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Sample records for glial-neuronal interactions contribute

  1. Where and how could intentional programs be generated in the brain? A hypothetical model based on glial-neuronal interactions.

    PubMed

    Mitterauer, B J

    2007-03-01

    Based on glial-neuronal interaction a formalism (negative language) for the generation of intentional programs is proposed. An intentional program generates a specific multirelational structure in an inner or outer appropriate environment according to the principle of feasibility. After description of the glial spatio-temporal boundary-setting function in its interaction with the neuronal system, it is hypothesized that intentional programs may be generated in glial networks (syncytia) in line with the formalism of negative language. Gap junctions are interpreted as multirelational negation operators, generating cycles in a permutation system. These cycles could represent intentional programs that can either be realized or not in neuronal networks embodying a permutation system. The feasibility of these intentional programs is essentially dependent on appropriate environmental information. Since the realization of intentional programs in neuronal networks allows high degrees of freedom, the problem of free will is tackled, as well. Free will is defined as the subjective freedom to choose between the inner determination of intentional programs and the overdetermination of their feasibility in an appropriate environment. Finally, the possible implementation of the proposed brain model in robot brains is briefly discussed.

  2. Modulating the Delicate Glial-Neuronal Interactions in Neuropathic Pain: Promises and Potential Caveats

    PubMed Central

    Tiwari, Vinod; Guan, Yun; Raja, Srinivasa N.

    2014-01-01

    During neuropathic pain, glial cells (mainly astrocytes and microglia) become activated and initiate a series of signaling cascades that modulate pain processing at both spinal and supraspinal levels. It has been generally accepted that glial cell activation contributes to neuropathic pain because glia release proinflammatory cytokines, chemokines, and factors such as calcitonin gene-related peptide, substance P, and glutamate, which are known to facilitate pain signaling. However, recent research has shown that activation of glia also leads to some beneficial outcomes. Glia release anti-inflammatory factors that protect against neurotoxicity and restore normal pain. Accordingly, use of glial inhibitors might compromise the protective functions of glia in addition to suppressing their detrimental effects. With a better understanding of how different conditions affect glial cell activation, we may be able to promote the protective function of glia and pave the way for future development of novel, safe, and effective treatments of neuropathic pain. PMID:24820245

  3. Region- and age-dependent alterations of glial-neuronal metabolic interactions correlate with CNS pathology in a mouse model of globoid cell leukodystrophy.

    PubMed

    Meisingset, Tore Wergeland; Ricca, Alessandra; Neri, Margherita; Sonnewald, Ursula; Gritti, Angela

    2013-07-01

    Globoid cell leukodystrophy (GLD) or Krabbe disease is a lysosomal storage disorder caused by genetic defects in the expression and activity of galactosylceramidase, a key enzyme in the catabolism of myelin-enriched sphingolipids. While there are several histologic, biochemical, and functional studies on GLD, correlations between morphologic and biochemical alterations in central nervous system (CNS) tissues during disease progression are lacking. Here, we combined immunohistochemistry and metabolic analysis using (1)H and (13)C magnetic resonance (MR) spectra of spinal cord, cerebellum, and forebrain to investigate glial-neuronal metabolic interactions and dysfunction in a GLD murine model that recapitulates the human pathology. In order to assess the temporal- and region-dependent disease progression and the potential metabolic correlates, we investigated CNS tissues at mildly symptomatic and fully symptomatic stages of the disease. When compared with age-matched controls, GLD mice showed glucose hypometabolism, alterations in neurotransmitter content, N-acetylaspartate, N-acetylaspartylglutamate, and osmolytes levels. Notably, age- and region-dependent patterns of metabolic disturbances were in close agreement with the progression of astrogliosis, microglia activation, apoptosis, and neurodegeneration. We suggest that MR spectroscopy could be used in vivo to monitor disease progression, as well as ex vivo and in vivo to provide criteria for the outcome of experimental therapies.

  4. Contribution of Hydrophobic Interactions to Protein Stability

    PubMed Central

    Pace, C. Nick; Fu, Hailong; Fryar, Katrina Lee; Landua, John; Trevino, Saul R.; Shirley, Bret A.; Hendricks, Marsha McNutt; Iimura, Satoshi; Gajiwala, Ketan; Scholtz, J. Martin; Grimsley, Gerald R.

    2011-01-01

    Our goal was to gain a better understanding of the contribution of hydrophobic interactions to protein stability. We measured the change in conformational stability, Δ(ΔG), for hydrophobic mutants of four proteins: villin head piece subdomain (VHP) with 36 residues, a surface protein from Borrelia burgdorferi (VlsE) with 341 residues, and two proteins previously studied in our laboratory, ribonucleases Sa and T1. We compare our results with previous studies and reach the following conclusions. 1. Hydrophobic interactions contribute less to the stability of a small protein, VHP (0.6 ± 0.3 kcal/mole per –CH2– group), than to the stability of a large protein, VlsE (1.6 ± 0.3 kcal/mol per –CH2– group). 2. Hydrophobic interactions make the major contribution to the stability of VHP (40 kcal/mol) and the major contributors are (in kcal/mol): Phe 18 (3.9), Met 13 (3.1), Phe 7 (2.9), Phe 11 (2.7), and Leu 21 (2.7). 3. Based on Δ(ΔG) values for 148 hydrophobic mutants in 13 proteins, burying a –CH2– group on folding contributes, on average, 1.1 ± 0.5 kcal/mol to protein stability. 4. The experimental Δ(ΔG) values for aliphatic side chains (Ala, Val, Ile, and Leu) are in good agreement with their ΔGtr values from water to cyclohexane. 5. For 22 proteins with 36 to 534 residues, hydrophobic interactions contribute 60 ± 4% and hydrogen bonds 40 ± 4% to protein stability. 6. Conformational entropy contributes about 2.4 kcal/mol per residue to protein instability. The globular conformation of proteins is stabilized predominately by hydrophobic interactions. PMID:21377472

  5. Spinal 5-HT(3) receptor activation induces behavioral hypersensitivity via a neuronal-glial-neuronal signaling cascade.

    PubMed

    Gu, Ming; Miyoshi, Kan; Dubner, Ronald; Guo, Wei; Zou, Shiping; Ren, Ke; Noguchi, Koichi; Wei, Feng

    2011-09-07

    Recent studies indicate that the descending serotonin (5-HT) system from the rostral ventromedial medulla (RVM) in the brainstem and the 5-HT(3) receptor subtype in the spinal dorsal horn are involved in enhanced descending pain facilitation after tissue and nerve injury. However, the mechanisms underlying the activation of the 5-HT(3) receptor and its contribution to facilitation of pain remain unclear. In the present study, activation of spinal 5-HT(3) receptor by intrathecal injection of a selective 5-HT(3) receptor agonist, SR57227, induced spinal glial hyperactivity, neuronal hyperexcitability, and pain hypersensitivity in rats. We found that there was neuron-to-microglia signaling via chemokine fractalkine, microglia to astrocyte signaling via the cytokine IL-18, astrocyte to neuronal signaling by IL-1β, and enhanced activation of GluN (NMDA) receptors in the spinal dorsal horn. In addition, exogenous brain-derived neurotrophic factor-induced descending pain facilitation was accompanied by upregulation of CD11b and GFAP expression in the spinal dorsal horn after microinjection in the RVM, and these events were significantly prevented by functional blockade of spinal 5-HT(3) receptors. Enhanced expression of spinal CD11b and GFAP after hindpaw inflammation was also attenuated by molecular depletion of the descending 5-HT system by intra-RVM Tph-2 shRNA interference. Thus, these findings offer new insights into the cellular and molecular mechanisms at the spinal level responsible for descending 5-HT-mediated pain facilitation during the development of persistent pain after tissue and nerve injury. New pain therapies should focus on prime targets of descending facilitation-induced glial involvement, and in particular the blocking of intercellular signaling transduction between neuron and glia.

  6. Spinal 5-HT3 receptor activation induces behavioral hypersensitivity via a neuronal-glial-neuronal signaling cascade

    PubMed Central

    Gu, Ming; Miyoshi, Kan; Dubner, Ronald; Guo, Wei; Zou, Shiping; Ren, Ke; Noguchi, Koichi; Wei, Feng

    2011-01-01

    Recent studies indicate that the descending serotonin (5-HT) system from the rostral ventromedial medulla (RVM) in brainstem and the 5-HT3 receptor subtype in the spinal dorsal horn are involved in enhanced descending pain facilitation after tissue and nerve injury. However, the mechanisms underlying the activation of the 5-HT3 receptor and its contribution to facilitation of pain remain unclear. In the present study, activation of spinal 5-HT3 receptor by intrathecal injection of a selective 5-HT3 receptor agonist SR 57227 induced spinal glial hyperactivity, neuronal hyperexcitability and pain hypersensitivity in rats. We found that there was neuron-to-microglia signaling via chemokine fractalkine, microglia to astrocyte signaling via cytokine IL-18, astrocyte to neuronal signaling by IL-1β, and enhanced activation of GluN (NMDA) receptors in the spinal dorsal horn. In addition, exogenous BDNF-induced descending pain facilitation was accompanied with up-regulation of CD11b and GFAP expression in the spinal dorsal horn after microinjection in the RVM, which were significantly prevented by functional blockade of spinal 5-HT3 receptors. Enhanced expression of spinal CD11b and GFAP after hindpaw inflammation was also attenuated by molecular depletion of the descending 5-HT system by intra-RVM Tph-2 shRNA interference. Thus, these findings offer new insights into the cellular and molecular mechanisms at the spinal level responsible for descending 5-HT-mediated pain facilitation during the development of persistent pain after tissue and nerve injury. New pain therapies should focus on prime targets of descending facilitation-induced glial involvement, and in particular the blocking of intercellular signaling transduction between neuron and glia. PMID:21900561

  7. Weak-interaction contributions to hyperfine splitting and Lamb shift

    SciTech Connect

    Eides, M.I.

    1996-05-01

    Weak-interaction contributions to hyperfine splitting and the Lamb shift in hydrogen and muonium are discussed. The problem of sign of the weak-interaction contribution to HFS is clarified, and simple physical arguments that make this sign evident are presented. It is shown that weak-interaction contributions to HFS in hydrogen and muonium have opposite signs. A weak-interaction contribution to the Lamb shift is obtained. {copyright} {ital 1996 The American Physical Society.}

  8. Contribution of cation-π interactions in iminium catalysis.

    PubMed

    Mori, Yukie; Yamada, Shinji

    2012-02-21

    Ab initio calculations were carried out for a benzyl-substituted iminium cation derived from (E)-crotonaldehyde and a chiral imidazolidinone that was developed as an organocatalyst by MacMillan et al. At the MP2 level of theory it is predicted that the phenyl group is close to the iminium moiety in the most stable conformer, suggesting that the cation-π interaction contributes to the stabilization of this conformer. Energy decomposition analyses on model systems indicate that the electrostatic and polarization terms make significant contribution to the attractive interactions between the benzene ring and the iminium cation.

  9. A Contribution to the Theory of Preferential Interaction Coefficients

    PubMed Central

    Schurr, J. Michael; Rangel, David P.; Aragon, Sergio R.

    2005-01-01

    A simple and complete derivation of the relation between concentration-based preferential interaction coefficients and integrals over the relevant pair correlation functions is presented for the first time. Certain omissions from the original treatment of pair correlation functions in multicomponent thermodynamics are also addressed. Connections between these concentration-based quantities and the more common molality-based preferential interaction coefficients are also derived. The pair correlation functions and preferential interaction coefficients of both solvent (water) and cosolvent (osmolyte) in the neighborhood of a macromolecule contain contributions from short-range repulsions and generic long-range attractions originating from the macromolecule, as well as from osmolyte-solvent exchange reactions beyond the macromolecular surface. These contributions are evaluated via a heuristic analysis that leads to simple insightful expressions for the preferential interaction coefficients in terms of the volumes excluded to the centers of the water and osmolyte molecules and a sum over the contributions of exchanging sites in the surrounding solution. The preferential interaction coefficients are predicted to exhibit the experimentally observed dependence on osmolyte concentration. Molality-based preferential interaction coefficients that were reported for seven different osmolytes interacting with bovine serum albumin are analyzed using the this formulation together with geometrical parameters reckoned from the crystal structure of human serum albumin. In all cases, the excluded volume contribution, which is the volume excluded to osmolyte centers minus that excluded to water centers in units of \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}{\\bar {V}}_{1},\\end

  10. Vibrational solvatochromism. III. Rigorous treatment of the dispersion interaction contribution

    NASA Astrophysics Data System (ADS)

    Błasiak, Bartosz; Cho, Minhaeng

    2015-10-01

    A rigorous first principles theory of vibrational solvatochromism including the intermolecular dispersion interaction, which is based on the effective fragment potential method, is developed. The present theory is an extended version of our previous vibrational solvatochromism model that took into account the Coulomb, exchange-repulsion, and induction interactions. We show that the frequency shifts of the amide I mode of N-methylacetamide in H2O and CDCl3, when combined with molecular dynamics simulations, can be quantitatively reproduced by the theory, which indicates that the dispersion interaction contribution to the vibrational frequency shift is not always negligibly small. Nonetheless, the reason that the purely Coulombic interaction model for vibrational solvatochromism works well for describing amide I mode frequency shifts in polar solvents is because the electrostatic contribution is strong and highly sensitive to the relative orientation of surrounding solvent molecules, which is in stark contrast with polarization, dispersion, and exchange-repulsion contributions. It is believed that the theory presented and discussed here will be of great use in quantitatively describing vibrational solvatochromism and electrochromism of infrared probes in not just polar solvent environments but also in biopolymers such as proteins.

  11. Vibrational solvatochromism. III. Rigorous treatment of the dispersion interaction contribution.

    PubMed

    Błasiak, Bartosz; Cho, Minhaeng

    2015-10-28

    A rigorous first principles theory of vibrational solvatochromism including the intermolecular dispersion interaction, which is based on the effective fragment potential method, is developed. The present theory is an extended version of our previous vibrational solvatochromism model that took into account the Coulomb, exchange-repulsion, and induction interactions. We show that the frequency shifts of the amide I mode of N-methylacetamide in H2O and CDCl3, when combined with molecular dynamics simulations, can be quantitatively reproduced by the theory, which indicates that the dispersion interaction contribution to the vibrational frequency shift is not always negligibly small. Nonetheless, the reason that the purely Coulombic interaction model for vibrational solvatochromism works well for describing amide I mode frequency shifts in polar solvents is because the electrostatic contribution is strong and highly sensitive to the relative orientation of surrounding solvent molecules, which is in stark contrast with polarization, dispersion, and exchange-repulsion contributions. It is believed that the theory presented and discussed here will be of great use in quantitatively describing vibrational solvatochromism and electrochromism of infrared probes in not just polar solvent environments but also in biopolymers such as proteins.

  12. Magnetic interactions in strongly correlated systems: Spin and orbital contributions

    SciTech Connect

    Secchi, A.; Lichtenstein, A.I.; Katsnelson, M.I.

    2015-09-15

    We present a technique to map an electronic model with local interactions (a generalized multi-orbital Hubbard model) onto an effective model of interacting classical spins, by requiring that the thermodynamic potentials associated to spin rotations in the two systems are equivalent up to second order in the rotation angles, when the electronic system is in a symmetry-broken phase. This allows to determine the parameters of relativistic and non-relativistic magnetic interactions in the effective spin model in terms of equilibrium Green’s functions of the electronic model. The Hamiltonian of the electronic system includes, in addition to the non-relativistic part, relativistic single-particle terms such as the Zeeman coupling to an external magnetic field, spin–orbit coupling, and arbitrary magnetic anisotropies; the orbital degrees of freedom of the electrons are explicitly taken into account. We determine the complete relativistic exchange tensors, accounting for anisotropic exchange, Dzyaloshinskii–Moriya interactions, as well as additional non-diagonal symmetric terms (which may include dipole–dipole interaction). The expressions of all these magnetic interactions are determined in a unified framework, including previously disregarded features such as the vertices of two-particle Green’s functions and non-local self-energies. We do not assume any smallness in spin–orbit coupling, so our treatment is in this sense exact. Finally, we show how to distinguish and address separately the spin, orbital and spin–orbital contributions to magnetism, providing expressions that can be computed within a tight-binding Dynamical Mean Field Theory.

  13. Neurobiological Mechanisms Contributing to Alcohol-Stress-Anxiety Interactions

    PubMed Central

    Silberman, Yuval; Bajo, Michal; Chappell, Ann M.; Christian, Daniel T.; Cruz, Maureen; Diaz, Marvin R.; Kash, Thomas; Lack, Anna K.; Messing, Robert O.; Siggins, George R.; Winder, Danny; Roberto, Marisa; McCool, Brian A.; Weiner, Jeff L.

    2009-01-01

    This article summarizes the proceedings of a symposium that was presented at a conference entitled “Alcoholism and Stress: A Framework for Future Treatment Strategies”. The conference was held in Volterra, Italy on May 6–9, 2008 and this symposium was chaired by Jeff L. Weiner. The overall goal of this session was to review recent findings that may shed new light on the neurobiological mechanisms that underlie the complex relationships between stress, anxiety, and alcoholism. Dr. Danny Winder described a novel interaction between D1 receptor activation and the CRF system that leads to an increase in glutamatergic synaptic transmission in the bed nucleus of the stria terminalis. Dr. Marisa Roberto presented recent data describing how PKCε, ethanol, and CRF interact to alter GABAergic inhibition in the central nucleus of the amygdala. Dr. Jeff Weiner presented recent advances in our understanding of inhibitory circuitry within the basolateral amygdala and how acute ethanol exposure enhances GABAergic inhibition in these pathways. Finally, Dr. Brian McCool discussed recent findings on complementary glutamatergic and GABAergic adaptations to chronic ethanol exposure and withdrawal in the basolateral amygdala. Collectively, these investigators have identified novel mechanisms through which neurotransmitter and neuropeptide systems interact to modulate synaptic activity in stress and anxiety circuits. Their studies have also begun to describe how acute and chronic ethanol exposure influence excitatory and inhibitory synaptic communication in these pathways. These findings point toward a number of novel neurobiological targets that may prove useful for the development of more effective treatment strategies for alcohol use disorders. PMID:19913194

  14. Neurobiological mechanisms contributing to alcohol-stress-anxiety interactions.

    PubMed

    Silberman, Yuval; Bajo, Michal; Chappell, Ann M; Christian, Daniel T; Cruz, Maureen; Diaz, Marvin R; Kash, Thomas; Lack, Anna K; Messing, Robert O; Siggins, George R; Winder, Danny; Roberto, Marisa; McCool, Brian A; Weiner, Jeff L

    2009-11-01

    This article summarizes the proceedings of a symposium that was presented at a conference entitled "Alcoholism and Stress: A Framework for Future Treatment Strategies." The conference was held in Volterra, Italy on May 6-9, 2008 and this symposium was chaired by Jeff L. Weiner. The overall goal of this session was to review recent findings that may shed new light on the neurobiological mechanisms that underlie the complex relationships between stress, anxiety, and alcoholism. Dr. Danny Winder described a novel interaction between D1 receptor activation and the corticotrophin-releasing factor (CRF) system that leads to an increase in glutamatergic synaptic transmission in the bed nucleus of the stria terminalis. Dr. Marisa Roberto presented recent data describing how protein kinase C epsilon, ethanol, and CRF interact to alter GABAergic inhibition in the central nucleus of the amygdala. Dr. Jeff Weiner presented recent advances in our understanding of inhibitory circuitry within the basolateral amygdala (BLA) and how acute ethanol exposure enhances GABAergic inhibition in these pathways. Finally, Dr. Brian McCool discussed recent findings on complementary glutamatergic and GABAergic adaptations to chronic ethanol exposure and withdrawal in the BLA. Collectively, these investigators have identified novel mechanisms through which neurotransmitter and neuropeptide systems interact to modulate synaptic activity in stress and anxiety circuits. Their studies have also begun to describe how acute and chronic ethanol exposure influence excitatory and inhibitory synaptic communication in these pathways. These findings point toward a number of novel neurobiological targets that may prove useful for the development of more effective treatment strategies for alcohol use disorders.

  15. Interactive Contributions of Cumulative Peer Stress and Executive Function Deficits to Depression in Early Adolescence

    ERIC Educational Resources Information Center

    Agoston, Anna M.; Rudolph, Karen D.

    2016-01-01

    Exposure to peer stress contributes to adolescent depression, yet not all youth experience these effects. Thus, it is important to identify individual differences that shape the consequences of peer stress. This research investigated the interactive contribution of cumulative peer stress during childhood (second-fifth grades) and executive…

  16. Subject Line Preferences and Other Factors Contributing to Coherence and Interaction in Student Discussion Forums

    ERIC Educational Resources Information Center

    Skogs, Julie

    2013-01-01

    A number of factors may affect student interaction in an asynchronous online discussion forum used in learning. This study deals with student preferences for the subject line of messages and in what ways the choice of subject line contributes to coherence and interaction reflected in the textual and interpersonal functions of the linguistic items…

  17. Shaping Learner Contributions in an EFL Classroom: Implications for L2 Classroom Interactional Competence

    ERIC Educational Resources Information Center

    Can Daskin, Nilüfer

    2015-01-01

    This study investigated the interactional patterns for shaping learner contributions in an EFL classroom with reference to Walsh's classroom interactional competence (CIC). In doing so, an EFL class at an English preparatory school in a Turkish state university was both videotaped and audiotaped in the course of six classroom hours. Conversation…

  18. Higher-order genetic interactions and their contribution to complex traits

    PubMed Central

    Taylor, Matthew B.; Ehrenreich, Ian M.

    2014-01-01

    The contribution of genetic interactions involving three or more loci to complex traits is poorly understood. Because these higher-order genetic interactions (HGIs) are difficult to detect in genetic mapping studies, very few examples of them have been described. However, the lack of data on HGIs should not be misconstrued as proof that this class of genetic effect is unimportant. To the contrary, evidence from model organisms suggests that HGIs frequently influence genetic studies and contribute to many complex traits. Here, we review the growing literature on HGIs and discuss the future of research on this topic. PMID:25284288

  19. Seeds of strategic and interactional psychotherapies: seminal contributions of Milton H. Erickson.

    PubMed

    Zeig, J K; Geary, B B

    1990-10-01

    The life and work of Milton H. Erickson exerts a considerable influence upon the development of strategic and interactional psychotherapies. In this paper we trace the historical course of Erickson's impact in these areas from his early associations with Gregory Bateson and Margaret Mead through his contributions to the ideologies of Jay Haley and practitioners at the Mental Research Institute. We have identified seven philosophical and methodological realms which represent the incorporation of Ericksonian principles into strategic and interactional family therapy models.

  20. Activities Contributing a Great Deal to the Students' Interactive Skills in Foreign Language Classes

    ERIC Educational Resources Information Center

    Asatryan, Susanna

    2016-01-01

    While teaching speaking it is desired to provide a rich environment in class for meaningful communication to take place. With this aim, various speaking activities can contribute a great deal to students in developing their interactive skills necessary for life. These activities make students active in the learning process and at the same time…

  1. Early Markers of Language and Attention: Mutual Contributions and the Impact of Parent-Infant Interactions

    ERIC Educational Resources Information Center

    Gartstein, Maria A.; Crawford, Jennifer; Robertson, Christopher D.

    2008-01-01

    This study was conducted to explore the contribution of attentional skills to early language, and the influence of early language markers on the development of attention, simultaneously examining the impact of parent-child interaction factors (reciprocity/synchrony and sensitivity/responsivity), including their potential moderator effects. All…

  2. Assessing Energetic Contributions to Binding from a Disordered Region in a Protein-Protein Interaction

    SciTech Connect

    S Cho; C Swaminathan; D Bonsor; M Kerzic; R Guan; J Yang; C Kieke; P Anderson; D Kranz; et al.

    2011-12-31

    Many functional proteins are at least partially disordered prior to binding. Although the structural transitions upon binding of disordered protein regions can influence the affinity and specificity of protein complexes, their precise energetic contributions to binding are unknown. Here, we use a model protein-protein interaction system in which a locally disordered region has been modified by directed evolution to quantitatively assess the thermodynamic and structural contributions to binding of disorder-to-order transitions. Through X-ray structure determination of the protein binding partners before and after complex formation and isothermal titration calorimetry of the interactions, we observe a correlation between protein ordering and binding affinity for complexes along this affinity maturation pathway. Additionally, we show that discrepancies between observed and calculated heat capacities based on buried surface area changes in the protein complexes can be explained largely by heat capacity changes that would result solely from folding the locally disordered region. Previously developed algorithms for predicting binding energies of protein-protein interactions, however, are unable to correctly model the energetic contributions of the structural transitions in our model system. While this highlights the shortcomings of current computational methods in modeling conformational flexibility, it suggests that the experimental methods used here could provide training sets of molecular interactions for improving these algorithms and further rationalizing molecular recognition in protein-protein interactions.

  3. Interaction of interstitial atoms and configurational contribution to their thermodynamic activity in V, Nb, and Ta

    NASA Astrophysics Data System (ADS)

    Blanter, M. S.; Dmitriev, V. V.; Mogutnov, B. M.; Ruban, A. V.

    2017-02-01

    The pairwise interaction energies of O-O and N-N in bcc metals of group VB, which were calculated earlier using first-principles methods, have been employed to analyze the effect of the interatomic interactions on the configurational contribution to the thermodynamic activity. The strong effect of interstitial- interstitial interaction has been shown. The configurational contribution grows in the row (Nb-N) → (V-N) → (Ta-N) → (Nb-O) → (V-O) → (Ta-O), which is caused by a weakening of the mutual attraction of interstitial atoms in these solid solutions. The strong repulsion that characterizes the majority of coordination shells only weakly affects the thermodynamic activity. The character of the temperature dependence of the configurational contribution is defined by the strength of the mutual attraction of the interstitial atoms, i.e., upon strong attraction, the contribution increases with increasing temperature (Nb-N, V-N, Ta-N, and Nb-O) and, upon weak attraction, it decreases (V-O and Ta-O).

  4. A bivariate mann-whitney approach for unraveling genetic variants and interactions contributing to comorbidity.

    PubMed

    Wen, Yalu; Schaid, Daniel J; Lu, Qing

    2013-04-01

    Although comorbidity among complex diseases (e.g., drug dependence syndromes) is well documented, genetic variants contributing to the comorbidity are still largely unknown. The discovery of genetic variants and their interactions contributing to comorbidity will likely shed light on underlying pathophysiological and etiological processes, and promote effective treatments for comorbid conditions. For this reason, studies to discover genetic variants that foster the development of comorbidity represent high-priority research projects, as manifested in the behavioral genetics studies now underway. The yield from these studies can be enhanced by adopting novel statistical approaches, with the capacity of considering multiple genetic variants and possible interactions. For this purpose, we propose a bivariate Mann-Whitney (BMW) approach to unravel genetic variants and interactions contributing to comorbidity, as well as those unique to each comorbid condition. Through simulations, we found BMW outperformed two commonly adopted approaches in a variety of underlying disease and comorbidity models. We further applied BMW to datasets from the Study of Addiction: Genetics and Environment, investigating the contribution of 184 known nicotine dependence (ND) and alcohol dependence (AD) single nucleotide polymorphisms (SNPs) to the comorbidity of ND and AD. The analysis revealed a candidate SNP from CHRNA5, rs16969968, associated with both ND and AD, and replicated the findings in an independent dataset with a P-value of 1.06 × 10(-03) .

  5. Contributions of cation-π interactions to the collagen triple helix stability.

    PubMed

    Chen, Chia-Ching; Hsu, Wei; Hwang, Kuo-Chu; Hwu, Jih Ru; Lin, Chun-Cheng; Horng, Jia-Cherng

    2011-04-01

    Cation-π interactions are found to be an important noncovalent force in proteins. Collagen is a right-handed triple helix composed of three left-handed PPII helices, in which (X-Y-Gly) repeats dominate in the sequence. Molecular modeling indicates that cation-π interactions could be formed between the X and Y positions in adjacent collagen strands. Here, we used a host-guest peptide system: (Pro-Hyp-Gly)(3)-(Pro-Y-Gly-X-Hyp-Gly)-(Pro-Hyp-Gly)(3), where X is an aromatic residue and Y is a cationic residue, to study the cation-π interaction in the collagen triple helix. Circular dichroism (CD) measurements and Tm data analysis show that the cation-π interactions involving Arg have a larger contribution to the conformational stability than do those involving Lys, and Trp forms a weaker cation-π interaction with cationic residues than expected as a result of steric effects. The results also show that the formation of cation-π interactions between Arg and Phe depends on their relative positions in the strand. Moreover, the fluorinated and methylated Phe substitutions show that an electron-withdrawing or electron-donating substituent on the aromatic ring can modulate its π-electron density and the cation-π interaction in collagen. Our data demonstrate that the cation-π interaction could play an important role in stabilizing the collagen triple helix.

  6. Conditioned place preference for social interaction in rats: contribution of sensory components.

    PubMed

    Kummer, Kai; Klement, Sabine; Eggart, Vincent; Mayr, Michael J; Saria, Alois; Zernig, Gerald

    2011-01-01

    A main challenge in the therapy of drug dependent individuals is to help them reactivate interest in non-drug-associated activities. We previously developed a rat experimental model based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of social interaction with a gender- and weight-matched male Sprague Dawley rat (1) reversed CPP from cocaine to social interaction despite continuing cocaine training and (2) prevented the reinstatement of cocaine CPP. In the present study, we investigated which of the sensory modalities of the composite stimulus "social interaction" contributes most to the rats' preference for it. If touch was limited by steel bars spaced at a distance of 2 cm and running across the whole length of a partitioning, CPP was still acquired, albeit to a lesser degree. If both rats were placed on the same side of a partitioning, rats did not develop CPP for social interaction. Thus, decreasing the available area for social interaction from 750 to 375 cm(2) prevented the acquisition of CPP to social interaction despite the fact that animals could touch each other more intensely than through the bars of the partitioning. When touch was fully restricted by a glass screen dividing the conditioning chambers, and the only sensory modalities left were visual and olfactory cues, place preference shifted to place aversion. Overall, our findings indicate that the major rewarding sensory component of the composite stimulus "social interaction" is touch (taction).

  7. Glycan-dependent and -independent Interactions Contribute to Cellular Substrate Recruitment by Calreticulin*

    PubMed Central

    Wijeyesakere, Sanjeeva J.; Rizvi, Syed M.; Raghavan, Malini

    2013-01-01

    Calreticulin is an endoplasmic reticulum chaperone with specificity for monoglucosylated glycoproteins. Calreticulin also inhibits precipitation of nonglycosylated proteins and thus contains generic protein-binding sites, but their location and contributions to substrate folding are unknown. We show that calreticulin binds glycosylated and nonglycosylated proteins with similar affinities but distinct interaction kinetics. Although both interactions involve the glycan-binding site or its vicinity, the arm-like proline-rich (P-) domain of calreticulin contributes to binding non/deglycosylated proteins. Correspondingly, ensemble FRET spectroscopy measurements indicate that glycosylated and nonglycosylated proteins induce “open” and “closed” P-domain conformations, respectively. The co-chaperone ERp57 influences substrate-binding kinetics and induces a closed P-domain conformation. Together with analysis of the interactions of calreticulin with cellular proteins, these findings indicate that the recruitment of monoglucosylated proteins to calreticulin is kinetically driven, whereas the P-domain and co-chaperone contribute to stable substrate binding. Substrate sequestration in the cleft between the glycan-binding site and P-domain is a likely mechanism for calreticulin-assisted protein folding. PMID:24100026

  8. An analysis of the correlation energy contribution to the interaction energy of inert gas dimers.

    PubMed

    Snook, Ian; Per, Manolo C; Russo, Salvy P

    2008-10-28

    An accurate description of electron correlation is essential for the calculation of interaction energies in cases where dispersion energy is a major component, for example, for the rare gas atoms, physisorption on graphite, and graphene-graphene interactions. Such calculations are computationally demanding using supermolecule methods and the energies calculated lack a simple, physical interpretation. Alternatively density functional theories (DFTs) may be used to give an approximate estimate of the correlation energy. However, the physical nature of this DFT estimate of electron correlation energy is not well understood and, in fact, most current DFT methods do not describe dispersion energy at all. Hence, an analysis of the correlation energy contribution to interaction energies where dispersion energy is important is needed. In order to do this we provide an analysis of the correlation energy contribution to the potential energy curves of He(2), Ne(2), and Ar(2) in terms of the Hartree-Fock (HF) interaction term DeltaE(int) (HF), a dispersion energy term E(disp) and an electron correlation term DeltaE(int) (C). DeltaE(int) (C) includes all other correlation energy effects besides E(disp) and is shown to be repulsive, of a similar short range character to, but of smaller magnitude than DeltaE(int) (HF). This analysis was used to develop a theoretical model which gives a very good estimate of the potential energy wells for He(2), Ne(2), Ar(2), HeNe, HeAr, and NeAr.

  9. Contributions of different tidal interactions to fortnightly variation in tidal duration asymmetry

    NASA Astrophysics Data System (ADS)

    Guo, Wenyun; Song, Dehai; Wang, Xiao Hua; Ding, Pingxing; Ge, Jianzhong

    2016-08-01

    The general framework for identifying tidal duration asymmetry proposed by Song et al. (2011) is extended to express fortnightly variability in duration asymmetry. The extended metrics are verified and studied using observed sea level data at 481 stations worldwide. The results reveal that fortnightly variability is universal and that duration asymmetry can be stronger during neap tide than during spring tide. The fortnightly variability in duration asymmetry is primarily induced by three types of tidal interactions: interactions within the principal tidal constituents, interactions between high-frequency and principal tidal constituents, and interactions between long-period and principal tidal constituents. Among these interactions, the first type is most important at most of the stations and is related to the form number F. The contributions of different interactions can be quantified using their frequencies, amplitudes and phases. Global patterns of the fortnightly variation are illustrated using TOPEX/Poseidon altimetry data. The findings show that remarkable fortnightly variation in the tidal duration asymmetry occurs in most open oceans and is significant around an amphidromic point. The metrics derived in this study can be used to examine any time-varying characteristics in tidal asymmetry (not limited to duration asymmetry) by selecting a suitable frequency threshold.

  10. CFL3D Contribution to the AIAA Supersonic Shock Boundary Layer Interaction Workshop

    NASA Technical Reports Server (NTRS)

    Rumsey, Christopher L.

    2010-01-01

    This paper documents the CFL3D contribution to the AIAA Supersonic Shock Boundary Layer Interaction Workshop, held in Orlando, Florida in January 2010. CFL3D is a Reynolds-averaged Navier-Stokes code. Four shock boundary layer interaction cases are computed using a one-equation turbulence model widely used for other aerodynamic problems of interest. Two of the cases have experimental data available at the workshop, and two of the cases do not. The effect of grid, flux scheme, and thin-layer approximation are investigated. Comparisons are made to the available experimental data. All four cases exhibit strong three-dimensional behavior in and near the interaction regions, resulting from influences of the tunnel side-walls.

  11. β-arrestin-1 contributes to brown fat function and directly interacts with PPARα and PPARγ

    PubMed Central

    Wang, Congcong; Zeng, Xianglu; Zhou, Zhaocai; Zhao, Jian; Pei, Gang

    2016-01-01

    The peroxisome proliferator-activated receptor (PPAR) family plays central roles in brown adipose tissue (BAT) adipogenesis and contributes to body temperature maintenance. The transcriptional activity of PPAR family has been shown to be tightly controlled by cellular signal networks. β-arrestins function as major secondary messengers of G protein-coupled receptors (GPCR) signaling by functional interactions with diverse proteins. Here, we report that β-arrestin-1 knock-out mice show enhanced cold tolerance. We found that β-arrestin-1 directly interacts with PPARα and PPARγ through a LXXXLXXXL motif, while D371 in PPARα and L311/N312/D380 in PPARγ are required for their interactions with β-arrestin-1. Further mechanistic studies showed that β-arrestin-1 promotes PPARα- but represses PPARγ-mediated transcriptional activities, providing potential regulatory pathway for BAT function. PMID:27301785

  12. Social inequalities in health: measuring the contribution of housing deprivation and social interactions for Spain

    PubMed Central

    2012-01-01

    Introduction Social factors have been proved to be main determinants of individuals’ health. Recent studies have also analyzed the contribution of some of those factors, such as education and job status, to socioeconomic inequalities in health. The aim of this paper is to provide new evidence about the factors driving socioeconomic inequalities in health for the Spanish population by including housing deprivation and social interactions as health determinants. Methods Cross-sectional study based on the Spanish sample of European Statistics on Income and Living Conditions (EU-SILC) for 2006. The concentration index measuring income-related inequality in health is decomposed into the contribution of each determinant. Several models are estimated to test the influence of different regressors for three proxies of ill-health. Results Health inequality favouring the better-off is observed in the distribution of self-assessed health, presence of chronic diseases and presence of limiting conditions. Inequality is mainly explained, besides age, by social factors such as labour status and financial deprivation. Housing deprivation contributes to pro-rich inequality in a percentage ranging from 7.17% to 13.85%, and social interactions from 6.16% to 10.19%. The contribution of some groups of determinants significantly differs depending on the ill-health variable used. Conclusions Health inequalities can be mostly reduced or shaped by policy, as they are mainly explained by social determinants such as labour status, education and other socioeconomic conditions. The major role played on health inequality by variables taking part in social exclusion points to the need to focus on the most vulnerable groups. JEL Codes H51, I14, I18 PMID:23241384

  13. Bacteria–bacteria interactions within the microbiota of the ancestral metazoan Hydra contribute to fungal resistance

    PubMed Central

    Fraune, Sebastian; Anton-Erxleben, Friederike; Augustin, René; Franzenburg, Sören; Knop, Mirjam; Schröder, Katja; Willoweit-Ohl, Doris; Bosch, Thomas CG

    2015-01-01

    Epithelial surfaces of most animals are colonized by diverse microbial communities. Although it is generally agreed that commensal bacteria can serve beneficial functions, the processes involved are poorly understood. Here we report that in the basal metazoan Hydra, ectodermal epithelial cells are covered with a multilayered glycocalyx that provides a habitat for a distinctive microbial community. Removing this epithelial microbiota results in lethal infection by the filamentous fungus Fusarium sp. Restoring the complex microbiota in gnotobiotic polyps prevents pathogen infection. Although mono-associations with distinct members of the microbiota fail to provide full protection, additive and synergistic interactions of commensal bacteria are contributing to full fungal resistance. Our results highlight the importance of resident microbiota diversity as a protective factor against pathogen infections. Besides revealing insights into the in vivo function of commensal microbes in Hydra, our findings indicate that interactions among commensal bacteria are essential to inhibit pathogen infection. PMID:25514534

  14. Contribution of excited states to stellar weak-interaction rates in odd-A nuclei

    NASA Astrophysics Data System (ADS)

    Sarriguren, P.

    2016-05-01

    Weak-interaction rates, including β decay and electron capture, are studied in several odd-A nuclei in the p f -shell region at various densities and temperatures of astrophysical interest. Special attention is paid to the relative contribution to these rates of thermally populated excited states in the decaying nucleus. The nuclear structure involved in the weak processes is studied within a quasiparticle random-phase approximation with residual interactions in both particle-hole and particle-particle channels on top of a deformed Skyrme Hartree-Fock mean field with pairing correlations. In the range of densities and temperatures considered, it is found that the total rates do not differ much from the rates of the ground state fully populated. In any case, the changes are not larger than the uncertainties due to the nuclear-model dependence of the rates.

  15. Isolating the non-polar contributions to the intermolecular potential for water-alkane interactions

    NASA Astrophysics Data System (ADS)

    Ballal, Deepti; Venkataraman, Pradeep; Fouad, Wael A.; Cox, Kenneth R.; Chapman, Walter G.

    2014-08-01

    Intermolecular potential models for water and alkanes describe pure component properties fairly well, but fail to reproduce properties of water-alkane mixtures. Understanding interactions between water and non-polar molecules like alkanes is important not only for the hydrocarbon industry but has implications to biological processes as well. Although non-polar solutes in water have been widely studied, much less work has focused on water in non-polar solvents. In this study we calculate the solubility of water in different alkanes (methane to dodecane) at ambient conditions where the water content in alkanes is very low so that the non-polar water-alkane interactions determine solubility. Only the alkane-rich phase is simulated since the fugacity of water in the water rich phase is calculated from an accurate equation of state. Using the SPC/E model for water and TraPPE model for alkanes along with Lorentz-Berthelot mixing rules for the cross parameters produces a water solubility that is an order of magnitude lower than the experimental value. It is found that an effective water Lennard-Jones energy ɛW/k = 220 K is required to match the experimental water solubility in TraPPE alkanes. This number is much higher than used in most simulation water models (SPC/E—ɛW/k = 78.2 K). It is surprising that the interaction energy obtained here is also higher than the water-alkane interaction energy predicted by studies on solubility of alkanes in water. The reason for this high water-alkane interaction energy is not completely understood. Some factors that might contribute to the large interaction energy, such as polarizability of alkanes, octupole moment of methane, and clustering of water at low concentrations in alkanes, are examined. It is found that, though important, these factors do not completely explain the anomalously strong attraction between alkanes and water observed experimentally.

  16. Isolating the non-polar contributions to the intermolecular potential for water-alkane interactions.

    PubMed

    Ballal, Deepti; Venkataraman, Pradeep; Fouad, Wael A; Cox, Kenneth R; Chapman, Walter G

    2014-08-14

    Intermolecular potential models for water and alkanes describe pure component properties fairly well, but fail to reproduce properties of water-alkane mixtures. Understanding interactions between water and non-polar molecules like alkanes is important not only for the hydrocarbon industry but has implications to biological processes as well. Although non-polar solutes in water have been widely studied, much less work has focused on water in non-polar solvents. In this study we calculate the solubility of water in different alkanes (methane to dodecane) at ambient conditions where the water content in alkanes is very low so that the non-polar water-alkane interactions determine solubility. Only the alkane-rich phase is simulated since the fugacity of water in the water rich phase is calculated from an accurate equation of state. Using the SPC/E model for water and TraPPE model for alkanes along with Lorentz-Berthelot mixing rules for the cross parameters produces a water solubility that is an order of magnitude lower than the experimental value. It is found that an effective water Lennard-Jones energy ε(W)/k = 220 K is required to match the experimental water solubility in TraPPE alkanes. This number is much higher than used in most simulation water models (SPC/E-ε(W)/k = 78.2 K). It is surprising that the interaction energy obtained here is also higher than the water-alkane interaction energy predicted by studies on solubility of alkanes in water. The reason for this high water-alkane interaction energy is not completely understood. Some factors that might contribute to the large interaction energy, such as polarizability of alkanes, octupole moment of methane, and clustering of water at low concentrations in alkanes, are examined. It is found that, though important, these factors do not completely explain the anomalously strong attraction between alkanes and water observed experimentally.

  17. Interacting partners of macrophage-secreted cathepsin B contribute to HIV-induced neuronal apoptosis

    PubMed Central

    CANTRES-ROSARIO, Yisel M.; HERNANDEZ, Natalia; NEGRON, Karla; PEREZ-LASPIUR, Juliana; LESZYK, John; SHAFFER, Scott A.; MELENDEZ, Loyda M.

    2015-01-01

    Objective HIV-1 infection of macrophages increases cathepsin B secretion and induces neuronal apoptosis, but the molecular mechanism remains unclear. Design We identified macrophage secreted cathepsin B protein interactions extracellularly and their contribution to neuronal death in vitro. Methods Cathepsin B was immunoprecipitated from monocyte-derived macrophage supernatants after 12 days post-infection. The cathepsin B interactome was quantified by label-free tandem mass spectrometry and compared to uninfected supernatants. Proteins identified were validated by western blot. Neurons were exposed to macrophage-conditioned media in presence or absence of antibodies against cathepsin B and interacting proteins. Apoptosis was measured using TUNEL labeling. Immunohistochemistry of post-mortem brain tissue samples from healthy, HIV-infected, and Alzheimer’s disease patients was performed to observe the ex vivo expression of the proteins identified. Results Nine proteins co-immunoprecipitated differentially with cathepsin B between uninfected and HIV-infected macrophages. Serum amyloid p component (SAPC) -cathepsin B interaction increased in HIV-infected macrophage supernatants, while matrix metalloprotease 9 (MMP-9) -cathepsin B interaction decreased. Pre-treatment of HIV-infected macrophage-conditioned media with antibodies against cathepsin B and SAPC decreased neuronal apoptosis. The addition of MMP-9 antibodies was not protective. SAPC was over-expressed in post-mortem brain tissue from HIV-positive neurocognitive impaired patients compared to HIV positive with normal cognition and healthy controls, while MMP-9 expression was similar in all tissues. Conclusions Inhibiting SAPC-cathepsin B interaction protects against HIV–induced neuronal death and may help to find alternative treatments for HIV-associated neurocognitive disorders. PMID:26208400

  18. Vapor-liquid equilibria simulation and an equation of state contribution for dipole-quadrupole interactions.

    PubMed

    Vrabec, Jadran; Gross, Joachim

    2008-01-10

    A systematic investigation on vapor-liquid equilibria (VLEs) of dipolar and quadrupolar fluids is carried out by molecular simulation to develop a new Helmholtz energy contribution for equations of state (EOSs). Twelve two-center Lennard-Jones plus point dipole and point quadrupole model fluids (2CLJDQ) are studied for different reduced dipolar moments micro*2=6 or 12, reduced quadrupolar moments Q*2=2 or 4 and reduced elongations L*=0, 0.505, or 1. Temperatures cover a wide range from about 55% to 95% of the critical temperature of each fluid. The NpT+test particle method is used for the calculation of vapor pressure, saturated densities, and saturated enthalpies. Critical data and the acentric factor are obtained from fits to the simulation data. On the basis of this data, an EOS contribution for the dipole-quadrupole cross-interactions of nonspherical molecules is developed. The expression is based on a third-order perturbation theory, and the model constants are adjusted to the present 2CLJDQ simulation results. When applied to mixtures, the model is found to be in excellent agreement with results from simulation and experiment. The new EOS contribution is also compatible with segment-based EOS, such as the various forms of the statistical associating fluid theory EOS.

  19. Contribution of temperament to eating disorder symptoms in emerging adulthood: Additive and interactive effects.

    PubMed

    Burt, Nicole M; Boddy, Lauren E; Bridgett, David J

    2015-08-01

    Temperament characteristics, such as higher negative emotionality (NE) and lower effortful control (EC), are individual difference risk factors for developmental psychopathology. Research has also noted relations between temperament and more specific manifestations of psychopathology, such as eating disorders (EDs). Although work is emerging that indicates that NE and EC may additively contribute to risk for ED symptoms, no studies have considered the interactive effects of NE and EC in relation to ED symptoms. In the current investigation, we hypothesized that (1) low EC would be associated with increased ED symptoms, (2) high NE would be associated with increased ED symptoms, and (3) these temperament traits would interact, such that the relationship between NE and ED symptoms would be strongest in the presence of low EC. After controlling for gender and child trauma history, emerging adults' (N=160) lower EC (i.e., more difficulties with self-regulation) was associated with more ED symptoms. NE did not emerge as a direct predictor of ED symptoms. However, the anticipated interaction of these temperament characteristics on ED symptoms was found. The association between NE and ED symptoms was only significant in the context of low EC. These findings provide evidence that elevated NE may only be a risk factor for the development of eating disorders when individuals also have self-regulation difficulties. The implications of these findings for research and interventions are discussed.

  20. Two Fundamentally Distinct PCNA Interaction Peptides Contribute to Chromatin Assembly Factor 1 Function▿

    PubMed Central

    Ben-Shahar, Tom Rolef; Castillo, Araceli G.; Osborne, Michael J.; Borden, Katherine L. B.; Kornblatt, Jack; Verreault, Alain

    2009-01-01

    Chromatin assembly factor 1 (CAF-1) deposits histones H3 and H4 rapidly behind replication forks through an interaction with the proliferating cell nuclear antigen (PCNA), a DNA polymerase processivity factor that also binds to a number of replication enzymes and other proteins that act on nascent DNA. The mechanisms that enable CAF-1 and other PCNA-binding proteins to function harmoniously at the replication fork are poorly understood. Here we report that the large subunit of human CAF-1 (p150) contains two distinct PCNA interaction peptides (PIPs). The N-terminal PIP binds strongly to PCNA in vitro but, surprisingly, is dispensable for nucleosome assembly and only makes a modest contribution to targeting p150 to DNA replication foci in vivo. In contrast, the internal PIP (PIP2) lacks one of the highly conserved residues of canonical PIPs and binds weakly to PCNA. Surprisingly, PIP2 is essential for nucleosome assembly during DNA replication in vitro and plays a major role in targeting p150 to sites of DNA replication. Unlike canonical PIPs, such as that of p21, the two p150 PIPs are capable of preferentially inhibiting nucleosome assembly, rather than DNA synthesis, suggesting that intrinsic features of these peptides are part of the mechanism that enables CAF-1 to function behind replication forks without interfering with other PCNA-mediated processes. PMID:19822659

  1. Tumor loci and their interactions on mouse chromosome 19 that contribute to testicular germ cell tumors

    PubMed Central

    2014-01-01

    Background Complex genetic factors underlie testicular germ cell tumor (TGCT) development. One experimental approach to dissect the genetics of TGCT predisposition is to use chromosome substitution strains, such as the 129.MOLF-Chr 19 (M19). M19 carries chromosome (Chr) 19 from the MOLF whereas all other chromosomes are from the 129 strain. 71% of M19 males develop TGCTs in contrast to 5% in 129 strain. To identify and map tumor loci from M19 we generated congenic strains harboring MOLF chromosome 19 segments on 129 strain background and monitored their TGCT incidence. Results We found 3 congenic strains that each harbored tumor promoting loci that had high (14%-32%) whereas 2 other congenics had low (4%) TGCT incidences. To determine how multiple loci influence TGCT development, we created double and triple congenic strains. We found additive interactions were predominant when 2 loci were combined in double congenic strains. Surprisingly, we found an example where 2 loci, both which do not contribute significantly to TGCT, when combined in a double congenic strain resulted in greater than expected TGCT incidence (positive interaction). In an opposite example, when 2 loci with high TGCT incidences were combined, males of the double congenic showed lower than expected TGCT incidence (negative interaction). For the triple congenic strain, depending on the analysis, the overall TGCT incidence could be additive or could also be due to a positive interaction of one region with others. Additionally, we identified loci that promote bilateral tumors or testicular abnormalities. Conclusions The congenic strains each with their characteristic TGCT incidences, laterality of tumors and incidence of testicular abnormalities, are useful for identification of TGCT susceptibility modifier genes that map to Chr 19 and also for studies on the genetic and environmental causes of TGCT development. TGCTs are a consequence of aberrant germ cell and testis development. By defining

  2. Interaction of Mycoplasma gallisepticum with Chicken Tracheal Epithelial Cells Contributes to Macrophage Chemotaxis and Activation

    PubMed Central

    Majumder, Sanjukta

    2015-01-01

    Mycoplasma gallisepticum colonizes the chicken respiratory mucosa and mediates a severe inflammatory response hallmarked by subepithelial leukocyte infiltration. We recently reported that the interaction of M. gallisepticum with chicken tracheal epithelial cells (TECs) mediated the upregulation of chemokine and inflammatory cytokine genes in these cells (S. Majumder, F. Zappulla, and L. K. Silbart, PLoS One 9:e112796, http://dx.doi.org/10.1371/journal.pone.0112796). The current study extends these observations and sheds light on how this initial interaction may give rise to subsequent inflammatory events. Conditioned medium from TECs exposed to the virulent Rlow strain induced macrophage chemotaxis to a much higher degree than the nonvirulent Rhigh strain. Coculture of chicken macrophages (HD-11) with TECs exposed to live mycoplasma revealed the upregulation of several proinflammatory genes associated with macrophage activation, including interleukin-1β (IL-1β), IL-6, IL-8, CCL20, macrophage inflammatory protein 1β (MIP-1β), CXCL-13, and RANTES. The upregulation of these genes was similar to that observed upon direct contact of HD-11 cells with live M. gallisepticum. Coculture of macrophages with Rlow-exposed TECs also resulted in prolonged expression of chemokine genes, such as those encoding CXCL-13, MIP-1β, RANTES, and IL-8. Taken together, these studies support the notion that the initial interaction of M. gallisepticum with host respiratory epithelial cells contributes to macrophage chemotaxis and activation by virtue of robust upregulation of inflammatory cytokine and chemokine genes, thereby setting the stage for chronic tissue inflammation. PMID:26527215

  3. The Contribution of Pin End-Cup Interactions to Clot Strength Assessed with Thrombelastography.

    PubMed

    Nielsen, Vance G

    2016-01-01

    Viscoelastic methods have been developed to assess the contribution of plasma proteins and platelets to coagulation in vitro to guide clinical transfusion therapy. One of the cardinal precepts of determining clot strength is making sure that the viscoelastic technique includes complete exposure of the plastic pin in the testing chamber with the fluid analyzed so as to assure maximal interaction of the cup wall with the pin surface. However, the various contributions of the pin surface area to final clot strength have not been investigated. That is, it is not clear what is more important in the in vitro determination of clot strength, the surface area shared between the cup and pin filled with fluid or the final viscoelastic resistance of the gel matrix formed. Thus, the purpose of this investigation was to determine the clot strength when only the tip of the pin was engaged with plasma thrombus and to compare these values with clot strength values obtained when the pin was completely in plasma. After determining the minimal amount of plasma required to cover a pin tip in a thrombelastographic system (30 μL), clot strength (elastic modulus, G) was determined in plasma samples of 30 or 360 μL final volume (n = 12 per condition) after tissue factor activation. The G value with 30 μL volume was 1057 ± 601 dynes/cm (mean ± SD; 95% confidence interval, 675-1439 dynes/cm), which was (P = 0.0015) smaller than the G value associated with 360-μL sample volumes, that was 1712 ± 48 dynes/cm (confidence interval, 1681-1742 dynes/cm). In conclusion, these data demonstrate that clot strength is not determined by a simple ratio of surface area of pin and cup to volume of sample, but rather strength is importantly influenced by the viscoelastic resistance of the fluid assessed.

  4. Interacting vegetative and thermal contributions to water movement in desert soil

    USGS Publications Warehouse

    Garcia, C.A.; Andraski, B.J.; Stonestrom, D.A.; Cooper, C.A.; Simunek, J.; Wheatcraft, S.W.

    2011-01-01

    Thermally driven water-vapor flow can be an important component of total water movement in bare soil and in deep unsaturated zones, but this process is often neglected when considering the effects of soil-plant-atmosphere interactions on shallow water movement. The objectives of this study were to evaluate the coupled and separate effects of vegetative and thermal-gradient contributions to soil water movement in desert environments. The evaluation was done by comparing a series of simulations with and without vegetation and thermal forcing during a 4.7-yr period (May 2001-December 2005). For vegetated soil, evapotranspiration alone reduced root-zone (upper 1 m) moisture to a minimum value (25 mm) each year under both isothermal and nonisothermal conditions. Variations in the leaf area index altered the minimum storage values by up to 10 mm. For unvegetated isothermal and nonisothermal simulations, root-zone water storage nearly doubled during the simulation period and created a persistent driving force for downward liquid fluxes below the root zone (total net flux ~1 mm). Total soil water movement during the study period was dominated by thermally driven vapor fluxes. Thermally driven vapor flow and condensation supplemented moisture supplies to plant roots during the driest times of each year. The results show how nonisothermal flow is coupled with plant water uptake, potentially influencing ecohydrologic relations in desert environments. ?? Soil Science Society of America 5585 Guilford Rd., Madison, WI 53711 USA. All rights reserved.

  5. Interacting vegetative and thermal contributions to water movement in desert soil

    USGS Publications Warehouse

    Garcia, C.A.; Andraski, B.J.; Stonestrom, D.A.; Cooper, C.A.; Šimůnek, J.; Wheatcraft, S.W.

    2011-01-01

    Thermally driven water-vapor flow can be an important component of total water movement in bare soil and in deep unsaturated zones, but this process is often neglected when considering the effects of soil–plant–atmosphere interactions on shallow water movement. The objectives of this study were to evaluate the coupled and separate effects of vegetative and thermal-gradient contributions to soil water movement in desert environments. The evaluation was done by comparing a series of simulations with and without vegetation and thermal forcing during a 4.7-yr period (May 2001–December 2005). For vegetated soil, evapotranspiration alone reduced root-zone (upper 1 m) moisture to a minimum value (25 mm) each year under both isothermal and nonisothermal conditions. Variations in the leaf area index altered the minimum storage values by up to 10 mm. For unvegetated isothermal and nonisothermal simulations, root-zone water storage nearly doubled during the simulation period and created a persistent driving force for downward liquid fluxes below the root zone (total net flux ~1 mm). Total soil water movement during the study period was dominated by thermally driven vapor fluxes. Thermally driven vapor flow and condensation supplemented moisture supplies to plant roots during the driest times of each year. The results show how nonisothermal flow is coupled with plant water uptake, potentially influencing ecohydrologic relations in desert environments.

  6. Anxious and Depressive Symptomatology Among Male Youth: The Joint and Interactive Contribution of Temperament and Executive Functioning.

    PubMed

    Latzman, Robert D; Shishido, Yuri; Latzman, Natasha E; Clark, Lee Anna

    2016-12-01

    Few studies have investigated the combined effects of temperament and executive functioning (EF) on anxious and depressive symptomatology in youth. The current study is the first to investigate the joint and interactive contribution of mother- and youth self-reported affective dimensions of temperament and EF to the explanation of anxious and depressive symptomatology. Participants included 174 adolescent males (M age = 13.6 ± 1.35). Results confirmed the joint and interactive contribution of temperament in the explanation of anxious and depressive symptomatology. Further, EF contributed to the explanation of anxious/depressive symptomatology via interaction with youth-, but not mother-reported, temperament; it was not a unique predictor. Results support the need to consider both affective dimensions of temperament and EF in etiological models of anxious and depressive symptomatology, which has implications for identifying at-risk youth and developing early intervention and targeted problem-specific prevention programs.

  7. Intermolecular interactions of oligothienoacenes: Do S⋯S interactions positively contribute to crystal structures of sulfur-containing aromatic molecules?

    PubMed

    Tsuzuki, Seiji; Orita, Hideo; Sato, Naoki

    2016-11-07

    Intermolecular interactions in the crystals of tetra- and penta-thienoacene were studied using ab initio molecular orbital calculations for evaluating the magnitude of characteristic S⋯S interactions with great attention paid to their origin. The interactions between the π-stacked neighboring molecules are significantly greater than those between the neighboring molecules exhibiting the S⋯S contact, although it has sometimes been claimed that the S⋯S interactions play important roles in adjusting the molecular arrangement of sulfur-containing polycyclic aromatic molecules in the crystals owing to short S⋯S contacts. The coupled cluster calculations with single and double substitutions with noniterative triple excitation interaction energies at the basis set limit estimated for the π-stacked and S⋯S contacted neighboring molecules in the tetrathienoacene crystal are -11.17 and -4.27 kcal/mol, respectively. Those for π-stacked molecules in the pentathienoacene crystal is -14.38 kcal/mol, while those for S⋯S contacted molecules are -7.02 and -6.74 kcal/mol. The dispersion interaction is the major source of the attraction between the π-stacked and S⋯S contacted molecules, while the orbital-orbital interactions are repulsive: The orbital-orbital interactions, which are significant for charge carrier transport properties, are not much more than the results of the short S⋯S contact caused by the strong dispersion interactions. Besides, the intermolecular interaction energy calculated for a trithienoacene dimer has strong orientation dependence.

  8. Mortality from desiccation contributes to a genotype–temperature interaction for cold survival in Drosophila melanogaster

    PubMed Central

    Kobey, Robert L.; Montooth, Kristi L.

    2013-01-01

    SUMMARY Survival at cold temperatures is a complex trait, primarily because of the fact that the physiological cause of injury may differ across degrees of cold exposure experienced within the lifetime of an ectothermic individual. In order to better understand how chill-sensitive insects experience and adapt to low temperatures, we investigated the physiological basis for cold survival across a range of temperature exposures from −4 to 6°C in five genetic lines of the fruit fly Drosophila melanogaster. Genetic effects on cold survival were temperature dependent and resulted in a significant genotype–temperature interaction for survival across cold temperature exposures that differ by as little as 2°C. We investigated desiccation as a potential mechanism of injury across these temperature exposures. Flies were dehydrated following exposures near 6°C, whereas flies were not dehydrated following exposures near −4°C. Furthermore, decreasing humidity during cold exposure decreased survival, and increasing humidity during cold exposure increased survival at 6°C, but not at −4°C. These results support the conclusion that in D. melanogaster there are multiple physiological mechanisms of cold-induced mortality across relatively small differences in temperature, and that desiccation contributes to mortality for exposures near 6°C but not for subzero temperatures. Because D. melanogaster has recently expanded its range from tropical to temperate latitudes, the complex physiologies underlying cold tolerance are likely to be important traits in the recent evolutionary history of this fruit fly. PMID:23197100

  9. Genome-wide interaction of genotype by erythrocyte n-3 PUFAs contributes to phenotypic variance of diabetes-related traits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While genome-wide association studies (GWAS) and candidate gene approach have identified many genetic variants that contribute to disease risk as main effects, the impact of genotype by environment (GxE) interactions remains rather under-surveyed. The present study aimed to examine variance contribu...

  10. Macrophages and Fc-receptor interactions contribute to the antitumour activities of the anti-CD40 antibody SGN-40.

    PubMed

    Oflazoglu, E; Stone, I J; Brown, L; Gordon, K A; van Rooijen, N; Jonas, M; Law, C-L; Grewal, I S; Gerber, H-P

    2009-01-13

    SGN-40 is a therapeutic antibody targeting CD40, which induces potent anti-lymphoma activities via direct apoptotic signalling cells and by cell-mediated cytotoxicity. Here we show antibody-dependent cellular phagocytosis (ADCP) by macrophages to contribute significantly to the therapeutic activities and that the antitumour effects of SGN-40 depend on Fc interactions.

