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Sample records for cavity-polariton interaction mediated

  1. Cavity-polariton interaction mediated by coherent acoustic phonons in semiconductor microcavities

    DEFF Research Database (Denmark)

    de Lima, Mauricio; Hey, Rudolf; Santos, Paul

    The strong coupling between excitons in a quantum well (QW) and photons in a semiconductor microcavity leads to the formation of quasi-particles known as cavity-polaritons. In this contribution, we investigate their interaction with coherent acoustic phonons in the form of surface acoustic waves ...

  2. Cavity-polariton interaction mediated by coherent acoustic phonons in semiconductor microcavities

    DEFF Research Database (Denmark)

    de Lima, Mauricio; Hey, Rudolf; Santos, Paul

    (SAWs) in a GaAs QW embedded in a (Al,Ga)As/AlAs microcavity. The periodic modulation introduced by the phonons folds the cavity-polariton dispersion within a mini-Brillouin zone (MBZ) defined by the phonon wave vector ($k_\\mathrm{SAW}$). The appearance of well-defined mini-gaps at the edge of the MBZ...... and the band-gap modulation of the GaAs QW caused by the SAW strain field....

  3. Cavity polaritons with Rydberg blockade and long-range interactions

    CERN Document Server

    Litinskaya, Marina; Pupillo, Guido

    2016-01-01

    We study interactions between polaritons, arising when photons strongly couple to collective excitations in an array of two-level atoms trapped in an optical lattice inside a cavity. We consider two types of interactions between atoms: Dipolar forces and atomic saturability, which ranges from hard-core repulsion to Rydberg blockade. We show that, in spite of the underlying repulsion in the subsystem of atomic excitations, saturability induces a broadband bunching of photons for two-polariton scattering states. We interpret this bunching as a result of interference, and trace it back to the mismatch of the quantization volumes for atomic excitations and photons. We examine also bound bipolaritonic states: These include states created by dipolar forces, as well as a gap bipolariton, which forms solely due to saturability effects in the atomic transition. Both types of bound states exhibit strong bunching in the photonic component. We discuss the dependence of bunching on experimentally relevant parameters.

  4. Modulation of cavity-polaritons by surface acoustic waves

    DEFF Research Database (Denmark)

    de Lima, M. M.; Poel, Mike van der; Hey, R.;

    2006-01-01

    We modulate cavity-polaritons using surface acoustic waves. The corresponding formation of a mini-Brillouin zone and band folding of the polariton dispersion is demonstrated for the first time. Results are in good agreement with model calculations.......We modulate cavity-polaritons using surface acoustic waves. The corresponding formation of a mini-Brillouin zone and band folding of the polariton dispersion is demonstrated for the first time. Results are in good agreement with model calculations....

  5. Modified relaxation dynamics and coherent energy exchange in coupled vibration-cavity polaritons

    Science.gov (United States)

    Dunkelberger, A. D.; Spann, B. T.; Fears, K. P.; Simpkins, B. S.; Owrutsky, J. C.

    2016-11-01

    Coupling vibrational transitions to resonant optical modes creates vibrational polaritons shifted from the uncoupled molecular resonances and provides a convenient way to modify the energetics of molecular vibrations. This approach is a viable method to explore controlling chemical reactivity. In this work, we report pump-probe infrared spectroscopy of the cavity-coupled C-O stretching band of W(CO)6 and the direct measurement of the lifetime of a vibration-cavity polariton. The upper polariton relaxes 10 times more quickly than the uncoupled vibrational mode. Tuning the polariton energy changes the polariton transient spectra and relaxation times. We also observe quantum beats, so-called vacuum Rabi oscillations, between the upper and lower vibration-cavity polaritons. In addition to establishing that coupling to an optical cavity modifies the energy-transfer dynamics of the coupled molecules, this work points out the possibility of systematic and predictive modification of the excited-state kinetics of vibration-cavity polariton systems.

  6. Condensation phase diagram of cavity polaritons in GaN-based microcavities: Experiment and theory

    Science.gov (United States)

    Levrat, Jacques; Butté, Raphaël; Feltin, Eric; Carlin, Jean-François; Grandjean, Nicolas; Solnyshkov, Dmitry; Malpuech, Guillaume

    2010-03-01

    The evolution of the polariton condensation threshold (Pthr) under incoherent optical pumping is investigated both theoretically and experimentally over a wide range of temperatures (4-340 K) and exciton-cavity photon detunings (-120-0meV) in a multiple quantum-well GaN-based microcavity. The condensation phase diagram of these bosonic quasiparticles is first theoretically described within the framework of Bose-Einstein condensation of polaritons in the thermodynamic limit. Then a qualitative picture of cavity polariton relaxation kinetics including the impact of detuning and temperature is given before introducing a modeling of cavity polariton relaxation kinetics with semiclassical Boltzmann equations. The results of the theoretical modeling are finally compared with systematic measurements of Pthr . At low temperature and negative detunings, the polariton gas is far from thermal equilibrium and the condensation threshold is governed by the efficiency of the relaxation kinetics of the particles. Conversely, at high temperature and for less negative detunings, the relaxation kinetics is efficient enough to allow the achievement of a thermal polariton distribution function with a critical density for condensation given by the thermodynamic theory of Bose-Einstein condensation. For temperatures ranging between ˜140 and 340 K, an optimum detuning is found experimentally, where the condensation threshold power is minimized. At high temperatures, polariton detrapping effects from the bottom of the trap formed in k∥ space by the lower polariton branch are found to play a supplementary role among the processes governing Pthr .

  7. Instability effects in cw FWM of cavity polaritons in planar microcavities

    Science.gov (United States)

    Kulakovskii, V. D.; Makhonin, M. N.; Krizhanovskii, D. N.; Tartakovskii, A. I.; Gippius, N. A.

    2005-02-01

    Two new surprising properties of stimulated parametric scattering of cavity polaritons in GaAs based MCs have been observed and discussed. First, the expected increase in the threshold power for the stimulated scattering Pthr with temperature T appears only in MCs with shallow LP branch. With deepening of the LP branch the dependence of Pthr(T) changes unexpectedly to opposite one. Second, at low T Pthr displays a drastic decrease already at very weak additional excitation above GaAs band gap generating hot excitons and free carriers. Our observations indicate that in addition to the FWM formalism describing only four waves participating in the parametric process, and bistability of the amplitude of pumped macrooccupied mode, the full physical picture including other relaxation channels should be taken into account to reproduce the observed non-linear behavior.

  8. Loss of coherence in cavity-polariton condensates: Effect of disorder versus exciton reservoir

    Science.gov (United States)

    Demenev, A. A.; Grishina, Ya. V.; Novikov, S. I.; Kulakovskii, V. D.; Schneider, C.; Höfling, S.

    2016-11-01

    Time evolution of long-range spatial coherence in a freely decaying cavity-polariton condensate excited resonantly in a high-Q GaAs microcavity is found to be qualitatively different from that in nonresonantly excited condensates. The first-order spatial correlation function g(1 )(r1,r2) in response to resonant 1.5 ps pump pulses at normal incidence leaving the exciton reservoir empty is found to be nearly independent of the excitation density. g(1 ) exceeds 0.7 within the excited spot and decreases very slowly in the decaying and expanding condensate. It remains above 0.5 until the polariton blue shift α | ψ2| gets comparable to the characteristic amplitude of the disorder potential δ EL P . The disorder is found to reveal itself at α | ψ2|≲δ EL P in fast and short-range phase fluctuations as well as vortex formation. They lead to oscillations in g(1 )(t ) , but have little effect on the overall coherence, which is well reproduced in the framework of the Gross-Pitaevskii equations.

  9. Two-Qubit Geometric Phase Gate for Quantum Dot Spins using Cavity Polariton Resonance

    CERN Document Server

    Puri, Shruti; Yamamoto, Yoshihisa

    2012-01-01

    We describe a design to implement a two-qubit geometric phase gate, by which a pair of electrons confined in adjacent quantum dots are entangled. The entanglement is a result of the Coulomb exchange interaction between the optically excited exciton-polaritons and the localized spins. This optical coupling, resembling the electron-electron Ruderman-Kittel-Kasuya-Yosida (RKKY) inter- actions, offers high speed, high fidelity two-qubit gate operation with moderate cavity quality factor Q. The errors due to the finite lifetime of the polaritons can be minimized by optimizing the optical pulse parameters (duration and energy). The proposed design, using electrostatic quantum dots, maximizes entanglement and ensures scalability.

  10. Notion of Mediators in Human Interaction

    OpenAIRE

    Josip Stepanic

    2003-01-01

    Many types of human interaction are mediated processes. However, regarding the details of human description, the mediating unit structure and dynamics is not developed appropriately. The explicit concentration on mediators contributes to understanding of interplay between value sets governing interaction, interaction roles in regular activities and interaction design for purpose. This article is a contribution to development of a concept of mediated human interaction through structuring of me...

  11. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    OpenAIRE

    Popescu, O.; Sumanovski, L. T.; I. Checiu; Elisabeta Popescu; G. N. Misevic

    1999-01-01

    Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals) have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of...

  12. LEGAL CULTURES AND MEDIATION. INTERACTIONS AND EVOLUTIONS

    Directory of Open Access Journals (Sweden)

    Claudiu Ramon D. BUTCULESCU

    2014-05-01

    Full Text Available Mediation, as an alternative dispute resolution method, is closely connected with the system of legal cultures. Mediation is an important link between legal culture and the judicial system. Mediation also acts as an interface between internal legal culture and external legal culture. This paper addresses the issues regarding the links and interactions between mediation and legal cultures, as well as the effects that arise from these interactions.

  13. LEGAL CULTURES AND MEDIATION. INTERACTIONS AND EVOLUTIONS

    OpenAIRE

    Claudiu Ramon D. BUTCULESCU

    2014-01-01

    Mediation, as an alternative dispute resolution method, is closely connected with the system of legal cultures. Mediation is an important link between legal culture and the judicial system. Mediation also acts as an interface between internal legal culture and external legal culture. This paper addresses the issues regarding the links and interactions between mediation and legal cultures, as well as the effects that arise from these interactions.

  14. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    Directory of Open Access Journals (Sweden)

    O.Popescu

    1999-01-01

    Full Text Available Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of isolated and purified glyconectins revealed the presence of specific carbohydrate structures, acidic glycans, different from classical glycosaminoglycans. Such acidic glycans of high molecular weight containing fucose, glucuronic or galacturonic acids, and sulfate groups, originally found in sponges and sea urchin embryos, may represent a new class of carbohydrate carcino-embryonal antigens in mice and humans. Such interactions between biological macromolecules are usually investigated by kinetic binding studies, calorimetric methods, X-ray diffraction, nuclear magnetic resonance, and other spectroscopic analyses. However, these methods do not supply a direct estimation of the intermolecular binding forces that are fundamental for the function of the ligand-receptor association. Recently, we have introduced atomic force microscopy to quantify the binding strength between cell adhesion proteoglycans. Measurement of binding forces intrinsic to cell adhesion proteoglycans is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. As a model, we selected the glyconectin 1, a cell adhesion proteoglycan isolated from the marine sponge Microciona prolifera. This glyconectin mediates in vivo cell recognition and aggregation via homophilic, species-specific, polyvalent, and calcium ion-dependent carbohydrate-carbohydrate interactions. Under physiological conditions, an adhesive force of up to 400 piconewtons

  15. Mediated Interactions and Musical Expression - A Survey

    NARCIS (Netherlands)

    Reidsma, Dennis; Radha, Mustafa; Nijholt, Antinus; Lee, Newton

    2014-01-01

    This chapter surveys the field of technologically mediated musical interaction and technologically enhanced musical expression. We look at several new technologies that enable new ways of musical expression and interaction, explore the micro-coordination that occurs in collaborative musical

  16. Mediation Revisited: The Interactive Organization of Mediation in Learning Environments

    OpenAIRE

    Pekarek Doehler, Simona

    2013-01-01

    This article is concerned with the social organization of mediation in learning environments. It seeks to further articulate the sociocultural notion of mediation in sociointeractional terms, combining insights from the sociocultural approach to cognition and the microinteractionist, especially ethnomethodological approach to social activities. A microanalysis of mediation in communicative 2nd-language classroom activities where the task at hand is the management of interaction itself is pres...

  17. Volatile-mediated interactions in the rhizosphere

    NARCIS (Netherlands)

    Cordovez da Cunha, Viviane

    2016-01-01

    Plants and microorganisms are constantly engaged in highly dynamic interactions both above- and belowground. Several of these interactions are mediated by volatile organic compounds (VOCs), small carbon-based compounds with high vapor pressure at ambient temperature. In the rhizosphere, VOCs have an

  18. Exploring Mediated Interactions: A Design Exercise

    NARCIS (Netherlands)

    Vyas, Dhaval; Dix, Alan; Nijholt, Antinus; Jorge, J

    2008-01-01

    With the emergence of personal and ubiquitous computing systems in the last decade, interaction designers have started designing products by employing quality oriented aspects such as user experience, playfulness, enchantment and others. In order to explore novel forms of mediated interactions,

  19. Mediated Interactions and Musical Expression - A Survey

    NARCIS (Netherlands)

    Reidsma, Dennis; Radha, Mustafa; Nijholt, Antinus; Lee, Newton

    2014-01-01

    This chapter surveys the field of technologically mediated musical interaction and technologically enhanced musical expression. We look at several new technologies that enable new ways of musical expression and interaction, explore the micro-coordination that occurs in collaborative musical performa

  20. 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…

  1. Interaction intensity and pollinator-mediated selection.

    Science.gov (United States)

    Trunschke, Judith; Sletvold, Nina; Ågren, Jon

    2017-02-27

    In animal-pollinated plants, the opportunity for selection and the strength of pollinator-mediated selection are expected to increase with the degree of pollen limitation. However, whether differences in pollen limitation can explain variation in pollinator-mediated and net selection among animal-pollinated species is poorly understood. In the present study, we quantified pollen limitation, variance in relative fitness and pollinator-mediated selection on five traits important for pollinator attraction (flowering start, plant height, flower number, flower size) and pollination efficiency (spur length) in natural populations of 12 orchid species. Pollinator-mediated selection was quantified by subtracting estimates of selection gradients for plants receiving supplemental hand-pollination from estimates obtained for open-pollinated control plants. Mean pollen limitation ranged from zero to 0.96. Opportunity for selection, pollinator-mediated selection and net selection were all positively related to pollen limitation, whereas nonpollinator-mediated selection was not. Opportunity for selection varied five-fold, strength of pollinator-mediated selection varied three-fold and net selection varied 1.5-fold among species. Supplemental hand-pollination reduced both opportunity for selection and selection on floral traits. The results show that the intensity of biotic interactions is an important determinant of the selection regime, and indicate that the potential for pollinator-mediated selection and divergence in floral traits is particularly high in species that are strongly pollen-limited.

  2. Proteinaceous molecules mediating Bifidobacterium-host interactions

    Directory of Open Access Journals (Sweden)

    Lorena Ruiz

    2016-08-01

    Full Text Available Bifidobacteria are commensal microoganisms found in the gastrointestinal tract.Several strains have been attributed beneficial traits at local and systemic levels, through pathogen exclusion or immune modulation, among other benefits. This has promoted a growing industrial and scientific interest in bifidobacteria as probiotic supplements. However, the molecular mechanisms mediating this cross-talk with the human host remain unknown. High-throughput technologies, from functional genomics to transcriptomics, proteomics and interactomics coupled to the development of both in vitro and in vivo models to study the dynamics of the intestinal microbiota and their effects on host cells, have eased the identification of key molecules in these interactions. Numerous secreted or surface-associated proteins or peptides have been identified as potential mediators of bifidobacteria-host interactions and molecular cross-talk, directly participating in sensing environmental factors, promoting intestinal colonization or mediating a dialogue with mucosa-associated immune cells. On the other hand, bifidobacteria induce the production of proteins in the intestine, by epithelial or immune cells, and other gut bacteria, which are key elements in orchestrating interactions among bifidobacteria, gut microbiota and host cells. This review aims to give a comprehensive overview on proteinaceous molecules described and characterized to date, as mediators of the dynamic interplay between bifidobacteria and the human host, providing a framework to identify knowledge gaps and future research needs.

  3. Coherent acoustic excitation of cavity polaritons

    DEFF Research Database (Denmark)

    Poel, Mike van der; de Lima, M. M.; Hey, R.

    and highly nonlinear optical response.Our sample consists of epitaxially grown GaAs/AlGaAs QWs located at the anti-node ofa high Q lambda cavity, which is resonant with the QW excitonic transition3. The SAWfield, which is excited by an interdigital transducer on the piezoelectric GaAs samplesurface...

  4. Acetic acid mediated interactions between alumina surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Kimiyasu, E-mail: sato.kimiyasu@aist.go.jp [National Institute of Advanced Industrial Science and Technology (AIST), Anagahora 2266-98, Shimoshidami, Moriyama-ku, Nagoya 463-8560 (Japan); Y Latin-Small-Letter-Dotless-I lmaz, Hueseyin [National Institute of Advanced Industrial Science and Technology (AIST), Anagahora 2266-98, Shimoshidami, Moriyama-ku, Nagoya 463-8560 (Japan); Gebze Institute of Technology, Materials Science and Engineering Department, 41400, Gebze-Kocaeli (Turkey); Ijuin, Atsuko; Hotta, Yuji; Watari, Koji [National Institute of Advanced Industrial Science and Technology (AIST), Anagahora 2266-98, Shimoshidami, Moriyama-ku, Nagoya 463-8560 (Japan)

    2012-02-01

    Low-molecular-weight organic acids have been known to modify colloidal stability of alumina-based suspensions. We investigated interaction forces between alumina surfaces mediated by acetic acid which is one of the simplest organic acids. Forces between alumina surfaces were measured using the colloid-probe method of atomic force microscope (AFM). Repulsive forces attributed to steric repulsion due to adsorbed molecules and electrostatic repulsion dominated the interaction. Results of rheological characterization of the alumina slurry containing acetic acid supported the finding.

  5. Solute-mediated interactions between active droplets

    Science.gov (United States)

    Moerman, Pepijn G.; Moyses, Henrique W.; van der Wee, Ernest B.; Grier, David G.; van Blaaderen, Alfons; Kegel, Willem K.; Groenewold, Jan; Brujic, Jasna

    2017-09-01

    Concentration gradients play a critical role in embryogenesis, bacterial locomotion, as well as the motility of active particles. Particles develop concentration profiles around them by dissolution, adsorption, or the reactivity of surface species. These gradients change the surface energy of the particles, driving both their self-propulsion and governing their interactions. Here, we uncover a regime in which solute gradients mediate interactions between slowly dissolving droplets without causing autophoresis. This decoupling allows us to directly measure the steady-state, repulsive force, which scales with interparticle distance as F ˜1 /r2 . Our results show that the dissolution process is diffusion rather than reaction rate limited, and the theoretical model captures the dependence of the interactions on droplet size and solute concentration, using a single fit parameter, l =16 ±3 nm , which corresponds to the length scale of a swollen micelle. Our results shed light on the out-of-equilibrium behavior of particles with surface reactivity.

  6. Forms of Mediation: The Case of Interpreter-Mediated Interactions in Medical Systems

    Science.gov (United States)

    Baraldi, Claudio

    2009-01-01

    This paper analyses the forms of mediation in interlinguistic interactions performed in Italian healthcare services and in contexts of migration. The literature encourages dialogic transformative mediation, empowering participants' voices and changing cultural presuppositions in social systems. It may be doubtful, however, whether mediation can…

  7. Water-mediated ionic interactions in protein structures

    Indian Academy of Sciences (India)

    R Sabarinathan; K Aishwarya; R Sarani; M Kirti Vaishnavi; K Sekar

    2011-06-01

    It is well known that water molecules play an indispensable role in the structure and function of biological macromolecules. The water-mediated ionic interactions between the charged residues provide stability and plasticity and in turn address the function of the protein structures. Thus, this study specifically addresses the number of possible water-mediated ionic interactions, their occurrence, distribution and nature found in 90% non-redundant protein chains. Further, it provides a statistical report of different charged residue pairs that are mediated by surface or buried water molecules to form the interactions. Also, it discusses its contributions in stabilizing various secondary structural elements of the protein. Thus, the present study shows the ubiquitous nature of the interactions that imparts plasticity and flexibility to a protein molecule.

  8. Torsion-mediated interaction between adjacent genes.

    Directory of Open Access Journals (Sweden)

    Sam Meyer

    2014-09-01

    Full Text Available DNA torsional stress is generated by virtually all biomolecular processes involving the double helix, in particular transcription where a significant level of stress propagates over several kilobases. If another promoter is located in this range, this stress may strongly modify its opening properties, and hence facilitate or hinder its transcription. This mechanism implies that transcribed genes distant of a few kilobases are not independent, but coupled by torsional stress, an effect for which we propose the first quantitative and systematic model. In contrast to previously proposed mechanisms of transcriptional interference, the suggested coupling is not mediated by the transcription machineries, but results from the universal mechanical features of the double-helix. The model shows that the effect likely affects prokaryotes as well as eukaryotes, but with different consequences owing to their different basal levels of torsion. It also depends crucially on the relative orientation of the genes, enhancing the expression of eukaryotic divergent pairs while reducing that of prokaryotic convergent ones. To test the in vivo influence of the torsional coupling, we analyze the expression of isolated gene pairs in the Drosophila melanogaster genome. Their orientation and distance dependence is fully consistent with the model, suggesting that torsional gene coupling may constitute a widespread mechanism of (coregulation in eukaryotes.

  9. Audio Interaction in Computer Mediated Games

    Directory of Open Access Journals (Sweden)

    J. R. Parker

    2008-01-01

    Full Text Available The use of sound in an interactive media environment has not been advanced, as a technology, as far as graphics or artificial intelligence. This discussion will explore the use of sound as a way to influence the player of a computer game, will show ways that a game can use sound as input, and will describe ways that the player can influence sound in a game. The role of sound in computer games will be explored some practical design ideas that can be used to improve the current state of the art will be given.

  10. Photon-mediated interactions between distant artificial atoms.

    Science.gov (United States)

    van Loo, Arjan F; Fedorov, Arkady; Lalumière, Kevin; Sanders, Barry C; Blais, Alexandre; Wallraff, Andreas

    2013-12-20

    Photon-mediated interactions between atoms are of fundamental importance in quantum optics, quantum simulations, and quantum information processing. The exchange of real and virtual photons between atoms gives rise to nontrivial interactions, the strength of which decreases rapidly with distance in three dimensions. Here, we use two superconducting qubits in an open one-dimensional transmission line to study much stronger photon-mediated interactions. Making use of the possibility to tune these qubits by more than a quarter of their transition frequency, we observe both coherent exchange interactions at an effective separation of 3λ/4 and the creation of super- and subradiant states at a separation of one photon wavelength λ. In this system, collective atom-photon interactions and applications in quantum communication may be explored.

  11. Membrane-mediated interaction between strongly anisotropic protein scaffolds.

    Directory of Open Access Journals (Sweden)

    Yonatan Schweitzer

    2015-02-01

    Full Text Available Specialized proteins serve as scaffolds sculpting strongly curved membranes of intracellular organelles. Effective membrane shaping requires segregation of these proteins into domains and is, therefore, critically dependent on the protein-protein interaction. Interactions mediated by membrane elastic deformations have been extensively analyzed within approximations of large inter-protein distances, small extents of the protein-mediated membrane bending and small deviations of the protein shapes from isotropic spherical segments. At the same time, important classes of the realistic membrane-shaping proteins have strongly elongated shapes with large and highly anisotropic curvature. Here we investigated, computationally, the membrane mediated interaction between proteins or protein oligomers representing membrane scaffolds with strongly anisotropic curvature, and addressed, quantitatively, a specific case of the scaffold geometrical parameters characterizing BAR domains, which are crucial for membrane shaping in endocytosis. In addition to the previously analyzed contributions to the interaction, we considered a repulsive force stemming from the entropy of the scaffold orientation. We computed this interaction to be of the same order of magnitude as the well-known attractive force related to the entropy of membrane undulations. We demonstrated the scaffold shape anisotropy to cause a mutual aligning of the scaffolds and to generate a strong attractive interaction bringing the scaffolds close to each other to equilibrium distances much smaller than the scaffold size. We computed the energy of interaction between scaffolds of a realistic geometry to constitute tens of kBT, which guarantees a robust segregation of the scaffolds into domains.

  12. Explanation in causal inference methods for mediation and interaction

    CERN Document Server

    VanderWeele, Tyler

    2015-01-01

    A comprehensive examination of methods for mediation and interaction, VanderWeele's book is the first to approach this topic from the perspective of causal inference. Numerous software tools are provided, and the text is both accessible and easy to read, with examples drawn from diverse fields. The result is an essential reference for anyone conducting empirical research in the biomedical or social sciences.

  13. Contactless nonlinear optics mediated by long-range Rydberg interactions

    Science.gov (United States)

    Busche, Hannes; Huillery, Paul; Ball, Simon W.; Ilieva, Teodora; Jones, Matthew P. A.; Adams, Charles S.

    2017-07-01

    In conventional nonlinear optics, linear quantum optics, and cavity quantum electrodynamics to create effective photon-photon interactions photons must have, at one time, interacted with matter inside a common medium. In contrast, in Rydberg quantum optics, optical photons are coherently and reversibly mapped onto collective atomic Rydberg excitations, giving rise to dipole-mediated effective photon-photon interactions that are long range. Consequently, a spatial overlap between the light modes is no longer required. We demonstrate such a contactless coupling between photons stored as collective Rydberg excitations in spatially separate optical media. The potential induced by each photon modifies the retrieval mode of its neighbour, leading to correlations between them. We measure these correlations as a function of interaction strength, distance and storage time, demonstrating an effective interaction between photons separated by 15 times their wavelength. Contactless effective photon-photon interactions are relevant for scalable multichannel photonic devices and the study of strongly correlated many-body dynamics using light.

  14. Contextual specificity in peptide-mediated protein interactions.

    Directory of Open Access Journals (Sweden)

    Amelie Stein

    Full Text Available Most biological processes are regulated through complex networks of transient protein interactions where a globular domain in one protein recognizes a linear peptide from another, creating a relatively small contact interface. Although sufficient to ensure binding, these linear motifs alone are usually too short to achieve the high specificity observed, and additional contacts are often encoded in the residues surrounding the motif (i.e. the context. Here, we systematically identified all instances of peptide-mediated protein interactions of known three-dimensional structure and used them to investigate the individual contribution of motif and context to the global binding energy. We found that, on average, the context is responsible for roughly 20% of the binding and plays a crucial role in determining interaction specificity, by either improving the affinity with the native partner or impeding non-native interactions. We also studied and quantified the topological and energetic variability of interaction interfaces, finding a much higher heterogeneity in the context residues than in the consensus binding motifs. Our analysis partially reveals the molecular mechanisms responsible for the dynamic nature of peptide-mediated interactions, and suggests a global evolutionary mechanism to maximise the binding specificity. Finally, we investigated the viability of non-native interactions and highlight cases of potential cross-reaction that might compensate for individual protein failure and establish backup circuits to increase the robustness of cell networks.

  15. Trait-mediated trophic interactions: is foraging theory keeping up?

    Science.gov (United States)

    Railsback, Steven F; Harvey, Bret C

    2013-02-01

    Many ecologists believe that there is a lack of foraging theory that works in community contexts, for populations of unique individuals each making trade-offs between food and risk that are subject to feedbacks from behavior of others. Such theory is necessary to reproduce the trait-mediated trophic interactions now recognized as widespread and strong. Game theory can address feedbacks but does not provide foraging theory for unique individuals in variable environments. 'State- and prediction-based theory' (SPT) is a new approach that combines existing trade-off methods with routine updating: individuals regularly predict future food availability and risk from current conditions to optimize a fitness measure. SPT can reproduce a variety of realistic foraging behaviors and trait-mediated trophic interactions with feedbacks, even when the environment is unpredictable.

  16. Social playware for mediating teleplay interaction over distance

    DEFF Research Database (Denmark)

    Lund, Henrik Hautop; Thorsteinsson, Tumi

    2011-01-01

    and Asia. With the social playware, players would compete against each other simultaneously in the three continents, Africa, Europe and Asia, and feel the presence of the competitors on the other continents expressed through the playware. The playware game is set up to motivate players to engage......We suggest that novel playware technology can function as a mediator for playful social interaction over distance, where people are separated by physical distance but feel the presence of each other mediated through the interaction with the playware technology. In order to investigate such social...... playware, we developed the Playware Soccer game and tested this with more than 1,000 users during the FIFA World Cup 2010 in South Africa. The test was conducted in townships, orphanages for HIV/AIDS children, markets, FIFA fan parks, etc. along with simultaneous tests with similar set-ups in Europe...

  17. Social playware for mediating tele-play interaction over distance

    DEFF Research Database (Denmark)

    Lund, Henrik Hautop; Thorsteinsson, Tumi

    2012-01-01

    to investigate such social playware, we developed the Playware Soccer game and tested it with more than 1000 users during the FIFA World Cup 2010 in South Africa. The test was conducted in townships, orphanages for HIV/AIDS children, markets, FIFA fan parks, etc., along with simultaneous tests with similar set......-ups in Europe and Asia. With the social playware, players would compete against each other simultaneously in three continents, Africa, Europe, and Asia, and feel the presence of the competitors on the other continents expressed through the playware. The playware game is set up to motivate players to engage......We suggest that novel playware technology can function as a mediator for playful social interaction over long distances, such as where people are separated by physical distance but feel the presence of each other mediated through their interaction with the playware technology. In order...

  18. Intramolecular hydrophobic interactions are critical mediators of STAT5 dimerization

    Science.gov (United States)

    Fahrenkamp, Dirk; Li, Jinyu; Ernst, Sabrina; Schmitz-van de Leur, Hildegard; Chatain, Nicolas; Küster, Andrea; Koschmieder, Steffen; Lüscher, Bernhard; Rossetti, Giulia; Müller-Newen, Gerhard

    2016-10-01

    STAT5 is an essential transcription factor in hematopoiesis, which is activated through tyrosine phosphorylation in response to cytokine stimulation. Constitutive activation of STAT5 is a hallmark of myeloid and lymphoblastic leukemia. Using homology modeling and molecular dynamics simulations, a model of the STAT5 phosphotyrosine-SH2 domain interface was generated providing first structural information on the activated STAT5 dimer including a sequence, for which no structural information is available for any of the STAT proteins. We identified a novel intramolecular interaction mediated through F706, adjacent to the phosphotyrosine motif, and a unique hydrophobic interface on the surface of the SH2 domain. Analysis of corresponding STAT5 mutants revealed that this interaction is dispensable for Epo receptor-mediated phosphorylation of STAT5 but essential for dimer formation and subsequent nuclear accumulation. Moreover, the herein presented model clarifies molecular mechanisms of recently discovered leukemic STAT5 mutants and will help to guide future drug development.

  19. Root signals that mediate mutualistic interactions in the rhizosphere.

    Science.gov (United States)

    Rasmann, Sergio; Turlings, Ted Cj

    2016-08-01

    A recent boom in research on belowground ecology is rapidly revealing a multitude of fascinating interactions, in particular in the rhizosphere. Many of these interactions are mediated by photo-assimilates that are excreted by plant roots. Root exudates are not mere waste products, but serve numerous functions to control abiotic and biotic processes. These functions range from changing the chemical and physical properties of the soil, inhibiting the growth of competing plants, combatting herbivores, and regulating the microbial community. Particularly intriguing are root-released compounds that have evolved to serve mutualistic interactions with soil-dwelling organisms. These mutually beneficial plant-mediated signals are not only of fundamental ecological interest, but also exceedingly important from an agronomical perspective. Here, we attempt to provide an overview of the plant-produced compounds that have so far been implicated in mutualistic interactions. We propose that these mutualistic signals may have evolved from chemical defenses and we point out that they can be (mis)used by specialized pathogens and herbivores. We speculate that many more signals and interactions remain to be uncovered and that a good understanding of the mechanisms and ecological implications can be the basis for exploitation and manipulation of the signals for crop improvement and protection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions.

    Science.gov (United States)

    Sawant, Kirti V; Poluri, Krishna Mohan; Dutta, Amit K; Sepuru, Krishna Mohan; Troshkina, Anna; Garofalo, Roberto P; Rajarathnam, Krishna

    2016-09-14

    The chemokine CXCL1/MGSA plays a pivotal role in the host immune response by recruiting and activating neutrophils for microbial killing at the tissue site. CXCL1 exists reversibly as monomers and dimers, and mediates its function by binding glycosaminoglycans (GAG) and CXCR2 receptor. We recently showed that both monomers and dimers are potent CXCR2 agonists, the dimer is the high-affinity GAG ligand, lysine and arginine residues located in two non-overlapping domains mediate GAG interactions, and there is extensive overlap between GAG and receptor-binding domains. To understand how these structural properties influence in vivo function, we characterized peritoneal neutrophil recruitment of a trapped monomer and trapped dimer and a panel of WT lysine/arginine to alanine mutants. Monomers and dimers were active, but WT was more active indicating synergistic interactions promote recruitment. Mutants from both domains showed reduced GAG heparin binding affinities and reduced neutrophil recruitment, providing compelling evidence that both GAG-binding domains mediate in vivo trafficking. Further, mutant of a residue that is involved in both GAG binding and receptor signaling showed the highest reduction in recruitment. We conclude that GAG interactions and receptor activity of CXCL1 monomers and dimers are fine-tuned to regulate neutrophil trafficking for successful resolution of tissue injury.

  1. Separating monocular and binocular neural mechanisms mediating chromatic contextual interactions.

    Science.gov (United States)

    D'Antona, Anthony D; Christiansen, Jens H; Shevell, Steven K

    2014-04-17

    When seen in isolation, a light that varies in chromaticity over time is perceived to oscillate in color. Perception of that same time-varying light may be altered by a surrounding light that is also temporally varying in chromaticity. The neural mechanisms that mediate these contextual interactions are the focus of this article. Observers viewed a central test stimulus that varied in chromaticity over time within a larger surround that also varied in chromaticity at the same temporal frequency. Center and surround were presented either to the same eye (monocular condition) or to opposite eyes (dichoptic condition) at the same frequency (3.125, 6.25, or 9.375 Hz). Relative phase between center and surround modulation was varied. In both the monocular and dichoptic conditions, the perceived modulation depth of the central light depended on the relative phase of the surround. A simple model implementing a linear combination of center and surround modulation fit the measurements well. At the lowest temporal frequency (3.125 Hz), the surround's influence was virtually identical for monocular and dichoptic conditions, suggesting that at this frequency, the surround's influence is mediated primarily by a binocular neural mechanism. At higher frequencies, the surround's influence was greater for the monocular condition than for the dichoptic condition, and this difference increased with temporal frequency. Our findings show that two separate neural mechanisms mediate chromatic contextual interactions: one binocular and dominant at lower temporal frequencies and the other monocular and dominant at higher frequencies (6-10 Hz).

  2. Water-mediated correlations in DNA-enzyme interactions

    CERN Document Server

    Capolupo, A; Kurian, P; Vitiello, G

    2016-01-01

    In this paper we consider dipole-mediated correlations between DNA and enzymes in the context of their water environment. Such correlations emerge from electric dipole-dipole interactions between aromatic ring structures in DNA and in enzymes, and they are mediated by radiative fields that stimulate transitions between the $l=0$ and $l=1$ rotational levels of the molecular water electric dipoles. We show that there are matching collective modes between DNA and enzyme dipole fields, and that a dynamic time-averaged polarization vanishes in the water dipole field only if either DNA, enzyme, or both are absent from the sample. This persistent field may serve as the electromagnetic image that, in popular colloquialisms about DNA biochemistry, allows enzymes to "scan" or "read" the double helix. Topologically nontrivial configurations in the coherent ground state requiring clamplike enzyme behavior on the DNA may stem, ultimately, from spontaneously broken gauge symmetries.

  3. Bilayer-thickness-mediated interactions between integral membrane proteins.

    Science.gov (United States)

    Kahraman, Osman; Koch, Peter D; Klug, William S; Haselwandter, Christoph A

    2016-04-01

    Hydrophobic thickness mismatch between integral membrane proteins and the surrounding lipid bilayer can produce lipid bilayer thickness deformations. Experiment and theory have shown that protein-induced lipid bilayer thickness deformations can yield energetically favorable bilayer-mediated interactions between integral membrane proteins, and large-scale organization of integral membrane proteins into protein clusters in cell membranes. Within the continuum elasticity theory of membranes, the energy cost of protein-induced bilayer thickness deformations can be captured by considering compression and expansion of the bilayer hydrophobic core, membrane tension, and bilayer bending, resulting in biharmonic equilibrium equations describing the shape of lipid bilayers for a given set of bilayer-protein boundary conditions. Here we develop a combined analytic and numerical methodology for the solution of the equilibrium elastic equations associated with protein-induced lipid bilayer deformations. Our methodology allows accurate prediction of thickness-mediated protein interactions for arbitrary protein symmetries at arbitrary protein separations and relative orientations. We provide exact analytic solutions for cylindrical integral membrane proteins with constant and varying hydrophobic thickness, and develop perturbative analytic solutions for noncylindrical protein shapes. We complement these analytic solutions, and assess their accuracy, by developing both finite element and finite difference numerical solution schemes. We provide error estimates of our numerical solution schemes and systematically assess their convergence properties. Taken together, the work presented here puts into place an analytic and numerical framework which allows calculation of bilayer-mediated elastic interactions between integral membrane proteins for the complicated protein shapes suggested by structural biology and at the small protein separations most relevant for the crowded membrane

  4. Self-interacting dark matter with naturally light mediator

    Science.gov (United States)

    Ma, Ernest

    2017-02-01

    A promising proposal for resolving the cusp-core anomaly in the density profile of dwarf galaxies is to allow dark matter to interact with itself through a light mediator of mass much less than a GeV. The theoretical challenge is to have a complete renormalizable theory where this happens naturally even though dark matter itself may be of the electroweak scale, i.e. 100 GeV to 1 TeV. I propose here such a model with just two neutral complex scalar singlets under a softly broken dark global U(1) symmetry.

  5. A fragrant neighborhood: volatile mediated bacterial interactions in soil.

    Science.gov (United States)

    Schulz-Bohm, Kristin; Zweers, Hans; de Boer, Wietse; Garbeva, Paolina

    2015-01-01

    There is increasing evidence that volatile organic compounds (VOCs) play essential roles in communication and competition between soil microorganisms. Here we assessed volatile-mediated interactions of a synthetic microbial community in a model system that mimics the natural conditions in the heterogeneous soil environment along the rhizosphere. Phylogenetic different soil bacterial isolates (Burkholderia sp., Dyella sp., Janthinobacterium sp., Pseudomonas sp., and Paenibacillus sp.) were inoculated as mixtures or monoculture in organic-poor, sandy soil containing artificial root exudates (ARE) and the volatile profile and growth were analyzed. Additionally, a two-compartment system was used to test if volatiles produced by inter-specific interactions in the rhizosphere can stimulate the activity of starving bacteria in the surrounding, nutrient-depleted soil. The obtained results revealed that both microbial interactions and shifts in microbial community composition had a strong effect on the volatile emission. Interestingly, the presence of a slow-growing, low abundant Paenibacillus strain significantly affected the volatile production by the other abundant members of the bacterial community as well as the growth of the interacting strains. Furthermore, volatiles released by mixtures of root-exudates consuming bacteria stimulated the activity and growth of starved bacteria. Besides growth stimulation, also an inhibition in growth was observed for starving bacteria exposed to microbial volatiles. The current work suggests that volatiles produced during microbial interactions in the rhizosphere have a significant long distance effect on microorganisms in the surrounding, nutrient-depleted soil.

  6. A fragrant neighborhood: Volatile mediated bacterial interactions in soil

    Directory of Open Access Journals (Sweden)

    Kristin eSchulz-Bohm

    2015-11-01

    Full Text Available There is increasing evidence that volatile organic compounds play essential roles in communication and competition between soil microorganisms. Here we assessed volatile-mediated interactions of a synthetic microbial community in a model system that mimics the natural conditions in the heterogeneous soil environment along the rhizosphere. Phylogenetic different soil bacterial isolates (Burkholderia sp., Dyella sp., Janthinobacterium sp., Pseudomonas sp., and Paenibacillus sp. were inoculated as mixtures or monoculture in organic-poor, sandy soil containing artificial root exudates and the volatile profile and growth were analyzed. Additionally, a two-compartment system was used to test if volatiles produced by inter-specific interactions in the rhizosphere can stimulate the activity of starving bacteria in the surrounding, nutrient-depleted soil. The obtained results revealed that both microbial interactions and shifts in microbial community composition had a strong effect on the volatile emission. Interestingly, the presence of a slow-growing, low abundant Paenibacillus strain significantly affected the volatile production by the other abundant members of the bacterial community as well as the growth of the interacting strains. Furthermore, volatiles released by mixtures of root-exudates consuming bacteria stimulated the activity and growth of starved bacteria. Besides growth stimulation, also an inhibition in growth was observed for starving bacteria exposed to microbial volatiles. The current work suggests that volatiles produced during microbial interactions in the rhizosphere have a significant long distance effect on microorganisms in the surrounding, nutrient-depleted soil.

  7. Plant-mediated interactions between whiteflies, herbivores, and natural enemies.

    Science.gov (United States)

    Inbar, Moshe; Gerling, Dan

    2008-01-01

    Whiteflies (Homoptera: Aleyrodidae) comprise tiny phloem-sucking insects. The sessile development of their immatures and their phloem-feeding habits (with minimal physical plant damage) often lead to plant-mediated interactions with other organisms. The main data come from the polyphagous pest species Bemisia tabaci (Gennadius) and Trialeurodes vaporariorum (Westwood), which are intricately associated with their host plants. Although these associations might not represent aleyrodids in general, we rely on them to highlight the fundamental role of host plants in numerous ecological interactions between whiteflies, other herbivores, and their natural enemies. Plant traits often affect the activity, preference, and performance of the whiteflies, as well as their entomopathogens, predators, and parasitoids. Leaf structure (primarily pubescence) and constitutive and induced chemical profiles (defensive and nutritional elements) are critically important determinants of whitefly fitness. Pest management-related and evolutionary biology studies could benefit from future research that will consider whiteflies in a multitrophic-level framework.

  8. New interactions in the dark sector mediated by dark energy

    CERN Document Server

    Brookfield, A W; Hall, L M H

    2007-01-01

    Cosmological observations have revealed the existence of a dark matter sector, which is commonly assumed to be made up of one particle species only. However, this sector might be more complicated than we currently believe: there might be more than one dark matter species (for example two components of cold dark matter or a mixture of hot and cold dark matter) and there may be new interactions between these particles. In this paper we study the possibility of multiple dark matter species and interactions mediated by a dark energy field. We study both the background and the perturbation evolution in these scenarios. We find that the background evolution of a system of multiple dark matter particles (with constant couplings) mimics a single fluid with a time-varying coupling parameter. However, this is no longer true on the perturbative level. We study the case of attractive and repulsive forces as well as a mixture of cold and hot dark matter particles.

  9. Performing Re-mediation in Graphical Cyberspace: Mediating Agency, Body and Identity in Virtual Interactional Practices

    DEFF Research Database (Denmark)

    McIlvenny, Paul

    and spectacular multi-media event raises many questions. How do we conceive of the recent developments in media technology and social computing that are impacting on what we have traditionally called 'the mass media'? How is interaction and talk mediated and adapted to new media genres? And how do participants...... the conference, avatar-embodied speakers using text chat performed to virtual audiences, 'webcams' (re)broadcast live video images of CNN and other remote sites, and a 'webcast' sent audiovisual representations captured by video camera of certain key participants in their physical locations. Such a novel...... construct and maintain senseful talk in a sometimes bewildering, 'inhabited', digitally re-mediated public environment? What is especially interesting about the cyberconference event is the ways in which participants themselves shaped their talk to constitute media spaces, presences and participation...

  10. Performing Re-mediation in Graphical Cyberspace: Mediating Agency, Body and Identity in Virtual Interactional Practices

    DEFF Research Database (Denmark)

    McIlvenny, Paul

    and spectacular multi-media event raises many questions. How do we conceive of the recent developments in media technology and social computing that are impacting on what we have traditionally called 'the mass media'? How is interaction and talk mediated and adapted to new media genres? And how do participants......Promoted as the first academic conference to be held completely in graphical cyberspace, Avatars 98 took place in November 1998. The virtual conference site was built and inhabited using software that supports multi-party presence over the Internet in a simulated, navigable environment. During...... construct and maintain senseful talk in a sometimes bewildering, 'inhabited', digitally re-mediated public environment? What is especially interesting about the cyberconference event is the ways in which participants themselves shaped their talk to constitute media spaces, presences and participation...

  11. Bilayer-thickness-mediated interactions between integral membrane proteins

    CERN Document Server

    Kahraman, Osman; Klug, William S; Haselwandter, Christoph A

    2016-01-01

    Hydrophobic thickness mismatch between integral membrane proteins and the surrounding lipid bilayer can produce lipid bilayer thickness deformations. Experiment and theory have shown that protein-induced lipid bilayer thickness deformations can yield energetically favorable bilayer-mediated interactions between integral membrane proteins, and large-scale organization of integral membrane proteins into protein clusters in cell membranes. Within the continuum elasticity theory of membranes, the energy cost of protein-induced bilayer thickness deformations can be captured by considering compression and expansion of the bilayer hydrophobic core, membrane tension, and bilayer bending, resulting in biharmonic equilibrium equations describing the shape of lipid bilayers for a given set of bilayer-protein boundary conditions. Here we develop a combined analytic and numerical methodology for the solution of the equilibrium elastic equations associated with protein-induced lipid bilayer deformations. Our methodology al...

  12. 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...

  13. Evolutionary classification of toxin mediated interactions in microorganisms.

    Science.gov (United States)

    Neumann, Gunther F; Jetschke, Gottfried

    2010-03-01

    A trade-off between the parameters of Lotka-Volterra systems is used to give verifications of relations between intrinsic growth rate and limiting capacity and the stability type of the resulting dynamical system. The well known rock-paper-scissors game serves as a template for toxin mediated interactions, which is best represented by the bacteriocin producing Escherichia coli bacteria. There, we have three strains of the same species. The producer produces a toxin lethal to the sensitive, while the resistant is able to protect itself from that toxin. Due to the fact that there are costs for production and for resistance, a dynamics similar to the rock-paper-scissors game results. By using an adaptive dynamics approach for competitive Lotka-Volterra systems and assuming an inverse relation (trade-off) between intrinsic growth rate (IGR) and limiting capacity (LC) we obtain evolutionary and convergence stable relations between the IGR's and the LC's. Furthermore this evolutionary process leads to a phase topology of the population dynamics with a globally stable interior fixed point by leaving the interaction parameters constant. While the inverse trade-off stabilizes coexistence and does not allow branching, toxicity itself can promote diversification. The results are discussed in view of several biological examples indicating that the above results are structurally valid. 2009 Elsevier Ireland Ltd. All rights reserved.

  14. Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros.

    Science.gov (United States)

    Valeri, Linda; Vanderweele, Tyler J

    2013-06-01

    Mediation analysis is a useful and widely employed approach to studies in the field of psychology and in the social and biomedical sciences. The contributions of this article are several-fold. First we seek to bring the developments in mediation analysis for nonlinear models within the counterfactual framework to the psychology audience in an accessible format and compare the sorts of inferences about mediation that are possible in the presence of exposure-mediator interaction when using a counterfactual versus the standard statistical approach. Second, the work by VanderWeele and Vansteelandt (2009, 2010) is extended here to allow for dichotomous mediators and count outcomes. Third, we provide SAS and SPSS macros to implement all of these mediation analysis techniques automatically, and we compare the types of inferences about mediation that are allowed by a variety of software macros.

  15. M-cadherin-mediated intercellular interactions activate satellite cell division.

    Science.gov (United States)

    Marti, Merce; Montserrat, Núria; Pardo, Cristina; Mulero, Lola; Miquel-Serra, Laia; Rodrigues, Alexandre Miguel Cavaco; Andrés Vaquero, José; Kuebler, Bernd; Morera, Cristina; Barrero, María José; Izpisua Belmonte, Juan Carlos

    2013-11-15

    Adult muscle stem cells and their committed myogenic precursors, commonly referred to as the satellite cell population, are involved in both muscle growth after birth and regeneration after damage. It has been previously proposed that, under these circumstances, satellite cells first become activated, divide and differentiate, and only later fuse to the existing myofiber through M-cadherin-mediated intercellular interactions. Our data show that satellite cells fuse with the myofiber concomitantly to cell division, and only when the nuclei of the daughter cells are inside the myofiber, do they complete the process of differentiation. Here we demonstrate that M-cadherin plays an important role in cell-to-cell recognition and fusion, and is crucial for cell division activation. Treatment of satellite cells with M-cadherin in vitro stimulates cell division, whereas addition of anti-M-cadherin antibodies reduces the cell division rate. Our results suggest an alternative model for the contribution of satellite cells to muscle development, which might be useful in understanding muscle regeneration, as well as muscle-related dystrophies.

  16. Lepton flavor violating non-standard interactions via light mediators

    Science.gov (United States)

    Farzan, Yasaman; Shoemaker, Ian M.

    2016-07-01

    Non-Standard neutral current Interactions (NSIs) of neutrinos with matter can alter the pattern of neutrino oscillation due to the coherent forward scattering of neutrinos on the medium. This effect makes long-baseline neutrino experiments such as NO νA and DUNE a sensitive probe of beyond standard model (BSM) physics. We construct light mediator models that can give rise to both lepton flavor conserving as well as Lepton Flavor Violating (LFV) neutral current NSI. We outline the present phenomenological viability of these models and future prospects to test them. We predict a lower bound on Br( H → μτ ) in terms of the parameters that can be measured by DUNE and NO νA, and show that the hint for H → μτ in current LHC data can be accommodated in our model. A large part of the parameter space of the model is already constrained by the bound on Br( τ → Z ' μ) and by the bounds on rare meson decays and can be in principle fully tested by improving these bounds.

  17. Ratio-of-Mediator-Probability Weighting for Causal Mediation Analysis in the Presence of Treatment-by-Mediator Interaction

    Science.gov (United States)

    Hong, Guanglei; Deutsch, Jonah; Hill, Heather D.

    2015-01-01

    Conventional methods for mediation analysis generate biased results when the mediator--outcome relationship depends on the treatment condition. This article shows how the ratio-of-mediator-probability weighting (RMPW) method can be used to decompose total effects into natural direct and indirect effects in the presence of treatment-by-mediator…

  18. Networked Mobilities and new sites of mediated interaction

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    2008-01-01

    as the relationship to sites and places. Furthermore, an increasing number of such mobile practices are mediated by technologies of tangible and less tangible sorts. The paper concludes with a research agenda for unfolding a ‘politics of visibility', engaging with the ambivalences of networked mobilities and mediated...

  19. DOMMINO 2.0: integrating structurally resolved protein-, RNA-, and DNA-mediated macromolecular interactions.

    Science.gov (United States)

    Kuang, Xingyan; Dhroso, Andi; Han, Jing Ginger; Shyu, Chi-Ren; Korkin, Dmitry

    2016-01-01

    Macromolecular interactions are formed between proteins, DNA and RNA molecules. Being a principle building block in macromolecular assemblies and pathways, the interactions underlie most of cellular functions. Malfunctioning of macromolecular interactions is also linked to a number of diseases. Structural knowledge of the macromolecular interaction allows one to understand the interaction's mechanism, determine its functional implications and characterize the effects of genetic variations, such as single nucleotide polymorphisms, on the interaction. Unfortunately, until now the interactions mediated by different types of macromolecules, e.g. protein-protein interactions or protein-DNA interactions, are collected into individual and unrelated structural databases. This presents a significant obstacle in the analysis of macromolecular interactions. For instance, the homogeneous structural interaction databases prevent scientists from studying structural interactions of different types but occurring in the same macromolecular complex. Here, we introduce DOMMINO 2.0, a structural Database Of Macro-Molecular INteractiOns. Compared to DOMMINO 1.0, a comprehensive database on protein-protein interactions, DOMMINO 2.0 includes the interactions between all three basic types of macromolecules extracted from PDB files. DOMMINO 2.0 is automatically updated on a weekly basis. It currently includes ∼1,040,000 interactions between two polypeptide subunits (e.g. domains, peptides, termini and interdomain linkers), ∼43,000 RNA-mediated interactions, and ∼12,000 DNA-mediated interactions. All protein structures in the database are annotated using SCOP and SUPERFAMILY family annotation. As a result, protein-mediated interactions involving protein domains, interdomain linkers, C- and N- termini, and peptides are identified. Our database provides an intuitive web interface, allowing one to investigate interactions at three different resolution levels: whole subunit network

  20. Soluble mediators and the interaction of drugs in IBD

    DEFF Research Database (Denmark)

    Rask-Madsen, J

    1998-01-01

    , which provides the clinical manifestations of IBD. Other important soluble mediators of inflammation include complement-derived and chemotactic peptides, specific adhesion molecules, neuropeptides and reactive metabolites of oxygen and nitrogen. Current established therapies, such as glucocorticoids...... and 5-aminosalicylic acid (5-ASA), inhibit raised concentrations of these interdependent soluble mediators of inflammation, which may amplify one another or have parallel effects. Future medical options for treatment of IBD aim at removing perpetuating antigens or inhibiting the entry of inflammatory...

  1. Root herbivore identity matters in plant-mediated interactions between root and shoot herbivores

    NARCIS (Netherlands)

    Wurst, S.; Putten, van der W.H.

    2007-01-01

    Plants are simultaneously attacked by a multitude of herbivores that affect plant responses and plant-mediated interactions in a variety of ways. So far, studies on indirect interactions between below- and aboveground herbivores have almost exclusively focused on interactions between only one root

  2. 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…

  3. 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…

  4. Water-Mediated Interactions between Hydrophilic and Hydrophobic Surfaces.

    Science.gov (United States)

    Kanduč, Matej; Schlaich, Alexander; Schneck, Emanuel; Netz, Roland R

    2016-09-01

    All surfaces in water experience at short separations hydration repulsion or hydrophobic attraction, depending on the surface polarity. These interactions dominate the more long-ranged electrostatic and van der Waals interactions and are ubiquitous in biological and colloidal systems. Despite their importance in all scenarios where the surface separation is in the nanometer range, the origin of these hydration interactions is still unclear. Using atomistic solvent-explicit molecular dynamics simulations, we analyze the interaction free energies of charge-neutral model surfaces with different elastic and water-binding properties. The surface polarity is shown to be the most important parameter that not only determines the hydration properties and thereby the water contact angle of a single surface but also the surface-surface interaction and whether two surfaces attract or repel. Elastic properties of the surfaces are less important. On the basis of surface contact angles and surface-surface binding affinities, we construct a universal interaction diagram featuring three different interaction regimes-hydration repulsion, cavitation-induced attraction-and for intermediate surface polarities-dry adhesion. On the basis of scaling arguments and perturbation theory, we establish simple combination rules that predict the interaction behavior for combinations of dissimilar surfaces.

  5. Infectious disease agents mediate interaction in food webs and ecosystems.

    NARCIS (Netherlands)

    Selakovic, Sanja; de Ruiter, P.C.; Heesterbeek, Hans|info:eu-repo/dai/nl/073321427

    2014-01-01

    Infectious agents are part of food webs and ecosystems via the relationship with their host species that, in turn, interact with both hosts and non-hosts. Through these interactions, infectious agents influence food webs in terms of structure, functioning and stability. The present literature shows

  6. Infectious disease agents mediate interaction in food webs and ecosystems

    NARCIS (Netherlands)

    Selakovic, S.; Ruiter, de P.C.; Heesterbeek, J.A.P.

    2014-01-01

    Infectious agents are part of food webs and ecosystems via the relationship with their host species that, in turn, interact with both hosts and non-hosts. Through these interactions, infectious agents influence food webs in terms of structure, functioning and stability. The present literature shows

  7. Parent-child mediated learning interactions as determinants of cognitive modifiability: recent research and future directions.

    Science.gov (United States)

    Tzuriel, D

    1999-05-01

    The main objectives of this article are to describe the effects of mediated learning experience (MLE) strategies in mother-child interactions on the child's cognitive modifiability, the effects of distal factors (e.g., socioeconomic status, mother's intelligence, child's personality) on MLE interactions, and the effects of situational variables on MLE processes. Methodological aspects of measurement of MLE interactions and of cognitive modifiability, using a dynamic assessment approach, are discussed. Studies with infants showed that the quality of mother-infant MLE interactions predict later cognitive functioning and that MLE patterns and children's cognitive performance change as a result of intervention programs. Studies with preschool and school-aged children showed that MLE interactions predict cognitive modifiability and that distal factors predict MLE interactions but not the child's cognitive modifiability. The child's cognitive modifiability was predicted by MLE interactions in a structured but not in a free-play situation. Mediation for transcendence (e.g., teaching rules and generalizations) appeared to be the strongest predictor of children's cognitive modifiability. Discussion of future research includes the consideration of a holistic transactional approach, which refers to MLE processes, personality, and motivational-affective factors, the cultural context of mediation, perception of the whole family as a mediational unit, and the "mediational normative scripts."

  8. Lepton Flavor Violating Non-Standard Interactions via Light Mediators

    CERN Document Server

    Farzan, Yasaman

    2016-01-01

    Non-Standard neutral current Interactions (NSIs) of neutrinos with matter can alter the pattern of neutrino oscillations due to the coherent forward scattering of neutrinos on the medium. This effect makes long-baseline neutrino experiments such as NO$\

  9. Density-mediated, context-dependent consumer-resource interactions between ants and extrafloral nectar plants.

    Science.gov (United States)

    Chamberlain, Scott A; Holland, J Nathaniel

    2008-05-01

    Interspecific interactions are often mediated by the interplay between resource supply and consumer density. The supply of a resource and a consumer's density response to it may in turn yield context-dependent use of other resources. Such consumer-resource interactions occur not only for predator-prey and competitive interactions, but for mutualistic ones as well. For example, consumer-resource interactions between ants and extrafloral nectar (EFN) plants are often mutualistic, as EFN resources attract and reward ants which protect plants from herbivory. Yet, ants also commonly exploit floral resources, leading to antagonistic consumer-resource interactions by disrupting pollination and plant reproduction. EFN resources associated with mutualistic ant-plant interactions may also mediate antagonistic ant-flower interactions through the aggregative density response of ants on plants, which could either exacerbate ant-flower interactions or alternatively satiate and distract ants from floral resources. In this study, we examined how EFN resources mediate the density response of ants on senita cacti in the Sonoran Desert and their context-dependent use of floral resources. Removal of EFN resources reduced the aggregative density of ants on plants, both on hourly and daily time scales. Yet, the increased aggregative ant density on plants with EFN resources decreased rather than increased ant use of floral resources, including contacts with and time spent in flowers. Behavioral assays showed no confounding effect of floral deterrents on ant-flower interactions. Thus, ant use of floral resources depends on the supply of EFN resources, which mediates the potential for both mutualistic and antagonistic interactions by increasing the aggregative density of ants protecting plants, while concurrently distracting ants from floral resources. Nevertheless, only certain years and populations of study showed an increase in plant reproduction through herbivore protection or ant

  10. Social Skills as a Mediator between Anxiety Symptoms and Peer Interactions among Children and Adolescents

    Science.gov (United States)

    Motoca, Luci M.; Williams, Sandra; Silverman, Wendy K.

