOT cost included pharmaceutical costs, drug preparation, distribution and dispensing, based on intake regimen (healthcare center or take-home) and type and frequency of dispensing (healthcare center or pharmacy), and medical visits. The cost of methadone also included single-dose bottles, monthly costs of custody at pharmacy, urine toxicology drug screenings and nursing visits. Potential interactions between AOT and concomitant treatments (antivirals, antibacterials/antifungals, antipsychotics, anxiolytics, antidepressant and anticonvulsants), were identified to determine the additional use of healthcare resources for each interaction management. The annual cost per patient of AOT was €1,525.97 for B/N and €1,467.29 for methadone. The average annual cost per patient of interaction management was €257.07 (infectious comorbidities), €114.03 (psychiatric comorbidities) and €185.55 (double comorbidity) with methadone and €7.90 with B/N in psychiatric comorbidities. Total annual costs of B/N were €1,525.97, €1,533.87 and €1,533.87 compared to €1,724.35, €1,581.32 and €1,652.84 for methadone per patient with infectious, psychiatric or double comorbidity respectively.Compared to methadone, the total cost per patient with OD was lower with B/N (€47.45-€198.38 per year). This is due to the differences in interaction management costs associated with the concomitant treatment of infectious and/or psychiatric comorbidities. PMID:26437312

  1. Lattice cluster theory of associating polymers. II. Enthalpy and entropy of self-assembly and Flory-Huggins interaction parameter χ for solutions of telechelic molecules.

    Science.gov (United States)

    Dudowicz, Jacek; Freed, Karl F; Douglas, Jack F

    2012-02-14

    The lattice cluster theory for solutions of telechelic polymer chains, developed in paper I, is applied to determine the enthalpy Δh(p) and entropy Δs(p) of self-assembly of linear telechelics and to evaluate the Flory-Huggins (FH) interaction parameter χ governing the phase behavior of these systems. Particular focus is placed on examining how these interaction variables depend on the composition of the solution, temperature, van der Waals and local "sticky" interaction energies, and the length of the individual telechelic chains. The FH interaction parameter χ is found to exhibit an entropy-enthalpy compensation effect between the "entropic" and "enthalpic" portions as either the composition or mass of the telechelic species is varied, providing unique theoretical insights into this commonly reported, yet, enigmatic phenomenon.

  2. Drought and root herbivory interact to alter the response of above-ground parasitoids to aphid infested plants and associated plant volatile signals

    OpenAIRE

    Muhammad Tariq; Wright, Denis J.; Bruce, Toby J. A.; Staley, Joanna T.

    2013-01-01

    Multitrophic interactions are likely to be altered by climate change but there is little empirical evidence relating the responses of herbivores and parasitoids to abiotic factors. Here we investigated the effects of drought on an above/below-ground system comprising a generalist and a specialist aphid species (foliar herbivores), their parasitoids, and a dipteran species (root herbivore).We tested the hypotheses that: (1) high levels of drought stress and below-ground herbivory interact to r...

  3. Computational Simulations to Predict Creatine Kinase-Associated Factors: Protein-Protein Interaction Studies of Brain and Muscle Types of Creatine Kinases

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    Wei-Jiang Hu

    2011-01-01

    Full Text Available Creatine kinase (CK; EC 2.7.3.2 is related to several skin diseases such as psoriasis and dermatomyositis. CK is important in skin energy homeostasis because it catalyzes the reversible transfer of a phosphoryl group from MgATP to creatine. In this study, we predicted CK binding proteins via the use of bioinformatic tools such as protein-protein interaction (PPI mappings and suggest the putative hub proteins for CK interactions. We obtained 123 proteins for brain type CK and 85 proteins for muscle type CK in the interaction networks. Among them, several hub proteins such as NFKB1, FHL2, MYOC, and ASB9 were predicted. Determination of the binding factors of CK can further promote our understanding of the roles of CK in physiological conditions.

  4. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.

    NARCIS (Netherlands)

    Strange, A.; Capon, F.; Spencer, C.C.; Knight, J.; Weale, M.E.; Allen, M.H.; Barton, A.; Band, G.; Bellenguez, C.; Bergboer, J.G.M.; Blackwell, J.M.; Bramon, E.; Bumpstead, S.J.; Casas, J.P.; Cork, M.J.; Corvin, A.; Deloukas, P.; Dilthey, A.; Duncanson, A.; Edkins, S.; Estivill, X.; Fitzgerald, O.; Freeman, C.; Giardina, E.; Gray, E.; Hofer, A.; Huffmeier, U.; Hunt, S.E.; Irvine, A.D.; Jankowski, J.; Kirby, B.; Langford, C.; Lascorz, J.; Leman, J.; Leslie, S.; Mallbris, L.; Markus, H.S.; Mathew, C.G.; McLean, W.H.I.; McManus, R.; Mossner, R.; Moutsianas, L.; Naluai, A.T.; Nestle, F.O.; Novelli, G.; Onoufriadis, A.; Palmer, C.N.; Perricone, C.; Pirinen, M.; Plomin, R.; Potter, S.C.; Pujol, R.M.; Rautanen, A.; Riveira-Munoz, E.; Ryan, A.W.; Salmhofer, W.; Samuelsson, L.; Sawcer, S.J.; Schalkwijk, J.; Smith, C.H.; Stahle, M.; Su, Z.; Tazi-Ahnini, R.; Traupe, H.; Viswanathan, A.C.; Warren, R.B.; Weger, W.; Wolk, K.; Wood, N.; Worthington, J.; Young, H.S.; Zeeuwen, P.L.J.M.; Hayday, A.; Burden, A.D.; Griffiths, C.E.; Kere, J.; Reis, A.; McVean, G.; Evans, D.M.; Brown, M.A.; Barker, J.N.; Peltonen, L.; Donnelly, P.; Trembath, R.C.

    2010-01-01

    To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (

  5. Logic Features Selection in Identification of the Most Important Interactions of Interleukin-6 and Two Important Single Nucleotide Polymorphisms of Its Gene (IL-6-174, IL-6-572) with Some Other Factors in Association with hypertension

    OpenAIRE

    Hamid Alavi Majd; Fatemeh Paknazar; Yadollah Mehrabi; Maryamossadat Daneshpour; Majid Mirmohammadkhani; Mahdi Hedayati; Fereidoun Azizi

    2012-01-01

    Introduction: The study aimed to identify important interactions between Interleukin-6 and two single nucleotide polymorphisms of its gene expression (IL-6-174, IL-6-572) with some other factors including gender, age group, BMI, as while as blood concentration of sugar, lipids, and C-reactive protein, in association with hypertension. Methods: In this cross-sectional study, the data of first phase of the "Evaluation of Novel Risk Factors of NCD" project conducted in 2001by the Research Instit...

  6. The functional interaction on in vitro gene expression of APOA5 SNPs, defining haplotype APOA5*2, and their paradoxical association with plasma triglyceride but not plasma apoAV levels

    OpenAIRE

    2008-01-01

    The functional interaction on in vitro gene expression of APOA5 SNPs, defining haplotype APOA5*2, and their paradoxical association with plasma triglyceride but not plasma apoAV levels correspondance: Corresponding author. Division of Cardiovascular Genetics, Department of Medicine, Rayne Building, University College London, 5 University Street, London WC1E 6JF, United Kingdom. Tel.: +44 20 7679 6968; fax: +44 20 7679 6212. (Talmud, Philippa J.) p....

  7. Binding of the biogenic polyamines to deoxyribonucleic acids of varying base composition: base specificity and the associated energetics of the interaction.

    Directory of Open Access Journals (Sweden)

    Ayesha Kabir

    Full Text Available BACKGROUND: The thermodynamics of the base pair specificity of the binding of the polyamines spermine, spermidine, putrescine, and cadaverine with three genomic DNAs Clostridium perfringens, 27% GC, Escherichia coli, 50% GC and Micrococcus lysodeikticus, 72% GC have been studied using titration calorimetry and the data supplemented with melting studies, ethidium displacement and circular dichroism spectroscopy results. METHODOLOGY/PRINCIPAL FINDINGS: Isothermal titration calorimetry, differential scanning calorimetry, optical melting studies, ethidium displacement, circular dichroism spectroscopy are the various techniques employed to characterize the interaction of four polyamines, spermine, spermidine, putersine and cadaverine with the DNAs. Polyamines bound stronger with AT rich DNA compared to the GC rich DNA and the binding varied depending on the charge on the polyamine as spermine>spermidine >putrescine>cadaverine. Thermodynamics of the interaction revealed that the binding was entropy driven with small enthalpy contribution. The binding was influenced by salt concentration suggesting the contribution from electrostatic forces to the Gibbs energy of binding to be the dominant contributor. Each system studied exhibited enthalpy-entropy compensation. The negative heat capacity changes suggested a role for hydrophobic interactions which may arise due to the non polar interactions between DNA and polyamines. CONCLUSION/SIGNIFICANCE: From a thermodynamic analysis, the AT base specificity of polyamines to DNAs has been elucidated for the first time and supplemented by structural studies.

  8. Senescence-associated barley NAC (NAM, ATAF1,2, CUC) transcription factor interacts with radical-induced cell death 1 through a disordered regulatory domain

    DEFF Research Database (Denmark)

    Kjaersgaard, Trine; Jensen, Michael K; Christiansen, Michael W;

    2011-01-01

    Senescence in plants involves massive nutrient relocation and age-related cell death. Characterization of the molecular components, such as transcription factors (TFs), involved in these processes is required to understand senescence. We found that HvNAC005 and HvNAC013 of the plant-specific NAC...... as a transcriptional activator suggesting that an involvement of HvNAC013 and HvNAC005 in senescence will be different. HvNAC013 interacted with barley radical-induced cell death 1 (RCD1) via the very C-terminal part of its TRD, outside of the region containing the LP motif. No significant secondary structure...... was induced in the HvNAC013 TRD upon interaction with RCD1. RCD1 also interacted with regions dominated by intrinsic disorder in TFs of the MYB and basic helix-loop-helix families. We propose that RCD1 is a regulatory protein capable of interacting with many different TFs by exploiting their intrinsic...

  9. The Use of "Circle of Friends" Strategy to Improve Social Interactions and Social Acceptance: A Case Study of a Child with Asperger's Syndrome and Other Associated Needs

    Science.gov (United States)

    O'Connor, Eileen

    2016-01-01

    The study outlined here was an attempt to examine the use of "Circle of Friends" as a single intervention approach in addressing the issue of inappropriate social interactions in a child with Asperger Syndrome. The child selected was in a mainstream setting, as the main feature of a circle of friends is peers supporting peers. The child…

  10. The Home Literacy Environment: Exploring How Media and Parent-Child Interactions Are Associated with Children's Language Production

    Science.gov (United States)

    Liebeskind, Kara G.; Piotrowski, Jessica T.; Lapierre, Matthew A.; Linebarger, Deborah 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 language skills. Using a national sample of…

  11. Monoamine Oxidase A (MAOA) and Catechol-O-Methyltransferase (COMT) Gene Polymorphisms Interact with Maternal Parenting in Association with Adolescent Reactive Aggression but not Proactive Aggression: Evidence of Differential Susceptibility.

    Science.gov (United States)

    Zhang, Wenxin; Cao, Cong; Wang, Meiping; Ji, Linqin; Cao, Yanmiao

    2016-04-01

    To date, whether and how gene-environment (G × E) interactions operate differently across distinct subtypes of aggression remains untested. More recently, in contrast with the diathesis-stress hypothesis, an alternative hypothesis of differential susceptibility proposes that individuals could be differentially susceptible to environments depending on their genotypes in a "for better and for worse" manner. The current study examined interactions between monoamine oxidase A (MAOA) T941G and catechol-O-methyltransferase (COMT) Val158Met polymorphisms with maternal parenting on two types of aggression: reactive and proactive. Moreover, whether these potential G × E interactions would be consistent with the diathesis-stress versus the differential susceptibility hypothesis was tested. Within the sample of 1399 Chinese Han adolescents (47.2 % girls, M age = 12.32 years, SD = 0.50), MAOA and COMT genes both interacted with positive parenting in their associations with reactive but not proactive aggression. Adolescents with T alleles/TT homozygotes of MAOA gene or Met alleles of COMT gene exhibited more reactive aggression when exposed to low positive parenting, but less reactive aggression when exposed to high positive parenting. These findings provide the first evidence for distinct G × E interaction effects on reactive versus proactive aggression and lend further support for the differential susceptibility hypothesis.

  12. Monoamine Oxidase A (MAOA) and Catechol-O-Methyltransferase (COMT) Gene Polymorphisms Interact with Maternal Parenting in Association with Adolescent Reactive Aggression but not Proactive Aggression: Evidence of Differential Susceptibility.