  11. Contributions of soil moisture interactions to future precipitation changes in the GLACE-CMIP5 experiment

    NASA Astrophysics Data System (ADS)

    May, Wilhelm; Rummukainen, Markku; Chéruy, Frederique; Hagemann, Stefan; Meier, Arndt

    2016-10-01

    Changes in soil moisture are likely to contribute to future changes in latent heat flux and various characteristics of daily precipitation. Such contributions during the second half of the twenty-first century are assessed using the simulations from the GLACE-CMIP5 experiment, applying a linear regression analysis to determine the magnitude of these contributions. As characteristics of daily precipitation, mean daily precipitation, the frequency of wet days and the intensity of precipitation on wet days are considered. Also, the frequency and length of extended wet and dry spells are studied. Particular focus is on the regional (for nine selected regions) as well as seasonal variations in the magnitude of the contributions of the projected differences in soil moisture to the future changes in latent heat flux and in the characteristics of daily precipitation. The results reveal the overall tendency that the projected differences in soil moisture contribute to the future changes in response to the anthropogenic climate forcing for all the meteorological variables considered here. These contributions are stronger and more robust (i.e., there are smaller deviations between individual climate models) for the latent heat flux than for the characteristics of daily precipitation. It is also found that the contributions of the differences in soil moisture to the future changes are generally stronger and more robust for the frequency of wet days than for the intensity of daily precipitation. Consistent with the contributions of the projected differences in soil moisture to the future changes in the frequency of wet days, soil moisture generally contributes to the future changes in the characteristics of wet and dry spells. The magnitude of these contributions does not differ systematically between the frequency and the length of such extended spells, but the contributions are generally slightly stronger for dry spells than for wet spells. Distinguishing between the nine

  12. Sense of Community in Graduate Online Education: Contribution of Learner to Learner Interaction

    ERIC Educational Resources Information Center

    Shackelford, Jo L.; Maxwell, Marge

    2012-01-01

    Distance learning technologies offer a multitude of ways to build interaction into online courses to support learning. Based on social constructivism theory, this study explored which types of interaction are most predictive of students' sense of community in online graduate courses at a regional comprehensive university. Surveys were used to…

  13. Interactions within the MHC contribute to the genetic architecture of celiac disease

    PubMed Central

    Abraham, Gad; Kikianty, Eder; Wang, Qiao; Rawlinson, Dave; Shi, Fan; Haviv, Izhak; Stern, Linda

    2017-01-01

    Interaction analysis of GWAS can detect signal that would be ignored by single variant analysis, yet few robust interactions in humans have been detected. Recent work has highlighted interactions in the MHC region between known HLA risk haplotypes for various autoimmune diseases. To better understand the genetic interactions underlying celiac disease (CD), we have conducted exhaustive genome-wide scans for pairwise interactions in five independent CD case-control studies, using a rapid model-free approach to examine over 500 billion SNP pairs in total. We found 14 independent interaction signals within the MHC region that achieved stringent replication criteria across multiple studies and were independent of known CD risk HLA haplotypes. The strongest independent CD interaction signal corresponded to genes in the HLA class III region, in particular PRRC2A and GPANK1/C6orf47, which are known to contain variants for non-Hodgkin's lymphoma and early menopause, co-morbidities of celiac disease. Replicable evidence for statistical interaction outside the MHC was not observed. Both within and between European populations, we observed striking consistency of two-locus models and model distribution. Within the UK population, models of CD based on both interactions and additive single-SNP effects increased explained CD variance by approximately 1% over those of single SNPs. The interactions signal detected across the five cohorts indicates the presence of novel associations in the MHC region that cannot be detected using additive models. Our findings have implications for the determination of genetic architecture and, by extension, the use of human genetics for validation of therapeutic targets. PMID:28282431

  14. Interactions within the MHC contribute to the genetic architecture of celiac disease.

    PubMed

    Goudey, Benjamin; Abraham, Gad; Kikianty, Eder; Wang, Qiao; Rawlinson, Dave; Shi, Fan; Haviv, Izhak; Stern, Linda; Kowalczyk, Adam; Inouye, Michael

    2017-01-01

    Interaction analysis of GWAS can detect signal that would be ignored by single variant analysis, yet few robust interactions in humans have been detected. Recent work has highlighted interactions in the MHC region between known HLA risk haplotypes for various autoimmune diseases. To better understand the genetic interactions underlying celiac disease (CD), we have conducted exhaustive genome-wide scans for pairwise interactions in five independent CD case-control studies, using a rapid model-free approach to examine over 500 billion SNP pairs in total. We found 14 independent interaction signals within the MHC region that achieved stringent replication criteria across multiple studies and were independent of known CD risk HLA haplotypes. The strongest independent CD interaction signal corresponded to genes in the HLA class III region, in particular PRRC2A and GPANK1/C6orf47, which are known to contain variants for non-Hodgkin's lymphoma and early menopause, co-morbidities of celiac disease. Replicable evidence for statistical interaction outside the MHC was not observed. Both within and between European populations, we observed striking consistency of two-locus models and model distribution. Within the UK population, models of CD based on both interactions and additive single-SNP effects increased explained CD variance by approximately 1% over those of single SNPs. The interactions signal detected across the five cohorts indicates the presence of novel associations in the MHC region that cannot be detected using additive models. Our findings have implications for the determination of genetic architecture and, by extension, the use of human genetics for validation of therapeutic targets.

  15. C-H…pi interactions in proteins: prevalence, pattern of occurrence, residue propensities, location, and contribution to protein stability.

    PubMed

    Kumar, Manjeet; Balaji, Petety V

    2014-02-01

    C-H…pi interactions are a class of non-covalent interactions found in different molecular systems including organic crystals, proteins and nucleic acids. High-resolution protein structures have been analyzed in the present study to delineate various aspects of C-H…pi interactions. Additionally, to determine the extent to which redundancy of a database biases the outcome, two datasets differing from each other in the level of redundancy have been analyzed. On average, only one out of six {with C-H(Aro) group} or eight {with C-H(Ali) group} residues in a protein participate as C-H group donors. Neither the frequency of occurrence in proteins nor the number of C-H groups present in it is correlated to the propensity of an amino acid to participate in C-H…pi interactions. Most of the residues that participate in C-H…pi interactions are solvent-shielded. Solvent shielded nature of most of the C-H…pi interactions and prevalence of intra- as well as inter-secondary structural element C-H…pi interactions suggest that the contribution of these interactions to the enthalpy of folded form will be significant. The separation in the primary structure between donor and acceptor residues is found to be correlated to secondary structure type. Other insights obtained from this study include the presence of networks of C-H…pi interactions spanning multiple secondary structural elements. To our knowledge this has not been reported so far. A substantial number of residues involved in C-H…pi interactions are found in catalytic and ligand binding sites suggesting their possible role in maintaining active site geometry. No significant differences of C-H…pi interactions in the two datasets are found for any of the parameters/features analyzed.

  16. Evidence for contributions of interactions of constituents to the anti-inflammatory activity of Hypericum perforatum.

    PubMed

    Hammer, Kimberly D P; Birt, Diane F

    2014-01-01

    Hypericum perforatum (Hp) extracts contain many different classes of constituents including flavonoids and biflavonoids, phloroglucinols, naphthodianthrones, caffeic acid derivatives, and unknown and/or unidentified compounds. Many constituents may be responsible for the anti-inflammatory activity of Hp including quercetin and derivatives, hyperforin, pseudohypericin, and amentoflavone. In line with antidepressant data, it appears that the interactions of constituents may be important for the anti-inflammatory activity of Hp. Interactions of constituents, tested in bioavailability models, may explain why synergistic mechanisms have been found to be important for antidepressant and antiproliferative bioactivities. This review highlights the relationship among individual constituents and the anti-inflammatory activity of Hp extracts and proposes that interactions of constituents may be important for the anti-inflammatory activity of botanical extracts, although the exact mechanisms of the interactions are still unclear.

  17. Contributions of host cellular trafficking and organization to the outcomes of plant-pathogen interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In recent years it has become increasingly apparent that dynamic changes in protein localization, membrane trafficking pathways, and cellular organization play a major role in determining the outcome of interactions between plants and pathogenic microorganisms. Plants have evolved sophisticated perc...

  18. Species distribution models contribute to determine the effect of climate and interspecific interactions in moving hybrid zones.

    PubMed

    Engler, J O; Rödder, D; Elle, O; Hochkirch, A; Secondi, J

    2013-11-01

    Climate is a major factor delimiting species' distributions. However, biotic interactions may also be prominent in shaping geographical ranges, especially for parapatric species forming hybrid zones. Determining the relative effect of each factor and their interaction of the contact zone location has been difficult due to the lack of broad scale environmental data. Recent developments in species distribution modelling (SDM) now allow disentangling the relative contributions of climate and species' interactions in hybrid zones and their responses to future climate change. We investigated the moving hybrid zone between the breeding ranges of two parapatric passerines in Europe. We conducted SDMs representing the climatic conditions during the breeding season. Our results show a large mismatch between the realized and potential distributions of the two species, suggesting that interspecific interactions, not climate, account for the present location of the contact zone. The SDM scenarios show that the southerly distributed species, Hippolais polyglotta, might lose large parts of its southern distribution under climate change, but a similar gain of novel habitat along the hybrid zone seems unlikely, because interactions with the other species (H. icterina) constrain its range expansion. Thus, whenever biotic interactions limit range expansion, species may become 'trapped' if range loss due to climate change is faster than the movement of the contact zone. An increasing number of moving hybrid zones are being reported, but the proximate causes of movement often remain unclear. In a global context of climate change, we call for more interest in their interactions with climate change.

  19. Interactions between visual attention and episodic retrieval: dissociable contributions of parietal regions during gist-based false recognition.

    PubMed

    Guerin, Scott A; Robbins, Clifford A; Gilmore, Adrian W; Schacter, Daniel L

    2012-09-20

    The interaction between episodic retrieval and visual attention is relatively unexplored. Given that systems mediating attention and episodic memory appear to be segregated, and perhaps even in competition, it is unclear how visual attention is recruited during episodic retrieval. We investigated the recruitment of visual attention during the suppression of gist-based false recognition, the tendency to falsely recognize items that are similar to previously encountered items. Recruitment of visual attention was associated with activity in the dorsal attention network. The inferior parietal lobule, often implicated in episodic retrieval, tracked veridical retrieval of perceptual detail and showed reduced activity during the engagement of visual attention, consistent with a competitive relationship with the dorsal attention network. These findings suggest that the contribution of the parietal cortex to interactions between visual attention and episodic retrieval entails distinct systems that contribute to different components of the task while also suppressing each other.

  20. Contribution of Physical Interactions to Signaling Specificity between a Diguanylate Cyclase and Its Effector

    PubMed Central

    Dahlstrom, Kurt M.; Giglio, Krista M.; Collins, Alan J.; Sondermann, Holger

    2015-01-01

    ABSTRACT Cyclic diguanylate (c-di-GMP) is a bacterial second messenger that controls multiple cellular processes. c-di-GMP networks have up to dozens of diguanylate cyclases (DGCs) that synthesize c-di-GMP along with many c-di-GMP-responsive target proteins that can bind and respond to this signal. For such networks to have order, a mechanism(s) likely exists that allow DGCs to specifically signal their targets, and it has been suggested that physical interactions might provide such specificity. Our results show a DGC from Pseudomonas fluorescens physically interacting with its target protein at a conserved interface, and this interface can be predictive of DGC-target protein interactions. Furthermore, we demonstrate that physical interaction is necessary for the DGC to maximally signal its target. If such “local signaling” is a theme for even a fraction of the DGCs used by bacteria, it becomes possible to posit a model whereby physical interaction allows a DGC to directly signal its target protein, which in turn may help curtail undesired cross talk with other members of the network. PMID:26670387

  1. Gene-gene interactions contribute to eye colour variation in humans.

    PubMed

    Pośpiech, Ewelina; Draus-Barini, Jolanta; Kupiec, Tomasz; Wojas-Pelc, Anna; Branicki, Wojciech

    2011-06-01

    Prediction of phenotypes from genetic data is considered to be the first practical application of data gained from association studies, with potential importance for medicine and the forensic sciences. Multiple genes and polymorphisms have been found to be associated with variation in human pigmentation. Their analysis enables prediction of blue and brown eye colour with a reasonably high accuracy. More accurate prediction, especially in the case of intermediate eye colours, may require better understanding of gene-gene interactions affecting this polygenic trait. Using multifactor dimensionality reduction and logistic regression methods, a study of gene-gene interactions was conducted based on variation in 11 known pigmentation genes examined in a cohort of 718 individuals of European descent. The study revealed significant interactions of a redundant character between the HERC2 and OCA2 genes affecting determination of hazel eye colour and between HERC2 and SLC24A4 affecting determination of blue eye colour. Our research indicates interactive effects of a synergistic character between HERC2 and OCA2, and also provides evidence for a novel strong synergistic interaction between HERC2 and TYRP1, both affecting determination of green eye colour.

  2. Infrared study of polysubstitution effects in benzophenones and acetophenones: contribution of inter and intracycle interaction mechanism

    NASA Astrophysics Data System (ADS)

    Goethals, G.; Nadio, L.; Uzan, R.

    The carbonyl stretching frequencies of substituted 2-Me,2,6-diMe, 2-MeO benzophenones and 2-Me, 2-MeO acetophenones have been measured in diluted CCI 4, solutions. Two interaction mechanisms are observed. In X, Y substituted benzophenones with X on the same cycle as the ortho group and Y on the other cycle, it is shown that for X=Y, the effect of Y is greater than that of X except for very strong electron-releasing substituents. In this last case, the observed enhancement is attributed to the joint effects of intercycle interactions exercised on X and Y and of intracycle interaction on X. These results are corroborated by the study of substituted acetophenones in which only the intracycle mechanism can play a role.

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

    PubMed

    Mattfeld, Aaron T; Stark, Craig E L

    2015-08-01

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

  4. Inverse gene-for-gene interactions contribute additively to tan spot susceptibility in wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tan spot of wheat, caused by Pyrenophora tritici-repentis, is an important disease in almost all wheat-growing areas of the world. The disease system is known to involve at least three fungal-produced necrotrophic effectors (NEs) that interact with corresponding host sensitivity (S) genes in an inv...

  5. Spin Relaxation in III-V Semiconductors in various systems: Contribution of Electron-Electron Interaction

    NASA Astrophysics Data System (ADS)

    Dogan, Fatih; Kesserwan, Hasan; Manchon, Aurelien

    2015-03-01

    In spintronics, most of the phenomena that we are interested happen at very fast time scales and are rich in structure in time domain. Our understanding, on the other hand, is mostly based on energy domain calculations. Many of the theoretical tools use approximations and simplifications that can be perceived as oversimplifications. We compare the structure, material, carrier density and temperature dependence of spin relaxation time in n-doped III-V semiconductors using Elliot-Yafet (EY) and D'yakanov-Perel'(DP) with real time analysis using kinetic spin Bloch equations (KSBE). The EY and DP theories fail to capture details as the system investigated is varied. KSBE, on the other hand, incorporates all relaxation sources as well as electron-electron interaction which modifies the spin relaxation time in a non-linear way. Since el-el interaction is very fast (~ fs) and spin-conserving, it is usually ignored in the analysis of spin relaxation. Our results indicate that electron-electron interaction cannot be neglected and its interplay with the other (spin and momentum) relaxation mechanisms (electron-impurity and electron-phonon scattering) dramatically alters the resulting spin dynamics. We use each interaction explicitly to investigate how, in the presence of others, each relaxation source behaves. We use GaAs and GaN for zinc-blend structure, and GaN and AlN for the wurtzite structure.

  6. Does Teachers' Negotiation of Personal Cases in an Interactive Cyber Forum Contribute to Their Professional Learning?

    ERIC Educational Resources Information Center

    Ben-Peretz, Miriam; Kupferberg, Irit

    2007-01-01

    In this article, we explore an interactive learning process in a digital forum that focused on personal cases drawn from student teachers' classroom experience. To this end, we combined theoretical and methodological frameworks of knowledge-based and discourse-analytic perspectives that enabled us to uncover evidence showing what the students may…

  7. Plasmid replication initiator interactions with origin 13-mers and polymerase subunits contribute to strand-specific replisome assembly

    PubMed Central

    Wawrzycka, Aleksandra; Gross, Marta; Wasaznik, Anna; Konieczny, Igor

    2015-01-01

    Although the molecular basis for replisome activity has been extensively investigated, it is not clear what the exact mechanism for de novo assembly of the replication complex at the replication origin is, or how the directionality of replication is determined. Here, using the plasmid RK2 replicon, we analyze the protein interactions required for Escherichia coli polymerase III (Pol III) holoenzyme association at the replication origin. Our investigations revealed that in E. coli, replisome formation at the plasmid origin involves interactions of the RK2 plasmid replication initiation protein (TrfA) with both the polymerase β- and α-subunits. In the presence of other replication proteins, including DnaA, helicase, primase and the clamp loader, TrfA interaction with the β-clamp contributes to the formation of the β-clamp nucleoprotein complex on origin DNA. By reconstituting in vitro the replication reaction on ssDNA templates, we demonstrate that TrfA interaction with the β-clamp and sequence-specific TrfA interaction with one strand of the plasmid origin DNA unwinding element (DUE) contribute to strand-specific replisome assembly. Wild-type TrfA, but not the TrfA QLSLF mutant (which does not interact with the β-clamp), in the presence of primase, helicase, Pol III core, clamp loader, and β-clamp initiates DNA synthesis on ssDNA template containing 13-mers of the bottom strand, but not the top strand, of DUE. Results presented in this work uncovered requirements for anchoring polymerase at the plasmid replication origin and bring insights of how the directionality of DNA replication is determined. PMID:26195759

  8. The contribution of nonlocal electro-opto-thermal interaction to single molecule nonlinear Raman enhancement.

    PubMed

    Tai, Chao-Yi; Yu, Wen-Hsiang

    2013-10-21

    we develop a precise modelling where nonlocal electro-opto-thermal interactions are comprehensively included for the analysis of nonlinear Raman enhancement and plasmonic heating. An interaction enhancement factor G(IEF) is introduced to quantify the coupling between the electromagnetic field and the temperature field which is rarely considered in the estimation of Raman enhancement. For the case of isolated single nanosphere, G(IEF) can be up to ten, indicating a thermal origin which well explains the observed temperature rise, shortened blinking period, and the nonlinearly enhanced Raman cross-section. For the case of nanodimer, the suppression of plasmon heating was analyzed, demonstrating the great capability to mitigate biomolecular degradation and blinking.

  9. Competing interactions contributing to alpha-helical stability in aqueous solution.

    PubMed Central

    Bodkin, M. J.; Goodfellow, J. M.

    1995-01-01

    The stability of a 15-residue peptide has been investigated using CD spectroscopy and molecular simulation techniques. The sequence of the peptide was designed to include key features that are known to stabilize alpha-helices, including ion pairs, helix dipole capping, peptide bond capping, and aromatic interactions. The degree of helicity has been determined experimentally by CD in three solvents (aqueous buffer, methanol, and trifluoroethanol) and at two temperatures. Simulations of the peptide in the aqueous system have been performed over 500 ps at the same two temperatures using a fully explicit solvent model. Consistent with the CD data, the degree of helicity is decreased at the higher temperature. Our analysis of the simulation results has focused on competition between different side-chain/side-chain and side-chain/main-chain interactions, which can, in principle, stabilize the helix. The unfolding in aqueous solution occurs at the amino terminus because the side-chain interactions are insufficient to stabilize both the helix dipole and the peptide hydrogen bonds. Loss of capping of the peptide backbone leads to water insertion within the first peptide hydrogen bond and hence unfolding. In contrast, the carboxy terminus of the alpha-helix is stable in both simulations because the C-terminal lysine residue stabilizes the helix dipole, but at the expense of an ion pair. PMID:7613460

  10. Kinetic Contributions to Gating by Interactions Unique to N-methyl-d-aspartate (NMDA) Receptors*

    PubMed Central

    Borschel, William F.; Cummings, Kirstie A.; Tindell, LeeAnn K.; Popescu, Gabriela K.

    2015-01-01

    Among glutamate-gated channels, NMDA receptors produce currents that subside with unusually slow kinetics, and this feature is essential to the physiology of central excitatory synapses. Relative to the homologous AMPA and kainate receptors, NMDA receptors have additional intersubunit contacts in the ligand binding domain that occur at both conserved and non-conserved sites. We examined GluN1/GluN2A single-channel currents with kinetic analyses and modeling to probe these class-specific intersubunit interactions for their role in glutamate binding and receptor gating. We found that substitutions that eliminate such interactions at non-conserved sites reduced stationary gating, accelerated deactivation, and imparted sensitivity to aniracetam, an AMPA receptor-selective positive modulator. Abolishing unique contacts at conserved sites also reduced stationary gating and accelerated deactivation. These results show that contacts specific to NMDA receptors, which brace the heterodimer interface within the ligand binding domain, stabilize actively gating receptor conformations and result in longer bursts and slower deactivations. They support the view that the strength of the heterodimer interface modulates gating in both NMDA and non-NMDA receptors and that unique interactions at this interface are responsible in part for basic differences between the kinetics of NMDA and non-NMDA currents at glutamatergic synapses. PMID:26370091

  11. Contribution of myocardium hydraulic skeleton to left ventricular wall interaction and synergy in dogs.

    PubMed

    Barra, Juan Gabriel; Crottogini, Alberto José; Willshaw, Peter; Lascano, Elena Catalina; Pichel, Ricardo Horacio

    2004-08-01

    The most premature motion change after coronary occlusion is early diastolic thinning of the ischemic left ventricular (LV) wall, with concomitant thickening of the normoperfused wall. We aimed 1). to demonstrate that these early changes are the result of the absence of fluid within the ischemic myocardium (hydraulic skeleton) rather than to cell anoxia and 2). to quantitate the contribution of the lack of hydraulic skeleton to left ventricular asynergy of contraction in seven anesthetized dogs submitted to acute, short-lasting circumflex artery (Cx) occlusion (ischemia) and to perfusion of the Cx with an oxygen-free solution (anoxia). We analyzed the time course of regional work index (WI, area of the LV pressure-wall thickness loop) and regional efficiency (defined as the ratio of WI to the maximum possible work). Interwall asynergy was defined as the difference between the regional efficiency of the anterior and posterior walls. After 9-10 s, posterior wall efficiency decreased 37 +/- 6% with anoxia and 72 +/- 3% with ischemia (P < 0.025), and interwall asynergy was 0 +/- 6% with anoxia and 32 +/- 5% with ischemia (P < 0.05). The contribution of absent hydraulic skeleton to interwall asynergy (calculated as the difference between %asynergy in anoxia and %asynergy in ischemia) was 30 +/- 8% (P < 0.05). In conclusion, the earliest wall motion change observed after acute coronary occlusion, namely ischemic wall thinning concomitant with normoperfused wall thickening during isovolumic relaxation, is the result of the absence of intracoronary fluid. The lack of hydraulic skeleton within the myocardium contributes approximately 30% to interwall asynergy.

  12. Peroxisome proliferator activated receptor-γ-Rho-kinase interactions contribute to vascular remodeling after chronic intrauterine pulmonary hypertension

    PubMed Central

    Tseng, Nancy; Seedorf, Gregory; Roe, Gates; Abman, Steven H.

    2013-01-01

    Peroxisome proliferator-activated receptor-γ (PPARγ) and Rho-kinase (ROCK) regulate smooth muscle cell (SMC) proliferation and contribute to vascular remodeling in adult pulmonary hypertension. Whether these pathways interact to contribute to the development of vascular remodeling in persistent pulmonary hypertension of the newborn (PPHN) remains unknown. We hypothesized that ROCK-PPARγ interactions increase SMC proliferation resulting in vascular remodeling in experimental PPHN. Pulmonary artery SMCs (PASMCs) were harvested from fetal sheep after partial ligation of the ductus arteriosus in utero (PPHN) and controls. Cell counts were performed daily for 5 days with or without PPARγ agonists and ROCK inhibition. PPARγ and ROCK protein expression/activity were measured by Western blot in normal and PPHN PASMCs. We assessed PPARγ-ROCK interactions by studying the effect of ROCK activation on PPARγ activity and PPARγ inhibition (siRNA) on ROCK activity and PASMC proliferation. At baseline, PPHN PASMC cell number was increased by 38% above controls on day 5. ROCK protein expression/activity were increased by 25 and 34% and PPARγ protein/activity decreased by 40 and 50% in PPHN PASMC. ROCK inhibition and PPARγ activation restored PPHN PASMC growth to normal values. ROCK inhibition increased PPARγ activity by 50% in PPHN PASMC, restoring PPARγ activity to normal. In normal PASMCs, ROCK activation decreased PPARγ activity and PPARγ inhibition increased ROCK activity and cell proliferation, resulting in a PPHN hyperproliferative PASMC phenotype. PPARγ-ROCK interactions regulate SMC proliferation and contribute to increased PPHN PASMC proliferation and vascular remodeling in PPHN. Restoring normal PPARγ-ROCK signaling may prevent vascular remodeling and improve outcomes in PPHN. PMID:24375792

  13. Dopamine and oxytocin interactions underlying behaviors: potential contributions to behavioral disorders.

    PubMed

    Baskerville, Tracey A; Douglas, Alison J

    2010-06-01

    Dopamine is an important neuromodulator that exerts widespread effects on the central nervous system (CNS) function. Disruption in dopaminergic neurotransmission can have profound effects on mood and behavior and as such is known to be implicated in various neuropsychiatric behavioral disorders including autism and depression. The subsequent effects on other neurocircuitries due to dysregulated dopamine function have yet to be fully explored. Due to the marked social deficits observed in psychiatric patients, the neuropeptide, oxytocin is emerging as one particular neural substrate that may be influenced by the altered dopamine levels subserving neuropathologic-related behavioral diseases. Oxytocin has a substantial role in social attachment, affiliation and sexual behavior. More recently, it has emerged that disturbances in peripheral and central oxytocin levels have been detected in some patients with dopamine-dependent disorders. Thus, oxytocin is proposed to be a key neural substrate that interacts with central dopamine systems. In addition to psychosocial improvement, oxytocin has recently been implicated in mediating mesolimbic dopamine pathways during drug addiction and withdrawal. This bi-directional role of dopamine has also been implicated during some components of sexual behavior. This review will discuss evidence for the existence dopamine/oxytocin positive interaction in social behavioral paradigms and associated disorders such as sexual dysfunction, autism, addiction, anorexia/bulimia, and depression. Preliminary findings suggest that whilst further rigorous testing has to be conducted to establish a dopamine/oxytocin link in human disorders, animal models seem to indicate the existence of broad and integrated brain circuits where dopamine and oxytocin interactions at least in part mediate socio-affiliative behaviors. A profound disruption to these pathways is likely to underpin associated behavioral disorders. Central oxytocin pathways may serve as a

  14. Glycation Contributes to Interaction Between Human Bone Alkaline Phosphatase and Collagen Type I.

    PubMed

    Halling Linder, Cecilia; Enander, Karin; Magnusson, Per

    2016-03-01

    Bone is a biological composite material comprised primarily of collagen type I and mineral crystals of calcium and phosphate in the form of hydroxyapatite (HA), which together provide its mechanical properties. Bone alkaline phosphatase (ALP), produced by osteoblasts, plays a pivotal role in the mineralization process. Affinity contacts between collagen, mainly type II, and the crown domain of various ALP isozymes were reported in a few in vitro studies in the 1980s and 1990s, but have not attracted much attention since, although such interactions may have important implications for the bone mineralization process. The objective of this study was to investigate the binding properties of human collagen type I to human bone ALP, including the two bone ALP isoforms B1 and B2. ALP from human liver, human placenta and E. coli were also studied. A surface plasmon resonance-based analysis, supported by electrophoresis and blotting, showed that bone ALP binds stronger to collagen type I in comparison with ALPs expressed in non-mineralizing tissues. Further, the B2 isoform binds significantly stronger to collagen type I in comparison with the B1 isoform. Human bone and liver ALP (with identical amino acid composition) displayed pronounced differences in binding, revealing that post-translational glycosylation properties govern these interactions to a large extent. In conclusion, this study presents the first evidence that glycosylation differences in human ALPs are of crucial importance for protein-protein interactions with collagen type I, although the presence of the ALP crown domain may also be necessary. Different binding affinities among the bone ALP isoforms may influence the mineral-collagen interface, mineralization kinetics, and degree of bone matrix mineralization, which are important factors determining the material properties of bone.

  15. The importance of interacting climate modes on Australia’s contribution to global carbon cycle extremes

    PubMed Central

    Cleverly, James; Eamus, Derek; Luo, Qunying; Restrepo Coupe, Natalia; Kljun, Natascha; Ma, Xuanlong; Ewenz, Cacilia; Li, Longhui; Yu, Qiang; Huete, Alfredo

    2016-01-01

    The global carbon cycle is highly sensitive to climate-driven fluctuations of precipitation, especially in the Southern Hemisphere. This was clearly manifested by a 20% increase of the global terrestrial C sink in 2011 during the strongest sustained La Niña since 1917. However, inconsistencies exist between El Niño/La Niña (ENSO) cycles and precipitation in the historical record; for example, significant ENSO–precipitation correlations were present in only 31% of the last 100 years, and often absent in wet years. To resolve these inconsistencies, we used an advanced temporal scaling method for identifying interactions amongst three key climate modes (El Niño, the Indian Ocean dipole, and the southern annular mode). When these climate modes synchronised (1999–2012), drought and extreme precipitation were observed across Australia. The interaction amongst these climate modes, more than the effect of any single mode, was associated with large fluctuations in precipitation and productivity. The long-term exposure of vegetation to this arid environment has favoured a resilient flora capable of large fluctuations in photosynthetic productivity and explains why Australia was a major contributor not only to the 2011 global C sink anomaly but also to global reductions in photosynthetic C uptake during the previous decade of drought. PMID:26976754

  16. Wind-US Code Contributions to the First AIAA Shock Boundary Layer Interaction Prediction Workshop

    NASA Technical Reports Server (NTRS)

    Georgiadis, Nicholas J.; Vyas, Manan A.; Yoder, Dennis A.

    2013-01-01

    This report discusses the computations of a set of shock wave/turbulent boundary layer interaction (SWTBLI) test cases using the Wind-US code, as part of the 2010 American Institute of Aeronautics and Astronautics (AIAA) shock/boundary layer interaction workshop. The experiments involve supersonic flows in wind tunnels with a shock generator that directs an oblique shock wave toward the boundary layer along one of the walls of the wind tunnel. The Wind-US calculations utilized structured grid computations performed in Reynolds-averaged Navier-Stokes mode. Four turbulence models were investigated: the Spalart-Allmaras one-equation model, the Menter Baseline and Shear Stress Transport k-omega two-equation models, and an explicit algebraic stress k-omega formulation. Effects of grid resolution and upwinding scheme were also considered. The results from the CFD calculations are compared to particle image velocimetry (PIV) data from the experiments. As expected, turbulence model effects dominated the accuracy of the solutions with upwinding scheme selection indicating minimal effects.

  17. Intramolecular interactions contributing for the conformational preference of bioactive diphenhydramine: Manifestation of the gauche effect

    NASA Astrophysics Data System (ADS)

    de Rezende, Fátima M. P.; Andrade, Laize A. F.; Freitas, Matheus P.

    2015-08-01

    Diphenhydramine is an antihistamine used to treat some symptoms of allergies and the common cold. It is usually marketed as the hydrochloride salt, and both the neutral and cation forms have the O-C-C-N fragment. The gauche effect is well known in fluorine-containing chains, because its main origin is hyperconjugative and the σ∗C-F is a low-lying acceptor orbital, allowing electron delocalization in the conformation where F and an adjacent electronegative substituent in an ethane fragment are in the gauche orientation. Our experimental (NMR) and theoretical findings indicate that diphenhydramine exhibits the gauche effect, since the preferential conformations have the O-C-C-N moiety in this orientation due especially to antiperiplanar σC-H → σ∗C-O and σC-H → σ∗C-N interactions. This conformational preference is strengthened in the protonated form due to an incremental electrostatic gauche effect. Because the gauche conformation matches the bioactive structure of diphenhydramine complexed with histamine methyltransferase, it is suggested that intramolecular interactions, and not only induced fit, rule its bioactive form.

  18. The chiral S = -1 meson-baryon interaction with new constraints on the NLO contributions

    NASA Astrophysics Data System (ADS)

    Ramos, A.; Feijoo, A.; Magas, V. K.

    2016-10-01

    We present a study of the S = - 1 meson-baryon interaction, employing a chiral SU(3) Lagrangian up to next-to-leading order (NLO) and implementing unitarization in coupled channels. The parameters of the model have been fitted to a large set of experimental scattering data in different two-body channels, to threshold branching ratios, and to the precise SIDDHARTA value of the energy shift and width of kaonic hidrogen. In contrast to other groups, we have taken into consideration the K- p →K+Ξ- ,K0Ξ0 reaction data, since we found in a previous work to be especially sensitive to the NLO parameters of the chiral Lagrangian. In the present work we also include the Born terms, which usually have very little effect, and find them to be non-negligible in the K- p → KΞ channels, correspondingly causing significant modifications to the NLO parameters. We furthermore show that the importance of the Born terms becomes more visible in the isospin projected amplitudes of the K- p → KΞ reactions. The measurement of processes that filter single isospin components, like the KL0 p →K+Ξ0 reaction that could be measured at the proposed secondary KL0 beam at Jlab, would put valuable constraints on the chiral models describing the meson-baryon interaction in the S = - 1 sector.

  19. The contribution of parent-child interactions to smoking experimentation in adolescence: implications for prevention.

    PubMed

    White, James

    2012-02-01

    Because few prospective studies have examined the independent influence of mothers and fathers on smoking experimentation, we tested the association between a set of parent-specific, familial and peer interactions with smoking experimentation in early adolescence. Data come from two cohorts in the British Youth Panel Survey (N = 1736; mean age at baseline, 11.26; SD = 0.65), a study of children resident with members of the British Household Panel Survey. Baseline data showed 8.2% of participants had smoked which increased to 40.3% after a 3-year follow-up. Multivariate logistic regression models showed risk factors for the onset of experimentation included frequent time spent with peers (P < 0.001), maternal smoking (P = 0.001), female gender and older participant age (P < 0.001). Parent-child quarrels, mother-child conversations, family meal frequency and household income were not significantly associated with experimentation. Frequent father-child conversations, about things which mattered to children, were the only type of parent-child contact associated with a reduced risk of experimentation (P < 0.001), and a significant interaction suggested that maternal smoking increased the likelihood of girls but not boys experimentation (P = 0.01). This study suggests that familial risk and protective factors operate independently and that more attention should be paid to the role of fathers in smoking prevention.

  20. Contribution of dipole-dipole interactions to the stability of the collagen triple helix.

    PubMed

    Improta, Roberto; Berisio, Rita; Vitagliano, Luigi

    2008-05-01

    Unveiling sequence-stability and structure-stability relationships is a major goal of protein chemistry and structural biology. Despite the enormous efforts devoted, answers to these issues remain elusive. In principle, collagen represents an ideal system for such investigations due to its simplified sequence and regular structure. However, the definition of the molecular basis of collagen triple helix stability has hitherto proved to be a difficult task. Particularly puzzling is the decoding of the mechanism of triple helix stabilization/destabilization induced by imino acids. Although the propensity-based model, which correlates the propensities of the individual imino acids with the structural requirements of the triple helix, is able to explicate most of the experimental data, it is unable to predict the rather high stability of peptides embedding Gly-Hyp-Hyp triplets. Starting from the available X-ray structures of this polypeptide, we carried out an extensive quantum chemistry analysis of the mutual interactions established by hydroxyproline residues located at the X and Y positions of the Gly-X-Y motif. Our data clearly indicate that the opposing rings of these residues establish significant van der Waals and dipole-dipole interactions that play an important role in triple helix stabilization. These findings suggest that triple helix stabilization can be achieved by distinct structural mechanisms. The interplay of these subtle but recurrent effects dictates the overall stability of this widespread structural motif.

  1. Contribution of lateral interactions in V1 to organization of response properties.

    PubMed

    Wright, J J; Alexander, D M; Bourke, P D

    2006-09-01

    We propose a model of self-organization of synaptic connections in V1, emphasizing lateral interactions. Subject to Hebbian learning with decay, evolution of synaptic strengths proceeds to a stable state in which all synapses are either saturated, or have minimum pre/post-synaptic coincidence. The most stable configuration gives rise to anatomically realistic "local maps", each of macro-columnar size, and each organized as Mobius projections of retinotopic space. A tiling of V1, constructed of approximately mirror-image reflections of each local map by its neighbors is formed, accounting for orientation-preference singularities, linear zones, and saddle points-with each map linked by connections between sites of common orientation preference. Ocular dominance columns are partly explained as a special case of the same process. The occurrence of direction preference fractures always in odd numbers around singularities is a specific feature explained by the Mobius configuration of the local map. Effects of stimulus velocity, orientation relative to direction of motion, and extension, upon orientation preference, which are not accounted for by spatial filtering, are explained by interactions between the classic receptive field and global V1.

  2. Water absorption in PEEK and PEI matrices. Contribution to the understanding of water-polar group interactions

    NASA Astrophysics Data System (ADS)

    Courvoisier, E.; Bicaba, Y.; Colin, X.

    2016-05-01

    The water absorption in two aromatic linear polymers (PEEK and PEI) was studied between 10% and 90% RH at 30, 50 and 70°C. It was found that these polymers display classical Henry and Fick's behaviors. Moreover, they have very close values of equilibrium water concentration C∞ and water diffusivity D presumably because their respective polar groups establish molecular interactions of the same nature with water. This assumption was checked from a literature compilation of values of C∞ and D for a large variety of linear and tridimensional polymers containing a single type of polar group. It was then evidenced that almost all types of carbonyl group (in particular, those belonging to imides, amides and ketones) have the same molar contribution to water absorption, except those belonging to esters which are much less hydrophilic. Furthermore, hydroxyl and sulfone groups are much more hydrophilic than carbonyl groups so that their molar contribution is located on another master curve. On this basis, semi-empirical structure/water transport property relationships were proposed. It was found that C∞ increases exponentially with the concentration of polar groups (presumably because water is doubly bonded), but also with the intensity of their molecular interactions with water. In contrast, D is inversely proportional to C∞, which means that polar group-water interactions slow down the rate of water diffusion.

  3. Anomalously interacting Z* bosons: an example of JINR's contribution to physics at LHC

    NASA Astrophysics Data System (ADS)

    Bednyakov, V. A.; Yeletskikh, I. V.; Chizhov, M. V.; Boyko, I. R.

    2016-04-01

    Fundamental particle physics research at the Joint Institute for Nuclear Research (JINR) has always included the use of highest-energy accelerator machines, and it is only natural that from its very beginning, the institute played an active role in work on developing, assembling, and upgrading both the Large Hadron Collider itself and its detectors. Along with providing hardware and software support to secure the failure-free operation of detectors and the gathering and processing of experimental data, JINR sets as its primary goal to effectively participate in the unprecedentedly comprehensive and important LHC research program. As part of this program, the experimental search for new heavy chiral Z* and W* bosons is carried out by the ATLAS collaboration, an effort whose necessity was fully justified and strategy exhaustively developed by JINR physicists. The search results from the first run of the LHC are briefly discussed, together with the decisive contribution from JINR and future prospects.

  4. PRICKLE1 Contributes to Cancer Cell Dissemination through Its Interaction with mTORC2.

    PubMed

    Daulat, Avais M; Bertucci, François; Audebert, Stéphane; Sergé, Arnauld; Finetti, Pascal; Josselin, Emmanuelle; Castellano, Rémy; Birnbaum, Daniel; Angers, Stéphane; Borg, Jean-Paul

    2016-05-23

    Components of the evolutionarily conserved developmental planar cell polarity (PCP) pathway were recently described to play a prominent role in cancer cell dissemination. However, the molecular mechanisms by which PCP molecules drive the spread of cancer cells remain largely unknown. PRICKLE1 encodes a PCP protein bound to the promigratory serine/threonine kinase MINK1. We identify RICTOR, a member of the mTORC2 complex, as a PRICKLE1-binding partner and show that the integrity of the PRICKLE1-MINK1-RICTOR complex is required for activation of AKT, regulation of focal adhesions, and cancer cell migration. Disruption of the PRICKLE1-RICTOR interaction results in a strong impairment of breast cancer cell dissemination in xenograft assays. Finally, we show that upregulation of PRICKLE1 in basal breast cancers, a subtype characterized by high metastatic potential, is associated with poor metastasis-free survival.

  5. Peripheral interactions between cannabinoid and opioid systems contribute to the antinociceptive effect of crotalphine

    PubMed Central

    Machado, F C; Zambelli, V O; Fernandes, A C O; Heimann, A S; Cury, Y; Picolo, G

    2014-01-01

    Background and Purpose Crotalphine is an antinociceptive peptide that, despite its opioid-like activity, does not induce some of the characteristic side effects of opioids, and its amino acid sequence has no homology to any known opioid peptide. Here, we evaluated the involvement of the peripheral cannabinoid system in the crotalphine effect and its interaction with the opioid system. Experimental Approach Hyperalgesia was evaluated using the rat paw pressure test. Involvement of the cannabinoid system was determined using a selective cannabinoid receptor antagonist. Cannabinoid and opioid receptor activation were evaluated in paw slices by immunofluorescence assays using conformation state-sensitive antibodies. The release of endogenous opioid peptides from skin tissue was measured using a commercial enzyme immunoassay (EIA). Key Results Both p.o. (0.008–1.0 μg·kg−1) and intraplantar (0.0006 μg per paw) administration of crotalphine induced antinociception in PGE2-induced hyperalgesia. Antinociception by p.o. crotalphine (1 μg·kg−1) was blocked by AM630 (50 μg per paw), a CB2 receptor antagonist, and by antiserum anti-dynorphin A (1 μg per paw). Immunoassay studies confirmed that crotalphine increased the activation of both κ-opioid (51.7%) and CB2 (28.5%) receptors in paw tissue. The local release of dynorphin A from paw skin was confirmed by in vitro EIA and blocked by AM630. Conclusions and Implications Crotalphine-induced antinociception involves peripheral CB2 cannabinoid receptors and local release of dynorphin A, which is dependent on CB2 receptor activation. These results enhance our understanding of the mechanisms involved in the peripheral effect of crotalphine, as well as the interaction between the opioid and cannabinoid systems. PMID:24460677

  6. Contribution to the beam plasma material interactions during material processing with TEA CO2 laser radiation

    NASA Astrophysics Data System (ADS)

    Jaschek, Rainer; Konrad, Peter E.; Mayerhofer, Roland; Bergmann, Hans W.; Bickel, Peter G.; Kowalewicz, Roland; Kuttenberger, Alfred; Christiansen, Jens

    1995-03-01

    The TEA-CO2-laser (transversely excited atmospheric pressure) is a tool for the pulsed processing of materials with peak power densities up to 1010 W/cm2 and a FWHM of 70 ns. The interaction between the laser beam, the surface of the work piece and the surrounding atmosphere as well as gas pressure and the formation of an induced plasma influences the response of the target. It was found that depending on the power density and the atmosphere the response can take two forms. (1) No target modification due to optical break through of the atmosphere and therefore shielding of the target (air pressure above 10 mbar, depending on the material). (2) Processing of materials (air pressure below 10 mbar, depending on the material) with melting of metallic surfaces (power density above 0.5 109 W/cm2), hole formation (power density of 5 109 W/cm2) and shock hardening (power density of 3.5 1010 W/cm2). All those phenomena are usually linked with the occurrence of laser supported combustion waves and laser supported detonation waves, respectively for which the mechanism is still not completely understood. The present paper shows how short time photography and spatial and temporal resolved spectroscopy can be used to better understand the various processes that occur during laser beam interaction. The spectra of titanium and aluminum are observed and correlated with the modification of the target. If the power density is high enough and the gas pressure above a material and gas composition specific threshold, the plasma radiation shows only spectral lines of the background atmosphere. If the gas pressure is below this threshold, a modification of the target surface (melting, evaporation and solid state transformation) with TEA-CO2- laser pulses is possible and the material specific spectra is observed. In some cases spatial and temporal resolved spectroscopy of a plasma allows the calculation of electron temperatures by comparison of two spectral lines.

  7. Under the radar: how unexamined biases in decision-making processes in clinical interactions can contribute to health care disparities.

    PubMed

    Dovidio, John F; Fiske, Susan T

    2012-05-01

    Several aspects of social psychological science shed light on how unexamined racial/ethnic biases contribute to health care disparities. Biases are complex but systematic, differing by racial/ethnic group and not limited to love-hate polarities. Group images on the universal social cognitive dimensions of competence and warmth determine the content of each group's overall stereotype, distinct emotional prejudices (pity, envy, disgust, pride), and discriminatory tendencies. These biases are often unconscious and occur despite the best intentions. Such ambivalent and automatic biases can influence medical decisions and interactions, systematically producing discrimination in health care and ultimately disparities in health. Understanding how these processes may contribute to bias in health care can help guide interventions to address racial and ethnic disparities in health.

  8. Porcine epidemic diarrhea virus nucleoprotein contributes to HMGB1 transcription and release by interacting with C/EBP-β

    PubMed Central

    Huan, Chang-chao; Wang, Hua-xia; Sheng, Xiang-xiang; Wang, Rui; Wang, Xin; Liao, Ying; Liu, Qin-fang; Tong, Guang-zhi; Ding, Chan; Fan, Hong-jie; Wu, Jia-qiang; Mao, Xiang

    2016-01-01

    Porcine epidemic diarrhea is a devastating swine enteric disease, which is caused by porcine epidemic diarrhea virus (PEDV) infection. Our studies demonstrated that PEDV infection resulted in the up-regulation of proinflammatory cytokines. Meanwhile, PEDV infection and overexpression of viral nucleoprotein resulted in the acetylation and release of high mobility group box 1 proteins in vitro, an important proinflammatory response mediator, which contributes to the pathogenesis of various inflammatory diseases. Our studies also showed that SIRT1, histone acetyltransferase, and NF-κB regulated the acetylation and release of HMGB1. Chromatin immunoprecipitation, dual-luciferase reporter gene assay, and co-immunoprecipitation experiments illustrated that PEDV-N could induce HMGB1 transcription by interacting with C/EBP-β, which could bind to C/EBP motif in HMGB1 promotor region. Collectively, our data indicate PEDV-N contributes to HMGB1 transcription and the subsequent release/acetylation of HMGB1 during PEDV infection. PMID:27634894

  9. Neuron-Glia Interactions in Neural Plasticity: Contributions of Neural Extracellular Matrix and Perineuronal Nets

    PubMed Central

    Dzyubenko, Egor; Gottschling, Christine

    2016-01-01

    Synapses are specialized structures that mediate rapid and efficient signal transmission between neurons and are surrounded by glial cells. Astrocytes develop an intimate association with synapses in the central nervous system (CNS) and contribute to the regulation of ion and neurotransmitter concentrations. Together with neurons, they shape intercellular space to provide a stable milieu for neuronal activity. Extracellular matrix (ECM) components are synthesized by both neurons and astrocytes and play an important role in the formation, maintenance, and function of synapses in the CNS. The components of the ECM have been detected near glial processes, which abut onto the CNS synaptic unit, where they are part of the specialized macromolecular assemblies, termed perineuronal nets (PNNs). PNNs have originally been discovered by Golgi and represent a molecular scaffold deposited in the interface between the astrocyte and subsets of neurons in the vicinity of the synapse. Recent reports strongly suggest that PNNs are tightly involved in the regulation of synaptic plasticity. Moreover, several studies have implicated PNNs and the neural ECM in neuropsychiatric diseases. Here, we highlight current concepts relating to neural ECM and PNNs and describe an in vitro approach that allows for the investigation of ECM functions for synaptogenesis. PMID:26881114

  10. The contribution of plant-soil interactions to biogeochemical cycles in a changing world

    NASA Astrophysics Data System (ADS)

    Pregitzer, K.

    2005-12-01

    -induced changes to the Earth's atmosphere will cascade through plants into the soil, where microbial communities mediate the ecosystem functions that regulate biogeochemical cycles. There are several key research opportunities as we attempt to understand how changes in the Earth's atmosphere cascade through terrestrial ecosystems to alter biogeochemical cycles. For example, far too little attention has been given to how the interactions between changes in atmospheric chemistry (e.g. carbon dioxide and nitrogen, or carbon dioxide and ozone) will impact C transformations in the soil. If we deliberately set out to understand how variable plant and microbial physiology are to interactive changes in atmospheric chemistry, it should be possible to build a deeper understanding of the fundamental processes controlling ecosystem response to global change.

  11. PE_PGRS33 Contributes to Mycobacterium tuberculosis Entry in Macrophages through Interaction with TLR2.

    PubMed

    Palucci, Ivana; Camassa, Serena; Cascioferro, Alessandro; Sali, Michela; Anoosheh, Saber; Zumbo, Antonella; Minerva, Mariachiara; Iantomasi, Raffaella; De Maio, Flavio; Di Sante, Gabriele; Ria, Francesco; Sanguinetti, Maurizio; Palù, Giorgio; Brennan, Michael J; Manganelli, Riccardo; Delogu, Giovanni

    2016-01-01

    PE_PGRS represent a large family of proteins typical of pathogenic mycobacteria whose members are characterized by an N-terminal PE domain followed by a large Gly-Ala repeat-rich C-terminal domain. Despite the abundance of PE_PGRS-coding genes in the Mycobacterium tuberculosis (Mtb) genome their role and function in the biology and pathogenesis still remains elusive. In this study, we generated and characterized an Mtb H37Rv mutant (MtbΔ33) in which the structural gene of PE_PGRS33, a prototypical member of the protein family, was inactivated. We showed that this mutant entered macrophages with an efficiency up to ten times lower than parental or complemented strains, while its efficiency in infecting pneumocytes remained unaffected. Interestingly, the lack of PE_PGRS33 did not affect the intracellular growth of this mutant in macrophages. Using a series of functional deletion mutants of the PE_PGRS33 gene to complement the MtbΔ33 strain, we demonstrated that the PGRS domain is required to mediate cell entry into macrophages, with the key domain encompassing position 140-260 amino acids of PE_PGRS33. PE_PGRS33-mediated entry into macrophages was abolished in TLR2-deficient mice, as well as following treatment with wortmannin or an antibody against the complement receptor 3 (CR3), indicating that PE_PGRS33-mediated entry of Mtb in macrophages occurs through interaction with TLR2.

  12. A neuron-glia interaction involving GABA Transaminase contributes to sleep loss in sleepless mutants

    PubMed Central

    Chen, Wen-Feng; Maguire, Sarah; Sowcik, Mallory; Luo, Wenyu; Koh, Kyunghee; Sehgal, Amita

    2014-01-01

    Sleep is an essential process and yet mechanisms underlying it are not well understood. Loss of the Drosophila quiver/sleepless (qvr/sss) gene increases neuronal excitability and diminishes daily sleep, providing an excellent model for exploring the underpinnings of sleep regulation. Here, we used a proteomic approach to identify proteins altered in sss brains. We report that loss of sleepless post-transcriptionally elevates the CG7433 protein, a mitochondrial γ-aminobutyric acid transaminase (GABAT), and reduces GABA in fly brains. Loss of GABAT increases daily sleep and improves sleep consolidation, indicating that GABAT promotes wakefulness. Importantly, disruption of the GABAT gene completely suppresses the sleep phenotype of sss mutants, demonstrating that GABAT is required for loss of sleep in sss mutants. While SSS acts in distinct populations of neurons, GABAT acts in glia to reduce sleep in sss flies. Our results identify a novel mechanism of interaction between neurons and glia that is important for the regulation of sleep. PMID:24637426

  13. Testing the relative contribution of positive and negative interactions in rocky intertidal communities

    SciTech Connect

    Bertness, M.D.; Leonard, G.H.; Levine, J.M.; Schmidt, P.R.; Ingraham, A.O.

    1999-12-01

    In contrast to many other biotic forces, such as competition and predation, the role played by habitat modification by plants and sessile animals in natural communities has not been given the experimental attention it deserves. To test the hypothesis that habitat modification by seaweed canopies can have direct positive effects on rocky intertidal communities, the authors quantified habitat amelioration by Ascophyllum nodosum canopies and its consequences on understory organisms in the Gulf of Maine, USA. At the upper and lower elevational borders of the algal canopy, the authors examined the recruitment, growth, and survivorship of common benthic organisms in canopy removal, and shaded canopy removal plots intended to mimic canopy habitat modifications. The algal canopy greatly reduced potential physical stresses, particularly at high tidal heights. Maximum daily rock temperatures were 5--10 C lower and evaporative water loss was in order of magnitude less under the canopy than in canopy removal plots. The response of understory organisms to canopy removal, however, was species specific and somewhat idiosyncratic. Nonetheless, in general, at the high intertidal border of the canopy the recruitment, growth, and survival of understory organisms were enhanced by the canopy, whereas at the low intertidal border canopy effects were negative or neutral. nearly half of the interactions the authors studied were positive in the high zone.

  14. Actin-Interacting Protein 1 Contributes to Intranuclear Rod Assembly in Dictyostelium discoideum

    PubMed Central

    Ishikawa-Ankerhold, Hellen C.; Daszkiewicz, Wioleta; Schleicher, Michael; Müller-Taubenberger, Annette

    2017-01-01

    Intranuclear rods are aggregates consisting of actin and cofilin that are formed in the nucleus in consequence of chemical or mechanical stress conditions. The formation of rods is implicated in a variety of pathological conditions, such as certain myopathies and some neurological disorders. It is still not well understood what exactly triggers the formation of intranuclear rods, whether other proteins are involved, and what the underlying mechanisms of rod assembly or disassembly are. In this study, Dictyostelium discoideum was used to examine appearance, stages of assembly, composition, stability, and dismantling of rods. Our data show that intranuclear rods, in addition to actin and cofilin, are composed of a distinct set of other proteins comprising actin-interacting protein 1 (Aip1), coronin (CorA), filactin (Fia), and the 34 kDa actin-bundling protein B (AbpB). A finely tuned spatio-temporal pattern of protein recruitment was found during formation of rods. Aip1 is important for the final state of rod compaction indicating that Aip1 plays a major role in shaping the intranuclear rods. In the absence of both Aip1 and CorA, rods are not formed in the nucleus, suggesting that a sufficient supply of monomeric actin is a prerequisite for rod formation. PMID:28074884

  15. Do Interactions Between Gut Ecology and Environmental Chemicals Contribute to Obesity and Diabetes?

    PubMed Central

    Snedeker, Suzanne M.

    2011-01-01

    Background: Gut microbiota are important factors in obesity and diabetes, yet little is known about their role in the toxicodynamics of environmental chemicals, including those recently found to be obesogenic and diabetogenic. Objectives: We integrated evidence that independently links gut ecology and environmental chemicals to obesity and diabetes, providing a framework for suggesting how these environmental factors may interact with these diseases, and identified future research needs. Methods: We examined studies with germ-free or antibiotic-treated laboratory animals, and human studies that evaluated how dietary influences and microbial changes affected obesity and diabetes. Strengths and weaknesses of studies evaluating how environmental chemical exposures may affect obesity and diabetes were summarized, and research gaps on how gut ecology may affect the disposition of environmental chemicals were identified. Results: Mounting evidence indicates that gut microbiota composition affects obesity and diabetes, as does exposure to environmental chemicals. The toxicology and pharmacology literature also suggests that interindividual variations in gut microbiota may affect chemical metabolism via direct activation of chemicals, depletion of metabolites needed for biotransformation, alteration of host biotransformation enzyme activities, changes in enterohepatic circulation, altered bioavailability of environmental chemicals and/or antioxidants from food, and alterations in gut motility and barrier function. Conclusions: Variations in gut microbiota are likely to affect human toxicodynamics and increase individual exposure to obesogenic and diabetogenic chemicals. Combating the global obesity and diabetes epidemics requires a multifaceted approach that should include greater emphasis on understanding and controlling the impact of interindividual gut microbe variability on the disposition of environmental chemicals in humans. PMID:22042266

  16. RACK1, a new ADAM12 interacting protein. Contribution to liver fibrogenesis.

    PubMed

    Bourd-Boittin, Katia; Le Pabic, Hélène; Bonnier, Dominique; L'Helgoualc'h, Annie; Théret, Nathalie

    2008-09-19

    ADAM12 belongs to a disintegrin-like and metalloproteinase-containing protein family that possesses multidomain structures composed of a pro-domain, a metalloprotease, disintegrin-like, cysteine-rich, epidermal growth factor-like, and transmembrane domains, and a cytoplasmic tail. Overexpression of several ADAMs has been reported in human cancer, and we recently described the involvement of ADAM12 in liver injury (Le Pabic, H., Bonnier, D., Wewer, U. M., Coutand, A., Musso, O., Baffet, G., Clement, B., and Theret, N. (2003) Hepatology 37, 1056-1066). In this study, we used a yeast two-hybrid screening of a cDNA library from human hepatocellular carcinoma to analyze binding partners of ADAM12. We identify RACK1, a receptor for activated protein kinase C (PKC), as a new ADAM12 interacting protein. RACK1 is up-regulated in patients with hepatocellular carcinoma and is highly expressed by activated hepatic stellate cells. We demonstrate the involvement of RACK1 in mediating the PKC-dependent translocation of ADAM12 to membranes of activated hepatic stellate cells. In particular, treatment of cells with phorbol esters enhances ADAM12 immunostaining in the membrane fractions and the co-immunoprecipitation of ternary complexes containing RACK1, ADAM12, and PKC. By using RNA interference, we demonstrate that inhibition of RACK1 expression diminishes the phorbol 12-myristate 13-acetate-dependent translocation of ADAM12 to membranes of hepatic stellate cells. Finally, hepatic stellate cells cultured on coated type I collagen induces relocalization of ADAM12 in the membrane, suggesting that this major matrix component in liver cancer and fibrogenesis might stimulate ADAM12 translocation to the cell membrane where its shedding activity takes place.

  17. Glucocorticoid and polyamine interactions in the plasticity of glutamatergic synapses that contribute to ethanol-associated dependence and neuronal injury

    PubMed Central

    Prendergast, Mark A.; Mulholland, Patrick J.

    2011-01-01

    Stress both contributes to the development of ethanol dependence and is a consequence of dependence. However, the complexity of physiological interactions between activation of the hypothalamic-pituitary-adrenal (HPA) axis and ethanol itself is not well delineated. Emerging evidence derived from examination of corticotropin releasing factor systems and glucocorticoid receptor systems in ethanol dependence suggests a role for pharmacological manipulation of the HPA axis in attenuating ethanol intake, though it is not clear how activation of the HPA axis may promote ethanol dependence or contribute to the neuroadaptative changes that accompany the development of dependence and the severity of ethanol withdrawal. This review examines the role that glucocorticoids, in particular, have in promoting ethanol-associated plasticity of glutamatergic synapses by influencing expression of endogenous linear polyamines and polyamine-sensitive polypeptide subunits of N-methyl-d-aspartate (NMDA)-type glutamate receptors. We provide evidence that interactions among glucocorticoid systems, polyamines and NMDA receptors are highly relevant to both the development of ethanol dependence and to behavioral and neuropathological sequelae associated with ethanol withdrawal. Examination of these issues is likely to be of critical importance not only in further elucidating the neurobiology of HPA axis dysregulation in ethanol dependence, but also with regard to identification of novel therapeutic targets that may be exploited in the treatment of ethanol dependence. PMID:21967628

  18. Nontrivial contribution of Fröhlich electron-phonon interaction to lattice thermal conductivity of wurtzite GaN

    NASA Astrophysics Data System (ADS)

    Yang, Jia-Yue; Qin, Guangzhao; Hu, Ming

    2016-12-01

    The macroscopic thermal transport is fundamentally determined by the intrinsic interactions among microscopic electrons and phonons. In conventional insulators and semiconductors, phonons dominate the thermal transport, and the contribution of electron-phonon interaction (EPI) is negligible. However, in polar semiconductors, the Fröhlich electron-phonon coupling is strong and its influence on phononic thermal transport is of great significance. In this work, the effect of EPI on phonon dispersion and lattice thermal conductivity of wurtzite gallium nitride (GaN) is comprehensively investigated from the atomistic level by performing first-principles calculations. Due to the existence of relatively large electronegativity difference between Ga and N atoms, the Fröhlich coupling in wurtzite GaN is remarkably strong. Consequently, the lattice thermal conductivity of natural wurtzite GaN at room temperature is reduced by ˜24%-34% when including EPI, and the resulted thermal conductivity value is in better agreement with experiments. Furthermore, the scattering rate of phonons due to EPI, the intrinsic phonon-phonon interaction (PPI) as well as isotope disorder is computed and analyzed. It shows that the EPI scattering rate is comparable to PPI for low-frequency heat-carrying phonons. This work attempts to explore the mechanism of thermal transport beyond intrinsic PPI for polar semiconductors, with a great potential of thermal conductivity engineering for desired performance.

  19. Manufactured and Airborne Nanoparticle Cardiopulmonary Interactions: A Review of Mechanisms and the Possible Contribution of Mast Cells

    PubMed Central

    Shannahan, Jonathan H.; Kodavanti, Urmila P.; Brown, Jared M.