    2012-01-01

    The present study used a cross-sectional design to examine the relations among youth anxiety symptoms, positive and negative peer interactions, and social skills. Also examined was the mediating role of social skills in the relations between youth anxiety symptoms and positive and negative peer interactions. Youth sex and age were examined as…

  11. Exosomes: messengers and mediators of tumor–stromal interactions

    Directory of Open Access Journals (Sweden)

    Shkarina K. A.

    2014-11-01

    Full Text Available Intercellular communication is one of the most important factors involved in the maintenance of tissue homeostasis. The alteration of intercellular interaction correlates with a lot of human diseases including cancerogenesis. There are several types of such interconnection. First of all, it is a direct cell-cell contact, as it takes place in epithelium. The disturbance of this communication is expressed as a loss of cell-cell, cell-matrix contacts, disturbances of cell polarity etc. Another way of intercellular interaction involves mutual influence via paracrine factors produced by corresponding cells. However, there is another kind of information exchange between the cells, namely microvesicular transportation. It was revealed that the exosomes take part in intercellular communication in normal tissues as well as in malignant neoplasia. The present review provides the recent information on the formation of exosomes, their composition and especially the exosome participation in tumor-stromal interactions.

  12. The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II

    DEFF Research Database (Denmark)

    Elmlund, Hans; Baraznenok, Vera; Lindahl, Martin

    2006-01-01

    CDK8 (cyclin-dependent kinase 8), along with CycC, Med12, and Med13, form a repressive module (the Cdk8 module) that prevents RNA polymerase II (pol II) interactions with Mediator. Here, we report that the ability of the Cdk8 module to prevent pol II interactions is independent of the Cdk8......-dependent kinase activity. We use electron microscopy and single-particle reconstruction to demonstrate that the Cdk8 module forms a distinct structural entity that binds to the head and middle region of Mediator, thereby sterically blocking interactions with pol II....

  13. Percolation of optical excitation mediated by near-field interactions

    CERN Document Server

    Naruse, Makoto; Takahashi, Taiki; Aono, Masashi; Akahane, Kouichi; D'Acunto, Mario; Hori, Hirokazu; Thylen, Lars; Katori, Makoto; Ohtsu, Motoichi

    2016-01-01

    Optical excitation transfer in nanostructured matter has been intensively studied in various material systems for versatile applications. Herein, we discuss the percolation of optical excitations in randomly organized nanostructures caused by optical near-field interactions governed by Yukawa potential in a two-dimensional stochastic model. The model results demonstrate the appearance of two phases of percolation of optical excitation as a function of the localization degree of near-field interaction. Moreover, it indicates sublinear scaling with percolation distance when the light localization is strong. The results provide fundamental insights into optical excitation transfer and will facilitate the design and analysis of nanoscale signal-transfer characteristics.

  14. On the ion-mediated interaction between protein and DNA

    CERN Document Server

    Barbi, Maria

    2013-01-01

    The mechanism allowing a protein to search of a target sequence on DNA is currently described as an intermittent process composed of 3D diffusion in bulk and 1D diffusion along the DNA molecule. Due to the relevant charge of protein and DNA, electrostatic interaction should play a crucial role during this search. In this paper, we explicitly derive the mean field theory allowing for a description of the protein-DNA electrostatics in solution. This approach leads to a unified model of the search process, where 1D and 3D diffusion appear as a natural consequence of the diffusion on an extended interaction energy profile.

  15. Microscopic evidence for Ca(2+) mediated pectin-pectin interactions in carrot-based suspensions.

    Science.gov (United States)

    Kyomugasho, Clare; Willemsen, Katleen L D D; Christiaens, Stefanie; Van Loey, Ann M; Hendrickx, Marc E

    2015-12-01

    This study explored the use of fluorescently labeled pectin to obtain evidence for Ca(2+) mediated pectin-pectin interactions in situ. Specifically, carrots were either blanched at low temperature (LTB) or blanched at high temperature (HTB) to activate or inactivate endogenous pectin methylesterase, respectively. Consequently, pectin in tissue particles of LTB and HTB carrots exhibited low degree of methylesterification (DM) and high DM, respectively. Pectin present in the LTB carrot serum exhibited a lower DM, was more branched, and showed a higher molar mass compared to HTB carrot serum pectin. Ca(2+) mediated pectin-pectin interactions were influenced by serum pectin molecular structure, increased with increasing pH and Ca(2+) concentration, and decreasing DM. Presence of more linear pectin in the serum created a competition, leading to less intense interactions between labeled pectin and pectin at tissue particle surfaces. Generally, the most intense Ca(2+) mediated pectin-pectin interactions were observed for pectin of LTB carrot particles.

  16. Volatile-mediated interactions between phylogenetically different soil bacteria

    NARCIS (Netherlands)

    Garbeva, P.; Hordijk, C.; Gerards, S.; Boer, de W.

    2014-01-01

    There is increasing evidence that organic volatiles play an important role in interactions between micro-organisms in the porous soil matrix. Here we report that volatile compounds emitted by different soil bacteria can affect the growth, antibiotic production and gene expression of the soil bacteri

  17. Systematic discovery of new recognition peptides mediating protein interaction networks

    DEFF Research Database (Denmark)

    Neduva, Victor; Linding, Rune; Su-Angrand, Isabelle

    2005-01-01

    Many aspects of cell signalling, trafficking, and targeting are governed by interactions between globular protein domains and short peptide segments. These domains often bind multiple peptides that share a common sequence pattern, or "linear motif" (e.g., SH3 binding to PxxP). Many domains are kn...

  18. Plant-mediated insect interactions on a perennial plant

    NARCIS (Netherlands)

    Stam, J.M.

    2016-01-01

    Plants interact with many organisms around them, and one of the most important groups that a plant has to deal with, are the herbivores. Insects represent the most diverse group of herbivores and have many different ways of using the plant as a food source. Plants can, however, defend themselves aga

  19. Fostering Computer-Mediated L2 Interaction beyond the Classroom

    Science.gov (United States)

    Barrs, Keith

    2012-01-01

    In language learning contexts a primary concern is how to maximise target language interaction both inside and outside of the classroom. With the development of digital technologies, the proliferation of language learning applications, and an increased awareness of how technology can assist in language education, educators are being presented with…

  20. Plant-mediated insect interactions on a perennial plant

    NARCIS (Netherlands)

    Stam, J.M.

    2016-01-01

    Plants interact with many organisms around them, and one of the most important groups that a plant has to deal with, are the herbivores. Insects represent the most diverse group of herbivores and have many different ways of using the plant as a food source. Plants can, however, defend themselves

  1. Characterization and control of surfactant-mediated Norovirus interactions.

    Science.gov (United States)

    Mertens, Brittany S; Velev, Orlin D

    2015-11-28

    Understanding of the colloidal interactions of Norovirus particles in aqueous medium could provide insights on the origins of the notorious stability and infectivity of these widespread viral agents. We characterized the effects of solution pH and surfactant type and concentration on the aggregation, dispersion, and disassembly of Norovirus virus-like particles (VLPs) using dynamic light scattering, electrophoretic light scattering, and transmission electron microscopy. Owing to net negative surface charge of the VLPs at neutral pH, low concentrations of cationic surfactant tend to aggregate the VLPs, whereas low concentrations of anionic surfactant tend to disperse the particles. Increasing the concentration of these surfactants beyond their critical micelle concentration leads to virus capsid disassembly and breakdown of aggregates. Non-ionic surfactants, however, had little effect on virus interactions and likely stabilized them additionally in suspension. The data were interpreted on the basis of simple models for surfactant binding and re-charging of the virus capsid. We used zeta potential data to characterize virus surface charge and interpret the mechanisms behind these demonstrated surfactant-virus interactions. The fundamental understanding and control of these interactions will aid in practical formulations for virus inactivation and removal from contaminated surfaces.

  2. Flow mediated interactions between two cylinders at finite Re numbers

    Science.gov (United States)

    Gazzola, Mattia; Mimeau, Chloe; Tchieu, Andrew A.; Koumoutsakos, Petros

    2012-04-01

    We present simulations of two interacting moving cylinders immersed in a two-dimensional incompressible, viscous flow. Simulations are performed by coupling a wavelet-adapted, remeshed vortex method with the Brinkman penalization and projection approach. This method is validated on benchmark problems and applied to simulations of a master-slave pair of cylinders. The master cylinder's motion is imposed and the slave cylinder is let free to respond to the flow. We study the relative role of viscous and inertia effects in the cylinders interactions and identify related sharp transitions in the response of the slave. The observed differences in the behavior of cylinders with respect to corresponding potential flow simulations are discussed. In addition, it is observed that in certain situations the finite size of the slave cylinders enhances the transport so that the cylinders are advected more effectively than passive tracers placed, respectively, at the same starting position.

  3. Interaction of two walkers: wave-mediated energy and force.

    Science.gov (United States)

    Borghesi, Christian; Moukhtar, Julien; Labousse, Matthieu; Eddi, Antonin; Fort, Emmanuel; Couder, Yves

    2014-12-01

    A bouncing droplet, self-propelled by its interaction with the waves it generates, forms a classical wave-particle association called a "walker." Previous works have demonstrated that the dynamics of a single walker is driven by its global surface wave field that retains information on its past trajectory. Here we investigate the energy stored in this wave field for two coupled walkers and how it conveys an interaction between them. For this purpose, we characterize experimentally the "promenade modes" where two walkers are bound and propagate together. Their possible binding distances take discrete values, and the velocity of the pair depends on their mutual binding. The mean parallel motion can be either rectilinear or oscillating. The experimental results are recovered analytically with a simple theoretical framework. A relation between the kinetic energy of the droplets and the total energy of the standing waves is established.

  4. Bacteriocin-Mediated Competitive Interactions of Bacterial Populations and Communities

    Science.gov (United States)

    Riley, Margaret A.

    Explaining the coexistence of competing species is a major challenge in community ecology. In bacterial systems, competition is often driven by the production of bacteriocins; narrow spectrum proteinaceous toxins that serve to kill closely related species providing the producer better access to limited resources. Bacteriocin producers have been shown to competitively exclude sensitive, nonproducing strains. However, the interaction dynamics between bacteriocin producers, each lethal to its competitor, are largely unknown. Several recent studies have revealed some of the complexity of these interactions, employing a suite of in vitro, in vivo, and in silico bacterial model systems. This chapter describes the current state of knowledge regarding the population and community ecology of this potent family of toxins.

  5. Percolation of optical excitation mediated by near-field interactions

    Science.gov (United States)

    Naruse, Makoto; Kim, Song-Ju; Takahashi, Taiki; Aono, Masashi; Akahane, Kouichi; D'Acunto, Mario; Hori, Hirokazu; Thylén, Lars; Katori, Makoto; Ohtsu, Motoichi

    2017-04-01

    Optical excitation transfer in nanostructured matter has been intensively studied in various material systems for versatile applications. Herein, we theoretically and numerically discuss the percolation of optical excitations in randomly organized nanostructures caused by optical near-field interactions governed by Yukawa potential in a two-dimensional stochastic model. The model results demonstrate the appearance of two phases of percolation of optical excitation as a function of the localization degree of near-field interaction. Moreover, it indicates sublinear scaling with percolation distances when the light localization is strong. Furthermore, such a character is maximized at a particular size of environments. The results provide fundamental insights into optical excitation transfer and will facilitate the design and analysis of nanoscale signal-transfer characteristics.

  6. Quantifying Rosette Formation Mediated by Receptor-ligand Interactions

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 IntroductionRosetting is a simple assay for specific cell-cell adhesion, in which receptor- (or ligand-) coated RBCs form the rosettes with ligand- (or receptor-) expressed nucleated cells~([1]). Although routinely used by immunologists to examine the functionality of the interacting receptors and ligands, however, it has not been regarded as a quantitative method, as the measured rosette fraction has not been quantitatively related to the underlying molecular properties.Recently, we have solved probabili...

  7. Argumentation in mathematics: mediation by means of digital interactive storytelling

    Directory of Open Access Journals (Sweden)

    Giovannina Albano

    2016-04-01

    Full Text Available This work is framed in a wider research aimed at outlining an online interactive platform model organizing mathematical learning activities based on a Vygotskian approach. This paper reports on a pilot study concerning a first implementation of a mathematical Learning Activity, as part of an interactive digital storytelling in mathematics, aiming at developing students’ argumentative competences. We present the outcomes of the protocols’ analysis and discuss them with respect two main points: the production of arguments for supporting of the solution to a question and the different functioning of the device according to the student’s attitude with respect to the story and the team work. L’argomentazione in matematica: la mediazione attraverso il digital interactive storytellingQuesto lavoro è inserito in una ricerca più ampia volta a realizzare un modello di piattaforma interattiva online che implementi Learning Activity in matematica basate su un approccio vygotskiano. Questo articolo riporta uno studio pilota riguardante una prima implementazione di un task matematico, come parte di un digital storytelling interattivo in matematica, che mira a sviluppare competenze argomentative negli studenti. Presentiamo i risultati delle analisi dei protocolli e li discutiamo rispetto a due punti principali: sviluppo nella produzione di argomentazioni a supporto della risoluzione ad un quesito e diverso funzionamento del dispositivo a seconda dell’atteggiamento dello studente rispetto alla storia e al lavoro di gruppo.

  8. Coilin phosphorylation mediates interaction with SMN and SmB'.

    Science.gov (United States)

    Toyota, Cory G; Davis, Misty D; Cosman, Angela M; Hebert, Michael D

    2010-04-01

    Cajal bodies (CBs) are subnuclear domains that participate in spliceosomal small nuclear ribonucleoprotein (snRNP) biogenesis and play a part in the assembly of the spliceosomal complex. The CB marker protein, coilin, interacts with survival of motor neuron (SMN) and Sm proteins. Several coilin phosphoresidues have been identified by mass spectrometric analysis. Phosphorylation of coilin affects its self-interaction and localization in the nucleus. We hypothesize that coilin phosphorylation also impacts its binding to SMN and Sm proteins. In vitro binding studies with a C-terminal fragment of coilin and corresponding phosphomimics show that SMN binds preferentially to dephosphorylated analogs and that SmB' binds preferentially to phosphomimetic constructs. Bacterially expressed full-length coilin binds more SMN and SmB' than does the C-terminal fragment. Co-immunoprecipitation and phosphatase experiments show that SMN also binds dephosphorylated coilin in vivo. These data show that phosphorylation of coilin influences interaction with its target proteins and, thus, may be significant in managing the flow of snRNPs through the CB.

  9. Coilin phosphorylation mediates interaction with SMN and SmB′

    Science.gov (United States)

    Toyota, Cory G.; Davis, Misty D.; Cosman, Angela M.; Hebert, Michael D.

    2010-01-01

    Cajal bodies (CBs) are subnuclear domains that participate in spliceosomal small nuclear ribonucleoprotein (snRNP) biogenesis and play a part in the assembly of the spliceosomal complex. The CB marker protein, coilin, interacts with survival of motor neuron (SMN) and Sm proteins. Several coilin phosphoresidues have been identified by mass spectrometric analysis. Phosphorylation of coilin affects its self-interaction and localization in the nucleus. We hypothesize that coilin phosphorylation also impacts its binding to SMN and Sm proteins. In vitro binding studies with a C-terminal fragment of coilin and corresponding phosphomimics show that SMN binds preferentially to dephosphorylated analogs and that SmB′ binds preferentially to phosphomimetic constructs. Bacterially expressed full-length coilin binds more SMN and SmB′ than does the C-terminal fragment. Co-immunoprecipitation and phosphatase experiments show that SMN also binds dephosphorylated coilin in vivo. These data show that phosphorylation of coilin influences interaction with its target proteins and, thus, may be significant in managing the flow of snRNPs through the CB. PMID:19997741

  10. Natural enemy-mediated indirect interactions among prey species: potential for enhancing biocontrol services in agroecosystems.

    Science.gov (United States)

    Chailleux, Anaïs; Mohl, Emily K; Teixeira Alves, Mickaël; Messelink, Gerben J; Desneux, Nicolas

    2014-12-01

    Understanding how arthropod pests and their natural enemies interact in complex agroecosystems is essential for pest management programmes. Theory predicts that prey sharing a predator, such as a biological control agent, can indirectly reduce each other's density at equilibrium (apparent competition). From this premise, we (i) discuss the complexity of indirect interactions among pests in agroecosystems and highlight the importance of natural enemy-mediated indirect interactions other than apparent competition, (ii) outline factors that affect the nature of enemy-mediated indirect interactions in the field and (iii) identify the way to manipulate enemy-mediated interactions for biological control. We argue that there is a need to increase the link between community ecology theory and biological control to develop better agroecological methods of crop protection via conservation biological control. In conclusion, we identify (i) interventions to be chosen depending on agroecosystem characteristics and (ii) several lines of research that will improve the potential for enemy-mediated indirect interactions to be applied to biological control. © 2014 Society of Chemical Industry.

  11. Volatile-mediated interactions between phylogenetically different soil bacteria

    Directory of Open Access Journals (Sweden)

    Paolina eGarbeva

    2014-06-01

    Full Text Available There is increasing evidence that organic volatiles play an important role in interactions between micro-organisms in the porous soil matrix. Here we report that volatile compounds emitted by different soil bacteria can affect the growth, antibiotic production and gene expression of the soil bacterium Pseudomonas fluorescens Pf0-1. We applied a novel cultivation approach that mimics the natural nutritional heterogeneity in soil in which P. fluorescens grown on nutrient-limited agar was exposed to volatiles produced by 4 phylogenetically different bacterial isolates (Collimonas pratensis, Serratia plymuthica, Paenibacillus sp. and Pedobacter sp. growing in sand containing artificial root exudates. Contrary to our expectation, the produced volatiles stimulated rather than inhibited the growth of P. fluorescens. A genome-wide, microarray-based analysis revealed that volatiles of all 4 bacterial strains affected gene expression of P. fluorescens, but with a different pattern of gene expression for each strain. Based on the annotation of the differently expressed genes, bacterial volatiles appear to induce a chemotactic motility response in P. fluorescens, but also an oxidative stress response. A more detailed study revealed that volatiles produced by C. pratensis triggered, antimicrobial secondary metabolite production in P. fluorescens. Our results indicate that bacterial volatiles can have an important role in communication, trophic - and antagonistic interactions within the soil bacterial community.

  12. Fibronectin on the Surface of Myeloma Cell-derived Exosomes Mediates Exosome-Cell Interactions.

    Science.gov (United States)

    Purushothaman, Anurag; Bandari, Shyam Kumar; Liu, Jian; Mobley, James A; Brown, Elizabeth E; Sanderson, Ralph D

    2016-01-22

    Exosomes regulate cell behavior by binding to and delivering their cargo to target cells; however, the mechanisms mediating exosome-cell interactions are poorly understood. Heparan sulfates on target cell surfaces can act as receptors for exosome uptake, but the ligand for heparan sulfate on exosomes has not been identified. Using exosomes isolated from myeloma cell lines and from myeloma patients, we identify exosomal fibronectin as a key heparan sulfate-binding ligand and mediator of exosome-cell interactions. We discovered that heparan sulfate plays a dual role in exosome-cell interaction; heparan sulfate on exosomes captures fibronectin, and on target cells it acts as a receptor for fibronectin. Removal of heparan sulfate from the exosome surface releases fibronectin and dramatically inhibits exosome-target cell interaction. Antibody specific for the Hep-II heparin-binding domain of fibronectin blocks exosome interaction with tumor cells or with marrow stromal cells. Regarding exosome function, fibronectin-mediated binding of exosomes to myeloma cells activated p38 and pERK signaling and expression of downstream target genes DKK1 and MMP-9, two molecules that promote myeloma progression. Antibody against fibronectin inhibited the ability of myeloma-derived exosomes to stimulate endothelial cell invasion. Heparin or heparin mimetics including Roneparstat, a modified heparin in phase I trials in myeloma patients, significantly inhibited exosome-cell interactions. These studies provide the first evidence that fibronectin binding to heparan sulfate mediates exosome-cell interactions, revealing a fundamental mechanism important for exosome-mediated cross-talk within tumor microenvironments. Moreover, these results imply that therapeutic disruption of fibronectin-heparan sulfate interactions will negatively impact myeloma tumor growth and progression.

  13. Ion-mediated nucleic acid helix-helix interactions.

    Science.gov (United States)

    Tan, Zhi-Jie; Chen, Shi-Jie

    2006-07-15

    Salt ions are essential for the folding of nucleic acids. We use the tightly bound ion (TBI) model, which can account for the correlations and fluctuations for the ions bound to the nucleic acids, to investigate the electrostatic free-energy landscape for two parallel nucleic acid helices in the solution of added salt. The theory is based on realistic atomic structures of the helices. In monovalent salt, the helices are predicted to repel each other. For divalent salt, while the mean-field Poisson-Boltzmann theory predicts only the repulsion, the TBI theory predicts an effective attraction between the helices. The helices are predicted to be stabilized at an interhelix distance approximately 26-36 A, and the strength of the attractive force can reach -0.37 k(B)T/bp for helix length in the range of 9-12 bp. Both the stable helix-helix distance and the strength of the attraction are strongly dependent on the salt concentration and ion size. With the increase of the salt concentration, the helix-helix attraction becomes stronger and the most stable helix-helix separation distance becomes smaller. For divalent ions, at very high ion concentration, further addition of ions leads to the weakening of the attraction. Smaller ion size causes stronger helix-helix attraction and stabilizes the helices at a shorter distance. In addition, the TBI model shows that a decrease in the solvent dielectric constant would enhance the ion-mediated attraction. The theoretical findings from the TBI theory agree with the experimental measurements on the osmotic pressure of DNA array as well as the results from the computer simulations.

  14. Effects of learning from interaction with physical or mediated devices.

    Science.gov (United States)

    Flanagan, Robin

    2013-05-01

    Online learning tools and course materials have not only taken root: they are fully established and thriving. However, some wonder whether the missing interaction with physical, rather than virtual, tools may be undermining the foundation of more abstract spatial and cognitive skills. Sixty third-grade (28 male and 32 female) children with a mean age of 8.95 years (SD = .56 years) were randomly assigned to practice new math skills on a physical wooden Chinese abacus or a virtual Chinese abacus, programmed using Hypercard. Later; the children did equally well on a paper and pencil recognition test, but the children who had practiced with the virtual Chinese abacus were significantly worse at building on their knowledge to figure out how to use the abacus for more advanced computation than those who had practiced with the wooden Chinese abacus. This could have important implications for the early development of the foundation of mathematical, spatial, and cognitive skills.

  15. Multivalent ion-mediated nucleic acid helix-helix interactions: RNA versus DNA

    OpenAIRE

    Wu, Yuan-Yan; Zhang, Zhong-Liang; Zhang, Jin-Si; Zhu, Xiao-Long; Tan, Zhi-Jie

    2015-01-01

    Ion-mediated interaction is critical to the structure and stability of nucleic acids. Recent experiments suggest that the multivalent ion-induced aggregation of double-stranded (ds) RNAs and DNAs may strongly depend on the topological nature of helices, while there is still lack of an understanding on the relevant ion-mediated interactions at atomistic level. In this work, we have directly calculated the potentials of mean force (PMF) between two dsRNAs and between two dsDNAs in Cobalt Hexamm...

  16. Transcription factors mediate long-range enhancer-promoter interactions.

    Science.gov (United States)

    Nolis, Ilias K; McKay, Daniel J; Mantouvalou, Eva; Lomvardas, Stavros; Merika, Menie; Thanos, Dimitris

    2009-12-01

    We examined how remote enhancers establish physical communication with target promoters to activate gene transcription in response to environmental signals. Although the natural IFN-beta enhancer is located immediately upstream of the core promoter, it also can function as a classical enhancer element conferring virus infection-dependent activation of heterologous promoters, even when it is placed several kilobases away from these promoters. We demonstrated that the remote IFN-beta enhancer "loops out" the intervening DNA to reach the target promoter. These chromatin loops depend on sequence-specific transcription factors bound to the enhancer and the promoter and thus can explain the specificity observed in enhancer-promoter interactions, especially in complex genetic loci. Transcription factor binding sites scattered between an enhancer and a promoter can work as decoys trapping the enhancer in nonproductive loops, thus resembling insulator elements. Finally, replacement of the transcription factor binding sites involved in DNA looping with those of a heterologous prokaryotic protein, the lambda repressor, which is capable of loop formation, rescues enhancer function from a distance by re-establishing enhancer-promoter loop formation.

  17. Peer mediation encourages student learning and context interaction

    Directory of Open Access Journals (Sweden)

    Concepción MONGE CRESPO

    2012-12-01

    Full Text Available Teenagers share time with «peers», with friends, while enjoying and feeling understood and accepted by them. For students of ESO, peers hold a central place in their life, hence their multiple and diverse experiences, for the most part, are performed along with them. During one course, the 2009/2010 academic year, I proposed that they also should share their educational tasks, support each other, help one another, and together achieve better and more efficiently the proposed objective: to pass learning together. Nowadays before this society, framed by new technologies of information and communication, it becomes very necessary for students to work in teams, think critically and creatively and think about their own learning process. Likewise, many studies hold that learning is most successful when it meets certain requirements such as: Taking place in real situations, having a direct and qualified feedback about lear- ning, working together in solving a problem, reflect on their performance and being able to perceive one’s self as competent persons capable of action. Relying on these conditions and knowing that learning is primarily a social process in which students learn best in collaboration with: peers, teachers, parents and/or other context agents where they live and interact provided they are actively engaged in meaningful and interesting tasks.This research was conducted with students from 2º ESO.

  18. Social Skills as a Mediator between Anxiety Symptoms and Peer Interactions among Children and Adolescents

    Science.gov (United States)

    Motoca, Luci M.; Williams, Sandra; Silverman, Wendy K.

    2012-01-01

    Objective The present study used a cross-sectional design to examine the relations among youth anxiety symptoms, positive and negative peer interactions, and social skills. Also examined was the mediating role of social skills in the relations between youth anxiety symptoms and positive and negative peer interactions. Youth sex and age were examined as moderators. Method The sample consisted of 397 children and adolescents (M = 10.11 years; 53.4% boys; 74.8% Hispanic Latino) referred to an anxiety disorders clinic. Anxiety symptoms, positive and negative peer interactions, and social skills were assessed using youth and parent ratings. Results Structural equation modeling results indicated that for youth ratings only, youth anxiety symptoms were negatively related to positive peer interactions controlling for primary social phobia and comorbid depressive disorders. For both youth and parent ratings, youth anxiety symptoms were positively related to negative peer interactions and negatively related to social skills. Also for both youth and parent ratings, social skills mediated the relations between youth anxiety symptoms and positive and negative peer interactions. For parent ratings only, the effects of youth anxiety symptoms and social skills on peer interactions were significantly moderated by youth age. Youth sex was not a significant moderator using youth and parent ratings. Conclusions Findings suggest difficulties with social skills and peer interactions are problematic features of youth referred for anxiety problems. Findings highlight the need to improve understanding of anxiety symptoms, social skills, and peer interactions in this population. PMID:22471319

  19. A Cross-Device Spatial Workspace Supporting Artifact-Mediated Collaboration in Interaction Design

    OpenAIRE

    Geyer, Florian; Reiterer, Harald

    2010-01-01

    In this paper we present our approach to support artifact-mediated collaboration in interaction design. We argue that the extensive number and the diversity of artifacts created and reflected upon during collaborative design activities as well as transitions between physical and digital representations impose both a challenge and opportunity for supporting interaction design practice. The design principles for our experimental tool that we introduce within this paper are based on a cross-devi...

  20. Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb.

    Science.gov (United States)

    Wang, Wei; Yao, Xiao; Huang, Yan; Hu, Xiangming; Liu, Runzhong; Hou, Dongming; Chen, Ruichuan; Wang, Gang

    2013-01-01

    The Mediator is a multi-subunit complex that transduces regulatory information from transcription regulators to the RNA polymerase II apparatus. Growing evidence suggests that Mediator plays roles in multiple stages of eukaryotic transcription, including elongation. However, the detailed mechanism by which Mediator regulates elongation remains elusive. In this study, we demonstrate that Mediator MED23 subunit controls a basal level of transcription by recruiting elongation factor P-TEFb, via an interaction with its CDK9 subunit. The mRNA level of Egr1, a MED23-controlled model gene, is reduced 4-5 fold in Med23 (-/-) ES cells under an unstimulated condition, but Med23-deficiency does not alter the occupancies of RNAP II, GTFs, Mediator complex, or activator ELK1 at the Egr1 promoter. Instead, Med23 depletion results in a significant decrease in P-TEFb and RNAP II (Ser2P) binding at the coding region, but no changes for several other elongation regulators, such as DSIF and NELF. ChIP-seq revealed that Med23-deficiency partially reduced the P-TEFb occupancy at a set of MED23-regulated gene promoters. Further, we demonstrate that MED23 interacts with CDK9 in vivo and in vitro. Collectively, these results provide the mechanistic insight into how Mediator promotes RNAP II into transcription elongation.

  1. Interaction between muscarinic receptor subtype signal transduction pathways mediating bladder contraction

    Science.gov (United States)

    BRAVERMAN, ALAN S.; TALLARIDA, RONALD J.; RUGGIERI, MICHAEL R.

    2012-01-01

    M3 muscarinic receptors mediate cholinergic-induced contraction in most smooth muscles. However, in the denervated rat bladder, M2 receptors participate in contraction because M3-selective antagonists [para-fluoro-hexahydro-sila-diphenidol (p-F-HHSiD) and 4-DAMP] have low affinities. However, the affinity of the M2-selective antagonist methoctramine in the denervated bladder is consistent with M3 receptor mediating contraction. It is possible that two pathways interact to mediate contraction: one mediated by the M2 receptor and one by the M3 receptor. To determine whether an interaction exists, the inhibitory potencies of combinations of methoctramine and p-F-HHSiD for reversing cholinergic contractions were measured. In normal bladders, all combinations gave additive effects. In denervated bladders, synergistic effects were seen with the 10:1 and 1:1 (methoctramine:p-F-HHSiD wt/wt) combinations. After application of the sarcoplasmic reticulum ATPase inhibitor thapsigargin to normal tissue, the 10:1 and 1:1 ratios became synergistic, mimicking denervated tissue. Thus in normal bladders both M2 and M3 receptors can induce contraction. In the denervated bladder, the M2 and the M3 receptors interact in a facilitatory manner to mediate contraction. PMID:12185001

  2. Interaction between muscarinic receptor subtype signal transduction pathways mediating bladder contraction.

    Science.gov (United States)

    Braverman, Alan S; Tallarida, Ronald J; Ruggieri, Michael R

    2002-09-01

    M(3) muscarinic receptors mediate cholinergic-induced contraction in most smooth muscles. However, in the denervated rat bladder, M(2) receptors participate in contraction because M(3)-selective antagonists [para-fluoro-hexahydro-sila-diphenidol (p-F-HHSiD) and 4-DAMP] have low affinities. However, the affinity of the M(2)-selective antagonist methoctramine in the denervated bladder is consistent with M(3) receptor mediating contraction. It is possible that two pathways interact to mediate contraction: one mediated by the M(2) receptor and one by the M(3) receptor. To determine whether an interaction exists, the inhibitory potencies of combinations of methoctramine and p-F-HHSiD for reversing cholinergic contractions were measured. In normal bladders, all combinations gave additive effects. In denervated bladders, synergistic effects were seen with the 10:1 and 1:1 (methoctramine:p-F-HHSiD wt/wt) combinations. After application of the sarcoplasmic reticulum ATPase inhibitor thapsigargin to normal tissue, the 10:1 and 1:1 ratios became synergistic, mimicking denervated tissue. Thus in normal bladders both M(2) and M(3) receptors can induce contraction. In the denervated bladder, the M(2) and the M(3) receptors interact in a facilitatory manner to mediate contraction.

  3. Extracellular Protein Interactions Mediated by the Neural Cell Adhesion Molecule, NCAM: Heterophilic Interactions Between NCAM and Cell Adhesion Molecules, Extracellular Matrix Proteins, and Viruses

    DEFF Research Database (Denmark)

    Nielsen, Janne; Kulahin, Nikolaj; Walmod, Peter

    2008-01-01

    Cell adhesion molecules (CAMs) mediate cell-to-cell interactions and interactions between cells and the extracellular matrix (ECM). The neural cell adhesion molecule (NCAM), a prototypic member of the immunoglobulin (Ig) superfamily of CAMs, mediates adhesion through homophilic and heterophilic i...

  4. Targeting CD47-SIRPα interactions for potentiating therapeutic antibody-mediated tumor cell destruction by phagocytes

    NARCIS (Netherlands)

    Zhao, X.W.

    2014-01-01

    The primary aim of the studies described in this thesis was to investigate the role of CD47-SIRPα interactions in therapeutic antibody-dependent tumor cell destruction by human phagocytes and also explore the killing mechanism(s) by which human phagocytes, and in particular human neutrophils, mediat

  5. Oral Computer-Mediated Interaction between L2 Learners: It's about Time!

    Science.gov (United States)

    Yanguas, Inigo

    2010-01-01

    This study explores task-based, synchronous oral computer-mediated communication (CMC) among intermediate-level learners of Spanish. In particular, this paper examines (a) how learners in video and audio CMC groups negotiate for meaning during task-based interaction, (b) possible differences between both oral CMC modes and traditional face-to-face…

  6. 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.,

  7. Children's Temperament and Academic Skill Development during First Grade: Teachers' Interaction Styles as Mediators

    Science.gov (United States)

    Viljaranta, Jaana; Aunola, Kaisa; Mullola, Sari; Virkkala, Johanna; Hirvonen, Riikka; Pakarinen, Eija; Nurmi, Jari-Erik

    2015-01-01

    The present study followed 156 Finnish children (M[subscript age] = 7.25 years) during the first grade of primary school to examine to what extent parent- and teacher-rated temperament impacts children's math and reading skill development during the first grade, and the extent to which this impact would be mediated by teachers' interaction styles…

  8. Plant-plant interactions mediate the plastic and genotypic response of Plantago asiatica to CO

    NARCIS (Netherlands)

    Loon, Van Marloes P.; Rietkerk, Max; Dekker, Stefan C.; Hikosaka, Kouki; Ueda, Miki U.; Anten, Niels P.R.

    2016-01-01

    Background and Aims The rising atmospheric CO2 concentration ([CO2]) is a ubiquitous selective force that may strongly impact species distribution and vegetation functioning. Plant-plant interactions could mediate the trajectory of vegetation responses to elevated [CO2<

  9. Children's Temperament and Academic Skill Development during First Grade: Teachers' Interaction Styles as Mediators

    Science.gov (United States)

    Viljaranta, Jaana; Aunola, Kaisa; Mullola, Sari; Virkkala, Johanna; Hirvonen, Riikka; Pakarinen, Eija; Nurmi, Jari-Erik

    2015-01-01

    The present study followed 156 Finnish children (M[subscript age] = 7.25 years) during the first grade of primary school to examine to what extent parent- and teacher-rated temperament impacts children's math and reading skill development during the first grade, and the extent to which this impact would be mediated by teachers' interaction styles…

  10. Tree-mediated interactions between the jack pine budworm and a mountain pine beetle fungal

    Science.gov (United States)

    Nadir Erbilgin; Jessie Colgan

    2012-01-01

    Coniferous trees deploy a combination of constitutive (pre-existing) and induced (post-invasion) structural and biochemical defenses against invaders. Induced responses can also alter host suitability for other organisms sharing the same host, which may result in indirect, plant-mediated, interactions between different species of attacking organisms. Current range and...

  11. Interaction Processes as a Mediating Factor between Children's Externalized Behaviour Difficulties and Engagement in Preschool

    Science.gov (United States)

    Sjöman, Madeleine; Granlund, Mats; Almqvist, Lena

    2016-01-01

    This study examined social interaction as a mediator between externalized behaviour difficulties and children's engagement in preschool. Data from 663 children (340 boys), aged 18-71 months, were collected at 81 Swedish preschool units in six municipalities to test a path model that included child, teacher, and child groups. The results indicated…

  12. Activity Theory and Technology Mediated Interaction: Cognitive Scaffolding Using Question-Based Consultation on "Facebook"

    Science.gov (United States)

    Rambe, Patient

    2012-01-01

    Studies that employed activity theory as a theoretical lens for exploring computer-mediated interaction have not adopted social media as their object of study. However, social media provides lecturers with personalised learning environments for diagnostic and prognostic assessments of student mastery of content and deep learning. The integration…

  13. Mediated Vocabulary in Native Speaker-Learner Interactions during an Oral Portfolio Activity

    Science.gov (United States)

    Tocaimaza-Hatch, C. Cecilia

    2016-01-01

    This project investigated vocabulary learning from a sociocultural perspective--in particular, the way in which lexical knowledge was mediated in Spanish second language (L2) learners' and native speakers' (NSs') interactions. Nine students who were enrolled in an advanced conversation course completed an oral portfolio assignment consisting of…

  14. Discourse Management Strategies in Face-to-Face and Computer-Mediated Decision Making Interactions.

    Science.gov (United States)

    Condon, Sherri L.; Cech, Claude G.

    1996-01-01

    Compares discourse management strategies in face-to-face and computer-mediated interactions involving four decision-making tasks. Examines these issues in qualitative and quantitative analyses of data using an utterance-unit coding system to identify discourse functions. Finds that participants compensate for decreased efficiency by adopting…

  15. Interaction Processes as a Mediating Factor between Children's Externalized Behaviour Difficulties and Engagement in Preschool

    Science.gov (United States)

    Sjöman, Madeleine; Granlund, Mats; Almqvist, Lena

    2016-01-01

    This study examined social interaction as a mediator between externalized behaviour difficulties and children's engagement in preschool. Data from 663 children (340 boys), aged 18-71 months, were collected at 81 Swedish preschool units in six municipalities to test a path model that included child, teacher, and child groups. The results indicated…

  16. 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,…

  17. 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…

  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. 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…

  20. 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…

  1. A conserved patch of hydrophobic amino acids modulates Myb activity by mediating protein-protein interactions.

    Science.gov (United States)

    Dukare, Sandeep; Klempnauer, Karl-Heinz

    2016-07-01

    The transcription factor c-Myb plays a key role in the control of proliferation and differentiation in hematopoietic progenitor cells and has been implicated in the development of leukemia and certain non-hematopoietic tumors. c-Myb activity is highly dependent on the interaction with the coactivator p300 which is mediated by the transactivation domain of c-Myb and the KIX domain of p300. We have previously observed that conservative valine-to-isoleucine amino acid substitutions in a conserved stretch of hydrophobic amino acids have a profound effect on Myb activity. Here, we have explored the function of the hydrophobic region as a mediator of protein-protein interactions. We show that the hydrophobic region facilitates Myb self-interaction and binding of the histone acetyl transferase Tip60, a previously identified Myb interacting protein. We show that these interactions are affected by the valine-to-isoleucine amino acid substitutions and suppress Myb activity by interfering with the interaction of Myb and the KIX domain of p300. Taken together, our work identifies the hydrophobic region in the Myb transactivation domain as a binding site for homo- and heteromeric protein interactions and leads to a picture of the c-Myb transactivation domain as a composite protein binding region that facilitates interdependent protein-protein interactions of Myb with regulatory proteins.

  2. Evaluating depressive symptom interactions on adolescent smoking prevention program mediators: a mediated moderation analysis.

    Science.gov (United States)

    Sakuma, Kari-Lyn Kobayakawa; Sun, Ping; Unger, Jennifer B; Johnson, C Anderson

    2010-11-01

    Smoking prevention interventions have been shown to be effective in reducing smoking prevalence in the United States. Further work is needed to address smoking in China, where over one third of the world's current smokers reside. China, with more than 60% of the male population being smokers, also presents a unique opportunity to test cognitive processes involved in depression, social influences, and smoking. Adolescents at-risk for developing depression may process social information differently from low-risk counterparts. The Wuhan Smoking Prevention Trial was a school-based longitudinal randomized controlled trial aimed at preventing initiation and escalation of adolescent smoking behaviors. Thousand three hundred and ninety-one male seventh-grade students were assessed with a 200-item paper-and-pencil baseline survey, and it was readministered 1 year later following program implementation. Friend prevalence estimates were significantly higher among 30-day smokers and among those at highest risk for depression symptoms. The program appeared to be successful in changing the perception of friend smoking prevalence only among adolescents with a comorbidity of high scores of depression symptoms and who have experimented previously with smoking. This Program x Comorbidity interaction on perceived friend smoking prevalence was significant in predicting 30-day smoking 1 year after program implementation. This study provides evidence that those adolescents with high levels of depressive symptoms may be more sensitive to social influences associated with smoking prevalence. Individual Disposition x Social Environmental Influences may be important when developing future effective prevention programming.

  3. New effects in the interaction between electromagnetic sources mediated by nonminimal Lorentz violating interactions

    CERN Document Server

    Borges, L H C; Barone, F A

    2016-01-01

    This paper is dedicated to the study of interactions between external sources for the electromagnetic field in a Lorentz symmetry breaking scenario. We focus on a particular higher derivative, Lorentz violating interaction that arises from a specific model that was argued to lead to interesting effects in the low energy phenomenology of light pseudoscalars interacting with photons. The kind of higher derivative Lorentz violating interaction we discuss do not appear in the well known Standard Model Extension, therefore they are called nonminimal. They are usually expected to be relevant only at very high energies, but we argue they might also induce relevant effects in low energy phenomena. Special attention is given for phenomena that have no counterpart in Maxwell theory.

  4. New effects in the interaction between electromagnetic sources mediated by nonminimal Lorentz violating interactions

    Energy Technology Data Exchange (ETDEWEB)

    Borges, L.H.C.; Ferrari, A.F. [Universidade Federal do ABC, Centro de Ciencias Naturais e Humanas, Santo Andre, SP (Brazil); Barone, F.A. [Universidade Federal de Itajuba, IFQ, Itajuba, MG (Brazil)

    2016-11-15

    This paper is dedicated to the study of interactions between external sources for the electromagnetic field in the presence of Lorentz symmetry breaking. We focus on a higher derivative, Lorentz violating interaction that arises from a specific model that was argued to lead to interesting effects in the low energy phenomenology of light pseudoscalars interacting with photons. The kind of higher derivative Lorentz violating interaction we discuss are called nonminimal. They are usually expected to be relevant only at very high energies, but we argue they might also induce relevant effects in low energy phenomena. Indeed, we show that the Lorentz violating background considered by us leads to several phenomena that have no counterpart in Maxwell theory, such as nontrivial torques on isolated electric dipoles, as well as nontrivial forces and torques between line currents and point like charges, as well as among Dirac strings and other electromagnetic sources. (orig.)

  5. WW domain-mediated interaction with Wbp2 is important for the oncogenic property of TAZ.

    Science.gov (United States)

    Chan, S W; Lim, C J; Huang, C; Chong, Y F; Gunaratne, H J; Hogue, K A; Blackstock, W P; Harvey, K F; Hong, W

    2011-02-03

    The transcriptional co-activators YAP and TAZ are downstream targets inhibited by the Hippo tumor suppressor pathway. YAP and TAZ both possess WW domains, which are important protein-protein interaction modules that mediate interaction with proline-rich motifs, most commonly PPXY. The WW domains of YAP have complex regulatory roles as exemplified by recent reports showing that they can positively or negatively influence YAP activity in a cell and context-specific manner. In this study, we show that the WW domain of TAZ is important for it to transform both MCF10A and NIH3T3 cells and to activate transcription of ITGB2 but not CTGF, as introducing point mutations into the WW domain of TAZ (WWm) abolished its transforming and transcription-promoting ability. Using a proteomic approach, we discovered potential regulatory proteins that interact with TAZ WW domain and identified Wbp2. The interaction of Wbp2 with TAZ is dependent on the WW domain of TAZ and the PPXY-containing C-terminal region of Wbp2. Knockdown of endogenous Wbp2 suppresses, whereas overexpression of Wbp2 enhances, TAZ-driven transformation. Forced interaction of WWm with Wbp2 by direct C-terminal fusion of full-length Wbp2 or its TAZ-interacting C-terminal domain restored the transforming and transcription-promoting ability of TAZ. These results suggest that the WW domain-mediated interaction with Wbp2 promotes the transforming ability of TAZ.

  6. Genome-wide occupancy profile of mediator and the Srb8-11 module reveals interactions with coding regions

    DEFF Research Database (Denmark)

    Zhu, Xuefeng; Wirén, Marianna; Sinha, Indranil

    2006-01-01

    to investigate genome-wide localization of Mediator and the Srb8-11 module in fission yeast. Mediator and the Srb8-11 module display similar binding patterns, and interactions with promoters and upstream activating sequences correlate with increased transcription activity. Unexpectedly, Mediator also interacts...... with the downstream coding region of many genes. These interactions display a negative bias for positions closer to the 5' ends of open reading frames (ORFs) and appear functionally important, because downregulation of transcription in a temperature-sensitive med17 mutant strain correlates with increased Mediator...

  7. Role of protein-protein interactions in cytochrome P450-mediated drug metabolism and toxicity.

    Science.gov (United States)

    Kandel, Sylvie E; Lampe, Jed N

    2014-09-15

    Through their unique oxidative chemistry, cytochrome P450 monooxygenases (CYPs) catalyze the elimination of most drugs and toxins from the human body. Protein-protein interactions play a critical role in this process. Historically, the study of CYP-protein interactions has focused on their electron transfer partners and allosteric mediators, cytochrome P450 reductase and cytochrome b5. However, CYPs can bind other proteins that also affect CYP function. Some examples include the progesterone receptor membrane component 1, damage resistance protein 1, human and bovine serum albumin, and intestinal fatty acid binding protein, in addition to other CYP isoforms. Furthermore, disruption of these interactions can lead to altered paths of metabolism and the production of toxic metabolites. In this review, we summarize the available evidence for CYP protein-protein interactions from the literature and offer a discussion of the potential impact of future studies aimed at characterizing noncanonical protein-protein interactions with CYP enzymes.

  8. Interactional justice as a mediator of the relationship between pay for performance and job satisfaction

    Directory of Open Access Journals (Sweden)

    Azman Ismail

    2011-11-01

    Full Text Available Purpose: This study was conducted to examine the effect of pay for performance and interactional justice on job satisfaction.Design/methodology/approach: A survey method was used to collect 107 usable questionnaires from employees who work in the US subsidiary manufacturing firm operating in a silicon valley in East Malaysia, Malaysia.Findings: The outcomes showed two important findings: first, relationship between interactional justice and adequacy of pay significantly correlated with job satisfaction. Second, relationship between interactional justice and participation in pay systems significantly correlated with job satisfaction. Statistically, this result confirms that interactional justice does act as a mediating variable in the pay for performance models of the studied organization.Originality/value: Most previous research tested a direct effect of pay for performance on job satisfaction. Unlike such research approach, this study discovers that interactional justice has strengthened the effect of pay for performance on job satisfaction in a compensation system framework.

  9. Multiple protein domains mediate interaction between Bcl10 and MALT1.

    Science.gov (United States)

    Langel, Felicia D; Jain, Nidhi A; Rossman, Jeremy S; Kingeter, Lara M; Kashyap, Anuj K; Schaefer, Brian C

    2008-11-21

    Bcl10 and MALT1 are essential mediators of NF-kappaB activation in response to the triggering of a diverse array of transmembrane receptors, including antigen receptors. Additionally, both proteins are translocation targets in MALT lymphoma. Thus, a detailed understanding of the interaction between these mediators is of considerable biological importance. Previous studies have indicated that a 13-amino acid region downstream of the Bcl10 caspase recruitment domain (CARD) is responsible for interacting with the immunoglobulin-like domains of MALT1. We now provide evidence that the death domain of MALT1 and the CARD of Bcl10 also contribute to Bcl10-MALT1 interactions. Although a direct interaction between the MALT1 death domain and Bcl10 cannot be detected via immunoprecipitation, FRET data strongly suggest that the death domain of MALT1 contributes significantly to the association between Bcl10 and MALT1 in T cells in vivo. Furthermore, analysis of point mutants of conserved residues of Bcl10 shows that the Bcl10 CARD is essential for interaction with the MALT1 N terminus. Mutations that disrupt proper folding of the Bcl10 CARD strongly impair Bcl10-MALT1 interactions. Molecular modeling and functional analyses of Bcl10 point mutants suggest that residues Asp(80) and Glu(84) of helix 5 of the Bcl10 CARD directly contact MALT1. Together, these data demonstrate that the association between Bcl10 and MALT1 involves a complex interaction between multiple protein domains. Moreover, the Bcl10-MALT1 interaction is the second reported example of interactions between a CARD and a non-CARD protein region, which suggests that many signaling cascades may utilize CARD interactions with non-CARD domains.

  10. Direct Detection Signatures of Self-Interacting Dark Matter with a Light Mediator

    CERN Document Server

    Del Nobile, Eugenio; Yu, Hai-Bo

    2015-01-01

    Self-interacting dark matter (SIDM) is a simple and well-motivated scenario that could explain long-standing puzzles in structure formation on small scales. If the required self-interaction arises through a light mediator (with mass $\\sim 10$ MeV) in the dark sector, this new particle must be unstable to avoid overclosing the universe. The decay of the light mediator could happen due to a weak coupling of the hidden and visible sectors, providing new signatures for direct detection experiments. The SIDM nuclear recoil spectrum is more peaked towards low energies compared to the usual case of contact interactions, because the mediator mass is comparable to the momentum transfer of nuclear recoils. We show that the SIDM signal could be distinguished from that of DM particles with contact interactions by considering the time-average energy spectrum in experiments employing different target materials, or the average and modulated spectra in a single experiment. Using current limits from LUX and SuperCDMS, we also...

  11. Direct detection signatures of self-interacting dark matter with a light mediator

    Energy Technology Data Exchange (ETDEWEB)

    Nobile, Eugenio Del [Department of Physics and Astronomy, University of California, Los Angeles,CA, 90095 (United States); Kaplinghat, Manoj [Department of Physics and Astronomy, University of California, Riverside,CA, 92507 (United States); Yu, Hai-Bo [Department of Physics and Astronomy, University of California, Irvine,CA, 92697 (United States)

    2015-10-27

    Self-interacting dark matter (SIDM) is a simple and well-motivated scenario that could explain long-standing puzzles in structure formation on small scales. If the required self-interaction arises through a light mediator (with mass ∼10 MeV) in the dark sector, this new particle must be unstable to avoid overclosing the universe. The decay of the light mediator could happen due to a weak coupling of the hidden and visible sectors, providing new signatures for direct detection experiments. The SIDM nuclear recoil spectrum is more peaked towards low energies compared to the usual case of contact interactions, because the mediator mass is comparable to the momentum transfer of nuclear recoils. We show that the SIDM signal could be distinguished from that of DM particles with contact interactions by considering the time-average energy spectrum in experiments employing different target materials, or the average and modulated spectra in a single experiment. Using current limits from LUX and SuperCDMS, we also derive strong bounds on the mixing parameter between hidden and visible sector.

  12. Pilot whales attracted to killer whale sounds: acoustically-mediated interspecific interactions in cetaceans.

    Directory of Open Access Journals (Sweden)

    Charlotte Curé

    Full Text Available In cetaceans' communities, interactions between individuals of different species are often observed in the wild. Yet, due to methodological and technical challenges very little is known about the mediation of these interactions and their effect on cetaceans' behavior. Killer whales (Orcinus orca are a highly vocal species and can be both food competitors and potential predators of many other cetaceans. Thus, the interception of their vocalizations by unintended cetacean receivers may be particularly important in mediating interspecific interactions. To address this hypothesis, we conducted playbacks of killer whale vocalizations recorded during herring-feeding activity to free-ranging long-finned pilot whales (Globicephala melas. Using a multi-sensor tag, we were able to track the whales and to monitor changes of their movements and social behavior in response to the playbacks. We demonstrated that the playback of killer whale sounds to pilot whales induced a clear increase in group size and a strong attraction of the animals towards the sound source. These findings provide the first experimental evidence that the interception of heterospecific vocalizations can mediate interactions between different cetacean species in previously unrecognized ways.

  13. Pilot whales attracted to killer whale sounds: acoustically-mediated interspecific interactions in cetaceans.

    Science.gov (United States)

    Curé, Charlotte; Antunes, Ricardo; Samarra, Filipa; Alves, Ana Catarina; Visser, Fleur; Kvadsheim, Petter H; Miller, Patrick J O

    2012-01-01

    In cetaceans' communities, interactions between individuals of different species are often observed in the wild. Yet, due to methodological and technical challenges very little is known about the mediation of these interactions and their effect on cetaceans' behavior. Killer whales (Orcinus orca) are a highly vocal species and can be both food competitors and potential predators of many other cetaceans. Thus, the interception of their vocalizations by unintended cetacean receivers may be particularly important in mediating interspecific interactions. To address this hypothesis, we conducted playbacks of killer whale vocalizations recorded during herring-feeding activity to free-ranging long-finned pilot whales (Globicephala melas). Using a multi-sensor tag, we were able to track the whales and to monitor changes of their movements and social behavior in response to the playbacks. We demonstrated that the playback of killer whale sounds to pilot whales induced a clear increase in group size and a strong attraction of the animals towards the sound source. These findings provide the first experimental evidence that the interception of heterospecific vocalizations can mediate interactions between different cetacean species in previously unrecognized ways.

  14. Benzodiazepine receptor-mediated behavioral effects of nitrous oxide in the rat social interaction test.

    Science.gov (United States)

    Quock, R M; Wetzel, P J; Maillefer, R H; Hodges, B L; Curtis, B A; Czech, D A

    1993-09-01

    The present study was conducted to ascertain whether an anxiolytic effect of nitrous oxide was demonstrable in rats using the social interaction test and whether this drug effect might be mediated by benzodiazepine receptors. Compared to behavior of vehicle-pretreated, room air-exposed rats, rat pairs exposed to nitrous oxide showed a generally inverted U-shaped dose-response curve with the maximum increase in social interaction encounters occurring at 25% and significant increase in time of active social interaction at 15-35%; higher concentrations produced a sedative effect that reduced social interaction. Treatment with 5.0 mg/kg of the anxiolytic benzodiazepine chlordiazepoxide also increased social interaction. Pretreatment with 10 mg/kg of the benzodiazepine receptor blocker flumazenil, which alone had no effect, significantly antagonized the social interaction-increasing effects of both nitrous oxide and chlordiazepoxide. In summary, these findings suggest that nitrous oxide produces a flumazenil-sensitive effect comparable to that of chlordiazepoxide and implicate central benzodiazepine mechanisms in mediation of the anxiolytic effect of nitrous oxide.

  15. Susceptibility to predation affects trait-mediated indirect interactions by reversing interspecific competition.

    Directory of Open Access Journals (Sweden)

    Sophie L Mowles

    Full Text Available Numerous studies indicate that the behavioral responses of prey to the presence of predators can have an important role in structuring assemblages through trait-mediated indirect interactions. Few studies, however, have addressed how relative susceptibility to predation influences such interactions. Here we examine the effect of chemical cues from the common shore crab Carcinus maenas on the foraging behavior of two common intertidal gastropod molluscs. Of the two model consumers studied, Littorina littorea is morphologically more vulnerable to crab predation than Gibbula umbilicalis, and it exhibited greater competitive ability in the absence of predation threat. However, Littorina demonstrated a greater anti-predator response when experimentally exposed to predation cues, resulting in a lower level of foraging. This reversed the competitive interaction, allowing Gibbula substantially increased access to shared resources. Our results demonstrate that the susceptibility of consumers to predation can influence species interactions, and suggest that inter-specific differences in trait-mediated indirect interactions are another mechanism through which non-consumptive predator effects may influence trophic interactions.

  16. From interaction to interaction: Exploring shared resources constructed through and mediating classroom science learning

    Science.gov (United States)

    Tang, Xiaowei

    Recent reform documents and science education literature emphasize the importance of scientific argumentation as a discourse and practice of science that should be supported in school science learning. Much of this literature focuses on the structure of argument, whether for assessing the quality of argument or designing instructional scaffolds. This study challenges the narrowness of this research paradigm and argues for the necessity of examining students' argumentative practices as rooted in the complex, evolving system of the classroom. Employing a sociocultural-historical lens of activity theory (Engestrom, 1987, 1999), discourse analysis is employed to explore how a high school biology class continuously builds affordances and constraints for argumentation practices through interactions. The ways in which argumentation occurs, including the nature of teacher and student participation, are influenced by learning goals, classroom norms, teacher-student relationships and epistemological stances constructed through a class' interactive history. Based on such findings, science education should consider promoting classroom scientific argumentation as a long-term process, requiring supportive resources that develop through continuous classroom interactions. Moreover, in order to understand affordances that support disciplinary learning in classroom, we need to look beyond just disciplinary interactions. This work has implications for classroom research on argumentation and teacher education, specifically, the preparation of teachers for secondary science teaching.

  17. Direct interaction between GluR2 and GAPDH regulates AMPAR-mediated excitotoxicity

    Directory of Open Access Journals (Sweden)

    Wang Min

    2012-04-01

    Full Text Available Abstract Over-activation of AMPARs (α−amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptors is implicated in excitotoxic neuronal death associated with acute brain insults, such as ischemic stroke. However, the specific molecular mechanism by which AMPARs, especially the calcium-impermeable AMPARs, induce neuronal death remains poorly understood. Here we report the identification of a previously unrecognized molecular pathway involving a direct protein-protein interaction that underlies GluR2-containing AMPAR-mediated excitotoxicity. Agonist stimulation of AMPARs promotes GluR2/GAPDH (glyceraldehyde-3-phosphate dehydrogenase complex formation and subsequent internalization. Disruption of GluR2/GAPDH interaction by administration of an interfering peptide prevents AMPAR-mediated excitotoxicity and protects against damage induced by oxygen-glucose deprivation (OGD, an in vitro model of brain ischemia.

  18. The prey's scent - Volatile organic compound mediated interactions between soil bacteria and their protist predators.

    Science.gov (United States)

    Schulz-Bohm, Kristin; Geisen, Stefan; Wubs, E R Jasper; Song, Chunxu; de Boer, Wietse; Garbeva, Paolina

    2017-03-01

    Protists are major predators of bacteria in soils. However, it remains unknown how protists sense their prey in this highly complex environment. Here, we investigated whether volatile organic compounds (VOCs) of six phylogenetic distinct soil bacteria affect the performance of three different soil protists and how that relates to direct feeding interactions. We observed that most bacteria affected protist activity by VOCs. However, the response of protists to the VOCs was strongly dependent on both the bacterial and protist interacting partner. Stimulation of protist activity by volatiles and in direct trophic interaction assays often coincided, suggesting that VOCs serve as signals for protists to sense suitable prey. Furthermore, bacterial terpene synthase mutants lost the ability to affect protists, indicating that terpenes represent key components of VOC-mediated communication. Overall, we demonstrate that volatiles are directly involved in protist-bacterial predator-prey interactions.