    Science.gov (United States)

    Zhang, Wenxin; Cao, Cong; Wang, Meiping; Ji, Linqin; Cao, Yanmiao

    2016-04-01

    To date, whether and how gene-environment (G × E) interactions operate differently across distinct subtypes of aggression remains untested. More recently, in contrast with the diathesis-stress hypothesis, an alternative hypothesis of differential susceptibility proposes that individuals could be differentially susceptible to environments depending on their genotypes in a "for better and for worse" manner. The current study examined interactions between monoamine oxidase A (MAOA) T941G and catechol-O-methyltransferase (COMT) Val158Met polymorphisms with maternal parenting on two types of aggression: reactive and proactive. Moreover, whether these potential G × E interactions would be consistent with the diathesis-stress versus the differential susceptibility hypothesis was tested. Within the sample of 1399 Chinese Han adolescents (47.2 % girls, M age = 12.32 years, SD = 0.50), MAOA and COMT genes both interacted with positive parenting in their associations with reactive but not proactive aggression. Adolescents with T alleles/TT homozygotes of MAOA gene or Met alleles of COMT gene exhibited more reactive aggression when exposed to low positive parenting, but less reactive aggression when exposed to high positive parenting. These findings provide the first evidence for distinct G × E interaction effects on reactive versus proactive aggression and lend further support for the differential susceptibility hypothesis. PMID:26932718

  13. Rice black-streaked dwarf virus P6 self-interacts to form punctate, viroplasm-like structures in the cytoplasm and recruits viroplasm-associated protein P9-1

    Directory of Open Access Journals (Sweden)

    Yu Jialin

    2011-01-01

    Full Text Available Abstract Background Rice black-streaked dwarf virus (RBSDV, a member of the genus Fijivirus within the family Reoviridae, can infect several graminaceous plant species including rice, maize and wheat, and is transmitted by planthoppers. Although several RBSDV proteins have been studied in detail, functions of the nonstructural protein P6 are still largely unknown. Results In the current study, we employed yeast two-hybrid assays, bimolecular fluorescence complementation and subcellular localization experiments to show that P6 can self-interact to form punctate, cytoplasmic viroplasm-like structures (VLS when expressed alone in plant cells. The region from residues 395 to 659 is necessary for P6 self-interaction, whereas two polypeptides (residues 580-620 and 615-655 are involved in the subcellular localization of P6. Furthermore, P6 strongly interacts with the viroplasm-associated protein P9-1 and recruits P9-1 to localize in VLS. The P6 395-659 region is also important for the P6-P9-1 interaction, and deleting any region of P9-1 abolishes this heterologous interaction. Conclusions RBSDV P6 protein has an intrinsic ability to self-interact and forms VLS without other RBSDV proteins or RNAs. P6 recruits P9-1 to VLS by direct protein-protein interaction. This is the first report on the functionality of RBSDV P6 protein. P6 may be involved in the process of viroplasm nucleation and virus morphogenesis.

  14. ERAP1 genetic variations associated with HLA-B27 interaction and disease severity of syndesmophytes formation in Taiwanese ankylosing spondylitis

    OpenAIRE

    Wang, Chin-Man; Ho, Huei-Huang; Chang, Su-Wei; Wu, Yeong-Jian Jan; Lin, Jing-Chi; Chang, Pi-Yueh; Wu, Jianming; Chen, Ji-Yih

    2012-01-01

    Introduction Ankylosing spondylitis (AS) is a familial, heritable disease specified by syndesmophyte formation leading to an ankylosed spine. Endoplasmic reticulum aminopeptidase 1 (ERAP1) genetic variations have been widely proved to be associated with AS in several ethnic populations. The aim of this study was to investigate whether ERAP1 single nucleotide polymorphisms (SNPs) are associated with AS susceptibility and disease severity in Taiwanese. Methods Four ERAP1 SNPs (rs27037, rs27980,...

  15. Interaction between PLA2R1 and HLA-DQA1 Variants Associates with Anti-PLA2R Antibodies and Membranous Nephropathy

    OpenAIRE

    Lv, Jicheng; Hou, Wanyin; Zhou, Xujie; Liu, Gang; Zhou, Fude; Zhao, Na; HOU, PING; Zhao, Minghui; Zhang, Hong

    2013-01-01

    Risk alleles at genome loci containing phospholipase A2 receptor 1 (PLA2R1) and HLA-DQA1 closely associate with idiopathic membranous nephropathy (IMN) in the European population, but it is unknown whether a similar association exists in the Chinese population and whether high-risk alleles promote the development of anti-PLA2R antibodies. Here, we genotyped 2132 Chinese individuals, including 1112 patients with IMN and 1020 healthy controls, for three single nucleotide polymorphisms (SNPs) wi...

  16. Gene-Gene and Gene-Environment Interactions in HIV-Associated Nephropathy: a Focus on the MYH9 Nephropathy Susceptibility Gene

    OpenAIRE

    Núñez, Marina; Saran, Anita M.; Freedman, Barry I.

    2010-01-01

    Human immunodeficiency virus-associated nephropathy (HIVAN) is a leading cause of end-stage renal disease in African Americans. The HIV-1 virus infects podocytes, cells integral to formation of the glomerular filtration barrier, often leading to focal segmental glomerulosclerosis. HIVAN is typically a complication of late-stage HIV infection, associated with low CD4 cell counts and elevated serum HIV RNA levels. Highly active antiretroviral therapy (HAART) is partially protective and has alte...

  17. 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

    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...... (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...

  18. 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

    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......-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....

  19. Drought and root herbivory interact to alter the response of above-ground parasitoids to aphid infested plants and associated plant volatile signals.

    Directory of Open Access Journals (Sweden)

    Muhammad Tariq

    Full Text Available Multitrophic interactions are likely to be altered by climate change but there is little empirical evidence relating the responses of herbivores and parasitoids to abiotic factors. Here we investigated the effects of drought on an above/below-ground system comprising a generalist and a specialist aphid species (foliar herbivores, their parasitoids, and a dipteran species (root herbivore.We tested the hypotheses that: (1 high levels of drought stress and below-ground herbivory interact to reduce the performance of parasitoids developing in aphids; (2 drought stress and root herbivory change the profile of volatile organic chemicals (VOCs emitted by the host plant; (3 parasitoids avoid ovipositing in aphids feeding on plants under drought stress and root herbivory. We examined the effect of drought, with and without root herbivory, on the olfactory response of parasitoids (preference, plant volatile emissions, parasitism success (performance, and the effect of drought on root herbivory. Under drought, percentage parasitism of aphids was reduced by about 40-55% compared with well watered plants. There was a significant interaction between drought and root herbivory on the efficacy of the two parasitoid species, drought stress partially reversing the negative effect of root herbivory on percent parasitism. In the absence of drought, root herbivory significantly reduced the performance (e.g. fecundity of both parasitoid species developing in foliar herbivores. Plant emissions of VOCs were reduced by drought and root herbivores, and in olfactometer experiments parasitoids preferred the odour from well-watered plants compared with other treatments. The present work demonstrates that drought stress can change the outcome of interactions between herbivores feeding above- and below-ground and their parasitoids, mediated by changes in the chemical signals from plants to parasitoids. This provides a new insight into how the structure of terrestrial

  20. Drought and root herbivory interact to alter the response of above-ground parasitoids to aphid infested plants and associated plant volatile signals.

    Science.gov (United States)

    Tariq, Muhammad; Wright, Denis J; Bruce, Toby J A; Staley, Joanna T

    2013-01-01

    Multitrophic interactions are likely to be altered by climate change but there is little empirical evidence relating the responses of herbivores and parasitoids to abiotic factors. Here we investigated the effects of drought on an above/below-ground system comprising a generalist and a specialist aphid species (foliar herbivores), their parasitoids, and a dipteran species (root herbivore).We tested the hypotheses that: (1) high levels of drought stress and below-ground herbivory interact to reduce the performance of parasitoids developing in aphids; (2) drought stress and root herbivory change the profile of volatile organic chemicals (VOCs) emitted by the host plant; (3) parasitoids avoid ovipositing in aphids feeding on plants under drought stress and root herbivory. We examined the effect of drought, with and without root herbivory, on the olfactory response of parasitoids (preference), plant volatile emissions, parasitism success (performance), and the effect of drought on root herbivory. Under drought, percentage parasitism of aphids was reduced by about 40-55% compared with well watered plants. There was a significant interaction between drought and root herbivory on the efficacy of the two parasitoid species, drought stress partially reversing the negative effect of root herbivory on percent parasitism. In the absence of drought, root herbivory significantly reduced the performance (e.g. fecundity) of both parasitoid species developing in foliar herbivores. Plant emissions of VOCs were reduced by drought and root herbivores, and in olfactometer experiments parasitoids preferred the odour from well-watered plants compared with other treatments. The present work demonstrates that drought stress can change the outcome of interactions between herbivores feeding above- and below-ground and their parasitoids, mediated by changes in the chemical signals from plants to parasitoids. This provides a new insight into how the structure of terrestrial communities may be

  1. Measuring ligand-dependent and ligand-independent interactions between nuclear receptors and associated proteins using Bioluminescence Resonance Energy Transfer (BRET2)

    OpenAIRE

    Koterba, Kristen L.; Rowan, Brian G.

    2006-01-01

    Bioluminescent resonance energy transfer (BRET2) is a recently developed technology for the measurement of protein-protein interactions in a live, cell-based system. BRET2 is characterized by the efficient transfer of excited energy between a bioluminescent donor molecule (Renilla luciferase) and a fluorescent acceptor molecule (a mutant of Green Fluorescent Protein (GFP2)). The BRET2 assay offers advantages over fluorescence resonance energy transfer (FRET) because it does not require an ext...

  2. Education modifies the association of wealth with obesity in women in middle-income but not low-income countries: an interaction study using seven national datasets, 2005-2010.

    Directory of Open Access Journals (Sweden)

    Amina Aitsi-Selmi

    Full Text Available BACKGROUND: Education and wealth may have different associations with female obesity but this has not been investigated in detail outside high-income countries. This study examines the separate and inter-related associations of education and household wealth in relation to obesity in women in a representative sample of low- and middle-income countries (LMICs. METHODS: The seven largest national surveys were selected from a list of Demographic and Health Surveys (DHS ordered by decreasing sample size and resulted in a range of country income levels. These were nationally representative data of women aged 15-49 years collected in the period 2005-2010. The separate and joint effects, unadjusted and adjusted for age group, parity, and urban/rural residence using a multivariate logistic regression model are presented. RESULTS: In the four middle-income countries (Colombia, Peru, Jordan, and Egypt, an interaction was found between education and wealth on obesity (P-value for interaction <0.001. Among women with no/primary education the wealth effect was positive whereas in the group with higher education it was either absent or inverted (negative. In the poorer countries (India, Nigeria, Benin, there was no evidence of an interaction. Instead, the associations between each of education and wealth with obesity were independent and positive. There was a statistically significant difference between the average interaction estimates for the low-income and middle-income countries (P<0.001. CONCLUSIONS: The findings suggest that education may protect against the obesogenic effects of increased household wealth as countries develop. Further research could examine the factors explaining the country differences in education effects.

  3. Early changes in apoplast composition associated with defence and disease in interactions between Phaseolus vulgaris and the halo blight pathogen Pseudomonas syringae Pv. phaseolicola.

    Science.gov (United States)

    O'Leary, Brendan M; Neale, Helen C; Geilfus, Christoph-Martin; Jackson, Robert W; Arnold, Dawn L; Preston, Gail M

    2016-10-01

    The apoplast is the arena in which endophytic pathogens such as Pseudomonas syringae grow and interact with plant cells. Using metabolomic and ion analysis techniques, this study shows how the composition of Phaseolus vulgaris leaf apoplastic fluid changes during the first six hours of compatible and incompatible interactions with two strains of P. syringae pv. phaseolicola (Pph) that differ in the presence of the genomic island PPHGI-1. Leaf inoculation with the avirulent island-carrying strain Pph 1302A elicited effector-triggered immunity (ETI) and resulted in specific changes in apoplast composition, including increases in conductivity, pH, citrate, γ-aminobutyrate (GABA) and K(+) , that are linked to the onset of plant defence responses. Other apoplastic changes, including increases in Ca(2+) , Fe(2/3+) Mg(2+) , sucrose, β-cyanoalanine and several amino acids, occurred to a relatively similar extent in interactions with both Pph 1302A and the virulent, island-less strain Pph RJ3. Metabolic footprinting experiments established that Pph preferentially metabolizes malate, glucose and glutamate, but excludes certain other abundant apoplastic metabolites, including citrate and GABA, until preferred metabolites are depleted. These results demonstrate that Pph is well-adapted to the leaf apoplast metabolic environment and that loss of PPHGI-1 enables Pph to avoid changes in apoplast composition linked to plant defences. PMID:27239727

  4. Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT.

    Science.gov (United States)

    Kawano, Miyuki; Kumagai, Keigo; Nishijima, Masahiro; Hanada, Kentaro

    2006-10-01

    Ceramide is synthesized at the endoplasmic reticulum (ER) and transported to the Golgi apparatus by CERT for its conversion to sphingomyelin in mammalian cells. CERT has a pleck-strin homology (PH) domain for Golgi targeting and a START domain catalyzing the intermembrane transfer of ceramide. The region between the two domains contains a short peptide motif designated FFAT, which is supposed to interact with the ER-resident proteins VAP-A and VAP-B. Both VAPs were actually co-immunoprecipitated with CERT, and the CERT/VAP interaction was abolished by mutations in the FFAT motif. These mutations did not affect the Golgi targeting activity of CERT. Whereas mutations of neither the FFAT motif nor the PH domain inhibited the ceramide transfer activity of CERT in a cell-free system, they impaired the ER-to-Golgi transport of ceramide in intact and in semi-intact cells at near endogenous expression levels. By contrast, when overexpressed, both the FFAT motif and the PH domain mutants of CERT substantially supported the transport of ceramide from the ER to the site where sphingomyelin is produced. These results suggest that the Golgi-targeting PH domain and ER-interacting FFAT motif of CERT spatially restrict the random ceramide transfer activity of the START domain in cells.