    2013-01-01

    Human inhalation exposures to manufactured nanoparticles (NP) and airborne ultrafine particles (UFP) continues to increase in both occupational and environmental settings. UFP exposures have been associated with increased cardiovascular mortality and morbidity, while ongoing research supports adverse systemic and cardiovascular health effects after NP exposures. Adverse cardiovascular health effects include alterations in heart rate variability, hypertension, thrombosis, arrhythmias, increased myocardial infarction, and atherosclerosis. Exactly how UFP and NP cause these negative cardiovascular effects is poorly understood, however a variety of mediators and mechanisms have been proposed. UFP and NP, as well as their soluble components, are known to systemically translocate from the lung. Translocated particles could mediate cardiovascular toxicity through direct interactions with the vasculature, blood, and heart. Recent study suggests that sensory nerve stimulation within the lung may also contribute to UFP- and NP-induced acute cardiovascular alterations. Activation of sensory nerves, such as C-fibers, within the lung may result in altered cardiac rhythm and function. Lastly, release of pulmonary-derived mediators into systemic circulation has been proposed to facilitate cardiovascular effects. In general, these proposed pulmonary-derived mediators include pro-inflammatory cytokines, oxidatively-modified macromolecules, vasoactive proteins, and prothrombotic factors. These pulmonary-derived mediators have been postulated to contribute to the subsequent prothrombotic, atherogenic, and inflammatory effects after exposure. This review will evaluate the potential contribution of individual mediators and mechanisms in facilitating cardiopulmonary toxicity following inhalation of UFP and NP. Lastly we will appraise the literature and propose a hypothesis regarding the possible role of mast cells in contributing to these systemic effects. PMID:22486349

  20. Direct Ca2+-dependent Heterophilic Interaction between Desmosomal Cadherins, Desmoglein and Desmocollin, Contributes to Cell–Cell Adhesion

    PubMed Central

    Chitaev, Nikolai A.; Troyanovsky, Sergey M.

    1997-01-01

    Human fibrosarcoma cells, HT-1080, feature extensive adherens junctions, lack mature desmosomes, and express a single known desmosomal protein, Desmoglein 2 (Dsg2). Transfection of these cells with bovine Desmocollin 1a (Dsc1a) caused dramatic changes in the subcellular distribution of endogenous Dsg2. Both cadherins clustered in the areas of the adherens junctions, whereas only a minor portion of Dsg2 was seen in these areas in the parental cells. Deletion mapping showed that intact extracellular cadherin-like repeats of Dsc1a (Arg1-Thr170) are required for the translocation of Dsg2. Deletion of the intracellular C-domain that mediates the interaction of Dsc1a with plakoglobin, or the CSI region that is involved in the binding to desmoplakin, had no effect. Coimmunoprecipitation experiments of cell lysates stably expressing Dsc1a with anti-Dsc or -Dsg antibodies demonstrate that the desmosomal cadherins, Dsg2 and Dsc1a, are involved in a direct Ca2+-dependent interaction. This conclusion was further supported by the results of solid phase binding experiments. These showed that the Dsc1a fragment containing cadherin-like repeats 1 and 2 binds directly to the extracellular portion of Dsg in a Ca2+-dependent manner. The contribution of the Dsg/ Dsc interaction to cell–cell adhesion was tested by coculturing HT-1080 cells expressing Dsc1a with HT-1080 cells lacking Dsc but expressing myc-tagged plakoglobin (MPg). In the latter cells, MPg and the endogenous Dsg form stable complexes. The observed specific coimmunoprecipitation of MPg by anti-Dsc antibodies in coculture indicates that an intercellular interaction between Dsc1 and Dsg is involved in cell–cell adhesion. PMID:9214392

  1. Functional contribution of chorismate synthase, anthranilate synthase, and chorismate mutase to penetration resistance in barley-powdery mildew interactions.

    PubMed

    Hu, Pingsha; Meng, Yan; Wise, Roger P

    2009-03-01

    Plant processes resulting from primary or secondary metabolism have been hypothesized to contribute to defense against microbial attack. Barley chorismate synthase (HvCS), anthranilate synthase alpha subunit 2 (HvASa2), and chorismate mutase 1 (HvCM1) occupy pivotal branch points downstream of the shikimate pathway leading to the synthesis of aromatic amino acids. Here, we provide functional evidence that these genes contribute to penetration resistance to Blumeria graminis f. sp. hordei, the causal agent of powdery mildew disease. Single-cell transient-induced gene silencing of HvCS and HvCM1 in mildew resistance locus a (Mla) compromised cells resulted in increased susceptibility. Correspondingly, overexpression of HvCS, HvASa2, and HvCM1 in lines carrying mildew resistance locus o (Mlo), a negative regulator of penetration resistance, significantly decreased susceptibility. Barley stripe mosaic virus-induced gene silencing of HvCS, HvASa2, and HvCM1 significantly increased B. graminis f. sp. hordei penetration into epidermal cells, followed by formation of haustoria and secondary hyphae. However, sporulation of B. graminis f. sp. hordei was not detected on the silenced host plants up to 3 weeks after inoculation. Taken together, these results establish a previously unrecognized role for the influence of HvCS, HvASa2, and HvCM1 on penetration resistance and on the rate of B. graminis f. sp. hordei development in Mla-mediated, barley-powdery mildew interactions.

  2. Different types of interaction between PCNA and PIP boxes contribute to distinct cellular functions of Y-family DNA polymerases

    PubMed Central

    Masuda, Yuji; Kanao, Rie; Kaji, Kentaro; Ohmori, Haruo; Hanaoka, Fumio; Masutani, Chikahide

    2015-01-01

    Translesion DNA synthesis (TLS) by the Y-family DNA polymerases Polη, Polι and Polκ, mediated via interaction with proliferating cell nuclear antigen (PCNA), is a crucial pathway that protects human cells against DNA damage. We report that Polη has three PCNA-interacting protein (PIP) boxes (PIP1, 2, 3) that contribute differentially to two distinct functions, stimulation of DNA synthesis and promotion of PCNA ubiquitination. The latter function is strongly associated with formation of nuclear Polη foci, which co-localize with PCNA. We also show that Polκ has two functionally distinct PIP boxes, like Polη, whereas Polι has a single PIP box involved in stimulation of DNA synthesis. All three polymerases were additionally stimulated by mono-ubiquitinated PCNA in vitro. The three PIP boxes and a ubiquitin-binding zinc-finger of Polη exert redundant and additive effects in vivo via distinct molecular mechanisms. These findings provide an integrated picture of the orchestration of TLS polymerases. PMID:26170230

  3. Partial Dominance, Overdominance, Epistasis and QTL by Environment Interactions Contribute to Heterosis in Two Upland Cotton Hybrids.

    PubMed

    Shang, Lianguang; Wang, Yumei; Cai, Shihu; Wang, Xiaocui; Li, Yuhua; Abduweli, Abdugheni; Hua, Jinping

    2015-12-29

    Based on two recombinant inbred line (RIL) populations, two corresponding backcross (BC) populations were constructed to elucidate the genetic basis of heterosis in Upland cotton (Gossypium hirsutum L.). The yield, and yield components, of these populations were evaluated in three environments. At the single-locus level, 78 and 66 quantitative trait loci (QTL) were detected using composite interval mapping in RIL and BC populations, respectively, and 29 QTL were identified based on mid-parental heterosis (MPH) data of two hybrids. Considering all traits together, a total of 50 (64.9%) QTL with partial dominance effect, and 27 (35.1%) QTL for overdominance effect were identified in two BC populations. At the two-locus level, 120 and 88 QTL with main effects (M-QTL), and 335 and 99 QTL involved in digenic interactions (E-QTL), were detected by inclusive composite interval mapping in RIL and BC populations, respectively. A large number of QTL by environment interactions (QEs) for M-QTL and E-QTL were detected in three environments. For most traits, average E-QTL explained a larger proportion of phenotypic variation than did M-QTL in two RIL populations and two BC populations. It was concluded that partial dominance, overdominance, epistasis, and QEs all contribute to heterosis in Upland cotton, and that partial dominance resulting from single loci and epistasis play a relatively more important role than other genetic effects in heterosis in Upland cotton.

  4. Enthalpy-entropy contributions to salt and osmolyte effects on molecular-scale hydrophobic hydration and interactions.

    PubMed

    Athawale, Manoj V; Sarupria, Sapna; Garde, Shekhar

    2008-05-08

    Salts and additives can significantly affect the strength of water-mediated interactions in solution. We present results from molecular dynamics simulations focused on the thermodynamics of hydrophobic hydration, association, and the folding-unfolding of a hydrophobic polymer in water and in aqueous solutions of NaCl and of an osmolyte trimethylamine oxide (TMAO). It is known that addition of NaCl makes the hydration of hydrophobic solutes unfavorable and, correspondingly, strengthens their association at the pair as well as the many-body level (Ghosh, T.; Kalra, A.; Garde, S. J. Phys. Chem. B 2005, 109, 642), whereas the osmolyte TMAO has an almost negligible effect on the hydrophobic hydration and association (Athawale, M. V.; Dordick, J. S.; Garde, S. Biophys. J. 2005, 89, 858). Whether these effects are enthalpic or entropic in origin is not fully known. Here we perform temperature-dependent simulations to resolve the free energy into entropy and enthalpy contributions. We find that in TMAO solutions, there is an almost precise entropy-enthalpy compensation leading to the negligible effect of TMAO on hydrophobic phenomena. In contrast, in NaCl solutions, changes in enthalpy dominate, making the salt-induced strengthening of hydrophobic interactions enthalpic in origin. The resolution of total enthalpy into solute-solvent and solvent-solvent terms further shows that enthalpy changes originate primarily from solvent-solvent energy terms. Our results are consistent with experimental data on the hydration of small hydrophobic solutes by Ben-Naim and Yaacobi (Ben-Naim, A.; Yaacobi, M. J. Phys. Chem. 1974, 78, 170). In combination with recent work by Zangi, Hagen, and Berne (Zangi, R.; Hagen, M.; Berne, B. J. J. Am. Chem. Soc. 2007, 129, 4678) and the experimental data on surface tensions of salt solutions by Matubayasi et al. (Matubayasi, N.; Matsuo, H.; Yamamoto, K.; Yamaguchi, S.; Matuzawa, A. J. Colloid Interface Sci. 1999, 209, 398), our results highlight

  5. Promoted Interaction of C/EBPα with Demethylated Cxcr3 Gene Promoter Contributes to Neuropathic Pain in Mice.

    PubMed

    Jiang, Bao-Chun; He, Li-Na; Wu, Xiao-Bo; Shi, Hui; Zhang, Wen-Wen; Zhang, Zhi-Jun; Cao, De-Li; Li, Chun-Hua; Gu, Jun; Gao, Yong-Jing

    2017-01-18

    DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes regulated by DNA methylation under neuropathic pain condition remain largely unknown. Here we investigated how chemokine receptor CXCR3 is regulated by DNA methylation and how it contributes to neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased Cxcr3 mRNA and protein expression in the neurons of the spinal cord. Meanwhile, the CpG (5'-cytosine-phosphate-guanine-3') island in the Cxcr3 gene promoter region was demethylated, and the expression of DNA methyltransferase 3b (DNMT3b) was decreased. SNL also increased the binding of CCAAT (cytidine-cytidine-adenosine-adenosine-thymidine)/enhancer binding protein α (C/EBPα) with Cxcr3 promoter and decreased the binding of DNMT3b with Cxcr3 promoter in the spinal cord. C/EBPα expression was increased in spinal neurons after SNL, and inhibition of C/EBPα by intrathecal small interfering RNA attenuated SNL-induced pain hypersensitivity and reduced Cxcr3 expression. Furthermore, SNL-induced mechanical allodynia and heat hyperalgesia were markedly reduced in Cxcr3(-/-) mice. Spinal inhibition of Cxcr3 by shRNA or CXCR3 antagonist also attenuated established neuropathic pain. Moreover, CXCL10, the ligand of CXCR3, was increased in spinal neurons and astrocytes after SNL. Superfusing spinal cord slices with CXCL10 enhanced spontaneous EPSCs and potentiated NMDA-induced and AMPA-induced currents of lamina II neurons. Finally, intrathecal injection of CXCL10 induced CXCR3-dependent pain hypersensitivity in naive mice. Collectively, our results demonstrated that CXCR3, increased by DNA demethylation and the enhanced interaction with C/EBPα, can be activated by CXCL10 to facilitate excitatory synaptic transmission and contribute to the maintenance of neuropathic pain.

  6. Promoted interaction of C/EBPα with demethylated Cxcr3 gene promoter contributes to neuropathic pain in mice.

    PubMed

    Jiang, Bao-Chun; He, Li-Na; Wu, Xiao-Bo; Shi, Hui; Zhang, Wen-Wen; Zhang, Zhi-Jun; Cao, De-Li; Li, Chun-Hua; Gu, Jun; Gao, Yong-Jing

    2016-12-09

    DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes that are regulated by DNA methylation under neuropathic pain condition remain largely unknown. Here we investigated how chemokine receptor CXCR3 is regulated by DNA methylation and its contribution to neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased Cxcr3 mRNA and protein expression in the neurons of spinal cord. Meanwhile, the CpG island in the Cxcr3 gene promoter region was demethylated, and the expression of DNA methyltransferase 3b (DNMT3b) was decreased. SNL also increased the binding of CCAAT/enhancer binding protein α (C/EBPα) with Cxcr3 promoter and decreased the binding of DNMT3b with Cxcr3 promoter in the spinal cord. C/EBPα expression was increased in spinal neurons after SNL, and inhibition of C/EBPα by intrathecal siRNA attenuated SNL-induced pain hypersensitivity and reduced Cxcr3 expression. Furthermore, SNL-induced mechanical allodynia and heat hyperalgesia were markedly reduced in Cxcr3(-/-) mice. Spinal inhibition of Cxcr3 by shRNA or CXCR3 antagonist also attenuated established neuropathic pain. Moreover, CXCL10, the ligand of CXCR3 was increased in spinal neurons and astrocytes after SNL. Superfusing spinal cord slices with CXCL10 enhanced spontaneous EPSCs and potentiated NMDA- and AMPA-induced currents of lamina II neurons. Finally, intrathecal injection of CXCL10 induced CXCR3-dependent pain hypersensitivity in naïve mice. Collectively, our results demonstrated that CXCR3, increased by DNA demethylation and the enhanced interaction with C/EBPα, can be activated by CXCL10 to facilitate excitatory synaptic transmission and contribute to the maintenance of neuropathic pain.

  7. Imbalanced K+ and Ca2+ subthreshold interactions contribute to increased hypothalamic presympathetic neuronal excitability in hypertensive rats

    PubMed Central

    Sonner, P M; Lee, S; Ryu, P D; Lee, S Y; Stern, J E

    2011-01-01

    We investigated here whether an opposing interplay between the subthreshold currents A-type potassium (IA) and T-type calcium (IT) influences membrane excitability in presympathetic neurones of the hypothalamic paraventricular nucleus (PVN) that innervate the rostral ventrolateral medulla (RVLM). Moreover, we assessed whether a shift in the balance between these two subthreshold currents contributed to increased neuronal activity in hypertension. To this end, we obtained simultaneous electrophysiological recordings, confocal Ca2+ imaging, and single-cell RT-PCR samples from identified PVN-RVLM neurones in sham and renovascular hypertensive rats. Our results indicate that IA and IT, displaying overlapping voltage-dependent and kinetic properties, are present in PVN-RVLM neurones. We found that the relative predominance of each current at hyperpolarized membrane potentials dictates whether PVN-RVLN neurones express a low-threshold spike (LTS) or a transient outward rectification (TOR). Moreover, we report the IA/IT balance to be correlated with the relative expression of Kv4.3 and Cav3.1 subunit mRNA within individual neurones. Pharmacological blockade of IA resulted in an enhanced IT-mediated LTS, as well as LTS-mediated somatodendritic Ca2+ transients. In hypertensive rats, we found a shift in the IT/IA balance, towards an IT predominance, due in part to a diminished Kv4.3 and enhanced Cav3.1 mRNA subunits expression. The imbalanced IT/IA relationship resulted in enhanced LTS, LTS-mediated somatodendritic Ca2+ transients, and increased firing activity in hypertensive rats. Taken together, our results support that a balanced IT/IA interaction influences membrane excitability and Ca2+ dynamics in PVN-RVLM neurones. Moreover, an imbalanced relationship favouring IT results in enhanced neuronal excitability and firing discharge in hypertensive rats, constituting thus a likely mechanism contributing to the characteristic sympathoexcitation observed in this disease. PMID

  8. Resolving the infection process reveals striking differences in the contribution of environment, genetics and phylogeny to host-parasite interactions

    PubMed Central

    2011-01-01

    Background Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them. Results Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes. Conclusions Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia-Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key force behind coevolutionary

  9. Lipid solvation effects contribute to the affinity of Gly-xxx-Gly motif-mediated helix-helix interactions.

    PubMed

    Johnson, Rachel M; Rath, Arianna; Melnyk, Roman A; Deber, Charles M

    2006-07-18

    Interactions between transmembrane helices are mediated by the concave Gly-xxx-Gly motif surface. Whether Gly residues per se are sufficient for selection of this motif has not been established. Here, we used the in vivo TOXCAT assay to measure the relative affinities of all 18 combinations of Gly, Ala, and Ser "small-xxx-small" mutations in glycophorin A (GpA) and bacteriophage M13 major coat protein (MCP) homodimers. Affinity values were compared with the accessibility to a methylene-sized probe of the total surface area of each helix monomer as a measure of solvation by membrane components. A strong inverse correlation was found between nonpolar-group lipid accessibility and dimer affinity (R = 0.75 for GpA, p = 0.013, and R = 0.81 for MCP, p = 0.004), suggesting that lipid as a poor membrane protein solvent, conceptually analogous to water in soluble protein folding, can contribute to dimer stability and help to define helix-helix interfaces.

  10. Downregulation of homeodomain-interacting protein kinase-2 contributes to bladder cancer metastasis by regulating Wnt signaling.

    PubMed

    Tan, Mingyue; Gong, Hua; Zeng, Yigang; Tao, Le; Wang, Jun; Jiang, Juntao; Xu, Dongliang; Bao, Erdun; Qiu, Jianxin; Liu, Zhihong

    2014-10-01

    Homeodomain-interacting protein kinase-2 (Hipk2) has been shown to have important regulatory roles in cancer biology, such as cancer cell proliferation, cell cycle, and cell invasion. However, the contributions of Hipk2 to bladder cancer metastasis remain largely unknown. In the current study, we assayed the expression level of Hipk2 in bladder cancer tissues by real-time PCR, and defined its biological functions. We found that Hipk2 levels were downregulated in most bladder cancer tissues compared with adjacent normal tissues, and Hipk2 levels were remarkably decreased in metastasized tumor tissues when compared with primary tumors. SiRNA-mediated Hipk2 silencing increased bladder cancer cell invasion. Hipk2 knockdown resulted in decrease of E-cadherin expression and increase of N-cadherin and fibronectin expression, indicated that epithelial-mesenchymal transition (EMT) was induced. We further demonstrated that Hipk2 knockdown induced Wnt signaling activation and β-catenin nuclear localization. Finally, we confirmed that Hipk2 inhibition promoted EMT and subsequent cell invasion, at least in part by activating Wnt signaling. These data suggest an important role of Hipk2 in regulating metastasis of bladder cancer and implicate the potential application of Hipk2 in bladder cancer therapy.

  11. Contributions of Phenylalanine 335 to Ligand Recognition by Human Surfactant Protein D: Ring Interactions with SP-D Ligands

    SciTech Connect

    Crouch,E.; McDonald, B.; Smith, K.; Cararella, T.; Seaton, B.; Head, J.

    2006-01-01

    Surfactant Protein D (SP-D) is an innate immune effector that contributes to antimicrobial host defense and immune regulation. Interactions of SP-D with microorganisms and organic antigens involve binding of glycoconjugates to the C-type lectin carbohydrate recognition domain (CRD). A trimeric fusion protein encoding the human neck+CRD (hNCRD) bound to the aromatic glycoside, p-nitrophenyl-alpha-D-maltoside, with nearly a log-fold higher affinity than maltose, the prototypical competitor. Maltotriose, which has the same linkage pattern as the maltoside, bound with intermediate affinity. Site-directed substitution of leucine for phenylalanine 335 (Phe335) decreased affinities for the maltoside and maltotriose without significantly altering the affinity for maltose or glucose, and substitution of tyrosine or tryptophan for leucine restored preferential binding to maltotriose and the maltoside. A mutant with alanine at this position failed to bind to mannan or maltose-substituted solid supports. Crystallographic analysis of the hNCRD complexed with maltotriose or p-nitrophenyl-maltoside showed stacking of the terminal glucose or nitrophenyl ring with the aromatic ring of Phe335. Our studies indicate that Phe335, which is evolutionarily conserved in all known SP-Ds, plays important - if not critical roles - in SP-D function.

  12. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb.

    PubMed

    Huettl, Rosa-Eva; Soellner, Heidi; Bianchi, Elisa; Novitch, Bennett G; Huber, Andrea B

    2011-02-01

    The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1) in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG), we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs.

  13. Permeant anions contribute to voltage dependence of ClC-2 chloride channel by interacting with the protopore gate

    PubMed Central

    Sánchez-Rodríguez, Jorge E; De Santiago-Castillo, José A; Arreola, Jorge

    2010-01-01

    It has been shown that the voltage (Vm) dependence of ClC Cl− channels is conferred by interaction of the protopore gate with H+ ions. However, in this paper we present evidence which indicates that permeant Cl− ions contribute to Vm-dependent gating of the broadly distributed ClC-2 Cl− channel. The apparent open probability (PA) of ClC-2 was enhanced either by changing the [Cl−]i from 10 to 200 mm or by keeping the [Cl−]i low (10 mm) and then raising [Cl−]o from 10 to 140 mm. Additionally, these changes in [Cl−] slowed down channel closing at positive Vm suggesting that high [Cl−] increased pore occupancy thus hindering closing of the protopore gate. The identity of the permeant anion was also important since the PA(Vm) curves were nearly identical with Cl− or Br− but shifted to negative voltages in the presence of SCN− ions. In addition, gating, closing rate and reversal potential displayed anomalous mole fraction behaviour in a SCN−/Cl− mixture in agreement with the idea that pore occupancy by different permeant anions modifies the Vm dependence ClC-2 gating. Based on the ec1-ClC anion pathway, we hypothesized that opening of the protopore gate is facilitated when Cl− ions dwell in the central binding site. In contrast, when Cl− ions dwell in the external binding site they prevent the gate from closing. Finally, this Cl−-dependent gating in ClC-2 channels is of physiological relevance since an increase in [Cl−]o enhances channel opening when the [Cl−]i is in the physiological range. PMID:20498235

  14. The Contribution of High-Order Metabolic Interactions to the Global Activity of a Four-Species Microbial Community

    PubMed Central

    Guo, Xiaokan

    2016-01-01

    The activity of a biological community is the outcome of complex processes involving interactions between community members. It is often unclear how to accurately incorporate these interactions into predictive models. Previous work has shown a range of positive and negative metabolic pairwise interactions between species. Here we examine the ability of a modified general Lotka-Volterra model with cell-cell interaction coefficients to predict the overall metabolic rate of a well-mixed microbial community comprised of four heterotrophic natural isolates, experimentally quantifying the strengths of two, three, and four-species interactions. Within this community, interactions between any pair of microbial species were positive, while higher-order interactions, between 3 or more microbial species, slightly modulated community metabolism. For this simple community, the metabolic rate of can be well predicted only with taking into account pairwise interactions. Simulations using the experimentally determined interaction parameters revealed that spatial heterogeneity in the distribution of cells increased the importance of multispecies interactions in dictating function at both the local and global scales. PMID:27623159

  15. The Contribution of the Dyadic Parent-Child Interaction Coding System (DPICS) Warm-Up Segments in Assessing Parent-Child Interactions

    ERIC Educational Resources Information Center

    Shanley, Jenelle R.; Niec, Larissa N.

    2011-01-01

    This study evaluated the inclusion of uncoded segments in the Dyadic Parent-Child Interaction Coding System, an analogue observation of parent-child interactions. The relationships between warm-up and coded segments were assessed, as well as the segments' associations with parent ratings of parent and child behaviors. Sixty-nine non-referred…

  16. To What Extent Do Teacher-Student Interaction Quality and Student Gender Contribute to Fifth Graders' Engagement in Mathematics Learning?

    ERIC Educational Resources Information Center

    Rimm-Kaufman, Sara E.; Baroody, Alison E.; Larsen, Ross A. A.; Curby, Timothy W.; Abry, Tashia

    2015-01-01

    This study examines concurrent teacher-student interaction quality and 5th graders' (n = 387) engagement in mathematics classrooms (n = 63) and considers how teacher-student interaction quality relates to engagement differently for boys and girls. Three approaches were used to measure student engagement in mathematics: Research assistants observed…

  17. Tertiary interactions between helices h13 and h44 in 16S RNA contribute to the fidelity of translation.

    PubMed

    Tran, Diem K; Finley, Jason; Vila-Sanjurjo, Antón; Lale, Ajit; Sun, Qing; O'Connor, Michael

    2011-11-01

    The A-minor interaction, formed between single-stranded adenosines and the minor groove of a receptor helix, is among the most common motifs found in rRNA. Among the A-minors found in 16S rRNA are a set of interactions between adenosines at positions 1433, 1434 and 1468 in helix 44 (h44) and their receptors in the nucleotide 320-340 region of helix 13 (h13). These interactions have been implicated in the maintenance of translational accuracy, because base substitutions at the adjacent C1469 increase miscoding errors. We have tested their functional significance through mutagenesis of h13 and h44. Mutations at the h44 A residues, or the A-minor receptors in h13, increase a variety of translational errors and a subset of the mutants show decreased association between 30S and 50S ribosomal subunits. These results are consistent with the involvement of h13-h44 interactions in the alignment and packing of these helices in the 30S subunit and the importance of this helical alignment for tRNA selection and subunit-subunit interaction.

  18. Functional Contribution of Chorismate Synthase, Anthranilate Synthase, and Chorismate Mutase to Penetration Resistance in Barley-Powdery Mildew Interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant processes resulting from primary or secondary metabolism have been hypothesized to contribute to defense against microbial attack. Barley chorismate synthase (HvCS), anthranilate synthase alpha subunit 2 (HvASa2) and chorismate mutase 1 (HvCM1) occupy pivotal branch-points downstream of the s...

  19. Mothers as a Resource in Times of Stress: Interactive Contributions of Socialization of Coping and Stress to Youth Psychopathology

    ERIC Educational Resources Information Center

    Abaied, Jamie L.; Rudolph, Karen D.

    2010-01-01

    This study examined the hypothesis that maternal socialization of coping would make a differential contribution to youth depression and externalizing psychopathology depending on youths' level of exposure to life stress. A sample of 155 youth (M age = 12.41, SD = 1.21) and their maternal caregivers completed semi-structured interviews and…

  20. What Are the Unique and Interacting Contributions of School and Family Factors to Early Adolescents' Empathic Concern and Perspective Taking?

    ERIC Educational Resources Information Center

    Batanova, Milena D.; Loukas, Alexandra

    2012-01-01

    Empathy in children has received considerable attention in the literature, but limited research has investigated the contributions of various socializing factors on both affective (e.g., empathic concern) and cognitive (e.g., perspective taking) components of empathy in early adolescents. Guided by socialization theories, this study examined the…

  1. Experimental assessment of the contribution of electrodynamic interactions to long-distance recruitment of biomolecular partners: Theoretical basis

    NASA Astrophysics Data System (ADS)

    Preto, Jordane; Floriani, Elena; Nardecchia, Ilaria; Ferrier, Pierre; Pettini, Marco

    2012-04-01

    Highly specific spatiotemporal interactions between cognate molecular partners essentially sustain all biochemical transactions in living matter. That such an exquisite level of accuracy may result from encountering forces solely driven by thermal diffusive processes is unlikely. Here we propose a yet unexplored strategy to experimentally tackle the long-standing question of a possibly active recruitment at a distance of cognate partners of biomolecular reactions via the action of resonant electrodynamic interactions. We considered two simplified models for a preliminary feasibility investigation of the devised methodology. By taking advantage of advanced experimental techniques nowadays available, we propose to measure the characteristic encounter time scales of dually interacting biopartners and to compare them with theoretical predictions worked out in both the presence and absence of putative long-range electromagnetic forces.

  2. Multivalent contacts of the Hsp70 Ssb contribute to its architecture on ribosomes and nascent chain interaction

    PubMed Central

    Hanebuth, Marie A.; Kityk, Roman; Fries, Sandra J.; Jain, Alok; Kriel, Allison; Albanese, Veronique; Frickey, Tancred; Peter, Christine; Mayer, Matthias P.; Frydman, Judith; Deuerling, Elke

    2016-01-01

    Hsp70 chaperones assist de novo folding of newly synthesized proteins in all cells. In yeast, the specialized Hsp70 Ssb directly binds to ribosomes. The structural basis and functional mode of recruitment of Ssb to ribosomes is not understood. Here, we present the molecular details underlying ribosome binding of Ssb in Saccharomyces cerevisiae. This interaction is multifaceted, involving the co-chaperone RAC and two specific regions within Ssb characterized by positive charges. The C-terminus of Ssb mediates the key contact and a second attachment point is provided by a KRR-motif in the substrate binding domain. Strikingly, ribosome binding of Ssb is not essential. Autonomous ribosome attachment becomes necessary if RAC is absent, suggesting a dual mode of Ssb recruitment to nascent chains. We propose, that the multilayered ribosomal interaction allows positioning of Ssb in an optimal orientation to the tunnel exit guaranteeing an efficient nascent polypeptide interaction. PMID:27917864

  3. Contribution of N- and C-terminal Kv4.2 channel domains to KChIP interaction [corrected].

    PubMed

    Callsen, Britta; Isbrandt, Dirk; Sauter, Kathrin; Hartmann, L Sven; Pongs, Olaf; Bähring, Robert

    2005-10-15

    Association of Shal gene-related voltage-gated potassium (Kv4) channels with cytoplasmic Kv channel interacting proteins (KChIPs) influences inactivation gating and surface expression. We investigated both functional and biochemical consequences of mutations in cytoplasmic N and C-terminal Kv4.2 domains to characterize structural determinants for KChIP interaction. We performed a lysine-scanning mutagenesis within the proximal 40 amino acid portion and a structure-based mutagenesis in the tetramerization 1 (T1) domain of Kv4.2. In addition, the cytoplasmic Kv4.2 C-terminus was truncated at various positions. Wild-type and mutant Kv4.2 channels were coexpressed with KChIP2 isoforms in mammalian cell lines. The KChIP2-induced modulation of Kv4.2 currents was studied with whole-cell patch clamp and the binding of KChIP2 isoforms to Kv4.2 channels with coimmunoprecipitation experiments. Our results define one major interaction site for KChIPs, including amino acids in the proximal N-terminus between residues 11 and 23, where binding and functional modulation are essentially equivalent. A further interaction site includes residues in the T1 domain. Notably, C-terminal deletions also had marked effects on KChIP2-dependent gating modulation and KChIP2 binding, revealing a previously unknown involvement of domains within the cytoplasmic Kv4.2 C-terminus in KChIP interaction. Less coincidence of binding and functional modulation indicates a more loose 'anchoring' at T1- and C-terminal interaction sites. Our results refine and extend previously proposed structural models for Kv4.2/KChIP complex formation.

  4. Contributions of Regulatable Quality and Teacher-Child Interaction to Children's Attachment Security with Day Care Teachers.

    ERIC Educational Resources Information Center

    Clawson, Mellisa A.

    This study examined regulatable quality and teacher-child interaction and, their influences on the quality of the attachment relationship developed by preschool children with their day care teachers. Observation and interview procedures were completed in 12 classrooms serving 194 preschoolers. Regulatable quality variables included teacher-child…

  5. The Contribution of Different Patterns of Teachers' Interactions to Young Children's Experiences of Democratic Values during Play

    ERIC Educational Resources Information Center

    Zachrisen, Berit

    2016-01-01

    Developing a sense of belonging and experiences about the value of community are important democratic values that children may learn during play in preschool. Through the different ways that teachers' interact with children during play, children can learn about democratic values. This study is part of a Nordic project on values education in early…

  6. Perceptual and Decisional Contributions to Audiovisual Interactions in the Perception of Apparent Motion: A Signal Detection Study

    ERIC Educational Resources Information Center

    Sanabria, Daniel; Spence, Charles; Soto-Faraco, Salvador

    2007-01-01

    Motion information available to different sensory modalities can interact at both perceptual and post-perceptual (i.e., decisional) stages of processing. However, to date, researchers have only been able to demonstrate the influence of one of these components at any given time, hence the relationship between them remains uncertain. We addressed…

  7. Regional aspects of the North American land surface: Atmosphere interactions and their contributions to the variability and predictability of the regional hydrologic cycle

    NASA Astrophysics Data System (ADS)

    Luo, Yan

    In this study, we investigate the pathways responsible for soil moisture-precipitation interactions and the mechanisms for soil moisture memory at regional scales through analysis of NCEP's North American Regional Reanalysis dataset, which is derived from a system using the mesoscale Eta model coupled with Noah land surface model. The consideration of the relative availability of water and energy leads to the relative strengths of land-atmosphere interaction and soil moisture memory, which are related to the predictability of the regional hydrologic cycle. The seasonal and geographical variations in estimated interaction and memory may establish the relative predictability among the North American basins. The potential for seasonal predictability of the regional hydrologic cycle is conditioned by the foreknowledge of the land surface soil state, which contributes significantly to summer precipitation: (i) The precipitation variability and predictability by strong land-atmosphere interactions are most important in the monsoon regions of Mexico; (ii) Although strong in interactions, the poor soil moisture memory in the Colorado basin and the western part of the Mississippi basin lowers the predictability; (iii) The Columbia basin and the eastern part of the Mississippi basin also stand out as low predictability basins, in that they have good soil moisture memory, but weak strength in interactions, limiting their predictabilities. Our analysis has revealed a highly physically and statistically consistent picture, providing solid support to studies of predictability based on model simulations.

  8. Nucleolin interacts with influenza A nucleoprotein and contributes to viral ribonucleoprotein complexes nuclear trafficking and efficient influenza viral replication

    PubMed Central

    Terrier, Olivier; Carron, Coralie; De Chassey, Benoît; Dubois, Julia; Traversier, Aurélien; Julien, Thomas; Cartet, Gaëlle; Proust, Anaïs; Hacot, Sabine; Ressnikoff, Denis; Lotteau, Vincent; Lina, Bruno; Diaz, Jean-Jacques; Moules, Vincent; Rosa-Calatrava, Manuel

    2016-01-01

    Influenza viruses replicate their single-stranded RNA genomes in the nucleus of infected cells and these replicated genomes (vRNPs) are then exported from the nucleus to the cytoplasm and plasma membrane before budding. To achieve this export, influenza viruses hijack the host cell export machinery. However, the complete mechanisms underlying this hijacking remain not fully understood. We have previously shown that influenza viruses induce a marked alteration of the nucleus during the time-course of infection and notably in the nucleolar compartment. In this study, we discovered that a major nucleolar component, called nucleolin, is required for an efficient export of vRNPs and viral replication. We have notably shown that nucleolin interacts with the viral nucleoprotein (NP) that mainly constitutes vRNPs. Our results suggest that this interaction could allow vRNPs to “catch” the host cell export machinery, a necessary step for viral replication. PMID:27373907

  9. Hsp90 interaction with Cdc2 and Plo1 kinases contributes to actomyosin ring condensation in fission yeast.

    PubMed

    Santino, Andrea; Tallada, Victor A; Jimenez, Juan; Garzón, Andrés

    2012-08-01

    In Schizosaccharomyces pombe, cytokinesis occurs by ordered recruitment of actomyosin components at the division site, followed by lateral condensation to produce a ring-like structure early in anaphase, which eventually matures and contracts at the end of mitosis. We found that in temperature-sensitive hsp90-w1 mutant cells, encoding an Hsp90 mutant protein, ring components were recruited to form a cortical network at the division site, but this network failed to condense into a compact ring, suggesting a role for Hsp90 in this particular step. hsp90-w1 mutant shows strong genetic interaction with specific mutant alleles of the fission yeast cdc2, such as cdc2-33. Interestingly, actomyosin ring defects in hsp90-w1 cdc2-33 mutant cells resembled that of hsp90-w1 single mutant at restrictive temperature. Noteworthy, similar genetic interaction was found with a mutant allele of polo-like kinase, plo1-ts4, suggesting that Hsp90 collaborates with Cdc2 and Plo1 cell cycle kinases to condense medial ring components. In vitro analyses suggested that Cdc2 and Plo1 physically interact with Hsp90. Association of Cdc2 to Hsp90 was ATP independent, while Plo1 binds to this chaperone in an ATP-dependent manner, indicating that these two kinases interact with different Hsp90 complexes. Overall, our analyses of hsp90-w1 reveal a possible role for this chaperone in medial ring condensation in association with Cdc2 and Plo1 kinases.

  10. Cell-cell and cell-surface interactions mediated by cellulose and a novel exopolysaccharide contribute to Pseudomonas putida biofilm formation and fitness under water-limiting conditions.

    PubMed

    Nielsen, Lindsey; Li, Xiaohong; Halverson, Larry J

    2011-05-01

    The composition of the exopolysaccharide matrix of Pseudomonas putida mt2 biofilms is relatively undefined as well as the contributions of each polymer to ecological fitness. Here, we describe the role of two putative exopolysaccharide gene clusters, putida exopolysaccharide A (pea) and bacterial cellulose (bcs) in biofilm formation and stability, rhizosphere colonization and matrix hydration under water-limiting conditions. Our findings suggest that pea is involved in the production of a novel glucose, galactose, and mannose-rich polymer that contributes to cell-cell interactions necessary for pellicle and biofilm formation and stability. In contrast, Bcs plays a minor role in biofilm formation and stability, although it does contribute to rhizosphere colonization based on a competition assay. We show that pea expression is highly induced transiently under water-limiting conditions but only slightly by high osmolarity, as determined by qRT-PCR. In contrast, both forms of water stress highly induced bcs expression. Cells deficient in making one or more exopolysaccharide experienced greater dehydration-mediated cell-envelope stress, leading to increased alginate promoter activity. However, this did not lead to increased exopolysaccharide production, except in bcs or pea mutants unable to produce alginate, indicating that P. putida compensates by producing, presumably more Pea or Bcs exopolysaccharides, to facilitate biofilm hydration. Collectively, the data suggest that Pea and Bcs contribute to biofilm formation and in turn their presence contributes to fitness under water-limiting conditions, but not to the extent of alginate.

  11. Electrostatic Contributions Drive the Interaction Between Staphylococcus aureus Protein Efb-C and its Complement Target C3d

    SciTech Connect

    Haspel, N.; Ricklin, D.; Geisbrecht, B.V.; Kavraki, L.E.; Lambris, J.D.

    2008-11-13

    The C3-inhibitory domain of Staphylococcus aureus extracellular fibrinogen-binding protein (Efb-C) defines a novel three-helix bundle motif that regulates complement activation. Previous crystallographic studies of Efb-C bound to its cognate subdomain of human C3 (C3d) identified Arg-131 and Asn-138 of Efb-C as key residues for its activity. In order to characterize more completely the physical and chemical driving forces behind this important interaction, we employed in this study a combination of structural, biophysical, and computational methods to analyze the interaction of C3d with Efb-C and the single-point mutants R131A and N138A. Our results show that while these mutations do not drastically affect the structure of the Efb-C/C3d recognition complex, they have significant adverse effects on both the thermodynamic and kinetic profiles of the resulting complexes. We also characterized other key interactions along the Efb-C/C3d binding interface and found an intricate network of salt bridges and hydrogen bonds that anchor Efb-C to C3d, resulting in its potent complement inhibitory properties.

  12. Electrostatic contributions drive the interaction between Staphylococcus aureus protein Efb-C and its complement target C3d.

    PubMed

    Haspel, Nurit; Ricklin, Daniel; Geisbrecht, Brian V; Kavraki, Lydia E; Lambris, John D

    2008-11-01

    The C3-inhibitory domain of Staphylococcus aureus extracellular fibrinogen-binding protein (Efb-C) defines a novel three-helix bundle motif that regulates complement activation. Previous crystallographic studies of Efb-C bound to its cognate subdomain of human C3 (C3d) identified Arg-131 and Asn-138 of Efb-C as key residues for its activity. In order to characterize more completely the physical and chemical driving forces behind this important interaction, we employed in this study a combination of structural, biophysical, and computational methods to analyze the interaction of C3d with Efb-C and the single-point mutants R131A and N138A. Our results show that while these mutations do not drastically affect the structure of the Efb-C/C3d recognition complex, they have significant adverse effects on both the thermodynamic and kinetic profiles of the resulting complexes. We also characterized other key interactions along the Efb-C/C3d binding interface and found an intricate network of salt bridges and hydrogen bonds that anchor Efb-C to C3d, resulting in its potent complement inhibitory properties.

  13. Gli2 gene-environment interactions contribute to the etiological complexity of holoprosencephaly: evidence from a mouse model.

    PubMed

    Heyne, Galen W; Everson, Joshua L; Ansen-Wilson, Lydia J; Melberg, Cal G; Fink, Dustin M; Parins, Kia F; Doroodchi, Padydeh; Ulschmid, Caden M; Lipinski, Robert J

    2016-11-01

    Holoprosencephaly (HPE) is a common and severe human developmental abnormality marked by malformations of the forebrain and face. Although several genetic mutations have been linked to HPE, phenotypic outcomes range dramatically, and most cases cannot be attributed to a specific cause. Gene-environment interaction has been invoked as a premise to explain the etiological complexity of HPE, but identification of interacting factors has been extremely limited. Here, we demonstrate that mutations in Gli2, which encodes a Hedgehog pathway transcription factor, can cause or predispose to HPE depending upon gene dosage. On the C57BL/6J background, homozygous GLI2 loss of function results in the characteristic brain and facial features seen in severe human HPE, including midfacial hypoplasia, hypotelorism and medial forebrain deficiency with loss of ventral neurospecification. Although normally indistinguishable from wild-type littermates, we demonstrate that mice with single-allele Gli2 mutations exhibit increased penetrance and severity of HPE in response to low-dose teratogen exposure. This genetic predisposition is associated with a Gli2 dosage-dependent attenuation of Hedgehog ligand responsiveness at the cellular level. In addition to revealing a causative role for GLI2 in HPE genesis, these studies demonstrate a mechanism by which normally silent genetic and environmental factors can interact to produce severe outcomes. Taken together, these findings provide a framework for the understanding of the extreme phenotypic variability observed in humans carrying GLI2 mutations and a paradigm for reducing the incidence of this morbid birth defect.

  14. HCI and mobile health interventions: How human-computer interaction can contribute to successful mobile health interventions.

    PubMed

    Poole, Erika S

    2013-12-01

    Advances in mobile computing offer the potential to change when, where, and how health interventions are delivered. Rather than relying on occasional in-clinic interactions, mobile health (mHealth) interventions may overcome constraints due to limited clinician time, poor patient adherence, and inability to provide meaningful interventions at the most appropriate time. Technological capability, however, does not equate with user acceptance and adoption. How then can we ensure that mobile technologies for behavior change meet the needs of their target audience? In this paper, we argue that overcoming acceptance and adoption barriers requires interdisciplinary collaborations, bringing together not only technologists and health researchers but also human-computer interaction (HCI) experts. We discuss the value of human-computer interaction research to the nascent field of mHealth and demonstrate how research from HCI can offer complementary insights on the creation of mobile health interventions. We conclude with a discussion of barriers to interdisciplinary collaborations in mobile health and suggest ways to overcome them.

  15. Gli2 gene-environment interactions contribute to the etiological complexity of holoprosencephaly: evidence from a mouse model

    PubMed Central

    Heyne, Galen W.; Everson, Joshua L.; Ansen-Wilson, Lydia J.; Melberg, Cal G.; Fink, Dustin M.; Parins, Kia F.; Doroodchi, Padydeh; Ulschmid, Caden M.

    2016-01-01

    ABSTRACT Holoprosencephaly (HPE) is a common and severe human developmental abnormality marked by malformations of the forebrain and face. Although several genetic mutations have been linked to HPE, phenotypic outcomes range dramatically, and most cases cannot be attributed to a specific cause. Gene-environment interaction has been invoked as a premise to explain the etiological complexity of HPE, but identification of interacting factors has been extremely limited. Here, we demonstrate that mutations in Gli2, which encodes a Hedgehog pathway transcription factor, can cause or predispose to HPE depending upon gene dosage. On the C57BL/6J background, homozygous GLI2 loss of function results in the characteristic brain and facial features seen in severe human HPE, including midfacial hypoplasia, hypotelorism and medial forebrain deficiency with loss of ventral neurospecification. Although normally indistinguishable from wild-type littermates, we demonstrate that mice with single-allele Gli2 mutations exhibit increased penetrance and severity of HPE in response to low-dose teratogen exposure. This genetic predisposition is associated with a Gli2 dosage-dependent attenuation of Hedgehog ligand responsiveness at the cellular level. In addition to revealing a causative role for GLI2 in HPE genesis, these studies demonstrate a mechanism by which normally silent genetic and environmental factors can interact to produce severe outcomes. Taken together, these findings provide a framework for the understanding of the extreme phenotypic variability observed in humans carrying GLI2 mutations and a paradigm for reducing the incidence of this morbid birth defect. PMID:27585885

  16. PARK2 and proinflammatory/anti-inflammatory cytokine gene interactions contribute to the susceptibility to leprosy: a case–control study of North Indian population

    PubMed Central

    Chopra, Rupali; Kalaiarasan, Ponnusamy; Ali, Shafat; Srivastava, Amit K; Aggarwal, Shweta; Garg, Vijay K; Bhattacharya, Sambit N; Bamezai, Rameshwar N K

    2014-01-01

    Objectives Cytokines and related molecules in immune-response pathways seem important in deciding the outcome of the host–pathogen interactions towards different polar forms in leprosy. We studied the role of significant and functionally important single-nucleotide polymorphisms (SNPs) in these genes, published independently from our research group, through combined interaction with an additional analysis of the in silico network outcome, to understand how these impact the susceptibility towards the disease, leprosy. Design The study was designed to assess an overall combined contribution of significantly associated individual SNPs to reflect on epistatic interactions and their outcome in the form of the disease, leprosy. Furthermore, in silico approach was adopted to carry out protein–protein interaction study between PARK2 and proinflammatory/anti-inflammatory cytokines. Setting Population-based case–control study involved the data of North India. Protein–protein interaction networks were constructed using cytoscape. Participants Study included the data available from 2305 Northern Indians samples (829 patients with leprosy; 1476 healthy controls), generated by our research group. Primary and secondary outcome measures For genotype interaction analysis, all possible genotype combinations between selected SNPs were used as an independent variable, using binary logistic regression with the forward likelihood ratio method, keeping the gender as a covariate. Results Interaction analysis between PARK2 and significant SNPs of anti-inflammatory/proinflammatory cytokine genes, including BAT1 to BTNL2-DR spanning the HLA (6p21.3) region in a case–control comparison, showed that the combined analysis of: (1) PARK2, tumour necrosis factor (TNF), BTNL2-DR, interleukin (IL)-10, IL-6 and TGFBR2 increased the risk towards leprosy (OR=2.54); (2) PARK2, BAT1, NFKBIL1, LTA, TNF-LTB, IL12B and IL10RB provided increased protection (OR=0.26) in comparison with their

  17. Gut microbiota in Drosophila melanogaster interacts with Wolbachia but does not contribute to Wolbachia-mediated antiviral protection.

    PubMed

    Ye, Yixin H; Seleznev, Andrei; Flores, Heather A; Woolfit, Megan; McGraw, Elizabeth A

    2017-02-01

    Animals experience near constant infection with microorganisms. A significant proportion of these microbiota reside in the alimentary tract. There is a growing appreciation for the roles gut microbiota play in host biology. The gut microbiota of insects, for example, have been shown to help the host overcome pathogen infection either through direct competition or indirectly by stimulating host immunity. These defenses may also be supplemented by coinfecting maternally inherited microbes such as Wolbachia. The presence of Wolbachia in a host can delay and/or reduce death caused by RNA viruses. Whether the gut microbiota of the host interacts with Wolbachia, or vice versa, the precise role of Wolbachia in antiviral protection is not known. In this study, we used 16S rDNA sequencing to characterise changes in gut microbiota composition in Drosophila melanogaster associated with Wolbachia infection and antibiotic treatment. We subsequently tested whether changes in gut composition via antibiotic treatment altered Wolbachia-mediated antiviral properties. We found that both antibiotics and Wolbachia significantly reduced the biodiversity of the gut microbiota without changing the total microbial load. We also showed that changing the gut microbiota composition with antibiotic treatment enhanced Wolbachia density but did not confer greater antiviral protection against Drosophila C virus to the host. We concluded there are significant interactions between Wolbachia and gut microbiota, but changing gut microbiota composition is not likely to be a means through which Wolbachia conveys antiviral protection to its host.

  18. Higher-order electric multipole contributions to retarded non-additive three-body dispersion interaction energies between atoms: equilateral triangle and collinear configurations.

    PubMed

    Salam, A

    2013-12-28

    The theory of molecular quantum electrodynamics (QED) is used to calculate higher electric multipole contributions to the dispersion energy shift between three atoms or molecules arranged in a straight line or in an equilateral triangle configuration. As in two-body potentials, three-body dispersion interactions are viewed in the QED formalism to arise from exchange of virtual photons between coupled pairs of particles. By employing an interaction Hamiltonian that is quadratic in the electric displacement field means that third-order perturbation theory can be used to yield the energy shift for a particular combination of electric multipole polarizable species, with only six time-ordered diagrams needing to be summed over. Specific potentials evaluated include dipole-dipole-quadrupole (DDQ), dipole-quadrupole-quadrupole (DQQ), and dipole-dipole-octupole (DDO) terms. For the geometries of interest, near-zone limiting forms are found to exhibit an R(-11) dependence on separation distance for the DDQ interaction, and an R(-13) behaviour for DQQ and DDO shifts, agreeing with an earlier semi-classical computation. Retardation weakens the potential in each case by R(-1) in the far-zone. It is found that by decomposing the octupole moment into its irreducible components of weights-1 and -3 that the former contribution to the DDO potential may be taken to be a higher-order correction to the leading triple dipole energy shift.

  19. Higher-order electric multipole contributions to retarded non-additive three-body dispersion interaction energies between atoms: Equilateral triangle and collinear configurations

    SciTech Connect

    Salam, A.

    2013-12-28

    The theory of molecular quantum electrodynamics (QED) is used to calculate higher electric multipole contributions to the dispersion energy shift between three atoms or molecules arranged in a straight line or in an equilateral triangle configuration. As in two-body potentials, three-body dispersion interactions are viewed in the QED formalism to arise from exchange of virtual photons between coupled pairs of particles. By employing an interaction Hamiltonian that is quadratic in the electric displacement field means that third-order perturbation theory can be used to yield the energy shift for a particular combination of electric multipole polarizable species, with only six time-ordered diagrams needing to be summed over. Specific potentials evaluated include dipole-dipole-quadrupole (DDQ), dipole-quadrupole-quadrupole (DQQ), and dipole-dipole-octupole (DDO) terms. For the geometries of interest, near-zone limiting forms are found to exhibit an R{sup −11} dependence on separation distance for the DDQ interaction, and an R{sup −13} behaviour for DQQ and DDO shifts, agreeing with an earlier semi-classical computation. Retardation weakens the potential in each case by R{sup −1} in the far-zone. It is found that by decomposing the octupole moment into its irreducible components of weights-1 and -3 that the former contribution to the DDO potential may be taken to be a higher-order correction to the leading triple dipole energy shift.

  20. New insights into the interactions between cork chemical components and pesticides. The contribution of π-π interactions, hydrogen bonding and hydrophobic effect.

    PubMed

    Olivella, M À; Bazzicalupi, C; Bianchi, A; Fiol, N; Villaescusa, I

    2015-01-01

    The role of chemical components of cork in the sorption of several pesticides has been investigated. For this purpose raw cork and three cork extracted fractions (i.e. cork free of aliphatic extractives, cork free of all extractives and cork free of all extractives and suberin) were used as sorbent of three ionic pesticides (propazine, 2,4-dichlorophenoxy acetic acid (2,4-D) and alachlor) and five non-ionic pesticides (chlorpyrifos, isoproturon, metamitron, methomyl and oxamyl) with a logKow within the range -0.47 to 4.92. The effect of cations on the ionic pesticides, propazine and 2,4-D sorption was also analyzed. Results indicated that the highest yields were obtained for chlorpyrifos and alachlor sorption onto raw cork (>55%). After removal of aliphatic extractives sorption of all pesticides increased that ranged from 3% for propazine to 31% for alachlor. In contrast, removal of phenolic extractives caused a sorption decrease. Low sorption yields were obtained for hydrophobic pesticides such as metamitron, oxamyl and methomyl (<11%) by using all cork fractions and extremely low when using raw cork (<1%). FTIR analysis was useful to indicate that lignin moieties were the main components involved on the sorption process. Modelling calculations evidenced that π-stacking interactions with the aromatic groups of lignin play a major role in determining the adsorption properties of cork toward aromatic pesticides. Results presented in this paper gain insights into the cork affinities for pesticides and the interactions involved in the sorption process and also enables to envisage sorption affinity of cork for other organic pollutants.

  1. Contribution of TRPV1-TRPA1 interaction to the single channel properties of the TRPA1 channel.

    PubMed

    Staruschenko, Alexander; Jeske, Nathaniel A; Akopian, Armen N

    2010-05-14

    Several lines of evidence suggest that TRPA1 and TRPV1 mutually control the transduction of inflammation-induced noxious stimuli in sensory neurons. It was recently shown that certain TRPA1 properties are modulated by TRPV1. However, direct interaction between TRPA1 and TRPV1 as well as regulation of TRPA1 intrinsic characteristics by the TRPV1 channel have not been examined. To address these questions, we have studied a complex formation between TRPA1 and TRPV1 and characterized the influence of TRPV1 on single channel TRPA1-mediated currents. Co-immunoprecipitation analysis revealed direct interactions between TRPA1 and TRPV1 in an expression system as well as in sensory neurons. Data generated with total internal reflection fluorescence-based fluorescence resonance energy transfer indicate that a TRPA1-TRPV1 complex can be formed on the plasma membrane. The fluorescence resonance energy transfer interaction between TRPA1 and TRPV1 channels is as effective as for TRPV1 or TRPA1 homomers. Single channel analysis in a heterologous expression system and in sensory neurons of wild type and TRPV1 knock-out mice demonstrated that co-expression of TRPV1 with TRPA1 results in outward rectification of single channel mustard oil (I(MO)) current-voltage relationships (I-V) and substantial modulation of the open probability at negative holding potentials. TRPV1 also does not influence the characteristics of single channel I(MO) in Ca(2+)-free extracellular solution. However, association of TRPA1 with TRPV1 was not affected in Ca(2+)-free media. To assess a role of intracellular Ca(2+) in TRPV1-dependent modulation of TRPA1 modulation, the TRPA1-mediated single channel WIN55,212-2-gated current (I(WIN)) was recorded in inside-out configuration. Our data indicate that single channel properties of TRPA1 are regulated by TRPV1 independently of intracellular Ca(2+). In summary, our results support the hypothesis that TRPV1 and TRPA1 form a complex and that TRPV1 influences

  2. Interaction between ZBP-89 and p53 mutants and its contribution to effects of HDACi on hepatocellular carcinoma.

    PubMed

    Zhang, Chris Z Y; Chen, George G; Merchant, Juanita L; Lai, Paul B S

    2012-01-15

    ZBP-89, a zinc finger transcription factor, participates in histone deacetylases inhibitors (HDACi)-mediated growth arrest and apoptosis in cancer cells. p53 mutants may interact with ZBP-89 that transcriptionally regulates p21(Waf1) (p21). However, this interaction and its consequence in cancer treatments are poorly understood. In this study, we demonstrate that ZBP‑89 is essentially required in HDACi-mediated p21 upregulation in hepetocellular carcinoma (HCC). Overexpression of ZBP-89 protein enhanced the lethal effectiveness of Trichostatin A (TSA). p53 mutant p53(G245D), but not p53(R249S), directly bound to ZBP-89 and prevented its translocation from cytoplasm to nucleus. Furthermore, p53(G245D) was shown to have a similar pattern of subcellular localization to ZBP-89 in tissues of HCC patients in Hong Kong. Functionally, the cytoplasmic accumulation of ZBP-89 by p53(G245D) significantly abrogated the induction of p21 caused by sodium butyrate (NaB) treatment and protected cells from TSA-induced death. The activations of several apoptotic proteins, such as Bid and PARP, were involved in p53(G245D)-mediated protection. Moreover, the resistance to HDACi in p53(G245D)-expressing cells was reversed by overexpression of ZBP-89. Taken together, these data suggest a potential mechanism via which mutant p53 enables tumor cells to resist chemotherapy and, therefore, establish a plausible link between mutant p53 binding to ZBP-89 and a decreased chemosensitivity of HCC cells.

  3. Comparison of MCNPX and GEANT4 to Predict the Contribution of Non-elastic Nuclear Interactions to Absorbed Dose in Water, PMMA and A150

    NASA Astrophysics Data System (ADS)

    Shtejer, K.; Arruda-Neto, J. D. T.; Schulte, R.; Wroe, A.; Rodrigues, T. E.; de Menezes, M. O.; Moralles, M.; Guzmán, F.; Manso, M. V.

    2008-08-01

    Proton induced non-elastic nuclear reactions play an important role in the dose distribution of clinically used proton beams as they deposit dose of high biological effectiveness both within the primary beam path as well as outside the beam to untargeted tissues. Non-elastic nuclear reactions can be evaluated using transport codes based on the Monte Carlo method. In this work, we have utilized the Los Alamos code MCNPX and the CERN GEANT4 toolkit, which are currently the most widely used Monte Carlo programs for proton radiation transport simulations in medical physics, to study the contribution of non-elastic nuclear interactions to the absorbed dose of proton beams in the therapeutic energy range. The impact of different available theoretical models to address the nuclear reaction process was investigated. The contribution of secondary particles from non-elastic nuclear reactions was calculated in three materials relevant in radiotherapy applications: water, PMMA and A150. The results evidence that there are differences in the calculated contribution of the secondary particles heavier than protons to the absorbed dose, with different approaches to model the nuclear reactions. The MCNPX calculation give rise to a larger contribution of d, t, α3He to the total dose compared to the GEANT4 physical models chosen in this work.

  4. Comparison of MCNPX and GEANT4 to Predict the Contribution of Non-elastic Nuclear Interactions to Absorbed Dose in Water, PMMA and A150

    SciTech Connect

    Shtejer, K.; Arruda-Neto, J. D. T.; Rodrigues, T. E.; Schulte, R.; Wroe, A.; Menezes, M. O. de; Moralles, M.

    2008-08-11

    Proton induced non-elastic nuclear reactions play an important role in the dose distribution of clinically used proton beams as they deposit dose of high biological effectiveness both within the primary beam path as well as outside the beam to untargeted tissues. Non-elastic nuclear reactions can be evaluated using transport codes based on the Monte Carlo method. In this work, we have utilized the Los Alamos code MCNPX and the CERN GEANT4 toolkit, which are currently the most widely used Monte Carlo programs for proton radiation transport simulations in medical physics, to study the contribution of non-elastic nuclear interactions to the absorbed dose of proton beams in the therapeutic energy range. The impact of different available theoretical models to address the nuclear reaction process was investigated. The contribution of secondary particles from non-elastic nuclear reactions was calculated in three materials relevant in radiotherapy applications: water, PMMA and A150. The results evidence that there are differences in the calculated contribution of the secondary particles heavier than protons to the absorbed dose, with different approaches to model the nuclear reactions. The MCNPX calculation give rise to a larger contribution of d, t, {alpha}{sup 3}He to the total dose compared to the GEANT4 physical models chosen in this work.

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

    PubMed

    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. Rhizobial synthesized cytokinins contribute to but are not essential for the symbiotic interaction between photosynthetic Bradyrhizobia and Aeschynomene legumes.

    PubMed

    Podlešáková, Kateřina; Fardoux, Joel; Patrel, Delphine; Bonaldi, Katia; Novák, Ondřej; Strnad, Miroslav; Giraud, Eric; Spíchal, Lukáš; Nouwen, Nico

    2013-10-01

    Cytokinins (CK) play an important role in the formation of nitrogen-fixing root nodules. It has been known for years that rhizobia secrete CK in the extracellular medium but whether they play a role in nodule formation is not known. We have examined this question using the photosynthetic Bradyrhizobium sp. strain ORS285 which is able to nodulate Aeschynomene afraspera and A. indica using a Nod-dependent or Nod-independent symbiotic process, respectively. CK profiling showed that the most abundant CK secreted by Bradyrhizobium sp. strain ORS285 are the 2MeS (2-methylthiol) derivatives of trans-zeatin and isopentenyladenine. In their pure form, these CK can activate legume CK receptors in vitro, and their exogenous addition induced nodule-like structures on host plants. Deletion of the miaA gene showed that transfer RNA degradation is the source of CK production in Bradyrhizobium sp. strain ORS285. In nodulation studies performed with A. indica and A. afraspera, the miaA mutant had a 1-day delay in nodulation and nitrogen fixation. Moreover, A. indica plants formed considerably smaller but more abundant nodules when inoculated with the miaA mutant. These data show that CK produced by Bradyrhizobium sp. strain ORS285 are not the key signal triggering nodule formation during the Nod-independent symbiosis but they contribute positively to nodule development in Aeschynomene plants.

  7. The genetic contribution of CIDEA polymorphisms, haplotypes and loci interaction to obesity in a Han Chinese population.

    PubMed

    Wu, Jingjing; Zhang, Ling; Zhang, Jie; Dai, Ying; Bian, Lili; Song, Manshu; Russell, Alyce; Wang, Wei

    2013-10-01

    To investigate the association of tag-SNPs and haplotype structures of the CIDEA gene with obesity in a Han Chinese population. Five single nucleotide polymorphisms (SNPs) (rs1154588/V115F, rs4796955/SNP1, rs8092502/SNP2, rs12962340/SNP3 and rs7230480/SNP4) in the CIDEA gene were genotyped in a case-control study. Genotyping was performed using the sequenom matrix-assisted laser desorption/ionization time-of-flight mass spectrometry iPLEX platform. There were significant differences between the obese and control groups in genotype distributions of V115F (P < 0.001), SNP1 (P = 0.006) and SNP2 (P = 0.005). Carriers of V115F-TT, SNP1-GG and SNP2-CC genotypes had a 2.84-fold (95 % CI 1.73-4.66), 2.19-fold (95 % CI 1.09-4.38) and 4.37-fold (95 % CI 1.21-15.08) increased risk for obesity, respectively. Haplotype analysis showed that GTTC (SNP1/SNP2/V115F/SNP4) had 1.41-fold (95 % CI 1.02-1.95) increased risk for obesity; whereas, haplotype TTGC had 0.48-fold (95 % CI 0.24-0.96) decreased risk for obesity. Using the multifactor dimensionality reduction method, the best model including SNP1, SNP2, V115F and SNP4 polymorphisms was identified with a maximum testing accuracy to 59.32 % and a perfect cross-validation consistency of 10/10 (P = 0.011). Logistic analysis indicated that there was a significant interaction between SNP1 and V115F associated with obesity. Subjects having both genotypes of SNP1/GG and V115F/TT were more susceptible to obesity in the Han Chinese population (OR 2.66, 95 %: 1.22-5.80). Genotypes of V115F/TT, SNP1/GG and SNP2/CC and haplotype GTTC of CIDEA gene were identified as risk factors for obesity in the Han Chinese population. The interaction between SNP1 and V115F could play a joint role in the development of obesity.