  19. Ion-wake-mediated particle interaction in a magnetized-plasma flow.

    Science.gov (United States)

    Carstensen, Jan; Greiner, Franko; Piel, Alexander

    2012-09-28

    The interaction forces between dust grains in a flowing plasma are strongly modified by the formation of ion wakes. Here, we study the interparticle forces mediated by ion wakes in the presence of a strong magnetic field parallel to the ion flow. For increasing magnetic flux densities a continuous decay of the interaction force is observed. This transition occurs at parameters, where the ion cyclotron frequency starts to exceed the ion plasma frequency, which is in agreement with theoretical predictions. The modification of the interparticle forces is important for the understanding of the structure and dynamics of magnetized dusty plasmas.

  20. Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion

    Science.gov (United States)

    Luisier, Raphaëlle; Unterberger, Elif B.; Goodman, Jay I.; Schwarz, Michael; Moggs, Jonathan; Terranova, Rémi; van Nimwegen, Erik

    2014-01-01

    Gene regulatory interactions underlying the early stages of non-genotoxic carcinogenesis are poorly understood. Here, we have identified key candidate regulators of phenobarbital (PB)-mediated mouse liver tumorigenesis, a well-characterized model of non-genotoxic carcinogenesis, by applying a new computational modeling approach to a comprehensive collection of in vivo gene expression studies. We have combined our previously developed motif activity response analysis (MARA), which models gene expression patterns in terms of computationally predicted transcription factor binding sites with singular value decomposition (SVD) of the inferred motif activities, to disentangle the roles that different transcriptional regulators play in specific biological pathways of tumor promotion. Furthermore, transgenic mouse models enabled us to identify which of these regulatory activities was downstream of constitutive androstane receptor and β-catenin signaling, both crucial components of PB-mediated liver tumorigenesis. We propose novel roles for E2F and ZFP161 in PB-mediated hepatocyte proliferation and suggest that PB-mediated suppression of ESR1 activity contributes to the development of a tumor-prone environment. Our study shows that combining MARA with SVD allows for automated identification of independent transcription regulatory programs within a complex in vivo tissue environment and provides novel mechanistic insights into PB-mediated hepatocarcinogenesis. PMID:24464994

  1. Constraining flavor changing interactions from LHC Run-2 dilepton bounds with vector mediators

    Science.gov (United States)

    Queiroz, Farinaldo S.; Siqueira, Clarissa; Valle, José W. F.

    2016-12-01

    Within the context of vector mediators, is a new signal observed in flavor changing interactions, particularly in the neutral mesons systems K0 -Kbar0, D0 -Dbar0 and B0 -B0 bar , consistent with dilepton resonance searches at the LHC? In the attempt to address this very simple question, we discuss the complementarity between flavor changing neutral current (FCNC) and dilepton resonance searches at the LHC run 2 at 13 TeV with 3.2 fb-1 of integrated luminosity, in the context of vector mediators at tree level. Vector mediators, are often studied in the flavor changing framework, specially in the light of the recent LHCb anomaly observed at the rare B decay. However, the existence of stringent dilepton bound severely constrains flavor changing interactions, due to restrictive limits on the Z‧ mass. We discuss this interplay explicitly in the well motivated framework of a 3-3-1 scheme, where fermions and scalars are arranged in the fundamental representation of the weak SU(3) gauge group. Due to the paucity of relevant parameters, we conclude that dilepton data leave little room for a possible new physics signal stemming from these systems, unless a very peculiar texture parametrization is used in the diagonalization of the CKM matrix. In other words, if a signal is observed in such flavor changing interactions, it unlikely comes from a 3-3-1 model.

  2. Constraining flavor changing interactions from LHC Run-2 dilepton bounds with vector mediators

    Directory of Open Access Journals (Sweden)

    Farinaldo S. Queiroz

    2016-12-01

    Full Text Available Within the context of vector mediators, is a new signal observed in flavor changing interactions, particularly in the neutral mesons systems K0−K¯0, D0−D¯0 and B0−B0¯, consistent with dilepton resonance searches at the LHC? In the attempt to address this very simple question, we discuss the complementarity between flavor changing neutral current (FCNC and dilepton resonance searches at the LHC run 2 at 13 TeV with 3.2 fb−1 of integrated luminosity, in the context of vector mediators at tree level. Vector mediators, are often studied in the flavor changing framework, specially in the light of the recent LHCb anomaly observed at the rare B decay. However, the existence of stringent dilepton bound severely constrains flavor changing interactions, due to restrictive limits on the Z′ mass. We discuss this interplay explicitly in the well motivated framework of a 3-3-1 scheme, where fermions and scalars are arranged in the fundamental representation of the weak SU(3 gauge group. Due to the paucity of relevant parameters, we conclude that dilepton data leave little room for a possible new physics signal stemming from these systems, unless a very peculiar texture parametrization is used in the diagonalization of the CKM matrix. In other words, if a signal is observed in such flavor changing interactions, it unlikely comes from a 3-3-1 model.

  3. Extracellular Matrix Proteins Mediate HIV-1 gp120 Interactions with α4β7.

    Science.gov (United States)

    Plotnik, David; Guo, Wenjin; Cleveland, Brad; von Haller, Priska; Eng, Jimmy K; Guttman, Miklos; Lee, Kelly K; Arthos, James; Hu, Shiu-Lok

    2017-08-16

    Gut-homing α4β7(high) CD4(+) T lymphocytes have been shown to be preferentially targeted by Human Immunodeficiency Virus-1 (HIV), and are implicated in HIV pathogenesis. Previous studies demonstrated that HIV envelope protein gp120 binds and signals through α4β7, and that this likely contributes to the infection of α4β7(high) T cells and promotes cell-to-cell virus transmission. Structures within the second variable loop (V2) of gp120, including the tripeptide motif LDV/I, are thought to mediate gp120-α4β7 binding. However, lack of α4β7 binding has been reported in gp120 proteins containing LDV/I, and the precise determinants of gp120-α4β7 binding are not fully defined. In this work, we report the novel finding that fibronectins mediate indirect gp120-α4β7 interactions. We show that Chinese Hamster Ovary (CHO) cells used to express recombinant gp120 produced fibronectins and other extracellular matrix proteins that co-purified with gp120. CHO fibronectins were able to mediate the binding of a diverse panel of gp120 proteins to α4β7 in an in vitro cell binding assay. The V2 loop was not required for fibronectin-mediated binding of gp120 to α4β7, nor did V2-specific antibodies block this interaction. Removal of fibronectin through anion exchange chromatography abrogated V2-independent gp120-α4β7 binding. Additionally, we showed a recombinant human fibronectin fragment mediated gp120-α4β7 interactions in a similar manner to CHO fibronectin. These findings provide an explanation for the apparent contradictory observations regarding the gp120-α4β7 interaction and offer new insights into the potential role of fibronectin and other extracellular matrix proteins in HIV-1 biology.IMPORTANCE Immune tissues within the gut are severely damaged by HIV, and this plays an important role in the development of AIDS. Integrin α4β7 plays a major role in the trafficking of lymphocytes, including CD4(+) T cells, into gut lymphoid tissues. Previous reports

  4. Med5(Nut1 and Med17(Srb4 are direct targets of mediator histone H4 tail interactions.

    Directory of Open Access Journals (Sweden)

    Zhongle Liu

    Full Text Available The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. In addition to its canonical role in transcriptional activation, recent studies have demonstrated that S. cerevisiae Mediator can interact directly with nucleosomes, and their histone tails. Mutations in Mediator subunits have shown that Mediator and certain chromatin structures mutually impact each other structurally and functionally in vivo. We have taken a UV photo cross-linking approach to further delineate the molecular basis of Mediator chromatin interactions and help determine whether the impact of certain Mediator mutants on chromatin is direct. Specifically, by using histone tail peptides substituted with an amino acid analog that is a UV activatible crosslinker, we have identified specific subunits within Mediator that participate in histone tail interactions. Using Mediator purified from mutant yeast strains we have evaluated the impact of these subunits on histone tail binding. This analysis has identified the Med5 subunit of Mediator as a target for histone tail interactions and suggests that the previously observed effect of med5 mutations on telomeric heterochromatin and silencing is direct.

  5. Intrathymic laminin-mediated interactions: role in T cell migration and development

    Directory of Open Access Journals (Sweden)

    Wilson eSavino

    2015-11-01

    Full Text Available Intrathymic T cell differentiation is a key process for the development and maintenance of cell-mediated immunity, and occurs concomitantly to highly regulated migratory events. We have proposed a multivectorial model for describing intrathymic thymocyte migration. One of the individual vectors comprises interactions mediated by laminins, a heterotrimeric protein family of the extracellular matrix. Several laminins are expressed in the thymus, being produced by microenvironmental cells, particularly thymic epithelial cells. Also, thymocytes and epithelial cells express integrin-type laminin receptors. Functionally, it has been reported that the dy/dy mutant mouse (lacking the laminin isoform 211 exhibits defective thymocyte differentiation. Several data show haptotactic effects of laminins upon thymocytes, as well as their adhesion on thymic epithelial cells; both effects being prevented by anti-laminin or anti-laminin receptor antibodies. Interestingly, laminin synergizes with chemokines to enhance thymocyte migration, whereas classe-3 semaphorins and B ephrins, which exhibit chemorepulsive effects in the thymus, downregulate laminin-mediated migratory responses of thymocytes. More recently, we showed that knocking down the ITGA6 gene (which encodes the α6 integrin chain of laminin receptors in human thymic epithelial cells, modulates a large number of cell-migration related genes, and results in changes of adhesion pattern of thymocytes onto the thymic epithelium. Overall, laminin-mediated interactions can be placed at the cross-road of the multivectorial process of thymocyte migration, with a direct influence per se, as well as by modulating other molecular interactions associated with the intrathymic trafficking events.

  6. Oxidative modification of caspase-9 facilitates its activation via disulfide-mediated interaction with Apaf-1

    Institute of Scientific and Technical Information of China (English)

    Yong Zuo; Binggang Xiang; Jie Yang; Xuxu Sun; Yumei Wang; Hui Cang; Jing Yi

    2009-01-01

    Intracellular reactive oxygen species (ROS) are known to regulate apoptosis. Activation of caspase-9, the initial caspase in the mitochondrial apoptotic cascade, is closely associated with ROS, but it is unclear whether ROS regulate caspase-9 via direct oxidative modification. The present study aims to elucidate the molecular mechanisms by which ROS mediate caspase-9 activation. Our results show that the cellular oxidative state facilitates caspase-9 activation. Hydrogen peroxide treatment causes the activation of caspase-9 and apoptosis, and promotes an interaction between caspase-9 and apoptotic protease-activating factor 1 (Apaf-1) via disulfide formation. In addition, in an in vitro mitochondria-free system, the thiol-oxidant diamide promotes auto-cleavage of caspase-9 and the caspase-9/ Apaf-1 interaction by facilitating the formation of disulfide-linked complexes. Finally, a point mutation at C403 of caspase-9 impairs both H202-promoted caspase-9 activation and interaction with Apaf-1 through the abolition of disulfide formation. The association between cytochrome c and the C403S mutant is significantly weaker than that between cytochrome c and wild-type caspase-9, indicating that oxidative modification of caspase-9 contributes to apoptosome formation under oxidative stress. Taken together, oxidative modification of caspase-9 by ROS can mediate its interaction with Apaf-1, and can thus promote its auto-cleavage and activation. This mechanism may facilitate apoptosome formation and caspase-9 activation under oxidative stress.

  7. The role of multipoles in counterion-mediated interactions between charged surfaces: strong and weak coupling

    Energy Technology Data Exchange (ETDEWEB)

    Kanduc, M; Podgornik, R [Department of Theoretical Physics, J Stefan Institute, SI-1000 Ljubljana (Slovenia); Naji, A [Department of Physics, Department of Chemistry and Biochemistry, Materials Research Laboratory, University of California, Santa Barbara, CA 93106 (United States); Jho, Y S; Pincus, P A [Materials Research Laboratory, University of California, Santa Barbara, CA 93106 (United States)

    2009-10-21

    We present general arguments for the importance, or lack thereof, of structure in the charge distribution of counterions for counterion-mediated interactions between bounding symmetrically charged surfaces. We show that on the mean field or weak coupling level, the charge quadrupole contributes the lowest order modification to the contact value theorem and thus to the intersurface electrostatic interactions. The image effects are non-existent on the mean field level even with multipoles. On the strong coupling level the quadrupoles and higher order multipoles contribute additional terms to the interaction free energy only in the presence of dielectric inhomogeneities. Without them, the monopole is the only multipole that contributes to the strong coupling electrostatics. We explore the consequences of these statements in all their generality.

  8. Thallophilic Tl(i)-Tl(i) contacts mediated by Tl-aryl interactions. A computational study.

    Science.gov (United States)

    Weston, Laura; Pownall, Barnaby T; Mair, Francis S; McDouall, Joseph J W

    2016-05-28

    A computational study is presented of a complex of thallium with a neutral β-triketimine ligand which was found to form dimers with close Tl-Tl interactions. Single point energies, using the crystallographic structures, suggest that the system is bound only when BArF counter ions are included in the calculations. Energy decomposition analysis of the system was carried out in order to investigate the nature of the bonding. Across the methods, calculations show the electrostatic interaction to be repulsive for the dimer with no counter ions, but attractive when BArF counter ions are included. This suggests the metallophilic interaction is counter ion-mediated, requiring the anions to provide favourable electrostatics, even in the case of spatially diffuse and distant counter ions such as the 3,5-bistrifluoromethylphenyl borate ions used here.

  9. Genetic Background, Maternal Age, and Interaction Effects Mediate Rates of Crossing Over in Drosophila melanogaster Females.

    Science.gov (United States)

    Hunter, Chad M; Robinson, Matthew C; Aylor, David L; Singh, Nadia D

    2016-05-03

    Meiotic recombination is a genetic process that is critical for proper chromosome segregation in many organisms. Despite being fundamental for organismal fitness, rates of crossing over vary greatly between taxa. Both genetic and environmental factors contribute to phenotypic variation in crossover frequency, as do genotype-environment interactions. Here, we test the hypothesis that maternal age influences rates of crossing over in a genotypic-specific manner. Using classical genetic techniques, we estimated rates of crossing over for individual Drosophila melanogaster females from five strains over their lifetime from a single mating event. We find that both age and genetic background significantly contribute to observed variation in recombination frequency, as do genotype-age interactions. We further find differences in the effect of age on recombination frequency in the two genomic regions surveyed. Our results highlight the complexity of recombination rate variation and reveal a new role of genotype by maternal age interactions in mediating recombination rate.

  10. Genetic Background, Maternal Age, and Interaction Effects Mediate Rates of Crossing Over in Drosophila melanogaster Females

    Directory of Open Access Journals (Sweden)

    Chad M. Hunter

    2016-05-01

    Full Text Available Meiotic recombination is a genetic process that is critical for proper chromosome segregation in many organisms. Despite being fundamental for organismal fitness, rates of crossing over vary greatly between taxa. Both genetic and environmental factors contribute to phenotypic variation in crossover frequency, as do genotype–environment interactions. Here, we test the hypothesis that maternal age influences rates of crossing over in a genotypic-specific manner. Using classical genetic techniques, we estimated rates of crossing over for individual Drosophila melanogaster females from five strains over their lifetime from a single mating event. We find that both age and genetic background significantly contribute to observed variation in recombination frequency, as do genotype–age interactions. We further find differences in the effect of age on recombination frequency in the two genomic regions surveyed. Our results highlight the complexity of recombination rate variation and reveal a new role of genotype by maternal age interactions in mediating recombination rate.

  11. Constraining Flavor Changing Interactions from LHC Run-2 Dilepton Bounds with Vector Mediators

    CERN Document Server

    Queiroz, Farinaldo S; Valle, José W F

    2016-01-01

    Within the context of vector mediators, is a new signal observed in flavor changing interactions, particularly in the neutral mesons systems $K^{0}-\\bar{K}^{0}$, $D^{0}-\\bar{D}^{0}$ and $B^0-\\bar{B^0}$, consistent with dilepton resonance searches at the LHC? In the attempt to address this very simple question, we discuss the complementarity between flavor changing neutral current (FCNC) and dilepton resonance searches at the LHC run 2 at $13$TeV with $3.2\\, {\\rm fb^{-1}}$ of integrated luminosity, in the context of vector mediators at tree level. Vector mediators, are often studied in the flavor changing framework, specially in the light of the recent LHCb anomaly observed at the rare B decay. However, the existence of stringent dilepton bound severely constrains flavor changing interactions, due to restrictive limits on the $Z^{\\prime}$ mass. We discuss this interplay explicitly in the well motivated framework of a 3-3-1 scheme, where fermions and scalars are arranged in the fundamental representation of the...

  12. TOC1–PIF4 interaction mediates the circadian gating of thermoresponsive growth in Arabidopsis

    Science.gov (United States)

    Zhu, Jia-Ying; Oh, Eunkyoo; Wang, Tina; Wang, Zhi-Yong

    2016-01-01

    Arabidopsis adapts to elevated temperature by promoting stem elongation and hyponastic growth through a temperature-responsive transcription factor PIF4. Here we show that the evening-expressed clock component TOC1 interacts with and inactivates PIF4, thereby suppressing thermoresponsive growth in the evening. We find that the expression of PIF4 target genes show circadian rhythms of thermosensitivity, with minimum responsiveness in the evening when TOC1 level is high. Loss of function of TOC1 and its close homologue PRR5 restores thermosensitivity in the evening, whereas TOC1 overexpression causes thermo insensitivity, demonstrating that TOC1 mediates the evening-specific inhibition of thermoresponses. We further show that PIF4 is required for thermoadaptation mediated by moderately elevated temperature. Our results demonstrate that the interaction between TOC1 and PIF4 mediates the circadian gating of thermoresponsive growth, which may serve to increase fitness by matching thermoresponsiveness with the day–night cycles of fluctuating temperature and light conditions. PMID:27966533

  13. Adhesins of Leptospira interrogans Mediate the Interaction to Fibrinogen and Inhibit Fibrin Clot Formation In Vitro

    Science.gov (United States)

    Oliveira, Rosane; Domingos, Renan F.; Siqueira, Gabriela H.; Fernandes, Luis G.; Souza, Natalie M.; Vieira, Monica L.; de Morais, Zenaide M.; Vasconcellos, Silvio A.; Nascimento, Ana L. T. O.

    2013-01-01

    We report in this work that Leptospira strains, virulent L. interrogans serovar Copenhageni, attenuated L. interrogans serovar Copenhageni and saprophytic L. biflexa serovar Patoc are capable of binding fibrinogen (Fg). The interaction of leptospires with Fg inhibits thrombin- induced fibrin clot formation that may affect the haemostatic equilibrium. Additionally, we show that plasminogen (PLG)/plasmin (PLA) generation on the surface of Leptospira causes degradation of human Fg. The data suggest that PLA-coated leptospires were capable to employ their proteolytic activity to decrease one substrate of the coagulation cascade. We also present six leptospiral adhesins and PLG- interacting proteins, rLIC12238, Lsa33, Lsa30, OmpL1, rLIC11360 and rLIC11975, as novel Fg-binding proteins. The recombinant proteins interact with Fg in a dose-dependent and saturable fashion when increasing protein concentration was set to react to a fix human Fg concentration. The calculated dissociation equilibrium constants (KD) of these reactions ranged from 733.3±276.8 to 128±89.9 nM for rLIC12238 and Lsa33, respectively. The interaction of recombinant proteins with human Fg resulted in inhibition of fibrin clot by thrombin-catalyzed reaction, suggesting that these versatile proteins could mediate Fg interaction in Leptospira. Our data reveal for the first time the inhibition of fibrin clot by Leptospira spp. and presents adhesins that could mediate these interactions. Decreasing fibrin clot would cause an imbalance of the coagulation cascade that may facilitate bleeding and help bacteria dissemination PMID:24009788

  14. Anisotropic surface-state-mediated RKKY interaction between adatoms on a hexagonal lattice

    Science.gov (United States)

    Patrone, Paul N.; Einstein, T. L.

    2012-01-01

    Motivated by recent numerical studies of Ag on Pt(111), we derive an expression for the RKKY interaction mediated by surface states, considering the effect of anisotropy in the Fermi edge. Our analysis is based on a stationary phase approximation. The main contribution to the interaction comes from electrons whose Fermi velocity vF is parallel to the vector R connecting the interacting adatoms; we show that, in general, the corresponding Fermi wave vector kF is not parallel to R. The interaction is oscillatory; the amplitude and wavelength of oscillations have angular dependence arising from the anisotropy of the surface-state band structure. The wavelength, in particular, is determined by the projection of this kF (corresponding to vF) onto the direction of R. Our analysis is easily generalized to other systems. For Ag on Pt(111), our results indicate that the RKKY interaction between pairs of adatoms should be nearly isotropic and so cannot account for the anisotropy found in the studies motivating our work. However, for metals with surface-state dispersions similar to Be(101¯0), we show that the RKKY interaction should have considerable anisotropy.

  15. Interaction of CarD with RNA polymerase mediates Mycobacterium tuberculosis viability, rifampin resistance, and pathogenesis.

    Science.gov (United States)

    Weiss, Leslie A; Harrison, Phillip G; Nickels, Bryce E; Glickman, Michael S; Campbell, Elizabeth A; Darst, Seth A; Stallings, Christina L

    2012-10-01

    Mycobacterium tuberculosis infection continues to cause substantial human suffering. New chemotherapeutic strategies, which require insight into the pathways essential for M. tuberculosis pathogenesis, are imperative. We previously reported that depletion of the CarD protein in mycobacteria compromises viability, resistance to oxidative stress and fluoroquinolones, and pathogenesis. CarD associates with the RNA polymerase (RNAP), but it has been unknown which of the diverse functions of CarD are mediated through the RNAP; this question must be answered to understand the CarD mechanism of action. Herein, we describe the interaction between the M. tuberculosis CarD and the RNAP β subunit and identify point mutations that weaken this interaction. The characterization of mycobacterial strains with attenuated CarD/RNAP β interactions demonstrates that the CarD/RNAP β association is required for viability and resistance to oxidative stress but not for fluoroquinolone resistance. Weakening the CarD/RNAP β interaction also increases the sensitivity of mycobacteria to rifampin and streptomycin. Surprisingly, depletion of the CarD protein did not affect sensitivity to rifampin. These findings define the CarD/RNAP interaction as a new target for chemotherapeutic intervention that could also improve the efficacy of rifampin treatment of tuberculosis. In addition, our data demonstrate that weakening the CarD/RNAP β interaction does not completely phenocopy the depletion of CarD and support the existence of functions for CarD independent of direct RNAP binding.

  16. Role of Rab GTPases and their interacting proteins in mediating metabolic signalling and regulation.

    Science.gov (United States)

    Chua, Christelle En Lin; Tang, Bor Luen

    2015-06-01

    The vesicular transport pathways, which shuttle materials to and from the cell surface and within the cell, and the metabolic (growth factor and nutrient) signalling pathways, which integrate a variety of extracellular and intracellular signals to mediate growth, proliferation or survival, are both important for cellular physiology. There is evidence to suggest that the transport and metabolic signalling pathways intersect-vesicular transport can affect the regulation of metabolic signals and vice versa. The Rab family GTPases regulate the specificity of vesicular transport steps in the cell. Together with their interacting proteins, Rabs would likely constitute the points of intersection between vesicular transport and metabolic signalling pathways. Examples of these points would include growth factor signalling, glucose and lipid metabolism, as well as autophagy. Many of these processes involve mechanistic/mammalian target of rapamycin (mTOR) complex 1 (mTORC1) in downstream cascades, or are regulated by TORC signalling. A general functionality of the vesicular transport processes controlled by the Rabs is also important for spatial and temporal regulation of the transmission of metabolic signals between the cell surface and the nucleus. In other cases, specific Rabs and their interacting proteins are known to function in recruiting metabolism-related proteins to target membranes, or may compete with other factors in the TORC signalling pathway as a means of metabolic regulation. We review and discuss herein examples of how Rabs and their interacting proteins can mediate metabolic signalling and regulation in cells.

  17. RBAP96 Mediates Radiosensitivity of Breast Cancer Cells via Interacting with Retinoblastoma Protein

    Institute of Scientific and Technical Information of China (English)

    Junling Zhang; Xiaolei Xue; Qinghui Meng; Lu Lu; Ming Cui; Saijun Fan

    2016-01-01

    Objective To identify a novel retinoblastoma protein(RB)-associated protein(RBAP 96)and to explore the impact of RBAP96 on radiosensitivity of human breast cancer cells.Methods An in vivo and in vitro association of RBAP96 with RB was determined by immunoprecipitation-Western blotting and GST pull-down assay.Protein expression was measured by Western blot assay.Cellular survival was evaluated by using a colony formation assay.Results In both in vitro and in vivo assays,we found that the RBAP96 and RB interaction required a 513LXCXE517 motif on the RBAP96 protein and an intact A/B binding pocket of RB.RBAP96 enhances RB-mediated transcriptional repression.Finally,enforced expression of RBAP96 caused an elevated radiosensitivity of human breast cancer cells bearing wtRB,but did not affect radiosensitivity of breast cancer cells bearing mutant RB.Expression of a full-length RBAP96 with an 513LXCXE517 inactivating mutation(LXCXE→RXRXH) failed to result in any radiosensitivity alteration.Conclusion This study for the first time characterizes a novel RB-interacting protein RBAP96 and demonstrates that enforced expression of RBAP96 causes an increase of RBAP96-mediated transcription activation and radiosensitivity via a RB-interacting dependent manner.

  18. Pili-mediated Interactions between Neisseria Gonorrhoeae Bacteria are the Driving Mechanism of Microcolony Merging

    Science.gov (United States)

    Poenisch, Wolfram; Weber, Christoph; Alzurqa, Khaled; Nasrollahi, Hadi; Biais, Nicolas; Zaburdaev, Vasily; Collective Dynamics of Cells Team; Mechano-Micro-Biology Lab Team

    2015-03-01

    During the early infection with Neisseria gonorrhoeae the bacteria form microcolonies consisting of a few hundreds to a few thousands of cells. The formation of colonies is mediated by type IV pili, thin and long filaments that are also involved in the motion of single cells over a substrate. A related process causes attractive cell-cell-interactions. While the motion of single cells has been extensively studied during the past years, the physical principles driving the growth of these colonies are poorly understood. One key mechanism of colony growth is coalescence of smaller colonies. Therefore we experimentally examine the process of merging of two Neisseria gonorrhoeae colonies. We develop a theoretical microscopic model of single cells interacting solely by their pili. The experimental data and the results obtained from our model are in excellent quantitative agreement. We observe a fast initial approach of the two merging colonies within a few minutes, that is followed by a slow relaxation of the colony shape with a characteristic time of several hours. These findings suggest that pili-mediated interactions are the primary driving mechanism of the microcolony merging process.

  19. Imaging the microanatomy of astrocyte-T-cell interactions in immune-mediated inflammation

    Directory of Open Access Journals (Sweden)

    Carlos eBarcia

    2013-04-01

    Full Text Available The role of astrocytes in the immune-mediated inflammatory response in the brain is more prominent than previously thought. Astrocytes become reactive in response to neuro-inflammatory stimuli through multiple pathways, contributing significantly to the machinery that modifies the parenchymal environment. In particular, astrocytic signaling induces the establishment of critical relationships with infiltrating blood cells, such as lymphocytes, which is a fundamental process for an effective immune response. The interaction between astrocytes and T-cells involves complex modifications to both cell types, which undergo micro-anatomical changes and the redistribution of their binding and secretory domains. These modifications are critical for different immunological responses, such as for the effectiveness of the T-cell response, for the specific infiltration of these cells and their homing in the brain parenchyma, and for their correct apposition with antigen-presenting cells to form immunological synapses. In this article, we review the current knowledge of the interactions between T-cells and astrocytes in the context of immune-mediated inflammation in the brain, based on the micro-anatomical imaging of these appositions by high-resolution confocal microscopy and three-dimensional rendering. The study of these dynamic interactions using detailed technical approaches contributes to understanding the function of astrocytes in inflammatory responses and paves the way for new therapeutic strategies.

  20. DNA-HMGB1 interaction: The nuclear aggregates of polyamine mediation.

    Science.gov (United States)

    Iacomino, Giuseppe; Picariello, Gianluca; Sbrana, Francesca; Raiteri, Roberto; D'Agostino, Luciano

    2016-10-01

    Nuclear aggregates of polyamines (NAPs) are supramolecular compounds generated by the self-assembly of protonated nuclear polyamines (spermine, spermidine and putrescine) and phosphate ions. In the presence of genomic DNA, the hierarchical process of self-structuring ultimately produces nanotube-like polymers that envelop the double helix. Because of their modular nature and their aggregation-disaggregation dynamics, NAPs confer plasticity and flexibility to DNA. Through the disposition of charges, NAPs also enable a bidirectional stream of information between the genome and interacting moieties. High mobility group (HMG) B1 is a non-histone chromosomal protein that binds to DNA and that influences multiple nuclear processes. Because genomic DNA binds to either NAPs or HMGB1 protein, we explored the ability of in vitro self-assembled NAPs (ivNAPs) to mediate the DNA-HMGB1 interaction. To this end, we structured DNA-NAPs-HMGB1 and DNA-HMGB1-NAPs ternary complexes in vitro through opportune sequential incubations. Mobility shift electrophoresis and atomic force microscopy showed that the DNA-ivNAPs-HGMB1 complex had conformational assets supposedly more suitable those of the DNA-HGMB1-ivNAPs to comply with the physiological and functional requirements of DNA. Our findings indicated that ivNAPs act as mediators of the DNA-HMGB1 interaction.

  1. CCL2 Mediates Neuron-Macrophage Interactions to Drive Proregenerative Macrophage Activation Following Preconditioning Injury.

    Science.gov (United States)

    Kwon, Min Jung; Shin, Hae Young; Cui, Yuexian; Kim, Hyosil; Thi, Anh Hong Le; Choi, Jun Young; Kim, Eun Young; Hwang, Dong Hoon; Kim, Byung Gon

    2015-12-01

    CNS neurons in adult mammals do not spontaneously regenerate axons after spinal cord injury. Preconditioning peripheral nerve injury allows the dorsal root ganglia (DRG) sensory axons to regenerate beyond the injury site by promoting expression of regeneration-associated genes. We have previously shown that peripheral nerve injury increases the number of macrophages in the DRGs and that the activated macrophages are critical to the enhancement of intrinsic regeneration capacity. The present study identifies a novel chemokine signal mediated by CCL2 that links regenerating neurons with proregenerative macrophage activation. Neutralization of CCL2 abolished the neurite outgrowth activity of conditioned medium obtained from neuron-macrophage cocultures treated with cAMP. The neuron-macrophage interactions that produced outgrowth-promoting conditioned medium required CCL2 in neurons and CCR2/CCR4 in macrophages. The conditioning effects were abolished in CCL2-deficient mice at 3 and 7 d after sciatic nerve injury, but CCL2 was dispensable for the initial growth response and upregulation of GAP-43 at the 1 d time point. Intraganglionic injection of CCL2 mimicked conditioning injury by mobilizing M2-like macrophages. Finally, overexpression of CCL2 in DRGs promoted sensory axon regeneration in a rat spinal cord injury model without harmful side effects. Our data suggest that CCL2-mediated neuron-macrophage interaction plays a critical role for amplification and maintenance of enhanced regenerative capacity by preconditioning peripheral nerve injury. Manipulation of chemokine signaling mediating neuron-macrophage interactions may represent a novel therapeutic approach to promote axon regeneration after CNS injury.

  2. 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…

  3. Diverse Roles of Lysin-Motif (LysM Proteins in Mediating Plant-Microbe Interactions

    Directory of Open Access Journals (Sweden)

    Jinrong WAN

    2015-08-01

    Full Text Available Lysin-motif (LysM is a protein domain initially identified in a phage protein responsible for binding peptidoglycan, an important component of bacterial cell walls. LysM-containing proteins are distributed in diverse organisms, ranging from microbes to plants and animals (including human beings. Recent studies demonstrated that this group of proteins plays different roles in mediating plant-microbe interactions, leading to defense, symbiosis, or suppression of host defense. These roles are probably related to their potential ability to recognize and bind a specific signal molecule, such as chitooligosaccharides, peptidoglycan, nodulation factors (NFs, and mycorrhization factors (MFs.

  4. Spin orbit interaction of light mediated by scattering from plasmonic nano-structures

    CERN Document Server

    Soni, Jalpa; Mansha, Shampy; Gupta, S Dutta; Banerjee, Ayan; Ghosh, Nirmalya

    2012-01-01

    The spin orbit interactions (SOI) of light mediated by single scattering from plasmon resonant metal nanoparticles (nanorods and nanospheres) are investigated using explicit theory based on Jones and Stokes-Mueller polarimetry formalism. The individual SOI effects are analyzed and interpreted via the Mueller matrix-derived, polarimetry characteristics, namely, diattenuation d and retardance {\\delta}. The results demonstrate that each of the contributing SOI effects can be controllably enhanced by exploiting the interference of two neighboring modes in plasmonic nanostructures (orthogonal electric dipolar modes in rods or electric dipolar and quadrupolar modes in spheres).

  5. Arbuscular Mycorrhizal Fungal Mediation of Plant-Plant Interactions in a Marshland Plant Community

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    2014-01-01

    Full Text Available Obligate aerobic AMF taxa have high species richness under waterlogged conditions, but their ecological role remains unclear. Here we focused on AM fungal mediation of plant interactions in a marshland plant community. Five cooccurring plant species were chosen for a neighbor removal experiment in which benomyl was used to suppress AMF colonization. A Phragmites australis removal experiment was also performed to study its role in promoting AMF colonization by increasing rhizosphere oxygen concentration. Mycorrhizal fungal effects on plant interactions were different for dominant and subdominant plant species. AMF colonization has driven positive neighbor effects for three subdominant plant species including Kummerowia striata, Leonurus artemisia, and Ixeris polycephala. In contrast, AMF colonization enhanced the negative effects of neighbors on the dominant Conyza canadensis and had no significant impact on the neighbor interaction to the dominant Polygonum pubescens. AM colonization was positively related to oxygen concentration. P. australis increased oxygen concentration, enhanced AMF colonization, and was thus indirectly capable of influencing plant interactions. Aerobic AM fungi appear to be ecologically relevant in this wetland ecosystem. They drive positive neighbor interactions for subdominant plant species, effectively increasing plant diversity. We suggest, therefore, that AM fungi may be ecologically important even under waterlogged conditions.

  6. Arbuscular mycorrhizal fungal mediation of plant-plant interactions in a marshland plant community.

    Science.gov (United States)

    Zhang, Qian; Sun, Qixiang; Koide, Roger T; Peng, Zhenhua; Zhou, Jinxing; Gu, Xungang; Gao, Weidong; Yu, Meng

    2014-01-01

    Obligate aerobic AMF taxa have high species richness under waterlogged conditions, but their ecological role remains unclear. Here we focused on AM fungal mediation of plant interactions in a marshland plant community. Five cooccurring plant species were chosen for a neighbor removal experiment in which benomyl was used to suppress AMF colonization. A Phragmites australis removal experiment was also performed to study its role in promoting AMF colonization by increasing rhizosphere oxygen concentration. Mycorrhizal fungal effects on plant interactions were different for dominant and subdominant plant species. AMF colonization has driven positive neighbor effects for three subdominant plant species including Kummerowia striata, Leonurus artemisia, and Ixeris polycephala. In contrast, AMF colonization enhanced the negative effects of neighbors on the dominant Conyza canadensis and had no significant impact on the neighbor interaction to the dominant Polygonum pubescens. AM colonization was positively related to oxygen concentration. P. australis increased oxygen concentration, enhanced AMF colonization, and was thus indirectly capable of influencing plant interactions. Aerobic AM fungi appear to be ecologically relevant in this wetland ecosystem. They drive positive neighbor interactions for subdominant plant species, effectively increasing plant diversity. We suggest, therefore, that AM fungi may be ecologically important even under waterlogged conditions.

  7. Anisotropic Surface State Mediated RKKY Interaction Between Adatoms on a Hexagonal Lattice

    Science.gov (United States)

    Einstein, Theodore; Patrone, Paul

    2012-02-01

    Motivated by recent numerical studies of Ag on Pt(111), we derive a far-field expression for the RKKY interaction mediated by surface states on a (111) FCC surface, considering the effect of anisotropy in the Fermi edge. The main contribution to the interaction comes from electrons whose Fermi velocity vF is parallel to the vector R connecting the interacting adatoms; we show that in general, the corresponding Fermi wave-vector kF is not parallel to R. The interaction is oscillatory; the amplitude and wavelength of oscillations have angular dependence arising from the anisotropy of the surface state band structure. The wavelength, in particular, is determined by the component of the aforementioned kF that is parallel to R. Our analysis is easily generalized to other systems. For Ag on Pt(111), our results indicate that the RKKY interaction between pairs of adatoms should be nearly isotropic and so cannot account for the anisotropy found in the studies motivating our work.

  8. 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...

  9. Deflected anomaly mediated SUSY breaking scenario with general messenger–matter interactions

    Directory of Open Access Journals (Sweden)

    Fei Wang

    2015-12-01

    Full Text Available We propose to introduce general messenger–matter interactions in the deflected anomaly mediated SUSY breaking scenario. The most general form for the resulting soft parameters is derived. New interference terms between the GMSB type and AMSB type contributions are the unique feature of this scenario. Messenger–matter interactions involving sleptons can be used to solve the tachyonic slepton problem and naturally lead to positive slepton masses regardless of the sign of deflection parameter. Besides, due to the new contributions, large |At| that will not trigger color-breaking stop VEV are also possible in this scenario, thus can easily give the 125 GeV higgs which was discovered by LHC. This type of deflected AMSB scenario need very few messenger species, thus can avoid possible non-perturbative gauge couplings below the GUT scale (or Landau pole below the Planck scale.

  10. Ultra-intense laser-plasma interaction toward Weibel-mediated collisionless shocks formation

    Science.gov (United States)

    Grassi, Anna; Grech, M.; Amiranoff, F.; Macchi, A.; Riconda, C.

    2016-10-01

    The rapid developments in laser technology will soon offer the opportunity to study in the laboratory the processes driving Weibel-mediated collisionless shocks, typical of various astrophysical scenarii. The interaction of an ultra-intense laser with an overdense plasma has been identified as the preferential configuration. Yet, the experimental requirements still need to be properly investigated. High performance computing simulations are a necessary tool for this study. In this work, we present a series of kinetic simulations performed with the PIC code SMILEI, varying the laser and plasma parameters. In particular, we will study the effect of the laser polarisation and plasma density to obtain the best conditions for the creation of a collisionless shock. The role of the electrons heated at the interaction surface and of particles accelerated via the Hole Boring (laser-piston) mechanism on the generation of the current filamentation instability and the subsequent shock front formation will be highlighted.

  11. Plant-Agrobacterium interaction mediated by ethylene and super-Agrobacterium conferring efficient gene transfer ability

    Directory of Open Access Journals (Sweden)

    Satoko eNonaka

    2014-12-01

    Full Text Available Agrobacterium tumefaciens has a unique ability to transfer genes into plant genomes. This ability has been utilized for plant genetic engineering. However, the efficiency is not sufficient for all plant species. Several studies have shown that ethylene decreased the Agrobacterium-mediated transformation frequency. Thus, A. tumefaciens with an ability to suppress ethylene evolution would increase the efficiency of Agrobacterium-mediated transformation. Some studies showed that plant growth-promoting rhizobacteria (PGPR can reduce ethylene levels in plants through 1-aminocyclopropane-1-carboxylic acid (ACC deaminase, which cleaves the ethylene precursor ACC into α-ketobutyrate and ammonia, resulting in reduced ethylene production. The whole genome sequence data showed that A. tumefaciens does not possess an ACC deaminase gene in its genome. Therefore, providing ACC deaminase activity to the bacteria would improve gene transfer. As expected, A. tumefaciens with ACC deaminase activity, designated as super-Agrobacterium, could suppress ethylene evolution and increase the gene transfer efficiency in several plant species. In this review, we summarize plant–Agrobacterium interactions and their applications for improving Agrobacterium-mediated genetic engineering techniques via super-Agrobacterium.

  12. Strategically Mediated Reflective Practice Framework In Terms of Task, Meaningful Learning, and Interaction

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    Mehdi Shokouhi

    2017-03-01

    Full Text Available It is widely accepted that reflective teaching in its purely cognitive and introspective sense cannot be responsive to the dilemmas and the problems with which teachers encounter during their teaching practice. Thus, the present study believes that the very tentative solution to this problem is introducing teacher education in general and reflective practice in particular from a sociocultural perspective where any sort of knowledge is dialogically constructed as a result of interaction among individuals. Although the shift in paradigm, i.e. moving from a cognitive position to a more situated and social epistemology in teacher education, has already been acknowledged and addressed by scholars such as Johnson (2006, 2009, Johnson and Golombek (2003, Golombek (2011, Freeman (2004, and Hawkins (2004, the current literature on teacher education reveals of no direct or serious attempt as a framework in which such a view has been put into practice in teacher education. As a result, the present study proposed a tentative framework under the rubric of ‘Strategically Mediated Reflective Practice’ (henceforth SMRP framework that treats reflective practice largely as an interactive process rather than an individualistic and demonstrates how reflective practice is strategically mediated with the help of more knowledgeable others and new insights emerge resulting from dialogical thinking, highlighting the Vygotskian notion of Concept development. More importantly, examining the SMRP framework with four participants, the present study evidently reports the affirmative and constructive outcome of this framework on the utilitarian ground language teaching.

  13. Multilingual interactions in clinical dental education: a focus on mediated interpreting.

    Science.gov (United States)

    Bridges, Susan M; Yiu, Cynthia K Y; McGrath, Colman P

    2011-01-01

    In clinical dental consultations in multilingual contexts, medical interpreting is often performed by the supporting staff as part of routine triadic formulations. As academic dentistry becomes increasingly internationalized, issues of language and culture add to the interactional complexity of clinical communication and education. A multivariate approach was adopted to investigate one case of multilingualism in dentistry in Asia. Collection of both survey (n = 86) and interactional data provided empirical evidence regarding language use and language demands across integrated Polyclinics. Descriptive statistics of Dental Surgery Assistant (DSA) perception data and conversation analysis (CA) of mediated interpretation indicate that, as members of the oral healthcare team, DSAs in Hong Kong are an essential resource in their role of intercultural mediators between patients and clinicians, both staff and students. Discussion of sociolinguistic notions of place-as-location and place-as-meaning supports a wider conceptualization of the role of support staff as interpreters in clinical settings. Implications are drawn for policy, curriculum and staff development.

  14. Evidence for water-mediated mechanisms in coral-algal interactions.

    Science.gov (United States)

    Jorissen, Hendrikje; Skinner, Christina; Osinga, Ronald; de Beer, Dirk; Nugues, Maggy M

    2016-08-17

    Although many coral reefs have shifted from coral-to-algal dominance, the consequence of such a transition for coral-algal interactions and their underlying mechanisms remain poorly understood. At the microscale, it is unclear how diffusive boundary layers (DBLs) and surface oxygen concentrations at the coral-algal interface vary with algal competitors and competitiveness. Using field observations and microsensor measurements in a flow chamber, we show that coral (massive Porites) interfaces with thick turf algae, macroalgae, and cyanobacteria, which are successful competitors against coral in the field, are characterized by a thick DBL and hypoxia at night. In contrast, coral interfaces with crustose coralline algae, conspecifics, and thin turf algae, which are poorer competitors, have a thin DBL and low hypoxia at night. Furthermore, DBL thickness and hypoxia at the interface with turf decreased with increasing flow speed, but not when thick turf was upstream. Our results support the importance of water-mediated transport mechanisms in coral-algal interactions. Shifts towards algal dominance, particularly dense assemblages, may lead to thicker DBLs, higher hypoxia, and higher concentrations of harmful metabolites and pathogens along coral borders, which in turn may facilitate algal overgrowth of live corals. These effects may be mediated by flow speed and orientation. © 2016 The Author(s).

  15. Transporter-Mediated Drug–Drug Interactions with Oral Antidiabetic Drugs

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    Jörg König

    2011-10-01

    Full Text Available Uptake transporters (e.g., members of the SLC superfamily of solute carriers and export proteins (e.g., members of the ABC transporter superfamily are important determinants for the pharmacokinetics of drugs. Alterations of drug transport due to concomitantly administered drugs that interfere with drug transport may alter the kinetics of drug substrates. In vitro and in vivo studies indicate that many drugs used for the treatment of metabolic disorders and cardiovascular diseases (e.g., oral antidiabetic drugs, statins are substrates for uptake transporters and export proteins expressed in the intestine, the liver and the kidney. Since most patients with type 2 diabetes receive more than one drug, transporter-mediated drug-drug interactions are important molecular mechanisms leading to alterations in oral antidiabetic drug pharmacokinetics with the risk of adverse drug reactions. This review focuses on uptake transporters of the SLCO/SLC21 (OATP and SLC22 (OCT/OAT family of solute carriers and export pumps of the ABC (ATP-binding cassette transporter superfamily (especially P-glycoprotein as well as the export proteins of the SLC47 (MATE family and their role for transporter-mediated drug-drug interactions with oral antidiabetic drugs.

  16. Multivalent ion-mediated nucleic acid helix-helix interactions: RNA versus DNA.

    Science.gov (United States)

    Wu, Yuan-Yan; Zhang, Zhong-Liang; Zhang, Jin-Si; Zhu, Xiao-Long; Tan, Zhi-Jie

    2015-07-13

    Ion-mediated interaction is critical to the structure and stability of nucleic acids. Recent experiments suggest that the multivalent ion-induced aggregation of double-stranded (ds) RNAs and DNAs may strongly depend on the topological nature of helices, while there is still lack of an understanding on the relevant ion-mediated interactions at atomistic level. In this work, we have directly calculated the potentials of mean force (PMF) between two dsRNAs and between two dsDNAs in Co(NH3)6 (3+) (Co-Hex) solutions by the atomistic molecular dynamics simulations. Our calculations show that at low [Co-Hex], the PMFs between B-DNAs and between A-RNAs are both (strongly) repulsive. However, at high [Co-Hex], the PMF between B-DNAs is strongly attractive, while those between A-RNAs and between A-DNAs are still (weakly) repulsive. The microscopic analyses show that for A-form helices, Co-Hex would become 'internal binding' into the deep major groove and consequently cannot form the evident ion-bridge between adjacent helices, while for B-form helices without deep grooves, Co-Hex would exhibit 'external binding' to strongly bridge adjacent helices. In addition, our further calculations show that, the PMF between A-RNAs could become strongly attractive either at very high [Co-Hex] or when the bottom of deep major groove is fixed with a layer of water.

  17. Multivalent ion-mediated nucleic acid helix-helix interactions: RNA versus DNA

    CERN Document Server

    Wu, Yuan-Yan; Zhang, Jin-Si; Zhu, Xiao-Long; Tan, Zhi-Jie

    2015-01-01

    Ion-mediated interaction is critical to the structure and stability of nucleic acids. Recent experiments suggest that the multivalent ion-induced aggregation of double-stranded (ds) RNAs and DNAs may strongly depend on the topological nature of helices, while there is still lack of an understanding on the relevant ion-mediated interactions at atomistic level. In this work, we have directly calculated the potentials of mean force (PMF) between two dsRNAs and between two dsDNAs in Cobalt Hexammine ion (Co-Hex) solutions by the atomistic molecular dynamics simulations. Our calculations show that at low [Co-Hex], the PMFs between B-DNAs and between A-RNAs are both (strongly) repulsive.However, at high [Co-Hex], the PMF between B-DNAs is strongly attractive, while those between A-RNAs and between A-DNAs are still (weakly) repulsive. The microscopic analyses show that for A-form helices, Co-Hex would become internal binding into the deep major groove and consequently cannot form the evident ion-bridge between adjac...

  18. Drosophila tribbles antagonizes insulin signaling-mediated growth and metabolism via interactions with Akt kinase.

    Directory of Open Access Journals (Sweden)

    Rahul Das

    Full Text Available Drosophila Tribbles (Trbl is the founding member of the Trib family of kinase-like docking proteins that modulate cell signaling during proliferation, migration and growth. In a wing misexpression screen for Trbl interacting proteins, we identified the Ser/Thr protein kinase Akt1. Given the central role of Akt1 in insulin signaling, we tested the function of Trbl in larval fat body, a tissue where rapid increases in size are exquisitely sensitive to insulin/insulin-like growth factor levels. Consistent with a role in antagonizing insulin-mediated growth, trbl RNAi knockdown in the fat body increased cell size, advanced the timing of pupation and increased levels of circulating triglyceride. Complementarily, overexpression of Trbl reduced fat body cell size, decreased overall larval size, delayed maturation and lowered levels of triglycerides, while circulating glucose levels increased. The conserved Trbl kinase domain is required for function in vivo and for interaction with Akt in a yeast two-hybrid assay. Consistent with direct regulation of Akt, overexpression of Trbl in the fat body decreased levels of activated Akt (pSer505-Akt while misexpression of trbl RNAi increased phospho-Akt levels, and neither treatment affected total Akt levels. Trbl misexpression effectively suppressed Akt-mediated wing and muscle cell size increases and reduced phosphorylation of the Akt target FoxO (pSer256-FoxO. Taken together, these data show that Drosophila Trbl has a conserved role to bind Akt and block Akt-mediated insulin signaling, and implicate Trib proteins as novel sites of signaling pathway integration that link nutrient availability with cell growth and proliferation.

  19. Polymorphism of DNA-anionic liposome complexes reveals hierarchy of ion-mediated interactions.

    Science.gov (United States)

    Liang, Hongjun; Harries, Daniel; Wong, Gerard C L

    2005-08-09

    Self-assembled DNA delivery systems based on anionic lipids (ALs) complexed with DNA mediated by divalent cations have been recently introduced as an alternative to cationic lipid-DNA complexes because of their low cytotoxicity. We investigate AL-DNA complexes induced by different cations by using synchrotron small angle x-ray scattering and confocal microscopy to show how different ion-mediated interactions are expressed in the self-assembled structures and phase behavior of AL-DNA complexes. The governing interactions in AL-DNA systems are complex: divalent ions can mediate strong attractions between different combinations of the components (such as DNA-DNA and membrane-membrane). Moreover, divalent cations can coordinate non-electrostatically with lipids and modify the resultant membrane structure. We find that at low membrane charge densities AL-DNA complexes organize into a lamellar structure of alternating DNA and membrane layers crosslinked by ions. At high membrane charge densities, a new phase with no analog in cationic lipid-DNA systems is observed: DNA is expelled from the complex, and a lamellar stack of membranes and intercalated ions is formed. For a subset of the ionic species, high ion concentrations generate an inverted hexagonal phase comprised of DNA strands wrapped by ion-coated lipid tubes. A simple theoretical model that takes into account the electrostatic and membrane elastic contributions to the free energy shows that this transition is consistent with an ion-induced change in the membrane spontaneous curvature, c0. Moreover, the crossover between the lamellar and inverted hexagonal phases occurs at a critical c0 that agrees well with experimental values.

  20. Plant chemical defense indirectly mediates aphid performance via interactions with tending ants.

    Science.gov (United States)

    Züst, Tobias; Agrawal, Anurag A

    2017-03-01

    The benefits of mutualistic interactions are often highly context dependent. We studied the interaction between the milkweed aphid Aphis asclepiadis and a tending ant, Formica podzolica. Although this interaction is generally considered beneficial, variation in plant genotype may alter it from mutualistic to antagonistic. Here we link the shift in strength and relative benefit of the ant-aphid interaction to plant genotypic variation in the production of cardenolides, a class of toxic defensive chemicals. In a field experiment with highly variable genotypes of the common milkweed (Asclepias syriaca), we show that plant cardenolides, especially polar forms, are ingested by aphids and excreted in honeydew proportionally to plant concentrations without directly affecting aphid performance. Ants consume honeydew, and aphids that excreted high amounts of cardenolides received fewer ant visits, which in turn reduced aphid survival. On at least some plant genotypes, aphid numbers per plant were reduced in the presence of ants to levels lower than in corresponding ant-exclusion treatments, suggesting antagonistic ant behavior. Although cardenolides appear ineffective as direct plant defenses against aphids, the multi-trophic context reveals an ant-mediated negative indirect effect on aphid performance and population dynamics. © 2016 by the Ecological Society of America.

  1. Constraining interactions mediated by axion-like particles with ultracold neutrons

    Directory of Open Access Journals (Sweden)

    S. Afach

    2015-05-01

    Full Text Available We report a new limit on a possible short range spin-dependent interaction from the precise measurement of the ratio of Larmor precession frequencies of stored ultracold neutrons and Hg199 atoms confined in the same volume. The measurement was performed in a ∼1μT vertical magnetic holding field with the apparatus searching for a permanent electric dipole moment of the neutron at the Paul Scherrer Institute. A possible coupling between freely precessing polarized neutron spins and unpolarized nucleons of the wall material can be investigated by searching for a tiny change of the precession frequencies of neutron and mercury spins. Such a frequency change can be interpreted as a consequence of a short range spin-dependent interaction that could possibly be mediated by axions or axion-like particles. The interaction strength is proportional to the CP violating product of scalar and pseudoscalar coupling constants gSgP. Our result confirms limits from complementary experiments with spin-polarized nuclei in a model-independent way. Limits from other neutron experiments are improved by up to two orders of magnitude in the interaction range of 10−6<λ<10−4m.

  2. Interparticle interactions mediated superspin glass to superferromagnetic transition in Ni-bacterial cellulose aerogel nanocomposites

    Science.gov (United States)

    Thiruvengadam, V.; Vitta, Satish

    2016-06-01

    The interparticle interactions in the magnetic nanocomposites play a dominant role in controlling phase transitions: superparamagnetic to superspin glass and to superferromagnetic. These interactions can be tuned by controlling the size and number density of nanoparticles. The aerogel composites, 0.3Ni-BC and 0.7Ni-BC, consisting of Ni nanoparticles distributed in the bacterial cellulose have been used as a model system to study these interactions. Contrary to conventional approach, size of Ni-nanoparticles is not controlled and allowed to form naturally in bacterial cellulose template. The uncontrolled growth of Ni results in the formation of nanoparticles with 3 different size distributions - 100 nm particles in voids formed by reticulate structure. At room temperature, the composites exhibit a weakly ferromagnetic behaviour with a coercivity of 40 Oe, which increases to 160 Oe at 10 K. The transition from weakly ferromagnetic state to superferromagnetic state at low temperatures is mediated by the superspin glass state at intermediate temperatures via the interparticle interactions aided by nanoparticles present along the length of fibres. A temperature dependent microstructural model has been developed to understand the magnetic behaviour of nanocomposite aerogels.

  3. Lectin receptor kinases participate in protein-protein interactions to mediate plasma membrane-cell wall adhesions in Arabidopsis

    NARCIS (Netherlands)

    Gouget, A.; Senchou, V.; Govers, F.; Sanson, A.; Barre, A.; Rougé, P.; Pont-Lezica, R.; Canut, H.

    2006-01-01

    Interactions between plant cell walls and plasma membranes are essential for cells to function properly, but the molecules that mediate the structural continuity between wall and membrane are unknown. Some of these interactions, which are visualized upon tissue plasmolysis in Arabidopsis (Arabidopsi

  4. Biotic interactions mediate the expansion of black mangrove (Avicennia germinans) into salt marshes under climate change.

    Science.gov (United States)

    Guo, Hongyu; Zhang, Yihui; Lan, Zhenjiang; Pennings, Steven C

    2013-09-01

    Many species are expanding their distributions to higher latitudes due to global warming. Understanding the mechanisms underlying these distribution shifts is critical for better understanding the impacts of climate changes. The climate envelope approach is widely used to model and predict species distribution shifts with changing climates. Biotic interactions between species, however, may also influence species distributions, and a better understanding of biotic interactions could improve predictions based solely on climate envelope models. Along the northern Gulf of Mexico coast, USA, subtropical black mangrove (Avicennia germinans) at the northern limit of its distribution grows sympatrically with temperate salt marsh plants in Florida, Louisiana, and Texas. In recent decades, freeze-free winters have led to an expansion of black mangrove into salt marshes. We examined how biotic interactions between black mangrove and salt marsh vegetation along the Texas coast varied across (i) a latitudinal gradient (associated with a winter-temperature gradient); (ii) the elevational gradient within each marsh (which creates different marsh habitats); and (iii) different life history stages of black mangroves (seedlings vs. juvenile trees). Each of these variables affected the strength or nature of biotic interactions between black mangrove and salt marsh vegetation: (i) Salt marsh vegetation facilitated black mangrove seedlings at their high-latitude distribution limit, but inhibited black mangrove seedlings at lower latitudes; (ii) mangroves performed well at intermediate elevations, but grew and survived poorly in high- and low-marsh habitats; and (iii) the effect of salt marsh vegetation on black mangroves switched from negative to neutral as black mangroves grew from seedlings into juvenile trees. These results indicate that the expansion of black mangroves is mediated by complex biotic interactions. A better understanding of the impacts of climate change on ecological

  5. Nuclear import of transcription factor BR-C is mediated by its interaction with RACK1.

    Directory of Open Access Journals (Sweden)

    Daojun Cheng

    Full Text Available The transcription factor Broad Complex (BR-C is an early ecdysone response gene in insects and contains two types of domains: two zinc finger domains for the activation of gene transcription and a Bric-a-brac/Tramtrack/Broad complex (BTB domain for protein-protein interaction. Although the mechanism of zinc finger-mediated gene transcription is well studied, the partners interacting with the BTB domain of BR-C has not been elucidated until now. Here, we performed a yeast two-hybrid screen using the BTB domain of silkworm BR-C as bait and identified the receptor for activated C-kinase 1 (RACK1, a scaffolding/anchoring protein, as the novel partner capable of interacting with BR-C. The interaction between BR-C and RACK1 was further confirmed by far-western blotting and pull-down assays. Importantly, the disruption of this interaction, via RNAi against the endogenous RACK1 gene or deletion of the BTB domain, abolished the nuclear import of BR-C in BmN4 cells. In addition, RNAi against the endogenous PKC gene as well as phosphorylation-deficient mutation of the predicted PKC phosphorylation sites at either Ser373 or Thr406 in BR-C phenocopied RACK1 RNAi and altered the nuclear localization of BR-C. However, when BTB domain was deleted, phosphorylation mimics of either Ser373 or Thr406 had no effect on the nuclear import of BR-C. Moreover, mutating the PKC phosphorylation sites at Ser373 and Thr406 or deleting the BTB domain significantly decreased the transcriptional activation of a BR-C target gene. Given that RACK1 is necessary for recruiting PKC to close and phosphorylate target proteins, we suggest that the PKC-mediated phosphorylation and nuclear import of BR-C is determined by its interaction with RACK1. This novel finding will be helpful for further deciphering the mechanism underlying the role of BR-C proteins during insect development.