  5. Intracellular interactions between APOBEC3G, RNA, and HIV-1 Gag: APOBEC3G multimerization is dependent on its association with RNA

    Directory of Open Access Journals (Sweden)

    Friew Yeshitila N

    2009-06-01

    Full Text Available Abstract Background Host restriction factor APOBEC3G (A3G blocks human immunodeficiency virus type 1 (HIV-1 replication by G-to-A hypermutation, and by inhibiting DNA synthesis and provirus formation. Previous reports have suggested that A3G is a dimer and its virion incorporation is mediated through interactions with viral or nonviral RNAs and/or HIV-1 Gag. We have now employed a bimolecular fluorescence complementation assay (BiFC to analyze the intracellular A3G-A3G, A3G-RNA, and A3G-Gag interactions in living cells by reconstitution of yellow fluorescent protein (YFP from its N- or C-terminal fragments. Results The results obtained with catalytic domain 1 and 2 (CD1 and CD2 mutants indicate that A3G-A3G and A3G-Gag multimerization is dependent on an intact CD1 domain, which is required for RNA binding. A mutant HIV-1 Gag that exhibits reduced RNA binding also failed to reconstitute BiFC with wild-type A3G, indicating a requirement for both HIV-1 Gag and A3G to bind to RNA for their multimerization. Addition of a non-specific RNA binding peptide (P22 to the N-terminus of a CD1 mutant of A3G restored BiFC and virion incorporation, but failed to inhibit viral replication, indicating that the mutations in CD1 resulted in additional defects that interfere with A3G's antiviral activity. Conclusion These studies establish a robust BiFC assay for analysis of intracellular interactions of A3G with other macromolecules. The results indicate that in vivo A3G is a monomer that forms multimers upon binding to RNA. In addition, we observed weak interactions between wild-type A3G molecules and RNA binding-defective mutants of A3G, which could explain previously described protein-protein interactions between purified A3G molecules.

  6. Orthodontic springs and auxiliary appliances: assessment of magnetic field interactions associated with 1.5 T and 3 T magnetic resonance systems

    International Nuclear Information System (INIS)

    The objective of this paper is to evaluate magnetic field interactions at 1.5 and 3 T for 20 orthodontic devices used for fixed orthodontic therapy. Twenty springs and auxiliary parts made from varying ferromagnetic alloys were tested for magnetic field interactions in the static magnetic field at 1.5 and 3 T. Magnetic translational force Fz (in millinewtons) was evaluated by determining the deflection angle β [American Society for Testing and Materials (ASTM standard test method)]. Magnetic-field-induced rotational force Frot was qualitatively determined using a five-point scale. β was found to be >45 in 13(15) devices at 1.5(3) T and translational force Fz exceeded gravitational force Fg on the particular object [Fz 10.17-261.4 mN (10.72-566.4 mN) at 1.5(3) T]. Fz was found to be up to 24.1(47.5)-fold higher than Fg at 1.5(3) T. Corresponding to this, Frot on the objects was shown to be high at both field strengths (≥ +3). Three objects (at 1.5 T) and one object (at 3 T) showed deflection angles rot was found to be ≥ +3 at both field strengths. For the remaining objects, β was below 45 and torque measurements ranged from 0 to +2. Of 20 objects investigated for magnetic field interactions at 1.5(3) T, 13(15) were unsafe in magnetic resonance (MR), based on the ASTM criteria of Fz. The implications of these results for orthodontic patients undergoing MRI are discussed. (orig.)

  7. Orthodontic springs and auxiliary appliances: assessment of magnetic field interactions associated with 1.5 T and 3 T magnetic resonance systems

    Energy Technology Data Exchange (ETDEWEB)

    Kemper, J.; Priest, A.N.; Adam, G. [University Medical Center of Hamburg-Eppendorf, Clinic of Diagnostic and Interventional Radiology, Hamburg (Germany); Schulze, D. [University Hospital of Freiburg, Department of Oral and Maxillofacial Surgery, Freiburg (Germany); Kahl-Nieke, B.; Klocke, A. [University Medical Center of Hamburg-Eppendorf, Department of Orthodontics, Hamburg (Germany)

    2007-02-15

    The objective of this paper is to evaluate magnetic field interactions at 1.5 and 3 T for 20 orthodontic devices used for fixed orthodontic therapy. Twenty springs and auxiliary parts made from varying ferromagnetic alloys were tested for magnetic field interactions in the static magnetic field at 1.5 and 3 T. Magnetic translational force F{sub z} (in millinewtons) was evaluated by determining the deflection angle {beta} [American Society for Testing and Materials (ASTM standard test method)]. Magnetic-field-induced rotational force F{sub rot} was qualitatively determined using a five-point scale. {beta} was found to be >45 in 13(15) devices at 1.5(3) T and translational force F{sub z} exceeded gravitational force F{sub g} on the particular object [F{sub z} 10.17-261.4 mN (10.72-566.4 mN) at 1.5(3) T]. F{sub z} was found to be up to 24.1(47.5)-fold higher than F{sub g} at 1.5(3) T. Corresponding to this, F{sub rot} on the objects was shown to be high at both field strengths ({>=} +3). Three objects (at 1.5 T) and one object (at 3 T) showed deflection angles <45 , but F{sub rot} was found to be {>=} +3 at both field strengths. For the remaining objects, {beta} was below 45 and torque measurements ranged from 0 to +2. Of 20 objects investigated for magnetic field interactions at 1.5(3) T, 13(15) were unsafe in magnetic resonance (MR), based on the ASTM criteria of F{sub z}. The implications of these results for orthodontic patients undergoing MRI are discussed. (orig.)

  8. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

    NARCIS (Netherlands)

    Winkler, Thomas W.; Justice, Anne E.; Graff, Mariaelisa; Barata, Llilda; Feitosa, Mary F.; Chu, Su; Czajkowski, Jacek; Esko, Tonu; Fall, Tove; Kilpelainen, Tuomas O.; Lu, Yingchang; Magi, Reedik; Mihailov, Evelin; Pers, Tune H.; Rueeger, Sina; Teumer, Alexander; Ehret, Georg B.; Ferreira, Teresa; Heard-Costa, Nancy L.; Karjalainen, Juha; Lagou, Vasiliki; Mahajan, Anubha; Neinast, Michael D.; Prokopenko, Inga; Simino, Jeannette; Teslovich, Tanya M.; Jansen, Rick; Westra, Harm-Jan; White, Charles C.; Absher, Devin; Ahluwalia, Tarunveer S.; Ahmad, Shafqat; Albrecht, Eva; Alves, Alexessander Couto; Bragg-Gresham, Jennifer L.; de Craen, Anton J. M.; Bis, Joshua C.; Bonnefond, Amelie; Boucher, Gabrielle; Cadby, Gemma; Cheng, Yu-Ching; Chiang, Charleston W. K.; Delgado, Graciela; Demirkan, Ayse; Dueker, Nicole; Eklund, Niina; Eiriksdottir, Gudny; Eriksson, Joel; Feenstra, Bjarke; Fischer, Krista; Frau, Francesca; Galesloot, Tessel E.; Geller, Frank; Goel, Anuj; Gorski, Mathias; Grammer, Tanja B.; Gustafsson, Stefan; Haitjema, Saskia; Hottenga, Jouke-Jan; Huffman, Jennifer E.; Jackson, Anne U.; Jacobs, Kevin B.; Johansson, Asa; Kaakinen, Marika; Kleber, Marcus E.; Lahti, Jari; Leach, Irene Mateo; Lehne, Benjamin; Liu, Youfang; Lo, Ken Sin; Lorentzon, Mattias; Luan, Jian'an; Madden, Pamela A. F.; Mangino, Massimo; McKnight, Barbara; Medina-Gomez, Carolina; Monda, Keri L.; Montasser, May E.; Mueller, Gabriele; Mueller-Nurasyid, Martina; Nolte, Ilja M.; Panoutsopoulou, Kalliope; Pascoe, Laura; Paternoster, Lavinia; Rayner, Nigel W.; Renstrom, Frida; Rizzi, Federica; Rose, Lynda M.; Ryan, Kathy A.; Salo, Perttu; Sanna, Serena; Scharnagl, Hubert; Shi, Jianxin; Smith, Albert Vernon; Southam, Lorraine; Stancakova, Alena; Steinthorsdottir, Valgerdur; Strawbridge, Rona J.; Sung, Yun Ju; Tachmazidou, Ioanna; Tanaka, Toshiko; Thorleifsson, Gudmar; Trompet, Stella; Pervjakova, Natalia; Tyrer, Jonathan P.; Vandenput, Liesbeth; van der Laan, Sander W.; van der Velde, Nathalie; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Vlachopoulou, Efthymia; Waite, Lindsay L.; Wang, Sophie R.; Wang, Zhaoming; Wild, Sarah H.; Willenborg, Christina; Wilson, James F.; Wong, Andrew; Yang, Jian; Yengo, Loic; Yerges-Armstrong, Laura M.; Yu, Lei; Zhang, Weihua; Zhao, Jing Hua; Andersson, Ehm A.; Bakker, Stephan J. L.; Baldassarre, Damiano; Banasik, Karina; Barcella, Matteo; Barlassina, Cristina; Bellis, Claire; Benaglio, Paola; Blangero, John; Blueher, Matthias; Bonnet, Fabrice; Bonnycastle, Lori L.; Boyd, Heather A.; Bruinenberg, Marcel; Buchman, Aron S.; Campbell, Harry; Chen, Yii-Der Ida; Chines, Peter S.; Claudi-Boehm, Simone; Cole, John; Collins, Francis S.; de Geus, Eco J. C.; de Groot, Lisette C. P. G. M.; Dimitriou, Maria; Duan, Jubao; Enroth, Stefan; Eury, Elodie; Farmaki, Aliki-Eleni; Forouhi, Nita G.; Friedrich, Nele; Gejman, Pablo V.; Gigante, Bruna; Glorioso, Nicola; Go, Alan S.; Gottesman, Omri; Graessler, Juergen; Grallert, Harald; Grarup, Niels; Gu, Yu-Mei; Broer, Linda; Ham, Annelies C.; Hansen, Torben; Harris, Tamara B.; Hartman, Catharina A.; Hassinen, Maija; Hastie, Nicholas; Hattersley, Andrew T.; Heath, Andrew C.; Henders, Anjali K.; Hernandez, Dena; Hillege, Hans; Holmen, Oddgeir; Hovingh, Kees G.; Hui, Jennie; Husemoen, Lise L.; Hutri-Kahonen, Nina; Hysi, Pirro G.; Illig, Thomas; De Jager, Philip L.; Jalilzadeh, Shapour; Jorgensen, Torben; Jukema, J. Wouter; Juonala, Markus; Kanoni, Stavroula; Karaleftheri, Maria; Khaw, Kay Tee; Kinnunen, Leena; Kittner, Steven J.; Koenig, Wolfgang; Kolcic, Ivana; Kovacs, Peter; Krarup, Nikolaj T.; Kratzer, Wolfgang; Krueger, Janine; Kuh, Diana; Kumari, Meena; Kyriakou, Theodosios; Langenberg, Claudia; Lannfelt, Lars; Lanzani, Chiara; Lotay, Vaneet; Launer, Lenore J.; Leander, Karin; Lindstrom, Jaana; Linneberg, Allan; Liu, Yan-Ping; Lobbens, Stephane; Luben, Robert; Lyssenko, Valeriya; Mannisto, Satu; Magnusson, Patrik K.; McArdle, Wendy L.; Menni, Cristina; Merger, Sigrun; Milani, Lili; Montgomery, Grant W.; Morris, Andrew P.; Narisu, Narisu; Nelis, Mari; Ong, Ken K.; Palotie, Aarno; Perusse, Louis; Pichler, Irene; Pilia, Maria G.; Pouta, Anneli; Rheinberger, Myriam; Ribel-Madsen, Rasmus; Richards, Marcus; Rice, Kenneth M.; Rice, Treva K.; Rivolta, Carlo; Salomaa, Veikko; Sanders, Alan R.; Sarzynski, Mark A.; Scholtens, Salome; Scott, Robert A.; Scott, William R.; Sebert, Sylvain; Sengupta, Sebanti; Sennblad, Bengt; Seufferlein, Thomas; Silveira, Angela; Slagboom, P. Eline; Smit, Jan H.; Sparso, Thomas H.; Stirrups, Kathleen; Stolk, Ronald P.; Stringham, Heather M.; Swertz, Morris A.; Swift, Amy J.; Syvanen, Ann-Christine; Tan, Sian-Tsung; Thorand, Barbara; Toenjes, Anke; Tremblay, Angelo; Tsafantakis, Emmanouil; van der Most, Peter J.; Voelker, Uwe; Vohl, Marie-Claude; Vonk, Judith M.; Waldenberger, Melanie; Walker, Ryan W.; Wennauer, Roman; Widen, Elisabeth; Willemsen, Gonneke; Wilsgaard, Tom; Wright, Alan F.; Zillikens, M. Carola; van Dijk, Suzanne C.; van Schoor, Natasja M.; Asselbergs, Folkert W.; de Bakker, Paul I. W.; Beckmann, Jacques S.; Beilby, John; Bennett, David A.; Bergman, Richard N.; Bergmann, Sven; Boeger, Carsten A.; Boehm, Bernhard O.; Boerwinkle, Eric; Boomsma, Dorret I.; Bornstein, Stefan R.; Bottinger, Erwin P.; Bouchard, Claude; Chambers, John C.; Chanock, Stephen J.; Chasman, Daniel I.; Cucca, Francesco; Cusi, Daniele; Dedoussis, George; Erdmann, Jeanette; Eriksson, Johan G.; Evans, Denis A.; de Faire, Ulf; Farrall, Martin; Ferrucci, Luigi; Ford, Ian; Franke, Lude; Franks, Paul W.; Froguel, Philippe; Gansevoort, Ron T.; Gieger, Christian; Gronberg, Henrik; Gudnason, Vilmundur; Gyllensten, Ulf; Hall, Per; Hamsten, Anders; van der Harst, Pim; Hayward, Caroline; Heliovaara, Markku; Hengstenberg, Christian; Hicks, Andrew A.; Hingorani, Aroon; Hofman, Albert; Hu, Frank; Huikuri, Heikki V.; Hveem, Kristian; James, Alan L.; Jordan, Joanne M.; Jula, Antti; Kaehoenen, Mika; Kajantie, Eero; Kathiresan, Sekar; Kiemeney, Lambertus A. L. M.; Kivimaki, Mika; Knekt, Paul B.; Koistinen, Heikki A.; Kooner, Jaspal S.; Koskinen, Seppo; Kuusisto, Johanna; Maerz, Winfried; Martin, Nicholas G.; Laakso, Markku; Lakka, Timo A.; Lehtimaki, Terho; Lettre, Guillaume; Levinson, Douglas F.; Lind, Lars; Lokki, Marja-Liisa; Mantyselka, Pekka; Melbye, Mads; Metspalu, Andres; Mitchell, Braxton D.; Moll, Frans L.; Murray, Jeffrey C.; Musk, Arthur W.; Nieminen, Markku S.; Njolstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J.; Oostra, Ben A.; Palmer, Lyle J.; Pankow, James S.; Pasterkamp, Gerard; Pedersen, Nancy L.; Pedersen, Oluf; Penninx, Brenda W.; Perola, Markus; Peters, Annette; Polasek, Ozren; Pramstaller, Peter P.; Psaty, Bruce M.; Qi, Lu; Quertermous, Thomas; Raitakari, Olli T.; Rankinen, Tuomo; Rauramaa, Rainer; Ridker, Paul M.; Rioux, John D.; Rivadeneira, Fernando; Rotter, Jerome I.; Rudan, Igor; den Ruijter, Hester M.; Saltevo, Juha; Sattar, Naveed; Schunkert, Heribert; Schwarz, Peter E. H.; Shuldiner, Alan R.; Sinisalo, Juha; Snieder, Harold; Sorensen, Thorkild I. A.; Spector, Tim D.; Staessen, Jan A.; Stefania, Bandinelli; Thorsteinsdottir, Unnur; Stumvoll, Michael; Tardif, Jean-Claude; Tremoli, Elena; Tuomilehto, Jaakko; Uitterlinden, Andre G.; Uusitupa, Matti; Verbeek, Andre L. M.; Vermeulen, Sita H.; Viikari, Jorma S.; Vitart, Veronique; Voelzke, Henry; Vollenweider, Peter; Waeber, Gerard; Walker, Mark; Wallaschofski, Henri; Wareham, Nicholas J.; Watkins, Hugh; Zeggini, Eleftheria; Chakravarti, Aravinda; Clegg, Deborah J.; Cupples, L. Adrienne; Gordon-Larsen, Penny; Jaquish, Cashell E.; Rao, D. C.; Abecasis, Goncalo R.; Assimes, Themistocles L.; Barroso, Ines; Berndt, Sonja I.; Boehnke, Michael; Deloukas, Panos; Fox, Caroline S.; Groop, Leif C.; Hunter, David J.; Ingelsson, Erik; Kaplan, Robert C.; McCarthy, Mark I.; Mohlke, Karen L.; O'Connell, Jeffrey R.; Schlessinger, David; Strachan, David P.; Stefansson, Kari; van Duijn, Cornelia M.; Hirschhorn, Joel N.; Lindgren, Cecilia M.; Heid, Iris M.; North, Kari E.; Borecki, Ingrid B.; Kutalik, Zoltan; Loos, Ruth J. F.