  8. The interaction of the cellular export adaptor protein Aly/REF with ICP27 contributes to the efficiency of herpes simplex virus 1 mRNA export.

    PubMed

    Tian, Xiaochen; Devi-Rao, Gayathri; Golovanov, Alexander P; Sandri-Goldin, Rozanne M

    2013-07-01

    Herpes simplex virus 1 (HSV-1) protein ICP27 enables viral mRNA export by accessing the cellular mRNA export receptor TAP/NXF, which guides mRNA through the nuclear pore complex. ICP27 binds viral mRNAs and interacts with TAP/NXF, providing a link to the cellular mRNA export pathway. ICP27 also interacts with the mRNA export adaptor protein Aly/REF, which binds cellular mRNAs and also interacts with TAP/NXF. Studies using small interfering RNA (siRNA) knockdown indicated that Aly/REF is not required for cellular mRNA export, and similar knockdown studies during HSV-1 infection led us to conclude that Aly/REF may be dispensable for viral RNA export. Recently, the structural basis of the interaction of ICP27 with Aly/REF was elucidated at atomic resolution, and it was shown that three ICP27 residues, W105, R107, and L108, interface with the RNA recognition motif (RRM) domain of Aly/REF. Here, to determine the role the interaction of ICP27 and Aly/REF plays during infection, these residues were mutated to alanine, and a recombinant virus, WRL-A, was constructed. Virus production was reduced about 10-fold during WRL-A infection, and export of ICP27 protein and most viral mRNAs was less efficient. We conclude that interaction of ICP27 with Aly/REF contributes to efficient viral mRNA export.

  9. An interaction between the serotonin transporter promoter region and dopamine transporter polymorphisms contributes to harm avoidance and reward dependence traits in normal healthy subjects.

    PubMed

    Kim, S J; Kim, Y S; Lee, H S; Kim, S Y; Kim, C-H

    2006-07-01

    There is evidence for an association between polymorphisms of serotonin- and dopamine-related genes and temperamental personality traits. Recent findings have shown that interactions between allelic variants of the different genes may contribute to personality traits. We examined the effects of serotonin transporter-linked promoter region (5-HTTLPR) and dopamine transporter (DAT1) gene polymorphisms for associations with the Temperament and Character Inventory (TCI) temperament subscales in 209 Koreans. We found that the variants of 5-HTTLPR interacted with the DAT1 gene polymorphism to influence the HA and RD temperament subscales of TCI. Neither of these two genes affected any subscales of TCI alone.Controlling for the effects of gender and age, we found significant interactions between 5-HTTLPR and DAT1 genes on Harm Avoidance (HA) and Reward Dependence (RD) as measured by the TCI (Hotelling's Trace = 3.0, P = 0.02). In the presence of the DAT1 10/10 genotype, subjects of group L of 5-HTTLPR had a significantly higher HA score and significantly lower RD score than those of group S (F = 5.04, df = 1, p = 0.03 and F = 8.35, df = 1, p = 0.004, respectively). These findings suggest that the variants of 5-HTTLPR interacted with the DAT1 gene polymorphism to influence the HA and RD temperament subscales of TCI.

  10. An evolutionarily conserved interaction of tumor suppressor protein Pdcd4 with the poly(A)-binding protein contributes to translation suppression by Pdcd4.

    PubMed

    Fehler, Olesja; Singh, Priyanka; Haas, Astrid; Ulrich, Diana; Müller, Jan P; Ohnheiser, Johanna; Klempnauer, Karl-Heinz

    2014-01-01

    The tumor suppressor protein programmed cell death 4 (Pdcd4) has been implicated in the translational regulation of specific mRNAs, however, the identities of the natural Pdcd4 target mRNAs and the mechanisms by which Pdcd4 affects their translation are not well understood. Pdcd4 binds to the eukaryotic translation initiation factor eIF4A and inhibits its helicase activity, which has suggested that Pdcd4 suppresses translation initiation of mRNAs containing structured 5'-untranslated regions. Recent work has revealed a second inhibitory mechanism, which is eIF4A-independent and involves direct RNA-binding of Pdcd4 to the target mRNAs. We have now identified the poly(A)-binding protein (PABP) as a novel direct interaction partner of Pdcd4. The ability to interact with PABP is shared between human and Drosophila Pdcd4, indicating that it has been highly conserved during evolution. Mutants of Pdcd4 that have lost the ability to interact with PABP fail to stably associate with ribosomal complexes in sucrose density gradients and to suppress translation, as exemplified by c-myb mRNA. Overall, our work identifies PABP as a novel functionally relevant Pdcd4 interaction partner that contributes to the regulation of translation by Pdcd4.

  11. MRNIP/C5orf45 Interacts with the MRN Complex and Contributes to the DNA Damage Response.

    PubMed

    Staples, Christopher J; Barone, Giancarlo; Myers, Katie N; Ganesh, Anil; Gibbs-Seymour, Ian; Patil, Abhijit A; Beveridge, Ryan D; Daye, Caroline; Beniston, Richard; Maslen, Sarah; Ahel, Ivan; Skehel, J Mark; Collis, Spencer J

    2016-09-06

    Through an RNAi-based screen for previously uncharacterized regulators of genome stability, we have identified the human protein C5orf45 as an important factor in preventing the accumulation of DNA damage in human cells. Here, we functionally characterize C5orf45 as a binding partner of the MRE11-RAD50-NBS1 (MRN) damage-sensing complex. Hence, we rename C5orf45 as MRNIP for MRN-interacting protein (MRNIP). We find that MRNIP is rapidly recruited to sites of DNA damage. Cells depleted of MRNIP display impaired chromatin loading of the MRN complex, resulting in reduced DNA end resection and defective ATM-mediated DNA damage signaling, a reduced ability to repair DNA breaks, and radiation sensitivity. Finally, we show that MRNIP phosphorylation on serine 115 leads to its nuclear localization, and this modification is required for MRNIP's role in promoting genome stability. Collectively, these data reveal that MRNIP is an important component of the human DNA damage response.

  12. Luman contributes to brefeldin A-induced prion protein gene expression by interacting with the ERSE26 element

    PubMed Central

    Déry, Marc-André; LeBlanc, Andréa C.

    2017-01-01

    The cellular prion protein (PrP) is essential for transmissible prion diseases, but its exact physiological function remains unclear. Better understanding the regulation of the human prion protein gene (PRNP) expression can provide insight into this elusive function. Spliced XBP1 (sXBP1) was recently shown to mediate endoplasmic reticulum (ER) stress-induced PRNP expression. In this manuscript, we identify Luman, a ubiquitous, non-canonical unfolded protein response (UPR), as a novel regulator of ER stress-induced PRNP expression. Luman activity was transcriptionally and proteolytically activated by the ER stressing drug brefeldin A (BFA) in human neurons, astrocytes, and breast cancer MCF-7 cells. Over-expression of active cleaved Luman (ΔLuman) increased PrP levels, while siRNA-mediated Luman silencing decreased BFA-induced PRNP expression. Site-directed mutagenesis and chromatin immunoprecipitation demonstrated that ΔLuman regulates PRNP expression by interacting with the ER stress response element 26 (ERSE26). Co-over-expression and siRNA-mediated silencing experiments showed that sXBP1 and ΔLuman both up-regulate ER stress-induced PRNP expression. Attempts to understand the function of PRNP up-regulation by Luman excluded a role in atorvastatin-induced neuritogenesis, ER-associated degradation, or proteasomal inhibition-induced cell death. Overall, these results refine our understanding of ER stress-induced PRNP expression and function. PMID:28205568

  13. Contribution of hydrophobic and electrostatic interactions to the membrane integration of the Shaker K+ channel voltage sensor domain.

    PubMed

    Zhang, Liyan; Sato, Yoko; Hessa, Tara; von Heijne, Gunnar; Lee, Jong-Kook; Kodama, Itsuo; Sakaguchi, Masao; Uozumi, Nobuyuki

    2007-05-15

    Membrane-embedded voltage-sensor domains in voltage-dependent potassium channels (K(v) channels) contain an impressive number of charged residues. How can such highly charged protein domains be efficiently inserted into biological membranes? In the plant K(v) channel KAT1, the S2, S3, and S4 transmembrane helices insert cooperatively, because the S3, S4, and S3-S4 segments do not have any membrane insertion ability by themselves. Here we show that, in the Drosophila Shaker K(v) channel, which has a more hydrophobic S3 helix than KAT1, S3 can both insert into the membrane by itself and mediate the insertion of the S3-S4 segment in the absence of S2. An engineered KAT1 S3-S4 segment in which the hydrophobicity of S3 was increased or where S3 was replaced by Shaker S3 behaves as Shaker S3-S4. Electrostatic interactions among charged residues in S2, S3, and S4, including the salt bridges between E283 or E293 in S2 and R368 in S4, are required for fully efficient membrane insertion of the Shaker voltage-sensor domain. These results suggest that cooperative insertion of the voltage-sensor transmembrane helices is a property common to K(v) channels and that the degree of cooperativity depends on a balance between electrostatic and hydrophobic forces.

  14. An interactive visualization tool to explore the biophysical properties of amino acids and their contribution to substitution matrices

    PubMed Central

    Bulka, Blazej; desJardins, Marie; Freeland, Stephen J

    2006-01-01

    Background Quantitative descriptions of amino acid similarity, expressed as probabilistic models of evolutionary interchangeability, are central to many mainstream bioinformatic procedures such as sequence alignment, homology searching, and protein structural prediction. Here we present a web-based, user-friendly analysis tool that allows any researcher to quickly and easily visualize relationships between these bioinformatic metrics and to explore their relationships to underlying indices of amino acid molecular descriptors. Results We demonstrate the three fundamental types of question that our software can address by taking as a specific example the connections between 49 measures of amino acid biophysical properties (e.g., size, charge and hydrophobicity), a generalized model of amino acid substitution (as represented by the PAM74-100 matrix), and the mutational distance that separates amino acids within the standard genetic code (i.e., the number of point mutations required for interconversion during protein evolution). We show that our software allows a user to recapture the insights from several key publications on these topics in just a few minutes. Conclusion Our software facilitates rapid, interactive exploration of three interconnected topics: (i) the multidimensional molecular descriptors of the twenty proteinaceous amino acids, (ii) the correlation of these biophysical measurements with observed patterns of amino acid substitution, and (iii) the causal basis for differences between any two observed patterns of amino acid substitution. This software acts as an intuitive bioinformatic exploration tool that can guide more comprehensive statistical analyses relating to a diverse array of specific research questions. PMID:16817972

  15. Signal regulatory protein-α interacts with the insulin receptor contributing to muscle wasting in chronic kidney disease.

    PubMed

    Thomas, Sandhya S; Dong, Yanjun; Zhang, Liping; Mitch, William E

    2013-08-01

    Insulin resistance from chronic kidney disease (CKD) stimulates muscle protein wasting but mechanisms causing this resistance are controversial. To help resolve this, we used microarray analyses to identify initiators of insulin resistance in the muscles of mice with CKD, glucose intolerance, and insulin resistance. CKD raised mRNAs of inflammatory cytokines in muscles and there was a 5.2-fold increase in signal regulatory protein-α (SIRP-α), a transmembrane glycoprotein principally present in muscle membranes. By immunoprecipitation we found it interacts with the insulin receptor and insulin receptor substrate-1 (IRS-1). Treatment of myotubes with a mixture of inflammatory cytokines showed that SIRP-α expression was increased by a NF-κB-dependent pathway. Blockade of NF-κB using a small-molecule chemical inhibitor or a dominant-negative IKKβ reduced cytokine-induced SIRP-α expression. The overexpression of SIRP-α in myotubes impaired insulin signaling and raised proteolysis while SIRP-α knockdown with siRNAs in skeletal muscle cells increased tyrosine phosphorylation of the insulin receptor and IRS-1 despite inclusion of cytokines. This led to increased p-Akt and suppression of protein degradation. Thus, SIRP-α is part of a novel mechanism for inflammation-mediated insulin resistance in muscle. In catabolic conditions with impaired insulin signaling, targeting SIRP-α may improve insulin sensitivity and prevent muscle atrophy.

  16. One-electron versus electron-electron interaction contributions to the spin-spin coupling mechanism in nuclear magnetic resonance spectroscopy: analysis of basic electronic effects.

    PubMed

    Gräfenstein, Jürgen; Cremer, Dieter

    2004-12-22

    For the first time, the nuclear magnetic resonance (NMR) spin-spin coupling mechanism is decomposed into one-electron and electron-electron interaction contributions to demonstrate that spin-information transport between different orbitals is not exclusively an electron-exchange phenomenon. This is done using coupled perturbed density-functional theory in conjunction with the recently developed J-OC-PSP [=J-OC-OC-PSP: Decomposition of J into orbital contributions using orbital currents and partial spin polarization)] method. One-orbital contributions comprise Ramsey response and self-exchange effects and the two-orbital contributions describe first-order delocalization and steric exchange. The two-orbital effects can be characterized as external orbital, echo, and spin transport contributions. A relationship of these electronic effects to zeroth-order orbital theory is demonstrated and their sign and magnitude predicted using simple models and graphical representations of first order orbitals. In the case of methane the two NMR spin-spin coupling constants result from totally different Fermi contact coupling mechanisms. (1)J(C,H) is the result of the Ramsey response and the self-exchange of the bond orbital diminished by external first-order delocalization external one-orbital effects whereas (2)J(H,H) spin-spin coupling is almost exclusively mitigated by a two-orbital steric exchange effect. From this analysis, a series of prediction can be made how geometrical deformations, electron lone pairs, and substituent effects lead to a change in the values of (1)J(C,H) and (2)J(H,H), respectively, for hydrocarbons.

  17. Retention of local conformational compactness in unfolding of barnase; Contribution of end-to-end interactions within quasi-modules.

    PubMed

    Shinoda, Kazuki; Takahashi, Ken-Ichi; Go, Mitiko

    2007-01-01

    To understand how protein reduces the conformational space to be searched for the native structure, it is crucial to characterize ensembles of conformations on the way of folding processes, in particular ensembles of relatively long-range structures connecting between an extensively unfolded state and a state with a native-like overall chain topology. To analyze such intermediate conformations, we performed multiple unfolding molecular dynamics simulations of barnase at 498K. Some short-range structures such as part of helix and turn were well sustained while most of the secondary structures and the hydrophobic cores were eventually lost, which is consistent with the results by other experimental and computational studies. The most important novel findings were persistence of long-range relatively compact substructures, which was captured by exploiting the concept of module. Module is originally introduced to describe the hierarchical structure of a globular protein in the native state. Modules are conceptually such relatively compact substructures that are resulted from partitioning the native structure of a globular protein completely into several contiguous segments with the least extended conformations. We applied this concept of module to detect a possible hierarchical structure of each snapshot structure in unfolding processes as well. Along with this conceptual extension, such detected relatively compact substructures are named quasi-modules. We found almost perfect persistence of quasi-module boundaries that are positioned close to the native module boundaries throughout the unfolding trajectories. Relatively compact conformations of the quasi-modules seemed to be retained mainly by hydrophobic interactions formed between residues located at both terminal regions within each module. From these results, we propose a hypothesis that hierarchical folding with the early formation of quasi-modules effectively reduces search space for the native structure.

  18. The capsid protein of satellite Panicum mosaic virus contributes to systemic invasion and interacts with its helper virus.

    PubMed

    Omarov, Rustem T; Qi, Dong; Scholthof, Karen-Beth G

    2005-08-01

    Satellite panicum mosaic virus (SPMV) depends on its helper Panicum mosaic virus (PMV) for replication and spread in host plants. The SPMV RNA encodes a 17-kDa capsid protein (CP) that is essential for formation of its 16-nm virions. The results of this study indicate that in addition to the expression of the full-length SPMV CP from the 5'-proximal AUG start codon, SPMV RNA also expresses a 9.4-kDa C-terminal protein from the third in-frame start codon. Differences in solubility between the full-length protein and its C-terminal product were observed. Subcellular fractionation of infected plant tissues showed that SPMV CP accumulates in the cytosol, cell wall-, and membrane-enriched fractions. However, the 9.4-kDa protein exclusively cofractionated with cell wall- and membrane-enriched fractions. Earlier studies revealed that the 5'-untranslated region (5'-UTR) from nucleotides 63 to 104 was associated with systemic infection in a host-specific manner in millet plants. This study shows that nucleotide deletions and insertions in the 5'-UTR plus simultaneous truncation of the N-terminal part of the CP impaired SPMV spread in foxtail millet, but not in proso millet plants. In contrast, the expression of the full-length version of SPMV CP efficiently compensated the negative effect of the 5'-UTR deletions in foxtail millet. Finally, immunoprecipitation assays revealed the presence of a specific interaction between the capsid proteins of SPMV and its helper virus (PMV). Our findings show that the SPMV CP has several biological functions, including facilitating efficient satellite virus infection and movement in millet plants.

  19. Do student self-efficacy and teacher-student interaction quality contribute to emotional and social engagement in fifth grade math?

    PubMed

    Martin, Daniel P; Rimm-Kaufman, Sara E

    2015-10-01

    This study examined (a) the contribution of math self-efficacy to students' perception of their emotional and social engagement in fifth grade math classes, and (b) the extent to which high quality teacher-student interactions compensated for students' low math self-efficacy in contributing to engagement. Teachers (n = 73) were observed three times during the year during math to measure the quality of teacher-student interactions (emotional, organizational, and instructional support). Fifth graders (n = 387) reported on their math self-efficacy at the beginning of the school year and then were surveyed about their feelings of engagement in math class three times during the year immediately after the lessons during which teachers were observed. Results of multi-level models indicated that students initially lower in math self-efficacy reported lower emotional and social engagement during math class than students with higher self-efficacy. However, in classrooms with high levels of teacher emotional support, students reported similar levels of both emotional and social engagement, regardless of their self-efficacy. No comparable findings emerged for organizational and instructional support. The discussion considers the significance of students' own feelings about math in relation to their engagement, as well as the ways in which teacher and classroom supports can compensate for students lack of agency. The work has implications for school psychologists and teachers eager to boost students' engagement in math class.

  20. Multiple metasomatic events recorded in Kilbourne Hole peridotite xenoliths: the relative contribution of host basalt interaction vs. silicate metasomatic glass

    NASA Astrophysics Data System (ADS)

    Hammond, S. J.; Yoshikawa, M.; Harvey, J.; Burton, K. W.

    2010-12-01

    Stark differences between bulk-rock lithophile trace element budgets and the sum of the contributions from their constituent minerals are common, if not ubiquitous in peridotite xenoliths [1]. In the absence of modal metasomatism this discrepancy is often attributed to the “catch-all”, yet often vague process of cryptic metasomatism. This study presents comprehensive Sr-Nd isotope ratios for variably metasomatized bulk-rock peridotites, host basalts, constituent peridotite mineral phases and interstitial glass from 13 spinel lherzolite and harzburgite xenoliths from the Kilbourne Hole volcanic maar, New Mexico, USA. Similar measurements were also made on hand-picked interstitial glass from one of the most highly metasomatized samples (KH03-16) in an attempt to unravel the effects of multiple metasomatic events. In all Kilbourne Hole peridotites analysed, hand-picked, optically clean clinopyroxenes preserve a more primitive Sr isotope signature than the corresponding bulk-rock; a pattern preserved in all but one sample for Nd isotope measurements. Reaction textures, avoided during hand-picking, around clinopyroxene grains are evident in the most metasomatized samples and accompanied by films of high-SiO2 interstitial glass. The margins of primary minerals appear partially resorbed and trails of glassy melt inclusions similar in appearance to those previously reported from the same locality [2], terminate in these films. Hand-picked glass from KH03-16 reveals the most enriched 87Sr/86Sr of any component recovered from these xenoliths (87Sr/86Sr = 0.708043 ± 0.00009; [Sr] = 81 ppm). Similarly, the 143Nd/144Nd of the glass is amongst the most enriched of the peridotite components (143Nd/144Nd = 0.512893 ± 0.000012; [Nd] = 10 ppm). However, the host basalt (87Sr/86Sr = 0.703953 ± 0.00012; 143Nd/144Nd = 0.512873 ± 0.000013), similar in composition to nearby contemporaneous Potrillo Volcanic Field basalts [3], contains nearly an order of magnitude more Sr and more

  1. Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression.

    PubMed

    Culverhouse, R C; Saccone, N L; Horton, A C; Ma, Y; Anstey, K J; Banaschewski, T; Burmeister, M; Cohen-Woods, S; Etain, B; Fisher, H L; Goldman, N; Guillaume, S; Horwood, J; Juhasz, G; Lester, K J; Mandelli, L; Middeldorp, C M; Olié, E; Villafuerte, S; Air, T M; Araya, R; Bowes, L; Burns, R; Byrne, E M; Coffey, C; Coventry, W L; Gawronski, K A B; Glei, D; Hatzimanolis, A; Hottenga, J-J; Jaussent, I; Jawahar, C; Jennen-Steinmetz, C; Kramer, J R; Lajnef, M; Little, K; Zu Schwabedissen, H M; Nauck, M; Nederhof, E; Petschner, P; Peyrot, W J; Schwahn, C; Sinnamon, G; Stacey, D; Tian, Y; Toben, C; Van der Auwera, S; Wainwright, N; Wang, J-C; Willemsen, G; Anderson, I M; Arolt, V; Åslund, C; Bagdy, G; Baune, B T; Bellivier, F; Boomsma, D I; Courtet, P; Dannlowski, U; de Geus, E J C; Deakin, J F W; Easteal, S; Eley, T; Fergusson, D M; Goate, A M; Gonda, X; Grabe, H J; Holzman, C; Johnson, E O; Kennedy, M; Laucht, M; Martin, N G; Munafò, M R; Nilsson, K W; Oldehinkel, A J; Olsson, C A; Ormel, J; Otte, C; Patton, G C; Penninx, B W J H; Ritchie, K; Sarchiapone, M; Scheid, J M; Serretti, A; Smit, J H; Stefanis, N C; Surtees, P G; Völzke, H; Weinstein, M; Whooley, M; Nurnberger, J I; Breslau, N; Bierut, L J

    2017-04-04

    The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations

  2. Tet38 Efflux Pump Affects Staphylococcus aureus Internalization by Epithelial Cells through Interaction with CD36 and Contributes to Bacterial Escape from Acidic and Nonacidic Phagolysosomes.

    PubMed

    Truong-Bolduc, Q C; Khan, N S; Vyas, J M; Hooper, D C

    2017-02-01

    We previously reported that the Tet38 efflux pump is involved in internalization of Staphylococcus aureus by A549 lung epithelial cells. A lack of tet38 reduced bacterial uptake by A549 cells to 36% of that of the parental strain RN6390. Using invasion assays coupled with confocal microscopy imaging, we studied the host cell receptor(s) responsible for bacterial uptake via interaction with Tet38. We also assessed the ability of S. aureus to survive following alkalinization of the phagolysosomes by chloroquine. Antibody to the scavenger receptor CD36 reduced the internalization of S. aureus RN6390 by A549 cells, but the dependence on CD36 was reduced in QT7 tet38, suggesting that an interaction between Tet38 and CD36 contributed to S. aureus internalization. Following fusion of the S. aureus-associated endosomes with lysosomes, alkalinization of the acidic environment with chloroquine led to a rapid increase in the number of S. aureus RN6390 bacteria in the cytosol, followed by a decrease shortly thereafter. This effect of chloroquine was not seen in the absence of intact Tet38 in mutant QT7. These data taken together suggest that Tet38 plays a role both in bacterial internalization via interaction with CD36 and in bacterial escape from the phagolysosomes.

  3. FF483–484 motif of human Polη mediates its interaction with the POLD2 subunit of Polδ and contributes to DNA damage tolerance

    PubMed Central

    Baldeck, Nadège; Janel-Bintz, Régine; Wagner, Jérome; Tissier, Agnès; Fuchs, Robert P.; Burkovics, Peter; Haracska, Lajos; Despras, Emmanuelle; Bichara, Marc; Chatton, Bruno; Cordonnier, Agnès M.

    2015-01-01

    Switching between replicative and translesion synthesis (TLS) DNA polymerases are crucial events for the completion of genomic DNA synthesis when the replication machinery encounters lesions in the DNA template. In eukaryotes, the translesional DNA polymerase η (Polη) plays a central role for accurate bypass of cyclobutane pyrimidine dimers, the predominant DNA lesions induced by ultraviolet irradiation. Polη deficiency is responsible for a variant form of the Xeroderma pigmentosum (XPV) syndrome, characterized by a predisposition to skin cancer. Here, we show that the FF483–484 amino acids in the human Polη (designated F1 motif) are necessary for the interaction of this TLS polymerase with POLD2, the B subunit of the replicative DNA polymerase δ, both in vitro and in vivo. Mutating this motif impairs Polη function in the bypass of both an N-2-acetylaminofluorene adduct and a TT-CPD lesion in cellular extracts. By complementing XPV cells with different forms of Polη, we show that the F1 motif contributes to the progression of DNA synthesis and to the cell survival after UV irradiation. We propose that the integrity of the F1 motif of Polη, necessary for the Polη/POLD2 interaction, is required for the establishment of an efficient TLS complex. PMID:25662213

  4. FF483-484 motif of human Polη mediates its interaction with the POLD2 subunit of Polδ and contributes to DNA damage tolerance.

    PubMed

    Baldeck, Nadège; Janel-Bintz, Régine; Wagner, Jérome; Tissier, Agnès; Fuchs, Robert P; Burkovics, Peter; Haracska, Lajos; Despras, Emmanuelle; Bichara, Marc; Chatton, Bruno; Cordonnier, Agnès M

    2015-02-27

    Switching between replicative and translesion synthesis (TLS) DNA polymerases are crucial events for the completion of genomic DNA synthesis when the replication machinery encounters lesions in the DNA template. In eukaryotes, the translesional DNA polymerase η (Polη) plays a central role for accurate bypass of cyclobutane pyrimidine dimers, the predominant DNA lesions induced by ultraviolet irradiation. Polη deficiency is responsible for a variant form of the Xeroderma pigmentosum (XPV) syndrome, characterized by a predisposition to skin cancer. Here, we show that the FF483-484 amino acids in the human Polη (designated F1 motif) are necessary for the interaction of this TLS polymerase with POLD2, the B subunit of the replicative DNA polymerase δ, both in vitro and in vivo. Mutating this motif impairs Polη function in the bypass of both an N-2-acetylaminofluorene adduct and a TT-CPD lesion in cellular extracts. By complementing XPV cells with different forms of Polη, we show that the F1 motif contributes to the progression of DNA synthesis and to the cell survival after UV irradiation. We propose that the integrity of the F1 motif of Polη, necessary for the Polη/POLD2 interaction, is required for the establishment of an efficient TLS complex.

  5. Investigation of the electronic structures of organolanthanide sandwich complex anions by photoelectron spectroscopy: 4f orbital contribution in the metal-ligand interaction.

    PubMed

    Hosoya, Natsuki; Yada, Keizo; Masuda, Tomohide; Nakajo, Erika; Yabushita, Satoshi; Nakajima, Atsushi

    2014-05-01

    The electronic structures of lanthanide (Ln) ions sandwiched between 1,3,5,7-cyclooctatetraene (COT), Ln(COT)2(-), have been investigated by anion photoelectron spectroscopy. Complexes of 12 Ln atoms were investigated (excluding promethium (Pm), europium (Eu), and ytterbium (Yb)). The 213 nm photoelectron (PE) spectra of Ln(COT)2(-) exhibit two peaks assignable to the highest occupied molecular orbital (HOMO; e2u) and the next HOMO (HOMO-1; e2g) approximately at 2.6 and 3.6 eV, respectively, and their energy gap increases as the central metal atom progresses from lanthanum (La) to lutetium (Lu). Since lanthanide contraction shortens the distance between the Ln atom and the COT ligands, the widening energy gap represents the destabilization of the e2u orbital as well as the stabilization of the e2g orbital. Evidence for 4f orbital contribution in the metal-ligand interaction has been revealed by the Ln atom dependence in which the same e2u orbital symmetry enables an interaction between the 4f orbital of Ln atoms and the π orbital of COT.

  6. Contributions of the electrostatic and the dispersion interaction to the solvent shift in a dye-polymer system, as investigated by hole-burning spectroscopy

    NASA Astrophysics Data System (ADS)

    Kador, L.; Jahn, S.; Haarer, D.; Silbey, R.

    1990-06-01

    Persistent spectral holes burned in the system octaethylporphin in poly(styrene) exhibit a symmetrical broadening varying in a linear fashion upon application of a static electric field. This effect is due to permanent electric-dipole moments induced in the dye molecules by the electric ``matrix field.'' The average value of the dipole-moment difference μ between the excited and the ground state of the guest molecules, which can be deduced from the broadening, shows a distinct increase from the blue to the red edge of the inhomogeneous absorption band, thus reflecting the varying dye-matrix interaction for centers with different solvent shift. A detailed analysis of this variation in the framework of a microscopic theory, based on a recent publication by Laird and Skinner [J. Chem. Phys. 90, 3274 (1989)], leads to the conclusion that the solvent shift of the absorption lines and also the μ variation across the inhomogeneous band is largely dominated by the dispersion interaction. The electrostatic contribution to the line shift is smaller by about 2 orders of magnitude.

  7. Interactions outside the proteinase-binding loop contribute significantly to the inhibition of activated coagulation factor XII by its canonical inhibitor from corn.

    PubMed

    Korneeva, Vera A; Trubetskov, Mikhail M; Korshunova, Alena V; Lushchekina, Sofya V; Kolyadko, Vladimir N; Sergienko, Olga V; Lunin, Vladimir G; Panteleev, Mikhail A; Ataullakhanov, Fazoil I

    2014-05-16

    Activated factor XII (FXIIa) is selectively inhibited by corn Hageman factor inhibitor (CHFI) among other plasma proteases. CHFI is considered a canonical serine protease inhibitor that interacts with FXIIa through its protease-binding loop. Here we examined whether the protease-binding loop alone is sufficient for the selective inhibition of serine proteases or whether other regions of a canonical inhibitor are involved. Six CHFI mutants lacking different N- and C-terminal portions were generated. CHFI-234, which lacks the first and fifth disulfide bonds and 11 and 19 amino acid residues at the N and C termini, respectively, exhibited no significant changes in FXIIa inhibition (Ki = 3.2 ± 0.4 nm). CHFI-123, which lacks 34 amino acid residues at the C terminus and the fourth and fifth disulfide bridges, inhibited FXIIa with a Ki of 116 ± 16 nm. To exclude interactions outside the FXIIa active site, a synthetic cyclic peptide was tested. The peptide contained residues 20-45 (Protein Data Bank code 1BEA), and a C29D substitution was included to avoid unwanted disulfide bond formation between unpaired cysteines. Surprisingly, the isolated protease-binding loop failed to inhibit FXIIa but retained partial inhibition of trypsin (Ki = 11.7 ± 1.2 μm) and activated factor XI (Ki = 94 ± 11 μm). Full-length CHFI inhibited trypsin with a Ki of 1.3 ± 0.2 nm and activated factor XI with a Ki of 5.4 ± 0.2 μm. Our results suggest that the protease-binding loop is not sufficient for the interaction between FXIIa and CHFI; other regions of the inhibitor also contribute to specific inhibition.

  8. Contribution of metabolites to P450 inhibition-based drug-drug interactions: scholarship from the drug metabolism leadership group of the innovation and quality consortium metabolite group.

    PubMed

    Yu, Hongbin; Balani, Suresh K; Chen, Weichao; Cui, Donghui; He, Ling; Humphreys, W Griffith; Mao, Jialin; Lai, W George; Lee, Anthony J; Lim, Heng-Keang; MacLauchlin, Christopher; Prakash, Chandra; Surapaneni, Sekhar; Tse, Susanna; Upthagrove, Alana; Walsky, Robert L; Wen, Bo; Zeng, Zhaopie

    2015-04-01

    Recent European Medicines Agency (final) and US Food and Drug Administration (draft) drug interaction guidances proposed that human circulating metabolites should be investigated in vitro for their drug-drug interaction (DDI) potential if present at ≥ 25% of the parent area under the time-concentration curve (AUC) (US Food and Drug Administration) or ≥ 25% of the parent and ≥ 10% of the total drug-related AUC (European Medicines Agency). To examine the application of these regulatory recommendations, a group of scientists, representing 18 pharmaceutical companies of the Drug Metabolism Leadership Group of the Innovation and Quality Consortium, conducted a scholarship to assess the risk of contributions by metabolites to cytochrome P450 (P450) inhibition-based DDIs. The group assessed the risk of having a metabolite as the sole contributor to DDI based on literature data and analysis of the 137 most frequently prescribed drugs, defined structural alerts associated with P450 inhibition/inactivation by metabolites, and analyzed current approaches to trigger in vitro DDI studies for metabolites. The group concluded that the risk of P450 inhibition caused by a metabolite alone is low. Only metabolites from 5 of 137 drugs were likely the sole contributor to the in vivo P450 inhibition-based DDIs. Two recommendations were provided when assessing the need to conduct in vitro P450 inhibition studies for metabolites: 1) consider structural alerts that suggest P450 inhibition potential, and 2) use multiple approaches (e.g., a metabolite cut-off value of 100% of the parent AUC and the R(met) strategy) to predict P450 inhibition-based DDIs caused by metabolites in the clinic.

  9. Contribution of the interaction between the rabies virus P protein and I-kappa B kinase ϵ to the inhibition of type I IFN induction signalling.

    PubMed

    Masatani, Tatsunori; Ozawa, Makoto; Yamada, Kentaro; Ito, Naoto; Horie, Masayuki; Matsuu, Aya; Okuya, Kosuke; Tsukiyama-Kohara, Kyoko; Sugiyama, Makoto; Nishizono, Akira

    2016-02-01

    The P protein of rabies virus (RABV) is known to interfere with the phosphorylation of the host IFN regulatory factor 3 (IRF-3) and to consequently inhibit type I IFN induction. Previous studies, however, have only tested P proteins from laboratory-adapted fixed virus strains, and to the best of our knowledge there is no report about the effect of P proteins from street RABV strains or other lyssaviruses on the IRF-3-mediated type I IFN induction system. In this study, we evaluated the inhibitory effect of P proteins from several RABV strains, including fixed and street virus strains and other lyssaviruses (Lagos bat, Mokola and Duvenhage viruses), on IRF-3 signalling. All P proteins tested inhibited retinoic acid-inducible gene-1 (RIG-I)- and TANK binding kinase 1 (TBK1)-mediated IRF-3-dependent IFN-β promoter activities. On the other hand, the P proteins from the RABV street strains 1088 and HCM-9, but not from fixed strains Nishigahara (Ni) and CVS-11 and other lyssaviruses tested, significantly inhibited I-kappa B kinase ϵ (IKKϵ)-inducible IRF-3-dependent IFN-β promoter activity. Importantly, we revealed that the P proteins from the 1088 and HCM-9 strains, but not from the remaining viruses, interacted with IKKϵ. By using expression plasmids encoding chimeric P proteins from the 1088 strain and Ni strain, we found that the C-terminal region of the P protein is important for the interaction with IKKϵ. These findings suggest that the P protein of RABV street strains may contribute to efficient evasion of host innate immunity.

  10. Catalytic ozonation of Orange-G through highly interactive contributions of hematite and SBA-16 - To better understand azo-dye oxidation in nature.

    PubMed

    Larouk, Safa; Ouargli, Rachida; Shahidi, Dariush; Olhund, Leanne; Shiao, Tze Chieh; Chergui, Nacira; Sehili, Tahar; Roy, René; Azzouz, Abdelkrim

    2017-02-01

    Hematite-SBA-16 mixture (HS) exhibited high catalytic activity in Orange-G (OG) ozonation in water. Total OG discoloration was achieved in half the time required with hematite or SBA-16 alone, all UV-Vis bands disappeared in less than 2 min. Liquid chromatography- Mass spectrometry (LC-MS) revealed that OG ozonation triggers via both hydroxylation and desulfonation of the aromatic rings into specific intermediates. Prolonged ozonation in the presence of hematite and SBA-16 alone resulted in different distributions of common derivatives. The latter were not detected after 25 min ozonation with HS. Stochastic modeling of the evolution in time of the UV-Vis bands of OG revealed strong binary interaction between the initial pH and catalyst concentration. This was explained in terms of reciprocal contributions of: i. the catalytic properties of hematite in spite of its low porosity; ii. the high specific surface area of SBA-16 for adsorption and surface reaction notwithstanding its low intrinsic catalytic activity. The weak basicity of SBA-16 surface seems to play a key-role in adsorption. These findings are of great interest for envisaging flexible oxidative treatments, where Fe(3+) containing soils or mixtures of sand and rust may also act as catalyst for total mineralization of various azo-dyes, regardless to their structures.

  11. An Interaction between RRP6 and SU(VAR)3-9 Targets RRP6 to Heterochromatin and Contributes to Heterochromatin Maintenance in Drosophila melanogaster

    PubMed Central

    Eberle, Andrea B.; Jordán-Pla, Antonio; Gañez-Zapater, Antoni; Hessle, Viktoria; Silberberg, Gilad; von Euler, Anne; Silverstein, Rebecca A.; Visa, Neus

    2015-01-01

    RNA surveillance factors are involved in heterochromatin regulation in yeast and plants, but less is known about the possible roles of ribonucleases in the heterochromatin of animal cells. Here we show that RRP6, one of the catalytic subunits of the exosome, is necessary for silencing heterochromatic repeats in the genome of Drosophila melanogaster. We show that a fraction of RRP6 is associated with heterochromatin, and the analysis of the RRP6 interaction network revealed physical links between RRP6 and the heterochromatin factors HP1a, SU(VAR)3-9 and RPD3. Moreover, genome-wide studies of RRP6 occupancy in cells depleted of SU(VAR)3-9 demonstrated that SU(VAR)3-9 contributes to the tethering of RRP6 to a subset of heterochromatic loci. Depletion of the exosome ribonucleases RRP6 and DIS3 stabilizes heterochromatic transcripts derived from transposons and repetitive sequences, and renders the heterochromatin less compact, as shown by micrococcal nuclease and proximity-ligation assays. Such depletion also increases the amount of HP1a bound to heterochromatic transcripts. Taken together, our results suggest that SU(VAR)3-9 targets RRP6 to a subset of heterochromatic loci where RRP6 degrades chromatin-associated non-coding RNAs in a process that is necessary to maintain the packaging of the heterochromatin. PMID:26389589

  12. Human Papillomavirus 16 E6 Contributes HIF-1α Induced Warburg Effect by Attenuating the VHL-HIF-1α Interaction

    PubMed Central

    Guo, Yi; Meng, Xiangkai; Ma, Jiaming; Zheng, Yahong; Wang, Qian; Wang, Yanan; Shang, Hong

    2014-01-01

    Cervical cancer is still one of the leading causes of cancer deaths in women worldwide, especially in the developing countries. It is a major metabolic character of cancer cells to consume large quantities of glucose and derive more energy by glycolysis even in the presence of adequate oxygen, which is called Warburg effect that can be exaggerated by hypoxia. The high risk subtype HPV16 early oncoprotein E6 contributes host cell immortalization and transformation through interacting with a number of cellular factors. Hypoxia-inducible factor 1α (HIF-1α), a ubiquitously expressed transcriptional regulator involved in induction of numerous genes associated with angiogenesis and tumor growth, is highly increased by HPV E6. HIF-1α is a best-known target of the von Hippel-Lindau tumor suppressor (VHL) as an E3 ligase for degradation. In the present work, we found that HPV16 E6 promotes hypoxia induced Warburg effect through hindering the association of HIF-1α and VHL. This disassociation attenuates VHL-mediated HIF-1α ubiquitination and causes HIF-1α accumulation. These results suggest that oncoprotein E6 plays a major role in the regulation of Warburg effect and can be a valuable therapeutic target for HPV-related cancer. PMID:24810689

  13. miR-21a-5p Contributes to Porcine Hemagglutinating Encephalomyelitis Virus Proliferation via Targeting CASK-Interactive Protein1 In vivo and vitro

    PubMed Central

    Lv, Xiaoling; Zhao, Kui; Lan, Yungang; Li, Zi; Ding, Ning; Su, Jingjing; Lu, Huijun; Song, Deguang; Gao, Feng; He, Wenqi

    2017-01-01

    Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus that can cause nervous symptoms in piglets with muscle tremors, hind limb paralysis, and nystagmus. Whether some factors affect virus replication and proliferation had not been fully understood in the course of nerve damage caused by PHEV infection. In recent years, some reports suggested that miRNA might play a key regulatory role in viral infection. In this study, we found the miR-21a-5p is notably up-regulated in the brains of mice and N2a cells infected with PHEV, and it down-regulated the expression of CASK-interactive protein1 (Caskin1) by directly targeting the 3′-UTR of Caskin1 using a Dual-Luciferase reporter assay. The over-expression of miR-21a-5p or Caskin1 knockdown in the host significantly contributes to PHEV proliferation. Conversely, the silencing of miR-21a-5p by miR-21a-5p inhibitors suppressed the virus proliferation. Taken together, our results indicate that Caskin1 is the direct target gene of miR-21a-5p, and it is advantageous to virus proliferation by down-regulating Caskin1. These findings may help in the development of strategies for therapeutic applications. PMID:28298907

  14. Chemokine contribution to neuropathic pain: respective induction of CXCL1 and CXCR2 in spinal cord astrocytes and neurons.

    PubMed

    Zhang, Zhi-Jun; Cao, De-Li; Zhang, Xin; Ji, Ru-Rong; Gao, Yong-Jing

    2013-10-01

    Recent studies have indicated an important role of chemokines such as CCL2 in the development of chronic pain. However, the distinct roles of different chemokines in the development and maintenance of neuropathic pain and in their interactions with neurons have not been clearly elucidated. We found that spinal nerve ligation (SNL) not only induced persistent neuropathic pain symptoms, including mechanical allodynia and heat hyperalgesia, but also produced sustained CXCL1 upregulation in the spinal cord. Double staining of immunofluorescence and in situ hybridization revealed that CXCL1 was primarily induced in spinal astrocytes. In cultured astrocytes, tumor necrosis factor-α induced robust CXCL1 expression via the activation of the c-jun N-terminal kinase. Intrathecal administration of CXCL1 neutralizing antibody transiently reduced SNL-induced pain hypersensitivity, suggesting an essential role of CXCL1 in neuropathic pain sensitization. In particular, intraspinal delivery of CXCL1 shRNA lentiviral vectors, either before or after SNL, persistently attenuated SNL-induced pain hypersensitivity. Spinal application of CXCL1 not only elicited pain hypersensitivity but also induced rapid neuronal activation, as indicated by the expression of phosphorylated extracellular signal-regulated kinase and cAMP response element binding protein, and c-Fos in spinal cord neurons. Interestingly, CXCR2, the primary receptor of CXCL1, was upregulated in dorsal horn neurons after SNL, and the CXCR2 antagonist SB225002 completely blocked the CXCL1-induced heat hyperalgesia. SB225002 also attenuated SNL-induced pain hypersensitivity. Collectively, our results have demonstrated a novel form of chemokine-mediated glial-neuronal interaction in the spinal cord that can drive neuropathic pain. Inhibition of the CXCL1-CXCR2 signaling may offer a new therapy for neuropathic pain management.

  15. Contributions of long-range electrostatic interactions to 4-chlorobenzoyl-CoA dehalogenase catalysis: a combined theoretical and experimental study.

    PubMed

    Wu, Jingbo; Xu, Dingguo; Lu, Xuefeng; Wang, Canhui; Guo, Hua; Dunaway-Mariano, Debra

    2006-01-10

    It is well established that electrostatic interactions play a vital role in enzyme catalysis. In this work, we report theory-guided mutation experiments that identified strong electrostatic contributions of a remote residue, namely, Glu232 located on the adjacent subunit, to 4-chlorobenzoyl-CoA dehalogenase catalysis. The Glu232Asp mutant was found to bind the substrate analogue 4-methylbenzoyl-CoA more tightly than does the wild-type dehalogenase. In contrast, the kcat for 4-chlorobenzoyl-CoA conversion to product was reduced 10000-fold in the mutant. UV difference spectra measured for the respective enzyme-ligand complexes revealed an approximately 3-fold shift in the equilibrium of the two active site conformers away from that inducing strong pi-electron polarization in the ligand benzoyl ring. Increased substrate binding, decreased ring polarization, and decreased catalytic efficiency indicated that the repositioning of the point charge in the Glu232Asp mutant might affect the orientation of the Asp145 carboxylate with respect to the substrate aromatic ring. The time course for formation and reaction of the arylated enzyme intermediate during a single turnover was measured for wild-type and Glu232Asp mutant dehalogenases. The accumulation of arylated enzyme in the wild-type dehalogenase was not observed in the mutant. This indicates that the reduced turnover rate in the mutant is the result of a slow arylation of Asp145, owing to decreased efficiency in substrate nucleophilic attack by Asp145. To rationalize the experimental observations, a theoretical model is proposed, which computes the potential of mean force for the nucleophilic aromatic substitution step using a hybrid quantum mechanical/molecular mechanical method. To this end, the removal or reorientation of the side chain charge of residue 232, modeled respectively by the Glu232Gln and Glu232Asp mutants, is shown to increase the rate-limiting energy barrier. The calculated 23.1 kcal/mol free energy

  16. The Mre11/Rad50/Nbs1 complex interacts with the mismatch repair system and contributes to temozolomide-induced G2 arrest and cytotoxicity.

    PubMed

    Mirzoeva, Olga K; Kawaguchi, Tomohiro; Pieper, Russell O

    2006-11-01

    The chemotherapeutic agent temozolomide produces O(6)-methylguanine (O6MG) in DNA, which triggers futile DNA mismatch repair, DNA double-strand breaks (DSB), G(2) arrest, and ultimately cell death. Because the protein complex consisting of Mre11/Rad50/Nbs1 (MRN complex) plays a key role in DNA damage detection and signaling, we asked if this complex also played a role in the cellular response to temozolomide. Temozolomide exposure triggered the assembly of MRN complex into chromatin-associated nuclear foci. MRN foci formed significantly earlier than gamma-H2AX and 53BP1 foci that assembled in response to temozolomide-induced DNA DSBs. MRN foci formation was suppressed in cells that incurred lower levels of temozolomide-induced O6MG lesions and/or had decreased mismatch repair capabilities, suggesting that the MRN foci formed not in response to temozolomide-induced DSB but rather in response to mismatch repair processing of mispaired temozolomide-induced O6MG lesions. Consistent with this idea, the MRN foci colocalized with those of proliferating cell nuclear antigen (a component of the mismatch repair complex), and the MRN complex component Nbs1 coimmunoprecipitated with the mismatch repair protein Mlh1 specifically in response to temozolomide treatment. Furthermore, small inhibitory RNA-mediated suppression of Mre11 levels decreased temozolomide-induced G(2) arrest and cytotoxicity in a manner comparable to that achieved by suppression of mismatch repair. These data show that temozolomide-induced O6MG lesions, acted upon by the mismatch repair system, drive formation of the MRN complex foci and the interaction of this complex with the mismatch repair machinery. The MRN complex in turn contributes to the control of temozolomide-induced G(2) arrest and cytotoxicity, and as such is an additional determining factor in glioma sensitivity to DNA methylating chemotherapeutic drugs such as temozolomide.

  17. Contribution of partial charge interactions and base stacking to the efficiency of primer extension at and beyond abasic sites in DNA.

    PubMed

    Xia, Shuangluo; Vashishtha, Ashwani; Bulkley, David; Eom, Soo Hyun; Wang, Jimin; Konigsberg, William H

    2012-06-19

    During DNA synthesis, base stacking and Watson-Crick (WC) hydrogen bonding increase the stability of nascent base pairs when they are in a ternary complex. To evaluate the contribution of base stacking to the incorporation efficiency of dNTPs when a DNA polymerase encounters an abasic site, we varied the penultimate base pairs (PBs) adjacent to the abasic site using all 16 possible combinations. We then determined pre-steady-state kinetic parameters with an RB69 DNA polymerase variant and solved nine structures of the corresponding ternary complexes. The efficiency of incorporation for incoming dNTPs opposite an abasic site varied between 2- and 210-fold depending on the identity of the PB. We propose that the A rule can be extended to encompass the fact that DNA polymerase can bypass dA/abasic sites more efficiently than other dN/abasic sites. Crystal structures of the ternary complexes show that the surface of the incoming base was stacked against the PB's interface and that the kinetic parameters for dNMP incorporation were consistent with specific features of base stacking, such as surface area and partial charge-charge interactions between the incoming base and the PB. Without a templating nucleotide residue, an incoming dNTP has no base with which it can hydrogen bond and cannot be desolvated, so that these surrounding water molecules become ordered and remain on the PB's surface in the ternary complex. When these water molecules are on top of a hydrophobic patch on the PB, they destabilize the ternary complex, and the incorporation efficiency of incoming dNTPs is reduced.

  18. Contribution of Partial Charge Interactions and Base Stacking to the Efficiency of Primer Extension at and beyond Abasic Sites in DNA

    SciTech Connect

    Xia, Shuangluo; Vashishtha, Ashwani; Bulkley, David; Eom, Soo Hyun; Wang, Jimin; Konigsberg, William H.

    2012-08-31

    During DNA synthesis, base stacking and Watson-Crick (WC) hydrogen bonding increase the stability of nascent base pairs when they are in a ternary complex. To evaluate the contribution of base stacking to the incorporation efficiency of dNTPs when a DNA polymerase encounters an abasic site, we varied the penultimate base pairs (PBs) adjacent to the abasic site using all 16 possible combinations. We then determined pre-steady-state kinetic parameters with an RB69 DNA polymerase variant and solved nine structures of the corresponding ternary complexes. The efficiency of incorporation for incoming dNTPs opposite an abasic site varied between 2- and 210-fold depending on the identity of the PB. We propose that the A rule can be extended to encompass the fact that DNA polymerase can bypass dA/abasic sites more efficiently than other dN/abasic sites. Crystal structures of the ternary complexes show that the surface of the incoming base was stacked against the PB's interface and that the kinetic parameters for dNMP incorporation were consistent with specific features of base stacking, such as surface area and partial charge-charge interactions between the incoming base and the PB. Without a templating nucleotide residue, an incoming dNTP has no base with which it can hydrogen bond and cannot be desolvated, so that these surrounding water molecules become ordered and remain on the PB's surface in the ternary complex. When these water molecules are on top of a hydrophobic patch on the PB, they destabilize the ternary complex, and the incorporation efficiency of incoming dNTPs is reduced.

  19. The Protein Interaction of RNA Helicase B (RhlB) and Polynucleotide Phosphorylase (PNPase) Contributes to the Homeostatic Control of Cysteine in Escherichia coli*

    PubMed Central

    Tseng, Yi-Ting; Chiou, Ni-Ting; Gogiraju, Rajinikanth; Lin-Chao, Sue

    2015-01-01

    PNPase, one of the major enzymes with 3′ to 5′ single-stranded RNA degradation and processing activities, can interact with the RNA helicase RhlB independently of RNA degradosome formation in Escherichia coli. Here, we report that loss of interaction between RhlB and PNPase impacts cysteine homeostasis in E. coli. By random mutagenesis, we identified a mutant RhlBP238L that loses 75% of its ability to interact with PNPase but retains normal interaction with RNase E and RNA, in addition to exhibiting normal helicase activity. Applying microarray analyses to an E. coli strain with impaired RNA degradosome formation, we investigated the biological consequences of a weakened interaction between RhlB and PNPase. We found significant increases in 11 of 14 genes involved in cysteine biosynthesis. Subsequent Northern blot analyses showed that the up-regulated transcripts were the result of stabilization of the cysB transcript encoding a transcriptional activator for the cys operons. Furthermore, Northern blots of PNPase or RhlB mutants showed that RhlB-PNPase plays both a catalytic and structural role in regulating cysB degradation. Cells expressing the RhlBP238L mutant exhibited an increase in intracellular cysteine and an enhanced anti-oxidative response. Collectively, this study suggests a mechanism by which bacteria use the PNPase-RhlB exosome-like complex to combat oxidative stress by modulating cysB mRNA degradation. PMID:26494621

  20. Comparative residue interaction analysis (CoRIA): a 3D-QSAR approach to explore the binding contributions of active site residues with ligands

    NASA Astrophysics Data System (ADS)

    Datar, Prasanna A.; Khedkar, Santosh A.; Malde, Alpeshkumar K.; Coutinho, Evans C.

    2006-06-01

    A novel approach termed comparative residue-interaction analysis (CoRIA), emphasizing the trends and principles of QSAR in a ligand-receptor environment has been developed to analyze and predict the binding affinity of enzyme inhibitors. To test this new approach, a training set of 36 COX-2 inhibitors belonging to nine families was selected. The putative binding (bioactive) conformations of inhibitors in the COX-2 active site were searched using the program DOCK. The docked configurations were further refined by a combination of Monte Carlo and simulated annealing methods with the Affinity program. The non-bonded interaction energies of the inhibitors with the individual amino acid residues in the active site were then computed. These interaction energies, plus specific terms describing the thermodynamics of ligand-enzyme binding, were correlated to the biological activity with G/PLS. The various QSAR models obtained were validated internally by cross validation and boot strapping, and externally using a test set of 13 molecules. The QSAR models developed on the CoRIA formalism were robust with good r 2, q 2 and r pred 2 values. The major highlights of the method are: adaptation of the QSAR formalism in a receptor setting to answer both the type (qualitative) and the extent (quantitative) of ligand-receptor binding, and use of descriptors that account for the complete thermodynamics of the ligand-receptor binding. The CoRIA approach can be used to identify crucial interactions of inhibitors with the enzyme at the residue level, which can be gainfully exploited in optimizing the inhibitory activity of ligands. Furthermore, it can be used with advantage to guide point mutation studies. As regards the COX-2 dataset, the CoRIA approach shows that improving Coulombic interaction with Pro528 and reducing van der Waals interaction with Tyr385 will improve the binding affinity of inhibitors.

  1. From Action to Interaction: Exploring the Contribution of Body Motion Cues to Social Understanding in Typical Development and in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Centelles, Laurie; Assaiante, Christine; Etchegoyhen, Katallin; Bouvard, Manuel; Schmitz, Christina

    2013-01-01

    Two studies investigated whether typically developing children (TD) and children with autism spectrum disorders (ASD) were able to decide whether two characters were communicating or not on the basis of point-light displays. Point-lights portrayed actors engaged or not in a social interaction. In study 1, TD children (4-10 years old; n = 36)…

  2. Parental Depressive Symptoms and Marital Intimacy at 4.5 Years: Joint Contributions to Mother-Child and Father-Child Interaction at 6.5 Years

    ERIC Educational Resources Information Center

    Engle, Jennifer M.; McElwain, Nancy L.

    2013-01-01

    Using data from a subset of 606 families who participated in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, we assessed emotional intimacy in the marriage as a buffer of the negative effects of parental depression on the quality of parent-child interaction. Maternal and paternal…

  3. Utilizing Resistivity Soundings and Forensic Geochemistry to Better Understand the Groundwater Contributions and the Interaction with Surface Water in a Streambed in the Texas Gulf Coast Area

    NASA Astrophysics Data System (ADS)

    Bighash, P.

    2012-12-01

    Water quality and quantity in a reservoir can be significantly affected by interactions between surface waters and adjacent aquifers. Environments that exhibit transient hydraulic conditions, such as changes in recharge and groundwater flow rates, are not well understood. The associated impacts to coastal water resources during elevated drought conditions can be better managed with a better understanding of the groundwater-surface water interaction and the transition zone. Proper characterization of the spatial and temporal extent of groundwater discharge is important for water resource management and contaminant migration pathways. The Texas coastal area has been experiencing exceptional drought conditions over the past few years which are expected to persist or intensify in the coming years. An investigation of how the hydrologic system is impacted by these conditions can be a valuable tool regarding water resource management, sustainability and conservation of the Gulf Coast region of South Texas. This study will be using resistivity soundings to vertically and laterally characterize groundwater-surface water interaction and provide a stratigraphic characterization of the transition zone in this area. Chemical and isotope tracers will be used to compliment the resistivity data in order to trace water sources in the surface water and transition zone. This information can aid in evaluating the extent of interaction and degree of mixing between the surface water and groundwater. The ultimate goal of this research is to provide new valuable information that could help professionals and researchers understand complex processes such as groundwater-surface water interaction using new methods that would improve the speed and accuracy of existing systems or techniques. This multidisciplinary approach can be useful in investigating land use impacts on groundwater inflow and in forecasting the availability of water resources in environmentally sensitive ecosystems such as

  4. Fermi surface versus Fermi sea contributions to intrinsic anomalous and spin Hall effects of multiorbital metals in the presence of Coulomb interaction and spin-Coulomb drag

    NASA Astrophysics Data System (ADS)

    Arakawa, Naoya

    2016-06-01

    Anomalous Hall effect (AHE) and spin Hall effect (SHE) are fundamental phenomena, and their potential for application is great. However, we understand the interaction effects unsatisfactorily, and should have clarified issues about the roles of the Fermi sea term and Fermi surface term of the conductivity of the intrinsic AHE or SHE of an interacting multiorbital metal and about the effects of spin-Coulomb drag on the intrinsic SHE. Here, we resolve the first issue and provide the first step about the second issue by developing a general formalism in the linear response theory with appropriate approximations and using analytic arguments. The most striking result is that even without impurities, the Fermi surface term, a non-Berry-curvature term, plays dominant roles at high or slightly low temperatures. In particular, this Fermi surface term causes the temperature dependence of the dc anomalous Hall or spin Hall conductivity due to the interaction-induced quasiparticle damping and the correction of the dc spin Hall conductivity due to the spin-Coulomb drag. Those results revise our understanding of the intrinsic AHE and SHE. We also find that the differences between the dc anomalous Hall and longitudinal conductivities arise from the difference in the dominant multiband excitations. This not only explains why the Fermi sea term such as the Berry-curvature term becomes important in clean and low-temperature case only for interband transports, but also provides the useful principles on treating the electron-electron interaction in an interacting multiorbital metal for general formalism of transport coefficients. Several correspondences between our results and experiments are finally discussed.

  5. Gravity Wave Dynamics and Tidal Interactions in the MLT and at the Bottomside F Layer and Their Potential Contributions to Neutral and Plasma Dynamics

    DTIC Science & Technology

    2012-04-16

    corresponding non-migrating modes, suggesting that the migrating modes must contribute at least as significantly to thermospheric and ionospheric ...became available. These focused on modeling GW dynamics 6 CHAMP ASC VAR Mar 2010 CHAMP DESC VAR Mar 2010 Figure 9. GW density variances computed...sources, including convection, topography, and auroral heating . Our modeling efforts addressing instability dynamics employed 2D and 3D simulations

  6. YAP1 and AR interactions contribute to the switch from androgen-dependent to castration-resistant growth in prostate cancer

    PubMed Central

    Kuser-Abali, Gamze; Alptekin, Ahmet; Lewis, Michael; Garraway, Isla P.; Cinar, Bekir

    2017-01-01

    The transcriptional co-activator Yes-associated protein 1 (YAP1), a key nuclear effector of the Hippo pathway, is a potent oncogene, and yet, the interaction between YAP1 and androgen receptor (AR) remains unexplored. Here we identify YAP1 as a physiological binding partner and positive regulator of AR in prostate cancer. YAP1 and AR co-localize and interact with each other predominantly within cell nuclei by an androgen-dependent mechanism in a hormone naive and an androgen-independent mechanism in castration-resistant prostate cancer cells. The growth suppressor MST1 kinase modulates androgen-dependent and -independent nuclear YAP1–AR interactions through directly regulating YAP1 nuclear accumulation. Disruption of YAP1 signalling by genetic (RNAi) and pharmacological (Verteporfin) approaches suppresses AR-dependent gene expression and prostate cancer cell growth. These findings indicate that the YAP1–AR axis may have a critical role in prostate cancer progression and serves as a viable drug target. PMID:28230103

  7. Interaction between β-hexachlorocyclohexane and ADIPOQ genotypes contributes to the risk of type 2 diabetes mellitus in East Chinese adults

    NASA Astrophysics Data System (ADS)

    Li, Shushu; Wang, Xichen; Yang, Lu; Yao, Shen; Zhang, Ruyang; Xiao, Xue; Zhang, Zhan; Wang, Li; Xu, Qiujin; Wang, Shou-Lin

    2016-11-01

    Growing evidence links environmental exposure to hexachlorocyclohexanes (HCHs) to the risk of type 2 diabetes mellitus (T2DM), and ADIPOQ that encodes adiponectin is considered as an important gene for T2DM. However, the role of ADIPOQ-HCH interaction on T2DM risk remains unclear. Thus, a paired case-control study was conducted in an East Chinese community. A total of 1446 subjects, including 723 cases and 723 controls matched on age, gender and residence, were enrolled, and 4 types of HCH isomers were measured in serum samples using GC-MS/MS. Additionally, 4 candidate ADIPOQ SNPs (rs182052, rs266729, rs6810075, and rs16861194) were genotyped by TaqMan assay, and plasma adiponectin was measured using ELISA. No associations between 4 SNPs and T2DM risk were found, but T2DM risk significantly increased with serum levels of β-HCH (P < 0.001). Furthermore, the synergistic interaction between β-HCH and rs182052 significantly increased T2DM risk (OR I-additive model = 2.20, OR I-recessive model = 2.13). Additionally, individuals carrying only rs182052 (A allele) with high levels of β-HCH had significant reduction in adiponectin levels (P = 0.016). These results indicate that the interaction between rs182052 and β-HCH might increase the risk of T2DM by jointly decreasing the adiponectin level and potentially trigger T2DM development.