  6. Evolving interactions between diazotrophic cyanobacterium and phage mediate nitrogen release and host competitive ability

    Science.gov (United States)

    Coloma, Sebastián; Sivonen, Kaarina

    2016-01-01

    Interactions between nitrogen-fixing (i.e. diazotrophic) cyanobacteria and their viruses, cyanophages, can have large-scale ecosystem effects. These effects are mediated by temporal alterations in nutrient availability in aquatic systems owing to the release of nitrogen and carbon sources from cells lysed by phages, as well as by ecologically important changes in the diversity and fitness of cyanobacterial populations that evolve in the presence of phages. However, ecological and evolutionary feedbacks between phages and nitrogen-fixing cyanobacteria are still relative poorly understood. Here, we used an experimental evolution approach to test the effect of interactions between a common filamentous, nitrogen-fixing cyanobacterium (Nodularia sp.) and its phage on cellular nitrogen release and host properties. Ecological, community-level effects of phage-mediated nitrogen release were tested with a phytoplankton bioassay. We found that cyanobacterial nitrogen release increased significantly as a result of viral lysis, which was associated with enhanced growth of phytoplankton species in cell-free filtrates compared with phage-resistant host controls in which lysis and subsequent nutrient release did not occur after phage exposure. We also observed an ecologically important change among phage-evolved cyanobacteria with phage-resistant phenotypes, a short-filamentous morphotype with reduced buoyancy compared with the ancestral long-filamentous morphotype. Reduced buoyancy might decrease the ability of these morphotypes to compete for light compared with longer, more buoyant filaments. Together, these findings demonstrate the potential of cyanobacteria–phage interactions to affect ecosystem biogeochemical cycles and planktonic community dynamics. PMID:28083116

  7. The Effective Field Theory approach towards membrane-mediated interactions between particles.

    Science.gov (United States)

    Yolcu, Cem; Haussman, Robert C; Deserno, Markus

    2014-06-01

    Fluid lipid membranes can mediate forces between particles bound to them: A local deformation of the surface geometry created by some object spreads to distant regions, where other objects can respond to it. The physical characteristics of these geometric interactions, and how they are affected by thermal fluctuations, are well described by the simple continuum curvature-elastic Hamiltonian proposed 40 years ago by Wolfgang Helfrich. Unfortunately, while the underlying principles are conceptually straightforward, the corresponding calculations are not-largely because one must enforce boundary conditions for finite-sized objects. This challenge has inspired several heuristic approaches for expressing the problem in a point particle language. While streamlining the calculations of leading order results and enabling predictions for higher order corrections, the ad hoc nature of the reformulation leaves its domain of validity unclear. In contrast, the framework of Effective Field Theory (EFT) provides a systematic way to construct a completely equivalent point particle description. In this review we present a detailed account for how this is accomplished. In particular, we use a familiar example from electrostatics as an analogy to motivate the key steps needed to construct an EFT, most notably capturing finite size information in point-like "polarizabilities," and determining their value through a suitable "matching procedure." The interaction (free) energy then emerges as a systematic cumulant expansion, for which powerful diagrammatic techniques exist, which we also briefly revisit. We then apply this formalism to derive series expansions for interactions between flat and curved particle pairs, multibody interactions, as well as corrections to all these interactions due to thermal fluctuations.

  8. Rodent-Mediated Interactions Among Seed Species of Differing Quality in a Shrubsteppe Ecosystem

    Science.gov (United States)

    Beard, Karen H.; Faulhaber, Craig A.; Howe, Frank P.; Edwards, Thomas C.

    2013-01-01

    Interactions among seeds, mediated by granivorous rodents, are likely to play a strong role in shrubsteppe ecosystem restoration. Past studies typically consider only pairwise interactions between preferred and less preferred seed species, whereas rangeland seedings are likely to contain more than 2 seed species, potentially leading to complex interactions. We examined how the relative proportion of seeds in a 3-species polyculture changes rodent seed selectivity (i.e., removal) and indirect interactions among seeds. We presented 2 rodent species, Peromyscus maniculatus (deer mice) and Perognathus parvus (pocket mice), in arenas with 3-species seed mixtures that varied in the proportion of a highly preferred, moderately preferred, and least preferred seed species, based on preferences determined in this study. We then conducted a field experiment in a pocket mouse—dominated ecosystem with the same 3-species seed mixtures in both “treated” (reduced shrub and increased forb cover) and “untreated” shrubsteppe. In the arena experiment, we found that rodents removed more of the highly preferred seed when the proportions of all 3 seeds were equal. Moderately preferred seeds experienced increased removal when the least preferred seed was in highest proportion. Removal of the least preferred seed increased when the highly preferred seed was in highest proportion. In the field experiment, results were similar to those from the arena experiment and did not differ between treated and untreated shrubsteppe areas. Though our results suggest that 3-species mixtures induce complex interactions among seeds, managers applying these results to restoration efforts should carefully consider the rodent community present and the potential fate of removed seeds.

  9. Reflexivity, mediations and education. The subject and the interaction with audiovisual screens

    Directory of Open Access Journals (Sweden)

    Juan David Zabala Sandoval

    2016-07-01

    Full Text Available Thinking about massive media is a task that should opt for a complex conception of its effects. Also, the importance in the process of constitution of the subject in their social environment. Specially, television that is a source of particular and group ways of seeing in the world and being part of it. Which at the same time, allows us to look back on it, giving rise to processes of identification and construction of social and daily realities. As well as, deal with the world from basic socialization processes in the education of subjects and subjectivities. Thus, it is interesting to understand, the interaction between the subject and the television screen from the critical approach of reception that proposes to understand the interaction of diverse institutional, situational and contextual mediations that make possible to understand the reception as a changing process. Process in which the subject is active, who negotiates senses, positions, values, and perceptions with the massive media of communication. Therefore, it is a way to study educational processes, reflection, and social construction of realities, which purpose is not only to prohibit the media consumption or think of massive media as products sections while alienating reality; but also, the intention is to perceive that television, as massive media, is a fundamental part of the current socializing process; thus, it is necessary, to propose alternative forms in order to understand the structure/production of the subject, as well as other forms of reading and interact with these commercial and educational contents.

  10. Child-to-Child Interaction and Corrective Feedback in a Computer Mediated L2 Class

    Directory of Open Access Journals (Sweden)

    Frank Morris

    2005-01-01

    Full Text Available The current study examined the provision of corrective feedback and learner repair following feedback in the interactional context of child-to-child conversations, particularly computer mediated, in an elementary Spanish immersion class. The relationship among error types, feedback types, and immediate learner repair were also examined. A total of 46, fifth-grade children participated in the study. Using Blackboard, the instructor randomly paired students and created a "virtual group" for each pair. Each pair was asked to interact and complete a jigsaw task in the "virtual classroom." Blackboard recorded the pairs' interactions, which were later printed and coded for types of error (syntactic/lexical, types of negative feedback (explicit/recasts/negotiation and immediate learner repairs. Findings indicate that learners did not provide explicit negative feedback. Learners provided implicit negative feedback (recasts and negotiation while completing the jigsaw task in the virtual classroom. The majority of lexical errors and syntactic errors were corrected using negotiation. Over half of feedback moves led to immediate repair. Negotiation moves proved more effective at leading to immediate repair of errors than did recasts.

  11. A conserved docking surface on calcineurin mediates interaction with substrates and immunosuppressants

    Science.gov (United States)

    Rodríguez, Antonio; Roy, Jagoree; Martínez-Martínez, Sara; López-Maderuelo, Ma Dolores; Niño-Moreno, Perla; Ortí, Leticia; Pantoja, David; Pineda-Lucena, Antonio; Cyert, Martha S.; Redondo, Juan Miguel

    2009-01-01

    SUMMARY The phosphatase calcineurin, target of the immunosuppressants cyclosporin A and FK506, dephosphorylates NFAT transcription factors to promote immune activation and development of the vascular and nervous systems. NFAT interacts with calcineurin through distinct binding motifs: the PxIXIT and LxVP sites. While many calcineurin substrates contain PxIxIT motifs, the generality of LxVP-mediated interactions is unclear. We define critical residues in the LxVP motif, and demonstrate its binding to a hydrophobic pocket at the interface of the two calcineurin subunits. Mutations in this region disrupt binding of mammalian calcineurin to NFATc1, and interaction of yeast calcineurin with substrates including Rcn1, which contains an LxVP motif. These mutations also interfere with calcineurin-immunosuppressant binding, and an LxVP-based peptide competes with immunosuppressant-immunophilin complexes for binding to calcineurin. These studies suggest that LxVP-type sites are a common feature of calcineurin substrates and that immunosuppressant-immunophilin complexes inhibit calcineurin by interfering with this mode of substrate recognition. PMID:19285944

  12. Constraining interactions mediated by axion-like particles with ultracold neutrons

    CERN Document Server

    Afach, S; Bison, G; Bodek, K; Burghoff, M; Daum, M; Fertl, M; Franke, B; Grujić, Z D; Hélaine, V; Kasprzak, M; Kermaïdic, Y; Kirch, K; Knowles, P; Koch, H -C; Komposch, S; Kozela, A; Krempel, J; Lauss, B; Lefort, T; Lemière, Y; Mtchedlishvili, A; Naviliat-Cuncic, O; Piegsa, F M; Pignol, G; Prashanth, P N; Quéméner, G; Rebreyend, D; Ries, D; Roccia, S; Schmidt-Wellenburg, P; Schnabel, A; Severijns, N; Voigt, J; Weis, A; Zejma, G Wyszynski J; Zenner, J; Zsigmond, G

    2014-01-01

    We report a new limit on a possible short range spin-dependent interaction from the precise measurement of the ratio of Larmor precession frequencies of stored ultracold neutrons and $^{199}$Hg atoms confined in the same volume. The measurement was performed in a $\\sim$1$\\mu$ T vertical magnetic holding field with the apparatus searching for a permanent electric dipole moment of the neutron at the Paul Scherrer Institute. A possible coupling between freely precessing polarized neutron spins and unpolarized nucleons of the wall material can be investigated by searching for a tiny change of the precession frequencies of neutron and mercury spins. Such a frequency change can be interpreted as a consequence of a short range spin-dependent interaction that could possibly be mediated by axions or axion-like particles. The interaction strength is proportional to the CP violating product of scalar and pseudoscalar coupling constants $g_Sg_P$. Our result confirms limits from complementary experiments with spin-polariz...

  13. PAS domain of the deduced Org35 protein mediates the interaction with NifA

    Institute of Scientific and Technical Information of China (English)

    TU Ran; CUI Yanhua; CHEN Sanfeng; LI Jilun

    2006-01-01

    NifA in Azospirillum brasilense plays a key role in regulating the synthesis of nitrogenase in response to ammonia and oxygen available. Recently,our laboratory has identified four clones, whose gene prodcuts interact with NifA, from A. brasilense Sp7genomic libraries by using the yeast two-hybrid system with NifA as bait. We are interested in clone S35,one of the four clones, because it contains a PAS-domain coding region. The entire open reading frame (ORF) for the PAS domain-containing protein was isolated and designated as org35 here. org35gene is 2211-bp long and encodes a protein of 736aa with a predicted molecular weight of about 78.4 kD.The predicted amino acid sequence of org35 has similarity to some two-component sensor kinase/response regulator hybrids of bacteria. Structural analyses showed that Org35 comprises at least three discrete conserved domains: the N-terminal PAS, the central histidine protein kinase (HPK) and the C-terminal response regulator (RR). The PAS domain of the deduced Org35 protein was found to interact directly with NifA, but the central HPK and the C-terminal RR domains of Org35 were not. These results indicated that interaction between NifA and Org35 was mediated by PAS domain.

  14. Cell-Cell Interactions Mediate the Response of Vascular Smooth Muscle Cells to Substrate Stiffness

    Science.gov (United States)

    Sazonova, Olga V.; Lee, Kristen L.; Isenberg, Brett C.; Rich, Celeste B.; Nugent, Matthew A.; Wong, Joyce Y.

    2011-01-01

    The vessel wall experiences progressive stiffening with age and the development of cardiovascular disease, which alters the micromechanical environment experienced by resident vascular smooth muscle cells (VSMCs). In vitro studies have shown that VSMCs are sensitive to substrate stiffness, but the exact molecular mechanisms of their response to stiffness remains unknown. Studies have also shown that cell-cell interactions can affect mechanotransduction at the cell-substrate interface. Using flexible substrates, we show that the expression of proteins associated with cell-matrix adhesion and cytoskeletal tension is regulated by substrate stiffness, and that an increase in cell density selectively attenuates some of these effects. We also show that cell-cell interactions exert a strong effect on cell morphology in a substrate-stiffness dependent manner. Collectively, the data suggest that as VSMCs form cell-cell contacts, substrate stiffness becomes a less potent regulator of focal adhesion signaling. This study provides insight into the mechanisms by which VSMCs respond to the mechanical environment of the blood vessel wall, and point to cell-cell interactions as critical mediators of VSMC response to vascular injury. PMID:21806930

  15. DNA-controlled dynamic colloidal nanoparticle systems for mediating cellular interaction

    Science.gov (United States)

    Ohta, Seiichi; Glancy, Dylan; Chan, Warren C. W.

    2016-02-01

    Precise control of biosystems requires development of materials that can dynamically change physicochemical properties. Inspired by the ability of proteins to alter their conformation to mediate function, we explored the use of DNA as molecular keys to assemble and transform colloidal nanoparticle systems. The systems consist of a core nanoparticle surrounded by small satellites, the conformation of which can be transformed in response to DNA via a toe-hold displacement mechanism. The conformational changes can alter the optical properties and biological interactions of the assembled nanosystem. Photoluminescent signal is altered by changes in fluorophore-modified particle distance, whereas cellular targeting efficiency is increased 2.5 times by changing the surface display of targeting ligands. These concepts provide strategies for engineering dynamic nanotechnology systems for navigating complex biological environments.

  16. Fumed silica nanoparticle mediated biomimicry for optimal cell-material interactions for artificial organ development.

    Science.gov (United States)

    de Mel, Achala; Ramesh, Bala; Scurr, David J; Alexander, Morgan R; Hamilton, George; Birchall, Martin; Seifalian, Alexander M

    2014-03-01

    Replacement of irreversibly damaged organs due to chronic disease, with suitable tissue engineered implants is now a familiar area of interest to clinicians and multidisciplinary scientists. Ideal tissue engineering approaches require scaffolds to be tailor made to mimic physiological environments of interest with specific surface topographical and biological properties for optimal cell-material interactions. This study demonstrates a single-step procedure for inducing biomimicry in a novel nanocomposite base material scaffold, to re-create the extracellular matrix, which is required for stem cell integration and differentiation to mature cells. Fumed silica nanoparticle mediated procedure of scaffold functionalization, can be potentially adapted with multiple bioactive molecules to induce cellular biomimicry, in the development human organs. The proposed nanocomposite materials already in patients for number of implants, including world first synthetic trachea, tear ducts and vascular bypass graft.

  17. Inflammatory Mediators and Angiogenic Factors in Choroidal Neovascularization: Pathogenetic Interactions and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Claudio Campa

    2010-01-01

    Full Text Available Choroidal neovascularization (CNV is a common and severe complication in heterogeneous diseases affecting the posterior segment of the eye, the most frequent being represented by age-related macular degeneration. Although the term may suggest just a vascular pathological condition, CNV is more properly definable as an aberrant tissue invasion of endothelial and inflammatory cells, in which both angiogenesis and inflammation are involved. Experimental and clinical evidences show that vascular endothelial growth factor is a key signal in promoting angiogenesis. However, many other molecules, distinctive of the inflammatory response, act as neovascular activators in CNV. These include fibroblast growth factor, transforming growth factor, tumor necrosis factor, interleukins, and complement. This paper reviews the role of inflammatory mediators and angiogenic factors in the development of CNV, proposing pathogenetic assumptions of mutual interaction. As an extension of this concept, new therapeutic approaches geared to have an effect on both the vascular and the extravascular components of CNV are discussed.

  18. Membrane-mediated interactions and the dynamics of dynamin oligomers on membrane tubes

    Energy Technology Data Exchange (ETDEWEB)

    Shlomovitz, R; Gov, N S [Department of Chemical Physics, Weizmann Institute of Science, PO Box 26, Rehovot, Israel 76100 (Israel); Roux, A, E-mail: nir.gov@weizmann.ac.il [Department of Biochemistry, University of Geneva, 30 quai Ernest Ansermet, CH-1211 Geneva (Switzerland)

    2011-06-15

    Dynamin is a protein that plays a key role in the transport and recycling of membrane tubes and vesicles within a living cell. This protein adsorbs from solution to PIP{sub 2}-containing membranes, and on these tubes it forms curved oligomers that condense into tight helical domains of uniform radius. The dynamics of this process is treated here in terms of the linear stability of a continuum model, whereby membrane-mediated interactions are shown to drive the spontaneous nucleation of condensed dynamin domains. We furthermore show that the deformation of the membrane outside the dynamin domains induces an energy barrier that can hinder the full coalescence of neighboring growing domains. We compare these calculations to experimental observations on dynamin dynamics in vitro.

  19. Insights into CYP2B6-mediated drug–drug interactions

    Directory of Open Access Journals (Sweden)

    William D. Hedrich

    2016-09-01

    Full Text Available Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug metabolism than was previously believed. The discovery of multiple important substrates of CYP2B6 as well as polymorphic differences has sparked increasing interest in the genetic and xenobiotic factors contributing to the expression and function of the enzyme. The expression of CYP2B6 is regulated primarily by the xenobiotic receptors constitutive androstane receptor (CAR and pregnane X receptor (PXR in the liver. In addition to CYP2B6, these receptors also mediate the inductive expression of CYP3A4, and a number of important phase II enzymes and drug transporters. CYP2B6 has been demonstrated to play a role in the metabolism of 2%–10% of clinically used drugs including widely used antineoplastic agents cyclophosphamide and ifosfamide, anesthetics propofol and ketamine, synthetic opioids pethidine and methadone, and the antiretrovirals nevirapine and efavirenz, among others. Significant inter-individual variability in the expression and function of the human CYP2B6 gene exists and can result in altered clinical outcomes in patients receiving treatment with CYP2B6-substrate drugs. These variances arise from a number of sources including genetic polymorphism, and xenobiotic intervention. In this review, we will provide an overview of the key players in CYP2B6 expression and function and highlight recent advances made in assessing clinical ramifications of important CYP2B6-mediated drug–drug interactions.

  20. Microbial metabolism mediates interactions between dissolved organic matter and clay minerals in streamwater

    Science.gov (United States)

    Hunter, W. R.; Battin, T. J.

    2016-08-01

    Sorption of organic molecules to mineral surfaces is an important control upon the aquatic carbon (C) cycle. Organo-mineral interactions are known to regulate the transport and burial of C within inland waters, yet the mechanisms that underlie these processes are poorly constrained. Streamwater contains a complex and dynamic mix of dissolved organic compounds that coexists with a range of organic and inorganic particles and microorganisms. To test how microbial metabolism and organo-mineral complexation alter amino acid and organic carbon fluxes we experimented with 13C-labelled amino acids and two common clay minerals (kaolinite and montmorillonite). The addition of 13C-labelled amino acids stimulated increased microbial activity. Amino acids were preferentially mineralized by the microbial community, concomitant with the leaching of other (non-labelled) dissolved organic molecules that were removed from solution by clay-mediated processes. We propose that microbial processes mediate the formation of organo-mineral particles in streamwater, with potential implications for the biochemical composition of organic matter transported through and buried within fluvial environments.

  1. Solvent fluctuations around solvophobic, solvophilic, and patchy nanostructures and the accompanying solvent mediated interactions

    Science.gov (United States)

    Chacko, Blesson; Evans, Robert; Archer, Andrew J.

    2017-03-01

    Using classical density functional theory (DFT), we calculate the density profile ρ (𝐫 ) and local compressibility χ (𝐫 ) of a simple liquid solvent in which a pair of blocks with (microscopic) rectangular cross section are immersed. We consider blocks that are solvophobic, solvophilic and also ones that have both solvophobic and solvophilic patches. Large values of χ (𝐫 ) correspond to regions in space where the liquid density is fluctuating most strongly. We seek to elucidate how enhanced density fluctuations correlate with the solvent mediated force between the blocks, as the distance between the blocks and the chemical potential of the liquid reservoir vary. For sufficiently solvophobic blocks, at small block separations and small deviations from bulk gas-liquid coexistence, we observe a strongly attractive (near constant) force, stemming from capillary evaporation to form a low density gas-like intrusion between the blocks. The accompanying χ (𝐫 ) exhibits a structure which reflects the incipient gas-liquid interfaces that develop. We argue that our model system provides a means to understanding the basic physics of solvent mediated interactions between nanostructures, and between objects such as proteins in water that possess hydrophobic and hydrophilic patches.

  2. Interaction of Mycobacterium tuberculosis RshA and SigH is mediated by salt bridges.

    Directory of Open Access Journals (Sweden)

    Shiva Kumar

    Full Text Available The alternate sigma factor sigH of Mycobacterium tuberculosis is expressed under stress and acts as a major regulator of several genes, including some other sigma factors and redox systems. While it is auto-regulated by its own promoter at the transcriptional level, its regulation at the post-translational level is through its cognate protein, an anti-sigma factor, RshA. Hither before RshA was believed to be a zinc-associated anti-sigma factor (ZAS and the binding of RshA to SigH is redox dependent. Here, we show that RshA coordinates a [2Fe-2S] cluster using cysteines as ligands and native RshA has more affinity to [2Fe-2S] cluster than to zinc. Furthermore, we used amide hydrogen deuterium exchange mass spectrometry (HDX-MS, followed by site-directed mutagenesis in SigH and RshA, to elucidate the interaction mechanism of RshA and SigH and the potential role of metal ion clustering in SigH regulation. Three regions in SigH, comprising of residues 1-25, 58-69, 90-111, 115-132 and 157-196 and residues 35-57 of RshA show decreased deuterium exchange and reflect decreased solvent accessibility upon complexation with SigH. Of the three RshA mutants, created based on the HDX results, the RsHA E37A mutant shows stronger interaction with SigH, relative to WT RshA, while the H49A mutant abolishes interactions and the C(53XXC(56AXXA mutant has no effect on complexation with SigH. The D22A, D160A and E162 SigH mutants show significantly decreased binding to RshA and the E168A mutant completely abolished interactions with RshA, indicating that the SigH-RshA interaction is mediated by salt bridges. In addition, SigH-RshA interaction does not require clustering of metal ions. Based on our results, we propose a molecular model of the SigH-RshA interaction.

  3. Leptin as a mediator of tumor-stromal interactions promotes breast cancer stem cell activity.

    Science.gov (United States)

    Giordano, Cinzia; Chemi, Francesca; Panza, Salvatore; Barone, Ines; Bonofiglio, Daniela; Lanzino, Marilena; Cordella, Angela; Campana, Antonella; Hashim, Adnan; Rizza, Pietro; Leggio, Antonella; Győrffy, Balázs; Simões, Bruno M; Clarke, Robert B; Weisz, Alessandro; Catalano, Stefania; Andò, Sebastiano

    2016-01-12

    Breast cancer stem cells (BCSCs) play crucial roles in tumor initiation, metastasis and therapeutic resistance. A strict dependency between BCSCs and stromal cell components of tumor microenvironment exists. Thus, novel therapeutic strategies aimed to target the crosstalk between activated microenvironment and BCSCs have the potential to improve clinical outcome. Here, we investigated how leptin, as a mediator of tumor-stromal interactions, may affect BCSC activity using patient-derived samples (n = 16) and breast cancer cell lines, and determined the potential benefit of targeting leptin signaling in these model systems. Conditioned media (CM) from cancer-associated fibroblasts and breast adipocytes significantly increased mammosphere formation in breast cancer cells and depletion of leptin from CM completely abrogated this effect. Mammosphere cultures exhibited increased leptin receptor (OBR) expression and leptin exposure enhanced mammosphere formation. Microarray analyses revealed a similar expression profile of genes involved in stem cell biology among mammospheres treated with CM and leptin. Interestingly, leptin increased mammosphere formation in metastatic breast cancers and expression of OBR as well as HSP90, a target of leptin signaling, were directly correlated with mammosphere formation in metastatic samples (r = 0.68/p = 0.05; r = 0.71/p = 0.036, respectively). Kaplan-Meier survival curves indicated that OBR and HSP90 expression were associated with reduced overall survival in breast cancer patients (HR = 1.9/p = 0.022; HR = 2.2/p = 0.00017, respectively). Furthermore, blocking leptin signaling by using a full leptin receptor antagonist significantly reduced mammosphere formation in breast cancer cell lines and patient-derived samples. Our results suggest that leptin/leptin receptor signaling may represent a potential therapeutic target that can block the stromal-tumor interactions driving BCSC-mediated disease progression.

  4. Sarm1-mediated axon degeneration requires both SAM and TIR interactions.

    Science.gov (United States)

    Gerdts, Josiah; Summers, Daniel W; Sasaki, Yo; DiAntonio, Aaron; Milbrandt, Jeffrey

    2013-08-14

    Axon degeneration is an evolutionarily conserved pathway that eliminates damaged or unneeded axons. Manipulation of this poorly understood pathway may allow treatment of a wide range of neurological disorders. In an RNAi-based screen performed in cultured mouse DRG neurons, we observed strong suppression of injury-induced axon degeneration upon knockdown of Sarm1 [SARM (sterile α-motif-containing and armadillo-motif containing protein)]. We find that a SARM-dependent degeneration program is engaged by disparate neuronal insults: SARM ablation blocks axon degeneration induced by axotomy or vincristine treatment, while SARM acts in parallel with a soma-derived caspase-dependent pathway following trophic withdrawal. SARM is a multidomain protein that associates with neuronal mitochondria. Deletion of the N-terminal mitochondrial localization sequence disrupts SARM mitochondrial localization in neurons but does not alter its ability to promote axon degeneration. In contrast, mutation of either the SAM (sterile α motif) or TIR (Toll-interleukin-1 receptor) domains abolishes the ability of SARM to promote axonal degeneration, while a SARM mutant containing only these domains elicits axon degeneration and nonapoptotic neuronal death even in the absence of injury. Protein-protein interaction studies demonstrate that the SAM domains are necessary and sufficient to mediate SARM-SARM binding. SARM mutants lacking a TIR domain bind full-length SARM and exhibit strong dominant-negative activity. These results indicate that SARM plays an integral role in the dismantling of injured axons and support a model in which SAM-mediated multimerization is necessary for TIR-dependent engagement of a downstream destruction pathway. These findings suggest that inhibitors of SAM and TIR interactions represent therapeutic candidates for blocking pathological axon loss and neuronal cell death.

  5. MDR- and CYP3A4-mediated drug-drug interactions.

    Science.gov (United States)

    Pal, Dhananjay; Mitra, Ashim K

    2006-09-01

    P-glycoprotein (P-gp), multiple drug resistance associated proteins (MRPs), and cytochrome P450 3A4 together constitute a highly efficient barrier for many orally absorbed drugs. Multidrug regimens and corresponding drug-drug interactions are known to cause many adverse drug reactions and treatment failures. Available literature, clinical reports, and in vitro studies from our laboratory indicate that many drugs are substrates for both P-gp and CYP3A4. Our primary hypothesis is that transport and metabolism of protease inhibitors (PIs) and NNRTIs will be altered when administered in combination with azole antifungals, macrolide, fluroquinolone antibiotics, statins, cardiovascular agents, immune modulators, and recreational drugs [benzodiazepines, cocaine, lysergic acid dithylamide (LSD), marijuana, amphetamine (Meth), 3,4-methylenedioxymethamphetamine (MDMA), and opiates] due to efflux, and/or metabolism at cellular targets. Therefore, such drug combinations could be a reason for the unexpected and unexplainable therapeutic outcomes. A number of clinical reports on drug interaction between PIs and other classes (macrolide antibiotics, azole antifungals, cholesterol lowering statins, cardiovascular medicines, and immunomodulators) are discussed in this article. MDCKII-MDR1 was employed as an in vitro model to evaluate the effects of antiretrovirals, azole antifungals, macrolide, and fluroquinolone antibiotics on efflux transporters. Ketoconazole (50 muM) enhanced the intracellular concentration of (3)H ritonavir. The inhibitory effects of ketoconazole and MK 571 on the efflux of (3)H ritonavir were comparable. An additive effect was observed with simultaneous incorporation of ketoconazole and MK 571. Results of (3)H ritonavir uptake studies were confirmed with transcellular transport studies. Several fluroquinolones were also evaluated on P-gp-mediated efflux of (3)H cyclosporin and 14C erythromycin. These in vitro studies indicate that grepafloxacin, levofloxacin

  6. Elastic scattering dynamics of cavity polaritons: Evidence for time-energy uncertainty and polariton localization

    DEFF Research Database (Denmark)

    Langbein, Wolfgang Werner; Hvam, Jørn Märcher

    2002-01-01

    The directional dynamics of the resonant Rayleigh scattering from a semiconductor microcavity is investigated. When optically exciting the lower polariton branch, the strong dispersion results in a directional emission on a ring. The coherent emission ring shows a reduction of its angular width...... for increasing time after excitation, giving direct evidence for the time-energy uncertainty in the dynamics of the scattering by disorder. The ring width converges with time to a finite value, a direct measure of an intrinsic momentum broadening of the polariton states localized by multiple disorder scattering....

  7. Ganglioside mediate the interaction between Nogo receptor 1 and LINGO-1.

    Science.gov (United States)

    Saha, Nayanendu; Kolev, Momchil V; Semavina, Mariya; Himanen, Juha; Nikolov, Dimitar B

    2011-09-16

    Upon spinal cord injury, the myelin inhibitors, including the myelin-associated glycoprotein (MAG), Nogo-A and the oligodendrocyte myelin glycoprotein (OMgp), bind to and signal via a single neuronal receptor/co-receptor complex comprising of Nogo receptor 1(NgR1)/LINGO-1 and p75 or TROY, impeding regeneration of injured axons. We employed a cell-free system to study the binding of NgR1 to its co-receptors and the myelin inhibitor Nogo-A, and show that gangliosides mediate the interaction of NgR1 with LINGO-1. Solid phase binding assays demonstrate that the sialic acid moieties of gangliosides and the stalk of NgR1 are the principal determinants of these molecular interactions. Moreover, the tripartite complex comprising of NgR1, LINGO-1 and ganglioside exhibits stronger binding to Nogo-A (Nogo-54) in the presence of p75, suggesting the gangliosides modulate the myelin inhibitor-receptor signaling.

  8. Formation of dilute adhesion domains driven by weak elasticity-mediated interactions

    CERN Document Server

    Dharan, Nadiv

    2016-01-01

    Cell-cell adhesion is established by specific binding of receptor and ligand proteins. The adhesion bonds attract each other and often aggregate into large clusters that are central to many biological processes. One possible origin of attractive interactions between adhesion bonds is the elastic response of the membranes to their deformation by the bonds. Here, we analyze these elasticity-mediated interactions using a novel mean-field approach. Analysis of systems at different densities of bonds, $\\phi$, reveals that the phase diagram exhibits a nearly-universal behavior when the temperature $T$ is plotted vs. the scaled density $x=\\phi \\xi^2$, where $\\xi$ is the linear size of the membrane's region affected by a single bond. The critical point $(\\phi_c,T_c)$ is located at very low densities and slightly below $T_c$ we identify phase coexistence between two low-density phases. Dense domains are observed only when the height by which the bonds deform the membranes, $h_0$, is much larger than their thermal roug...

  9. Evolutionary trace-based peptides identify a novel asymmetric interaction that mediates oligomerization in nuclear receptors.

    Science.gov (United States)

    Gu, Peili; Morgan, Daniel H; Sattar, Minawar; Xu, Xueping; Wagner, Ryan; Raviscioni, Michele; Lichtarge, Olivier; Cooney, Austin J

    2005-09-01

    Germ cell nuclear factor (GCNF) is an orphan nuclear receptor that plays important roles in development and reproduction, by repressing the expression of essential genes such as Oct4, GDF9, and BMP15, through binding to DR0 elements. Surprisingly, whereas recombinant GCNF binds to DR0 sequences as a homodimer, endogenous GCNF does not exist as a homodimer but rather as part of a large complex termed the transiently retinoid-induced factor (TRIF). Here, we use evolutionary trace (ET) analysis to design mutations and peptides that probe the molecular basis for the formation of this unusual complex. We find that GCNF homodimerization and TRIF complex formation are DNA-dependent, and ET suggests that dimerization involves key functional sites on both helix 3 and helix 11, which are located on opposing surfaces of the ligand binding domain. Targeted mutations in either helix of GCNF disrupt the formation of both the homodimer and the endogenous TRIF complex. Moreover, peptide mimetics of both of these ET-determined sites inhibit dimerization and TRIF complex formation. This suggests that a novel helix 3-helix 11 heterotypic interaction mediates GCNF interaction and would facilitate oligomerization. Indeed, it was determined that the endogenous TRIF complex is composed of a GCNF oligomer. These findings shed light on an evolutionarily selected mechanism that reveals the unusual DNA-binding, dimerization, and oligomerization properties of GCNF.

  10. Influence of Solvent-Solvent and Solute-Solvent Interaction Properties on Solvent-Mediated Potential

    Institute of Scientific and Technical Information of China (English)

    ZHOU Shi-Qi

    2005-01-01

    A recently proposed universal calculational recipe for solvent-mediated potential is applied to calculate excess potential of mean force between two large Lennard-Jones (LJ) or hard core attractive Yukawa particles immersed in small LJ solvent bath at supercritical state. Comparison between the present prediction with a hypernetted chain approximation adopted for solute-solute correlation at infinitely dilute limit and existing simulation data shows high accuracy for the region with large separation, and qualitative reliability for the solute particle contact region. The calculational simplicity of the present recipe allows for a detailed investigation on the effect of the solute-solvent and solvent-solvent interaction details on the excess potential of mean force. The resultant conclusion is that gathering of solvent particles near a solute particle leads to repulsive excess PMF, while depletion of solvent particles away from the solute particle leads to attractive excess PMF, and minor change of the solvent-solvent interaction range has large influence on the excess PMF.

  11. Intracellular Generation of a Diterpene-Peptide Conjugate that Inhibits 14-3-3-Mediated Interactions.

    Science.gov (United States)

    Parvatkar, Prakash; Kato, Nobuo; Uesugi, Motonari; Sato, Shin-Ichi; Ohkanda, Junko

    2015-12-23

    Synthetic agents that disrupt intracellular protein-protein interactions (PPIs) are highly desirable for elucidating signaling networks and developing new therapeutics. However, designing cell-penetrating large molecules equipped with the many functional groups necessary for binding to large interfaces remains challenging. Here, we describe a rational strategy for the intracellular oxime ligation-mediated generation of an amphipathic bivalent inhibitor composed of a peptide and diterpene natural product, fusicoccin, which binds 14-3-3 protein with submicromolar affinity. Our results demonstrate that co-treatment of cells with small module molecules, the aldehyde-containing fusicoccin 1 and the aminooxy-containing peptide 2, generates the corresponding conjugate 3 in cells, resulting in significant cytotoxicity. In contrast, chemically synthesized 3 is not cytotoxic, likely due to its inability to penetrate cells. Compound 3, but not 1 or 2, disrupts endogenous 14-3-3/cRaf interactions, suggesting that cell death is caused by inhibition of 14-3-3 activity. These results suggest that intracellular generation of large-sized molecules may serve as a new approach for modulating PPIs.

  12. p62 regulates CD40-mediated NFκB activation in macrophages through interaction with TRAF6

    Energy Technology Data Exchange (ETDEWEB)

    Seibold, Kristina; Ehrenschwender, Martin, E-mail: martin.ehrenschwender@ukr.de

    2015-08-14

    CD40 is a member of the tumor necrosis factor (TNF) receptor family. Activation-induced recruitment of adapter proteins, so-called TNF-receptor-associated factors (TRAFs) to the cytoplasmic tail of CD40 triggers signaling cascades important in the immune system, but has also been associated with excessive inflammation in diseases such as atherosclerosis and rheumatoid arthritis. Especially, pro-inflammatory nuclear factor κB (NFκB) signaling emanating from CD40-associated TRAF6 appears to be a key pathogenic driving force. Consequently, targeting the CD40-TRAF6 interaction is emerging as a promising therapeutic strategy, but the underlying molecular machinery of this signaling axis is to date poorly understood. Here, we identified the multifunctional adaptor protein p62 as a critical regulator in CD40-mediated NFκB signaling via TRAF6. CD40 activation triggered formation of a TRAF6-p62 complex. Disturbing this interaction tremendously reduced CD40-mediated NFκB signaling in macrophages, while TRAF6-independent signaling pathways remained unaffected. This highlights p62 as a potential target in hyper-inflammatory, CD40-associated pathologies. - Highlights: • CD40 activation triggers interaction of the adapter protein TRAF6 with p62. • TRAF6-p62 interaction regulates CD40-mediated NFκB signaling in macrophages. • Defective TRAF6-p62 interaction reduces CD40-mediated NFκB activation in macrophages.

  13. Interactions between HIV-1 Gag molecules in solution: an inositol phosphate-mediated switch.

    Science.gov (United States)

    Datta, Siddhartha A K; Zhao, Zhuojun; Clark, Patrick K; Tarasov, Sergey; Alexandratos, Jerry N; Campbell, Stephen J; Kvaratskhelia, Mamuka; Lebowitz, Jacob; Rein, Alan

    2007-01-19

    Retrovirus particle assembly is mediated by the Gag protein. Gag is a multi-domain protein containing discrete domains connected by flexible linkers. When recombinant HIV-1 Gag protein (lacking myristate at its N terminus and the p6 domain at its C terminus) is mixed with nucleic acid, it assembles into virus-like particles (VLPs) in a fully defined system in vitro. However, this assembly is defective in that the radius of curvature of the VLPs is far smaller than that of authentic immature virions. This defect can be corrected to varying degrees by addition of inositol phosphates to the assembly reaction. We have now explored the binding of inositol hexakisphosphate (IP6) to Gag and its effects upon the interactions between Gag protein molecules in solution. Our data indicate that basic regions at both ends of the protein contribute to IP6 binding. Gag is in monomer-dimer equilibrium in solution, and mutation of the previously described dimer interface within its capsid domain drastically reduces Gag dimerization. In contrast, when IP6 is added, Gag is in monomer-trimer rather than monomer-dimer equilibrium. The Gag protein with a mutation at the dimer interface also remains almost exclusively monomeric in IP6; thus the "dimer interface" is essential for the trimeric interaction in IP6. We discuss possible explanations for these results, including a change in conformation within the capsid domain induced by the binding of IP6 to other domains within the protein. The participation of both ends of Gag in IP6 interaction suggests that Gag is folded over in solution, with its ends near each other in three-dimensional space; direct support for this conclusion is provided in a companion manuscript. As Gag is an extended rod in immature virions, this apparent proximity of the ends in solution implies that it undergoes a major conformational change during particle assembly.

  14. Carbohydrate-Carbohydrate Interactions Mediated by Sulfate Esters and Calcium Provide the Cell Adhesion Required for the Emergence of Early Metazoans

    National Research Council Canada - National Science Library

    Vilanova, Eduardo; Santos, Gustavo R C; Aquino, Rafael S; Valle-Delgado, Juan J; Anselmetti, Dario; Fernàndez-Busquets, Xavier; Mourão, Paulo A S

    2016-01-01

    .... Cell adhesion in sponges is mediated by the calcium-dependent multivalent self-interactions of sulfated polysaccharides components of extracellular membrane-bound proteoglycans, namely aggregation factors...

  15. Interactions between multiple recruitment drivers: post-settlement predation mortality and flow-mediated recruitment.

    Directory of Open Access Journals (Sweden)

    Antony M Knights

    Full Text Available BACKGROUND: Dispersal is a primary driver in shaping the future distribution of species in both terrestrial and marine systems. Physical transport by advection can regulate the distance travelled and rate of propagule supply to a habitat but post-settlement processes such as predation can decouple supply from recruitment. The effect of flow-mediated recruitment and predation on the recruitment success of an intertidal species, the eastern oyster Crassostrea virginica was evaluated in two-replicated field experiments. Two key crab species were manipulated to test predator identity effects on oyster mortality. FINDINGS: Recruitment was ∼58% higher in high flow compared to low flow, but predation masked those differences. Predation mortality was primarily attributed to the blue crab Callinectes sapidus, whilst the mud crab Panopeus herbstii had no effect on recruit mortality. Recruit mortality from predation was high when recruit densities were high, but when recruit density was low, predation effects were not seen. Under high recruitment (supply, predation determined maximum population size and in low flow environments, recruitment success is likely determined by a combination of recruitment and resource limitation but not predation. CONCLUSIONS: Four processes are demonstrated: (1 Increases in flow rate positively affect recruitment success; (2 In high flow (recruitment environments, resource availability is less important than predation; (3 predation is an important source of recruit mortality, but is dependent upon recruit density; and (4 recruitment and/or resource limitation is likely a major driver of population structure and functioning, modifying the interaction between predators and prey. Simultaneous testing of flow-mediated recruitment and predation was required to differentiate between the role of each process in determining population size. Our results reinforce the importance of propagule pressure, predation and post

  16. Linear response approximation in effective field theory for the calculation of elastically mediated interactions in one dimension.

    Science.gov (United States)

    Koleski, Goce; Fournier, Jean-Baptiste

    2016-05-01

    The linear response approximation, used within effective field theory to calculate mediated interactions between inclusions, is studied for an exactly solvable one-dimensional model. We show that it works poorly in the case of inclusions imposing absolute deformations to the field, while it works well for massless theories in the case of inclusions imposing relative deformations to the field.

  17. Learning, Interactional, and Motivational Outcomes in One-to-One Synchronous Computer-Mediated versus Face-to-Face Tutoring

    Science.gov (United States)

    Siler, Stephanie Ann; VanLehn, Kurt

    2009-01-01

    Face-to-face (FTF) human-human tutoring has ranked among the most effective forms of instruction. However, because computer-mediated (CM) tutoring is becoming increasingly common, it is instructive to evaluate its effectiveness relative to face-to-face tutoring. Does the lack of spoken, face-to-face interaction affect learning gains and…

  18. Learning, Interactional, and Motivational Outcomes in One-to-One Synchronous Computer-Mediated versus Face-to-Face Tutoring

    Science.gov (United States)

    Siler, Stephanie Ann; VanLehn, Kurt

    2009-01-01

    Face-to-face (FTF) human-human tutoring has ranked among the most effective forms of instruction. However, because computer-mediated (CM) tutoring is becoming increasingly common, it is instructive to evaluate its effectiveness relative to face-to-face tutoring. Does the lack of spoken, face-to-face interaction affect learning gains and…

  19. Increasing Responsive Parent-Child Interactions and Joint Engagement: Comparing the Influence of Parent-Mediated Intervention and Parent Psychoeducation

    Science.gov (United States)

    Shire, Stephanie Y.; Gulsrud, Amanda; Kasari, Connie

    2016-01-01

    Enhancing immediate and contingent responding by caregivers to children's signals is an important strategy to support social interactions between caregivers and their children with autism. Yet, there has been limited examination of parents' responsive behaviour in association with children's social behaviour post caregiver-mediated intervention.…

  20. 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.…

  1. Distinct parietal sites mediate the influences of mood, arousal, and their interaction on human recognition memory.

    Science.gov (United States)

    Greene, Ciara M; Flannery, Oliver; Soto, David

    2014-12-01

    The two dimensions of emotion, mood valence and arousal, have independent effects on recognition memory. At present, however, it is not clear how those effects are reflected in the human brain. Previous research in this area has generally dealt with memory for emotionally valenced or arousing stimuli, but the manner in which interacting mood and arousal states modulate responses in memory substrates remains poorly understood. We investigated memory for emotionally neutral items while independently manipulating mood valence and arousal state by means of music exposure. Four emotional conditions were created: positive mood/high arousal, positive mood/low arousal, negative mood/high arousal, and negative mood/low arousal. We observed distinct effects of mood valence and arousal in parietal substrates of recognition memory. Positive mood increased activity in ventral posterior parietal cortex (PPC) and orbitofrontal cortex, whereas arousal condition modulated activity in dorsal PPC and the posterior cingulate. An interaction between valence and arousal was observed in left ventral PPC, notably in a parietal area distinct from the those identified for the main effects, with a stronger effect of mood on recognition memory responses here under conditions of relative high versus low arousal. We interpreted the PPC activations in terms of the attention-to-memory hypothesis: Increased arousal may lead to increased top-down control of memory, and hence dorsal PPC activation, whereas positive mood valence may result in increased activity in ventral PPC regions associated with bottom-up attention to memory. These findings indicate that distinct parietal sites mediate the influences of mood, arousal, and their interplay during recognition memory.

  2. Interleukin-6 mediates epithelial-stromal interactions and promotes gastric tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Hiroto Kinoshita

    Full Text Available Interleukin-6 (IL-6 is a pleiotropic cytokine that affects various functions, including tumor development. Although the importance of IL-6 in gastric cancer has been documented in experimental and clinical studies, the mechanism by which IL-6 promotes gastric cancer remains unclear. In this study, we investigated the role of IL-6 in the epithelial-stromal interaction in gastric tumorigenesis. Immunohistochemical analysis of human gastritis, gastric adenoma, and gastric cancer tissues revealed that IL-6 was frequently detected in the stroma. IL-6-positive cells in the stroma showed positive staining for the fibroblast marker α-smooth muscle actin, suggesting that stromal fibroblasts produce IL-6. We compared IL-6 knockout (IL-6(-/- mice with wild-type (WT mice in a model of gastric tumorigenesis induced by the chemical carcinogen N-methyl-N-nitrosourea. The stromal fibroblasts expressed IL-6 in tumors from WT mice. Gastric tumorigenesis was attenuated in IL-6(-/- mice, compared with WT mice. Impaired tumor development in IL-6(-/- mice was correlated with the decreased activation of STAT3, a factor associated with gastric cancer cell proliferation. In vitro, when gastric cancer cell line was co-cultured with primary human gastric fibroblast, STAT3-related genes including COX-2 and iNOS were induced in gastric cancer cells and this response was attenuated with neutralizing anti-IL-6 receptor antibody. IL-6 production from fibroblasts was increased when fibroblasts were cultured in the presence of gastric cancer cell-conditioned media. IL-6 production from fibroblasts was suppressed by an interleukin-1 (IL-1 receptor antagonist and siRNA inhibition of IL-1α in the fibroblasts. IL-1α mRNA and protein were increased in fibroblast lysate, suggesting that cell-associated IL-1α in fibroblasts may be involved. Our results suggest the importance of IL-6 mediated stromal-epithelial cell interaction in gastric tumorigenesis.

  3. Ketamine, propofol and the EEG: a neural field analysis of HCN1-mediated interactions

    Directory of Open Access Journals (Sweden)

    Ingo eBojak

    2013-04-01

    Full Text Available Ketamine and propofol are two well-known, powerful anesthetic agents, yet at first sight this appears to be their only commonality. Ketamine is a dissociative anesthetic agent, whose main mechanism of action is considered to be N-methyl-D-aspartate (NMDA antagonism; whereas propofol is a general anesthetic agent, which is assumed to primarily potentiate currents gated by γ-aminobutyric acid type A (GABA A receptors. However, several experimental observations suggest a closer relationship. First, the effect of ketamine on the electroencephalogram (EEG is markedly changed in the presence of propofol: on its own ketamine increases theta (4–8 Hz and decreases alpha (8–13 Hz oscillations, whereas ketamine induces a significant shift to beta band frequencies (13–30 Hz in the presence of propofol. Second, both ketamine and propofol cause inhibition of the inward pacemaker current Ih, by binding to the corresponding hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 (HCN1 subunit. The resulting effect is a hyperpolarization of the neuron’s resting membrane potential. Third, the ability of both ketamine and propofol to induce hypnosis is reduced in HCN1-knockout mice. Here we show that one can theoretically understand the observed spectral changes of the EEG based on HCN1-mediated hyperpolarizations alone, without involving the supposed main mechanisms of action of these drugs through NMDA and GABA A, respectively. On the basis of our successful EEG model we conclude that ketamine and propofol should be antagonistic to each other in their interaction at HCN1 subunits. Such a prediction is in accord with the results of clinical experiment in which it is found that ketamine and propofol interact in an infra-additive manner with respect to the endpoints of hypnosis and immobility.

  4. Neto-mediated intracellular interactions shape postsynaptic composition at the Drosophila neuromuscular junction.

    Directory of Open Access Journals (Sweden)

    Cathy I Ramos

    2015-04-01

    Full Text Available The molecular mechanisms controlling the subunit composition of glutamate receptors are crucial for the formation of neural circuits and for the long-term plasticity underlying learning and memory. Here we use the Drosophila neuromuscular junction (NMJ to examine how specific receptor subtypes are recruited and stabilized at synaptic locations. In flies, clustering of ionotropic glutamate receptors (iGluRs requires Neto (Neuropillin and Tolloid-like, a highly conserved auxiliary subunit that is essential for NMJ assembly and development. Drosophila neto encodes two isoforms, Neto-α and Neto-β, with common extracellular parts and distinct cytoplasmic domains. Mutations that specifically eliminate Neto-β or its intracellular domain were generated. When Neto-β is missing or is truncated, the larval NMJs show profound changes in the subtype composition of iGluRs due to reduced synaptic accumulation of the GluRIIA subunit. Furthermore, neto-β mutant NMJs fail to accumulate p21-activated kinase (PAK, a critical postsynaptic component implicated in the synaptic stabilization of GluRIIA. Muscle expression of either Neto-α or Neto-β rescued the synaptic transmission at neto null NMJs, indicating that Neto conserved domains mediate iGluRs clustering. However, only Neto-β restored PAK synaptic accumulation at neto null NMJs. Thus, Neto engages in intracellular interactions that regulate the iGluR subtype composition by preferentially recruiting and/or stabilizing selective receptor subtypes.

  5. Thioredoxin interacting protein mediates lipid-induced impairment of glucose uptake in skeletal muscle.

    Science.gov (United States)

    Mandala, Ashok; Das, Nabanita; Bhattacharjee, Sudarshan; Mukherjee, Bidisha; Mukhopadhyay, Satinath; Roy, Sib Sankar

    2016-10-28

    Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of circulating FFA leads to intra-myocellular lipid accumulation that induces mitochondrial ROS generation and worsens IR. However, the molecular mechanisms behind are unclear. We identified thioredoxin interacting protein (TxNIP), which is overexpressed in T2DM, to be a promoter of ROS-induced IR. We observed upregulation of TxNIP upon palmitate treatment in skeletal muscle cells that led to ROS generation and Glut-4 downregulation resulting in impaired glucose-uptake. FFA-induced overexpression of TxNIP gene was mediated through the activation of its bona-fide trans activator, ChREBP. Further, Palmitate-induced impairment in AMPK-SIRT-1 pathway resulted in overexpression of ChREBP. While Fenofibrate, abrogated PA-induced TxNIP expression and ROS generation in skeletal muscle cells, Saroglitazar, a dual PPARα/γ-agonist, not only inhibited PA-induced TXNIP expression but also led to greater improvement in glucose uptake. Taken together, TxNIP appears to be an important factor in FFA-induced ROS generation and IR in skeletal muscle cells, which can be modulated for the management of this complex disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Conformational diversity in the TPR domain-mediated interaction of protein phosphatase 5 with Hsp90.

    Science.gov (United States)

    Cliff, Matthew J; Harris, Richard; Barford, David; Ladbury, John E; Williams, Mark A

    2006-03-01

    Protein phosphatase 5 (Ppp5) is one of several proteins that bind to the Hsp90 chaperone via a tetratricopeptide repeat (TPR) domain. We report the solution structure of a complex of the TPR domain of Ppp5 with the C-terminal pentapeptide of Hsp90. This structure has the "two-carboxylate clamp" mechanism of peptide binding first seen in the Hop-TPR domain complexes with Hsp90 and Hsp70 peptides. However, NMR data reveal that the Ppp5 clamp is highly dynamic, and that there are multiple modes of peptide binding and mobility throughout the complex. Although this interaction is of very high affinity, relatively few persistent contacts are found between the peptide and the Ppp5-TPR domain, thus explaining its promiscuity in binding both Hsp70 and Hsp90 in vivo. We consider the possible implications of this dynamic structure for the mechanism of relief of autoinhibition in Ppp5 and for the mechanisms of TPR-mediated recognition of Hsp90 by other proteins.

  7. 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions.

    Science.gov (United States)

    Callen, Elsa; Di Virgilio, Michela; Kruhlak, Michael J; Nieto-Soler, Maria; Wong, Nancy; Chen, Hua-Tang; Faryabi, Robert B; Polato, Federica; Santos, Margarida; Starnes, Linda M; Wesemann, Duane R; Lee, Ji-Eun; Tubbs, Anthony; Sleckman, Barry P; Daniel, Jeremy A; Ge, Kai; Alt, Frederick W; Fernandez-Capetillo, Oscar; Nussenzweig, Michel C; Nussenzweig, André

    2013-06-06

    The DNA damage response (DDR) protein 53BP1 protects DNA ends from excessive resection in G1, and thereby favors repair by nonhomologous end-joining (NHEJ) as opposed to homologous recombination (HR). During S phase, BRCA1 antagonizes 53BP1 to promote HR. The pro-NHEJ and antirecombinase functions of 53BP1 are mediated in part by RIF1, the only known factor that requires 53BP1 phosphorylation for its recruitment to double-strand breaks (DSBs). Here, we show that a 53BP1 phosphomutant, 53BP18A, comprising alanine substitutions of the eight most N-terminal S/TQ phosphorylation sites, mimics 53BP1 deficiency by restoring genome stability in BRCA1-deficient cells yet behaves like wild-type 53BP1 with respect to immunoglobulin class switch recombination (CSR). 53BP18A recruits RIF1 but fails to recruit the DDR protein PTIP to DSBs, and disruption of PTIP phenocopies 53BP18A. We conclude that 53BP1 promotes productive CSR and suppresses mutagenic DNA repair through distinct phosphodependent interactions with RIF1 and PTIP.

  8. Multivalent ligand-receptor-mediated interaction of small filled vesicles with a cellular membrane

    Science.gov (United States)

    Zhdanov, Vladimir P.

    2017-07-01

    The ligand-receptor-mediated contacts of small sub-100-nm-sized lipid vesicles (or nanoparticles) with the cellular membrane are of interest in the contexts of cell-to-cell communication, endocytosis of membrane-coated virions, and drug (RNA) delivery. In all these cases, the interior of vesicles is filled by biologically relevant content. Despite the diversity of such systems, the corresponding ligand-receptor interaction possesses universal features. One of them is that the vesicle-membrane contacts can be accompanied by the redistribution of ligands and receptors between the contact and contact-free regions. In particular, the concentrations of ligands and receptors may become appreciably higher in the contact regions and their composition may there be different compared to that in the suspended state in the solution. A statistical model presented herein describes the corresponding distribution of various ligands and receptors and allows one to calculate the related change of the free energy with variation of the vesicle-engulfment extent. The results obtained are used to clarify the necessary conditions for the vesicle-assisted pathway of drug delivery.

  9. Tumour–stromal interactions in acid-mediated invasion: A mathematical model

    KAUST Repository

    Martin, Natasha K.

    2010-12-01

    It is well established that the tumour microenvironment can both promote and suppress tumour growth and invasion, however, most mathematical models of invasion view the normal tissue as inhibiting tumour progression via immune modulation or spatial constraint. In particular, the production of acid by tumour cells and the subsequent creation of a low extracellular pH environment has been explored in several \\'acid-mediated tumour invasion\\' models where the acidic environment facilitates normal cell death and permits tumour invasion. In this paper, we extend the acid-invasion model developed by Gatenby and Gawlinski (1996) to include both the competitive and cooperative interactions between tumour and normal cells, by incorporating the influence of extracellular matrix and protease production at the tumour-stroma interface. Our model predicts an optimal level of tumour acidity which produces both cell death and matrix degradation. Additionally, very aggressive tumours prevent protease production and matrix degradation by excessive normal cell destruction, leading to an acellular (but matrix filled) gap between the tumour and normal tissue, a feature seen in encapsulated tumours. These results suggest, counterintuitively, that increasing tumour acidity may, in some cases, prevent tumour invasion.

  10. Induction of Erythropoiesis by MHC-Mediated Cognate Interactions between B- and T-Cells.

    Science.gov (United States)

    Guha, A; Tuck, D P; Cone, R E; Dainiak, N

    1997-01-01

    We have previously shown that the expression of membrane burst-promoting activity (mBPA), an erythropoietic cytokine, by B-lymphocytes is augmented by the addition of allogeneic effector cells to the B-cells. Here, we have examined immune mechanisms involved in the induction/promotion of erythropoiesis as assessed by the capacity of autologous and allogeneic peripheral blood lymphocytes to augment burst-forming unit-erythroid (BFU-E) in normal human bone marrow cells in vitro. Preincubation of mBPA-expressing human B-cells with monoclonal antibodies to major histocompatibility complex (MHC) antigens, abrogated erythropoietic activity of both autologous and allogeneic lymphocytes, suggesting that MHC antigens play a role in regulating the expression of the erythroid growth factor. Inhibition of BFU-E proliferation was also evident when antibodies to MHC class-I or class-II antigens were added directly to marrow culture. Furthermore, addition of anti-CD4 antibody to the cultures of PBL and autologous target BM cells markedly reduced erythroid proliferation induced by PBL. By contrast, anti-CD8 and control (UPC-10) monoclonal antibodies had no effect. These results provide evidence that MHC-mediated cognate interactions between T- and B-lymphocytes may participate in the control of erythropoiesis, either directly or by modulating mBPA function.

  11. Impact of robot-mediated interaction system on joint attention skills for children with autism.

    Science.gov (United States)

    Zheng, Zhi; Zhang, Lian; Bekele, Esubalew; Swanson, Amy; Crittendon, Julie A; Warren, Zachary; Sarkar, Nilanjan

    2013-06-01

    With Centers for Disease Control and Prevention prevalence estimates for children with autism spectrum disorder 1 in 88, identification and effective treatment of autism spectrum disorder (ASD) is often characterized as a public health emergency. There is an urgent need for more efficacious treatments whose realistic application will yield more substantial impact on the neurodevelopmental trajectories of young children with ASD. Robotic technology appears particularly promising for potential application to ASD intervention. Initial results applying robotic technology to ASD intervention have consistently demonstrated a unique potential to elicit interest and attention in young children with ASD. As such, technologies capable of intelligently harnessing this potential, along with capabilities for detecting and meaningfully responding to young children's attention and behavior, may represent intervention platforms with substantial promise for impacting early symptoms of ASD. Our current work describes development and application of a novel adaptive robot-mediated interaction technology for facilitating early joint attention skills for children with ASD. The system is composed of a humanoid robot endowed with a prompt decision hierarchy to alter behavior in concert with reinforcing stimuli within an intervention environment to promote joint attention skills. Results of implementation of this system over time, including specific analyses of attentional bias and performance enhancement, with 6 young children with ASD are presented.

