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Sample records for allosteric communication mediated

  1. Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

    CERN Document Server

    Amor, Benjamin R C; Yaliraki, Sophia N; Barahona, Mauricio

    2016-01-01

    Allosteric regulation is central to many biochemical processes. Allosteric sites provide a target to fine-tune protein activity, yet we lack computational methods to predict them. Here, we present an efficient graph-theoretical approach for identifying allosteric sites and the mediating interactions that connect them to the active site. Using an atomistic graph with edges weighted by covalent and non-covalent bond energies, we obtain a bond-to-bond propensity that quantifies the effect of instantaneous bond fluctuations propagating through the protein. We use this propensity to detect the sites and communication pathways most strongly linked to the active site, assessing their significance through quantile regression and comparison against a reference set of 100 generic proteins. We exemplify our method in detail with three well-studied allosteric proteins: caspase-1, CheY, and h-Ras, correctly predicting the location of the allosteric site and identifying key allosteric interactions. Consistent prediction of...

  2. Calculated pKa Variations Expose Dynamic Allosteric Communication Networks.

    Science.gov (United States)

    Lang, Eric J M; Heyes, Logan C; Jameson, Geoffrey B; Parker, Emily J

    2016-02-17

    Allosteric regulation of protein function, the process by which binding of an effector molecule provokes a functional response from a distal site, is critical for metabolic pathways. Yet, the way the allosteric signal is communicated remains elusive, especially in dynamic, entropically driven regulation mechanisms for which no major conformational changes are observed. To identify these dynamic allosteric communication networks, we have developed an approach that monitors the pKa variations of ionizable residues over the course of molecular dynamics simulations performed in the presence and absence of an allosteric regulator. As the pKa of ionizable residues depends on their environment, it represents a simple metric to monitor changes in several complex factors induced by binding an allosteric effector. These factors include Coulombic interactions, hydrogen bonding, and solvation, as well as backbone motions and side chain fluctuations. The predictions that can be made with this method concerning the roles of ionizable residues for allosteric communication can then be easily tested experimentally by changing the working pH of the protein or performing single point mutations. To demonstrate the method's validity, we have applied this approach to the subtle dynamic regulation mechanism observed for Neisseria meningitidis 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase, the first enzyme of aromatic biosynthesis. We were able to identify key communication pathways linking the allosteric binding site to the active site of the enzyme and to validate these findings experimentally by reestablishing the catalytic activity of allosterically inhibited enzyme via modulation of the working pH, without compromising the binding affinity of the allosteric regulator.

  3. Extracellular Loop 2 of the Free Fatty Acid Receptor 2 Mediates Allosterism of a Phenylacetamide Ago-Allosteric ModulatorS⃞

    Science.gov (United States)

    Smith, Nicola J.; Ward, Richard J.; Stoddart, Leigh A.; Hudson, Brian D.; Kostenis, Evi; Ulven, Trond; Morris, Joanne C.; Tränkle, Christian; Tikhonova, Irina G.; Adams, David R.

    2011-01-01

    Allosteric agonists are powerful tools for exploring the pharmacology of closely related G protein-coupled receptors that have nonselective endogenous ligands, such as the short chain fatty acids at free fatty acid receptors 2 and 3 (FFA2/GPR43 and FFA3/GPR41, respectively). We explored the molecular mechanisms mediating the activity of 4-chloro-α-(1-methylethyl)-N-2-thiazolylbenzeneacetamide (4-CMTB), a recently described phenylacetamide allosteric agonist and allosteric modulator of endogenous ligand function at human FFA2, by combining our previous knowledge of the orthosteric binding site with targeted examination of 4-CMTB structure-activity relationships and mutagenesis and chimeric receptor generation. Here we show that 4-CMTB is a selective agonist for FFA2 that binds to a site distinct from the orthosteric site of the receptor. Ligand structure-activity relationship studies indicated that the N-thiazolyl amide is likely to provide hydrogen bond donor/acceptor interactions with the receptor. Substitution at Leu173 or the exchange of the entire extracellular loop 2 of FFA2 with that of FFA3 was sufficient to reduce or ablate, respectively, allosteric communication between the endogenous and allosteric agonists. Thus, we conclude that extracellular loop 2 of human FFA2 is required for transduction of cooperative signaling between the orthosteric and an as-yet-undefined allosteric binding site of the FFA2 receptor that is occupied by 4-CMTB. PMID:21498659

  4. Quantifying Allosteric Communication via Both Concerted Structural Changes and Conformational Disorder with CARDS.

    Science.gov (United States)

    Singh, Sukrit; Bowman, Gregory R

    2017-04-11

    Allosteric (i.e., long-range) communication within proteins is crucial for many biological processes, such as the activation of signaling cascades in response to specific stimuli. However, the physical basis for this communication remains unclear. Existing computational methods for identifying allostery focus on the role of concerted structural changes, but recent experimental work demonstrates that disorder is also an important factor. Here, we introduce the Correlation of All Rotameric and Dynamical States (CARDS) framework for quantifying correlations between both the structure and disorder of different regions of a protein. To quantify disorder, we draw inspiration from methods for quantifying "dynamic heterogeneity" from chemical physics to classify segments of a dihedral's time evolution as being in either ordered or disordered regimes. To demonstrate the utility of this approach, we apply CARDS to the Catabolite Activator Protein (CAP), a transcriptional activator that is regulated by Cyclic Adenosine MonoPhosphate (cAMP) binding. We find that CARDS captures allosteric communication between the two cAMP-Binding Domains (CBDs). Importantly, CARDS reveals that this coupling is dominated by disorder-mediated correlations, consistent with NMR experiments that establish allosteric coupling between the CBDs occurs without a concerted structural change. CARDS also recapitulates an enhanced role for disorder in the communication between the DNA-Binding Domains (DBDs) and CBDs in the S62F variant of CAP. Finally, we demonstrate that using CARDS to find communication hotspots identifies regions of CAP that are in allosteric communication without foreknowledge of their identities. Therefore, we expect CARDS to be of great utility for both understanding and predicting allostery.

  5. Causality, transfer entropy, and allosteric communication landscapes in proteins with harmonic interactions.

    Science.gov (United States)

    Hacisuleyman, Aysima; Erman, Burak

    2017-06-01

    A fast and approximate method of generating allosteric communication landscapes in proteins is presented by using Schreiber's entropy transfer concept in combination with the Gaussian Network Model of proteins. Predictions of the model and the allosteric communication landscapes generated show that information transfer in proteins does not necessarily take place along a single path, but an ensemble of pathways is possible. The model emphasizes that knowledge of entropy only is not sufficient for determining allosteric communication and additional information based on time delayed correlations should be introduced, which leads to the presence of causality in proteins. The model provides a simple tool for mapping entropy sink-source relations into pairs of residues. By this approach, residues that should be manipulated to control protein activity may be determined. This should be of great importance for allosteric drug design and for understanding the effects of mutations on function. The model is applied to determine allosteric communication in three proteins, Ubiquitin, Pyruvate Kinase, and the PDZ domain. Predictions are in agreement with molecular dynamics simulations and experimental evidence. Proteins 2017; 85:1056-1064. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Small-world networks of residue interactions in the Abl kinase complexes with cancer drugs: topology of allosteric communication pathways can determine drug resistance effects.

    Science.gov (United States)

    Tse, A; Verkhivker, G M

    2015-07-01

    The human protein kinases play a fundamental regulatory role in orchestrating functional processes in complex cellular networks. Understanding how conformational equilibrium between functional kinase states can be modulated by ligand binding or mutations is critical for quantifying molecular basis of allosteric regulation and drug resistance. In this work, molecular dynamics simulations of the Abl kinase complexes with cancer drugs (Imatinib and Dasatinib) were combined with structure-based network modeling to characterize dynamics of the residue interaction networks in these systems. The results have demonstrated that structural architecture of kinase complexes can produce a small-world topology of the interaction networks. Our data have indicated that specific Imatinib binding to a small number of highly connected residues could lead to network-bridging effects and allow for efficient allosteric communication, which is mediated by a dominant pathway sensitive to the unphosphorylated Abl state. In contrast, Dasatinib binding to the active kinase form may activate a broader ensemble of allosteric pathways that are less dependent on the phosphorylation status of Abl and provide a better balance between the efficiency and resilience of signaling routes. Our results have unveiled how differences in the residue interaction networks and allosteric communications of the Abl kinase complexes can be directly related to drug resistance effects. This study offers a plausible perspective on how efficiency and robustness of the residue interaction networks and allosteric pathways in kinase structures may be associated with protein responses to drug binding.

  7. Guanine nucleotide binding to the Bateman domain mediates the allosteric inhibition of eukaryotic IMP dehydrogenases

    Science.gov (United States)

    Buey, Rubén M.; Ledesma-Amaro, Rodrigo; Velázquez-Campoy, Adrián; Balsera, Mónica; Chagoyen, Mónica; de Pereda, José M.; Revuelta, José L.

    2015-11-01

    Inosine-5'-monophosphate dehydrogenase (IMPDH) plays key roles in purine nucleotide metabolism and cell proliferation. Although IMPDH is a widely studied therapeutic target, there is limited information about its physiological regulation. Using Ashbya gossypii as a model, we describe the molecular mechanism and the structural basis for the allosteric regulation of IMPDH by guanine nucleotides. We report that GTP and GDP bind to the regulatory Bateman domain, inducing octamers with compromised catalytic activity. Our data suggest that eukaryotic and prokaryotic IMPDHs might have developed different regulatory mechanisms, with GTP/GDP inhibiting only eukaryotic IMPDHs. Interestingly, mutations associated with human retinopathies map into the guanine nucleotide-binding sites including a previously undescribed non-canonical site and disrupt allosteric inhibition. Together, our results shed light on the mechanisms of the allosteric regulation of enzymes mediated by Bateman domains and provide a molecular basis for certain retinopathies, opening the door to new therapeutic approaches.

  8. Guanine nucleotide binding to the Bateman domain mediates the allosteric inhibition of eukaryotic IMP dehydrogenases

    Science.gov (United States)

    Buey, Rubén M.; Ledesma-Amaro, Rodrigo; Velázquez-Campoy, Adrián; Balsera, Mónica; Chagoyen, Mónica; de Pereda, José M.; Revuelta, José L.

    2015-01-01

    Inosine-5′-monophosphate dehydrogenase (IMPDH) plays key roles in purine nucleotide metabolism and cell proliferation. Although IMPDH is a widely studied therapeutic target, there is limited information about its physiological regulation. Using Ashbya gossypii as a model, we describe the molecular mechanism and the structural basis for the allosteric regulation of IMPDH by guanine nucleotides. We report that GTP and GDP bind to the regulatory Bateman domain, inducing octamers with compromised catalytic activity. Our data suggest that eukaryotic and prokaryotic IMPDHs might have developed different regulatory mechanisms, with GTP/GDP inhibiting only eukaryotic IMPDHs. Interestingly, mutations associated with human retinopathies map into the guanine nucleotide-binding sites including a previously undescribed non-canonical site and disrupt allosteric inhibition. Together, our results shed light on the mechanisms of the allosteric regulation of enzymes mediated by Bateman domains and provide a molecular basis for certain retinopathies, opening the door to new therapeutic approaches. PMID:26558346

  9. Structural basis for cAMP-mediated allosteric control of the catabolite activator protein.

    Science.gov (United States)

    Popovych, Nataliya; Tzeng, Shiou-Ru; Tonelli, Marco; Ebright, Richard H; Kalodimos, Charalampos G

    2009-04-28

    The cAMP-mediated allosteric transition in the catabolite activator protein (CAP; also known as the cAMP receptor protein, CRP) is a textbook example of modulation of DNA-binding activity by small-molecule binding. Here we report the structure of CAP in the absence of cAMP, which, together with structures of CAP in the presence of cAMP, defines atomic details of the cAMP-mediated allosteric transition. The structural changes, and their relationship to cAMP binding and DNA binding, are remarkably clear and simple. Binding of cAMP results in a coil-to-helix transition that extends the coiled-coil dimerization interface of CAP by 3 turns of helix and concomitantly causes rotation, by approximately 60 degrees , and translation, by approximately 7 A, of the DNA-binding domains (DBDs) of CAP, positioning the recognition helices in the DBDs in the correct orientation to interact with DNA. The allosteric transition is stabilized further by expulsion of an aromatic residue from the cAMP-binding pocket upon cAMP binding. The results define the structural mechanisms that underlie allosteric control of this prototypic transcriptional regulatory factor and provide an illustrative example of how effector-mediated structural changes can control the activity of regulatory proteins.

  10. Computational modeling of allosteric communication reveals organizing principles of mutation-induced signaling in ABL and EGFR kinases.

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    Anshuman Dixit

    2011-10-01

    Full Text Available The emerging structural information about allosteric kinase complexes and the growing number of allosteric inhibitors call for a systematic strategy to delineate and classify mechanisms of allosteric regulation and long-range communication that control kinase activity. In this work, we have investigated mechanistic aspects of long-range communications in ABL and EGFR kinases based on the results of multiscale simulations of regulatory complexes and computational modeling of signal propagation in proteins. These approaches have been systematically employed to elucidate organizing molecular principles of allosteric signaling in the ABL and EGFR multi-domain regulatory complexes and analyze allosteric signatures of the gate-keeper cancer mutations. We have presented evidence that mechanisms of allosteric activation may have universally evolved in the ABL and EGFR regulatory complexes as a product of a functional cross-talk between the organizing αF-helix and conformationally adaptive αI-helix and αC-helix. These structural elements form a dynamic network of efficiently communicated clusters that may control the long-range interdomain coupling and allosteric activation. The results of this study have unveiled a unifying effect of the gate-keeper cancer mutations as catalysts of kinase activation, leading to the enhanced long-range communication among allosterically coupled segments and stabilization of the active kinase form. The results of this study can reconcile recent experimental studies of allosteric inhibition and long-range cooperativity between binding sites in protein kinases. The presented study offers a novel molecular insight into mechanistic aspects of allosteric kinase signaling and provides a quantitative picture of activation mechanisms in protein kinases at the atomic level.

  11. Computational Analysis of Residue Interaction Networks and Coevolutionary Relationships in the Hsp70 Chaperones: A Community-Hopping Model of Allosteric Regulation and Communication.

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    Gabrielle Stetz

    2017-01-01

    Full Text Available Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks and signaling pathways. We found that functional sites involved in allosteric regulation of Hsp70 may be characterized by structural stability, proximity to global hinge centers and local structural environment that is enriched by highly coevolving flexible residues. These specific characteristics may be necessary for regulation of allosteric structural transitions and could distinguish regulatory sites from nonfunctional conserved residues. The observed confluence of dynamics correlations and coevolutionary residue couplings with global networking features may determine modular organization of allosteric interactions and dictate localization of key mediating sites. Community analysis of the residue interaction networks revealed that concerted rearrangements of local interacting modules at the inter-domain interface may be responsible for global structural changes and a population shift in the DnaK chaperone. The inter-domain communities in the Hsp70 structures harbor the majority of regulatory residues involved in allosteric signaling, suggesting that these sites could be integral to the network organization and coordination of structural changes. Using a network-based formalism of

  12. Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

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    Amor, B. R. C.; Schaub, M. T.; Yaliraki, S. N.; Barahona, M.

    2016-08-01

    Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites.

  13. Computer Mediated Communication

    Science.gov (United States)

    Fano, Robert M.

    1984-08-01

    The use of computers in organizations is discussed in terms of its present and potential role in facilitating and mediating communication between people. This approach clarifies the impact that computers may have on the operation of organizations and on the individuals comprising them. Communication, which is essential to collaborative activities, must be properly controlled to protect individual and group privacy, which is equally essential. Our understanding of the human and organizational aspects of controlling communication and access to information presently lags behind our technical ability to implement the controls that may be needed.

  14. Mediatization and Government Communication

    DEFF Research Database (Denmark)

    Laursen, Bo; Valentini, Chiara

    2015-01-01

    in the light of mediatization and government communication theories. Without one pan-European public sphere, the European Parliament, like the other European Union (EU) institutions, competes with national actors for the news media’s attention in the EU’s twenty-eight national public spheres, where EU affairs...

  15. Lipid-Mediated Regulation of Embedded Receptor Kinases via Parallel Allosteric Relays.

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    Ghosh, Madhubrata; Wang, Loo Chien; Ramesh, Ranita; Morgan, Leslie K; Kenney, Linda J; Anand, Ganesh S

    2017-02-28

    Membrane-anchored receptors are essential cellular signaling elements for stimulus sensing, propagation, and transmission inside cells. However, the contributions of lipid interactions to the function and dynamics of embedded receptor kinases have not been described in detail. In this study, we used amide hydrogen/deuterium exchange mass spectrometry, a sensitive biophysical approach, to probe the dynamics of a membrane-embedded receptor kinase, EnvZ, together with functional assays to describe the role of lipids in receptor kinase function. Our results reveal that lipids play an important role in regulating receptor function through interactions with transmembrane segments, as well as through peripheral interactions with nonembedded domains. Specifically, the lipid membrane allosterically modulates the activity of the embedded kinase by altering the dynamics of a glycine-rich motif that is critical for phosphotransfer from ATP. This allostery in EnvZ is independent of membrane composition and involves direct interactions with transmembrane and periplasmic segments, as well as peripheral interactions with nonembedded domains of the protein. In the absence of the membrane-spanning regions, lipid allostery is propagated entirely through peripheral interactions. Whereas lipid allostery impacts the phosphotransferase function of the kinase, extracellular stimulus recognition is mediated via a four-helix bundle subdomain located in the cytoplasm, which functions as the osmosensing core through osmolality-dependent helical stabilization. Our findings emphasize the functional modularity in a membrane-embedded kinase, separated into membrane association, phosphotransferase function, and stimulus recognition. These components are integrated through long-range communication relays, with lipids playing an essential role in regulation.

  16. Extracellular loop 2 of the free Fatty Acid receptor 2 mediates allosterism of a phenylacetamide ago-allosteric modulator

    DEFF Research Database (Denmark)

    Smith, Nicola J; Ward, Richard J; Stoddart, Leigh A;

    2011-01-01

    Allosteric agonists are powerful tools for exploring the pharmacology of closely related G protein-coupled receptors that have nonselective endogenous ligands, such as the short chain fatty acids at free fatty acid receptors 2 and 3 (FFA2/GPR43 and FFA3/GPR41, respectively). We explored the molec...

  17. Mediatization and Government Communication

    DEFF Research Database (Denmark)

    Laursen, Bo; Valentini, Chiara

    2015-01-01

    in the light of mediatization and government communication theories. Without one pan-European public sphere, the European Parliament, like the other European Union (EU) institutions, competes with national actors for the news media’s attention in the EU’s twenty-eight national public spheres, where EU affairs......, and particularly into the thinking that guides the efforts of these European Parliament officials to increase European citizens’ awareness of, and support for, the European Parliament that is meant to voice the citizens’ concerns in political processes at the EU level....

  18. Allosteric modulation of sigma-1 receptors by SKF83959 inhibits microglia-mediated inflammation.

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    Wu, Zhuang; Li, Linlang; Zheng, Long-Tai; Xu, Zhihong; Guo, Lin; Zhen, Xuechu

    2015-09-01

    Recent studies have shown that sigma-1 receptor orthodox agonists can inhibit neuroinflammation. SKF83959 (3-methyl-6-chloro-7,8-hydroxy-1-[3-methylphenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine), an atypical dopamine receptor-1 agonist, has been recently identified as a potent allosteric modulator of sigma-1 receptor. Here, we investigated the anti-inflammatory effects of SKF83959 in lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results indicated that SKF83959 significantly suppressed the expression/release of the pro-inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), and inhibited the generation of reactive oxygen species. All of these responses were blocked by selective sigma-1 receptor antagonists (BD1047 or BD1063) and by ketoconazole (an inhibitor of enzyme cytochrome c17 to inhibit the synthesis of endogenous dehydroepiandrosterone, DHEA). Additionally, we found that SKF83959 promoted the binding activity of DHEA with sigma-1 receptors, and enhanced the inhibitory effects of DHEA on LPS-induced microglia activation in a synergic manner. Furthermore, in a microglia-conditioned media system, SKF83959 inhibited the cytotoxicity of conditioned medium generated by LPS-activated microglia toward HT-22 neuroblastoma cells. Taken together, our study provides the first evidence that allosteric modulation of sigma-1 receptors by SKF83959 inhibits microglia-mediated inflammation. SKF83959 is a potent allosteric modulator of sigma-1 receptor. Our results indicated that SKF83959 enhanced the activity of endogenous dehydroepiandrosterone (DHEA) in a synergic manner, and inhibited the activation of BV2 microglia and the expression/release of the pro-inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS).

  19. Allosteric site-mediated active site inhibition of PBP2a using Quercetin 3-O-rutinoside and its combination.

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    Rani, Nidhi; Vijayakumar, Saravanan; P T V, Lakshmi; Arunachalam, Annamalai

    2016-08-01

    Recent crystallographic study revealed the involvement of allosteric site in active site inhibition of penicillin binding protein (PBP2a), where one molecule of Ceftaroline (Cef) binds to the allosteric site of PBP2a and paved way for the other molecule (Cef) to bind at the active site. Though Cef has the potency to inhibit the PBP2a, its adverse side effects are of major concern. Previous studies have reported the antibacterial property of Quercetin derivatives, a group of natural compounds. Hence, the present study aims to evaluate the effect of Quercetin 3-o-rutinoside (Rut) in allosteric site-mediated active site inhibition of PBP2a. The molecular docking studies between allosteric site and ligands (Rut, Que, and Cef) revealed a better binding efficiency (G-score) of Rut (-7.790318) and Cef (-6.194946) with respect to Que (-5.079284). Molecular dynamic (MD) simulation studies showed significant changes at the active site in the presence of ligands (Rut and Cef) at allosteric site. Four different combinations of Rut and Cef were docked and their G-scores ranged between -6.320 and -8.623. MD studies revealed the stability of the key residue (Ser403) with Rut being at both sites, compared to other complexes. Morphological analysis through electron microscopy confirmed that combination of Rut and Cefixime was able to disturb the bacterial cell membrane in a similar fashion to that of Rut and Cefixime alone. The results of this study indicate that the affinity of Rut at both sites were equally good, with further validations Rut could be considered as an alternative for inhibiting MRSA growth.

  20. Allosteric communication in myosin V: from small conformational changes to large directed movements.

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    M Cecchini

    Full Text Available The rigor to post-rigor transition in myosin, a consequence of ATP binding, plays an essential role in the Lymn-Taylor functional cycle because it results in the dissociation of the actomyosin complex after the powerstroke. On the basis of the X-ray structures of myosin V, we have developed a new normal mode superposition model for the transition path between the two states. Rigid-body motions of the various subdomains and specific residues at the subdomain interfaces are key elements in the transition. The allosteric communication between the nucleotide binding site and the U50/L50 cleft is shown to result from local changes due to ATP binding, which induce large amplitude motions that are encoded in the structure of the protein. The triggering event is the change in the interaction of switch I and the P-loop, which is stabilized by ATP binding. The motion of switch I, which is a relatively rigid element of the U50 subdomain, leads directly to a partial opening of the U50/L50 cleft; the latter is expected to weaken the binding of myosin to actin. The calculated transition path demonstrates the nature of the subdomain coupling and offers an explanation for the mutual exclusion of ATP and actin binding. The mechanism of the uncoupling of the converter from the motor head, an essential part of the transition, is elucidated. The origin of the partial untwisting of the central beta-sheet in the rigor to post-rigor transition is described.

  1. Structure-based network analysis of activation mechanisms in the ErbB family of receptor tyrosine kinases: the regulatory spine residues are global mediators of structural stability and allosteric interactions.

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    Kevin A James

    Full Text Available The ErbB protein tyrosine kinases are among the most important cell signaling families and mutation-induced modulation of their activity is associated with diverse functions in biological networks and human disease. We have combined molecular dynamics simulations of the ErbB kinases with the protein structure network modeling to characterize the reorganization of the residue interaction networks during conformational equilibrium changes in the normal and oncogenic forms. Structural stability and network analyses have identified local communities integrated around high centrality sites that correspond to the regulatory spine residues. This analysis has provided a quantitative insight to the mechanism of mutation-induced "superacceptor" activity in oncogenic EGFR dimers. We have found that kinase activation may be determined by allosteric interactions between modules of structurally stable residues that synchronize the dynamics in the nucleotide binding site and the αC-helix with the collective motions of the integrating αF-helix and the substrate binding site. The results of this study have pointed to a central role of the conserved His-Arg-Asp (HRD motif in the catalytic loop and the Asp-Phe-Gly (DFG motif as key mediators of structural stability and allosteric communications in the ErbB kinases. We have determined that residues that are indispensable for kinase regulation and catalysis often corresponded to the high centrality nodes within the protein structure network and could be distinguished by their unique network signatures. The optimal communication pathways are also controlled by these nodes and may ensure efficient allosteric signaling in the functional kinase state. Structure-based network analysis has quantified subtle effects of ATP binding on conformational dynamics and stability of the EGFR structures. Consistent with the NMR studies, we have found that nucleotide-induced modulation of the residue interaction networks is not

  2. The allosteric behavior of Fur mediates oxidative stress signal transduction in Helicobacter pylori

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    Simone ePelliciari

    2015-08-01

    Full Text Available The microaerophilic gastric pathogen Helicobacter pylori is exposed to oxidative stress originating from the aerobic environment, the oxidative burst of phagocytes and the formation of reactive oxygen species, catalyzed by iron excess. Accordingly, the expression of genes involved in oxidative stress defense have been repeatedly linked to the ferric uptake regulator Fur. Moreover, mutations in the Fur protein affect the resistance to metronidazole, likely due to loss-of-function in the regulation of genes involved in redox control. Although many advances in the molecular understanding of HpFur function were made, little is known about the mechanisms that enable Fur to mediate the responses to oxidative stress.Here we show that iron-inducible, apo-Fur repressed genes, such as pfr and hydA, are induced shortly after oxidative stress, while their oxidative induction is lost in a fur knockout strain. On the contrary, holo-Fur repressed genes, such as frpB1 and fecA1, vary modestly in response to oxidative stress. This indicates that the oxidative stress signal specifically targets apo-Fur repressed genes, rather than impairing indiscriminately the regulatory function of Fur. Footprinting analyses showed that the oxidative signal strongly impairs the binding affinity of Fur towards apo-operators, while the binding towards holo-operators is less affected. Further evidence is presented that a reduced state of Fur is needed to maintain apo-repression, while oxidative conditions shift the preferred binding architecture of Fur towards the holo-operator binding conformation, even in the absence of iron. Together the results demonstrate that the allosteric regulation of Fur enables transduction of oxidative stress signals in H. pylori, supporting the concept that apo-Fur repressed genes can be considered oxidation inducible Fur regulatory targets. These findings may have important implications in the study of H. pylori treatment and resistance to

  3. The Use of Communication Strategies in Computer-Mediated Communication.

    Science.gov (United States)

    Smith, Bryan

    2003-01-01

    Examines communication strategy use among adult learners of English in a computer-mediated environment. Specifically explored communication strategies employed during problem-free discourse as well as compensatory strategy use during task-based computer-mediated communication. Strategy use was also examined relative to communicative task type.…

  4. Integrating Computer-Mediated Communication Strategy Instruction

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    McNeil, Levi

    2016-01-01

    Communication strategies (CSs) play important roles in resolving problematic second language interaction and facilitating language learning. While studies in face-to-face contexts demonstrate the benefits of communication strategy instruction (CSI), there have been few attempts to integrate computer-mediated communication and CSI. The study…

  5. Computer-Mediated Communication on the Internet.

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    Herring, Susan C.

    2002-01-01

    This review of computer-mediated communication (CMC) on the Internet focuses on empirical research in noninstitutional and nonorganizational contexts. Highlights include modes of CMC; appropriate uses; social effects; effects on language and communication; freedom of expression; community; personal impacts; privacy; ethics; democracy;…

  6. Differential effects of CSF-1R D802V and KIT D816V homologous mutations on receptor tertiary structure and allosteric communication.

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    Priscila Da Silva Figueiredo Celestino Gomes

    Full Text Available The colony stimulating factor-1 receptor (CSF-1R and the stem cell factor receptor KIT, type III receptor tyrosine kinases (RTKs, are important mediators of signal transduction. The normal functions of these receptors can be compromised by gain-of-function mutations associated with different physiopatological impacts. Whereas KIT D816V/H mutation is a well-characterized oncogenic event and principal cause of systemic mastocytosis, the homologous CSF-1R D802V has not been identified in human cancers. The KIT D816V oncogenic mutation triggers resistance to the RTK inhibitor Imatinib used as first line treatment against chronic myeloid leukemia and gastrointestinal tumors. CSF-1R is also sensitive to Imatinib and this sensitivity is altered by mutation D802V. Previous in silico characterization of the D816V mutation in KIT evidenced that the mutation caused a structure reorganization of the juxtamembrane region (JMR and facilitated its departure from the kinase domain (KD. In this study, we showed that the equivalent CSF-1R D802V mutation does not promote such structural effects on the JMR despite of a reduction on some key H-bonds interactions controlling the JMR binding to the KD. In addition, this mutation disrupts the allosteric communication between two essential regulatory fragments of the receptors, the JMR and the A-loop. Nevertheless, the mutation-induced shift towards an active conformation observed in KIT D816V is not observed in CSF-1R D802V. The distinct impact of equivalent mutation in two homologous RTKs could be associated with the sequence difference between both receptors in the native form, particularly in the JMR region. A local mutation-induced perturbation on the A-loop structure observed in both receptors indicates the stabilization of an inactive non-inhibited form, which Imatinib cannot bind.

  7. Variations in clique and community patterns in protein structures during allosteric communication: investigation of dynamically equilibrated structures of methionyl tRNA synthetase complexes.

    Science.gov (United States)

    Ghosh, Amit; Vishveshwara, Saraswathi

    2008-11-04

    The allosteric concept has played a key role in understanding the biological functions of proteins. The rigidity or plasticity and the conformational population are the two important ideas invoked in explaining the allosteric effect. Although molecular insights have been gained from a large number of structures, a precise assessment of the ligand-induced conformational changes in proteins at different levels, ranging from gross topology to intricate details, remains a challenge. In this study, we have explored the conformational changes in the complexes of methionyl tRNA synthetase (MetRS) through novel network parameters such as cliques and communities, which identify the rigid regions in the protein structure networks (PSNs) constructed from the noncovalent interactions of amino acid side chains. MetRS belongs to the aminoacyl tRNA synthetase (aaRS) family that plays a crucial role in the translation of genetic code. These enzymes are modular with distinct domains from which extensive genetic, kinetic, and structural data are available, highlighting the role of interdomain communication. The network parameters evaluated here on the conformational ensembles of MetRS complexes, generated from molecular dynamics simulations, have enabled us to understand the interdomain communication in detail. Additionally, the characterization of conformational changes in terms of cliques and communities has also become possible, which had eluded conventional analyses. Furthermore, we find that most of the residues participating in cliques and communities are strikingly different from those that take part in long-range communication. The cliques and communities evaluated here for the first time on PSNs have beautifully captured the local geometries in detail within the framework of global topology. Here the allosteric effect is revealed at the residue level via identification of the important residues specific for structural rigidity and functional flexibility in MetRS. This ought

  8. Allosteric activation of protein phosphatase 2C by D-chiro-inositol-galactosamine, a putative mediator mimetic of insulin action.

    Science.gov (United States)

    Brautigan, D L; Brown, M; Grindrod, S; Chinigo, G; Kruszewski, A; Lukasik, S M; Bushweller, J H; Horal, M; Keller, S; Tamura, S; Heimark, D B; Price, J; Larner, A N; Larner, J

    2005-08-23

    Insulin-stimulated glucose disposal in skeletal muscle proceeds predominantly through a nonoxidative pathway with glycogen synthase as a rate-limiting enzyme, yet the mechanisms for insulin activation of glycogen synthase are not understood despite years of investigation. Isolation of putative insulin second messengers from beef liver yielded a pseudo-disaccharide consisting of pinitol (3-O-methyl-d-chiro-inositol) beta-1,4 linked to galactosamine chelated with Mn(2+) (called INS2). Here we show that chemically synthesized INS2 has biological activity that significantly enhances insulin reduction of hyperglycemia in streptozotocin diabetic rats. We used computer modeling to dock INS2 onto the known three-dimensional crystal structure of protein phosphatase 2C (PP2C). Modeling and FlexX/CScore energy minimization predicted a unique favorable site on PP2C for INS2 in a surface cleft adjacent to the catalytic center. Binding of INS2 is predicted to involve formation of multiple H-bonds, including one with residue Asp163. Wild-type PP2C activity assayed with a phosphopeptide substrate was potently stimulated in a dose-dependent manner by INS2. In contrast, the D163A mutant of PP2C was not activated by INS2. The D163A mutant and wild-type PP2C in the absence of INS2 had the same Mn(2+)-dependent phosphatase activity with p-nitrophenyl phosphate as a substrate, showing that this mutation did not disrupt the catalytic site. We propose that INS2 allosterically activates PP2C, fulfilling the role of a putative mediator mimetic of insulin signaling to promote protein dephosphorylation and metabolic responses.

  9. Computer Mediated Communication (CMC e Second Life

    Directory of Open Access Journals (Sweden)

    Annalisa Boniello

    2013-03-01

    Full Text Available In questo contributo sono riportate alcune esperienze e sperimentazioni didattiche che descrivono occasioni di comunicazione formativa (Computer Mediated Communication – CMC attraverso ambienti 3D quali Second Life (SL. Sono inoltre evidenziati e descritti i principali strumenti di comunicazione in SL e il loro utilizzo.

  10. Computer-Mediated Communication and Interpersonal Perceptions.

    Science.gov (United States)

    Adkins, Mark E.

    A study investigated the conditions under which computer-mediated communication (CMC) (electronic mail) senders were perceived as self-absorbed by CMC receivers. Experience with electronic mail was the independent variable and perceived self-absorption, attraction, and homophily were the dependent variables. Two-hundred fifty volunteers from a…

  11. Computer-Mediated Communication: An Experimental Study.

    Science.gov (United States)

    Smith, William E.

    1994-01-01

    Investigates the effectiveness of a computer-mediated communication system in supplementing traditional instruction in a media law course. Finds mixed results on measures of satisfaction and no significant improvement on exam scores. Notes that the system required more time from the instructor and students. (SR)

  12. Teaching Responsibly with Technology-Mediated Communication

    Science.gov (United States)

    Veltsos, Jennifer R.; Veltsos, Christophe

    2010-01-01

    Technology-mediated communication, or "new media," such as blogs, Twitter, wikis, and social network sites, can be an endless source of ideas for activities or inspiration for classroom discussion. Many instructors ask students to monitor current events by following keywords and industry leaders on Twitter and reading both corporate and trade…

  13. Teaching Responsibly with Technology-Mediated Communication

    Science.gov (United States)

    Veltsos, Jennifer R.; Veltsos, Christophe

    2010-01-01

    Technology-mediated communication, or "new media," such as blogs, Twitter, wikis, and social network sites, can be an endless source of ideas for activities or inspiration for classroom discussion. Many instructors ask students to monitor current events by following keywords and industry leaders on Twitter and reading both corporate and…

  14. Synchronous Computer-Mediated Communication and Interaction

    Science.gov (United States)

    Ziegler, Nicole

    2016-01-01

    The current study reports on a meta-analysis of the relative effectiveness of interaction in synchronous computer-mediated communication (SCMC) and face-to-face (FTF) contexts. The primary studies included in the analysis were journal articles and dissertations completed between 1990 and 2012 (k = 14). Results demonstrate that interaction in SCMC…

  15. Conversation Analysis of Computer-Mediated Communication

    Science.gov (United States)

    Gonzalez-Lloret, Marta

    2011-01-01

    The potential of computer-mediated communication (CMC) for language learning resides mainly in the possibility that learners have to engage with other speakers of the language, including L1 speakers. The inclusion of CMC in the L2 classroom provides an opportunity for students to utilize authentic language in real interaction, rather than the more…

  16. Exosomes: mediators of communication in eukaryotes.

    Science.gov (United States)

    Lopez-Verrilli, María A; Court, Felipe A

    2013-01-01

    In addition to the established mechanisms of intercellular signaling, a new way of communication has gained much attention in the last decade: communication mediated by exosomes. Exosomes are nanovesicles (with a diameter of 40-120 nm) secreted into the extracellular space by the multivesicular endosome after its outer membrane fuses with the plasma membrane. Once released, exosomes modulate the response of the recipient cells that recognize them. This indicates that exosomes operate in a specific manner and participate in the regulation of the target cell. Remarkably, exosomes occur from unicellular organisms to mammals, suggesting an evolutionarily conserved mechanism of communication. In this review we describe the cascade of exosome formation, intracellular traffic, secretion, and internalization by recipient cells, and review their most relevant effects. We also highlight important steps that are still poorly understood.

  17. Selective peptide inhibitors of bifunctional thymidylate synthase-dihydrofolate reductase from Toxoplasma gondii provide insights into domain-domain communication and allosteric regulation.

    Science.gov (United States)

    Landau, Mark J; Sharma, Hitesh; Anderson, Karen S

    2013-09-01

    The bifunctional enzyme thymidylate synthase-dihydrofolate reductase (TS-DHFR) plays an essential role in DNA synthesis and is unique to several species of pathogenic protozoans, including the parasite Toxoplasma gondii. Infection by T. gondii causes the prevalent disease toxoplasmosis, for which TS-DHFR is a major therapeutic target. Here, we design peptides that target the dimer interface between the TS domains of bifunctional T. gondii TS-DHFR by mimicking β-strands at the interface, revealing a previously unknown allosteric target. The current study shows that these β-strand mimetic peptides bind to the apo-enzyme in a species-selective manner to inhibit both the TS and distal DHFR. Fluorescence spectroscopy was used to monitor conformational switching of the TS domain and demonstrate that these peptides induce a conformational change in the enzyme. Using structure-guided mutagenesis, nonconserved residues in the linker between TS and DHFR were identified that play a key role in domain-domain communication and in peptide inhibition of the DHFR domain. These studies validate allosteric inhibition of apo-TS, specifically at the TS-TS interface, as a potential target for novel, species-specific therapeutics for treating T. gondii parasitic infections and overcoming drug resistance. © 2013 The Protein Society.

  18. An allosteric conduit facilitates dynamic multisite substrate recognition by the SCFCdc4 ubiquitin ligase

    Science.gov (United States)

    Csizmok, Veronika; Orlicky, Stephen; Cheng, Jing; Song, Jianhui; Bah, Alaji; Delgoshaie, Neda; Lin, Hong; Mittag, Tanja; Sicheri, Frank; Chan, Hue Sun; Tyers, Mike; Forman-Kay, Julie D.

    2017-01-01

    The ubiquitin ligase SCFCdc4 mediates phosphorylation-dependent elimination of numerous substrates by binding one or more Cdc4 phosphodegrons (CPDs). Methyl-based NMR analysis of the Cdc4 WD40 domain demonstrates that Cyclin E, Sic1 and Ash1 degrons have variable effects on the primary Cdc4WD40 binding pocket. Unexpectedly, a Sic1-derived multi-CPD substrate (pSic1) perturbs methyls around a previously documented allosteric binding site for the chemical inhibitor SCF-I2. NMR cross-saturation experiments confirm direct contact between pSic1 and the allosteric pocket. Phosphopeptide affinity measurements reveal negative allosteric communication between the primary CPD and allosteric pockets. Mathematical modelling indicates that the allosteric pocket may enhance ultrasensitivity by tethering pSic1 to Cdc4. These results suggest negative allosteric interaction between two distinct binding pockets on the Cdc4WD40 domain may facilitate dynamic exchange of multiple CPD sites to confer ultrasensitive dependence on substrate phosphorylation.

  19. The structure and allosteric regulation of glutamate dehydrogenase.

    Science.gov (United States)

    Li, Ming; Li, Changhong; Allen, Aron; Stanley, Charles A; Smith, Thomas J

    2011-09-01

    Glutamate dehydrogenase (GDH) has been extensively studied for more than 50 years. Of particular interest is the fact that, while considered by most to be a 'housekeeping' enzyme, the animal form of GDH is heavily regulated by a wide array of allosteric effectors and exhibits extensive inter-subunit communication. While the chemical mechanism for GDH has remained unchanged through epochs of evolution, it was not clear how or why animals needed to evolve such a finely tuned form of this enzyme. As reviewed here, recent studies have begun to elucidate these issues. Allosteric regulation first appears in the Ciliates and may have arisen to accommodate evolutionary changes in organelle function. The occurrence of allosteric regulation appears to be coincident with the formation of an 'antenna' like feature rising off the tops of the subunits that may be necessary to facilitate regulation. In animals, this regulation further evolved as GDH became integrated into a number of other regulatory pathways. In particular, mutations in GDH that abrogate GTP inhibition result in dangerously high serum levels of insulin and ammonium. Therefore, allosteric regulation of GDH plays an important role in insulin homeostasis. Finally, several compounds have been identified that block GDH-mediated insulin secretion that may be to not only find use in treating these insulin disorders but to kill tumors that require glutamine metabolism for cellular energy.

  20. The anglicisms in computer-mediated communication

    Directory of Open Access Journals (Sweden)

    Jan Lazar

    2012-01-01

    Full Text Available Although French is a Romance language descendant from the Latin, there is of course some influence of other languages on it. English is perhaps the most important source of loan-words for the present French language. Our article is focused on new forms of written communication, mainly computer-mediated communication (CMC. The main aim of this article is to analyze the loan-words, especially the anglicisms that are used by chatters in various French chats. After examining the motivations of loan, the article studies the frequency of anglicisms in three chats and observes their grammatical adaptation in the context of CMC. A huge richness of anglicisms is illustrated by concrete examples taken from our corpus.

  1. Using THz time-scale infrared spectroscopy to examine the role of collective, thermal fluctuations in the formation of myoglobin allosteric communication pathways and ligand specificity.

    Science.gov (United States)

    Woods, K N

    2014-06-28

    In this investigation we use THz time-scale spectroscopy to conduct an initial set of studies on myoglobin with the aim of providing further insight into the global, collective thermal fluctuations in the protein that have been hypothesized to play a prominent role in the dynamic formation of transient ligand channels as well as in shaping the molecular level basis for ligand discrimination. Using the two ligands O2 and CO, we have determined that the perturbation from the heme-ligand complex has a strong influence on the characteristics of the myoglobin collective dynamics that are excited upon binding. Further, the differences detected in the collective protein motions in Mb-O2 compared with those in Mb-CO appear to be intimately tied with the pathways of long-range allosteric communication in the protein, which ultimately determine the trajectories selected by the respective ligands on the path to and from the heme-binding cavity.

  2. An allosteric binding site at the human serotonin transporter mediates the inhibition of escitalopram by R-citalopram: kinetic binding studies with the ALI/VFL-SI/TT mutant.

    Science.gov (United States)

    Zhong, Huailing; Hansen, Kasper B; Boyle, Noel J; Han, Kiho; Muske, Galina; Huang, Xinyan; Egebjerg, Jan; Sánchez, Connie

    2009-10-25

    The human serotonin transporter (hSERT) has primary and allosteric binding sites for escitalopram and R-citalopram. Previous studies have established that the interaction of these two compounds at a low affinity allosteric binding site of hSERT can affect the dissociation of [(3)H]escitalopram from hSERT. The allosteric binding site involves a series of residues in the 10th, 11th, and 12th trans-membrane domains of hSERT. The low affinity allosteric activities of escitalopram and R-citalopram are essentially eliminated in a mutant hSERT with changes in some of these residues, namely A505V, L506F, I507L, S574T, I575T, as measured in dissociation binding studies. We confirm that in association binding experiments, R-citalopram at clinically relevant concentrations reduces the association rate of [(3)H]escitalopram as a ligand to wild type hSERT. We demonstrate that the ability of R-citalopram to reduce the association rate of escitalopram is also abolished in the mutant hSERT (A505V, L506F, I507L, S574T, I575T), along with the expected disruption the low affinity allosteric function on dissociation binding. This suggests that the allosteric binding site mediates both the low affinity and higher affinity interactions between R-citalopram, escitalopram, and hSERT. Our data add an additional structural basis for the different efficacies of escitalopram compared to racemic citalopram reported in animal studies and clinical trials, and substantiate the hypothesis that hSERT has complex allosteric mechanisms underlying the unexplained in vivo activities of its inhibitors.

  3. A Theory of Electronic Propinquity: Mediated Communication in Organizations

    Science.gov (United States)

    Korzenny, Felipe

    1978-01-01

    Proposes a theoretical approach to mediated communication in organizations suggesting that man-machine interface in mediated human communication is more effectively dealt with by using a comprehensive theoretical approach rather than separate communication devices that are tested as they appear in the market. (MH)

  4. Exosome mediated communication within the tumor microenvironment.

    Science.gov (United States)

    Milane, Lara; Singh, Amit; Mattheolabakis, George; Suresh, Megha; Amiji, Mansoor M

    2015-12-10

    It is clear that exosomes (endosome derived vesicles) serve important roles in cellular communication both locally and distally and that the exosomal process is abnormal in cancer. Cancer cells are not malicious cells; they are cells that represent 'survival of the fittest' at its finest. All of the mutations, abnormalities, and phenomenal adaptations to a hostile microenvironment, such as hypoxia and nutrient depletion, represent the astute ability of cancer cells to adapt to their environment and to intracellular changes to achieve a single goal - survival. The aberrant exosomal process in cancer represents yet another adaptation that promotes survival of cancer. Cancer cells can secrete more exosomes than healthy cells, but more importantly, the content of cancer cells is distinct. An illustrative distinction is that exosomes derived from cancer cells contain more microRNA than healthy cells and unlike exosomes released from healthy cells, this microRNA can be associated with the RNA-induced silencing complex (RISC) which is required for processing mature and biologically active microRNA. Cancer derived exosomes have the ability to transfer metastatic potential to a recipient cell and cancer exosomes function in the physical process of invasion. In this review we conceptualize the aberrant exosomal process (formation, content selection, loading, trafficking, and release) in cancer as being partially attributed to cancer specific differences in the endocytotic process of receptor recycling/degradation and plasma membrane remodeling and the function of the endosome as a signaling entity. We discuss this concept and, to advance comprehension of exosomal function in cancer as mediators of communication, we detail and discuss exosome biology, formation, and communication in health and cancer; exosomal content in cancer; exosomal biomarkers in cancer; exosome mediated communication in cancer metastasis, drug resistance, and interfacing with the immune system; and

  5. Wide-Area Computer-Mediated Communication in Business Writing.

    Science.gov (United States)

    Howard, Tharon

    1992-01-01

    Discusses the differences between computer-mediated communication (CMC) and print or oral communication. Describes advantages and problems of using electronic mail in a business context. Recommends research and teaching of CMC in the business writing classroom. (MM)

  6. Intergroup differentiation in computer-mediated communication : Effects of depersonalization

    NARCIS (Netherlands)

    Postmes, T; Spears, R; Lea, M

    2002-01-01

    Two studies examined intergroup discussions via computer-mediated communication systems. It was hypothesized that depersonalization, in comparison with individuated interaction, would increase the tendency for intergroup differentiation in attitudes and stereotypes, In Study 1, 24 groups communicate

  7. The nonverbal communication functions of emoticons in computer-mediated communication.

    Science.gov (United States)

    Lo, Shao-Kang

    2008-10-01

    Most past studies assume that computer-mediated communication (CMC) lacks nonverbal communication cues. However, Internet users have devised and learned to use emoticons to assist their communications. This study examined emoticons as a communication tool that, although presented as verbal cues, perform nonverbal communication functions. We therefore termed emoticons quasi-nonverbal cues.

  8. Professional networking using computer-mediated communication.

    Science.gov (United States)

    Washer, Peter

    Traditionally, professionals have networked with others in their field through attending conferences, professional organizations, direct mailing, and via the workplace. Recently, there have been new possibilities to network with other professionals using the internet. This article looks at the possibilities that the internet offers for professional networking, particularly e-mailing lists, newsgroups and membership databases, and compares them against more traditional methods of professional networking. The different types of computer-mediated communication are discussed and their relative merits and disadvantages are examined. The benefits and potential pitfalls of internet professional networking, as it relates to the nursing profession, are examined. Practical advice is offered on how the internet can be used as a means to foster professional networks of academic, clinical or research interests.

  9. Lid L11 of the glutamine amidotransferase domain of CTP synthase mediates allosteric GTP activation of glutaminase activity

    DEFF Research Database (Denmark)

    Willemoës, Martin; Mølgaard, Anne; Johansson, Eva

    2005-01-01

    of CTP synthase. In the GATase domain of the recently published structures of the Escherichia coli and Thermus thermophilus CTP synthases a loop region immediately proceeding amino acid residues forming the oxy-anion hole and named lid L11 is shown for the latter enzyme to be flexible and change position......GTP is an allosteric activator of CTP synthase and acts to increase the k(cat) for the glutamine-dependent CTP synthesis reaction. GTP is suggested, in part, to optimally orient the oxy-anion hole for hydrolysis of glutamine that takes place in the glutamine amidotransferase class I (GATase) domain...... with lid L11 and indicate that the GTP activation of glutamine dependent CTP synthesis may be explained by structural rearrangements around the oxy-anion hole of the GATase domain...

  10. The formation of group norms in computer-mediated communication

    NARCIS (Netherlands)

    Postmes, T; Spears, R; Lea, M

    2000-01-01

    The formation of group norms in computer-mediated communication (CMC) was examined among students who used e-mail as part of a course. A network analysis of group structures revealed that (a) content and form of communication is normative, group norms defining communication patterns within groups, (

  11. The formation of group norms in computer-mediated communication

    NARCIS (Netherlands)

    Postmes, T; Spears, R; Lea, M

    2000-01-01

    The formation of group norms in computer-mediated communication (CMC) was examined among students who used e-mail as part of a course. A network analysis of group structures revealed that (a) content and form of communication is normative, group norms defining communication patterns within groups, (

  12. Cross-Cultural Communication Patterns in Computer Mediated Communication

    Science.gov (United States)

    Panina, Daria; Kroumova, Maya

    2015-01-01

    There are important cultural differences in attitudes towards and use of electronic text communication. Consistent with Hall's high-context/low-context conceptualization of culture, electronic inter-cultural communication, just as verbal inter-cultural communication, is affected by the culturally-specific assumptions and preferences of message…

  13. Identification of the allosteric regulatory site of insulysin.

    Directory of Open Access Journals (Sweden)

    Nicholas Noinaj

    Full Text Available BACKGROUND: Insulin degrading enzyme (IDE is responsible for the metabolism of insulin and plays a role in clearance of the Aβ peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP. PRINCIPAL FINDINGS: The crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. In addition, changes in the dimer interface suggest a basis for communication between subunits. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.

  14. Identification of the Allosteric Regulatory Site of Insulysin

    Energy Technology Data Exchange (ETDEWEB)

    Noinaj, Nicholas; Bhasin, Sonia K.; Song, Eun Suk; Scoggin, Kirsten E.; Juliano, Maria A.; Juliano, Luiz; Hersh, Louis B.; Rodgers, David W.; Gerrard, Juliet Ann

    2011-06-24

    Background Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the Aβ peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP. Principal Findings The crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant) with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. In addition, changes in the dimer interface suggest a basis for communication between subunits. Conclusions/Significance Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.

  15. Identification of the Allosteric Regulatory Site of Insulysin

    Energy Technology Data Exchange (ETDEWEB)

    Noinaj, Nicholas; Bhasin, Sonia K.; Song, Eun Suk; Scoggin, Kirsten E.; Juliano, Maria A.; Juliano, Luiz; Hersh, Louis B.; Rodgers, David W. (U. Sao Paulo); (Kentucky)

    2012-05-25

    Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the A{beta} peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP. The crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant) with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. In addition, changes in the dimer interface suggest a basis for communication between subunits. Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.

  16. Lay Theories Regarding Computer-Mediated Communication in Remote Collaboration

    Directory of Open Access Journals (Sweden)

    Karl Parke

    2017-03-01

    Full Text Available Computer-mediated communication and remote collaboration has become an unexceptional norm as an educational modality for distance and open education, therefore the need to research and analyze students' online learning experience is necessary. This paper seeks to examine the assumptions and expectations held by students in regard to computer-mediated communication and how their lay theories developed and changed within the context of their practical experiences in conducting a remote collaborative project, through computer-mediated communication. We conducted a qualitative content analysis of students' final reports from an inter-institutional online course on computer-mediated communication and remote collaboration. The results show that students’ assumptions were altered and indicate the strong benefits of teaching how to collaborate remotely, especially if a blended approach of theory and practical application are combined.

  17. HUMAN COMMUNICATION AS MEDIATING THE UNITS OF PARAMETERISED ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    Josip Stepanic

    2004-06-01

    Full Text Available Human communication is prevalently a mediated process. Mediators are units of environment, which are attributed functions within the local value set. They are utilised in such a way as to optimise the change of human states. In this article, a mediator-centred interpretation of the human communication is given. The interpretation follows closely the concept of mediated interaction developed within physics. It is conjectured that collection of mediators, which the humans use, has a well-defined average. The averaged collection permits reliable interpretation as a human communication spectrum. Relation of the intensity of a spectral component with regard to different senses, and with regard to intensity of interaction is discussed.

  18. Computer-Mediated Communication Modality and Psychological Well-Being

    Science.gov (United States)

    Ess, Brian C.

    2013-01-01

    The growth of Internet usage in American society has added new modes of communication, primarily through computer-mediated communication (CMC)on the Internet. Research on the relationship between Internet use and psychological well-being has been mixed and this study attempted to reconcile the discrepancies in results by exploring the…

  19. Incorporating Computer-Mediated Communication in Project Work

    Science.gov (United States)

    Musa, Faridah; Mohamed, Maslawati; Mufti, Norlaila; Latiff, Rozmel Abdul; Amin, Maryam Mohamad

    2015-01-01

    In line with the new trend of using computer-mediated communication (CMC) as an innovative technique in teaching and learning at higher institutions, Facebook as a channel of CMC was employed in carrying out a project work in an Academic Communication Course. For this project, students worked in groups to discuss their work and share information…

  20. An Integrated Review of Emoticons in Computer-Mediated Communication

    OpenAIRE

    Aldunate, Nerea; González-Ibáñez, Roberto

    2017-01-01

    Facial expressions constitute a rich source of non-verbal cues in face-to-face communication. They provide interlocutors with resources to express and interpret verbal messages, which may affect their cognitive and emotional processing. Contrarily, computer-mediated communication (CMC), particularly text-based communication, is limited to the use of symbols to convey a message, where facial expressions cannot be transmitted naturally. In this scenario, people use emoticons as paralinguistic c...

  1. Mediated Communities in the Age of Electronic Communication

    Directory of Open Access Journals (Sweden)

    Gábor Szécsi

    2012-01-01

    Full Text Available The electronically mediated communication has transformed our notionof the relation between place and community. With a greater proportionof our communicative acts taking place via electronic media, physical co-presence, the co-located interpersonal relations are diminishing as determinants of the nature of human interactions. This paper argues that the electronically mediated communication contributes to the construction of new, mediated forms of communities which are based on the interaction or operational synthesis of virtual and physical communities. The appearance of these new forms of communitiesleads to a new conceptualization of the relation between self and community. The aim of this paper is to show that the medium of the mediatization and new conceptualization of community is a specific pictorial language of electronically mediated communication, the semantic structure of which offers new opportunities to grasp and understand the complex notion of new mediated communities and to adopt the idea of a new global, community building language in local and national communities.