  8. Outer membrane protein OlpA contributes to Moraxella catarrhalis serum resistance via interaction with factor H and the alternative pathway.

    PubMed

    Bernhard, Sara; Fleury, Christophe; Su, Yu-Ching; Zipfel, Peter F; Koske, Iris; Nordström, Therése; Riesbeck, Kristian

    2014-10-15

    Factor H is an important complement regulator of the alternative pathway commonly recruited by pathogens to achieve increased rates of survival in the human host. The respiratory pathogen Moraxella catarrhalis, which resides in the mucosa, is highly resistant to the bactericidal activity of serum and causes otitis media in children and respiratory tract infections in individuals with underlying diseases. In this study, we show that M. catarrhalis binds factor H via the outer membrane protein OlpA. M. catarrhalis serum resistance was dramatically decreased in the absence of either OlpA or factor H, demonstrating that this inhibition of the alternative pathway significantly contributes to the virulence of M. catarrhalis.

  9. Interaction between β-hexachlorocyclohexane and ADIPOQ genotypes contributes to the risk of type 2 diabetes mellitus in East Chinese adults

    PubMed Central

    Li, Shushu; Wang, Xichen; Yang, Lu; Yao, Shen; Zhang, Ruyang; Xiao, Xue; Zhang, Zhan; Wang, Li; Xu, Qiujin; Wang, Shou-Lin

    2016-01-01

    Growing evidence links environmental exposure to hexachlorocyclohexanes (HCHs) to the risk of type 2 diabetes mellitus (T2DM), and ADIPOQ that encodes adiponectin is considered as an important gene for T2DM. However, the role of ADIPOQ-HCH interaction on T2DM risk remains unclear. Thus, a paired case-control study was conducted in an East Chinese community. A total of 1446 subjects, including 723 cases and 723 controls matched on age, gender and residence, were enrolled, and 4 types of HCH isomers were measured in serum samples using GC-MS/MS. Additionally, 4 candidate ADIPOQ SNPs (rs182052, rs266729, rs6810075, and rs16861194) were genotyped by TaqMan assay, and plasma adiponectin was measured using ELISA. No associations between 4 SNPs and T2DM risk were found, but T2DM risk significantly increased with serum levels of β-HCH (P < 0.001). Furthermore, the synergistic interaction between β-HCH and rs182052 significantly increased T2DM risk (OR I-additive model = 2.20, OR I-recessive model = 2.13). Additionally, individuals carrying only rs182052 (A allele) with high levels of β-HCH had significant reduction in adiponectin levels (P = 0.016). These results indicate that the interaction between rs182052 and β-HCH might increase the risk of T2DM by jointly decreasing the adiponectin level and potentially trigger T2DM development. PMID:27883041

  10. Cyclophilin A (CypA) Interacts with NF-κB Subunit, p65/RelA, and Contributes to NF-κB Activation Signaling

    PubMed Central

    Zhang, James Beiji; Ha, Albert; Yokoyama, Kazunari K.; Chiu, Robert H.

    2014-01-01

    Background Peptidyl-prolyl isomerase cyclophilin A (CypA) plays important roles in signaling, protein translocation, inflammation, and cancer formation. However, little is known about the mechanisms by which CypA exerts its effects. C57BL/6 Ppia (encoding CypA)-deficient embryonic fibroblasts show reduced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), the p65/RelA subunit, suggesting that CypA may mediate modulation of NF-κB activity to exert its biological effects. Methodology Western blotting and qRT-PCR analyses were used to evaluate the association of CypA deficiency with reduced activation of NF-κB/p65 at the protein level. GST pull-down and co-immunoprecipitation were used to examine interactions between CypA and p65/RelA. Truncation mutants and site-directed mutagenesis were used to determine the sequences of p65/RelA required for interactions with CypA. Enhancement of p65/RelA nuclear translocation by CypA was assessed by co-transfection and immunofluorescent imaging. Treatment of cells with cycloheximide that were harvested at various time points for Western blot analyses was carried out to evaluate p65/RelA protein stability. The functional activity of NF-κB was assessed by electrophoretic mobility-shift assays (EMSA), luciferase assays, and changes in expression levels of target genes. Results GST pull-down assays in vitro and co-immunoprecipitation analyses in vivo provided evidence for protein-protein interactions. These interactions were further supported by identification of a CypA-binding consensus-like sequence within NF-κB subunit p65 at the N-terminal 170–176 amino acid residues. Significantly, CypA provided stability for NF-κB p65 and promoted NF-κB p65 nuclear translocation, resulting in increased nuclear accumulation and enhanced NF-κB activity. Conclusions Our findings revealed important mechanisms that regulate NF-κB activation, and offer new insights into the role of CypA in aberrant

  11. Analytical description of the slope of the APD-restitution curve to assess the interacting contribution of conduction and repolarization dynamics.

    PubMed

    Orini, Michele; Taggart, Peter; Hayward, Martin; Lambiase, Pier D

    2015-08-01

    The restitution of the action potential duration (APDR) is a mechanism whereby cardiac excitation and relaxation adapt to changes in heart rate. Several studies, mainly carried out in-vitro and in-silico, have demonstrated that a steep APDR curve is associated with increased vulnerability to fatal arrhythmias. However, the mechanisms that link the steepness of the APDR curve to arrhythmogenesis remain undetermined. Although APDR is known to interact with conduction dynamics, few studies have focused on these interactions. In this paper, an analytical expression of the slope of the APDR is derived. This expression explicitly describes the dependency of the slope of the APDR curve on the activation time and/or conduction velocity changes. The study of this expression shows that conduction dynamics are among the main determinants of the slope of the APDR curve. A small absolute increment in the steepness of the activation time restitution slope can cause the steepness of the APDR slope to dramatically increase. Theoretically, the APDR slope quickly diverges to infinity when the increase in activation time matches the decrease in the pacing interval. High density epicardial mapping performed in a patient undergoing open heart surgery, shows excellent agreement between measures of the slope of the APDR curve and its analytical prediction (linear correlation > 0.95). The in-vivo recordings suggest that activation time restitution is the main determinant of the slope of the APDR curve.

  12. FUS/TLS contributes to replication-dependent histone gene expression by interaction with U7 snRNPs and histone-specific transcription factors

    PubMed Central

    Raczynska, Katarzyna Dorota; Ruepp, Marc-David; Brzek, Aleksandra; Reber, Stefan; Romeo, Valentina; Rindlisbacher, Barbara; Heller, Manfred; Szweykowska-Kulinska, Zofia; Jarmolowski, Artur; Schümperli, Daniel

    2015-01-01

    Replication-dependent histone genes are up-regulated during the G1/S phase transition to meet the requirement for histones to package the newly synthesized DNA. In mammalian cells, this increment is achieved by enhanced transcription and 3′ end processing. The non-polyadenylated histone mRNA 3′ ends are generated by a unique mechanism involving the U7 small ribonucleoprotein (U7 snRNP). By using affinity purification methods to enrich U7 snRNA, we identified FUS/TLS as a novel U7 snRNP interacting protein. Both U7 snRNA and histone transcripts can be precipitated by FUS antibodies predominantly in the S phase of the cell cycle. Moreover, FUS depletion leads to decreased levels of correctly processed histone mRNAs and increased levels of extended transcripts. Interestingly, FUS antibodies also co-immunoprecipitate histone transcriptional activator NPAT and transcriptional repressor hnRNP UL1 in different phases of the cell cycle. We further show that FUS binds to histone genes in S phase, promotes the recruitment of RNA polymerase II and is important for the activity of histone gene promoters. Thus, FUS may serve as a linking factor that positively regulates histone gene transcription and 3′ end processing by interacting with the U7 snRNP and other factors involved in replication-dependent histone gene expression. PMID:26250115

  13. Orosomucoid Proteins Interact with the Small Subunit of Serine Palmitoyltransferase and Contribute to Sphingolipid Homeostasis and Stress Responses in Arabidopsis[OPEN

    PubMed Central

    Li, Jian; Yin, Jian; Rong, Chan; Li, Kai-En; Wu, Jian-Xin; Huang, Li-Qun; Zeng, Hong-Yun; Sahu, Sunil Kumar; Yao, Nan

    2016-01-01

    Serine palmitoyltransferase (SPT), a pyridoxyl-5′-phosphate-dependent enzyme, catalyzes the first and rate-limiting step in sphingolipid biosynthesis. In humans and yeast, orosomucoid proteins (ORMs) negatively regulate SPT and thus play an important role in maintaining sphingolipid levels. Despite the importance of sphingoid intermediates as bioactive molecules, the regulation of sphingolipid biosynthesis through SPT is not well understood in plants. Here, we identified and characterized the Arabidopsis thaliana ORMs, ORM1 and ORM2. Loss of function of both ORM1 and ORM2 (orm1 amiR-ORM2) stimulated de novo sphingolipid biosynthesis, leading to strong sphingolipid accumulation, especially of long-chain bases and ceramides. Yeast two-hybrid, bimolecular fluorescence complementation, and coimmunoprecipitation assays confirmed that ORM1 and ORM2 physically interact with the small subunit of SPT (ssSPT), indicating that ORMs inhibit ssSPT function. We found that orm1 amiR-ORM2 plants exhibited an early-senescence phenotype accompanied by H2O2 production at the cell wall and in mitochondria, active vesicular trafficking, and formation of cell wall appositions. Strikingly, the orm1 amiR-ORM2 plants showed increased expression of genes related to endoplasmic reticulum stress and defenses and also had enhanced resistance to oxidative stress and pathogen infection. Taken together, our findings indicate that ORMs interact with SPT to regulate sphingolipid homeostasis and play a pivotal role in environmental stress tolerance in plants. PMID:27923879

  14. Adenosine produced from adenine nucleotides through an interaction between apoptotic cells and engulfing macrophages contributes to the appearance of transglutaminase 2 in dying thymocytes.

    PubMed

    Sándor, Katalin; Pallai, Anna; Duró, Edina; Legendre, Pascal; Couillin, Isabelle; Sághy, Tibor; Szondy, Zsuzsa

    2017-03-01

    Transglutaminase 2 (TG2) has been known for a long time to be associated with the in vivo apoptosis program of various cell types, including T cells. Though the expression of the enzyme is strongly induced in mouse thymocytes following apoptosis induction in vivo, no significant induction of TG2 can be detected, when thymocytes are induced to die by the same stimuli in vitro indicating that signals arriving from the tissue environment are required for the proper in vivo induction of the enzyme. Previous studies from our laboratory have demonstrated that two of these signals, transforming growth factor-β (TGF-β) and retinoids, are produced by macrophages engulfing apoptotic cells. However, in addition to TGF-β and retinoids, engulfing macrophages produce adenosine as well. Here, we show that in vitro adenosine, adenosine, and retinoic acid or adenosine, TGF-β and retinoic acids together can significantly enhance the TG2 mRNA expression in dying thymocytes. The effect of adenosine is mediated via adenosine A2A receptors (A2ARs) and the A2AR-triggered adenylate cyclase signaling pathway. In accordance, loss of A2ARs in A2AR null mice significantly attenuates the in vivo induction of TG2 following apoptosis induction in the thymus indicating that adenosine indeed contributes in vivo to the apoptosis-related appearance of the enzyme. We also demonstrate that adenosine is produced extracellularly during engulfment of apoptotic thymocytes, partly from adenine nucleotides released via thymocyte pannexin-1 channels. Our data reveal a novel crosstalk between macrophages and apoptotic cells, in which apoptotic cell uptake-related adenosine production contributes to the appearance of TG2 in the dying thymocytes.

  15. Drug interaction between sunitinib and cimetidine and contribution of the efflux transporter ATP-binding cassette C2 to biliary excretion of sunitinib in rats.

    PubMed

    Arakawa-Todo, Maki; Ueyama, Jun; Nomura, Hiroshi; Abe, Fumie; Tsukiyama, Ikuto; Matsuura, Katsuhiko; Hasegawa, Takaaki

    2013-08-01

    The present study investigated the effect of the H2 antagonist cimetidine on the pharmacokinetics of a multi-targeted receptor tyrosine kinase (RTK) inhibitor, sunitinib, in Sprague-Dawley (SD) rats and Eisai hyperbilirubinemic mutant rats (EHBR) lacking the efflux transporter, ATP-binding cassette C2 protein (ABCC2). Rats received an intraperitoneal injection of cimetidine (10 mg/kg) once a day for three days. On day 4, sunitinib (3 mg/kg) was administered intravenously 30 min after the final injection of cimetidine or saline to SD rats. Disappearance of sunitinib from plasma was significantly delayed by cimetidine. The pharmacokinetic parameter of sunitinib, systemic clearance (CLSYS), was significantly reduced and the half-life was significantly prolonged, with no change in the volume of distribution at steady-state (VSS). When the effect of cimetidine on the biliary excretion of sunitinib at steady-state condition was investigated in SD rats, cimetidine had no effect on some transporter-mediated biliary excretion of sunitinib. Furthermore, the contribution of ABCC2 to the biliary excretion of sunitinib was also examined in SD rats and EHBR. The biliary clearance of sunitinib was significantly lower in EHBR, but the biliary excretion rate of EHBR was not different from that of SD rats, and the contribution of biliary excretion to systemic elimination was small, suggesting that sunitinib is mainly eliminated by cytochrome P450 3A4 (CYP3A4)-mediated metabolism and is not excreted into the bile via ABCC2. These findings indicate that co-administration of cimetidine alters the pharmacokinetics of sunitinib probably due to inhibition of CYP3A4, suggesting the possibility that cimetidine should be used carefully for patients with cancer being treated with sunitinib therapy.

  16. Electron micrographic study of precipitates formed by interaction of silicic acid and alkaline phosphatase: contribution to a study of silica urolithiasis in cattle.

    PubMed

    Bailey, C B; Cheng, K J; Costerton, J W

    1982-12-01

    Association of alkaline phosphatase with silicic acid in precipitates formed in dilute solution was studied as a model for the nonspecific reaction between silicic acid and protein. Precipitates contained 68-83% of the silicic acid and 52-83% of the enzyme in the original mixture and were in the form of aggregates of roundish particles 150-800 nm in diameter. Enzyme protein formed a tightly bound layer on the surface of particles formed in solutions of freshly prepared silicic acid. The similarity between the ultrastructural features of precipitates from solutions of silicic acid and of internal portions of siliceous urinary calculi from cattle suggests that deposition of silica during development of such calculi is due, at least in part, to the interaction of protein with silicic acid in urine.

  17. Behavioral profiles of affected and unaffected siblings of children with autism: contribution of measures of mother-infant interaction and nonverbal communication.

    PubMed

    Rozga, Agata; Hutman, Ted; Young, Gregory S; Rogers, Sally J; Ozonoff, Sally; Dapretto, Mirella; Sigman, Marian

    2011-03-01

    We investigated whether deficits in social gaze and affect and in joint attention behaviors are evident within the first year of life among siblings of children with autism who go on to be diagnosed with autism or ASD (ASD) and siblings who are non-diagnosed (NoASD-sib) compared to low-risk controls. The ASD group did not differ from the other two groups at 6 months of age in the frequency of gaze, smiles, and vocalizations directed toward the caregiver, nor in their sensitivity to her withdrawal from interaction. However, by 12 months, infants in the ASD group exhibited lower rates of joint attention and requesting behaviors. In contrast, NoASD-sibs did not differ from comparison infants on any variables of interest at 6 and 12 months.

  18. A Transient Interaction between the Phosphate Binding Loop and Switch I Contributes to the Allosteric Network between Receptor and Nucleotide in Gαi1*

    PubMed Central

    Thaker, Tarjani M.; Sarwar, Maruf; Preininger, Anita M.; Hamm, Heidi E.; Iverson, T. M.

    2014-01-01

    Receptor-mediated activation of the Gα subunit of heterotrimeric G proteins requires allosteric communication between the receptor binding site and the guanine nucleotide binding site, which are separated by >30 Å. Structural changes in the allosteric network connecting these sites are predicted to be transient in the wild-type Gα subunit, making studies of these connections challenging. In the current work, site-directed mutants that alter the energy barriers between the activation states are used as tools to better understand the transient features of allosteric signaling in the Gα subunit. The observed differences in relative receptor affinity for intact Gαi1 subunits versus C-terminal Gαi1 peptides harboring the K345L mutation are consistent with this mutation modulating the allosteric network in the protein subunit. Measurement of nucleotide exchange rates, affinity for metarhodopsin II, and thermostability suggest that the K345L Gαi1 variant has reduced stability in both the GDP-bound and nucleotide-free states as compared with wild type but similar stability in the GTPγS-bound state. High resolution x-ray crystal structures reveal conformational changes accompanying the destabilization of the GDP-bound state. Of these, the conformation for Switch I was stabilized by an ionic interaction with the phosphate binding loop. Further site-directed mutagenesis suggests that this interaction between Switch I and the phosphate binding loop is important for receptor-mediated nucleotide exchange in the wild-type Gαi1 subunit. PMID:24596087

  19. A Tripartite Interaction Between Spartina alterniflora, Fusarium palustre, and the Purple Marsh Crab (Sesarma reticulatum) Contributes to Sudden Vegetation Dieback of Salt Marshes in New England.

    PubMed

    Elmer, Wade H

    2014-10-01

    Tripartite interactions are common and occur when one agent (an arthropod or pathogen) changes the host plant in a manner that alters the attack of the challenging agent. We examined herbivory from the purple marsh crab (Sesarma reticulatum) on Spartina alterniflora following exposure to drought or inoculation with Fusarium palustre in mecocosms in the greenhouse and in crab-infested creek banks along intertidal salt marshes. Initially, drought stress on S. alterniflora and disease from F. palustre were examined in the greenhouse. Then, a second challenger, the purple marsh crab, was introduced to determine how drought and disease from F. palustre affected the attraction and consumption of S. alterniflora. Plant height and shoot and root weights were reduced in plants subjected to severe drought treatment when compared with normally irrigated plants. When the drought treatment was combined with inoculation with F. palustre, plants were significantly more stunted and symptomatic, had less fresh weight, more diseased roots, and a greater number of Fusarium colonies growing from the roots (P < 0.001) than noninoculated plants. The effects were additive, and statistical interactions were not detected between drought and inoculation. Estimates of herbivory (number of grass blades cut or biomass consumption) by the purple marsh crab were significantly greater on drought-stressed, diseased plants than on healthy plants irrigated normally. Drought increased attraction to the purple marsh crab more than inoculation with F. palustre. However, when only mild drought conditions were imposed, plant consumption was greater on inoculated plants. Healthy, nonstressed transplants set into plots in crabinfested intertidal creek banks were grazed less each year than inoculated plants or plants that were exposed to drought. Several hypotheses relating to nutrition, chemotaxis, and visual attraction are presented to explain how stress from drought or disease might favor herbivory.

  20. Unraveling the contributions of hydrogen-bonding interactions to the activity of native and non-native ligands in the quorum-sensing receptor LasR

    PubMed Central

    Gerdt, Joseph P.; McInnis, Christine E.; Schell, Trevor L.; Blackwell, Helen E.

    2014-01-01

    Quorum sensing (QS) via the synthesis and detection of N-acyl L-homoserine lactone (AHL) signals regulates important pathogenic and mutualistic phenotypes in many bacteria. Over the past two decades, the development of non-native molecules that modulate this cell-cell signaling process has become an active area of research. The majority of these compounds were designed for block binding of the native AHL signal to its cognate LuxR-type receptor, and much effort has focused on LasR in the opportunistic pathogen Pseudomonas aeruginosa. Despite a small set of reported LasR structural data, it remains unclear which polar interactions are most important for either (i) activation of the LasR receptor by its native AHL signal, N-(3-oxo)-dodecanoyl L-homoserine lactone (OdDHL), or (ii) activation or inhibition of LasR by related AHL analogs. Herein, we report our investigations into the activity of OdDHL and five synthetic analogs in wild-type LasR and in nine LasR mutants with modifications to key polar residues in their ligand binding sites. Our results allowed us to rank, for the first time, the relative importance of each LasR:OdDHL hydrogen bond for LasR activation and provide strong evidence for the five synthetic ligands binding LasR in a very similar orientation as OdDHL. By delineating the specific molecular interactions that are important for LasR modulation by AHLs, these findings should aid in the design of new synthetic modulators of LasR (and homologous LuxR-type receptors) with improved potencies and selectivities. PMID:25474181

  1. JPH-2 INTERACTS WITH Cai-HANDLING PROTEINS AND ION CHANNELS IN DYADS: CONTRIBUTION TO PREMATURE VENTRICULAR CONTRACTION-INDUCED CARDIOMYOPATHY

    PubMed Central

    Jiang, Min; Zhang, Mei; Howren, Maureen; Wang, Yuhong; Tan, Alex; Balijepalli, Ravi C.; Huizar, Jose F.; Tseng, Gea-Ny

    2015-01-01

    Background In a canine model of premature ventricular contraction-induced cardiomyopathy (PVC-CM), Cav1.2 is downregulated and misplaced from t-tubules. Junctophilin-2 (JPH-2) is also downregulated. Objective To understand the role of JPH-2 in PVC-CM, and to probe changes in other proteins involved in dyad structure and function. Methods We quantify t-tubule contents (di-8-ANEPPS fluorescence in live myocytes), examine myocyte ultra-structures (electron microscopy), probe JPH-2 interacting proteins (co-immunoprecipitation), quantify dyad and non-dyad protein levels (immunoblotting), and examine subcellular distributions of dyad proteins (immunofluorescence/confocal microscopy). We also test direct JPH-2 modulation of channel function (vs indirect modulation through dyad formation) using heterologous expression. Results PVC myocytes have reduced t-tubule contents but otherwise normal ultra-structures. Among nineteen proteins examined, only JPH-2, bridging-integrator-1 (BIN-1) and Cav1.2 are highly downregulated in PVC hearts. However, statistical analysis indicates a general reduction of dyad protein levels when JPH-2 is downregulated. Furthermore, several dyad proteins, including Na/Ca exchanger, are missing or shifted from dyads to peripheral surface in PVC myocytes. JPH-2 directly or indirectly interacts with Cai-handling proteins, Cav1.2 and KCNQ1, although not BIN-1 or other scaffolding proteins tested. Expression in mammalian cells, that do not have dyads, confirms direct JPH-2 modulation of ICaL (Cav1.2/Cavβ2) and IKs (KCNQ1/KCNE1). Conclusion JPH-2 is more than a ‘dyad glue’: it can modulate Cai-handling and ion channel function in the dyad region. Downregulation of JPH-2, BIN-1 and Cav1.2 plays a deterministic role in PVC-CM. Dissecting the hierarchical relationship among the three is necessary for the design of therapeutic interventions to prevent the progression of PVC-CM. PMID:26538326

  2. Interactive contributions of self-regulation deficits and social motivation to psychopathology: unraveling divergent pathways to aggressive behavior and depressive symptoms.

    PubMed

    Rudolph, Karen D; Troop-Gordon, Wendy; Llewellyn, Nicole

    2013-05-01

    Poor self-regulation has been implicated as a significant risk factor for the development of multiple forms of psychopathology. This research examined the proposition that self-regulation deficits differentially predict aggressive behavior and depressive symptoms, depending on children's social approach versus avoidance motivation. A prospective, multiple-informant approach was used to test this hypothesis in 419 children (M age = 8.92, SD = 0.36). Parents rated children's inhibitory control. Children completed measures of social approach-avoidance motivation and depressive symptoms. Teachers rated children's aggressive behavior. As anticipated, poor inhibitory control predicted aggressive behavior in boys with high but not low approach motivation and low but not high avoidance motivation, whereas poor inhibitory control predicted depressive symptoms in girls with high but not low avoidance motivation. This research supports several complementary theoretical models of psychopathology and provides insight into the differential contributions of poor self-regulation to maladaptive developmental outcomes. The findings suggest the need for targeted intervention programs that consider heterogeneity among children with self-regulatory deficits.

  3. Structural elucidation, density functional calculations and contribution of intermolecular interactions in cholest-4-en-3-one crystals: Insights from X-ray and Hirshfeld surface analysis

    NASA Astrophysics Data System (ADS)

    Khanam, Hena; Mashrai, Ashraf; Siddiqui, Nazish; Ahmad, Musheer; Alam, Mohammad Jane; Ahmad, Shabbir; Shamsuzzaman

    2015-03-01

    The foremost objective of the present work is systematic analysis of intermolecular interactions in crystal structure of cholest-4-en-3-one (2) molecule. It is accomplished by Hirshfeld surface analysis and fingerprint plot. Hirshfeld surface analysis has been used to visualize the fidelity of the crystal structure. This method permitted for the identification of individual types of intermolecular contacts and their impact on the complete packing. Molecules are linked by a combination of Cdbnd O--H, Csbnd H--H, and C--H contacts, which have clear signatures in the fingerprint plots. The theoretical study was attempted to predict the optimized geometry and computed spectra by the Density Functional Theory (DFT) using the B3LYP function with the 6-311++G(d,p) basis set. Atomic charges, MEP mapping, HOMO-LUMO, various thermodynamic and molecular properties have been reported. In addition thermal stability, optical, morphological, and microstructral properties of the title compound (2) have also been explored.

  4. In Vivo-Induced InvA-Like Autotransporters Ifp and InvC of Yersinia pseudotuberculosis Promote Interactions with Intestinal Epithelial Cells and Contribute to Virulence

    PubMed Central

    Pisano, Fabio; Kochut, Annika; Uliczka, Frank; Geyer, Rebecca; Stolz, Tatjana; Thiermann, Tanja; Rohde, Manfred

    2012-01-01

    The Yersinia pseudotuberculosis Ifp and InvC molecules are putative autotransporter proteins with a high homology to the invasin (InvA) protein. To characterize the function of these surface proteins, we expressed both factors in Escherichia coli K-12 and demonstrated the attachment of Ifp- and InvC-expressing bacteria to human-, mouse-, and pig-derived intestinal epithelial cells. Ifp also was found to mediate microcolony formation and internalization into polarized human enterocytes. The ifp and invC genes were not expressed under in vitro conditions but were found to be induced in the Peyer's patches of the mouse intestinal tract. In a murine coinfection model, the colonization of the Peyer's patches and the mesenteric lymph nodes of mice by the ifp-deficient strain was significantly reduced, and considerably fewer bacteria reached liver and spleen. The absence of InvC did not have a severe influence on bacterial colonization in the murine infection model, and it resulted in only a slightly reduced number of invC mutants in the Peyer's patches. The analysis of the host immune response demonstrated that the presence of Ifp and InvC reduced the recruitment of professional phagocytes, especially neutrophils, in the Peyer's patches. These findings support a role for the adhesins in modulating host-pathogen interactions that are important for immune defense. PMID:22158741

  5. KRT6 interacting with notch1 contributes to progression of renal cell carcinoma, and aliskiren inhibits renal carcinoma cell lines proliferation in vitro.

    PubMed

    Hu, Jing; Zhang, Li-Chao; Song, Xu; Lu, Jian-Rao; Jin, Zhu

    2015-01-01

    Notch signaling is a conserved and widely expressed signaling pathway, which mediates various physiological processes including tumorigenesis. This study aims to explore the potential role and mechanism of notch1 interacting with KRT6B in the progression of RCC. The results indicated that the mRNA and protein expression of notch1 and KRT6 were significantly increased in tumor tissues, and highly positive correlation existed between notch1 and KRT6. Moreover, the patients with high notch1 expression had a significantly poorer prognosis than those of low expression patients. In vitro, KRT6 loss-of-function could inhibit the expression of notch1 and induce renal carcinoma cell death. Eventually, we found that renin inhibitor, aliskiren, could inhibit cell proliferation and decrease the expression of notch1 and KRT6 as well as regulate apoptosis-related protein expression in 786-O and ACHN renal carcinoma cell lines. These results suggested that the upregulation of notch1 and KRT6B might be involved in the development, progression and prognosis of human RCC, and aliskiren could suppress renal carcinoma cell proliferation, at least partially, through downregulation the expression of notch1 and KRT6.

  6. Gut microbial adaptation to dietary consumption of fructose, artificial sweeteners and sugar alcohols: implications for host-microbe interactions contributing to obesity.

    PubMed

    Payne, A N; Chassard, C; Lacroix, C

    2012-09-01

    The Western diet, comprised of highly refined carbohydrates and fat but reduced complex plant polysaccharides, has been attributed to the prevalence of obesity. A concomitant rise in the consumption of fructose and sugar substitutes such as sugar alcohols, artificial sweeteners, even rare sugars, has mirrored this trend, as both probable contributor and solution to the epidemic. Acknowledgement of the gut microbiota as a factor involved in obesity has sparked much controversy as to the cause and consequence of this relationship. Dietary intakes are a known modulator of gut microbial phylogeny and metabolic activity, frequently exploited to stimulate beneficial bacteria, promoting health benefits. Comparably little research exists on the impact of 'unconscious' dietary modulation on the resident commensal community mediated by increased fructose and sugar substitute consumption. This review highlights mechanisms of potential host and gut microbial fructose and sugar substitute metabolism. Evidence is presented suggesting these sugar compounds, particularly fructose, condition the microbiota, resulting in acquisition of a westernized microbiome with altered metabolic capacity. Disturbances in host-microbe interactions resulting from fructose consumption are also explored.

  7. The transcriptional regulatory network of Corynebacterium jeikeium K411 and its interaction with metabolic routes contributing to human body odor formation.

    PubMed

    Barzantny, Helena; Schröder, Jasmin; Strotmeier, Jasmin; Fredrich, Eugenie; Brune, Iris; Tauch, Andreas

    2012-06-15

    Lipophilic corynebacteria are involved in the generation of volatile odorous products in the process of human body odor formation by degrading skin lipids and specific odor precursors. Therefore, these bacteria represent appropriate model systems for the cosmetic industry to examine axillary malodor formation on the molecular level. To understand the transcriptional control of metabolic pathways involved in this process, the transcriptional regulatory network of the lipophilic axilla isolate Corynebacterium jeikeium K411 was reconstructed from the complete genome sequence. This bioinformatic approach detected a gene-regulatory repertoire of 83 candidate proteins, including 56 DNA-binding transcriptional regulators, nine two-component systems, nine sigma factors, and nine regulators with diverse physiological functions. Furthermore, a cross-genome comparison among selected corynebacterial species of the taxonomic cluster 3 revealed a common gene-regulatory repertoire of 44 transcriptional regulators, including the MarR-like regulator Jk0257, which is exclusively encoded in the genomes of this taxonomical subline. The current network reconstruction comprises 48 transcriptional regulators and 674 gene-regulatory interactions that were assigned to five interconnected functional modules. Most genes involved in lipid degradation are under the combined control of the global cAMP-sensing transcriptional regulator GlxR and the LuxR-family regulator RamA, probably reflecting the essential role of lipid degradation in C. jeikeium. This study provides the first genome-scale in silico analysis of the transcriptional regulation of metabolism in a lipophilic bacterium involved in the formation of human body odor.

  8. Functional requirements for interactions between CD84 and Src homology 2 domain-containing proteins and their contribution to human T cell activation.

    PubMed

    Tangye, Stuart G; Nichols, Kim E; Hare, Nathan J; van de Weerdt, Barbara C M

    2003-09-01

    Cell surface receptors belonging to the CD2 subset of the Ig superfamily of molecules include CD2, CD48, CD58, 2B4, signaling lymphocytic activation molecule (SLAM), Ly9, CD84, and the recently identified molecules NTB-A/Ly108/SLAM family (SF) 2000, CD84H-1/SF2001, B lymphocyte activator macrophage expressed (BLAME), and CRACC (CD2-like receptor-activating cytotoxic cells)/CS-1. Some of these receptors, such as CD2, SLAM, 2B4, CRACC, and NTB-A, contribute to the activation and effector function of T cells and NK cells. Signaling pathways elicited via some of these receptors are believed to involve the Src homology 2 (SH2) domain-containing cytoplasmic adaptor protein SLAM-associated protein (SAP), as it is recruited to SLAM, 2B4, CD84, NTB-A, and Ly-9. Importantly, mutations in SAP cause the inherited human immunodeficiency X-linked lymphoproliferative syndrome (XLP), suggesting that XLP may result from perturbed signaling via one or more of these SAP-associating receptors. We have now studied the requirements for SAP recruitment to CD84 and lymphocyte activation elicited following ligation of CD84 on primary and transformed human T cells. CD84 was found to be rapidly tyrosine phosphorylated following receptor ligation on activated T cells, an event that involved the Src kinase Lck. Phosphorylation of CD84 was indispensable for the recruitment of SAP, which was mediated by Y(262) within the cytoplasmic domain of CD84 and by R(32) within the SH2 domain of SAP. Furthermore, ligating CD84 enhanced the proliferation of anti-CD3 mAb-stimulated human T cells. Strikingly, this effect was also apparent in SAP-deficient T cells obtained from patients with XLP. These results reveal a novel function of CD84 on human lymphocytes and suggest that CD84 can activate human T cells via a SAP-independent mechanism.

  9. CD9 may contribute to the survival of human germinal center B cells by facilitating the interaction with follicular dendritic cells

    PubMed Central

    Yoon, Sun-Ok; Lee, In Yong; Zhang, Xin; Zapata, Mariana C.; Choi, Yong Sung

    2014-01-01

    The germinal center (GC) is a dynamic microenvironment where antigen (Ag)-activated B cells rapidly expand and differentiate, generating plasma cells (PC) that produce high-affinity antibodies. Precise regulation of survival and proliferation of Ag-activated B cells within the GC is crucial for humoral immune responses. The follicular dendritic cells (FDC) are the specialized stromal cells in the GC that prevent apoptosis of GC-B cells. Recently, we reported that human GC-B cells consist of CD9+ and CD9− populations and that it is the CD9+ cells that are committed to the PC lineage. In this study, we investigated the functional role of CD9 on GC-B cells. Tonsillar tissue section staining revealed that in vivo CD9+ GC-B cells localized in the light zone FDC area. Consistent this, in vitro CD9+ GC-B cells survived better than CD9− GC-B cells in the presence of HK cells, an FDC line, in a cell–cell contact-dependent manner. The frozen tonsillar tissue section binding assay showed that CD9+ GC-B cells bound to the GC area of tonsillar tissues significantly more than the CD9− GC-B cells did and that the binding was significantly inhibited by neutralizing anti-integrin β1 antibody. Furthermore, CD9+ cells bound to soluble VCAM-1 more than CD9− cells did, resulting in activation and stabilization of the active epitope of integrin β1. All together, our data suggest that CD9 on GC-B cells contributes to survival by strengthening their binding to FDC through the VLA4/VCAM-1 axis. PMID:24918051

  10. Contributions of ionic interactions and protein dynamics to cytochrome P450 2D6 (CYP2D6) substrate and inhibitor binding.

    PubMed

    Wang, An; Stout, C David; Zhang, Qinghai; Johnson, Eric F

    2015-02-20

    P450 2D6 contributes significantly to the metabolism of >15% of the 200 most marketed drugs. Open and closed crystal structures of P450 2D6 thioridazine complexes were obtained using different crystallization conditions. The protonated piperidine moiety of thioridazine forms a charge-stabilized hydrogen bond with Asp-301 in the active sites of both complexes. The more open conformation exhibits a second molecule of thioridazine bound in an expanded substrate access channel antechamber with its piperidine moiety forming a charge-stabilized hydrogen bond with Glu-222. Incubation of the crystalline open thioridazine complex with alternative ligands, prinomastat, quinidine, quinine, or ajmalicine, displaced both thioridazines. Quinine and ajmalicine formed charge-stabilized hydrogen bonds with Glu-216, whereas the protonated nitrogen of quinidine is equidistant from Asp-301 and Glu-216 with protonated nitrogen H-bonded to a water molecule in the access channel. Prinomastat is not ionized. Adaptations of active site side-chain rotamers and polypeptide conformations were evident between the complexes, with the binding of ajmalicine eliciting a closure of the open structure reflecting in part the inward movement of Glu-216 to form a hydrogen bond with ajmalicine as well as sparse lattice restraints that would hinder adaptations. These results indicate that P450 2D6 exhibits sufficient elasticity within the crystal lattice to allow the passage of compounds between the active site and bulk solvent and to adopt a more closed form that adapts for binding alternative ligands with different degrees of closure. These crystals provide a means to characterize substrate and inhibitor binding to the enzyme after replacement of thioridazine with alternative compounds.

  11. An interaction between glucagon-like peptide-1 and adenosine contributes to cardioprotection of a dipeptidyl peptidase 4 inhibitor from myocardial ischemia-reperfusion injury.

    PubMed

    Ihara, Madoka; Asanuma, Hiroshi; Yamazaki, Satoru; Kato, Hisakazu; Asano, Yoshihiro; Shinozaki, Yoshihiro; Mori, Hidezo; Minamino, Tetsuo; Asakura, Masanori; Sugimachi, Masaru; Mochizuki, Naoki; Kitakaze, Masafumi

    2015-05-15

    Dipeptidyl peptidase 4 (DPP4) inhibitors suppress the metabolism of the potent antihyperglycemic hormone glucagon-like peptide-1 (GLP-1). DPP4 was recently shown to provide cardioprotection through a reduction of infarct size, but the mechanism for this remains elusive. Known interactions between DPP4 and adenosine deaminase (ADA) suggest an involvement of adenosine signaling in DPP4 inhibitor-mediated cardioprotection. We tested whether the protective mechanism of the DPP4 inhibitor alogliptin against myocardial ischemia-reperfusion injury involves GLP-1- and/or adenosine-dependent signaling in canine hearts. In anesthetized dogs, the coronary artery was occluded for 90 min followed by reperfusion for 6 h. A 4-day pretreatment with alogliptin reduced the infarct size from 43.1 ± 2.5% to 17.1 ± 5.0% without affecting collateral flow and hemodynamic parameters, indicating a potent antinecrotic effect. Alogliptin also suppressed apoptosis as demonstrated by the following analysis: 1) reduction in the Bax-to-Bcl2 ratio; 2) cytochrome c release, 3) an increase in Bad phosphorylation in the cytosolic fraction; and 4) terminal deoxynucleotidyl transferase dUTP nick end labeling assay. This DPP4 inhibitor did not affect blood ADA activity or adenosine concentrations. In contrast, the nonselective adenosine receptor blocker 8-(p-sulfophenyl)theophylline (8SPT) completely blunted the effect of alogliptin. Alogliptin did not affect Erk1/2 phosphorylation, but it did stimulate phosphorylation of Akt, glycogen synthase kinase-3β, and cAMP response element-binding protein (CREB). Only 8SPT prevented alogliptin-induced CREB phosphorylation. In conclusion, the DPP4 inhibitor alogliptin suppresses ischemia-reperfusion injury via adenosine receptor- and CREB-dependent signaling pathways.

  12. The relative contribution of short-term versus long-term effects in shrub-understory species interactions under arid conditions.

    PubMed

    Noumi, Zouhaier; Chaieb, Mohamed; Le Bagousse-Pinguet, Yoann; Michalet, Richard

    2016-02-01

    Plant-plant interactions (competition and facilitation) in terrestrial ecosystems include: (1) short-term effects, primarily quantified with experimental removals; and (2) long-term effects, mostly due to soil weathering processes, primarily quantified with observational methods. It has been argued that these effects are likely to vary in contrasting directions with increasing drought stress in arid systems. However, few studies have used appropriate methodology to assess both types of effects and their variation across nurse species and environmental conditions, in particular in arid systems. This knowledge is crucial for predicting variation in the mediating role of facilitation with climate change and assessing the importance of nurse effects in ecological restoration. In the arid climate of central-south Tunisia, understory species' biomass, abundance and composition and soil parameters were compared in shrub-control, shrub-removed and open areas for three shrub species and in two habitats with contrasting soil moisture conditions. Long-term effects were dominant, positive for all three shrub species and associated with increasing nutrient content in shrub patches. Short-term effects, mainly related to water consumption, were weaker, mostly negative and dependent on shrub species. Additionally, long-term effects were less positive and short-term effects more negative in the dry habitat than in the wet habitat. Our study provides evidence of the primary influence of positive (facilitative) long-term effects in this arid system. However, the net effects of shrubs could be less beneficial for other species with increasing aridity under climate change, due to both a decrease in positive long-term effects and an increase in negative short-term effects.

  13. Modelling entomological-climatic interactions of Plasmodium falciparum malaria transmission in two Colombian endemic-regions: contributions to a National Malaria Early Warning System

    PubMed Central

    Ruiz, Daniel; Poveda, Germán; Vélez, Iván D; Quiñones, Martha L; Rúa, Guillermo L; Velásquez, Luz E; Zuluaga, Juan S

    2006-01-01

    Background Malaria has recently re-emerged as a public health burden in Colombia. Although the problem seems to be climate-driven, there remain significant gaps of knowledge in the understanding of the complexity of malaria transmission, which have motivated attempts to develop a comprehensive model. Methods The mathematical tool was applied to represent Plasmodium falciparum malaria transmission in two endemic-areas. Entomological exogenous variables were estimated through field campaigns and laboratory experiments. Availability of breeding places was included towards representing fluctuations in vector densities. Diverse scenarios, sensitivity analyses and instabilities cases were considered during experimentation-validation process. Results Correlation coefficients and mean square errors between observed and modelled incidences reached 0.897–0.668 (P > 0.95) and 0.0002–0.0005, respectively. Temperature became the most relevant climatic parameter driving the final incidence. Accordingly, malaria outbreaks are possible during the favourable epochs following the onset of El Niño warm events. Sporogonic and gonotrophic cycles showed to be the entomological key-variables controlling the transmission potential of mosquitoes' population. Simulation results also showed that seasonality of vector density becomes an important factor towards understanding disease transmission. Conclusion The model constitutes a promising tool to deepen the understanding of the multiple interactions related to malaria transmission conducive to outbreaks. In the foreseeable future it could be implemented as a tool to diagnose possible dynamical patterns of malaria incidence under several scenarios, as well as a decision-making tool for the early detection and control of outbreaks. The model will be also able to be merged with forecasts of El Niño events to provide a National Malaria Early Warning System. PMID:16882349

  14. Antidepressant activity: contribution of brain microdialysis in knock-out mice to the understanding of BDNF/5-HT transporter/5-HT autoreceptor interactions

    PubMed Central

    Gardier, Alain M.

    2013-01-01

    Why antidepressants vary in terms of efficacy is currently unclear. Despite the leadership of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression, the precise neurobiological mechanisms involved in their therapeutic action are poorly understood. A better knowledge of molecular interactions between monoaminergic system, pre- and post-synaptic partners, brain neuronal circuits and regions involved may help to overcome limitations of current treatments and identify new therapeutic targets. Intracerebral in vivo microdialysis (ICM) already provided important information about the brain mechanism of action of antidepressants first in anesthetized rats in the early 1990s, and since then in conscious wild-type or knock-out mice. The principle of ICM is based on the balance between release of neurotransmitters (e.g., monoamines) and reuptake by selective transporters [e.g., serotonin transporter for serotonin 5-hydroxytryptamine (5-HT)]. Complementary to electrophysiology, this technique reflects pre-synaptic monoamines release and intrasynaptic events corresponding to ≈80% of whole brain tissue content. The inhibitory role of serotonergic autoreceptors infers that they limit somatodendritic and nerve terminal 5-HT release. It has been proposed that activation of 5-HT1A and 5-HT1B receptor sub-types limits the antidepressant-like activity of SSRIs. This hypothesis is based partially on results obtained in ICM experiments performed in naïve, non-stressed rodents. The present review will first remind the principle and methodology of ICM performed in mice. The crucial need of developing animal models that display anxiety and depression-like behaviors, neurochemical and brain morphological phenotypes reminiscent of these mood disorders in humans, will be underlined. Recently developed genetic mouse models have been generated to independently manipulate 5-HT1A auto and heteroreceptors and ICM helped to clarify the role of the pre-synaptic component

  15. An evaluation of the CYP2D6 and CYP3A4 inhibition potential of metoprolol metabolites and their contribution to drug-drug and drug-herb interaction by LC-ESI/MS/MS.

    PubMed

    Borkar, Roshan M; Bhandi, Murali Mohan; Dubey, Ajay P; Ganga Reddy, V; Komirishetty, Prashanth; Nandekar, Prajwal P; Sangamwar, Abhay T; Kamal, Ahmed; Banerjee, Sanjay K; Srinivas, R

    2016-10-01

    The aim of the present study was to evaluate the contribution of metabolites to drug-drug interaction and drug-herb interaction using the inhibition of CYP2D6 and CYP3A4 by metoprolol (MET) and its metabolites. The peak concentrations of unbound plasma concentration of MET, α-hydroxy metoprolol (HM), O-desmethyl metoprolol (ODM) and N-desisopropyl metoprolol (DIM) were 90.37 ± 2.69, 33.32 ± 1.92, 16.93 ± 1.70 and 7.96 ± 0.94 ng/mL, respectively. The metabolites identified, HM and ODM, had a ratio of metabolic area under the concentration-time curve (AUC) to parent AUC of ≥0.25 when either total or unbound concentration of metabolite was considered. In vitro CYP2D6 and CYP3A4 inhibition by MET, HM and ODM study revealed that MET, HM and ODM were not inhibitors of CYP3A4-catalyzed midazolam metabolism and CYP2D6-catalyzed dextromethorphan metabolism. However, DIM only met the criteria of >10% of the total drug related material and <25% of the parent using unbound concentrations. If CYP inhibition testing is solely based on metabolite exposure, DIM metabolite would probably not be considered. However, the present study has demonstrated that DIM contributes significantly to in vitro drug-drug interaction. Copyright © 2016 John Wiley & Sons, Ltd.

  16. The Role of Glia in the Peripheral and Central Auditory System Following Noise Overexposure: Contribution of TNF-α and IL-1β to the Pathogenesis of Hearing Loss

    PubMed Central

    Fuentes-Santamaría, Verónica; Alvarado, Juan Carlos; Melgar-Rojas, Pedro; Gabaldón-Ull, María C.; Miller, Josef M.; Juiz, José M.

    2017-01-01

    Repeated noise exposure induces inflammation and cellular adaptations in the peripheral and central auditory system resulting in pathophysiology of hearing loss. In this study, we analyzed the mechanisms by which noise-induced inflammatory-related events in the cochlea activate glial-mediated cellular responses in the cochlear nucleus (CN), the first relay station of the auditory pathway. The auditory function, glial activation, modifications in gene expression and protein levels of inflammatory mediators and ultrastructural changes in glial-neuronal interactions were assessed in rats exposed to broadband noise (0.5–32 kHz, 118 dB SPL) for 4 h/day during 4 consecutive days to induce long-lasting hearing damage. Noise-exposed rats developed a permanent threshold shift which was associated with hair cell loss and reactive glia. Noise-induced microglial activation peaked in the cochlea between 1 and 10D post-lesion; their activation in the CN was more prolonged reaching maximum levels at 30D post-exposure. RT-PCR analyses of inflammatory-related genes expression in the cochlea demonstrated significant increases in the mRNA expression levels of pro- and anti-inflammatory cytokines, inducible nitric oxide synthase, intercellular adhesion molecule and tissue inhibitor of metalloproteinase-1 at 1 and 10D post-exposure. In noise-exposed cochleae, interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α) were upregulated by reactive microglia, fibrocytes, and neurons at all time points examined. In the CN, however, neurons were the sole source of these cytokines. These observations suggest that noise exposure causes peripheral and central inflammatory reactions in which TNF-α and IL-1β are implicated in regulating the initiation and progression of noise-induced hearing loss. PMID:28280462

  17. Strategy of integrated evaluation on treatment of traditional Chinese medicine as 'interaction of system to system' and establishment of novel fuzzy target contribution recognition with herb-pairs, a case study on Astragali Radix-Fructus Corni.

    PubMed

    Duan, Yu; Pei, Ke; Cai, Hao; Tu, Sicong; Cheng, Xinwei; Zhang, Zhengwei; Fan, Kailei; Qiao, Fengxian; Qin, Kunming; Cai, Baochang

    2016-10-15

    To date, in the struggle against diseases and the development of TCM, what we lack is wisdom rather than knowledge. Studies on pharmacology of traditional Chinese medicine are facing critical challenges on how to select the proper parameters or targets to represent the pharmacological evaluation system. With seven steps of optimized modules established by ourselves, we can re-evaluate TCM in a panorama view with a proper pharmacological evaluation system. In this article, with the treatment of TCM as 'interaction of system to system', a novel and generally applicable approach called fuzzy target contribution recognition was established and agents from Astragali Radix-Fructus Corni in resisting diabetic nephropathy were successfully discovered for the first time. CG6, a promising agent from this herb-pair on the treatment of diabetic nephropathy, was finally acquired and its possible molecular mechanism was explored through a nuclear factor erythroid 2-Like 2 (NFE2L2) activation-dependent pathway.

  18. Orientational mechanisms in liquid crystalline systems. 2. The contribution to solute ordering from the reaction field interaction between the solute electric quadrupole moment and the solvent electric field gradient.

    PubMed

    Celebre, Giorgio; Ionescu, Andreea

    2010-01-14

    In the previous paper of this issue, [Celebre, G.; Ionescu, A. J. Phys. Chem. B doi: 10.1021/jp907310g], following a generalized reaction field approach in the linear response approximation, we were successful in obtaining an analytical compact expression for the mean-field anisotropic orientational potential U(Q-EFG) theoretically experienced by a highly idealized nonionic and apolar solute, considered as a point quadrupole immersed in a uniaxial polarizable continuum medium (model of a nematic solvent comprised of dipolar mesogenic molecules). The term U(Q-EFG) describes the electrostatic interaction between the electric quadrupole of the solute and the electric field gradient induced at the solute by the surrounding medium polarized by the distribution of electric charges representing the quadrupolar solute itself. In the present paper, the obtained potential has been considered as an additional orientational interaction contributing to the solute ordering, besides the well-recognized and very effective "short-range" (size-and-shape-dictated) mechanisms. Since in our theory the solvent is characterized by its dielectric tensor, the model has been widely tested by taking as references the experimental order parameters of several uniaxial and biaxial different small rigid probe molecules (H(2), N(2), acetylene, allene, propyne, benzene, hexafluorobenzene, 1,4-difluorobenzene, and norbornadiene) dissolved in the nematic solvents ZLI1132 (Deltaepsilon > 0) and EBBA (Deltaepsilon < 0); moreover, the order parameters of the same solutes in the so-called nematic "magic mixture" (45 wt % EBBA + 55 wt % ZLI1132), where the short-range orientational effects are commonly believed to be very dominant, have been conventionally assumed as reference of the absence of electrostatic orientational effects. The experimental order parameters of the treated solutes, obtained in the past by liquid crystal NMR and available from literature, have been then compared with those

  19. Acetate metabolism does not reflect astrocytic activity, contributes directly to GABA synthesis, and is increased by silent information regulator 1 activation.

    PubMed

    Rowlands, Benjamin D; Klugmann, Matthias; Rae, Caroline D

    2017-03-01

    interpreted as modulation of metabolism through changes in cellular energetic status via altered enzyme acetylation levels rather than simply as an adjustment of glial-neuronal metabolic activity.

  20. Dynamic Interactive Learning Systems

    ERIC Educational Resources Information Center

    Sabry, Khaled; Barker, Jeff

    2009-01-01

    This paper reviews and discusses the notions of interactivity and dynamicity of learning systems in relation to information technologies and design principles that can contribute to interactive and dynamic learning. It explores the concept of dynamic interactive learning systems based on the emerging generation of information as part of a…

  1. Genetic interactions between diverged alleles of Early heading date 1 (Ehd1) and Heading date 3a (Hd3a)/ RICE FLOWERING LOCUS T1 (RFT1) control differential heading and contribute to regional adaptation in rice (Oryza sativa).

    PubMed

    Zhao, Jing; Chen, Hongyi; Ren, Ding; Tang, Huiwu; Qiu, Rong; Feng, Jinglei; Long, Yunming; Niu, Baixiao; Chen, Danping; Zhong, Tianyu; Liu, Yao-Guang; Guo, Jingxin

    2015-11-01

    Initiation of flowering, also called heading, in rice (Oryza sativa) is determined by the florigens encoded by Heading date 3a (Hd3a) and RICE FLOWERING LOCUS T1 (RFT1). Early heading date 1 (Ehd1) regulates Hd3a and RFT1. However, different rice varieties have diverged alleles of Ehd1 and Hd3a/RFT1 and their genetic interactions remain largely unclear. Here we generated three segregating populations for different combinations of diverged Ehd1 and Hd3a/RFT1 alleles, and analyzed their genetic interactions between these alleles. We demonstrated that, in an ehd1 mutant background, Hd3a was silenced, but RFT1 was expressed (although at lower levels than in plants with a functional Ehd1) under short-day (SD) and long-day (LD) conditions. We identified a nonfunctional RFT1 allele (rft1); the lines carrying homozygous ehd1 and Hd3a/rft1 failed to induce the floral transition under SD and LD conditions. Like Hd3a, RFT1 also interacted with 14-3-3 proteins, the florigen receptors, but a nonfunctional RFT1 with a crucial E105K mutation failed to interact with 14-3-3 proteins. Furthermore, analyses of sequence variation and geographic distribution suggested that functional RFT1 alleles were selected during rice adaptation to high-latitude regions. Our results demonstrate the important roles of RFT1 in rice flowering and regional adaptation.

  2. Interaction between SWP9 and Polar Tube Proteins of the Microsporidian Nosema bombycis and Function of SWP9 as a Scaffolding Protein Contribute to Polar Tube Tethering to the Spore Wall.

    PubMed

    Yang, Donglin; Pan, Lixia; Peng, Pai; Dang, Xiaoqun; Li, Chunfeng; Li, Tian; Long, Mengxian; Chen, Jie; Wu, Yujiao; Du, Huihui; Luo, Bo; Song, Yue; Tian, Rui; Luo, Jie; Zhou, Zeyang; Pan, Guoqing

    2017-03-01

    All microsporidia possess a unique, highly specialized invasion mechanism that involves the polar tube and spore wall. The interaction between spore wall proteins (SWPs) and polar tube proteins (PTPs) in the formation, arrangement, orderly orientation, and function of the polar tube and spore wall remains to be determined. This study was undertaken to examine the protein interactions of Nosema bombycis SWP7 (NbSWP7), NbSWP9, and PTPs. Coimmunoprecipitation, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and yeast two-hybrid data demonstrated that NbSWP9, but not NbSWP7, interacts with NbPTP1 and NbPTP2. Furthermore, immunoelectron microscopy (IEM) showed that NbSWP9 was localized mainly in the developing polar tube of sporoblasts, while NbSWP7 was found randomly in the cytoplasm. However, both NbSWP9 and NbSWP7 were located in the polar tube and spore wall of N. bombycis mature spores. The reason why NbSWP7 was localized to the polar tube may be due to the interaction between NbSWP9 and NbSWP7. Interestingly, the majority of NbSWP9, but not NbSWP7, accumulated in the beginning part of the extruded polar tube and the ruptured spore wall called the anchoring disk (AD) when the mature spores germinated under weak-alkaline environmental stimulation. Additionally, anti-NbSWP9 antibody reduced spore germination in a dose-dependent manner. In conclusion, our study further confirmed that NbSWP9 is a scaffolding protein that not only anchors and holds the polar tube but also tethers the polar tube to the spore wall.

  3. A Reciprocal Shift in Transient Receptor Potential Channel 1 (TRPC1) and Stromal Interaction Molecule 2 (STIM2) Contributes to Ca2+ Remodeling and Cancer Hallmarks in Colorectal Carcinoma Cells*

    PubMed Central

    Sobradillo, Diego; Hernández-Morales, Miriam; Ubierna, Daniel; Moyer, Mary P.; Núñez, Lucía; Villalobos, Carlos

    2014-01-01

    We have investigated the molecular basis of intracellular Ca2+ handling in human colon carcinoma cells (HT29) versus normal human mucosa cells (NCM460) and its contribution to cancer features. We found that Ca2+ stores in colon carcinoma cells are partially depleted relative to normal cells. However, resting Ca2+ levels, agonist-induced Ca2+ increases, store-operated Ca2+ entry (SOCE), and store-operated currents (ISOC) are largely enhanced in tumor cells. Enhanced SOCE and depleted Ca2+ stores correlate with increased cell proliferation, invasion, and survival characteristic of tumor cells. Normal mucosa cells displayed small, inward Ca2+ release-activated Ca2+ currents (ICRAC) mediated by ORAI1. In contrast, colon carcinoma cells showed mixed currents composed of enhanced ICRAC plus a nonselective ISOC mediated by TRPC1. Tumor cells display increased expression of TRPC1, ORAI1, ORAI2, ORAI3, and STIM1. In contrast, STIM2 protein was nearly depleted in tumor cells. Silencing data suggest that enhanced ORAI1 and TRPC1 contribute to enhanced SOCE and differential store-operated currents in tumor cells, whereas ORAI2 and -3 are seemingly less important. In addition, STIM2 knockdown decreases SOCE and Ca2+ store content in normal cells while promoting apoptosis resistance. These data suggest that loss of STIM2 may underlie Ca2+ store depletion and apoptosis resistance in tumor cells. We conclude that a reciprocal shift in TRPC1 and STIM2 contributes to Ca2+ remodeling and tumor features in colon cancer. PMID:25143380

  4. A reciprocal shift in transient receptor potential channel 1 (TRPC1) and stromal interaction molecule 2 (STIM2) contributes to Ca2+ remodeling and cancer hallmarks in colorectal carcinoma cells.

    PubMed

    Sobradillo, Diego; Hernández-Morales, Miriam; Ubierna, Daniel; Moyer, Mary P; Núñez, Lucía; Villalobos, Carlos

    2014-10-17

    We have investigated the molecular basis of intracellular Ca(2+) handling in human colon carcinoma cells (HT29) versus normal human mucosa cells (NCM460) and its contribution to cancer features. We found that Ca(2+) stores in colon carcinoma cells are partially depleted relative to normal cells. However, resting Ca(2+) levels, agonist-induced Ca(2+) increases, store-operated Ca(2+) entry (SOCE), and store-operated currents (ISOC) are largely enhanced in tumor cells. Enhanced SOCE and depleted Ca(2+) stores correlate with increased cell proliferation, invasion, and survival characteristic of tumor cells. Normal mucosa cells displayed small, inward Ca(2+) release-activated Ca(2+) currents (ICRAC) mediated by ORAI1. In contrast, colon carcinoma cells showed mixed currents composed of enhanced ICRAC plus a nonselective ISOC mediated by TRPC1. Tumor cells display increased expression of TRPC1, ORAI1, ORAI2, ORAI3, and STIM1. In contrast, STIM2 protein was nearly depleted in tumor cells. Silencing data suggest that enhanced ORAI1 and TRPC1 contribute to enhanced SOCE and differential store-operated currents in tumor cells, whereas ORAI2 and -3 are seemingly less important. In addition, STIM2 knockdown decreases SOCE and Ca(2+) store content in normal cells while promoting apoptosis resistance. These data suggest that loss of STIM2 may underlie Ca(2+) store depletion and apoptosis resistance in tumor cells. We conclude that a reciprocal shift in TRPC1 and STIM2 contributes to Ca(2+) remodeling and tumor features in colon cancer.

  5. Positive and Negative Contributions in the Solvation Enthalpy due to Specific Interactions in Binary Mixtures of C1-C4 n-Alkanols and Chloroform with Butan-2-one.

    PubMed

    Varfolomeev, Mikhail A; Rakipov, Ilnaz T; Solomonov, Boris N; Lodowski, Piotr; Marczak, Wojciech

    2015-06-25

    In the paper, results of calorimetric measurements, IR spectra, and calculated ab initio stabilization energies of dimers are reported for binary systems butan-2-one + (methanol, ethanol, propan-1-ol, butan-1-ol, and chloroform). Changes in the total enthalpy of specific interactions due to dissolution of butan-2-one in the alcohols, calculated using equations derived in previous works, are positive. That results from the endothermic breaking of the O-H···O-H bonds not completely compensated by the exothermic effects of formation of the O-H···O═C ones. Moreover, the concentration of nonbonded molecules of butan-2-one is significant even in dilute solutions, as is evidenced by the shape of the C═O stretching vibrations band in the IR spectra. Apart from that, the spectra do not confirm 1:2 complexes in spite of two lone electron pairs in the carbonyl group of butan-2-one capable of forming the hydrogen bonds. The changes in enthalpy of specific interactions are negative for dilute solutions of alcohols and chloroform in butan-2-one and of butan-2-one in chloroform, because no hydrogen bonds occur in pure butan-2-one. The experimental results are positively correlated with the enthalpies estimated from the ab initio energies using a simple "chemical reaction" approach.

  6. Mathematics: Contributions by Women.

    ERIC Educational Resources Information Center

    Dewar, Jacqueline M.