  12. Avidin-biotin interaction mediated peptide assemblies as efficient gene delivery vectors for cancer therapy.

    Science.gov (United States)

    Qu, Wei; Chen, Wei-Hai; Kuang, Ying; Zeng, Xuan; Cheng, Si-Xue; Zhou, Xiang; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2013-01-01

    Gene therapy offers a bright future for the treatment of cancers. One of the research highlights focuses on smart gene delivery vectors with good biocompatibility and tumor-targeting ability. Here, a novel gene vector self-assembled through avidin-biotin interaction with optimized targeting functionality, biotinylated tumor-targeting peptide/avidin/biotinylated cell-penetrating peptide (TAC), was designed and prepared to mediate the in vitro and in vivo delivery of p53 gene. TAC exhibited efficient DNA-binding ability and low cytotoxicity. In in vitro transfection assay, TAC/p53 complexes showed higher transfection efficiency and expression amount of p53 protein in MCF-7 cells as compared with 293T and HeLa cells, primarily due to the specific recognition between tumor-targeting peptides and receptors on MCF-7 cells. Additionally, by in situ administration of TAC/p53 complexes into tumor-bearing mice, the expression of p53 gene was obviously upregulated in tumor cells, and the tumor growth was significantly suppressed. This study provides an alternative and unique strategy to assemble functionalized peptides, and the novel self-assembled vector TAC developed is a promising gene vector for cancer therapy.

  13. Fungal-mediated multitrophic interactions--do grass endophytes in diet protect voles from predators?

    Directory of Open Access Journals (Sweden)

    Susanna Saari

    Full Text Available Plant-associated micro-organisms such as mycotoxin-producing endophytes commonly have direct negative effects on herbivores. These effects may be carried over to natural enemies of the herbivores, but this has been rarely explored. We examined how feeding on Neotyphodium endophyte infected (E+ and endophyte free (E- meadow ryegrass (Scherodonus pratensis affects body mass, population size and mobility of sibling voles (Microtus levis, and whether the diet mediates the vulnerability of voles to least weasel (Mustela nivalis nivalis predation. Because least weasels are known to be olfactory hunters, we also examined whether they are able to distinguish olfactory cues of voles fed on E+ and E- diets. Neither body mass of voles nor population size differed between diets. However, contrary to our prediction, least weasels preyed more often on voles fed with E- grass than on voles fed with E+ grass. The mobility of voles fed on E+ grass was reduced compared to voles fed on E- grass, but this effect was unrelated to risk of predation. Least weasels appeared unable to distinguish between excrement odours of voles between the two treatments. Our results suggest that consumption of endophytic grass is not directly deleterious to sibling voles. What's more, consumption of endophytes appears to be advantageous to voles by reducing risk of mammalian predation. Our study is thus the first to demonstrate an effect of plant-associated microbial symbionts on herbivore-predator interactions in vertebrate communities.

  14. Fungal-mediated multitrophic interactions--do grass endophytes in diet protect voles from predators?

    Science.gov (United States)

    Saari, Susanna; Sundell, Janne; Huitu, Otso; Helander, Marjo; Ketoja, Elise; Ylönen, Hannu; Saikkonen, Kari

    2010-03-24

    Plant-associated micro-organisms such as mycotoxin-producing endophytes commonly have direct negative effects on herbivores. These effects may be carried over to natural enemies of the herbivores, but this has been rarely explored. We examined how feeding on Neotyphodium endophyte infected (E+) and endophyte free (E-) meadow ryegrass (Scherodonus pratensis) affects body mass, population size and mobility of sibling voles (Microtus levis), and whether the diet mediates the vulnerability of voles to least weasel (Mustela nivalis nivalis) predation. Because least weasels are known to be olfactory hunters, we also examined whether they are able to distinguish olfactory cues of voles fed on E+ and E- diets. Neither body mass of voles nor population size differed between diets. However, contrary to our prediction, least weasels preyed more often on voles fed with E- grass than on voles fed with E+ grass. The mobility of voles fed on E+ grass was reduced compared to voles fed on E- grass, but this effect was unrelated to risk of predation. Least weasels appeared unable to distinguish between excrement odours of voles between the two treatments. Our results suggest that consumption of endophytic grass is not directly deleterious to sibling voles. What's more, consumption of endophytes appears to be advantageous to voles by reducing risk of mammalian predation. Our study is thus the first to demonstrate an effect of plant-associated microbial symbionts on herbivore-predator interactions in vertebrate communities.

  15. JNK interaction with Sab mediates ER stress induced inhibition of mitochondrial respiration and cell death.

    Science.gov (United States)

    Win, S; Than, T A; Fernandez-Checa, J C; Kaplowitz, N

    2014-01-09

    Our aim was to better understand the mechanism and importance of sustained c-Jun N-terminal kinase (JNK) activation in endoplasmic reticulum (ER) stress and effects of ER stress on mitochondria by determining the role of mitochondrial JNK binding protein, Sab. Tunicamycin or brefeldin A induced a rapid and marked decline in basal mitochondrial respiration and reserve-capacity followed by delayed mitochondrial-mediated apoptosis. Knockdown of mitochondrial Sab prevented ER stress-induced sustained JNK activation, impaired respiration, and apoptosis, but did not alter the magnitude or time course of activation of ER stress pathways. P-JNK plus adenosine 5'-triphosphate (ATP) added to isolated liver mitochondria promoted superoxide production, which was amplified by addition of calcium and inhibited by a blocking peptide corresponding to the JNK binding site on Sab (KIM1). This peptide also blocked tunicamycin-induced inhibition of cellular respiration. In conclusion, ER stress triggers an interaction of JNK with mitochondrial Sab, which leads to impaired respiration and increased mitochondrial reactive oxygen species, sustaining JNK activation culminating in apoptosis.

  16. The Legionella pneumophila collagen-like protein mediates sedimentation, autoaggregation, and pathogen-phagocyte interactions.

    Science.gov (United States)

    Abdel-Nour, Mena; Duncan, Carla; Prashar, Akriti; Rao, Chitong; Ginevra, Christophe; Jarraud, Sophie; Low, Donald E; Ensminger, Alexander W; Terebiznik, Mauricio R; Guyard, Cyril

    2014-02-01

    Although only partially understood, multicellular behavior is relatively common in bacterial pathogens. Bacterial aggregates can resist various host defenses and colonize their environment more efficiently than planktonic cells. For the waterborne pathogen Legionella pneumophila, little is known about the roles of autoaggregation or the parameters which allow cell-cell interactions to occur. Here, we determined the endogenous and exogenous factors sufficient to allow autoaggregation to take place in L. pneumophila. We show that isolates from Legionella species which do not produce the Legionella collagen-like protein (Lcl) are deficient in autoaggregation. Targeted deletion of the Lcl-encoding gene (lpg2644) and the addition of Lcl ligands impair the autoaggregation of L. pneumophila. In addition, Lcl-induced autoaggregation requires divalent cations. Escherichia coli producing surface-exposed Lcl is able to autoaggregate and shows increased biofilm production. We also demonstrate that L. pneumophila infection of Acanthamoeba castellanii and Hartmanella vermiformis is potentiated under conditions which promote Lcl dependent autoaggregation. Overall, this study shows that L. pneumophila is capable of autoaggregating in a process that is mediated by Lcl in a divalent-cation-dependent manner. It also reveals that Lcl potentiates the ability of L. pneumophila to come in contact, attach, and infect amoebae.

  17. Neuroimmune Interaction in the Regulation of Peripheral Opioid-Mediated Analgesia in Inflammation.

    Science.gov (United States)

    Hua, Susan

    2016-01-01

    Peripheral immune cell-mediated analgesia in inflammation is an important endogenous mechanism of pain control. Opioid receptors localized on peripheral sensory nerve terminals are activated by endogenous opioid peptides released from immune cells to produce significant analgesia. Following transendothelial migration of opioid-containing leukocytes into peripheral sites of inflammation, opioid peptides are released into a harsh milieu associated with an increase in temperature, low pH, and high proteolytic activity. Together, this microenvironment has been suggested to increase the activity of opioid peptide metabolism. Therefore, the proximity of immune cells and nerve fibers may be essential to produce adequate analgesic effects. Close associations between opioid-containing immune cells and peripheral nerve terminals have been observed. However, it is not yet determined whether these immune cells actually form synaptic-like contacts with peripheral sensory terminals and/or whether they secrete opioids in a paracrine manner. This review will provide novel insight into the peripheral mechanisms of immune-derived analgesia in inflammation, in particular, the importance of direct interactions between immune cells and the peripheral nervous system.

  18. INTERACTIONS MEDIATED BY TECHNOLOGY IN THE CLASSROOM: THE USE OF SOCIAL NETWORKS AND THE DIGITAL DIVIDE

    Directory of Open Access Journals (Sweden)

    Ranice Hoehr Pedrazzi Pozzer

    2017-10-01

    Full Text Available The National Program for Access to Secondary Education and Employment (Pronatec, created by the federal government has offered, in recent years, training in technical courses at post-secondary level for young people and adults inserted in the educational system and who were attending or finishing high school, including the Youth and Adult Education system (EJA. Thus, some classes of technical courses presented a varied profile of students from teenagers who attend public schools and even older adults who are returning to school after years of absence from the education system. The present study analyzed four groups of students aged between 15 and 63 years. This age difference, how the oldest students use or not technology and the kind of relationship between the students in the classroom raised questions about their relationship on social networks. This network usage by the students significantly influenced the pedagogical practice during the course, considering that the students asked the teacher to use it as a teaching and learning resource. The students transit from reality to virtual world with the naturalness of people who were born inserted in this context of interactions mediated by technology.

  19. Overcoming target-mediated quinolone resistance in topoisomerase IV by introducing metal-ion-independent drug-enzyme interactions.

    Science.gov (United States)

    Aldred, Katie J; Schwanz, Heidi A; Li, Gangqin; McPherson, Sylvia A; Turnbough, Charles L; Kerns, Robert J; Osheroff, Neil

    2013-12-20

    Quinolones, which target gyrase and topoisomerase IV, are the most widely prescribed antibacterials worldwide. Unfortunately, their use is threatened by the increasing prevalence of target-mediated drug resistance. Greater than 90% of mutations that confer quinolone resistance act by disrupting enzyme-drug interactions coordinated by a critical water-metal ion bridge. Quinazolinediones are quinolone-like drugs but lack the skeletal features necessary to support the bridge interaction. These compounds are of clinical interest, however, because they retain activity against the most common quinolone resistance mutations. We utilized a chemical biology approach to determine how quinazolinediones overcome quinolone resistance in Bacillus anthracis topoisomerase IV. Quinazolinediones that retain activity against quinolone-resistant topoisomerase IV do so primarily by establishing novel interactions through the C7 substituent, rather than the drug skeleton. Because some quinolones are highly active against human topoisomerase IIα, we also determined how clinically relevant quinolones discriminate between the bacterial and human enzymes. Clinically relevant quinolones display poor activity against topoisomerase IIα because the human enzyme cannot support drug interactions mediated by the water-metal ion bridge. However, the inclusion of substituents that allow quinazolinediones to overcome topoisomerase IV-mediated quinolone resistance can cause cross-reactivity against topoisomerase IIα. Therefore, a major challenge in designing drugs that overcome quinolone resistance lies in the ability to identify substituents that mediate strong interactions with the bacterial, but not the human, enzymes. On the basis of our understanding of quinolone-enzyme interactions, we have identified three compounds that display high activity against quinolone-resistant B. anthracis topoisomerase IV but low activity against human topoisomerase IIα.

  20. Young children accessing the learning of others: mediation through the ‘witnessing’ of others’ gestural interactions

    Directory of Open Access Journals (Sweden)

    Karl Wall

    2006-05-01

    Full Text Available Contextualisation Children’s interactions in the classroom arguably underpin many of the learning events and activities they experience. These may involve their classroom teacher, teaching assistants, other adults (including, in the primary school, context, parents / carers, their peers or other children entering the room where they are working. The paper that follows, reflects on the nature of such interactions, focusing on gestural behaviours, observed as part of a programme of doctoral study. It explores the notion of how the ‘witnessing’ of others’ interactions may contribute to and inform the behaviour, understanding and learning of a child, as they work with their peers and a teacher on a grouped task. In so doing, it re-examines the notion of the more experienced other, associated with Vygotsky’s ideas on social interaction in a pedagogic context and draws on a range of disciplines for both practical and theoretical inspiration. Abstract: Arising from a study of grouped 5-6 year olds’ gestural interactions, an extension to Vygotskian notions of mediation is proposed. This is developed through a consideration of ideas grounded in: cultural psychology, situated learning, distributed cognition , the analysis of ‘task affordances’. The potential significance and role of a child’s ‘witnessing’ of the mediational interactions of others is discussed informed by data drawn from the author’s current research. The implications for teachers’ practice as a more ‘experienced other’, in such interactions, are briefly discussed.

  1. DMPD: Signal transduction pathways mediated by the interaction of CpG DNA withToll-like receptor 9. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14751759 Signal transduction pathways mediated by the interaction of CpG DNA withTo...;16(1):17-22. (.png) (.svg) (.html) (.csml) Show Signal transduction pathways mediated by the interaction of... CpG DNA withToll-like receptor 9. PubmedID 14751759 Title Signal transduction pa

  2. 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.

  3. AGE-RAGE interaction in the TGFβ2-mediated epithelial to mesenchymal transition of human lens epithelial cells.

    Science.gov (United States)

    Raghavan, Cibin T; Nagaraj, Ram H

    2016-08-01

    Basement membrane (BM) proteins accumulate chemical modifications with age. One such modification is glycation, which results in the formation of advanced glycation endproducts (AGEs). In a previous study, we reported that AGEs in the human lens capsule (BM) promote the TGFβ2-mediated epithelial-to-mesenchymal transition (EMT) of lens epithelial cells, which we proposed as a mechanism for posterior capsule opacification (PCO) or secondary cataract formation. In this study, we investigated the role of a receptor for AGEs (RAGE) in the TGFβ2-mediated EMT in a human lens epithelial cell line (FHL124). RAGE was present in FHL124 cells, and its levels were unaltered in cells cultured on either native or AGE-modified BM or upon treatment with TGFβ2. RAGE overexpression significantly enhanced the TGFβ2-mediated EMT responses in cells cultured on AGE-modified BM compared with the unmodified matrix. In contrast, treatment of cells with a RAGE antibody or EN-RAGE (an endogenous ligand for RAGE) resulted in a significant reduction in the TGFβ2-mediated EMT response. This was accompanied by a reduction in TGFβ2-mediated Smad signaling and ROS generation. These results imply that the interaction of matrix AGEs with RAGE plays a role in the TGFβ2-mediated EMT of lens epithelial cells and suggest that the blockade of RAGE could be a strategy to prevent PCO and other age-associated fibrosis.

  4. Complement-mediated solubilization of immune complexes and their interaction with complement C3 receptors

    DEFF Research Database (Denmark)

    Petersen, Ivan; Baatrup, Gunnar; Jepsen, H H;

    1985-01-01

    Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components of the me......Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components...

  5. Integrin-mediated interactions with extracellular matrix proteins for nucleus pulposus cells of the human intervertebral disc.

    Science.gov (United States)

    Bridgen, D T; Gilchrist, C L; Richardson, W J; Isaacs, R E; Brown, C R; Yang, K L; Chen, J; Setton, L A

    2013-10-01

    The extracellular matrix (ECM) of the human intervertebral disc is rich in molecules that interact with cells through integrin-mediated attachments. Porcine nucleus pulposus (NP) cells have been shown to interact with laminin (LM) isoforms LM-111 and LM-511 through select integrins that regulate biosynthesis and cell attachment. Since human NP cells lose many phenotypic characteristics with age, attachment and interaction with the ECM may be altered. Expression of LM-binding integrins was quantified for human NP cells using flow cytometry. The cell-ECM attachment mechanism was determined by quantifying cell attachment to LM-111, LM-511, or type II collagen after functionally blocking specific integrin subunits. Human NP cells express integrins β1, α3, and α5, with over 70% of cells positive for each subunit. Blocking subunit β1 inhibited NP cell attachment to all substrates. Blocking subunits α1, α2, α3, and α5 simultaneously, but not individually, inhibits NP cell attachment to laminins. While integrin α6β1 mediated porcine NP cell attachment to LM-111, we found integrins α3, α5, and β1 instead contributed to human NP cell attachment. These findings identify integrin subunits that may mediate interactions with the ECM for human NP cells and could be used to promote cell attachment, survival, and biosynthesis in cell-based therapeutics.

  6. Mediating Language Learning: Teacher Interactions with ESL Students in a Content-Based Classroom.

    Science.gov (United States)

    Gibbons, Pauline

    2003-01-01

    Draws on constructs of "mediation" from sociocultural theory and "mode continuum" from systemic functional linguistics to investigate how student-teacher talk in a content-based classroom contributes to learners' language development. Shows how teachers mediate between students' linguistic levels in English and their…

  7. RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion.

    Science.gov (United States)

    Lafuente, Esther M; van Puijenbroek, André A F L; Krause, Matthias; Carman, Christopher V; Freeman, Gordon J; Berezovskaya, Alla; Constantine, Erica; Springer, Timothy A; Gertler, Frank B; Boussiotis, Vassiliki A

    2004-10-01

    The small GTPase Rap1 induces integrin-mediated adhesion and changes in the actin cytoskeleton. The mechanisms that mediate these effects of Rap1 are poorly understood. We have identified RIAM as a Rap1-GTP-interacting adaptor molecule. RIAM defines a family of adaptor molecules that contain a RA-like (Ras association) domain, a PH (pleckstrin homology) domain, and various proline-rich motifs. RIAM also interacts with Profilin and Ena/VASP proteins, molecules that regulate actin dynamics. Overexpression of RIAM induced cell spreading and lamellipodia formation, changes that require actin polymerization. In contrast, RIAM knockdown cells had reduced content of polymerized actin. RIAM overexpression also induced integrin activation and cell adhesion. RIAM knockdown displaced Rap1-GTP from the plasma membrane and abrogated Rap1-induced adhesion. Thus, RIAM links Rap1 to integrin activation and plays a role in regulating actin dynamics.

  8. Light-regulated stapled peptides to inhibit protein-protein interactions involved in clathrin-mediated endocytosis.

    Science.gov (United States)

    Nevola, Laura; Martín-Quirós, Andrés; Eckelt, Kay; Camarero, Núria; Tosi, Sébastien; Llobet, Artur; Giralt, Ernest; Gorostiza, Pau

    2013-07-22

    Control of membrane traffic: Photoswitchable inhibitors of protein-protein interactions were applied to photoregulate clathrin-mediated endocytosis (CME) in living cells. Traffic light (TL) peptides acting as "stop" and "go" signals for membrane traffic can be used to dissect the role of CME in receptor internalization and in cell growth, division, and differentiation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Ultrafast fluorescent decay induced by metal-mediated dipole-dipole interaction in two-dimensional molecular aggregates

    CERN Document Server

    Hu, Qing; Nam, Sang Hoon; Xiao, Jun; Liu, Yongmin; Zhang, Xiang; Fang, Nicholas X

    2016-01-01

    Two-dimensional molecular aggregate (2DMA), a thin sheet of strongly interacting dipole molecules self-assembled at close distance on an ordered lattice, is a fascinating fluorescent material. It is distinctively different from the single or colloidal dye molecules or quantum dots in most previous research. In this paper, we verify for the first time that when a 2DMA is placed at a nanometric distance from a metallic substrate, the strong and coherent interaction between the dipoles inside the 2DMA dominates its fluorescent decay at picosecond timescale. Our streak-camera lifetime measurement and interacting lattice-dipole calculation reveal that the metal-mediated dipole-dipole interaction shortens the fluorescent lifetime to about one half and increases the energy dissipation rate by ten times than expected from the noninteracting single-dipole picture. Our finding can enrich our understanding of nanoscale energy transfer in molecular excitonic systems and may designate a new direction for developing fast a...

  10. INTERACTION-MEDIATED GROWTH OF CARBON NANOTUBES ON ACICULAR SILICA-COATED α-Fe CATALYST BY CHEMICAL VAPOR DEPOSITION

    Institute of Scientific and Technical Information of China (English)

    Qixiang Wang; Guoqing Ning; Fei Wei; Guohua Luo

    2003-01-01

    Multi-walled carbon nanotubes (MWNTs) with 20 nm outer diameter were prepared by chemical vapor deposition of ethylene using ultrafine surface-modified acicular α-Fe catalyst particles. The growth mechanism of MWNTs on the larger catalyst particles are attributed to the interaction between the Fe nanoparticles with the surface-modified silica layer. This interaction-mediated growth mechanism is illustrated by studying the electronic, atomic and crystal properties of surface-modified catalysts and MWNTs products by characterization with X-ray diffraction (XRD), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), thermal gravimetric analysis (TGA) and Raman spectra.

  11. Ganglioside GM2 mediates migration of tumor cells by interacting with integrin and modulating the downstream signaling pathway.

    Science.gov (United States)

    Kundu, Manjari; Mahata, Barun; Banerjee, Avisek; Chakraborty, Sohini; Debnath, Shibjyoti; Ray, Sougata Sinha; Ghosh, Zhumur; Biswas, Kaushik

    2016-07-01

    The definitive role of ganglioside GM2 in mediating tumor-induced growth and progression is still unknown. Here we report a novel role of ganglioside GM2 in mediating tumor cell migration and uncovered its mechanism. Data shows differential expression levels of GM2-synthase as well as GM2 in different human cancer cells. siRNA mediated knockdown of GM2-synthase in CCF52, A549 and SK-RC-26B cells resulted in significant inhibition of tumor cell migration as well as invasion in vitro without affecting cellular proliferation. Over-expression of GM2-synthase in low-GM2 expressing SK-RC-45 cells resulted in a consequent increase in migration thus confirming the potential role GM2 and its downstream partners play in tumor cell migration and motility. Further, treatment of SK-RC-45 cells with exogenous GM2 resulted in a dramatic increase in migratory and invasive capacity with no change in proliferative capacity, thereby confirming the role of GM2 in tumorigenesis specifically by mediating tumor migration and invasion. Gene expression profiling of GM2-synthase silenced cells revealed altered expression of several genes involved in cell migration primarily those controlling the integrin mediated signaling. GM2-synthase knockdown resulted in decreased phosphorylation of FAK, Src as well as Erk, while over-expression and/or exogenous GM2 treatment caused increased FAK and Erk phosphorylation respectively. Again, GM2 mediated invasion and Erk phosphorylation is blocked in integrin knockdown SK-RC-45 cells, thus confirming that GM2 mediated migration and phosphorylation of Erk is integrin dependent. Finally, confocal microscopy suggested co-localization while co-immunoprecipitation and surface plasmon resonance (SPR) confirmed direct interaction of membrane bound ganglioside, GM2 with the integrin receptor.

  12. BRCA1 interacts with Smad3 and regulates Smad3-mediated TGF-beta signaling during oxidative stress responses.

    Directory of Open Access Journals (Sweden)

    Huchun Li

    Full Text Available BACKGROUND: BRCA1 is a key regulatory protein participating in cell cycle checkpoint and DNA damage repair networks. BRCA1 plays important roles in protecting numerous cellular processes in response to cell damaging signals. Transforming growth factor-beta (TGF-beta is a potent regulator of growth, apoptosis and invasiveness of tumor cells. TFG-beta activates Smad signaling via its two cell surface receptors, the TbetaRII and ALK5/TbetaRI, leading to Smad-mediated transcriptional regulation. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report an important role of BRCA1 in modulating TGF-beta signaling during oxidative stress responses. Wild-type (WT BRCA1, but not mutated BRCA1 failed to activate TGF-beta mediated transactivation of the TGF-beta responsive reporter, p3TP-Lux. Further, WT-BRCA1, but not mutated BRCA1 increased the expression of Smad3 protein in a dose-dependent manner, while silencing of WT-BRCA1 by siRNA decreased Smad3 and Smad4 interaction induced by TGF-beta in MCF-7 breast cancer cells. BRCA1 interacted with Smad3 upon TGF-beta1 stimulation in MCF-7 cells and this interaction was mediated via the domain of 298-436aa of BRCA1 and Smad3 domain of 207-426aa. In addition, H(2O(2 increased the colocalization and the interaction of Smad3 with WT-BRCA1. Interestingly, TGF-beta1 induced Smad3 and Smad4 interaction was increased in the presence of H(2O(2 in cells expressing WT-BRCA1, while the TGF-beta1 induced interaction between Smad3 and Smad4 was decreased upon H(2O(2 treatment in a dose-dependent manner in HCC1937 breast cancer cells, deficient for endogenous BRCA1. This interaction between Smad3 and Smad4 was increased in reconstituted HCC1937 cells expressing WT-BRCA1 (HCC1937/BRCA1. Further, loss of BRCA1 resulted in H(2O(2 induced nuclear export of phosphor-Smad3 protein to the cytoplasm, resulting decreased of Smad3 and Smad4 interaction induced by TGF-beta and in significant decrease in Smad3 and Smad4 transcriptional

  13. Receptor-like kinases as surface regulators for RAC/ROP-mediated pollen tube growth and interaction with the pistil

    Science.gov (United States)

    Zou, Yanjiao; Aggarwal, Mini; Zheng, Wen-Guang; Wu, Hen-Ming; Cheung, Alice Y.

    2011-01-01

    Background RAC/ROPs are RHO-type GTPases and are known to play diverse signalling roles in plants. Cytoplasmic RAC/ROPs are recruited to the cell membrane and activated in response to extracellular signals perceived and mediated by cell surface-located signalling assemblies, transducing the signals to regulate cellular processes. More than any other cell types in plants, pollen tubes depend on continuous interactions with an extracellular environment produced by their surrounding tissues as they grow within the female organ pistil to deliver sperm to the female gametophyte for fertilization. Scope We review studies on pollen tube growth that provide compelling evidence indicating that RAC/ROPs are crucial for regulating the cellular processes that underlie the polarized cell growth process. Efforts to identify cell surface regulators that mediate extracellular signals also point to RAC/ROPs being the molecular switches targeted by growth-regulating female factors for modulation to mediate pollination and fertilization. We discuss a large volume of work spanning more than two decades on a family of pollen-specific receptor kinases and some recent studies on members of the FERONIA family of receptor-like kinases (RLKs). Significance The research described shows the crucial roles that two RLK families play in transducing signals from growth regulatory factors to the RAC/ROP switch at the pollen tube apex to mediate and target pollen tube growth to the female gametophyte and signal its disintegration to achieve fertilization once inside the female chamber. PMID:22476487

  14. Exploration of CH···π mediated stacking interactions in saccharide: aromatic residue complexes through conformational sampling.

    Science.gov (United States)

    Kumari, Manju; Sunoj, Raghavan B; Balaji, Petety V

    2012-11-01

    Saccharides interact with aromatic residues mostly through CH···π mediated stacking interactions. The energetics of such interactions depends upon the mutual position-orientations (POs) of the two moieties. The POs found in the crystal structures are only a subset of the various possible ways of interaction. Hence, potential energy surfaces of saccharide-aromatic residue complexes have been explored by mixed Monte Carlo multiple minimum/low mode sampling. The saccharides considered in this study are α/β-D-glucose, β-D-galactose, α-D-mannose, and α/β-L-fucose. p-Hydroxytoluene, toluene, and 3-methylindole were used as analogs of tyrosine, phenylalanine, and tryptophan, respectively. The saccharides interact from either above or below the π-cloud of an aromatic ring but not along the edges. The POs preferred by different saccharides, both in the preferred chair and skew-boat forms, for interacting with different aromatic amino acid residue analogs have been identified. Aromatic residues can interact with the same -CH group in many POs but not so with the -OH groups. Changes in the configurations of pyranose ring carbon atoms cause remarkable changes in stacking preferences. β-D-Galactose and β-L-fructose interact only through their b- and a-faces, respectively. Saccharides use a wide variety of apolar patches for stacking against aromatic residues and these have been analyzed in detail. As many as four -CH groups can simultaneously participate in CH···π interactions, especially with 3-methylindole owing to its larger surface area.

  15. Examining Perceived Distance and Personal Authenticity as Mediators of the Effects of Ghost-Tweeting on Parasocial Interaction.

    Science.gov (United States)

    Cohen, Elizabeth L; Tyler, William J

    2016-05-01

    A number of high-profile public figures hire ghost-tweeters to post to their social media accounts on their behalf, but no research has examined how this social media practice can affect followers' feelings of connection to the public figures. College students (n = 132) participated in an online experiment to examine the effect of ghost-tweeting practices on parasocial interaction (PSI) with social media figures. Tweet authorship (use of a ghost-tweeter or not) was manipulated. Ghost-tweeting resulted in reduced PSI. Perceptions of distance, but not personal authenticity mediated this effect. However, authenticity and distance did serially mediate the relationship between ghost-tweeting and PSI. These findings shed light on the process of PSI with celebrities and other media figures on social network sites.

  16. Feedback regulation on PTEN/AKT pathway by the ER stress kinase PERK mediated by interaction with the Vault complex

    DEFF Research Database (Denmark)

    Zhang, Wei; Neo, Suat Peng; Gunaratne, Jayantha

    2015-01-01

    The high proliferation rate of cancer cells, together with environmental factors such as hypoxia and nutrient deprivation can cause Endoplasmic Reticulum (ER) stress. The protein kinase PERK is an essential mediator in one of the three ER stress response pathways. Genetic and pharmacological...... inhibition of PERK has been reported to limit tumor growth in xenograft models. Here we provide evidence that inactive PERK interacts with the nuclear pore-associated Vault complex protein and that this compromises Vault-mediated nuclear transport of PTEN. Pharmacological inhibition of PERK under ER stress...... results is abnormal sequestration of the Vault complex, leading to increased cytoplasmic PTEN activity and lower AKT activation. As the PI3K/PTEN/AKT pathway is crucial for many aspects of cell growth and survival, this unexpected effect of PERK inhibitors on AKT activity may have implications...

  17. Predicting Parental Mediation Behaviors: The Direct and Indirect Influence of Parents' Critical Thinking about Media and Attitudes about Parent-Child Interactions

    Science.gov (United States)

    Rasmussen, Eric C.; White, Shawna R.; King, Andy J.; Holiday, Steven; Densley, Rebecca L.

    2016-01-01

    Many parents fail to interact with their children regularly about media content and past research has identified few predictors of parents' engagement in parental mediation behaviors. This correlational study explored the relationship between parents' critical thinking about media and parents' provision of both active and restrictive mediation of…

  18. Predicting Parental Mediation Behaviors: The Direct and Indirect Influence of Parents' Critical Thinking about Media and Attitudes about Parent-Child Interactions

    Science.gov (United States)

    Rasmussen, Eric C.; White, Shawna R.; King, Andy J.; Holiday, Steven; Densley, Rebecca L.

    2016-01-01

    Many parents fail to interact with their children regularly about media content and past research has identified few predictors of parents' engagement in parental mediation behaviors. This correlational study explored the relationship between parents' critical thinking about media and parents' provision of both active and restrictive mediation of…

  19. Shared-Screen Interaction: Engaging Groups in Map-Mediated Nonverbal Communication

    Science.gov (United States)

    Chorianopoulos, Konstantinos; Rieniets, Tim

    This chapter describes the design and development of an interactive video installation that allows participants to explore a map narrative, and engage in group interactions through a shared screen. For this purpose, several layers of cartographic information were employed in a computer application, which was programmed with motion-tracking libraries in the open source tool processing. The interactive video installation has been chosen as a medium to achieve the following aims: (1) The visualization of urban-conflict as an interactive map narrative, and (2) the encouragement of social encounters through a shared screen. The development process begins with the design of interaction between the system and the participants, as well as between the participants themselves. Then we map the interaction design concepts into multimedia and architectural design. Finally, we provide a discussion on the creative process and the collaboration between different disciplines, such as architecture, urban planning, cartography, computer engineering, and media studies.

  20. Contrasting patterns of short-term indirect seed-seed interactions mediated by scatter-hoarding rodents.

    Science.gov (United States)

    Xiao, Zhishu; Zhang, Zhibin

    2016-09-01

    It is well known that direct effects of seed predators or dispersers can have strong effects on seedling establishment. However, we have limited knowledge about the indirect species interactions between seeds of different species that are mediated by shared seed predators and/or dispersers and their consequences for plant demography and diversity. Because scatter-hoarding rodents as seed dispersers may leave some hoarded seeds uneaten, scatter hoarding may serve to increase seed survival and dispersal. Consequently, the presence of heterospecific seeds could alter whether the indirect interactions mediated by scatter-hoarding rodents have a net positive effect, creating apparent mutualism between seed species, or a net negative effect, creating apparent competition between seed species. We present a testable framework to measure short-term indirect effects between co-occurring plant species mediated by seed scatter-hoarding rodents. We tested this framework in a subtropical forest in south-west China using a replacement design and tracked the fate of individually tagged seeds in experimental patches. We manipulated the benefits to rodents by using low-tannin dormant chestnuts as palatable food and high-tannin non-dormant acorns as unpalatable food. We found that seed palatability changed the amount of scatter hoarding that occurred when seeds co-occurred either among or within patches. Consistent with our predictions, scatter-hoarding rodents created apparent mutualism through increasing seed removal and seed caching, and enhancing survival, of both plant species in mixed patches compared with monospecific patches. However, if we ignore scatter hoarding and treat all seed harvest as seed predation (and not dispersal), then apparent competition between palatable chestnuts and unpalatable acorns was also observed. This study is the first to demonstrate that foraging decisions by scatter-hoarding animals to scatter hoard seeds for later consumption (or loss) or

  1. 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…

  2. Plurilingual Learners' Beliefs and Practices toward Native and Nonnative Language Mediation during Learner-Learner Interaction

    Science.gov (United States)

    Payant, Caroline

    2015-01-01

    Due to the growing number of plurilingual learners in the world today (Hammarberg, 2010), the present multiple case study examines four plurilingual participants' beliefs toward first language (L1) and second language (L2) mediation in the acquisition of French as a third language (L3). During a 16-week classroom-based study in a French university…

  3. Interactive Learning through Web-Mediated Peer Review of Student Science Reports

    Science.gov (United States)

    Trautmann, Nancy M.

    2009-01-01

    Two studies analyzed impacts of writing and receiving web-mediated peer reviews on revision of research reports by undergraduate science students. After conducting toxicology experiments, 77 students posted draft reports and exchanged double-blind reviews. The first study randomly assigned students to four groups representing full, partial, or no…

  4. Facebook Mediated Interaction and Learning in Distance Learning at Makerere University

    Science.gov (United States)

    Mayende, Godfrey; Muyinda, Paul Birevu; Isabwe, Ghislain Maurice Norbert; Walimbwa, Michael; Siminyu, Samuel Ndeda

    2014-01-01

    This paper reports on an investigation of the use of Facebook as a tool to mediate learning amongst distance learners at Makerere University, a dual-mode institution offering both conventional and distance learning programs. While conventional courses take 17 weeks in a semester, the distance learners come in for two residential sessions, each…

  5. Water-mediated interactions influence the binding of thapsigargin to sarco/endoplasmic reticulum calcium adenosinetriphosphatase

    DEFF Research Database (Denmark)

    Paulsen, Eleonora S.; Villadsen, Jesper; Tenori, Eleonora;

    2013-01-01

    A crystal structure suggests four water molecules are present in the binding cavity of thapsigargin in sarco/endoplasmic reticulum calcium ATPase (SERCA). Computational chemistry indicates that three of these water molecules mediate an extensive hydrogen-bonding network between thapsigargin...

  6. Plurilingual Learners' Beliefs and Practices toward Native and Nonnative Language Mediation during Learner-Learner Interaction

    Science.gov (United States)

    Payant, Caroline

    2015-01-01

    Due to the growing number of plurilingual learners in the world today (Hammarberg, 2010), the present multiple case study examines four plurilingual participants' beliefs toward first language (L1) and second language (L2) mediation in the acquisition of French as a third language (L3). During a 16-week classroom-based study in a French university…

  7. 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…

  8. PDZ domain-mediated interactions of G protein-coupled receptors with postsynaptic density protein 95

    DEFF Research Database (Denmark)

    Møller, Thor C; Wirth, Volker F; Roberts, Nina Ingerslev;

    2013-01-01

    G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome. Their signaling is regulated by scaffold proteins containing PDZ domains, but although these interactions are important for GPCR function, they are still poorly understood. We here present...... with colocalization of the full-length proteins in cells and with previous studies, we suggest that the range of relevant interactions might extend to interactions with K i = 450 µM in the in vitro assays. Within this range, we identify novel PSD-95 interactions with the chemokine receptor CXCR2, the neuropeptide Y...

  9. Interacting with presence: HCI and the sense of presence in computer-mediated environments

    National Research Council Canada - National Science Library

    Riva, Giuseppe; Waterworth, John; Murray, Dianne

    2014-01-01

    ...”, is key to understanding developments in applications such as interactive entertainment, gaming, psychotherapy, education, scientific visualisation, sports training and rehabilitation, and many...

  10. FHL2 mediates tooth development and human dental pulp cell differentiation into odontoblasts, partially by interacting with Runx2.

    Science.gov (United States)

    Du, Jianxin; Wang, Qiang; Yang, Pishan; Wang, Xiaoying

    2016-04-01

    The differentiation of mesenchymal cells in tooth germ and dental pulp cells into odontoblasts is crucial for dentin formation, and the transcription factor runt-related transcription factor (Runx2) is necessary for odontoblast differentiation. Our previous study demonstrated that four and a half LIM domains 2 (FHL2) may play an important role in tooth development and human dental pulp cell differentiation. This study aimed to determine whether FHL2 mediated the mesenchymal cells in tooth development and human dental pulp cell differentiation into odontoblasts by interacting with Runx2. The expression patterns of FHL2 and Runx2 were examined at the early stages of mouse molar development using double immunofluorescence staining. Western blot analysis and co-immunoprecipitation (Co-IP) were conducted for the preliminary study of the relationship between FHL2 and Runx2 in human dental pulp cell differentiation into odontoblasts. Results of double immunofluorescence staining showed that FHL2 and Runx2 exhibited similar expression patterns at the early stages of tooth development. Western blot analysis indicated that the expression patterns of FHL2 and Runx2 were synchronized on day 7 of induction, whereas those on day 14 differed. Co-IP analysis revealed positive bands of protein complexes, revealing the interaction of FHL2 and Runx2 on days 0, 7 and 14 of induction. Our data suggested that FHL2 might interact with Runx2 to mediate mesenchymal cell differentiation at the early stages of tooth development and human dental pulp cell differentiation.

  11. Immune-Mediated Nephropathy and Systemic Autoimmunity in Mice Does Not Require Receptor Interacting Protein Kinase 3 (RIPK3)

    Science.gov (United States)

    Corradetti, Chelsea; Jog, Neelakshi R.; Gallucci, Stefania; Madaio, Michael; Balachandran, Siddharth

    2016-01-01

    Immune mediated nephropathy is one of the most serious manifestations of lupus and is characterized by severe inflammation and necrosis that, if untreated, eventually leads to renal failure. Although lupus has a higher incidence in women, both sexes can develop lupus glomerulonephritis; nephritis in men develops earlier and is more severe than in women. It is therefore important to understand the cellular and molecular mechanisms mediating nephritis in each sex. Previous work by our lab found that the absence or pharmacological inhibition of Poly [ADP-ribose] polymerase 1 (PARP-1), an enzyme involved in DNA repair and necrotic cell death, affects only male mice and results in milder nephritis, with less in situ inflammation, and diminished incidence of necrotic lesions, allowing for higher survival rates. A second pathway mediating necrosis involves Receptor-Interacting Serine-Threonine Kinase 3 (RIPK3); in this study we sought to investigate the impact of RIPK3 on the development of lupus and nephritis in both sexes. To this end, we used two inducible murine models of lupus: chronic graft versus host disease (cGvHD) and pristane-induced lupus; and nephrotoxic serum (NTS)-induced nephritis as a model of immune mediated nephropathy. We found that the absence of RIPK3 has neither positive nor negative impact on the disease development or progression of lupus and nephritis in all three models, and in both male and female mice. We conclude that RIPK3 is dispensable for the pathogenesis of lupus and immune mediated nephropathy as to accelerate, worsen or ameliorate the disease. PMID:27669412

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

    Science.gov (United States)

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

    2009-11-01

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

  13. Synchronous Computer-Mediated Communication and Interaction: A Research Synthesis and Meta-Analysis

    Science.gov (United States)

    Ziegler, Nicole

    2013-01-01

    The interaction approach to second language acquisition (SLA) suggests that changes that occur during conversation facilitate second language development by providing learners with opportunities to receive modified comprehensible input and interactional feedback, to produce output, and to notice gaps between their interlanguage and the target…

  14. Ion-mediated interactions between net-neutral slabs: Weak and strong disorder effects

    Science.gov (United States)

    Ghodrat, Malihe; Naji, Ali; Komaie-Moghaddam, Haniyeh; Podgornik, Rudolf

    2015-12-01

    We investigate the effective interaction between two randomly charged but otherwise net-neutral, planar dielectric slabs immersed in an asymmetric Coulomb fluid containing a mixture of mobile monovalent and multivalent ions. The presence of charge disorder on the apposed bounding surfaces of the slabs leads to substantial qualitative changes in the way they interact, as compared with the standard picture provided by the van der Waals and image-induced, ion-depletion interactions. While, the latter predict purely attractive interactions between strictly neutral slabs, we show that the combined effects from surface charge disorder, image depletion, Debye (or salt) screening, and also, in particular, their coupling with multivalent ions, give rise to a more diverse behavior for the effective interaction between net-neutral slabs at nano-scale separations. Disorder effects show large variation depending on the properly quantified strength of disorder, leading either to non-monotonic effective interaction with both repulsive and attractive branches when the surface charges are weakly disordered (small disorder variance) or to a dominating attractive interaction that is larger both in its range and magnitude than what is predicted from the van der Waals and image-induced, ion-depletion interactions, when the surfaces are strongly disordered (large disorder variance).

  15. Interactive and Lightweight Mechanisms to Coordinate Interpersonal Privacy in Mediated Communication

    Science.gov (United States)

    Romero, Natalia; Boer, Laurens; Markopoulos, Panos

    In this paper we describe three mechanisms that enable people to coordinate their interaction needs with others in their social network. The proposed designs are based on the Privacy Grounding Model [4] that argues the need for lightweight and interactive coordination mechanisms to support the dynamic and dialectic nature of interpersonal privacy coordination.

  16. Tuning interaction in dinuclear ruthenium complexes : HOMO versus LUMO mediated superexchange through azole and azine bridges

    NARCIS (Netherlands)

    Browne, Wesley; Hage, R; Vos, Johannes G.

    2006-01-01

    In this review the interaction between metal centers in dinuclear complexes based on azole and azine containing bridging ligands is reviewed. The focus of the review is on the manner in which the interaction pathway can be manipulated by variations in the nature of both the direct bridging unit and

  17. Ion-mediated interactions between net-neutral slabs: Weak and strong disorder effects.

    Science.gov (United States)

    Ghodrat, Malihe; Naji, Ali; Komaie-Moghaddam, Haniyeh; Podgornik, Rudolf

    2015-12-21

    We investigate the effective interaction between two randomly charged but otherwise net-neutral, planar dielectric slabs immersed in an asymmetric Coulomb fluid containing a mixture of mobile monovalent and multivalent ions. The presence of charge disorder on the apposed bounding surfaces of the slabs leads to substantial qualitative changes in the way they interact, as compared with the standard picture provided by the van der Waals and image-induced, ion-depletion interactions. While, the latter predict purely attractive interactions between strictly neutral slabs, we show that the combined effects from surface charge disorder, image depletion, Debye (or salt) screening, and also, in particular, their coupling with multivalent ions, give rise to a more diverse behavior for the effective interaction between net-neutral slabs at nano-scale separations. Disorder effects show large variation depending on the properly quantified strength of disorder, leading either to non-monotonic effective interaction with both repulsive and attractive branches when the surface charges are weakly disordered (small disorder variance) or to a dominating attractive interaction that is larger both in its range and magnitude than what is predicted from the van der Waals and image-induced, ion-depletion interactions, when the surfaces are strongly disordered (large disorder variance).

  18. Protein-spanning water networks and implications for prediction of protein-protein interactions mediated through hydrophobic effects.

    Science.gov (United States)

    Cui, Di; Ou, Shuching; Patel, Sandeep

    2014-12-01

    Hydrophobic effects, often conflated with hydrophobic forces, are implicated as major determinants in biological association and self-assembly processes. Protein-protein interactions involved in signaling pathways in living systems are a prime example where hydrophobic effects have profound implications. In the context of protein-protein interactions, a priori knowledge of relevant binding interfaces (i.e., clusters of residues involved directly with binding interactions) is difficult. In the case of hydrophobically mediated interactions, use of hydropathy-based methods relying on single residue hydrophobicity properties are routinely and widely used to predict propensities for such residues to be present in hydrophobic interfaces. However, recent studies suggest that consideration of hydrophobicity for single residues on a protein surface require accounting of the local environment dictated by neighboring residues and local water. In this study, we use a method derived from percolation theory to evaluate spanning water networks in the first hydration shells of a series of small proteins. We use residue-based water density and single-linkage clustering methods to predict hydrophobic regions of proteins; these regions are putatively involved in binding interactions. We find that this simple method is able to predict with sufficient accuracy and coverage the binding interface residues of a series of proteins. The approach is competitive with automated servers. The results of this study highlight the importance of accounting of local environment in determining the hydrophobic nature of individual residues on protein surfaces.

  19. Peer Mediated Theatrical Engagement for Improving Reciprocal Social Interaction in Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Blythe A Corbett

    2014-10-01

    Full Text Available The hallmark characteristic of autism spectrum disorder (ASD is poor reciprocal social communication. Interventions designed to improve this core deficit are critically needed. Social skills interventions such as direct training, peer mediation, and video modeling have contributed to improvements in various social skills in children with ASD. This paper reviews existing social competence interventions available for children with ASD while highlighting hypothesized critical components for advancing, maintaining and generalizing skills, which include 1 peer mediation, 2 active learning, and 3 implementation in supportive, natural contexts. As a framework for these approaches, this conceptual paper describes SENSE Theatre, a novel intervention that combines trained peers that facilitate the performance-based theatrical treatment delivered in a supportive, community-based environment. A review of previous research shows early feasibility, setting the stage for more rigorous studies to aid in developing a standardized intervention package.

  20. Peer-mediated theatrical engagement for improving reciprocal social interaction in autism spectrum disorder.

    Science.gov (United States)

    Corbett, Blythe A; Qualls, Lydia R; Valencia, Blythe; Fecteau, Stéphanie-M; Swain, Deanna M

    2014-01-01

    The hallmark characteristic of autism spectrum disorder (ASD) is poor reciprocal social communication. Interventions designed to improve this core deficit are critically needed. Social skills interventions such as direct training, peer mediation, and video modeling have contributed to improvements in various social skills in children with ASD. This paper reviews existing social competence interventions available for children with ASD while highlighting hypothesized critical components for advancing, maintaining, and generalizing skills, which include (1) peer mediation, (2) active learning, and (3) implementation in supportive, natural contexts. As a framework for these approaches, this conceptual paper describes SENSE Theatre, a novel intervention that combines trained peers that facilitate the performance-based theatrical treatment delivered in a supportive, community-based environment. A review of previous research shows early feasibility, setting the stage for more rigorous studies to aid in developing a standardized intervention package.

  1. Set7 mediated interactions regulate transcriptional networks in embryonic stem cells.

    Science.gov (United States)

    Tuano, Natasha K; Okabe, Jun; Ziemann, Mark; Cooper, Mark E; El-Osta, Assam

    2016-11-02

    Histone methylation by lysine methyltransferase enzymes regulate the expression of genes implicated in lineage specificity and cellular differentiation. While it is known that Set7 catalyzes mono-methylation of histone and non-histone proteins, the functional importance of this enzyme in stem cell differentiation remains poorly understood. We show Set7 expression is increased during mouse embryonic stem cell (mESC) differentiation and is regulated by the pluripotency factors, Oct4 and Sox2. Transcriptional network analyses reveal smooth muscle (SM) associated genes are subject to Set7-mediated regulation. Furthermore, pharmacological inhibition of Set7 activity confirms this regulation. We observe Set7-mediated modification of serum response factor (SRF) and mono-methylation of histone H4 lysine 4 (H3K4me1) regulate gene expression. We conclude the broad substrate specificity of Set7 serves to control key transcriptional networks in embryonic stem cells.

  2. In vitro human immunodeficiency virus and sperm cell interaction mediated by the mannose receptor.

    Science.gov (United States)

    Cardona-Maya, Walter; Velilla, Paula A; Montoya, Carlos Julio; Cadavid, Ángela; Rugeles, María T

    2011-12-01

    Leukocytes are considered to be the main source of HIV-1 infection in semen. However, HIV-1 interaction with spermatozoa has also been demonstrated, suggesting that both spermatozoa and leukocytes might play a role during sexual transmission of HIV-1. The purpose of the present study was to evaluate if HIV-1 particles interact with sperm cells through the mannose receptor (MR), and then to determine the ability of "infected" sperm cells to transmit the virus to susceptible targets. The expression of classical HIV-1 receptor and co-receptors and the MR by sperm cells was determined by flow cytometry; the interaction in vitro between sperm and HIV-1 was evaluated by fluorescence microscopy. Additionally, the in vitro interaction of sperm cells and HIV-1 was determined detecting viral nucleic acids by PCR. D-Mannose was used to block HIV-1-sperm cell interaction. Sperm cells preincubated with HIV-1 particles and activated mononuclear cells were co-cultured to determine viral transmission. The presence of viral RNA was detected in 28% of the samples in which sperm cells were preincubated with HIV-1 particles. Mannose was able to block interaction in 75% of the cases. Finally, we demonstrated that "infected" sperm cells were able to transmit the HIV-1 infection to susceptible targets. In conclusion, these results indicate that the MR is involved in sperm cell-HIV-1 interaction. Our results also suggest that sperm cells could be an important source of infection.

  3. Information-based or resource-based systems may mediate Cycas-herbivore interactions

    OpenAIRE

    Marler, Thomas E; Lindström, Anders; Terry, L. Irene

    2012-01-01

    Invasive arthropod herbivores comprise one of the greatest threats to cycad conservation both in situ and ex situ. We discuss two mechanisms, not necessarily mutually exclusive, that may underlie the disparity in Chilades pandava damage among Cycas species. In an information-based system, plant infochemicals may differentially influence oviposition behavior of Ch. pandava adults or host finding behavior of this butterfly’s natural enemies. Alternatively, heterogeneity in damage may be mediate...

  4. Interactions between medical residents and drug companies: a national survey after the Mediator® affair.

    Directory of Open Access Journals (Sweden)

    François Montastruc

    Full Text Available BACKGROUND: The present study aimed to describe exposure and attitudes of French medical residents towards pharmaceutical industry. The study was performed shortly after the Mediator affair which revealed several serious conflicts of interest inside the French health system. METHODS AND FINDINGS: A cross-sectional study was implemented among residents from 6 French medical faculties. Independent education in pharmacology, attitudes towards the practices of pharmaceutical sales representatives, opinions concerning the pharmaceutical industry, quality of information provided by the pharmaceutical industry, and opinions about pharmaceutical company sponsorship were investigated through a web-based questionnaire. We also assessed potential changes in resident attitudes following the Mediator affair. The mean value of exposure to drug companies was 1.9 times per month. Global opinions towards drug company information were negative for 42.7% of the residents and positive for only 8.2%. Surprisingly, 81.6% of residents claimed that they had not changed their practices regarding drug information since the Mediator affair. Multivariate analyses found that residents in anesthesiology were less likely to be exposed than others (OR = 0.17 CI95% [0.05-0.61], exposure was significantly higher at the beginning of residence (p<0.001 and residents who had a more positive opinion were more frequently exposed to drug companies (OR = 2.12 CI95% [1.07-4.22]. CONCLUSIONS: Resident exposure to drug companies is around 1 contact every 2 weeks. Global opinion towards drug information provided by pharmaceutical companies was negative for around 1 out of 2 residents. In contrast, residents tend to consider the influences of the Mediator affair on their practice as relatively low. This survey enabled us to identify profiles of residents who are obviously less exposed to pharmaceutical industry. Current regulatory provisions are not sufficient, indicating that

  5. c-Myb protein interacts with Rcd-1, a component of the CCR4 transcription mediator complex.

    Science.gov (United States)

    Haas, Martin; Siegert, Michaela; Schürmann, André; Sodeik, Beate; Wolfes, Heiner

    2004-06-29

    Transcriptional initiation of eukaryotic genes depends on the cooperative interaction of various transcription factors. Using the yeast two-hybrid assay, we have identified the murine Rcd-1 protein as a cofactor of the c-myb proto-oncogene product. Rcd-1 is evolutionarily conserved among many species, and moreover the yeast homologue CAF40 is part of the carbon catabolite repressor protein transcriptional mediator thought to be involved in the negative regulation of genes transcribed by RNA polymerase II. Rcd-1 is located mainly in the nucleus, and it interacts with c-Myb both in vitro and in vivo. The activation of the myeloid c-myb-specific mim-1 promoter is repressed by Rcd-1. Interestingly, rcd-1 is an erythropoietin regulated gene, which also represses the action of the AP-1 transcription factor on its target genes.

  6. Structure of the Membrane-tethering GRASP Domain Reveals a Unique PDZ Ligand Interaction That Mediates Golgi Biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    S Truschel; D Sengupta; A Foote; A Heroux; M Macbeth; A Linstedt

    2011-12-31

    Biogenesis of the ribbon-like membrane network of the mammalian Golgi requires membrane tethering by the conserved GRASP domain in GRASP65 and GRASP55, yet the tethering mechanism is not fully understood. Here, we report the crystal structure of the GRASP55 GRASP domain, which revealed an unusual arrangement of two tandem PDZ folds that more closely resemble prokaryotic PDZ domains. Biochemical and functional data indicated that the interaction between the ligand-binding pocket of PDZ1 and an internal ligand on PDZ2 mediates the GRASP self-interaction, and structural analyses suggest that this occurs via a unique mode of internal PDZ ligand recognition. Our data uncover the structural basis for ligand specificity and provide insight into the mechanism of GRASP-dependent membrane tethering of analogous Golgi cisternae.

  7. Structure of the Membrane-tethering GRASP Domain Reveals a Unique PDZ Ligand Interaction That Mediates Golgi Biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Truschel, S.T.; Heroux, A.; Sengupta, D.; Foote, A.; Macbeth, M. R.; Linstedt, A. D.

    2011-06-10

    Biogenesis of the ribbon-like membrane network of the mammalian Golgi requires membrane tethering by the conserved GRASP domain in GRASP65 and GRASP55, yet the tethering mechanism is not fully understood. Here, we report the crystal structure of the GRASP55 GRASP domain, which revealed an unusual arrangement of two tandem PDZ folds that more closely resemble prokaryotic PDZ domains. Biochemical and functional data indicated that the interaction between the ligand-binding pocket of PDZ1 and an internal ligand on PDZ2 mediates the GRASP self-interaction, and structural analyses suggest that this occurs via a unique mode of internal PDZ ligand recognition. Our data uncover the structural basis for ligand specificity and provide insight into the mechanism of GRASP-dependent membrane tethering of analogous Golgi cisternae.

  8. MicroRNAs as mediators of insect host-pathogen interactions and immunity.

    Science.gov (United States)

    Hussain, Mazhar; Asgari, Sassan

    2014-11-01

    Insects are the most successful group of animals on earth, owing this partly to their very effective immune responses to microbial invasion. These responses mainly include cellular and humoral responses as well as RNA interference (RNAi). Small non-coding RNAs (snRNAs) produced through RNAi are important molecules in the regulation of gene expression in almost all living organisms; contributing to important processes such as development, differentiation, immunity as well as host-microorganism interactions. The main snRNAs produced by the RNAi response include short interfering RNAs, microRNAs and piwi-interacting RNAs. In addition to the host snRNAs, some microorganisms encode snRNAs that affect the dynamics of host-pathogen interactions. In this review, we will discuss the latest developments in regards to the role of microRNA in insect host-pathogen interactions and provide some insights into this rapidly developing area of research.

  9. Jasmonic acid-related resistance in tomato mediates interactions between whitefly and whitefly-transmitted virus

    National Research Council Canada - National Science Library

    Yan-Chun Sun; Li-Long Pan; Feng-Ze Ying; Ping Li; Xiao-Wei Wang; Shu-Sheng Liu

    2017-01-01

      The indirect interactions between insect vectors, such as whiteflies, and the viruses they transmit, such as begomoviruses, via host plants may produce a range of outcome depending on the species...

  10. Natural enemy-mediated indirect interactions among prey species: potential for enhancing biocontrol services in agroecosystems

    NARCIS (Netherlands)

    Chailleux, A.; Mohl, E.K.; Teixeira Alves, M.; Messelink, G.J.; Desneux, N.

    2014-01-01

    Understanding how arthropod pests and their natural enemies interact in complex agroecosystems is essential for pest management programmes. Theory predicts that prey sharing a predator, such as a biological control agent, can indirectly reduce each other's density at equilibrium (apparent

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

    Directory of Open Access Journals (Sweden)

    Debasree Sarkar

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

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

    Science.gov (United States)

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

    2016-01-01

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

  13. SGT1 interacts with the Prf resistance protein and is required for Prf accumulation and Prf-mediated defense signaling.

    Science.gov (United States)

    Kud, Joanna; Zhao, Zhulu; Du, Xinran; Liu, Yule; Zhao, Yun; Xiao, Fangming

    2013-02-15

    The highly conserved eukaryotic co-chaperone SGT1 (suppressor of the G2 allele of skp1) is an important signaling component of plant defense responses and positively regulates disease resistance conferred by many resistance (R) proteins. In this study, we investigated the contribution of SGT1 in the Prf-mediated defense responses in both Nicotiana benthamiana and tomato (Solanum lycopersicum). SGT1 was demonstrated to interact with Prf in plant cells by co-immunoprecipitation. The requirement of SGT1 in the accumulation of Prf or autoactive Prf(D1416V) was determined by the degradation of these proteins in N. benthamiana, in which SGT1 was repressed by virus-induced gene silencing (VIGS). Pseudomonas pathogen assay on the SGT1-silenced tomato plants implicates SGT1 is required for the Prf-mediated full resistance to Pseudomonas syringae pv. tomato (Pst). These results suggest that, in both N. benthamiana and tomato, SGT1 contributes to the Prf-mediated defense responses by stabilizing Prf protein via its co-chaperone activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Grancalcin (GCA) modulates Toll-like receptor 9 (TLR9) mediated signaling through its direct interaction with TLR9.