  2. Improving Undergraduates' Critique via Computer Mediated Communication

    Science.gov (United States)

    Mohamad, Maslawati; Musa, Faridah; Amin, Maryam Mohamed; Mufti, Norlaila; Latiff, Rozmel Abdul; Sallihuddin, Nani Rahayu

    2014-01-01

    Our current university students, labeled as "Generation Y" or Millennials, are different from previous generations due to wide exposure to media. Being technologically savvy, they are accustomed to Internet for information and social media for socializing. In line with this current trend, teaching through computer mediated communication…

  3. INTERCULTURAL COMMUNICATION PATTERNS AND LANGUAGE USE IN COMPUTER MEDIATED-COMMUNICATION

    Directory of Open Access Journals (Sweden)

    Adriana Teodorescu

    2012-11-01

    Full Text Available This paper aims at analyzing the degree to which intercultural communication patterns are embedded in computer-mediated communication. Drawing on Hall’s and Hofstede’s intercultural communication dimensions, this study evaluates empirically high-versus-low context cultural orientations as reflected in the electronic medium, namely the blog, in three different cultures. Cultural variation is also analyzed in linguistic features and communication style in a synchronous mode of communication, by investigating data from several popular blogs from Japan, Germany and Italy.

  4. Pair Interactions and Mode of Communication: Comparing Face-to-Face and Computer Mediated Communication

    Science.gov (United States)

    Tan, Lan Liana; Wigglesworth, Gillian; Storch, Neomy

    2010-01-01

    In today's second language classrooms, students are often asked to work in pairs or small groups. Such collaboration can take place face-to-face, but now more often via computer mediated communication. This paper reports on a study which investigated the effect of the medium of communication on the nature of pair interaction. The study involved…

  5. Learners' Willingness to Communicate in Face-to-Face versus Oral Computer-Mediated Communication

    Science.gov (United States)

    Yanguas, Íñigo; Flores, Alayne

    2014-01-01

    The present study had two main goals: to explore performance differences in a task-based environment between face-to-face (FTF) and oral computer-mediated communication (OCMC) groups, and to investigate the relationship between trait-like willingness to communicate (WTC) and performance in the FTF and OCMC groups. Students from two intact…

  6. LIVING LONG-DISTANCE RELATIONSHIPS THROUGH COMPUTER-MEDIATED COMMUNICATION

    OpenAIRE

    Almond Pilar N. Aguila

    2009-01-01

    Overseas Filipino Workers (OFWs) and their loved ones in thePhilippines manage to have dynamic relationships despite physical distance with Computer-Mediated Communication (CMC) or the use of new media (the Internet and cellular phone). Theoretically guided by Marshall McLuhan and Stuart Hall, this paper presents three case studies that depict how individuals mindfully use communication technology to enact their relationships. Such interactions also entail the exchange of new ideas on gender ...

  7. LIVING LONG-DISTANCE RELATIONSHIPS THROUGH COMPUTER-MEDIATED COMMUNICATION

    OpenAIRE

    Almond Pilar N. Aguila

    2009-01-01

    Overseas Filipino Workers (OFWs) and their loved ones in thePhilippines manage to have dynamic relationships despite physical distance with Computer-Mediated Communication (CMC) or the use of new media (the Internet and cellular phone). Theoretically guided by Marshall McLuhan and Stuart Hall, this paper presents three case studies that depict how individuals mindfully use communication technology to enact their relationships. Such interactions also entail the exchange of new ideas on gender ...

  8. Patterns of Programmers' Use of Computer-Mediated Communications Systems

    Directory of Open Access Journals (Sweden)

    Chatpong Tangmanee

    2003-11-01

    Full Text Available Communication behavior of programmers plays an essential role in success of software development. Computer-mediated communication (CMC system, such as e-mail, or the World Wide Web (WWW, have substantial implications for coordinating work of programmers. Yet, no studies have dealt systematically with CMC behaviors of programmers. Drawing upon theories in organizational studies, information science, computer-mediated communication and software engineering, this research examines what programmers accomplish through CMC systems. Data were gathered from survey questionnaires mailed to 730 programmers, who are members of the Association of Computing Machinery (ACM and are involved in a variety of programming work. Based on factor analysis, the study found that programmers use CMC systems (1 to achieve progress in work-related tasks (i.e., task-related purposes, (2 to satisfy their social and emotional needs (i.e., socio-emotional purposes, and (3 to explore for information (i.e., exploring purposes. The findings of this research extend an insight into important patterns for which programmers use CMC systems. This insight has advanced theories of computer-mediated communication in the context of computer programmers. Also, practitioners, especially in software development, may use the results as guidelines in fostering a firm’s feasible network policy that fits with what their programming staff accomplish through computer-mediated communication.

  9. Communication as group process mediator of aircrew performance

    Science.gov (United States)

    Kanki, Barbara G.; Foushee, H. Clayton

    1989-01-01

    Considering recent operating experience as a group-level input factor, aspects of the communication process between crewmembers (captain and first officer) were explored as a possible mediator to performance. Communication patterns were defined by a speech-act typology adapted for the flight-deck setting and distinguished crews that had previously flown together (FT) from those that had not flown together (NFT). A more open communication channel and greater first officer participation in task-related topics was shown by FT crews, while NFT crews engaged in more nontask discourse.

  10. Communication as group process mediator of aircrew performance

    Science.gov (United States)

    Kanki, Barbara G.; Foushee, H. Clayton

    1989-01-01

    Considering recent operating experience as a group-level input factor, aspects of the communication process between crewmembers (captain and first officer) were explored as a possible mediator to performance. Communication patterns were defined by a speech-act typology adapted for the flight-deck setting and distinguished crews that had previously flown together (FT) from those that had not flown together (NFT). A more open communication channel and greater first officer participation in task-related topics was shown by FT crews, while NFT crews engaged in more nontask discourse.

  11. Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-mediated Allosteric Regulation of Factor VIIa Activity

    DEFF Research Database (Denmark)

    Sorensen, Anders B.; Madsen, Jesper Jonasson; Svensson, L. Anders;

    2016-01-01

    The complex of coagulation factor VIIa (FVIIa), a trypsin-like serine protease, and membrane-bound tissue factor (TF) initiates blood coagulation upon vascular injury. Binding of TF to FVIIa promotes allosteric conformational changes in the FVIIa protease domain and improves its catalytic propert...

  12. The utilization of Computer Mediated Communication for case study collaboration.

    Science.gov (United States)

    Gwozdek, Anne E; Klausner, Christine P; Kerschbaum, Wendy E

    2008-01-01

    Computer Mediated Communication (CMC) can be used as an effective tool for student communication and collaboration. First-year, first-semester dental hygiene students self-selected groups to develop dental hygiene process of care treatment plans, written reports, and oral case presentations based on assigned clinical cases. In consultation with the University of Michigan (UM) Digital Media Commons Collaborative Technologies Teams, CMC options were identified. Two chat rooms were established within the UM's Course Management System (CTools) to provide opportunities for synchronous (simultaneous, real-time) communication. One course blog site and 8 case blog sites were developed to provide students and instructors with electronic asynchronous (nonsimultaneous) communication formats. The purpose of this study was to evaluate the effectiveness of these technologies during group case study projects. CMC has the potential to provide an effective means of collaboration and communication when the technologies align with the purpose of the project and compliment the dynamics of student groups.

  13. Mapping a molecular link between allosteric inhibition and activation of the glycine receptor.

    Science.gov (United States)

    Miller, Paul S; Topf, Maya; Smart, Trevor G

    2008-10-01

    Cys-loop ligand-gated ion channels mediate rapid neurotransmission throughout the central nervous system. They possess agonist recognition sites and allosteric sites where modulators regulate ion channel function. Using strychnine-sensitive glycine receptors, we identified a scaffold of hydrophobic residues enabling allosteric communication between glycine-agonist binding loops A and D, and the Zn(2+)-inhibition site. Mutating these hydrophobic residues disrupted Zn(2+) inhibition, generating novel Zn(2+)-activated receptors and spontaneous channel activity. Homology modeling and electrophysiology revealed that these phenomena are caused by disruption to three residues on the '-' loop face of the Zn(2+)-inhibition site, and to D84 and D86, on a neighboring beta3 strand, forming a Zn(2+)-activation site. We provide a new view for the activation of a Cys-loop receptor where, following agonist binding, the hydrophobic core and interfacial loops reorganize in a concerted fashion to induce downstream gating.

  14. Synchronous-Voice Computer-Mediated Communication: Effects on Pronunciation

    Science.gov (United States)

    Bueno Alastuey, Maria Camino

    2010-01-01

    Communicative competence is the ultimate goal of most learners of a second language and intelligible pronunciation a fundamental part of it. Unfortunately, learners often lack the opportunity to explore how intelligible their speech is for different audiences. Our research investigates whether synchronous-voice computer-mediated communication…

  15. Two Studies Examining Argumentation in Asynchronous Computer Mediated Communication

    Science.gov (United States)

    Joiner, Richard; Jones, Sarah; Doherty, John

    2008-01-01

    Asynchronous computer mediated communication (CMC) would seem to be an ideal medium for supporting development in student argumentation. This paper investigates this assumption through two studies. The first study compared asynchronous CMC with face-to-face discussions. The transactional and strategic level of the argumentation (i.e. measures of…

  16. Lay Theories Regarding Computer-Mediated Communication in Remote Collaboration

    Science.gov (United States)

    Parke, Karl; Marsden, Nicola; Connolly, Cornelia

    2017-01-01

    Computer-mediated communication and remote collaboration has become an unexceptional norm as an educational modality for distance and open education, therefore the need to research and analyze students' online learning experience is necessary. This paper seeks to examine the assumptions and expectations held by students in regard to…

  17. Judgments of Gender in Computer-Mediated Communication.

    Science.gov (United States)

    Savicki, V.; Kelley, M.; Oesterreich, E.

    1999-01-01

    Describes a study of undergraduates that investigated the ability of readers of computer-mediated communication (CMC) such as electronic mail to identify the gender of the author when messages were selected for language characteristics identified in previous studies as being associated with both group development and gender. (Author/LRW)

  18. How To Achieve Better Impressions in Computer-Mediated Communication?

    Science.gov (United States)

    Liu, Yuliang; Ginther, Dean

    This paper presents a review of the literature on impression formation in face-to-face (FtF) and computer-mediated communication (CMC) and provides impression management recommendations for CMC users in a variety of environments. The first section provides an introduction to impression formation. Factors affecting impression formation in FtF and…

  19. The Influence of Computer-Mediated Communication Systems on Community

    Science.gov (United States)

    Rockinson-Szapkiw, Amanda J.

    2012-01-01

    As higher education institutions enter the intense competition of the rapidly growing global marketplace of online education, the leaders within these institutions are challenged to identify factors critical for developing and for maintaining effective online courses. Computer-mediated communication (CMC) systems are considered critical to…

  20. Constructivism and Computer-Mediated Communication in Distance Education.

    Science.gov (United States)

    Jonassen, David; And Others

    1995-01-01

    Describes the assumptions of a constructivist epistemology, contrasts them with objectivist assumptions, and describes instructional systems that can support constructive learning at a distance. Highlights include paradigm shifts in learning and instructional design theory; computer-mediated communication; computer-supported collaborative work;…

  1. Taking Computer-Mediated Communication(CMC) As Electronic Genre

    Institute of Scientific and Technical Information of China (English)

    黄静雅

    2009-01-01

    The concept of genre has changed considerably over the last several decades. Computer-mediated communica-tion (CMC) refers to any form of communication enabled through the use of computers. It includes not only person-to-person and person-to-group communication, but also person-to-remote-computer contacts, as when individuals read or download documents on the World Wide Web. The following essay is looking at on-line discourse through the frame of genre suggests a focus on:he regularities of form and content of the communication;the nature of the discourse communi- ty;the underlying expectations and conventions.From the view of situated genre theory, CMC has many defining characteristics distinguishing it from any other off-line genre.

  2. Computer-Mediated Communication: A vehicle for learning

    Directory of Open Access Journals (Sweden)

    Linda D. Grooms

    2003-10-01

    Full Text Available The axiom of humanity’s basic need to communicate provides the impetus to explore the nature and quality of computer-mediated communication as a vehicle for learning in higher education. This exploratory study examined the experiential communication perceptions of online doctoral students during the infancy of their program. Eighty-five students were electronically queried through a 32 item open-ended questionnaire within a 13 day time frame. Preliminary findings supported the experience of Seagren and Watwood (1996 at the Lincoln Campus of the University of Nebraska, that “more information widens learning opportunities, but without interaction, learning is not enhanced” (p. 514. The overarching implications stress that faculty development and instructional planning are essential for the effective delivery of online courses, and even more so when collaborative learning is used. Facilitating group communication and interaction are areas beckoning attention as we continue to effectively organize the online classroom of this new millennium.

  3. Communicator-Related and Message-Related Thoughts as Mediators of the Influence of Communicator Credibility on Persuasion.

    Science.gov (United States)

    Pallak, Suzanne R.; Francia, Rosina

    A study was conducted to test the hypothesis that for an "uninvolving topic" the persuasiveness of a highly credible communicator would be mediated by the favorability of the communicator-related thoughts generated, while for an "involving topic" the effect of the communicator's credibility would be mediated by the favorability of the message.…

  4. Communicator-Related and Message-Related Thoughts as Mediators of the Influence of Communicator Credibility on Persuasion.

    Science.gov (United States)

    Pallak, Suzanne R.; Francia, Rosina

    A study was conducted to test the hypothesis that for an "uninvolving topic" the persuasiveness of a highly credible communicator would be mediated by the favorability of the communicator-related thoughts generated, while for an "involving topic" the effect of the communicator's credibility would be mediated by the favorability…

  5. The nicotinic acetylcholine receptor and its prokaryotic homologues: Structure, conformational transitions & allosteric modulation.

    Science.gov (United States)

    Cecchini, Marco; Changeux, Jean-Pierre

    2015-09-01

    Pentameric ligand-gated ion channels (pLGICs) play a central role in intercellular communications in the nervous system by converting the binding of a chemical messenger - a neurotransmitter - into an ion flux through the postsynaptic membrane. Here, we present an overview of the most recent advances on the signal transduction mechanism boosted by X-ray crystallography of both prokaryotic and eukaryotic homologues of the nicotinic acetylcholine receptor (nAChR) in conjunction with time-resolved analyses based on single-channel electrophysiology and Molecular Dynamics simulations. The available data consistently point to a global mechanism of gating that involves a large reorganization of the receptor mediated by two distinct quaternary transitions: a global twisting and a radial expansion/contraction of the extracellular domain. These transitions profoundly modify the organization of the interface between subunits, which host several sites for orthosteric and allosteric modulatory ligands. The same mechanism may thus mediate both positive and negative allosteric modulations of pLGICs ligand binding at topographically distinct sites. The emerging picture of signal transduction is expected to pave the way to new pharmacological strategies for the development of allosteric modulators of nAChR and pLGICs in general. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. An Integrated Review of Emoticons in Computer-Mediated Communication.

    Science.gov (United States)

    Aldunate, Nerea; González-Ibáñez, Roberto

    2016-01-01

    Facial expressions constitute a rich source of non-verbal cues in face-to-face communication. They provide interlocutors with resources to express and interpret verbal messages, which may affect their cognitive and emotional processing. Contrarily, computer-mediated communication (CMC), particularly text-based communication, is limited to the use of symbols to convey a message, where facial expressions cannot be transmitted naturally. In this scenario, people use emoticons as paralinguistic cues to convey emotional meaning. Research has shown that emoticons contribute to a greater social presence as a result of the enrichment of text-based communication channels. Additionally, emoticons constitute a valuable resource for language comprehension by providing expressivity to text messages. The latter findings have been supported by studies in neuroscience showing that particular brain regions involved in emotional processing are also activated when people are exposed to emoticons. To reach an integrated understanding of the influence of emoticons in human communication on both socio-cognitive and neural levels, we review the literature on emoticons in three different areas. First, we present relevant literature on emoticons in CMC. Second, we study the influence of emoticons in language comprehension. Finally, we show the incipient research in neuroscience on this topic. This mini review reveals that, while there are plenty of studies on the influence of emoticons in communication from a social psychology perspective, little is known about the neurocognitive basis of the effects of emoticons on communication dynamics.

  7. An Integrated Review of Emoticons in Computer-Mediated Communication

    Science.gov (United States)

    Aldunate, Nerea; González-Ibáñez, Roberto

    2017-01-01

    Facial expressions constitute a rich source of non-verbal cues in face-to-face communication. They provide interlocutors with resources to express and interpret verbal messages, which may affect their cognitive and emotional processing. Contrarily, computer-mediated communication (CMC), particularly text-based communication, is limited to the use of symbols to convey a message, where facial expressions cannot be transmitted naturally. In this scenario, people use emoticons as paralinguistic cues to convey emotional meaning. Research has shown that emoticons contribute to a greater social presence as a result of the enrichment of text-based communication channels. Additionally, emoticons constitute a valuable resource for language comprehension by providing expressivity to text messages. The latter findings have been supported by studies in neuroscience showing that particular brain regions involved in emotional processing are also activated when people are exposed to emoticons. To reach an integrated understanding of the influence of emoticons in human communication on both socio-cognitive and neural levels, we review the literature on emoticons in three different areas. First, we present relevant literature on emoticons in CMC. Second, we study the influence of emoticons in language comprehension. Finally, we show the incipient research in neuroscience on this topic. This mini review reveals that, while there are plenty of studies on the influence of emoticons in communication from a social psychology perspective, little is known about the neurocognitive basis of the effects of emoticons on communication dynamics.

  8. Integrating Computer-Mediated Communication into an EAP course

    Institute of Scientific and Technical Information of China (English)

    Li Xiao; Cao Ru-hua

    2006-01-01

    The development of the computer along with the widespread use of the Internet has rapidly promoted Computer-Mediated Communication (CMC) as a very important communication media,which can be used widely and effectively in foreign language teaching and learning.This essay tries to explore the advantages of CMC as well as its proposed application,beginning with the introduction of some concepts related to CMC.From the research history,the rationale of using CMC in foreign language learning is summarised.The context of an EAP course is introduced and some suggestions on using CMC in this course are proposed.

  9. The benefits of computer-mediated communication in nursing research.

    Science.gov (United States)

    East, Leah; Jackson, Debra; O'Brien, Louise; Peters, Kathleen

    2008-08-01

    Use of the Internet, and the opportunity to utilise computer-mediated communication (CMC) provides new alternatives for nurse researchers to collect data. The use of CMC for research purposes is advantageous for both researchers and participants. Through this mode of communication, recruitment of participants can be enhanced through reaching individuals who are geographically distant, and nurses have the opportunity to provide participants with true anonymity, which may be beneficial when exploring sensitive issues. This paper explores the existing literature and draws on healthcare studies that have used CMC as a data collection tool.

  10. Sex differences in perceived attributes of computer-mediated communication.

    Science.gov (United States)

    Harper, Vernon B

    2003-02-01

    Researchers have pointed to the influence of sex with respect to the attributes of the computer medium. The author elaborates upon possible sex differences in reference to perceived attributes of the computer medium, i.e., Richness, Accessibility, Velocity, Interactivity, Plasticity, and Immediacy. Data from both a pilot and main study are reported and interpreted. The pilot study included 78 participants, while the main study involved 211. The independent samples were composed of Communication Studies students enrolled at two Mid-Atlantic universities. Nine items with anchors of 1: strongly disagree and 7: strongly agree were taken from the 2000 Computer Mediated Communication Competence Scale of Spitzberg to assess the attributes of computer-mediated interaction. The results indicate that women scored higher than men on perceptions of Accessibility, Velocity, Interactivity, and Immediacy.

  11. Signal molecule-mediated hepatic cell communication during liver regeneration

    Institute of Scientific and Technical Information of China (English)

    Zhen-Yu Zheng; Shun-Yan Weng; Yan Yu

    2009-01-01

    Liver regeneration is a complex and well-orchestrated process, during which hepatic cells are activated to produce large signal molecules in response to liver injury or mass reduction. These signal molecules, in turn, set up the connections and cross-talk among liver cells to promote hepatic recovery. In this review, we endeavor to summarize the network of signal molecules that mediates hepatic cell communication in the regulation of liver regeneration.

  12. Piroxicam inhibits NMDA receptor-mediated excitotoxicity through allosteric inhibition of the GluN2B subunit: an in silico study elucidating a novel mechanism of action of the drug.

    Science.gov (United States)

    Mazumder, Muhammed Khairujjaman; Borah, Anupom

    2014-12-01

    Hyperactivation of GluN2B subunit containing N-methyl-d-aspartate receptors (NMDARs) significantly contributes to the development of several neurodegenerative diseases through a process called excitotoxicity. NMDARs are voltage-gated Ca2+ channels which when activated lead to excessive influx of Ca2+ into neurons thereby exacerbating several calcium-dependent pathways that cause oxidative stress and apoptosis. Several drugs are presently in use to counter the NMDAR-mediated excitotoxic events among which Ifenprodil and its derivatives are GluN2B selective allosteric antagonists. Certain non-steroidal anti-inflammatory drugs (NSAIDs) have also been reported to inhibit NMDARs and the resultant pathologies. Meanwhile, Piroxicam, which is a NSAID, has been reported to be protective in cerebral ischemia-induced neurodegeneration through various pathways. Since Piroxicam has more number of interacting groups as compared to other NSAIDs and also has structural similarities with Ifenprodil, we thought it prudent that Piroxicam may inhibit NMDARs similar to Ifenprodil. By using molecular docking as a tool, we validated the hypothesis and hereby report for the first time that Piroxicam can inhibit GluN2B containing NMDARs through allosteric mode similar to the well known selective antagonist--Ifenprodil; and thus can be a therapeutic drug for the prevention of excitotoxic neurodegeneration.

  13. TEACHER IMMEDIACY BEHAVIORS AND PARTICIPATION IN COMPUTER MEDIATED COMMUNICATION

    Directory of Open Access Journals (Sweden)

    Mestan KUCUK

    2009-04-01

    Full Text Available Few concepts in instructional communication literature have received as much attention as teacher immediacy. However, educational communication scholars have thoroughly studied immediacy behaviors mainly in traditional classrooms and these studies are mostly related to student attitudes and learning. Thanks to some growing attempts, recent research has extended these findings to distance education. The difference of this study is to examine the relationship between teacher immediacy behaviors and participation in an online setting. Results indicated that affective and interactive indicators were the least used immediacy behaviors while cohesive indicators were mostly used by teacher in this case. Also data show that teachers’ interactive immediacy behaviors and immediate feedback determine students’ participation in asynchronous computer-mediated communication environment.

  14. Metalloregulatory proteins: metal selectivity and allosteric switching.

    Science.gov (United States)

    Reyes-Caballero, Hermes; Campanello, Gregory C; Giedroc, David P

    2011-07-01

    Prokaryotic organisms have evolved the capacity to quickly adapt to a changing and challenging microenvironment in which the availability of both biologically required and non-essential transition metal ions can vary dramatically. In all bacteria, a panel of metalloregulatory proteins controls the expression of genes encoding membrane transporters and metal trafficking proteins that collectively manage metal homeostasis and resistance. These "metal sensors" are specialized allosteric proteins, in which the direct binding of a specific or small number of "cognate" metal ion(s) drives a conformational change in the regulator that allosterically activates or inhibits operator DNA binding, or alternatively, distorts the promoter structure thereby converting a poor promoter to a strong one. In this review, we discuss our current understanding of the features that control metal specificity of the allosteric response in these systems, and the role that structure, thermodynamics and conformational dynamics play in mediating allosteric activation or inhibition of DNA binding. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Video-mediated communication to support distant family connectedness.

    Science.gov (United States)

    Furukawa, Ryoko; Driessnack, Martha

    2013-02-01

    It can be difficult to maintain family connections with geographically distant members. However, advances in computer-human interaction (CHI) systems, including video-mediated communication (VMC) are emerging. While VMC does not completely substitute for physical face-to-face communication, it appears to provide a sense of virtual copresence through the addition of visual and contextual cues to verbal communication between family members. The purpose of this study was to explore current patterns of VMC use, experiences, and family functioning among self-identified VMC users separated geographically from their families. A total of 341 participants (ages 18 to above 70) completed an online survey and Family APGAR. Ninty-six percent of the participants reported that VMC was the most common communication method used and 60% used VMC at least once/week. The most common reason cited for using VMC over other methods of communication was the addition of visual cues. A significant difference between the Family APGAR scores and the number of positive comments about VMC experience was also found. This exploratory study provides insight into the acceptance of VMC and its usefulness in maintaining connections with distant family members.

  16. Structure and allosteric effects of low-molecular-weight activators on the protein kinase PDK1

    DEFF Research Database (Denmark)

    Hindie, Valerie; Stroba, Adriana; Zhang, Hua

    2009-01-01

    Protein phosphorylation transduces a large set of intracellular signals. One mechanism by which phosphorylation mediates signal transduction is by prompting conformational changes in the target protein or interacting proteins. Previous work described an allosteric site mediating phosphorylation-d...

  17. An Exploratory Analysis of Computer Mediated Communications on Cyberstalking Severity

    Directory of Open Access Journals (Sweden)

    Stephen D. Barnes

    2007-09-01

    Full Text Available The interaction between disjunctive interpersonal relationships, those where the parties to the relationship disagree on the goals of the relationship, and the use of computer mediated communications channels is a relatively unexplored domain.  Bargh (2002 suggests that CMC channels can amplify the development of interpersonal relationships, and notes that the effect is not constant across communications activities.  This proposal suggests a line of research that explores the interaction between computer mediated communications (CMC and stalking, which is a common form of disjunctive relationships.  Field data from cyberstalking cases will be used to look at the effects of CMC channels on stalking case severity, and exploring the relative impacts of CMC channel characteristics on such cases.  To accomplish this, a ratio scaled measure of stalking case severity is proposed for use in exploring the relationship between case severity and CMC media characteristics, anonymity, and the prior relationship between the stalker and the victim.  Expected results are identified, and follow-up research is proposed. 

  18. LIVING LONG-DISTANCE RELATIONSHIPS THROUGH COMPUTER-MEDIATED COMMUNICATION

    Directory of Open Access Journals (Sweden)

    Almond Pilar N. Aguila

    2009-12-01

    Full Text Available Overseas Filipino Workers (OFWs and their loved ones in thePhilippines manage to have dynamic relationships despite physical distance with Computer-Mediated Communication (CMC or the use of new media (the Internet and cellular phone. Theoretically guided by Marshall McLuhan and Stuart Hall, this paper presents three case studies that depict how individuals mindfully use communication technology to enact their relationships. Such interactions also entail the exchange of new ideas on gender roles, family relations, and dominant-subordinate roles that lead to cultural change. Conclusively, technology has made it easier for OFWs and their loved ones to overcome their aversion to being in long-distance relationships and overseas employment.

  19. Controlling allosteric networks in proteins

    Science.gov (United States)

    Dokholyan, Nikolay

    2013-03-01

    We present a novel methodology based on graph theory and discrete molecular dynamics simulations for delineating allosteric pathways in proteins. We use this methodology to uncover the structural mechanisms responsible for coupling of distal sites on proteins and utilize it for allosteric modulation of proteins. We will present examples where inference of allosteric networks and its rewiring allows us to ``rescue'' cystic fibrosis transmembrane conductance regulator (CFTR), a protein associated with fatal genetic disease cystic fibrosis. We also use our methodology to control protein function allosterically. We design a novel protein domain that can be inserted into identified allosteric site of target protein. Using a drug that binds to our domain, we alter the function of the target protein. We successfully tested this methodology in vitro, in living cells and in zebrafish. We further demonstrate transferability of our allosteric modulation methodology to other systems and extend it to become ligh-activatable.

  20. Gap-junction-mediated cell-to-cell communication.

    Science.gov (United States)

    Hervé, Jean-Claude; Derangeon, Mickaël

    2013-04-01

    Cells of multicellular organisms need to communicate with each other and have evolved various mechanisms for this purpose, the most direct and quickest of which is through channels that directly connect the cytoplasms of adjacent cells. Such intercellular channels span the two plasma membranes and the intercellular space and result from the docking of two hemichannels. These channels are densely packed into plasma-membrane spatial microdomains termed "gap junctions" and allow cells to exchange ions and small molecules directly. A hemichannel is a hexameric torus of junctional proteins around an aqueous pore. Vertebrates express two families of gap-junction proteins: the well-characterized connexins and the more recently discovered pannexins, the latter being related to invertebrate innexins ("invertebrate connexins"). Some gap-junctional hemichannels also appear to mediate cell-extracellular communication. Communicating junctions play crucial roles in the maintenance of homeostasis, morphogenesis, cell differentiation and growth control in metazoans. Gap-junctional channels are not passive conduits, as previously long regarded, but use "gating" mechanisms to open and close the central pore in response to biological stimuli (e.g. a change in the transjunctional voltage). Their permeability is finely tuned by complex mechanisms that have just begun to be identified. Given their ubiquity and diversity, gap junctions play crucial roles in a plethora of functions and their dysfunctions are involved in a wide range of diseases. However, the exact mechanisms involved remain poorly understood.

  1. Exosomes as mediators of intercellular communication: clinical implications.

    Science.gov (United States)

    Nazimek, Katarzyna; Bryniarski, Krzysztof; Santocki, Michał; Ptak, Włodzimierz

    2015-01-01

    Cells of multicellular organisms exchange informative signals by diverse mechanisms. Recent findings uncovered the special role of extracellular vesicles, especially exosomes, in intercellular communication. Exosomes, present in all tested human bodily fluids, carry various functional compounds including proteins, lipids, and diverse RNA molecules. The composition of exosome cargo in vivo is likely formed by a regulated selection of specific components and can express the current status of the exosome-secreting cell. Therefore, particular emphasis is now placed on the extremely high potential of exosomes as essentially noninvasive prognostic and diagnostic biomarkers, but also as therapeutic nanocarriers, especially after the discovery that their cargo as well as cell-targeting specificity could be shaped in vitro. In addition, targeting the exosomes mediating pathological intercellular communication may also express high therapeutic potential. Hence, numerous studies are conducted to explore the profile and function of exosomes and their cargo in health and disease and to shape their properties to facilitate their clinical application. The present review summarizes the current knowledge on the role of exosomes in different physiological and pathological mechanisms of intercellular communication with a particular focus on the use of exosomes in the diagnosis and treatment of various inflammatory, cardiovascular, metabolic, and neurodegenerative disorders as well as malignant neoplasms.

  2. Effects of Training on Computer-Mediated Communication in Single or Mixed Gender Small Task Groups.

    Science.gov (United States)

    Savicki, Victor; Kelley, Merle; Ammon, Benjamin

    2002-01-01

    Investigates group gender composition and communication styles in small task groups involved in computer-mediated communication. Describes a study that tried to train small task groups in the use of one communication style and suggests further research in the area of communication training for online task groups. (Author/LRW)

  3. Gender and Computer-Mediated Communication: Group Processes in Problem Solving.

    Science.gov (United States)

    Adrianson, L.

    2001-01-01

    Reports results from a study of university students in Sweden that investigated aspects of communicative processes using face-to-face and computer-mediated communication. Examined influences of gender on communication equality, social relations, and communicative processes and studied differences in self-awareness. Results showed few significant…

  4. The role of emotion in computer-mediated communication: A review

    NARCIS (Netherlands)

    Derks, D.; Fischer, A.H.; Bos, A.E.R.

    2008-01-01

    It has been argued that the communication of emotions is more difficult in computer-mediated communication (CMC) than in face-to-face (F2F) communication. The aim of this paper is to review the empirical evidence in order to gain insight in whether emotions are communicated differently in these diff

  5. Peplau in cyberspace: an analysis of Peplau's Interpersonal Relations Theory and computer-mediated communication.

    Science.gov (United States)

    Hrabe, David P

    2005-05-01

    This paper explores the applicability of Peplau's Interpersonal Relations Theory to the context of computer-mediated communication. Although Peplau never intended her theory be applied to this mode of communication, research from the fields of communication and social psychology suggest that such application may be possible. After Peplau's theory is briefly summarized, research and theory dealing with computer-mediated communication are explored, and questions for future research endeavors are offered.

  6. Extracellular vesicles as mediators of neuron-glia communication

    Directory of Open Access Journals (Sweden)

    Carsten eFrühbeis

    2013-10-01

    Full Text Available In the nervous system, glia cells maintain homeostasis, synthesize myelin, provide metabolic support, and participate in immune defense. The communication between glia and neurons is essential to synchronize these diverse functions with brain activity. Evidence is accumulating that secreted extracellular vesicles (EVs, such as exosomes and shedding microvesicles, are key players in intercellular signaling. Among others, the cells of the nervous system secrete EVs, which carry protein and RNA cargo from one cell to another. After delivery, the cargo has the ability to modify the target cell phenotype. Here, we review the recent advances in understanding the role of EV secretion by astrocytes, microglia, and oligodendrocytes in the central nervous system. Current work has demonstrated that oligodendrocytes transfer exosomes to neurons as a result of neurotransmitter signaling suggesting that these vesicles may mediate glial support of neurons.

  7. Meta-Analysis and Computer-Mediated Communication.

    Science.gov (United States)

    Taylor, Alan M

    2016-04-01

    Because of the use of human participants and differing contextual variables, research in second language acquisition often produces conflicting results, leaving practitioners confused and unsure of the effectiveness of specific treatments. This article provides insight into a recent seminal meta-analysis on the effectiveness of computer-mediated communication, providing further statistical evidence of the importance of its results. The significance of the study is examined by looking at the p values included in the references, to demonstrate how results can easily be misconstrued by practitioners and researchers. Lin's conclusion regarding the research setting of the study reports is also evaluated. In doing so, other possible explanations of what may be influencing the results can be proposed.

  8. Conversational Awareness in Text-Based Computer Mediated Communication

    Science.gov (United States)

    Tran, Minh Hong; Yang, Yun; Raikundalia, Gitesh K.

    Text-based computer-mediated communication (TxtCMC) supports an instant exchange of messages among geographically distributed people. TxtCMC, such as Instant Messaging and chat tools, has increasingly become widespread and popular at home and at work. Supporting conversational awareness is an important aspect of TxtCMC. Conversational awareness provides a user with information about the presence and activity of others, and therefore helps to establish a context for the user’s own activity. Unfortunately, current interface design of TxtCMC provides inadequate support for conversational awareness, especially in support for awareness of turn-taking, conversational context and multiple concurrent conversations. This research aims to address these three issues by (1) conducting an empirical study to identify the user need for conversational awareness and (2) designing an interface to support this type of awareness. This chapter presents two innovative prototypes, namely Relaxed Instant Messenger (RIM) and Conversational Dock (ConDock). RIM integrates a sequential interface with an adaptive threaded interface to support awareness of turn-taking and conversational context. ConDock adopts a focus + context visualisation technique to support awareness of multiple conversations. The evaluations of the two prototypes show that they meet their design objectives and were found useful in enhancing group communication.

  9. ESL STUDENTS' COMPUTER-MEDIATED COMMUNICATION PRACTICES: CONTEXT CONFIGURATION

    Directory of Open Access Journals (Sweden)

    Dong-Shin Shin

    2006-09-01

    Full Text Available This paper examines how context is configured in ESL students’ language learning practices through computer-mediated communication (CMC. Specifically, I focus on how a group of ESL students jointly constructed the context of their CMC activities through interactional patterns and norms, and how configured affordances within the CMC environment mediated their learning experiences. After a brief review of relevant studies of CMC in the literature, I discuss ecological perspectives of language learning as a core construct of this study, to explain contextual fluidity in relation to learners’ agency in their learning. Next, I present an ethnographic study of how members of an ESL class constructed a community of social practices through synchronous CMC. The findings indicate that (a the constructed interactional patterns and norms of the students’ CMC activities represented group dynamics among the participants, (b the participants’ roles in joint construction of the activities reflected their language socialization experiences, and (c the activities provided a way for spousal participants to assume academic identities, while becoming a social space for academic gatherings. This study highlights the fluidity of CMC language learning contexts; fluid contexts entail learners’ agency in dialogic engagements with the contextual elements of the learning environment as language socialization processes.

  10. The Use of Computer-Mediated Communication To Enhance Subsequent Face-to-Face Discussions.

    Science.gov (United States)

    Dietz-Uhler, Beth; Bishop-Clark, Cathy

    2001-01-01

    Describes a study of undergraduate students that assessed the effects of synchronous (Internet chat) and asynchronous (Internet discussion board) computer-mediated communication on subsequent face-to-face discussions. Results showed that face-to-face discussions preceded by computer-mediated communication were perceived to be more enjoyable.…

  11. An experimental test of processes underlying self-disclosure in computer-mediated communication

    NARCIS (Netherlands)

    Schouten, A.P.; Valkenburg, P.M.; Peter, J.

    2009-01-01

    A consistent finding in computer-mediated communication (CMC) and Internet research is that, compared to face-toface communication, CMC results in higher levels of self-disclosure. We identified four possible mediators that may carry the influence of CMC on self-disclosure: self-presentation,

  12. An Empirical Analysis of the Effect of Text-Based Computer-Mediated Communication on Communicative Competence

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-na

    2016-01-01

    It has been suggested that text-based computer-mediated communication can help learners to use target language both in classrooms and in social contexts. It’s necessary to investigate the effect of text-based CMC on learners’communicative com-petence by conducting the method of systematic review. The findings implied that text-based CMC settings allowed learners to interact. The interaction provided learners with more opportunities to develop their communicative competence of target lan-guage.

  13. Ethics and computer-mediated communication: implications for practice and policy.

    Science.gov (United States)

    Torrance, Rebecca J; Lasome, Caterina E M; Agazio, Janice B

    2002-06-01

    Computer-mediated communication, or email, has become a common workplace practice. Interviews with Army nurse managers (n = 9) and their staff nurses (n = 13) revealed that nurses incorporate the ethical principles of autonomy, beneficence, nonmaleficence, and justice into their computer-mediated communication use, but to varying degrees. Without clearly defined policies to guide computer-mediated communication practices, informal norms evolve that have an impact on both individual and corporate communication. The authors provide insight into the ethical considerations that have an impact on computer-mediated communication use. The spectrum of participant interpretation of appropriate use of this type of communication suggests the need for policies to establish clear boundaries for workplace usage. Policy recommendations are included.

  14. Defining Business Communication Using the Movie "The Insider" as Mediator of Students' Thought Processes.

    Science.gov (United States)

    Rodriguez-Talavera, Leticia

    Business communication is different from other domains in that its contextual meaning requires previous metacognitive mediation of signs. The communicative process in business is aimed at accomplishing a specific outcome. Various forms of meaning come into play in business communication such as denotative, connotative, stylistic, affective,…

  15. Effects of Gender on Computer-Mediated Communication: A Survey of University Faculty

    Science.gov (United States)

    Valenziano, Laura

    2007-01-01

    The influence of gender on computer-mediated communication is a research area with tremendous growth. This study sought to determine what gender effects exist in email communication between professors and students. The study also explored the amount of lying and misinterpretation that occurs through online communication. The study results indicate…

  16. Virtual microscopy: merging of computer mediated communication and intuitive interfacing

    Science.gov (United States)

    de Ridder, Huib; de Ridder-Sluiter, Johanna G.; Kluin, Philip M.; Christiaans, Henri H. C. M.

    2009-02-01

    Ubiquitous computing (or Ambient Intelligence) is an upcoming technology that is usually associated with futuristic smart environments in which information is available anytime anywhere and with which humans can interact in a natural, multimodal way. However spectacular the corresponding scenarios may be, it is equally challenging to consider how this technology may enhance existing situations. This is illustrated by a case study from the Dutch medical field: central quality reviewing for pathology in child oncology. The main goal of the review is to assess the quality of the diagnosis based on patient material. The sharing of knowledge in social face-to-face interaction during such meeting is an important advantage. At the same time there is the disadvantage that the experts from the seven Dutch academic medical centers have to travel to the review meeting and that the required logistics to collect and bring patient material and data to the meeting is cumbersome and time-consuming. This paper focuses on how this time-consuming, nonefficient way of reviewing can be replaced by a virtual collaboration system by merging technology supporting Computer Mediated Collaboration and intuitive interfacing. This requires insight in the preferred way of communication and collaboration as well as knowledge about preferred interaction style with a virtual shared workspace.

  17. Intergenerational transmission of educational attainment: Three levels of parent-child communication as mediators.

    Science.gov (United States)

    Chi, Liping

    2013-04-01

    Although the intergenerational transmission of educational attainment has been confirmed by many researchers, its mechanism still remains controversial. Parent-child communication has been regarded as one of the important mediators. The present study primarily aimed to examine the potentially mediating role of parent-child communication in the transmission of educational attainment, based on a sample of 366 Chinese fifth and sixth graders. Parent-child communication was measured against the three levels of the parents' communication ability, the quality of the father-child and mother-child communications, and the relation between the two dyadic communications. The results duplicated the positive effect of parents' educational attainment on children's academic achievement. Moreover, it was found that parents' communication ability alone played a mediating role, and that the three levels of parent-child communication constructed a "mediator chain" between the parents' educational attainment and the children's academic achievement. Finally, the intergenerational transmission of educational attainment in China and the mediating role of the three levels of parent-child communication were discussed. © 2012 The Institute of Psychology, Chinese Academy of Sciences and Blackwell Publishing Asia Pty Ltd.

  18. How interpersonal communication mediates the relationship of multichannel communication connections to health-enhancing and health-threatening behaviors.

    Science.gov (United States)

    Seo, Mihye; Matsaganis, Matthew D

    2013-08-01

    This article examines how everyday media use and interpersonal communication for health information could influence health behaviors beyond intervention or campaign contexts. The authors argue that interpersonal communication works as an independent information channel and mediates the relation between media channels and health behaviors. In addition, the authors investigate whether interpersonal communication differently influences the relation between media connections and health behaviors for more and less educated individuals. Using data from the 2008 Annenberg National Health Communication Survey, the authors show that multiple communication channels for health information encourage health-enhancing behaviors but do not have significant relations with health-threatening behaviors. Interpersonal communication is directly linked to health-enhancing behaviors, but it also mediates the influence of individuals' multichannel media environment on health-enhancing behaviors. The mediating role of interpersonal health communication was only significant for less educated people. In addition, among media channels, television was a more important instigator of health-related conversations with family and friends for the less educated group. The theoretical and practical implications of these findings, as well as suggestions for future research directions, are discussed.

  19. Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?

    DEFF Research Database (Denmark)

    Schwartz, Thue W; Holst, Birgitte

    2007-01-01

    Many small-molecule agonists also display allosteric properties. Such ago-allosteric modulators act as co-agonists, providing additive efficacy--instead of partial antagonism--and they can affect--and often improve--the potency of the endogenous agonist. Surprisingly, the apparent binding sites o...... process because a compound that acts with--rather than against--the endogenous agonist could be an optimal agonist drug.......Many small-molecule agonists also display allosteric properties. Such ago-allosteric modulators act as co-agonists, providing additive efficacy--instead of partial antagonism--and they can affect--and often improve--the potency of the endogenous agonist. Surprisingly, the apparent binding sites...... of several ordinary allosteric enhancers and ago-allosteric modulators seem to overlap with those of the endogenous agonists. Different molecular scenarios are proposed to explain this discrepancy from classical allosteric models. In one scenario, the ago-allosteric modulator can interchange between...

  20. Convergent transmission of RNAi guide-target mismatch information across Argonaute internal allosteric network.

    Directory of Open Access Journals (Sweden)

    Thomas T Joseph

    Full Text Available In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand "seed region" have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the

  1. Convergent Transmission of RNAi Guide-Target Mismatch Information across Argonaute Internal Allosteric Network

    Science.gov (United States)

    Joseph, Thomas T.; Osman, Roman

    2012-01-01

    In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA) is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC) that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand “seed region” have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the cumulative

  2. Is intercultural mediation necessary? An approach from a communications perspective

    Directory of Open Access Journals (Sweden)

    Susana Ridao Rodrigo

    2014-10-01

    Full Text Available Institutionalized intercultural mediation is expanding as a result of the increase in the number of immigrants in our country. Institutionalized intercultural mediation, which started in the early Nineties in Spain, is understood to mean activities carried out by ONGs and by the social services of the host nation. In line with Giménez (1997: 127, we understand intercultural mediation as a modality within the broader field of mediation. Because of its recent expansion, there is not at present a unique methodology accepted by experts in this field. In this paper, our aims are focused on describing various mediation techniques and the possibility of their application within intercultural contexts

  3. ASBench: benchmarking sets for allosteric discovery.

    Science.gov (United States)

    Huang, Wenkang; Wang, Guanqiao; Shen, Qiancheng; Liu, Xinyi; Lu, Shaoyong; Geng, Lv; Huang, Zhimin; Zhang, Jian

    2015-08-01

    Allostery allows for the fine-tuning of protein function. Targeting allosteric sites is gaining increasing recognition as a novel strategy in drug design. The key challenge in the discovery of allosteric sites has strongly motivated the development of computational methods and thus high-quality, publicly accessible standard data have become indispensable. Here, we report benchmarking data for experimentally determined allosteric sites through a complex process, including a 'Core set' with 235 unique allosteric sites and a 'Core-Diversity set' with 147 structurally diverse allosteric sites. These benchmarking sets can be exploited to develop efficient computational methods to predict unknown allosteric sites in proteins and reveal unique allosteric ligand-protein interactions to guide allosteric drug design.

  4. Allosteric small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    -molecule allosteric inhibitor trametinib in 2013, the progress of more than 10 other allosteric inhibitors in clinical trials, and the emergence of a pipeline of highly selective and potent preclinical molecules, have been reported in the past decade. In this article, we present the current knowledge on allosteric...... inhibition in terms of conception, classification, potential advantages, and summarized debatable topics in the field. Recent progress and allosteric inhibitors that were identified in the past three years are highlighted in this paper....

  5. A case study on support for students' thinking through computer-mediated communication.

    Science.gov (United States)

    Sannomiya, M; Kawaguchi, A

    2000-08-01

    This is a case study on support for thinking through computer-mediated communication. Two graduate students were supervised in their research using computer-mediated communication, which was asynchronous and written; the supervisor was not present. The students' reports pointed out there was more planning and editing and low interactivity in this approach relative to face-to-face communication. These attributes were confirmed by their supervisor's report. The students also suggested that the latter was effective in support of a production stage of thinking in research, while the former approach was effective in support of examination of thinking. For distance education to be successful, an appropriate combination of communication media must consider students' thinking stages. Finally, transient and permanent effects should be discriminated in computer-mediated communication.

  6. Statistical Mechanics of Allosteric Enzymes.

    Science.gov (United States)

    Einav, Tal; Mazutis, Linas; Phillips, Rob

    2016-07-07

    The concept of allostery in which macromolecules switch between two different conformations is a central theme in biological processes ranging from gene regulation to cell signaling to enzymology. Allosteric enzymes pervade metabolic processes, yet a simple and unified treatment of the effects of allostery in enzymes has been lacking. In this work, we take a step toward this goal by modeling allosteric enzymes and their interaction with two key molecular players-allosteric regulators and competitive inhibitors. We then apply this model to characterize existing data on enzyme activity, comment on how enzyme parameters (such as substrate binding affinity) can be experimentally tuned, and make novel predictions on how to control phenomena such as substrate inhibition.

  7. Structural Insights into the Calcium-Mediated Allosteric Transition in the C-Terminal Domain of Calmodulin from Nuclear Magnetic Resonance Measurements.

    Science.gov (United States)

    Kukic, Predrag; Lundström, Patrik; Camilloni, Carlo; Evenäs, Johan; Akke, Mikael; Vendruscolo, Michele

    2016-01-12

    Calmodulin is a two-domain signaling protein that becomes activated upon binding cooperatively two pairs of calcium ions, leading to large-scale conformational changes that expose its binding site. Despite significant advances in understanding the structural biology of calmodulin functions, the mechanistic details of the conformational transition between closed and open states have remained unclear. To investigate this transition, we used a combination of molecular dynamics simulations and nuclear magnetic resonance (NMR) experiments on the Ca(2+)-saturated E140Q C-terminal domain variant. Using chemical shift restraints in replica-averaged metadynamics simulations, we obtained a high-resolution structural ensemble consisting of two conformational states and validated such an ensemble against three independent experimental data sets, namely, interproton nuclear Overhauser enhancements, (15)N order parameters, and chemical shift differences between the exchanging states. Through a detailed analysis of this structural ensemble and of the corresponding statistical weights, we characterized a calcium-mediated conformational transition whereby the coordination of Ca(2+) by just one oxygen of the bidentate ligand E140 triggers a concerted movement of the two EF-hands that exposes the target binding site. This analysis provides atomistic insights into a possible Ca(2+)-mediated activation mechanism of calmodulin that cannot be achieved from static structures alone or from ensemble NMR measurements of the transition between conformations.

  8. Using THz Spectroscopy, Evolutionary Network Analysis Methods, and MD Simulation to Map the Evolution of Allosteric Communication Pathways in c-Type Lysozymes.

    Science.gov (United States)

    Woods, Kristina N; Pfeffer, Juergen

    2016-01-01

    It is now widely accepted that protein function is intimately tied with the navigation of energy landscapes. In this framework, a protein sequence is not described by a distinct structure but rather by an ensemble of conformations. And it is through this ensemble that evolution is able to modify a protein's function by altering its landscape. Hence, the evolution of protein functions involves selective pressures that adjust the sampling of the conformational states. In this work, we focus on elucidating the evolutionary pathway that shaped the function of individual proteins that make-up the mammalian c-type lysozyme subfamily. Using both experimental and computational methods, we map out specific intermolecular interactions that direct the sampling of conformational states and accordingly, also underlie shifts in the landscape that are directly connected with the formation of novel protein functions. By contrasting three representative proteins in the family we identify molecular mechanisms that are associated with the selectivity of enhanced antimicrobial properties and consequently, divergent protein function. Namely, we link the extent of localized fluctuations involving the loop separating helices A and B with shifts in the equilibrium of the ensemble of conformational states that mediate interdomain coupling and concurrently moderate substrate binding affinity. This work reveals unique insights into the molecular level mechanisms that promote the progression of interactions that connect the immune response to infection with the nutritional properties of lactation, while also providing a deeper understanding about how evolving energy landscapes may define present-day protein function.

  9. Use Patterns of Visual Cues in Computer-Mediated Communication

    Science.gov (United States)

    Bolliger, Doris U.

    2009-01-01

    Communication in the virtual environment can be challenging for participants because it lacks physical presence and nonverbal elements. Participants may have difficulties expressing their intentions and emotions in a primarily text-based course. Therefore, the use of visual communication elements such as pictographic and typographic marks can be…

  10. Establishing Goals and Maintaining Coherence in Multiparty Computer-Mediated Communication

    Science.gov (United States)

    Groen, Martin; Noyes, Jan

    2013-01-01

    Communicating via text-only computer-mediated communication (CMC) channels is associated with a number of issues that would impair users in achieving dialogue coherence and goals. It has been suggested that humans have devised novel adaptive strategies to deal with those issues. However, it could be that humans rely on "classic"…

  11. Family Communication Patterns and Relational Maintenance Behavior: Direct and Mediated Associations with Friendship Closeness

    Science.gov (United States)

    Ledbetter, Andrew M.

    2009-01-01

    In this study, both face-to-face and online relational maintenance behaviors were tested as mediators of family communication patterns and closeness with a same-sex friend. Participants included 417 young adults recruited from communication courses at a large university in the Midwestern United States. The obtained structural model demonstrated…

  12. Written and Computer-Mediated Accounting Communication Skills: An Employer Perspective

    Science.gov (United States)

    Jones, Christopher G.

    2011-01-01

    Communication skills are a fundamental personal competency for a successful career in accounting. What is not so obvious is the specific written communication skill set employers look for and the extent those skills are computer mediated. Using survey research, this article explores the particular skills employers desire and their satisfaction…

  13. An Instructional Paradigm for the Teaching of Computer-Mediated Communication

    Science.gov (United States)

    Howard, Craig D.

    2012-01-01

    This article outlines an instructional paradigm that guides the design of interventions that build skills in computer-mediated communication (CMC). It is applicable to learning at multiple levels of communicative proficiency and aims to heighten awareness, the understanding of the impact of media configurations, the role of cultures and social…

  14. Learning Opportunities in Synchronous Computer-Mediated Communication and Face-to-Face Interaction

    Science.gov (United States)

    Kim, Hye Yeong

    2014-01-01

    This study investigated how synchronous computer-mediated communication (SCMC) and face-to-face (F2F) oral interaction influence the way in which learners collaborate in language learning and how they solve their communicative problems. The findings suggest that output modality may affect how learners produce language, attend to linguistic forms,…

  15. Written and Computer-Mediated Accounting Communication Skills: An Employer Perspective

    Science.gov (United States)

    Jones, Christopher G.

    2011-01-01

    Communication skills are a fundamental personal competency for a successful career in accounting. What is not so obvious is the specific written communication skill set employers look for and the extent those skills are computer mediated. Using survey research, this article explores the particular skills employers desire and their satisfaction…

  16. Computer-Mediated Communication with Distant Friends: Relations with Adjustment during Students' First Semester in College

    Science.gov (United States)

    Ranney, John D.; Troop-Gordon, Wendy

    2012-01-01

    Because of recent technological innovations, college freshmen can readily communicate with friends who they see infrequently (e.g., friends from home). The current study addressed whether computer-mediated communication with these distant friends can compensate for a lack of high-quality on-campus friendships during students' first semester of…

  17. The Construction of Knowledge through Social Interaction via Computer-Mediated Communication

    Science.gov (United States)

    Saritas, Tuncay

    2008-01-01

    With the advance in information and communication technologies, computer-mediated communication--more specifically computer conferencing systems (CCS)--has captured the interest of educators as an ideal tool to create a learning environment featuring active, participative, and reflective learning. Educators are increasingly adapting the features…

  18. Social Identification and Interpersonal Communication in Computer-Mediated Communication: What You Do versus Who You Are in Virtual Groups

    Science.gov (United States)

    Wang, Zuoming; Walther, Joseph B.; Hancock, Jeffrey T.

    2009-01-01

    This study investigates the influence of interpersonal communication and intergroup identification on members' evaluations of computer-mediated groups. Participants (N= 256) in 64 four-person groups interacted through synchronous computer chat. Subgroup assignments to minimal groups instilled significantly greater in-group versus out-group…

  19. Differences in Electronic Exchanges in Synchronous and Asynchronous Computer-Mediated Communication: The Effect of Culture as a Mediating Variable

    Science.gov (United States)

    Angeli, Charoula; Schwartz, Neil H.

    2016-01-01

    Two hundred and eighty undergraduates from universities in two countries were asked to read didactic material, and then think and write about potential solutions to an ill-defined problem. The writing was conducted within a synchronous or asynchronous computer-mediated communication (CMC) environment. Asynchronous CMC took the form of email…

  20. Differences in Electronic Exchanges in Synchronous and Asynchronous Computer-Mediated Communication: The Effect of Culture as a Mediating Variable

    Science.gov (United States)

    Angeli, Charoula; Schwartz, Neil H.

    2016-01-01

    Two hundred and eighty undergraduates from universities in two countries were asked to read didactic material, and then think and write about potential solutions to an ill-defined problem. The writing was conducted within a synchronous or asynchronous computer-mediated communication (CMC) environment. Asynchronous CMC took the form of email…

  1. Virtual collaboration: face-to-face versus videoconference, audioconference, and computer-mediated communications

    Science.gov (United States)

    Wainfan, Lynne; Davis, Paul K.

    2004-08-01

    As we increase our reliance on mediated communication, it is important to be aware the media's influence on group processes and outcomes. A review of 40+ years of research shows that all media-videoconference, audioconference, and computer-mediated communication--change the context of the communication to some extent, reducing cues used to regulate and understand conversation, indicate participants' power and status, and move the group towards agreement. Text-based computer-mediated communication, the "leanest" medum, reduces status effects, domination, and consensus. This has been shown useful in broadening the range of inputs and ideas. However, it has also been shown to increase polarization, deindividuation, and disinhibition, and the time to reach a conclusion. For decision-making tasks, computer-mediated communication can increase choice shift and the likelihood of more risky or extreme decisions. In both videoconference and audioconference, participants cooperate less with linked collaborators, and shift their opinions toward extreme options, compared with face-to-face collaboration. In videoconference and audioconference, local coalitions can form where participants tend to agree more with those in the same room than those on the other end of the line. There is also a tendency in audioconference to disagree with those on the other end of the phone. This paper is a summary of a much more extensive forthcoming report; it reviews the research literature and proposes strategies to leverage the benefits of mediated communication while mitigating its adverse effects.