    1991-01-01

    Describes a core course in a women's-studies program at Loyola Marymount University. Provides information, resources, and an annotated bibliography useful for making students more aware of women's contributions to mathematics. Contains 38 references. (ASK)

  7. Deep brain stimulation: Are astrocytes a key driver behind the scene?

    PubMed Central

    Fenoy, Albert J.; Goetz, Laurent; Chabardès, Stéphan; Xia, Ying

    2014-01-01

    Despite its widespread use, the underlying mechanism of deep brain stimulation (DBS) remains unknown. Once thought to impart a "functional inactivation", there is now increasing evidence showing that DBS actually can both inhibit neurons and activate axons, generating a wide range of effects. This implies that the mechanisms that underlie DBS work not only locally but also at the network level. Therefore, not only may DBS induce membrane or synaptic plastic changes in neurons over a wide network, but it may also trigger celllular and molecular changes in other cells, especially astrocytes, where together the glial-neuronal interactions may explain effects that are not clearly rationalized by simple activation/inhibition theories alone. Recent studies suggest that 1) High frequency stimulation (HFS) activates astrocytes and leads to the release of gliotransmitters that can regulate surrounding neurons at the synapse; 2) Activated astrocytes modulate synaptic activity and increase axonal activation; 3) Activated astrocytes can signal further astrocytes across large networks, contributing to observed network effects induced by DBS; 4) Activated astrocytes can help explain the disparate effects of activation and inhibition induced by HFS at different sites; 5) Astrocytes contribute to synaptic plasticity through long-term potentiation (LTP) and depression (LTD), possibly helping to mediate the long term effects of DBS; and 6) DBS may increase delta-opioid receptor activity in astrcoytes to confer neuroprotection. Together, the plastic changes in these glial-neuronal interactions network-wide likely underlie the range of effects seen, from the variable temporal latencies to observed effect to global activation patterns. This article reviews recent research progress in the literature on how astrocytes play a key role in DBS efficacy. PMID:24456263

  8. Selective Interactions between Vertebrate Polycomb Homologs and the SUV39H1 Histone Lysine Methyltransferase Suggest that Histone H3-K9 Methylation Contributes to Chromosomal Targeting of Polycomb Group Proteins

    PubMed Central

    Sewalt, Richard G. A. B.; Lachner, Monika; Vargas, Mark; Hamer, Karien M.; den Blaauwen, Jan L.; Hendrix, Thijs; Melcher, Martin; Schweizer, Dieter; Jenuwein, Thomas; Otte, Arie P.

    2002-01-01

    Polycomb group (PcG) proteins form multimeric chromatin-associated protein complexes that are involved in heritable repression of gene activity. Two distinct human PcG complexes have been characterized. The EED/EZH2 PcG complex utilizes histone deacetylation to repress gene activity. The HPC/HPH PcG complex contains the HPH, RING1, BMI1, and HPC proteins. Here we show that vertebrate Polycomb homologs HPC2 and XPc2, but not M33/MPc1, interact with the histone lysine methyltransferase (HMTase) SUV39H1 both in vitro and in vivo. We further find that overexpression of SUV39H1 induces selective nuclear relocalization of HPC/HPH PcG proteins but not of the EED/EZH2 PcG proteins. This SUV39H1-dependent relocalization concentrates the HPC/HPH PcG proteins to the large pericentromeric heterochromatin domains (1q12) on human chromosome 1. Within these PcG domains we observe increased H3-K9 methylation. Finally, we show that H3-K9 HMTase activity is associated with endogenous HPC2. Our findings suggest a role for the SUV39H1 HMTase and histone H3-K9 methylation in the targeting of human HPC/HPH PcG proteins to modified chromatin structures. PMID:12101246

  9. Selective interactions between vertebrate polycomb homologs and the SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 methylation contributes to chromosomal targeting of Polycomb group proteins.

    PubMed

    Sewalt, Richard G A B; Lachner, Monika; Vargas, Mark; Hamer, Karien M; den Blaauwen, Jan L; Hendrix, Thijs; Melcher, Martin; Schweizer, Dieter; Jenuwein, Thomas; Otte, Arie P

    2002-08-01

    Polycomb group (PcG) proteins form multimeric chromatin-associated protein complexes that are involved in heritable repression of gene activity. Two distinct human PcG complexes have been characterized. The EED/EZH2 PcG complex utilizes histone deacetylation to repress gene activity. The HPC/HPH PcG complex contains the HPH, RING1, BMI1, and HPC proteins. Here we show that vertebrate Polycomb homologs HPC2 and XPc2, but not M33/MPc1, interact with the histone lysine methyltransferase (HMTase) SUV39H1 both in vitro and in vivo. We further find that overexpression of SUV39H1 induces selective nuclear relocalization of HPC/HPH PcG proteins but not of the EED/EZH2 PcG proteins. This SUV39H1-dependent relocalization concentrates the HPC/HPH PcG proteins to the large pericentromeric heterochromatin domains (1q12) on human chromosome 1. Within these PcG domains we observe increased H3-K9 methylation. Finally, we show that H3-K9 HMTase activity is associated with endogenous HPC2. Our findings suggest a role for the SUV39H1 HMTase and histone H3-K9 methylation in the targeting of human HPC/HPH PcG proteins to modified chromatin structures.

  10. Differences in the C-terminus contribute to variations in trafficking between rat and human 5-HT(2A) receptor isoforms: identification of a primate-specific tripeptide ASK motif that confers GRK-2 and beta arrestin-2 interactions.

    PubMed

    Bhattacharya, Aditi; Sankar, Shobhana; Panicker, Mitradas M

    2010-02-01

    Internalization and recycling of G-protein coupled receptors are important cellular processes regulating receptor function. These are receptor-subtype and cell type-specific. Although important, trafficking variations between receptor isoforms of different species has received limited attention. We report here, differences in internalization and recycling between rat and human serotonin 2A receptor (5-HT(2A)R) isoforms expressed in human embryonic kidney 293 cells in response to serotonin. Although the human and rat 5-HT(2A)Rs differ by only a few amino acids, the human receptor takes longer to recycle to the cell surface after internalization, with the additional involvement of beta arrestin-2 and G-protein receptor kinase 2. The interaction of beta arrestin-2 with the human receptor causes the delay in recycling and is dependent on a primate-specific ASK motif present in the C-terminus of the receptor. Conversion of this motif to NCT, the corresponding sequence present in the rat isoform, results in the human isoform trafficking like the rat receptor. Replacing the serine 457 with alanine in the ASK motif of human isoform resulted in faster recycling, although with continued arrestin-dependent internalization. This study establishes significant differences between the two isoforms with important implications in our understanding of the human 5-HT(2A)R functions; and indicates that extrapolating results from non-human receptor isoforms to human subtypes is not without caveats.

  11. Transcriptome and Metabolite Profiling of the Infection Cycle of Zymoseptoria tritici on Wheat Reveals a Biphasic Interaction with Plant Immunity Involving Differential Pathogen Chromosomal Contributions and a Variation on the Hemibiotrophic Lifestyle Definition1[OPEN

    PubMed Central

    Rudd, Jason J.; Kanyuka, Kostya; Hassani-Pak, Keywan; Derbyshire, Mark; Andongabo, Ambrose; Devonshire, Jean; Lysenko, Artem; Saqi, Mansoor; Desai, Nalini M.; Powers, Stephen J.; Hooper, Juliet; Ambroso, Linda; Bharti, Arvind; Farmer, Andrew; Hammond-Kosack, Kim E.; Dietrich, Robert A.; Courbot, Mikael

    2015-01-01

    The hemibiotrophic fungus Zymoseptoria tritici causes Septoria tritici blotch disease of wheat (Triticum aestivum). Pathogen reproduction on wheat occurs without cell penetration, suggesting that dynamic and intimate intercellular communication occurs between fungus and plant throughout the disease cycle. We used deep RNA sequencing and metabolomics to investigate the physiology of plant and pathogen throughout an asexual reproductive cycle of Z. tritici on wheat leaves. Over 3,000 pathogen genes, more than 7,000 wheat genes, and more than 300 metabolites were differentially regulated. Intriguingly, individual fungal chromosomes contributed unequally to the overall gene expression changes. Early transcriptional down-regulation of putative host defense genes was detected in inoculated leaves. There was little evidence for fungal nutrient acquisition from the plant throughout symptomless colonization by Z. tritici, which may instead be utilizing lipid and fatty acid stores for growth. However, the fungus then subsequently manipulated specific plant carbohydrates, including fructan metabolites, during the switch to necrotrophic growth and reproduction. This switch coincided with increased expression of jasmonic acid biosynthesis genes and large-scale activation of other plant defense responses. Fungal genes encoding putative secondary metabolite clusters and secreted effector proteins were identified with distinct infection phase-specific expression patterns, although functional analysis suggested that many have overlapping/redundant functions in virulence. The pathogenic lifestyle of Z. tritici on wheat revealed through this study, involving initial defense suppression by a slow-growing extracellular and nutritionally limited pathogen followed by defense (hyper) activation during reproduction, reveals a subtle modification of the conceptual definition of hemibiotrophic plant infection. PMID:25596183

  12. X-ray spectroscopic characterization of Co(IV) and metal–metal interactions in Co4O4: Electronic structure contributions to the formation of high-valent states relevant to the oxygen evolution reaction

    DOE PAGES

    Hadt, Ryan G.; Hayes, Dugan; Brodsky, Casey N.; ...

    2016-08-12

    In this paper, the formation of high-valent states is a key factor in making highly active transition metal-based catalysts of the oxygen-evolving reaction (OER). These high oxidation states will be strongly influenced by the local geometric and electronic structures of the metal ion, which is difficult to study due to spectroscopically active and complex backgrounds, short lifetimes, and limited concentrations. Here, we use a wide range of complementary X-ray spectroscopies coupled to DFT calculations to study Co4O4 cubanes, which provide insight into the high-valent Co(IV) centers responsible for the activity of molecular and heterogeneous OER catalysts. The combination of X-raymore » absorption and 1s3p resonant inelastic X-ray scattering (Kβ RIXS) allow Co(IV) to be isolated and studied against a spectroscopically active Co(III) background. Co K- and L-edge X-ray absorption data allow for a detailed characterization of the 3d-manifold of effectively localized Co(IV) centers and provide a direct handle on the ligand field environment and covalency of the t2g-based redox active molecular orbital. Kβ RIXS is also shown to provide a powerful probe of Co(IV), and specific spectral features are sensitive to the degree of oxo-mediated metal-metal coupling across Co4O4. Guided by the data, calculations show electron-hole delocalization can actually oppose Co(IV) formation. Computational extension of Co4O4 to CoM3O4 structures (M = redox-inactive metal) defines electronic structure contri-butions to Co(IV) formation. Redox activity is shown to be linearly related to covalency, and M(III) oxo inductive effects on Co(IV) oxo bonding can tune the covalency of high-valent sites over a large range and thereby tune E0 over hundreds of mVs.« less

  13. Mode Contributions to the Casimir Effect

    NASA Astrophysics Data System (ADS)

    Intravaia, F.; Henkel, C.

    2010-04-01

    Applying a sum-over-modes approach to the Casimir interaction between two plates with finite conductivity, we isolate and study the contributions of surface plasmons and Foucault (eddy current) modes. We show in particular that for the TE-polarization eddy currents provide a repulsive force that cancels, at high temperatures, the Casimir free energy calculated with the plasma model.

  14. Contributed Papers, 1967.

    ERIC Educational Resources Information Center

    Special Libraries Association, New York, NY. Documentation Div.

    Included are six papers from the Special Libraries Association Documentation Division's Contributed Papers Session at the National Conference in New York, May 28 - June 1, 1967, which were not included in the November, 1967 issue of Special Libraries. The papers are: (1) "The Bibliographical Control of Aerospace Industry Conference Literature…

  15. Avicenna's contribution to cardiology.

    PubMed

    Chamsi-Pasha, Mohammed A R; Chamsi-Pasha, Hassan

    2014-01-01

    Ibn Sina, known in the West as Avicenna, was the most famous and influential of all the Islamic philosopher-scientists. His most important medical works are the Canon of Medicine medical encyclopedia and a treatise on cardiac drugs. His Canon of Medicine remained the standard text in both the East and West until the 16(th) century. Avicenna's description of cardiac diseases was logically presented perhaps for the first time in the history of medicine. Avicenna was the first to describe carotid sinus hypersensitivity, which presents with vasovagal syncope. He was a pioneer in pulsology and the first correct explanation of pulsation was given by Avicenna, after he refined Galen's theory of the pulse. Besides, he discussed the action of available drugs on the heart in details and mentioned their indications and contraindications. In conclusion, Avicenna made important contributions to cardiology. This article describes some of his contributions in this field.

  16. Abstracts of contributed papers

    SciTech Connect

    Not Available

    1994-08-01

    This volume contains 571 abstracts of contributed papers to be presented during the Twelfth US National Congress of Applied Mechanics. Abstracts are arranged in the order in which they fall in the program -- the main sessions are listed chronologically in the Table of Contents. The Author Index is in alphabetical order and lists each paper number (matching the schedule in the Final Program) with its corresponding page number in the book.

  17. Behavioral science space contributions.

    PubMed

    Harris, P R

    1989-07-01

    In anticipation of longer missions on the space stations, Mir and Freedom, as well as a potential return to the Moon and the exploration of Mars, human survival and the quality of life aloft will be increasingly dependent upon research in the behavioral and biological sciences. This article reviews the possible contributions to space habitation of the behavioral sciences--especially anthropology, psychology, and sociology. Before space settlements become a reality, the author makes a case for the broadening of the engineering approach to human factor studies, and consideration of the integrative living systems theory in space planning and management.

  18. Examining suicide: imaging's contributions.

    PubMed

    Church, Elizabeth J

    2015-01-01

    For many people, the death of hope leads inexorably to the conclusion that the only viable solution, the only way to put an end to unendurable pain, is suicide. What leads a person to commit this final, desperate act, and how might we predict, intervene, and prevent suicide? Health care workers, including radiologic technologists, can play an important role in detecting warning signs in patients and in better understanding what factors may lead to suicide. Although certain forms of suicide such as suicide bombings and assisted suicide are beyond its scope, this article explores medical imaging's contributions to the study of this phenomenon.

  19. A contemporary Kleinian contribution to understanding racism.

    PubMed

    Rasmussen, Brian; Salhani, Daniel

    2010-01-01

    This article applies a contemporary Kleinian understanding to the problem of racism and, in particular, to microaggressions. The article contributes to the social work literature on racism by (1) moving closer to an explanatory model of the relation between the social and the psyche; (2) adding depth and structure to the concept of unconscious racism; and (3) highlighting a range of Kleinian concepts, such as projection, projective identification, splitting, developmental positions, envy, and reparation, that contribute to understanding the internal and external dimensions of racialized encounters. The dynamic interaction of the psyche and the social is central to understanding racism and to effective antiracist intervention strategies.

  20. [The electrostatic contribution to interactions of some enzymes with polyelectrolytes].

    PubMed

    Saburova, E A; Dybovskaia, Iu N; Sivezhelezov, V S; Elfamova, L I

    2005-01-01

    To explain the inhibitory action of polyelectrolytes on enzymes and, in particular, to define potentially reactive zones for the binding of polyelectrolyte, the electric potential of enzymes lactate dehydrogenase and glutamate dehydrogenase was calculated using the solution of the Poisson-Boltzmann equation by a numerical method with the use of the Gauss-Seidel relaxation method at three pH values: 6.5, 7.0, and 8.0 and three values of ionic strength: 50, 100, and 150 mm. On the basis of these calculations and their visualization, representative sites for favorable binding of polyanions were determined as extended areas on the surface of proteins with the positive potential in the neutral pH region. It was shown that there is a correlation between the area of positive potential and the efficiency of enzyme inactivation for a number of pH values and concentrations of salt for two enzymes. The calculations performed allowed one to explain the inhibitory action of polyelectrolytes on the specified enzymes to understand the difference between the values of polyelectrolyte inactivation constants for the two enzymes and estimate the minimal areas of the positive potential on the protein surface that provide their effective inhibition.

  1. Epigenetics and migraine; complex mitochondrial interactions contributing to disease susceptibility.

    PubMed

    Roos-Araujo, Deidré; Stuart, Shani; Lea, Rod A; Haupt, Larisa M; Griffiths, Lyn R

    2014-06-10

    Migraine is a common neurological disorder classified by the World Health Organisation (WHO) as one of the top twenty most debilitating diseases in the developed world. Current therapies are only effective for a proportion of sufferers and new therapeutic targets are desperately needed to alleviate this burden. Recently the role of epigenetics in the development of many complex diseases including migraine has become an emerging topic. By understanding the importance of acetylation, methylation and other epigenetic modifications, it then follows that this modification process is a potential target to manipulate epigenetic status with the goal of treating disease. Bisulphite sequencing and methylated DNA immunoprecipitation have been used to demonstrate the presence of methylated cytosines in the human D-loop of mitochondrial DNA (mtDNA), proving that the mitochondrial genome is methylated. For the first time, it has been shown that there is a difference in mtDNA epigenetic status between healthy controls and those with disease, especially for neurodegenerative and age related conditions. Given co-morbidities with migraine and the suggestive link between mitochondrial dysfunction and the lowered threshold for triggering a migraine attack, mitochondrial methylation may be a new avenue to pursue. Creative thinking and new approaches are needed to solve complex problems and a systems biology approach, where multiple layers of information are integrated is becoming more important in complex disease modelling.

  2. A Profile of Corporate Contributions.

    ERIC Educational Resources Information Center

    Smith, Hayden W.

    The extent and distribution of charitable contributions by corporations were studied. In addition to a history of giving from 1936 to 1981, information is presented on corporate contributions in 1977 in terms of the distribution of companies (1) by size of contributions, (2) by contributions as percentage of net income, (3) by industry, and (4) by…

  3. Cardiac and Arterial Contribution to Blood Pressure

    DTIC Science & Technology

    2007-11-02

    heart to the blood pressure . We conclude that when the heart hypertrophies, as a result of the hypertension , the changed cardiac behavior, in turn...Plenary Talks Cardiac and Arterial Contribution to Blood Pressure N.Westerhof, Lab. for Physiology, Institute for Cardiovascular Research...Vrije Universiteit of Amsterdam Blood pressure and blood flow result from the interaction of the heart, the pump, and the arterial system, the load

  4. Minisuperspace models as infrared contributions

    NASA Astrophysics Data System (ADS)

    Bojowald, Martin; Brahma, Suddhasattwa

    2016-06-01

    A direct correspondence of quantum mechanics as a minisuperspace model for a self-interacting scalar quantum-field theory is established by computing, in several models, the infrared contributions to 1-loop effective potentials of Coleman-Weinberg type. A minisuperspace approximation rather than truncation is thereby obtained. By this approximation, the spatial averaging scale of minisuperspace models is identified with an infrared scale (but not a regulator or cutoff) delimiting the modes included in the minisuperspace model. Some versions of the models studied here have discrete space or modifications of the Hamiltonian expected from proposals of loop quantum gravity. They shed light on the question of how minisuperspace models of quantum cosmology can capture features of full quantum gravity. While it is shown that modifications of the Hamiltonian can be well described by minisuperspace truncations, some related phenomena such as signature change, confirmed and clarified here for modified scalar field theories, require at least a perturbative treatment of inhomogeneity beyond a strict minisuperspace model. The new methods suggest a systematic extension of minisuperspace models by a canonical effective formulation of perturbative inhomogeneity.

  5. EMSL Contribution Plan

    SciTech Connect

    Campbell, Allison A.

    2008-12-01

    This Contribution Plan is EMSL’s template for achieving our vision of simultaneous excellence in all aspects of our mission as a national scientific user facility. It reflects our understanding of the long-term stewardship we must work toward to meet the scientific challenges faced by the Department of Energy (DOE) and the nation. During the next decade, we will implement the strategies contained in this Plan, working closely with the scientific community, our advisory committees, DOE’s Office of Biological and Environmental Research, and other key stakeholders. This Plan is fully aligned with the strategic plans of DOE, its Office of Science, and the Pacific Northwest National Laboratory (PNNL). We recognize that shifts in science and technology, national priorities, and resources made available through the Federal budget process create planning uncertainties and, ultimately, a highly dynamic planning environment. Accordingly, this Plan should be viewed as a living document and we continually evaluate the changing needs and opportunities posed by our stakeholders (i.e., DOE, users, staff, advisory committees), work closely with them to understand and respond to those changes, and align our strategy accordingly. This Plan is organized around two sections. Section 1 describes our vision and four strategic outcomes: 1) Scientific Innovation, 2) Capabilities that Transform Science, 3) Outstanding Management and Operations, and Engaged and Proactive Users. These outcomes provide the framework for seven critical actions we must take during the next 3 to 5 years: 1) Establishing leadership in EMSL science themes, 2) building and deploying transformational capabilities, 3) integrating computation with experiment, 4) ensuring EMSL’s workforce meets the scientific challenges of the future, 5) creating partnerships, 6) attracting and engaging users in EMSL’s long-term strategy, and 7) building a research infrastructure that meets emerging scientific needs. Section 2

  6. Mexican contributions to Noncommutative Theories

    SciTech Connect

    Vergara, J. David; Garcia-Compean, H.

    2006-09-25

    In this paper we summarize the Mexican contributions to the subject of Noncommutative theories. These contributions span several areas: Quantum Groups, Noncommutative Field Theories, Hopf algebra of renormalization, Deformation Quantization, Noncommutative Gravity, and Noncommutative Quantum Mechanics.

  7. Group Contribution Methods for Phase Equilibrium Calculations.

    PubMed

    Gmehling, Jürgen; Constantinescu, Dana; Schmid, Bastian

    2015-01-01

    The development and design of chemical processes are carried out by solving the balance equations of a mathematical model for sections of or the whole chemical plant with the help of process simulators. For process simulation, besides kinetic data for the chemical reaction, various pure component and mixture properties are required. Because of the great importance of separation processes for a chemical plant in particular, a reliable knowledge of the phase equilibrium behavior is required. The phase equilibrium behavior can be calculated with the help of modern equations of state or g(E)-models using only binary parameters. But unfortunately, only a very small part of the experimental data for fitting the required binary model parameters is available, so very often these models cannot be applied directly. To solve this problem, powerful predictive thermodynamic models have been developed. Group contribution methods allow the prediction of the required phase equilibrium data using only a limited number of group interaction parameters. A prerequisite for fitting the required group interaction parameters is a comprehensive database. That is why for the development of powerful group contribution methods almost all published pure component properties, phase equilibrium data, excess properties, etc., were stored in computerized form in the Dortmund Data Bank. In this review, the present status, weaknesses, advantages and disadvantages, possible applications, and typical results of the different group contribution methods for the calculation of phase equilibria are presented.

  8. Mechanism Design for Incentivizing Social Media Contributions

    NASA Astrophysics Data System (ADS)

    Singh, Vivek K.; Jain, Ramesh; Kankanhalli, Mohan

    Despite recent advancements in user-driven social media platforms, tools for studying user behavior patterns and motivations remain primitive. We highlight the voluntary nature of user contributions and that users can choose when (and when not) to contribute to the common media pool. A Game theoretic framework is proposed to study the dynamics of social media networks where contribution costs are individual but gains are common. We model users as rational selfish agents, and consider domain attributes like voluntary participation, virtual reward structure, network effect, and public-sharing to model the dynamics of this interaction. The created model describes the most appropriate contribution strategy from each user's perspective and also highlights issues like 'free-rider' problem and individual rationality leading to irrational (i.e. sub-optimal) group behavior. We also consider the perspective of the system designer who is interested in finding the best incentive mechanisms to influence the selfish end-users so that the overall system utility is maximized. We propose and compare multiple mechanisms (based on optimal bonus payment, social incentive leveraging, and second price auction) to study how a system designer can exploit the selfishness of its users, to design incentive mechanisms which improve the overall task-completion probability and system performance, while possibly still benefiting the individual users.

  9. Enthalpic and Entropic Contributions to Hydrophobicity

    PubMed Central

    2016-01-01

    Hydrophobic hydration plays a key role in a vast variety of biological processes, ranging from the formation of cells to protein folding and ligand binding. Hydrophobicity scales simplify the complex process of hydration by assigning a value describing the averaged hydrophobic character to each amino acid. Previously published scales were not able to calculate the enthalpic and entropic contributions to the hydrophobicity directly. We present a new method, based on Molecular Dynamics simulations and Grid Inhomogeneous Solvation Theory, that calculates hydrophobicity from enthalpic and entropic contributions. Instead of deriving these quantities from the temperature dependence of the free energy of hydration or as residual of the free energy and the enthalpy, we directly obtain these values from the phase space occupied by water molecules. Additionally, our method is able to identify regions with specific enthalpic and entropic properties, allowing to identify so-called “unhappy water” molecules, which are characterized by weak enthalpic interactions and unfavorable entropic constraints. PMID:27442443

  10. 75 FR 32659 - Contributed Property

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-09

    ... partnership, and any consolidated group of which the partner in the partnership is a member (within the... described in Sec. 1.704-3, paragraphs (b), (c) and (d), apply only with respect to the contributions of... treated as owned by the partner; (ii) disregarding one or more contributions or (iii) disregarding one...

  11. Interacting faults

    NASA Astrophysics Data System (ADS)

    Peacock, D. C. P.; Nixon, C. W.; Rotevatn, A.; Sanderson, D. J.; Zuluaga, L. F.

    2017-04-01

    The way that faults interact with each other controls fault geometries, displacements and strains. Faults rarely occur individually but as sets or networks, with the arrangement of these faults producing a variety of different fault interactions. Fault interactions are characterised in terms of the following: 1) Geometry - the spatial arrangement of the faults. Interacting faults may or may not be geometrically linked (i.e. physically connected), when fault planes share an intersection line. 2) Kinematics - the displacement distributions of the interacting faults and whether the displacement directions are parallel, perpendicular or oblique to the intersection line. Interacting faults may or may not be kinematically linked, where the displacements, stresses and strains of one fault influences those of the other. 3) Displacement and strain in the interaction zone - whether the faults have the same or opposite displacement directions, and if extension or contraction dominates in the acute bisector between the faults. 4) Chronology - the relative ages of the faults. This characterisation scheme is used to suggest a classification for interacting faults. Different types of interaction are illustrated using metre-scale faults from the Mesozoic rocks of Somerset and examples from the literature.

  12. Contribution mapping: a method for mapping the contribution of research to enhance its impact

    PubMed Central

    2012-01-01

    Background At a time of growing emphasis on both the use of research and accountability, it is important for research funders, researchers and other stakeholders to monitor and evaluate the extent to which research contributes to better action for health, and find ways to enhance the likelihood that beneficial contributions are realized. Past attempts to assess research 'impact' struggle with operationalizing 'impact', identifying the users of research and attributing impact to research projects as source. In this article we describe Contribution Mapping, a novel approach to research monitoring and evaluation that aims to assess contributions instead of impacts. The approach focuses on processes and actors and systematically assesses anticipatory efforts that aim to enhance contributions, so-called alignment efforts. The approach is designed to be useful for both accountability purposes and for assisting in better employing research to contribute to better action for health. Methods Contribution Mapping is inspired by a perspective from social studies of science on how research and knowledge utilization processes evolve. For each research project that is assessed, a three-phase process map is developed that includes the main actors, activities and alignment efforts during research formulation, production and knowledge extension (e.g. dissemination and utilization). The approach focuses on the actors involved in, or interacting with, a research project (the linked actors) and the most likely influential users, who are referred to as potential key users. In the first stage, the investigators of the assessed project are interviewed to develop a preliminary version of the process map and first estimation of research-related contributions. In the second stage, potential key-users and other informants are interviewed to trace, explore and triangulate possible contributions. In the third stage, the presence and role of alignment efforts is analyzed and the preliminary

  13. Imagined Interactions

    ERIC Educational Resources Information Center

    Honeycutt, James M.

    2010-01-01

    Social scientists have been studying imagined interactions since the mid-1980s and have measured numerous physiological correlates (Honeycutt, 2010). In this commentary I assess the research reported in Crisp and Turner (May-June 2009) and highlight the underlying mechanisms of imagined interactions that have empirically been laid out across…

  14. Interacting parasites

    USGS Publications Warehouse

    Lafferty, Kevin D.

    2010-01-01

    Parasitism is the most popular life-style on Earth, and many vertebrates host more than one kind of parasite at a time. A common assumption is that parasite species rarely interact, because they often exploit different tissues in a host, and this use of discrete resources limits competition (1). On page 243 of this issue, however, Telfer et al. (2) provide a convincing case of a highly interactive parasite community in voles, and show how infection with one parasite can affect susceptibility to others. If some human parasites are equally interactive, our current, disease-by-disease approach to modeling and treating infectious diseases is inadequate (3).

  15. 75 FR 43799 - Employee Contribution Elections and Contribution Allocations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-27

    ... practice, however, the Agency will soon require a notarized signature for all withdrawal requests...' TSP accounts from fraudulent withdrawals. One commenter requested affirmation that contribution... withdrawal penalty tax). (2) A participant who requests a refund will receive the amount of any...

  16. Cross-border contributions to obesity research and interventions: a review of Canadian and American occupational therapy contributions.

    PubMed

    Forhan, Mary; Gill, Simone

    2013-04-01

    This paper identifies the contributions of Canadian and American occupational therapists to the empirical discourse on obesity. This scoping study includes an independent review of the published literature followed by a series of meetings during which key themes and contributions were categorized. The Person, Environment, Occupation, and Performance Model (Baum & Christiansen, 2005) was used to organize the themes reported in the literature. Although occupational therapists contribute to knowledge about body systems and functions as well as activity limitations and participation restrictions for persons with obesity, the majority of work has a focus on the environment and the person, with limited attention to occupation. Occupational therapy practitioners and researchers are contributing in areas valued in obesity research and practice but can do more to promote consideration of the interaction of personal, environmental, and occupational factors which may cause obesity or contribute to the participation in everyday living for persons with obesity.

  17. Epigenetic Contributions to Cognitive Aging: Disentangling Mindspan and Lifespan

    ERIC Educational Resources Information Center

    Spiegel, Amy M.; Sewal, Angila S.; Rapp, Peter R.

    2014-01-01

    Epigenetic modifications of chromatin structure provide a mechanistic interface for gene-environment interactions that impact the individualization of health trajectories across the lifespan. A growing body of research indicates that dysfunctional epigenetic regulation contributes to poor cognitive outcomes among aged populations. Here we review…

  18. Estimates of isospin breaking contributions to baryon masses

    SciTech Connect

    Ha, Phuoc

    2007-10-01

    We estimate the isospin breaking contributions to the baryon masses which we analyzed recently using a loop expansion in the heavy-baryon chiral effective field theory. To one loop, the isospin breaking corrections come from the effects of the d, u quark mass difference, the Coulomb and magnetic moment interactions, and effective point interactions attributable to color-magnetic effects. The addition of the first meson loop corrections introduces new structure. We estimate the resulting low-energy, long-range contributions to the mass splittings by regularizing the loop integrals using connections to dynamical models for finite-size baryons. We find that the resulting contributions to the isospin breaking corrections are of the right general size, have the correct sign pattern, and agree with the experimental values within the margin of error.

  19. Assessing Contributions to Group Assignments

    ERIC Educational Resources Information Center

    Johnston, Lucy; Miles, Lynden

    2004-01-01

    We report the use of a combination of self- and peer-assessment in an undergraduate social psychology laboratory course. Students worked in small groups on a self-directed empirical project that they each wrote up independently as a laboratory report. Marks for the written assignment were moderated by a contribution index measure based on the…

  20. Contributions to environmental mechanics: Introduction

    NASA Astrophysics Data System (ADS)

    Raats, Peter A. C.; Smiles, David E.; Warrick, Arthur W.

    In the second half of the 20th century, environmental mechanics developed from a collection of loosely connected principles and techniques t o a coherent quantitative treatment of flow and transport in the soil-plant-atmosphere continuum. John Philip was in many respects the life and soul of this adventure . He contributed foremost to the physics of water in unsaturated soils, but also to micrometeorology and physical ecology. In this introductory chapter we briefly review how his contributions influenced and are related to the activities of his colleagues and provide an overview of the present status of theory of soil water movement. We also indicate how the various contributions to this volume fit in this context. We start with a discussion of the nature, foundation, and application of the Richards equation, with emphasis on the dominant role of John Philip in finding analytical solutions of this equation. This is followed by a discussion of various developments beyond the Richards equation: multiphase flow, simultaneous transport of water and heat, flow of water in soils subject to swelling-shrinkage, transport of solutes in unsaturated soils, and flow and transport processes at various scales in space and time. The varied contributions of John Philip to micrometeorology and physical ecology are also reviewed briefly. In the concluding section, some challenges for environmental mechanics are indicated.

  1. Feminist Contributions to Counseling Psychology.

    ERIC Educational Resources Information Center

    Gilbert, Lucia Albino; Osipow, Samuel H.

    1991-01-01

    The feminist movement has influenced counseling psychology in the following areas: (1) policy and leadership; (2) theory and research; (3) training and practice; and (4) recognition of feminist scholarship and contributions by women. Tracing these areas of impact reveals feminism as a major force in developing inquiry and practice. (SLD)

  2. Supporting Enterprise. A College Contribution.

    ERIC Educational Resources Information Center

    Bolton, John F.; Cook, David

    This report describes the experience of one college--Percival Whitley College in Calderdale, England--in contributing to the strategy for economic regeneration of the surrounding metropolitan district. It charts the success of the borough and the college working together to attract national and European funding. A checklist for implementing…

  3. Processed foods: contributions to nutrition.

    PubMed

    Weaver, Connie M; Dwyer, Johanna; Fulgoni, Victor L; King, Janet C; Leveille, Gilbert A; MacDonald, Ruth S; Ordovas, Jose; Schnakenberg, David

    2014-06-01

    Both fresh and processed foods make up vital parts of the food supply. Processed food contributes to both food security (ensuring that sufficient food is available) and nutrition security (ensuring that food quality meets human nutrient needs). This ASN scientific statement focuses on one aspect of processed foods: their nutritional impacts. Specifically, this scientific statement 1) provides an introduction to how processed foods contribute to the health of populations, 2) analyzes the contribution of processed foods to "nutrients to encourage" and "constituents to limit" in the American diet as recommended by the Dietary Guidelines for Americans, 3) identifies the responsibilities of various stakeholders in improving the American diet, and 4) reviews emerging technologies and the research needed for a better understanding of the role of processed foods in a healthy diet. Analyses of the NHANES 2003-2008 show that processed foods provide both nutrients to encourage and constituents to limit as specified in the 2010 Dietary Guidelines for Americans. Of the nutrients to encourage, processed foods contributed 55% of dietary fiber, 48% of calcium, 43% of potassium, 34% of vitamin D, 64% of iron, 65% of folate, and 46% of vitamin B-12. Of the constituents to limit, processed foods contributed 57% of energy, 52% of saturated fat, 75% of added sugars, and 57% of sodium. Diets are more likely to meet food guidance recommendations if nutrient-dense foods, either processed or not, are selected. Nutrition and food science professionals, the food industry, and other stakeholders can help to improve the diets of Americans by providing a nutritious food supply that is safe, enjoyable, affordable, and sustainable by communicating effectively and accurately with each other and by working together to improve the overall knowledge of consumers.

  4. Strong Interaction

    SciTech Connect

    Karsch, F.; Vogelsang, V.

    2009-09-29

    We will give here an overview of our theory of the strong interactions, Quantum Chromo Dynamics (QCD) and its properties. We will also briefly review the history of the study of the strong interactions, and the discoveries that ultimately led to the formulation of QCD. The strong force is one of the four known fundamental forces in nature, the others being the electromagnetic, the weak and the gravitational force. The strong force, usually referred to by scientists as the 'strong interaction', is relevant at the subatomic level, where it is responsible for the binding of protons and neutrons to atomic nuclei. To do this, it must overcome the electric repulsion between the protons in an atomic nucleus and be the most powerful force over distances of a few fm (1fm=1 femtometer=1 fermi=10{sup -15}m), the typical size of a nucleus. This property gave the strong force its name.

  5. Weak Interactions

    DOE R&D Accomplishments Database

    Lee, T. D.

    1957-06-01

    Experimental results on the non-conservation of parity and charge conservation in weak interactions are reviewed. The two-component theory of the neutrino is discussed. Lepton reactions are examined under the assumption of the law of conservation of leptons and that the neutrino is described by a two- component theory. From the results of this examination, the universal Fermi interactions are analyzed. Although reactions involving the neutrino can be described, the same is not true of reactions which do not involve the lepton, as the discussion of the decay of K mesons and hyperons shows. The question of the invariance of time reversal is next examined. (J.S.R.)

  6. Gut Microbiota: A Contributing Factor to Obesity

    PubMed Central

    Harakeh, Steve M.; Khan, Imran; Kumosani, Taha; Barbour, Elie; Almasaudi, Saad B.; Bahijri, Suhad M.; Alfadul, Sulaiman M.; Ajabnoor, Ghada M. A.; Azhar, Esam I.

    2016-01-01

    Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD) and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gut microbiota (GM) have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD. Around 1014 microorganisms reside within the lower human intestine and many of these 1014 microorganisms have developed mutualistic or commensal associations with the host and actively involved in many physiological processes of the host. However, dysbiosis (altered gut microbial composition) with other predisposing genetic and environmental factors, may contribute to host metabolic disorders resulting in many ailments. Therefore, delineating the role of GM as a contributing factor to obesity is the main objective of this review. Obesity research, as a field is expanding rapidly due to major advances in nutrigenomics, metabolomics, RNA silencing, epigenetics, and other disciplines that may result in the emergence of new technologies and methods to better interpret causal relationships between microbiota and obesity. PMID:27625997

  7. Interactive Astronomy.

    ERIC Educational Resources Information Center

    Martin, Jean K.

    1997-01-01

    Presents guiding principles for developing interactive lessons for the World Wide Web. Describes "Amazing Space: Education Online from the Hubble Space Telescope", a program where students study spectacular Hubble Space Telescope images of stars and star-forming regions to learn about the life cycle of stars and the creation of atoms. (JRH)

  8. Interacting Compasses

    ERIC Educational Resources Information Center

    Riveros, Hector G.; Betancourt, Julian

    2009-01-01

    The use of multiple compasses to map and visualize magnetic fields is well-known. The magnetic field exerts a torque on the compasses aligning them along the lines of force. Some science museums show the field of a magnet using a table with many compasses in a closely packed arrangement. However, the very interesting interactions that occur…

  9. Changes in accounting for contributions.

    PubMed

    Pelfrey, S

    1992-03-01

    A proposed accounting change in the timing of income recognition for restricted contributions and pledges can greatly impact a hospital's excess of revenue over expenses (net income). The author addresses steps that administrators can take to lessen its impact. With this knowledge, nurse administrators and other hospital executives can plan alternatives to reduce the income recognition and prepare themselves to answer questions posed by patients and members of the community regarding increased hospital profits.

  10. Townes' contribution to nonlinear optics

    NASA Astrophysics Data System (ADS)

    Garmire, Elsa

    2015-03-01

    In honour of the Fiftieth Anniversary of the Nobel Prize in Physics, this talk introduced the contributions of Nicholas Basov and Alexei Prokhorov, who shared the prize with Charles Townes. The talk then detailed the quantum electronics research of Townes, particularly at MIT, which was related to nonlinear optics. The years from 1961 to 1968 were particularly exciting, as the ruby laser enabled a wide variety of new physics to be discovered and explored.

  11. Cochlear contributions to the precedence effect.

    PubMed

    Verhulst, Sarah; Bianchi, Federica; Dau, Torsten

    2013-01-01

    Normal-hearing individuals have sharply tuned auditory filters, and consequently their basilar-membrane (BM) impulse responses (IRs) have durations of several ms at frequencies in the range from 0 to 5 kHz. When presenting clicks that are several ms apart, the BM IRs to the individual clicks will overlap in time, giving rise to complex interactions that have not been fully understood in the human cochlea. The perceptual consequences of these BM IR interactions are of interest as lead-lag click pairs are often used to study localization and the precedence effect. The present study aimed at characterizing perceptual consequences of BM IR interactions in individual listeners based on click-evoked otoacoustic emissions (CEOAEs) and auditory brainstem responses (ABRs). Lag suppression, denoting the level difference between the CEOAE or wave-V response amplitude evoked by the first and the second clicks, was observed for inter-click intervals (ICIs) between 1 and 4 ms. Behavioral correlates of lag suppression were obtained for the same individuals by investigating the percept of the lead-lag click pairs presented either monaurally or binaurally. The click pairs were shown to give rise to fusion (i.e., the inability to hear out the second click in a lead-lag click pair), regardless of monaural or binaural presentation. In both cases, the ICI range where the percept was a fused image correlated well with the ICI range for which monaural lag suppression occurred in the CEOAE and ABR (i.e., for ICIs below 4.3 ms). Furthermore, the lag suppression observed in the wave-V amplitudes to binaural stimulation did not show additional contributions to the lag suppression obtained monaurally, suggesting that peripheral lag suppression up to the level of the brainstem is dominant in the perception of the precedence effect.

  12. 5 CFR 1600.12 - Contribution elections.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Contribution elections. 1600.12 Section... ELECTIONS AND CONTRIBUTION ALLOCATIONS Elections § 1600.12 Contribution elections. (a) An employee may make a contribution election at any time. (b) A participant must submit a contribution election to his...

  13. [Pharmacokinetic interactions].

    PubMed

    Arazo Garcés, Piedad; de los Santos Gil, Ignacio

    2013-06-01

    Rilpivirine (RPV) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) that has been approved for use in treatment-naïve patients and which has potent antiviral activity. Its adverse effects profile differs from that of first-generation NNRTs. The pharmacological interactions produced by RPV are due to its effects on the CYP450 system; RPV is a substrate and mild inducer of CYP3A4. Moreover, in vitro, RPV inhibits glycoprotein-P. RPV has clinically significant pharmacological interactions, especially with protease inhibitors (except boosted darunavir and lopinavir) and the NNRTIs efavirenz and nevirapine. Coadministration of RPV with drugs that increase gastric pH, such as omeprazole, or those inducing CYP3A4, such as rifampicin, can significantly reduce RPV concentrations and is contraindicated. The concomitant use of RPV with a CYP3A4 inhibitor (such as clarithromycin) can increase RPV concentrations. Administration of PRV with food is recommended to obtain better absorption and adequate plasma values.

  14. Methanotrophs Contribute to Peatland Nitrogen

    NASA Astrophysics Data System (ADS)

    Larmola, Tuula; Leppänen, Sanna M.; Tuittila, Eeva-Stiina; Aarva, Maija; Merilä, Päivi; Fritze, Hannu; Tiirola, Marja

    2016-04-01

    Atmospheric nitrogen (N2) fixation is potentially an important N input mechanism to peatland ecosystems, but the extent of this process may have been underestimated because of the methods traditionally used inhibit the activity of methanothrophs. We examined the linkage of methane (CH4) oxidation and N2 fixation using 15N2 technique. Dominant flark and hummock Sphagnum species were collected from twelve pristine peatlands in Siikajoki, Finland, which varied in age from 200 to 2,500 y due to the postglacial rebound. The mosses were incubated in a two-day field 15N2 and 13CH4 pulse labelling experiment and the incorporation of 15N2 and 13CH4 in biomass was measured with Isotope Ratio Mass Spectrometer. The rates of Sphagnum-associated N2 fixation (0.1-2.9 g N m-2 y-1) were up to 10 times the current N deposition rates. Methane-induced N2 fixation contributed to over 1/3 of moss-associated N2 fixation in younger stages, but was switched off in old successional stages, despite active CH4 oxidation in these stages. Both the N2 fixation rates and the methanotrophic contribution to N2 fixation during peatland succession were primarily constrained by phosphorus availability. Previously overlooked methanotrophic N contribution may explain rapid peat and N accumulation during fen stages of peatland development. Reference. Larmola T., Leppänen S.M., Tuittila E.-S, Aarva M., Merilä P., Fritze H., Tiirola M. (2014) Methanotrophy induces nitrogen fixation during peatland development. Proceedings of the National Academy of Sciences USA 111 (2): 734-739.

  15. IVS contribution to ITRF2014

    NASA Astrophysics Data System (ADS)

    Bachmann, Sabine; Thaller, Daniela; Roggenbuck, Ole; Lösler, Michael; Messerschmitt, Linda

    2016-07-01

    Every few years the International Terrestrial Reference System (ITRS) Center of the International Earth Rotation and Reference Systems Service (IERS) decides to generate a new version of the International Terrestrial Reference Frame (ITRF). For the upcoming ITRF2014 the official contribution of the International VLBI Service for Geodesy and Astrometry (IVS) comprises 5796 combined sessions in SINEX file format from 1979.6 to 2015.0 containing 158 stations, overall. Nine AC contributions were included in the combination process, using five different software packages. Station coordinate time series of the combined solution show an overall repeatability of 3.3 mm for the north, 4.3 mm for the east and 7.5 mm for the height component over all stations. The minimum repeatabilities are 1.5 mm for north, 2.1 mm for east and 2.9 mm for height. One of the important differences between the IVS contribution to the ITRF2014 and the routine IVS combination is the omission of the correction for non-tidal atmospheric pressure loading (NTAL). Comparisons between the amplitudes of the annual signals derived by the VLBI observations and the annual signals from an NTAL model show that for some stations, NTAL has a high impact on station height variation. For other stations, the effect of NTAL is low. Occasionally other loading effects have a higher influence (e.g. continental water storage loading). External comparisons of the scale parameter between the VTRF2014 (a TRF based on combined VLBI solutions), DTRF2008 (DGFI-TUM realization of ITRS) and ITRF2008 revealed a significant difference in the scale. A scale difference of 0.11 ppb (i.e. 0.7 mm on the Earth's surface) has been detected between the VTRF2014 and the DTRF2008, and a scale difference of 0.44 ppb (i.e. 2.8 mm on the Earth's surface) between the VTRF2014 and ITRF2008. Internal comparisons between the EOP of the combined solution and the individual solutions from the AC contributions show a WRMS in X- and Y-Pole between

  16. The Viennese contribution to venereology.

    PubMed Central

    Wauch, M

    1977-01-01

    A history of venereology in Vienna from the first manifestations of the French disease in 1498 until the first half of the twentieth century is described. Notable events were the founding of the old Vienna School by van Swieten in the years after 1745, followed by the revival one hundred years later by von Hebra of the scientific basis for dermatovenereology. An account is given of teachers and discoverers of venereological importance after von Hebra and Sigmund to Arzt. The importance of Landsteiner's and Wagner von Jauregg's contributions finalise the historical account. PMID:336146

  17. 11 CFR 9034.2 - Matchable contributions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... political dinner or reception. (7) Contributions received from a joint fundraising activity conducted in... the joint fundraising agreement when they are submitted for matching. (8) Contributions by credit...

  18. Lightning Model Development: Contribution to High Power Electromagnetics

    NASA Astrophysics Data System (ADS)

    Gardner, R. L.

    As the accompanying articles can attest, Dr. Carl E. Baum has had a varied career with fundamental contributions to many subjects. Lightning is one of those technical areas in which he has provided deep insight into the mechanisms of a very complex physical phenomenon. His contributions include fundamental measurements of lightning properties, basic models of important physical characteristics, lightning simulation characterization, and finally, lightning interaction with important systems like aircraft. The foundations of these techniques have helped him form the foundation of the general subject of high power electromagnetics.

  19. Nobel prizes: contributions to cardiology.

    PubMed

    Mesquita, Evandro Tinoco; Marchese, Luana de Decco; Dias, Danielle Warol; Barbeito, Andressa Brasil; Gomes, Jonathan Costa; Muradas, Maria Clara Soares; Lanzieri, Pedro Gemal; Gismondi, Ronaldo Altenburg

    2015-08-01

    The Nobel Prize was created by Alfred Nobel. The first prize was awarded in 1901 and Emil Adolf von Behring was the first laureate in medicine due to his research in diphtheria serum. Regarding cardiology, Nobel Prize's history permits a global comprehension of progress in pathophysiology, diagnosis and therapeutics of various cardiac diseases in last 120 years. The objective of this study was to review the major scientific discoveries contemplated by Nobel Prizes that contributed to cardiology. In addition, we also hypothesized why Carlos Chagas, one of our most important scientists, did not win the prize in two occasions. We carried out a non-systematic review of Nobel Prize winners, selecting the main studies relevant to heart diseaseamong the laureates. In the period between 1901 and 2013, 204 researches and 104 prizes were awarded in Nobel Prize, of which 16 (15%) studies were important for cardiovascular area. There were 33 (16%) laureates, and two (6%) were women. Fourteen (42%) were American, 15 (45%) Europeans and four (13%) were from other countries. There was only one winner born in Brazil, Peter Medawar, whose career was all in England. Reviewing the history of the Nobel Prize in physiology or medicine area made possible to identify which researchers and studies had contributed to advances in the diagnosis, prevention and treatment of cardiovascular diseases. Most winners were North Americans and Europeans, and male.

  20. Nobel Prizes: Contributions to Cardiology

    PubMed Central

    Mesquita, Evandro Tinoco; Marchese, Luana de Decco; Dias, Danielle Warol; Barbeito, Andressa Brasil; Gomes, Jonathan Costa; Muradas, Maria Clara Soares; Lanzieri, Pedro Gemal; Gismondi, Ronaldo Altenburg

    2015-01-01

    The Nobel Prize was created by Alfred Nobel. The first prize was awarded in 1901 and Emil Adolf von Behring was the first laureate in medicine due to his research in diphtheria serum. Regarding cardiology, Nobel Prize’s history permits a global comprehension of progress in pathophysiology, diagnosis and therapeutics of various cardiac diseases in last 120 years. The objective of this study was to review the major scientific discoveries contemplated by Nobel Prizes that contributed to cardiology. In addition, we also hypothesized why Carlos Chagas, one of our most important scientists, did not win the prize in two occasions. We carried out a non-systematic review of Nobel Prize winners, selecting the main studies relevant to heart diseaseamong the laureates. In the period between 1901 and 2013, 204 researches and 104 prizes were awarded in Nobel Prize, of which 16 (15%) studies were important for cardiovascular area. There were 33 (16%) laureates, and two (6%) were women. Fourteen (42%) were American, 15 (45%) Europeans and four (13%) were from other countries. There was only one winner born in Brazil, Peter Medawar, whose career was all in England. Reviewing the history of the Nobel Prize in physiology or medicine area made possible to identify which researchers and studies had contributed to advances in the diagnosis, prevention and treatment of cardiovascular diseases. Most winners were North Americans and Europeans, and male. PMID:25945466

  1. Inclusion in Practice: Sofia's Situations for Interaction

    ERIC Educational Resources Information Center

    Alexandersson, Ulla

    2011-01-01

    The aim of this article is to present findings from a study (Alexandersson, 2007) about how one student--called Sofia--with intellectual disability interacts and communicates with her classmates and her teachers in an inclusive setting. Furthermore, the aim is also to analyse in what way the interaction contributes to Sofia's social participation…

  2. IDS contribution to ITRF2008

    NASA Astrophysics Data System (ADS)

    Valette, J.; Lemoine, F.; Ferrage, P.; Altamimi, Z.; Willis, P.; Stepanek, P.; Otten, M.; Govind, R.; Kuzin, S.; Le Bail, K.; Moore, P.; Yaya, P.; Soudarin, L.

    2009-12-01

    The International DORIS Service (IDS), in operation since 2003, submitted three sets of solutions to ITRF2005 from the IGN/JPL, LEGOS/CLS, and INASAN analysis centers, but no DORIS technique combination. Since that time new analysis centers have become operational including the Geodetic Observatory Pecny (GOP), the European Space Operations Center (ESOC), Geoscience Australia (GAU), the NASA Goddard Space Flight Center (GSC), and the University of Newcastle (NCL). These analysis centers run different software, including Gypsy (IGN & INASAN), GINS (LCA), Bernese (GOP), NAPEOS (ESOC), GEODYN (Geoscience Australia and NASA GSFC) and FAUST (NCL). In order to contribute to ITRF2008, seven analysis centers processed DORIS data from TOPEX/Poseidon, SPOT2, SPOT3, SPOT4, SPOT5, and ENVISAT from 1992 to 2008, producing weekly SINEX solutions or normal equations. The weekly SINEX files from seven AC’s were processed with the CATREF software. Three iterations of an IDS weekly combined time series were completed. The IDS-1, and IDS-2 combinations were preliminary station-only solutions. In the final combination, IDS-3, both stations and the Earth Orientation Paramters (EOP’s) were adjusted. Between each of the IDS combinations, the combination strategy (station filtering, outliers, weighting, scale or geocenter contributions) was improved and the AC’s SINEX series were refined. Some series were extended in data span while others were recomputed to correct anomalies or to improve the quality of the submissions, based on feedback from the combination analyses and intercenter comparisons. For example in IDS-1, both the GAU and GSC solutions were affected by a 20 mm scale offset that was removed in IDS-2 and IDS-3 after the application of improved troposphere modelling in the GEODYN software. The analysis for IDS-1 showed a higher station position WRMS in the vicinity of the high solar flux periods (late 2001-2002). Consequently for IDS-2, several AC’s (LCA, GAU, GSC

  3. Sibling interaction.

    PubMed

    Balsam, Rosemary H

    2013-01-01

    Sibling interactions traditionally were conceived psychoanalytically in "vertical" and parentified oedipal terms and overlooked in their own right, for complicated reasons (Colonna and Newman 1983). Important work has been done to right this, from the 1980s and onward, with conferences and writings. Juliet Mitchell's 2000 and, in particular, her 2003 books, for example, have brought "lateral" sibling relations forcefully to the forefront of insights, especially about sex and violence, with the added interdisciplinary impact of illuminating upheaval in global community interactions as well as having implications for clinicians. A clinical example from the analysis of an adult woman with a ten-years-younger sister will show here how we need both concepts to help us understand complex individual psychic life. The newer "lateral" sibling emphasis, including Mitchell's "Law of the Mother" and "seriality," can be used to inform the older "vertical" take, to enrich the full dimensions of intersubjective oedipal and preoedipal reciprocities that have been foundational in shaping that particular analysand's inner landscape. Some technical recommendations for heightening sensitivity to the import of these dynamics will be offered along the way here, by invoking Hans Loewald's useful metaphor of the analytic situation as theater.

  4. Carl Neumann's Contributions to Electrodynamics

    NASA Astrophysics Data System (ADS)

    Schlote, Karl-Heinz

    2004-09-01

    I examine the publications of Carl Neumann (1832 1925) on electrodynamics, which constitute a major part of his work and which illuminate his approach to mathematical physics. I show how Neumann contributed to physics at an important stage in its development and how his work led to a polemic with Hermann Helmholtz (1821 1894). Neumann advanced and extended the ideas of the Königsberg school of mathematical physics. His investigations were aimed at founding a mathematically exact physical theory of electrodynamics, following the approach of Carl G.J. Jacobi (1804 1851) on the foundation of a physical theory as outlined in Jacobi’s lectures on analytical mechanics. Neumann’s work also shows how he clung to principles that impeded him in appreciating and developing new ideas such as those on field theory that were proposed by Michael Faraday (1791 1867) and James Clerk Maxwell (1831 1879).

  5. Factors contributing to adolescent obesity.

    PubMed

    Al-Kloub, Manal I; Froelicher, Erika S

    2009-06-01

    Obesity in children is a significant public health concern. The prevalence of overweight and obesity in Jordanian children, and adolescents has increased in the last decade. The consequences of obesity to health in childhood and adulthood have both medical, and economic cost to individuals and society. This paper reviews the factors that contribute to adolescent obesity and emphasizes behavioral and environmental factors. An individual's behaviors such as increased consumption of high caloric foods, increased sedentary activity while decreasing physical activity has been identified as key issues in the development of obesity. Additionally, the current environment in homes, schools, and neighborhoods tend to discourage a healthy lifestyle. A comprehensive approach that involves the whole community is the best strategy for preventing adolescent obesity. Nurses are in a unique position to provide leadership in developing programs for healthier lifestyle choices for adolescents' and adoption of these goals into their daily lives.

  6. Hadron Contribution to Vacuum Polarisation

    NASA Astrophysics Data System (ADS)

    Davier, M.; Hoecker, A.; Malaescu, B.; Zhang, Z.

    2016-10-01

    Precision tests of the Standard Theory require theoretical predictions taking into account higher-order quantum corrections. Among these vacuum polarisation plays a predominant role. Vacuum polarisation originates from creation and annihilation of virtual particle-antiparticle states. Leptonic vacuum polarisation can be computed from quantum electrodynamics. Hadronic vacuum polarisation cannot because of the non-perturbative nature of QCD at low energy. The problem is remedied by establishing dispersion relations involving experimental data on the cross section for e+ e- annihilation into hadrons. This chapter sets the theoretical and experimental scene and reviews the progress achieved in the last decades thanks to more precise and complete data sets. Among the various applications of hadronic vacuum polarisation calculations, two are emphasised: the contribution to the anomalous magnetic moment of the muon, and the running of the fine structure constant α to the Z mass scale. They are fundamental ingredients to high precision tests of the Standard Theory.

  7. Possible NASA Contributions to HEAT

    NASA Technical Reports Server (NTRS)

    Shepherd, J. M.

    2004-01-01

    A four-year experiment (HEAT) has been proposed (one summer in the field, 2005) to determine the sources and causes for the enhanced cloud-to-ground lightning over Houston, Texas, in association with simultaneous experiments by the Environmental Protection Agency (EPA) and the Texas Natural Resource Conservation Commission (TNRCC). Houston is the third most populous city in the United States and the region contains 50% of the petroleum refining capacity of the United States. Recent studies covering the period 1989-2000 document a 50% increase of cloud-to-ground lightning in the Houston area as compared to background values, which is second in flash density only to the Tampa Bay, Florida area. It is suggested that the elevated flash densities could result from several factors, including, 1) the convergence due to the urban heat island effect and complex sea breeze, and 2) the increasing levels of air pollution from anthropogenic sources producing numerous small droplets and thereby suppressing mean droplet size. The latter effect would enable more cloud water to reach the mixed phase region where it is involved in the formation of precipitation and the separation of electric charge, leading to an enhancement of lightning. The primary goals of HEAT are to examine the effects of (1) pollution, (2) the urban heat island, and (3) the complex coastline, on storms and lightning characteristics in the Houston area. The project is a multi- agency effort and will employ numerous observing capabilities and expertise. Dr. Shepherd has been asked to serve as a possible co- investigator to contribute expertise in areas related to urban impacts on precipitation variability. Dr. Shepherd is also a key NASA representative in the interagency effort. This presentation will provide an overview of recent NASA research focused on urban rainfall in Houston and offer potential NASA capabilities that could contribute to HEAT.

  8. CTC-Endothelial Cell Interactions during Metastasis

    DTIC Science & Technology

    2014-06-01

    study of CTC-Endothelial interactions, as it introduced cell aggregation in the chamber, likely because of the presence of contaminating RBCs in PBMC...interactions, as it introduced cell aggregation in the chamber, likely because of the presence of contaminating RBCs in PBMC preparations, which disturbed the...microvascular endothelium via E- selectin/E-selectin ligand interactions under shear flow theoretically promote extravasation and contribute to the

  9. 5 CFR 890.501 - Government contributions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Government contributions. 890.501 Section... (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Contributions and Withholdings § 890.501 Government contributions. (a) The Government contribution toward subscription charges under all health benefits plans,...

  10. 5 CFR 890.501 - Government contributions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Government contributions. 890.501 Section... (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Contributions and Withholdings § 890.501 Government contributions. (a) The Government contribution toward subscription charges under all health benefits plans,...

  11. 5 CFR 890.501 - Government contributions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Government contributions. 890.501 Section... (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Contributions and Withholdings § 890.501 Government contributions. (a) The Government contribution toward subscription charges under all health benefits plans,...

  12. 5 CFR 890.501 - Government contributions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Government contributions. 890.501 Section... (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Contributions and Withholdings § 890.501 Government contributions. (a) The Government contribution toward subscription charges under all health benefits plans,...

  13. 5 CFR 1604.3 - Contribution elections.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Contribution elections. 1604.3 Section... § 1604.3 Contribution elections. A service member may make contribution elections as described in 5 CFR... incentive pay when the contribution election is made); those elections will take effect when the...

  14. 7 CFR 550.15 - Resource contribution.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Resource contribution. 550.15 Section 550.15... Agreements § 550.15 Resource contribution. Each party must contribute resources towards the successful completion of the project. Required resource contributions must be substantial enough to substantiate a...

  15. 7 CFR 550.15 - Resource contribution.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Resource contribution. 550.15 Section 550.15... Agreements § 550.15 Resource contribution. Each party must contribute resources towards the successful completion of the project. Required resource contributions must be substantial enough to substantiate a...

  16. 7 CFR 550.15 - Resource contribution.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Resource contribution. 550.15 Section 550.15... Agreements § 550.15 Resource contribution. Each party must contribute resources towards the successful completion of the project. Required resource contributions must be substantial enough to substantiate a...

  17. 7 CFR 550.15 - Resource contribution.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Resource contribution. 550.15 Section 550.15... Agreements § 550.15 Resource contribution. Each party must contribute resources towards the successful completion of the project. Required resource contributions must be substantial enough to substantiate a...

  18. 7 CFR 550.15 - Resource contribution.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Resource contribution. 550.15 Section 550.15... Agreements § 550.15 Resource contribution. Each party must contribute resources towards the successful completion of the project. Required resource contributions must be substantial enough to substantiate a...

  19. 13 CFR 120.911 - Land contributions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Land contributions. 120.911... Company Loan Program (504) The Borrower's Contribution § 120.911 Land contributions. The Borrower's contribution may be land (including buildings, structures and other site improvements which will be part of...

  20. 13 CFR 120.911 - Land contributions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Land contributions. 120.911... Company Loan Program (504) The Borrower's Contribution § 120.911 Land contributions. The Borrower's contribution may be land (including buildings, structures and other site improvements which will be part of...

  1. 13 CFR 120.911 - Land contributions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Land contributions. 120.911... Company Loan Program (504) The Borrower's Contribution § 120.911 Land contributions. The Borrower's contribution may be land (including buildings, structures and other site improvements which will be part of...

  2. 13 CFR 120.911 - Land contributions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Land contributions. 120.911... Company Loan Program (504) The Borrower's Contribution § 120.911 Land contributions. The Borrower's contribution may be land (including buildings, structures and other site improvements which will be part of...

  3. 13 CFR 120.911 - Land contributions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Land contributions. 120.911... Company Loan Program (504) The Borrower's Contribution § 120.911 Land contributions. The Borrower's contribution may be land (including buildings, structures and other site improvements which will be part of...