    2015-01-01

    Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially betw

  9. Quantifying the effect of interactions between disease control, nitrogen supply and land use change on the greenhouse gas emissions associated with wheat production

    DEFF Research Database (Denmark)

    Berry, P M; Kindred, D R; Olesen, Jørgen E;

    2010-01-01

    A method for calculating the effect of disease control on greenhouse gas (GHG) emissions associated with wheat production, reported previously, was developed further to account for effects of disease control on the amount of fertilizer nitrogen (N) which should be applied and on changes in land use...

  10. Environmental neurotoxin interaction with proteins: Dose-dependent increase of free and protein-associated BMAA (β-N-methylamino-L-alanine) in neonatal rat brain.

    Science.gov (United States)

    Karlsson, Oskar; Jiang, Liying; Ersson, Lisa; Malmström, Tim; Ilag, Leopold L; Brittebo, Eva B

    2015-01-01

    β-Methylamino-L-alanine (BMAA) is implicated in the aetiology of neurodegenerative disorders. Neonatal exposure to BMAA induces cognitive impairments and progressive neurodegenerative changes including intracellular fibril formation in the hippocampus of adult rats. It is unclear why the neonatal hippocampus is especially vulnerable and the critical cellular perturbations preceding BMAA-induced toxicity remains to be elucidated. The aim of this study was to compare the level of free and protein-associated BMAA in neonatal rat brain and peripheral tissues after different exposures to BMAA. Ultra-high performance liquid chromatography-tandem mass spectrometry analysis revealed that BMAA passed the neonatal blood-brain barrier and was distributed to all studied brain areas. BMAA was also associated to proteins in the brain, especially in the hippocampus. The level in the brain was, however, considerably lower compared to the liver that is not a target organ for BMAA. In contrast to the liver there was a significantly increased level of protein-association of BMAA in the hippocampus and other brain areas following repeated administration suggesting that the degradation of BMAA-associated proteins may be lower in neonatal brain than in the liver. Additional evidence is needed in support of a role for protein misincorporation in the neonatal hippocampus for long-term effects of BMAA.

  11. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

    NARCIS (Netherlands)

    Winkler, T.W.; Justice, A.E.; Graff, M.; Barata, L.; Feitosa, M.F.; Chu, S.; Czajkowski, J.; Esko, T.; Fall, T.; Kilpelainen, T.O.; Lu, Y.; Magi, R.; Mihailov, E.; Pers, T.H.; Rueger, S.; Teumer, A.; Ehret, G.B.; Ferreira, T.; Heard-Costa, N.L.; Karjalainen, J.; Lagou, V.; Mahajan, A.; Neinast, M.D.; Prokopenko, I.; Simino, J.; Teslovich, T.M.; Jansen, R.; Westra, H.J.; White, C.C.; Absher, D.; Ahluwalia, T.S.; Ahmad, S.; Albrecht, E.; Ferreira Alves, A.C.; Bragg-Gresham, J.L.; Craen, A.J. de; Bis, J.C.; Bonnefond, A.; Boucher, G.; Cadby, G.; Cheng, Y.C.; Chiang, C.W.; Delgado, G.; Demirkan, A.; Dueker, N.; Eklund, N.; Eiriksdottir, G.; Eriksson, J.; Feenstra, B.; Fischer, K.; Frau, F.; Galesloot, T.E.; Geller, F.; Goel, A.; Gorski, M.; Grammer, T.B.; Gustafsson, S.; Haitjema, S.; Hottenga, J.J.; Huffman, J.E.; Jackson, A.U.; Jacobs, K.B.; Johansson, A; Kaakinen, M.; Kleber, M.E.; Lahti, J.; Leach, I.M.; Lehne, B.; Liu, Y.; Lo, K.S.; Lorentzon, M.; Luan, J.; Madden, P.A.F.; Mangino, M.; McKnight, B.; Medina-Gomez, C.; Monda, K.L.; Montasser, M.E.; Muller, G.; Muller-Nurasyid, M.; Nolte, I.M.; Panoutsopoulou, K.; Pascoe, L.; Paternoster, L.; Rayner, N.W.; Renstrom, F.; Rizzi, F.; Rose, L.M.; Ryan, K.A.; Salo, P.; Sanna, S.; Scharnagl, H.; Shi, J.; Smith, A.V.; Southam, L.; Stancakova, A.; Steinthorsdottir, V.; Strawbridge, R.J.; Sung, Y.J.; Tachmazidou, I.; Kiemeney, B.; Vermeulen, S.H.

    2015-01-01

    Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially betw

  12. Position of the kissing-loop interaction associated with PTE-type 3’CITEs can affect enhancement of cap-independent translation

    OpenAIRE

    Chattopadhyay, Maitreyi; Kuhlmann, Micki M.; Kumar, Kalyani; Simon, Anne E.

    2014-01-01

    The Panicum mosaic virus-like translation enhancer (PTE) functions as a cap-independent translation enhancer (3’CITE) in members of several Tombusviridae genera including 7/19 carmoviruses. For nearly all PTE, a kissing-loop connects the element with a hairpin found in several conserved locations in the genomic RNA (5’ terminal hairpin or ~100 nt from the 5’end) and small subgenomic RNA (~63 nt from the 5’end). Moving the interaction closer to the 5’end in reporter mRNAs using Saguaro cactus ...

  13. The -250G>A promoter variant in hepatic lipase associates with elevated fasting serum high-density lipoprotein cholesterol modulated by interaction with physical activity in a study of 16,156 Danish subjects

    DEFF Research Database (Denmark)

    Grarup, Niels; Andreasen, Camilla H; Andersen, Mette K;

    2008-01-01

    of variants in LIPC on metabolic traits and type 2 diabetes in a large sample of Danes. Because behavioral factors influence hepatic lipase activity, we furthermore examined possible gene-environment interactions in the population-based Inter99 study. DESIGN: The LIPC -250G>A (rs2070895) variant was genotyped...... Treatment in People with Screen Detected Diabetes in Primary Care study [0.038 mmol/liter per allele (95% CI 0.024-0.053); P = 2 x 10(-7)). The allelic effect on HDL-c was modulated by interaction with self-reported physical activity (P(interaction) = 0.002) because vigorous physically active homozygous A......-allele carriers had a 0.30 mmol/liter (95% CI 0.22-0.37) increase in HDL-c compared with homozygous G-allele carriers. CONCLUSIONS: We validate the association of LIPC promoter variation with fasting serum HDL-c and present data supporting an interaction with physical activity implying an increased effect on HDL...

  14. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study

    DEFF Research Database (Denmark)

    Milne, Roger L; Gaudet, Mia M; Spurdle, Amanda B;

    2010-01-01

    Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the...... Breast Cancer Association Consortium....

  15. Virulence of, and interactions among mountain pine beetle associated blue-stain fungi on two pine species and their hybrids in Alberta

    OpenAIRE

    Rice, A V; M.N. Thormann; Langor, D W

    2007-01-01

    Mountain pine beetle (MPB) is the most serious pest of lodgepole pine in western Canada, and it is predicted to spread into boreal jack pine within the next few years. Colonization of host trees by MPB-associated blue-stain fungi appears to be required for successful beetle reproduction. Three species of blue-stain fungi, Grosmannia clavigera (Robinson-Jeffery and Davidson) Zipfel, de Beer, and Wingfield (≡ Ophiostoma clavigerum (Robinson-Jeffery and Davidson) Harrington), Ophiostoma montium ...

  16. Quadratic-nonlinear Landau-Zener transition for association of an atomic Bose-Einstein condensate with inter-particle elastic interactions included

    OpenAIRE

    Ishkhanyan, A.; Sokhoyan, R.; Suominen, K. -A.; Leroy, C.; Jauslin, H. -R.

    2009-01-01

    We study the strong coupling limit of a quadratic-nonlinear Landau-Zener problem for coherent photo- and magneto-association of cold atoms taking into account the atom-atom, atom-molecule, and molecule-molecule elastic scattering. Using an exact third-order nonlinear differential equation for the molecular state probability, we develop a variational approach which enables us to construct a highly accurate and simple analytic approximation describing the time dynamics of the coupled atom-molec...

  17. Genetic Polymorphisms of Stromal Interaction Molecule 1 Associated with the Erythrocyte Sedimentation Rate and C-Reactive Protein in HLA-B27 Positive Ankylosing Spondylitis Patients

    OpenAIRE

    Wei, James Cheng-Chung; Hung, Kuo-Sheng; Hsu, Yu-Wen; Wong, Ruey-Hong; Huang, Chun-Huang; Jan, Ming-Shiou; Wu, Shyh-Jong; Juan, Yung-Shun; Chang, Wei-Chiao

    2012-01-01

    Ankylosing spondylitis (AS) is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. The development of ankylosing spondylitis is still unclear. Genetics factors such as human leukocyte antigen HLA-B27 and ERAP1 have been widely reported to associate to AS susceptibility. In this study, we enrolled 361 AS patients and selected four tagging single nucleotides polymorphisms (tSNPs) at STIM1 gene. The correlation between STIM1 genetic polymorphisms and AS activity index (...

  18. The enhancement of astrocytic-derived monocyte chemoattractant protein-1 induced by the interaction of opiate and HIV tat in HIV-associated dementia

    Institute of Scientific and Technical Information of China (English)

    Xiao Han

    2009-01-01

    HIV-assodated dementia (HAD) is a public health problem and is particularly prevalent in drug abusers. The neuropathogenesis of human immunodeficiency virus (HIV) infection involves a complex cascade of inflammatory events, including monocyte/macrophage infiltration in the brain, glial immune activation and release of neurotoxic substances. In these events, astrocytic-derived monocyte chemoattractant protein-1 (MCP-1) plays an important role, whose release is elevated by HIV transactivator of transcription (HIV tat) and could be further elevated by opiates. This review will also consider some critical factors and events in MCP-1 enhancement induced by the interactions of opiate and HIV tat, including the mediating role of mu opioid receptor (MOR) and CCR2 as well as the possible signal transduction pathways within the cells. Finally, it will make some future perspectives on the exact pathways, new receptors and target cells, and the vulnerability to neurodegeneration with HIV and opiates.