  2. Effective Communication Modes in Multilingual Encounters: Comparing Alternatives in Computer Mediated Communication (CMC)

    Science.gov (United States)

    van Mulken, Margot; Hendriks, Berna

    2017-01-01

    This paper reports on an experimental study investigating alternative communication modes to English as a Lingua Franca. The purpose was to examine the effectiveness of different modes of communication and to gain insight in communication strategies used by interlocutors to solve referential conflicts. Findings show that ELF may not necessarily be…

  3. Effective Communication Modes in Multilingual Encounters: Comparing Alternatives in Computer Mediated Communication (CMC)

    Science.gov (United States)

    van Mulken, Margot; Hendriks, Berna

    2017-01-01

    This paper reports on an experimental study investigating alternative communication modes to English as a Lingua Franca. The purpose was to examine the effectiveness of different modes of communication and to gain insight in communication strategies used by interlocutors to solve referential conflicts. Findings show that ELF may not necessarily be…

  4. Allosteric Modulation: An Alternate Approach Targeting the Cannabinoid CB1 Receptor.

    Science.gov (United States)

    Nguyen, Thuy; Li, Jun-Xu; Thomas, Brian F; Wiley, Jenny L; Kenakin, Terry P; Zhang, Yanan

    2016-11-23

    The cannabinoid CB1 receptor is a G protein coupled receptor and plays an important role in many biological processes and physiological functions. A variety of CB1 receptor agonists and antagonists, including endocannabinoids, phytocannabinoids, and synthetic cannabinoids, have been discovered or developed over the past 20 years. In 2005, it was discovered that the CB1 receptor contains allosteric site(s) that can be recognized by small molecules or allosteric modulators. A number of CB1 receptor allosteric modulators, both positive and negative, have since been reported and importantly, they display pharmacological characteristics that are distinct from those of orthosteric agonists and antagonists. Given the psychoactive effects commonly associated with CB1 receptor agonists and antagonists/inverse agonists, allosteric modulation may offer an alternate approach to attain potential therapeutic benefits while avoiding inherent side effects of orthosteric ligands. This review details the complex pharmacological profiles of these allosteric modulators, their structure-activity relationships, and efforts in elucidating binding modes and mechanisms of actions of reported CB1 allosteric modulators. The ultimate development of CB1 receptor allosteric ligands could potentially lead to improved therapies for CB1-mediated neurological disorders.

  5. Managing Impression Formation in Computer-Mediated Communication.

    Science.gov (United States)

    Liu, Yuliang; Ginther, Dean

    2001-01-01

    Offers suggestions for online instructors regarding verbal and nonverbal impression management. The recommendations should facilitate computer mediated teacher-student or manager-client interactions and help develop constructive relationships that promote learning and productivity. (EV)

  6. Allosteric regulation of phenylalanine hydroxylase.

    Science.gov (United States)

    Fitzpatrick, Paul F

    2012-03-15

    The liver enzyme phenylalanine hydroxylase is responsible for conversion of excess phenylalanine in the diet to tyrosine. Phenylalanine hydroxylase is activated by phenylalanine; this activation is inhibited by the physiological reducing substrate tetrahydrobiopterin. Phosphorylation of Ser16 lowers the concentration of phenylalanine for activation. This review discusses the present understanding of the molecular details of the allosteric regulation of the enzyme.

  7. Allosteric Regulation of Phenylalanine Hydroxylase

    OpenAIRE

    Fitzpatrick, Paul F.

    2011-01-01

    The liver enzyme phenylalanine hydroxylase is responsible for conversion of excess phenylalanine in the diet to tyrosine. Phenylalanine hydroxylase is activated by phenylalanine; this activation is inhibited by the physiological reducing substrate tetrahydrobiopterin. Phosphorylation of Ser16 lowers the concentration of phenylalanine for activation. This review discusses the present understanding of the molecular details of the allosteric regulation of the enzyme.

  8. Intersections between the Autism Spectrum and the Internet: Perceived Benefits and Preferred Functions of Computer-Mediated Communication

    Science.gov (United States)

    Gillespie-Lynch, Kristen; Kapp, Steven K.; Shane-Simpson, Christina; Smith, David Shane; Hutman, Ted

    2014-01-01

    An online survey compared the perceived benefits and preferred functions of computer-mediated communication of participants with (N = 291) and without ASD (N = 311). Participants with autism spectrum disorder (ASD) perceived benefits of computer-mediated communication in terms of increased comprehension and control over communication, access to…

  9. Hotspots for allosteric regulation on protein surfaces

    Science.gov (United States)

    Reynolds, Kimberly A.; McLaughlin, Richard N.; Ranganathan, Rama

    2012-01-01

    Recent work indicates a general architecture for proteins in which sparse networks of physically contiguous and co-evolving amino acids underlie basic aspects of structure and function. These networks, termed sectors, are spatially organized such that active sites are linked to many surface sites distributed throughout the structure. Using the metabolic enzyme dihydrofolate reductase as a model system, we show that (1) the sector is strongly correlated to a network of residues undergoing millisecond conformational fluctuations associated with enzyme catalysis and (2) sector-connected surface sites are statistically preferred locations for the emergence of allosteric control in vivo. Thus, sectors represent an evolutionarily conserved “wiring” mechanism that can enable perturbations at specific surface positions to rapidly initiate conformational control over protein function. These findings suggest that sectors enable the evolution of intermolecular communication and regulation. PMID:22196731

  10. Inhibitory Mechanism of an Allosteric Antibody Targeting the Glucagon Receptor*

    OpenAIRE

    Mukund, Susmith; Shang, Yonglei; Clarke, Holly J.; Madjidi, Azadeh; Jacob E Corn; Kates, Lance; Kolumam, Ganesh; Chiang, Vicky; Luis, Elizabeth; Murray, Jeremy; Zhang, Yingnan; Hötzel, Isidro; Koth, Christopher M.; Allan, Bernard B.

    2013-01-01

    Elevated glucagon levels and increased hepatic glucagon receptor (GCGR) signaling contribute to hyperglycemia in type 2 diabetes. We have identified a monoclonal antibody that inhibits GCGR, a class B G-protein coupled receptor (GPCR), through a unique allosteric mechanism. Receptor inhibition is mediated by the binding of this antibody to two distinct sites that lie outside of the glucagon binding cleft. One site consists of a patch of residues that are surface-exposed on the face of the ext...

  11. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  12. Computer-mediated communication: task performance and satisfaction.

    Science.gov (United States)

    Simon, Andrew F

    2006-06-01

    The author assessed satisfaction and performance on 3 tasks (idea generation, intellective, judgment) among 75 dyads (N = 150) working through 1 of 3 modes of communication (instant messaging, videoconferencing, face to face). The author based predictions on the Media Naturalness Theory (N. Kock, 2001, 2002) and on findings from past researchers (e.g., D. M. DeRosa, C. Smith, & D. A. Hantula, in press) of the interaction between tasks and media. The present author did not identify task performance differences, although satisfaction with the medium was lower among those dyads communicating through an instant-messaging system than among those interacting face to face or through videoconferencing. The findings support the Media Naturalness Theory. The author discussed them in relation to the participants' frequent use of instant messaging and their familiarity with new communication media.

  13. Nurses' Perception of Necessary Factors in Gaining Consent from Patients: Verbal-mediated Communication and Non-verbal Communication

    OpenAIRE

    Takao, Kenji; Mizuko, Manabu; KANEMITSU, Yoshihiro

    2009-01-01

    This research analyzed factors necessary for obtaining consent from the patient as perceived by nurses. Explaining things to patients and listening to the patient's voice were defined as factors of verbal-mediated communication. The attitude toward patients (such as nods, making eye contact) and the tone of voice were defined as factors of non-verbal communication. A questionnaire survey was administered to nurses (n=142) (Mean age=30.2, SD=8.7) in December, 2007. The respondents were asked t...

  14. Using Computer-Mediated Communication (CMC) in Language Teaching

    Science.gov (United States)

    Goertler, Senta

    2009-01-01

    This article discusses how new and familiar computer technology tools can be used in a communicative language classroom. It begins by outlining the benefits and challenges of using such technology for language teaching in general, and it describes some sample activities that the author has used. Readers are shown how to implement various computer…

  15. Web-Mediated Communication: in Search of Togetherness

    NARCIS (Netherlands)

    Cesar Garcia, P.S.; Bulterman, D.C.A.; Guimarães, R.L.; Kegel, I.

    2010-01-01

    This paper introduces a community-based video sharing environment to support asynchronous communication among heterogeneous participants within a restricted social community. Unlike other community sharing efforts, our work is predicated on the desire to strengthen existing strong ties among group m

  16. Using Computer-Mediated Communication (CMC) in Language Teaching

    Science.gov (United States)

    Goertler, Senta

    2009-01-01

    This article discusses how new and familiar computer technology tools can be used in a communicative language classroom. It begins by outlining the benefits and challenges of using such technology for language teaching in general, and it describes some sample activities that the author has used. Readers are shown how to implement various computer…

  17. Change in allosteric network affects binding affinities of PDZ domains: analysis through perturbation response scanning.

    Directory of Open Access Journals (Sweden)

    Z Nevin Gerek

    2011-10-01

    Full Text Available The allosteric mechanism plays a key role in cellular functions of several PDZ domain proteins (PDZs and is directly linked to pharmaceutical applications; however, it is a challenge to elaborate the nature and extent of these allosteric interactions. One solution to this problem is to explore the dynamics of PDZs, which may provide insights about how intramolecular communication occurs within a single domain. Here, we develop an advancement of perturbation response scanning (PRS that couples elastic network models with linear response theory (LRT to predict key residues in allosteric transitions of the two most studied PDZs (PSD-95 PDZ3 domain and hPTP1E PDZ2 domain. With PRS, we first identify the residues that give the highest mean square fluctuation response upon perturbing the binding sites. Strikingly, we observe that the residues with the highest mean square fluctuation response agree with experimentally determined residues involved in allosteric transitions. Second, we construct the allosteric pathways by linking the residues giving the same directional response upon perturbation of the binding sites. The predicted intramolecular communication pathways reveal that PSD-95 and hPTP1E have different pathways through the dynamic coupling of different residue pairs. Moreover, our analysis provides a molecular understanding of experimentally observed hidden allostery of PSD-95. We show that removing the distal third alpha helix from the binding site alters the allosteric pathway and decreases the binding affinity. Overall, these results indicate that (i dynamics plays a key role in allosteric regulations of PDZs, (ii the local changes in the residue interactions can lead to significant changes in the dynamics of allosteric regulations, and (iii this might be the mechanism that each PDZ uses to tailor their binding specificities regulation.

  18. The Impact of a Video-Mediated Communication on Separated Perinatal Couples in Japan.

    Science.gov (United States)

    Furukawa, Ryoko; Driessnack, Martha; Kobori, Eiko

    2017-02-01

    Japanese communication relies heavily on nonverbal cues and context. The purpose of this study was to examine the impact of video-mediated communication (VMC) on communication satisfaction and marital relationships in young couples separated during the perinatal period as they honor the Japanese tradition of Satogaeri Bunben. Couples were assigned to the VMC treatment group ( n = 14) or control group ( n = 13). A mixed-methods approach to data collection and analysis was used. Longitudinal quantitative analysis from the Primary Communication Inventory and Intimate Bond Measure revealed significant differences between the Husband groups. Primary Communication Inventory and Intimate Bond Measure were strongly correlated regardless of group. Qualitative analysis of participant diaries revealed the addition of visual cues helped create a sense of "virtual co-presence," which was both positive and negative. In conclusion, VMC appears to improve communication in the separated Japanese perinatal couples, especially through the addition of visual cues provided with VMC.

  19. The associations among computer-mediated communication, relationships, and well-being.

    Science.gov (United States)

    Schiffrin, Holly; Edelman, Anna; Falkenstern, Melissa; Stewart, Cassandra

    2010-06-01

    Social support provided by interpersonal relationships is one of the most robust correlates of well-being. Self-disclosure serves as a basic building block of these relationships. With the rapid growth of the Internet in recent years, the question remains how self-disclosure, and subsequently relationships and well-being, differ when people communicate over the Internet rather than in person. The purpose of this article is to describe current Internet usage patterns as well as explore the association of Internet usage and well-being. Additionally, it directly compares the perceived benefits of face-to-face communication and computer-mediated communication. A questionnaire was administered to 99 undergraduates to measure Internet usage patterns, communication partners, self-disclosure, extraversion, and subjective well-being. Although Internet communication was found to be common, individuals perceived computer-mediated communication to be less useful than face-to-face communication. In addition, increased Internet usage was associated with decreased well-being. Implications are discussed in terms of a new Internet paradox in which people increasingly use the Internet for communication, although they perceive it to be less beneficial than face-to-face interactions and it is associated with reduced well-being.

  20. Patient Health Communication Mediating Effects Between Gastrointestinal Symptoms and Gastrointestinal Worry in Pediatric Inflammatory Bowel Disease.

    Science.gov (United States)

    Varni, James W; Shulman, Robert J; Self, Mariella M; Saeed, Shehzad A; Patel, Ashish S; Nurko, Samuel; Neigut, Deborah A; Saps, Miguel; Zacur, George M; Dark, Chelsea V; Bendo, Cristiane B; Pohl, John F

    2017-05-01

    To investigate the effects of patient health communication regarding their inflammatory bowel disease (IBD) to their health care providers and significant others in their daily life as a mediator in the relationship between gastrointestinal symptoms and gastrointestinal worry in pediatric patients. The Pediatric Quality of Life Inventory Gastrointestinal Symptoms, Gastrointestinal Worry, and Communication Scales, and Pediatric Quality of Life Inventory 4.0 Generic Core Scales were completed in a 9-site study by 252 pediatric patients with IBD. Gastrointestinal Symptoms Scales measuring stomach pain, constipation, or diarrhea and patient communication were tested for bivariate and multivariate linear associations with Gastrointestinal Worry Scales specific to patient worry about stomach pain or bowel movements. Mediational analyses were conducted to test the hypothesized mediating effects of patient health communication as an intervening variable in the relationship between gastrointestinal symptoms and gastrointestinal worry. The predictive effects of gastrointestinal symptoms on gastrointestinal worry were mediated in part by patient health communication with health care providers/significant others in their daily life. In predictive models using multiple regression analyses, the full conceptual model of demographic variables, gastrointestinal symptoms (stomach pain, constipation, or diarrhea), and patient communication significantly accounted for 46, 43, and 54 percent of the variance in gastrointestinal worry (all Ps < 0.001), respectively, reflecting large effect sizes. Patient health communication explains in part the effects of gastrointestinal symptoms on gastrointestinal worry in pediatric patients with IBD. Supporting patient disease-specific communication to their health care providers and significant others may improve health-related quality of life for pediatric patients with IBD.

  1. Being private and public at home : an architectural perspective on video mediated communication in smart homes

    OpenAIRE

    Junestrand, Stefan

    2004-01-01

    Video mediated communication (VMC) is a two way real time audio and video communication between remote places. VMC has the potential to be applied favourably to many activities, services and functions in smart homes. The concept of smart homes refers to homes equipped with technological systems and appliances enabling centralised or remotely controllable integrated functionalities and services. The main question for the current research work is formulated accordingly: How can spaces for video...

  2. The Allosteric Switching Mechanism in Bacteriophage MS2

    CERN Document Server

    Perkett, Matthew R

    2015-01-01

    In this article we use all-atom simulations to elucidate the mechanisms underlying conformational switching and allostery within the coat protein of the bacteriophage MS2. Assembly of most icosahedral virus capsids requires that the capsid protein adopt different conformations at precise locations within the capsid. It has been shown that a 19 nucleotide stem loop (TR) from the MS2 genome acts as an allosteric effector, guiding conformational switching of the coat protein during capsid assembly. Since the principal conformational changes occur far from the TR binding site, it is important to understand the molecular mechanism underlying this allosteric communication. To this end, we use all-atom simulations with explicit water combined with a path sampling technique to sample the MS2 coat protein conformational transition, in the presence and absence of TR-binding. The calculations find that TR binding strongly alters the transition free energy profile, leading to a switch in the favored conformation. We disc...

  3. Kissing and nanotunneling mediate intermitochondrial communication in the heart.

    Science.gov (United States)

    Huang, Xiaohu; Sun, Lei; Ji, Shuangxi; Zhao, Ting; Zhang, Wanrui; Xu, Jiejia; Zhang, Jue; Wang, Yanru; Wang, Xianhua; Franzini-Armstrong, Clara; Zheng, Ming; Cheng, Heping

    2013-02-19

    Mitochondria in many types of cells are dynamically interconnected through constant fusion and fission, allowing for exchange of mitochondrial contents and repair of damaged mitochondria. However, constrained by the myofibril lattice, the ∼6,000 mitochondria in the adult mammalian cardiomyocyte display little motility, and it is unclear how, if at all, they communicate with each other. By means of target-expressing photoactivatable green fluorescent protein (PAGFP) in the mitochondrial matrix or on the outer mitochondrial membrane, we demonstrated that the local PAGFP signal propagated over the entire population of mitochondria in cardiomyocytes on a time scale of ∼10 h. Two elemental steps of intermitochondrial communications were manifested as either a sudden PAGFP transfer between a pair of adjacent mitochondria (i.e., "kissing") or a dynamic nanotubular tunnel (i.e., "nanotunneling") between nonadjacent mitochondria. The average content transfer index (fractional exchange) was around 0.5; the rate of kissing was 1‰ s(-1) per mitochondrial pair, and that of nanotunneling was about 14 times smaller. Electron microscopy revealed extensive intimate contacts between adjacent mitochondria and elongated nanotubular protrusions, providing a structural basis for the kissing and nanotunneling, respectively. We propose that, through kissing and nanotunneling, the otherwise static mitochondria in a cardiomyocyte form one dynamically continuous network to share content and transfer signals.

  4. [Gap junction-mediated intercellular communication in astrocytes and neuroprotection].

    Science.gov (United States)

    Giaume, C; Froger, N; Koulakoff, A

    2005-06-01

    Neuroglial interaction represents a concept that is now more and more integrated in the attempts to understand who does what and how in neuronal processing and survival, in normal as well as in pathological situations. The purpose of the review is to provide an overlook about the role of glial cells, mainly astrocytes, in neuroprotection. Since a typical feature of glia is to be connected by gap junctions that allow them to be organized as a communicating network(s), we will focus this review on what is known about the contribution of astrocyte gap junctions (AGJ) in neuronal survival. As neuroglial interaction and AGJ are both affected during neurodegenerative diseases, we will also consider the above mentioned glial properties in a pathological context with a special interest in Alzheimer's disease.

  5. The Computer-Mediated Communication (CMC) Classroom: A Challenge of Medium, Presence, Interaction, Identity, and Relationship

    Science.gov (United States)

    Sherblom, John C.

    2010-01-01

    There is a "prevalence of computer-mediated communication (CMC) in education," and a concern for its negative psychosocial consequences and lack of effectiveness as an instructional tool. This essay identifies five variables in the CMC research literature and shows their moderating effect on the psychosocial, instructional expevrience of the CMC…

  6. Can Synchronous Computer-Mediated Communication (CMC) Help Beginning-Level Foreign Language Learners Speak?

    Science.gov (United States)

    Ko, Chao-Jung

    2012-01-01

    This study investigated the possibility that initial-level learners may acquire oral skills through synchronous computer-mediated communication (SCMC). Twelve Taiwanese French as a foreign language (FFL) students, divided into three groups, were required to conduct a variety of tasks in one of the three learning environments (video/audio, audio,…

  7. Building a Sense of Community for Text-Based Computer-Mediated Communication Courses

    Science.gov (United States)

    Yang, Harrison Hao; Liu, Yuliang

    2008-01-01

    Building a strong sense of community in text-based computer-mediated communication courses can be a challenge to instructors. This article presents how a sound practical approach called STEP is implemented into one text-based fully online course and one hybrid course at a university in the northeastern region of the United States. Students'…

  8. Computer Mediated Communication in the Universal Design for Learning Framework for Preparation of Special Education Teachers

    Science.gov (United States)

    Basham, James D.; Lowrey, K. Alisa; deNoyelles, Aimee

    2010-01-01

    This study investigated the Universal Design for Learning (UDL) framework as a basis for a bi-university computer mediated communication (CMC) collaborative project. Participants in the research included 78 students from two special education programs enrolled in teacher education courses. The focus of the investigation was on exploring the…

  9. Online Social Presence: Score Validity of the Computer-Mediated Communication Questionnaire

    Science.gov (United States)

    Yen, Cherng-Jyh

    2008-01-01

    The purpose of this study was to conduct a confirmatory factor analysis of the Computer-Mediated Communication Questionnaire scores, using structural equation modeling, to assess the consistency between the empirical data and the hypothesized factor structure of the CMCQ in the proposed models, which is stipulated by the theoretical framework and…

  10. Discourse Functions and Vocabulary Use in English Language Learners' Synchronous Computer-Mediated Communication

    Science.gov (United States)

    Rabab'ah, Ghaleb

    2013-01-01

    This study explores the discourse generated by English as a foreign language (EFL) learners using synchronous computer-mediated communication (CMC) as an approach to help English language learners to create social interaction in the classroom. It investigates the impact of synchronous CMC mode on the quantity of total words, lexical range and…

  11. Computer-Mediated Communication and Virtual Groups: Applications to Interethnic Conflict

    Science.gov (United States)

    Walther, Joseph B.

    2009-01-01

    This essay concerns applications of computer-mediated communication (CMC) research in groups toward the enhancement of relations between members of potentially hostile ethnopolitical groups. The characteristics of CMC offer several possible means of facilitating the reduction of animosity through online contact among intergroup constituents. The…

  12. Task Effects on Focus on Form in Synchronous Computer-Mediated Communication

    Science.gov (United States)

    Yilmaz, Yucel

    2011-01-01

    Previous research on synchronous computer-mediated communication (SCMC) has shown that SCMC interaction could draw learners' attention to form in ways that are similar to face-to-face interaction. However, the role of task type in focusing learners' attention on form has not been widely researched. In a repeated-measures design, this study…

  13. Fluid Centrality: A Social Network Analysis of Social-Technical Relations in Computer-Mediated Communication

    Science.gov (United States)

    Enriquez, Judith Guevarra

    2010-01-01

    In this article, centrality is explored as a measure of computer-mediated communication (CMC) in networked learning. Centrality measure is quite common in performing social network analysis (SNA) and in analysing social cohesion, strength of ties and influence in CMC, and computer-supported collaborative learning research. It argues that measuring…

  14. Computer Mediated Communication for Social and Academic Purposes: Profiles of Use and University Students' Gratifications

    Science.gov (United States)

    Vrocharidou, Anatoli; Efthymiou, Ilias

    2012-01-01

    The present study approaches the Internet as a social space, where university students make use of computer mediated communication (CMC) applications, i.e. e-mail, instant messaging and social network sites, in order to satisfy social and academic needs. We focus on university students, because they represent one of the most avid groups of CMC…

  15. Computer-mediated communication in adults with high-functioning autism spectrum disorders and controls

    NARCIS (Netherlands)

    van der Aa, Christine; Pollmann, Monique; Plaat, Aske; van der Gaag, Rutger Jan

    2016-01-01

    It has been suggested that people with Autism Spectrum Disorders (ASD) are attracted to computer-mediated communication (CMC). In this study, we compare CMC use in adults with high-functioning ASD (N = 113) and a control group (N = 72). We find that people with ASD spend more time on CMC than contro

  16. Personality Types and Megabytes: Student Attitudes toward Computer Mediated Communication (CMC) in the Language Classroom.

    Science.gov (United States)

    Beauvois, Margaret Healy; Eledge, Jean

    1996-01-01

    Describes the results of a pilot study to examine the attitudes of university students toward the use of computer-mediated communication in their French conversation and composition course. Results indicate that both introvert and extrovert personality types generally perceive the use of a local area network as a beneficial experience. (15…

  17. Computer-mediated communication: from a cognitive to a discursive model

    NARCIS (Netherlands)

    Lamerichs, J.M.W.J.; Molder, te H.F.M.

    2003-01-01

    In this article, we evaluate the ways in which computer-mediated communication (CMC) has thus far been conceptualized, proposing an alternative approach. It is argued that traditional perspectives ignore participants' everyday understanding of media use and media characteristics by relying on an ind

  18. Breaching or building social boundaries? : SIDE-effects of computer-mediated communication

    NARCIS (Netherlands)

    Postmes, T; Spears, R; Lea, M

    1998-01-01

    Computer-mediated communication (CMC) is sometimes heralded for its power to break down social boundaries and to liberate individuals from social influence, group pressure, and status and power differentials that characterize much face-to-face interaction. We review research conducted within the

  19. Nurturing Students' Problem-Solving Skills and Engagement in Computer-Mediated Communications (CMC)

    Science.gov (United States)

    Chen, Ching-Huei

    2014-01-01

    The present study sought to investigate how to enhance students' well- and ill-structured problem-solving skills and increase productive engagement in computer-mediated communication with the assistance of external prompts, namely procedural and reflection. Thirty-three graduate students were randomly assigned to two conditions: procedural and…

  20. Gender and Group Composition in Small Task Groups Using Computer-Mediated Communication.

    Science.gov (United States)

    Savicki, Victor; And Others

    1996-01-01

    Gender and group composition variables in a computer-mediated communication context are examined. Subjects were 36 undergraduate male and female psychology students. Findings are analyzed in terms of choice of language; participation; satisfaction; and interpersonal conflict. Ten tables present study results. (Author/AEF)

  1. Negotiation of Meaning in Synchronous Computer-Mediated Communication in Relation to Task Types

    Science.gov (United States)

    Cho, Hye-jin

    2011-01-01

    The present study explored how negotiation of meaning occurred in task-based synchronous computer-mediated communication (SCMC) environment among college English learners. Based on the theoretical framework of the interaction hypothesis and negotiation of meaning, four research questions arose: (1) how negotiation of meaning occur in non-native…

  2. You Have Been Framed! How Antecedents of Information Need Mediate the Effects of Risk Communication Messages

    NARCIS (Netherlands)

    Terpstra, T.; Zaalberg, R.; Boer, de J.; Botzen, W.J.W.

    2014-01-01

    This study investigates the processes that mediate the effects of framing flood risks on people's information needs. Insight into the effects of risk frames is important for developing balanced risk communication that explains both risks and benefits of living near water. The research was inspired b

  3. Interactive uncertainty reduction strategies and verbal affection in computer-mediated communication

    NARCIS (Netherlands)

    Antheunis, M.L.; Schouten, A.P.; Valkenburg, P.M.; Peter, J.

    2012-01-01

    The goal of this study was to investigate the language-based strategies that computer-mediated communication (CMC) users employ to reduce uncertainty in the absence of nonverbal cues. Specifically, this study investigated the prevalence of three interactive uncertainty reduction strategies (i.e.,

  4. A quality of experience testbed for video-mediated group communication

    NARCIS (Netherlands)

    Schmitt, M.R.; Gunkel, S.; Cesar Garcia, P.S.

    2013-01-01

    Video-Mediated group communication is quickly moving from the office to the home, where network conditions might fluctuate. If we are to provide a software component that can, in real-time, monitor the Quality of Experience (QoE), we would have to carry out extensive experiments under different vary

  5. Breaching or building social boundaries? : SIDE-effects of computer-mediated communication

    NARCIS (Netherlands)

    Postmes, T; Spears, R; Lea, M

    1998-01-01

    Computer-mediated communication (CMC) is sometimes heralded for its power to break down social boundaries and to liberate individuals from social influence, group pressure, and status and power differentials that characterize much face-to-face interaction. We review research conducted within the fra

  6. Social influence in computer-mediated communication : The effects of anonymity on group behavior

    NARCIS (Netherlands)

    Postmes, T; Spears, R; Sakhel, K; de Groot, D

    2001-01-01

    Two studies examined hypotheses derived from a Social Identity model of Deindividuation Effects (SIDE) as applied to social influence in computer-mediated communication (CMC) in groups. This model predicts that anonymity can increase social influence if a common group identity is salient. In a first

  7. PANACEA OR PANOPTICON : THE HIDDEN POWER IN COMPUTER-MEDIATED COMMUNICATION

    NARCIS (Netherlands)

    SPEARS, R; LEA, M

    1994-01-01

    This article examines how interaction by means of computer-mediated communication (CMC) affects the operation of both status differentials and power relations. The authors attempt to provide a corrective to the dominant assessment, particularly within social psychological analyses, that CMC tends to

  8. Investigating the Impact of Mediated Learning Experiences on Cooperative Peer Communication during Group Initiatives

    Science.gov (United States)

    White, Robert; Dinos, Sokratis

    2010-01-01

    This study investigates how structured Mediated Learning Experiences may improve peer-cooperative communication within problem-solving task exercises. Two groups (n = 22) of Year 8 students (mean age 13 +/- 5 months) were randomly selected to participate in this study. The study began with two one-hour sessions of activity-based problem-solving…

  9. Computer-mediated communication as a channel for social resistance : The strategic side of SIDE

    NARCIS (Netherlands)

    Spears, R; Lea, M; Corneliussen, RA; Postmes, T; Ter Haar, W

    2002-01-01

    In two studies, the authors tested predictions derived from the social identity model of deindividuation effects (SIDE) concerning the potential of computer-mediated communication (CMC) to serve as a means to resist powerful out-groups. Earlier research using the SIDE model indicates that the anonym

  10. Gender, Group Composition, and Task Type in Small Task Groups Using Computer-Mediated Communication.

    Science.gov (United States)

    Savicki, Victor; And Others

    1996-01-01

    To investigate gender effects on computer-mediated communication, undergraduate psychology students were put in small groups (males, females, or mixed) and were assigned feminine content (decision making) and masculine content (intellective) task types. Groups of females, regardless of task, sent more words per e-mail message, were more satisfied…

  11. Nurturing Students' Problem-Solving Skills and Engagement in Computer-Mediated Communications (CMC)

    Science.gov (United States)

    Chen, Ching-Huei

    2014-01-01

    The present study sought to investigate how to enhance students' well- and ill-structured problem-solving skills and increase productive engagement in computer-mediated communication with the assistance of external prompts, namely procedural and reflection. Thirty-three graduate students were randomly assigned to two conditions: procedural…

  12. Computer-Mediated Communication in Education: A Review of Recent Research

    Science.gov (United States)

    Hrastinski, Stefan; Keller, Christina

    2007-01-01

    The field of research on computer-mediated communication (CMC) in education is a relatively new research area. A summary of the latest research is useful to show what methodologies and research topics have been emphasized in order to be better prepared for the future by uncovering areas where there is a lack of research. The study examines…

  13. Musicians Crossing Musical Instrument Gender Stereotypes: A Study of Computer-Mediated Communication

    Science.gov (United States)

    Abeles, Harold F.; Hafeli, Mary; Sears, Colleen

    2014-01-01

    This study examined computer-mediated communication (CMC) -- blogs and responses to YouTube postings -- to better understand how CMCs reflect adolescents' attitudes towards musicians playing instruments that cross gender stereotypes. Employing purposive sampling, we used specific search terms, such as "girl drummer", to identify a…

  14. Computer-Mediated Communication (CMC) in L2 Oral Proficiency Development: A Meta-Analysis

    Science.gov (United States)

    Lin, Huifen

    2015-01-01

    The ever growing interest in the development of foreign or second (L2) oral proficiency in a computer-mediated communication (CMC) classroom has resulted in a large body of studies looking at both the direct and indirect effects of CMC interventions on the acquisition of oral competences. The present study employed a quantitative meta-analytic…

  15. The Provision of Feedback Types to EFL Learners in Synchronous Voice Computer Mediated Communication

    Science.gov (United States)

    Ko, Chao-Jung

    2015-01-01

    This study examined the relationship between Synchronous Voice Computer Mediated Communication (SVCMC) interaction and the use of feedback types, especially pronunciation feedback types, in distance tutoring contexts. The participants, divided into two groups (explicit and recast), were twelve beginning/low-intermediate level English as a Foreign…

  16. Leveraging Computer-Mediated Communication Technologies to Enhance Interactions in Online Learning

    Science.gov (United States)

    Wright, Linda J.

    2011-01-01

    Computer-mediated communication (CMC) technologies have been an integral part of distance education for many years. They are found in both synchronous and asynchronous platforms and are intended to enhance the learning experience for students. CMC technologies add an interactive element to the online learning environment. The findings from this…

  17. Revisiting Synchronous Computer-Mediated Communication: Learner Perception and the Meaning of Corrective Feedback

    Science.gov (United States)

    Kim, Hye Yeong

    2014-01-01

    Effectively exploring the efficacy of synchronous computer-mediated communication (SCMC) for pedagogical purposes can be achieved through the careful investigation of potentially beneficial, inherent attributes of SCMC. This study provides empirical evidence for the capacity of task-based SCMC to draw learner attention to linguistic forms by…

  18. Mutually Beneficial Foreign Language Learning: Creating Meaningful Interactions through Video-Synchronous Computer-Mediated Communication

    Science.gov (United States)

    Kato, Fumie; Spring, Ryan; Mori, Chikako

    2016-01-01

    Providing learners of a foreign language with meaningful opportunities for interactions, specifically with native speakers, is especially challenging for instructors. One way to overcome this obstacle is through video-synchronous computer-mediated communication tools such as Skype software. This study reports quantitative and qualitative data from…

  19. Negotiating Pragmatic Competence in Computer Mediated Communication: The Case of Korean Address Terms

    Science.gov (United States)

    Kim, Eun Young; Brown, Lucien

    2014-01-01

    This paper examines how L2 learners of Korean manifest pragmatic competence in their use of address terms in computer mediated communication (CMC) and how they use these terms to negotiate their identities. Four UK-based learners of Korean with competence levels ranging from Novice High through Intermediate High participated in the study,…

  20. Nurturing Students' Problem-Solving Skills and Engagement in Computer-Mediated Communications (CMC)

    Science.gov (United States)

    Chen, Ching-Huei

    2014-01-01

    The present study sought to investigate how to enhance students' well- and ill-structured problem-solving skills and increase productive engagement in computer-mediated communication with the assistance of external prompts, namely procedural and reflection. Thirty-three graduate students were randomly assigned to two conditions: procedural and…

  1. Individual versus Interactive Task-Based Performance through Voice-Based Computer-Mediated Communication

    Science.gov (United States)

    Granena, Gisela

    2016-01-01

    Interaction is a necessary condition for second language (L2) learning (Long, 1980, 1996). Research in computer-mediated communication has shown that interaction opportunities make learners pay attention to form in a variety of ways that promote L2 learning. This research has mostly investigated text-based rather than voice-based interaction. The…

  2. Undergraduate Taiwanese Students' Perceptions of Using Computer-Mediated Communication in a TOEIC Preparation Course

    Science.gov (United States)

    Tai, Shu-hui April

    2016-01-01

    The aim of this study is to investigate Taiwanese undergraduate students' perception of using computer-mediated communication (CMC) in a TOEIC preparation course and determine if using an online format motivates them to succeed. As a result, five factors are addressed in the study, namely, attitude, motivation, study habit, feedback, and…

  3. Person-Centered Emotional Support and Gender Attributions in Computer-Mediated Communication

    Science.gov (United States)

    Spottswood, Erin L.; Walther, Joseph B.; Holmstrom, Amanda J.; Ellison, Nicole B.

    2013-01-01

    Without physical appearance, identification in computer-mediated communication is relatively ambiguous and may depend on verbal cues such as usernames, content, and/or style. This is important when gender-linked differences exist in the effects of messages, as in emotional support. This study examined gender attribution for online support…

  4. Learners' Perceived Information Overload in Online Learning via Computer-Mediated Communication

    Science.gov (United States)

    Chen, Chun-Ying; Pedersen, Susan; Murphy, Karen L.

    2011-01-01

    Many studies report information overload as one of the main problems that students encounter in online learning via computer-mediated communication. This study aimed to explore the sources of online students' information overload and offer suggestions for increasing students' cognitive resources for learning. Participants were 12 graduate students…

  5. Chinese EFL Teachers' Social Interaction and Socio-Cognitive Presence in Synchronous Computer-Mediated Communication

    Science.gov (United States)

    Wu, Heping; Gao, Junde; Zhang, Weimin

    2014-01-01

    The present study examines the professional growth of three Chinese English teachers by analyzing their interactional patterns and their social and cognitive presence in an online community. The data from social network analysis (SNA) and content analysis revealed that computer-mediated communication (CMC) created new opportunities for teachers to…

  6. Task-Based Oral Computer-Mediated Communication and L2 Vocabulary Acquisition

    Science.gov (United States)

    Yanguas, Inigo

    2012-01-01

    The present study adds to the computer-mediated communication (CMC) literature by exploring oral learner-to-learner interaction using Skype, a free and widely used Internet software program. In particular, this task-based study has a two-fold goal. Firstly, it explores possible differences between two modes of oral CMC (audio and video) and…

  7. ESL Students' Interaction in Second Life: Task-Based Synchronous Computer-Mediated Communication

    Science.gov (United States)

    Jee, Min Jung

    2010-01-01

    The purpose of the present study was to explore ESL students' interactions in task-based synchronous computer-mediated communication (SCMC) in Second Life, a virtual environment by which users can interact through representational figures. I investigated Low-Intermediate and High-Intermediate ESL students' interaction patterns before, during, and…

  8. COMPUTER-MEDIATED COMMUNICATION IN FOREIGN LANGUAGE EDUCATION: Use of Target Language and Learner Perceptions

    Directory of Open Access Journals (Sweden)

    Nesrin OZDENER

    2008-04-01

    Full Text Available Among the challenges many teachers face in facilitating the improvement of speaking skills are sparing sufficient time for practice to enable students to achieve fluency in speaking through internalizing the structures, and establishing a balance between fluency and accuracy. This study aimed to seek an answer to the question as to whether Computer-Mediated Communication Technologies be a solution for overcoming these problems. The study was conducted as additional practice to the foreign language lessons with the participation of 60 students. Task-based language teaching principles were taken as basis in preparation of the teaching materials in the study, in which text and voice chat applications among the Computer-Mediated Communication Technologies were used. During the applications data were collected in several ways: participants’ perspectives regarding their changing experiences and the types of tasks used were investigated through the use of open-ended questionnaires after each session; a general insight was obtained into the students’ experiences with close-ended questionnaires given at the end of the study; and the use of the target language in communications among students were determined by investigating the text communication logs. From a user-oriented perspective, the results of the study shed light on the strategies that can be used in computer-mediated communication technologies valuing the experiences and perceptions of the learners.

  9. Mediation Training for the Physician: Expanding the Communication Toolkit to Manage Conflict.

    Science.gov (United States)

    Kayser, Joshua B

    2015-01-01

    Good communication is critical to the practice of medicine. This is particularly true when outcomes are unpredictable and/or patients lack the capacity to participate in medical decision making. Disputes may develop that cannot be addressed using basic communication skills. Conflict of this nature can burden patients, families, and medical staff and may result in increased suffering for all parties. Many physicians lack the necessary communication tools to handle difficult conversations. Training in bioethics mediation provides physicians with skills that can promote healing by empowering participants to engage in effective discourse and break down barriers to find common ground. Mediation training for physicians can expand their capacity to connect with patients and enhance their ability to identify potential conflict early on, in order to collaborate more effectively. Competency in the processes of negotiation and conflict resolution should therefore be seen as essential elements of medical training.

  10. Say it with flowers! An fMRI study of object mediated communication

    DEFF Research Database (Denmark)

    Tylén, Kristian; Wallentin, Mikkel; Roepstorff, Andreas

    2009-01-01

    with verbal language and semantics. In addition, we found that right-hemisphere inferior frontal cortex is recruited as a function of the increasing unconventionality of communicative objects. Together these findings support an interpretation of the traditional language areas as playing a more general role......Human communicational interaction can be mediated by a host of expressive means from words in a natural language to gestures and material symbols. Given the proper contextual setting even an everyday object can gain a mediating function in a communicational situation. In this study we used event......-related fMRI to study the brain activity caused by everyday material objects when they are perceived as signals. We found that comprehension of material signals activates bilaterally areas of the ventral stream and pars triangularis of the inferior frontal cortex, that is, areas traditionally associated...

  11. THE ROLE OF CUSTOMER SATISFACTION IN MEDIATING MARKETING COMMUNICATION EFFECT ON CUSTOMER LOYALTY

    Directory of Open Access Journals (Sweden)

    Mohamad Dimyati,

    2015-11-01

    Full Text Available This study aims to test the effect of a marketing communication on customer satisfaction; b marketing communication on customer loyalty; c customer satisfaction on customer loyalty; and d to identify the role of customer satisfaction in mediating marketing communication effect on customer loyalty of the IM3 user community in Jember regency, East Java province. The study was designed in a form confirmatory research, with the whole IM3 community members in the regency as the study population. By using random sampling, 100 respondents were taken as the samples. Structural Equation Modeling (SEM was applied as the data analysis model. The result shows that: a marketing communication has a significantly positive effect on customer satisfaction; b marketing communication has a significantly positive effect on customer loyalty; c customer satisfaction has a significantly positive effect on customer loyalty; and d customer satisfaction has a very important role in mediating marketing communication effect on customer loyalty of the IM3 user community in Jember regency

  12. Unraveling structural mechanisms of allosteric drug action.

    Science.gov (United States)

    Nussinov, Ruth; Tsai, Chung-Jung

    2014-05-01

    Orthosteric drugs block the active site to obstruct function; allosteric drugs modify the population of the active state, to modulate function. Available data lead us to propose that allosteric drugs can constitute anchors and drivers. The anchor docks into an allosteric pocket. The conformation with which it interacts is unchanged during the transition between the inactive and active states. The anchor provides the foundation that allows the driver to exert a 'pull' and/or 'push' action that shifts the receptor population from the inactive to the active state. The presence or absence of driver atom in an allosteric drug can exert opposite agonism. We map a strategy for driver identification and expect the allosteric trigger concept to transform agonist/antagonist drug discovery.

  13. Establishing an Empirical Link between Computer-Mediated Communication (CMC) and SLA: A Meta-Analysis of the Research

    Science.gov (United States)

    Lin, Huifen

    2014-01-01

    Drawing on interactionist and socio-cultural theories, tools provided in computer-mediated communication (CMC) environments have long been considered able to create an environment that shares many communicative features with face-to-face communication. Over the past two decades, researchers have employed a variety of strategies to examine the…

  14. Content and Processes in Problem-Based Learning: A Comparison of Computer-Mediated and Face-to-Face Communication

    Science.gov (United States)

    Stromso, H. I.; Grottum, P.; Lycke, K. H.

    2007-01-01

    There has been an increasing interest in the use of computer-mediated communication (CMC) in problem-based learning. One line of research has been to introduce synchronous, or simultaneous, communication attempting to create text-based digital real-time interaction. Compared with face-to-face (F2F) communication, CMC may be a poorer medium…

  15. Establishing an Empirical Link between Computer-Mediated Communication (CMC) and SLA: A Meta-Analysis of the Research

    Science.gov (United States)

    Lin, Huifen

    2014-01-01

    Drawing on interactionist and socio-cultural theories, tools provided in computer-mediated communication (CMC) environments have long been considered able to create an environment that shares many communicative features with face-to-face communication. Over the past two decades, researchers have employed a variety of strategies to examine the…

  16. Health-related Support Groups on the Internet: Linking Empirical Findings to Social Support and Computer-mediated Communication Theory.

    Science.gov (United States)

    Wright, Kevin B; Bell, Sally B; Wright, Kevin B; Bell, Sally B

    2003-01-01

    This literature review of research on health-related computer-mediated support groups links features of these groups to existing theory from the areas of social support and computer-mediated communication research. The article exams computer-mediated support groups as weak tie networks, focuses on how these support groups facilitate participant similarity and empathic support and identifies changes in supportive communication due to characteristics of the medium.

  17. Communication of Science Shop Mediation: A Kaleidoscope of University-Society Relations

    CERN Document Server

    Leydesdorff, Loet

    2009-01-01

    The Science Shop model was initiated in the Netherlands in the 1970s. Part of the model is the modest scale of the operation. The crucial idea behind the Science Shops involves a working relationship between knowledge-producing institutions like universities and citizen groups that need relevant questions answered. In providing this link, the relations between science and the public can be stimulated by providing such groups with access to the university and by offering active mediation of these questions. This research addresses the question of the external visibility of Science Shop work in terms of communications which reach beyond the local context of the participants. In addition to the question of the effects of this specific type of communication in terms of publications, institutional development, and curriculum development, we study the communication of the results in the press, the popular and grey literature, and other means of communication insofar as retrievable on distance through the Internet.

  18. Emoticons in computer-mediated communication: social motives and social context.

    Science.gov (United States)

    Derks, Daantje; Bos, Arjan E R; von Grumbkow, Jasper

    2008-02-01

    This study investigated the role of emoticons in computer-mediated communication (CMC). The study consisted of an online questionnaire about the social motives for emoticon use and an experimental part in which participants (N = 1,251) had to respond to short Internet chats. In these chats, the interaction partner (friend vs. stranger) and the valence of the context (positive vs. negative) were manipulated. Results showed that emoticons are mostly used to express emotion, to strengthen a message, and to express humor. Furthermore, more emoticons were used in communication with friends than in communication with strangers, and more emoticons were used in a positive context than in a negative context. Participants seem to use emoticons in a way similar to facial behavior in face-to-face communication with respect to social context and interaction partner.

  19. Inhibitory mechanism of an allosteric antibody targeting the glucagon receptor.

    Science.gov (United States)

    Mukund, Susmith; Shang, Yonglei; Clarke, Holly J; Madjidi, Azadeh; Corn, Jacob E; Kates, Lance; Kolumam, Ganesh; Chiang, Vicky; Luis, Elizabeth; Murray, Jeremy; Zhang, Yingnan; Hötzel, Isidro; Koth, Christopher M; Allan, Bernard B

    2013-12-13

    Elevated glucagon levels and increased hepatic glucagon receptor (GCGR) signaling contribute to hyperglycemia in type 2 diabetes. We have identified a monoclonal antibody that inhibits GCGR, a class B G-protein coupled receptor (GPCR), through a unique allosteric mechanism. Receptor inhibition is mediated by the binding of this antibody to two distinct sites that lie outside of the glucagon binding cleft. One site consists of a patch of residues that are surface-exposed on the face of the extracellular domain (ECD) opposite the ligand-binding cleft, whereas the second binding site consists of residues in the αA helix of the ECD. A docking model suggests that the antibody does not occlude the ligand-binding cleft. We solved the crystal structure of GCGR ECD containing a naturally occurring G40S mutation and found a shift in the register of the αA helix that prevents antibody binding. We also found that alterations in the αA helix impact the normal function of GCGR. We present a model for the allosteric inhibition of GCGR by a monoclonal antibody that may form the basis for the development of allosteric modulators for the treatment of diabetes and other class B GPCR-related diseases.

  20. Mediatisation or PR-ization of Public--Media Communication--Analysis of Mediated Communication of Zoran Milanović.

    Science.gov (United States)

    Tanta, Ivan; Lesinger, Gordana

    2015-12-01

    Politicians and their public relations advisors depend on the mass communication media to transmit messages dailyand communicate effectively. The development of the mass media, from traditional to new, has changed the working conditions of these professions where one inevitably affects the other. Consequently, the way of formatting information in the newshas changed, along with the way of monitoring the political developments and informs the public on political activities. Amajor role in this process, over and above the political actors, has advisers for public relations, who choose moments andevents to publicise (PR-ization). With the increasing influence of public relations to media reports, politics also changes thepicture of the media and the impact on media coverage. Similarly, the impact on the manner in which the media reportprocess, what topics will be discussed topics and what tone the given information will have. We are living in a world characterized by mediation (Mazzoleni and Schulz, 1999) of the politics and the society as a whole, because politics and publicrelations necessarily need the media to communicate with their audiences. In this regard, we can talk about PR-izationmedia as the fundamental role of public relations practitioners affect attitudes, which skillfully make careful design ofmessages and events that are not included herein are the three professions each other should one without the other does notmake sense. This paper will focus on the influence of the media on politics and on influence of the public relations as profession in the content media perception. In view of the drawn by daily public appearances of Prime Minister, Zoran Milanovi6,and as says Lali63 few politics-related phenomena have over the past twenty years engaged so many reviews by experts andscholars as the Prime Minister's rhetoric. The particular form of the political communication will be reviewed in this paper.Through the interviews and the content analysis of key

  1. Brief Report: Mediation of Treatment Effect in a Communication Intervention for Pre-School Children with Autism

    Science.gov (United States)

    Aldred, Catherine; Green, Jonathan; Emsley, Richard; McConachie, Helen

    2012-01-01

    Tests of mediation in treatment trials can illuminate processes of change and suggest causal influences in development. We conducted a mediation analysis of a previously published randomised controlled trial of parent-mediated communication-focused treatment for autism against ordinary care, with 28 children aged 2-5 years (Aldred et al. in J…

  2. Are You Satisfied? Exploring the Mediating Effects of Mentoring Communication Strategies in Predicting Chinese International Graduate Students' Program Satisfaction

    Science.gov (United States)

    Yang, Qinghua; Orrego Dunleavy, Victoria; Phillips, Jasmine Rene

    2016-01-01

    This study examined how mentoring initiation and maintenance strategies mediate the relationship between acculturative stress and intercultural communication competence on Chinese graduate students' program satisfaction. Results supported a partial mediation effect for mentoring maintenance strategies. By specifying the mediating effect, the model…

  3. Are You Satisfied? Exploring the Mediating Effects of Mentoring Communication Strategies in Predicting Chinese International Graduate Students' Program Satisfaction

    Science.gov (United States)

    Yang, Qinghua; Orrego Dunleavy, Victoria; Phillips, Jasmine Rene

    2016-01-01

    This study examined how mentoring initiation and maintenance strategies mediate the relationship between acculturative stress and intercultural communication competence on Chinese graduate students' program satisfaction. Results supported a partial mediation effect for mentoring maintenance strategies. By specifying the mediating effect, the model…

  4. Staying Connected: Computer-Mediated and Face-to-Face Communication in College Students' Dating Relationships.

    Science.gov (United States)

    Boyle, Andrea M; O'Sullivan, Lucia F

    2016-05-01

    Little is known about the features, depth, and quality of communication in heterosexual dating relationships that include computer-mediated communication (CMC). This study examined these features as well as CMC's potential to facilitate self-disclosure and information-seeking. It also evaluated whether partner CMC interactions play a role in partner intimacy and communication quality. Young adults (N = 359; 18-24) attending postsecondary education institutions completed an online survey about their CMC use. To be included in the study, all participants were in established dating relationships at the time of the study and reported daily communication with their partner. CMC was linked to partners' disclosure of nonintimate information. This personal self-disclosure was linked positively to relationship intimacy and communication quality, beyond contributions from face-to-face interactions. Breadth (not depth) of self-disclosure and positively valenced interactions, in particular, proved key to understanding greater levels of intimacy in dating relationships and better communication quality as a function of CMC. CMC provides opportunities for partners to stay connected and to improve the overall quality of their intimacy and communication.

  5. Getting Real: A Naturalistic Methodology for Using Smartphones to Collect Mediated Communications

    Directory of Open Access Journals (Sweden)

    Chad C. Tossell

    2012-01-01

    Full Text Available This paper contributes an intentionally naturalistic methodology using smartphone logging technology to study communications in the wild. Smartphone logging can provide tremendous access to communications data from real environments. However, researchers must consider how it is employed to preserve naturalistic behaviors. Nine considerations are presented to this end. We also provide a description of a naturalistic logging approach that has been applied successfully to collecting mediated communications from iPhones. The methodology was designed to intentionally decrease reactivity and resulted in data that were more accurate than self-reports. Example analyses are also provided to show how data collected can be analyzed to establish empirical patterns and identify user differences. Smartphone logging technologies offer flexible capabilities to enhance access to real communications data, but methodologies employing these techniques must be designed appropriately to avoid provoking naturally occurring behaviors. Functionally, this methodology can be applied to establish empirical patterns and test specific hypotheses within the field of HCI research. Topically, this methodology can be applied to domains interested in understanding mediated communications such as mobile content and systems design, teamwork, and social networks.

  6. A Web-based System for Observing and Analyzing Computer Mediated Communications

    CERN Document Server

    May, Madeth; Prévôt, Patrick

    2007-01-01

    Tracking data of user's activities resulting from Computer Mediated Communication (CMC) tools (forum, chat, etc.) is often carried out in an ad-hoc manner, which either confines the reusability of data in different purposes or makes data exploitation difficult. Our research works are biased toward methodological challenges involved in designing and developing a generic system for tracking user's activities while interacting with asynchronous communication tools like discussion forums. We present in this paper, an approach for building a Web-based system for observing and analyzing user activity on any type of discussion forums.

  7. SERVANT LEADERSHIP AND ORGANIZATIONAL TRUST: THE MEDIATING EFFECT OF THE LEADER TRUST AND ORGANIZATIONAL COMMUNICATION

    Directory of Open Access Journals (Sweden)

    Morad Rezaei

    2012-01-01

    Full Text Available The purpose of this paper aims to clarify the relationship between servant leadership and organizational trust, and tries to demonstrate the mediator role of leader trust and organizational communication in this relationship. The study sample included 258 employees of Guilan province Tax Administration and for sampling we used cluster method. Previous studies have also focused on the positive impact of servant leadership in organizational trust and in this article the results show that there is a significant relationship between servant leadership, organizational trust, leader trust and organizational communication.

  8. Mediators of the effects of cold-warm communication on attraction toward online service providers.

    Science.gov (United States)

    Singh, Ramadhar; Lee, Clara Yulin

    2008-06-01

    Undergraduate students (N = 120) in Singapore sought advice from the experimenter's confederate via e-mail or phone. After receiving a scripted warm or cold reply from the online service provider, participants rated their general attitude toward the service provided, positive and negative affect, and attraction toward the service provider. The effect of warm versus cold communication on attraction toward the online service provider was partly mediated by general attitude, positive affect, and negative affect. The results indicate that attitude that influences attraction through affect can itself be a mediator when it is formed through online interactions.

  9. [Mediate evaluation of replicating a Training Program in Nonverbal Communication in Gerontology].

    Science.gov (United States)

    Schimidt, Teresa Cristina Gioia; Duarte, Yeda Aparecida de Oliveira; Silva, Maria Julia Paes da

    2015-04-01

    Replicating the training program in non-verbal communication based on the theoretical framework of interpersonal communication; non-verbal coding, valuing the aging aspects in the perspective of active aging, checking its current relevance through the content assimilation index after 90 days (mediate) of its application. A descriptive and exploratory field study was conducted in three hospitals under direct administration of the state of São Paulo that caters exclusively to Unified Health System (SUS) patients. The training lasted 12 hours divided in three meetings, applied to 102 health professionals. Revealed very satisfactory and satisfactory mediate content assimilation index in 82.9%. The program replication proved to be relevant and updated the setting of hospital services, while remaining efficient for healthcare professionals.