  4. Rotational ratchets with dipolar interactions.

    PubMed

    Jäger, Sebastian; Klapp, Sabine H L

    2012-12-01

    We report results from a computer simulation study on the rotational ratchet effect in systems of magnetic particles interacting via dipolar interactions. The ratchet effect consists of directed rotations of the particles in an oscillating magnetic field, which lacks a net rotating component. Our investigations are based on Brownian dynamics simulations of such many-particle systems. We investigate the influence of both the random and deterministic contributions to the equations of motion on the ratchet effect. As a main result, we show that dipolar interactions can have an enhancing as well as a dampening effect on the ratchet behavior depending on the dipolar coupling strength of the system under consideration. The enhancement is shown to be caused by an increase in the effective field on a particle generated by neighboring magnetic particles, while the dampening is due to restricted rotational motion in the effective field. Moreover, we find a nontrivial influence of the short-range, repulsive interaction between the particles.

  5. Contribution to the Theory of Magnetoelectric Effect in Magnetic Semiconductors

    NASA Astrophysics Data System (ADS)

    Kuivalainen, P.; Sinkkonen, J.; Stubb, T.

    1980-01-01

    A generation of a d.c. electric field at ferromagnetic resonance or the magnetoelectric effect in magnetic semiconductors is studied theoretically in the whole magnon wave vector space. The magnetoelectric effect in the classical regime kl < 1 and contributions of different electron-magnon interactions to the magnon drag effect in the quantum regime kl > 1 are calculated. All the calculated static electric fields are compared with experimental results. At low-microwave power levels the non-linear electrodynamic interaction due to a mixing of the oscillating magnetization (k = 0) and the induced electric field seems to dominate the magnetoelectric effect. In some cases the classical drag effect may also be significant. At sufficiently high power levels the quantum mechanical magnon drag can make the largest contribution. It is shown that in the magnon drag effect the induced static electric field is proportional to the damping coefficient of magnons.

  6. Interact - Access to the Arctic

    NASA Astrophysics Data System (ADS)

    Johansson, M.; Callaghan, T. V.

    2013-12-01

    INTERACT is currently a network of 50 terrestrial research stations from all Arctic countries, but is still growing. The network was inaugurated in January 2011 when it received an EU 7th Framework award. INTERACT's main objective is to build capacity for identifying, understanding, predicting and responding to diverse environmental changes throughout the wide environmental and land-use envelopes of the Arctic. Implicit in this objective is the task to build capacity for monitoring, research, education and outreach. INTERACT is increasing access to the Arctic: 20 INTERACT research stations in Europe and Russia are offering Transnational Access and so far, 5600 person-days of access have been granted from the total of 10,000 offered. An INTERACT Station Managers' Forum facilitates a dialogue among station managers on subjects such as best practice in station management and standardised monitoring. The Station Managers' Forum has produced a unique 'one-stop-shop' for information from 45 research stations in an informative and attractive Station Catalogue that is available in hard copy and on the INTERACT web site (www.eu-interact.org). INTERACT also includes three joint research activities that are improving monitoring in remote, harsh environments and are making data capture and dissemination more efficient. Already, new equipment for measuring feedbacks from the land surface to the climate system has been installed at several locations, while best practices for sensor networking have been established. INTERACT networks with most of the high-level Arctic organisations: it includes AMAP and WWF as partners, is endorsed by IASC and CBMP, has signed MoUs with ISAC and the University of the Arctic, is a task within SAON, and contributes to the Cold Region community within GEO/GEOSS. INTERACT welcomes other interactions.

  7. Contribution of rock fragments to soil fertility

    NASA Astrophysics Data System (ADS)

    Korboulewsky, Nathalie; Besnault, Adeline; Tétégan, Marion; Cousin, Isabelle

    2010-05-01

    Research in plant-soil interactions has focused on the role played by the finest particles, but much less attention has been devoted to quantify the contribution of rock fragments. While the coarse soil fraction is known to affect soil physical properties, such as bulk density, porosity, water infiltration and storage, its contribution to the biogeochemical cycle is neglected. In particular in plant nutrition studies, only the fine fraction (< 2 mm) of soils is sampled and analysed while the coarse fraction (> 2 mm) is considered chemically inert. However, several recent studies have showed that rock fragments contribute significantly to nutrient content and the cation exchange capacity of soils. Considering that stony soils cover about 30% of the surface soils of Western Europe, and 60% in the Mediterranean area, new data on the potential contribution of rock fragments to soil fertility may give new insights that will re-evaluate their role in models on biogeochemical cycling. We attempt to study nutrient availability differents types of rock fragments, and started with five types of pebbles: oolitic limestone, marly limestone, lithographic limestone, chert, and flint. Pebbles were collected in topsoils, brushed thoroughly, and dried before chemical analyses. Exchangeable cations (Ca, Mg, and K) were extracted after immersion of whole pebbles in an ammonium acetate solution (1M) under agitation for 48h. We had previously established the kinetic of extraction over 6 days (after 1, 3.5, 7, 24, 48, 72 and 144 h) and showed that a plateau was reached at 48h, and with a good repeatability. The pattern of release differed among the three studied exchangeable cations, and among pebbles of different origin. The capacity of pebbles to release exchangeable calcium and magnesium was in the following decreasing order: lithographic limestone = marly limestone > oolitic limestone >> chert > flint. As expected, the greatest difference was found between limestones and the two

  8. Cosmic Interactions

    NASA Astrophysics Data System (ADS)

    2008-01-01

    An image based on data taken with ESO's Very Large Telescope reveals a triplet of galaxies intertwined in a cosmic dance. ESO PR Photo 02/08 ESO PR Photo 02/08 NGC 7173, 7174, and 7176 The three galaxies, catalogued as NGC 7173 (top), 7174 (bottom right) and 7176 (bottom left), are located 106 million light-years away towards the constellation of Piscis Austrinus (the 'Southern Fish'). NGC 7173 and 7176 are elliptical galaxies, while NGC 7174 is a spiral galaxy with quite disturbed dust lanes and a long, twisted tail. This seems to indicate that the two bottom galaxies - whose combined shape bears some resemblance to that of a sleeping baby - are currently interacting, with NGC 7176 providing fresh material to NGC 7174. Matter present in great quantity around the triplet's members also points to the fact that NGC 7176 and NGC 7173 have interacted in the past. Astronomers have suggested that the three galaxies will finally merge into a giant 'island universe', tens to hundreds of times as massive as our own Milky Way. ESO PR Photo 02/08 ESO PR Photo 02b/08 NGC 7173, 7174, and 7176 The triplet is part of a so-called 'Compact Group', as compiled by Canadian astronomer Paul Hickson in the early 1980s. The group, which is the 90th entry in the catalogue and is therefore known as HCG 90, actually contains four major members. One of them - NGC 7192 - lies above the trio, outside of this image, and is another peculiar spiral galaxy. Compact groups are small, relatively isolated, systems of typically four to ten galaxies in close proximity to one another. Another striking example is Robert's Quartet. Compact groups are excellent laboratories for the study of galaxy interactions and their effects, in particular the formation of stars. As the striking image reveals, there are many other galaxies in the field. Some are distant ones, while others seem to be part of the family. Studies made with other telescopes have indeed revealed that the HCG 90 group contains 16 members

  9. Electroweak interactions

    SciTech Connect

    Bjorken, J.D.

    1980-10-01

    A point of view of the electroweak interaction is presented. It begins phenomenologically and moves in stages toward the conventional gauge theory formalism containing elementary scalar Higgs-fields and then beyond. The purpose in so doing is that the success of the standard SU(2) x U(1) theory in accounting for low energy phenomena need not automatically imply success at high energies. It is deemed unlikely by most theorists that the predicted W/sup + -/ or Z/sup 0/ does not exist or does not have the mass and/or couplings anticipated in the standard model. However, the odds that the standard predictions will work are not 100%. Therefore there is some reason to look at the subject as one would were he forced by a wrong experimental outcome - to go back to fundamentals and ascertain what is the minimal amount of theory necessary to account for the data.

  10. Managing Learner Contributions in the Adult ESL Classroom: A Conversation Analytic and Ethnographic Examination of Teacher Practices and Cognition

    ERIC Educational Resources Information Center

    Fagan, Drew Stephen

    2013-01-01

    Although contemporary second language learning scholars assert that teacher management of learner contributions in classroom interaction is key to promoting learning opportunities, research has yet to make explicit teachers' real-time management practices. Studies on classroom interaction have illuminated how learner contributions are elicited via…

  11. TROY and LINGO-1 expression in astrocytes and macrophages/microglia in multiple sclerosis lesions.

    PubMed

    Satoh, J; Tabunoki, H; Yamamura, T; Arima, K; Konno, H

    2007-02-01

    Nogo constitutes a family of neurite outgrowth inhibitors contributing to a failure of axonal regeneration in the adult central nervous system (CNS). Nogo-A is expressed exclusively on oligodendrocytes where Nogo-66 segment binds to Nogo receptor (NgR) expressed on neuronal axons. NgR signalling requires a coreceptor p75(NTR) or TROY in combination with an adaptor LINGO-1. To characterize the cell types expressing the NgR complex in the human CNS, we studied demyelinating lesions of multiple sclerosis (MS) brains by immunohistochemistry. TROY and LINGO-1 were identified in subpopulations of reactive astrocytes, macrophages/microglia and neurones but not in oligodendrocytes. TROY was up-regulated, whereas LINGO-1 was reduced in MS brains by Western blot. These results suggest that the ternary complex of NgR/TROY/LINGO-1 expressed on astrocytes, macrophages/microglia and neurones, by interacting with Nogo-A on oligodendrocytes, might modulate glial-neuronal interactions in demyelinating lesions of MS.

  12. Resolving the Brainstem Contributions to Attentional Analgesia

    PubMed Central

    Brooks, Jonathan C.W.; Davies, Wendy-Elizabeth

    2017-01-01

    the periaqueductal gray (PAG). Animal data indicate that the PAG acts via caudal brainstem structures to control nociception. We investigated this issue within an attentional analgesia paradigm with brainstem-optimized fMRI and analysis using a probabilistic brainstem atlas. We find pain intensity encoding in several forebrain structures, including the insula and attentional activation of the PAG. Discrete regions of the rostral ventromedial medulla bidirectionally influence pain perception, and locus coeruleus activity mirrors the interaction between attention and nociception. This approach has enabled the resolution of contributions from a hub of key brainstem structures to endogenous analgesia. PMID:28096471

  13. Molecular biology research in neuropsychiatry: India's contribution.

    PubMed

    Sathyanarayana Rao, T S; Ramesh, B N; Vasudevaraju, P; Rao, K S J

    2010-01-01

    Neuropsychiatric disorders represent the second largest cause of morbidity worldwide. These disorders have complex etiology and patho-physiology. The major lacunae in the biology of the psychiatric disorders include genomics, biomarkers and drug discovery, for the early detection of the disease, and have great application in the clinical management of disease. Indian psychiatrists and scientists played a significant role in filling the gaps. The present annotation provides in depth information related to research contributions on the molecular biology research in neuropsychiatric disorders in India. There is a great need for further research in this direction as to understand the genetic association of the neuropsychiatric disorders; molecular biology has a tremendous role to play. The alterations in gene expression are implicated in the pathogenesis of several neuropsychiatric disorders, including drug addiction and depression. The development of transgenic neuropsychiatric animal models is of great thrust areas. No studies from India in this direction. Biomarkers in neuropsychiatric disorders are of great help to the clinicians for the early diagnosis of the disorders. The studies related to gene-environment interactions, DNA instability, oxidative stress are less studied in neuropsychiatric disorders and making efforts in this direction will lead to pioneers in these areas of research in India. In conclusion, we provided an insight for future research direction in molecular understanding of neuropsychiatry disorders.

  14. Contribution to a symbiogenic approach in astrobiology

    NASA Astrophysics Data System (ADS)

    Carrapiço, Francisco; Pereira, Luísa; Rodrigues, Telma

    2007-09-01

    This article intends to continue our previous work on the symbiogenic approach to chemical and biological evolution. We believe that cooperative and synergistic processes were responsible, using terrestrial and extraterrestrial materials, for the creation of a large prebiotic pool, closely related to geochemical contexts, and intense interactions within. Probably, a series of synergistic and cooperative effects produced a wide source of creativity, and functional advantages that pushed the emergence of complex and functionally integrated biological systems, through the evolution of self-organization and auto-catalysis. It was only after this biochemical evolution of structures, which produced the informational capabilities necessary for self-replication, that the Darwinian mechanisms could arise. This way of perceiving the emergence of life follows the proposals regarding life's initial evolution in which the progenote proposed consisted in an open community of very diverse primitive cellular entities with intense symbiotic associations, antagonisms, and competition, and with a rapid and reticulate pattern of evolution. We believe this symbiogenic approach should be considered in the understanding of chemical and biological evolution. This discussion contributes to the development of astrobiological knowledge, since it gives other perspectives about life's appearance and development on Earth and elsewhere.

  15. Quantification of social contributions to earthquake mortality

    NASA Astrophysics Data System (ADS)

    Main, I. G.; NicBhloscaidh, M.; McCloskey, J.; Pelling, M.; Naylor, M.

    2013-12-01

    Death tolls in earthquakes, which continue to grow rapidly, are the result of complex interactions between physical effects, such as strong shaking, and the resilience of exposed populations and supporting critical infrastructures and institutions. While it is clear that the social context in which the earthquake occurs has a strong effect on the outcome, the influence of this context can only be exposed if we first decouple, as much as we can, the physical causes of mortality from our consideration. (Our modelling assumes that building resilience to shaking is a social factor governed by national wealth, legislation and enforcement and governance leading to reduced levels of corruption.) Here we attempt to remove these causes by statistically modelling published mortality, shaking intensity and population exposure data; unexplained variance from this physical model illuminates the contribution of socio-economic factors to increasing earthquake mortality. We find that this variance partitions countries in terms of basic socio-economic measures and allows the definition of a national vulnerability index identifying both anomalously resilient and anomalously vulnerable countries. In many cases resilience is well correlated with GDP; people in the richest countries are unsurprisingly safe from even the worst shaking. However some low-GDP countries rival even the richest in resilience, showing that relatively low cost interventions can have a positive impact on earthquake resilience and that social learning between these countries might facilitate resilience building in the absence of expensive engineering interventions.

  16. Proteomic Contributions to Personalized Cancer Care*

    PubMed Central

    Koomen, John M.; Haura, Eric B.; Bepler, Gerold; Sutphen, Rebecca; Remily-Wood, Elizabeth R.; Benson, Kaaron; Hussein, Mohamad; Hazlehurst, Lori A.; Yeatman, Timothy J.; Hildreth, Lynne T.; Sellers, Thomas A.; Jacobsen, Paul B.; Fenstermacher, David A.; Dalton, William S.

    2008-01-01

    Cancer impacts each patient and family differently. Our current understanding of the disease is primarily limited to clinical hallmarks of cancer, but many specific molecular mechanisms remain elusive. Genetic markers can be used to determine predisposition to tumor development, but molecularly targeted treatment strategies that improve patient prognosis are not widely available for most cancers. Individualized care plans, also described as personalized medicine, still must be developed by understanding and implementing basic science research into clinical treatment. Proteomics holds great promise in contributing to the prevention and cure of cancer because it provides unique tools for discovery of biomarkers and therapeutic targets. As such, proteomics can help translate basic science discoveries into the clinical practice of personalized medicine. Here we describe how biological mass spectrometry and proteome analysis interact with other major patient care and research initiatives and present vignettes illustrating efforts in discovery of diagnostic biomarkers for ovarian cancer, development of treatment strategies in lung cancer, and monitoring prognosis and relapse in multiple myeloma patients. PMID:18664563

  17. Neutrino Interactions

    SciTech Connect

    Kamyshkov, Yuri; Handler, Thomas

    2016-10-24

    The neutrino group of the University of Tennessee, Knoxville was involved from 05/01/2013 to 04/30/2015 in the neutrino physics research funded by DOE-HEP grant DE-SC0009861. Contributions were made to the Double Chooz nuclear reactor experiment in France where second detector was commissioned during this period and final series of measurements has been started. Although Double Chooz was smaller experimental effort than competitive Daya Bay and RENO experiments, its several advantages make it valuable for understanding of systematic errors in measurements of neutrino oscillations. Double Chooz was the first experiment among competing three that produced initial result for neutrino angle θ13 measurement, giving other experiments the chance to improve measured value statistically. Graduate student Ben Rybolt defended his PhD thesis on the results of Double Chooz experiment in 2015. UT group has fulfilled all the construction and analysis commitments to Double Chooz experiment, and has withdrawn from the collaboration by the end of the mentioned period to start another experiment. Larger effort of UT neutrino group during this period was devoted to the participation in another DOE-HEP project - NOvA experiment. The 14,000-ton "FAR" neutrino detector was commissioned in northern Minnesota in 2014 together with 300-ton "NEAR" detector located at Fermilab. Following that, the physics measurement program has started when Fermilab accelerator complex produced the high-intensity neutrino beam propagating through Earth to detector in MInnessota. UT group contributed to NOvA detector construction and developments in several aspects. Our Research Associate Athanasios Hatzikoutelis was managing (Level 3 manager) the construction of the Detector Control System. This work was successfully accomplished in time with the commissioning of the detectors. Group was involved in the development of the on-line software and study of the signatures of the cosmic ray backgrounds

  18. Orbital, Rotational, and Climatic Interactions

    NASA Technical Reports Server (NTRS)

    Bills, Bruce G. (Editor)

    1992-01-01

    The report of an international meeting on the topic of Orbital, Rotational, and Climatic Interactions, which was held 9-11 Jul. 1991 at the Johns Hopkins University is presented. The meeting was attended by 22 researchers working on various aspects of orbital and rotational dynamics, paleoclimate data analysis and modeling, solid-Earth deformation studies, and paleomagnetic analyses. The primary objective of the workshop was to arrive at a better understanding of the interactions between the orbital, rotational, and climatic variations of the Earth. This report contains a brief introduction and 14 contributed papers which cover most of the topics discussed at the meeting.

  19. Interaction of caldesmon with phospholipids.

    PubMed Central

    Czuryło, E A; Zborowski, J; Dabrowska, R

    1993-01-01

    The interaction of caldesmon with liposomes composed of various phospholipids has been examined by tryptophan fluorescence spectroscopy. The results indicate that caldesmon makes its strongest complex with phosphatidylserine (PS) vesicles (Kass. = 1.45 x 10(5) M-1). Both electrostatic and hydrophobic interactions contribute to the stability of this complex. The site for strong binding of PS seems to be located in the N-terminal part of the 34 kDa C-terminal fragment of caldesmon. Binding of PS at this site results in displacement of calmodulin from its complex with caldesmon. Images Figure 4 PMID:8484721

  20. Designing "Interaction": How Do Interaction Design Students Address Interaction?

    ERIC Educational Resources Information Center

    Karlgren, Klas; Ramberg, Robert; Artman, Henrik

    2016-01-01

    Interaction design is usually described as being concerned with interactions with and through artifacts but independent of a specific implementation. Design work has been characterized as a conversation between the designer and the situation and this conversation poses a particular challenge for interaction design as interactions can be elusive…

  1. Phosphorylation of poly(rC) binding protein 1 (PCBP1) contributes to stabilization of mu opioid receptor (MOR) mRNA via interaction with AU-rich element RNA-binding protein 1 (AUF1) and poly A binding protein (PABP)

    PubMed Central

    Hwang, Cheol Kyu; Wagley, Yadav; Law, Ping-Yee; Wei, Li-Na; Loh, Horace H.

    2016-01-01

    Gene regulation at the post-transcriptional level is frequently based on cis- and trans-acting factors on target mRNAs. We found a C-rich element (CRE) in mu-opioid receptor (MOR) 3′-untranslated region (UTR) to which poly (rC) binding protein 1 (PCBP1) binds, resulting in MOR mRNA stabilization. RNA immunoprecipitation and RNA EMSA revealed the formation of PCBP1-RNA complexes at the element. Knockdown of PCBP1 decreased MOR mRNA half-life and protein expression. Stimulation by forskolin increased cytoplasmic localization of PCBP1 and PCBP1/MOR 3′-UTR interactions via increased serine phosphorylation that was blocked by protein kinase A (PKA) or (phosphatidyl inositol-3) PI3-kinase inhibitors. The forskolin treatment also enhanced serine- and tyrosine-phosphorylation of AU-rich element binding protein (AUF1), concurrent with its increased binding to the CRE, and led to an increased interaction of poly A binding protein (PABP) with the CRE and poly(A) sites. AUF1 phosphorylation also led to an increased interaction with PCBP1. These findings suggest that a single co-regulator, PCBP1, plays a crucial role in stabilizing MOR mRNA, and is induced by PKA signaling by conforming to AUF1 and PABP. PMID:27836661

  2. The microbial contribution to macroecology

    PubMed Central

    Barberán, Albert; Casamayor, Emilio O.; Fierer, Noah

    2014-01-01

    There has been a recent explosion of research within the field of microbial ecology that has been fueled, in part, by methodological improvements that make it feasible to characterize microbial communities to an extent that was inconceivable only a few years ago. Furthermore, there is increasing recognition within the field of ecology that microorganisms play a critical role in the health of organisms and ecosystems. Despite these developments, an important gap still persists between the theoretical framework of macroecology and microbial ecology. We highlight two idiosyncrasies of microorganisms that are fundamental to understanding macroecological patterns and their mechanistic drivers. First, high dispersal rates provide novel opportunities to test the relative importance of niche, stochastic, and historical processes in structuring biological communities. Second, high speciation rates potentially lead to the convergence of ecological and evolutionary time scales. After reviewing these unique aspects, we discuss strategies for improving the conceptual integration of microbes into macroecology. As examples, we discuss the use of phylogenetic ecology as an integrative approach to explore patterns across the tree of life. Then we demonstrate how two general theories of biodiversity (i.e., the recently developed theory of stochastic geometry and the neutral theory) can be adapted to microorganisms. We demonstrate how conceptual models that integrate evolutionary and ecological mechanisms can contribute to the unification of microbial ecology and macroecology. PMID:24829564

  3. Georgius Agricola's contributions to hydrology

    NASA Astrophysics Data System (ADS)

    Barton, Isabel F.

    2015-04-01

    Georgius Agricola's 1546 book De Ortu et Causis Subterraneorum (On the Source and Causes of What is Underground) was the first European work since antiquity to focus on hydrology and helped to shape the thought of Nicolaus Steno, Pierre Perrault, A.G. Werner, and other important figures in the history of hydrology and geology. De Ortu contains the first known expressions of numerous concepts important in modern hydrology: erosion as an active process, groundwater movement through pores and fissures, hydrofracturing, water-rock reaction, and others. The concepts of groundwater origins, movement, and nature in De Ortu were also the foundation for the theories of ore deposit formation for which Agricola is better known. In spite of their importance, most of Agricola's contributions to the study of groundwater are unrecognized today because De Ortu, alone of his major works, has never been translated out of Latin and no existing vernacular summary of it is longer than two pages. This article presents the first detailed description of Agricola's work on hydrology and discusses the derivation and impact of his ideas.

  4. Maternal contributions to preterm delivery.

    PubMed

    Boyd, Heather A; Poulsen, Gry; Wohlfahrt, Jan; Murray, Jeffrey C; Feenstra, Bjarke; Melbye, Mads

    2009-12-01

    Preterm delivery (PTD) is a complex trait with a significant familial component. However, no specific inheritance patterns have been established. The authors examined the contribution of PTDs in both the woman's family and her partner's family to her risk of PTD. The authors linked birth information from Danish national registers with pedigree information from the Danish Family Relations Database for 1,107,124 live singleton deliveries occurring from 1978 to 2004. Risk ratios were estimated comparing women with and without various PTD histories. Women with previous PTDs were at greatly increased risk of recurrent PTD (risk ratio = 5.6, 95% confidence interval: 5.5, 5.8); however, their PTD risk was unaffected by a partner's history of preterm children with other women. PTDs to a woman's mother, full sisters, or maternal half-sisters also increased her PTD risk (risk ratio = 1.6, 95% confidence interval: 1.5, 1.6), whereas PTDs in her paternal half-sisters, the female partners of her male relatives, or members of her partner's family did not affect her PTD risk. Inheritance patterns were similar for all gestational ages from very early through late PTD. The substantial portion of PTD risk explained by effects passed through the female line suggests a role for either imprinting or mitochondrial inheritance.

  5. Cloud Interactions

    NASA Technical Reports Server (NTRS)

    2004-01-01

    [figure removed for brevity, see original site]

    Released 1 July 2004 The atmosphere of Mars is a dynamic system. Water-ice clouds, fog, and hazes can make imaging the surface from space difficult. Dust storms can grow from local disturbances to global sizes, through which imaging is impossible. Seasonal temperature changes are the usual drivers in cloud and dust storm development and growth.

    Eons of atmospheric dust storm activity has left its mark on the surface of Mars. Dust carried aloft by the wind has settled out on every available surface; sand dunes have been created and moved by centuries of wind; and the effect of continual sand-blasting has modified many regions of Mars, creating yardangs and other unusual surface forms.

    This image was acquired during mid-spring near the North Pole. The linear water-ice clouds are now regional in extent and often interact with neighboring cloud system, as seen in this image. The bottom of the image shows how the interaction can destroy the linear nature. While the surface is still visible through most of the clouds, there is evidence that dust is also starting to enter the atmosphere.

    Image information: VIS instrument. Latitude 68.4, Longitude 258.8 East (101.2 West). 38 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration

  6. Aerosol contributions to speleothem geochemistry

    NASA Astrophysics Data System (ADS)

    Dredge, J. A.; Fairchild, I. J.; Harrison, R.; Woodhead, J. D.; Hellstrom, J.

    2011-12-01

    The term "aerosols" encompasses the suspension of both fine solid or liquid particles within a gaseous medium. Aerosols become suspended into the earth's atmosphere through a multitude of processes both natural and anthropogenic. Atmospheric aerosols enter cave networks as a result of cave ventilation processes and are either deposited, or cycled and removed from the system. Speleothem offer a multiproxy palaeoclimate resource; many of the available proxies have been extensively investigated and utilised for palaeoclimatic reconstructions in a range of studies. The potential contribution of aerosols to speleothem chemistry and their applicability for palaeoenvironmental reconstructions remains untested and the extent of their value as an addition to palaeoclimate sciences unknown. Aerosols through incorporation into speleothem may provide a novel palaeoenvironmental resource. The aerosol component of interest is that which is transported into the cave atmosphere and deposited and are available for incorporation into precipitated calcite. Aerosol deposition and therefore distribution in the cave has shown to be a complex function of ventilation and changing environmental factors. Through detailed monitoring aerosols have been detected, identified, characterised and quantified to determine their prominence in the cave system. Investigations are on a case study basis, searching for suitable aerosol proxies of environmentally significant emission processes. Case studies include: Palaeofires at Yarrangobilly Caves, Australia; anthropogenic emissions at St Michaels Cave, Gibraltar and Cheddar gorge, UK; and drip water aerosol production and geochemical addition in Obir cave, Austria. Monitoring has allowed for the temporal and spatial determination of aerosols in karst networks. Speleothem samples will be analysed in combination with in-situ monitoring to determine incorporation factors and record preservation. By understanding how aerosols are transmitted within the

  7. 31 CFR 543.408 - Charitable contributions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., including contributions to relieve human suffering, such as food, clothing or medicine, may be made by, to... avoid the bar on the provision of contributions by, to, or for the benefit of such a person....

  8. 31 CFR 547.408 - Charitable contributions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., or technology, including contributions to relieve human suffering, such as food, clothing or medicine..., to evade, or to avoid the bar on the provision of contributions by, to, or for the benefit of such...

  9. 31 CFR 547.408 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., or technology, including contributions to relieve human suffering, such as food, clothing or medicine..., to evade, or to avoid the bar on the provision of contributions by, to, or for the benefit of such...

  10. 31 CFR 547.408 - Charitable contributions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., or technology, including contributions to relieve human suffering, such as food, clothing or medicine..., to evade, or to avoid the bar on the provision of contributions by, to, or for the benefit of such...

  11. 31 CFR 549.408 - Charitable contributions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., including contributions to relieve human suffering, such as food, clothing or medicine, may be made by, to... evade, or to avoid the bar on the provision of contributions by, to, or for the benefit of such a...

  12. 31 CFR 544.408 - Charitable contributions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., services, or technology, including contributions to relieve human suffering, such as food, clothing, or..., to evade, or to avoid the bar on the provision of contributions by, to, or for the benefit of such...

  13. 31 CFR 546.408 - Charitable contributions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., including contributions to relieve human suffering, such as food, clothing, or medicine, may be made by, to... avoid the bar on the provision of contributions by, to, or for the benefit of such a person....

  14. 31 CFR 588.408 - Charitable contributions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., including contributions to relieve human suffering, such as food, clothing or medicine, may be made by, to... evade, or to avoid the bar on the provision of contributions by, to, or for the benefit of such a...

  15. 31 CFR 594.409 - Charitable contributions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... technology, including contributions or donations to relieve human suffering, such as food, clothing, or... if made in an attempt to violate, to evade, or to avoid the bar on the provision of contributions...

  16. 31 CFR 576.409 - Charitable contributions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., or technology, including contributions to relieve human suffering, such as food, clothing or medicine... violate, to evade, or to avoid the bar on the provision of contributions by, to, or for the benefit...

  17. 31 CFR 546.408 - Charitable contributions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., including contributions to relieve human suffering, such as food, clothing, or medicine, may be made by, to... avoid the bar on the provision of contributions by, to, or for the benefit of such a person....

  18. 31 CFR 544.408 - Charitable contributions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., services, or technology, including contributions to relieve human suffering, such as food, clothing, or..., to evade, or to avoid the bar on the provision of contributions by, to, or for the benefit of such...

  19. 31 CFR 576.409 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., or technology, including contributions to relieve human suffering, such as food, clothing or medicine... violate, to evade, or to avoid the bar on the provision of contributions by, to, or for the benefit...

  20. 31 CFR 544.408 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., services, or technology, including contributions to relieve human suffering, such as food, clothing, or..., to evade, or to avoid the bar on the provision of contributions by, to, or for the benefit of such...

  1. 31 CFR 544.408 - Charitable contributions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., services, or technology, including contributions to relieve human suffering, such as food, clothing, or..., to evade, or to avoid the bar on the provision of contributions by, to, or for the benefit of such...

  2. 31 CFR 594.409 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... technology, including contributions or donations to relieve human suffering, such as food, clothing, or... if made in an attempt to violate, to evade, or to avoid the bar on the provision of contributions...

  3. 31 CFR 576.409 - Charitable contributions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., or technology, including contributions to relieve human suffering, such as food, clothing or medicine... violate, to evade, or to avoid the bar on the provision of contributions by, to, or for the benefit...

  4. 31 CFR 543.408 - Charitable contributions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., including contributions to relieve human suffering, such as food, clothing or medicine, may be made by, to... avoid the bar on the provision of contributions by, to, or for the benefit of such a person....

  5. 31 CFR 547.408 - Charitable contributions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., or technology, including contributions to relieve human suffering, such as food, clothing or medicine..., to evade, or to avoid the bar on the provision of contributions by, to, or for the benefit of such...

  6. 31 CFR 576.409 - Charitable contributions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., or technology, including contributions to relieve human suffering, such as food, clothing or medicine... violate, to evade, or to avoid the bar on the provision of contributions by, to, or for the benefit...

  7. 31 CFR 588.408 - Charitable contributions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., including contributions to relieve human suffering, such as food, clothing or medicine, may be made by, to... evade, or to avoid the bar on the provision of contributions by, to, or for the benefit of such a...

  8. 31 CFR 549.408 - Charitable contributions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., including contributions to relieve human suffering, such as food, clothing or medicine, may be made by, to... evade, or to avoid the bar on the provision of contributions by, to, or for the benefit of such a...

  9. 31 CFR 588.408 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing or medicine, may be made by,...

  10. 31 CFR 588.408 - Charitable contributions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing or medicine, may be made by,...

  11. 31 CFR 543.408 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing or medicine, may be made by,...

  12. 31 CFR 543.408 - Charitable contributions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing or medicine, may be made by,...

  13. 31 CFR 542.408 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing, or medicine, may be made by, to, or for the benefit of, or received...

  14. 31 CFR 595.408 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... technology, including contributions or donations to relieve human suffering, such as food, clothing, or... organizations who donate or contribute funds, goods, services, or technology without knowledge or reason to...

  15. 31 CFR 560.426 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing or medicine, may be made by,...

  16. 31 CFR 546.408 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing, or medicine, may be made by,...

  17. 31 CFR 549.408 - Charitable contributions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing or medicine, may be made by,...

  18. 31 CFR 548.408 - Charitable contributions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing or medicine, may be made by,...

  19. 31 CFR 549.408 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing or medicine, may be made by,...

  20. 31 CFR 560.426 - Charitable contributions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing or medicine, may be made by,...

  1. 31 CFR 537.414 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing, or medicine, may be made by, to, or for the benefit of, or received...

  2. 31 CFR 543.408 - Charitable contributions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing or medicine, may be made by,...

  3. 31 CFR 546.408 - Charitable contributions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing, or medicine, may be made by,...

  4. 31 CFR 548.408 - Charitable contributions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing or medicine, may be made by,...

  5. 31 CFR 546.408 - Charitable contributions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing, or medicine, may be made by,...

  6. 31 CFR 548.408 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Control pursuant to this part, no charitable contribution of funds, goods, services, or technology, including contributions to relieve human suffering, such as food, clothing or medicine, may be made by,...

  7. 31 CFR 595.408 - Charitable contributions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... technology, including contributions or donations to relieve human suffering, such as food, clothing, or... organizations who donate or contribute funds, goods, services, or technology without knowledge or reason to...

  8. 31 CFR 29.352 - Refunded contributions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... employee contributions made by police officers and firefighters through pay period 13. If pay period... in calendar year 1997, and 48 percent of the retirement contributions made to police officers...

  9. Groundwater and Wetland Contributions to Stream Acidification: An Isotopic Analysis

    NASA Astrophysics Data System (ADS)

    Wels, Christoph; Cornett, R. Jack; Lazerte, Bruce D.

    1990-12-01

    Stream water pH may be influenced by (1) the flow paths and (2) the residence time of water that contributes to streamflow, when these hydrologic factors interact with the biogeochemical processes that neutralize H+ ions in the catchment. This paper presents measures of the volumes of groundwater contributing to streamflow, the groundwater residence times, and the sources of stream water acidity found during spring runoff in three basins on the Canadian Shield. Isotopic hydrograph separations were used to estimate the relative contributions of groundwater to spring runoff. The contributions of old (premelt) groundwater to spring runoff were greater (60%) in a well-buffered, third-order basin than in a more acidic first-order basin (49%). Using a simple mixing model, a larger groundwater reservoir (420 mm unit depth) and longer residence time (162 days) were estimated in the third-order basin. The lowest stream pH (4.8) was observed in a second-order basin with a wetland that collects drainage from about 79% of the basin. In this basin the principal source of H+ ions was the conifer-sphagnum wetland. We conclude that the hypotheses that the pH of these streams was proportional to (1) a fraction of streamflow contributed by groundwater or (2) the residence time of water in a basin are rejected. More attention must be focused upon the source of acidity generated in wetlands, since these are ubiquitous in small basins.

  10. Quarkonium Contribution to Meson Molecules

    NASA Astrophysics Data System (ADS)

    Cincioglu, E.; Nieves, J.; Ozpineci, A.; Yilmazer, A. U.

    2016-10-01

    Starting from a molecular picture for the X(3872) resonance, this state and its J^{PC}=2^{++} heavy-quark spin symmetry partner [X_2(4012)] are analyzed within a model which incorporates possible mixings with 2 P charmonium (cbar{c}) states. Since it is reasonable to expect the bare χ _{c1}(2P) to be located above the Dbar{D}^* threshold, but relatively close to it, the presence of the charmonium state provides an effective attraction that will contribute to binding the X(3872), but it will not appear in the 2^{++} sector. Indeed in the latter sector, the χ _{c2}(2P) should provide an effective small repulsion, because it is placed well below the D^*bar{D}^* threshold. We show how the 1^{++} and 2^{++} bare charmonium poles are modified due to the D^{(*)}bar{D}^{(*)} loop effects, and the first one is moved to the complex plane. The meson loops produce, besides some shifts in the masses of the charmonia, a finite width for the 1^{++} dressed charmonium state. On the other hand, X(3872) and X_2(4012) start developing some charmonium content, which is estimated by means of the compositeness Weinberg sum rule. It turns out that in the heavy-quark limit, there is only one coupling between the 2 P charmonia and the D^{(*)}bar{D}^{(*)} pairs. We also show that, for reasonable values of this coupling, leading to X(3872) molecular probabilities of around 70-90 %, the X_2 resonance destabilizes and disappears from the spectrum, becoming either a virtual state or one being located deep into the complex plane, with decreasing influence in the D^{*}bar{D}^{*} scattering line. Moreover, we also discuss how around 10-30 % charmonium probability in the X(3872) might explain the ratio of radiative decays of this resonance into ψ (2S)γ and J/ψ γ . Finally, we qualitatively discuss within this scheme, the hidden bottom flavor sector, paying a special attention to the implications for the X_b and X_{b2} states, heavy-quark spin-flavor partners of the X(3872).

  11. 11 CFR 9032.4 - Contribution.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Contribution. 9032.4 Section 9032.4 Federal Elections FEDERAL ELECTION COMMISSION PRESIDENTIAL ELECTION CAMPAIGN FUND: PRESIDENTIAL PRIMARY MATCHING FUND DEFINITIONS § 9032.4 Contribution. For purposes of this subchapter, contribution has the...

  12. 11 CFR 9002.13 - Contribution.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Contribution. 9002.13 Section 9002.13 Federal Elections FEDERAL ELECTION COMMISSION PRESIDENTIAL ELECTION CAMPAIGN FUND: GENERAL ELECTION FINANCING DEFINITIONS § 9002.13 Contribution. Contribution has the same meaning given the term under 2 U.S.C....

  13. 5 CFR 891.401 - Government contributions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Government contributions. 891.401 Section... (CONTINUED) RETIRED FEDERAL EMPLOYEES HEALTH BENEFITS Contributions and Withholdings § 891.401 Government... receive a Government contribution toward his or her cost of coverage for: (A) A private health...

  14. 5 CFR 891.401 - Government contributions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Government contributions. 891.401 Section... (CONTINUED) RETIRED FEDERAL EMPLOYEES HEALTH BENEFITS Contributions and Withholdings § 891.401 Government... receive a Government contribution toward his or her cost of coverage for: (A) A private health...

  15. 5 CFR 891.401 - Government contributions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Government contributions. 891.401 Section... (CONTINUED) RETIRED FEDERAL EMPLOYEES HEALTH BENEFITS Contributions and Withholdings § 891.401 Government... receive a Government contribution toward his or her cost of coverage for: (A) A private health...

  16. 5 CFR 891.401 - Government contributions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Government contributions. 891.401 Section... (CONTINUED) RETIRED FEDERAL EMPLOYEES HEALTH BENEFITS Contributions and Withholdings § 891.401 Government... receive a Government contribution toward his or her cost of coverage for: (A) A private health...

  17. Relationality and social interaction.

    PubMed

    Bottero, Wendy

    2009-06-01

    This paper explores Bourdieu's account of a relational social space, and his relative neglect of social interaction within this framework. Bourdieu includes social capital as one of the key relational elements of his social space, but says much less about it than economic or cultural capital, and levels of social capital are rarely measured in his work. Bourdieu is reluctant to focus on the content of social networks as part of his rejection of substantialist thinking. The neglect of substantive networks creates problems for Bourdieu's framework, because many of Bourdieu's core concepts rest upon assumptions about their interactional properties (in particular, the prevalence of homophilous differential association) which are left unexamined. It is argued here that Bourdieu's neglect of the substance of social networks is related to the criticisms that Bourdieu's framework often encounters, and that this neglect bears re-examination, since it is helpful to think of the ways in which differentiated social networks contribute to the development of habitus, help form fields, and so constitute the intersubjective social relations within which sociality, and practice more generally, occur.

  18. Quantifying the contributions of structure to annulus fibrosus mechanical function using a nonlinear, anisotropic, hyperelastic model.

    PubMed

    Guerin, Heather Lynch; Elliott, Dawn M

    2007-04-01

    The annulus fibrosus of the intervertebral disc is comprised of concentric lamella of oriented collagen fibers embedded in a hydrated proteoglycan matrix with smaller amounts of minor collagens, elastin, and small proteoglycans. Its structure and composition enable the disc to withstand complex loads and result in inhomogeneous, anisotropic, and nonlinear mechanical behaviors. The specific contributions of the annulus fibrosus constituent structures to mechanical function remain unclear. Therefore, the objective of this study was to use a structurally motivated, anisotropic, nonlinear strain energy model of annulus fibrosus to determine the relative contributions of its structural components to tissue mechanical behavior. A nonlinear, orthotropic hyperelastic model was developed for the annulus fibrosus. Terms to describe fibers, matrix, and interactions between annulus fibrosus structures (shear and normal to the fiber directions) were explicitly included. The contributions of these structures were analyzed by including or removing terms and determining the effect on the fit to multidimensional experimental data. Correlation between experimental and model-predicted stress, a Bland-Altman analysis of bias and standard deviation of residuals, and the contribution of structural terms to overall tissue stress were calculated. Both shear and normal interaction terms were necessary to accurately model multidimensional behavior. Inclusion of shear interactions more accurately described annulus fibrosus nonlinearity. Fiber stretch and shear interactions dominated contributions to circumferential direction stress, while normal and shear interactions dominated axial stress. The results suggest that interactions between fibers and matrix, perhaps facilitated by crosslinks, elastin, or minor collagens, augment traditional (i.e., fiber-uncrimping) models of nonlinearity.

  19. Dispersive interactions in graphitic nanostructures

    NASA Astrophysics Data System (ADS)

    Woods, L. M.; Popescu, A.; Drosdoff, D.; Bondarev, I. V.

    2013-02-01

    The Casimir interaction between graphitic nanostructures, such as carbon nanotubes and graphene sheets, is investigated at the quantum mechanical limit (T = 0 K) using a quantum electrodynamical approach for absorbing and dispersive media. It is found that the nanotube/nanotube interaction in a double wall carbon nanotube configuration is profoundly affected by the collective low frequency excitations of individual nanotubes. It is shown that pronounced, low frequency peaks in the nanotube electron energy loss spectra are a main factor contributing to the strength of the intertube attraction. The graphene/graphene force is also investigated. It is obtained that the graphene optical transparency is the main reason for the reduced attraction as compared to the one for perfect metals. This study presents a unified approach for electromagnetic interactions in graphitic nanostructures, which is able to account for their unique electronic and response properties and geometry configurations.

  20. Stress, the Autonomic Nervous System, and the Immune-kynurenine Pathway in the Etiology of Depression

    PubMed Central

    Won, Eunsoo; Kim, Yong-Ku

    2016-01-01

    The autonomic nervous system is one of the major neural pathways activated by stress. In situations that are often associated with chronic stress, such as major depressive disorder, the sympathetic nervous system can be continuously activated without the normal counteraction of the parasympathetic nervous system. As a result, the immune system can be activated with increased levels of pro-inflammatory cytokines. These inflammatory conditions have been repeatedly observed in depression. In the search for the mechanism by which the immune system might contribute to depression, the enhanced activity of indoleamine 2,3-dioxygenase by pro-inflammatory cytokines has been suggested to play an important role. Indoleamine 2,3-dioxygenase is the first enzyme in the kynurenine pathway that converts tryptophan to kynurenine. Elevated activity of this enzyme can cause imbalances in downstream kynurenine metabolites. This imbalance can induce neurotoxic changes in the brain and create a vulnerable glial-neuronal network, which may render the brain susceptible to depression. This review focuses on the interaction between stress, the autonomic nervous system and the immune system which can cause imbalances in the kynurenine pathway, which may ultimately lead to major depressive disorder. PMID:27640517

  1. Extracellular Cyclophilins Contribute to the Regulation of Inflammatory Responses1

    PubMed Central

    Arora, Kamalpreet; Gwinn, William M.; Bower, Molly A.; Watson, Alan; Okwumabua, Ifeanyi; MacDonald, H. Robson; Bukrinsky, Michael I.; Constant, Stephanie L.

    2010-01-01

    The main regulators of leukocyte trafficking during inflammatory responses are chemokines. However, another class of recently identified chemotactic agents is extracellular cyclophilins, the proteins mostly known as receptors for the immunosuppressive drug, cyclosporine A. Cyclophilins can induce leukocyte chemotaxis in vitro and have been detected at elevated levels in inflamed tissues, suggesting that they might contribute to inflammatory responses. We recently identified CD147 as the main signaling receptor for cyclophilin A. In the current study we examined the contribution of cyclophilin-CD147 interactions to inflammatory responses in vivo using a mouse model of acute lung injury. Blocking cyclophilin-CD147 interactions by targeting CD147 (using anti-CD147 Ab) or cyclophilin (using nonimmunosuppressive cyclosporine A analog) reduced tissue neutrophilia by up to 50%, with a concurrent decrease in tissue pathology. These findings are the first to demonstrate the significant contribution of cyclophilins to inflammatory responses and provide a potentially novel approach for reducing inflammation-mediated diseases. PMID:15972687

  2. 26 CFR 1.401(m)-1 - Employee contributions and matching contributions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... contributions. 1.401(m)-1 Section 1.401(m)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Plans, Etc. § 1.401(m)-1 Employee contributions and matching contributions. (a) General... contributions satisfies the nondiscrimination test of section 401(m) under paragraph (b) of this section and...

  3. IDENTIFYING KEY CONTRIBUTIONS TO INFORMATION SCIENCE,

    DTIC Science & Technology

    Several alternative approaches were examined to determine how one might identify some of the key (written) contributions to ’ information science ’. The...references. The unclear selective patterns in current bibliographies in the information science field also present problems. It is suggested that in...identifying key contributions we are far from common agreement on the conceptual, methodological or practical contributions to the information science field

  4. [Original contributions of Latin Americans to anesthesiology].

    PubMed

    Aldrete, J A

    1998-10-01

    The original contributions of Latin American physicians to the science of anesthesiology are described. Many contributions have been unfairly ignored mainly because they were never published in English, but others have likewise been passed over even when published in the most prestigious journals in the field. Although many discoveries by Latin Americans have been made in the area of regional anesthesia, a considerable number of contributions have involved other aspects of anesthesia as well.

  5. Formation et interaction (Teacher Education and Interaction).

    ERIC Educational Resources Information Center

    Bertocchini, Paola; Costanzo, Edwige

    1989-01-01

    Effective interaction is as important in inservice education programs for language teachers as it is in the foreign language classroom. Techniques are described for improving the quality of interaction in teacher workshops through simulation exercises. (MSE)

  6. 44 CFR 361.4 - Matching contributions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... HOMELAND SECURITY PREPAREDNESS NATIONAL EARTHQUAKE HAZARDS REDUCTION ASSISTANCE TO STATE AND LOCAL GOVERNMENTS Earthquake Hazards Reduction Assistance Program § 361.4 Matching contributions. (a) All...

  7. 44 CFR 361.4 - Matching contributions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... HOMELAND SECURITY PREPAREDNESS NATIONAL EARTHQUAKE HAZARDS REDUCTION ASSISTANCE TO STATE AND LOCAL GOVERNMENTS Earthquake Hazards Reduction Assistance Program § 361.4 Matching contributions. (a) All...

  8. 44 CFR 361.4 - Matching contributions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... HOMELAND SECURITY PREPAREDNESS NATIONAL EARTHQUAKE HAZARDS REDUCTION ASSISTANCE TO STATE AND LOCAL GOVERNMENTS Earthquake Hazards Reduction Assistance Program § 361.4 Matching contributions. (a) All...

  9. 44 CFR 361.4 - Matching contributions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... HOMELAND SECURITY PREPAREDNESS NATIONAL EARTHQUAKE HAZARDS REDUCTION ASSISTANCE TO STATE AND LOCAL GOVERNMENTS Earthquake Hazards Reduction Assistance Program § 361.4 Matching contributions. (a) All...

  10. 44 CFR 361.4 - Matching contributions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... HOMELAND SECURITY PREPAREDNESS NATIONAL EARTHQUAKE HAZARDS REDUCTION ASSISTANCE TO STATE AND LOCAL GOVERNMENTS Earthquake Hazards Reduction Assistance Program § 361.4 Matching contributions. (a) All...

  11. 7 CFR 966.45 - Contributions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Order... contributions but these shall only be used for production research, market research and development...

  12. 7 CFR 966.45 - Contributions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Order... contributions but these shall only be used for production research, market research and development...

  13. 7 CFR 966.45 - Contributions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Order... contributions but these shall only be used for production research, market research and development...

  14. 7 CFR 966.45 - Contributions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Order... contributions but these shall only be used for production research, market research and development...

  15. Separation of intra- and intermolecular contributions to the PELDOR signal

    NASA Astrophysics Data System (ADS)

    Schöps, Philipp; Plackmeyer, Jörn; Marko, Andriy

    2016-08-01

    Pulsed Electron-electron Double Resonance (PELDOR) is commonly used to measure distances between native paramagnetic centers or spin labels attached to complex biological macromolecules. In PELDOR the energies of electron magnetic dipolar interactions are measured by analyzing the oscillation frequencies of the recorded time resolved signal. Since PELDOR is an ensemble method, the detected signal contains contributions from intramolecular, as well as intermolecular electron spin interactions. The intramolecular part of the signal contains the information about the structure of the studied molecules, thus it is very important to accurately separate intra- and intermolecular contributions to the total signal. This separation can become ambiguous, when the length of the PELDOR signal is not much longer than twice the oscillation period of the signal. In this work we suggest a modulation depth scaling method, which can use short PELDOR signals in order to extract the intermolecular contribution. Using synthetic data we demonstrate the advantages of the new approach and analyze its stability with regard to signal noise. The method was also successfully tested on experimental data of three systems measured at Q-Band frequencies, two model compounds in deuterated and protonated solvents and one biological sample, namely BetP. The application of the new method with an assigned value of the signal modulation depth enables us to determine the interspin distances in all cases. This is especially interesting for the model compound with an interspin distance of 5.2 nm in the protonated solvent and the biological sample, since an accurate separation of the intra- and intermolecular PELDOR signal contributions would be difficult with the standard approach in those cases.

  16. X-ray spectroscopic characterization of Co(IV) and metal–metal interactions in Co4O4: Electronic structure contributions to the formation of high-valent states relevant to the oxygen evolution reaction

    SciTech Connect

    Hadt, Ryan G.; Hayes, Dugan; Brodsky, Casey N.; Ullman, Andrew M.; Casa, Diego M.; Upton, Mary H.; Nocera, Daniel G.; Chen, Lin X.

    2016-08-12

    In this paper, the formation of high-valent states is a key factor in making highly active transition metal-based catalysts of the oxygen-evolving reaction (OER). These high oxidation states will be strongly influenced by the local geometric and electronic structures of the metal ion, which is difficult to study due to spectroscopically active and complex backgrounds, short lifetimes, and limited concentrations. Here, we use a wide range of complementary X-ray spectroscopies coupled to DFT calculations to study Co4O4 cubanes, which provide insight into the high-valent Co(IV) centers responsible for the activity of molecular and heterogeneous OER catalysts. The combination of X-ray absorption and 1s3p resonant inelastic X-ray scattering (Kβ RIXS) allow Co(IV) to be isolated and studied against a spectroscopically active Co(III) background. Co K- and L-edge X-ray absorption data allow for a detailed characterization of the 3d-manifold of effectively localized Co(IV) centers and provide a direct handle on the ligand field environment and covalency of the t2g-based redox active molecular orbital. Kβ RIXS is also shown to provide a powerful probe of Co(IV), and specific spectral features are sensitive to the degree of oxo-mediated metal-metal coupling across Co4O4. Guided by the data, calculations show electron-hole delocalization can actually oppose Co(IV) formation. Computational extension of Co4O4 to CoM3O4 structures (M = redox-inactive metal) defines electronic structure contri-butions to Co(IV) formation. Redox activity is shown to be linearly related to covalency, and M(III) oxo inductive effects on Co(IV) oxo bonding can tune the covalency of high-valent sites over a large range and thereby tune E0 over hundreds of mVs.

  17. Functional contributions of electrical synapses in sensory and motor networks.

    PubMed

    Szczupak, Lidia

    2016-12-01

    Intercellular interactions in the nervous system are mediated by two types of dedicated structural arrangements: electrical and chemical synapses. Several characteristics distinguish these two mechanisms of communication, such as speed, reliability and the fact that electrical synapses are, potentially, bidirectional. Given these properties, electrical synapses can subserve, in addition to synchrony, three main interrelated network functions: signal amplification, noise reduction and/or coincidence detection. Specific network motifs in sensory and motor systems of invertebrates and vertebrates illustrate how signal transmission through electrical junctions contributes to a complex processing of information.

  18. Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens.

    PubMed

    Halberstadt, Adam L; Geyer, Mark A

    2011-09-01

    Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce remarkably similar subjective effects in humans, and induce cross-tolerance. The phenylalkylamine hallucinogens are selective 5-HT(2) receptor agonists, whereas the indoleamines are relatively non-selective for serotonin (5-HT) receptors. There is extensive evidence, from both animal and human studies, that the characteristic effects of hallucinogens are mediated by interactions with the 5-HT(2A) receptor. Nevertheless, there is also evidence that interactions with other receptor sites contribute to the psychopharmacological and behavioral effects of the indoleamine hallucinogens. This article reviews the evidence demonstrating that the effects of indoleamine hallucinogens in a variety of animal behavioral paradigms are mediated by both 5-HT(2) and non-5-HT(2) receptors.

  19. Glycosaminoglycan-lipoprotein interaction.

    PubMed

    Olsson, U; Ostergren-Lundén, G; Moses, J

    2001-10-01

    Glycosaminoglycans (GAGs) bound to various proteoglycans (PGs) present in the cardiovascular system have been proposed to perform a wide range of functions. These include conferring viscoelastic properties; interacting with and modulating growth factors and enzymes; and as receptors and co-receptors in lipoprotein metabolism. Binding of apoB-100 lipoproteins, particularly low density lipoproteins (LDL), to GAGs of extracellular matrix PGs in arteries has been proposed to be an initiating event in development of atherosclerosis. This study was initiated with the aim of getting an overview of the binding patterns of different lipoprotein subclasses with individual GAG categories. We thus evaluated the interaction of lipoproteins with GAGs commonly found in the cardiovascular system using a gel mobility-shift assay developed for this purpose. The same procedure was used to measure lipoproteins binding to metabolically [(35)S]-labeled whole PGs prepared from three cell types, arterial smooth muscle cells, THP-1 macrophages and from HepG2 cells. The effect of GAG composition on PGs on lipoprotein binding was evaluated by enzymatic degradation of the carbohydrate chains. Heparan sulfate was found to bind beta very low density lipoproteins (beta-VLDL) and a chylomicron remnant model (beta-VLDL+apoE), but not LDL. Dermatan sulfate was found to bind LDL, but not beta-VLDL or the chylomicron remnant model. Chondroitin sulfate and heparin were found to bind all lipoproteins tested (LDL, beta-VLDL and beta-VLDL+apoE) although with different affinities. We can conclude that each lipoprotein subclass tested binds a specific assortment of the GAGs tested. The observations made contribute to the understanding of new and complex mechanisms by which carbohydrate and lipid metabolism may be linked.

  20. Contributions of Psychology to War and Peace

    ERIC Educational Resources Information Center

    Christie, Daniel J.; Montiel, Cristina J.

    2013-01-01

    The contributions of American psychologists to war have been substantial and responsive to changes in U.S. national security threats and interests for nearly 100 years. These contributions are identified and discussed for four periods of armed conflict: World Wars I and II, the Cold War, and the Global War on Terror. In contrast, about 50 years…

  1. 10 CFR 603.1225 - Cash contributions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Cash contributions. 603.1225 Section 603.1225 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms... toward cost sharing, including expenditures of money that third parties contributed to the recipient....

  2. National contributions to observed global warming

    NASA Astrophysics Data System (ADS)

    Damon Matthews, H.; Graham, Tanya L.; Keverian, Serge; Lamontagne, Cassandra; Seto, Donny; Smith, Trevor J.

    2014-01-01

    There is considerable interest in identifying national contributions to global warming as a way of allocating historical responsibility for observed climate change. This task is made difficult by uncertainty associated with national estimates of historical emissions, as well as by difficulty in estimating the climate response to emissions of gases with widely varying atmospheric lifetimes. Here, we present a new estimate of national contributions to observed climate warming, including CO2 emissions from fossil fuels and land-use change, as well as methane, nitrous oxide and sulfate aerosol emissions While some countries’ warming contributions are reasonably well defined by fossil fuel CO2 emissions, many countries have dominant contributions from land-use CO2 and non-CO2 greenhouse gas emissions, emphasizing the importance of both deforestation and agriculture as components of a country’s contribution to climate warming. Furthermore, because of their short atmospheric lifetime, recent sulfate aerosol emissions have a large impact on a country’s current climate contribution We show also that there are vast disparities in both total and per-capita climate contributions among countries, and that across most developed countries, per-capita contributions are not currently consistent with attempts to restrict global temperature change to less than 2 °C above pre-industrial temperatures.

  3. How sonochemistry contributes to green chemistry?

    PubMed

    Chatel, Gregory

    2017-03-15

    Based on the analyses of papers from the literature, and especially those published in Ultrasonics Sonochemistry journal, the contribution of sonochemistry to green chemistry area has been discussed here. Important reminders and insights on the good practices and considerations have been made to understand and demonstrate how sonochemistry can continue to efficiently contribute to green chemistry area in the further studies.

  4. Factors Contributing to Institutions Achieving Environmental Sustainability

    ERIC Educational Resources Information Center

    James, Matthew; Card, Karen

    2012-01-01

    Purpose: The purpose of this paper is to determine what factors contributed to three universities achieving environmental sustainability. Design/methodology/approach: A case study methodology was used to determine how each factor contributed to the institutions' sustainability. Site visits, fieldwork, document reviews, and interviews with…

  5. 7 CFR 3560.203 - Tenant contributions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Tenant contributions. 3560.203 Section 3560.203 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF AGRICULTURE DIRECT MULTI-FAMILY HOUSING LOANS AND GRANTS Rents § 3560.203 Tenant contributions. (a)...

  6. 7 CFR 3560.203 - Tenant contributions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Tenant contributions. 3560.203 Section 3560.203 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF AGRICULTURE DIRECT MULTI-FAMILY HOUSING LOANS AND GRANTS Rents § 3560.203 Tenant contributions. (a)...

  7. 7 CFR 3560.203 - Tenant contributions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Tenant contributions. 3560.203 Section 3560.203 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF AGRICULTURE DIRECT MULTI-FAMILY HOUSING LOANS AND GRANTS Rents § 3560.203 Tenant contributions. (a)...

  8. 7 CFR 3560.203 - Tenant contributions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Tenant contributions. 3560.203 Section 3560.203 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF AGRICULTURE DIRECT MULTI-FAMILY HOUSING LOANS AND GRANTS Rents § 3560.203 Tenant contributions. (a)...

  9. 7 CFR 3560.203 - Tenant contributions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Tenant contributions. 3560.203 Section 3560.203 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF AGRICULTURE DIRECT MULTI-FAMILY HOUSING LOANS AND GRANTS Rents § 3560.203 Tenant contributions. (a)...

  10. Capabilities and Contributions of Unwed Fathers

    ERIC Educational Resources Information Center

    Lerman, Robert I.

    2010-01-01

    Young, minority, and poorly educated fathers in fragile families have little capacity to support their children financially and are hard-pressed to maintain stability in raising those children. In this article, Robert Lerman examines the capabilities and contributions of unwed fathers, how their capabilities and contributions fall short of those…

  11. Louis Guttman's Contributions to Classical Test Theory

    ERIC Educational Resources Information Center

    Zimmerman, Donald W.; Williams, Richard H.; Zumbo, Bruno D.; Ross, Donald

    2005-01-01

    This article focuses on Louis Guttman's contributions to the classical theory of educational and psychological tests, one of the lesser known of his many contributions to quantitative methods in the social sciences. Guttman's work in this field provided a rigorous mathematical basis for ideas that, for many decades after Spearman's initial work,…

  12. 13 CFR 120.912 - Borrowed contributions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... borrow its cash contribution from the CDC or a third party. If any of the contribution is borrowed, the interest rate must be reasonable. If the loan is secured by any of the Project assets, the loan must be subordinate to the liens securing the 504 Loan, and the loan may not be repaid at a faster rate than the...

  13. 5 CFR 1620.21 - Contributions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... and Judges § 1620.21 Contributions. (a) An individual covered under this subpart can make.... (b) The following amounts are not basic pay and no TSP contributions can be made from them: (1) An annuity or salary received by a justice or judge of the United States (as defined in 28 U.S.C. 451) who...

  14. 5 CFR 831.1004 - Agency contributions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Agency contributions. 831.1004 Section 831.1004 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT CSRS Offset § 831.1004 Agency contributions. The employing agency, the Secretary...

  15. 5 CFR 831.1004 - Agency contributions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Agency contributions. 831.1004 Section 831.1004 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT CSRS Offset § 831.1004 Agency contributions. The employing agency, the Secretary...

  16. 5 CFR 831.1004 - Agency contributions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Agency contributions. 831.1004 Section 831.1004 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT CSRS Offset § 831.1004 Agency contributions. The employing agency, the Secretary...

  17. 5 CFR 831.1004 - Agency contributions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Agency contributions. 831.1004 Section 831.1004 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT CSRS Offset § 831.1004 Agency contributions. The employing agency, the Secretary...

  18. Magnetostrictive contribution to Poisson ratio of galfenol

    NASA Astrophysics Data System (ADS)

    Paes, V. Z. C.; Mosca, D. H.

    2013-09-01

    In this work we present a detailed study on the magnetostrictive contribution to Poisson ratio for samples under applied mechanical stress. Magnetic contributions to strain and Poisson ratio for cubic materials were derived by accounting elastic and magneto-elastic anisotropy contributions. We apply our theoretical results for a material of interest in magnetomechanics, namely, galfenol (Fe1-xGax). Our results show that there is a non-negligible magnetic contribution in the linear portion of the curve of stress versus strain. The rotation of the magnetization towards [110] crystallographic direction upon application of mechanical stress leads to an auxetic behavior, i.e., exhibiting Poisson ratio with negative values. This magnetic contribution to auxetic behavior provides a novel insight for the discussion of theoretical and experimental developments of materials that display unusual mechanical properties.