    Science.gov (United States)

    Kim, Tae Whan; Hong, Seunghee; Talukder, Amjad H; Pascual, Virginia; Liu, Yong-Jun

    2016-03-01

    Toll-like receptors (TLRs) are playing important roles in stimulating the innate immune response and intensifying adaptive immune response against invading pathogens. Appropriate regulation of TLR activation is important to maintain a balance between preventing tumor activation and inhibiting autoimmunity. Toll-like receptor 9 (TLR9) senses microbial DNA in the endosomes of plasmacytoid dendritic cells and triggers myeloid differentiation primary response gene 88 (MyD88) dependent nuclear factor kappa B (NF-κB) pathways and type I interferon (IFN) responses. However, mechanisms of how TLR9 signals are mediated and which molecules are involved in controlling TLR9 functions remain poorly understood. Here, we report that penta EF-hand protein grancalcin (GCA) interacts and binds with TLR9 in a yeast two-hybrid system and an overexpression system. Using siRNA-mediated knockdown experiments, we also revealed that GCA positively regulates type I IFN production, cytokine/chemokine production through nuclear localization of interferon regulatory factor 7 (IRF7), NF-κB activation, and mitogen-activated protein kinase (MAPK) activation in plasmacytoid dendritic cells. Our results indicate that heterodimerization of GCA and TLR9 is important for TLR9-mediated downstream signaling and might serve to fine tune processes against viral infection. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Thermotoga maritima NusG: domain interaction mediates autoinhibition and thermostability

    Science.gov (United States)

    Drögemüller, Johanna; Schneider, Christin; Schweimer, Kristian; Strauß, Martin; Wöhrl, Birgitta M.; Rösch, Paul; Knauer, Stefan H.

    2017-01-01

    NusG, the only universally conserved transcription factor, comprises an N- and a C-terminal domain (NTD, CTD) that are flexibly connected and move independently in Escherichia coli and other organisms. In NusG from the hyperthermophilic bacterium Thermotoga maritima (tmNusG), however, NTD and CTD interact tightly. This closed state stabilizes the CTD, but masks the binding sites for the interaction partners Rho, NusE and RNA polymerase (RNAP), suggesting that tmNusG is autoinhibited. Furthermore, tmNusG and some other bacterial NusGs have an additional domain, DII, of unknown function. Here we demonstrate that tmNusG is indeed autoinhibited and that binding to RNAP may stabilize the open conformation. We identified two interdomain salt bridges as well as Phe336 as major determinants of the domain interaction. By successive weakening of this interaction we show that after domain dissociation tmNusG-CTD can bind to Rho and NusE, similar to the Escherichia coli NusG-CTD, indicating that these interactions are conserved in bacteria. Furthermore, we show that tmNusG-DII interacts with RNAP as well as nucleic acids with a clear preference for double stranded DNA. We suggest that tmNusG-DII supports tmNusG recruitment to the transcription elongation complex and stabilizes the tmNusG:RNAP complex, a necessary adaptation to high temperatures. PMID:27899597

  16. Characteristics and Kinetic Analysis of AQS Transformation and Microbial Goethite Reduction:Insight into "Redox mediator-Microbe-Iron oxide" Interaction Process.

    Science.gov (United States)

    Zhu, Weihuang; Shi, Mengran; Yu, Dan; Liu, Chongxuan; Huang, Tinglin; Wu, Fengchang

    2016-01-01

    The characteristics and kinetics of redox transformation of a redox mediator, anthraquinone-2-sulfonate (AQS), during microbial goethite reduction by Shewanella decolorationis S12, a dissimilatory iron reduction bacterium (DIRB), were investigated to provide insights into "redox mediator-iron oxide" interaction in the presence of DIRB. Two pre-incubation reaction systems of the "strain S12- goethite" and the "strain S12-AQS" were used to investigate the dynamics of goethite reduction and AQS redox transformation. Results show that the concentrations of goethite and redox mediator, and the inoculation cell density all affect the characteristics of microbial goethite reduction, kinetic transformation between oxidized and reduced species of the redox mediator. Both abiotic and biotic reactions and their coupling regulate the kinetic process for "Quinone-Iron" interaction in the presence of DIRB. Our results provide some new insights into the characteristics and mechanisms of interaction among "quinone-DIRB- goethite" under biotic/abiotic driven.

  17. Two distinct domains of Flo8 activator mediates its role in transcriptional activation and the physical interaction with Mss11.

    Science.gov (United States)

    Kim, Hye Young; Lee, Sung Bae; Kang, Hyen Sam; Oh, Goo Taeg; Kim, TaeSoo

    2014-06-27

    Flo8 is a transcriptional activator essential for the inducible expression of a set of target genes such as STA1, FLO11, and FLO1 encoding an extracellular glucoamylase and two cell surface proteins, respectively. However, the molecular mechanism of Flo8-mediated transcriptional activation remains largely elusive. By generating serial deletion constructs, we revealed here that a novel transcriptional activation domain on its extreme C-terminal region plays a crucial role in activating transcription. On the other hand, the N-terminal LisH motif of Flo8 appears to be required for its physical interaction with another transcriptional activator, Mss11, for their cooperative transcriptional regulation of the shared targets. Additionally, GST pull-down experiments uncovered that Flo8 and Mss11 can directly form either a heterodimer or a homodimer capable of binding to DNA, and we also showed that this formed complex of two activators interacts functionally and physically with the Swi/Snf complex. Collectively, our findings provide valuable clues for understanding the molecular mechanism of Flo8-mediated transcriptional control of multiple targets.

  18. Constraining Dark Matter Interactions with Pseudoscalar and Scalar Mediators Using Collider Searches for Multijets plus Missing Transverse Energy.

    Science.gov (United States)

    Buchmueller, Oliver; Malik, Sarah A; McCabe, Christopher; Penning, Bjoern

    2015-10-30

    The monojet search, looking for events involving missing transverse energy (E_{T}) plus one or two jets, is the most prominent collider dark matter search. We show that multijet searches, which look for E_{T} plus two or more jets, are significantly more sensitive than the monojet search for pseudoscalar- and scalar-mediated interactions. We demonstrate this in the context of a simplified model with a pseudoscalar interaction that explains the excess in GeV energy gamma rays observed by the Fermi Large Area Telescope. We show that multijet searches already constrain a pseudoscalar interpretation of the excess in much of the parameter space where the mass of the mediator M_{A} is more than twice the dark matter mass m_{DM}. With the forthcoming run of the Large Hadron Collider at higher energies, the remaining regions of the parameter space where M_{A}>2m_{DM} will be fully explored. Furthermore, we highlight the importance of complementing the monojet final state with multijet final states to maximize the sensitivity of the search for the production of dark matter at colliders.

  19. FGF1-mediated cardiomyocyte cell cycle reentry depends on the interaction of FGFR-1 and Fn14.

    Science.gov (United States)

    Novoyatleva, Tatyana; Sajjad, Amna; Pogoryelov, Denys; Patra, Chinmoy; Schermuly, Ralph T; Engel, Felix B

    2014-06-01

    Fibroblast growth factors (FGFs) signal through FGF receptors (FGFRs) mediating a broad range of cellular functions during embryonic development, as well as disease and regeneration during adulthood. Thus, it is important to understand the underlying molecular mechanisms that modulate this system. Here, we show that FGFR-1 can interact with the TNF receptor superfamily member fibroblast growth factor-inducible molecule 14 (Fn14) resulting in cardiomyocyte cell cycle reentry. FGF1-induced cell cycle reentry in neonatal cardiomyocytes could be blocked by Fn14 inhibition, while TWEAK-induced cell cycle activation was inhibited by blocking FGFR-1 signaling. In addition, costimulation experiments revealed a synergistic effect of FGF1 and TWEAK in regard to cardiomyocyte cell cycle induction via PI3K/Akt signaling. Overexpression of Fn14 with either FGFR-1 long [FGFR-1(L)] or FGFR-1 short [FGFR-1(S)] isoforms resulted after FGF1/TWEAK stimulation in cell cycle reentry of >40% adult cardiomyocytes. Finally, coimmunoprecipitation and proximity ligation assays indicated that endogenous FGFR-1 and Fn14 interact with each other in cardiomyocytes. This interaction was strongly enhanced in the presence of their corresponding ligands, FGF1 and TWEAK. Taken together, our data suggest that FGFR-1/Fn14 interaction may represent a novel endogenous mechanism to modulate the action of these receptors and their ligands and to control cardiomyocyte cell cycle reentry.

  20. Benzene on Cu(111): II. Molecular assembly due to Lateral van der Waals and Surface-State-Mediated Indirect Interactions

    Science.gov (United States)

    Hyldgaard, Per; Berland, Kristian; Einstein, T. L.

    2010-03-01

    Experiments show that benzene condenses into two different structural phases: a compact and a sparse phase, both of approximately hexagonal symmetry. The vdW-DF calculations demonstrate that the denser benzene-overlayer phase, with lattice constant 6.74 ,s due to direct benzene-benzene vdW attraction. The structure of the second, sparser phase, with lattice spacing 10.24 ,s attributed to the indirect electronic interactions mediated by the well-known metallic surface state on Cu(111). To support this claim, we use a formal Harris-functional approach to evaluate nonperturbatively the asymptotic form of this indirect interaction. Our extended vdW-DF scheme---which combines calculations of molecular physisorption, of direct intermolecular vdW coupling, and of indirect electronic interactions between the molecular adsorbates---accounts well for the structural phases of benzene on Cu(111). Our preliminary vdW-DF study of acene and quinone interactions provides building blocks for modeling of anthraquinone assembly on Cu(111).footnotetextG. Pawin, , L. Bartels, Science 313 (2006) 961

  1. SARM modulates MyD88-mediated TLR activation through BB-loop dependent TIR-TIR interactions.

    Science.gov (United States)

    Carlsson, Emil; Ding, Jeak Ling; Byrne, Bernadette

    2016-02-01

    Toll-like receptors (TLRs) recognise invading pathogens and initiate an innate immune response by recruiting intracellular adaptor proteins via heterotypic Toll/interleukin-1 receptor (TIR) domain interactions. Of the five TIR domain-containing adaptor proteins identified, Sterile α- and armadillo-motif-containing protein (SARM) is functionally unique; suppressing immune signalling instead of promoting it. Here we demonstrate that the recombinantly expressed and purified SARM TIR domain interacts with both the major human TLR adaptors, MyD88 and TRIF. A single glycine residue located in the BB-loop of the SARM TIR domain, G601, was identified as essential for interaction. A short peptide derived from this motif was also found to interact with MyD88 in vitro. SARM expression in HEK293 cells was found to significantly suppress lipopolysaccharide (LPS)-mediated upregulation of inflammatory cytokines, IL-8 and TNF-α, an effect lost in the G601A mutant. The same result was observed with cytokine activation initiated by MyD88 expression and stimulation of TLR2 with lipoteichoic acid (LTA), suggesting that SARM is capable of suppressing both TRIF- and MyD88- dependent TLR signalling. Our findings indicate that SARM acts on a broader set of target proteins than previously thought, and that the BB-loop motif is functionally important, giving further insight into the endogenous mechanisms used to suppress inflammation in immune cells. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Cui, Di; Ou, Shuching; Patel, Sandeep

    2014-07-01

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

  3. Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) and related psychostimulants: mechanisms and mediators

    Science.gov (United States)

    Vanattou-Saïfoudine, N; McNamara, R; Harkin, A

    2012-01-01

    Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine-related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’), which has been most recently described and characterized. Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co-administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug-induced toxicity comprising MDMA-related enhancement of dopamine release coupled to a caffeine-mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine-related drug interactions with cocaine, d-amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug-related toxicity, resulting from concomitant caffeine consumption. PMID:22671762

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

    Directory of Open Access Journals (Sweden)

    Ifeoma Jane Nwigwe

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

  5. Competitive interactions are mediated in a sex-specific manner by arbuscular mycorrhiza in Antennaria dioica.

    Science.gov (United States)

    Varga, S; Vega-Frutis, R; Kytöviita, M-M

    2017-03-01

    Plants usually interact with other plants, and the outcome of such interaction ranges from facilitation to competition depending on the identity of the plants, including their sexual expression. Arbuscular mycorrhizal (AM) fungi have been shown to modify competitive interactions in plants. However, few studies have evaluated how AM fungi influence plant intraspecific and interspecific interactions in dioecious species. The competitive abilities of female and male plants of Antennaria dioica were examined in a greenhouse experiment. Females and males were grown in the following competitive settings: (i) without competition, (ii) with intrasexual competition, (iii) with intersexual competition, and (iv) with interspecific competition by Hieracium pilosella - a plant with similar characteristics to A. dioica. Half of the pots were grown with Claroideoglomus claroideum, an AM fungus isolated from the same habitat as the plant material. We evaluated plant survival, growth, flowering phenology, and production of AM fungal structures. Plant survival was unaffected by competition or AM fungi. Competition and the presence of AM fungi reduced plant biomass. However, the sexes responded differently to the interaction between fungal and competition treatments. Both intra- and interspecific competition results were sex-specific, and in general, female performance was reduced by AM colonization. Plant competition or sex did not affect the intraradical structures, extraradical hyphae, or spore production of the AM fungus. These findings suggest that plant sexual differences affect fundamental processes such as competitive ability and symbiotic relationships with AM fungi. © 2016 German Botanical Society and The Royal Botanical Society of the Netherlands.

  6. The role of protein interactions in mediating essentiality and synthetic lethality.

    Science.gov (United States)

    Talavera, David; Robertson, David L; Lovell, Simon C

    2013-01-01

    Genes are characterized as essential if their knockout is associated with a lethal phenotype, and these "essential genes" play a central role in biological function. In addition, some genes are only essential when deleted in pairs, a phenomenon known as synthetic lethality. Here we consider genes displaying synthetic lethality as "essential pairs" of genes, and analyze the properties of yeast essential genes and synthetic lethal pairs together. As gene duplication initially produces an identical pair or sets of genes, it is often invoked as an explanation for synthetic lethality. However, we find that duplication explains only a minority of cases of synthetic lethality. Similarly, disruption of metabolic pathways leads to relatively few examples of synthetic lethality. By contrast, the vast majority of synthetic lethal gene pairs code for proteins with related functions that share interaction partners. We also find that essential genes and synthetic lethal pairs cluster in the protein-protein interaction network. These results suggest that synthetic lethality is strongly dependent on the formation of protein-protein interactions. Compensation by duplicates does not usually occur mainly because the genes involved are recent duplicates, but is more commonly due to functional similarity that permits preservation of essential protein complexes. This unified view, combining genes that are individually essential with those that form essential pairs, suggests that essentiality is a feature of physical interactions between proteins protein-protein interactions, rather than being inherent in gene and protein products themselves.

  7. Phytophagous arthropods and a pathogen sharing a host plant: evidence for indirect plant-mediated interactions.

    Directory of Open Access Journals (Sweden)

    Raphaëlle Mouttet

    Full Text Available In ecological systems, indirect interactions between plant pathogens and phytophagous arthropods can arise when infestation by a first attacker alters the common host plant so that although a second attacker could be spatially or temporally separated from the first one, the former could be affected. The induction of plant defense reactions leading to the production of secondary metabolites is thought to have an important role since it involves antagonistic and/or synergistic cross-talks that may determine the outcome of such interactions. We carried out experiments under controlled conditions on young rose plants in order to assess the impact of these indirect interactions on life history traits of three pests: the necrotrophic fungus Botrytis cinerea Pers.: Fr. (Helotiales: Sclerotiniaceae, the aphid Rhodobium porosum Sanderson (Hemiptera: Aphididae and the thrips Frankliniella occidentalis Pergande (Thysanoptera: Thripidae. Our results indicated (i a bi-directional negative interaction between B. cinerea and R. porosum, which is conveyed by decreased aphid growth rate and reduced fungal lesion area, as well as (ii an indirect negative effect of B. cinerea on insect behavior. No indirect effect was observed between thrips and aphids. This research highlights several complex interactions that may be involved in structuring herbivore and plant pathogen communities within natural and managed ecosystems.

  8. The role of protein interactions in mediating essentiality and synthetic lethality.

    Directory of Open Access Journals (Sweden)

    David Talavera

    Full Text Available Genes are characterized as essential if their knockout is associated with a lethal phenotype, and these "essential genes" play a central role in biological function. In addition, some genes are only essential when deleted in pairs, a phenomenon known as synthetic lethality. Here we consider genes displaying synthetic lethality as "essential pairs" of genes, and analyze the properties of yeast essential genes and synthetic lethal pairs together. As gene duplication initially produces an identical pair or sets of genes, it is often invoked as an explanation for synthetic lethality. However, we find that duplication explains only a minority of cases of synthetic lethality. Similarly, disruption of metabolic pathways leads to relatively few examples of synthetic lethality. By contrast, the vast majority of synthetic lethal gene pairs code for proteins with related functions that share interaction partners. We also find that essential genes and synthetic lethal pairs cluster in the protein-protein interaction network. These results suggest that synthetic lethality is strongly dependent on the formation of protein-protein interactions. Compensation by duplicates does not usually occur mainly because the genes involved are recent duplicates, but is more commonly due to functional similarity that permits preservation of essential protein complexes. This unified view, combining genes that are individually essential with those that form essential pairs, suggests that essentiality is a feature of physical interactions between proteins protein-protein interactions, rather than being inherent in gene and protein products themselves.

  9. The Relationship between Parent-Child Interactions and Prosocial Behavior among Fifth- and Sixth-Grade Students: Gratitude as a Mediating Variable

    Science.gov (United States)

    Wu, Ho-Tang; Tseng, Shu-Feng; Wu, Pai-Lu; Chen, Chun-Miao

    2016-01-01

    Parent-child interaction, gratitude and prosocial behavior have a crucial impact on psychological development. According to our literature review, these three variables are positively related to one another. Therefore, the authors created a model that treats parent-child interaction as an exogenous variable, gratitude as a mediating variable, and…

  10. Eph/ephrins mediated thymocyte-thymic epithelial cell interactions control numerous processes of thymus biology

    Directory of Open Access Journals (Sweden)

    Javier eGarcia-Ceca

    2015-06-01

    Full Text Available Numerous studies emphasize the relevance of thymocyte-thymic epithelial cell (TECs interactions for the functional maturation of intrathymic T lymphocytes. The tyrosine kinase receptors Ephs (Erythropoietin-producing hepatocyte kinases and their ligands, ephrins (Eph receptor interaction proteins, are molecules known to be involved in the regulation of numerous biological systems in which cell-to-cell interactions are particularly relevant. In the last years, we and other authors have demonstrated the importance of these molecules in the thymic functions and the T-cell development. In the present report, we review data on the effects of Ephs and ephrins, in the functional maturation of both thymic epithelial microenvironment and thymocyte maturation as well as on their role in the lymphoid progenitor recruitment into the thymus.

  11. Interaction strength between different grazers and macroalgae mediated by ocean acidification over warming gradients.

    Science.gov (United States)

    Sampaio, E; Rodil, I F; Vaz-Pinto, F; Fernández, A; Arenas, F

    2017-04-01

    Since the past century, rising CO2 levels have led to global changes (ocean warming and acidification) with subsequent effects on marine ecosystems and organisms. Macroalgae-herbivore interactions have a main role in the regulation of marine community structure (top-down control). Gradients of warming prompt complex non-linear effects on organism metabolism, cascading into altered trophic interactions and community dynamics. However, not much is known on how will acidification and grazer assemblage composition shape these effects. Within this context, we aimed to assess the combined effects of warming gradients and acidification on macroalgae-herbivore interactions, using three cosmopolitan species, abundant in the Iberian Peninsula and closely associated in nature: the amphipod Melita palmata, the gastropod Gibbula umbilicalis, and the green macroalga Ulva rigida. Under two CO2 treatments (ΔCO2 ≃ 450 μatm) across a temperature gradient (13.5, 16.6, 19.9 and 22.1 °C), two mesocosm experiments were performed to assess grazer consumption rates and macroalgae-herbivore interaction, respectively. Warming (Experiment I and II) and acidification (Experiment II) prompted negative effects in grazer's survival and species-specific differences in consumption rates. M. palmata was shown to be the stronger grazer per biomass (but not per capita), and also the most affected by climate stressors. Macroalgae-herbivore interaction strength was markedly shaped by the temperature gradient, while simultaneous acidification lowered thermal optimal threshold. In the near future, warming and acidification are likely to strengthen top-down control, but further increases in disturbances may lead to bottom-up regulated communities. Finally, our results suggest that grazer assemblage composition may modulate future macroalgae-herbivore interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Electron-mediated nuclear-spin interactions between distant nitrogen-vacancy centers.

    Science.gov (United States)

    Bermudez, A; Jelezko, F; Plenio, M B; Retzker, A

    2011-10-07

    We propose a scheme enabling controlled quantum coherent interactions between separated nitrogen-vacancy centers in diamond in the presence of strong magnetic fluctuations. The proposed scheme couples nuclear qubits employing the magnetic dipole-dipole interaction between the electron spins and, crucially, benefits from the suppression of the effect of environmental magnetic field fluctuations thanks to a strong microwave driving. This scheme provides a basic building block for a full-scale quantum-information processor or quantum simulator based on solid-state technology.

  13. Electron-Mediated Nuclear-Spin Interactions Between Distant NV Centers

    CERN Document Server

    Bermudez, A; Plenio, M B; Retzker, A

    2011-01-01

    We propose a scheme enabling controlled quantum coherent interactions between separated nitrogen-vacancy centers in diamond in the presence of strong magnetic fluctuations. The proposed scheme couples nuclear qubits employing the magnetic dipole-dipole interaction between the electron spins and, crucially, benefits from the suppression of the effect of environmental magnetic field fluctuations thanks to a strong microwave driving. This scheme provides a basic building block for a full-scale quantum information processor or quantum simulator based on solid-state technology.

  14. Substrate-mediated interactions and intermolecular forces between molecules adsorbed on surfaces.

    Science.gov (United States)

    Sykes, E Charles H; Han, Patrick; Kandel, S Alex; Kelly, Kevin F; McCarty, Gregory S; Weiss, Paul S

    2003-12-01

    Adsorbate interactions and reactions on metal surfaces have been investigated using scanning tunneling microscopy. The manners in which adsorbates perturb the surface electronic structure in their vicinity are discussed. The effects these perturbations have on other molecules are shown to be important in overlayer growth. Interactions of molecules with surface steps are addressed, and each molecule's electron affinity is shown to dictate its adsorption sites at step edges. Standing waves emanating from steps are demonstrated to effect transient molecular adsorption up to 40 A away from the step edge. Halobenzene derivatives are used to demonstrate how the surface is important in aligning reactive intermediates.

  15. Eph/ephrin-B-mediated cell-to-cell interactions govern MTS20(+) thymic epithelial cell development.

    Science.gov (United States)

    Montero-Herradón, Sara; García-Ceca, Javier; Sánchez Del Collado, Beatriz; Alfaro, David; Zapata, Agustín G

    2016-08-01

    Thymus development is a complex process in which cell-to-cell interactions between thymocytes and thymic epithelial cells (TECs) are essential to allow a proper maturation of both thymic cell components. Although signals that control thymocyte development are well known, mechanisms governing TEC maturation are poorly understood, especially those that regulate the maturation of immature TEC populations during early fetal thymus development. In this study, we show that EphB2-deficient, EphB2LacZ and EphB3-deficient fetal thymuses present a lower number of cells and delayed maturation of DN cell subsets compared to WT values. Moreover, deficits in the production of chemokines, known to be involved in the lymphoid seeding into the thymus, contribute in decreased proportions of intrathymic T cell progenitors (PIRA/B(+)) in the mutant thymuses from early stages of development. These features correlate with increased proportions of MTS20(+) cells but fewer MTS20(-) cells from E13.5 onward in the deficient thymuses, suggesting a delayed development of the first epithelial cells. In addition, in vitro the lack of thymocytes or the blockade of Eph/ephrin-B-mediated cell-to-cell interactions between either thymocytes-TECs or TECs-TECs in E13.5 fetal thymic lobes coursed with increased proportions of MTS20(+) TECs. This confirms, for the first time, that the presence of CD45(+) cells, corresponding at these stages to DN1 and DN2 cells, and Eph/ephrin-B-mediated heterotypic or homotypic cell interactions between thymocytes and TECs, or between TECs and themselves, contribute to the early maturation of MTS20(+) TECs.

  16. Murine junctional adhesion molecules JAM-B and JAM-C mediate endothelial and stellate cell interactions during hepatic fibrosis.

    Science.gov (United States)

    Hintermann, Edith; Bayer, Monika; Ehser, Janine; Aurrand-Lions, Michel; Pfeilschifter, Josef M; Imhof, Beat A; Christen, Urs

    2016-07-03

    Classical junctional adhesion molecules JAM-A, JAM-B and JAM-C influence vascular permeability, cell polarity as well as leukocyte recruitment and immigration into inflamed tissue. As the vasculature becomes remodelled in chronically injured, fibrotic livers we aimed to determine distribution and role of junctional adhesion molecules during this pathological process. Therefore, livers of naïve or carbon tetrachloride-treated mice were analyzed by immunohistochemistry to localize all 3 classical junctional adhesion molecules. Hepatic stellate cells and endothelial cells were isolated and subjected to immunocytochemistry and flow cytometry to determine localization and functionality of JAM-B and JAM-C. Cells were further used to perform contractility and migration assays and to study endothelial tubulogenesis and pericytic coverage by hepatic stellate cells. We found that in healthy tissue, JAM-A was ubiquitously expressed whereas JAM-B and JAM-C were restricted to the vasculature. During fibrosis, JAM-B and JAM-C levels increased in endothelial cells and JAM-C was de novo generated in myofibroblastic hepatic stellate cells. Soluble JAM-C blocked contractility but increased motility in hepatic stellate cells. Furthermore, soluble JAM-C reduced endothelial tubulogenesis and endothelial cell/stellate cell interaction. Thus, during liver fibrogenesis, JAM-B and JAM-C expression increase on the vascular endothelium. More importantly, JAM-C appears on myofibroblastic hepatic stellate cells linking them as pericytes to JAM-B positive endothelial cells. This JAM-B/JAM-C mediated interaction between endothelial cells and stellate cells stabilizes vessel walls and may control the sinusoidal diameter. Increased hepatic stellate cell contraction mediated by JAM-C/JAM-C interaction may cause intrahepatic vasoconstriction, which is a major complication in liver cirrhosis.

  17. Surface mediated cooperative interactions of drugs enhance mechanical forces for antibiotic action

    Science.gov (United States)

    Ndieyira, Joseph W.; Bailey, Joe; Patil, Samadhan B.; Vögtli, Manuel; Cooper, Matthew A.; Abell, Chris; McKendry, Rachel A.; Aeppli, Gabriel

    2017-02-01

    The alarming increase of pathogenic bacteria that are resistant to multiple antibiotics is now recognized as a major health issue fuelling demand for new drugs. Bacterial resistance is often caused by molecular changes at the bacterial surface, which alter the nature of specific drug-target interactions. Here, we identify a novel mechanism by which drug-target interactions in resistant bacteria can be enhanced. We examined the surface forces generated by four antibiotics; vancomycin, ristomycin, chloroeremomycin and oritavancin against drug-susceptible and drug-resistant targets on a cantilever and demonstrated significant differences in mechanical response when drug-resistant targets are challenged with different antibiotics although no significant differences were observed when using susceptible targets. Remarkably, the binding affinity for oritavancin against drug-resistant targets (70 nM) was found to be 11,000 times stronger than for vancomycin (800 μM), a powerful antibiotic used as the last resort treatment for streptococcal and staphylococcal bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Using an exactly solvable model, which takes into account the solvent and membrane effects, we demonstrate that drug-target interactions are strengthened by pronounced polyvalent interactions catalyzed by the surface itself. These findings further enhance our understanding of antibiotic mode of action and will enable development of more effective therapies.

  18. Using sentence openers to foster student interaction in computer-mediated learning environments.

    NARCIS (Netherlands)

    Lazonder, Adrianus W.; Wilhelm, P.; Ootes, S.A.W.

    2003-01-01

    This paper reports two studies into the efficacy of sentence openers to foster online peer-to-peer interaction. Sentence openers are pre-defined ways to start an utterance that are implemented in communication facilities as menu's or buttons. In the first study, typical opening phrases were derived

  19. Surface mediated cooperative interactions of drugs enhance mechanical forces for antibiotic action

    Science.gov (United States)

    Ndieyira, Joseph W.; Bailey, Joe; Patil, Samadhan B.; Vögtli, Manuel; Cooper, Matthew A.; Abell, Chris; McKendry, Rachel A.; Aeppli, Gabriel

    2017-01-01

    The alarming increase of pathogenic bacteria that are resistant to multiple antibiotics is now recognized as a major health issue fuelling demand for new drugs. Bacterial resistance is often caused by molecular changes at the bacterial surface, which alter the nature of specific drug-target interactions. Here, we identify a novel mechanism by which drug-target interactions in resistant bacteria can be enhanced. We examined the surface forces generated by four antibiotics; vancomycin, ristomycin, chloroeremomycin and oritavancin against drug-susceptible and drug-resistant targets on a cantilever and demonstrated significant differences in mechanical response when drug-resistant targets are challenged with different antibiotics although no significant differences were observed when using susceptible targets. Remarkably, the binding affinity for oritavancin against drug-resistant targets (70 nM) was found to be 11,000 times stronger than for vancomycin (800 μM), a powerful antibiotic used as the last resort treatment for streptococcal and staphylococcal bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Using an exactly solvable model, which takes into account the solvent and membrane effects, we demonstrate that drug-target interactions are strengthened by pronounced polyvalent interactions catalyzed by the surface itself. These findings further enhance our understanding of antibiotic mode of action and will enable development of more effective therapies. PMID:28155918

  20. Learning Motivation Mediates Gene-by-Socioeconomic Status Interaction on Mathematics Achievement in Early Childhood

    Science.gov (United States)

    Tucker-Drob, Elliot M.; Harden, K. Paige

    2012-01-01

    There is accumulating evidence that genetic influences on achievement are more pronounced among children living in higher socioeconomic status homes, and that these gene-by-environment interactions occur prior to children's entry into formal schooling. We hypothesized that one pathway through which socioeconomic status promotes genetic influences…

  1. N-cadherin-mediated interaction with multiple myeloma cells inhibits osteoblast differentiation

    NARCIS (Netherlands)

    Groen, R.W.J.; de Rooij, M.F.M.; Kocemba, K.A.; Reijmers, R.M.; de Haan-Kramer, A.; Overdijk, M.B.; Aalders, L.; Rozemuller, H.; Martens, A.C.M.; Bergsagel, P.L.; Kersten, M.J.; Pals, S.T.; Spaargaren, M.

    2011-01-01

    Background Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow

  2. Evidence for water-mediated mechanisms in coral–algal interactions

    NARCIS (Netherlands)

    Jorissen, Hendrikje; Skinner, Christina; Osinga, Ronald; Beer, De Dirk; Nugues, Maggy M.

    2016-01-01

    Although many coral reefs have shifted from coral-to-algal dominance, the consequence of such a transition for coral–algal interactions and their underlying mechanisms remain poorly understood. At the microscale, it is unclear how diffusive boundary layers (DBLs) and surface oxygen concentrations

  3. Data from: Evidence for water-mediated mechanisms in coral–algal interactions

    NARCIS (Netherlands)

    Jorissen, Hendrikje; Skinner, Christina; Osinga, R.; Beer, De Dirk; Nugues, Maggy M.

    2016-01-01

    Although many coral reefs have shifted from coral-to-algal dominance, the consequence of such a transition for coral–algal interactions and their underlying mechanisms remain poorly understood. At the microscale, it is unclear how diffusive boundary layers (DBLs) and surface oxygen concentrations at

  4. Pyoverdine and PQS Mediated Subpopulation Interactions Involved in Pseudomonas aeruginosa Biofilm Formation

    DEFF Research Database (Denmark)

    Yang, Liang; Nilsson, Martin; Gjermansen, Morten;

    2009-01-01

    Using flow chamber-grown Pseudomonas aeruginosa biofilms as model system, we show in the present study that formation of heterogeneous biofilms may occur through mechanisms that involve complex subpopulation interactions. One example of this phenomenon is expression of the iron...

  5. PDZ domain-mediated interactions of G protein-coupled receptors with postsynaptic density protein 95

    DEFF Research Database (Denmark)

    Møller, Thor C; Wirth, Volker F; Roberts, Nina Ingerslev;

    2013-01-01

    G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome. Their signaling is regulated by scaffold proteins containing PDZ domains, but although these interactions are important for GPCR function, they are still poorly understood. We here present...

  6. Sexual Assertiveness Mediates the Effect of Social Interaction Anxiety on Sexual Victimization Risk among College Women

    Science.gov (United States)

    Schry, Amie R.; White, Susan W.

    2013-01-01

    Sexual victimization is prevalent among college women and is associated with adverse psychological consequences. Social anxiety, particularly related to interpersonal interaction, may increase risk of sexual victimization among college women by decreasing sexual assertiveness and decreasing the likelihood of using assertive resistance techniques.…

  7. SIgA binding to mucosal surfaces is mediated by mucin-mucin interactions.

    Directory of Open Access Journals (Sweden)

    Hannah L Gibbins

    Full Text Available The oral mucosal pellicle is a layer of absorbed salivary proteins, including secretory IgA (SIgA, bound onto the surface of oral epithelial cells and is a useful model for all mucosal surfaces. The mechanism by which SIgA concentrates on mucosal surfaces is examined here using a tissue culture model with real saliva. Salivary mucins may initiate the formation of the mucosal pellicle through interactions with membrane-bound mucins on cells. Further protein interactions with mucins may then trigger binding of other pellicle proteins. HT29 colon cell lines, which when treated with methotrexate (HT29-MTX produce a gel-forming mucin, were used to determine the importance of these mucin-mucin interactions. Binding of SIgA to cells was then compared using whole mouth saliva, parotid (mucin-free saliva and a source of purified SIgA. Greatest SIgA binding occurred when WMS was incubated with HT29-MTX expressing mucus. Since salivary MUC5B was only able to bind to cells which produced mucus and purified SIgA showed little binding to the same cells we conclude that most SIgA binding to mucosal cells occurs because SIgA forms complexes with salivary mucins which then bind to cells expressing membrane-bound mucins. This work highlights the importance of mucin interactions in the development of the mucosal pellicle.

  8. Towards hot electron mediated charge exchange in hyperthermal energy ion-surface interactions

    DEFF Research Database (Denmark)

    Ray, M. P.; Lake, R. E.; Thomsen, Lasse Bjørchmar;

    2010-01-01

    electrons useful for driving chemical reactions at surfaces. Using the binary collision approximation and a nonadiabatic model that takes into account the time-varying nature of the ion–surface interaction, the energy loss of the ions is reproduced. The energy loss for Na + ions incident on the devices...

  9. Predator-prey interactions mediated by prey personality and predator hunting mode.

    Science.gov (United States)

    Belgrad, Benjamin A; Griffen, Blaine D

    2016-04-13

    Predator-prey interactions are important drivers in structuring ecological communities. However, despite widespread acknowledgement that individual behaviours and predator species regulate ecological processes, studies have yet to incorporate individual behavioural variations in a multipredator system. We quantified a prevalent predator avoidance behaviour to examine the simultaneous roles of prey personality and predator hunting mode in governing predator-prey interactions. Mud crabs, Panopeus herbstii, reduce their activity levels and increase their refuge use in the presence of predator cues. We measured mud crab mortality and consistent individual variations in the strength of this predator avoidance behaviour in the presence of predatory blue crabs, Callinectes sapidus, and toadfish, Opsanus tau We found that prey personality and predator species significantly interacted to affect mortality with blue crabs primarily consuming bold mud crabs and toadfish preferentially selecting shy crabs. Additionally, the strength of the predator avoidance behaviour depended upon the predation risk from the predator species. Consequently, the personality composition of populations and predator hunting mode may be valuable predictors of both direct and indirect predator-prey interaction strength. These findings support theories postulating mechanisms for maintaining intraspecies diversity and have broad implications for community dynamics.

  10. Video Mediated Social Interaction Between Groups: System Requirements and Technology Challenges

    NARCIS (Netherlands)

    Williams, D.; Usrsu, M.F.; Meenowa, J.; Cesar Garcia, P.S.; Kegel, I.; Bergström, K.; Bergström, K.

    2011-01-01

    This paper discusses results from research related to the use of television as a device that supports social interaction between close-knit groups in settings that include more than two locations, each location being potentially equipped with more than one camera. The paper introduces the notion of

  11. Intermolecular forces, spontaneous emission, and superradiance in a dielectric medium : Polariton-mediated interactions

    NARCIS (Netherlands)

    Knoester, Jasper; Mukamel, Shaul

    1989-01-01

    A reduced equation of motion that describes the excited-state dynamics of interacting two-level impurity molecules in a dielectric host crystal is derived starting from a microscopic model for the total system. Our theory generalizes the derivation of the conventional superradiance master equation f

  12. Intellectual Interest Mediates Gene x Socioeconomic Status Interaction on Adolescent Academic Achievement

    Science.gov (United States)

    Tucker-Drob, Elliot M.; Harden, K. Paige

    2012-01-01

    Recent studies have demonstrated that genetic influences on cognitive ability and academic achievement are larger for children raised in higher socioeconomic status (SES) homes. However, little work has been done to document the psychosocial processes that underlie this Gene x Environment interaction. One process may involve the conversion of…

  13. Reciprocal Trust Mediates Deep Transfer of Learning between Games of Strategic Interaction

    Science.gov (United States)

    Juvina, Ion; Saleem, Muniba; Martin, Jolie M.; Gonzalez, Cleotilde; Lebiere, Christian

    2013-01-01

    We studied transfer of learning across two games of strategic interaction. We found that the interpersonal relation between two players during and across two games influence development of reciprocal trust and transfer of learning from one game to another. We show that two types of similarities between the games affect transfer: (1) deep…

  14. Literature-Based Discovery of IFN-γ and Vaccine-Mediated Gene Interaction Networks

    Directory of Open Access Journals (Sweden)

    Arzucan Özgür

    2010-01-01

    Full Text Available Interferon-gamma (IFN-γ regulates various immune responses that are often critical for vaccine-induced protection. In order to annotate the IFN-γ-related gene interaction network from a large amount of IFN-γ research reported in the literature, a literature-based discovery approach was applied with a combination of natural language processing (NLP and network centrality analysis. The interaction network of human IFN-γ (Gene symbol: IFNG and its vaccine-specific subnetwork were automatically extracted using abstracts from all articles in PubMed. Four network centrality metrics were further calculated to rank the genes in the constructed networks. The resulting generic IFNG network contains 1060 genes and 26313 interactions among these genes. The vaccine-specific subnetwork contains 102 genes and 154 interactions. Fifty six genes such as TNF, NFKB1, IL2, IL6, and MAPK8 were ranked among the top 25 by at least one of the centrality methods in one or both networks. Gene enrichment analysis indicated that these genes were classified in various immune mechanisms such as response to extracellular stimulus, lymphocyte activation, and regulation of apoptosis. Literature evidence was manually curated for the IFN-γ relatedness of 56 genes and vaccine development relatedness for 52 genes. This study also generated many new hypotheses worth further experimental studies.

  15. Factors Mediating the Interactions between Adviser and Advisee during the Master's Thesis Project: A Quantitative Approach

    Science.gov (United States)

    Rodrigues Jr., Jose Florencio; Lehmann, Angela Valeria Levay; Fleith, Denise De Souza

    2005-01-01

    Building on previous studies centred on the interaction between adviser and advisee in masters thesis projects, in which a qualitative approach was used, the present study uses factor analysis to identify the factors that determine either a successful or unsuccessful outcome for the masters thesis project. There were five factors relating to the…

  16. Prebiotics Mediate Microbial Interactions in a Consortium of the Infant Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Daniel A. Medina

    2017-10-01

    Full Text Available Composition of the gut microbiome is influenced by diet. Milk or formula oligosaccharides act as prebiotics, bioactives that promote the growth of beneficial gut microbes. The influence of prebiotics on microbial interactions is not well understood. Here we investigated the transformation of prebiotics by a consortium of four representative species of the infant gut microbiome, and how their interactions changed with dietary substrates. First, we optimized a culture medium resembling certain infant gut parameters. A consortium containing Bifidobacterium longum subsp. infantis, Bacteroides vulgatus, Escherichia coli and Lactobacillus acidophilus was grown on fructooligosaccharides (FOS or 2′-fucosyllactose (2FL in mono- or co-culture. While Bi. infantis and Ba. vulgatus dominated growth on 2FL, their combined growth was reduced. Besides, interaction coefficients indicated strong competition, especially on FOS. While FOS was rapidly consumed by the consortium, B. infantis was the only microbe displaying significant consumption of 2FL. Acid production by the consortium resembled the metabolism of microorganisms dominating growth in each substrate. Finally, the consortium was tested in a bioreactor, observing similar predominance but more pronounced acid production and substrate consumption. This study indicates that the chemical nature of prebiotics modulate microbial interactions in a consortium of infant gut species.

  17. Intellectual Interest Mediates Gene x Socioeconomic Status Interaction on Adolescent Academic Achievement

    Science.gov (United States)

    Tucker-Drob, Elliot M.; Harden, K. Paige

    2012-01-01

    Recent studies have demonstrated that genetic influences on cognitive ability and academic achievement are larger for children raised in higher socioeconomic status (SES) homes. However, little work has been done to document the psychosocial processes that underlie this Gene x Environment interaction. One process may involve the conversion of…

  18. Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat.

    Science.gov (United States)

    Korim, Willian Seiji; Ferreira-Neto, Marcos L; Pedrino, Gustavo R; Pilowsky, Paul M; Cravo, Sergio L

    2012-12-01

    In the nucleus tractus solitarii (NTS) of rats, blockade of extracellular ATP breakdown to adenosine reduces arterial blood pressure (AP) increases that follow stimulation of the hypothalamic defense area (HDA). The effects of ATP on NTS P2 receptors, during stimulation of the HDA, are still unclear. The aim of this study was to determine whether activation of P2 receptors in the NTS mediates cardiovascular responses to HDA stimulation. Further investigation was taken to establish if changes in hindlimb vascular conductance (HVC) elicited by electrical stimulation of the HDA, or activation of P2 receptors in the NTS, are relayed in the rostral ventrolateral medulla (RVLM); and if those responses depend on glutamate release by ATP acting on presynaptic terminals. In anesthetized and paralyzed rats, electrical stimulation of the HDA increased AP and HVC. Blockade of P2 or glutamate receptors in the NTS, with bilateral microinjections of suramin (10 mM) or kynurenate (50 mM) reduced only the evoked increase in HVC by 75 % or more. Similar results were obtained with the blockade combining both antagonists. Blockade of P2 and glutamate receptors in the RVLM also reduced the increases in HVC to stimulation of the HDA by up to 75 %. Bilateral microinjections of kynurenate in the RVLM abolished changes in AP and HVC to injections of the P2 receptor agonist α,β-methylene ATP (20 mM) into the NTS. The findings suggest that HDA-NTS-RVLM pathways in control of HVC are mediated by activation of P2 and glutamate receptors in the brainstem in alerting-defense reactions.

  19. HIV-1 replication through hHR23A-mediated interaction of Vpr with 26S proteasome.

    Directory of Open Access Journals (Sweden)

    Ge Li

    Full Text Available HIV-1 Vpr is a virion-associated protein. Its activities link to viral pathogenesis and disease progression of HIV-infected patients. In vitro, Vpr moderately activates HIV-1 replication in proliferating T cells, but it is required for efficient viral infection and replication in vivo in non-dividing cells such as macrophages. How exactly Vpr contributes to viral replication remains elusive. We show here that Vpr stimulates HIV-1 replication at least in part through its interaction with hHR23A, a protein that binds to 19S subunit of the 26S proteasome and shuttles ubiquitinated proteins to the proteasome for degradation. The Vpr-proteasome interaction was initially discovered in fission yeast, where Vpr was shown to associate with Mts4 and Mts2, two 19S-associated proteins. The interaction of Vpr with the 19S subunit of the proteasome was further confirmed in mammalian cells where Vpr associates with the mammalian orthologues of fission yeast Mts4 and S5a. Consistently, depletion of hHR23A interrupts interaction of Vpr with proteasome in mammalian cells. Furthermore, Vpr promotes hHR23A-mediated protein-ubiquitination, and down-regulation of hHR23A using RNAi significantly reduced viral replication in non-proliferating MAGI-CCR5 cells and primary macrophages. These findings suggest that Vpr-proteasome interaction might counteract certain host restriction factor(s to stimulate viral replication in non-dividing cells.

  20. Selective transformations between nanoparticle superlattices via the reprogramming of DNA-mediated interactions.

    Science.gov (United States)

    Zhang, Yugang; Pal, Suchetan; Srinivasan, Babji; Vo, Thi; Kumar, Sanat; Gang, Oleg

    2015-08-01

    The rapid development of self-assembly approaches has enabled the creation of materials with desired organization of nanoscale components. However, achieving dynamic control, wherein the system can be transformed on demand into multiple entirely different states, is typically absent in atomic and molecular systems and has remained elusive in designed nanoparticle systems. Here, we demonstrate with in situ small-angle X-ray scattering that, by using DNA strands as inputs, the structure of a three-dimensional lattice of DNA-coated nanoparticles can be switched from an initial 'mother' phase into one of multiple 'daughter' phases. The introduction of different types of reprogramming DNA strands modifies the DNA shells of the nanoparticles within the superlattice, thereby shifting interparticle interactions to drive the transformation into a particular daughter phase. Moreover, we mapped quantitatively with free-energy calculations the selective reprogramming of interactions onto the observed daughter phases.

  1. Suppressing membrane height fluctuations leads to a membrane-mediated interaction among proteins.

    Science.gov (United States)

    Sapp, Kayla; Maibaum, Lutz

    2016-11-01

    Membrane-induced interactions can play a significant role in the spatial distribution of membrane-bound proteins. We develop a model that combines a continuum description of lipid bilayers with a discrete particle model of proteins to probe the emerging structure of the combined membrane-protein system. Our model takes into account the membrane's elastic behavior, the steric repulsion between proteins, and the quenching of membrane shape fluctuations due to the presence of the proteins. We employ coupled Langevin equations to describe the dynamics of the system. We show that coupling to the membrane induces an attractive interaction among proteins, which may contribute to the clustering of proteins in biological membranes. We investigate the lateral protein diffusion and find that it is reduced due to transient fluctuations in membrane shape.

  2. Charge-transfer interaction mediated organogels from 18β-glycyrrhetinic acid appended pyrene

    Directory of Open Access Journals (Sweden)

    Jun Hu

    2013-12-01

    Full Text Available We describe herein the two-component charge-transfer (CT interaction induced organogel formation with 18β-glycyrrhetinic acid appended pyrene (GA-pyrene, 3 as the donor, and 2,4,7-trinitrofluorenone (TNF, 4 as the acceptor. The use of TNF (4 as a versatile electron acceptor in the formation of CT gels is demonstrated through the formation of gels in a variety of solvents. Thermal stability, stoichiometry, scanning electron microscopy (SEM, optical micrographs, and circular dichroism (CD are performed on these CT gels to investigate their thermal and assembly properties. UV–vis, fluorescence, mass spectrometric as well as variable-temperature 1H NMR experiments on these gels suggest that the CT interaction is one of the major driving forces for the formation of these organogels.

  3. Thermal expression of intersubjectivity offers new possibilities to human-machine and technologically mediated interactions.

    Science.gov (United States)

    Merla, Arcangelo

    2014-01-01

    The evaluation of the psychophysiological state of the interlocutor is an important element of interpersonal relationships and communication. Thermal infrared (IR) imaging has proved to be a reliable tool for non-invasive and contact-less evaluation of vital signs, psychophysiological responses, and emotional states. This technique is quickly spreading in many fields, from psychometrics to social and developmental psychology; and from the touch-less monitoring of vital signs and stress, up to the human-machine interaction. In particular, thermal IR imaging promises to be of use for gathering information about affective states in social situations. This paper presents the state of the art of thermal IR imaging in psychophysiology and in the assessment of affective states. The goal is to provide insights about its potentialities and limits for its use in human-artificial agent interaction in order to contribute to a major issue in the field: the perception by an artificial agent of human psychophysiological and affective states.

  4. Suppressing membrane height fluctuations leads to a membrane-mediated interaction among proteins

    Science.gov (United States)

    Sapp, Kayla; Maibaum, Lutz

    2016-11-01

    Membrane-induced interactions can play a significant role in the spatial distribution of membrane-bound proteins. We develop a model that combines a continuum description of lipid bilayers with a discrete particle model of proteins to probe the emerging structure of the combined membrane-protein system. Our model takes into account the membrane's elastic behavior, the steric repulsion between proteins, and the quenching of membrane shape fluctuations due to the presence of the proteins. We employ coupled Langevin equations to describe the dynamics of the system. We show that coupling to the membrane induces an attractive interaction among proteins, which may contribute to the clustering of proteins in biological membranes. We investigate the lateral protein diffusion and find that it is reduced due to transient fluctuations in membrane shape.

  5. Interactions Between Charged Macroions Mediated by Molecules with Rod-like Charged Structures

    Directory of Open Access Journals (Sweden)

    Bohinc, K.

    2014-03-01

    Full Text Available A short review of recent theoretical advances in studies of the interaction between highly charged systems embedded in a solution of rod-like molecules is presented. The system is theoretically described by the functional density theory, where the correlations within the rod-like molecules are accounted for. We show that for sufficiently long molecules and large surface charge densities, an attractive force between like-charged surfaces arises due to the spatially distributed charges within the molecules. The added salt has an influence on the condition for the attractive force between like-charged surfaces. The theoretical results are compared with Monte Carlo simulations. Many phenomena motivate the study of the interaction between like-charged surfaces (DNA condensation, virus aggregation, yeast flocculation, cohesion of cement paste.

  6. 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions

    DEFF Research Database (Denmark)

    Callen, E.; Wong, N.; Chen, H.-T.;

    2013-01-01

    deficiency by restoring genome stability in BRCA1-deficient cells yet behaves like wild-type 53BP1 with respect to immunoglobulin class switch recombination (CSR). 53BP1 recruits RIF1 but fails to recruit the DDR protein PTIP to DSBs, and disruption of PTIP phenocopies 53BP1. We conclude that 53BP1 promotes...... productive CSR and suppresses mutagenic DNA repair through distinct phosphodependent interactions with RIF1 and PTIP. © 2013 Elsevier Inc....

  7. Simulation of Fluid-Structure and Fluid-Mediated Structure-Structure Interactions in Stokes Regime Using Immersed Boundary Method

    Directory of Open Access Journals (Sweden)

    Masoud Baghalnezhad

    2014-01-01

    Full Text Available The Stokes flow induced by the motion of an elastic massless filament immersed in a two-dimensional fluid is studied. Initially, the filament is deviated from its equilibrium state and the fluid is at rest. The filament will induce fluid motion while returning to its equilibrium state. Two different test cases are examined. In both cases, the motion of a fixed-end massless filament induces the fluid motion inside a square domain. However, in the second test case, a deformable circular string is placed in the square domain and its interaction with the Stokes flow induced by the filament motion is studied. The interaction between the fluid and deformable body/bodies can become very complicated from the computational point of view. An immersed boundary method is used in the present study. In order to substantiate the accuracy of the numerical method employed, the simulated results associated with the Stokes flow induced by the motion of an extending star string are compared well with those obtained by the immersed interface method. The results show the ability and accuracy of the IBM method in solving the complicated fluid-structure and fluid-mediated structure-structure interaction problems happening in a wide variety of engineering and biological systems.

  8. The retromer component SNX6 interacts with dynactin p150~(Glued)and mediates endosome-to-TGN transport

    Institute of Scientific and Technical Information of China (English)

    Zhi Hong; Yanrui Yang; Cheng Zhang; Yang Niu; Ke Li; Xi Zhao; Jia-Jia Liu

    2009-01-01

    The retromer is a protein complex that mediates retrograde transport of transmembrane cargoes from endosomes to the fraws-Golgi network (TGN). It is comprised of a cargo-selection subcomplex of Vps26, Vps29 and Vps35 and a membrane-binding coat subcomplex of sorting nexins (SNXs). Previous studies identified SNX1/2 as one of the components of the SNX subcomplex, and SNX5/6 as candidates for the second SNX. How the retromer-associated cargoes are recognized and transported by molecular motors are largely unknown. In this study, we found that one of SNXl/2's dimerization partners, SNX6, interacts with the pl50~(Glued) subunit of the dynein/dynactin motor complex. We present evidence that SNX6 is a component of the retromer, and that recruitment of the motor complex to the membrane-associated retromer requires the SNX6-pl50~(Glued) interaction. Disruption of the SNX6-pl50~(Ghied) interaction causes failure in formation and detachment of the tubulovesicular sorting structures from endosomes and results in block of CI-MPR retrieval from endosomes to the TGN. These observations indicate that in addition to SNX 1/2, SNX6 in association with the dynein/dynactin complex drives the formation and movement of tubular retrograde intermediates.

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

    Science.gov (United States)

    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.

  10. Activating social strategies: Face-to-face interaction in technology-mediated citizen science.

    Science.gov (United States)

    Cappa, Francesco; Laut, Jeffrey; Nov, Oded; Giustiniano, Luca; Porfiri, Maurizio

    2016-11-01

    The use of crowds in research activities by public and private organizations is growing under different forms. Citizen science is a popular means of engaging the general public in research activities led by professional scientists. By involving a large number of amateur scientists, citizen science enables distributed data collection and analysis on a scale that would be otherwise difficult and costly to achieve. While advancements in information technology in the past few decades have fostered the growth of citizen science through online participation, several projects continue to fail due to limited participation. Such web-based projects may isolate the citizen scientists from the researchers. By adopting the perspective of social strategy, we investigate within a measure-manipulate-measure experiment if motivations to participate in a citizen science project can be positively influenced by a face-to-face interaction with the scientists leading the project. Such an interaction provides the participants with the possibility of asking questions on the spot and obtaining a detailed explanation of the citizen science project, its scientific merit, and environmental relevance. Social and cultural factors that moderate the effect brought about by face-to-face interactions on the motivations are also dissected and analyzed. Our findings provide an exploratory insight into a means for motivating crowds to participate in online environmental monitoring projects, also offering possible selection criteria of target audience.

  11. Nuclear Targeting of Methyl-Recycling Enzymes in Arabidopsis thaliana Is Mediated by Specific Protein Interactions

    Institute of Scientific and Technical Information of China (English)

    Sanghyun Lee; Andrew C. Doxey; Brendan J. McConkey; Barbara A. Moffatt

    2012-01-01

    Numerous transmethylation reactions are required for normal plant growth and development.S-adenosylhomocysteine hydrolase (SAHH) and adenosine kinase (ADK) act coordinately to recycle the by-product of these reactions,S-adenosylhomocysteine (SAH) that would otherwise competitively inhibit methyltransferase (MT) activities.Here,we report on investigations to understand how the SAH produced in the nucleus is metabolized by SAHH and ADK.Localization analyses using green fluorescent fusion proteins demonstrated that both enzymes are capable of localizing to the cytoplasm and the nucleus,although no obvious nuclear localization signal was found in their sequences.Deletion analysis revealed that a 41-amino-acid segment of SAHH (Gly1 50-Lys190) is required for nuclear targeting of this enzyme.This segment is surface exposed,shows unique sequence conservation patterns in plant SAHHs,and possesses additional features of protein-protein interaction motifs.ADK and SAHH interact in Arabidopsis via this segment and also interact with an mRNA cap MT.We propose that the targeting of this complex is directed by the nuclear localization signal of the MT; other MTs may similarly target SAHH/ADK to other subcellular compartments to ensure uninterrupted transmethylation.

  12. AMP-activated protein kinase (AMPK mediates nutrient regulation of thioredoxin-interacting protein (TXNIP in pancreatic beta-cells.

    Directory of Open Access Journals (Sweden)

    Maayan Shaked

    Full Text Available Thioredoxin-interacting protein (TXNIP regulates critical biological processes including inflammation, stress and apoptosis. TXNIP is upregulated by glucose and is a critical mediator of hyperglycemia-induced beta-cell apoptosis in diabetes. In contrast, the saturated long-chain fatty acid palmitate, although toxic to the beta-cell, inhibits TXNIP expression. The mechanisms involved in the opposing effects of glucose and fatty acids on TXNIP expression are unknown. We found that both palmitate and oleate inhibited TXNIP in a rat beta-cell line and islets. Palmitate inhibition of TXNIP was independent of fatty acid beta-oxidation or esterification. AMP-activated protein kinase (AMPK has an important role in cellular energy sensing and control of metabolic homeostasis; therefore we investigated its involvement in nutrient regulation of TXNIP. As expected, glucose inhibited whereas palmitate stimulated AMPK. Pharmacologic activators of AMPK mimicked fatty acids by inhibiting TXNIP. AMPK knockdown increased TXNIP expression in presence of high glucose with and without palmitate, indicating that nutrient (glucose and fatty acids effects on TXNIP are mediated in part via modulation of AMPK activity. TXNIP is transcriptionally regulated by carbohydrate response element-binding protein (ChREBP. Palmitate inhibited glucose-stimulated ChREBP nuclear entry and recruitment to the Txnip promoter, thereby inhibiting Txnip transcription. We conclude that AMPK is an important regulator of Txnip transcription via modulation of ChREBP activity. The divergent effects of glucose and fatty acids on TXNIP expression result in part from their opposing effects on AMPK activity. In light of the important role of TXNIP in beta-cell apoptosis, its inhibition by fatty acids can be regarded as an adaptive/protective response to glucolipotoxicity. The finding that AMPK mediates nutrient regulation of TXNIP may have important implications for the pathophysiology and treatment

  13. Forces and torques on rigid inclusions in an elastic environment: resulting matrix-mediated interactions, displacements, and rotations

    CERN Document Server

    Puljiz, Mate

    2016-01-01

    Embedding rigid inclusions into elastic matrix materials is a procedure of high practical relevance, for instance for the fabrication of elastic composite materials. We theoretically analyze the following situation. Rigid spherical inclusions are enclosed by a homogeneous elastic medium under stick boundary conditions. Forces and torques are directly imposed from outside onto the inclusions, or are externally induced between them. The inclusions respond to these forces and torques by translations and rotations against the surrounding elastic matrix. This leads to elastic matrix deformations, and in turn results in mutual long-ranged matrix-mediated interactions between the inclusions. Adapting a well-known approach from low-Reynolds-number hydrodynamics, we explicitly calculate the displacements and rotations of the inclusions from the externally imposed or induced forces and torques. Analytical expressions are presented as a function of the inclusion configuration in terms of displaceability and rotateabilit...