  10. Mediate evaluation of replicating a Training Program in Nonverbal Communication in Gerontology

    Directory of Open Access Journals (Sweden)

    Teresa Cristina Gioia Schimidt

    2015-04-01

    Full Text Available OBJECTIVE Replicating the training program in non-verbal communication based on the theoretical framework of interpersonal communication; non-verbal coding, valuing the aging aspects in the perspective of active aging, checking its current relevance through the content assimilation index after 90 days (mediate of its application. METHOD A descriptive and exploratory field study was conducted in three hospitals under direct administration of the state of São Paulo that caters exclusively to Unified Health System (SUS patients. The training lasted 12 hours divided in three meetings, applied to 102 health professionals. RESULTS Revealed very satisfactory and satisfactory mediate content assimilation index in 82.9%. CONCLUSION The program replication proved to be relevant and updated the setting of hospital services, while remaining efficient for healthcare professionals.

  11. Allosteric regulation of deubiquitylase activity through ubiquitination

    Directory of Open Access Journals (Sweden)

    Serena eFaggiano

    2015-02-01

    Full Text Available Ataxin-3, the protein responsible for spinocerebellar ataxia type-3, is a cysteine protease that specifically cleaves poly-ubiquitin chains and participates in the ubiquitin proteasome pathway. The enzymatic activity resides in the N-terminal Josephin domain. An unusual feature of ataxin-3 is its low enzymatic activity especially for mono-ubiquitinated substrates and short ubiquitin chains. However, specific ubiquitination at lysine 117 in the Josephin domain activates ataxin-3 through an unknown mechanism. Here, we investigate the effects of K117 ubiquitination on the structure and enzymatic activity of the protein. We show that covalently linked ubiquitin rests on the Josephin domain, forming a compact globular moiety and occupying a ubiquitin binding site previously thought to be essential for substrate recognition. In doing so, ubiquitination enhances enzymatic activity by locking the enzyme in an activated state. Our results indicate that ubiquitin functions both as a substrate and as an allosteric regulatory factor. We provide a novel example in which a conformational switch controls the activity of an enzyme that mediates deubiquitination.

  12. Computer-mediated communication and the Gallaudet University community: a preliminary report.

    Science.gov (United States)

    Hogg, Nanette M; Lomicky, Carol S; Weiner, Stephen F

    2008-01-01

    The study examined the use of computer-mediated communication (CMC) among individuals involved in a conflict sparked by the appointment of an administrator as president-designate of Gallaudet University in 2006. CMC was defined as forms of communication used for transmitting (sharing) information through networks with digital devices. There were 662 survey respondents. Respondents reported overwhelmingly (98%) that they used CMC to communicate. Students and alumni reported CMC use in larger proportions than any other group. The favorite devices among all respondents were Sidekicks, stationary computers, and laptops. Half of all respondents also reported using some form of video device. Nearly all reported using e-mail; respondents also identified Web surfing, text messaging, and blogging as popular CMC activities. The authors plan another article reporting on computer and electronic technology use as a mechanism connecting collective identity to social movements.

  13. [Web-ring of sites for pathologists in the internet: a computer-mediated communication environment].

    Science.gov (United States)

    Khramtsov, A I; Isianov, N N; Khorzhevskiĭ, V A

    2009-01-01

    The recently developed Web-ring of pathology-related Web-sites has transformed computer-mediated communications for Russian-speaking pathologists. Though the pathologists may be geographically dispersed, the network provides a complex of asynchronous and synchronous conferences for the purposes of diagnosis, consultations, education, communication, and collaboration in the field of pathology. This paper describes approaches to be used by participants of the pathology-related Web-ring. The approaches are analogous to the tools employed in telepathology and digital microscopy. One of the novel methodologies is the use of Web-based conferencing systems, in which the whole slide digital images of tissue microarrays were jointly reviewed online by pathologists at distant locations. By using ImageScope (Aperio Technologies) and WebEx connect desktop management technology, they shared presentations and images and communicated in realtime. In this manner, the Web-based forums and conferences will be a powerful addition to a telepathology.

  14. Supporting the Collaborative Learning of Practical Skills with Computer-Mediated Communications Technology

    Directory of Open Access Journals (Sweden)

    Mark A. Edwards

    2001-01-01

    Full Text Available Based on a collaborative approach to learning, a student cohort taking an introductory level University course in computing was provided with information and asynchronous communications technology (including learning resources, e-mail, bulletin board and FAQ, as a means of enhancing their collaborative efforts on a web authoring exercise within a flexible learning environment. The qualitative investigative paradigm used was ‘action research’. By use of ethnographic techniques (questionnaires and focus group interviews, evidence was gained indicating that while a collaborative approach promoted improved learning, usage of computer-mediated communication technology and its contribution to collaboration was limited in an activity that was skills-oriented, requiring practical experience. Reasons for this are then discussed and a number of barriers to the take-up of communications technology are identified, and implications for educators are drawn from these.

  15. Student participation and interactivity using asynchronous computer-mediated communication for resolution of an undergraduate capstone management case study.

    Science.gov (United States)

    Miller, Paulette J

    2012-01-01

    Online discussion activities are designed for computer-mediated learning activities in face-to-face, hybrid, and totally online courses. The use of asynchronous computer-mediated communication (A-CMC) coupled with authentic workplace case studies provides students in the protected learning environment with opportunities to practice workplace decision making and communication. In this study, communication behaviors of transmitter and receiver were analyzed to determine participation and interactivity in communication among small-group participants in a health information management capstone management course.

  16. Alexithymia and marital quality: the mediating roles of loneliness and intimate communication.

    Science.gov (United States)

    Frye-Cox, Nick E; Hesse, Colin R

    2013-04-01

    This study examined the mediating roles of loneliness and intimate communication in the association between alexithymia and marital quality. Guided by a personality-behavioral approach to loneliness and affection exchange theory (AET), two actor-partner interdependence models (APIMs) were examined to test the associations among the variables. Path models (N = 155 couples) indicated that, for both spouses, loneliness and intimate communication fully mediated the association between alexithymia and marital quality. More specifically, higher alexithymia was associated with greater loneliness, which predicted lower intimate communication, which was related to lower marital quality. Multiple specific indirect effects were also significant, suggesting that the association between alexithymia and marital quality may be explained through divergent intrapersonal and interpersonal pathways. Although the magnitude of the intrapersonal associations was similar for both spouses, the results revealed gender differences in spousal interpersonal associations. For husbands, consistent differences were found between intrapersonal and interpersonal associations. Conversely, for wives, no significant differences were found between intrapersonal and interpersonal associations, suggesting that their marital quality was most strongly predicted by their own and their spouse's alexithymia, loneliness, and perceptions of intimate communication. Theoretical implications and future directions for research are also discussed. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  17. Preventing and De-Escalating Ethical Conflict: A Communication-Training Mediation Model.

    Science.gov (United States)

    Levin, Tomer T; Parker, Patricia A

    2015-01-01

    While ethical conflicts in the provision of healthcare are common, the current third-party mediator model is limited by a lack of expert ethical mediators, who are often not on site when conflict escalates. In order to improve clinical outcomes in situations such as conflicts at the end of life, we suggest that clinicians-physicians, nurses and social workers-be trained to prevent and de-escalate emerging conflicts. This can be achieved using a mediation model framed by a communication-training approach. A case example is presented and the model is discussed. The implication of this preventative/early intervention model for improving clinical outcomes, in particular end-of life conflict, is considered.

  18. SAR studies on carboxylic acid series M(1) selective positive allosteric modulators (PAMs).

    Science.gov (United States)

    Kuduk, Scott D; Beshore, Douglas C

    2014-01-01

    There is mounting evidence from preclinical and early proof-of-concept studies suggesting that selective modulation of the M1 muscarinic receptor is efficacious in cognitive models of Alzheimer's disease (AD). A number of nonselective M1 muscarinic agonists have previously shown positive effects on cognitive function in AD patients, but were limited due to cholinergic adverse events thought to be mediated by pan activation of the M2 to M5 sub-types. Thus, there is a need to identify selective activators of the M1 receptor to evaluate their potential in cognitive disorders. One strategy to confer selectivity for M1 is the identification of allosteric agonists or positive allosteric modulators, which would target an allosteric site on the M1 receptor rather than the highly conserved orthosteric acetylcholine binding site. BQCA has been identified as a highly selective carboxylic acid M1 PAM and this review focuses on an extensive lead optimization campaign undertaken on this compound.

  19. Dynamic Coupling and Allosteric Networks in the α Subunit of Heterotrimeric G Proteins*

    Science.gov (United States)

    Yao, Xin-Qiu; Malik, Rabia U.; Griggs, Nicholas W.; Skjærven, Lars; Traynor, John R.; Sivaramakrishnan, Sivaraj; Grant, Barry J.

    2016-01-01

    G protein α subunits cycle between active and inactive conformations to regulate a multitude of intracellular signaling cascades. Important structural transitions occurring during this cycle have been characterized from extensive crystallographic studies. However, the link between observed conformations and the allosteric regulation of binding events at distal sites critical for signaling through G proteins remain unclear. Here we describe molecular dynamics simulations, bioinformatics analysis, and experimental mutagenesis that identifies residues involved in mediating the allosteric coupling of receptor, nucleotide, and helical domain interfaces of Gαi. Most notably, we predict and characterize novel allosteric decoupling mutants, which display enhanced helical domain opening, increased rates of nucleotide exchange, and constitutive activity in the absence of receptor activation. Collectively, our results provide a framework for explaining how binding events and mutations can alter internal dynamic couplings critical for G protein function. PMID:26703464

  20. Exploring the use of computer-mediated video communication in engineering projects in South Africa

    Directory of Open Access Journals (Sweden)

    Meyer, Izak P.

    2016-08-01

    Full Text Available Globally-expanding organisations that are trying to capitalise on distributed skills are increasingly using virtual project teams to shorten product development time and increase quality. These virtual teams, which are distributed across countries, cultures, and time zones, are required to use faster and better ways of interacting. Past research has shown that virtual teams that use computer-mediated communication (CMC instead of face-to-face communication are less cohesive because they struggle with mistrust, controlling behaviour , and communication breakdowns. This study aims to determine whether project practitioners in South Africa perceive virtual teams that use videoconferencing as suffering from the same CMC disadvantages described in past research in other environments; and if they do, what the possible causes could be. This paper reports on a survey of 106 project practitioners in South Africa. The results show that these project practitioners prefer face- to-face communication over CMC, and perceive virtual teams using videoconferencing to be less cohesive and to suffer from mistrust and communication breakdowns, but not from increased conflict and power struggles. The perceived shortcomings of videoconferencing might result from virtual teams that use this medium having less time to build interpersonal relationships.

  1. Media Education towards peace cultures. Future professionals of the communication sector as citizens-mediators

    Directory of Open Access Journals (Sweden)

    Eloísa NOS ALDÁS

    2012-12-01

    Full Text Available This paper presents a pioneering experience for Spanish University Communication degrees. It deals with the elective subject «Audiovisual Discourses and Peace Culture» offered in the fourth year of the Audiovisual Communication University Degree at Universitat Jaume I of Castellón. This learning project is focused on the proposals of peace research as a complementary and coincident research and educative project to educommunication. In this course students realize their role as citizens professionals of communication, and, therefore, their responsibility and that of their communicative acts in the configuration of society and culture. It focuses on the possibilities and consequences of their discourses as mediators in public communication scenarios to participate of the debate towards cultures for peace. The paper shares the design, development and results of this subject during 6 years as a university teaching project that can be extrapolated to other learning contexts. It is presented as well as an epistemological and methodological reflection that can be applied to all main subjects in the different communication university curricula so that students graduate being prepared both from a technical and commercial perspective but also from an educommunicative, critical, civic, social and cultural one. This text pays special attention to the audiovisual examples (films and documentaries above all used in the classes, to the ideas commented on them and to the methods for analyzing them taught from a cultural efficacy perspective and with the aim of detecting the discourse strategies of awareness communication to train citizenry in conflict transformation and solidarity.

  2. Identity as a Moderator and Mediator of Communication Effects: Evidence and Implications for Message Design.

    Science.gov (United States)

    Comello, Maria Leonora G; Farman, Lisa

    2016-10-02

    Advertisements, movies, and other forms of media content have potential to change behaviors and antecedent psychological states by appealing to identity. However, the mechanisms that are responsible for persuasive effects of such content have not been adequately specified. A recently proposed model of communication effects (the prism model) advances the study of mechanisms and argues that identity can serve as both a moderator and mediator of communication effects on behavior-relevant outcomes. These intervening roles are made possible by the complex nature of identity (including multiple self-concepts and sensitivity to cues) and messages that cue the importance of and activate particular self-concepts. This article builds on development of the model by presenting empirical support based on re-analysis of an experiment in which participants viewed either a more-stigmatizing or less-stigmatizing portrayal of a recovering drug addict. In line with the model's propositions, exposure to the less-stigmatizing condition led to increases in perspective taking which then led to more acceptance (mediation by identity), while level of perspective taking also changed the effect of condition on acceptance (moderation by identity). These results provide support for the model's proposition of simultaneous intervening roles. The authors discuss implications for strategic communication research and practice.

  3. Designing Communication Protocols for a Computer-Mediated Laboratory for Problem-Based Learning

    Science.gov (United States)

    Koschmann, T.D.; Feltovich, P.J.; Myers, A.; Barrows, H.S.

    1990-01-01

    This paper describes some of the design criteria for a facility to support problem-based tutorials, known as the Computer-Mediated Tutorial Laboratory (CMTL). In the CMTL, a networked workstation will be provided for the tutor and each of the students. The tutor's workstation will be connected to a projection system, permitting the entire group to view the tutor's screen. The software used in the CMTL will have three components: a Patient Simulation Stack (PSS), the group/student Tutorial Stacks (TSs) and the network communication interface. The PSS represents a clinical problem; it is designed to realistically simulate an encounter with an actual patient. The TSs serve as a personalized record of what transpired in the tutorial session. Each student will maintain a private TS and the tutor will maintain a shared TS, viewable by all members of the group. The network communication interface will permit the participants in the tutorial to direct electronic messages to each other. The communication interface has two components: the client software available on the student's and tutor's workstation and the server software. The CMTL client software consists of two applications-one for sending messages and one for viewing the stream of incoming messages. Research is planned to investigate the effects of computer-mediation on the tutorial process.

  4. Seeing through the Screen: Is Evaluative Feedback Communicated More Effectively in Face-to-Face or Computer-Mediated Exchanges?

    Science.gov (United States)

    Hebert, Brenda G.; Vorauer, Jacquie D.

    2003-01-01

    Describes a study of college students that examined how the use of computer mediated communication affected the transmission of performance and interpersonal appraisal information. Examined whether interpersonal judgments obtained through face-to-face communication resulted in greater positivity, but compromised accuracy, relative to…

  5. Employing a Structured Interface to Advance Primary Students' Communicative Competence in a Text-Based Computer Mediated Environment

    Science.gov (United States)

    Chiu, Chiung-Hui; Wu, Chiu-Yi; Hsieh, Sheng-Jieh; Cheng, Hsiao-Wei; Huang, Chung-Kai

    2013-01-01

    This study investigated whether a structured communication interface fosters primary students' communicative competence in a synchronous typewritten computer-mediated collaborative learning environment. The structured interface provided a set of predetermined utterance patterns for elementary students to use or imitate to develop communicative…

  6. Employing a Structured Interface to Advance Primary Students' Communicative Competence in a Text-Based Computer Mediated Environment

    Science.gov (United States)

    Chiu, Chiung-Hui; Wu, Chiu-Yi; Hsieh, Sheng-Jieh; Cheng, Hsiao-Wei; Huang, Chung-Kai

    2013-01-01

    This study investigated whether a structured communication interface fosters primary students' communicative competence in a synchronous typewritten computer-mediated collaborative learning environment. The structured interface provided a set of predetermined utterance patterns for elementary students to use or imitate to develop communicative…

  7. Computer-mediated communication and interpersonal attraction: an experimental test of two explanatory hypotheses.

    Science.gov (United States)

    Antheunis, Marjolijn L; Valkenburg, Patti M; Peter, Jochen

    2007-12-01

    The aims of this study were (a) to investigate the influence of computer-mediated communication (CMC) on interpersonal attraction and (b) to examine two underlying processes in the CMC-interpersonal attraction relationship. We identified two variables that may mediate the influence of CMC on interpersonal attraction: self-disclosure and direct questioning. Focusing on these potential mediating variables, we tested two explanatory hypotheses: the CMC-induced direct questioning hypothesis and the CMC-induced self-disclosure hypothesis. Eighty-one cross-sex dyads were randomly assigned to one of three experimental conditions: text-only CMC, visual CMC, and face-to-face communication. We did not find a direct effect of CMC on interpersonal attraction. However, we did find two positive indirect effects of text-only CMC on interpersonal attraction: text-only CMC stimulated both self-disclosure and direct questioning, both of which in turn enhanced interpersonal attraction. Results are discussed in light of uncertainty reduction theory and CMC theories.

  8. Talking about Quitting: Interpersonal Communication as a Mediator of Campaign Effects on Smokers’ Quit Behaviors

    Science.gov (United States)

    Jeong, Michelle; Tan, Andy; Brennan, Emily; Gibson, Laura; Hornik, Robert C.

    2015-01-01

    This study examined the role of interpersonal communication in the context of a mass media anti-smoking campaign. Specifically, it explored whether conversations about campaign ads and/or about quitting mediated campaign exposure effects on two quitting behaviors (sought help to quit and tried to quit smoking completely), as well as the relationship between ad-related and quitting-related conversations. Data were collected prior to the campaign and monthly for 16 months during the campaign through cross-sectional telephone surveys among a sample of 3277 adult Philadelphian smokers. Follow-up interviews were conducted among 877 participants three months after their first survey. Cross-sectional and longitudinal mediation models with bootstrap procedures assessed the indirect effects of campaign exposure on outcomes through conversations, and of conversations about ads on outcomes through conversations about quitting. In addition, lagged regression analyses tested the causal direction of associations between the variables of interest. The results partially support hypotheses that conversations about quitting mediate campaign effects on quitting-related behaviors, and, in line with previous research, that conversations about the ads have indirect effects on quitting-related behaviors by triggering conversations about quitting. These findings demonstrate the importance of considering interpersonal communication as a route of campaign exposure effects when evaluating and designing future public health campaigns. PMID:26147367

  9. Talking About Quitting: Interpersonal Communication as a Mediator of Campaign Effects on Smokers' Quit Behaviors.

    Science.gov (United States)

    Jeong, Michelle; Tan, Andy S L; Brennan, Emily; Gibson, Laura; Hornik, Robert C

    2015-01-01

    This study examined the role of interpersonal communication in the context of a mass media anti-smoking campaign. Specifically, it explored whether conversations about campaign ads and/or about quitting mediated campaign exposure effects on 2 quitting behaviors (sought help to quit and tried to quit smoking completely), as well as the relation between ad-related and quitting-related conversations. Data were collected before the campaign and monthly for 16 months during the campaign through cross-sectional telephone surveys among a sample of 3,277 adult Philadelphia smokers. Follow-up interviews were conducted among 877 participants 3 months after their first survey. Cross-sectional and longitudinal mediation models with bootstrap procedures assessed the indirect effects of campaign exposure on outcomes through conversations, and the indirect effects of conversations about ads on outcomes through conversations about quitting. In addition, lagged regression analyses tested the causal direction of associations between the variables of interest. The results partially support hypotheses that conversations about quitting mediate campaign effects on quitting-related behaviors and, in line with previous research, that conversations about the ads have indirect effects on quitting-related behaviors by triggering conversations about quitting. These findings demonstrate the importance of considering interpersonal communication as a route of campaign exposure effects when evaluating and designing future public health campaigns.

  10. Mediating effect of self-efficacy in relationship between emotional intelligence and clinical communication competency of nurses

    OpenAIRE

    B. Zhu; C.-R. Chen; Z.-Y. Shi; H.-X. Liang; Liu, B.

    2016-01-01

    Objective: This study investigates the emotional intelligence (EI), self-efficacy, and clinical communication ability of clinical nurses to explore the correlation among these three variables, and verify the mediating effect of self-efficacy on relationship between EI and communication skills. Methods: A total of 865 nurses were recruited and investigated using Wong and Law's Emotional Intelligence Scale, General Self-Efficacy Scale, and nurse clinical communication scale. Results: The ...

  11. Computer-Mediated Communication in Korean-English Chat Rooms: Tandem Learning in an International Languages Program

    Science.gov (United States)

    Chung, Yang-Gyun; Graves, Barbara; Wesche, Mari; Barfurth, Marion

    2005-01-01

    This longitudinal case study draws on sociocultural theory to investigate language learning as a socially mediated process through computer-mediated communicative tasks in an international languages class. The study reports on the design, implementation, and outcomes of a thematic, task-based curricular innovation in which paired Korean-and…

  12. Site-to-site interdomain communication may mediate different loss-of-function mechanisms in a cancer-associated NQO1 polymorphism

    Science.gov (United States)

    Medina-Carmona, Encarnación; Neira, Jose L.; Salido, Eduardo; Fuchs, Julian E.; Palomino-Morales, Rogelio; Timson, David J.; Pey, Angel L.

    2017-01-01

    Disease associated genetic variations often cause intracellular enzyme inactivation, dysregulation and instability. However, allosteric communication of mutational effects to distant functional sites leading to loss-of-function remains poorly understood. We characterize here interdomain site-to-site communication by which a common cancer-associated single nucleotide polymorphism (c.C609T/p.P187S) reduces the activity and stability in vivo of NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 is a FAD-dependent, two-domain multifunctional stress protein acting as a Phase II enzyme, activating cancer pro-drugs and stabilizing p53 and p73α oncosuppressors. We show that p.P187S causes structural and dynamic changes communicated to functional sites far from the mutated site, affecting the FAD binding site located at the N-terminal domain (NTD) and accelerating proteasomal degradation through dynamic effects on the C-terminal domain (CTD). Structural protein:protein interaction studies reveal that the cancer-associated polymorphism does not abolish the interaction with p73α, indicating that oncosuppressor destabilization largely mirrors the low intracellular stability of p.P187S. In conclusion, we show how a single disease associated amino acid change may allosterically perturb several functional sites in an oligomeric and multidomain protein. These results have important implications for the understanding of loss-of-function genetic diseases and the identification of novel structural hot spots as targets for pharmacological intervention. PMID:28291250

  13. Unsubscribe, pleeezz!!!: management and training of media competence in computer-mediated communication.

    Science.gov (United States)

    Jonas, Kai J; Boos, Margarete; Sassenberg, Kai

    2002-08-01

    Computer-mediated communication (CMC) has created a new communication divide. Mostly, this division is due to technical and access problems. Overlooked is yet another divide in terms of user communication competence. This contribution focuses on media competence based on theories about communication competence and theories about CMC. Two field studies are presented: an analysis of a virtual seminar chat communication (22 participants, 3 weeks' duration) and an analysis of unsubscribe-failures within 2 years of a German mailing list (average of 1,000 subscriptions). Data from both studies reveal that help-seeking CMC users with low media-specific competence experience setbacks in terms of interpersonal relations and information gathering. There is a spiral of neutral to negative reactions and an increase in stress and aggression-related language in the reaction of the addressed peers. From the perspective of external raters, we found a contraintuitive result: The style, content, and wording of the message of the respondent is considered as an indicator for a less competent and socially attractive person behind the follow-up message than those of the initial message. On the one hand, media experts are needed and appreciated as technical problem-solvers; on the other hand, they might be perceived as socially narrow-minded freaks who are less interested in the task itself than in CMC-based task completion. This leads to the question of how sensibility for the social context, task orientation, and media competence can be combined (and trained for) in one person. Two competence trainings for text-based synchronous and asynchronous communication are introduced as interventions.

  14. An evolutionary examination of telemedicine: a health and computer-mediated communication perspective.

    Science.gov (United States)

    Breen, Gerald-Mark; Matusitz, Jonathan

    2010-01-01

    Telemedicine, the use of advanced communication technologies in the healthcare context, has a rich history and a clear evolutionary course. In this paper, the authors identify telemedicine as operationally defined, the services and technologies it comprises, the direction telemedicine has taken, along with its increased acceptance in the healthcare communities. The authors also describe some of the key pitfalls warred with by researchers and activists to advance telemedicine to its full potential and lead to an unobstructed team of technicians to identify telemedicine's diverse utilities. A discussion and future directions section is included to provide fresh ideas to health communication and computer-mediated scholars wishing to delve into this area and make a difference to enhance public understanding of this field.

  15. Shyness, sociability, and the use of computer-mediated communication in relationship development.

    Science.gov (United States)

    Sheeks, Miranda S; Birchmeier, Zachary P

    2007-02-01

    Computer-mediated communication (CMC) offers its users a reduced-cues environment, a chosen degree of identifiability to others, and a forum to express facets of one's self. Previous research suggests CMC is more appealing than traditional forms of communication to certain individuals whose desires to be sociable with others are prohibited by social inhibitions. The present study predicted that individuals who indicated higher levels of both shyness and sociability would be able to express their true-selves to a greater extent online. Their relationships online would grow more quickly and be more satisfying relative to others. The pattern of results supports our hypotheses, except for the predicted relationship between true-self expression and CMC use. Suggestions for future research as well as implications for the application of CMC use in therapy for certain populations are addressed.

  16. Knowledge work in nursing and midwifery: an evaluation through computer-mediated communication.

    Science.gov (United States)

    Brooks, Fiona; Scott, Peter

    2006-01-01

    Recent changes in policy and culture require health workers to incorporate "knowledge work" as a routine component of professional practice. Innovative computer-mediated communication technologies provide the opportunity to evaluate the nature of "knowledge work" within nursing and midwifery. This study embedded an online discussion system into an acute NHS Trust to support interaction within communities of practice. The complete record of online communications was analysed. Nurses were found to predominantly engage in information work with knowledge work restricted to senior-to-senior level exchanges. In contrast, midwives were observed to employ the technology to support knowledge work between all grades. The study indicates that technology can support knowledge work, including conveying tacit knowledge effectively.

  17. Meaning Making Through Minimal Linguistic Forms in Computer-Mediated Communication

    Directory of Open Access Journals (Sweden)

    Muhammad Shaban Rafi

    2014-05-01

    Full Text Available The purpose of this study was to investigate the linguistic forms, which commonly constitute meanings in the digital environment. The data were sampled from 200 Bachelor of Science (BS students (who had Urdu as their primary language of communication and English as one of the academic languages or the most prestigious second language of five universities situated in Lahore, Pakistan. The procedure for analysis was conceived within much related theoretical work on text analysis. The study reveals that cyber-language is organized through patterns of use, which can be broadly classified into minimal linguistic forms constituting a meaning-making resource. In addition, the expression of syntactic mood, and discourse roles the participants technically assume tend to contribute to the theory of meaning in the digital environment. It is hoped that the study would make some contribution to the growing literature on multilingual computer-mediated communication (CMC.

  18. Identifiability and self-presentation: computer-mediated communication and intergroup interaction.

    Science.gov (United States)

    Douglas, K M; McGarty, C

    2001-09-01

    This research investigated the intergroup properties of hostile 'flaming' behaviour in computer-mediated communication and how flaming language is affected by Internet identifiability, or identifiability by name and e-mail address/geographical location as is common to Internet communication. According to the Social Identity Model of Deindividuation Effects (SIDE; e.g. Reicher, Spears, & Postmes, 1995) there may be strategic reasons for identifiable groups members to act in a more group-normative manner in the presence of an audience, to gain acceptance from the in-group, to avoid punishment from the out-group, or to assert their identity to the out-group. For these reasons, it was predicted that communicators would produce more stereotype-consistent (group-normative) descriptions of out-group members' behaviours when their descriptions were identifiable to an audience. In one archival and three experimental studies, it was found that identifiability to an in-group audience was associated with higher levels of stereotype-consistent language when communicators described anonymous out-group targets. These results extend SIDE and suggest the importance of an in-group audience for the expression of stereotypical views.

  19. Review:Introduction:Sociolinguistics and Computer-Mediated Communi-cation

    Institute of Scientific and Technical Information of China (English)

    WANG Sai

    2016-01-01

    This paper is a brief review of Introduction: sociolinguisitcs and computer-mediated communication. The author of this paper makes analysis of this paper from four parts. The first part is the introduction which is briefly concerned with the ba-sic information of this paper. Part two deals with the most important concept in this paper CMC. The main body part of this pa-per is the third part which reviews this paper from structural and content aspects. The last part is about disadvantages of this part.

  20. The Application of Intentional Subjective Properties and Mediated Communication Tools to Software Agents in Online Disputes Resolution Environments

    Directory of Open Access Journals (Sweden)

    Renzo Gobbin

    2004-11-01

    Full Text Available This paper examines the use of subjective properties in modeling an architecture for cooperative agents using Agent Communication Language (ACL that is used as a mediating tool for cooperative communication activities between and within software agents. The role that subjective and objective properties have in explaining and modeling agent internalization and externalization of ACL messages is investigated and related to Vygotsky’s developmental learning theories such as Mediated Activity Theory. A novel agent architecture ALMA (Agent Language Mediated Activity based on the integration of agents’ subjective and objective properties within an agent communication activity framework will be presented. The relevance of software agents subjective properties in modeling applications such as e-Law Online Dispute Resolution for e-business contractual arrangements using natural language subject/object relation in their communication patterns will be discussed.

  1. Allosteric sensitization of proapoptotic BAX.

    Science.gov (United States)

    Pritz, Jonathan R; Wachter, Franziska; Lee, Susan; Luccarelli, James; Wales, Thomas E; Cohen, Daniel T; Coote, Paul; Heffron, Gregory J; Engen, John R; Massefski, Walter; Walensky, Loren D

    2017-09-01

    BCL-2-associated X protein (BAX) is a critical apoptotic regulator that can be transformed from a cytosolic monomer into a lethal mitochondrial oligomer, yet drug strategies to modulate it are underdeveloped due to longstanding difficulties in conducting screens on this aggregation-prone protein. Here, we overcame prior challenges and performed an NMR-based fragment screen of full-length human BAX. We identified a compound that sensitizes BAX activation by binding to a pocket formed by the junction of the α3-α4 and α5-α6 hairpins. Biochemical and structural analyses revealed that the molecule sensitizes BAX by allosterically mobilizing the α1-α2 loop and BAX BH3 helix, two motifs implicated in the activation and oligomerization of BAX, respectively. By engaging a region of core hydrophobic interactions that otherwise preserve the BAX inactive state, the identified compound reveals fundamental mechanisms for conformational regulation of BAX and provides a new opportunity to reduce the apoptotic threshold for potential therapeutic benefit.

  2. Anxiety about speaking a foreign language as a mediator of the relation between motivation and willingness to communicate.

    Science.gov (United States)

    Wu, Chia-Pei; Lin, Huey-Ju

    2014-12-01

    The purpose of this study was to examine whether anxiety about speaking a foreign language mediated the relation between motivation and a willingness to communicate among 107 Taiwanese students sampled from two public universities and one private university. A regression analysis indicated that motivation was negatively related to university students' anxiety about speaking a foreign language and positively related to willingness to communicate. Furthermore, anxiety about speaking a foreign language was negatively related to university students' willingness to communicate, and also partially mediated the relationship between motivation and willingness to communicate. The findings suggest that high motivation and low anxiety about speaking a foreign language are needed for Taiwanese students to demonstrate a stronger willingness to communicate.

  3. Plasmin Regulation through Allosteric, Sulfated, Small Molecules

    Directory of Open Access Journals (Sweden)

    Rami A. Al-Horani

    2015-01-01

    Full Text Available Plasmin, a key serine protease, plays a major role in clot lysis and extracellular matrix remodeling. Heparin, a natural polydisperse sulfated glycosaminoglycan, is known to allosterically modulate plasmin activity. No small allosteric inhibitor of plasmin has been discovered to date. We screened an in-house library of 55 sulfated, small glycosaminoglycan mimetics based on nine distinct scaffolds and varying number and positions of sulfate groups to discover several promising hits. Of these, a pentasulfated flavonoid-quinazolinone dimer 32 was found to be the most potent sulfated small inhibitor of plasmin (IC50 = 45 μM, efficacy = 100%. Michaelis-Menten kinetic studies revealed an allosteric inhibition of plasmin by these inhibitors. Studies also indicated that the most potent inhibitors are selective for plasmin over thrombin and factor Xa, two serine proteases in coagulation cascade. Interestingly, different inhibitors exhibited different levels of efficacy (40%–100%, an observation alluding to the unique advantage offered by an allosteric process. Overall, our work presents the first small, synthetic allosteric plasmin inhibitors for further rational design.

  4. Tumor vasculature is regulated by FGF/FGFR signaling-mediated angiogenesis and bone marrow-derived cell recruitment: this mechanism is inhibited by SSR128129E, the first allosteric antagonist of FGFRs.

    Science.gov (United States)

    Fons, Pierre; Gueguen-Dorbes, Geneviève; Herault, Jean-Pascal; Geronimi, Fabien; Tuyaret, Joël; Frédérique, Dol; Schaeffer, Paul; Volle-Challier, Cécile; Herbert, Jean-Marc; Bono, Françoise

    2015-01-01

    Tumor angiogenesis is accompanied by vasculogenesis, which is involved in the differentiation and mobilization of human bone marrow cells. In order to further characterize the role of vasculogenesis in the tumor growth process, the effects of FGF2 on the differentiation of human bone marrow AC133(+) cells (BM-AC133(+)) into vascular precursors were studied in vitro. FGF2, like VEGFA, induced progenitor cell differentiation into cell types with endothelial cell characteristics. SSR128129E, a newly discovered specific FGFR antagonist acting by allosteric interaction with FGFR, abrogated FGF2-induced endothelial cell differentiation, showing that FGFR signaling is essential during this process. To assess the involvement of the FGF/FRGR signaling in vivo, the pre-clinical model of Lewis lung carcinoma (LL2) in mice was used. Subcutaneous injection of LL2 cells into mice induced an increase of circulating EPCs from peripheral blood associated with tumor growth and an increase of intra-tumoral vascular index. Treatment with the FGFR antagonist SSR128129E strongly decreased LL2 tumor growth as well as the intra-tumoral vascular index (41% and 50% decrease vs. vehicle-treated mice respectively, P FGFR pathway by SSR128129E reduces EPC recruitment during angiogenesis-dependent tumor growth. In this context, circulating EPCs could be a reliable surrogate marker for tumor growth and angiogenic activity.

  5. Learners' perceived information overload in online learning via computer-mediated communication

    Directory of Open Access Journals (Sweden)

    Karen L. Murphy

    2011-12-01

    Full Text Available Many studies report information overload as one of the main problems that students encounter in online learning via computer-mediated communication. This study aimed to explore the sources of online students' information overload and offer suggestions for increasing students' cognitive resources for learning. Participants were 12 graduate students from two online courses in the United States. Their learning experiences in both online discussions and on the course website were explored through semi-structured interviews. They also completed a background questionnaire that assessed three constructs that limit learner readiness and are likely to lead to online students' perceived information overload: inadequate prior knowledge, inadequate English proficiency, and lack of technical skills for participating in computer-mediated communications. The findings suggest that varied learner characteristics led some students to be more susceptible than others to information overload. Emerging data-driven risk factors were: lack of efficiency in reading from computer screens, visual and auditory learning preferences, and time constraints. Difficulties associated with students' perceptions of information overload are addressed and implications for course design are offered.

  6. The oxidative environment: a mediator of interspecies communication that drives symbiosis evolution.

    Science.gov (United States)

    Moné, Yves; Monnin, David; Kremer, Natacha

    2014-06-22

    Symbiotic interactions are ubiquitous in nature and play a major role in driving the evolution of life. Interactions between partners are often mediated by shared signalling pathways, which strongly influence both partners' biology and the evolution of the association in various environments. As an example of 'common language', the regulation of the oxidative environment plays an important role in driving the evolution of symbiotic associations. Such processes have been occurring for billions of years, including the increase in Earth's atmospheric oxygen and the subsequent evolution of mitochondria. The effect of reactive oxygen species and reactive nitrogen species (RONS) has been characterized functionally, but the molecular dialogue between partners has not been integrated within a broader evolutionary context yet. Given the pleiotropic role of RONS in cell-cell communication, development and immunity, but also their associated physiological costs, we discuss here how their regulation can influence the establishment, the maintenance and the breakdown of various symbiotic associations. By synthesizing recent developments in redox biology, we aim to provide an interdisciplinary understanding of the influence of such mediators of interspecies communication on the evolution and stability of symbioses, which in turn can shape ecosystems and play a role in health and disease.

  7. Microvesicles as mediators of intercellular communication in cancer--the emerging science of cellular 'debris'.

    Science.gov (United States)

    Lee, Tae Hoon; D'Asti, Esterina; Magnus, Nathalie; Al-Nedawi, Khalid; Meehan, Brian; Rak, Janusz

    2011-09-01

    Cancer cells emit a heterogeneous mixture of vesicular, organelle-like structures (microvesicles, MVs) into their surroundings including blood and body fluids. MVs are generated via diverse biological mechanisms triggered by pathways involved in oncogenic transformation, microenvironmental stimulation, cellular activation, stress, or death. Vesiculation events occur either at the plasma membrane (ectosomes, shed vesicles) or within endosomal structures (exosomes). MVs are increasingly recognized as mediators of intercellular communication due to their capacity to merge with and transfer a repertoire of bioactive molecular content (cargo) to recipient cells. Such processes may occur both locally and systemically, contributing to the formation of microenvironmental fields and niches. The bioactive cargo of MVs may include growth factors and their receptors, proteases, adhesion molecules, signalling molecules, as well as DNA, mRNA, and microRNA (miRs) sequences. Tumour cells emit large quantities of MVs containing procoagulant, growth regulatory and oncogenic cargo (oncosomes), which can be transferred throughout the cancer cell population and to non-transformed stromal cells, endothelial cells and possibly to the inflammatory infiltrates (oncogenic field effect). These events likely impact tumour invasion, angiogenesis, metastasis, drug resistance, and cancer stem cell hierarchy. Ongoing studies explore the molecular mechanisms and mediators of MV-based intercellular communication (cancer vesiculome) with the hope of using this information as a possible source of therapeutic targets and disease biomarkers in cancer.

  8. Picture Exchange Communication System and Pals: A Peer-Mediated Augmentative and Alternative Communication Intervention for Minimally Verbal Preschoolers With Autism.

    Science.gov (United States)

    Thiemann-Bourque, Kathy; Brady, Nancy; McGuff, Sara; Stump, Keenan; Naylor, Amy

    2016-10-01

    This study was conducted to investigate the effectiveness of a social intervention that integrates peer-mediated approaches and the Picture Exchange Communication System (PECS). Effects were evaluated using a series of A-B designs replicated across 4 children with severe autism and limited verbal skills. Seven peers without disabilities were trained to use PECS and facilitative social skills. Measures of changes included rates of communication behaviors, modes, functions, and engagement. Outcomes revealed an intervention effect for 1 child with autism, and this effect was replicated across 3 other children. All children improved in peer-directed communication, with greater increases for 2 children during snack time. For each child with autism, the primary communication behavior was to initiate with picture symbols to request; the peer's primary communication was to respond. Two children increased communicative functions to comment and to share, and all 4 children showed improved social engagement. All peers increased their communication with the children with autism. These findings add to the limited research on the benefits of teaching typically developing peers to be responsive listeners to preschoolers with autism by learning to use PECS. These results invite further investigation of teaching peers other augmentative and alternative communication approaches and how to increase children's communication with peers for different purposes.

  9. Plasmodesmata-Mediated Cell-to-Cell Communication in the Shoot Apical Meristem: How Stem Cells Talk.

    Science.gov (United States)

    Kitagawa, Munenori; Jackson, David

    2017-03-01

    Positional information is crucial for the determination of plant cell fates, and it is established based on coordinated cell-to-cell communication, which in turn is essential for plant growth and development. Plants have evolved a unique communication pathway, with tiny channels called plasmodesmata (PD) spanning the cell wall. PD interconnect most cells in the plant and generate a cytoplasmic continuum, to mediate short- and long-distance trafficking of various molecules. Cell-to-cell communication through PD plays a role in transmitting positional signals, however, the regulatory mechanisms of PD-mediated trafficking are still largely unknown. The induction and maintenance of stem cells in the shoot apical meristem (SAM) depends on PDmediated cell-to-cell communication, hence, it is an optimal model for dissecting the regulatory mechanisms of PD-mediated cell-to-cell communication and its function in specifying cell fates. In this review, we summarize recent knowledge of PD-mediated cell-to-cell communication in the SAM, and discuss mechanisms underlying molecular trafficking through PD and its role in plant development.

  10. Plasmodesmata-Mediated Cell-to-Cell Communication in the Shoot Apical Meristem: How Stem Cells Talk

    Directory of Open Access Journals (Sweden)

    Munenori Kitagawa

    2017-03-01

    Full Text Available Positional information is crucial for the determination of plant cell fates, and it is established based on coordinated cell-to-cell communication, which in turn is essential for plant growth and development. Plants have evolved a unique communication pathway, with tiny channels called plasmodesmata (PD spanning the cell wall. PD interconnect most cells in the plant and generate a cytoplasmic continuum, to mediate short- and long-distance trafficking of various molecules. Cell-to-cell communication through PD plays a role in transmitting positional signals, however, the regulatory mechanisms of PD-mediated trafficking are still largely unknown. The induction and maintenance of stem cells in the shoot apical meristem (SAM depends on PDmediated cell-to-cell communication, hence, it is an optimal model for dissecting the regulatory mechanisms of PD-mediated cell-to-cell communication and its function in specifying cell fates. In this review, we summarize recent knowledge of PD-mediated cell-to-cell communication in the SAM, and discuss mechanisms underlying molecular trafficking through PD and its role in plant development.

  11. The allosteric switching mechanism in bacteriophage MS2

    Science.gov (United States)

    Perkett, Matthew R.; Mirijanian, Dina T.; Hagan, Michael F.

    2016-07-01

    We use all-atom simulations to elucidate the mechanisms underlying conformational switching and allostery within the coat protein of the bacteriophage MS2. Assembly of most icosahedral virus capsids requires that the capsid protein adopts different conformations at precise locations within the capsid. It has been shown that a 19 nucleotide stem loop (TR) from the MS2 genome acts as an allosteric effector, guiding conformational switching of the coat protein during capsid assembly. Since the principal conformational changes occur far from the TR binding site, it is important to understand the molecular mechanism underlying this allosteric communication. To this end, we use all-atom simulations with explicit water combined with a path sampling technique to sample the MS2 coat protein conformational transition, in the presence and absence of TR-binding. The calculations find that TR binding strongly alters the transition free energy profile, leading to a switch in the favored conformation. We discuss changes in molecular interactions responsible for this shift. We then identify networks of amino acids with correlated motions to reveal the mechanism by which effects of TR binding span the protein. We find that TR binding strongly affects residues located at the 5-fold and quasi-sixfold interfaces in the assembled capsid, suggesting a mechanism by which the TR binding could direct formation of the native capsid geometry. The analysis predicts amino acids whose substitution by mutagenesis could alter populations of the conformational substates or their transition rates.

  12. Advances in automated deception detection in text-based computer-mediated communication

    Science.gov (United States)

    Adkins, Mark; Twitchell, Douglas P.; Burgoon, Judee K.; Nunamaker, Jay F., Jr.

    2004-08-01

    The Internet has provided criminals, terrorists, spies, and other threats to national security a means of communication. At the same time it also provides for the possibility of detecting and tracking their deceptive communication. Recent advances in natural language processing, machine learning and deception research have created an environment where automated and semi-automated deception detection of text-based computer-mediated communication (CMC, e.g. email, chat, instant messaging) is a reachable goal. This paper reviews two methods for discriminating between deceptive and non-deceptive messages in CMC. First, Document Feature Mining uses document features or cues in CMC messages combined with machine learning techniques to classify messages according to their deceptive potential. The method, which is most useful in asynchronous applications, also allows for the visualization of potential deception cues in CMC messages. Second, Speech Act Profiling, a method for quantifying and visualizing synchronous CMC, has shown promise in aiding deception detection. The methods may be combined and are intended to be a part of a suite of tools for automating deception detection.

  13. Computer-mediated communication preferences predict biobehavioral measures of social-emotional functioning.

    Science.gov (United States)

    Babkirk, Sarah; Luehring-Jones, Peter; Dennis-Tiwary, Tracy A

    2016-12-01

    The use of computer-mediated communication (CMC) as a form of social interaction has become increasingly prevalent, yet few studies examine individual differences that may shed light on implications of CMC for adjustment. The current study examined neurocognitive individual differences associated with preferences to use technology in relation to social-emotional outcomes. In Study 1 (N = 91), a self-report measure, the Social Media Communication Questionnaire (SMCQ), was evaluated as an assessment of preferences for communicating positive and negative emotions on a scale ranging from purely via CMC to purely face-to-face. In Study 2, SMCQ preferences were examined in relation to event-related potentials (ERPs) associated with early emotional attention capture and reactivity (the frontal N1) and later sustained emotional processing and regulation (the late positive potential (LPP)). Electroencephalography (EEG) was recorded while 22 participants passively viewed emotional and neutral pictures and completed an emotion regulation task with instructions to increase, decrease, or maintain their emotional responses. A greater preference for CMC was associated with reduced size of and satisfaction with social support, greater early (N1) attention capture by emotional stimuli, and reduced LPP amplitudes to unpleasant stimuli in the increase emotion regulatory task. These findings are discussed in the context of possible emotion- and social-regulatory functions of CMC.

  14. Learner Use of Holistic Language Units in Multimodal, Task-Based Synchronous Computer-Mediated Communication

    Directory of Open Access Journals (Sweden)

    Karina Collentine

    2009-06-01

    Full Text Available Second language acquisition (SLA researchers strive to understand the language and exchanges that learners generate in synchronous computer-mediated communication (SCMC. Doughty and Long (2003 advocate replacing open-ended SCMC with task-based language teaching (TBLT design principles. Since most task-based SCMC (TB-SCMC research addresses an interactionist view (e.g., whether uptake occurs, we know little about holistic language units generated by learners even though research suggests that task demands make TB-SCMC communication notably different from general SCMC communication. This study documents and accounts for discourse-pragmatic and sociocultural behaviors learners exhibit in TB-SCMC. To capture a variety of such behaviors, it documents holistic language units produced by intermediate and advanced learners of Spanish during two multimodal, TB-SCMC activities. The study found that simple assertions were most prevalent (a with dyads at the lower level of instruction and (b when dyads had a relatively short amount of time to chat. Additionally, interpersonal, sociocultural behaviors (e.g., joking, off-task discussions were more likely to occur (a amongst dyads at the advanced level and (b when they had relatively more time to chat. Implications explain how tasks might mitigate the potential processing overload that multimodal materials could incur.

  15. Communication Processes that Mediate Family Communication Patterns and Mental Well-Being: A Mean and Covariance Structures Analysis of Young Adults from Divorced and Nondivorced Families

    Science.gov (United States)

    Schrodt, Paul; Ledbetter, Andrew M.

    2007-01-01

    In this study, demand/withdraw patterns and feeling caught were tested as mediators of family communication patterns and young adults' mental well-being. Participants included 567 young adults from divorced and nondivorced families. For young adults in nondivorced families, family conversation orientations had both a positive, direct effect on…

  16. Learners' Use of Communication Strategies in Text-Based and Video-Based Synchronous Computer-Mediated Communication Environments: Opportunities for Language Learning

    Science.gov (United States)

    Hung, Yu-Wan; Higgins, Steve

    2016-01-01

    This study investigates the different learning opportunities enabled by text-based and video-based synchronous computer-mediated communication (SCMC) from an interactionist perspective. Six Chinese-speaking learners of English and six English-speaking learners of Chinese were paired up as tandem (reciprocal) learning dyads. Each dyad participated…

  17. TLR2 mediates gap junctional intercellular communication through connexin-43 in intestinal epithelial barrier injury.

    Science.gov (United States)

    Ey, Birgit; Eyking, Annette; Gerken, Guido; Podolsky, Daniel K; Cario, Elke

    2009-08-14

    Gap junctional intercellular communication (GJIC) coordinates cellular functions essential for sustaining tissue homeostasis; yet its regulation in the intestine is not well understood. Here, we identify a novel physiological link between Toll-like receptor (TLR) 2 and GJIC through modulation of Connexin-43 (Cx43) during acute and chronic inflammatory injury of the intestinal epithelial cell (IEC) barrier. Data from in vitro studies reveal that TLR2 activation modulates Cx43 synthesis and increases GJIC via Cx43 during IEC injury. The ulcerative colitis-associated TLR2-R753Q mutant targets Cx43 for increased proteasomal degradation, impairing TLR2-mediated GJIC during intestinal epithelial wounding. In vivo studies using mucosal RNA interference show that TLR2-mediated mucosal healing depends functionally on intestinal epithelial Cx43 during acute inflammatory stress-induced damage. Mice deficient in TLR2 exhibit IEC-specific alterations in Cx43, whereas administration of a TLR2 agonist protects GJIC by blocking accumulation of Cx43 and its hyperphosphorylation at Ser368 to prevent spontaneous chronic colitis in MDR1alpha-deficient mice. Finally, adding the TLR2 agonist to three-dimensional intestinal mucosa-like cultures of human biopsies preserves intestinal epithelial Cx43 integrity and polarization ex vivo. In conclusion, Cx43 plays an important role in innate immune control of commensal-mediated intestinal epithelial wound repair.

  18. Allosteric Inhibition of Macrophage Migration Inhibitory Factor Revealed by Ibudilast

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Y.; Crichlow, G; Vermeire, J; Leng, L; Du, X; Hodsdon, M; Bucala, R; Cappello, M; Gross, M; et al.

    2010-01-01

    AV411 (ibudilast; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine) is an antiinflammatory drug that was initially developed for the treatment of bronchial asthma but which also has been used for cerebrovascular and ocular indications. It is a nonselective inhibitor of various phosphodiesterases (PDEs) and has varied antiinflammatory activity. More recently, AV411 has been studied as a possible therapeutic for the treatment of neuropathic pain and opioid withdrawal through its actions on glial cells. As described herein, the PDE inhibitor AV411 and its PDE-inhibition-compromised analog AV1013 inhibit the catalytic and chemotactic functions of the proinflammatory protein, macrophage migration inhibitory factor (MIF). Enzymatic analysis indicates that these compounds are noncompetitive inhibitors of the p-hydroxyphenylpyruvate (HPP) tautomerase activity of MIF and an allosteric binding site of AV411 and AV1013 is detected by NMR. The allosteric inhibition mechanism is further elucidated by X-ray crystallography based on the MIF/AV1013 binary and MIF/AV1013/HPP ternary complexes. In addition, our antibody experiments directed against MIF receptors indicate that CXCR2 is the major receptor for MIF-mediated chemotaxis of peripheral blood mononuclear cells.

  19. Structural Analysis of Iac Repressor Bound to Allosteric Effectors

    Energy Technology Data Exchange (ETDEWEB)

    Daber,R.; Stayrook, S.; Rosenberg, A.; Lewis, M.

    2007-01-01

    The lac operon is a model system for understanding how effector molecules regulate transcription and are necessary for allosteric transitions. The crystal structures of the lac repressor bound to inducer and anti-inducer molecules provide a model for how these small molecules can modulate repressor function. The structures of the apo repressor and the repressor bound to effector molecules are compared in atomic detail. All effectors examined here bind to the repressor in the same location and are anchored to the repressor through hydrogen bonds to several hydroxyl groups of the sugar ring. Inducer molecules form a more extensive hydrogen-bonding network compared to anti-inducers and neutral effector molecules. The structures of these effector molecules suggest that the O6 hydroxyl on the galactoside is essential for establishing a water-mediated hydrogen bonding network that bridges the N-terminal and C-terminal sub-domains. The altered hydrogen bonding can account in part for the different structural conformations of the repressor, and is vital for the allosteric transition.

  20. Molecular basis of positive allosteric modulation of GluN2B NMDA receptors by polyamines.

    Science.gov (United States)

    Mony, Laetitia; Zhu, Shujia; Carvalho, Stéphanie; Paoletti, Pierre

    2011-06-17

    NMDA receptors (NMDARs) form glutamate-gated ion channels that have central roles in neuronal communication and plasticity throughout the brain. Dysfunctions of NMDARs are involved in several central nervous system disorders, including stroke, chronic pain and schizophrenia. One hallmark of NMDARs is that their activity can be allosterically regulated by a variety of extracellular small ligands. While much has been learned recently regarding allosteric inhibition of NMDARs, the structural determinants underlying positive allosteric modulation of these receptors remain poorly defined. Here, we show that polyamines, naturally occurring polycations that selectively enhance NMDARs containing the GluN2B subunit, bind at a dimer interface between GluN1 and GluN2B subunit N-terminal domains (NTDs). Polyamines act by shielding negative charges present on GluN1 and GluN2B NTD lower lobes, allowing their close apposition, an effect that in turn prevents NTD clamshell closure. Our work reveals the mechanistic basis for positive allosteric modulation of NMDARs. It provides the first example of an intersubunit binding site in this class of receptors, a discovery that holds promise for future drug interventions.

  1. The relationship between the external environment and physician e-mail communication: The mediating role of health information technology availability.

    Science.gov (United States)

    Mazurenko, Olena; Hearld, Larry R; Menachemi, Nir

    Physician e-mail communication, with patients and other providers, is one of the cornerstones of effective care coordination but varies significantly across physicians. A physician's external environment may contribute to such variations by enabling or constraining a physician's ability to adopt innovations such as health information technology (HIT) that can be used to support e-mail communication. The aim of the study was to examine whether the relationship of the external environment and physician e-mail communication with patients and other providers is mediated by the practice's HIT availability. The data were obtained from the Health Tracking Physician Survey (2008) and the Area Resource File (2008). Cross-sectional multivariable subgroup path analysis was used to investigate the mediating role of HIT availability across 2,850 U.S. physicians. Solo physicians' perceptions about malpractice were associated with 0.97 lower odds (p communication with patients and other providers, as compared to group and hospital practices, even when mediated by HIT availability. Subgroup analyses indicated that different types of practices are responsive to the different dimensions of the external environment. Specifically, solo practitioners were more responsive to the availability of resources in their environment, with per capita income associated with lower likelihood of physician e-mail communication (OR = 0.99, p information technology availability, which in turn was associated with a greater likelihood of communicating via e-mail with patients (OR = 1.02, p communication and the external environment is mediated by the practice's HIT availability. Efforts to improve physician e-mail communication and HIT adoption may need to reflect the varied perceptions of different types of practices.

  2. Using Bourdieu in Critical Mediatization Research: Communicational Doxa and Osmotic Pressures in the Field of UN Organizations

    Directory of Open Access Journals (Sweden)

    André Jansson

    2015-05-01

    Full Text Available This article develops a Bourdieusian approach to mediatization. It is argued that the Bourdieusian theories of doxa and fields can make valuable contributions to a critical perspective on mediatization, one that moves beyond the divides between institutionalist, social-constructivist and materialist understandings (e.g., Bourdieu, 1972/1977. Mediatization is here seen as the historically growing dependence on media technologies and institutions within diverse social fields and settings. In order to establish the link between mediatization and Bourdieu’s theories (ibid., the article introduces the concept of communicational doxa, which refers to the taken for granted communicational conventions and demands that regulate the inclusion of membership within a particular field. The article also shows how communicational doxa can be applied as an analytical concept. Findings from qualitative fieldwork carried out among highly mobile and skilled professionals within the field of UN organizations in Geneva, show how the autonomy of social agents is negotiated in relation to an increasingly mediatized communicational doxa.