  19. Interactive effects of ocean acidification and warming on coral reef associated epilithic algal communities under past, present-day and future ocean conditions

    Science.gov (United States)

    Vogel, N.; Cantin, N. E.; Strahl, J.; Kaniewska, P.; Bay, L.; Wild, C.; Uthicke, S.

    2016-06-01

    Epilithic algal communities play critical ecological roles on coral reefs, but their response to individual and interactive effects of ocean warming (OW) and ocean acidification (OA) is still largely unknown. We investigated growth, photosynthesis and calcification of early epilithic algal community assemblages exposed for 6 months to four temperature profiles (-1.1, ±0.0, +0.9, +1.6 °C) that were crossed with four carbon dioxide partial pressure (pCO2) levels (360, 440, 650, 940 µatm), under flow-through conditions and natural light regimes. Additionally, we compared the cover of heavily calcified crustose coralline algae (CCA) and lightly calcified red algae of the genus Peyssonnelia among treatments. Increase in cover of epilithic communities showed optima under moderately elevated temperatures and present pCO2, while cover strongly decreased under high temperatures and high-pCO2 conditions, particularly due to decreasing cover of CCA. Similarly, community calcification rates were strongly decreased at high pCO2 under both measured temperatures. While final cover of CCA decreased under high temperature and pCO2 (additive negative effects), cover of Peyssonnelia spp. increased at high compared to annual average and moderately elevated temperatures. Thus, cover of Peyssonnelia spp. increased in treatment combinations with less CCA, which was supported by a significant negative correlation between organism groups. The different susceptibility to stressors most likely derived from a different calcification intensity and/or mineral. Notably, growth of the epilithic communities and final cover of CCA were strongly decreased under reduced-pCO2 conditions compared to the present. Thus, CCA may have acclimatized from past to present-day pCO2 conditions, and changes in carbonate chemistry, regardless in which direction, negatively affect them. However, if epilithic organisms cannot further acclimatize to OW and OA, the interacting effects of both factors may change

  20. Association of the Genetic Polymorphisms in Transcription Factor 7-Like 2 and Peroxisome Proliferator-Activated Receptors-γ2 with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status in Emirati Population

    Directory of Open Access Journals (Sweden)

    Habiba Al-Safar

    2015-01-01

    Full Text Available Background. Transcription factor 7-like 2 gene (TCF7L2 and peroxisome proliferator-activated receptors-γ2 (PPAR-γ2 have a profound effect on the incidence of type 2 diabetes mellitus (T2DM and had previously been found to be associated with T2DM risk in various ppopulations. However, studies in the Arab population are inconsistent. We conducted a case control study to confirm the association of variants rs10885409 of TCF7L2 and Pro12Ala (rs1801282 of PPAR-γ2 with risk of T2DM and related complications in Emirati population of Arab origin. We also investigated the interaction of these associations with obesity status. Methods. DNA was extracted from the saliva samples of 272 T2DM patients and 216 nondiabetic Emiratis. Genotyping for rs10885409 (TCF7L2 and rs1801282 (PPAR-γ2 P12A variants was accomplished with a TaqMan assay. The subgroups were constituted according to obesity status. Results. In the nonobese group, the rs10885409 C allele in the recessive model was significantly associated with the incidence of T2DM (OR 1.975 [95% CI 1.127–3.461], P=0.017, but this association was not observed in the obese group or when BMI was not considered. PPAR-γ2 risk allele Pro12 frequency (0.96 was similar in the groups tested and more than 90% population was homozygous for this allele. Conclusions. Our case-control study is the first of its kind in Emiratis which establishes TCF7L2 rs10885409 C allele as a T2DM risk factor in Emiratis and this association is modulated by obesity status. We also confirmed that Pro12Ala mutation in PPAR-γ2 is not associated with T2DM risk in this population.

  1. The enhancement of astrocytic-derived monocyte chemoattractant protein-1 induced by the interaction of opiate and HIV tat in HIV-associated dementia

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    HIV-associated dementia(HAD)is a public health problem and is particularly prevalent in drug abusers.The neuropathogenesis of human immunodeficiency virus(HIV)infection involves a complex cascade of inflammatory events,including monocyte/macrophage infiltration in the brain,glial immune activation and release of neurotoxic substances.In these events,astrocytic-derived monocyte chemoattractant protein-1(MCP-1)plays an important role,whose release is elevated by HIV transactivator of transcription(HIV tat)and...

  2. The influence of age and sex on genetic associations with adult body size and shape: a large-scale genome-wide interaction study

    OpenAIRE

    Winkler, Thomas W; Heid, Iris M.; Gorski, Mathias

    2015-01-01

    Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of Eu...

  3. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

    OpenAIRE

    Winkler, Thomas W.; Justice, Anne E; Graff, Mariaelisa; Barata, Llilda; Feitosa, Mary F.; Chu, Su,; Czajkowski, Jacek; Esko, Tonu; Fall, Tove; Kilpelainen, Tuomas O.; Lu, Yingchang; Magi, Reedik; Mihailov, Evelin; Pers, Tune H; Rueeger, Sina

    2015-01-01

    Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of Eur...

  4. Aging and depression vulnerability interaction results in decreased serotonin innervation associated with reduced BDNF levels in hippocampus of rats bred for learned helplessness

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders B; Santini, Martin A;

    2010-01-01

    Epidemiological studies have revealed a strong genetic contribution to the risk for depression. Both reduced hippocampal serotonin neurotransmission and brain-derived neurotrophic factor (BDNF) levels have been associated with increased depression vulnerability and are also regulated during aging....... These observations indicate that aging should be taken into account when studying the neurobiological factors behind the vulnerability for depression and that understanding the effect of aging on genetically predisposed individuals may contribute to a better understanding of the pathophysiology behind depression......, particularly in the elderly....

  5. Aging and depression vulnerability interaction results in decreased serotonin innervation associated with reduced BDNF levels in hippocampus of rats bred for learned helplessness

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders B; Santini, Martin A;

    2010-01-01

    Epidemiological studies have revealed a strong genetic contribution to the risk for depression. Both reduced hippocampal serotonin neurotransmission and brain-derived neurotrophic factor (BDNF) levels have been associated with increased depression vulnerability and are also regulated during aging...... density. Hippocampal BDNF protein levels were measured by ELISA. An exacerbated age-related loss of serotonin fiber density specific for the CA1 area was observed in the cLH animals, whereas reduced hippocampal BDNF levels were seen in young and old cLH when compared with age-matched cNLH controls...

  6. Genetic polymorphisms of stromal interaction molecule 1 associated with the erythrocyte sedimentation rate and C-reactive protein in HLA-B27 positive ankylosing spondylitis patients.

    Directory of Open Access Journals (Sweden)

    James Cheng-Chung Wei

    Full Text Available Ankylosing spondylitis (AS is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. The development of ankylosing spondylitis is still unclear. Genetics factors such as human leukocyte antigen HLA-B27 and ERAP1 have been widely reported to associate to AS susceptibility. In this study, we enrolled 361 AS patients and selected four tagging single nucleotides polymorphisms (tSNPs at STIM1 gene. The correlation between STIM1 genetic polymorphisms and AS activity index (BASDAI, BASFI, BAS-G as well as laboratory parameters of inflammation (erythrocyte sedimentation rate (ESR and C-reactive protein (CRP were tested. Our results indicated that HLA-B27 positive AS patients who are carrying the minor allele homozygous G/G genotype of SNP rs3750996 significantly associated with a higher level of ESR in serum. Furthermore, rs3750996/rs3750994 pairwise allele analysis indicated that G-C haplotypes also significantly correlated with higher level of ESR as well as CRP. These findings provide a better understanding of STIM1 genetic contribution to the pathogenesis of AS.

  7. Position of the kissing-loop interaction associated with PTE-type 3’CITEs can affect enhancement of cap-independent translation

    Science.gov (United States)

    Chattopadhyay, Maitreyi; Kuhlmann, Micki M.; Kumar, Kalyani; Simon, Anne E.

    2014-01-01

    The Panicum mosaic virus-like translation enhancer (PTE) functions as a cap-independent translation enhancer (3’CITE) in members of several Tombusviridae genera including 7/19 carmoviruses. For nearly all PTE, a kissing-loop connects the element with a hairpin found in several conserved locations in the genomic RNA (5’ terminal hairpin or ~100 nt from the 5’end) and small subgenomic RNA (~63 nt from the 5’end). Moving the interaction closer to the 5’end in reporter mRNAs using Saguaro cactus virus (SCV) sequences had either a minimal or substantial negative effect on translation. Movement of the kissing loop from position 104 to the SCV 5’ terminal hairpin also reduced translation by 4-fold. These results suggest that relocating the PTE kissing loop closer to the 5’end reduces PTE efficiency, in contrast to results for the Barley yellow dwarf BTE and Tomato bushy stunt virus Y-shaped 3’CITEs , suggesting that different 3’CITEs have different bridging requirements. PMID:24928038

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

    Directory of Open Access Journals (Sweden)

    Blier Pierre

    2007-12-01

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

  9. Amygdalar interaction with the mediodorsal nucleus of the thalamus and the ventromedial prefrontal cortex in stimulus-reward associative learning in the monkey.

    Science.gov (United States)

    Gaffan, D; Murray, E A

    1990-11-01

    Cynomolgus monkeys (Macaca fascicularis) were assessed for their ability to associate visual stimuli with food reward. They learned a series of new 2-choice visual discriminations between colored patterns displayed on a monitor screen. The feedback for correct choice was the delivery of food. In order to promote associative learning between the visual stimuli and the incentive value of the food reward, reward delivery was not accompanied by any distinctive visual feedback on the display screen. The rate of learning new problems was assessed before and after surgery in a total of 16 monkeys. Three groups of 3 monkeys received bilaterally symmetrical ablations in either the amygdala, the mediodorsal nucleus of the thalamus, or the ventromedial prefrontal cortex. All these groups showed a severe postoperative learning impairment. Seven other animals were given a unilateral ablation in 1 of those 3 structures and a second unilateral ablation, in each case contralateral to and different from the first, in order to produce 2 groups in which a putative amygdalo-thalamo-prefrontal pathway had been disconnected by crossed unilateral lesions. One disconnection group had lesions in the amygdala and ventromedial prefrontal cortex; the other had lesions in the amygdala and the mediodorsal nucleus of the thalamus. The disconnection groups showed a significant impairment, but the effect of the disconnection surgeries was significantly milder than the effect of any of the 3 bilaterally symmetrical lesions. Therefore, symmetrical bilateral lesions in either the amygdala, the mediodorsal nucleus, or the ventromedial prefrontal cortex produce similar impairments in the present task, implying that these structures are functionally related to each other; but the relatively mild effect of disconnecting these structures from each other argues against the hypothesis that they are serial stages in a single, tightly linked functional pathway. PMID:2230939

  10. Logic Features Selection in Identification of the Most Important Interactions of Interleukin-6 and Two Important Single Nucleotide Polymorphisms of Its Gene (IL-6-174, IL-6-572 with Some Other Factors in Association with hypertension

    Directory of Open Access Journals (Sweden)

    Hamid Alavi Majd

    2012-10-01

    Full Text Available Introduction: The study aimed to identify important interactions between Interleukin-6 and two single nucleotide polymorphisms of its gene expression (IL-6-174, IL-6-572 with some other factors including gender, age group, BMI, as while as blood concentration of sugar, lipids, and C-reactive protein, in association with hypertension. Methods: In this cross-sectional study, the data of first phase of the "Evaluation of Novel Risk Factors of NCD" project conducted in 2001by the Research Institute for Endocrine Sciences was used. To identify the interactions we used logic Features Selection approach. Analyses were done by logistic regression models using adjusted odds ratio (OR to demonstrate the associations of interest. Results: Based on final selected model on data of 126 men and 208 women with age of 18 or more, significant regression coefficients were reported for individual variables including fasting blood sugar≥126mg/dl (P=0.001, body mass index>25 (P=0.03, and age>40 years of old (P200 mg/dl+ age>40+ interloukin-6 >29+ fasting blood sugar<126mg/dl (P=0.003.Conclusion: Findings suggested that in addition to age, body mass index and fasting blood sugar, having high level of interleukin-6 besides high plasma concentration of total cholesterol in older adults with non diabetic fasting blood sugar can significantly increase hypertension prevalence, applying logic Features Selection approach.

  11. Direct interaction and functional coupling between human 5-HT6 receptor and the light chain 1 subunit of the microtubule-associated protein 1B (MAP1B-LC1.