  14. Colloidal interactions of inorganic nanoparticles grafted with zwitterionic polymer brushes and gels by surface-mediated seeded polymerization.

    Science.gov (United States)

    An, Soyoun; Choi, Sang Koo; Cho, Jang Woo; Kim, Hyun Tae; Kim, Jin Woong

    2014-08-01

    A robust and straightforward approach is introduced to synthesize inorganic nanoparticles chemically grafted with a zwitterionic poly(2-methacryroyloxyethylphosphorylcholine) (PMPC) thin layers. The synthesis method is based on the surface-mediated seeded polymerization. In order to observe how the polymer chain architectures affect colloidal interactions, the zinc oxide nanoparticles are grafted with linear brushes and with a thin hydrogel layer, respectively. The thickness of PMPC shell layers spans a few nanometers. The studies on suspension rheology for the nanoparticles show that the nanoparticles with PMPC brushes show the stronger repulsive force than those with the PMPC gel shell due to the entropic stabilization. When the shear force is applied to the Pickering emulsion produced by assembly of the nanoparticles, it is noticeable that the presence of PMPC brushes on the particles rather enhances the drop-to-drop attraction, which presumably stems from the entanglement of polymer chains between the contacted interfacial planes of the emulsion droplets during shearing.

  15. Thioredoxin-Interacting Protein Mediates NLRP3 Inflammasome Activation Involved in the Susceptibility to Ischemic Acute Kidney Injury in Diabetes

    Directory of Open Access Journals (Sweden)

    Ye Da Xiao

    2016-01-01

    Full Text Available Kidney in diabetic state is more sensitive to ischemic acute kidney injury (AKI. However, the underlying mechanisms remain unclear. Herein, we examined the impact of diabetes mellitus on thioredoxin-interacting protein (TXNIP expression and whether mediated NLRP3 activation was associated with renal ischemia/reperfusion- (I/R- induced AKI. In an in vivo model, streptozotocin-induced diabetic rats showed higher susceptibility to I/R injury with increased TXNIP expression, which was significantly attenuated by resveratrol (RES treatment (10 mg/kg intraperitoneal daily injection for 7 consecutive days prior to I/R induction. RES treatment significantly inhibited TXNIP binding to NLRP3 in diabetic rats subjected to renal I/R injury. Furthermore, RES treatment significantly reduced cleaved caspase-1 expression and production of IL-1β and IL-18. In an in vitro study using cultured human kidney proximal tubular cell (HK-2 cells in high glucose condition (HG, 30 mM subjected to hypoxia/reoxygenation (H/R, HG combined H/R (HH/R stimulated TXNIP expression which was accompanied by increased NLRP3 expression, ROS generation, caspase-1 activity and IL-1β levels, and aggravated HK-2 cells apoptosis. All these changes were significantly attenuated by TXNIP RNAi and RES treatment. In conclusion, our results demonstrate that TXNIP-mediated NLRP3 activation through oxidative stress is a key signaling mechanism in the susceptibility to AKI in diabetic models.

  16. Interaction between misfolded PrP and the ubiquitin-proteasome system in prion-mediated neurodegeneration.

    Science.gov (United States)

    Lin, Zhu; Zhao, Deming; Yang, Lifeng

    2013-06-01

    Prion diseases are associated with the conformational conversion of cellular prion protein (PrP(C)) to pathological β-sheet isoforms (PrP(Sc)), which is the infectious agent beyond comprehension. Increasing evidence indicated that an unknown toxic gain of function of PrP(sc) underlies neuronal death. Conversely, strong evidence indicated that cellular prion protein might be directly cytotoxic by mediating neurotoxic signaling of β-sheet-rich conformers independent of prion replication. Furthermore, the common properties of β-sheet-rich isoform such as PrP(Sc) and β amyloid protein become the lynchpin that interprets the general pathological mechanism of protein misfolding diseases. Dysfunction of the ubiquitin-proteasome system (UPS) has been implicated in various protein misfolding diseases. However, the mechanisms of this impairment remain unknown in many cases. In prion disease, prion-infected mouse brains have increased levels of ubiquitin conjugates, which correlate with decreased proteasome function. Both PrP(C) and PrP(Sc) accumulate in cells after proteasome inhibition, which leads to increased cell death. A direct interaction between 20S core particle and PrP isoforms was demonstrated. Here we review the ability of misfolded PrP and UPS to affect each other, which might contribute to the pathological features of prion-mediated neurodegeneration.

  17. Genetic interaction of two abscisic acid signaling regulators, HY5 and FIERY1, in mediating lateral root formation

    KAUST Repository

    Chen, Hao

    2011-01-01

    Root architecture is continuously shaped in a manner that helps plants to better adapt to the environment. Gene regulation at the transcriptional or post-transcriptional levels largely controls this environmental response. Recently, RNA silencing has emerged as an important player in gene regulation and is involved in many aspects of plant development, including lateral root formation. In a recent study, we found that FIERY1, a bifunctional abiotic stress and abscisic acid (ABA) signaling regulator and an endogenous RNA silencing suppressor, mediates auxin response during lateral root formation in Arabidopsis. We proposed that FRY1 regulates lateral root development through its activity on adenosine 3,5-bisphosphate (PAP), a strong inhibitor of exoribonucleases (XRNs). Interestingly, some of the phenotypes of fry1, such as enhanced response to light in repressing hypocotyl elongation and hypersensitivity to ABA in lateral root growth, are opposite to those of another light- and ABA-signaling mutant, hy5. Here we analyzed the hy5 fry1 double mutant for root and hypocotyl growth. We found that the hy5 mutation can suppress the enhanced light sensitivity in fry1 hypocotyl elongation and restore the lateral root formation. The genetic interaction between HY5 and FRY1 indicates that HY5 and FRY1 may act in overlapping pathways that mediate light signaling and lateral root development. © 2011 Landes Bioscience.

  18. A critical role of CXCR2 PDZ-mediated interactions in endothelial progenitor cell homing and angiogenesis

    Directory of Open Access Journals (Sweden)

    Yuning Hou

    2015-03-01

    Full Text Available Bone marrow-derived endothelial progenitor cells (EPCs contribute to neovessel formation in response to growth factors, cytokines, and chemokines. Chemokine receptor CXCR2 and its cognate ligands are reported to mediate EPC recruitment and angiogenesis. CXCR2 possesses a consensus PSD-95/DlgA/ZO-1 (PDZ motif which has been reported to modulate cellular signaling and functions. Here we examined the potential role of the PDZ motif in CXCR2-mediated EPC motility and angiogenesis. We observed that exogenous CXCR2 C-tail significantly inhibited in vitro EPC migratory responses and angiogenic activities, as well as in vivo EPC angiogenesis. However, the CXCR2 C-tail that lacks the PDZ motif (ΔTTL did not cause any significant changes of these functions in EPCs. In addition, using biochemical assays, we demonstrated that the PDZ scaffold protein NHERF1 specifically interacted with CXCR2 and its downstream effector, PLC-β3, in EPCs. This suggests that NHERF1 might cluster CXCR2 and its relevant signaling molecules into a macromolecular signaling complex modulating EPC cellular functions. Taken together, our data revealed a critical role of a PDZ-based CXCR2 macromolecular complex in EPC homing and angiogenesis, suggesting that targeting this complex might be a novel and effective strategy to treat angiogenesis-dependent diseases.

  19. Sirt1 physically interacts with Tip60 and negatively regulates Tip60-mediated acetylation of H2AX

    Energy Technology Data Exchange (ETDEWEB)

    Yamagata, Kazutsune, E-mail: kyamagat@ncc.go.jp [Department of Molecular Oncology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Kitabayashi, Issay [Department of Molecular Oncology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

    2009-12-25

    Sirt1 appear to be NAD(+)-dependent deacetylase that deacetylates histones and several non-histone proteins. In this study, we identified Sirt1 as a physical interaction partner of Tip60, which is a mammalian MYST-type histone acetyl-transferase that specifically acetylates histones H2A and H4. Although Tip60 also acetylates DNA damage-specific histone H2A variant H2AX in response to DNA damage, which is a process required for appropriate DNA damage response, overexpression of Sirt1 represses Tip60-mediated acetylation of H2AX. Furthermore, Sirt1 depletion by RNAi causes excessive acetylation of H2AX, and enhances accumulation of {gamma}-ray irradiation-induced MDC1, BRCA1, and Rad51 foci in nuclei. These findings suggest that Sirt1 functions as negative regulator of Tip60-mediated acetylation of H2AX. Moreover, Sirt1 deacetylates an acetylated Tip60 in response to DNA damage and stimulates proteasome-dependent Tip60 degradation in vivo, suggesting that Sirt1 negatively regulates the protein level of Tip60 in vivo. Sirt1 may thus repress excessive activation of the DNA damage response and Rad51-homologous recombination repair by suppressing the function of Tip60.

  20. Interaction between misfolded PrP and the ubiquitin-proteasome system in prion-mediated neurodegeneration

    Institute of Scientific and Technical Information of China (English)

    Zhu Lin; Deming Zhao; Lifeng Yang

    2013-01-01

    Prion diseases are associated with the conformational conversion of cellular prion protein (PrPC) to pathological β-sheet isoforms (PrpSc),which is the infectious agent beyond comprehension.Increasing evidence indicated that an unknown toxic gain of function of PrPSc underlies neuronal death.Conversely,strong evidence indicated that cellular prion protein might be directly cytotoxic by mediating neurotoxic signaling of β-sheet-rich conformers independent of prion replication.Furthermore,the common properties of β-sheet-rich isoform such as PrPSc and β amyloid protein become the lynchpin that interprets the general pathological mechanism of protein misfolding diseases.Dysfunction of the ubiquitin-proteasome system (UPS) has been implicated in various protein misfolding diseases.However,the mechanisms of this impairment remain unknown in many cases.In prion disease,prioninfected mouse brains have increased levels of ubiquitin conjugates,which correlate with decreased proteasome function.Both PrPC and PrPsc accumulate in cells after proteasome inhibition,which leads to increased cell death.A direct interaction between 20S core particle and PrP isoforms was demonstrated.Here we review the ability of misfolded PrP and UPS to affect each other,which might contribute to the pathological features of prion-mediated neurodegeneration.

  1. Inositol hexakisphosphate (IP6) generated by IP5K mediates cullin-COP9 signalosome interactions and CRL function.

    Science.gov (United States)

    Scherer, Paul C; Ding, Yan; Liu, Zhiqing; Xu, Jing; Mao, Haibin; Barrow, James C; Wei, Ning; Zheng, Ning; Snyder, Solomon H; Rao, Feng

    2016-03-29

    The family of cullin-RING E3 Ligases (CRLs) and the constitutive photomorphogenesis 9 (COP9) signalosome (CSN) form dynamic complexes that mediate ubiquitylation of 20% of the proteome, yet regulation of their assembly/disassembly remains poorly understood. Inositol polyphosphates are highly conserved signaling molecules implicated in diverse cellular processes. We now report that inositol hexakisphosphate (IP6) is a major physiologic determinant of the CRL-CSN interface, which includes a hitherto unidentified electrostatic interaction between the N-terminal acidic tail of CSN subunit 2 (CSN2) and a conserved basic canyon on cullins. IP6, with an EC50 of 20 nM, acts as an intermolecular "glue," increasing cullin-CSN2 binding affinity by 30-fold, thereby promoting assembly of the inactive CRL-CSN complexes. The IP6 synthase, Ins(1,3,4,5,6)P5 2-kinase (IPPK/IP5K) binds to cullins. Depleting IP5K increases the percentage of neddylated, active Cul1 and Cul4A, and decreases levels of the Cul1/4A substrates p27 and p21. Besides dysregulating CRL-mediated cell proliferation and UV-induced apoptosis, IP5K depletion potentiates by 28-fold the cytotoxic effect of the neddylation inhibitor MLN4924. Thus, IP5K and IP6 are evolutionarily conserved components of the CRL-CSN system and are potential targets for cancer therapy in conjunction with MLN4924.

  2. Platelets Roll on Stimulated Endothelium in vivo: An Interaction Mediated by Endothelial P-Selectin

    Science.gov (United States)

    Frenette, Paul S.; Johnson, Robert C.; Hynes, Richard O.; Wagner, Denisa D.

    1995-08-01

    P-selectin, found in storage granules of platelets and endothelial cells, can be rapidly expressed upon stimulation. Mice lacking this membrane receptor exhibit a severe impairment of leukocyte rolling. We observed that, in addition to leukocytes, platelets were rolling in mesenteric venules of wild-type mice. To investigate the role of P-selectin in this process, resting or activated platelets from wild-type or P-selectin-deficient mice were fluorescently labeled and transfused into recipients of either genotype. Platelet-endothelial interactions were monitored by intravital microscopy. We observed rolling of either wild-type or P-selectin-deficient resting platelets on wild-type endothelium. Endothelial stimulation with the calcium ionophore A23187 increased the number of platelets rolling 4-fold. Activated P-selectin-deficient platelets behaved similarly, whereas activated wild-type platelets bound to leukocytes and were seen rolling together. Platelets of either genotype, resting or activated, interacted minimally with mutant endothelium even after A23187 treatment. The velocity of platelet rolling was 6- to 9-fold greater than that of leukocytes. Our results demonstrate that (i) platelets roll on endothelium in vivo, (ii) this interaction requires endothelial but not platelet P-selectin, and (iii) platelet rolling appears to be independent of platelet activation, indicating constitutive expression of a P-selectin ligand(s) on platelets. We have therefore observed an interesting parallel between platelets and leukocytes in that both of these blood cell types roll on stimulated vessel wall and that this process is dependent on the expression of endothelial P-selectin.

  3. 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.

  4. Defect mediated magnetic interaction and high Tc ferromagnetism in Co doped ZnO nanoparticles.

    Science.gov (United States)

    Pal, Bappaditya; Giri, P K

    2011-10-01

    Structural, optical and magnetic studies have been carried out for the Co-doped ZnO nanoparticles (NPs). ZnO NPs are doped with 3% and 5% Co using ball milling and ferromagnetism (FM) is studied at room temperature and above. A high Curie temperature (Tc) has been observed from the Co doped ZnO NPs. X-ray diffraction and high resolution transmission electron microscopy analysis confirm the absence of metallic Co clusters or any other phase different from würtzite-type ZnO. UV-visible absorption and photoluminescence studies on the doped samples show change in band structure and oxygen vacancy defects, respectively. Micro-Raman studies of doped samples shows defect related additional strong bands at 547 and 574 cm(-1) confirming the presence of oxygen vacancy defects in ZnO lattice. The field dependence of magnetization (M-H curve) measured at room temperature exhibits the clear M-H loop with saturation magnetization and coercive field of the order of 4-6 emu/g and 260 G, respectively. Temperature dependence of magnetization measurement shows sharp ferromagnetic to paramagnetic transition with a high Tc = 791 K for 3% Co doped ZnO NPs. Ferromagnetic ordering is interpreted in terms of overlapping of polarons mediated through oxygen vacancy defects based on the bound magnetic polaron (BMP) model. We show that the observed FM data fits well with the BMP model involving localised carriers and magnetic cations.

  5. MGluR5 mediates the interaction between late-LTP, network activity, and learning.

    Directory of Open Access Journals (Sweden)

    Arthur Bikbaev

    Full Text Available Hippocampal synaptic plasticity and learning are strongly regulated by metabotropic glutamate receptors (mGluRs and particularly by mGluR5. Here, we investigated the mechanisms underlying mGluR5-modulation of these phenomena. Prolonged pharmacological blockade of mGluR5 with MPEP produced a profound impairment of spatial memory. Effects were associated with 1 a reduction of mGluR1a-expression in the dentate gyrus; 2 impaired dentate gyrus LTP; 3 enhanced CA1-LTP and 4 suppressed theta (5-10 Hz and gamma (30-100 Hz oscillations in the dentate gyrus. Allosteric potentiation of mGluR1 after mGluR5 blockade significantly ameliorated dentate gyrus LTP, as well as suppression of gamma oscillatory activity. CA3-lesioning prevented MPEP effects on CA1-LTP, suggesting that plasticity levels in CA1 are driven by mGluR5-dependent synaptic and network activity in the dentate gyrus. These data support the hypothesis that prolonged mGluR5-inactivation causes altered hippocampal LTP levels and network activity, which is mediated in part by impaired mGluR1-expression in the dentate gyrus. The consequence is impairment of long-term learning.

  6. Ultraslow Water-Mediated Transmembrane Interactions Regulate the Activation of A2A Adenosine Receptor.

    Science.gov (United States)

    Lee, Yoonji; Kim, Songmi; Choi, Sun; Hyeon, Changbong

    2016-09-20

    Water molecules inside a G-protein coupled receptor (GPCR) have recently been spotlighted in a series of crystal structures. To decipher the dynamics and functional roles of internal water molecules in GPCR activity, we studied the A2A adenosine receptor using microsecond molecular-dynamics simulations. Our study finds that the amount of water flux across the transmembrane (TM) domain varies depending on the receptor state, and that the water molecules of the TM channel in the active state flow three times more slowly than those in the inactive state. Depending on the location in solvent-protein interface as well as the receptor state, the average residence time of water in each residue varies from ∼O(10(2)) ps to ∼O(10(2)) ns. Especially, water molecules, exhibiting ultraslow relaxation (∼O(10(2)) ns) in the active state, are found around the microswitch residues that are considered activity hotspots for GPCR function. A continuous allosteric network spanning the TM domain, arising from water-mediated contacts, is unique in the active state, underscoring the importance of slow water molecules in the activation of GPCRs. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  7. Plant-microbe rhizosphere interactions mediated by Rehmannia glutinosa root exudates under consecutive monoculture

    Science.gov (United States)

    Wu, Linkun; Wang, Juanying; Huang, Weimin; Wu, Hongmiao; Chen, Jun; Yang, Yanqiu; Zhang, Zhongyi; Lin, Wenxiong

    2015-10-01

    Under consecutive monoculture, the biomass and quality of Rehmannia glutinosa declines significantly. Consecutive monoculture of R. glutinosa in a four-year field trial led to significant growth inhibition. Most phenolic acids in root exudates had cumulative effects over time under sterile conditions, but these effects were not observed in the rhizosphere under monoculture conditions. It suggested soil microbes might be involved in the degradation and conversion of phenolic acids from the monocultured plants. T-RFLP and qPCR analysis demonstrated differences in both soil bacterial and fungal communities during monoculture. Prolonged monoculture significantly increased levels of Fusarium oxysporum, but decreased levels of Pseudomonas spp. Abundance of beneficial Pseudomonas spp. with antagonistic activity against F. oxysporum was lower in extended monoculture soils. Phenolic acid mixture at a ratio similar to that found in the rhizosphere could promote mycelial growth, sporulation, and toxin (3-Acetyldeoxynivalenol, 15-O-Acetyl-4-deoxynivalenol) production of pathogenic F. oxysporum while inhibiting growth of the beneficial Pseudomonas sp. W12. This study demonstrates that extended monoculture can alter the microbial community of the rhizosphere, leading to relatively fewer beneficial microorganisms and relatively more pathogenic and toxin-producing microorganisms, which is mediated by the root exudates.

  8. Psychotherapeutic discourse in problematizing transnational identities in computer-mediated interaction:

    DEFF Research Database (Denmark)

    Klausen, Julia Zhukova

    2017-01-01

    )identification and subjectivation with the concerns and methods of socio-semiotics and interactional linguistics in order to reveal how the actors both mobilize the expert authority of psy discourse and practices and render themselves the freedom to not accept a particular type of relationship with the transnational selves which...... this authority offers. Through this examination, I take a critical stance towards the technologies of transnational identification that construct transnational living as deviant and inherently unsound. At the same time, I highlight the discursive acts of resistance to problematizing transnational belonging...

  9. Smad4-Shh-Nfic signaling cascade-mediated epithelial-mesenchymal interaction is crucial in regulating tooth root development.

    Science.gov (United States)

    Huang, Xiaofeng; Xu, Xun; Bringas, Pablo; Hung, Yee Ping; Chai, Yang

    2010-05-01

    Transforming growth factor beta (TGF-beta)/bone morphogenetic protein (BMP) signaling is crucial for regulating epithelial-mesenchymal interaction during organogenesis, and the canonical Smad pathway-mediated TGF-beta/BMP signaling plays important roles during development and disease. During tooth development, dental epithelial cells, known as Hertwig's epithelial root sheath (HERS), participate in root formation following crown development. However, the functional significance of HERS in regulating root development remains unknown. In this study we investigated the signaling mechanism of Smad4, the common Smad for TGF-beta/BMP signaling, in HERS in regulating root development. Tissue-specific inactivation of Smad4 in HERS results in abnormal enamel and dentin formation in K14-Cre;Smad4(fl/fl) mice. HERS enlarges but cannot elongate to guide root development without Smad4. At the molecular level, Smad4-mediated TGF-beta/BMP signaling is required for Shh expression in HERS and Nfic (nuclear factor Ic) expression in the cranial neural crest (CNC)-derived dental mesenchyme. Nfic is crucial for root development, and loss of Nfic results in a CNC-derived dentin defect similar to the one of K14-Cre;Smad4(fl/fl) mice. Significantly, we show that ectopic Shh induces Nfic expression in dental mesenchyme and partially rescues root development in K14-Cre;Smad4(fl/fl) mice. Taken together, our study has revealed an important signaling mechanism in which TGF-beta/BMP signaling relies on a Smad-dependent mechanism in regulating Nfic expression via Shh signaling to control root development. The interaction between HERS and the CNC-derived dental mesenchyme may guide the size, shape, and number of tooth roots.

  10. Long-Range Chromosome Interactions Mediated by Cohesin Shape Circadian Gene Expression.

    Directory of Open Access Journals (Sweden)

    Yichi Xu

    2016-05-01

    Full Text Available Mammalian circadian rhythm is established by the negative feedback loops consisting of a set of clock genes, which lead to the circadian expression of thousands of downstream genes in vivo. As genome-wide transcription is organized under the high-order chromosome structure, it is largely uncharted how circadian gene expression is influenced by chromosome architecture. We focus on the function of chromatin structure proteins cohesin as well as CTCF (CCCTC-binding factor in circadian rhythm. Using circular chromosome conformation capture sequencing, we systematically examined the interacting loci of a Bmal1-bound super-enhancer upstream of a clock gene Nr1d1 in mouse liver. These interactions are largely stable in the circadian cycle and cohesin binding sites are enriched in the interactome. Global analysis showed that cohesin-CTCF co-binding sites tend to insulate the phases of circadian oscillating genes while cohesin-non-CTCF sites are associated with high circadian rhythmicity of transcription. A model integrating the effects of cohesin and CTCF markedly improved the mechanistic understanding of circadian gene expression. Further experiments in cohesin knockout cells demonstrated that cohesin is required at least in part for driving the circadian gene expression by facilitating the enhancer-promoter looping. This study provided a novel insight into the relationship between circadian transcriptome and the high-order chromosome structure.

  11. Thermal expression of intersubjectivity offers new possibilities to human-machine and technologically mediated interactions

    Directory of Open Access Journals (Sweden)

    Arcangelo eMerla

    2014-07-01

    Full Text Available The evaluation of the psychophysiological state of the interlocutor is an important element of interpersonal relationships and communication. Thermal infrared imaging has proved to be a reliable tool for non-invasive and contact-less evaluation of vital signs, psychophysiological responses and emotional states. This technique is quickly spreading in many fields, from psychometrics to social and developmental psychology; and from the touch-less monitoring of vital signs and stress, up to the human-machine interaction. In particular, thermal IR imaging promises to be of use for gathering information about affective states in social situations. This paper presents the state of the art of thermal infrared imaging in psychophysiology and in the assessment of affective states. The goal is to provide insights about its potentialities and limits for its use in human-artificial agent interaction in order to contribute to a major issue in the field: the perception by an artificial agent of human psychophysiological and affective states.

  12. Protein phosphatase 2A subunit PR70 interacts with pRb and mediates its dephosphorylation.

    Science.gov (United States)

    Magenta, Alessandra; Fasanaro, Pasquale; Romani, Sveva; Di Stefano, Valeria; Capogrossi, Maurizio C; Martelli, Fabio

    2008-01-01

    The retinoblastoma tumor suppressor protein (pRb) regulates cell proliferation and differentiation via phosphorylation-sensitive interactions with specific targets. While the role of cyclin/cyclin-dependent kinase complexes in the modulation of pRb phosphorylation has been extensively studied, relatively little is known about the molecular mechanisms regulating phosphate removal by phosphatases. Protein phosphatase 2A (PP2A) is constituted by a core dimer bearing catalytic activity and one variable B regulatory subunit conferring target specificity and subcellular localization. We previously demonstrated that PP2A core dimer binds pRb and dephosphorylates pRb upon oxidative stress. In the present study, we identified a specific PP2A-B subunit, PR70, that was associated with pRb both in vitro and in vivo. PR70 overexpression caused pRb dephosphorylation; conversely, PR70 knockdown prevented both pRb dephosphorylation and DNA synthesis inhibition induced by oxidative stress. Moreover, we found that intracellular Ca(2+) mobilization was necessary and sufficient to trigger pRb dephosphorylation and PP2A phosphatase activity of PR70 was Ca(2+) induced. These data underline the importance of PR70-Ca(2+) interaction in the signal transduction mechanisms triggered by redox imbalance and leading to pRb dephosphorylation.

  13. Crabs mediate interactions between native and invasive salt marsh plants: a mesocosm study.

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Zhang

    Full Text Available Soil disturbance has been widely recognized as an important factor influencing the structure and dynamics of plant communities. Although soil reworkers were shown to increase habitat complexity and raise the risk of plant invasion, their role in regulating the interactions between native and invasive species remains unclear. We proposed that crab activities, via improving soil nitrogen availability, may indirectly affect the interactions between invasive Spartina alterniflora and native Phragmites australis and Scirpus mariqueter in salt marsh ecosystems. We conducted a two-year mesocosm experiment consisting of five species combinations, i.e., monocultures of three species and pair-wise mixtures of invasive and native species, with crabs being either present or absent for each combination. We found that crabs could mitigate soil nitrogen depletion in the mesocosm over the two years. Plant performance of all species, at both the ramet-level (height and biomass per ramet and plot-level (density, total above- and belowground biomass, were promoted by crab activities. These plants responded to crab disturbance primarily by clonal propagation, as plot-level performance was more sensitive to crabs than ramet-level. Moreover, crab activities altered the competition between Spartina and native plants in favor of the former, since Spartina was more promoted than native plants by crab activities. Our results suggested that crab activities may increase the competition ability of Spartina over native Phragmites and Scirpus through alleviating soil nitrogen limitation.

  14. Pellino Proteins Contain a Cryptic FHA Domain that Mediates Interaction with Phosphorylated IRAK1

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chun-Chi; Huoh, Yu-San; Schmitz, Karl R.; Jensen, Liselotte E.; Ferguson, Kathryn M. (UPENN-MED)

    2009-03-23

    Pellino proteins are RING E3 ubiquitin ligases involved in signaling events downstream of the Toll and interleukin-1 (IL-1) receptors, key initiators of innate immune and inflammatory responses. Pellino proteins associate with and ubiquitinate proteins in these pathways, including the interleukin-1 receptor associated kinase-1 (IRAK1). We determined the X-ray crystal structure of a Pellino2 fragment lacking only the RING domain. This structure reveals that the IRAK1-binding region of Pellino proteins consists largely of a previously unidentified forkhead-associated (FHA) domain. FHA domains are well-characterized phosphothreonine-binding modules, and this cryptic example in Pellino2 can drive interaction of this protein with phosphorylated IRAK1. The Pellino FHA domain is decorated with an unusual appendage or wing composed of two long inserts that lie within the FHA homology region. Delineating how this E3 ligase associates with substrates, and how these interactions are regulated by phosphorylation, is crucial for a complete understanding of Toll/IL-1 receptor signaling.

  15. Chemical signals might mediate interactions between females and juveniles of Latrodectus geometricus (Araneae: Theridiidae).

    Science.gov (United States)

    Guimarães, Ingrid de Carvalho; Cardoso, Claudia Andrea Lima; Lima, Sandro Marcio; Andrade, Luis Humberto da Cunha; Antonialli Junior, William Fernnando

    2016-05-01

    Studies related to communication on spiders show that, as in other invertebrates, the interactions between conspecifics are also made through chemical signals. Therefore, in order to assess whether the composition of cuticular compounds might be involved in interactions that occur during the days after the emergence of juveniles in Latrodectus geometricus, we conducted behavioral and cuticular chemical profiles analysis of females and juveniles of different ages. The results show that females, regardless of their reproductive state, tolerate juveniles of other females with up to 40 days post-emergence and attack juveniles of 80 days post-emergence. Cuticlar chemical analysis shows that while the profile of juveniles is similar to adult's profile, they can remain in the web without being confused with threat or prey. Also, cuticular chemical profiles vary between different populations probably due to genetic and environmental differences or similarities between them. Finally, females in incubation period are able to detect the presence of eggs within any egg sac, but cannot distinguish egg sacs produced by conspecifics from the ones they had produced.

  16. Trichomonas vaginalis and Tritrichomonas foetus: interaction with fibroblasts and muscle cells - new insights into parasite-mediated host cell cytotoxicity

    Directory of Open Access Journals (Sweden)

    Ricardo Chaves Vilela

    2012-09-01

    Full Text Available Trichomonas vaginalis and Tritrichomonas foetus are parasitic, flagellated protists that inhabit the urogenital tract of humans and bovines, respectively. T. vaginalis causes the most prevalent non-viral sexually transmitted disease worldwide and has been associated with an increased risk for human immunodeficiency virus-1 infection in humans. Infections by T. foetus cause significant losses to the beef industry worldwide due to infertility and spontaneous abortion in cows. Several studies have shown a close association between trichomonads and the epithelium of the urogenital tract. However, little is known concerning the interaction of trichomonads with cells from deeper tissues, such as fibroblasts and muscle cells. Published parasite-host cell interaction studies have reported contradictory results regarding the ability of T. foetus and T. vaginalis to interact with and damage cells of different tissues. In this study, parasite-host cell interactions were examined by culturing primary human fibroblasts obtained from abdominal biopsies performed during plastic surgeries with trichomonads. In addition, mouse 3T3 fibroblasts, primary chick embryo myogenic cells and L6 muscle cells were also used as models of target cells. The parasite-host cell cultures were processed for scanning and transmission electron microscopy and were tested for cell viability and cell death. JC-1 staining, which measures mitochondrial membrane potential, was used to determine whether the parasites induced target cell damage. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling staining was used as an indicator of chromatin damage. The colorimetric crystal violet assay was performed to ana-lyse the cytotoxicity induced by the parasite. The results showed that T. foetus and T. vaginalis adhered to and were cytotoxic to both fibroblasts and muscle cells, indicating that trichomonas infection of the connective and muscle tissues is likely to occur; such

  17. Superspin glass state in a diluted nanoparticle system stabilized by interparticle interactions mediated by an antiferromagnetic matrix

    Science.gov (United States)

    Margaris, G.; Vasilakaki, M.; Peddis, D.; Trohidou, K. N.; Laureti, S.; Binns, C.; Agostinelli, E.; Rinaldi, D.; Mathieu, R.; Fiorani, D.

    2017-01-01

    In nanoparticle systems consisting of two magnetic materials (bi-magnetic nanoparticles or nanoparticles embedded in a magnetic matrix), there is a constantly growing interest in the investigation of the interplay between interparticle interactions and the nanoparticle-matrix interface exchange coupling, because of its enormous impact on a number of technological applications. The understanding of the mechanisms of such interplay is a great challenge, as it would allow controlling equilibrium and non-equilibrium magnetization dynamics of exchange coupled nanoparticles systems and finely tuning their anisotropy. Here, we provide evidence that this interplay leads to a collective superspin glass (SSG) behavior in a system of diluted ferromagnetic (FM) nanoparticles embedded in an antiferromagnetic (AFM) matrix (5% volume fraction of Co particles in Mn film matrix). We have developed a novel mesoscopic model to study the influence of interparticle interaction on the exchange bias (EB) and the dynamical behavior of assemblies of FM nanoparticles embedded in a granular AFM matrix. Our mesoscopic model is based on reducing the amount of simulated spins to the minimum number necessary to describe the magnetic structure of the system and introducing the adequate exchange parameters between the different spins. The model replicates remarkably well the observed static and dynamical SSG properties as well as the EB behavior. In addition, the proposed model well explains the role of the significant Co/Mn alloying and of the granularity of the matrix in mediating interparticle interactions through exchange and dipole-dipole coupling between the uncompensated moments of its grains and the exchange interaction at the Co/Mn interface.

  18. Plasmid-mediated quinolone resistance; interactions between human, animal and environmental ecologies

    Directory of Open Access Journals (Sweden)

    Laurent ePOIREL

    2012-02-01

    Full Text Available Resistance to quinolones and fluoroquinolones is being increasingly reported among human but also veterinary isolates during the last two to three decades, very likely as a consequence of the large clinical usage of those antibiotics. Even if the principle mechanisms of resistance to quinolones are chromosome-encoded, due to modifications of molecular targets (DNA gyrase and topoisomerase IV, decreased outer-membrane permeability (porin defect and overexpression of naturally-occurring efflux, the emergence of plasmid-mediated quinolone resistance (PMQR has been reported since 1998. Although these PMQR determinants confer low-level resistance to quinolones and/or fluoroquinolones, they are a favorable background for selection of additional chromosome-encoded quinolone resistance mechanisms. Different transferable mechanisms have been identified, corresponding to the production of Qnr proteins, of the aminoglycoside acetyltransferase AAC(6’-Ib-cr, or of the QepA-type or OqxAB-type efflux pumps. Qnr proteins protect target enzymes (DNA gyrase and type IV topoisomerase from quinolone inhibition (mostly nalidixic acid. The AAC(6’-Ib-cr determinant acetylates several fluoroquinolones, such as norfloxacin and ciprofloxacin. Finally, the QepA and OqxAB efflux pumps extrude fluoroquinolones from the bacterial cell. A series of studies have identified the environment to be a reservoir of PMQR genes, with farm animals and aquatic habitats being significantly involved. In addition, the origin of the qnr genes has been identified, corresponding to the waterborne species Shewanella sp. Altogether, the recent observations suggest that the aquatic environment might constitute the original source of PMQR genes, that would secondly spread among animal or human isolates.

  19. Role of 5'TG3'-interacting factors (TGIFs) in Vorinostat (HDAC inhibitor)-mediated Corneal Fibrosis Inhibition.

    Science.gov (United States)

    Sharma, Ajay; Sinha, Nishant R; Siddiqui, Saad; Mohan, Rajiv R

    2015-01-01

    We have previously reported that vorinostat, an FDA-approved, clinically used histone deacetylase (HDAC) inhibitor, attenuates corneal fibrosis in vivo in rabbits by blocking transforming growth factor β (TGFβ). The 5'TG3'-interacting factors (TGIFs) are transcriptional repressors of TGFβ1 signaling via the Smad pathway. The present study was designed to explore the expression of TGIFs in human corneal fibroblasts and to investigate their role in mediating the antifibrotic effect of vorinostat. Human corneal fibroblast cultures were generated from donor corneas. RNA isolation, cDNA preparation, and PCR were performed to detect the presence of TGIF1 and TGIF2 transcripts. The cultures were exposed to vorinostat (2.5 µM) to test its effect on TGIF mRNA and protein levels using qPCR and immunoblotting. Myofibroblast formation was induced with TGFβ1 (5 ng/ml) treatment under serum-free conditions. The changes in fibrosis parameters were quantified by measuring fibrosis marker α-smooth muscle actin (αSMA) mRNA and protein levels with qPCR, immunostaining, and immunoblotting. Smad2/3/4 and TGIF knockdowns were performed using pre-validated RNAi/siRNAs and a commercially available transfection reagent. Human corneal fibroblasts showed the expression of TGIF1 and TGIF2. Vorinostat (2.5 µM) caused a 2.8-3.3-fold increase in TGIF1 and TGIF2 mRNA levels and a 1.4-1.8-fold increase in TGIF1 and TGIF2 protein levels. Vorinostat treatment also caused a significant increase in acetylhistone H3 and acetylhistone H4. Vorinostat-induced increases in TGIF1 and TGIF2 were accompanied by a concurrent decrease in corneal fibrosis, as indicated by a decrease in αSMA mRNA by 83±7.7% and protein levels by 97±5%. The RNAi-mediated knockdown of Smad2, Smad3, and Smad4 markedly attenuated TGFβ1-evoked transdifferentiation of fibroblasts to myofibroblasts. The siRNA-mediated knockdown of TGIF1 and TGIF2 neutralized vorinostat-evoked decreases in αSMA mRNA by 31%-45% and protein

  20. 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.

  1. Adsorbate-mediated strong metal-support interactions in oxide-supported Rh catalysts.

    Science.gov (United States)

    Matsubu, John C; Zhang, Shuyi; DeRita, Leo; Marinkovic, Nebojsa S; Chen, Jingguang G; Graham, George W; Pan, Xiaoqing; Christopher, Phillip

    2017-02-01

    The optimization of supported metal catalysts predominantly focuses on engineering the metal site, for which physical insights based on extensive theoretical and experimental contributions have enabled the rational design of active sites. Although it is well known that supports can influence the catalytic properties of metals, insights into how metal-support interactions can be exploited to optimize metal active-site properties are lacking. Here we utilize in situ spectroscopy and microscopy to identify and characterize a support effect in oxide-supported heterogeneous Rh catalysts. This effect is characterized by strongly bound adsorbates (HCOx) on reducible oxide supports (TiO2 and Nb2O5) that induce oxygen-vacancy formation in the support and cause HCOx-functionalized encapsulation of Rh nanoparticles by the support. The encapsulation layer is permeable to reactants, stable under the reaction conditions and strongly influences the catalytic properties of Rh, which enables rational and dynamic tuning of CO2-reduction selectivity.

  2. Dark matter with pseudoscalar-mediated interactions explains the DAMA signal and the galactic center excess.

    Science.gov (United States)

    Arina, Chiara; Del Nobile, Eugenio; Panci, Paolo

    2015-01-01

    We study a Dirac dark matter particle interacting with ordinary matter via the exchange of a light pseudoscalar, and analyze its impact on both direct and indirect detection experiments. We show that this candidate can accommodate the long-standing DAMA modulated signal and yet be compatible with all exclusion limits at 99(S)% C.L. This result holds for natural choices of the pseudoscalar-quark couplings (e.g., flavor universal), which give rise to a significant enhancement of the dark matter-proton coupling with respect to the coupling to neutrons. We also find that this candidate can accommodate the observed 1-3 GeV gamma-ray excess at the Galactic center and at the same time have the correct relic density today. The model could be tested with measurements of rare meson decays, flavor changing processes, and searches for axionlike particles with mass in the MeV range.

  3. Interaction between thyrotropin-releasing hormone (TRH) and NMDA-receptor-mediated responses in hypoglossal motoneurones

    DEFF Research Database (Denmark)

    Rekling, J C

    1992-01-01

    -50 microM TRH markedly potentiated the response to iontophoretically applied NMDA, whereas no potentiation of the response to glutamate, aspartate or quisqualic acid was seen. Voltage clamp experiments showed that TRH did not increase the current flowing through NMDA channels, thus a direct modulatory role......The effect of thyrotropin-releasing hormone (TRH) on the responses to excitatory amino acids was investigated in hypoglossal motoneurones in an in vitro preparation of the brainstem from guinea pigs using current clamp and discontinuous single electrode voltage clamp (dSEVC). Bath application of 20...... of TRH on NMDA channels was not a likely explanation of the potentiation. Voltage clamp studies of the current-voltage relationship showed that the potentiation of the response to NMDA and lack of potentiation of the response to quisqualic acid was a result of an interaction between the actions of TRH...

  4. Near field magnetostatics and Neel Brownian interactions mediated magnetorheological characteristics of highly stable nano ferrocolloids

    CERN Document Server

    Katiyar, Ajay; Das, Sarit K; Nandi, Tandra

    2015-01-01

    Magnetic nanocolloids with synthesized super paramagnetic Fe3O4 nanoparticles (SPION) (5 to 15 nm) dispersed in insitu developed Polyethylene Glycol (PEG 400) and nano silica complex have been synthesized. The PEG nano Silica complex physically encapsulates the SPIONs, ensuring no phase separation under high magnetic fields (1.2 T). Exhaustive magnetorheological investigations have been performed to comprehend the structural behavior and response of the ferrocolloids. Remarkable stability and reversibility have been observed under magnetic field for concentrated systems. The results exhibit the impact of particle concentration, size and encapsulation efficiency on parameters such as shear viscosity, yield stress, viscoelastic moduli, magnetoviscous hysteresis etc. Analytical models to reveal the system mechanism and mathematically predict the magnetoviscosity and magneto yield stress has been theorized. The mechanistic approach based on near field magnetostatics and Neel Brownian interactivities can predict t...

  5. Neuron-glia interactions through the Heartless FGF receptor signaling pathway mediate morphogenesis of Drosophila astrocytes.

    Science.gov (United States)

    Stork, Tobias; Sheehan, Amy; Tasdemir-Yilmaz, Ozge E; Freeman, Marc R

    2014-07-16

    Astrocytes are critically important for neuronal circuit assembly and function. Mammalian protoplasmic astrocytes develop a dense ramified meshwork of cellular processes to form intimate contacts with neuronal cell bodies, neurites, and synapses. This close neuron-glia morphological relationship is essential for astrocyte function, but it remains unclear how astrocytes establish their intricate morphology, organize spatial domains, and associate with neurons and synapses in vivo. Here we characterize a Drosophila glial subtype that shows striking morphological and functional similarities to mammalian astrocytes. We demonstrate that the Fibroblast growth factor (FGF) receptor Heartless autonomously controls astrocyte membrane growth, and the FGFs Pyramus and Thisbe direct astrocyte processes to ramify specifically in CNS synaptic regions. We further show that the shape and size of individual astrocytes are dynamically sculpted through inhibitory or competitive astrocyte-astrocyte interactions and Heartless FGF signaling. Our data identify FGF signaling through Heartless as a key regulator of astrocyte morphological elaboration in vivo.

  6. Integrin-Mediated Cell-Matrix Interaction in Physiological and Pathological Blood Vessel Formation

    Directory of Open Access Journals (Sweden)

    Stephan Niland

    2012-01-01

    Full Text Available Physiological as well as pathological blood vessel formation are fundamentally dependent on cell-matrix interaction. Integrins, a family of major cell adhesion receptors, play a pivotal role in development, maintenance, and remodeling of the vasculature. Cell migration, invasion, and remodeling of the extracellular matrix (ECM are integrin-regulated processes, and the expression of certain integrins also correlates with tumor progression. Recent advances in the understanding of how integrins are involved in the regulation of blood vessel formation and remodeling during tumor progression are highlighted. The increasing knowledge of integrin function at the molecular level, together with the growing repertoire of integrin inhibitors which allow their selective pharmacological manipulation, makes integrins suited as potential diagnostic markers and therapeutic targets.

  7. The Trichoderma-plant interaction is mediated by avirulence proteins produced by this fungus

    Institute of Scientific and Technical Information of China (English)

    Ruocco M; Kip N; P J G M de Wit; Lorito M; Lanzuise S; Woo S L; Ambrosino P; Marra R; Turrà D; Gigante S; Formisno E; Scala F

    2004-01-01

    @@ The molecular basis of Trichoderma -plant interaction is very complex and still not completely understood. The colonization of the root system by rhizosphere competent strains of Trichoderma results in increased development of root/aerial systems, in improved yields and in plant disease control.Other beneficial effects, such as the induction of plant systemic resistance, have also been described.To understand the mechanisms involved we are using different approaches, including the making of transformants expressing genes that encode for compounds able to affect plant response to pathogens.Trichoderma transformants carrying the avirulence gene Avr4 from Cladosporium fulvum under the control of constitutive and inducible promoters were obtained and tested on tomato plants having the Cf4 resistance gene. Necrosis and suberification zones, similar to the symptoms appearing during Cladosporium-tomato interaction, were found when the roots of the Cf4 plants were treated with Avr4-Trichoderma. This demonstrates that selected Trichoderma strains are able to transfer to the plant molecules that may deeply affect metabolism, disease resistance etc. Therefore, these beneficial fungi can be regarded as biotechnological tools to provide a variety of crops with useful compounds.Moreover, in in vitro competition assays the transformants were found to be more effective as antagonists against Alternaria alternata than the wild type. Trichoderma sends a variety of biochemical signals to the plants including avirulence molecules; therefore the presence of avr-like proteins in the fungus proteome was investigated. Proteome analysis has permitted us to isolate and sequence many proteins potentially having this function. From the extraeellular protein extracts, we have purified and sequenced a protein with structural characteristics similar to Avr4 of C. fulvum.The protein, Hytra1, was found to be a hydrophobin with chitin binding activity, the typical 8cysteine residues, and 4

  8. Direct and interaction-mediated effects of environmental changes on peatland bryophytes.

    Science.gov (United States)

    Bu, Zhao-Jun; Rydin, Håkan; Chen, Xu

    2011-06-01

    Ecosystem processes of northern peatlands are largely governed by the vitality and species composition in the bryophyte layer, and may be affected by global warming and eutrophication. In a factorial experiment in northeast China, we tested the effects of raised levels of nitrogen (0, 1 and 2 g m(-2) year(-1)), phosphorus (0, 0.1 and 0.2 g m(-2) year(-1)) and temperature (ambient and +3°C) on Polytrichum strictum, Sphagnum magellanicum and S. palustre, to see if the effects could be altered by inter-specific interactions. In all species, growth declined with nitrogen addition and increased with phosphorus addition, but only P. strictum responded to raised temperature with increased production of side-shoots (branching). In Sphagnum, growth and branching changed in the same direction, but in Polytrichum, the two responses were uncoupled: with nitrogen addition there was a decrease in growth (smaller than in Sphagnum) but an increase in branching; with phosphorus addition growth increased but branching was unaffected. There were no two-way interactions among the P, N and T treatments. With increasing temperature, our results indicate that S. palustre should decrease relative to P. strictum (Polytrichum increased its branching and had a negative neighbor effect on S. palustre). With a slight increase in phosphorus availability, the increase in length growth and production of side-shoots in P. strictum and S. magellanicum may give them a competitive superiority over S. palustre. The negative response in Sphagnum to nitrogen could favor the expansion of vascular plants, but P. strictum may endure thanks to its increased branching.

  9. Detection of Interaction of Binding Affinity of Aromatic Hydrocarbon Receptor to the Specific DNA by Exonuclease Protection Mediated PCR Assay

    Institute of Scientific and Technical Information of China (English)

    SUN Xi; XU Shunqing

    2005-01-01

    A novel exonuclease protection mediated PCR assay (EPM-PCR) to detect the interaction of protein and DNA at a dioxin-responsive enhancer (DRE) upstream of the CYP1A1 gene in rat hepatic cytosol was established. A double-stranded DNA fragment containing two binding sites was designed and incubated with the aryl hydrocarbon receptor (AhR) transformed by 2,3,7,8-tet rachlorodibenzo p dioxin (TCDD) to generate TCDD: AhR: DNA complex which could protect receptor-binding DNA against exonuclease Ⅲ (Exo Ⅲ) digestion. With ExoⅢ treatment, free DNAs were digested and receptor-bound DNAs remained that could be amplified by PCR. By agarose gel electrophoreses a clear band (285bp) was detected using TCDD-treated sample, while nothing with control samples. To detect transformed AhR-DRE complex, 2 fmol DNAs and 3 ug cytosol proteins were found to be sufficient in the experiment. Compared with gel retardation assay, this new method is more sensitive for monitoring the Ah receptor-enhancer interaction without radioactive pollution.

  10. Identification of genetic modules mediating the Jekyll and Hyde interaction of Dinoroseobacter shibae with the dinoflagellate Prorocentrum minimum

    Directory of Open Access Journals (Sweden)

    Hui eWang

    2015-11-01

    Full Text Available The co-cultivation of the alphaproteobacterium Dinoroseobacter shibae with the dinoflagellate Prorocentrum minimum is characterized by a mutualistic phase followed by a pathogenic phase in which the bacterium kills aging algae. Thus it resembles the Jekyll-and-Hyde interaction that has been proposed for other algae and Roseobacter. Here we identified key genetic components of this interaction. Analysis of the transcriptome of D. shibae in co-culture with P. minimum revealed growth phase dependent changes in the expression of quorum sensing (QS, the CtrA phosphorelay, and flagella biosynthesis genes. Deletion of the histidine kinase gene cckA which is part of the CtrA phosphorelay or the flagella genes fliC or flgK resulted in complete lack of growth stimulation of P. minimum in co-culture with the D. shibae mutants. By contrast, pathogenicity was entirely dependent on one of the extrachromosomal elements of D. shibae, the 191 kb plasmid. The data show that flagella and the CtrA phosphorelay are required for establishing mutualism and prove a cell density dependent killing effect of D. shibae on P. minimum which is mediated by an unknown factor encoded on the 191 kb plasmid.

  11. Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum.

    Science.gov (United States)

    Uemura, Takeshi; Lee, Sung-Jin; Yasumura, Misato; Takeuchi, Tomonori; Yoshida, Tomoyuki; Ra, Moonjin; Taguchi, Ryo; Sakimura, Kenji; Mishina, Masayoshi

    2010-06-11

    Elucidation of molecular mechanisms that regulate synapse formation is required for the understanding of neural wiring, higher brain functions, and mental disorders. Despite the wealth of in vitro information, fundamental questions about how glutamatergic synapses are formed in the mammalian brain remain unanswered. Glutamate receptor (GluR) delta2 is essential for cerebellar synapse formation in vivo. Here, we show that the N-terminal domain (NTD) of GluRdelta2 interacts with presynaptic neurexins (NRXNs) through cerebellin 1 precursor protein (Cbln1). The synaptogenic activity of GluRdelta2 is abolished in cerebellar primary cultures from Cbln1 knockout mice and is restored by recombinant Cbln1. Knockdown of NRXNs in cerebellar granule cells also hinders the synaptogenic activity of GluRdelta2. Both the NTD of GluRdelta2 and the extracellular domain of NRXN1beta suppressed the synaptogenic activity of Cbln1 in cerebellar primary cultures and in vivo. These results suggest that GluRdelta2 mediates cerebellar synapse formation by interacting with presynaptic NRXNs through Cbln1.

  12. Facilitatory effect of dopamine on neuromuscular transmission mediated via dopamine D1-like receptors and prospective interaction with nicotine.

    Science.gov (United States)

    AlQot, H E; Elnozahi, N A; Mohy El-Din, M M; Bistawroos, A E; Abou Zeit-Har, M S

    2015-10-15

    The objective of this study is to probe the effects of dopamine and potential interactions with nicotine at the motor end plate. To accomplish this, we measured the amplitude of nerve-evoked muscle twitches of the isolated rat phrenic hemi-diaphragm preparation. Dopamine potentiated indirect muscle twitches in normal and gallamine-presensitized preparations amounting to a maximum of 31.14±0.71% and 69.23±1.96%, respectively. The dopamine-induced facilitation was well maintained in presence of 10 µM propranolol but greatly reduced in presence of 6 µM SCH 23390 or 3 µM dantrolene. In addition, SKF 81297 attained a plateau at 16 µM as opposed to 64 µM dopamine, with a percentage potentiation of 69.47±1.76. The facilitatory effect of dopamine was potentiated in nicotine treated rats. This study revealed for the first time that the facilitatory effect exerted by dopamine on neuromuscular transmission is mediated via the dopamine D1-like receptors. In addition, it highlighted the possible dependency of dopamine effects on intracellular calcium and signified potential interaction among dopamine and nicotine. Clinically, the findings generated by this study reveal potential targets for approaching motor deficit syndromes.

  13. Ecosystem consequences of enhanced solar ultraviolet radiation: secondary plant metabolites as mediators of multiple trophic interactions in terrestrial plant communities.

    Science.gov (United States)

    Bassman, John H

    2004-05-01

    The potential role of ultraviolet-B (UV-B)-induced secondary plant metabolites as mediators of multiple trophic responses in terrestrial ecosystems is considered through review of the major classes of secondary metabolites, the pathways for their biosynthesis, interactions with primary and secondary consumers and known UV effects on their induction. Gross effects of UV-B radiation on plant growth and survival under realistic spectral balances in the field have been generally lacking, but subtle changes in carbon allocation and partitioning induced by UV-B, in particular production of secondary metabolites, can affect ecosystem-level processes. Secondary metabolites are important in plant-herbivore interactions and may affect pathogens. They act as feeding or oviposition deterrents to generalists and nonadapted specialists, but adapted specialists are stimulated to feed by these same compounds, which they detoxify and often sequester for use against their predators. This provides a route for tritrophic effects of enhanced UV-B radiation whereby herbivory may be increased while predation on the herbivore is simultaneously reduced. It is in this context that secondary metabolites may manifest their most important role. They can be the demonstrable mechanism establishing cause and effect at higher trophic levels because the consequences of their induction can be established at all trophic levels.

  14. Identification of Genetic Modules Mediating the Jekyll and Hyde Interaction of Dinoroseobacter shibae with the Dinoflagellate Prorocentrum minimum.

    Science.gov (United States)

    Wang, Hui; Tomasch, Jürgen; Michael, Victoria; Bhuju, Sabin; Jarek, Michael; Petersen, Jörn; Wagner-Döbler, Irene

    2015-01-01

    The co-cultivation of the alphaproteobacterium Dinoroseobacter shibae with the dinoflagellate Prorocentrum minimum is characterized by a mutualistic phase followed by a pathogenic phase in which the bacterium kills aging algae. Thus it resembles the "Jekyll-and-Hyde" interaction that has been proposed for other algae and Roseobacter. Here, we identified key genetic components of this interaction. Analysis of the transcriptome of D. shibae in co-culture with P. minimum revealed growth phase dependent changes in the expression of quorum sensing, the CtrA phosphorelay, and flagella biosynthesis genes. Deletion of the histidine kinase gene cckA which is part of the CtrA phosphorelay or the flagella genes fliC or flgK resulted in complete lack of growth stimulation of P. minimum in co-culture with the D. shibae mutants. By contrast, pathogenicity was entirely dependent on one of the extrachromosomal elements of D. shibae, the 191 kb plasmid. The data show that flagella and the CtrA phosphorelay are required for establishing mutualism and prove a cell density dependent killing effect of D. shibae on P. minimum which is mediated by an unknown factor encoded on the 191 kb plasmid.

  15. Leishmania-induced IRAK-1 inactivation is mediated by SHP-1 interacting with an evolutionarily conserved KTIM motif.

    Directory of Open Access Journals (Sweden)

    Issa Abu-Dayyeh

    Full Text Available Parasites of the Leishmania genus can rapidly alter several macrophage (MØ signalling pathways in order to tame down the innate immune response and inflammation, therefore favouring their survival and propagation within their mammalian host. Having recently reported that Leishmania and bacterial LPS generate a significantly stronger inflammatory response in animals and phagocytes functionally deficient for the Src homology 2 domain-containing protein tyrosine phosphatase (SHP-1, we hypothesized that Leishmania could exploit SHP-1 to inactivate key kinases involved in Toll-like receptor (TLR signalling and innate immunity such as IL-1 receptor-associated kinase 1 (IRAK-1. Here we show that upon infection, SHP-1 rapidly binds to IRAK-1, completely inactivating its intrinsic kinase activity and any further LPS-mediated activation as well as MØ functions. We also demonstrate that the SHP-1/IRAK-1 interaction occurs via an evolutionarily conserved ITIM-like motif found in the kinase domain of IRAK-1, which we named KTIM (Kinase Tyrosyl-based Inhibitory Motif. This regulatory motif appeared in early vertebrates and is not found in any other IRAK family member. Our study additionally reveals that several other kinases (e.g. Erk1/2, IKKalpha/beta involved in downstream TLR signalling also bear KTIMs in their kinase domains and interact with SHP-1. We thus provide the first demonstration that a pathogen can exploit a host protein tyrosine phosphatase, namely SHP-1, to directly inactivate IRAK-1 through a generally conserved KTIM motif.

  16. Chemically-mediated interactions between macroalgae Dictyota spp. and multiple life-history stages of the coral Porites astreoides

    Science.gov (United States)

    Paul, Valerie J.; Kuffner, Ilsa B.; Walters, Linda J.; Ritson-Williams, Raphael; Beach, Kevin S.; Becerro, Mikel A.

    2011-01-01

    Competition between corals and macroalgae is often assumed to occur on reefs, especially those that have undergone shifts from coral to algal dominance; however, data examining these competitive interactions, especially during the early life-history stages of corals, are scarce. We conducted a series of field and outdoor seawater-table experiments to test the hypothesis that allelopathy (chemical inhibition) mediates interactions between 2 common brown macroalgae, Dictyota pulchella and D. pinnatifida, and the coral Porites astreoides at different life-history stages of the coral. D. pinnatifida significantly reduced larval survival and larval recruitment. The extracts of both D. pinnatifida and D. pulchella significantly reduced larval survival, and the extract of D. pulchella also negatively influenced larval recruitment. There was no measurable effect of the crude extracts from Dictyota spp. on the photophysiology of adult corals. Our results provide evidence that these Dictyota species chemically compete with P. astreoides by negatively affecting larval settlement and recruitment as well as the survival of larvae and new recruits. Macroalgae may perpetuate their dominance on degraded reefs by chemically inhibiting the process of coral recruitment.

  17. Chemically mediated interactions between macroalgae Dictyota spp. and multiple life-history stages of the coral Porites astreoides

    Science.gov (United States)

    Paul, V.J.; Kuffner, I.B.; Walters, L.J.; Ritson-Williams, R.; Beach, K.S.; Becerro, M.A.

    2011-01-01

    Competition between corals and macroalgae is often assumed to occur on reefs, especially those that have undergone shifts from coral to algal dominance; however, data examining these competitive interactions, especially during the early life-history stages of corals, are scarce. We conducted a series of field and outdoor seawater-table experiments to test the hypothesis that allelopathy (chemical inhibition) mediates interactions between 2 common brown macroalgae, Dictyota pulchella and D. pinnatifida, and the coral Porites astreoides at different life-history stages of the coral. D. pinnatifida significantly reduced larval survival and larval recruitment. The extracts of both D. pinnatifida and D. pulchella significantly reduced larval survival, and the extract of D. pulchella also negatively influenced larval recruitment. There was no measurable effect of the crude extracts from Dictyota spp. on the photophysiology of adult corals. Our results provide evidence that these Dictyota species chemically compete with P. astreoides by negatively affecting larval settlement and recruitment as well as the survival of larvae and new recruits. Macroalgae may perpetuate their dominance on degraded reefs by chemically inhibiting the process of coral recruitment. ?? 2011 Inter-Research.