  3. Allosteric effects on oxidative and nitrosative reactions of cell-free hemoglobins.

    Science.gov (United States)

    Bonaventura, Celia; Henkens, Robert; Alayash, Abdu I; Crumbliss, Alvin L

    2007-01-01

    A review of the oxidative and nitrosative reactions of cell-free hemoglobin-based oxygen carriers (HBOCs) shows that these reactions are intimately linked and are subject to allosteric control. Cross-linking reactions used to produce HBOCs introduce conformational constraints and result in Hbs with reduced responses to heterotropic and homotropic allosteric effectors. The Nernst plots of heme oxidation of cross-linked HBOCs are shifted to higher potentials relative to unmodified Hb in the absence of allosteric effectors, in accord with their T-state stabilization and right-shifted Hill plots of O(2) binding. They exhibit enhanced rates of autoxidation and nitrite-induced oxidation, features that appear due to their having more solvent-accessible heme pockets. The stability of their NO-Hb derivatives varies as a result of allosteric effects on the extent of formation of pentacoordinate NO-heme geometry by alpha chains and subsequent oxidation of partner beta chains. The physiological implications of these findings on the safety, efficacy and design of second generation HBOCs are discussed in the framework of a reaction scheme showing linkages between Hb-mediated redox reactions. These redox reactions can drive formation of SNO-Hb and other reactive species and are of significance for the use of cell-free Hbs in vivo.

  4. THE ROLE OF OFFLINE METALANGUAGE TALK IN ASYNCHRONOUS COMPUTER-MEDIATED COMMUNICATION

    Directory of Open Access Journals (Sweden)

    Keiko Kitade

    2008-02-01

    Full Text Available In order to demonstrate how learners utilize the text-based asynchronous attributes of the Bulletin Board System, this study explored Japanese-as-a-second-language learners' metalanguage episodes (Swain & Lapkin, 1995, 1998 in offline verbal peer speech and online asynchronous discussions with their Japanese key pals. The findings suggest the crucial role of offline collaborative dialogue, the interactional modes in which the episodes occur, and the unique discourse structure of metalanguage episodes concerning online and offline interactions. A high score on the posttest also suggests the high retention of linguistic knowledge constructed through offline peer dialogue. In the offline mode, the learners were able to collaboratively construct knowledge with peers in the stipulated time, while simultaneously focusing on task content in the online interaction. The retrospective interviews and questionnaires reveal the factors that could affect the benefits of the asynchronous computer-mediated communication medium for language learning.

  5. Influence of Perceived Information Overload on Learning in Computer-Mediated Communication

    Science.gov (United States)

    Chen, Chun-Ying

    Information overload (IO) is frequently reported as one of the main problems caused by computer-mediated communication (CMC), yet the literature is unclear about the impact of IO on student learning. This study therefore aimed to investigate the influence of online students’ perceived IO on quality learning in CMC. Quality learning was defined as learning that is achievable by (a) reflective thinking through a deep level of information processing, and by (b) active learning through interaction with other people. The results suggest that students’ perceived IO does not influence their deep processing as observed in their discussion messages, but might influence their participation and interaction with others in online discussions. Students’ amount of invested mental effort put into study was observed as a major determinant of levels of information processing in this study.

  6. Caregiver communication to the child as moderator and mediator of genes for language.

    Science.gov (United States)

    Onnis, Luca

    2017-05-15

    Human language appears to be unique among natural communication systems, and such uniqueness impinges on both nature and nurture. Human babies are endowed with cognitive abilities that predispose them to learn language, and this process cannot operate in an impoverished environment. To be effectively complete the acquisition of human language in human children requires highly socialised forms of learning, scaffolded over years of prolonged and intense caretaker-child interactions. How genes and environment operate in shaping language is unknown. These two components have traditionally been considered as independent, and often pitted against each other in terms of the nature versus nurture debate. This perspective article considers how innate abilities and experience might instead work together. In particular, it envisages potential scenarios for research, in which early caregiver verbal and non-verbal attachment practices may mediate or moderate the expression of human genetic systems for language. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Social Communication Effects of Peer-Mediated Recess Intervention for Children with Autism.

    Science.gov (United States)

    McFadden, Brandon; Kamps, Debra; Heitzman-Powell, Linda

    2014-12-01

    Children with ASD face enormous challenges in the area of social functioning. Research has shown that impairments in social functioning distinguish this population from both typically developing children and children with disabilities. This study incorporated several evidence-based social skills-teaching procedures (i.e., direct instruction, priming, prompting, peer-mediation, contingent reinforcement, and token economies) directly in the recess setting to increase appropriate social behaviors for four children with ASD (ages 6-8). Elements of Peer Networks and Pivotal Response Training (two types of social skills intervention packages in the literature) were included. Results showed significant increases in social communication between focus children and their peers, as well as generalization of skills to non-intervention recesses.

  8. Allosteric small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    current barriers of kinase inhibitors, including poor selectivity and emergence of drug resistance. In spite of the small number of identified allosteric inhibitors in comparison with that of inhibitors targeting the ATP pocket, encouraging results, such as the FDA-approval of the first small...

  9. Computation of conformational coupling in allosteric proteins.

    Directory of Open Access Journals (Sweden)

    Brian A Kidd

    2009-08-01

    Full Text Available In allosteric regulation, an effector molecule binding a protein at one site induces conformational changes, which alter structure and function at a distant active site. Two key challenges in the computational modeling of allostery are the prediction of the structure of one allosteric state starting from the structure of the other, and elucidating the mechanisms underlying the conformational coupling of the effector and active sites. Here we approach these two challenges using the Rosetta high-resolution structure prediction methodology. We find that the method can recapitulate the relaxation of effector-bound forms of single domain allosteric proteins into the corresponding ligand-free states, particularly when sampling is focused on regions known to change conformation most significantly. Analysis of the coupling between contacting pairs of residues in large ensembles of conformations spread throughout the landscape between and around the two allosteric states suggests that the transitions are built up from blocks of tightly coupled interacting sets of residues that are more loosely coupled to one another.

  10. Communication

    NARCIS (Netherlands)

    Sigafoos, J.; Lancioni, G.E.; O'Reilly, M.F.; Lang, R.; Singh, N.N.; Didden, H.C.M.; Green, V.A.; Marschik, P.B.

    2016-01-01

    Communication disorders are common among people with intellectual disabilities. Consequently, enhancing the communication skills of such individuals is a major intervention priority. This chapter reviews the nature and prevalence of the speech, language, and communication problems associated with

  11. Computer-mediated cross-cultural collaboration: attributing communication errors to the person versus the situation.

    Science.gov (United States)

    Vignovic, Jane A; Thompson, Lori Foster

    2010-03-01

    Computer-mediated communication, such as e-mail, facilitates cross-cultural interactions by enabling convenient communication. During these exchanges, the absence of contextual or situational information may cause e-mail recipients to form dispositional explanations for behavior that might in fact be driven by unseen situational constraints. To gain insight into the manner in which e-mail recipients explain behavior, the authors conducted an experiment examining how technical language violations (i.e., spelling and grammatical errors) and deviations from etiquette norms (i.e., short messages lacking a conversational tone) affect a recipient's perceptions of an e-mail sender's conscientiousness, intelligence, agreeableness, extraversion, affective trustworthiness, and cognitive trustworthiness. This study also investigated whether the effects of technical and etiquette language violations depend on the availability of information indicating the e-mail sender is from a foreign culture. Results reveal that participants formed negative perceptions of the sender of an e-mail containing technical language violations. However, most of these negative perceptions were reduced when participants had situational information indicating that the e-mail sender was from a different culture. Conversely, negative attributions stemming from etiquette violations were not significantly mitigated by knowledge that the e-mail sender was from a foreign culture.

  12. DISCOURSE FUNCTIONS AND VOCABULARY USE IN ENGLISH LANGUAGE LEARNERS' SYNCHRONOUS COMPUTER-MEDIATED COMMUNICATION

    Directory of Open Access Journals (Sweden)

    Ghaleb RABAB'AH

    2013-04-01

    Full Text Available This study explores the discourse generated by English as a foreign language (EFL learners using synchronous computer-mediated communication (CMC as an approach to help English language learners to create social interaction in the classroom. It investigates the impact of synchronous CMC mode on the quantity of total words, lexical range and discourse functions of EFL learners’ writing from different genders (males vs. females. Thirty-two intermediate EFL students discussed four topics in four CMC sessions. The findings reveal that gender plays a major role in shaping the quantity of discourse (total words, lexical range (variety, and linguistic output (i.e., the quantity and type of discourse functions the participants’ generated using synchronous CMC mode. Generally, the female participants produced more words, complex lexical range and output discourse functions than males in CMC setting. In addition, the study showed that the participants produced discourse functions shaped by the particularities of local social arrangements. Users found opportunities in the virtual world of CMC which enable them to blind their identities, so people in subordinate conditions such as females in certain conservative societies, EFL learners, and shy students may find CMC useful for fostering their communicative competence.

  13. The effect of computer-mediated social support in online communities on patient empowerment and doctor-patient communication.

    Science.gov (United States)

    Oh, Hyun Jung; Lee, Byoungkwan

    2012-01-01

    In the context of diabetes, this study tested a mechanism through which Korean diabetes patients' exchange of computer-mediated social support (CMSS) in diabetes online communities influences their sense of empowerment and intention to actively communicate with the doctor. Analysis of data from 464 Korean diabetes patients indicates significant relationships among diabetes patients' online community activities, perceived CMSS, sense of empowerment, and their intention to actively communicate with the doctor. Diabetes patients who have engaged more in online community activities perceived greater social support from other members of the community. Perceived CMSS significantly predicted their intention to actively communicate with the doctor through sense of empowerment. Sense of empowerment was a valid underlying mechanism that explains how patients' perceived CMSS influences their intention to actively communicate with the doctor. The implications for health communication research and practice are discussed.

  14. Mediating the social and psychological impacts of terrorist attacks: the role of risk perception and risk communication.

    Science.gov (United States)

    Rogers, M Brooke; Amlôt, Richard; Rubin, G James; Wessely, Simon; Krieger, Kristian

    2007-06-01

    The public's understanding of chemical, biological, radiological and nuclear (CBRN) related issues and their likely actions following a CBRN incident is an issue of great concern, as public psychological and behavioural responses will help determine subsequent morbidity and mortality rates. This paper explores the role of effective government communication with the public and its role in mediating the social and psychological impact of terrorist attacks. We examine the importance of effective communication in reducing morbidity and mortality in the event of a terrorist attack and explore the impact of risk perceptions in determining the success or failure of risk communication strategies. This includes the examination of the role of fear as a health risk, and the identification of factors relevant to public trust in risk communication. Finally, an investigation of the type of information desired by members of the public leads the authors to make risk communication recommendations targeted at the promotion of more adaptive behaviours in response to CBRN attacks.

  15. Exosome-Mediated Intercellular Communication between Hepatitis C Virus-Infected Hepatocytes and Hepatic Stellate Cells.

    Science.gov (United States)

    Devhare, Pradip B; Sasaki, Reina; Shrivastava, Shubham; Di Bisceglie, Adrian M; Ray, Ranjit; Ray, Ratna B

    2017-03-15

    Fibrogenic pathways in the liver are principally regulated by activation of hepatic stellate cells (HSC). Fibrosis is associated with chronic hepatitis C virus (HCV) infection, although the mechanism is poorly understood. HSC comprise the major population of nonparenchymal cells in the liver. Since HCV does not replicate in HSC, we hypothesized that exosomes secreted from HCV-infected hepatocytes activate HSC. Primary or immortalized human hepatic stellate (LX2) cells were exposed to exosomes derived from HCV-infected hepatocytes (HCV-exo), and the expression of fibrosis-related genes was examined. Our results demonstrated that HCV-exo internalized to HSC and increased the expression of profibrotic markers. Further analysis suggested that HCV-exo carry miR-19a and target SOCS3 in HSC, which in turn activates the STAT3-mediated transforming growth factor β (TGF-β) signaling pathway and enhances fibrosis marker genes. The higher expression of miR-19a in exosomes was also observed from HCV-infected hepatocytes and in sera of chronic HCV patients with fibrosis compared to healthy volunteers and non-HCV-related liver disease patients with fibrosis. Together, our results demonstrated that miR-19a carried through the exosomes from HCV-infected hepatocytes activates HSC by modulating the SOCS-STAT3 axis. Our results implicated a novel mechanism of exosome-mediated intercellular communication in the activation of HSC for liver fibrosis in HCV infection.IMPORTANCE HCV-associated liver fibrosis is a critical step for end-stage liver disease progression. However, the molecular mechanisms for hepatic stellate-cell activation by HCV-infected hepatocytes are underexplored. Here, we provide a role for miR-19a carried through the exosomes in intercellular communication between HCV-infected hepatocytes and HSC in fibrogenic activation. Furthermore, we demonstrate the role of exosomal miR-19a in activation of the STAT3-TGF-β pathway in HSC. This study contributes to the

  16. Learners' Reflections on and Perceptions of Computer-Mediated Communication in a Language Classroom: A Vietnamese Perspective

    Science.gov (United States)

    Nguyen, Long V.

    2011-01-01

    The paper examines Vietnamese learners' reflections on and perceptions of the application of computer-mediated communication (CMC) into collaborative learning. Data for analysis included an evaluation questionnaire, consisting of 24 4-point Likert scale items, appended with six open-ended questions, and transcripts of 15, out of 30, teacher…

  17. Effects of Synchronous and Asynchronous Computer-Mediated Communication (CMC) Oral Conversations on English Language Learners' Discourse Functions

    Science.gov (United States)

    AbuSeileek, Ali Farhan; Qatawneh, Khaleel

    2013-01-01

    This study aimed to explore the effects of synchronous and asynchronous computer mediated communication (CMC) oral discussions on question types and strategies used by English as a Foreign Language (EFL) learners. The participants were randomly assigned to two treatment conditions/groups; the first group used synchronous CMC, while the second…

  18. Perceived Benefits and Drawbacks of Synchronous Voice-Based Computer-Mediated Communication in the Foreign Language Classroom

    Science.gov (United States)

    Bueno Alastuey, M. C.

    2011-01-01

    This study explored the benefits and drawbacks of synchronous voice-based computer-mediated communication (CMC) in a blended course of English for specific purposes. Quantitative and qualitative data from two groups following the same syllabus, except for the oral component, were compared. Oral tasks were carried out face-to-face with same L1…

  19. An Analysis of Computer-Mediated Communication between Middle School Students and Scientist Role Models: A Pilot Study.

    Science.gov (United States)

    Murfin, Brian

    1994-01-01

    Reports on a study of the effectiveness of computer-mediated communication (CMC) in providing African American and female middle school students with scientist role models. Quantitative and qualitative data gathered by analyzing messages students and scientists posted on a shared electronic bulletin board showed that CMC could be an effective…

  20. The Mediator Effect of Career Development between Personality Traits and Organizational Commitment: The Example of Sport Communication Technology Talents

    Science.gov (United States)

    Lo, Hung-Jen; Lin, Chun-Hung; Tung-Hsing, Lin; Tu, Peng-Fei

    2014-01-01

    This paper explored the relationships among career development, personality trait, and organizational commitment and examines whether career development mediates the relationship between personality trait and organizational commitment. The sample was 275 sport communication technology talents in Taiwan. The instrument included the Personality…

  1. The importance of source and credibility perceptions in times of crisis: crisis communication in a socially mediated era

    NARCIS (Netherlands)

    van Zoonen, W.; van der Meer, T.

    2015-01-01

    Social media are invaluable sources of information during organizational crises. Although recent research confirms this fundamental role in crisis communication, this article is aimed at deepening the understanding about the role of the source of information in this socially mediated era by comparin

  2. The Impact of Computer-Mediated Communication Environments on Foreign Language Learning: A Review of the Literature

    Science.gov (United States)

    Mahdi, Hassan Saleh

    2014-01-01

    This article reviews the literature on the implementation of computer-mediated communication (CMC) in language learning, aiming at understanding how CMC environments have been implemented to foster language learning. The paper draws on 40 recent research articles selected from 10 peer-reviewed journals, 2 book chapters and one conference…

  3. A Meta-Synthesis of Empirical Research on the Effectiveness of Computer-Mediated Communication (CMC) in SLA

    Science.gov (United States)

    Lin, Huifen

    2015-01-01

    This meta-analysis reports the results of a systematic synthesis of primary studies on the effectiveness of computer-mediated communication (CMC) in second language acquisition (SLA) for the period 2000-2012. By extracting information on 21 features from each primary study, this meta-analysis intends to summarize the CMC research literature for…

  4. The Influence of Perceived Information Overload on Student Participation and Knowledge Construction in Computer-Mediated Communication

    Science.gov (United States)

    Chen, Chun-Ying; Pedersen, Susan; Murphy, Karen L.

    2012-01-01

    Computer-mediated communication (CMC) has been used widely to engage learners in academic discourse for knowledge construction. Due to the features of the task environment, one of the main problems caused by the medium is information overload (IO). Yet the literature is unclear about the impact of IO on student learning. This study therefore…

  5. Learners' Reflections on and Perceptions of Computer-Mediated Communication in a Language Classroom: A Vietnamese Perspective

    Science.gov (United States)

    Nguyen, Long V.

    2011-01-01

    The paper examines Vietnamese learners' reflections on and perceptions of the application of computer-mediated communication (CMC) into collaborative learning. Data for analysis included an evaluation questionnaire, consisting of 24 4-point Likert scale items, appended with six open-ended questions, and transcripts of 15, out of 30, teacher…

  6. Perceived Benefits and Drawbacks of Synchronous Voice-Based Computer-Mediated Communication in the Foreign Language Classroom

    Science.gov (United States)

    Bueno Alastuey, M. C.

    2011-01-01

    This study explored the benefits and drawbacks of synchronous voice-based computer-mediated communication (CMC) in a blended course of English for specific purposes. Quantitative and qualitative data from two groups following the same syllabus, except for the oral component, were compared. Oral tasks were carried out face-to-face with same L1…

  7. The importance of source and credibility perceptions in times of crisis: crisis communication in a socially mediated era

    NARCIS (Netherlands)

    van Zoonen, W.; van der Meer, T.

    2015-01-01

    Social media are invaluable sources of information during organizational crises. Although recent research confirms this fundamental role in crisis communication, this article is aimed at deepening the understanding about the role of the source of information in this socially mediated era by

  8. Computer-Mediated Word-of-Mouth Communication: The Influence of Mixed Reviews on Student Perceptions of Instructors and Courses

    Science.gov (United States)

    Edwards, Autumn; Edwards, Chad

    2013-01-01

    The purpose of this experiment was to test the influence of mixed reviews appearing as computer-mediated word-of-mouth communication (WOM) on student perceptions of instructors (attractiveness and credibility) and attitudes toward learning course content (affective learning and state motivation). Using the heuristic-systematic processing model, it…

  9. Adult Attachment and Male Aggression in Couple Relationships: The Demand-Withdraw Communication Pattern and Relationship Satisfaction as Mediators

    Science.gov (United States)

    Fournier, Benoit; Brassard, Audrey; Shaver, Phillip R.

    2011-01-01

    This study examines men's domestic aggression as a function of attachment insecurities, considering the mediating roles of the demand-withdraw communication pattern and relationship satisfaction. The sample included 55 Canadian men undergoing counseling for relationship difficulties including aggression. The men completed questionnaires assessing…

  10. Multilevel Leadership and Organizational Effectiveness in Indian Technical Education: The Mediating Role of Communication, Power and Culture

    Science.gov (United States)

    Gochhayat, Jyotiranjan; Giri, Vijai N.; Suar, Damodar

    2017-01-01

    This study provides a new conceptualization of educational leadership with a multilevel and integrative approach. It examines the impact of multilevel leadership (MLL) on the effectiveness of technical educational institutes through the mediating effects of organizational communication, bases of power and organizational culture. Data were…

  11. Content Analysis in Computer-Mediated Communication: Analyzing Models for Assessing Critical Thinking through the Lens of Social Constructivism

    Science.gov (United States)

    Buraphadeja, Vasa; Dawson, Kara

    2008-01-01

    This article reviews content analysis studies aimed to assess critical thinking in computer-mediated communication. It also discusses theories and content analysis models that encourage critical thinking skills in asynchronous learning environments and reviews theories and factors that may foster critical thinking skills and new knowledge…

  12. Learning Style and Task Performance in Synchronous Computer-Mediated Communication: A Case Study of Iranian EFL Learners

    Science.gov (United States)

    Hedayati, Mohsen; Foomani, Elham Mohammadi

    2015-01-01

    The study reported here explores whether English as a foreign Language (EFL) learners' preferred ways of learning (i.e., learning styles) affect their task performance in computer-mediated communication (CMC). As Ellis (2010) points out, while the increasing use of different sorts of technology is witnessed in language learning contexts, it is…

  13. A Meta-Synthesis of Empirical Research on the Effectiveness of Computer-Mediated Communication (CMC) in SLA

    Science.gov (United States)

    Lin, Huifen

    2015-01-01

    This meta-analysis reports the results of a systematic synthesis of primary studies on the effectiveness of computer-mediated communication (CMC) in second language acquisition (SLA) for the period 2000-2012. By extracting information on 21 features from each primary study, this meta-analysis intends to summarize the CMC research literature for…

  14. The Influence of Perceived Information Overload on Student Participation and Knowledge Construction in Computer-Mediated Communication

    Science.gov (United States)

    Chen, Chun-Ying; Pedersen, Susan; Murphy, Karen L.

    2012-01-01

    Computer-mediated communication (CMC) has been used widely to engage learners in academic discourse for knowledge construction. Due to the features of the task environment, one of the main problems caused by the medium is information overload (IO). Yet the literature is unclear about the impact of IO on student learning. This study therefore…

  15. Content Analysis in Computer-Mediated Communication: Analyzing Models for Assessing Critical Thinking through the Lens of Social Constructivism

    Science.gov (United States)

    Buraphadeja, Vasa; Dawson, Kara

    2008-01-01

    This article reviews content analysis studies aimed to assess critical thinking in computer-mediated communication. It also discusses theories and content analysis models that encourage critical thinking skills in asynchronous learning environments and reviews theories and factors that may foster critical thinking skills and new knowledge…

  16. EFL Learners' Perceived Use of Conversation Maintenance Strategies during Synchronous Computer-Mediated Communication with Native English Speakers

    Science.gov (United States)

    Ino, Atsushi

    2014-01-01

    This study investigated the perceived use of conversation maintenance strategies during synchronous computer-mediated communication with native English speakers. I also correlated the relationships of the strategies used with students' speaking ability and comprehensive proficiency level. The research questions were: (1) how were the learners'…

  17. The Nature of Negotiations in Face-to-Face versus Computer-Mediated Communication in Pair Interactions

    Science.gov (United States)

    Rouhshad, Amir; Wigglesworth, Gillian; Storch, Neomy

    2016-01-01

    The Interaction Approach argues that negotiation for meaning and form is conducive to second language development. To date, most of the research on negotiations has been either in face-to-face (FTF) or text-based synchronous computer-mediated communication (SCMC) modes. Very few studies have compared the nature of negotiations across the modes.…

  18. Molecular sites for the positive allosteric modulation of glycine receptors by endocannabinoids.

    Directory of Open Access Journals (Sweden)

    Gonzalo E Yévenes

    Full Text Available Glycine receptors (GlyRs are transmitter-gated anion channels of the Cys-loop superfamily which mediate synaptic inhibition at spinal and selected supraspinal sites. Although they serve pivotal functions in motor control and sensory processing, they have yet to be exploited as drug targets partly because of hitherto limited possibilities for allosteric control. Endocannabinoids (ECs have recently been characterized as direct allosteric GlyR modulators, but the underlying molecular sites have remained unknown. Here, we show that chemically neutral ECs (e.g. anandamide, AEA are positive modulators of α(1, α(2 and α(3 GlyRs, whereas acidic ECs (e.g. N-arachidonoyl-glycine; NA-Gly potentiate α(1 GlyRs but inhibit α(2 and α(3. This subunit-specificity allowed us to identify the underlying molecular sites through analysis of chimeric and mutant receptors. We found that alanine 52 in extracellular loop 2, glycine 254 in transmembrane (TM region 2 and intracellular lysine 385 determine the positive modulation of α(1 GlyRs by NA-Gly. Successive substitution of non-conserved extracellular and TM residues in α(2 converted NA-Gly-mediated inhibition into potentiation. Conversely, mutation of the conserved lysine within the intracellular loop between TM3 and TM4 attenuated NA-Gly-mediated potentiation of α(1 GlyRs, without affecting inhibition of α(2 and α(3. Notably, this mutation reduced modulation by AEA of all three GlyRs. These results define molecular sites for allosteric control of GlyRs by ECs and reveal an unrecognized function for the TM3-4 intracellular loop in the allosteric modulation of Cys-loop ion channels. The identification of these sites may help to understand the physiological role of this modulation and facilitate the development of novel therapeutic approaches to diseases such as spasticity, startle disease and possibly chronic pain.

  19. Learning experiences of science teachers in a computer-mediated communication context

    Science.gov (United States)

    Chung, Chia-Jung

    The use of computer-mediated-communication (CMC) has been applied increasingly in staff development efforts for teachers. Many teacher education programs are looking to CMC, particularly computer conferencing systems, as an effective and low-cost medium for the delivery of teacher educational programs anytime, anywhere. Based on constructivist learning theories, this study focused on examining the use of an online discussion board in a graduate course as a place where forty-six inservice teachers shared experiences and ideas. Data collection focused on online discussion transcripts of all the messages from three separate weeks, and supplemented by interviews and teacher self-evaluation reports. The nature and development of the discussions were studied over one semester by analyzing teacher online discussions in two domains: critical reflections and social-interpersonal rapport. In effect, this study provided insights into how to employ computer conferencing technology in facilitating inservice teachers' teaching practices and their professional development. Major findings include: (1) Participation: The level of participation varied during the semester but was higher at the beginning of the semester and lower at the end of the semester. (2) Critical Reflection: Teachers' critical reflection developed over time as a result of the online discussion board according to mean critical thinking scores during the three selected weeks. Cognitive presence was found mostly in focused discussion forums and social presence mainly existed in the unfocused discussion forums. (3) Social-Interpersonal Rapport: The number of social cues in the messages increased initially but declined significantly over time. When teachers focused more on on-task discussions or critical reflection, there was less social conversation. (4) Teaching Practices and Professional Development: The researcher, the instructor, and teachers identified some advantages for using computer conferencing for

  20. Control of lipid metabolism by adipocyte FGFR1-mediated adipohepatic communication during hepatic stress

    Directory of Open Access Journals (Sweden)

    Yang Chaofeng

    2012-10-01

    Full Text Available Abstract Background Endocrine FGF19 and FGF21 exert their effects on metabolic homeostasis through fibroblast growth factor receptor (FGFR and co-factor betaKlotho (KLB. Ileal FGF19 regulates bile acid metabolism through specifically FGFR4-KLB in hepatocytes where FGFR1 is not significant. Both FGF19 and FGF21 activate FGFR1-KLB whose function predominates in adipocytes. Recent studies using administration of FGF19 and FGF21 and genetic ablation of KLB or adipocyte FGFR1 indicate that FGFR1-KLB mediates the response of adipocytes to both FGF21 and FGF19. Here we show that adipose FGFR1 regulates lipid metabolism through direct effect on adipose tissue and indirect effects on liver under starvation conditions that cause hepatic stress. Methods We employed adipocyte-specific ablations of FGFR1 and FGFR2 genes in mice, and analyzed metabolic consequences in adipose tissue, liver and systemic parameters under normal, fasting and starvation conditions. Results Under normal conditions, the ablation of adipose FGFR1 had little effect on adipocytes, but caused shifts in expression of hepatic genes involved in lipid metabolism. Starvation conditions precipitated a concurrent elevation of serum triglycerides and non-esterified fatty acids, and increased hepatic steatosis and adipose lipolysis in the FGFR1-deficient mice. Little effect on glucose or ketone bodies due to the FGFR1 deficiency was observed. Conclusions Our results suggest an adipocyte-hepatocyte communication network mediated by adipocyte FGFR1 that concurrently dampens hepatic lipogenesis and adipocyte lipolysis. We propose that this serves overall to mete out and extend lipid reserves for neural fuels (glucose and ketone bodies, while at the same time governing extent of hepatosteatosis during metabolic extremes and other conditions causing hepatic stress.

  1. Sulforaphane counteracts aggressiveness of pancreatic cancer driven by dysregulated Cx43-mediated gap junctional intercellular communication

    Science.gov (United States)

    Zhang, Yiyao; Isayev, Orkhan; Heilmann, Katharina; Schoensiegel, Frank; Liu, Li; Nessling, Michelle; Richter, Karsten; Labsch, Sabrina; Nwaeburu, Clifford C.; Mattern, Juergen; Gladkich, Jury; Giese, Nathalia; Werner, Jens; Schemmer, Peter; Gross, Wolfgang; Gebhard, Martha M.; Gerhauser, Clarissa; Schaefer, Michael; Herr, Ingrid

    2014-01-01

    The extreme aggressiveness of pancreatic ductal adenocarcinoma (PDA) has been associated with blocked gap junctional intercellular communication (GJIC) and the presence of cancer stem cells (CSCs). We examined whether disturbed GJIC is responsible for a CSC phenotype in established and primary cancer cells and patient tissue of PDA using interdisciplinary methods based in physiology, cell and molecular biology, histology and epigenetics. Flux of fluorescent dyes and gemcitabine through gap junctions (GJs) was intact in less aggressive cells but not in highly malignant cells with morphological dysfunctional GJs. Among several connexins, only Cx43 was expressed on the cell surface of less aggressive and GJIC-competent cells, whereas Cx43 surface expression was absent in highly malignant, E-cadherin-negative and GJIC-incompetent cells. The levels of total Cx43 protein and Cx43 phosphorylated at Ser368 and Ser279/282 were high in normal tissue but low to absent in malignant tissue. si-RNA-mediated inhibition of Cx43 expression in GJIC-competent cells prevented GJIC and induced colony formation and the expression of stem cell-related factors. The bioactive substance sulforaphane enhanced Cx43 and E-cadherin levels, inhibited the CSC markers c-Met and CD133, improved the functional morphology of GJs and enhanced GJIC. Sulforaphane altered the phosphorylation of several kinases and their substrates and inhibition of GSK3, JNK and PKC prevented sulforaphane-induced CX43 expression. The sulforaphane-mediated expression of Cx43 was not correlated with enhanced Cx43 RNA expression, acetylated histone binding and Cx43 promoter de-methylation, suggesting that posttranslational phosphorylation is the dominant regulatory mechanism. Together, the absence of Cx43 prevents GJIC and enhances aggressiveness, whereas sulforaphane counteracts this process, and our findings highlight dietary co-treatment as a viable treatment option for PDA. PMID:24742583

  2. The sociocognitive psychology of computer-mediated communication: the present and future of technology-based interactions.

    Science.gov (United States)

    Riva, Giuseppe

    2002-12-01

    The increased diffusion of the Internet has made computer-mediated communication (CMC) very popular. However, a difficult question arises for psychologists and communication researchers: "What are the communicative characteristics of CMC?" According to the "cues-filtered-out" approach, CMC lacks the specifically relational features (social cues), which enable the interlocutors to identify correctly the kind of interpersonal situations they find themselves in. This paper counters this vision by integrating in its theoretical frame the different psycho-social approaches available in current literature. In particular, the paper describes the characteristics of the socio-cognitive processes-emotional expression, context definition, and identity creation-used by the interlocutors to make order and create relationships out of the miscommunication processes typical of CMC. Moreover, it presents the emerging forms of CMC-instant messaging, shared hypermedia, weblogs, and graphical chats-and their possible social and communicative effects.

  3. Identifiability, reducibility, and adaptability in allosteric macromolecules.

    Science.gov (United States)

    Bohner, Gergő; Venkataraman, Gaurav

    2017-05-01

    The ability of macromolecules to transduce stimulus information at one site into conformational changes at a distant site, termed "allostery," is vital for cellular signaling. Here, we propose a link between the sensitivity of allosteric macromolecules to their underlying biophysical parameters, the interrelationships between these parameters, and macromolecular adaptability. We demonstrate that the parameters of a canonical model of the mSlo large-conductance Ca(2+)-activated K(+) (BK) ion channel are non-identifiable with respect to the equilibrium open probability-voltage relationship, a common functional assay. We construct a reduced model with emergent parameters that are identifiable and expressed as combinations of the original mechanistic parameters. These emergent parameters indicate which coordinated changes in mechanistic parameters can leave assay output unchanged. We predict that these coordinated changes are used by allosteric macromolecules to adapt, and we demonstrate how this prediction can be tested experimentally. We show that these predicted parameter compensations are used in the first reported allosteric phenomena: the Bohr effect, by which hemoglobin adapts to varying pH. © 2017 Bohner and Venkataraman.

  4. Allosteric control in a metalloprotein dramatically alters function.

    Science.gov (United States)

    Baxter, Elizabeth Leigh; Zuris, John A; Wang, Charles; Vo, Phu Luong T; Axelrod, Herbert L; Cohen, Aina E; Paddock, Mark L; Nechushtai, Rachel; Onuchic, Jose N; Jennings, Patricia A

    2013-01-15

    Metalloproteins (MPs) comprise one-third of all known protein structures. This diverse set of proteins contain a plethora of unique inorganic moieties capable of performing chemistry that would otherwise be impossible using only the amino acids found in nature. Most of the well-studied MPs are generally viewed as being very rigid in structure, and it is widely thought that the properties of the metal centers are primarily determined by the small fraction of amino acids that make up the local environment. Here we examine both theoretically and experimentally whether distal regions can influence the metal center in the diabetes drug target mitoNEET. We demonstrate that a loop (L2) 20 Å away from the metal center exerts allosteric control over the cluster binding domain and regulates multiple properties of the metal center. Mutagenesis of L2 results in significant shifts in the redox potential of the [2Fe-2S] cluster and orders of magnitude effects on the rate of [2Fe-2S] cluster transfer to an apo-acceptor protein. These surprising effects occur in the absence of any structural changes. An examination of the native basin dynamics of the protein using all-atom simulations shows that twisting in L2 controls scissoring in the cluster binding domain and results in perturbations to one of the cluster-coordinating histidines. These allosteric effects are in agreement with previous folding simulations that predicted L2 could communicate with residues surrounding the metal center. Our findings suggest that long-range dynamical changes in the protein backbone can have a significant effect on the functional properties of MPs.

  5. Exploiting protein flexibility to predict the location of allosteric sites

    Directory of Open Access Journals (Sweden)

    Panjkovich Alejandro

    2012-10-01

    Full Text Available Abstract Background Allostery is one of the most powerful and common ways of regulation of protein activity. However, for most allosteric proteins identified to date the mechanistic details of allosteric modulation are not yet well understood. Uncovering common mechanistic patterns underlying allostery would allow not only a better academic understanding of the phenomena, but it would also streamline the design of novel therapeutic solutions. This relatively unexplored therapeutic potential and the putative advantages of allosteric drugs over classical active-site inhibitors fuel the attention allosteric-drug research is receiving at present. A first step to harness the regulatory potential and versatility of allosteric sites, in the context of drug-discovery and design, would be to detect or predict their presence and location. In this article, we describe a simple computational approach, based on the effect allosteric ligands exert on protein flexibility upon binding, to predict the existence and position of allosteric sites on a given protein structure. Results By querying the literature and a recently available database of allosteric sites, we gathered 213 allosteric proteins with structural information that we further filtered into a non-redundant set of 91 proteins. We performed normal-mode analysis and observed significant changes in protein flexibility upon allosteric-ligand binding in 70% of the cases. These results agree with the current view that allosteric mechanisms are in many cases governed by changes in protein dynamics caused by ligand binding. Furthermore, we implemented an approach that achieves 65% positive predictive value in identifying allosteric sites within the set of predicted cavities of a protein (stricter parameters set, 0.22 sensitivity, by combining the current analysis on dynamics with previous results on structural conservation of allosteric sites. We also analyzed four biological examples in detail, revealing

  6. Producing Irony in Adolescence: A Comparison Between Face-to-Face and Computer-Mediated Communication

    Directory of Open Access Journals (Sweden)

    Aguert Marc

    2016-12-01

    Full Text Available The literature suggests that irony production expands in the developmental period of adolescence. We aimed to test this hypothesis by investigating two channels: face-to-face and computer-mediated communication (CMC. Corpora were collected by asking seventh and 11th graders to freely discuss some general topics (e.g., music, either face-to-face or on online forums. Results showed that 6.2% of the 11th graders’ productions were ironic utterances, compared with just 2.5% of the seventh graders’ productions, confirming the major development of irony production in adolescence. Results also showed that adolescents produced more ironic utterances in CMC than face-to-face. The analysis suggested that irony use is a strategy for increasing in-group solidarity and compensating for the distance intrinsic to CMC, as it was mostly inclusive and well-marked on forums. The present study also confirmed previous studies showing that irony is compatible with CMC.

  7. Utilizing usernames for sex categorization in computer-mediated communication: examining perceptions and accuracy.

    Science.gov (United States)

    Cornetto, Karen M; Nowak, Kristine L

    2006-08-01

    As more interpersonal interactions move online, people increasingly get to know and recognize one another by their self-selected identifiers called usernames. Early research predicted that the lack of available cues in text based computer-mediated communication (CMC) would make primitive categories such as biological sex irrelevant in online interactions. Little is known about the types of perceptions people make about one another based on this information, but some limited research has shown that questions about gender are the first to be asked in online interactions and sex categorization has maintained salience. The current project was designed to examine the extent to which individuals might include obvious gender information in their usernames, as well as how easily gender could be attributed from usernames. Seventy-five coders were asked whether or not they could assign 298 people to a sex category based only on their username, and then to rate how confident they were in making the attribution. Results indicated that coders were fairly inaccurate in making these attributions, but moderately confident. Additionally, the results indicated that neither women nor men were more accurate in attributing gender from usernames, and that neither women nor men tended to use more obvious gender markers in their usernames. Additionally, those who did use obvious gender markers in their username tended to have less experience with computer chat. The results are discussed in conjunction with the limitations of the present investigation, and possibilities for future research.

  8. Advanced practice registered nurse usability testing of a tailored computer-mediated health communication program.

    Science.gov (United States)

    Lin, Carolyn A; Neafsey, Patricia J; Anderson, Elizabeth

    2010-01-01

    This study tested the usability of a touch-screen-enabled Personal Education Program with advanced practice RNs. The Personal Education Program is designed to enhance medication adherence and reduce adverse self-medication behaviors in older adults with hypertension. An iterative research process was used, which involved the use of (1) pretrial focus groups to guide the design of system information architecture, (2) two different cycles of think-aloud trials to test the software interface, and (3) post-trial focus groups to gather feedback on the think-aloud studies. Results from this iterative usability-testing process were used to systematically modify and improve the three Personal Education Program prototype versions-the pilot, prototype 1, and prototype 2. Findings contrasting the two separate think-aloud trials showed that APRN users rated the Personal Education Program system usability, system information, and system-use satisfaction at a moderately high level between trials. In addition, errors using the interface were reduced by 76%, and the interface time was reduced by 18.5% between the two trials. The usability-testing processes used in this study ensured an interface design adapted to APRNs' needs and preferences to allow them to effectively use the computer-mediated health-communication technology in a clinical setting.

  9. A filter-mediated communication model for design collaboration in building construction.

    Science.gov (United States)

    Lee, Jaewook; Jeong, Yongwook; Oh, Minho; Hong, Seung Wan

    2014-01-01

    Multidisciplinary collaboration is an important aspect of modern engineering activities, arising from the growing complexity of artifacts whose design and construction require knowledge and skills that exceed the capacities of any one professional. However, current collaboration in the architecture, engineering, and construction industries often fails due to lack of shared understanding between different participants and limitations of their supporting tools. To achieve a high level of shared understanding, this study proposes a filter-mediated communication model. In the proposed model, participants retain their own data in the form most appropriate for their needs with domain-specific filters that transform the neutral representations into semantically rich ones, as needed by the participants. Conversely, the filters can translate semantically rich, domain-specific data into a neutral representation that can be accessed by other domain-specific filters. To validate the feasibility of the proposed model, we computationally implement the filter mechanism and apply it to a hypothetical test case. The result acknowledges that the filter mechanism can let the participants know ahead of time what will be the implications of their proposed actions, as seen from other participants' points of view.

  10. Challenges of mediated communication, disclosure and patient autonomy in cross-cultural cancer care.

    Science.gov (United States)

    Kai, J; Beavan, J; Faull, C

    2011-09-27

    Evidence concerning the influence of ethnic diversity on clinical encounters in cancer care is sparse. We explored health providers' experiences in this context. Focus groups were conducted with a purposeful sample of 106 health professionals of differing disciplines, in 18 UK primary and secondary care settings. Qualitative data were analysed using constant comparison and processes for validation. Communication and the quality of information exchanged with patients about cancer and their treatment was commonly frustrated within interpreter-mediated consultations, particularly those involving a family member. Relatives' approach to ownership of information and decision making could hinder assessment, informed consent and discussion of care with patients. This magnified the complexity of disclosing information sensitively and appropriately at the end of life. Professionals' concern to be patient-centred, and regard for patient choice and autonomy, were tested in these circumstances. Health professionals require better preparation to work effectively not only with trained interpreters, but also with the common reality of patients' families interpreting for patients, to improve quality of cancer care. Greater understanding of cultural and individual variations in concepts of disclosure, patient autonomy and patient-centredness is needed. The extent to which these concepts may be ethnocentric and lack universality deserves wider consideration.

  11. Computer-mediated communication as an autonomy-enhancement tool for advanced learners of English

    Directory of Open Access Journals (Sweden)

    Aleksandra Wach

    2012-10-01

    Full Text Available This article examines the relevance of modern technology for the development of learner autonomy in the process of learning English as a foreign language. Computer-assisted language learning and computer mediated communication (CMC appear to be particularly conducive to fostering autonomous learning, as they naturally incorporate many elements of autonomy that give learners control over and responsibility for their own learning, such as choosing the materials used, managing their contact with various genres and types of interaction, often in authentic contexts, and evaluating their own progress, measured through their success in understanding and conveying meanings. However, providing access to language resources does not automatically lead to the development of autonomy, as much depends on other factors, such as the learners’ level or previous experience in learner training. The present study investigated whether advanced learners of English made use of out-of-class CMC engagement for the purpose of learning English autonomously. The results indicate that most of the participants were eager to use CMC opportunities to deliberately practice their English, although, quite naturally, leisure and social reasons for using CMC predominated. The expressed willingness to deliberately focus on practicing English during beyond-theclassroom meaning-oriented online interactions confirms the great potential of CMC as an autonomy enhancement tool.

  12. Usability Testing by Older Adults of a Computer-Mediated Health Communication Program

    Science.gov (United States)

    Lin, Carolyn A.; Neafsey, Patricia J.; Strickler, Zoe

    2010-01-01

    This study tested the usability of a touch-screen enabled “Personal Education Program” (PEP) with Advanced Practice Registered Nurses (APRN). The PEP is designed to enhance medication adherence and reduce adverse self-medication behaviors in older adults with hypertension. An iterative research process was employed, which involved the use of: (1) pre-trial focus groups to guide the design of system information architecture, (2) two different cycles of think-aloud trials to test the software interface, and (3) post-trial focus groups to gather feedback on the think-aloud studies. Results from this iterative usability testing process were utilized to systematically modify and improve the three PEP prototype versions—the pilot, Prototype-1 and Prototype-2. Findings contrasting the two separate think-aloud trials showed that APRN users rated the PEP system usability, system information and system-use satisfaction at a moderately high level between trials. In addition, errors using the interface were reduced by 76 percent and the interface time was reduced by 18.5 percent between the two trials. The usability testing processes employed in this study ensured an interface design adapted to APRNs’ needs and preferences to allow them to effectively utilize the computer-mediated health-communication technology in a clinical setting. PMID:19283536

  13. Potential microRNA-mediated oncogenic intercellular communication revealed by pan-cancer analysis

    Science.gov (United States)

    Li, Yue; Zhang, Zhaolei

    2014-11-01

    Carcinogenesis consists of oncogenesis and metastasis, and intriguingly microRNAs (miRNAs) are involved in both processes. Although aberrant miRNA activities are prevalent in diverse tumor types, the exact mechanisms for how they regulate cancerous processes are not always clear. To this end, we performed a large-scale pan-cancer analysis via a novel probabilistic approach to infer recurrent miRNA-target interactions implicated in 12 cancer types using data from The Cancer Genome Atlas. We discovered ~20,000 recurrent miRNA regulations, which are enriched for cancer-related miRNAs/genes. Notably, miRNA 200 family (miR-200/141/429) is among the most prominent miRNA regulators, which is known to be involved in metastasis. Importantly, the recurrent miRNA regulatory network is not only enriched for cancer pathways but also for extracellular matrix (ECM) organization and ECM-receptor interactions. The results suggest an intriguing cancer mechanism involving miRNA-mediated cell-to-cell communication, which possibly involves delivery of tumorigenic miRNA messengers to adjacent cells via exosomes. Finally, survival analysis revealed 414 recurrent-prognostic associations, where both gene and miRNA involved in each interaction conferred significant prognostic power in one or more cancer types. Together, our comprehensive pan-cancer analysis provided not only biological insights into metastasis but also brought to bear the clinical relevance of the proposed recurrent miRNA-gene associations.

  14. Discovery of a novel allosteric modulator of 5-HT3 receptor

    DEFF Research Database (Denmark)

    Trattnig, Sarah M; Harpsøe, Kasper; Thygesen, Sarah B

    2012-01-01

    The ligand-gated ion channels in the Cysloop receptor superfamily mediate the effects of neurotransmitters acetylcholine, serotonin, GABA and glycine. Cysloop receptor signaling is susceptible to modulation by ligands acting through numerous allosteric sites. Here we report the discovery of a novel...... receptor guided by a homology model, PU02 is demonstrated to act through a transmembrane intersubunit site situated in the upper three helical turns of TM2 and TM3 in the (+)subunit and TM1 and TM2 in the (minus)subunit. The Ser248, Leu288, Ile290, Thr294 and Gly306 residues are identified as important...... and inhibiting 5-HT-evoked signaling through these mutants at low and high concentrations, respectively. The PU02 binding site in the 5HT3R corresponds to allosteric sites in anionic Cysloop receptors, which emphasizes the uniform nature of the molecular events underlying signaling through the receptors...

  15. Allosteric pathway identification through network analysis: from molecular dynamics simulations to interactive 2D and 3D graphs.

    Science.gov (United States)

    Allain, Ariane; Chauvot de Beauchêne, Isaure; Langenfeld, Florent; Guarracino, Yann; Laine, Elodie; Tchertanov, Luba

    2014-01-01

    Allostery is a universal phenomenon that couples the information induced by a local perturbation (effector) in a protein to spatially distant regulated sites. Such an event can be described in terms of a large scale transmission of information (communication) through a dynamic coupling between structurally rigid (minimally frustrated) and plastic (locally frustrated) clusters of residues. To elaborate a rational description of allosteric coupling, we propose an original approach - MOdular NETwork Analysis (MONETA) - based on the analysis of inter-residue dynamical correlations to localize the propagation of both structural and dynamical effects of a perturbation throughout a protein structure. MONETA uses inter-residue cross-correlations and commute times computed from molecular dynamics simulations and a topological description of a protein to build a modular network representation composed of clusters of residues (dynamic segments) linked together by chains of residues (communication pathways). MONETA provides a brand new direct and simple visualization of protein allosteric communication. A GEPHI module implemented in the MONETA package allows the generation of 2D graphs of the communication network. An interactive PyMOL plugin permits drawing of the communication pathways between chosen protein fragments or residues on a 3D representation. MONETA is a powerful tool for on-the-fly display of communication networks in proteins. We applied MONETA for the analysis of communication pathways (i) between the main regulatory fragments of receptors tyrosine kinases (RTKs), KIT and CSF-1R, in the native and mutated states and (ii) in proteins STAT5 (STAT5a and STAT5b) in the phosphorylated and the unphosphorylated forms. The description of the physical support for allosteric coupling by MONETA allowed a comparison of the mechanisms of (a) constitutive activation induced by equivalent mutations in two RTKs and (b) allosteric regulation in the activated and non

  16. The allosteric regulation of pyruvate kinase.

    Science.gov (United States)

    Valentini, G; Chiarelli, L; Fortin, R; Speranza, M L; Galizzi, A; Mattevi, A

    2000-06-16

    Pyruvate kinase (PK) is critical for the regulation of the glycolytic pathway. The regulatory properties of Escherichia coli were investigated by mutating six charged residues involved in interdomain salt bridges (Arg(271), Arg(292), Asp(297), and Lys(413)) and in the binding of the allosteric activator (Lys(382) and Arg(431)). Arg(271) and Lys(413) are located at the interface between A and C domains within one subunit. The R271L and K413Q mutant enzymes exhibit altered kinetic properties. In K413Q, there is partial enzyme activation, whereas R271L is characterized by a bias toward the T-state in the allosteric equilibrium. In the T-state, Arg(292) and Asp(297) form an intersubunit salt bridge. The mutants R292D and D297R are totally inactive. The crystal structure of R292D reveals that the mutant enzyme retains the T-state quaternary structure. However, the mutation induces a reorganization of the interface with the creation of a network of interactions similar to that observed in the crystal structures of R-state yeast and M1 PK proteins. Furthermore, in the R292D structure, two loops that are part of the active site are disordered. The K382Q and R431E mutations were designed to probe the binding site for fructose 1, 6-bisphosphate, the allosteric activator. R431E exhibits only slight changes in the regulatory properties. Conversely, K382Q displays a highly altered responsiveness to the activator, suggesting that Lys(382) is involved in both activator binding and allosteric transition mechanism. Taken together, these results support the notion that domain interfaces are critical for the allosteric transition. They couple changes in the tertiary and quaternary structures to alterations in the geometry of the fructose 1, 6-bisphosphate and substrate binding sites. These site-directed mutagenesis data are discussed in the light of the molecular basis for the hereditary nonspherocytic hemolytic anemia, which is caused by mutations in human erythrocyte PK gene.

  17. Learner Perceptions of Asynchronous Oral Computer-mediated Communication: Proficiency and Second Langauge Selves

    Directory of Open Access Journals (Sweden)

    Jesse Gleason

    2012-06-01

    Full Text Available Abstract The present study addresses the perceptions of international teaching assistants regarding the role of language learning tasks using Wimba Voice (WV in aiding the improvement of their second language (L2 oral skills. It specifically examines how this asynchronous computer-mediated communication (CMC technology can foster the development of these learners’ L2 selves. According to Dörnyei (2009, the more clearly learners can envision their future L2 selves, the more motivated they will be to achieve their L2 goals. With increased planning of oral production, access to instructor and peer feedback, and additional opportunities for self-reflection, asynchronous CMC technologies have been found to enable L2 learners to express their thoughts at their own pace and feel more relaxed and confident than in more threatening face-to-face situations (Sun, 2009. The findings suggest that learners have a variety of opinions regarding the role of asynchronous WV tasks in motivating them to develop their L2 oral proficiency. Also, many may prefer oral CMC environments that facilitate interaction and meaning negotiation. Results were inconclusive concerning the effect of WV-based tasks on students' perceptions of their future L2 selves; however, this may have been due to the short time frame in which these activities were employed. Résumé Nous étudions ici les perceptions d’un groupe d’assistants internationaux sur le rôle des tâches d’apprentissage linguistique à l’aide de Wimba Voice (WV. Le projet avait pour but d’améliorer les compétences orales des participants dans leur langue seconde. La présente étude examine en particulier la voie par laquelle cette technologie de la communication asynchrone par ordinateur peut favoriser l’évolution de la langue seconde des apprenants. Selon Dörnyei (2009, plus les apprenants peuvent envisager clairement un futur emploi de leur langue seconde, plus ils seront motivés à atteindre

  18. Computer-mediated communication and time pressure induce higher cardiovascular responses in the preparatory and execution phases of cooperative tasks.

    Science.gov (United States)

    Costa Ferrer, Raquel; Serrano Rosa, Miguel Ángel; Zornoza Abad, Ana; Salvador Fernández-Montejo, Alicia

    2010-11-01

    The cardiovascular (CV) response to social challenge and stress is associated with the etiology of cardiovascular diseases. New ways of communication, time pressure and different types of information are common in our society. In this study, the cardiovascular response to two different tasks (open vs. closed information) was examined employing different communication channels (computer-mediated vs. face-to-face) and with different pace control (self vs. external). Our results indicate that there was a higher CV response in the computer-mediated condition, on the closed information task and in the externally paced condition. These role of these factors should be considered when studying the consequences of social stress and their underlying mechanisms.

  19. Communication of Ca(2+) signals via tunneling membrane nanotubes is mediated by transmission of inositol trisphosphate through gap junctions.

    Science.gov (United States)

    Lock, Jeffrey T; Parker, Ian; Smith, Ian F

    2016-10-01

    Tunneling membrane nanotubes (TNTs) are thin membrane projections linking cell bodies separated by many micrometers, which are proposed to mediate signaling and even transfer of cytosolic contents between distant cells. Several reports describe propagation of Ca(2+) signals between distant cells via TNTs, but the underlying mechanisms remain poorly understood. Utilizing a HeLa M-Sec cell line engineered to upregulate TNTs we replicated previous findings that mechanical stimulation elicits robust cytosolic Ca(2+) elevations that propagate to surrounding, physically separate cells. However, whereas this was previously interpreted to involve intercellular communication through TNTs, we found that Ca(2+) signal propagation was abolished - even in TNT-connected cells - after blocking ATP-mediated paracrine signaling with a cocktail of extracellular inhibitors. To then establish whether gap junctions may enable cell-cell signaling via TNTs under these conditions, we expressed sfGFP-tagged connexin-43 (Cx43) in HeLa M-Sec cells. We observed robust communication of mechanically-evoked Ca(2+) signals between distant but TNT-connected cells, but only when both cells expressed Cx43. Moreover, we also observed communication of Ca(2+) signals evoked in one cell by local photorelease of inositol 1,4,5-trisphosphate (IP3). Ca(2+) responses in connected cells began after long latencies at intracellular sites several microns from the TNT connection site, implicating intercellular transfer of IP3 and subsequent IP3-mediated Ca(2+) liberation, and not Ca(2+) itself, as the mediator between TNT-connected, Cx43-expressing cells. Our results emphasize the need to control for paracrine transmission in studies of cell-cell signaling via TNTs and indicate that, in this cell line, TNTs do not establish cytosolic continuity between connected cells but rather point to the crucial importance of connexins to enable communication of cytosolic Ca(2+) signals via TNTs.

  20. Are socioeconomic disparities in health behavior mediated by differential media use? Test of the communication inequality theory.

    Science.gov (United States)

    Ishikawa, Yoshiki; Kondo, Naoki; Kawachi, Ichiro; Viswanath, Kasisomayajula

    2016-11-01

    Communication inequality has been offered as one potential mechanism through which social determinants influence multiple health behaviors. The purpose of this study was to examine the underlying mechanisms between communication inequality and health behaviors. Data from a nationally representative cross-sectional survey of 18,426 people aged 18 years and above in the United States were used for secondary analysis. Measures included socio-demographic characteristics, social participation (structural social capital), health media use (TV, print, and the Internet), and five health behaviors (physical activity, cigarette smoking, alcohol use, and intake of fruit and vegetable). Path analysis was performed to examine the linkages between social determinants, health media use, social participation, and social gradients in health behaviors. Path analysis revealed that socioeconomic gradients in health behaviors is mediated by: 1) inequalities in health media use; 2) disparities in social participation, which leads to differential media use; and 3) disparities in social participation that are not mediated by media use. Consistent with the theory of communication inequality, socioeconomic disparities in media use partially mediate disparities in multiple health behaviors. To address health inequalities, it is important to utilize health media to target populations with low socioeconomic statuses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Does contemporary computer-mediated epistolary communication need pedagogical interventions: The case of a student-teacher relationship

    Directory of Open Access Journals (Sweden)

    Prodanović Marijana M.