    Directory of Open Access Journals (Sweden)

    Soon-Hee Kim

    Full Text Available Serotonin (5-HT receptors of type 6 (5-HT6R play important roles in mood, psychosis, and eating disorders. Recently, a growing number of studies support the use of 5-HT6R-targeting compounds as promising drug candidates for treating cognitive dysfunction associated with Alzheimer's disease. However, the mechanistic linkage between 5-HT6R and such functions remains poorly understood. By using yeast two-hybrid, GST pull-down, and co-immunoprecipitation assays, here we show that human 5-HT6R interacts with the light chain 1 (LC1 subunit of MAP1B protein (MAP1B-LC1, a classical microtubule-associated protein highly expressed in the brain. Functionally, we have found that expression of MAP1B-LC1 regulates serotonin signaling in a receptor subtype-specific manner, specifically controlling the activities of 5-HT6R, but not those of 5-HT4R and 5-HT7R. In addition, we have demonstrated that MAP1B-LC1 increases the surface expression of 5-HT6R and decreases its endocytosis, suggesting that MAP1B-LC1 is involved in the desensitization and trafficking of 5-HT6R via a direct interaction. Together, we suggest that signal transduction pathways downstream of 5-HT6R are regulated by MAP1B, which might play a role in 5-HT6R-mediated signaling in the brain.

  12. Biochemical and structural characterization of the interface mediating interaction between the influenza A virus non-structural protein-1 and a monoclonal antibody

    Science.gov (United States)

    Wu, Jianping; Mok, Chee-Keng; Chow, Vincent Tak Kwong; Yuan, Y. Adam; Tan, Yee-Joo

    2016-01-01

    We have previously shown that a non-structural protein 1 (NS1)-binding monoclonal antibody, termed as 2H6, can significantly reduce influenza A virus (IAV) replication when expressed intracellularly. In this study, we further showed that 2H6 binds stronger to the NS1 of H5N1 than A/Puerto Rico/8/1934(H1N1) because of an amino acid difference at residue 48. A crystal structure of 2H6 fragment antigen-binding (Fab) has also been solved and docked onto the NS1 structure to reveal the contacts between specific residues at the interface of antibody-antigen complex. In one of the models, the predicted molecular contacts between residues in NS1 and 2H6-Fab correlate well with biochemical results. Taken together, residues N48 and T49 in H5N1 NS1 act cooperatively to maintain a strong interaction with mAb 2H6 by forming hydrogen bonds with residues found in the heavy chain of the antibody. Interestingly, the pandemic H1N1-2009 and the majority of seasonal H3N2 circulating in humans since 1968 has N48 in NS1, suggesting that mAb 2H6 could bind to most of the currently circulating seasonal influenza A virus strains. Consistent with the involvement of residue T49, which is well-conserved, in RNA binding, mAb 2H6 was also found to inhibit the interaction between NS1 and double-stranded RNA. PMID:27633136

  13. Biophysical alterations in lipid rafts from human cerebral cortex associate with increased BACE1/AβPP interaction in early stages of Alzheimer's disease.

    Science.gov (United States)

    Díaz, Mario; Fabelo, Noemí; Martín, Virginia; Ferrer, Isidre; Gómez, Tomás; Marín, Raquel

    2015-01-01

    In the present study, we have assessed the biophysical properties of lipid rafts from different brain areas in subjects exhibiting early neuropathological stages of Alzheimer's disease (AD). By means of steady-state fluorescence polarization analyses using two environment-sensitive fluorescent probes, we demonstrate that lipid rafts from cerebellum, and frontal and entorhinal cortices, exhibit different biophysical behaviors depending on the stage of the disease. Thus, while membrane anisotropies were similar in the cerebellum along stages, lipid rafts from frontal and entorhinal cortices at AD stages I/II and AD III were significantly more liquid-ordered than in control subjects, both at the aqueous interface and hydrophobic core of the raft membrane. Thermotropic analyses demonstrated the presence of Arrhenius breakpoints between 28.3-32.0 °C, which were not influenced by the disease stage. However, analyses of membrane microviscosity (ηapp) demonstrate that frontal and entorhinal lipid rafts are notably more viscous and liquid-ordered all across the membrane from early stages of the disease. These physicochemical alterations in lipid rafts do not correlate with changes in cholesterol or sphingomyelin levels, but to reduced unsaturation index and increased saturate/polyunsaturated ratios in phospholipid acyl chains. Moreover, we demonstrate that β-secretase/AβPP (amyloid-β protein precursor) interaction and lipid raft microviscosity are strongly, and positively, correlated in AD frontal and entorhinal cortices. These observations strengthens the hypothesis that physical properties of these microdomains modulate the convergence of amyloidogenic machinery toward lipid rafts, and also points to a critical role of polyunsaturated fatty acids in amyloidogenic processing of AβPP.

  14. Regulation of loquat fruit low temperature response and lignification involves interaction of heat shock factors and genes associated with lignin biosynthesis.

    Science.gov (United States)

    Zeng, Jiao-Ke; Li, Xian; Zhang, Jing; Ge, Hang; Yin, Xue-Ren; Chen, Kun-Song

    2016-08-01

    Transcriptional regulatory mechanisms underlying lignin metabolism have been widely studied in model plants and woody trees, as well as fruit, such as loquat (Eriobotrya japonica). Unlike the well-known NAC, MYB and AP2/ERF transcription factors, the roles of heat shock factors (HSFs) in lignin regulation have been rarely reported. Two treatments (heat treatment, HT; low temperature conditioning, LTC) were applied to alleviate low temperature-induced lignification in loquat fruit. Gene expression analysis indicated that EjHSF1 transcript abundance, in parallel with heat shock protein genes (EjHsp), was induced by HT, while expression of EjHSF3 was repressed by LTC. Using dual-luciferase assays, EjHSF1 and EjHSF3 trans-activated the promoters of EjHsp genes and lignin biosynthesis-related genes, respectively. Thus, two distinct regulatory mechanisms of EjHSF transcription factors in chilling injury-induced fruit lignification are proposed: EjHSF1 transcriptionally regulated EjHsp genes are involved in chilling tolerance, while EjHSF3 transcriptionally regulated lignin biosynthesis. Furthermore, the relations between EjHSF3 and previously characterized fruit lignification regulators, including EjAP2-1, EjMYB1 and EjMYB2, were also investigated. Yeast-two hybrid (Y2H) and biomolecular fluorescence complementation (BiFC) assays demonstrated protein-protein interaction between EjHSF3 and EjAP2-1. Thus, the involvement of EjHSF3 in fruit lignification is via both lignin biosynthetic genes and the regulator, EjAP2-1. PMID:27006258

  15. G359.97-0.038: A HARD X-RAY FILAMENT ASSOCIATED WITH A SUPERNOVA SHELL-MOLECULAR CLOUD INTERACTION

    Energy Technology Data Exchange (ETDEWEB)

    Nynka, Melania; Hailey, Charles J.; Zhang, Shuo; Gotthelf, Eric V.; Mori, Kaya; Perez, Kerstin M. [Columbia Astrophysics Laboratory, Columbia University, New York, NY 10027 (United States); Morris, Mark M. [Department of Physics and Astronomy, University of California, Los Angeles, CA 90095 (United States); Zhao, Jun-Hui [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, MS 78, Cambridge, MA 02138 (United States); Goss, Miller [NRAO, P.O. Box O, Socorro, NM 87801 (United States); Bauer, Franz E. [Instituto de Astrofísica, Facultad de Física, Pontificia Universidad Católica de Chile, 306, Santiago 22 (Chile); Boggs, Stephen E.; Craig, William W. [Space Sciences Laboratory, University of California, Berkeley, CA 94720 (United States); Christensen, Finn E. [DTU Space-National Space Institute, Technical University of Denmark, Elektrovej 327, DK-2800 Lyngby (Denmark); Harrison, Fiona A. [Cahill Center for Astronomy and Astrophysics, California Institute of Technology, Pasadena, CA 91125 (United States); Stern, Daniel [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); Zhang, William W. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

    2015-02-20

    We present the first high-energy X-ray (>10 keV) observations of the non-thermal filament G359.97-0.038 using the Nuclear Spectroscopic Telescope Array (NuSTAR). This filament is one of approximately 20 X-ray filaments of unknown origin located in the central 20 pc region in the Galactic Center near Sgr A*. Its NuSTAR and Chandra broadband spectrum is characterized by a single power law with Γ = 1.3 ± 0.3 that extends from 2 to 50 keV, with an unabsorbed luminosity of 1.3 × 10{sup 33} erg s{sup –1} (d/8 kpc){sup 2} in the 2-8 keV band. Despite possessing a cometary X-ray morphology that is typical of a pulsar wind nebula (PWN) in high-resolution Chandra imaging, our spatially resolved Chandra spectral analysis found no significant spectral softening along the filament as would be expected from particle synchrotron cooling. Coincident radio emission is detected using the Very Large Array at 5.5 and 8.3 GHz. We examine and subsequently discard a PWN or magnetic flux tube as the origin of G359.97-0.038. We use broadband spectral characteristics and a morphological analysis to show that G359.97-0.038 is likely an interaction site between the shell of Sgr A East and an adjacent molecular cloud. This is supported by CS molecular line spectroscopy and the presence of an OH maser.

  16. Two AAA family peroxins, PpPex1p and PpPex6p, interact with each other in an ATP-dependent manner and are associated with different subcellular membranous structures distinct from peroxisomes.

    Science.gov (United States)

    Faber, K N; Heyman, J A; Subramani, S

    1998-02-01

    Two peroxins of the AAA family, PpPex1p and PpPex6p, are required for peroxisome biogenesis in the yeast Pichia pastoris. Cells from the corresponding deletion strains (Pp delta pex1 and Pp delta pex6) contain only small vesicular remnants of peroxisomes, the bulk of peroxisomal matrix proteins is mislocalized to the cytosol, and these cells cannot grow in peroxisome-requiring media (J. A. Heyman, E. Monosov, and S. Subramani, J. Cell Biol. 127:1259-1273, 1994; A. P. Spong and S. Subramani, J. Cell Biol. 123:535-548, 1993). We demonstrate that PpPex1p and PpPex6p interact in an ATP-dependent manner. Genetically, the interaction was observed in a suppressor screen with a strain harboring a temperature-sensitive allele of PpPEX1 and in the yeast two-hybrid system. Biochemially, these proteins were coimmunoprecipitated with antibodies raised against either of the proteins, but only in the presence of ATP. The protein complex formed under these conditions was 320 to 400 kDa in size, consistent with the formation of a heterodimeric PpPex1p-PpPex6p complex. Subcellular fractionation revealed PpPex1p and PpPex6p to be predominantly associated with membranous subcellular structures distinct from peroxisomes. Based on their behavior in subcellular fractionation experiments including flotation gradients and on the fact that these structures are also present in a Pp delta pex3 strain in which no morphologically detectable peroxisomal remnants have been observed, we propose that these structures are small vesicles. The identification of vesicle-associated peroxins is novel and implies a role for these vesicles in peroxisome biogenesis. We discuss the possible role of the ATP-dependent interaction between PpPex1p and PpPex6p in regulating peroxisome biogenesis events. PMID:9447990

  17. Interaction between ALDH2*1*1 and DRD2/ANKK1 TaqI A1A1 genes may be associated with antisocial personality disorder not co-morbid with alcoholism.

    Science.gov (United States)

    Lu, Ru-Band; Lee, Jia-Fu; Huang, San-Yuan; Lee, Sheng-Yu; Chang, Yun-Hsuan; Kuo, Po-Hsiu; Chen, Shiou-Lan; Chen, Shih-Heng; Chu, Chun-Hsien; Lin, Wei-Wen; Wu, Pei-Lin; Ko, Huei-Chen

    2012-09-01

    Previous studies on acetaldehyde dehydrogenase 2 (ALDH2) focused on drinking behavior or alcoholism because the ALDH2*2 allele protects against the risk of developing alcoholism. The mechanism provides that the ALDH2 gene's protective effect is also involved in dopamine metabolism. The interaction of the ALDH2 gene with neurotransmitters, such as dopamine, is suggested to be related to alcoholism. Because alcoholism is often co-morbid with antisocial personality disorder (ASPD), previous association studies on antisocial alcoholism cannot differentiate whether those genes relate to ASPD with alcoholism or ASPD only. This study examined the influence of the interaction effect of the ALDH2*1*1, *1*2 or *2*2 polymorphisms with the dopamine 2 receptor (DRD2) Taq I polymorphism on ASPD. Our 541 Han Chinese male participants were classified into three groups: antisocial alcoholism (ASPD co-morbid with alcohol dependence, antisocial ALC; n = 133), ASPD without alcoholism (ASPD not co-morbid with alcohol dependence, antisocial non-ALC; n = 164) and community controls (healthy volunteers from the community; n = 244). Compared with healthy controls, individuals with the DRD2 A1/A1 and the ALDH2*1/*1 genotypes were at a 5.39 times greater risk for antisocial non-ALC than were those with other genotypes. Our results suggest that the DRD2/ANKK1 and ALDH2 genes interacted in the antisocial non-ALC group; a connection neglected in previous studies caused by not separating antisocial ALC from ASPD. Our study made this distinction and showed that these two genes may be associated ASPD without co-morbid alcoholism.

  18. OS9 Protein Interacts with Na-K-2Cl Co-transporter (NKCC2) and Targets Its Immature Form for the Endoplasmic Reticulum-associated Degradation Pathway.