  19. The interactions of peripheral membrane proteins with biological membranes

    DOE PAGES

    Johs, Alexander; Whited, A. M.

    2015-01-01

    The interactions of peripheral proteins with membrane surfaces are critical to many biological processes, including signaling, recognition, membrane trafficking, cell division and cell structure. On a molecular level, peripheral membrane proteins can modulate lipid composition, membrane dynamics and protein-protein interactions. Biochemical and biophysical studies have shown that these interactions are in fact highly complex, dominated by several different types of interactions, and have an interdependent effect on both the protein and membrane. Here we examine three major mechanisms underlying the interactions between peripheral membrane proteins and membranes: electrostatic interactions, hydrophobic interactions, and fatty acid modification of proteins. While experimental approachesmore » continue to provide critical insights into specific interaction mechanisms, emerging bioinformatics resources and tools contribute to a systems-level picture of protein-lipid interactions. Through these recent advances, we begin to understand the pivotal role of protein-lipid interactions underlying complex biological functions at membrane interfaces.« less

  20. The interactions of peripheral membrane proteins with biological membranes

    SciTech Connect

    Johs, Alexander; Whited, A. M.

    2015-01-01

    The interactions of peripheral proteins with membrane surfaces are critical to many biological processes, including signaling, recognition, membrane trafficking, cell division and cell structure. On a molecular level, peripheral membrane proteins can modulate lipid composition, membrane dynamics and protein-protein interactions. Biochemical and biophysical studies have shown that these interactions are in fact highly complex, dominated by several different types of interactions, and have an interdependent effect on both the protein and membrane. Here we examine three major mechanisms underlying the interactions between peripheral membrane proteins and membranes: electrostatic interactions, hydrophobic interactions, and fatty acid modification of proteins. While experimental approaches continue to provide critical insights into specific interaction mechanisms, emerging bioinformatics resources and tools contribute to a systems-level picture of protein-lipid interactions. Through these recent advances, we begin to understand the pivotal role of protein-lipid interactions underlying complex biological functions at membrane interfaces.

  1. Light nuclei from chiral EFT interactions

    NASA Astrophysics Data System (ADS)

    Navrátil, P.; Gueorguiev, V. G.; Vary, J. P.; Ormand, W. E.; Nogga, A.; Quaglioni, S.

    2008-12-01

    Recent developments in nuclear theory allow us to make a connection between quantum chromodynamics (QCD) and low-energy nuclear physics. First, chiral effective field theory (χEFT) provides a natural hierarchy to define two-nucleon ( NN), three-nucleon ( NNN), and even four-nucleon interactions. Second, ab-initio methods have been developed capable to test these interactions for light nuclei. In this contribution, we discuss ab-initio no-core shell-model (NCSM) calculations for s-shell and p-shell nuclei with NN and NNN interactions derived within χEFT.

  2. The hyperon-nucleon interaction

    NASA Astrophysics Data System (ADS)

    Haidenbauer, J.

    2007-11-01

    Results of two recent hyperon-nucleon interaction potentials, both developed by the Bonn-Jülich group, are presented that are derived either in the conventional meson-exchange picture or within leading order chiral effective field theory. The chiral potential consists of one-pseudoscalar-meson exchanges and non-derivative four-baryon contact terms. The most salient feature of the new meson-exchange hyperon-nucleon model is that the contributions in the scalar-isoscalar (σ) and vector-isovector (ρ) exchange channels are constrained by a microscopic model of correlated ππ and KK¯ exchange.

  3. Interactive Whiteboards and All that Jazz: The Contribution of Musical Metaphors to the Analysis of Classroom Activity with Interactive Technologies

    ERIC Educational Resources Information Center

    Beauchamp, Gary; Kennewell, Steve; Tanner, Howard; Jones, Sonia

    2010-01-01

    The teacher's role has often been described as one of "orchestration", and this musical analogy is a powerful one in characterising the manipulation of features in the classroom setting in order to generate activity or "performance" which leads to learning. However, a classical view of orchestration would fail to recognise the extent to which…

  4. Astronomy education through interactive materials

    NASA Astrophysics Data System (ADS)

    Voelzke, Marcos Rincon; Antunes de Macêdo, Josué

    2015-08-01

    This study presents results of a survey conducted at the Federal Institution of Education, Science and Technology in the North of Minas Gerais (IFNMG), and aimed to investigate the potentialities of the use of interactive materials in the teaching of astronomy. An advanced training course with involved learning activities about basic concepts of astronomy was offered to thirty-two Licenciate students in Physics, Mathematics and Biological Sciences, using the mixed methodology, combined with the three pedagogical moments. Among other aspects, the viability of the use of resources was noticed, involving digital technologies and interactive materials on teaching of astronomy, which may contribute to the broadening of methodological options for future teachers and meet their training needs.

  5. Arabidopsis thaliana—Aphid Interaction

    PubMed Central

    Louis, Joe; Singh, Vijay; Shah, Jyoti

    2012-01-01

    Aphids are important pests of plants that use their stylets to tap into the sieve elements to consume phloem sap. Besides the removal of photosynthates, aphid infestation also alters source-sink patterns. Most aphids also vector viral diseases. In this chapter, we will summarize on recent significant findings in plant-aphid interaction, and how studies involving Arabidopsis thaliana and Myzus persicae (Sülzer), more commonly known as the green peach aphid (GPA), are beginning to provide important insights into the molecular basis of plant defense and susceptibility to aphids. The recent demonstration that expression of dsRNA in Arabidopsis can be used to silence expression of genes in GPA has further expanded the utility of Arabidopsis for evaluating the contribution of the aphid genome-encoded proteins to this interaction. PMID:22666177

  6. OVERFLOW-Interaction with Industry

    NASA Technical Reports Server (NTRS)

    Buning, Pieter G.; George, Michael W. (Technical Monitor)

    1996-01-01

    A Navier-Stokes flow solver, OVERFLOW, has been developed by researchers at NASA Ames Research Center to use overset (Chimera) grids to simulate the flow about complex aerodynamic shapes. Primary customers of the OVERFLOW flow solver and related software include McDonnell Douglas and Boeing, as well as the NASA Focused Programs for Advanced Subsonic Technology (AST) and High Speed Research (HSR). Code development has focused on customer issues, including improving code performance, ability to run on workstation clusters and the NAS SP2, and direct interaction with industry on accuracy assessment and validation. Significant interaction with NAS has produced a capability tailored to the Ames computing environment, and code contributions have come from a wide range of sources, both within and outside Ames.

  7. Stacking interactions in PUF-RNA complexes

    SciTech Connect

    Yiling Koh, Yvonne; Wang, Yeming; Qiu, Chen; Opperman, Laura; Gross, Leah; Tanaka Hall, Traci M; Wickens, Marvin

    2012-07-02

    Stacking interactions between amino acids and bases are common in RNA-protein interactions. Many proteins that regulate mRNAs interact with single-stranded RNA elements in the 3' UTR (3'-untranslated region) of their targets. PUF proteins are exemplary. Here we focus on complexes formed between a Caenorhabditis elegans PUF protein, FBF, and its cognate RNAs. Stacking interactions are particularly prominent and involve every RNA base in the recognition element. To assess the contribution of stacking interactions to formation of the RNA-protein complex, we combine in vivo selection experiments with site-directed mutagenesis, biochemistry, and structural analysis. Our results reveal that the identities of stacking amino acids in FBF affect both the affinity and specificity of the RNA-protein interaction. Substitutions in amino acid side chains can restrict or broaden RNA specificity. We conclude that the identities of stacking residues are important in achieving the natural specificities of PUF proteins. Similarly, in PUF proteins engineered to bind new RNA sequences, the identity of stacking residues may contribute to 'target' versus 'off-target' interactions, and thus be an important consideration in the design of proteins with new specificities.

  8. Interactive Distance Education: A Cognitive Load Perspective

    ERIC Educational Resources Information Center

    Kalyuga, Slava

    2012-01-01

    Evidence-based approaches to the design of the next generation of interactive distance education need to take into account established multimedia learning principles. Cognitive load theory is a theory that has significantly contributed to the development of such principles. It has applied our knowledge of major features and processing limitations…

  9. DOTI: Databank of Oral Teletandem Interactions

    ERIC Educational Resources Information Center

    Aranha, Solange; Leone, Paola

    2016-01-01

    This contribution aims at (1) discussing the characteristics of collecting, filing and storing data to have a databank of oral interactions between university students whose main objective is the learning of a second language through teletandem; and (2) defining the steps for further collections and storage. Our data are Skype sessions of foreign…

  10. Interactions Dominate the Dynamics of Visual Cognition

    ERIC Educational Resources Information Center

    Stephen, Damian G.; Mirman, Daniel

    2010-01-01

    Many cognitive theories have described behavior as the summation of independent contributions from separate components. Contrasting views have emphasized the importance of multiplicative interactions and emergent structure. We describe a statistical approach to distinguishing additive and multiplicative processes and apply it to the dynamics of…

  11. Binding Pose Flip Explained via Enthalpic and Entropic Contributions

    PubMed Central

    2017-01-01

    The anomalous binding modes of five highly similar fragments of TIE2 inhibitors, showing three distinct binding poses, are investigated. We report a quantitative rationalization for the changes in binding pose based on molecular dynamics simulations. We investigated five fragments in complex with the transforming growth factor β receptor type 1 kinase domain. Analyses of these simulations using Grid Inhomogeneous Solvation Theory (GIST), pKA calculations, and a tool to investigate enthalpic differences upon binding unraveled the various thermodynamic contributions to the different binding modes. While one binding mode flip can be rationalized by steric repulsion, the second binding pose flip revealed a different protonation state for one of the ligands, leading to different enthalpic and entropic contributions to the binding free energy. One binding pose is stabilized by the displacement of entropically unfavored water molecules (binding pose determined by solvation entropy), ligands in the other binding pose are stabilized by strong enthalpic interactions, overcompensating the unfavorable water entropy in this pose (binding pose determined by enthalpic interactions). This analysis elucidates unprecedented details determining the flipping of the binding modes, which can elegantly explain the experimental findings for this system. PMID:28079371

  12. Anesthetics interacting with lipid rafts.

    PubMed

    Bandeiras, Cátia; Serro, Ana Paula; Luzyanin, Konstantin; Fernandes, Anabela; Saramago, Benilde

    2013-01-23

    The exact mechanism by which anesthetics induce cell membrane-mediated modifications is still an open question. Although the fluidization effect of the anesthetic molecules on the cellular membrane is widely recognized, it is not known if anesthetics show any preference for specific membrane domains, namely the lipid rafts. The importance of these membrane micro-domains derives from the fact that they have been associated with cell signaling pathways, as well as with specific drug interactions. The objective of this work is to contribute for the elucidation of this question through the comparison of the anesthetic interactions with membranes of various lipid compositions. Liposomes prepared with an equimolar mixture of POPC, sphingomyelin and cholesterol, were chosen as models for lipid rafts. The interactions of these liposomes with two local anesthetics, tetracaine and lidocaine, and one general anesthetic, propofol, were studied. The effect of cholesterol was investigated by comparing anesthetic interactions with POPC/SM liposomes and POPC/SM/CHOL liposomes. The following experimental techniques were used: quartz crystal microbalance with dissipation, differential scanning calorimetry and phosphorus nuclear magnetic resonance. Although the liposomes investigated by the different techniques are not in the same conditions, it is possible to assemble the information obtained from all experimental techniques employed to reach a general conclusion. Tetracaine interacts more with raftlike domains, lidocaine induces stronger modifications on POPC/SM liposomes and the results for propofol are not fully conclusive but it seems to be the least prone to lipid interactions. The results were compared with those obtained with DMPC-containing liposomes, reported in a previous work.

  13. The unity of the fundamental interactions

    SciTech Connect

    Zichichi, A.

    1983-01-01

    This book offers a collection of authoritative papers which provides the reader with a plenary survey of some of the latest developments in the field of high-energy interactions. The contributing physicists offer a comprehensive review of recent significant findings from both theoretical and experimental studies in high-energy interactions. Topics include the end of the high-energy frontier, monopoles, numerical studies of gauge field theories, expectations for the next generation of experiments, unified models, cosmology, supersymmetry, neutrino physics at Fermilab, heavy flavor production in the highest-energy (pp) interactions, b-quark physics, hadron production in e/sup +/e/sup -/ annihilation, the search for new particles and electroweak interference effects in e/sup +/e/sup -/ interactions, CP violation, and high-energy soft (pp) interactions. Includes essays by Edward Teller and P.A.M. Dirac on their lives as physicists, and one by E.P. Wigner on ''the glorious days of physics.''

  14. Cluster virial expansion of the equation of state for hydrogen plasma with e -H2 contributions

    NASA Astrophysics Data System (ADS)

    Omarbakiyeva, Y. A.; Reinholz, H.; Röpke, G.

    2015-04-01

    The equation of state of partially ionized hydrogen plasma is considered with special focus on the contribution of the e -H2 interaction. Traditional semiempirical concepts such as the excluded volume are improved using microscopic approaches to treat the e -H2 problem. Within a cluster virial expansion, the Beth-Uhlenbeck formula is applied to infer the contribution of bound and scattering states to the temperature-dependent second virial coefficient. The scattering states are calculated using the phase expansion method for the polarization interaction that incorporates experimental data for the e -H2 scattering cross section. We present results for the scattering phase shifts, differential scattering cross sections, and the second virial coefficient due to the e -H2 interaction. The influence of this interaction on the composition of the partially ionized hydrogen plasma is confined to the parameter range where both the H2 and the free-electron components are abundant.

  15. 26 CFR 1.401(m)-1 - Employee contributions and matching contributions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... contributions. 1.401(m)-1 Section 1.401(m)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE.... § 1.401(m)-1 Employee contributions and matching contributions. (a) General nondiscrimination rules—(1... the nondiscrimination test of section 401(m) under paragraph (b) of this section and the...

  16. Achieving teamwork in stroke units: the contribution of opportunistic dialogue.

    PubMed

    Clarke, David J

    2010-05-01

    Collaborative interdisciplinary working is central to contemporary health policy. The specialized and co-ordinated multidisciplinary care provided in stroke units is considered to contribute to improved patient outcomes in such units. However, how stroke unit teams co-ordinate their work is not clearly understood. This paper reports on a grounded theory study which explains how health professionals in two stroke units in northern England achieved teamwork. Data were generated through 220 hours of participant observation and 34 semi-structured interviews. Interviews were undertaken during and following participant observations. A basic social process common to teamworking in both units was identified; this was termed "opportunistic dialogue". The division of labour in respect of rehabilitation activities was negotiated through this interactional process. Co-location of most team members led to repeated engagement in sharing patient information and in exploring different perspectives. Opportunistic dialoguing contributed to mutual learning and explained the shift in thinking and team culture as team members moved from concern with discrete disciplinary actions to dialogue and negotiations focused on meeting patients' needs. The findings indicate that routinely incorporating periods of joint working in which team members articulate the reasoning for their decisions and interventions, contributes to achieving interdisciplinary teamworking in rehabilitation settings.

  17. PIC: Protein Interactions Calculator

    PubMed Central

    Tina, K. G.; Bhadra, R.; Srinivasan, N.

    2007-01-01

    Interactions within a protein structure and interactions between proteins in an assembly are essential considerations in understanding molecular basis of stability and functions of proteins and their complexes. There are several weak and strong interactions that render stability to a protein structure or an assembly. Protein Interactions Calculator (PIC) is a server which, given the coordinate set of 3D structure of a protein or an assembly, computes various interactions such as disulphide bonds, interactions between hydrophobic residues, ionic interactions, hydrogen bonds, aromatic–aromatic interactions, aromatic–sulphur interactions and cation–π interactions within a protein or between proteins in a complex. Interactions are calculated on the basis of standard, published criteria. The identified interactions between residues can be visualized using a RasMol and Jmol interface. The advantage with PIC server is the easy availability of inter-residue interaction calculations in a single site. It also determines the accessible surface area and residue-depth, which is the distance of a residue from the surface of the protein. User can also recognize specific kind of interactions, such as apolar–apolar residue interactions or ionic interactions, that are formed between buried or exposed residues or near the surface or deep inside. PMID:17584791

  18. PIC: Protein Interactions Calculator.

    PubMed

    Tina, K G; Bhadra, R; Srinivasan, N

    2007-07-01

    Interactions within a protein structure and interactions between proteins in an assembly are essential considerations in understanding molecular basis of stability and functions of proteins and their complexes. There are several weak and strong interactions that render stability to a protein structure or an assembly. Protein Interactions Calculator (PIC) is a server which, given the coordinate set of 3D structure of a protein or an assembly, computes various interactions such as disulphide bonds, interactions between hydrophobic residues, ionic interactions, hydrogen bonds, aromatic-aromatic interactions, aromatic-sulphur interactions and cation-pi interactions within a protein or between proteins in a complex. Interactions are calculated on the basis of standard, published criteria. The identified interactions between residues can be visualized using a RasMol and Jmol interface. The advantage with PIC server is the easy availability of inter-residue interaction calculations in a single site. It also determines the accessible surface area and residue-depth, which is the distance of a residue from the surface of the protein. User can also recognize specific kind of interactions, such as apolar-apolar residue interactions or ionic interactions, that are formed between buried or exposed residues or near the surface or deep inside.

  19. The contribution of glacier melt to streamflow

    SciTech Connect

    Schaner, Neil; Voisin, Nathalie; Nijssen, Bart; Lettenmaier, D. P.

    2012-09-13

    Ongoing and projected future changes in glacier extent and water storage globally have lead to concerns about the implications for water supplies. However, the current magnitude of glacier contributions to river runoff is not well known, nor is the population at risk to future glacier changes. We estimate an upper bound on glacier melt contribution to seasonal streamflow by computing the energy balance of glaciers globally. Melt water quantities are computed as a fraction of total streamflow simulated using a hydrology model and the melt fraction is tracked down the stream network. In general, our estimates of the glacier melt contribution to streamflow are lower than previously published values. Nonetheless, we find that globally an estimated 225 (36) million people live in river basins where maximum seasonal glacier melt contributes at least 10% (25%) of streamflow, mostly in the High Asia region.

  20. 31 CFR 594.409 - Charitable contributions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., services, or technology, including those to relieve human suffering, such as food, clothing, or medicine... evade or to avoid the bar on the provision of contributions or donations to such a person....

  1. 31 CFR 593.408 - Charitable contributions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... donation of funds, goods, services, or technology, including those to relieve human suffering, such as food... if made in an attempt to violate, to evade, or to avoid the bar on the provision of contributions...

  2. 31 CFR 593.408 - Charitable contributions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... donation of funds, goods, services, or technology, including those to relieve human suffering, such as food... if made in an attempt to violate, to evade, or to avoid the bar on the provision of contributions...

  3. 31 CFR 594.409 - Charitable contributions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., services, or technology, including those to relieve human suffering, such as food, clothing, or medicine... evade or to avoid the bar on the provision of contributions or donations to such a person....

  4. 31 CFR 593.408 - Charitable contributions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... donation of funds, goods, services, or technology, including those to relieve human suffering, such as food... if made in an attempt to violate, to evade, or to avoid the bar on the provision of contributions...

  5. 31 CFR 593.408 - Charitable contributions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... donation of funds, goods, services, or technology, including those to relieve human suffering, such as food... if made in an attempt to violate, to evade, or to avoid the bar on the provision of contributions...

  6. Divergence in sink contributions to population persistence

    EPA Science Inventory

    Population sinks present unique conservation challenges. The loss of animals in sinks can compromise persistence. Conversely, sinks can bolster population sizes, improving viability. To assess the contribution of sinks to regional persistence, we simulated the removal of sink hab...

  7. Contribution of Hydrogen Bonds to Protein Stability

    NASA Astrophysics Data System (ADS)

    Pace, Nick

    2014-03-01

    I will discuss the contribution of the burial of polar groups and their hydrogen bonds to the conformational stability of proteins. We measured the change in stability, Δ(Δ G), for a series of hydrogen bonding mutants in four proteins: villin head piece subdomain (VHP) containing 36 residues, a surface protein from Borrelia burgdorferi (VlsE) containing 341 residues, and two proteins previously studied in our laboratory, ribonucleases Sa (RNase Sa) and T1 (RNase T1). Crystal structures were determined for three of the hydrogen bonding mutants of RNase Sa: S24A (1.1Å), Y51F(1.5Å), and T95A(1.3Å). The structures are very similar to wild type RNase Sa and the hydrogen bonding partners always form intermolecular hydrogen bonds to water in the mutants. We compare our results with previous studies of similar mutants in other proteins and reach the following conclusions: 1) Hydrogen bonds contribute favorably to protein stability. 2) The contribution of hydrogen bonds to protein stability is strongly context dependent. 3) Hydrogen bonds by side chains and peptide groups make similar contributions to protein stability. 4) Polar group burial can make a favorable contribution to protein stability even if the polar groups are not hydrogen bonded. 5) The contribution of hydrogen bonds to protein stability is similar for VHP, a small protein, and VlsE, a large protein.

  8. Exploring Learner to Content Interaction as a Success Factor in Online Courses

    ERIC Educational Resources Information Center

    Zimmerman, Tekeisha Denise

    2012-01-01

    Interaction plays a critical role in the learning process. For online course participants, interaction with the course content (learner-content interaction) is especially important because it can contribute to successful learning outcomes and course completion. This study aims to examine the relationship between learner-content interaction and…

  9. Albedo protons and electrons at ISS - an important contribution to astronaut dose?

    NASA Astrophysics Data System (ADS)

    Norman, R. B.; Slaba, T. C.; Badavi, F. F.; Mertens, C. J.; Blattnig, S.

    2015-12-01

    Albedo particles, which are created by cosmic ray interactions in the atmosphere and are moving upwards away from the surface of the earth, are often considered a negligible contribution to astronaut radiation exposure on the International Space Station (ISS). Models of astronaut exposure, however, consistently underestimate measurements onboard ISS when these albedo particles are neglected. Recent measurements by instruments on ISS (AMS, PAMELA, and SEDA-AP) hint that there are high energy protons and electrons which are not being modeled and that may contribute to radiation exposure on ISS. Estimates of the contribution of radiation exposure on ISS due to albedo particles, along with open questions, will be discussed.

  10. Unmodelled magnetic contributions in satellite-based models

    NASA Astrophysics Data System (ADS)

    Tozzi, Roberta; Mandea, Mioara; De Michelis, Paola

    2016-06-01

    A complex system of electric currents flowing in the ionosphere and magnetosphere originates from the interaction of the solar wind and the Interplanetary Magnetic Field (IMF) with the Earth's magnetic field. These electric currents generate magnetic fields contributing themselves to those measured by both ground observatories and satellites. Here, low-resolution (1 Hz) magnetic vector data recorded between 1 March 2014 and 31 May 2015 by the recently launched Swarm constellation are considered. The core and crustal magnetic fields and part of that originating in the magnetosphere are removed from Swarm measurements using CHAOS-5 model. Low- and mid-latitude residuals of the geomagnetic field representing the ionospheric and the unmodelled magnetospheric contributions are investigated, in the Solar Magnetic frame, according to the polarity of IMF B y (azimuthal) and B z (north-south) components and to different geomagnetic activity levels. The proposed approach makes it possible to investigate the features of unmodelled contributions due to the external sources of the geomagnetic field. Results show, on one side, the existence of a relation between the analysed residuals and IMF components B y and B z , possibly due to the long distance effect of high-latitude field-aligned currents. On the other side, they suggest the presence of a contribution due to the partial ring current that is activated during the main phase of geomagnetic storms. The perturbation observed on residuals is also compatible with the effect of the net field-aligned currents. Moreover, we have quantitatively estimated the effect of these current systems on computed residuals.

  11. Estimating the contribution of genetic variants to difference in incidence of disease between population groups.

    PubMed

    Moonesinghe, Ramal; Ioannidis, John P A; Flanders, W Dana; Yang, Quanhe; Truman, Benedict I; Khoury, Muin J

    2012-08-01

    Genome-wide association studies have identified multiple genetic susceptibility variants to several complex human diseases. However, risk-genotype frequency at loci showing robust associations might differ substantially among different populations. In this paper, we present methods to assess the contribution of genetic variants to the difference in the incidence of disease between different population groups for different scenarios. We derive expressions for the contribution of a single genetic variant, multiple genetic variants, and the contribution of the joint effect of a genetic variant and an environmental factor to the difference in the incidence of disease. The contribution of genetic variants to the difference in incidence increases with increasing difference in risk-genotype frequency, but declines with increasing difference in incidence between the two populations. The contribution of genetic variants also increases with increasing relative risk and the contribution of joint effect of genetic and environmental factors increases with increasing relative risk of the gene-environmental interaction. The contribution of genetic variants to the difference in incidence between two populations can be expressed as a function of the population attributable risks of the genetic variants in the two populations. The contribution of a group of genetic variants to the disparity in incidence of disease could change considerably by adding one more genetic variant to the group. Any estimate of genetic contribution to the disparity in incidence of disease between two populations at this stage seems to be an elusive goal.

  12. Food and Drug Interactions.

    PubMed

    Choi, Jong Hwan; Ko, Chang Mann

    2017-01-01

    Natural foods and vegetal supplements have recently become increasingly popular for their roles in medicine and as staple foods. This has, however, led to the increased risk of interaction between prescribed drugs and the bioactive ingredients contained in these foods. These interactions range from pharmacokinetic interactions (absorption, distribution, metabolism, and excretion influencing blood levels of drugs) to pharmacodynamic interactions (drug effects). In a quantitative respect, these interactions occur mainly during metabolism. In addition to the systemic metabolism that occurs mainly in the liver, recent studies have focused on the metabolism in the gastrointestinal tract endothelium before absorption. Inhibition of metabolism causes an increase in the blood levels of drugs and could have adverse reactions. The food-drug interactions causing increased blood levels of drugs may have beneficial or detrimental therapeutic effects depending on the intensity and predictability of these interactions. It is therefore important to understand the potential interactions between foods and drugs should and the specific outcomes of such interactions.

  13. Effective interactions between fluid membranes

    NASA Astrophysics Data System (ADS)

    Lu, Bing-Sui; Podgornik, Rudolf

    2015-08-01

    A self-consistent theory is proposed for the general problem of interacting undulating fluid membranes subject to the constraint that they do not interpenetrate. We implement the steric constraint via an exact functional integral representation and, through the use of a saddle-point approximation, transform it into a novel effective steric potential. The steric potential is found to consist of two contributions: one generated by zero-mode fluctuations of the membranes and the other by thermal bending fluctuations. For membranes of cross-sectional area S , we find that the bending fluctuation part scales with the intermembrane separation d as d-2 for d ≪√{S } but crosses over to d-4 scaling for d ≫√{S } , whereas the zero-mode part of the steric potential always scales as d-2. For membranes interacting exclusively via the steric potential, we obtain closed-form expressions for the effective interaction potential and for the rms undulation amplitude σ , which becomes small at low temperatures T and/or large bending stiffnesses κ . Moreover, σ scales as d for d ≪√{S } but saturates at √{kBT S /κ } for d ≫√{S } . In addition, using variational Gaussian theory, we apply our self-consistent treatment to study intermembrane interactions subject to different types of potentials: (i) the Moreira-Netz potential for a pair of strongly charged membranes with an intervening solution of multivalent counterions, (ii) an attractive square well, (iii) the Morse potential, and (iv) a combination of hydration and van der Waals interactions.

  14. Interactions between Chemokines

    PubMed Central

    Cook, Anna; Hippensteel, Randi; Shimizu, Saori; Nicolai, Jaclyn; Fatatis, Alessandro; Meucci, Olimpia

    2010-01-01

    The soluble form of the chemokine fractalkine/CX3CL1 regulates microglia activation in the central nervous system (CNS), ultimately affecting neuronal survival. This study aims to determine whether CXCL12, another chemokine constitutively expressed in the CNS (known as stromal cell-derived factor 1; SDF-1), regulates cleavage of fractalkine from neurons. To this end, ELISA was used to measure protein levels of soluble fractalkine in the medium of rat neuronal cultures exposed to SDF-1. Gene arrays, quantitative RT-PCR, and Western blot were used to measure overall fractalkine expression in neurons. The data show that the rate of fractalkine shedding in healthy cultures positively correlates with in vitro differentiation and survival. In analogy to non-neuronal cells, metalloproteinases (ADAM10/17) are involved in cleavage of neuronal fractalkine as indicated by studies with pharmacologic inhibitors. Moreover, treatment of the neuronal cultures with SDF-1 stimulates expression of the inducible metalloproteinase ADAM17 and increases soluble fractalkine content in culture medium. The effect of SDF-1 is blocked by an inhibitor of both ADAM10 and -17, but only partially affected by a more specific inhibitor of ADAM10. In addition, SDF-1 also up-regulates expression of the fractalkine gene. Conversely, exposure of neurons to an excitotoxic stimulus (i.e. NMDA) inhibits α-secretase activity and markedly diminishes soluble fractalkine levels, leading to cell death. These results, along with previous findings on the neuroprotective role of both SDF-1 and fractalkine, suggest that this novel interaction between the two chemokines may contribute to in vivo regulation of neuronal survival by modulating microglial neurotoxic properties. PMID:20124406

  15. Nutrition and parasite interaction.

    PubMed

    Coop, R L; Holmes, P H

    1996-01-01

    This overview focuses on the interaction between nutritional status and gastrointestinal nematode infection in ruminants and considers: (i) the influence of the parasite on host metabolism; and (ii) the effect of host nutrition on the establishment and survival of parasite populations, the development of the host-immune response and the pathophysiology of infection. Gastrointestinal nematodes reduce voluntary feed intake and efficiency of feed utilisation, a key feature being an increased endogenous loss of protein into the gastrointestinal tract. Overall there is movement of protein from productive processes into repair of the gastrointestinal tract, synthesis of plasma proteins and mucoprotein production. Although reduction in feed intake is a major factor contributing to the reduced performance of parasitised ruminants, the underlying mechanisms of the anorexia are poorly understood. Supplementation of the diet with additional protein does not appear to affect initial establishment of nematode infections but the pathophysiological consequences are generally more severe on lower planes of protein nutrition. The main effect of protein supplementation is to increase the rate of acquisition of immunity and increase resistance to reinfection and this has been associated with an enhanced cellular immune response in the gastrointestinal mucosa. The unresponsiveness of the young lamb can be improved by dietary protein supplementation. Recent trials have shown that growing sheep offered a free choice between a low and a high protein ration are able to modify their diet selection in order to alleviate the increase in protein requirements which result from gastrointestinal nematode infection. Studies on the influence of nutrition on the expression of genotype have shown that the benefits of a superior genotype are not lost on a low protein diet whereas a high protein diet can partially emeliorate the disadvantages of an inferior genotype. In addition to dietary protein

  16. Genomics-Guided Discovery of Traits Contributing to Interactions of Pseudomonas fluorescens with Other Organisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pseudomonas fluorescens is a diverse bacterial species known for its ubiquity in natural habitats and the production of structurally diverse, bioactive secondary metabolites. The high degree of ecological and metabolic diversity represented in P. fluorescens is reflected in the genomic diversity di...

  17. Ram seminal plasma proteins contribute to sperm capacitation and modulate sperm-zona pellucida interaction.

    PubMed

    Luna, C; Colás, C; Casao, A; Serrano, E; Domingo, J; Pérez-Pé, R; Cebrián-Pérez, J A; Muiño-Blanco, T

    2015-03-01

    Incubation of ram spermatozoa in capacitating conditions with cAMP-elevating agents promotes a progressive time-dependent increase in the capacitated sperm subpopulation. In this study, the fertilizing capacity of ram spermatozoa (ability to bind to the zona pellucida, ZBA rate) capacitated in these conditions was determined. The results showed an increase (P < 0.001) in ZBA rate related to control samples in basal medium that contained BSA, calcium, and bicarbonate (1.97 ± 0.19 vs. 1.31 ± 0.09 sperm bound/oocyte, respectively). A significant correlation between protein tyrosine phosphorylation and ZBA rate (P < 0.05, r = 0.501) corroborated that incubation in a "high-cAMP" environment improves the fertilizing ability of ram spermatozoa. Likewise, the presence of two seminal plasma (SP) proteins able to protect sperm against cold shock (RSVP14 and RSVP20) was evidenced in both SP and the ram sperm surface, and their influence in the fertilizing ability of spermatozoa capacitated in basal medium or with cAMP-elevating agents was determined. The results verified that RSVP14 and RSVP20 act as decapacitating factors given that their addition to SP-free sperm samples previously to capacitation maintained high proportions of the noncapacitated sperm pattern with no increase in protein tyrosine phosphorylation. However, the obtained ZBA rate in the high-cAMP-containing samples was increased in the presence of RSVP20 (P < 0.05). These findings would indicate that the stimulating effect exerted by this protein on the sperm-oocyte binding occurs downstream from the cAMP generation and that the mechanisms by which RSVP20 promotes the zona pellucida binding might be independent of protein tyrosine phosphorylation.

  18. Contributions of speech science to the technology of man-machine voice interactions

    NASA Technical Reports Server (NTRS)

    Lea, Wayne A.

    1977-01-01

    Research in speech understanding was reviewed. Plans which include prosodics research, phonological rules for speech understanding systems, and continued interdisciplinary phonetics research are discussed. Improved acoustic phonetic analysis capabilities in speech recognizers are suggested.

  19. Androctonus australis hector venom contributes to the interaction between neuropeptides and mast cells in pulmonary hyperresponsiveness.

    PubMed

    Chaïr-Yousfi, Imène; Laraba-Djebari, Fatima; Hammoudi-Triki, Djelila

    2015-03-01

    Lung injury and respiratory distress syndrome are frequent symptoms observed in the most severe cases of scorpion envenomation. The uncontrolled transmigration of leukocyte cells into the lung interstitium and alveolar space and pulmonary edema may be the cause of death. Mast cells can release various inflammatory mediators known to be involved in the development of lung edema following scorpion venom injection. The present study was designed to determine the evidence of neurokinin 1 (NK1) receptor and the involvement of mast cell activation to induce pulmonary edema and to increase vascular permeability after Androctonus australis hector (Aah) venom administration. To this end, mast cells were depleted using compound 48/80 (C48/80). Furthermore, the involvement of tachykinin NK1 receptors expressed on mast cell membranes was elucidated by their blocking with an antagonist. On the other hand, the ability of Aah venom to increase vascular permeability and to induce edema was also assessed by measuring the amount of Evans blue dye (EBD) extravasation in bronchoalveolar lavage (BAL) fluid and in the lungs of mice. Pulmonary edema, as assessed by the levels of EBD extravasation, was completely inhibited in compound 48/80-treated animals. Depletion by stimuli non-immunological C48/80 component markedly reduced induced inflammatory response following the venom administration. The mast cells seem to play an important role in the development of lung injury and the increase of vascular permeability in mice following the subcutaneous administration of Aah scorpion venom through the NK1 receptor.

  20. Prefrontal and Hippocampal Contributions to Visual Associative Recognition: Interactions between Cognitive Control and Episodic Retrieval

    ERIC Educational Resources Information Center

    Bunge, S. A.; Burrows, B.; Wagner, A. D.

    2004-01-01

    The ability to recover episodic associations is thought to depend on medial-temporal lobe mnemonic mechanisms and frontal lobe cognitive control processes. The present study examined the neural circuitry underlying non-verbal associative retrieval, and considered the consequences of successful retrieval on cognitive control demands. Event-related…

  1. Contributions of the Interaction between Dietary Protein and Gut Microbiota to Intestinal Health.

    PubMed

    Ma, Ning; Tian, Yanan; Wu, Yi; Ma, Xi

    2017-02-16

    There is growing recognition that composition and metabolic activity of the gut microbiota can be modulated by the dietary proteins which in turn impact health. The amino acid composition and digestibility of proteins, which are influenced by its source and amount of intake, play a pivotal role in determining the microbiota. Reciprocally, it appears that the gut microbiota is also able to affect protein metabolism which give rise to the view that function between the microbiota and protein can proceed in both directions. In response to the alterations in dietary protein components, there are significant changes in the microbial metabolites including short chain fatty acids (SCFAs), ammonia, amines, gases such as hydrogen, sulfide and methane which are cytotoxins, genotoxins and carcinogens associated with development of colon cancer and inflammatory bowel diseases. A suitable ratio between protein and carbohydrate or even a low protein diet is recommended based on the evidence that excessive protein intake adversely affect health. Supplying high and undigested proteins will encourage pathogens and protein-fermenting bacteria to increase the risk of diseases. These changes of microbiota can affect gut barrier and immune system by regulating genes expression in relevant signaling pathways and by regulating the secretion of metabolites. The objective of this review is to assess the impact of dietary proteins on microbiota composition and activity in the gastro-intestinal tract. The attention should be give to the dietary strategies with judicious selection of source and supplementation of dietary protein to benefit gut health.

  2. Contributions to Engineering Models of Human-Computer Interaction. Volume 1.

    DTIC Science & Technology

    1988-05-06

    3.5.1.1 The Task 33 3.5.1.2 Method 35 3.5.1.3 Results 36 3.5.2 The Fitts & Seeger Task 37 3.5.3 The Duncan Task 39 3.5.4 The Morin & Forrn Task 41...experimental conditions from Morin & 42 Forrin, 1962, p. 138. Figure 3-9: Predicted vs. observed response time for the Morin & ForrIn 43 experiment. Figure...and observed response times for the Morin & Forrin 42 experiment. Table 3-9: Perceptual, cognitive and motor parameter definitions and 44 estimated

  3. Interactive Media and Its Contribution to the Construction and Destruction of Values and Character.

    ERIC Educational Resources Information Center

    Kane, Harrison D.; Taub, Gordon E.; Hayes, B. Grant

    2000-01-01

    This article discusses the prevalence of violence in many media forms, including the Internet. It considers the role of the media in perpetuating violence and discusses the ways in which the media influence values and individual character development, particularly in children. (Author/JDM)

  4. Interactional Perspectives on Communicative Needs of Zulu Work Seekers.

    ERIC Educational Resources Information Center

    Chick, Keith

    1986-01-01

    Examines the interactional sociolinguists' treatment of context and its contribution to understanding how sociocultural information enters into the interpretation of intent and evaluation of motives and abilities. Negative perceptions of Zulus by White "gatekeepers" are explained in terms of interactional asynchrony stemming from…

  5. Considering the Activity in Interactivity: A Multimodal Perspective

    ERIC Educational Resources Information Center

    Schwartz, Ruth N.

    2010-01-01

    What factors contribute to effective multimedia learning? Increasingly, interactivity is considered a critical component that can foster learning in multimedia environments, including simulations and games. Although a number of recent studies investigate interactivity as a factor in the effective design of multimedia instruction, most examine only…

  6. Alterations of chemotherapeutic pharmacokinetic profiles by drug–drug interactions

    PubMed Central

    Ghalib, Mohammed; Chaudhary, Imran; Goel, Sanjay

    2012-01-01

    Background Drug interactions in oncology are common place and largely ignored as we tolerate high thresholds of ‘toxic’ drug responses in these patients. However, in the era of ‘targeted’ or seemingly ‘less toxic’ therapy, these interactions are more commonly flagged and contribute significantly towards poor ‘quality of life’ and medical fatalities. Objective This review and opinion article focuses on alteration of chemotherapeutic pharmacokinetic profiles by drug interactions in the setting of polypharmacy. The assumption is that the drugs, with changes in their pharmacokinetics, will contribute towards changes in their pharmacodynamics. Methods The examples cited for such drug–drug interactions are culled from published literature with an emphasis on those interactions that have been well characterized at the molecular level. Results Although very few drug interaction studies have been performed on approved oncology based drugs, it is clear that drugs whose pharmacokinetics profiles are closely related to their pharmacodynamics will indeed result in clinically important drug interactions. Some newer mechanisms are described that involve interactions at the level of gene transcription, whereby, drug metabolism is significantly altered. However, for any given drug interaction, there does not seem to be a comprehensive model describing interactions. Conclusions Mechanisms based drug interactions are plentiful in oncology; however, there is an absolute lack of a comprehensive model that would predict drug–drug interactions. PMID:19239394

  7. Interacting dark sector with transversal interaction

    SciTech Connect

    Chimento, Luis P.; Richarte, Martín G.

    2015-03-26

    We investigate the interacting dark sector composed of dark matter, dark energy, and dark radiation for a spatially flat Friedmann-Robertson-Walker (FRW) background by introducing a three-dimensional internal space spanned by the interaction vector Q and solve the source equation for a linear transversal interaction. Then, we explore a realistic model with dark matter coupled to a scalar field plus a decoupled radiation term, analyze the amount of dark energy in the radiation era and find that our model is consistent with the recent measurements of cosmic microwave background anisotropy coming from Planck along with the future constraints achievable by CMBPol experiment.

  8. Incentives to Encourage Scientific Web Contribution (Invited)

    NASA Astrophysics Data System (ADS)

    Antunes, A. K.

    2010-12-01

    We suggest improvements to citation standards and creation of remuneration opportunities to encourage career scientist contributions to Web2.0 and social media science channels. At present, agencies want to accomplish better outreach and engagement with no funding, while scientists sacrifice their personal time to contribute to web and social media sites. Securing active participation by scientists requires career recognition of the value scientists provide to web knowledge bases and to the general public. One primary mechanism to encourage participation is citation standards, which let a contributor improve their reputation in a quantifiable way. But such standards must be recognized by their scientific and workplace communities. Using case studies such as the acceptance of web in the workplace and the growth of open access journals, we examine what agencies and individual can do as well as the time scales needed to secure increased active contribution by scientists. We also discuss ways to jumpstart this process.

  9. Contributions of psychology to war and peace.

    PubMed

    Christie, Daniel J; Montiel, Cristina J

    2013-10-01

    The contributions of American psychologists to war have been substantial and responsive to changes in U.S. national security threats and interests for nearly 100 years. These contributions are identified and discussed for four periods of armed conflict: World Wars I and II, the Cold War, and the Global War on Terror. In contrast, about 50 years ago, largely in reaction to the threat of nuclear war, some psychologists in the United States and around the world broke with the tradition of supporting war and began focusing their scholarship and activism on the prevention of war and promotion of peace. Today, peace psychology is a vibrant area of psychology, with theory and practice aimed at understanding, preventing, and mitigating both episodes of organized violence and the pernicious worldwide problem of structural violence. The growth, scope, and content of peace psychology are reviewed along with contributions to policies that promote peace, social justice, and human well-being.

  10. Indian – American contributions to psychiatric research

    PubMed Central

    Pandurangi, Anand K.

    2010-01-01

    The Indian Diaspora, especially in North America, is a visible force in the field of psychiatric medicine. An estimated 5000 persons of Indian origin practice psychiatry in the USA and Canada, and an estimated 10% of these are in academic psychiatry. Wide ranging contributions, from molecular biology of psychiatric disorders to community and cultural psychiatry, are being made by this vibrant group of researchers. This article is a brief summary and work-in-progress report of the contributions by Indian – American psychiatric researchers. Although not exhaustive in coverage, it is meant to give the reader an overview of the contributions made by three waves of researchers over a span of 50 years. PMID:21836715

  11. Individual muscle contributions to circular turning mechanics.

    PubMed

    Ventura, Jessica D; Klute, Glenn K; Neptune, Richard R

    2015-04-13

    Turning is an activity of daily living that involves both the acceleration of the body center-of-mass (COM) towards the center of curvature and rotation of the pelvis towards the new heading. The purpose of this study was to understand which muscles contribute to turning using experimentation, musculoskeletal modeling and simulation. Ten healthy adults consented to walk around a 1-m radius circular path at their self-selected walking speed and then along a straight line at the same speed. Forward dynamics simulations of the individual subjects during the turning and straight-line walking tasks were generated to identify the contributions of individual muscle groups to the body mediolateral and anterior-posterior COM acceleration impulse and to the pelvis angular acceleration impulse. The stance leg gluteus medius and ankle plantarflexor muscles and the swing leg adductor muscles were the primary contributors to redirect the body's COM relative to straight-line walking. In some cases, contributions to mediolateral COM acceleration were modulated through changes in leg orientation rather than through changes in muscle force. While modulation of the muscle contributions generally occurred in both the inner and outer legs, greater changes were observed during inner single-leg support than during outer single-leg support. Total pelvis angular acceleration was minimal during the single-support phase, but the swing leg muscles contributed significantly to balancing the internal and external rotation of the pelvis. The understanding of which muscles contribute to turning the body during walking may help guide the development of more effective locomotor therapies for those with movement impairments.

  12. Profile of drug interactions in hospitalized children

    PubMed Central

    Martinbiancho, Jacqueline; Zuckermann, Joice; Dos Santos, Luciana; Silva, Mariane M.

    Introduction The expected therapeutic response may be affected by the presence of drug interactions. With the high number of reports on new drug interactions, it has been difficult for health professionals to keep constantly updated. For this reason, computer systems have helped identify such interactions. Objectives To verify the rate and profile of drug interactions in medical prescriptions to hospitalized pediatric patients. Methods A descriptive study investigated prescriptions to hospitalized pediatric patients. The study included patients between 0 and 12 years old, containing 4 or more drugs in their prescriptions. The analysis of interaction and incompatibility possibilities in prescribed drugs used Micromedex / Drug-Reax® program. Results From 2005 to 2006, 3,170 patients were investigated, and 11,181 prescriptions were analyzed, a mean value of 3.5 prescriptions/patient. In total, 6,857 drug interactions were found, which corresponds to 1.9 interaction/prescription. Among them, relevance to ampicillin and gentamicin, found in 220 (3.2%) prescriptions. In total, 2,411 drug incompatibilities in via y were found, a mean value of 0.5/prescription, with emphasis on vancomycin and cefepime, found in 243 (10.0%) prescriptions. Conclusion The presence of drug interactions is a permanent risk in hospitals. This way, the utilization of computer programs, pharmacotherapy monitoring of patients and the pharmacist presence in the multidisciplinary team are some manners of contributing to hospitalized patients’ treatment. PMID:25170352

  13. 5 CFR 1620.42 - Processing TSP contribution elections.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... she must make a new contribution election to begin current contributions. (b) Makeup contribution... within 60 days of the participant's reemployment or return to pay status. (c) Makeup contributions. Makeup contributions will be processed as follows: (1) If the employee had a valid contribution...

  14. 5 CFR 1620.42 - Processing TSP contribution elections.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... she must make a new contribution election to begin current contributions. (b) Makeup contribution... within 60 days of the participant's reemployment or return to pay status. (c) Makeup contributions. Makeup contributions will be processed as follows: (1) If the employee had a valid contribution...

  15. 5 CFR 1620.42 - Processing TSP contribution elections.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... she must make a new contribution election to begin current contributions. (b) Makeup contribution... within 60 days of the participant's reemployment or return to pay status. (c) Makeup contributions. Makeup contributions will be processed as follows: (1) If the employee had a valid contribution...

  16. 5 CFR 1620.42 - Processing TSP contribution elections.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... she must make a new contribution election to begin current contributions. (b) Makeup contribution... within 60 days of the participant's reemployment or return to pay status. (c) Makeup contributions. Makeup contributions will be processed as follows: (1) If the employee had a valid contribution...

  17. 5 CFR 1600.22 - Maximum employee contributions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Revenue Code (26 U.S.C.). (b) A participant may make traditional contributions and Roth contributions... contributions and Roth contributions cannot exceed the applicable Internal Revenue Code elective deferral limit... employee contributions and Roth contributions made to both accounts cannot exceed the Internal Revenue...

  18. 5 CFR 1600.22 - Maximum employee contributions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Revenue Code (26 U.S.C.). (b) A participant may make traditional contributions and Roth contributions... contributions and Roth contributions cannot exceed the applicable Internal Revenue Code elective deferral limit... employee contributions and Roth contributions made to both accounts cannot exceed the Internal Revenue...

  19. Canadian contributions studies for the WFIRST instruments

    NASA Astrophysics Data System (ADS)

    Lavigne, J.-F.; Rowlands, N.; Grandmont, F. J.; Lafrenière, D.; Marois, C.; Daigle, O.; Thibault, S.; Schade, D.; Artigau, É.; Brousseau, D.; Maire, J.; Cretot-Richert, G.; Ducharme, M.-È.; Levesque, L. E.; Laurin, D.; Dupuis, J.

    2016-07-01

    WFIRST-AFTA is the NASA's highest ranked astrophysics mission for the next decade that was identified in the New World, New Horizon survey. The mission scientific drivers correspond to some of the deep questions identified in the Canadian LRP2010, and are also of great interest for the Canadian scientists. Given that there is also a great interest in having an international collaboration in this mission, the Canadian Space Agency awarded two contracts to study a Canadian participation in the mission, one related to each instrument. This paper presents a summary of the technical contributions that were considered for a Canadian contribution to the coronagraph and wide field instruments.

  20. Contribution to encyclopedia of thermal stresses

    NASA Astrophysics Data System (ADS)

    Taler, Jan; Ocłoń, Pawel

    2015-06-01

    This paper lists the contribution in the international interdisciplinary reference - Encyclopedia of Thermal Stresses (ETS). The ETS, edited by the world famous expert in field of Thermal Stresses - Professor Richard Hetnarski from Rochester Institute of Technology, was published by Springer in 2014. This unique Encyclopedia, subdivided into 11 volumes is the most extensive and comprehensive work related to the Thermal Stresses topic. The entries were carefully prepared by specialists in the field of thermal stresses, elasticity, heat conduction, optimization among others. The Polish authors' contribution within this work is significant; over 70 entries were prepared by them.

  1. Magnetic field contribution to the Lorentz model.

    PubMed

    Oughstun, Kurt E; Albanese, Richard A

    2006-07-01

    The classical Lorentz model of dielectric dispersion is based on the microscopic Lorentz force relation and Newton's second law of motion for an ensemble of harmonically bound electrons. The magnetic field contribution in the Lorentz force relation is neglected because it is typically small in comparison with the electric field contribution. Inclusion of this term leads to a microscopic polarization density that contains both perpendicular and parallel components relative to the plane wave propagation vector. The modified parallel and perpendicular polarizabilities are both nonlinear in the local electric field strength.

  2. Method for Tracking Core-Contributed Publications

    PubMed Central

    Loomis, Cynthia A.; Curchoe, Carol Lynn

    2012-01-01

    Accurately tracking core-contributed publications is an important and often difficult task. Many core laboratories are supported by programmatic grants (such as Cancer Center Support Grant and Clinical Translational Science Awards) or generate data with instruments funded through S10, Major Research Instrumentation, or other granting mechanisms. Core laboratories provide their research communities with state-of-the-art instrumentation and expertise, elevating research. It is crucial to demonstrate the specific projects that have benefited from core services and expertise. We discuss here the method we developed for tracking core contributed publications. PMID:23204927

  3. Predicting Anthropogenic Noise Contributions to US Waters.

    PubMed

    Gedamke, Jason; Ferguson, Megan; Harrison, Jolie; Hatch, Leila; Henderson, Laurel; Porter, Michael B; Southall, Brandon L; Van Parijs, Sofie

    2016-01-01

    To increase understanding of the potential effects of chronic underwater noise in US waters, the National Oceanic and Atmospheric Administration (NOAA) organized two working groups in 2011, collectively called "CetSound," to develop tools to map the density and distribution of cetaceans (CetMap) and predict the contribution of human activities to underwater noise (SoundMap). The SoundMap effort utilized data on density, distribution, acoustic signatures of dominant noise sources, and environmental descriptors to map estimated temporal, spatial, and spectral contributions to background noise. These predicted soundscapes are an initial step toward assessing chronic anthropogenic noise impacts on the ocean's varied acoustic habitats and the animals utilizing them.

  4. Dynamics of two interacting active Janus particles

    NASA Astrophysics Data System (ADS)

    Bayati, Parvin; Najafi, Ali

    2016-04-01

    Starting from a microscopic model for a spherically symmetric active Janus particle, we study the interactions between two such active motors. The ambient fluid mediates a long range hydrodynamic interaction between two motors. This interaction has both direct and indirect hydrodynamic contributions. The direct contribution is due to the propagation of fluid flow that originated from a moving motor and affects the motion of the other motor. The indirect contribution emerges from the re-distribution of the ionic concentrations in the presence of both motors. Electric force exerted on the fluid from this ionic solution enhances the flow pattern and subsequently changes the motion of both motors. By formulating a perturbation method for very far separated motors, we derive analytic results for the translation and rotational dynamics of the motors. We show that the overall interaction at the leading order modifies the translational and rotational speeds of motors which scale as O (" separators=" [ 1 / D ] 3 ) and O (" separators=" [ 1 / D ] 4 ) with their separation, respectively. Our findings open up the way for studying the collective dynamics of synthetic micro-motors.

  5. Autoinducer-2 Production in Campylobacter jejuni Contributes to Chicken Colonization ▿

    PubMed Central

    Quiñones, Beatriz; Miller, William G.; Bates, Anna H.; Mandrell, Robert E.

    2009-01-01

    Inactivation of luxS, encoding an AI-2 biosynthesis enzyme, in Campylobacter jejuni strain 81-176 significantly reduced colonization of the chick lower gastrointestinal tract, chemotaxis toward organic acids, and in vitro adherence to LMH chicken hepatoma cells. Thus, AI-2 production in C. jejuni contributes to host colonization and interactions with epithelial cells. PMID:19011073

  6. Effects of Water and Nitrogen Availability on Nitrogen Contribution by the Legume, Lupinus argenteus Pursh.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nitrogen-fixing species contribute to ecosystem nitrogen budgets, but background resource levels influence nodulation, fixation, and plant growth. We conducted a greenhouse experiment to examine the separate and interacting effects of water and N availability on biomass production, tissue N concentr...

  7. The Contribution of Ernst Mach to Embodied Cognition and Mathematics Education

    ERIC Educational Resources Information Center

    Zudini, Verena; Zuccheri, Luciana

    2016-01-01

    A study of the interactions between mathematics and cognitive science, carried out within a historical perspective, is important for a better understanding of mathematics education in the present. This is evident when analysing the contribution made by the epistemological theories of Ernst Mach. On the basis of such theories, a didactic method was…

  8. Understanding the Online Doctoral Learning Experience: Factors That Contribute to Students' Sense of Community

    ERIC Educational Resources Information Center

    Byrd, Jeremy Carl

    2016-01-01

    As the number of students taking online courses continues to grow steadily, it is becoming increasingly important to inquire about the experiences of these students in order to understand the factors that contribute to their success. It is imperative that the social needs of students be understood, as interaction is an important aspect of the…

  9. A Twin Study of Heritable and Shared Environmental Contributions to Autism

    ERIC Educational Resources Information Center

    Frazier, Thomas W.; Thompson, Lee; Youngstrom, Eric A.; Law, Paul; Hardan, Antonio Y.; Eng, Charis; Morris, Nathan

    2014-01-01

    The present study examined genetic and shared environment contributions to quantitatively-measured autism symptoms and categorically-defined autism spectrum disorders (ASD). Participants included 568 twins from the Interactive Autism Network. Autism symptoms were obtained using the Social Communication Questionnaire and Social Responsiveness…

  10. Gestalt Interactional Groups

    ERIC Educational Resources Information Center

    Harman, Robert L.; Franklin, Richard W.

    1975-01-01

    Gestalt therapy in groups is not limited to individual work in the presence of an audience. Describes several ways to involve gestalt groups interactionally. Interactions described focus on learning by doing and discovering, and are noninterpretive. (Author/EJT)

  11. Computerized Interactive Harness Engineering

    NASA Technical Reports Server (NTRS)

    Billitti, J. W.

    1985-01-01

    Computerized interactive harness engineering program inexpensive, interactive system for learning and using engineering approach to interconnection systems. Basically data-base system that stores information as files of individual connectors and handles wiring information in circuit groups stored as records.

  12. Microfluidic large scale integration of viral-host interaction analysis.

    PubMed

    Ben-Ari, Ya'ara; Glick, Yair; Kipper, Sarit; Schwartz, Nika; Avrahami, Dorit; Barbiro-Michaely, Efrat; Gerber, Doron

    2013-06-21

    Viral-host interactions represent potential drug targets for novel antiviral strategies (Flisiak et al., Hepatology, 2008, 47, 817-26). Hence, it is important to establish an adequate platform for identifying and analyzing such interactions. In this review, we discuss bottlenecks in conventional protein-protein interaction methodologies and present the contribution of innovative microfluidic-based technologies towards a solution to these problems with respect to viral-host proteomics.

  13. Interactions between magnetohydrodynamical discontinuities

    SciTech Connect

    Dai, W.; Woodward, P.R. )

    1994-11-01

    Interactions between magnetohydrodynamical (MHD) discontinuities are studied through numerical simulations for the set of one-dimensional MHD equations. The interactions include the impact of a shock on a contact discontinuity, the collision of two shocks, and the catchup of a shock over another shock. The shocks involved in the interactions may be very strong. Each shock in an interaction may be either a fast or a slow shock.

  14. Interracial roommate relationships: negotiating daily interactions.

    PubMed

    Trail, Thomas E; Shelton, J Nicole; West, Tessa V

    2009-06-01

    Jobs, social group memberships, or living arrangements lead many people to interact every day with another person from a different racial background. Given that research has shown that interracial interactions are often stressful, it is important to know how these daily interactions unfold across time and what factors contribute to the success or failure of these interactions. Both members of same-race and mixed-race college roommate pairs completed daily questionnaires measuring their emotional experiences and their perceptions of their roommate. Results revealed that roommates in mixed-race dyads experienced less positive emotions and intimacy toward their roommates than did roommates in same-race dyads and that the experience of positive emotions declined over time for ethnic minority students with White roommates. Mediation analyses showed that the negative effects of roommate race were mediated by the level of intimacy-building behaviors performed by the roommate. Implications for future research and university policies are discussed.

  15. Effect of solute interactions in columbium /Nb/ on creep strength

    NASA Technical Reports Server (NTRS)

    Klein, M. J.; Metcalfe, A. G.

    1973-01-01

    The creep strength of 17 ternary columbium (Nb)-base alloys was determined using an abbreviated measuring technique, and the results were analyzed to identify the contributions of solute interactions to creep strength. Isostrength creep diagrams and an interaction strengthening parameter, ST, were used to present and analyze data. It was shown that the isostrength creep diagram can be used to estimate the creep strength of untested alloys and to identify compositions with the most economical use of alloy elements. Positive values of ST were found for most alloys, showing that interaction strengthening makes an important contribution to the creep strength of these ternary alloys.

  16. Interactivity: A Forgotten Art?

    ERIC Educational Resources Information Center

    Sims, Rod

    1997-01-01

    This paper promotes further discussion and analysis of interactivity in learning environments and contains a classification of interaction types appropriate for consideration in multimedia settings. Through an examination of related factors associated with navigation and control, a matrix of interactive dimensions is proposed. (Author)

  17. Global Interaction in Design

    ERIC Educational Resources Information Center

    Bennett, Audrey Grace

    2010-01-01

    Based on a virtual conference, Glide'08 (Global Interaction in Design Education), that brought international design scholars together online, this special issue expands on the topics of cross-cultural communication and design and the technological affordances that support such interaction. The author discusses the need for global interaction in…

  18. Contributions of Neutrophils to Resolution of Mucosal Inflammation

    PubMed Central

    Colgan, Sean P.; Ehrentraut, Stefan F.; Glover, Louise E.; Kominsky, Douglas J.; Campbell, Eric L.

    2014-01-01

    Neutrophil (PMN) recruitment from the blood stream into surrounding tissues involves a regulated series of events central to acute responses in host defense. Accumulation of PMN within mucosal tissues have historically been considered pathognomonic features of both acute and chronic inflammatory conditions. Historically PMNs have been deemed necessary but detrimental when recruited, given the potential for tissue damage that results from a variety of mechanisms. Recent work, however, has altered our preconcieved notions of PMN contributions to inflammatory processes. In particular, significant evidence implicates a central role for the PMN in triggering inflammatory resolution. Such mechanisms involve both metabolic and biochemical crosstalk pathways during the intimate interactions of PMN with other cell types at inflammatory sites. Here, we highlight several recent examples of how PMN coordinate the resolution of ongoing inflammation, with a particular focus on the gastrointestinal mucosa. PMID:22968707

  19. [Scientific contributions of Jules Hirsch regarding the physiopathogenesis of obesity].

    PubMed

    Zárate, Arturo; Manuel, Leticia

    2016-01-01

    Jules Hirsch was born in New York City and died at age 88 after a long illness. He was considered notorious leader in the study of human metabolism mainly in the area of lipids and obesity. His research at The Rockefeller University helps establish the mechanism of obesity and lipids metabolism. Hirsch joined Rockefeller´s faculty in 1954 and remained there for the rest of his career. Hirsch´s research helped to support the idea of dynamic interactions among diet, physical activity, general metabolism and obesity. At that time most scientific considered adipose tissue to be biologically inert such as a passive insulator in which the body reserved energy in the form of triglycerides. Hirsch had a natural characteristic of showing a nice smile and greeting for everyone he worked with at the university. Another important contribution was there relationship between diet and cardiovascular ailments as well as metabolism disturbance.

  20. Contribution of arginine-glutamate salt bridges to helix stability.

    PubMed

    Walker, Kristin D; Causgrove, Timothy P

    2009-10-01

    Peptide side chain interactions were studied by molecular dynamics simulation using explicit solvent on a peptide with the sequence AAARAAAAEAAEAAAARA. Three different protonation states of the glutamic acid side chains were simulated for four 20 ns runs each, a total simulation time of 240 ns. Two different salt bridge geometries were observed and the preferred geometry was found to depend on Glu - Arg residue spacing. Stable charge clusters were also observed, particularly in the fully charged peptide. Salt bridges were selectively interrupted upon protonation, with concomitant changes in secondary structure. The fully charged peptide was highly helical between residues 9 and 13, although protonation increased helicity near the N-terminus. The contribution of salt bridges to helix stability therefore depends on both position and relative position of charged residues within a sequence.