    2016-01-01

    Full Text Available The vast majority of messages we exchange on a daily basis is digital in its nature, and it could be said that computer-mediated communication has become common in all spheres of human endeavour. Despite the fact that CMC is an omnipresent phenomenon, it is usually the case that the choices regarding the language patterns to be used are made on our own; namely, it seems that there is no precise writing etiquette to be followed. This aim of this paper is to analyse the nature of computer-mediated communication performed in an academic environment. Using a language corpus composed of authentic email requests, sent by university students (Serbian native speakers to a faculty staff member, in a time frame encompassing a few semesters, the language formulae used in email openings and closings and the orientation of the posed requestive head acts have been examined. The results of the analysis have shown that hearer orientation is dominantly employed in the requests and that the choices with regard to salutations and complimentary closings are rather inconsistent. Finally, the study answers questions regarding the appropriateness of such e-communication patterns; it also sheds some light on the role of educators and/or educational institutions in communication processes of this kind and their forms.

  2. The Health Belief Model as an explanatory framework in communication research: exploring parallel, serial, and moderated mediation.

    Science.gov (United States)

    Jones, Christina L; Jensen, Jakob D; Scherr, Courtney L; Brown, Natasha R; Christy, Katheryn; Weaver, Jeremy

    2015-01-01

    The Health Belief Model (HBM) posits that messages will achieve optimal behavior change if they successfully target perceived barriers, benefits, self-efficacy, and threat. While the model seems to be an ideal explanatory framework for communication research, theoretical limitations have limited its use in the field. Notably, variable ordering is currently undefined in the HBM. Thus, it is unclear whether constructs mediate relationships comparably (parallel mediation), in sequence (serial mediation), or in tandem with a moderator (moderated mediation). To investigate variable ordering, adults (N = 1,377) completed a survey in the aftermath of an 8-month flu vaccine campaign grounded in the HBM. Exposure to the campaign was positively related to vaccination behavior. Statistical evaluation supported a model where the indirect effect of exposure on behavior through perceived barriers and threat was moderated by self-efficacy (moderated mediation). Perceived barriers and benefits also formed a serial mediation chain. The results indicate that variable ordering in the Health Belief Model may be complex, may help to explain conflicting results of the past, and may be a good focus for future research.

  3. Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity

    Science.gov (United States)

    Winkelmann, Donald A.; Forgacs, Eva; Miller, Matthew T.; Stock, Ann M.

    2015-08-01

    Omecamtiv Mecarbil (OM) is a small molecule allosteric effector of cardiac myosin that is in clinical trials for treatment of systolic heart failure. A detailed kinetic analysis of cardiac myosin has shown that the drug accelerates phosphate release by shifting the equilibrium of the hydrolysis step towards products, leading to a faster transition from weak to strong actin-bound states. The structure of the human β-cardiac motor domain (cMD) with OM bound reveals a single OM-binding site nestled in a narrow cleft separating two domains of the human cMD where it interacts with the key residues that couple lever arm movement to the nucleotide state. In addition, OM induces allosteric changes in three strands of the β-sheet that provides the communication link between the actin-binding interface and the nucleotide pocket. The OM-binding interactions and allosteric changes form the structural basis for the kinetic and mechanical tuning of cardiac myosin.

  4. Allosteric motions in structures of yeast NAD+-specific isocitrate dehydrogenase.

    Science.gov (United States)

    Taylor, Alexander B; Hu, Gang; Hart, P John; McAlister-Henn, Lee

    2008-04-18

    Mitochondrial NAD(+)-specific isocitrate dehydrogenases (IDHs) are key regulators of flux through biosynthetic and oxidative pathways in response to cellular energy levels. Here we present the first structures of a eukaryotic member of this enzyme family, the allosteric, hetero-octameric, NAD(+)-specific IDH from yeast in three forms: 1) without ligands, 2) with bound analog citrate, and 3) with bound citrate + AMP. The structures reveal the molecular basis for ligand binding to homologous but distinct regulatory and catalytic sites positioned at the interfaces between IDH1 and IDH2 subunits and define pathways of communication between heterodimers and heterotetramers in the hetero-octamer. Disulfide bonds observed at the heterotetrameric interfaces in the unliganded IDH hetero-octamer are reduced in the ligand-bound forms, suggesting a redox regulatory mechanism that may be analogous to the "on-off" regulation of non-allosteric bacterial IDHs via phosphorylation. The results strongly suggest that eukaryotic IDH enzymes are exquisitely tuned to ensure that allosteric activation occurs only when concentrations of isocitrate are elevated.

  5. Allosteric Motions in Structures of Yeast NAD+-Specific Isocitrate Dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Taylor,A.; Hu, G.; Hart, P.; McAlister-Henn, L.

    2008-01-01

    Mitochondrial NAD+-specific isocitrate dehydrogenases (IDHs) are key regulators of flux through biosynthetic and oxidative pathways in response to cellular energy levels. Here we present the first structures of a eukaryotic member of this enzyme family, the allosteric, hetero-octameric, NAD+-specific IDH from yeast in three forms: (1) without ligands, (2) with bound analog citrate, and (3) with bound citrate + AMP. The structures reveal the molecular basis for ligand binding to homologous but distinct regulatory and catalytic sites positioned at the interfaces between IDH1 and IDH2 subunits and define pathways of communication between heterodimers and heterotetramers in the hetero-octamer. Disulfide bonds observed at the heterotetrameric interfaces in the unliganded IDH hetero-octamer are reduced in the ligand-bound forms, suggesting a redox regulatory mechanism that may be analogous to the 'on-off' regulation of non-allosteric bacterial IDHs via phosphorylation. The results strongly suggest that eukaryotic IDH enzymes are exquisitely tuned to ensure that allosteric activation occurs only when concentrations of isocitrate are elevated.

  6. Modulation of global low-frequency motions underlies allosteric regulation: demonstration in CRP/FNR family transcription factors.

    Directory of Open Access Journals (Sweden)

    Thomas L Rodgers

    2013-09-01

    Full Text Available Allostery is a fundamental process by which ligand binding to a protein alters its activity at a distinct site. There is growing evidence that allosteric cooperativity can be communicated by modulation of protein dynamics without conformational change. The mechanisms, however, for communicating dynamic fluctuations between sites are debated. We provide a foundational theory for how allostery can occur as a function of low-frequency dynamics without a change in structure. We have generated coarse-grained models that describe the protein backbone motions of the CRP/FNR family transcription factors, CAP of Escherichia coli and GlxR of Corynebacterium glutamicum. The latter we demonstrate as a new exemplar for allostery without conformation change. We observe that binding the first molecule of cAMP ligand is correlated with modulation of the global normal modes and negative cooperativity for binding the second cAMP ligand without a change in mean structure. The theory makes key experimental predictions that are tested through an analysis of variant proteins by structural biology and isothermal calorimetry. Quantifying allostery as a free energy landscape revealed a protein "design space" that identified the inter- and intramolecular regulatory parameters that frame CRP/FNR family allostery. Furthermore, through analyzing CAP variants from diverse species, we demonstrate an evolutionary selection pressure to conserve residues crucial for allosteric control. This finding provides a link between the position of CRP/FNR transcription factors within the allosteric free energy landscapes and evolutionary selection pressures. Our study therefore reveals significant features of the mechanistic basis for allostery. Changes in low-frequency dynamics correlate with allosteric effects on ligand binding without the requirement for a defined spatial pathway. In addition to evolving suitable three-dimensional structures, CRP/FNR family transcription factors have

  7. Improving computer-mediated synchronous communication of doctors in rural communities through cloud computing: A case study of rural hospitals in South Africa

    CSIR Research Space (South Africa)

    Coleman, A

    2012-10-01

    Full Text Available This paper investigated how doctors in remote rural hospitals in South Africa use computer-mediated tool to communicate with experienced and specialist doctors for professional advice to improve on their clinical practices. A case study approach...

  8. Allosteric reversion of Haemophilus influenzae β-carbonic anhydrase via a proline shift.

    Science.gov (United States)

    Hoffmann, Katherine M; Million-Perez, H Rachael; Merkhofer, Richard; Nicholson, Hilary; Rowlett, Roger S

    2015-01-20

    suggests a new hypothesis to explain HICA allosteric communication that is mediated by the N-terminal helices and anion binding at the dimer interface.

  9. International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: recommendations for the nomenclature of receptor allosterism and allosteric ligands.

    Science.gov (United States)

    Christopoulos, Arthur; Changeux, Jean-Pierre; Catterall, William A; Fabbro, Doriano; Burris, Thomas P; Cidlowski, John A; Olsen, Richard W; Peters, John A; Neubig, Richard R; Pin, Jean-Philippe; Sexton, Patrick M; Kenakin, Terry P; Ehlert, Frederick J; Spedding, Michael; Langmead, Christopher J

    2014-10-01

    Allosteric interactions play vital roles in metabolic processes and signal transduction and, more recently, have become the focus of numerous pharmacological studies because of the potential for discovering more target-selective chemical probes and therapeutic agents. In addition to classic early studies on enzymes, there are now examples of small molecule allosteric modulators for all superfamilies of receptors encoded by the genome, including ligand- and voltage-gated ion channels, G protein-coupled receptors, nuclear hormone receptors, and receptor tyrosine kinases. As a consequence, a vast array of pharmacologic behaviors has been ascribed to allosteric ligands that can vary in a target-, ligand-, and cell-/tissue-dependent manner. The current article presents an overview of allostery as applied to receptor families and approaches for detecting and validating allosteric interactions and gives recommendations for the nomenclature of allosteric ligands and their properties.

  10. Allosteric “beta-blocker” isolated from a DNA-encoded small molecule library

    Science.gov (United States)

    Ahn, Seungkirl; Kahsai, Alem W.; Pani, Biswaranjan; Wang, Qin-Ting; Zhao, Shuai; Wall, Alissa L.; Strachan, Ryan T.; Staus, Dean P.; Wingler, Laura M.; Sun, Lillian D.; Sinnaeve, Justine; Choi, Minjung; Cho, Ted; Xu, Thomas T.; Hansen, Gwenn M.; Burnett, Michael B.; Lamerdin, Jane E.; Bassoni, Daniel L.; Gavino, Bryant J.; Husemoen, Gitte; Olsen, Eva K.; Franch, Thomas; Costanzi, Stefano; Chen, Xin; Lefkowitz, Robert J.

    2017-01-01

    The β2-adrenergic receptor (β2AR) has been a model system for understanding regulatory mechanisms of G-protein–coupled receptor (GPCR) actions and plays a significant role in cardiovascular and pulmonary diseases. Because all known β-adrenergic receptor drugs target the orthosteric binding site of the receptor, we set out to isolate allosteric ligands for this receptor by panning DNA-encoded small-molecule libraries comprising 190 million distinct compounds against purified human β2AR. Here, we report the discovery of a small-molecule negative allosteric modulator (antagonist), compound 15 [([4-((2S)-3-(((S)-3-(3-bromophenyl)-1-(methylamino)-1-oxopropan-2-yl)amino)-2-(2-cyclohexyl-2-phenylacetamido)-3-oxopropyl)benzamide], exhibiting a unique chemotype and low micromolar affinity for the β2AR. Binding of 15 to the receptor cooperatively enhances orthosteric inverse agonist binding while negatively modulating binding of orthosteric agonists. Studies with a specific antibody that binds to an intracellular region of the β2AR suggest that 15 binds in proximity to the G-protein binding site on the cytosolic surface of the β2AR. In cell-signaling studies, 15 inhibits cAMP production through the β2AR, but not that mediated by other Gs-coupled receptors. Compound 15 also similarly inhibits β-arrestin recruitment to the activated β2AR. This study presents an allosteric small-molecule ligand for the β2AR and introduces a broadly applicable method for screening DNA-encoded small-molecule libraries against purified GPCR targets. Importantly, such an approach could facilitate the discovery of GPCR drugs with tailored allosteric effects. PMID:28130548

  11. Allosteric modulation of GABA(B) receptor function in human frontal cortex.

    Science.gov (United States)

    Olianas, Maria C; Ambu, Rossano; Garau, Luciana; Onali, Pierluigi

    2005-01-01

    In the present study, the effects of different allosteric modulators on the functional activity of gamma-aminobutyric acid (GABA)B receptors in membranes of post-mortem human frontal cortex were examined. Western blot analysis indicated that the tissue preparations expressed both GABA(B1) and GABA(B2) subunits of the GABA(B) receptor heterodimer. In [35S]-GTPgammaS binding assays, Ca2+ ion (1 mM) enhanced the potency of the agonists GABA and 3-aminopropylphosphinic acid (3-APA) and that of the antagonist CGP55845, but not that of the GABA(B) receptor agonist (-)-baclofen. CGP7930 (2,6-di-t-Bu-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol), a positive allosteric modulator of GABA(B) receptors, potentiated both GABA(B) receptor-mediated stimulation of [35S]-GTPgammaS binding and inhibition of forskolin (FSK)-stimulated adenylyl cyclase activity. Chelation of Ca2+ ion by EGTA reduced the CGP7930 enhancement of GABA potency in stimulating [35S]-GTPgammaS binding by two-fold. Fendiline, also reported to act as a positive allosteric modulator of GABA(B) receptors, failed to enhance GABA stimulation of [35S]-GTPgammaS binding but inhibited the potentiating effect of CGP7930. The inhibitory effect was mimicked by the phenothiazine antipsychotic trifluoperazine (TFP), but not by other compounds, such as verapamil or diphenydramine (DPN). These data demonstrate that the function of GABA(B) receptors of human frontal cortex is positively modulated by Ca2+ ion and CGP7930, which interact synergistically. Conversely, fendiline and trifluoperazine negatively affect the allosteric regulation by CGP7930.

  12. Analyzing Effective Communication in Mathematics Group Work: The Role of Visual Mediators and Technical Terms

    Science.gov (United States)

    Ryve, Andreas; Nilsson, Per; Pettersson, Kerstin

    2013-01-01

    Analyzing and designing productive group work and effective communication constitute ongoing research interests in mathematics education. In this article we contribute to this research by using and developing a newly introduced analytical approach for examining effective communication within group work in mathematics education. By using data from…

  13. Analyzing Effective Communication in Mathematics Group Work: The Role of Visual Mediators and Technical Terms

    Science.gov (United States)

    Ryve, Andreas; Nilsson, Per; Pettersson, Kerstin

    2013-01-01

    Analyzing and designing productive group work and effective communication constitute ongoing research interests in mathematics education. In this article we contribute to this research by using and developing a newly introduced analytical approach for examining effective communication within group work in mathematics education. By using data from…

  14. How conversations change over time in face-to-face and video-mediated communication

    NARCIS (Netherlands)

    Kleij, van der Rick; Schraagen, Jan Maarten; Werkhoven, Peter; Dreu, de Carsten K.W.

    2009-01-01

    An experiment was conducted to examine how communication patterns and task performance differ as a function of the group's communication environment and how these processes change over time. In a longitudinal design, three-person groups had to select and argue the correct answer out of a set of thre

  15. How Conversations Change Over Time in Face-to-Face and Video-Mediated Communication

    NARCIS (Netherlands)

    Kleij, R van der; Schraagen, J.M.C.; Werkhoven, P.; Dreu, C.K.W. de

    2009-01-01

    An experiment was conducted to examine how communication patterns and task performance differ as a function of the group’s communication environment and how these processes change over time. In a longitudinal design, three-person groups had to select and argue the correct answer out of a set of thre

  16. Molecular mechanism of the allosteric regulation of the αγ heterodimer of human NAD-dependent isocitrate dehydrogenase

    Science.gov (United States)

    Ma, Tengfei; Peng, Yingjie; Huang, Wei; Ding, Jianping

    2017-01-01

    Human NAD-dependent isocitrate dehydrogenase catalyzes the decarboxylation of isocitrate (ICT) into α-ketoglutarate in the Krebs cycle. It exists as the α2βγ heterotetramer composed of the αβ and αγ heterodimers. Previously, we have demonstrated biochemically that the α2βγ heterotetramer and αγ heterodimer can be allosterically activated by citrate (CIT) and ADP. In this work, we report the crystal structures of the αγ heterodimer with the γ subunit bound without or with different activators. Structural analyses show that CIT, ADP and Mg2+ bind adjacent to each other at the allosteric site. The CIT binding induces conformational changes at the allosteric site, which are transmitted to the active site through the heterodimer interface, leading to stabilization of the ICT binding at the active site and thus activation of the enzyme. The ADP binding induces no further conformational changes but enhances the CIT binding through Mg2+-mediated interactions, yielding a synergistic activation effect. ICT can also bind to the CIT-binding subsite, which induces similar conformational changes but exhibits a weaker activation effect. The functional roles of the key residues are verified by mutagenesis, kinetic and structural studies. Our structural and functional data together reveal the molecular mechanism of the allosteric regulation of the αγ heterodimer. PMID:28098230

  17. A3 Adenosine Receptor Allosteric Modulator Induces an Anti-Inflammatory Effect: In Vivo Studies and Molecular Mechanism of Action

    Directory of Open Access Journals (Sweden)

    Shira Cohen

    2014-01-01

    Full Text Available The A3 adenosine receptor (A3AR is overexpressed in inflammatory cells and in the peripheral blood mononuclear cells of individuals with inflammatory conditions. Agonists to the A3AR are known to induce specific anti-inflammatory effects upon chronic treatment. LUF6000 is an allosteric compound known to modulate the A3AR and render the endogenous ligand adenosine to bind to the receptor with higher affinity. The advantage of allosteric modulators is their capability to target specifically areas where adenosine levels are increased such as inflammatory and tumor sites, whereas normal body cells and tissues are refractory to the allosteric modulators due to low adenosine levels. LUF6000 administration induced anti-inflammatory effect in 3 experimental animal models of rat adjuvant induced arthritis, monoiodoacetate induced osteoarthritis, and concanavalin A induced liver inflammation in mice. The molecular mechanism of action points to deregulation of signaling proteins including PI3K, IKK, IκB, Jak-2, and STAT-1, resulting in decreased levels of NF-κB, known to mediate inflammatory effects. Moreover, LUF6000 induced a slight stimulatory effect on the number of normal white blood cells and neutrophils. The anti-inflammatory effect of LUF6000, mechanism of action, and the differential effects on inflammatory and normal cells position this allosteric modulator as an attractive and unique drug candidate.

  18. Language Use in Computer-Mediated Communication: An Investigation into the Genre of Workplace Emails

    Directory of Open Access Journals (Sweden)

    Mohammad Awad AlAfnan

    2015-01-01

    Full Text Available This study investigated the moves and communicative purposes used in 522 email messages that were exchanged in a Malaysian private educational institute. Using Swales’s (1990 move approach, this study revealed that email writers used fourteen moves that are mainly six framing and eight content moves. Content moves included four main, one intertextual, one supporting and two follow-up moves. The four main content moves reflected the main communicative purposes of the emails that are discussing issues, enquiring about issues, couriering (delivering documents and informing about organizational and academic issues. The four communicative purposes varied in their structural organization, number of recipients and reaction to receiving the email. Keywords: Genre analysis; Email communication; Rhetorical moves; Communicative purposes; Discourse community

  19. Human Resource Management - Emotional Intelligence: Communication Effectiveness mediates the Relationship between Stress Management and Job Satisfaction

    Directory of Open Access Journals (Sweden)

    Hassan Jorfi

    2011-12-01

    Full Text Available Stress management remains a key topic of concern among managers and employees worldwide. The mostsignificant contribution of this research is the discovery the stress management related to communicationeffectiveness, and on the other hand, communication effectiveness related to job satisfaction withinorganizations of Iran. Communication effectiveness is a crucial factor for organization's performance andgrowth and plays an important role in stress management, and job satisfaction of today’s competitiveorganizations. According to literature on business area and logical arguments we proposed thatcommunication effectiveness can moderators the link between stress management with job satisfaction. Therespondents consist of 133 form educational administrations and Agriculture Bank of Iran. The method thatused to maintain the stress management, communication effectiveness and job satisfaction is Kendall’scoefficient of concordance. Results indicate stress management of emotional intelligence has a positiverelationship with communication effectiveness and also communication effectiveness plays a key role in jobsatisfaction.

  20. Are AMPA Receptor Positive Allosteric Modulators Potential Pharmacotherapeutics for Addiction?

    Directory of Open Access Journals (Sweden)

    Lucas R. Watterson

    2013-12-01

    Full Text Available Positive allosteric modulators (PAMs of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptors are a diverse class of compounds that increase fast excitatory transmission in the brain. AMPA PAMs have been shown to facilitate long-term potentiation, strengthen communication between various cortical and subcortical regions, and some of these compounds increase the production and release of brain-derived neurotrophic factor (BDNF in an activity-dependent manner. Through these mechanisms, AMPA PAMs have shown promise as broad spectrum pharmacotherapeutics in preclinical and clinical studies for various neurodegenerative and psychiatric disorders. In recent years, a small collection of preclinical animal studies has also shown that AMPA PAMs may have potential as pharmacotherapeutic adjuncts to extinction-based or cue-exposure therapies for the treatment of drug addiction. The present paper will review this preclinical literature, discuss novel data collected in our laboratory, and recommend future research directions for the possible development of AMPA PAMs as anti-addiction medications.

  1. Biased signaling of lipids and allosteric actions of synthetic molecules for GPR119

    DEFF Research Database (Denmark)

    Hassing, Helle A; Fares, Suzan; Larsen, Olav

    2016-01-01

    GPR119 is a Gαs-coupled lipid-sensor in the gut, where it mediates release of incretin hormones from the enteroendocrine cells and in pancreatic α-cells, where it releases insulin. Naturally occurring lipids such as monoacylglycerols (MAGs) and N-acylethanolamines (NAEs), like oleoylethanolamide......231453. Our studies uncovering broad and biased signaling, masked constitutive activity by endogenous MAGs, and ago-allosteric properties of synthetic ligands may explain why many GPR119 drug-discovery programs have failed so far....

  2. Psychological underpinnings of intrafamilial computer-mediated communication: a preliminary exploration of CMC uptake with parents and siblings.

    Science.gov (United States)

    Goby, Valerie Priscilla

    2011-06-01

    This preliminary study investigates the uptake of computer-mediated communication (CMC) with parents and siblings, an area on which no research appears to have been conducted. Given the lack of relevant literature, grounded theory methodology was used and online focus group discussions were conducted in an attempt to generate suitable hypotheses for further empirical studies. Codification of the discussion data revealed various categories of meaning, namely: a perceived inappropriateness of CMC with members of family of origin; issues relating to the family generational gap; the nature of the offline sibling/parent relationship; the non-viability of online affordances such as planned self-disclosure, deception, identity construction; and disinhibition in interactions with family-of-origin members. These themes could be molded into hypotheses to assess the psychosocial limitations of CMC and to determine if it can indeed become a ubiquitous alternative to traditional communication modes as some scholars have claimed.

  3. Motivations for Social Media Use and Impact on Political Participation in China: A Cognitive and Communication Mediation Approach.

    Science.gov (United States)

    Chen, Zhuo; Chan, Michael

    2017-02-01

    Integrating uses and gratifications theory and the cognitive/communication mediation model: this study examines Chinese students' use of social media and subsequent impact on political participation. An integrative framework is proposed where media use, political expression, and political cognitions (efficacy and knowledge) play important mediating roles between audience motivations and participation. Structural equation analyses showed support for the integrated model. Guidance and social utility motivations exhibited different indirect effects on online and offline participation through social media news, discussion, and political efficacy. Entertainment motivations exhibited no direct or indirect effects. Contrary to expectations and previous literature, surveillance motivations exhibited negative direct and indirect effects on offline participation, which may be attributed to the particular Chinese social and political context. Implications of the findings are discussed.

  4. Communications

    Science.gov (United States)

    Bailenson, Jeremy; Buzzanell, Patrice; Deetz, Stanley; Tewksbury, David; Thompson, Robert J.; Turow, Joseph; Bichelmeyer, Barbara; Bishop, M. J.; Gayeski, Diane

    2013-01-01

    Scholars representing the field of communications were asked to identify what they considered to be the most exciting and imaginative work currently being done in their field, as well as how that work might change our understanding. The scholars included Jeremy Bailenson, Patrice Buzzanell, Stanley Deetz, David Tewksbury, Robert J. Thompson, and…

  5. Language Use in Computer-Mediated Communication: An Investigation into the Genre of Workplace Emails

    OpenAIRE

    Mohammad Awad AlAfnan

    2015-01-01

    This study investigated the moves and communicative purposes used in 522 email messages that were exchanged in a Malaysian private educational institute. Using Swales’s (1990) move approach, this study revealed that email writers used fourteen moves that are mainly six framing and eight content moves. Content moves included four main, one intertextual, one supporting and two follow-up moves. The four main content moves reflected the main communicative purposes of the emails that are discussin...

  6. Media Education towards peace cultures. Future professionals of the communication sector as citizens-mediators

    OpenAIRE

    Nos Aldás, Eloísa

    2012-01-01

    This paper presents a pioneering experience for Spanish University Communication degrees. It deals with the elective subject «Audiovisual Discourses and Peace Culture» offered in the fourth year of the Audiovisual Communication University Degree at Universitat Jaume I of Castellón. This learning project is focused on the proposals of peace research as a complementary and coincident research and educative project to educommunication. In this course students realize their role as citizens profe...

  7. Human Resource Management - Emotional Intelligence: Communication Effectiveness mediates the Relationship between Stress Management and Job Satisfaction

    OpenAIRE

    Hassan Jorfi; Hashim Fauzy Bin Yaccob; Ishak Md Shah

    2011-01-01

    Stress management remains a key topic of concern among managers and employees worldwide. The mostsignificant contribution of this research is the discovery the stress management related to communicationeffectiveness, and on the other hand, communication effectiveness related to job satisfaction withinorganizations of Iran. Communication effectiveness is a crucial factor for organization's performance andgrowth and plays an important role in stress management, and job satisfaction of today’s c...

  8. Amiloride and GMQ Allosteric Modulation of the GABA-A ρ1 Receptor: Influences of the Intersubunit Site

    Science.gov (United States)

    Snell, Heather D.

    2015-01-01

    Amiloride, a diuretic used in the treatment of hypertension and congestive heart failure, and 2-guanidine-4-methylquinazoline (GMQ) are guanidine compounds that modulate acid-sensing ion channels. Both compounds have demonstrated affinity for a variety of membrane proteins, including members of the Cys-loop family of ligand-gated ion channels, such as the heteromeric GABA-A αβγ receptors. The actions of these guanidine compounds on the homomeric GABA-A ρ1 receptor remains unclear, especially in light of how many GABA-A αβγ receptor modulators have different effects in the GABA-A ρ1 receptors. We sought to characterize the influence of amiloride and GMQ on the human GABA-A ρ1 receptors using whole-cell patch-clamp electrophysiology. The diuretic amiloride potentiated the human GABA-A ρ1 GABA-mediated current, whereas GMQ antagonized the receptor. Furthermore, a GABA-A second transmembrane domain site, the intersubunit site, responsible for allosteric modulation in the heteromeric GABA-A receptors mediated amiloride’s positive allosteric actions. In contrast, the mutation did not remove GMQ antagonism but only changed the guanidine compound’s potency within the human GABA-A ρ1 receptor. Through modeling and introduction of point mutations, we propose that the GABA-A ρ1 intersubunit site plays a role in mediating the allosteric effects of amiloride and GMQ. PMID:25829529

  9. Mediating Effect of Role Ambiguity on Communication Climate: A Meta Analysis

    Directory of Open Access Journals (Sweden)

    Nasser S. Al-Kahtani

    2015-05-01

    Full Text Available The current investigation was an attempt to explore the relationship and contribution of supportive and defensive communication climate with role ambiguity amongst subordinate staff of Salman bin Abdulaziz University, Kingdom of Saudi Arabia. The total questionnaires included in the study were 368 subordinate staff working in different divisions in the university. Communication climate inventory and role ambiguity scale were used to explore the experiences of subordinate staff. The data were analyzed by means of Pearson’s product-moment correlation and step wise multiple regression. The results appeared that (i strategy one of the facet of defensive communication climate were showed inverse significant relationship with role ambiguity, (ii strategy and control facets of defensive communication climate were emerged most dominant predictors of role ambiguity, (iii supportive communication climate and their dimensions were found positive significant relationship with role ambiguity and (iv total supportive communication climate revealed as one of the most significant predictor of role ambiguity. Implication of this investigation and suggestions for future research were discussed to add value in the current areas of knowledge.

  10. Allosteric Regulation by a Critical Membrane

    CERN Document Server

    Kimchi, Ofer; Machta, Benjamin B

    2016-01-01

    Many of the processes that underly neural computation are carried out by ion channels embedded in the plasma membrane, a two-dimensional liquid that surrounds all cells. Recent experiments have demonstrated that this membrane is poised close to a liquid-liquid critical point in the Ising universality class. Here we use both exact and stochastic techniques on the lattice Ising model to explore the ramifications of proximity to criticality for proteins that are allosterically coupled to Ising composition modes. Owing to diverging generalized susceptibilities, such a protein's activity becomes strongly influenced by perturbations that influence the two relevant parameters of the critical point, especially the critical temperature. In addition, the protein's kinetics acquire a range of time scales from its surrounding membrane, naturally leading to non-Markovian dynamics.

  11. Untangling the glutamate dehydrogenase allosteric nightmare.

    Science.gov (United States)

    Smith, Thomas J; Stanley, Charles A

    2008-11-01

    Glutamate dehydrogenase (GDH) is found in all living organisms, but only animal GDH is regulated by a large repertoire of metabolites. More than 50 years of research to better understand the mechanism and role of this allosteric network has been frustrated by its sheer complexity. However, recent studies have begun to tease out how and why this complex behavior evolved. Much of GDH regulation probably occurs by controlling a complex ballet of motion necessary for catalytic turnover and has evolved concomitantly with a long antenna-like feature of the structure of the enzyme. Ciliates, the 'missing link' in GDH evolution, might have created the antenna to accommodate changing organelle functions and was refined in humans to, at least in part, link amino acid catabolism with insulin secretion.

  12. An evolution-based strategy for engineering allosteric regulation

    Science.gov (United States)

    Pincus, David; Resnekov, Orna; Reynolds, Kimberly A.

    2017-04-01

    Allosteric regulation provides a way to control protein activity at the time scale of milliseconds to seconds inside the cell. An ability to engineer synthetic allosteric systems would be of practical utility for the development of novel biosensors, creation of synthetic cell signaling pathways, and design of small molecule pharmaceuticals with regulatory impact. To this end, we outline a general approach—termed rational engineering of allostery at conserved hotspots (REACH)—to introduce novel regulation into a protein of interest by exploiting latent allostery that has been hard-wired by evolution into its structure. REACH entails the use of statistical coupling analysis (SCA) to identify ‘allosteric hotspots’ on protein surfaces, the development and implementation of experimental assays to test hotspots for functionality, and a toolkit of allosteric modulators to impinge on endogenous cellular circuitry. REACH can be broadly applied to rewire cellular processes to respond to novel inputs.

  13. Ligand Binding to Macromolecules: Allosteric and Sequential Models of Cooperativity.

    Science.gov (United States)

    Hess, V. L.; Szabo, Attila

    1979-01-01

    A simple model is described for the binding of ligands to macromolecules. The model is applied to the cooperative binding by hemoglobin and aspartate transcarbamylase. The sequential and allosteric models of cooperative binding are considered. (BB)

  14. Bridge- and Solvent-Mediated Intramolecular Electronic Communications in Ubiquinone-Based Biomolecular Wires

    Science.gov (United States)

    Liu, Xiao-Yuan; Ma, Wei; Zhou, Hao; Cao, Xiao-Ming; Long, Yi-Tao

    2015-05-01

    Intramolecular electronic communications of molecular wires play a crucial role for developing molecular devices. In the present work, we describe different degrees of intramolecular electronic communications in the redox processes of three ubiquinone-based biomolecular wires (Bis-CoQ0s) evaluated by electrochemistry and Density Functional Theory (DFT) methods in different solvents. We found that the bridges linkers have a significant effect on the electronic communications between the two peripheral ubiquinone moieties and solvents effects are limited and mostly depend on the nature of solvents. The DFT calculations for the first time indicate the intensity of the electronic communications during the redox processes rely on the molecular orbital elements VL for electron transfer (half of the energy splitting of the LUMO and LUMO+1), which is could be affected by the bridges linkers. The DFT calculations also demonstrates the effect of solvents on the latter two-electron transfer of Bis-CoQ0s is more significant than the former two electrons transfer as the observed electrochemical behaviors of three Bis-CoQ0s. In addition, the electrochemistry and theoretical calculations reveal the intramolecular electronic communications vary in the four-electron redox processes of three Bis-CoQ0s.

  15. Computational study on the inhibitor binding mode and allosteric regulation mechanism in hepatitis C virus NS3/4A protein.

    Directory of Open Access Journals (Sweden)

    Weiwei Xue

    Full Text Available HCV NS3/4A protein is an attractive therapeutic target responsible for harboring serine protease and RNA helicase activities during the viral replication. Small molecules binding at the interface between the protease and helicase domains can stabilize the closed conformation of the protein and thus block the catalytic function of HCV NS3/4A protein via an allosteric regulation mechanism. But the detailed mechanism remains elusive. Here, we aimed to provide some insight into the inhibitor binding mode and allosteric regulation mechanism of HCV NS3/4A protein by using computational methods. Four simulation systems were investigated. They include: apo state of HCV NS3/4A protein, HCV NS3/4A protein in complex with an allosteric inhibitor and the truncated form of the above two systems. The molecular dynamics simulation results indicate HCV NS3/4A protein in complex with the allosteric inhibitor 4VA adopts a closed conformation (inactive state, while the truncated apo protein adopts an open conformation (active state. Further residue interaction network analysis suggests the communication of the domain-domain interface play an important role in the transition from closed to open conformation of HCV NS3/4A protein. However, the inhibitor stabilizes the closed conformation through interaction with several key residues from both the protease and helicase domains, including His57, Asp79, Asp81, Asp168, Met485, Cys525 and Asp527, which blocks the information communication between the functional domains interface. Finally, a dynamic model about the allosteric regulation and conformational changes of HCV NS3/4A protein was proposed and could provide fundamental insights into the allosteric mechanism of HCV NS3/4A protein function regulation and design of new potent inhibitors.

  16. Impact of Mediated Intimate Interaction on Education: A Huggable Communication Medium that Encourages Listening.

    Science.gov (United States)

    Nakanishi, Junya; Sumioka, Hidenobu; Ishiguro, Hiroshi

    2016-01-01

    In this paper, we propose the introduction of human-like communication media as a proxy for teachers to support the listening of children in school education. Three case studies are presented on storytime fieldwork for children using our huggable communication medium called Hugvie, through which children are encouraged to concentrate on listening by intimate interaction between children and storytellers. We investigate the effect of Hugvie on children's listening and how they and their teachers react to it through observations and interviews. Our results suggest that Hugvie increased the number of children who concentrated on listening to a story and was welcomed by almost all the children and educators. We also discuss improvement and research issues to introduce huggable communication media into classrooms, potential applications, and their contributions to other education situations through improved listening.

  17. Transformations of the Political Communication in Social Media Era – from Mediatization to Decentralization

    Directory of Open Access Journals (Sweden)

    Tănase Tasente

    2014-06-01

    Full Text Available The political communication in media era performs on two dimensions: the horizontal dimension – between political actors and journalists – and on vertical dimension – the media product is decentralized to the consumer public. In Social Media Era, the horizontal dimension completely disappears and the communication is routed by the online opinion leaders in the social groups. Thus, in the new public space, the main communication actors are not journalists and politicians, but publicreceptor, which plays the role of opinion leaders. In Social Media, we can talk a lot about “the power of the receptor”, that is decentralizing, without intermediaries, the political message to discuss it in the social groups to which they belong.

  18. From Protein Communication to Drug Discovery.

    Science.gov (United States)

    Persico, Marco; Di Dato, Antonio; Orteca, Nausicaa; Fattorusso, Caterina; Novellino, Ettore; Andreoli, Mirko; Ferlini, Cristiano

    2015-01-01

    The majority of functionally important biological processes are regulated by allosteric communication within individual proteins and across protein complexes. The proteins controlling these communication networks respond to changes in the cellular environment by switching between different conformational states. Targeting the interface residues mediating these processes through the rational identification of molecules modulating or mimicking their effects holds great therapeutic potential. Protein-protein interactions (PPIs) have shown to have a high degree of plasticity since they occur through small regions, called hot spots, which are included in binding surfaces or in binding clefts of the proteins and are characterized by a high degree of complementarity. This prompted several researchers to compare the protein structure to human grammar proposing terms like "protein language". The decoding of this language represent a new paradigm not only to clarify the dynamics of many biological processes but also to improve the opportunities in drug discovery. In this review, we try to give an overview on intra-molecular and inter-molecular protein communication mechanisms describing the protein interaction domains (PIDs) and short linear motifs (SLiMs), which delineate the authentic syntactic and semantic units in a protein. Moreover, we illustrate some novel approaches performed on natural compounds and on synthetic derivatives aimed at developing new classes of potential drugs able to interfere with intra-molecular and inter-molecular protein communication.

  19. The Influence of Green Viral Communications on Green Purchase Intentions: The Mediating Role of Consumers’ Susceptibility to Interpersonal Influences

    Directory of Open Access Journals (Sweden)

    Sheng-Hsiung Chang

    2015-04-01

    Full Text Available This paper aims to incorporate the diffusion of innovation theory and conformity theory to explain consumers’ green purchase intentions. To this end, a conceptual model has been proposed and subjected to empirical verification with the use of a survey method. Using a sample of Taiwanese consumers who had the actual purchase experience of green detergents, this study employed structural equation modeling to verify the hypothesis proposed. The empirical results suggested that green viral communication was positively related to normative interpersonal influence, informational interpersonal influence and green purchase intention. Informational interpersonal influence also had a positive impact on green purchase intention. However, the relationship between consumer’s normative interpersonal influence and green purchase intention was not supported. Thus, this study concludes that green marketers must strengthen their green viral communications skills to enhance consumers’ purchase intentions. In addition, this study also contributes to the literature by stating that consumers’ susceptibility to informational interpersonal relationships is an important mediator in the green viral communication and green purchase intentions relationship. This study discusses implications of the findings and research limitations at the end of the paper.

  20. Dynamical network of residue-residue contacts reveals coupled allosteric effects in recognition, catalysis, and mutation.

    Science.gov (United States)

    Doshi, Urmi; Holliday, Michael J; Eisenmesser, Elan Z; Hamelberg, Donald

    2016-04-26

    Detailed understanding of how conformational dynamics orchestrates function in allosteric regulation of recognition and catalysis remains ambiguous. Here, we simulate CypA using multiple-microsecond-long atomistic molecular dynamics in explicit solvent and carry out NMR experiments. We analyze a large amount of time-dependent multidimensional data with a coarse-grained approach and map key dynamical features within individual macrostates by defining dynamics in terms of residue-residue contacts. The effects of substrate binding are observed to be largely sensed at a location over 15 Å from the active site, implying its importance in allostery. Using NMR experiments, we confirm that a dynamic cluster of residues in this distal region is directly coupled to the active site. Furthermore, the dynamical network of interresidue contacts is found to be coupled and temporally dispersed, ranging over 4 to 5 orders of magnitude. Finally, using network centrality measures we demonstrate the changes in the communication network, connectivity, and influence of CypA residues upon substrate binding, mutation, and during catalysis. We identify key residues that potentially act as a bottleneck in the communication flow through the distinct regions in CypA and, therefore, as targets for future mutational studies. Mapping these dynamical features and the coupling of dynamics to function has crucial ramifications in understanding allosteric regulation in enzymes and proteins, in general.

  1. Incendiary Discourse: Reconsidering Flaming, Authority, and Democratic Subjectivity in Computer-Mediated Communication

    Science.gov (United States)

    Oleksiak, Timothy

    2012-01-01

    This article explores the relationship between teacher authority and flaming in asynchronous online communication. Teachers who rely on what I call stabilization and universal applicability--two concepts emerging from a liberal democratic theory--may actually be preventing a full and robust understanding of the complexities of 21st-century…

  2. Communication self-efficacy in optometry: the mediating role of mindfulness.

    NARCIS (Netherlands)

    Sundling, V.; Dulmen, S. van; Elde, H.

    2016-01-01

    The aim of this study was to examine the relationship between optometry students’ communication self-efficacy and their level of mindfulness and empathy. The study had a cross-sectional design. The sample included qualified optometrists in their first year of the Masters’ degree programme. The stude

  3. On Lying and Being Lied to: A Linguistic Analysis of Deception in Computer-Mediated Communication

    Science.gov (United States)

    Hancock, Jeffrey T.; Curry, Lauren E.; Goorha, Saurabh; Woodworth, Michael

    2008-01-01

    This study investigated changes in both the liar's and the conversational partner's linguistic style across truthful and deceptive dyadic communication in a synchronous text-based setting. An analysis of 242 transcripts revealed that liars produced more words, more sense-based words (e.g., seeing, touching), and used fewer self-oriented but more…

  4. Design for Social Presence and Exploring Its Mediating Effect in Mobile Data Communication Services

    Science.gov (United States)

    Ogara, Solomon Omondi

    2011-01-01

    The mobility, flexibility, convenience, and ubiquity of mobile data services (MDS) have contributed to their enormous growth and popularity with users. MDS allow users to communicate through mobile texting (mTexting), mobile Instant Messaging (mIM), multimedia messaging services (MMS), and email. A unique feature of MDS that enhances its…

  5. Communication self-efficacy in optometry: the mediating role of mindfulness.

    NARCIS (Netherlands)

    Sundling, V.; Dulmen, S. van; Elde, H.

    2016-01-01

    The aim of this study was to examine the relationship between optometry students’ communication self-efficacy and their level of mindfulness and empathy. The study had a cross-sectional design. The sample included qualified optometrists in their first year of the Masters’ degree programme. The

  6. Exosomal transfer of functional small RNAs mediates cancer-stroma communication in human endometrium.

    Science.gov (United States)

    Maida, Yoshiko; Takakura, Masahiro; Nishiuchi, Takumi; Yoshimoto, Tanihiro; Kyo, Satoru

    2016-02-01

    Exosomes are small membrane vesicles secreted from a variety of cell types. Recent evidence indicates that human cells communicate with each other by exchanging exosomes. Cancer cells closely interact with neighboring stromal cells, and together they cooperatively promote disease via bidirectional communication. Here, we investigated whether exosomes can play roles in intercellular communication between cancer cells and neighboring fibroblasts. Endometrial fibroblasts were isolated from normal endometrial tissues and from endometrial cancer tissues, and cell-to-cell transfer of endometrial cancer cell line Ishikawa-derived exosomes was examined. The isolated fibroblasts were cultured in conditioned media from CD63-GFP-expressing Ishikawa cells, and we found that GFP-positive exosomes were transferred from Ishikawa cells to the fibroblasts. Next, we introduced a shRNA for a luciferase gene into Ishikawa cells. This shRNA was encapsulated into exosomes, was transferred to the fibroblasts, and then downregulated luciferase expression in the fibroblasts. The mature microRNAs naturally expressed in Ishikawa-derived exosomes were also transported into the endometrial fibroblasts, and they altered the microRNA expression profiles of the fibroblasts. These results indicated that endometrial cancer cells could transmit small regulatory RNAs to endometrial fibroblasts via exosomes. Our findings document a previously unknown mode of intercellular communication between cancer cells and related fibroblasts in human endometrium.

  7. Communication self-efficacy in optometry: the mediating role of mindfulness.

    NARCIS (Netherlands)

    Sundling, V.; Dulmen, S. van; Elde, H.

    2016-01-01

    The aim of this study was to examine the relationship between optometry students’ communication self-efficacy and their level of mindfulness and empathy. The study had a cross-sectional design. The sample included qualified optometrists in their first year of the Masters’ degree programme. The stude

  8. Improving Computer-Mediated Synchronous Communication of Doctors in Rural Communities Through Cloud Computing: A Case Study of Rural Hospitals in South Africa

    Directory of Open Access Journals (Sweden)

    Alfred Coleman

    2012-11-01

    Full Text Available This paper investigated how doctors in remote rural hospitals in South Africa use computer-mediated toolto communicate with experienced and specialist doctors for professional advice to improve on their clinicalpractices. A case study approach was used. Ten doctors were purposively selected from ten hospitals in theNorth West Province. Data was collected using semi-structured open ended interview questions. Theinterviewees were asked to tell in their own words the average number of patients served per week,processes used in consultation with other doctors, communication practices using computer-mediated tool,transmission speed of the computer-mediated tool and satisfaction in using the computer-mediatedcommunication tool. The findings revealed that an average of 15 consultations per doctor to a specialistdoctor per week was done through face to face or through telephone conversation instead of using acomputer-mediated tool. Participants cited reasons for not using computer-mediated tool forcommunication due to slow transmission speed of the Internet and regular down turn of the Internetconnectivity, constant electricity power outages and lack of e-health application software to support realtime computer-mediated communication. The results led to the recommendation of a hybrid cloudcomputing architecture for improving communication between doctors in hospitals.

  9. COMMUNICATIONS

    CERN Document Server

    A. Petrilli

    2013-01-01

    The organisation of the Open Days at the end of September was the single biggest effort of the CMS Communications Group this year. We would like to thank all volunteers for their hard work to show our Point 5 facilities and explain science and technology to the general public. During two days more than 5,000 people visited the CMS detector underground and profited from the surface activities, which included an exhibition on CMS, a workshop on superconductivity, and an activity for our younger visitors involving wooden Kapla blocks. The Communications Group took advantage of the preparations to produce new CMS posters that can be reused at other venues. Event display images have been produced not just for this occasion but also for other exhibits, education purposes, publications etc. During the Open Days, Gilles Jobin, 2012 winner of CERN Collide@CERN prize, performed his Quantum show in Point 5, with the light installation of German artist Julius von Bismarck. Image 3: CERN Open Days at CMS wel...

  10. COMMUNICATIONS

    CERN Multimedia

    L. Taylor and D. Barney

    2010-01-01

    CMS Centres, Outreach and the 7 TeV Media Event The new CMS Communications group is now established and is addressing three areas that are critical to CMS as it enters the physics operations phase: - Communications Infrastructure, including almost 50 CMS Centres Worldwide, videoconferencing systems, and CERN meeting rooms - Information systems, including the internal and external Web sites as well as the document preparation and management systems - Outreach and Education activities, including working with print, radio and TV media, visits to CMS, and exhibitions. The group has been active in many areas, with the highest priority being accorded to needs of CMS operations and preparations for the major media event planned for 7 TeV collisions. Unfortunately the CMS Centre@CERN suffered a major setback when, on 21st December, a cooling water pipe froze and burst on the floor above the CMS Centre main room. Water poured through the ceiling, flooding the floor and soaking some of the consoles, before e...

  11. Convergent and Divergent Computer-Mediated Communication Tasks in an English for Academic Purposes Course

    Science.gov (United States)

    Jackson, Daniel O.

    2011-01-01

    This article describes the implementation of technology-mediated tasks in an English for academic purposes (EAP) curriculum at a Japanese university. The course addressed the needs of English majors at the school by enabling more efficient completion of academic work, including essay writing. One way that technology supported this goal was through…

  12. Computer-Mediated Communication in Undergraduate Teaching: Web-based Conferencing with Lotus Notes/Domino.

    Science.gov (United States)

    Vincent, Peter

    2000-01-01

    Examines the outcomes of a two-year trial of computer-mediated conferencing (CMC) conducted at a British university during the final-year undergraduate course in glacial and periglacial geomorphology. Discusses the issues related to CMC and describes the experience over the last two years of using CMC conferencing. (CMK)

  13. Virtual Experience: The Impact of Mediated Communication in a Democratic Society.

    Science.gov (United States)

    Swartz, James D.; Hatcher, Tim

    1996-01-01

    Defines virtual experience as machine-based experience, of which virtual reality is a subconcept. Topics include a history of virtual experience; criticism of the influence of machine-mediated experiences such as computer games; virtual reality environments; and Heidegger's views on technology. (LRW)

  14. Effects of Interpersonal Goals on Inadvertent Intrapersonal Influence in Computer-Mediated Communication

    Science.gov (United States)

    Walther, Joseph B.; Van Der Heide, Brandon; Tong, Stephanie Tom; Carr, Caleb T.; Atkin, Charles K.

    2010-01-01

    This research explores a sequence of effects pertaining to the influence of relational goals on online information seeking, the use of information and arguments as relational management strategies in computer-mediated chat, and the intrapersonal attitude change resulting from these processes. Affinity versus disaffinity goals affected…

  15. Implementation of communication-mediating domains for non-ribosomal peptide production in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Siewers, Verena; San-Bento, Rita; Nielsen, Jens

    2010-01-01

    Saccharomyces cerevisiae has in several cases been proven to be a suitable host for the production of natural products and was recently exploited for the production of non-ribosomal peptides. Synthesis of non-ribosomal peptides (NRPs) is mediated by NRP synthetases (NRPSs), modular enzymes, which...

  16. Computer-Mediated Communication in Undergraduate Teaching: Web-based Conferencing with Lotus Notes/Domino.

    Science.gov (United States)

    Vincent, Peter

    2000-01-01

    Examines the outcomes of a two-year trial of computer-mediated conferencing (CMC) conducted at a British university during the final-year undergraduate course in glacial and periglacial geomorphology. Discusses the issues related to CMC and describes the experience over the last two years of using CMC conferencing. (CMK)

  17. Extending the Similarity-Attraction Effect : The effects of When-Similarity in mediated communication

    NARCIS (Netherlands)

    Kaptein, M.C.; Castaneda, D.; Fernandez, N.; Nass, C.

    2014-01-01

    The feeling of connectedness experienced in computer-mediated relationships can be explained by the similarity-attraction effect (SAE). Though SAE is well established in psychology, the effects of some types of similarity have not yet been explored. In 2 studies, we demonstrate similarity-attraction

  18. Using a Diagnosis-Based Approach to Individualize Instructional Explanations in Computer-Mediated Communication

    Science.gov (United States)

    Wittwer, Jorg; Nuckles, Matthias; Renkl, Alexander

    2010-01-01

    To maximize the effectiveness of instructional explanations, they should be tailored to an individual learner. However, instructors are often not able to collect diagnostically relevant information about a learner to individualize their explanations. This is particularly true in computer-mediated settings where it is more difficult to thoroughly…

  19. Voltage- and temperature-dependent allosteric modulation of alpha7 nicotinic receptors by PNU120596

    Directory of Open Access Journals (Sweden)

    Fabrio eSitzia

    2011-12-01

    Full Text Available Alpha7 nicotinic receptors (a7nAChR are widely distributed throughout the central nervous system (CNS and are found at particularly high levels in the hippocampus and cortex. Several lines of evidence indicate that pharmacological enhancement of a7nAChRs function could be a potential therapeutic route to alleviate disease-related cognitive deficits. A recent pharmacological approach adopted to increase a7nAChR activity has been to identify selective positive allosteric modulators (PAMs. a7nAChR PAMs have been divided into two classes: type I PAMs increase agonist potency with only subtle effects on kinetics, whereas type II agents produce additional dramatic effects on desensitization and deactivation kinetics. Here we report novel observations concerning the pharmacology of the canonical type II PAM, PNU120596. Using patch clamp analysis of acetylcholine (ACh-mediated currents through recombinant rat a7nAChR we show that positive allosteric modulation measured in two different ways is greatly attenuated when the temperature is raised to near physiological levels. Furthermore, PNU120596 largely removes the strong inward rectification usually exhibited by a7nAChR-mediated responses.

  20. The tight junction protein ZO-2 and Janus kinase 1 mediate intercellular communications in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Tkachuk, Natalia; Tkachuk, Sergey; Patecki, Margret [Department of Nephrology, Hannover Medical School, Hannover D-30625 (Germany); Kusch, Angelika [Department of Nephrology and Intensive Care Medicine, Charite Campus Virchow-Klinikum, Berlin D-13353 (Germany); Korenbaum, Elena; Haller, Hermann [Department of Nephrology, Hannover Medical School, Hannover D-30625 (Germany); Dumler, Inna, E-mail: dumler.inna@mh-hannover.de [Department of Nephrology, Hannover Medical School, Hannover D-30625 (Germany)

    2011-07-08

    Highlights: {yields} The tight junction protein ZO-2 associates with Jak1 in vascular smooth muscle cells via ZO-2 N-terminal fragment. {yields} Jak1 mediates ZO-2 tyrosine phosphorylation and ZO-2 localization to the sites of homotypic intercellular contacts. {yields} The urokinase receptor uPAR regulates ZO-2/Jak1 functional association. {yields} The ZO-2/Jak1/uPAR signaling complex is required for vascular smooth muscle cells functional network formation. -- Abstract: Recent evidence points to a multifunctional role of ZO-2, the tight junction protein of the MAGUK (membrane-associated guanylate kinase-like) family. Though ZO-2 has been found in cell types lacking tight junction structures, such as vascular smooth muscle cells (VSMC), little is known about ZO-2 function in these cells. We provide evidence that ZO-2 mediates specific homotypic cell-to-cell contacts between VSMC. Using mass spectrometry we found that ZO-2 is associated with the non-receptor tyrosine kinase Jak1. By generating specific ZO-2 constructs we further found that the N-terminal fragment of ZO-2 molecule is responsible for this interaction. Adenovirus-based expression of Jak1 inactive mutant demonstrated that Jak1 mediates ZO-2 tyrosine phosphorylation. By means of RNA silencing, expression of Jak1 mutant form and fluorescently labeled ZO-2 fusion protein we further specified that active Jak1, but not Jak1 inactive mutant, mediates ZO-2 localization to the sites of intercellular contacts. We identified the urokinase receptor uPAR as a pre-requisite for these cellular events. Functional requirement of the revealed signaling complex for VSMC network formation was confirmed in experiments using Matrigel and in contraction assay. Our findings imply involvement of the ZO-2 tight junction independent signaling complex containing Jak1 and uPAR in VSMC intercellular communications. This mechanism may contribute to vascular remodeling in occlusive cardiovascular diseases and in arteriogenesis.

  1. Teacher-student Relationship and SNS-mediated Communication: Perceptions of both role-players

    Directory of Open Access Journals (Sweden)

    Arnon Hershkovitz

    2015-12-01

    Full Text Available Teacher-student relationships are vital for academic and social development of students, for teachers’ professional and personal development, and for having a supportive learning environment. In the digital age, these relationships can extend beyond bricks and mortar and beyond school hours. Specifically, these relationships are extended today while teachers and students communicate via social networking sites (SNS. This paper characterizes differences between teachers (N=160 and students (N=587 who are willing to connect with their students/teachers via Facebook and those who do not wish to connect. The quantitative research reported here within is based on data collection of personal characteristics, attitudes towards Facebook, and perceptions of teacher-student relationship. Findings suggest differences in characteristics of the two groups (willing to connect vs. not willing to connect within both populations (teachers and students. Also, in both populations, those who were willing to connect, compared to those who were not willing to connect, present more positive attitudes towards using Facebook for teaching/learning and are more opposed to a banning policy of student-teacher SNS-based communication. We also found that students who were willing to connect showed a greater degree of closeness with their teachers compared to those who were not willing to connect. This study may assist policymakers when setting up regulations regarding teacher-student communication via social networking sites.

  2. Social Communication Effects of Peer-Mediated Recess Intervention for Children with Autism

    OpenAIRE

    McFadden, Brandon; Kamps, Debra; Heitzman-Powell, Linda

    2014-01-01

    Children with ASD face enormous challenges in the area of social functioning. Research has shown that impairments in social functioning distinguish this population from both typically developing children and children with disabilities. This study incorporated several evidence-based social skills-teaching procedures (i.e., direct instruction, priming, prompting, peer-mediation, contingent reinforcement, and token economies) directly in the recess setting to increase appropriate social behavior...