    Science.gov (United States)

    Seaayfan, Elie; Defontaine, Nadia; Demaretz, Sylvie; Zaarour, Nancy; Laghmani, Kamel

    2016-02-26

    Mutations in the renal specific Na-K-2Cl co-transporter (NKCC2) lead to type I Bartter syndrome, a life-threatening kidney disease featuring arterial hypotension along with electrolyte abnormalities. We have previously shown that NKCC2 and its disease-causing mutants are subject to regulation by endoplasmic reticulum-associated degradation (ERAD). The aim of the present study was to identify the protein partners specifically involved in ERAD of NKCC2. To this end, we screened a kidney cDNA library through a yeast two-hybrid assay using NKCC2 C terminus as bait. We identified OS9 (amplified in osteosarcomas) as a novel and specific binding partner of NKCC2. Co-immunoprecipitation assays in renal cells revealed that OS9 association involves mainly the immature form of NKCC2. Accordingly, immunocytochemistry analysis showed that NKCC2 and OS9 co-localize at the endoplasmic reticulum. In cells overexpressing OS9, total cellular NKCC2 protein levels were markedly decreased, an effect blocked by the proteasome inhibitor MG132. Pulse-chase and cycloheximide-chase assays demonstrated that the marked reduction in the co-transporter protein levels was essentially due to increased protein degradation of the immature form of NKCC2. Conversely, knockdown of OS9 by small interfering RNA increased NKCC2 expression by increasing the co-transporter stability. Inactivation of the mannose 6-phosphate receptor homology domain of OS9 had no effect on its action on NKCC2. In contrast, mutations of NKCC2 N-glycosylation sites abolished the effects of OS9, indicating that OS9-induced protein degradation is N-glycan-dependent. In summary, our results demonstrate the presence of an OS9-mediated ERAD pathway in renal cells that degrades immature NKCC2 proteins. The identification and selective modulation of ERAD components specific to NKCC2 and its disease-causing mutants might provide novel therapeutic strategies for the treatment of type I Bartter syndrome.

  19. Tax posttranslational modifications and interaction with calreticulin in MT-2 cells and human peripheral blood mononuclear cells of human T cell lymphotropic virus type-I-associated myelopathy/tropical spastic paraparesis patients.

    Science.gov (United States)

    Medina, Fernando; Quintremil, Sebastian; Alberti, Carolina; Barriga, Andres; Cartier, Luis; Puente, Javier; Ramírez, Eugenio; Ferreira, Arturo; Tanaka, Yuetsu; Valenzuela, Maria Antonieta

    2014-04-01

    The human retrovirus human T cell lymphotropic virus type-I (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Axonal degeneration in HAM/TSP patients occurs without neuron infection, with the secreted viral Tax protein proposed to be involved. We previously found that Tax secreted into the culture medium of MT-2 cells (HTLV-1-infected cell line) produced neurite retraction in neuroblastoma cells differentiated to neuronal type. To assess the relevance of Tax posttranslational modifications on this effect, we addressed the question of whether Tax secreted by MT-2 cells and peripheral blood mononuclear cells (PBMCs) of HTLV-1-infected subjects is modified. The interaction of Tax with calreticulin (CRT) that modulates intracellular Tax localization and secretion has been described. We studied Tax localization and modifications in MT-2 cells and its interaction with CRT. Intracellular Tax in MT-2 cells was assessed by flow cytometry, corresponding mainly to a 71-kDa protein followed by western blot. This protein reported as a chimera with gp21 viral protein-confirmed by mass spectrometry-showed no ubiquitination or SUMOylation. The Tax-CRT interaction was determined by confocal microscopy and coimmunoprecipitation. Extracellular Tax from HAM/TSP PBMCs is ubiquitinated according to western blot, and its interaction with CRT was shown by coimmunoprecipitation. A positive correlation between Tax and CRT secretion was observed in HAM/TSP PBMCs and asymptomatic carriers. For both proteins inhibitors and activators of secretion showed secretion through the endoplasmic reticulum-Golgi complex. Tax, present in PBMC culture medium, produced neurite retraction in differentiated neuroblastoma cells. These results suggest that Tax, whether ubiquitinated or not, is active for neurite retraction.

  20. Tax posttranslational modifications and interaction with calreticulin in MT-2 cells and human peripheral blood mononuclear cells of human T cell lymphotropic virus type-I-associated myelopathy/tropical spastic paraparesis patients.

    Science.gov (United States)

    Medina, Fernando; Quintremil, Sebastian; Alberti, Carolina; Barriga, Andres; Cartier, Luis; Puente, Javier; Ramírez, Eugenio; Ferreira, Arturo; Tanaka, Yuetsu; Valenzuela, Maria Antonieta

    2014-04-01

    The human retrovirus human T cell lymphotropic virus type-I (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Axonal degeneration in HAM/TSP patients occurs without neuron infection, with the secreted viral Tax protein proposed to be involved. We previously found that Tax secreted into the culture medium of MT-2 cells (HTLV-1-infected cell line) produced neurite retraction in neuroblastoma cells differentiated to neuronal type. To assess the relevance of Tax posttranslational modifications on this effect, we addressed the question of whether Tax secreted by MT-2 cells and peripheral blood mononuclear cells (PBMCs) of HTLV-1-infected subjects is modified. The interaction of Tax with calreticulin (CRT) that modulates intracellular Tax localization and secretion has been described. We studied Tax localization and modifications in MT-2 cells and its interaction with CRT. Intracellular Tax in MT-2 cells was assessed by flow cytometry, corresponding mainly to a 71-kDa protein followed by western blot. This protein reported as a chimera with gp21 viral protein-confirmed by mass spectrometry-showed no ubiquitination or SUMOylation. The Tax-CRT interaction was determined by confocal microscopy and coimmunoprecipitation. Extracellular Tax from HAM/TSP PBMCs is ubiquitinated according to western blot, and its interaction with CRT was shown by coimmunoprecipitation. A positive correlation between Tax and CRT secretion was observed in HAM/TSP PBMCs and asymptomatic carriers. For both proteins inhibitors and activators of secretion showed secretion through the endoplasmic reticulum-Golgi complex. Tax, present in PBMC culture medium, produced neurite retraction in differentiated neuroblastoma cells. These results suggest that Tax, whether ubiquitinated or not, is active for neurite retraction. PMID:24321043

  1. Study on the interaction between three benzimidazole anthelmintics and eosin Y by high performance liquid chromatography associating with resonance light scattering and its application.

    Science.gov (United States)

    Pan, Ziyu; Peng, Jingdong; Zang, Xu; Lei, Gang; He, Yan; Liu, Di

    2016-07-01

    A novel, highly selective, and sensitive resonance light scattering (RLS) detection approach coupled with high performance liquid chromatography (HPLC) was researched and developed for the synchronous analysis of three kinds of benzimidazole anthelmintics, including mebendazole (MBZ), albendazole (ABZ), and fenbendazole (FBZ) for the first time. In the pH range of 3.5-3.7 Britton-Robinson buffer medium, three kinds of anthelmintics, which were separated by HPLC, reacted with eosin Y (EY) to form 1:1 ion-association complexes, resulting in significantly enhanced RLS signals and the maximum peak located at 335 nm. The enhanced RLS intensity was in proportion to the MBZ, ABZ, and FBZ concentration in the range 0.2-25, 0.2-23, and 0.15-20 μg/mL, respectively. The limit of detection was in the range of 0.064-0.16 μg/mL. In addition, human urine was determined to validate the proposed method by spiked samples and real urine samples. Satisfactory results were obtained by HPLC-RLS method. Graphical Abstract The diagram mechanism of generating resonance between emitted light and scattered light. PMID:27209593

  2. Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) interacts with neurofilament L and inhibits its filament association.

    Science.gov (United States)

    Ozaki, Hana; Katoh, Tsuyoshi; Nakagawa, Ryoko; Ishihara, Yasuhiro; Sueyoshi, Noriyuki; Kameshita, Isamu; Taniguchi, Takanobu; Hirano, Tetsuo; Yamazaki, Takeshi; Ishida, Atsuhiko

    2016-09-01

    Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) is a Ser/Thr phosphatase that belongs to the PPM family. Growing evidence suggests that PPM phosphatases including CaMKP act as a complex with other proteins to regulate cellular functions. In this study, using the two-dimensional far-western blotting technique with digoxigenin-labeled CaMKP as a probe, in conjunction with peptide mass fingerprinting analysis, we identified neurofilament L (NFL) as a CaMKP-binding protein in a Triton-insoluble fraction of rat brain. We confirmed binding of fluorescein-labeled CaMKP (F-CaMKP) to NFL in solution by fluorescence polarization. The analysis showed that the dissociation constant of F-CaMKP for NFL is 73 ± 17 nM (n = 3). Co-immunoprecipitation assay using a cytosolic fraction of NGF-differentiated PC12 cells showed that endogenous CaMKP and NFL form a complex in cells. Furthermore, the effect of CaMKP on self-assembly of NFL was examined. Electron microscopy revealed that CaMKP markedly prevented NFL from forming large filamentous aggregates, suggesting that CaMKP-binding to NFL inhibits its filament association. These findings may provide new insights into a novel mechanism for regulating network formation of neurofilaments during neuronal differentiation. PMID:27369073

  3. Petrogenesis of adakite and high-Nb basalt association in the SW of Sabzevar Zone, NE of Iran: Evidence for slab melt-mantle interaction

    Science.gov (United States)

    Mazhari, Seyed Ali

    2016-04-01

    Adakitic rocks appear in close association with high Nb basaltic (HNB) rocks in the SW of Sabzevar ophiolitic belt. Adakites are calc-alkaline and include trachy-andesite, teachy-dacite and dacite. These rocks are rich in Na2O, Al2O3 and Sr and show depletion in MgO, Y and Yb. Adakitic samples are defined by high Sr/Y (88-128) and La/Yb (20-45) ratios; as well as a lack of Eu anomaly (Eu/Eu∗ = 0.92-0.99) in REE patterns. Geochemical composition indicates that adakites were generated from slab melting in a high pressure-high heat flow subducting setting. Different adakitic rocks have been formed by various slab partial melting degrees and reaction of adakitic magma with heterogeneous mantle wedge rocks. HNB rocks are alkaline, nepheline normative and sodic (Na2O/K2O = 2.7-3.4) with high concentration of Al2O3, TiO2, MgO, P2O5, LILE and HFSE, especially Nb (30-56 ppm). These basalts show fractionated REE patterns with elevated LREE/HREE (LaN/YbN = 20-25) and trace elements contents suggest their generation by low partial melting degrees (<2%) from garnet-peridotite origin which have already metasomatized by adakitic melts.

  4. PARP16/ARTD15 is a novel endoplasmic-reticulum-associated mono-ADP-ribosyltransferase that interacts with, and modifies karyopherin-ß1.

    Directory of Open Access Journals (Sweden)

    Simone Di Paola

    Full Text Available BACKGROUND: Protein mono-ADP-ribosylation is a reversible post-translational modification that modulates the function of target proteins. The enzymes that catalyze this reaction in mammalian cells are either bacterial pathogenic toxins or endogenous cellular ADP-ribosyltransferases. The latter include members of three different families of proteins: the well characterized arginine-specific ecto-enzymes ARTCs, two sirtuins and, more recently, novel members of the poly(ADP-ribose polymerase (PARP/ARTD family that have been suggested to act as cellular mono-ADP-ribosyltransferases. Here, we report on the characterisation of human ARTD15, the only known ARTD family member with a putative C-terminal transmembrane domain. METHODOLOGY/PRINCIPAL FINDINGS: Immunofluorescence and electron microscopy were performed to characterise the sub-cellular localisation of ARTD15, which was found to be associated with membranes of the nuclear envelope and endoplasmic reticulum. The orientation of ARTD15 was determined using protease protection assay, and is shown to be a tail-anchored protein with a cytosolic catalytic domain. Importantly, by combining immunoprecipitation with mass spectrometry and using cell lysates from cells over-expressing FLAG-ARTD15, we have identified karyopherin-ß1, a component of the nuclear trafficking machinery, as a molecular partner of ARTD15. Finally, we demonstrate that ARTD15 is a mono-ADP-ribosyltransferase able to induce the ADP-ribosylation of karyopherin-ß1, thus defining the first substrate for this enzyme. CONCLUSIONS/SIGNIFICANCE: Our data reveal that ARTD15 is a novel ADP-ribosyltransferase enzyme with a new intracellular location. Finally, the identification of karyopherin-ß1 as a target of ARTD15-mediated ADP-ribosylation, hints at a novel regulatory mechanism of karyopherin-ß1 functions.

  5. Human Dynactin-Associated Protein Transforms NIH3T3 Cells to Generate Highly Vascularized Tumors with Weak Cell-Cell Interaction.

    Directory of Open Access Journals (Sweden)

    Tatsuki Kunoh

    Full Text Available Human dynactin-associated protein (dynAP is a transmembrane protein that promotes AktSer473 phosphorylation. Here, we report the oncogenic properties of dynAP. In contrast to control NIH3T3 cells expressing LacZ (NIH3T3LacZ, NIH3T3dynAP cells vigorously formed foci in two-dimensional culture, colonies on soft agar, and spheroids in anchorage-deficient three-dimensional culture. NIH3T3dynAP cells injected into nude mice produced tumors with abundant blood vessels and weak cell-cell contacts. Expression of dynAP elevated the level of rictor (an essential subunit of mTORC2 and promoted phosphorylation of FOXO3aSer253. FOXO3a is a transcriptional factor that stimulates expression of pro-apoptotic genes and phosphorylation of FOXO3a abrogates its function, resulting in promoted cell survival. Knockdown of rictor in NIH3T3dynAP cells reduced AktSer473 phosphorylation and formation of foci, colony in soft agar and spheroid, indicating that dynAP-induced activation of the mTORC2/AktSer473 pathway for cell survival contributes to cell transformation. E-cadherin and its mRNA were markedly reduced upon expression of dynAP, giving rise to cells with higher motility, which may be responsible for the weak cell-cell adhesion in tumors. Thus, dynAP could be a new oncoprotein and a target for cancer therapy.