  3. ETA-receptor antagonists or allosteric modulators?

    DEFF Research Database (Denmark)

    De Mey, Jo G R; Compeer, Matthijs G; Lemkens, Pieter

    2011-01-01

    The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects. In resista......The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects....... In resistance arteries, the long-lasting contractile effects can only be partly and reversibly relaxed by low-molecular-weight ET(A) antagonists (ERAs). However, the neuropeptide calcitonin-gene-related peptide selectively terminates binding of ET1 to ET(A). We propose that ET1 binds polyvalently to ET(A......) and that ERAs and the physiological antagonist allosterically reduce ET(A) functions. Combining the two-state model and the two-domain model of GPCR function and considering receptor activation beyond agonist binding might lead to better anti-endothelinergic drugs. Future studies could lead to compounds...

  4. Ryanodine receptors: allosteric ion channel giants.

    Science.gov (United States)

    Van Petegem, Filip

    2015-01-16

    The endoplasmic reticulum (ER) and sarcoplasmic reticulum (SR) form major intracellular Ca(2+) stores. Ryanodine receptors (RyRs) are large tetrameric ion channels in the SR and ER membranes that can release Ca(2+) upon triggering. With molecular masses exceeding 2.2MDa, they represent the pinnacle of ion channel complexity. RyRs have adopted long-range allosteric mechanisms, with pore opening resulting in conformational changes over 200Å away. Together with tens of protein and small molecule modulators, RyRs have adopted rich and complex regulatory mechanisms. Structurally related to inositol-1,4,5-trisphosphate receptors (IP3Rs), RyRs have been studied extensively using cryo-electron microscopy (cryo-EM). Along with more recent X-ray crystallographic analyses of individual domains, these have resulted in pseudo-atomic models. Over 500 mutations in RyRs have been linked to severe genetic disorders, which underscore their role in the contraction of cardiac and skeletal muscles. Most of these have been linked to gain-of-function phenotypes, resulting in premature or prolonged leak of Ca(2+) in the cytosol. This review outlines our current knowledge on the structure of RyRs at high and low resolutions, their relationship to IP3Rs, an overview of the most commonly studied regulatory mechanisms, and models that relate disease-causing mutations to altered channel function.

  5. Intrasteric control of AMPK via the gamma1 subunit AMP allosteric regulatory site.

    Science.gov (United States)

    Adams, Julian; Chen, Zhi-Ping; Van Denderen, Bryce J W; Morton, Craig J; Parker, Michael W; Witters, Lee A; Stapleton, David; Kemp, Bruce E

    2004-01-01

    AMP-activated protein kinase (AMPK) is a alphabetagamma heterotrimer that is activated in response to both hormones and intracellular metabolic stress signals. AMPK is regulated by phosphorylation on the alpha subunit and by AMP allosteric control previously thought to be mediated by both alpha and gamma subunits. Here we present evidence that adjacent gamma subunit pairs of CBS repeat sequences (after Cystathionine Beta Synthase) form an AMP binding site related to, but distinct from the classical AMP binding site in phosphorylase, that can also bind ATP. The AMP binding site of the gamma(1) CBS1/CBS2 pair, modeled on the structures of the CBS sequences present in the inosine monophosphate dehydrogenase crystal structure, contains three arginine residues 70, 152, and 171 and His151. The yeast gamma homolog, snf4 contains a His151Gly substitution, and when this is introduced into gamma(1), AMP allosteric control is substantially lost and explains why the yeast snf1p/snf4p complex is insensitive to AMP. Arg70 in gamma(1) corresponds to the site of mutation in human gamma(2) and pig gamma(3) genes previously identified to cause an unusual cardiac phenotype and glycogen storage disease, respectively. Mutation of any of AMP binding site Arg residues to Gln substantially abolishes AMP allosteric control in expressed AMPK holoenzyme. The Arg/Gln mutations also suppress the previously described inhibitory properties of ATP and render the enzyme constitutively active. We propose that ATP acts as an intrasteric inhibitor by bridging the alpha and gamma subunits and that AMP functions to derepress AMPK activity.

  6. Robust Stimulation of W1282X-CFTR Channel Activity by a Combination of Allosteric Modulators.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    Full Text Available W1282X is a common nonsense mutation among cystic fibrosis patients that results in the production of a truncated Cystic Fibrosis Transmembrane Conductance Regulator (CFTR channel. Here we show that the channel activity of the W1282X-CFTR polypeptide is exceptionally low in excised membrane patches at normally saturating doses of ATP and PKA (single channel open probability (PO 0.9 when treated with both modulators. VX-770 and curcumin also additively stimulated W1282X-CFTR mediated currents in polarized FRT epithelial monolayers. In this setting, however, the stimulated W1282X-CFTR currents were smaller than those mediated by wild type CFTR (3-5% due presumably to lower expression levels or cell surface targeting of the truncated protein. Combining allosteric modulators of different mechanistic classes is worth considering as a treatment option for W1282X CF patients perhaps when coupled with maneuvers to increase expression of the truncated protein.

  7. Allosteric modulators for the treatment of schizophrenia: targeting glutamatergic networks.

    Science.gov (United States)

    Menniti, Frank S; Lindsley, Craig W; Conn, P Jeffrey; Pandit, Jayvardhan; Zagouras, Panayiotis; Volkmann, Robert A

    2013-01-01

    Schizophrenia is a highly debilitating mental disorder which afflicts approximately 1% of the global population. Cognitive and negative deficits account for the lifelong disability associated with schizophrenia, whose symptoms are not effectively addressed by current treatments. New medicines are needed to treat these aspects of the disease. Neurodevelopmental, neuropathological, genetic, and behavioral pharmacological data indicate that schizophrenia stems from a dysfunction of glutamate synaptic transmission, particularly in frontal cortical networks. A number of novel pre- and postsynaptic mechanisms affecting glutamatergic synaptic transmission have emerged as viable targets for schizophrenia. While developing orthosteric glutamatergic agents for these targets has proven extremely difficult, targeting allosteric sites of these targets has emerged as a promising alternative. From a medicinal chemistry perspective, allosteric sites provide an opportunity of finding agents with better drug-like properties and greater target specificity. Furthermore, allosteric modulators are better suited to maintaining the highly precise temporal and spatial aspects of glutamatergic synaptic transmission. Herein, we review neuropathological and genomic/genetic evidence underscoring the importance of glutamate synaptic dysfunction in the etiology of schizophrenia and make a case for allosteric targets for therapeutic intervention. We review progress in identifying allosteric modulators of AMPA receptors, NMDA receptors, and metabotropic glutamate receptors, all with the aim of restoring physiological glutamatergic synaptic transmission. Challenges remain given the complexity of schizophrenia and the difficulty in studying cognition in animals and humans. Nonetheless, important compounds have emerged from these efforts and promising preclinical and variable clinical validation has been achieved.

  8. Perturbation-based Markovian transmission model for probing allosteric dynamics of large macromolecular assembling: a study of GroEL-GroES.

    Directory of Open Access Journals (Sweden)

    Hsiao-Mei Lu

    2009-10-01

    Full Text Available Large macromolecular assemblies are often important for biological processes in cells. Allosteric communications between different parts of these molecular machines play critical roles in cellular signaling. Although studies of the topology and fluctuation dynamics of coarse-grained residue networks can yield important insights, they do not provide characterization of the time-dependent dynamic behavior of these macromolecular assemblies. Here we develop a novel approach called Perturbation-based Markovian Transmission (PMT model to study globally the dynamic responses of the macromolecular assemblies. By monitoring simultaneous responses of all residues (>8,000 across many (>6 decades of time spanning from the initial perturbation until reaching equilibrium using a Krylov subspace projection method, we show that this approach can yield rich information. With criteria based on quantitative measurements of relaxation half-time, flow amplitude change, and oscillation dynamics, this approach can identify pivot residues that are important for macromolecular movement, messenger residues that are key to signal mediating, and anchor residues important for binding interactions. Based on a detailed analysis of the GroEL-GroES chaperone system, we found that our predictions have an accuracy of 71-84% judged by independent experimental studies reported in the literature. This approach is general and can be applied to other large macromolecular machineries such as the virus capsid and ribosomal complex.

  9. Communicating about the risks and benefits of genetically modified foods: The mediating role of trust

    DEFF Research Database (Denmark)

    Frewer, Lynn J.; Scholderer, Joachim; Bredahl, Lone

    2003-01-01

    Recent research suggests that public attitudes towards emerging technologies are mainly driven by trust in the institutions promoting and regulating these technologies. Alternative views maintain that trust should be seen as a consequence rather than a cause of such attitudes. To test its actual...... role, direct as well as mediating effects of trust were tested in an attitude change experiment involving 1203 consumers from Denmark, Germany, Italy and the UK. After prior attitudes to genetic modification in food production had been assessed, participants received different information materials...

  10. A Study of Cooperative Principle in Computer-Mediated Communication (CMC)

    Institute of Scientific and Technical Information of China (English)

    夏梦伊

    2015-01-01

    With the continuous development of Internet technology and the advancement of globalization,China Internet Directindustry has become the biggest network in the world.Accordingly,netizens has communicated through social networking tools,which means that their communication is across time and space.Obviously,as a new language carrier,the network is theoretical,autonomic,open,inclusive and diverse. These characteristics are different from traditional language carrier.Therefore,"CMC" has become a new type of writing. The language commonly used and widely circulated on the Internet,has gradually formed its own system.It not only has its own unique vocabulary,and even the rules of grammar and pragmatic features are different from the traditional language.This paper aims to apply the Cooperative Principle and its maxims to analyse whether CMC violates the cooperative principle in the living examples.Meanwhile,the paper also tries to interpret their conversational implicature and the reasons to fully recognize this new type of writing.

  11. A Study of Cooperative Principle in ComputerMediated Communication(CMC)

    Institute of Scientific and Technical Information of China (English)

    夏梦伊

    2015-01-01

    With the continuous development of Internet technology and the advacement of globalization, China Internet Directindustry has become the biggest network in the world.Accordingly,netizens has communicated through social networking tools,which means that their communication is across time and space.Obviously,as a new language carrier,the network is theoretical,autonomic,open,inclusive and diverse.These characteristics are different from traditional language carrier.Therefore,"CMC" has become a new type of writing.The language commonly used and widely circulated on the Internet,has gradually formed its own system.It not only has its own unique vocabulary,and even the rules of grammar and pragmatic features are different from the traditional language.This paper aims to apply the Cooperative Principle and its maxims to analyse whether CMC violates the cooperative principle in the living examples.Meanwhile,the paper also tries to interpret their conversational implicature and the reasons to fully recognize this new type of writing.

  12. PACS-2 controls endoplasmic reticulum-mitochondria communication and Bid-mediated apoptosis.

    Science.gov (United States)

    Simmen, Thomas; Aslan, Joseph E; Blagoveshchenskaya, Anastassia D; Thomas, Laurel; Wan, Lei; Xiang, Yang; Feliciangeli, Sylvain F; Hung, Chien-Hui; Crump, Colin M; Thomas, Gary

    2005-02-23

    The endoplasmic reticulum (ER) and mitochondria form contacts that support communication between these two organelles, including synthesis and transfer of lipids, and the exchange of calcium, which regulates ER chaperones, mitochondrial ATP production, and apoptosis. Despite the fundamental roles for ER-mitochondria contacts, little is known about the molecules that regulate them. Here we report the identification of a multifunctional sorting protein, PACS-2, that integrates ER-mitochondria communication, ER homeostasis, and apoptosis. PACS-2 controls the apposition of mitochondria with the ER, as depletion of PACS-2 causes BAP31-dependent mitochondria fragmentation and uncoupling from the ER. PACS-2 also controls formation of ER lipid-synthesizing centers found on mitochondria-associated membranes and ER homeostasis. However, in response to apoptotic inducers, PACS-2 translocates Bid to mitochondria, which initiates a sequence of events including the formation of mitochondrial truncated Bid, the release of cytochrome c, and the activation of caspase-3, thereby causing cell death. Together, our results identify PACS-2 as a novel sorting protein that links the ER-mitochondria axis to ER homeostasis and the control of cell fate, and provide new insights into Bid action.

  13. MicroRNAs transported by exosomes in body fluids as mediators of intercellular communication in cancer

    Directory of Open Access Journals (Sweden)

    Salido-Guadarrama I

    2014-07-01

    Full Text Available Iván Salido-Guadarrama,1 Sandra Romero-Cordoba,1 Oscar Peralta-Zaragoza,2 Alfredo Hidalgo-Miranda,1 Mauricio Rodríguez-Dorantes1 1Oncogenomics Laboratory, National Institute of Genomics Medicine, Mexico City, Mexico; 2Direction of Chronic Infections and Cancer, Research Center in Infectious Diseases, National Institute of Public Health, Cuernavaca, Morelos, Mexico Abstract: Cancer-cell communication is an important and complex process, achieved through a diversity of mechanisms that allows tumor cells to mold and influence their environment. In recent years, evidence has accumulated indicating that cells communicate via the release and delivery of microRNAs (miRNAs packed into tumor-released (TR exosomes. Understanding the role and mode of action of miRNAs from TR exosomes is of paramount importance in the field of cancer biomarker discovery and for the development of new biomedical applications for cancer therapeutics. In this review, we focus on miRNAs secreted via TR exosomes, which by acting in a paracrine or endocrine manner, facilitate a diversity of signaling mechanisms between cancer cells. We address their contribution as signaling molecules, to the establishment, maintenance, and enhancement of the tumor microenvironment and the metastatic niche in cancer. Finally, we address the potential role of these molecules as biomarkers in cancer diagnosis and prognosis and their impact as a biomedical tool in cancer therapeutics. Keywords: tumor cells, multivesicular bodies, interference RNA, biomarkers and therapeutics

  14. How do individuals with Asperger syndrome respond to nonliteral language and inappropriate requests in computer-mediated communication?

    Science.gov (United States)

    Rajendran, Gnanathusharan; Mitchell, Peter; Rickards, Hugh

    2005-08-01

    Computer-mediated communication in individuals with Asperger syndrome, Tourette syndrome and normal controls was explored with a program called Bubble Dialogue (Gray, Creighton, McMahon, and Cunninghamn (1991)) in which the users type text into speech bubbles. Two scenarios, based on Happé (1994) were adapted to investigate understanding of figure of speech and sarcasm, and a third, developed by ourselves, looked at responses to inappropriate requests (lending money and disclosing home address on a first meeting). Dialogue transcripts were assessed by 62 raters who were blind to the clinical diagnoses. Hierarchical linear modelling revealed that rated understanding of a figure of speech was predicted mainly by verbal ability and executive ability, as well as by clinical diagnosis, whereas handling inappropriate requests was predicted by age, verbal ability, executive ability and diagnosis. Notably, the Tourette comparison group showed better understanding than the Asperger group in interpreting a figure of speech and handling inappropriate requests, and differences between these groups were possibly attributable to individual differences in executive ability. In contrast, understanding sarcasm was predicted by age but not by either verbal ability, executive ability or clinical diagnosis. Evidently, there is a complicated relation between Asperger syndrome, verbal ability and executive abilities with respect to communicative performance.

  15. Dioscin augments HSV-tk-mediated suicide gene therapy for melanoma by promoting connexin-based intercellular communication

    Science.gov (United States)

    Li, Bin; Wu, Yingya; Liu, Xijuan; Tan, Yuhui; Du, Biaoyan

    2017-01-01

    Suicide gene therapy is a promising strategy against melanoma. However, the low efficiency of the gene transfer technique can limit its application. Our preliminary data showed that dioscin, a glucoside saponin, could upregulate the expression of connexins Cx26 and Cx43, major components of gap junctions, in melanoma cells. We hypothesized that dioscin may increase the bystander effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) through increasing the formation of gap junctions. Further analysis showed that dioscin indeed could increase the gap junctional intercellular communication in B16 melanoma cells, resulting in more efficient GCV-induced bystander killing in B16tk cells. By contrast, overexpression of dominant negative Cx43 impaired the cell-cell communication of B16 cells and subsequently weakened the bystander effect of HSV-tk/GCV gene therapy. In vivo, combination treatment with dioscin and GCV of tumor-bearing mice with 30% positive B16tk cells and 70% wild-type B16 cells caused a significant reduction in tumor volume and weight compared to treatment with GCV or dioscin alone. Taken together, these results demonstrated that dioscin could augment the bystander effect of the HSV-tk/GCV system through increasing connexin-mediated gap junction coupling. PMID:27903977

  16. Integrating on campus problem based learning and practice based learning: issues and challenges in using computer mediated communication.

    Science.gov (United States)

    Conway, J; Sharkey, R

    2002-10-01

    The Faculty of Nursing, University of Newcastle, Australia, has been keen to initiate strategies that enhance student learning and nursing practice. Two strategies are problem based learning (PBL) and clinical practice. The Faculty has maintained a comparatively high proportion of the undergraduate hours in the clinical setting in times when financial constraints suggest that simulations and on campus laboratory experiences may be less expensive.Increasingly, computer based technologies are becoming sufficiently refined to support the exploration of nursing practice in a non-traditional lecture/tutorial environment. In 1998, a group of faculty members proposed that computer mediated instruction would provide an opportunity for partnership between students, academics and clinicians that would promote more positive outcomes for all and maintain the integrity of the PBL approach. This paper discusses the similarities between problem based and practice based learning and presents the findings of an evaluative study of the implementation of a practice based learning model that uses computer mediated communication to promote integration of practice experiences with the broader goals of the undergraduate curriculum.

  17. Psychotherapy mediated by remote communication technologies: a meta-analytic review

    Directory of Open Access Journals (Sweden)

    Richards David

    2008-07-01

    Full Text Available Abstract Background Access to psychotherapy is limited by psychopathology (e.g. agoraphobia, physical disability, occupational or social constraints and/or residency in under-served areas. For these populations, interventions delivered via remote communication technologies (e.g. telephone, internet may be more appropriate. However, there are concerns that such delivery may influence the therapeutic relationship and thus reduce therapy effectiveness. This review aimed to determine the clinical effectiveness of remotely communicated, therapist-delivered psychotherapy. Methods Systematic review (including electronic database searching and correspondence with authors of randomised trials of individual remote psychotherapy. Electronic databases searched included MEDLINE (1966–2006, PsycInfo (1967–2006, EMBASE (1980–2006 and CINAHL databases (1982–2006. The Cochrane Central Register of Controlled Trials (CENTRAL and the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDAN-CTR. All searches were conducted to include studies with a publication date to July 2006. Results Thirteen studies were identified, ten assessing psychotherapy by telephone, two by internet and one by videoconference. Pooled effect sizes for remote therapy versus control conditions were 0.44 for depression (95%CI 0.29 to 0.59, 7 comparisons, n = 726 and 1.15 for anxiety-related disorders (95%CI 0.81 to 1.49, 3 comparisons, n = 168. There were few comparisons of remote versus face-to-face psychotherapy. Conclusion Remote therapy has the potential to overcome some of the barriers to conventional psychological therapy services. Telephone-based interventions are a particularly popular research focus and as a means of therapeutic communication may confer specific advantages in terms of their widespread availability and ease of operation. However, the available evidence is limited in quantity and quality. More rigorous trials are required to

  18. Study on the Model for Regulation of the Allosteric Enzyme Activity

    Institute of Scientific and Technical Information of China (English)

    LI,Qian-Zhong(李前忠); LUO,Liao-Fu(罗辽复); ZHANG,Li-Rong(张利绒)

    2002-01-01

    The effects of activator molecule and repressive molecule on binding process between allosteric enzyme and substrate are disused by considering the heterotropic effect of the regulating molecule that binds to allosteric enzyme. A model of allosteric enzyme with heterotropic effect is presented. The cooperativity and anticooperativity in the regulation process are studied.

  19. Usability testing by older adults of a computer-mediated health communication program.

    Science.gov (United States)

    Lin, Carolyn A; Neafsey, Patricia J; Strickler, Zoe

    2009-03-01

    Failure to adhere to an antihypertensive regimen and interactions between antihypertensives and other medicines represent serious health threats to older adults. This study tested the usability of a touch-screen-enabled personal education program (PEP). Findings showed that older adults rated the PEP system usability, system usefulness, and system-use satisfaction at a moderately high level for prototype-1 and at an exceptionally high level for prototype-2. A 201.91% reduction in interface errors and a 31.08% decrease in interface time also were found between the two trials. This participatory usability design was highly successful in tailoring its program interface design to accommodate older users to enhance their health communication and technology use efficacy.

  20. THE MECHANISMS OF MEN’S SELF-PRESENTATION IN ENGLISH COMPUTER-MEDIATED COMMUNICATION

    Directory of Open Access Journals (Sweden)

    Gukosyants Olga Yuryevna

    2014-06-01

    Full Text Available This article characterizes the peculiarities of verbal self-presentation of a masculine personality, analyzes the linguistic means differentiated by the degree of gender preferability, contains a number of traditional features of masculine speech and points out the gender markers in English chat communication and blogs. The author studies the male speech markers which have not been touched upon in scientific works: use of contraction (in chats, higher level of text cohesion (in blogs and chats. According to the obtained data, the author determines the mechanisms of men's self-presentation in blogs (distance determination; expressing aggression, scandal provocation; direct ordering; simplification of one's own speech perception by others and chats (expressing aggression, scandal provocation, simplification of one's own speech perception by others.

  1. The art of antibacterial warfare: Deception through interference with quorum sensing-mediated communication.

    Science.gov (United States)

    Rampioni, Giordano; Leoni, Livia; Williams, Paul

    2014-08-01

    Almost a century on from the discovery of penicillin, the war against bacterial infection still rages compounded by the emergence of strains resistant to virtually every clinically approved antibiotic and the dearth of new antibacterial agents entering the clinic. Consequently there is renewed interest in drugs which attenuate virulence rather than bacterial growth. Since the metaphors of warfare are often used to describe the battle between pathogen and host, we will describe in such a context, the molecular communication (quorum sensing) mechanisms used by bacteria to co-ordinate virulence at the population level. Recent progress in exploiting this information through the design of anti-virulence deception strategies that disrupt quorum sensing through signal molecule inactivation, inhibition of signal molecule biosynthesis or the blockade of signal transduction and their advantages and disadvantages are considered.

  2. Inter-plant communication through mycorrhizal networks mediates complex adaptive behaviour in plant communities.

    Science.gov (United States)

    Gorzelak, Monika A; Asay, Amanda K; Pickles, Brian J; Simard, Suzanne W

    2015-01-01

    Adaptive behaviour of plants, including rapid changes in physiology, gene regulation and defence response, can be altered when linked to neighbouring plants by a mycorrhizal network (MN). Mechanisms underlying the behavioural changes include mycorrhizal fungal colonization by the MN or interplant communication via transfer of nutrients, defence signals or allelochemicals. We focus this review on our new findings in ectomycorrhizal ecosystems, and also review recent advances in arbuscular mycorrhizal systems. We have found that the behavioural changes in ectomycorrhizal plants depend on environmental cues, the identity of the plant neighbour and the characteristics of the MN. The hierarchical integration of this phenomenon with other biological networks at broader scales in forest ecosystems, and the consequences we have observed when it is interrupted, indicate that underground 'tree talk' is a foundational process in the complex adaptive nature of forest ecosystems.

  3. Niemann-Pick type C2 protein mediating chemical communication in the worker ant.

    Science.gov (United States)

    Ishida, Yuko; Tsuchiya, Wataru; Fujii, Takeshi; Fujimoto, Zui; Miyazawa, Mitsuhiro; Ishibashi, Jun; Matsuyama, Shigeru; Ishikawa, Yukio; Yamazaki, Toshimasa

    2014-03-11

    Ants are eusocial insects that are found in most regions of the world. Within its caste, worker ants are responsible for various tasks that are required for colony maintenance. In their chemical communication, α-helical carrier proteins, odorant-binding proteins, and chemosensory proteins, which accumulate in the sensillum lymph in the antennae, play essential roles in transferring hydrophobic semiochemicals to chemosensory receptors. It has been hypothesized that semiochemicals are recognized by α-helical carrier proteins. The number of these proteins, however, is not sufficient to interact with a large number of semiochemicals estimated from chemosensory receptor genes. Here we shed light on this conundrum by identifying a Niemann-Pick type C2 (NPC2) protein from the antenna of the worker Japanese carpenter ant, Camponotus japonicus (CjapNPC2). CjapNPC2 accumulated in the sensillum cavity in the basiconic sensillum. The ligand-binding pocket of CjapNPC2 was composed of a flexible β-structure that allowed it to bind to a wide range of potential semiochemicals. Some of the semiochemicals elicited electrophysiolgical responses in the worker antenna. In vertebrates, NPC2 acts as an essential carrier protein for cholesterol from late endosomes and lysosomes to other cellular organelles. However, the ants have evolved an NPC2 with a malleable ligand-binding pocket as a moderately selective carrier protein in the sensillum cavity of the basiconic sensillum. CjapNPC2 might be able to deliver various hydrophobic semiochemicals to chemosensory receptor neurons and plays crucial roles in chemical communication required to perform the worker ant tasks.

  4. Climatic change, cientific consensus and mediatic construction. The paradigm of the communication for the sustainable development

    Directory of Open Access Journals (Sweden)

    Dr. Bernando Díaz Nosty, nosty@infoamerica.org

    2009-01-01

    Full Text Available The climatic change, the global warming and the sustainable development are concepts integrated in the agenda setting of the media that reveal preoccupations and alert in the scientific consensus. Nevertheless, the reflections of the information about these aspects reveal deficiency in the constructivist techniques of journalism, moreover things that have to do with politics, economic and cultural interest. This article has to do with the evolution and tendencies of the informative flow in relation to climatic change as well as dissonances between scientific and media messages. It also has to do with the growing interest of the communication studies, especially in the Anglo-Saxon world about the environmental crisis up to the point to suggest the development of a flowing oriented to journalistic communication and sustainable innovation.El cambio climático, el calentamiento global y la sostenibilidad son conceptos integrados en la agenda de los medios, que reflejan preocupaciones y alertas amparadas en un amplio consenso científico. No obstante, el reflejo de la información sobre estos aspectos revela carencias en las técnicas constructivas del periodismo, además de aquellas que responden a cruces de intereses políticos, económicos y culturales. En este artículo se refiere la evolución y tendencias de los flujos informativos relativos al cambio climático, así como a las disonancias entre los mensajes científico y el mediático. También, se hace hincapié en el creciente interés de los estudios de comunicación, especialmente en el mundo anglosajón, sobre la crisis medioambiental, hasta el punto de sugerir el desarrollo de una corriente orientada a la comunicación periodística y la innovación sostenible.

  5. Allosteric dynamics of SAMHD1 studied by molecular dynamics simulations

    Science.gov (United States)

    Patra, K. K.; Bhattacharya, A.; Bhattacharya, S.

    2016-10-01

    SAMHD1 is a human cellular enzyme that blocks HIV-1 infection in myeloid cells and non-cycling CD4+T cells. The enzyme is an allosterically regulated triphosphohydrolase that modulates the level of cellular dNTP. The virus restriction is attributed to the lowering of the pool of dNTP in the cell to a point where reverse-transcription is impaired. Mutations in SAMHD1 are also implicated in Aicardi-Goutieres syndrome. A mechanistic understanding of the allosteric activation of the enzyme is still elusive. We have performed molecular dynamics simulations to examine the allosteric site dynamics of the protein and to examine the connection between the stability of the tetrameric complex and the Allosite occupancy.

  6. Novel Inhibitors Complexed with Glutamate Dehydrogenase: ALLOSTERIC REGULATION BY CONTROL OF PROTEIN DYNAMICS

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ming; Smith, Christopher J.; Walker, Matthew T.; Smith, Thomas J.; (Danforth)

    2009-12-01

    Mammalian glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of L-glutamate to 2-oxoglutarate using NAD(P){sup +} as coenzyme. Unlike its counterparts from other animal kingdoms, mammalian GDH is regulated by a host of ligands. The recently discovered hyperinsulinism/hyperammonemia disorder showed that the loss of allosteric inhibition of GDH by GTP causes excessive secretion of insulin. Subsequent studies demonstrated that wild-type and hyperinsulinemia/hyperammonemia forms of GDH are inhibited by the green tea polyphenols, epigallocatechin gallate and epicatechin gallate. This was followed by high throughput studies that identified more stable inhibitors, including hexachlorophene, GW5074, and bithionol. Shown here are the structures of GDH complexed with these three compounds. Hexachlorophene forms a ring around the internal cavity in GDH through aromatic stacking interactions between the drug and GDH as well as between the drug molecules themselves. In contrast, GW5074 and bithionol both bind as pairs of stacked compounds at hexameric 2-fold axes between the dimers of subunits. The internal core of GDH contracts when the catalytic cleft closes during enzymatic turnover. None of the drugs cause conformational changes in the contact residues, but all bind to key interfaces involved in this contraction process. Therefore, it seems likely that the drugs inhibit enzymatic turnover by inhibiting this transition. Indeed, this expansion/contraction process may play a major role in the inter-subunit communication and allosteric regulation observed in GDH.

  7. Short communication: N-Acetylcysteine-mediated modulation of antibiotic susceptibility of bovine mastitis pathogens.

    Science.gov (United States)

    Yang, F; Liu, L H; Li, X P; Luo, J Y; Zhang, Z; Yan, Z T; Zhang, S D; Li, H S

    2016-06-01

    The aim of this study was to investigate the effects of N-acetylcysteine (NAC) on antibiotic susceptibility of bovine mastitis pathogens including Staphylococcus aureus, Streptococcus dysgalactiae, Escherichia coli, and Streptococcus agalactiae. Minimum inhibitory concentrations (MIC) were tested by the agar-based E-test method. The presence of 10mM NAC reduced the MIC of penicillin and ampicillin but enhanced the MIC of erythromycin and ciprofloxacin for all of the strains. In addition, NAC-mediated modulation of MIC of kanamycin, tetracycline, and vancomycin was diverse, depending on the target bacterial pathogen and antibiotic being used. The results suggest that NAC is an important modulator of antibiotic activity against the major bovine mastitis pathogens. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. Communicating about the risks and benefits of genetically modified foods: The mediating role of trust

    DEFF Research Database (Denmark)

    Frewer, Lynn J.; Scholderer, Joachim; Bredahl, Lone

    2003-01-01

    of information strategy adopted had almost no impact on post-experimental attitudes. The extent to which people trusted the information sources appeared to be driven by people's attitudes to genetically modified foods, rather than trust influencing the way that people reacted to the information. Trust......Recent research suggests that public attitudes towards emerging technologies are mainly driven by trust in the institutions promoting and regulating these technologies. Alternative views maintain that trust should be seen as a consequence rather than a cause of such attitudes. To test its actual...... role, direct as well as mediating effects of trust were tested in an attitude change experiment involving 1203 consumers from Denmark, Germany, Italy and the UK. After prior attitudes to genetic modification in food production had been assessed, participants received different information materials...

  9. Communicating about the risks and benefits of genetically modified foods: the mediating role of trust.

    Science.gov (United States)

    Frewer, Lynn J; Scholderer, Joachim; Bredahl, Lone

    2003-12-01

    Recent research suggests that public attitudes toward emerging technologies are mainly driven by trust in the institutions promoting and regulating these technologies. Alternative views maintain that trust should be seen as a consequence rather than a cause of such attitudes. To test its actual role, direct as well as mediating effects of trust were tested in an attitude change experiment involving 1,405 consumers from Denmark, Germany, Italy, and the United Kingdom. After prior attitudes to genetic modification in food production had been assessed, participants received different information materials (either product-specific information or balanced/general information about genetic modification in food production) and were asked to evaluate different types of genetically modified foods (either beer or yoghurt). The information materials were attributed to different information sources (either an industry association, a consumer organization, or a government source). After completion, perceived risk and perceived benefit were assessed, and participants indicated their trust in the information sources to which the materials had been attributed. Direct and trust-mediated attitude change effects were estimated in a multi-sample structural equation model. The results showed that information provision had little effect on people's attitudes toward genetically modified foods, and that perceptions of information source characteristics contributed very little to attitude change. Furthermore, the type of information strategy adopted had almost no impact on postexperimental attitudes. The extent to which people trusted the information sources appeared to be driven by people's attitudes to genetically modified foods, rather than trust influencing the way that people reacted to the information. Trust was not driving risk perception-rather, attitudes were informing perceptions of the motivation of the source providing the information.

  10. Experimental Tests of Normative Group Influence and Representation Effects in Computer-Mediated Communication: When Interacting Via Computers Differs from Interacting With Computers.

    Science.gov (United States)

    Lee, Eun-Ju; Nass, Clifford

    2002-01-01

    Presents two experiments to address the questions of if and how normative social influence operates in anonymous computer-mediated communication and human-computer interaction. Finds that the perception of interaction partner (human vs. computer) moderated the group conformity effect such that the undergraduate student subjects expressed greater…

  11. Effects of Gendered Language on Gender Stereotyping in Computer-Mediated Communication: The Moderating Role of Depersonalization and Gender-Role Orientation

    Science.gov (United States)

    Lee, Eun-Ju

    2007-01-01

    This experiment examined what situational and dispositional features moderate the effects of linguistic gender cues on gender stereotyping in anonymous, text-based computer-mediated communication. Participants played a trivia game with an ostensible partner via computer, whose comments represented either prototypically masculine or feminine…

  12. The Effect of Dynamic Assessment in Synchronous Computer-Mediated Communication on Iranian EFL Learners' Listening Comprehension Ability at Upper-Intermediate Level

    Science.gov (United States)

    Heidar, Davood Mashhadi; Afghari, Akbar

    2015-01-01

    The present paper concentrates on a web-based inquiry in the synchronous computer-mediated communication (SCMC) via Web 2.0 technologies of Talk and Write and Skype. It investigates EFL learners' socio-cognitive progress through dynamic assessment (DA), which follows Vygotsky's inclination for supportive interchange in the zone of proximal…

  13. Exploring Taiwanese College Students' Perceptions of Text-Based, Computer-Mediated Communication Technology in Learning Japanese as a Foreign Language

    Science.gov (United States)

    Tanaka, Makiko

    2015-01-01

    The use of computers as an educational tool has become very popular in the context of language teaching and learning. Research into computer mediated communication (CMC) in a Japanese as a foreign language (JFL) learning and teaching context can take advantage of various pedagogical possibilities, just as in the English classroom. This study…

  14. Hotspot mutations in KIT receptor differentially modulate its allosterically coupled conformational dynamics: impact on activation and drug sensitivity.

    Directory of Open Access Journals (Sweden)

    Isaure Chauvot de Beauchêne

    2014-07-01

    Full Text Available Receptor tyrosine kinase KIT controls many signal transduction pathways and represents a typical allosterically regulated protein. The mutation-induced deregulation of KIT activity impairs cellular physiological functions and causes serious human diseases. The impact of hotspots mutations (D816H/Y/N/V and V560G/D localized in crucial regulatory segments, the juxtamembrane region (JMR and the activation (A- loop, on KIT internal dynamics was systematically studied by molecular dynamics simulations. The mutational outcomes predicted in silico were correlated with in vitro and in vivo activation rates and drug sensitivities of KIT mutants. The allosteric regulation of KIT in the native and mutated forms is described in terms of communication between the two remote segments, JMR and A-loop. A strong correlation between the communication profile and the structural and dynamical features of KIT in the native and mutated forms was established. Our results provide new insight on the determinants of receptor KIT constitutive activation by mutations and resistance of KIT mutants to inhibitors. Depiction of an intra-molecular component of the communication network constitutes a first step towards an integrated description of vast communication pathways established by KIT in physiopathological contexts.

  15. A substrate-driven allosteric switch that enhances PDI catalytic activity.

    Science.gov (United States)

    Bekendam, Roelof H; Bendapudi, Pavan K; Lin, Lin; Nag, Partha P; Pu, Jun; Kennedy, Daniel R; Feldenzer, Alexandra; Chiu, Joyce; Cook, Kristina M; Furie, Bruce; Huang, Mingdong; Hogg, Philip J; Flaumenhaft, Robert

    2016-08-30

    Protein disulfide isomerase (PDI) is an oxidoreductase essential for folding proteins in the endoplasmic reticulum. The domain structure of PDI is a-b-b'-x-a', wherein the thioredoxin-like a and a' domains mediate disulfide bond shuffling and b and b' domains are substrate binding. The b' and a' domains are connected via the x-linker, a 19-amino-acid flexible peptide. Here we identify a class of compounds, termed bepristats, that target the substrate-binding pocket of b'. Bepristats reversibly block substrate binding and inhibit platelet aggregation and thrombus formation in vivo. Ligation of the substrate-binding pocket by bepristats paradoxically enhances catalytic activity of a and a' by displacing the x-linker, which acts as an allosteric switch to augment reductase activity in the catalytic domains. This substrate-driven allosteric switch is also activated by peptides and proteins and is present in other thiol isomerases. Our results demonstrate a mechanism whereby binding of a substrate to thiol isomerases enhances catalytic activity of remote domains.

  16. Interdomain allosteric regulation of Polo kinase by Aurora B and Map205 is required for cytokinesis.

    Science.gov (United States)

    Kachaner, David; Pinson, Xavier; El Kadhi, Khaled Ben; Normandin, Karine; Talje, Lama; Lavoie, Hugo; Lépine, Guillaume; Carréno, Sébastien; Kwok, Benjamin H; Hickson, Gilles R; Archambault, Vincent

    2014-10-27

    Drosophila melanogaster Polo and its human orthologue Polo-like kinase 1 fulfill essential roles during cell division. Members of the Polo-like kinase (Plk) family contain an N-terminal kinase domain (KD) and a C-terminal Polo-Box domain (PBD), which mediates protein interactions. How Plks are regulated in cytokinesis is poorly understood. Here we show that phosphorylation of Polo by Aurora B is required for cytokinesis. This phosphorylation in the activation loop of the KD promotes the dissociation of Polo from the PBD-bound microtubule-associated protein Map205, which acts as an allosteric inhibitor of Polo kinase activity. This mechanism allows the release of active Polo from microtubules of the central spindle and its recruitment to the site of cytokinesis. Failure in Polo phosphorylation results in both early and late cytokinesis defects. Importantly, the antagonistic regulation of Polo by Aurora B and Map205 in cytokinesis reveals that interdomain allosteric mechanisms can play important roles in controlling the cellular functions of Plks.

  17. Quality of life and adolescents' communication with their significant others (mother, father, and best friend): the mediating effect of attachment to pets.

    Science.gov (United States)

    Marsa-Sambola, Ferran; Williams, Joanne; Muldoon, Janine; Lawrence, Alistair; Connor, Melanie; Currie, Candace

    2017-06-01

    The relationship between adolescents' communication with their significant others (mother, father, and best friend) and quality of life (KIDSCREEN) was investigated in 2262 Scottish adolescent pet owners. The variable attachment to pets was also tested and assessed as a mediator of this relationship. A positive relationship between adolescents' communication with their significant other (mother, father, and best friend) and quality of life decreased when controlling for attachment to dogs. In cat owners, a positive relationship between communication with a best friend and quality of life decreased when controlling for attachment to cats. In cat and dog owners, attachment to these pets predicted higher levels of quality of life. Higher attachment to dogs and cats was explained by good best friend (IV) and attachment to pets (DV) and best friends. Mediation effects of attachment to dogs and cats might be explained in terms of the caring activities associated with these types of pets.

  18. The place of information and communication technology-mediated consultations in primary care: GPs' perspectives.

    Science.gov (United States)

    Hanna, Lisa; May, Carl; Fairhurst, Karen

    2012-06-01

    New information and communication technologies such as email and text messaging have been shown to be useful in some aspects of primary care service delivery. Little is known about Scottish GPs' attitudes towards the adoption of these technologies as routine consultation tools. To explore GPs' perceptions of the potential place of new non-face-to-face consultation technologies in the routine delivery of primary care; to explore GPs' perceived barriers to the introduction of these technologies and to identify the processes by which GPs feel that new consultation technologies could be incorporated into routine primary care. Qualitative interview study: 20 in-depth semi-structured interviews carried out with maximum variation sample of GPs across Scotland. Whilst the face-to-face consultation was seen as central to much of the clinical and diagnostic work of primary care, many GPs were conditionally willing to consider using new technologies in the future, particularly to carry out administrative or less complex tasks and therefore maximize practice efficiency and patient convenience. Key considerations were access to appropriate training, IT support and medico-legal guidance. GPs are conditionally willing to use new consultation media if clinically appropriate and if medico-legal and technical support is available.

  19. 5-(N, N-Hexamethylene) amiloride is a GABA-A ρ1 receptor positive allosteric modulator.

    Science.gov (United States)

    Snell, Heather D; Gonzales, Eric B

    2016-11-01

    Guanidine compounds act as ion channel modulators. In the case of Cys-loop receptors, the guanidine compound amiloride antagonized the heteromeric GABA-A, glycine, and nicotinic acetylcholine receptors. However, amiloride exhibits characteristics consistent with a positive allosteric modulator for the human GABA-A (hGABA-A) ρ1 receptor. Site-directed mutagenesis revealed that the positive allosteric modulation was influenced by the GABA-A ρ1 second transmembrane domain 15' position, a site implicated in ligand allosteric modulation of Cys-loop receptors. There are a variety of amiloride derivatives that provide opportunities to assess the significance of amiloride functional groups (e.g., the guanidine group, the pyrazine ring, etc.) in the modulation of the GABA-A ρ1 receptor activity. We utilized 3 amiloride derivatives (benzamil, phenamil, and 5-(N, N-Hexamethylene) amiloride) to assess the contribution of these groups toward the potentiation of the GABA-A ρ1 receptor. Benzamil and phenamil failed to potentiate on the wild type GABA-A ρ1 GABA-mediated current while HMA demonstrated efficacy only at the highest concentration studied. The hGABA-A ρ1 (I15'N) mutant receptor activity was potentiated by lower HMA concentrations compared to the wild type receptor. Our findings suggest that an exposed guanidine group on amiloride and amiloride derivatives is critical for modulating the GABA-A ρ1 receptor. The present study provides a conceptual framework for predicting which amiloride derivatives will demonstrate positive allosteric modulation of the GABA-A ρ1 receptor.

  20. How allosteric effectors can bind to the same protein residue and produce opposite shifts in the allosteric equilibrium.

    Science.gov (United States)

    Abraham, D J; Safo, M K; Boyiri, T; Danso-Danquah, R E; Kister, J; Poyart, C

    1995-11-21

    Monoaldehyde allosteric effectors of hemoglobin were designed, using molecular modeling software (GRID), to form a Schiff base adduct with the Val 1 alpha N-terminal nitrogens and interact via a salt bridge with Arg 141 alpha of the opposite subunit. The designed molecules were synthesized if not available. It was envisioned that the molecules, which are aldehyde acids, would produce a high-affinity hemoglobin with potential interest as antisickling agents similar to other aldehyde acids reported earlier. X-ray crystallographic analysis indicated that the aldehyde acids did bind as modeled de novo in symmetry-related pairs to the alpha subunit N-terminal nitrogens. However, oxygen equilibrium curves run on solutions obtained from T- (tense) state hemoglobin crystals of reacted effector molecules produced low-affinity hemoglobins. The shift in the allosteric equilibrium was opposite to that expected. We conclude that the observed shift in allosteric equilibrium was due to the acid group on the monoaldehyde aromatic ring that forms a salt bridge with the guanidinium ion of Arg 141 alpha on the opposite subunit. This added constraint to the T-state structure that ties two subunits across the molecular symmetry axis shifts the equilibrium further toward the T-state. We tested this idea by comparing aldehydes that form Schiff base interactions with the same Val 1 alpha residues but do not interact across the dimer subunit symmetry axis (a new one in this study with no acid group and others that have had determined crystal structures). The latter aldehydes shift the allosteric equilibrium toward the R-state. A hypothesis to predict the direction in shift of the allosteric equilibrium is made and indicates that it is not exclusively where the molecule binds but how it interacts with the protein to stabilize or destabilize the T- (tense) allosteric state.

  1. Functional Impact of Allosteric Agonist Activity of Selective Positive Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 in Regulating Central Nervous System Function

    OpenAIRE

    Noetzel, Meredith J.; Rook, Jerri M.; Vinson, Paige N.; Cho, Hyekyung P.; Days, Emily; Zhou, Y.; Rodriguez, Alice L.; Lavreysen, Hilde; Stauffer, Shaun R.; Niswender, Colleen M.; Xiang, Zixiu; Daniels, J. Scott; Jones, Carrie K.; Lindsley, Craig W.; Weaver, C. David

    2012-01-01

    Positive allosteric modulators (PAMs) of metabotropic glutamate receptor subtype 5 (mGlu5) have emerged as an exciting new approach for the treatment of schizophrenia and other central nervous system (CNS) disorders. Of interest, some mGlu5 PAMs act as pure PAMs, only potentiating mGlu5 responses to glutamate whereas others [allosteric agonists coupled with PAM activity (ago-PAMs)] potentiate responses to glutamate and have intrinsic allosteric agonist activity in mGlu5-expressing cell lines....

  2. Ago-allosteric modulation and other types of allostery in dimeric 7TM receptors

    DEFF Research Database (Denmark)

    Schwartz, Thue W; Holst, Birgitte

    2006-01-01

    Conventionally, an allosteric modulator is neutral in respect of efficacy and binds to a receptor site distant from the orthosteric site of the endogenous agonist. However, recently compounds being ago-allosteric modulators have been described i.e., compounds acting both as agonists on their own...... influence the potency of the endogenous agonist. It is of interest that at least some endogenous agonists can only occupy one protomer of a dimeric 7TM receptor complex at a time and thereby they leave the orthosteric binding site in the allosteric protomer free, potentially for binding of exogenous......, allosteric modulators. If the allosteric modulator is an agonist, it is an ago-allosteric modulator; if it is neutral, it is a classical enhancer. Molecular mapping in hetero-dimeric class-C receptors, where the endogenous agonist clearly binds only in one protomer, supports the notion that allosteric...

  3. An allosteric inhibitor of protein arginine methyltransferase 3.

    Science.gov (United States)

    Siarheyeva, Alena; Senisterra, Guillermo; Allali-Hassani, Abdellah; Dong, Aiping; Dobrovetsky, Elena; Wasney, Gregory A; Chau, Irene; Marcellus, Richard; Hajian, Taraneh; Liu, Feng; Korboukh, Ilia; Smil, David; Bolshan, Yuri; Min, Jinrong; Wu, Hong; Zeng, Hong; Loppnau, Peter; Poda, Gennadiy; Griffin, Carly; Aman, Ahmed; Brown, Peter J; Jin, Jian; Al-Awar, Rima; Arrowsmith, Cheryl H; Schapira, Matthieu; Vedadi, Masoud

    2012-08-01

    PRMT3, a protein arginine methyltransferase, has been shown to influence ribosomal biosynthesis by catalyzing the dimethylation of the 40S ribosomal protein S2. Although PRMT3 has been reported to be a cytosolic protein, it has been shown to methylate histone H4 peptide (H4 1-24) in vitro. Here, we report the identification of a PRMT3 inhibitor (1-(benzo[d][1,2,3]thiadiazol-6-yl)-3-(2-cyclohexenylethyl)urea; compound 1) with IC50 value of 2.5 μM by screening a library of 16,000 compounds using H4 (1-24) peptide as a substrate. The crystal structure of PRMT3 in complex with compound 1 as well as kinetic analysis reveals an allosteric mechanism of inhibition. Mutating PRMT3 residues within the allosteric site or using compound 1 analogs that disrupt interactions with allosteric site residues both abrogated binding and inhibitory activity. These data demonstrate an allosteric mechanism for inhibition of protein arginine methyltransferases, an emerging class of therapeutic targets.

  4. Structures of pyruvate kinases display evolutionarily divergent allosteric strategies.

    Science.gov (United States)

    Morgan, Hugh P; Zhong, Wenhe; McNae, Iain W; Michels, Paul A M; Fothergill-Gilmore, Linda A; Walkinshaw, Malcolm D

    2014-09-01

    The transition between the inactive T-state (apoenzyme) and active R-state (effector bound enzyme) of Trypanosoma cruzi pyruvate kinase (PYK) is accompanied by a symmetrical 8° rigid body rocking motion of the A- and C-domain cores in each of the four subunits, coupled with the formation of additional salt bridges across two of the four subunit interfaces. These salt bridges provide increased tetramer stability correlated with an enhanced specificity constant (k cat/S 0.5). A detailed kinetic and structural comparison between the potential drug target PYKs from the pathogenic protists T. cruzi, T. brucei and Leishmania mexicana shows that their allosteric mechanism is conserved. By contrast, a structural comparison of trypanosomatid PYKs with the evolutionarily divergent PYKs of humans and of bacteria shows that they have adopted different allosteric strategies. The underlying principle in each case is to maximize (k cat/S 0.5) by stabilizing and rigidifying the tetramer in an active R-state conformation. However, bacterial and mammalian PYKs have evolved alternative ways of locking the tetramers together. In contrast to the divergent allosteric mechanisms, the PYK active sites are highly conserved across species. Selective disruption of the varied allosteric mechanisms may therefore provide a useful approach for the design of species-specific inhibitors.

  5. Molecular mechanism of allosteric substrate activation in a thiamine diphosphate-dependent decarboxylase.

    Science.gov (United States)

    Versées, Wim; Spaepen, Stijn; Wood, Martin D H; Leeper, Finian J; Vanderleyden, Jos; Steyaert, Jan

    2007-11-30

    Thiamine diphosphate-dependent enzymes are involved in a wide variety of metabolic pathways. The molecular mechanism behind active site communication and substrate activation, observed in some of these enzymes, has since long been an area of debate. Here, we report the crystal structures of a phenylpyruvate decarboxylase in complex with its substrates and a covalent reaction intermediate analogue. These structures reveal the regulatory site and unveil the mechanism of allosteric substrate activation. This signal transduction relies on quaternary structure reorganizations, domain rotations, and a pathway of local conformational changes that are relayed from the regulatory site to the active site. The current findings thus uncover the molecular mechanism by which the binding of a substrate in the regulatory site is linked to the mounting of the catalytic machinery in the active site in this thiamine diphosphate-dependent enzyme.

  6. Conducting Creativity Brainstorming Sessions in Small and Medium-Sized Enterprises Using Computer-Mediated Communication Tools

    Science.gov (United States)

    Murthy, Uday S.

    A variety of Web-based low cost computer-mediated communication (CMC) tools are now available for use by small and medium-sized enterprises (SME). These tools invariably incorporate chat systems that facilitate simultaneous input in synchronous electronic meeting environments, allowing what is referred to as “electronic brainstorming.” Although prior research in information systems (IS) has established that electronic brainstorming can be superior to face-to-face brainstorming, there is a lack of detailed guidance regarding how CMC tools should be optimally configured to foster creativity in SMEs. This paper discusses factors to be considered in using CMC tools for creativity brainstorming and proposes recommendations for optimally configuring CMC tools to enhance creativity in SMEs. The recommendations are based on lessons learned from several recent experimental studies on the use of CMC tools for rich brainstorming tasks that require participants to invoke domain-specific knowledge. Based on a consideration of the advantages and disadvantages of the various configuration options, the recommendations provided can form the basis for selecting a CMC tool for creativity brainstorming or for creating an in-house CMC tool for the purpose.

  7. COMPUTER-MEDIATED COMMUNICATION AS A TOOL FOR IMPROVING THE ENGLISH LANGUAGE AMONG ADULT LEARNERS IN TVET PROGRAMME

    Directory of Open Access Journals (Sweden)

    Berhannudin Mohd Salleh

    2010-05-01

    Full Text Available This article highlighted the computer mediated communication skills students need to become lifelong learners in an information society. Among these skills are the abilities to: use technology tools to enhance learning; use telecommunications to collaborate with and interact with peers; use technology to locate and collect information from a variety of sources; and use technology for informed decision-making. The need to master the English language has always been a never ending quest especially among ESL adult learners in Malaysia. Mastery in the language will not only enhance academic achievements but promote one’s status in the community. Despite the many years of learning English command of the language among Malaysian ESL learners is still yet to be desired. This paper thus presents the findings of an innovative approach to learn the English language the technology way. Using an online platform that is freely available in the Internet participants comprising adult TVET teacher trainee of Universiti Tun Hussein Onn Malaysia took part in an online discussion using the English language via the Internet for a semester. Findings of the study revealed that the online platform has helped the students improve themselves in many aspects of the learning process. There was an increase in confidence and frequency of use of the target language, improved thinking ability and least but not last provided joy for learning the English language.

  8. Fractalkine Mediates Communication between Pathogenic Proteins and Microglia: Implications of Anti-Inflammatory Treatments in Different Stages of Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Nicole M. Desforges

    2012-01-01

    Full Text Available The role of inflammation in neurodegenerative diseases has been widely demonstrated. Intraneuronal protein accumulation may regulate microglial activity via the fractalkine (CX3CL1 signaling pathway that provides a mechanism through which neurons communicate with microglia. CX3CL1 levels fluctuate in different stages of neurodegenerative diseases and in various animal models, warranting further investigation of the mechanisms underlying microglial response to pathogenic proteins, including Tau, β-amyloid (Aβ, and α-synuclein. The temporal relationship between microglial activity and localization of pathogenic proteins (intra- versus extracellular likely determines whether neuroinflammation mitigates or exacerbates disease progression. Evidence in transgenic models suggests a beneficial effect of microglial activity on clearance of proteins like Aβ and a detrimental effect on Tau modification, but the role of CX3CL1 signaling in α-synucleinopathies is less clear. Here we review the nature of fractalkine-mediated neuronmicroglia interaction, which has significant implications for the efficacy of anti-inflammatory treatments during different stages of neurodegenerative pathology. Specifically, it is likely that anti-inflammatory treatment in early stages of disease during intraneuronal accumulation of proteins could be beneficial, while anti-inflammatory treatment in later stages when proteins are secreted to the extracellular space could exacerbate disease progression.

  9. The Sexual Behaviour of Chagas' Disease Vectors: Chemical Signals Mediating Communication between Male and Female Triatomine Bugs

    Directory of Open Access Journals (Sweden)

    Gabriel Manrique

    2012-01-01

    Full Text Available Chemical communication mechanisms that mediate sexual behaviour in triatomine bugs are reviewed with regard to source, identity, and function of sex pheromones. Males attempt to copulate but may be rejected, depending on female age and nutritional status. Triatomine males locate partners through sex pheromones emitted by the metasternal glands (MGs of females. These activate males, inducing them to leave their refuges and initiate flight. Wandering males display anemotactic orientation modulated by chemical signals emitted from female MGs. Analyses of the MG secretions of several species resulted in the identification of numerous ketones, acetals, and alcohols. Occlusion experiments showed that Brindley’s gland products were not required for mating. Metasternal gland volatiles are emitted by virgin male and female bugs, with detection over females occurring more consistently, especially during the early scotophase, suggesting female calling behaviour. Mating triatomine females have been reported to attract males that tend to copulate successively with them. Mating males prolong mating and postcopulatory mate guarding in the presence of other males. This is indicative of a polyandrous mating system in several triatomine species. Its potential advantages remain unknown, and comparative studies are required to increase our understanding of triatomine reproductive strategies.

  10. The Mediating Role of Partner Communication Frequency on Condom Use Among African-American Adolescent Females Participating in an HIV Prevention Intervention

    Science.gov (United States)

    Sales, Jessica M.; Lang, Delia L.; DiClemente, Ralph J.; Latham, Teaniese P; Wingood, Gina M.; Hardin, James W.; Rose, Eve S.

    2011-01-01

    Objective Although effective HIV prevention interventions have been developed for adolescents, few interventions have explored whether components of the intervention are responsible for the observed changes in behaviors post-intervention. This study examined the mediating role of partner communication frequency on African-American adolescent females’ condom use post-participation in a demonstrated efficacious HIV risk-reduction intervention. Main Outcome Measures Percent condom use in the past 60 days and consistent condom use in the past 6o days across the 12-month follow-up period. Design As part of a randomized controlled trial of African-American adolescent females (N=715), 15-21 years, seeking sexual health services, completed a computerized interview at baseline (prior to intervention) and again 6- and 12-month follow-up post-intervention participation. The interview assessed adolescents’ sexual behavior and partner communication skills, among other variables, at each time point. Using generalized estimating equation (GEE) techniques, both logistic and linear regression models were employed to test mediation over the 12-month follow-up period. Additional tests were conducted to assess the significance of the mediated models. Results Mediation analyses observed that partner communication frequency was a significant partial mediator of both proportion condom-protected sex acts (p =.001) and consistent condom use (p = .001). Conclusion Partner communication frequency, an integral component of this HIV intervention, significantly increased as a function of participating in the intervention partially explaining the change in condom use observed 12-months post-intervention. Understanding what intervention components are associated with behavior change is important for future intervention development. PMID:21843001

  11. Mechanism of allosteric regulation of β2-adrenergic receptor by cholesterol

    DEFF Research Database (Denmark)

    Manna, Moutusi; Niemelä, Miia; Tynkkynen, Joona

    2016-01-01

    ) - a prototypical G protein-coupled receptor - is modulated by cholesterol in an allosteric fashion. Extensive atomistic simulations show that cholesterol regulates b2AR by limiting its conformational variability. The mechanism of action is based on the binding of cholesterol at specific high-affinity sites located...... near the transmembrane helices 5-7 of the receptor. The alternative mechanism, where the β2AR conformation would be modulated by membrane-mediated interactions, plays only a minor role. Cholesterol analogues also bind to cholesterol binding sites and impede the structural flexibility of β2AR, however...... cholesterol generates the strongest effect. The results highlight the capacity of lipids to regulate the conformation of membrane receptors through specific interactions....

  12. Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase.

    Science.gov (United States)

    Ramos-Espiritu, Lavoisier; Kleinboelting, Silke; Navarrete, Felipe A; Alvau, Antonio; Visconti, Pablo E; Valsecchi, Federica; Starkov, Anatoly; Manfredi, Giovanni; Buck, Hannes; Adura, Carolina; Zippin, Jonathan H; van den Heuvel, Joop; Glickman, J Fraser; Steegborn, Clemens; Levin, Lonny R; Buck, Jochen

    2016-10-01

    The prototypical second messenger cAMP regulates a wide variety of physiological processes. It can simultaneously mediate diverse functions by acting locally in independently regulated microdomains. In mammalian cells, two types of adenylyl cyclase generate cAMP: G-protein-regulated transmembrane adenylyl cyclases and bicarbonate-, calcium- and ATP-regulated soluble adenylyl cyclase (sAC). Because each type of cyclase regulates distinct microdomains, methods to distinguish between them are needed to understand cAMP signaling. We developed a mass-spectrometry-based adenylyl cyclase assay, which we used to identify a new sAC-specific inhibitor, LRE1. LRE1 bound to the bicarbonate activator binding site and inhibited sAC via a unique allosteric mechanism. LRE1 prevented sAC-dependent processes in cellular and physiological systems, and it will facilitate exploration of the therapeutic potential of sAC inhibition.

  13. Mechanism of allosteric regulation of β2- adrenergic receptor by cholesterol

    DEFF Research Database (Denmark)

    Manna, Moutusi; Niemelä, Miia; Tynkkynen, Joona

    2016-01-01

    ) - a prototypical G protein-coupled receptor - is modulated by cholesterol in an allosteric fashion. Extensive atomistic simulations show that cholesterol regulates β2AR by limiting its conformational variability. The mechanism of action is based on the binding of cholesterol at specific high-affinity sites located...... near the transmembrane helices 5-7 of the receptor. The alternative mechanism, where the β2AR conformation would be modulated by membrane-mediated interactions, plays only a minor role. Cholesterol analogues also bind to cholesterol binding sites and impede the structural flexibility of β2AR, however...... cholesterol generates the strongest effect. The results highlight the capacity of lipids to regulate the conformation of membrane receptors through specific interactions....

  14. The mediating role of sexual and nonsexual communication between relationship and sexual satisfaction in a sample of college-age heterosexual couples.

    Science.gov (United States)

    Mark, Kristen P; Jozkowski, Kristen N

    2013-01-01

    This study aimed to examine in a sample of college-age heterosexual couples the relations between (a) relationship and sexual satisfaction and (b) sexual and nonsexual communication. The authors tested a mediation model whereby couples' relationship satisfaction was hypothesized to predict couples' sexual satisfaction by way of sexual and nonsexual communication levels. Participants were 266 individuals (133 couples) who completed measures of satisfaction and communication independently of their partner. A mediation model, tested with structural equation modeling, showed the degree to which couples were relationally satisfied was positively related to their level of sexual and nonsexual communication, which, in turn, was positively associated with their degree of sexual satisfaction. Results indicate that levels of sexual and nonsexual communication among couples affect the link between relationship and sexual satisfaction. Such findings may have important implications for college-age couples in committed relationships who are looking to improve satisfaction as well as for therapists, counselors, and educators who work with these couples to improve relationship and/or sexual satisfaction.

  15. Social presence reinforcement and computer-mediated communication: the effect of the solicitor's photography on compliance to a survey request made by e-mail.

    Science.gov (United States)

    Guéguen, Nicolas; Jacob, Céline

    2002-04-01

    Personal information is scarce in computer-mediated communication. So when information about the sender is attached with an e-mail, this could induce a positive feeling toward the sender. An experiment was carried out where a male and a female student-solicitor, by way of an e-mail, requested a student-subject to participate in a survey. In half of the cases, a digital photograph of the solicitor appeared at the end of the e-mail. Results show that subjects agreed more readily to the request in the experimental condition than in the control condition where no digital photograph was sent with the e-mail. The importance of social information on computer-mediated communication is used to explain such results.

  16. Social communication mediates the relationship between emotion perception and externalizing behaviors in young adult survivors of pediatric traumatic brain injury (TBI).

    Science.gov (United States)

    Ryan, Nicholas P; Anderson, Vicki; Godfrey, Celia; Eren, Senem; Rosema, Stefanie; Taylor, Kaitlyn; Catroppa, Cathy

    2013-12-01

    Traumatic brain injury (TBI) is a common cause of childhood disability, and is associated with elevated risk for long-term social impairment. Though social (pragmatic) communication deficits may be among the most debilitating consequences of childhood TBI, few studies have examined very long-term communication outcomes as children with TBI make the transition to young adulthood. In addition, the extent to which reduced social function contributes to externalizing behaviors in survivors of childhood TBI remains poorly understood. The present study aimed to evaluate the extent of social communication difficulty among young adult survivors of childhood TBI (n=34, injury age: 1.0-7.0 years; M time since injury: 16.55 years) and examine relations among aspects of social function including emotion perception, social communication and externalizing behaviors rated by close-other proxies. Compared to controls the TBI group had significantly greater social communication difficulty, which was associated with more frequent externalizing behaviors and poorer emotion perception. Analyses demonstrated that reduced social communication mediated the association between poorer emotion perception and more frequent externalizing behaviors. Our findings indicate that socio-cognitive impairments may indirectly increase the risk for externalizing behaviors among young adult survivors of childhood TBI, and underscore the need for targeted social skills interventions delivered soon after injury, and into the very long-term. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  17. Modulation of neuronal microcircuit activities within the medial prefrontal cortex by mGluR5 positive allosteric modulator.

    Science.gov (United States)

    Pollard, Marie; Bartolome, Jose Manuel; Conn, P Jeffrey; Steckler, Thomas; Shaban, Hamdy

    2014-10-01

    Suppressing anxiety and fear memory relies on bidirectional projections between the medial prefrontal cortex and the amygdala. Positive allosteric modulators of mGluR5 improve cognition in animal models of schizophrenia and retrieval of newly formed associations such as extinction of fear-conditioned behaviour. The increase in neuronal network activities of the medial prefrontal cortex is influenced by both mGluR1 and mGluR5; however, it is not well understood how they modulate network activities and downstream information processing. To map mGluR5-mediated network activity in relation to its emergence as a viable cognitive enhancer, we tested group I mGluR compounds on medial prefrontal cortex network activity via multi-electrode array neuronal spiking and whole-cell patch clamp recordings. Results indicate that mGluR5 activation promotes feed-forward inhibition that depends on recruitment of neuronal activity by carbachol-evoked up states. The rate of neuronal spiking activity under the influence of carbachol was reduced by the mGluR5 positive allosteric modulator, N-(1,3-Diphenyl-1H-pyrazolo-5-yl)-4-nitrobenzamide (VU-29), and enhanced by the mGluR5 negative allosteric modulator, 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride (MTEP). Spontaneous inhibitory post-synaptic currents were increased upon application of carbachol and in combination with VU-29. These results emphasize a bias towards tonic mGluR5-mediated inhibition that might serve as a signal-to-noise enhancer of sensory inputs projected from associated limbic areas onto the medial prefrontal cortex neuronal microcircuit.

  18. Gap junction intercellular communication mediated by connexin43 in astrocytes is essential for their resistance to oxidative stress.

    Science.gov (United States)

    Le, Hoa T; Sin, Wun Chey; Lozinsky, Shannon; Bechberger, John; Vega, José Luis; Guo, Xu Qiu; Sáez, Juan C; Naus, Christian C

    2014-01-17

    Oxidative stress induced by reactive oxygen species (ROS) is associated with various neurological disorders including aging, neurodegenerative diseases, as well as traumatic and ischemic insults. Astrocytes have an important role in the anti-oxidative defense in the brain. The gap junction protein connexin43 (Cx43) forms intercellular channels as well as hemichannels in astrocytes. In the present study, we investigated the contribution of Cx43 to astrocytic death induced by the ROS hydrogen peroxide (H2O2) and the mechanism by which Cx43 exerts its effects. Lack of Cx43 expression or blockage of Cx43 channels resulted in increased ROS-induced astrocytic death, supporting a cell protective effect of functional Cx43 channels. H2O2 transiently increased hemichannel activity, but reduced gap junction intercellular communication (GJIC). GJIC in wild-type astrocytes recovered after 7 h, but was absent in Cx43 knock-out astrocytes. Blockage of Cx43 hemichannels incompletely inhibited H2O2-induced hemichannel activity, indicating the presence of other hemichannel proteins. Panx1, which is predicted to be a major hemichannel contributor in astrocytes, did not appear to have any cell protective effect from H2O2 insults. Our data suggest that GJIC is important for Cx43-mediated ROS resistance. In contrast to hypoxia/reoxygenation, H2O2 treatment decreased the ratio of the hypophosphorylated isoform to total Cx43 level. Cx43 has been reported to promote astrocytic death induced by hypoxia/reoxygenation. We therefore speculate the increase in Cx43 dephosphorylation may account for the facilitation of astrocytic death. Our findings suggest that the role of Cx43 in response to cellular stress is dependent on the activation of signaling pathways leading to alteration of Cx43 phosphorylation states.

  19. [G-protein-coupled receptors targeting: the allosteric approach].

    Science.gov (United States)

    Sebag, Julien A; Pantel, Jacques

    2012-10-01

    G-protein-coupled receptors (GPCR) are a major family of drug targets. Essentially all drugs targeting these receptors on the market compete with the endogenous ligand (agonists or antagonists) for binding the receptor. Recently, non-competitive compounds binding to distinct sites from the cognate ligand were documented in various classes of these receptors. These compounds, called allosteric modulators, generally endowed of a better selectivity are able to modulate specifically the endogenous signaling of the receptor. To better understand the promising potential of this class of GPCRs targeting compounds, this review highlights the properties of allosteric modulators, the strategies used to identify them and the challenges associated with the development of these compounds.

  20. Surface Sites for Engineering Allosteric Control in Proteins

    Science.gov (United States)

    Lee, Jeeyeon; Natarajan, Madhusudan; Nashine, Vishal C.; Socolich, Michael; Vo, Tina; Russ, William P.; Benkovic, Stephen J.; Ranganathan, Rama

    2010-01-01

    Statistical analyses of protein families reveal networks of coevolving amino acids that functionally link distantly positioned functional surfaces. Such linkages suggest a concept for engineering allosteric control into proteins: The intramolecular networks of two proteins could be joined across their surface sites such that the activity of one protein might control the activity of the other. We tested this idea by creating PAS-DHFR, a designed chimeric protein that connects a light-sensing signaling domain from a plant member of the Per/Arnt/Sim (PAS) family of proteins with Escherichia coli dihydrofolate reductase (DHFR). With no optimization, PAS-DHFR exhibited light-dependent catalytic activity that depended on the site of connection and on known signaling mechanisms in both proteins. PAS-DHFR serves as a proof of concept for engineering regulatory activities into proteins through interface design at conserved allosteric sites. PMID:18927392

  1. An allosteric photoredox catalyst inspired by photosynthetic machinery.

    Science.gov (United States)

    Lifschitz, Alejo M; Young, Ryan M; Mendez-Arroyo, Jose; Stern, Charlotte L; McGuirk, C Michael; Wasielewski, Michael R; Mirkin, Chad A

    2015-03-30

    Biological photosynthetic machinery allosterically regulate light harvesting via conformational and electronic changes at the antenna protein complexes as a response to specific chemical inputs. Fundamental limitations in current approaches to regulating inorganic light-harvesting mimics prevent their use in catalysis. Here we show that a light-harvesting antenna/reaction centre mimic can be regulated by utilizing a coordination framework incorporating antenna hemilabile ligands and assembled via a high-yielding, modular approach. As in nature, allosteric regulation is afforded by coupling the conformational changes to the disruptions in the electrochemical landscape of the framework upon recognition of specific coordinating analytes. The hemilabile ligands enable switching using remarkably mild and redox-inactive inputs, allowing one to regulate the photoredox catalytic activity of the photosynthetic mimic reversibly and in situ. Thus, we demonstrate that bioinspired regulatory mechanisms can be applied to inorganic light-harvesting arrays displaying switchable catalytic properties and with potential uses in solar energy conversion and photonic devices.

  2. The use of mediation analysis to assess the effects of a behaviour change communication strategy on bed net ideation and household universal coverage in Tanzania.

    Science.gov (United States)

    Ricotta, Emily E; Boulay, Marc; Ainslie, Robert; Babalola, Stella; Fotheringham, Megan; Koenker, Hannah; Lynch, Matthew

    2015-01-21

    SBCC campaigns are designed to act on cognitive, social and emotional factors at the individual or community level. The combination of these factors, referred to as 'ideation', play a role in determining behaviour by reinforcing and confirming decisions about a particular health topic. This study introduces ideation theory and mediation analysis as a way to evaluate the impact of a malaria SBCC campaign in Tanzania, to determine whether exposure to a communication programme influenced universal coverage through mediating ideational variables. A household survey in three districts where community change agents (CCAs) were active was conducted to collect information on ITN use, number of ITNs in the household, and perceptions about ITN use and ownership. Variables relating to attitudes and beliefs were combined to make 'net ideation'. Using an ideational framework, a mediation analysis was conducted to see the impact exposure to a CCA only, mass media and community (M & C) messaging only, or exposure to both, had on household universal coverage, through the mediating variable net ideation. All three levels of exposure (CCA, M & C messaging, or exposure to both) were significantly associated with increased net ideation (CCA: 0.283, 95% CI: 0.136-0.429, p-value: controlling for net ideation. The results of this study indicate that mediation analysis is an applicable new tool to assess SBCC campaigns. Ideation as a mediator of the effects of communication exposure on household universal coverage has implications for designing SBCC to support both mass and continuous distribution efforts, since both heavily rely on consumer participation to obtain and maintain ITNs. Such systems can be strengthened by SBCC programming, generating demand through improving social norms about net ownership and use, perceived benefits of nets, and other behavioural constructs.

  3. Allosteric process of human glucokinase conducive to fight against diabetes

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ More than 200 million people worldwide have diabetes. In China alone, about 60 million people are suffering from the disease.Fortunately, scientists are pushing back its boundaries. For instance, a recent study by CAS researchers may shed new light on the treatment of the disease by making cutting-edge progress on studies of the allosteric process of human glucokinase, which has been published by the latest issue of the Proceedings of National Academy of Sciences.

  4. Novel bivalent positive allosteric modulators of AMPA receptor.

    Science.gov (United States)

    Lavrov, M I; Grigor'ev, V V; Bachurin, S O; Palyulin, V A; Zefirov, N S

    2015-01-01

    A positive allosteric modulator of AMPA receptors has been designed using computer-aided molecular modeling techniques. It possessed a record high experimentally confirmed potency in the picomolar concentration range and belongs to a new type of bivalent AMPA receptor ligands containing bicyclo[3.3.1]nonane scaffold. The suggested structure could serve as a basis for further optimization and development of drugs for the treatment of neurodegenerative diseases, cognition enhancement, and improvement of memory.

  5. Modeling the allosteric modulation of CCR5 function by Maraviroc.

    Science.gov (United States)

    Lagane, Bernard; Garcia-Perez, Javier; Kellenberger, Esther

    2013-01-01

    Maraviroc is a non-peptidic, low molecular weight CC chemokine receptor 5 (CCR5) ligand that has recently been marketed for the treatment of HIV infected individuals. This review discusses recent molecular modeling studies of CCR5 by homology to CXC chemokine receptor 4, their contribution to the understanding of the allosteric mode of action of the inhibitor and their potential for the development of future drugs with improved efficiency and preservation of CCR5 biological functions.

  6. Cooperative binding interaction of ethidium with allosteric DNA.

    Science.gov (United States)

    Suh, D

    1999-09-30

    The specific association of drugs with deoxyoligonucleotides, containing a B-Z junction between left-handed Z-DNA and right-handed B-DNA, was examined by fluorescence and circular dichroism (CD) technique. Ethidium was chosen for a simple DNA binding compound because it binds to right-handed DNA and hybrid B-Z forms containing a B-Z junction in a highly cooperative manner. The binding isotherms were analyzed by an allosteric model in order to describe the cooperativity of association. Binding of ethidium to the DNA that are initially in the hybrid B-Z forms showed over an order of magnitude higher affinity than other DNA which were entirely in the B-form. The conformational transitions of deoxyoligonucleotides containing a B-Z junction as a result of ethidium binding were monitored by CD and the influence of NaCl on the complex formation was also determined by the CD spectra. The singular value decomposition (SVD) analysis was used to characterize a family of CD spectra of the species in binding equilibria. The results of SVD analysis showed a strikingly complex thermodynamic equilibria of cooperative binding of drugs to the allosterically converted DNA forms. The results also showed that these DNA forms in low- and high-salt were different in the absence or presence of drug. These results demonstrate that DNA-binding-drugs can preferentially interact with specific DNA structures and that these interactions are accompanied by allosteric changes of DNA conformations.

  7. Use of binding enthalpy to drive an allosteric transition.

    Science.gov (United States)

    Brown, Patrick H; Beckett, Dorothy

    2005-03-01

    The Escherichia coli biotin repressor is an allosteric DNA binding protein and is activated by the small molecule bio-5'-AMP. Binding of this small molecule promotes transcription repression complex assembly between the repressor and the biotin operator of the biotin biosynthetic operon. The ability of the adenylate to activate the assembly process reflects its effect on biotin repressor dimerization. Thus concomitant with small molecule binding the free energy of repressor dimerization becomes more favorable by approximately -4 kcal/mol. The structural, dynamic, and energetic changes in the repressor monomer that accompany allosteric activation are not known. In this work the thermodynamics of binding of four allosteric activators to the repressor have been characterized by isothermal titration calorimetry. While binding of two of the effectors results in relatively modest activation of the dimerization process, binding of the other two small molecules, including the physiological effector, leads to large changes in repressor dimerization energetics. Results of the calorimetric measurements indicate that strong effector binding is accompanied by an enthalpically costly transition in the protein. This transition is "paid for" by the enthalpy that would have otherwise been realized from the formation of noncovalent bonds between the ligand and repressor monomer.

  8. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

    Directory of Open Access Journals (Sweden)

    Francisco Andrés Peralta

    2016-07-01

    Full Text Available Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel’s ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators.

  9. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

    Science.gov (United States)

    Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo

    2016-01-01

    Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel’s ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators. PMID:27384555

  10. Glutamate dehydrogenase: structure, allosteric regulation, and role in insulin homeostasis.

    Science.gov (United States)

    Li, Ming; Li, Changhong; Allen, Aron; Stanley, Charles A; Smith, Thomas J

    2014-01-01

    Glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of L-glutamate to 2-oxoglutarate. Only in the animal kingdom is this enzyme heavily allosterically regulated by a wide array of metabolites. The major activators are ADP and leucine and inhibitors include GTP, palmitoyl CoA, and ATP. Spontaneous mutations in the GTP inhibitory site that lead to the hyperinsulinism/hyperammonemia (HHS) syndrome have shed light as to why mammalian GDH is so tightly regulated. Patients with HHS exhibit hypersecretion of insulin upon consumption of protein and concomitantly extremely high levels of ammonium in the serum. The atomic structures of four new inhibitors complexed with GDH complexes have identified three different allosteric binding sites. Using a transgenic mouse model expressing the human HHS form of GDH, at least three of these compounds blocked the dysregulated form of GDH in pancreatic tissue. EGCG from green tea prevented the hyper-response to amino acids in whole animals and improved basal serum glucose levels. The atomic structure of the ECG-GDH complex and mutagenesis studies is directing structure-based drug design using these polyphenols as a base scaffold. In addition, all of these allosteric inhibitors are elucidating the atomic mechanisms of allostery in this complex enzyme.

  11. The structure and allosteric regulation of mammalian glutamate dehydrogenase.

    Science.gov (United States)

    Li, Ming; Li, Changhong; Allen, Aron; Stanley, Charles A; Smith, Thomas J

    2012-03-15

    Glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of l-glutamate to 2-oxoglutarate. Only in the animal kingdom is this enzyme heavily allosterically regulated by a wide array of metabolites. The major activators are ADP and leucine, while the most important inhibitors include GTP, palmitoyl CoA, and ATP. Recently, spontaneous mutations in the GTP inhibitory site that lead to the hyperinsulinism/hyperammonemia (HHS) syndrome have shed light as to why mammalian GDH is so tightly regulated. Patients with HHS exhibit hypersecretion of insulin upon consumption of protein and concomitantly extremely high levels of ammonium in the serum. The atomic structures of four new inhibitors complexed with GDH complexes have identified three different allosteric binding sites. Using a transgenic mouse model expressing the human HHS form of GDH, at least three of these compounds were found to block the dysregulated form of GDH in pancreatic tissue. EGCG from green tea prevented the hyper-response to amino acids in whole animals and improved basal serum glucose levels. The atomic structure of the ECG-GDH complex and mutagenesis studies is directing structure-based drug design using these polyphenols as a base scaffold. In addition, all of these allosteric inhibitors are elucidating the atomic mechanisms of allostery in this complex enzyme.

  12. Allosteric indicator displacement enzyme assay for a cyanogenic glycoside.

    Science.gov (United States)

    Jose, D Amilan; Elstner, Martin; Schiller, Alexander

    2013-10-18

    Indicator displacement assays (IDAs) represent an elegant approach in supramolecular analytical chemistry. Herein, we report a chemical biosensor for the selective detection of the cyanogenic glycoside amygdalin in aqueous solution. The hybrid sensor consists of the enzyme β-glucosidase and a boronic acid appended viologen together with a fluorescent reporter dye. β-Glucosidase degrades the cyanogenic glycoside amygdalin into hydrogen cyanide, glucose, and benzaldehyde. Only the released cyanide binds at the allosteric site of the receptor (boronic acid) thereby inducing changes in the affinity of a formerly bound fluorescent indicator dye at the other side of the receptor. Thus, the sensing probe performs as allosteric indicator displacement assay (AIDA) for cyanide in water. Interference studies with inorganic anions and glucose revealed that cyanide is solely responsible for the change in the fluorescent signal. DFT calculations on a model compound revealed a 1:1 binding ratio of the boronic acid and cyanide ion. The fluorescent enzyme assay for β-glucosidase uses amygdalin as natural substrate and allows measuring Michaelis-Menten kinetics in microtiter plates. The allosteric indicator displacement assay (AIDA) probe can also be used to detect cyanide traces in commercial amygdalin samples. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Yi; Qin, Ling; Ortiz Zacarías, Natalia V.; de Vries, Henk; Han, Gye Won; Gustavsson, Martin; Dabros, Marta; Zhao, Chunxia; Cherney, Robert J.; Carter, Percy; Stamos, Dean; Abagyan, Ruben; Cherezov, Vadim; Stevens, Raymond C.; IJzerman, Adriaan P.; Heitman, Laura H.; Tebben, Andrew; Kufareva, Irina; Handel , Tracy M. (Vertex Pharm); (Leiden-MC); (USC); (BMS); (UCSD)

    2016-12-07

    CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases2 including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer3. These disease associations have motivated numerous preclinical studies and clinical trials4 (see http://www.clinicaltrials.gov) in search of therapies that target the CCR2–chemokine axis. To aid drug discovery efforts5, here we solve a structure of CCR2 in a ternary complex with an orthosteric (BMS-681 (ref. 6)) and allosteric (CCR2-RA-[R]7) antagonist. BMS-681 inhibits chemokine binding by occupying the orthosteric pocket of the receptor in a previously unseen binding mode. CCR2-RA-[R] binds in a novel, highly druggable pocket that is the most intracellular allosteric site observed in class A G-protein-coupled receptors so far; this site spatially overlaps the G-protein-binding site in homologous receptors. CCR2-RA-[R] inhibits CCR2 non-competitively by blocking activation-associated conformational changes and formation of the G-protein-binding interface. The conformational signature of the conserved microswitch residues observed in double-antagonist-bound CCR2 resembles the most inactive G-protein-coupled receptor structures solved so far. Like other protein–protein interactions, receptor–chemokine complexes are considered challenging therapeutic targets for small molecules, and the present structure suggests diverse pocket epitopes that can be exploited to overcome obstacles in drug design.

  14. Computer mediated parent-teacher communication / La comunicación entre padre-maestro mediada por computadora

    OpenAIRE

    Juniu Susana

    2009-01-01

    Abstract:Parent-teacher communication is crucial to children’s education. The literature reveals that parents’ involvement in their children’s education improves outcomes in areas such as learning, attendance, behavior, and graduation rates. Increased and meaningful communication between home and school is likely to enhance parent involvement and may consequently support students’ learning. Schools are using various forms of technology to increase school/home communication, including voice ma...

  15. Allosteric Effects on Substrate Dissociation from Cytochrome P450 3A4 in Nanodiscs Observed by Ensemble and Single-Molecule Fluorescence Spectroscopy

    Science.gov (United States)

    Nath, Abhinav; Koo, Peter K.; Rhoades, Elizabeth; Atkins, William M.

    2009-01-01

    Cytochrome P450 3A4 is a major human drug-metabolizing enzyme, and displays pharmacologically-relevant allosteric kinetics caused by multiple substrate and/or effector binding. Here, in the first single-molecule fluorescence studies of CYPs, we use total internal reflection fluorescence microscopy to measure residence times of the fluorescent dye Nile Red in CYP3A4 incorporated in surface-immobilized lipid Nanodiscs, with and without the effector α-naphthoflavone. We find direct evidence that CYP3A4 effectors can decrease substrate off-rates, providing a possible mechanism for effector-mediated enhancement of substrate metabolism. These interesting results highlight the potential of SM methods in studies of CYP allosteric mechanisms. PMID:18980315

  16. A mechanistic understanding of allosteric immune escape pathways in the HIV-1 envelope glycoprotein.

    Directory of Open Access Journals (Sweden)

    Anurag Sethi

    Full Text Available The HIV-1 envelope (Env spike, which consists of a compact, heterodimeric trimer of the glycoproteins gp120 and gp41, is the target of neutralizing antibodies. However, the high mutation rate of HIV-1 and plasticity of Env facilitates viral evasion from neutralizing antibodies through various mechanisms. Mutations that are distant from the antibody binding site can lead to escape, probably by changing the conformation or dynamics of Env; however, these changes are difficult to identify and define mechanistically. Here we describe a network analysis-based approach to identify potential allosteric immune evasion mechanisms using three known HIV-1 Env gp120 protein structures from two different clades, B and C. First, correlation and principal component analyses of molecular dynamics (MD simulations identified a high degree of long-distance coupled motions that exist between functionally distant regions within the intrinsic dynamics of the gp120 core, supporting the presence of long-distance communication in the protein. Then, by integrating MD simulations with network theory, we identified the optimal and suboptimal communication pathways and modules within the gp120 core. The results unveil both strain-dependent and -independent characteristics of the communication pathways in gp120. We show that within the context of three structurally homologous gp120 cores, the optimal pathway for communication is sequence sensitive, i.e. a suboptimal pathway in one strain becomes the optimal pathway in another strain. Yet the identification of conserved elements within these communication pathways, termed inter-modular hotspots, could present a new opportunity for immunogen design, as this could be an additional mechanism that HIV-1 uses to shield vulnerable antibody targets in Env that induce neutralizing antibody breadth.

  17. GGPP-Mediated Protein Geranylgeranylation in Oocyte Is Essential for the Establishment of Oocyte-Granulosa Cell Communication and Primary-Secondary Follicle Transition in Mouse Ovary.

    Directory of Open Access Journals (Sweden)

    Chen Jiang

    2017-01-01

    Full Text Available Folliculogenesis is a progressive and highly regulated process, which is essential to provide ova for later reproductive life, requires the bidirectional communication between the oocyte and granulosa cells. This physical connection-mediated communication conveys not only the signals from the oocyte to granulosa cells that regulate their proliferation but also metabolites from the granulosa cells to the oocyte for biosynthesis. However, the underlying mechanism of establishing this communication is largely unknown. Here, we report that oocyte geranylgeranyl diphosphate (GGPP, a metabolic intermediate involved in protein geranylgeranylation, is required to establish the oocyte-granulosa cell communication. GGPP and geranylgeranyl diphosphate synthase (Ggpps levels in oocytes increased during early follicular development. The selective depletion of GGPP in mouse oocytes impaired the proliferation of granulosa cells, primary-secondary follicle transition and female fertility. Mechanistically, GGPP depletion inhibited Rho GTPase geranylgeranylation and its GTPase activity, which was responsible for the accumulation of cell junction proteins in the oocyte cytoplasm and the failure to maintain physical connection between oocyte and granulosa cells. GGPP ablation also blocked Rab27a geranylgeranylation, which might account for the impaired secretion of oocyte materials such as Gdf9. Moreover, GGPP administration restored the defects in oocyte-granulosa cell contact, granulosa cell proliferation and primary-secondary follicle transition in Ggpps depletion mice. Our study provides the evidence that GGPP-mediated protein geranylgeranylation contributes to the establishment of oocyte-granulosa cell communication and then regulates the primary-secondary follicle transition, a key phase of folliculogenesis essential for female reproductive function.

  18. NASA/DOD Aerospace Knowledge Diffusion Research Project. Paper 38: Computer Mediated Communication (CMC) and the communication of technical information in aerospace

    Science.gov (United States)

    Murphy, Daniel J.; Pinelli, Thomas E.

    1994-01-01

    This paper discusses the use of computers as a medium for communication (CMC) used by aerospace engineers and scientists to obtain and/or provide technical information related to research and development activities. The data were obtained from a questionnaire survey that yielded 1006 mail responses. In addition to communication media, the research also investigates degrees of task uncertainty, environmental complexity, and other relevant variables that can affect aerospace workers' information-seeking strategies. While findings indicate that many individuals report CMC is an important function in their communication patterns, the research indicates that CMC is used less often and deemed less valuable than other more conventional media, such as paper documents, group meetings, telephone and face-to-face conversations. Fewer than one third of the individuals in the survey account for nearly eighty percent of the reported CMC use, and another twenty percent indicate they do not use the medium at all, its availability notwithstanding. These preliminary findings suggest that CMC is not as pervasive a communication medium among aerospace workers as the researcher expect a priori. The reasons underlying the reported media use are not yet fully known, and this suggests that continuing research in this area may be valuable.

  19. Anxiety and Self-Esteem as Mediators of the Relation between Family Communication and Indecisiveness in Adolescence

    Science.gov (United States)

    Lo Cascio, Valentina; Guzzo, Giovanni; Pace, Francesco; Pace, Ugo

    2013-01-01

    In this study, we explored the unique and common contributions of anxiety, self-esteem, and family communication on indecisiveness among adolescents. Three hundred and fifty pupils from 13 to 16 years of age completed self-report measures on indecisiveness, quality of family communication, trait anxiety, and self-esteem. The findings in this study…

  20. Exploring the Complex Computer-Mediated Communication Needs of Learners in a Multilingual, Multicultural Online Learning Environment

    Science.gov (United States)

    Burger, William Peter

    2013-01-01

    The purpose of this study was to understand student perceptions of social presence that resulted from communicating and collaborating via different forms of Internet-based communication technologies in a diverse, multicultural, multilingual online learning environment. In that it describes how non-native English speaking students from different…

  1. Anxiety and Self-Esteem as Mediators of the Relation between Family Communication and Indecisiveness in Adolescence

    Science.gov (United States)

    Lo Cascio, Valentina; Guzzo, Giovanni; Pace, Francesco; Pace, Ugo

    2013-01-01

    In this study, we explored the unique and common contributions of anxiety, self-esteem, and family communication on indecisiveness among adolescents. Three hundred and fifty pupils from 13 to 16 years of age completed self-report measures on indecisiveness, quality of family communication, trait anxiety, and self-esteem. The findings in this study…

  2. Comunicación, lenguaje y pedagogía: una mirada desde las mediaciones Communication, language and pedagogy: a view from the mediations

    Directory of Open Access Journals (Sweden)

    Tomás Vásquez Arrieta

    2009-06-01

    Full Text Available El presente trabajo se propone exponer, de modo general, el concepto de mediación y su importancia para la comprensión de la comunicación y el lenguaje y su importancia en la práctica pedagógica. En un primer momento se presenta una breve semblanza histórica del concepto de mediación en la tradición filosófica. Posteriormente, se presentan algunas consideraciones de la mediación en el marco de la problemática de la comunicación y del lenguaje desde la propuesta fenomenológica de Merleau-Ponty. Finalmente, se relaciona la reflexión anterior con algunas consideraciones sobre el campo de la pedagogía.This paper presents, in a general way, the concept of mediation and its importance for the comprehension of communication and language, as well as its importance in the pedagogical context. First, there is a short historical description about the concept of mediation in the philosophy tradition. After, some considerations of mediation from the point of view of communication and language and the phenomenological proposal of language of Merleau-Ponty are presented. Finally, the relationship between the reflections made and some considerations about the pedagogical field are shown.

  3. Virtual Screening for Potential Allosteric Inhibitors of Cyclin-Dependent Kinase 2 from Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Fang Lu

    2016-09-01

    Full Text Available Cyclin-dependent kinase 2 (CDK2, a member of Cyclin-dependent kinases (CDKs, plays an important role in cell division and DNA replication. It is regarded as a desired target to treat cancer and tumor by interrupting aberrant cell proliferation. Compared to lower subtype selectivity of CDK2 ATP-competitive inhibitors, CDK2 allosteric inhibitor with higher subtype selectivity has been used to treat CDK2-related diseases. Recently, the first crystal structure of CDK2 with allosteric inhibitor has been reported, which provides new opportunities to design pure allosteric inhibitors of CDK2. The binding site of the ATP-competition inhibitors and the allosteric inhibitors are partially overlapped in space position, so the same compound might interact with the two binding sites. Thus a novel screening strategy was essential for the discovery of pure CDK2 allosteric inhibitors. In this study, pharmacophore and molecular docking were used to screen potential CDK2 allosteric inhibitors and ATP-competition inhibitors from Traditional Chinese Medicine (TCM. In the docking result of the allosteric site, the compounds which can act with the CDK2 ATP site were discarded, and the remaining compounds were regarded as the potential pure allosteric inhibitors. Among the results, prostaglandin E1 and nordihydroguaiaretic acid (NDGA were available and their growth inhibitory effect on human HepG2 cell lines was determined by MTT assay. The two compounds could substantially inhibit the growth of HepG2 cell lines with an estimated IC50 of 41.223 μmol/L and 45.646 μmol/L. This study provides virtual screening strategy of allosteric compounds and a reliable method to discover potential pure CDK2 allosteric inhibitors from TCM. Prostaglandin E1 and NDGA could be regarded as promising candidates for CDK2 allosteric inhibitors.

  4. As formas de comunicação pedagógica "midiatizada": o socioeducativo e o didático Two specific forms of pedagogical mediated communication: instructional and socio-educational communication

    Directory of Open Access Journals (Sweden)

    Daniel Peraya

    1997-08-01

    Full Text Available O autor analisa os conceitos principais descrevendo diferentes tipos de comunicação pedagógica "midiatizada". Ele tenta demonstrar que o conceito do discurso parece ser um dos mais importantes para se analisar estas formas de comunicação pedagógica "midiatizada". Distingue duas formas principais que podem ser consideradas como pólos de uma taxonomia e caracteriza cada uma delas pelas suas características principais relacionadas a conteúdo; objetivos; público-alvo; currículo, avaliação; cenário de interação social; referências material, humana, institucional e sociocultural etc. Finalmente, ele mostra que este tipo de distinção é um modo para se dar diretriz à comunicação "midiatizada" com base em capacitação e ensino.The author analyses the main concepts of the different types of pedagogical mediated communication. He tries to demonstrate that discourse seems to be one of the most important concepts in analysing these forms of pedagogical mediated communication. He distinguishes two main forms that could be considered as the poles of a taxonomy, and characterizes each of them by their main features related to: contents; aims and goals; target-public; curriculum; assessment; the social interaction scene; the material, human, institutional and socio-cultural frame of reference etc. Finally, he shows that such a distinction is a way to provide guidelines for mediated communication based training and teaching.

  5. The use of electronic mail at the reference desk: impact of a computer-mediated communication technology on librarian-client interactions.

    Science.gov (United States)

    Schilling-Eccles, K; Harzbecker, J J

    1998-01-01

    Commonly recognized computer-mediated communication (CMC) tools include virtual environments, bibliographic databases, listservers, newsgroups, group teleconferencing, interactive messaging systems and electronic mail. The use of these technologies in libraries has grown exponentially over the past decade. Electronic mail has emerged as an especially popular communication tool for librarians, and their colleagues and patrons. This paper explores the use of a reference department electronic mail service and its impact on reference services and librarian-client interactions. Several issues related to the implementation of CMC technologies are presented, including the maintenance and monitoring of reference electronic mail systems, the types of questions that are typically posted, and potential barriers to the implementation and use of reference e-mail.

  6. Exploring the ‘ultimate’ step in the mediatization of political parties - Members of the Danish Parliament and their communication skills 1981-2015

    DEFF Research Database (Denmark)

    Ørsten, Mark; Willig, Ida; Pedersen, Leif Hemming

    , parties may begin to especially focus on candidates who are skilled in communicating with the news media (Strömbäck & Van Alest, 2013).So far, research into the fourth dimension of mediatization in Denmark has focused mostly on the first two steps (Blach-Ørsten, 2016; Elmelund-Præstekær & Hopmann, 2016......). In this article we explore the third step by looking at the publically recorded resumes of all elected (or re-elected) members of the Danish Parliament from 1981 to 2015 (n=2148). Based on the resumes we ask if more members of the Danish Parliament can be said to have ‘communication skills’ as part of either...... their education or prior work experience. We find that of the candidates elected to the Danish Folketing in 1981 just 16 percent had ‘communication skills’ as part of their public resumes, whereas 27 percent of new members of the Danish Parliament elected in 2015 had communication skills as part of their resumes...

  7. Feedback inhibition of ammonium uptake by a phospho-dependent allosteric mechanism in Arabidopsis.

    Science.gov (United States)

    Lanquar, Viviane; Loqué, Dominique; Hörmann, Friederike; Yuan, Lixing; Bohner, Anne; Engelsberger, Wolfgang R; Lalonde, Sylvie; Schulze, Waltraud X; von Wirén, Nicolaus; Frommer, Wolf B

    2009-11-01

    The acquisition of nutrients requires tight regulation to ensure optimal supply while preventing accumulation to toxic levels. Ammonium transporter/methylamine permease/rhesus (AMT/Mep/Rh) transporters are responsible for ammonium acquisition in bacteria, fungi, and plants. The ammonium transporter AMT1;1 from Arabidopsis thaliana uses a novel regulatory mechanism requiring the productive interaction between a trimer of subunits for function. Allosteric regulation is mediated by a cytosolic C-terminal trans-activation domain, which carries a conserved Thr (T460) in a critical position in the hinge region of the C terminus. When expressed in yeast, mutation of T460 leads to inactivation of the trimeric complex. This study shows that phosphorylation of T460 is triggered by ammonium in a time- and concentration-dependent manner. Neither Gln nor l-methionine sulfoximine-induced ammonium accumulation were effective in inducing phosphorylation, suggesting that roots use either the ammonium transporter itself or another extracellular sensor to measure ammonium concentrations in the rhizosphere. Phosphorylation of T460 in response to an increase in external ammonium correlates with inhibition of ammonium uptake into Arabidopsis roots. Thus, phosphorylation appears to function in a feedback loop restricting ammonium uptake. This novel autoregulatory mechanism is capable of tuning uptake capacity over a wide range of supply levels using an extracellular sensory system, potentially mediated by a transceptor (i.e., transporter and receptor).

  8. Allosteric transitions of Torpedo acetylcholine receptor in lipids, detergent and amphipols

    DEFF Research Database (Denmark)

    Martinez, Karen L.; Gohon, Yann; Corringer, Pierre Jean

    2002-01-01

    kinetics was similar in the membrane and in amphipols, demonstrating that the receptor can display unaltered allosteric transitions outside its natural lipid environment. In contrast, allosteric equilibria were strongly shifted towards the desensitized state in CHAPS. Therefore, the effect of CHAPS likely...

  9. Discovery and Characterization of Biased Allosteric Agonists of the Chemokine Receptor CXCR3

    DEFF Research Database (Denmark)

    Milanos, Lampros; Brox, Regine; Frank, Theresa

    2016-01-01

    In this work we report a design, synthesis, and detailed functional characterization of unique strongly biased allosteric agonists of CXCR3 that contain tetrahydroisoquinoline carboxamide cores. Compound 11 (FAUC1036) is the first strongly biased allosteric agonist of CXCR3 that selectively induc...

  10. Allosteric regulation of pyruvate kinase M2 isozyme involves a cysteine residue in the intersubunit contact.

    Science.gov (United States)

    Ikeda, Y; Noguchi, T

    1998-05-15

    Pyruvate kinase M2 isozyme mutants with amino acid substitutions in the subunit interface were prepared and characterized. The substitutions were made in the allosteric M2 isozyme by the corresponding residues of the nonallosteric M1 isozyme to identify the residue involved in the allosteric effects. The replacement of Cys-423 by Leu led to substantial loss of both homotropic and heterotropic allosteric effects while the substitutions at Phe-389, Arg-398, Ala-401, Pro-402, Thr-408, and Ile-427 did not. The altered kinetic properties of the Cys-423-substituted mutant resulted from the shift of the allosteric transition toward the active R-state since the mutant exhibits the allosteric properties in the presence of an allosteric inhibitor, L-phenylalanine. The inverse correlation between the hydrophobicity of residue 423 and the extent of stabilization of the R-state was found by analysis of mutants with un-ionizable amino acids at position 423. Furthermore, the modification of Cys-423 with methyl methanethiosulfonate led to a shift of the allosteric transition toward the R-state, probably the result of increased hydrophobicity of the residue. These results suggest that Cys-423 is involved in the allosteric regulation of the enzyme through hydrophobic interactions.

  11. The Effects of Word of Mouth Communication on The Sub Dimensions of Consumer Based Brand Equity: The Mediating Role of Brand Image

    Directory of Open Access Journals (Sweden)

    Erkan Yıldız

    2015-07-01

    Full Text Available Including an increase in the sales order information and communication possibilities of today's consumers are exposed to excessive information. Consumers also need to hear more and does not have enough time non-purposeful sales gained extensive knowledge of the surrounding environment as well as the proposal to evaluate this information. Word of mouth communication of environmental information reaching the consumer may also be active in the buying decision. Today, a large number of similar types on the market, offering goods and services that the company has lead to violent competition. To survive in the long term business in a highly competitive environment, representing a value for the consumer and depends on having a strong brand and brand equity will constantly be put forward their purchase. The purpose of this study is to investigate the effects of word of mouth communication on the sub dimensions of consumer-based brand equity; brand awareness, brand association, perceived quality and brand loyalty. At the same time making determinations the mediating role of brand image on among these relations. For this purpose, a study was conducted in Ankara with the participation of mobile phone subscribers with 384 consumers. The data of the research was compiled by the convenience sampling method and by online questionnaire. The structural equation modeling was empoyed during the tests of the hypothesis and the effects of the mediating role. In the result of the research it was observed that word of mouth communication has a meaningful effect in the positive direction on all the dimensions of the consumer based brand equity. It was also understood that, brand image has a complete association effect on; brand awareness, brand association and brand loyalty while it has partial association effects on perceived quality dimension.

  12. CMC架构的网络环境与网络协作学习%Web Environments Oriented from Computer Mediated Communication and Collaborative Learning

    Institute of Scientific and Technical Information of China (English)

    江凤娟; 吴峰

    2005-01-01

    大量的实证研究表明,交流协作是影响网络学习质量的一个重要因素.本文根据CMC(computer mediated communication)建构的环境特征,探讨CMC与协作学习技术、CMC与协作学习方式以及如何在CMC环境下如何进行有效的学习的教学策略.

  13. Allosteric activation mechanism of the cys-loop receptors

    Institute of Scientific and Technical Information of China (English)

    Yong-chang CHANG; Wen WU; Jian-liang ZHANG; Yao HUANG

    2009-01-01

    Binding of a neurotransmitter to its ionotropic receptor opens a distantly located ion channel, a process termed allosteric activation. Here we review recent advances in the molecular mechanism by which the cys-loop receptors are activated with emphasis on the best studied nicotinic acetylcholine receptors (nAChRs). With a combination of affinity labeling, mutagenesis, electrophysiology, kinetic modeling, electron microscopy (EM), and crystal structure analysis, the allosteric activation mechanism is emerging. Specifically, the binding domain and gating domain are interconnected by an allosteric activation network. Agonist binding induces conformational changes, resulting in the rotation of a β sheet of amino-terminal domain and outward movement of loop 2, loop F, and cys-loop, which are coupled to the M2-M3 linker to pull the channel to open. However, there are still some controversies about the movement of the channel-lining domain M2. Nine angstrom resolution EM structure of a nAChR imaged in the open state suggests that channel opening is the result of rotation of the M2 domain. In contrast, recent crystal structures of bacterial homologues of the cys-loop receptor family in apparently open state have implied an M2 tilting model with pore dilation and quaternary twist of the whole pentameric receptor. An elegant study of the nAChR using protonation scanning of M2 domain supports a similar pore dilation activation mechanism with minimal rotation of M2. This remains to be validated with other approaches including high resolution structure determination of the mammalian cys-loop receptors in the open state.

  14. Indole-based allosteric inhibitors of HIV-1 integrase.

    Science.gov (United States)

    Patel, Pratiq A; Kvaratskhelia, Nina; Mansour, Yara; Antwi, Janet; Feng, Lei; Koneru, Pratibha; Kobe, Mathew J; Jena, Nivedita; Shi, Guqin; Mohamed, Mosaad S; Li, Chenglong; Kessl, Jacques J; Fuchs, James R

    2016-10-01

    Employing a scaffold hopping approach, a series of allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) have been synthesized based on an indole scaffold. These compounds incorporate the key elements utilized in quinoline-based ALLINIs for binding to the IN dimer interface at the principal LEDGF/p75 binding pocket. The most potent of these compounds displayed good activity in the LEDGF/p75 dependent integration assay (IC50=4.5μM) and, as predicted based on the geometry of the five- versus six-membered ring, retained activity against the A128T IN mutant that confers resistance to many quinoline-based ALLINIs.

  15. Bioinformatic scaling of allosteric interactions in biomedical isozymes

    Science.gov (United States)

    Phillips, J. C.

    2016-09-01

    Allosteric (long-range) interactions can be surprisingly strong in proteins of biomedical interest. Here we use bioinformatic scaling to connect prior results on nonsteroidal anti-inflammatory drugs to promising new drugs that inhibit cancer cell metabolism. Many parallel features are apparent, which explain how even one amino acid mutation, remote from active sites, can alter medical results. The enzyme twins involved are cyclooxygenase (aspirin) and isocitrate dehydrogenase (IDH). The IDH results are accurate to 1% and are overdetermined by adjusting a single bioinformatic scaling parameter. It appears that the final stage in optimizing protein functionality may involve leveling of the hydrophobic limits of the arms of conformational hydrophilic hinges.

  16. Structural insights into Ca(2+)-activated long-range allosteric channel gating of RyR1.

    Science.gov (United States)

    Wei, Risheng; Wang, Xue; Zhang, Yan; Mukherjee, Saptarshi; Zhang, Lei; Chen, Qiang; Huang, Xinrui; Jing, Shan; Liu, Congcong; Li, Shuang; Wang, Guangyu; Xu, Yaofang; Zhu, Sujie; Williams, Alan J; Sun, Fei; Yin, Chang-Cheng

    2016-09-01

    Ryanodine receptors (RyRs) are a class of giant ion channels with molecular mass over 2.2 mega-Daltons. These channels mediate calcium signaling in a variety of cells. Since more than 80% of the RyR protein is folded into the cytoplasmic assembly and the remaining residues form the transmembrane domain, it has been hypothesized that the activation and regulation of RyR channels occur through an as yet uncharacterized long-range allosteric mechanism. Here we report the characterization of a Ca(2+)-activated open-state RyR1 structure by cryo-electron microscopy. The structure has an overall resolution of 4.9 Å and a resolution of 4.2 Å for the core region. In comparison with the previously determined apo/closed-state structure, we observed long-range allosteric gating of the channel upon Ca(2+) activation. In-depth structural analyses elucidated a novel channel-gating mechanism and a novel ion selectivity mechanism of RyR1. Our work not only provides structural insights into the molecular mechanisms of channel gating and regulation of RyRs, but also sheds light on structural basis for channel-gating and ion selectivity mechanisms for the six-transmembrane-helix cation channel family.

  17. Allosteric modulators of the hERG K{sup +} channel

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Zhiyi, E-mail: z.yu@lacdr.leidenuniv.nl; Klaasse, Elisabeth, E-mail: elisabethklaasse@hotmail.com; Heitman, Laura H., E-mail: l.h.heitman@lacdr.leidenuniv.nl; IJzerman, Adriaan P., E-mail: ijzerman@lacdr.leidenuniv.nl

    2014-01-01

    Drugs that block the cardiac K{sup +} channel encoded by the human ether-à-go-go gene (hERG) have been associated with QT interval prolongation leading to proarrhythmia, and in some cases, sudden cardiac death. Because of special structural features of the hERG K{sup +} channel, it has become a promiscuous target that interacts with pharmaceuticals of widely varying chemical structures and a reason for concern in the pharmaceutical industry. The structural diversity suggests that multiple binding sites are available on the channel with possible allosteric interactions between them. In the present study, three reference compounds and nine compounds of a previously disclosed series were evaluated for their allosteric effects on the binding of [{sup 3}H]astemizole and [{sup 3}H]dofetilide to the hERG K{sup +} channel. LUF6200 was identified as an allosteric inhibitor in dissociation assays with both radioligands, yielding similar EC{sub 50} values in the low micromolar range. However, potassium ions increased the binding of the two radioligands in a concentration-dependent manner, and their EC{sub 50} values were not significantly different, indicating that potassium ions behaved as allosteric enhancers. Furthermore, addition of potassium ions resulted in a concentration-dependent leftward shift of the LUF6200 response curve, suggesting positive cooperativity and distinct allosteric sites for them. In conclusion, our investigations provide evidence for allosteric modulation of the hERG K{sup +} channel, which is discussed in the light of findings on other ion channels. - Highlights: • Allosteric modulators on the hERG K{sup +} channel were evaluated in binding assays. • LUF6200 was identified as a potent allosteric inhibitor. • Potassium ions were found to behave as allosteric enhancers. • Positive cooperativity and distinct allosteric sites for them were proposed.

  18. Gender Differences in Computer Mediated Communication%网络交际中的性别差异

    Institute of Scientific and Technical Information of China (English)

    张晓梅

    2005-01-01

    不同的性别有着自身不同的性别文化,男性和女性按照各自的性别文化规则来规范自己的交际行为。在网络这个虚拟空间,男性和女性的交际与面对面交际一样反映出根深蒂固的性别文化差异。笔者尝试从男性与女性在网络交际与面对面交际中的文化差异、男性与女性网络交际的风格及网络交际道德规范等方面探讨网络交际的性别文化差异,并针对网络交际中出现的性骚扰等现象提出一些看法。%This paper discusses gender differences in cyberspace communication by analyzing gender differences between communication online and face to face, differences in online style and in communication ethics. Like face-to-face, differ ences in onlone style and in communication ethics. Like face-to-face communication ,gender differendces in online communication indicate that some stereotypes of men and women are rooted in culture, no matter people communication face to face, or in cyberspace, these notions will be reflected. The author of this paper also gives some suggestions on harassment online.

  19. COMPUTER MEDIATED PARENT-TEACHER COMMUNICATION (LA COMUNICACIÓN ENTRE PADRE-MAESTRO MEDIADA POR COMPUTADORA

    Directory of Open Access Journals (Sweden)

    Juniu Susana

    2009-12-01

    Full Text Available Abstract:Parent-teacher communication is crucial to children’s education. The literature reveals that parents’ involvement in their children’s education improves outcomes in areas such as learning, attendance, behavior, and graduation rates. Increased and meaningful communication between home and school is likely to enhance parent involvement and may consequently support students’ learning. Schools are using various forms of technology to increase school/home communication, including voice mail, e-mail, school and classroom websites, and web access to individual student information such as attendance, grades, and student portfolios; however, this use is not consistent or widespread. This paper examines the most prevalent parent-teacher communication in a K-12 educational setting and explores various communication options to improve parent-teacher communication. The focus is to examine the communication needs between teacher and parents and the benefits of combining traditional synchronous and asynchronous communication with newer communication technologies to meet these needs.Resumen:La comunicación entre padres y maestros es crucial para la educación de los niños. La literatura revela que la participación de los padres en la educación de sus hijos mejora los resultados en áreas como el aprendizaje, asistencia, conducta, y en las tasas de graduación. Una comunicación efectiva entre la familia y la escuela aumenta la participación de los padres en la educación de sus niños y consecuentemente mejora el aprendizaje de los estudiantes. Las instituciones educativas están utilizando diversas formas de tecnología para incrementar la comunicación familia-escuela, entre ellas están el buzón de voz, el correo electrónico, páginas Web de las escuelas con acceso a la información personal de cada estudiante (asistencia, calificaciones, y actividades escolares. No obstante, este uso no es consistente o masivo. Este ensayo examina

  20. Communication competence, psychological well-being, and the mediating role of coping efforts among women with breast cancer: cross-sectional and longitudinal evidence.

    Science.gov (United States)

    Shim, Minsun; Mercer Kollar, Laura M; Roberts, Linda J; Gustafson, David H

    2015-01-01

    Despite existing research identifying psychological benefits of patients' interpersonal competence in various contexts, little longitudinal research has addressed underlying mechanism(s). To address this limitation, we examined both the cross-sectional and longitudinal associations between cancer patients' communication competence in close relationships and psychological well-being, as well as the mediating role of coping efforts. Data came from a larger project with women with breast cancer (N = 661), recruited from April 2005 to May 2007 at three large university-affiliated cancer centers in the U.S. to study the effects of an Internet-based system providing patients and families with a range of services. The present study focused on survey data at baseline, 6 weeks, and 12 weeks after the intervention (controlling for the possible effects of the intervention). Results from both cross-sectional and longitudinal analyses indicated that competence in open communication between patients and their close support persons had a positive association with patients' psychological well-being and that approach coping efforts partially mediated this association. We discussed the implications and limitations of the study.