  6. Regulation of T-cell interaction with fibronectin by transforming growth factor-beta is associated with altered Pyk2 phosphorylation.

    Science.gov (United States)

    Brill, A; Franitza, S; Lider, O; Hershkoviz, R

    2001-10-01

    Although the involvement of transforming growth factor-beta (TGF-beta) in inflammatory reactions has been extensively studied, its mode of action in the context of the extracellular matrix (ECM) is still not fully understood. We undertook this study in an attempt to reveal the putative roles of TGF-beta in T-cell adhesion and migration. We found that a 60-min treatment of T cells with TGF-beta regulates T-cell adhesion to fibronectin (FN), a prototype cell adhesion protein of the ECM, depending on the presence of other activators. At 5 pg/ml to 1 ng/ml, TGF-beta alone induced T-cell adhesion to FN in an integrin alpha4/beta1- and integrin alpha5/beta1-dependent manner. TGF-beta also attenuated T-cell migration on the stromal cell-derived factor (SDF)-1alpha gradients. These effects of TGF-beta were not accompanied by alteration in the expression of very-late activation antigen type 4 (VLA-4) and VLA-5, nor were they mediated by the cyclo-oxygenase pathway. The cellular mechanism underlying the adhesion-regulating activities of TGF-beta involves adhesion-associated cytoskeletal elements. TGF-beta induced the phosphorylation of focal adhesion kinase Pyk2, but not extracellular signal-regulated kinase (ERK), and this effect was markedly increased in the presence of immobilized FN, suggesting a collaborative role for FN-specific integrins. Indeed, TGF-beta-induced Pyk2 phosphorylation was inhibited by monoclonal antibodies against VLA-4, VLA-5 and CD29. Thus, TGF-beta, which may appear at extravascular sites during inflammation, affects the adhesion of T cells to ECM glycoproteins and their migration by its ability to differentially induce or inhibit the phosphorylation of Pyk2. PMID:11683954

  7. Interaction of Hydrophobically Associating Polyacrylamide with Gemini Surfactant%疏水缔合聚丙烯酰胺与双子表面活性剂的相互作用

    Institute of Scientific and Technical Information of China (English)

    陈洪; 李二晓; 叶仲斌; 韩利娟; 罗平亚

    2011-01-01

    A fatty acid disulfonate anionic gemini surfactant was prepared and the structure of the surfactant was characterized by 1H-NMR. Hydrophobically associating polyacrylamide was prepared according to a procedure from literature. The interaction between the hydrophobically associating polyacrylamide (HAPAM) and the anionic gemini surfactant was studied by surface/interfacial tension,apparent viscosity, and atomic force microscopy (AFM). Experimental results show that HAPAM can form a network structure in the aqueous solution by self assembly. Mixed micelles are formed by the interaction of gemini surfactant micelles and the hydrophobic microdomain of the hydrophobically associating polyacrylamide in aqueous solution, which plays a remarkable role in the surfactant and polymer assembly. Mixed micelles can enhance the inter- or intra-molecular association between the polymer molecules and the surfactant, which increases the strength of the network formed by the hydrophobically associating polyacrylamide. The apparent viscosity of the solution increased by the addition of the gemini surfactant. When the addition of the gemini surfactant exceeded a certain amount, the association between the hydrophobic groups of the polymer decreased and the network formed by hydrophobically associating interaction was weakened by the surfactant micelles, which led to a decrease in solution viscosity. The polymer also largely influenced the interfacial properties of the gemini surfactant, especially the dynamical interracial tension. A high polymer concentration led to an increase in the time required to reach equilibrium.%制备了一种脂肪酸酯双磺酸盐型双子表面活性剂,利用粘度法、界面张力法和原子力显微镜研究了疏水缔合聚丙烯酰胺与双子表面活性剂在溶液中的相互作用.实验结果表明:疏水缔合聚丙烯酰胺在溶液中能够通过自组装形成疏水微区并发展成网络结构,疏水微区与表面活性剂在溶液中

  8. Conformational Changes and Association of Membrane-Interacting Peptides in Myelin Membrane Models: A Case of the C-Terminal Peptide of Proteolipid Protein and the Antimicrobial Peptide Melittin.

    Science.gov (United States)

    Appadu, Ashtina; Jelokhani-Niaraki, Masoud; DeBruin, Lillian

    2015-11-25

    Model membranes composed of various lipid mixtures can segregate into liquid-ordered (Lo) and liquid-disordered (Ld) phases. In this study, lipid vesicles composed of mainly Lo or Ld phases as well as complex lipid systems representing the cytosolic leaflet of the myelin membrane were characterized by fluorescence resonance energy transfer with a donor/acceptor pair that preferentially partitioned into Lo or Ld phases, respectively. The fluidity of the lipid systems containing >30% cholesterol was modulated in the presence of the amphipathic peptide melittin. With all the studied lipid systems, melittin attained an α-helical conformation as determined by CD spectroscopy and attained varying degrees of membrane association and penetration as determined by intrinsic Trp fluorescence. The other protein domain utilized was a putative amphipathic helical peptide derived from the cytosolic C-terminal sequence of proteolipid protein (PLP) which is the most abundant protein in the myelin membrane. The C-terminal PLP peptide transitioned from a random coil to an α-helix in the presence of trifluoroethanol. Upon interacting with each of lipid vesicle system, the PLP peptide also folded into a helix; however, at high concentrations of the peptide with fluid lipid systems, associated helices transmuted into a β-sheet conformer. The membrane-associated aggregation of the cytosolic C-termini could be a mechanism by which the transmembrane PLP multimerizes in the myelin membrane. PMID:26561987

  9. Mutagenesis of the Agrobacterium VirE2 single-stranded DNA-binding protein identifies regions required for self-association and interaction with VirE1 and a permissive site for hybrid protein construction.

    Science.gov (United States)

    Zhou, X R; Christie, P J

    1999-07-01

    The VirE2 single-stranded DNA-binding protein (SSB) of Agrobacterium tumefaciens is required for delivery of T-DNA to the nuclei of susceptible plant cells. By yeast two-hybrid and immunoprecipitation analyses, VirE2 was shown to self-associate and to interact with VirE1. VirE2 mutants with small deletions or insertions of a 31-residue oligopeptide (i31) at the N or C terminus or with an i31 peptide insertion at Leu236 retained the capacity to form homomultimers. By contrast, VirE2 mutants with modifications outside a central region located between residues 320 and 390 retained the capacity to interact with VirE1. These findings suggest the tertiary structure of VirE2 is important for homomultimer formation whereas a central domain mediates formation of a complex with VirE1. The capacity of VirE2 mutants to interact with full-length VirE2 in the yeast Saccharomyces cerevisiae correlated with the abundance of the mutant proteins in A. tumefaciens, suggesting that VirE2 is stabilized by homomultimerization in the bacterium. We further characterized the promoter and N- and C-terminal sequence requirements for synthesis of functional VirE2. A PvirB::virE2 construct yielded functional VirE2 protein as defined by complementation of a virE2 null mutation. By contrast, PvirE or Plac promoter constructs yielded functional VirE2 only if virE1 was coexpressed with virE2. Deletion of 10 or 9 residues from the N or C terminus of VirE2, respectively, or addition of heterologous peptides or proteins to either terminus resulted in a loss of protein function. However, an i31 peptide insertion at Tyr39 had no effect on protein function as defined by the capacity of the mutant protein to (i) interact with native VirE2, (ii) interact with VirE1, (iii) accumulate at abundant levels in A. tumefaciens, and (iv) restore wild-type virulence to a virE2 null mutant. We propose that Tyr39 of VirE2 corresponds to a permissive site for insertion of heterologous peptides or proteins of interest

  10. Strongly interacting new physics

    International Nuclear Information System (INIS)

    In this talk. I will describe two aspects of the breaking of electroweak symmetry by new, strong interactions. First I will review the model independent approach to the low energy form of such new interactions emdash the electroweak chiral Lagrangian. Next I will summarize some of the phenomenological challenges facing technicolor theories, in particular those associated with the generation of the top and bottom masses. copyright 1997 American Institute of Physics

  11. Detecção de risco de interações entre fármacos antidepressivos e associados prescritos a pacientes adultos Interaction risk detection between antidepressant and associated drugs prescribed for adult patients

    Directory of Open Access Journals (Sweden)

    Kassia Fernanda Campigotto

    2008-01-01

    Full Text Available CONTEXTO: O uso de fármacos combinados para o tratamento de patologias diversas em psiquiatria tem aumentado progressivamente. Os antidepressivos estão envolvidos em diversas interações farmacológicas clinicamente importantes. OBJETIVO: Detectar risco de interações entre fármacos antidepressivos e associados prescritos a pacientes adultos. MÉTODOS: Pesquisa retrospectiva e descritiva foi desenvolvida em uma farmácia magistral da cidade de Cascavel, Paraná. Os dados foram coletados de 151 receituários médicos de pacientes adultos (19 anos ou mais, envolvendo fármacos antidepressivos e associados entre outubro e novembro de 2005. O estudo limitou-se às variáveis registradas no receituário médico (sexo, idade, fármaco antidepressivo e associado prescrito. RESULTADOS: A categoria de 31 a 40 anos de idade foi a mais freqüente (32,46% e o sexo foi o feminino (64,90%. Os fármacos antidepressivos tricíclicos (ADT e associados apresentaram um total de oito episódios de interações relativos ao grau de severidade, sendo quatro de grau moderado e quatro menor. Em relação aos fármacos antidepressivos inibidores seletivos da recaptura de serotonina (ISRS e associados, o risco de ocorrência foi de 16 casos; quatro de severidade menor, dez moderada e dois maior. CONCLUSÃO: Os dados mostram que os pacientes com prescrição de fármacos ISRS e associados possuíam mais risco de interações de maior severidade, totalizando o dobro de interações em relação aos ADTs.BACKGROUND: The combination of drugs for the treatment of psychiatric disorders has become a relatively frequent practice. The antidepressants are involved in several clinically important pharmacological interactions. OBJECTIVES: To detect the risk of interactions between antidepressants and associated drugs prescribed for adults patients. METHODS: Data on 151 medical prescriptions of antidepressants and other psychiatric drugs were retrospectively assessed at a

  12. Search for associated production of a Z boson with a single top quark and for tZ flavour-changing interactions in pp collisions at $\\sqrt{s}=8~\\mathrm{TeV}$

    CERN Document Server

    CMS Collaboration

    2016-01-01

    A search for the production of a single top quark in association with a Z boson is presented, both to identify the expected standard model (SM) process and to search for flavour changing neutral current (FCNC) interactions. The data sample corresponds to an integrated luminosity of $19.7~\\mathrm{fb}^{-1}$ recorded by the CMS experiment at the LHC in proton-proton collisions at $\\sqrt{s} = 8~\\mathrm{TeV}$. Final states with three leptons, electrons or muons, and at least one jet are investigated. A moderate excess of events compatible with SM tZq production is observed, and the corresponding cross section is measured to be $\\sigma ({\\rm tZq \\rightarrow \\ell} \

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

    Directory of Open Access Journals (Sweden)

    Qianqian Chen

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

  14. Floor interaction

    DEFF Research Database (Denmark)

    Petersen, Marianne Graves; Krogh, Peter; Ludvigsen, Martin;

    2005-01-01

    Within architecture, there is a long tradition of careful design of floors. The design has been concerned with both decorating floors and designing floors to carry information. Ubiquitous computing technology offers new opportunities for designing interactive floors. This paper presents three...... different interactive floor concepts. Through an urban perspective it draws upon the experiences of floors in architecture, and provides a set of design issues for designing interactive floors....

  15. Dynamical behaviour of two interacting dipoles

    International Nuclear Information System (INIS)

    We study the deterministic spin dynamic of two interacting magnetic moments with dipolar interaction under the presence of an applied magnetic field, by using the Landau-Lifshitz equation with damping term. Due to the two kinds of interactions, two time scales appear, a long time scale associated with the dipolar interaction and a short time scale associated with the Zeeman interaction. We found that the total magnetization is not conserved and it strongly depends of the control parameters.

  16. Playful Interaction

    DEFF Research Database (Denmark)

    2003-01-01

    The video Playful Interaction describes a future architectural office, and envisions ideas and concepts for playful interactions between people, materials and appliances in a pervasive and augmented working environment. The video both describes existing developments, technologies and designs...... as well as ideas not yet implemented such as playful modes of interaction with an augmented ball. Playful Interaction has been used as a hybrid of a vision video and a video prototype (1). Externally the video has been used to visualising our new ideas, and internally the video has also worked to inspire...... and encourage dialogue between the different disciplines involved in the EU funded, ‘Disappearing Computer’ project WorkSPACE....

  17. Association of progerin-interactive partner proteins with lamina proteins:Mel18 is associated with emerin in HGPS%Progerin作用的伴侣蛋白和核纤层蛋白问的相互作用:在早老症中Mel18与emerin的相互作用

    Institute of Scientific and Technical Information of China (English)

    Wei-na JU; W. Ted BROWN; Nanbert ZHONG

    2009-01-01

    Objective :The Hutchinson-Gilford progeria syndrome (HGPS or progeria) is a childhood disorder with features of premature aging and is caused by mutations in the lamin A gene resulting in the production of an abnormal protein, termed progerin. To investigate the underlying pathogenic mecha-nism, we studied the nuclear co-localization and association of progerin interactive partner proteins (PIPPs) with lamina pr