  18. Proteins mediating the Neospora caninum-host cell interaction as targets for vaccination.

    Science.gov (United States)

    Hemphill, Andrew; Debache, Karim; Monney, Thierry; Schorer, Michelle; Guionaud, Christophe; Alaeddine, Ferial; Mueller, Norbert; Mueller, Joachim

    2013-01-01

    Neospora caninum is an apicomplexan parasite that is capable of infecting, a wide range of tissues. The fact that Neospora represents an important abortion-causing parasite in cattle has transformed neosporosis research from an earlier, rather esoteric field, to a significant research topic, and considerable investments have been made in the last years to develop an efficacious vaccine or other means of intervention that would prevent infection and abortion due to N. caninum infection in cattle. Antigenic molecules associated with proteins involved in adhesion/invasion or other parasite-host-cell interaction processes can confer protection against Neospora caninum infection, and such proteins represent valuable targets for the development of a vaccine to limit economical losses due to neosporosis. Although not ideal, small laboratory animal models that mimic cerebral infection, acute disease and fetal loss upon infection during pregnancy have been used for the assessment of vaccine candidates, in parallel with studies on experimental infections in cattle. Herein, we review and critically assess these vaccination approaches and discuss potential options for improvements.

  19. Akt1 mediates neuronal differentiation in zebrafish via a reciprocal interaction with notch signaling.

    Directory of Open Access Journals (Sweden)

    Yi-Chuan Cheng

    Full Text Available Akt1 is well known for its role in regulating cell proliferation, differentiation, and apoptosis and is implicated in tumors and several neurological disorders. However, the role of Akt1 in neural development has not been well defined. We have isolated zebrafish akt1 and shown that this gene is primarily transcribed in the developing nervous system, and its spatiotemporal expression pattern suggests a role in neural differentiation. Injection of akt1 morpholinos resulted in loss of neuronal precursors with a concomitant increase in post-mitotic neurons, indicating that knockdown of Akt1 is sufficient to cause premature differentiation of neurons. A similar phenotype was observed in embryos deficient for Notch signaling. Both the ligand (deltaA and the downstream target of Notch (her8a were downregulated in akt1 morphants, indicating that Akt1 is required for Delta-Notch signaling. Furthermore, akt1 expression was downregulated in Delta-Notch signaling-deficient embryos and could be induced by constitutive activation of Notch signaling. In addition, knockdown of Akt1 was able to nullify the inhibition of neuronal differentiation caused by constitutive activation of Notch signaling. Taken together, these results provide in vivo evidence that Akt1 interacts with Notch signaling reciprocally and provide an explanation of why Akt1 is essential for the inhibition of neuronal differentiation.

  20. Synergistic parasite-pathogen interactions mediated by host immunity can drive the collapse of honeybee colonies.

    Directory of Open Access Journals (Sweden)

    Francesco Nazzi

    Full Text Available The health of the honeybee and, indirectly, global crop production are threatened by several biotic and abiotic factors, which play a poorly defined role in the induction of widespread colony losses. Recent descriptive studies suggest that colony losses are often related to the interaction between pathogens and other stress factors, including parasites. Through an integrated analysis of the population and molecular changes associated with the collapse of honeybee colonies infested by the parasitic mite Varroa destructor, we show that this parasite can de-stabilise the within-host dynamics of Deformed wing virus (DWV, transforming a cryptic and vertically transmitted virus into a rapidly replicating killer, which attains lethal levels late in the season. The de-stabilisation of DWV infection is associated with an immunosuppression syndrome, characterized by a strong down-regulation of the transcription factor NF-κB. The centrality of NF-κB in host responses to a range of environmental challenges suggests that this transcription factor can act as a common currency underlying colony collapse that may be triggered by different causes. Our results offer an integrated account for the multifactorial origin of honeybee losses and a new framework for assessing, and possibly mitigating, the impact of environmental challenges on honeybee health.

  1. Synergistic parasite-pathogen interactions mediated by host immunity can drive the collapse of honeybee colonies.

    Science.gov (United States)

    Nazzi, Francesco; Brown, Sam P; Annoscia, Desiderato; Del Piccolo, Fabio; Di Prisco, Gennaro; Varricchio, Paola; Della Vedova, Giorgio; Cattonaro, Federica; Caprio, Emilio; Pennacchio, Francesco

    2012-01-01

    The health of the honeybee and, indirectly, global crop production are threatened by several biotic and abiotic factors, which play a poorly defined role in the induction of widespread colony losses. Recent descriptive studies suggest that colony losses are often related to the interaction between pathogens and other stress factors, including parasites. Through an integrated analysis of the population and molecular changes associated with the collapse of honeybee colonies infested by the parasitic mite Varroa destructor, we show that this parasite can de-stabilise the within-host dynamics of Deformed wing virus (DWV), transforming a cryptic and vertically transmitted virus into a rapidly replicating killer, which attains lethal levels late in the season. The de-stabilisation of DWV infection is associated with an immunosuppression syndrome, characterized by a strong down-regulation of the transcription factor NF-κB. The centrality of NF-κB in host responses to a range of environmental challenges suggests that this transcription factor can act as a common currency underlying colony collapse that may be triggered by different causes. Our results offer an integrated account for the multifactorial origin of honeybee losses and a new framework for assessing, and possibly mitigating, the impact of environmental challenges on honeybee health.

  2. Endophyte-mediated interactions between cauliflower, the herbivore Spodoptera litura, and the ectoparasitoid Bracon hebetor.

    Science.gov (United States)

    Kaur, Tamanreet; Singh, Bahaderjeet; Kaur, Amarjeet; Kaur, Sanehdeep

    2015-10-01

    Fungal endosymbionts in plants may influence interactions among plants, herbivores and their parasitoids through the production of secondary metabolites. We used a lepidopteran pest and its generalist parasitoid to test the effect of endophyte-infected plants on a third trophic level. Endophytic fungi, Aspergillus flavus and Aspergillus niger, isolated from Acacia arabica, were used to infect cauliflower plants. We found that the presence of the endophyte in the plants significantly extended the development period of Spodoptera litura (Fab.) larvae. Feeding of the host on endophyte-infected plants further adversely affected the development and performance of its parasitoid, Bracon hebetor (Say). A negative impact was also recorded for longevity and fecundity of endophyte-naive parasitoid females due to the parasitization of host larvae fed on endophyte-infected plants. The presence of endophytes in the diet of the host larvae significantly prolonged the development of the parasitoid. A strong detrimental effect was also recorded for larval survival and emergence of parasitoid adults. The longevity and parasitism rate of female wasps were reduced significantly due to the ingestion of endophyte-infected cauliflower plants by S. litura larvae. Overall, we found that both endophytic fungi had a negative impact on the parasitoid.

  3. Translational arrest by a prokaryotic signal recognition particle is mediated by RNA interactions.

    Science.gov (United States)

    Beckert, Bertrand; Kedrov, Alexej; Sohmen, Daniel; Kempf, Georg; Wild, Klemens; Sinning, Irmgard; Stahlberg, Henning; Wilson, Daniel N; Beckmann, Roland

    2015-10-01

    The signal recognition particle (SRP) recognizes signal sequences of nascent polypeptides and targets ribosome-nascent chain complexes to membrane translocation sites. In eukaryotes, translating ribosomes are slowed down by the Alu domain of SRP to allow efficient targeting. In prokaryotes, however, little is known about the structure and function of Alu domain-containing SRPs. Here, we report a complete molecular model of SRP from the Gram-positive bacterium Bacillus subtilis, based on cryo-EM. The SRP comprises two subunits, 6S RNA and SRP54 or Ffh, and it facilitates elongation slowdown similarly to its eukaryotic counterpart. However, protein contacts with the small ribosomal subunit observed for the mammalian Alu domain are substituted in bacteria by RNA-RNA interactions of 6S RNA with the α-sarcin-ricin loop and helices H43 and H44 of 23S rRNA. Our findings provide a structural basis for cotranslational targeting and RNA-driven elongation arrest in prokaryotes.

  4. Centlein mediates an interaction between C-Nap1 and Cep68 to maintain centrosome cohesion.

    Science.gov (United States)

    Fang, Guoliang; Zhang, Dachuan; Yin, Huilong; Zheng, Lu; Bi, Xiaolin; Yuan, Li

    2014-04-15

    Centrosome cohesion, mostly regarded as a proteinaceous linker between parental centrioles, ensures that the interphase centrosome(s) function as a single microtubule-organizing center. Impairment of centrosome cohesion leads to the splitting of centrosomes. Although the list of cohesion proteins is growing, the precise composition and regulation of centrosome cohesion are still largely unknown. In this study, we show that the centriolar protein centlein (also known as CNTLN) localizes to the proximal ends of the centrioles and directly interacts with both C-Nap1 (also known as Cep250) and Cep68. Moreover, centlein complexes with C-Nap1 and Cep68 at the proximal ends of centrioles during interphase and functions as a molecular link between C-Nap1 and Cep68. Depletion of centlein impairs recruitment of Cep68 to the centrosomes and, in turn, results in centrosome splitting. Both centlein and Cep68 are novel Nek2A substrates. Collectively, our data demonstrate that centrosome cohesion is maintained by the newly identified complex of C-Nap1-centlein-Cep68.

  5. Trichomonas vaginalis exosomes deliver cargo to host cells and mediate host∶parasite interactions.

    Directory of Open Access Journals (Sweden)

    Olivia Twu

    Full Text Available Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogential tract where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Here, we use a combination of methodologies including cell fractionation, immunofluorescence and electron microscopy, RNA, proteomic and cytokine analyses and cell adherence assays to examine pathogenic properties of T. vaginalis. We have found that T.vaginalis produces and secretes microvesicles with physical and biochemical properties similar to mammalian exosomes. The parasite-derived exosomes are characterized by the presence of RNA and core, conserved exosomal proteins as well as parasite-specific proteins. We demonstrate that T. vaginalis exosomes fuse with and deliver their contents to host cells and modulate host cell immune responses. Moreover, exosomes from highly adherent parasite strains increase the adherence of poorly adherent parasites to vaginal and prostate epithelial cells. In contrast, exosomes from poorly adherent strains had no measurable effect on parasite adherence. Exosomes from parasite strains that preferentially bind prostate cells increased binding of parasites to these cells relative to vaginal cells. In addition to establishing that parasite exosomes act to modulate host∶parasite interactions, these studies are the first to reveal a potential role for exosomes in promoting parasite∶parasite communication and host cell colonization.

  6. Complex interactions mediate the effects of fish farming on benthic chemistry within a region of Scotland.

    Science.gov (United States)

    Mayor, Daniel J; Solan, Martin

    2011-07-01

    Fish farms typically generate a localised gradient of both organic and inorganic pollutants in the underlying sediments. The factors governing the extent of such impacts remain poorly understood, particularly when multiple sites are considered. We used regression-type techniques to examine the drivers of sediment chemistry patterns around five Scottish fish farms that ranged in size (120-2106 tonnes) and fish species, but were located within farm illustrate that between-site variability can be high, even at this regional-scale. These effects must be accounted for when comparing the effects of fish farming at different locations. All measured chemical parameters declined rapidly as a function of distance from the cage edge, with the rate of decline depending on local current speeds. Only phosphorus concentrations increased directly with farm size. Increasing current speeds at farms carbon in the underlying sediments, whereas the opposite occurred at larger farms. The counterintuitive effect of current speed at farms above the threshold size suggests that the physical properties of the seabed at these locations favour the accumulation of organic wastes and/or that the underlying communities have a lower assimilative capacity. These imply that the environmental efficiency of fish farming activities may be further optimised by taking into account the interaction between current speed, substrate complexity and the functional characteristics of the benthos. Collectively, our analyses demonstrate that the fate of fish farm-derived wastes is complex and highlight the need for site-specific management techniques.

  7. Lectin receptor kinases participate in protein-protein interactions to mediate plasma membrane-cell wall adhesions in Arabidopsis.

    Science.gov (United States)

    Gouget, Anne; Senchou, Virginie; Govers, Francine; Sanson, Arnaud; Barre, Annick; Rougé, Pierre; Pont-Lezica, Rafael; Canut, Hervé

    2006-01-01

    Interactions between plant cell walls and plasma membranes are essential for cells to function properly, but the molecules that mediate the structural continuity between wall and membrane are unknown. Some of these interactions, which are visualized upon tissue plasmolysis in Arabidopsis (Arabidopsis thaliana), are disrupted by the RGD (arginine-glycine-aspartic acid) tripeptide sequence, a characteristic cell adhesion motif in mammals. In planta induced-O (IPI-O) is an RGD-containing protein from the plant pathogen Phytophthora infestans that can disrupt cell wall-plasma membrane adhesions through its RGD motif. To identify peptide sequences that specifically bind the RGD motif of the IPI-O protein and potentially play a role in receptor recognition, we screened a heptamer peptide library displayed in a filamentous phage and selected two peptides acting as inhibitors of the plasma membrane RGD-binding activity of Arabidopsis. Moreover, the two peptides also disrupted cell wall-plasma membrane adhesions. Sequence comparison of the RGD-binding peptides with the Arabidopsis proteome revealed 12 proteins containing amino acid sequences in their extracellular domains common with the two RGD-binding peptides. Eight belong to the receptor-like kinase family, four of which have a lectin-like extracellular domain. The lectin domain of one of these, At5g60300, recognized the RGD motif both in peptides and proteins. These results imply that lectin receptor kinases are involved in protein-protein interactions with RGD-containing proteins as potential ligands, and play a structural and signaling role at the plant cell surfaces.

  8. Lectin Receptor Kinases Participate in Protein-Protein Interactions to Mediate Plasma Membrane-Cell Wall Adhesions in Arabidopsis1

    Science.gov (United States)

    Gouget, Anne; Senchou, Virginie; Govers, Francine; Sanson, Arnaud; Barre, Annick; Rougé, Pierre; Pont-Lezica, Rafael; Canut, Hervé

    2006-01-01

    Interactions between plant cell walls and plasma membranes are essential for cells to function properly, but the molecules that mediate the structural continuity between wall and membrane are unknown. Some of these interactions, which are visualized upon tissue plasmolysis in Arabidopsis (Arabidopsis thaliana), are disrupted by the RGD (arginine-glycine-aspartic acid) tripeptide sequence, a characteristic cell adhesion motif in mammals. In planta induced-O (IPI-O) is an RGD-containing protein from the plant pathogen Phytophthora infestans that can disrupt cell wall-plasma membrane adhesions through its RGD motif. To identify peptide sequences that specifically bind the RGD motif of the IPI-O protein and potentially play a role in receptor recognition, we screened a heptamer peptide library displayed in a filamentous phage and selected two peptides acting as inhibitors of the plasma membrane RGD-binding activity of Arabidopsis. Moreover, the two peptides also disrupted cell wall-plasma membrane adhesions. Sequence comparison of the RGD-binding peptides with the Arabidopsis proteome revealed 12 proteins containing amino acid sequences in their extracellular domains common with the two RGD-binding peptides. Eight belong to the receptor-like kinase family, four of which have a lectin-like extracellular domain. The lectin domain of one of these, At5g60300, recognized the RGD motif both in peptides and proteins. These results imply that lectin receptor kinases are involved in protein-protein interactions with RGD-containing proteins as potential ligands, and play a structural and signaling role at the plant cell surfaces. PMID:16361528

  9. Predator effects on a detritus-based food web are primarily mediated by non-trophic interactions.

    Science.gov (United States)

    Majdi, Nabil; Boiché, Anatole; Traunspurger, Walter; Lecerf, Antoine

    2014-07-01

    Predator effects on ecosystems can extend far beyond their prey and are often not solely lethally transmitted. Change in prey traits in response to predation risk can have important repercussions on community assembly and key ecosystem processes (i.e. trait-mediated indirect effects). In addition, some predators themselves alter habitat structure or nutrient cycling through ecological engineering effects. Tracking these non-trophic pathways is thus an important, yet challenging task to gain a better grasp of the functional role of predators. Multiple lines of evidence suggest that, in detritus-based food webs, non-trophic interactions may prevail over purely trophic interactions in determining predator effects on plant litter decomposition. This hypothesis was tested in a headwater stream by modulating the density of a flatworm predator (Polycelis felina) in enclosures containing oak (Quercus robur) leaf litter exposed to natural colonization by small invertebrates and microbial decomposers. Causal path modelling was used to infer how predator effects propagated through the food web. Flatworms accelerated litter decomposition through positive effects on microbial decomposers. The biomass of prey and non-prey invertebrates was not negatively affected by flatworms, suggesting that net predator effect on litter decomposition was primarily determined by non-trophic interactions. Flatworms enhanced the deposition and retention of fine sediments on leaf surface, thereby improving leaf colonization by invertebrates - most of which having strong affinities with interstitial habitats. This predator-induced improvement of habitat availability was attributed to the sticky nature of the mucus that flatworms secrete in copious amount while foraging. Results of path analyses further indicated that this bottom-up ecological engineering effect was as powerful as the top-down effect on invertebrate prey. Our findings suggest that predators have the potential to affect substantially

  10. Interaction of dipeptide prodrugs of saquinavir with multidrug resistance protein-2 (MRP-2): evasion of MRP-2 mediated efflux.

    Science.gov (United States)

    Jain, Ritesh; Agarwal, Sheetal; Mandava, Nanda Kishore; Sheng, Ye; Mitra, Ashim K

    2008-10-01

    Saquinavir (SQV), the first protease inhibitor approved by FDA to treat HIV-1 infection. This drug is a well-known substrate for multidrug resistance protein-2 (MRP-2). The objective of this study was to investigate whether derivatization of SQV to dipeptide prodrugs, valine-valine-saquinavir (Val-Val-SQV) and glycine-valine-saquinavir (Gly-Val-SQV), targeting peptide transporter can circumvent MRP-2 mediated efflux. Uptake and transport studies were carried out across MDCKII-MRP2 cell monolayers to investigate the interaction of SQV and its prodrugs with MRP-2. In situ single pass intestinal perfusion experiments in rat jejunum were performed to calculate intestinal absorption rate constants and permeabilities of SQV, Val-Val-SQV and Gly-Val-SQV. Uptake studies demonstrated that the prodrugs have significantly lower interaction with MRP-2 relative to SQV. Transepithelial transport of Val-Val-SQV and Gly-Val-SQV across MDCKII-MRP2 cells exhibited an enhanced absorptive flux and reduced secretory flux as compared to SQV. Intestinal perfusion studies revealed that synthesized prodrugs have higher intestinal permeabilities relative to SQV. Enhanced absorption of Val-Val-SQV and Gly-Val-SQV relative to SQV can be attributed to their translocation by the peptide transporter in the jejunum. In the presence of MK-571, a MRP family inhibitor, there was a significant increase in the permeabilities of SQV and Gly-Val-SQV indicating that these compounds are probably substrates for MRP-2. However, there was no change in the permeability of Val-Val-SQV with MK-571 indicating lack of any interaction of Val-Val-SQV with MRP-2. In conclusion, peptide transporter targeted prodrug modification of MRP-2 substrates may lead to shielding of these drug molecules from MRP-2 efflux pumps.

  11. Seed trait-mediated selection by rodents affects mutualistic interactions and seedling recruitment of co-occurring tree species.

    Science.gov (United States)

    Zhang, Hongmao; Yan, Chuan; Chang, Gang; Zhang, Zhibin

    2016-02-01

    As mutualists, seed dispersers may significantly affect mutualistic interactions and seedling recruitment of sympatric plants that share similar seed dispersers, but studies are rare. Here, we compared seed dispersal fitness in two co-occurring plant species (Armeniaca sibirica and Amygdalus davidiana) that inhabit warm temperate deciduous forest in northern China. We tested the hypothesis that seed trait-mediated selection by rodents may influence mutualistic interactions with rodents and then seedling establishment of co-occurring plant species. A. davidiana seeds are larger and harder (thick endocarps) than A. sibirica seeds, but they have similar levels of nutrients (crude fat, crude protein), caloric value and tannin. More A. sibirica seedlings are found in the field. Semi-natural enclosure tests indicated that the two seed species were both harvested by the same six rodent species, but that A. sibirica had mutualistic interactions (scatter hoarding) with four rodent species (Apodemus peninsulae, A. agrarius, Sciurotamias davidianus, Tamias sibiricus), and A. davidiana with only one (S. davidianus). Tagged seed dispersal experiments in the field indicated that more A. sibirica seeds were scatter-hoarded by rodents, and more A. sibirica seeds survived to the next spring and became seedlings. A. sibirica seeds derive more benefit from seed dispersal by rodents than A. davidiana seeds, particularly in years with limited seed dispersers, which well explained the higher seedling recruitment of A. sibirica compared with that of A. davidiana under natural conditions. Our results suggest that seed dispersers may play a significant role in seedling recruitment and indirect competition between co-occurring plant species.

  12. Citrus tristeza virus p23: a unique protein mediating key virus-host interactions

    Directory of Open Access Journals (Sweden)

    Ricardo eFlores

    2013-05-01

    Full Text Available The large RNA genome of CTV (ca. 20 kb contains 12 open reading frames (ORFs, with the 3’-terminal one corresponding to a protein of 209 amino acids (p23 that is expressed from an abundant subgenomic RNA. p23, an RNA-binding protein with a putative Zn-finger domain and some basic motifs, is unique to CTV because no homologues have been found in other closteroviruses, including the type species of the genus Beet yellows virus (despite both viruses having many homologous genes. Consequently, p23 might have evolved for the specific interaction of CTV with its citrus hosts. From a functional perspective p23 has been involved in many roles: i regulation of the asymmetrical accumulation of CTV RNA strands, ii induction of the seedling yellows syndrome in sour orange and grapefruit, iii intracellular suppression of RNA silencing, iv elicitation of CTV-like symptoms when expressed ectopically as a transgene in several Citrus spp., and v enhancement of systemic infection (and virus accumulation in sour orange and CTV release from the phloem in p23-expressing transgenic sweet and sour orange. Moreover, transformation of Mexican lime with intron-hairpin constructs designed for the co-inactivation of p23 and the two other CTV silencing suppressors results in complete resistance against the homologous virus. From a cellular point of view, recent data indicate that p23 accumulates preferentially in the nucleolus, being the first closterovirus protein with such a subcellular localization, as well as in plasmodesmata. These major accumulation sites most likely determine some of the functional roles of p23.

  13. Infochemical-mediated intraguild interactions among three predatory mites on cassava plants.

    Science.gov (United States)

    Gnanvossou, Désiré; Hanna, Rachid; Dicke, Marcel

    2003-03-01

    Carnivorous arthropods exhibit complex intraspecific and interspecific behaviour among themselves when they share the same niche or habitat and food resources. They should simultaneously search for adequate food for themselves and their offspring and in the meantime avoid becoming food for other organisms. This behaviour is of great ecological interest in conditions of low prey availability. We examined by means of an olfactometer, how volatile chemicals from prey patches with conspecific or heterospecific predators might contribute to shaping the structure of predator guilds. To test this, we used the exotic predatory mites Typhlodromalus manihoti and T. aripo, and the native predatory mite Euseius fustis, with Mononychellus tanajoa as the common prey species for the three predatory mite species. We used as odour sources M. tanajoa-infested cassava leaves or apices with or without predators. T. manihoti avoided patches inhabited by the heterospecifics T. aripo and E. fustis or by conspecifics when tested against a patch without predators. Similarly, both T. aripo and E. fustis females avoided patches with con- or heterospecifics when tested against a patch without predators. When one patch contained T. aripo and the other T. manihoti, females of the latter preferred the patch with T. aripo. Thus, T. manihoti is able to discriminate between odours from patches with con- and heterospecifics. Our results show that the three predatory mite species are able to assess prey patch profitability using volatiles. Under natural conditions, particularly when their food sources are scarce, the three predatory mite species might be involved in interspecific and/or intraspecific interactions that can substantially affect population dynamics of the predators and their prey.

  14. Spatial refugia mediate juvenile coral survival during coral-predator interactions

    Science.gov (United States)

    Gallagher, Clare; Doropoulos, Christopher

    2017-03-01

    Coral recruitment and juvenile growth are essential processes for coral population maintenance and recovery. A growing body of research has evaluated the influence of reef microstructure on coral settlement and post-settlement survival, showing that physical refugia enhance recruitment. These studies have evaluated coral recruit morality from competition with macroalgae and indirect predation by grazing organisms, but the impact of direct predation by corallivorous piscine species on juvenile corals and how this interacts with reef microstructure is relatively unknown. This study examined whether refugia provided by micro-crevices enhance juvenile coral survival from corallivory. Juvenile corals from two different functional groups, the slow-growing massive Porites lobata and fast-growing branching Pocillopora damicornis, with average nubbin sizes of 1.4 cm × 0.3 cm and 0.5 cm × 1.0 cm (diameter × height), respectively, were attached to experimental tiles using small (1.44 cm3) and large (8.0 cm3) crevice sizes and were monitored for 29 d on a forereef in Palau. Full crevices (four sided) enhanced coral survival compared to exposed microhabitats in both coral taxa, but crevice size did not alter survival rates. Corallivores targeted recruits within crevices regardless of crevice size; dominant predators included small triggerfish (Balistidae), butterflyfish ( Chaetodon), and wrasse ( Cheilinus). Overall, Pocillopora suffered much higher rates of mortality than Porites. All Pocillopora were consumed by day 8 of the experiment, but mortality was significantly delayed in full crevices compared to exposed and partial crevice (three sided) microhabitats. In contrast, Por. lobata located in all microhabitats survived the entire experiment up to 29 d, with high survival in full (>90%) and partial crevices (70%), but only 28% survival in exposed microhabitats. These findings show the importance of crevices as spatial refugia from predators for juvenile corals and

  15. Smart RISUG: A potential new contraceptive and its magnetic field-mediated sperm interaction

    Directory of Open Access Journals (Sweden)

    Rakhi K Jha

    2009-03-01

    Full Text Available Rakhi K Jha1,2, Pradeep K Jha1,3, Sujoy K Guha11School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India; 2Toxicology Laboratory, Department of Zoology, ChCS University, Meerut, UP, India; 3Department of Management studies, VIET, UP Tech. Univ., Lucknow, UP, IndiaAbstract: The rationale and technique underlying a novel concept of noninvasive fertility control by a new Cuproferrogel contraceptive drug, iron oxide–copper–styrene maleic anhydride–dimethyl sulphoxide (Fe3O4–Cu–SMA–DMSO composite named ‘Smart RISUG’ (smart reversible inhibition of sperm under guidance in presence of pulsed magnetic field (PMF; 1 mT to 800 mT is explained. It was synthesized by dispersing iron oxide particles and copper particles into SMA-DMSO (male contraceptive RISUG and characterized for particle distribution, particle size measurement and transmittance peaks, etc. Interaction of the RISUG particles as well as Smart RISUG particles with Albino rat sperm cell was studied in presence as well as absence of PMF. To find an explanation to increased reaching of the Smart RISUG drug into sperm under influence of magnetic field, the transport properties were characterized by high resolution transmission electron microscopy and atomic force microscopy. Smart RISUG could be mobilized into sperm cell membrane at the PMF, 760 mT in about 50 seconds. Adoption of novel drug Smart RISUG involving new technique may open the pathway for non surgical control of drug distribution, detection and restoration of the normal fertility after removal of the contraceptive from the male/female reproductive tube in presence of electromagnetic field.Keywords: smart RISUG, pulsed magnetic field, noninvasive fertility control, drug distribution, sperm cell

  16. In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell - endothelial cell interaction

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    Mees Soeren T

    2010-04-01

    Full Text Available Abstract Background Metastasis formation is the leading cause of death among colon cancer patients. We established a new in-situ model of in vivo microscopy of the lung to analyse initiating events of metastatic tumor cell adhesion within this typical metastatic target of colon cancer. Methods Anaesthetized CD rats were mechanically ventilated and 106 human HT-29LMM and T84 colon cancer cells were injected intracardially as single cell suspensions. Quantitative in vivo microscopy of the lung was performed in 10 minute intervals for a total of 40 minutes beginning with the time of injection. Results After vehicle treatment of HT-29LMM controls 15.2 ± 5.3; 14.2 ± 7.5; 11.4 ± 5.5; and 15.4 ± 6.5 cells/20 microscopic fields were found adherent within the pulmonary microvasculature in each 10 minute interval. Similar numbers were found after injection of the lung metastasis derived T84 cell line and after treatment of HT-29LMM with unspecific mouse control-IgG. Subsequently, HT-29LMM cells were treated with function blocking antibodies against β1-, β4-, and αv-integrins wich also did not impair tumor cell adhesion in the lung. In contrast, after hydrolization of sialylated glycoproteins on the cells' surface by neuraminidase, we observed impairment of tumor cell adhesion by more than 50% (p Conclusions These results demonstrate that the initial colon cancer cell adhesion in the capillaries of the lung is predominantly mediated by tumor cell - endothelial cell interactions, possibly supported by platelets. In contrast to reports of earlier studies that metastatic tumor cell adhesion occurs through integrin mediated binding of extracellular matrix proteins in liver, in the lung, the continuously lined endothelium appears to be specifically targeted by circulating tumor cells.

  17. White light-mediated Cu (II)-5FU interaction augments the chemotherapeutic potential of 5-FU: an in vitro study.

    Science.gov (United States)

    Chibber, Sandesh; Farhan, Mohd; Hassan, Iftekhar; Naseem, Imrana

    2011-10-01

    5-Fluorouracil (5-FU) is a potent photosensitizer used in colon and rectal cancers. 5-FU on galvanostatic electrolysis or radiation-induced oxidation of aqueous solution yields N(1)-C(5)-linked dimmer hydrate of 5-FU. Copper is presently associated with chromatin; in cancer cells the concentration of copper is very high. It has been shown to be capable of mediating the action of several anticancer drugs through the production of reactive oxygen species (ROS). The objective of the present study is to determine the Cu (II)-mediated anticancer mechanism of 5-FU under photo-illumination as well as 5-FU alone. We have shown that a pro-oxidant action was enhanced when Cu (II) was used with 5-FU as compared to 5-FU alone. This may be due to the inhibition of dimerization of 5-FU when present in combination with Cu (II) under photo-illumination. It was also shown that 5-FU alone as well as in combination with Cu (II) was able to generate oxidative stress in lymphocyte which is inhibited by scavengers of ROS. Moreover, the results of Fourier-transformed infrared spectra lead to the conclusion that the dimerization of 5-FU was inhibited when used in combination with Cu (II). It was due to the interaction of 5-FU with Cu (II). Hence, we propose that during chemoradiotherapy with 5-FU, the endogenous copper is mobilized by 5-FU, leading to the generation of ROS which cause oxidative stress and possibly cancer cell death by apoptosis.

  18. Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide-Induced Inflammation and Acute Respiratory Distress Syndrome in Mice.

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    Linlin Wang

    Full Text Available Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS. Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3. However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP, mixed lineage kinase domain-like protein (MLKL, total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI staining. Levels of TNF-a, Interleukin (IL-1β, IL-6, IL-1α, IL-10 and HMGB1, tissue myeloperoxidase (MPO activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1α/β, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in

  19. Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Choudhury, Kamalika Roy [Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India); Centre for Neuroscience, Indian Institute of Science, Bangalore 560012 (India); Bhattacharyya, Nitai P., E-mail: nitai_sinp@yahoo.com [Biomedical Genomics Centre, PG Polyclinic Building, 5, Suburbun Hospital Road, Kolkata 700020 (India)

    2015-01-02

    Highlights: • HYPK reduces mutant HTT-mediated aggregate formation and cytotoxicity. • Interaction of HYPK with HTT requires N-terminal 17 amino acid of HTT (HTT-N17). • Deletion of HTT-N17 leads to SDS-soluble, smaller, nuclear aggregates. • These smaller aggregates do not associate with HYPK and are more cytotoxic. • Maybe, interaction of HYPK with amphipathic HTT-N17 block HTT aggregate formation. - Abstract: Huntington’s disease is a polyglutamine expansion disorder, characterized by mutant HTT-mediated aggregate formation and cytotoxicity. Many reports suggests roles of N-terminal 17 amino acid domain of HTT (HTT-N17) towards subcellular localization, aggregate formation and subsequent pathogenicity induced by N-terminal HTT harboring polyQ stretch in pathogenic range. HYPK is a HTT-interacting chaperone which can reduce N-terminal mutant HTT-mediated aggregate formation and cytotoxicity in neuronal cell lines. However, how HYPK interacts with N-terminal fragment of HTT remained unknown. Here we report that specific interaction of HYPK with HTT-N17 is crucial for the chaperone activity of HYPK. Deletion of HTT-N17 leads to formation of tinier, SDS-soluble nuclear aggregates formed by N-terminal mutant HTT. The increased cytotoxicity imparted by these tiny aggregates might be contributed due to loss of interaction with HYPK.

  20. Partial mediation role of self-efficacy between positive social interaction and mental health in family caregivers for dementia patients in Shanghai.

    Directory of Open Access Journals (Sweden)

    Shuying Zhang

    Full Text Available We explored the mediation effect of caregiver self-efficacy on the influences of behavioral and psychological symptoms (BPSD of dementia care recipients (CRs or family caregivers' (CGs social supports (informational, tangible and affectionate support and positive social interaction on CGs' mental health. We interviewed 196 CGs, using a battery of measures including demographic data of the dyads, CRs' dementia-related impairments, and CGs' social support, self-efficacy and the Medical Outcome Study (MOS Short-Form (SF-36 Health Survey. Multiple regression analyses showed that gathering information on self-efficacy and managing CG distress self-efficacy were the partial mediators of the relationship between positive social interaction and CG mental health. Managing caregiving distress self-efficacy also partial mediated the impact of BPSD on CG mental health. We discuss implications of the results for improving mental health of the target population in mainland China.

  1. Plant-plant interactions mediate the plastic and genotypic response of Plantago asiatica to CO2 : an experiment with plant populations from naturally high CO2 areas

    NARCIS (Netherlands)

    van Loon, Marloes P; Rietkerk, Max; Dekker, Stefan C; Hikosaka, Kouki; Ueda, Miki U; Anten, Niels P R

    2016-01-01

    Background and Aims The rising atmospheric CO2 concentration ([CO2]) is a ubiquitous selective force that may strongly impact species distribution and vegetation functioning. Plant–plant interactions could mediate the trajectory of vegetation responses to elevated [CO2], because some plants may bene

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-08-12

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

  3. Interaction between cardiac sympathetic afferent reflex and chemoreflex is mediated by the NTS AT1 receptors in heart failure.

    Science.gov (United States)

    Wang, Wei-Zhong; Gao, Lie; Wang, Han-Jun; Zucker, Irving H; Wang, Wei

    2008-09-01

    Several sympathoexcitatory reflexes, such as the cardiac sympathetic afferent reflex (CSAR) and arterial chemoreflex, are significantly augmented and contribute to elevated sympathetic outflow in chronic heart failure (CHF). This study was undertaken to investigate the interaction between the CSAR and the chemoreflex in CHF and to further identify the involvement of angiotensin II type 1 receptors (AT1Rs) in the nucleus of the tractus solitarius (NTS) in this interaction. CHF was induced in rats by coronary ligation. Acute experiments were performed in anesthetized rats. The chemoreflex-induced increase in cardiovascular responses was significantly greater in CHF than in sham-operated rats after either chemical or electrical activation of the CSAR. The inhibition of the CSAR by epicardial lidocaine reduced the chemoreflex-induced effects in CHF rats but not in sham-operated rats. Bilateral NTS injection of the AT1R antagonist losartan (10 and 100 pmol) dose-dependently decreased basal sympathetic nerve activity in CHF but not in sham-operated rats. This procedure also abolished the CSAR-induced enhancement of the chemoreflex. The discharge and chemosensitivity of NTS chemosensitive neurons were significantly increased following the stimulation of the CSAR in sham-operated and CHF rats, whereas CSAR inhibition by epicardial lidocaine significantly attenuated chemosensitivity of NTS neurons in CHF but not in sham-operated rats. Finally, the protein expression of AT1R in the NTS was significantly higher in CHF than in sham-operated rats. These results demonstrate that the enhanced cardiac sympathetic afferent input contributes to an excitatory effect of chemoreflex function in CHF, which is mediated by an NTS-AT1R-dependent mechanism.

  4. Close But Not Stuck: Understanding Social Distance in Human-Robot Interaction Through a Computer Mediation Approach

    Directory of Open Access Journals (Sweden)

    Daniel Haplem

    2013-01-01

    Full Text Available We draw on the social information processing (SIP model to argue that users’ earlier experiences with online social environments tend to attribute human-like characteristics to robots. Specifically, when users engage in socially-charged electronic environments to interact and communicate electronically with others, they find ways to overcome the relative lack of cues to adapt to the medium; this includes in terms of reacting to emotional relationships (Walther, 1997. We hypothesize that individuals who have a high sense of online community, engage with avatars and have higher levels of competence communicating with information and communication technologies (ICT, are more likely to recognize humanlike cues in robots. This in turn leads them to accept robots as part of their social and physical environments. A “robotic” social distance scale was developed to measure willingness to accept robots, and the results based on this scale, from an empirical study of college students (N = 874 are explored. The findings show that whereas avatar engagement and sense of online community have a strong effect on robots acceptance, recognition of human-like characteristics partially mediates the association between these concepts; this is even after accounting for predictors expected to affect attitudes toward robots such as religion, gender, age and robots’ appearance. The article ends by exploring the implications of this research for greater social acceptability of robots in various human domains.

  5. A new class of organogelators based on triphenylmethyl derivatives of primary alcohols: hydrophobic interactions alone can mediate gelation

    Directory of Open Access Journals (Sweden)

    Wangkhem P. Singh

    2017-01-01

    Full Text Available In the present work, we have explored the use of the triphenylmethyl group, a commonly used protecting group for primary alcohols as a gelling structural component in the design of molecular gelators. We synthesized a small library of triphenylmethyl derivatives of simple primary alcohols and studied their gelation properties in different solvents. Gelation efficiency for some of the derivatives was moderate to excellent with a minimum gelation concentration ranging between 0.5–4.0% w/v and a gel–sol transition temperature range of 31–75 °C. 1,8-Bis(trityloxyoctane, the ditrityl derivative of 1,8-octanediol was the most efficient organogelator. Detailed characterizations of the gel were carried out using scanning electron microscopy, FTIR spectroscopy, rheology and powder XRD techniques. This gel also showed a good absorption profile for a water soluble dye. Given the non-polar nature of this molecule, gel formation is likely to be mediated by hydrophobic interactions between the triphenylmethyl moieties and alkyl chains. Possible self-assembled packing arrangements in the gel state for 1,8-bis(trityloxyoctane and (hexadecyloxymethanetriyltribenzene are presented. Results from this study strongly indicate that triphenylmethyl group is a promising gelling structural unit which may be further exploited in the design of small molecule based gelators.

  6. An interaction between BZR1 and DELLAs mediates direct signaling crosstalk between brassinosteroids and gibberellins in Arabidopsis.

    Science.gov (United States)

    Li, Qian-Feng; Wang, Chunming; Jiang, Lei; Li, Shuo; Sun, Samuel S M; He, Jun-Xian

    2012-10-02

    Plant growth and development are coordinated by several groups of small-molecule hormones, including brassinosteroids (BRs) and gibberellins (GAs). Physiological and molecular studies have suggested the existence of crosstalk between BR and GA signaling. We report that BZR1, a key transcription factor activated by BR signaling, interacts in vitro and in vivo with REPRESSOR OF ga1-3 (RGA), a member of the DELLA family of transcriptional regulators that inhibits the GA signaling pathway in Arabidopsis thaliana. Genetic analyses of plants with mutations in the genes encoding RGA and BZR1 revealed that RGA suppressed root and hypocotyl elongation of the gain-of-function mutant bzr1-1D. Ectopic expression of proteins of the DELLA family reduced the abundance and transcriptional activity of BZR1. Reporter gene analyses further indicated that BZR1 and RGA antagonize each other's transcriptional activity. Our data indicated that BZR1 and RGA served as positive and negative regulators, respectively, of both the BR and the GA signaling pathways and establish DELLAs as mediators of signaling crosstalk between BRs and GAs in controlling cell elongation and regulation of plant growth.

  7. ENGLISH LEARNING TASKS MEDIATED BY THE INTERACTIVE WHITEBOARD: THE MOTIVATIONAL EFFECTS ON PROBLEM-SOLVING AND SHARING PERSONAL EXPERIENCES TASKS

    Directory of Open Access Journals (Sweden)

    Samara Freitas OLIVEIRA

    2014-06-01

    Full Text Available Some authors have already suggested that different learning tasks influence L2 learners motivation in distinct ways. In this article, we seek (a to understand how English learners motivation varies along two Problem-solving and Sharing Personal Experiences tasks mediated by the Interactive Whiteboard (IWB and (b to analyze what may have caused the variability of these learners motivation. We consider the diachronic, situational and complex dimension of motivation based on the concepts of the Process-oriented model of L2 motivation by Dörnyei and Ottó (1998, the motivational basis of tasks (JULKÜNEN, 2001; DÖRNYEI; TSENG, 2009 and the IWB as a motivating element in L2 classes (BEELAND JR., 2002; MERCER; HENNESSY; WARWICK, 2010. This cross-sectional mixed methods study was carried out in a private language school with 29 English learners. We used observation notes during the learning tasks and Situational Scales as instruments of data collection. Results indicate, for instance, that tasks have different situational motivation patterns in consequence of the choice of the task topic, the teacher support, (insufficient self-regulatory strategies to sustain motivation, among others.

  8. Girdin-mediated interactions between cadherin and the actin cytoskeleton are required for epithelial morphogenesis in Drosophila.

    Science.gov (United States)

    Houssin, Elise; Tepass, Ulrich; Laprise, Patrick

    2015-05-15

    E-cadherin-mediated cell-cell adhesion is fundamental for epithelial tissue morphogenesis, physiology and repair. E-cadherin is a core transmembrane constituent of the zonula adherens (ZA), a belt-like adherens junction located at the apicolateral border in epithelial cells. The anchorage of ZA components to cortical actin filaments strengthens cell-cell cohesion and allows for junction contractility, which shapes epithelial tissues during development. Here, we report that the cytoskeletal adaptor protein Girdin physically and functionally interacts with components of the cadherin-catenin complex during Drosophila embryogenesis. Fly Girdin is broadly expressed throughout embryonic development and enriched at the ZA in epithelial tissues. Girdin associates with the cytoskeleton and co-precipitates with the cadherin-catenin complex protein α-Catenin (α-Cat). Girdin mutations strongly enhance adhesion defects associated with reduced DE-cadherin (DE-Cad) expression. Moreover, the fraction of DE-Cad molecules associated with the cytoskeleton decreases in the absence of Girdin, thereby identifying Girdin as a positive regulator of adherens junction function. Girdin mutant embryos display isolated epithelial cell cysts and rupture of the ventral midline, consistent with defects in cell-cell cohesion. In addition, loss of Girdin impairs the collective migration of epithelial cells, resulting in dorsal closure defects. We propose that Girdin stabilizes epithelial cell adhesion and promotes morphogenesis by regulating the linkage of the cadherin-catenin complex to the cytoskeleton.

  9. The Influence of Receptor-Mediated Interactions on Reaction-Diffusion Mechanisms of Cellular Self-organisation

    KAUST Repository

    Klika, Václav

    2011-11-10

    Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction. © 2011 Society for Mathematical Biology.

  10. A new class of organogelators based on triphenylmethyl derivatives of primary alcohols: hydrophobic interactions alone can mediate gelation.

    Science.gov (United States)

    Singh, Wangkhem P; Singh, Rajkumar S

    2017-01-01

    In the present work, we have explored the use of the triphenylmethyl group, a commonly used protecting group for primary alcohols as a gelling structural component in the design of molecular gelators. We synthesized a small library of triphenylmethyl derivatives of simple primary alcohols and studied their gelation properties in different solvents. Gelation efficiency for some of the derivatives was moderate to excellent with a minimum gelation concentration ranging between 0.5-4.0% w/v and a gel-sol transition temperature range of 31-75 °C. 1,8-Bis(trityloxy)octane, the ditrityl derivative of 1,8-octanediol was the most efficient organogelator. Detailed characterizations of the gel were carried out using scanning electron microscopy, FTIR spectroscopy, rheology and powder XRD techniques. This gel also showed a good absorption profile for a water soluble dye. Given the non-polar nature of this molecule, gel formation is likely to be mediated by hydrophobic interactions between the triphenylmethyl moieties and alkyl chains. Possible self-assembled packing arrangements in the gel state for 1,8-bis(trityloxy)octane and (hexadecyloxymethanetriyl)tribenzene are presented. Results from this study strongly indicate that triphenylmethyl group is a promising gelling structural unit which may be further exploited in the design of small molecule based gelators.

  11. Plant structural complexity and mechanical defenses mediate predator-prey interactions in an odonate-bird system.

    Science.gov (United States)

    Grof-Tisza, Patrick; LoPresti, Eric; Heath, Sacha K; Karban, Richard

    2017-03-01

    Habitat-forming species provide refuges for a variety of associating species; these refuges may mediate interactions between species differently depending on the functional traits of the habitat-forming species. We investigated refuge provisioning by plants with different functional traits for dragonfly and damselfly (Odonata: Anisoptera and Zygoptera) nymphs emerging from water bodies to molt into their adult stage. During this period, nymphs experience high levels of predation by birds. On the shores of a small pond, plants with mechanical defenses (e.g., thorns and prickles) and high structural complexity had higher abundances of odonate exuviae than nearby plants which lacked mechanical defenses and exhibited low structural complexity. To disentangle the relative effects of these two potentially important functional traits on nymph emergence-site preference and survival, we conducted two fully crossed factorial field experiments using artificial plants. Nymphs showed a strong preference for artificial plants with high structural complexity and to a lesser extent, mechanical defenses. Both functional traits increased nymph survival but through different mechanisms. We suggest that future investigations attempt to experimentally separate the elements contributing to structural complexity to elucidate the mechanistic underpinnings of refuge provisioning.

  12. A Cytotoxic, Co-operative Interaction Between Energy Deprivation and Glutamate Release From System xc− Mediates Aglycemic Neuronal Cell Death

    Directory of Open Access Journals (Sweden)

    Trista L. Thorn

    2015-11-01

    Full Text Available The astrocyte cystine/glutamate antiporter (system xc− contributes substantially to the excitotoxic neuronal cell death facilitated by glucose deprivation. The purpose of this study was to determine the mechanism by which this occurred. Using pure astrocyte cultures, as well as, mixed cortical cell cultures containing both neurons and astrocytes, we found that neither an enhancement in system xc− expression nor activity underlies the excitotoxic effects of aglycemia. In addition, using three separate bioassays, we demonstrate no change in the ability of glucose-deprived astrocytes—either cultured alone or with neurons—to remove glutamate from the extracellular space. Instead, we demonstrate that glucose-deprived cultures are 2 to 3 times more sensitive to the killing effects of glutamate or N-methyl-D-aspartate when compared with their glucose-containing controls. Hence, our results are consistent with the weak excitotoxic hypothesis such that a bioenergetic deficiency, which is measureable in our mixed but not astrocyte cultures, allows normally innocuous concentrations of glutamate to become excitotoxic. Adding to the burgeoning literature detailing the contribution of astrocytes to neuronal injury, we conclude that under our experimental paradigm, a cytotoxic, co-operative interaction between energy deprivation and glutamate release from astrocyte system xc− mediates aglycemic neuronal cell death.

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

    Science.gov (United States)

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

    2006-07-18

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

  14. [Involvement of soluble mediators of inflammation in the pathogenic agent interaction--immune system in acute bacterial meningitis].

    Science.gov (United States)

    Lerescu, L; Tucureanu, C; Caraş, Iuliana; Pitica, Ramona; Ungureanu, Vasilica; Sălăgeanu, Aurora

    2008-01-01

    Acute Bacterial Meningitis is a medical emergency, which warrants early diagnosis and aggressive therapy, which in most cases must be initiated as an "empirical" treatment. Such an approach needs permanent epidemiological surveillance due to the major variability of the etiological agents depending upon time, geographical areas and demographic characteristics of the population. A program for the surveillance of meningitis is in progress in Romania, but the available clinical inbformation is incomplete and not well documented by paraclinical data, poorly reflecting the real incidence of the disease. The specific anatomic localization of the disease has major influences on the antiinfectious immune response. Inflammation is involved in the disease pathogenesis, especially in promotion and evolution of neurological sequelae (neuronal demyelinisation and degeneration) even in case of pathogen clearance following antimicrobial therapy. Activation of the immune response in a immunologically "privileged "region can lead to the break of tolerance and induction of autoimmunity (neuronal degenerescence). On the other hand, an efficient immune response is necessary for the clearance of pathogenic agents. A detailed investigation of the interaction between pathogenic agents and the immune system in relation to the particular meningeal localization and also a study on the involvement of soluble mediators of inflammation (cytokines, chemokines) in the pathogenesis of meningitis might prove useful for differential diagnosis (viral or "aseptic" meningitis) and also for elucidating the mechanisms which that underlie the disease pathogenesis/neurological complications.

  15. Biocontrol agents-mediated suppression of oxalic acid induced cell death during Sclerotinia sclerotiorum-pea interaction.

    Science.gov (United States)

    Jain, Akansha; Singh, Akanksha; Singh, Surendra; Sarma, Birinchi Kumar; Singh, Harikesh Bahadur

    2015-05-01

    Oxalic acid (OA) is an important pathogenic factor during early Sclerotinia sclerotiorum-host interaction and might work by reducing hydrogen peroxide production (H2 O2 ). In the present investigation, oxalic acid-induced cell death in pea was studied. Pea plants treated with biocontrol agents (BCAs) viz., Pseudomonas aeruginosa PJHU15, Bacillus subtilis BHHU100, and Trichoderma harzianum TNHU27 either singly and/or in consortium acted on S. sclerotiorum indirectly by enabling plants to inhibit the OA-mediated suppression of oxidative burst via induction of H2 O2 . Our results showed that BCA treated plants upon treatment with culture filtrate of the pathogen, conferred the resistance via. significantly decreasing relative cell death of pea against S. sclerotiorum compared to control plants without BCA treatment but treated with the culture filtrate of the pathogen. The results obtained from the present study indicate that the microbes especially in consortia play significant role in protection against S. sclerotiorum by modulating oxidative burst and partially enhancing tolerance by increasing the H2 O2 generation, which is otherwise suppressed by OA produced by the pathogen.

  16. A new class of organogelators based on triphenylmethyl derivatives of primary alcohols: hydrophobic interactions alone can mediate gelation

    Science.gov (United States)

    Singh, Wangkhem P

    2017-01-01

    In the present work, we have explored the use of the triphenylmethyl group, a commonly used protecting group for primary alcohols as a gelling structural component in the design of molecular gelators. We synthesized a small library of triphenylmethyl derivatives of simple primary alcohols and studied their gelation properties in different solvents. Gelation efficiency for some of the derivatives was moderate to excellent with a minimum gelation concentration ranging between 0.5–4.0% w/v and a gel–sol transition temperature range of 31–75 °C. 1,8-Bis(trityloxy)octane, the ditrityl derivative of 1,8-octanediol was the most efficient organogelator. Detailed characterizations of the gel were carried out using scanning electron microscopy, FTIR spectroscopy, rheology and powder XRD techniques. This gel also showed a good absorption profile for a water soluble dye. Given the non-polar nature of this molecule, gel formation is likely to be mediated by hydrophobic interactions between the triphenylmethyl moieties and alkyl chains. Possible self-assembled packing arrangements in the gel state for 1,8-bis(trityloxy)octane and (hexadecyloxymethanetriyl)tribenzene are presented. Results from this study strongly indicate that triphenylmethyl group is a promising gelling structural unit which may be further exploited in the design of small molecule based gelators. PMID:28228855

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  18. A Cytotoxic, Co-operative Interaction Between Energy Deprivation and Glutamate Release From System xc- Mediates Aglycemic Neuronal Cell Death.

    Science.gov (United States)

    Thorn, Trista L; He, Yan; Jackman, Nicole A; Lobner, Doug; Hewett, James A; Hewett, Sandra J

    2015-01-01

    The astrocyte cystine/glutamate antiporter (system xc(-)) contributes substantially to the excitotoxic neuronal cell death facilitated by glucose deprivation. The purpose of this study was to determine the mechanism by which this occurred. Using pure astrocyte cultures, as well as, mixed cortical cell cultures containing both neurons and astrocytes, we found that neither an enhancement in system xc(-) expression nor activity underlies the excitotoxic effects of aglycemia. In addition, using three separate bioassays, we demonstrate no change in the ability of glucose-deprived astrocytes--either cultured alone or with neurons--to remove glutamate from the extracellular space. Instead, we demonstrate that glucose-deprived cultures are 2 to 3 times more sensitive to the killing effects of glutamate or N-methyl-D-aspartate when compared with their glucose-containing controls. Hence, our results are consistent with the weak excitotoxic hypothesis such that a bioenergetic deficiency, which is measureable in our mixed but not astrocyte cultures, allows normally innocuous concentrations of glutamate to become excitotoxic. Adding to the burgeoning literature detailing the contribution of astrocytes to neuronal injury, we conclude that under our experimental paradigm, a cytotoxic, co-operative interaction between energy deprivation and glutamate release from astrocyte system xc(-) mediates aglycemic neuronal cell death.

  19. Culture as a mediator of gene-environment interaction: Cultural consonance, childhood adversity, a 2A serotonin receptor polymorphism, and depression in urban Brazil.

    Science.gov (United States)

    Dressler, William W; Balieiro, Mauro C; Ferreira de Araújo, Luiza; Silva, Wilson A; Ernesto Dos Santos, José

    2016-07-01

    Research on gene-environment interaction was facilitated by breakthroughs in molecular biology in the late 20th century, especially in the study of mental health. There is a reliable interaction between candidate genes for depression and childhood adversity in relation to mental health outcomes. The aim of this paper is to explore the role of culture in this process in an urban community in Brazil. The specific cultural factor examined is cultural consonance, or the degree to which individuals are able to successfully incorporate salient cultural models into their own beliefs and behaviors. It was hypothesized that cultural consonance in family life would mediate the interaction of genotype and childhood adversity. In a study of 402 adult Brazilians from diverse socioeconomic backgrounds, conducted from 2011 to 2014, the interaction of reported childhood adversity and a polymorphism in the 2A serotonin receptor was associated with higher depressive symptoms. Further analysis showed that the gene-environment interaction was mediated by cultural consonance in family life, and that these effects were more pronounced in lower social class neighborhoods. The findings reinforce the role of the serotonergic system in the regulation of stress response and learning and memory, and how these processes in turn interact with environmental events and circumstances. Furthermore, these results suggest that gene-environment interaction models should incorporate a wider range of environmental experience and more complex pathways to better understand how genes and the environment combine to influence mental health outcomes.

  20. Polymer-mediated interactions and their effect on the coagulation-fragmentation of nano-colloids: a self-consistent field theory approach.

    Science.gov (United States)

    Chervanyov, Alexander I

    2015-02-14

    This feature paper reviews our recent efforts to theoretically model the effect of polymer mediated interactions on the coagulation-fragmentation of nano-colloids in different settings encountered in practical systems. The polymer-mediated interactions among nanoparticles play a key role in many biological and technological processes such as red blood cell aggregation, protein crystallization, self-healing of polymer composites, filler reinforcement of rubbers used in tire technology, etc. By developing and making use of the novel potential theory, we investigate several important cases of these interactions acting between nanoparticles in diverse nano-polymer composites. As a demonstration of its practical applicability, we use the developed theory to investigate the effect of polymer mediated interactions on the coagulation-fragmentation of fillers and their kinetic stability in the presence of non-adsorbing and adsorbing polymers. In particular, we use our findings to develop a pragmatic way of evaluating the kinetic stability of nano-filler agglomerates critical for understanding the filler reinforcement of rubbers. Finally, we perform thorough comparison of the present theoretical findings with the available experimental data and simulations.

  1. Parasocial interaction with my avatar: effects of interdependent self-construal and the mediating role of self-presence in an avatar-based console game, Wii.

    Science.gov (United States)

    Jin, Seung-A Annie; Park, Namkee

    2009-12-01

    The "self" concept has grown increasingly important in interactive media environments. This study investigated self-related processes in an avatar-based game console, Wii. A key feature of the Wii is its motion-sensing capability that empowers players to manipulate and interact with items on-screen via movement. The present study examined the effects of video game players' self-construal on parasocial interaction with their avatars and feelings of self-presence. In this study, parasocial interaction was operationally defined as the extent of game players' interpersonal involvement with their avatar and the extent to which game players perceive themselves as interacting with the avatar. Self-presence was defined as the degree to which video game players feel as if their avatar on the screen were their real self. Based on an experiment, the study discovered that game players with high interdependent self-construal showed closer parasocial interaction and higher level of self-presence than those with low interdependent self-construal. Results also showed that self-presence mediated the effects of interdependent self-construal on the parasocial relationship with game players' avatars. Thus, the study discovered an important individual difference factor, interdependent self-construal, affecting the degree to which people form a parasocial relationship with their virtual self that is visually manifested in the form of an avatar. In addition, the present study added empirical evidence about the mediating role played by self-presence in avatar-based video games.

  2. NMDA and PACAP receptor signaling interact to mediate retinal-induced scn cellular rhythmicity in the absence of light.

    Directory of Open Access Journals (Sweden)

    Ian C Webb

    Full Text Available The "core" region of the suprachiasmatic nucleus (SCN, a central clock responsible for coordinating circadian rhythms, shows a daily rhythm in phosphorylation of extracellular regulated kinase (pERK. This cellular rhythm persists under constant darkness and, despite the absence of light, is dependent upon inputs from the eye. The neural signals driving this rhythmicity remain unknown and here the roles of glutamate and PACAP are examined. First, rhythmic phosphorylation of the NR1 NMDA receptor subunit (pNR1, a marker for receptor activation was shown to coincide with SCN core pERK, with a peak at circadian time (CT 16. Enucleation and intraocular TTX administration attenuated the peak in the pERK and pNR1 rhythms, demonstrating that activation of the NMDA receptor and ERK in the SCN core at CT16 are dependent on retinal inputs. In contrast, ERK and NR1 phosphorylation in the SCN shell region were unaffected by these treatments. Intraventricular administration of the NMDA receptor antagonist MK-801 also attenuated the peak in SCN core pERK, indicating that ERK phosphorylation in this region requires NMDA receptor activation. As PACAP is implicated in photic entrainment and is known to modulate glutamate signaling, the effects of a PAC1 receptor antagonist (PACAP 6-38 on SCN core pERK and pNR1 also were examined. PACAP 6-38 administration attenuated SCN core pERK and pNR1, suggesting that PACAP induces pERK directly, and indirectly via a modulation of NMDA receptor signaling. Together, these data indicate that, in the absence of light, retinal-mediated NMDA and PAC1 receptor activation interact to induce cellular rhythms in the SCN core. These results highlight a novel function for glutamate and PACAP release in the hamster SCN apart from their well-known roles in the induction of photic circadian clock resetting.

  3. The PE_PGRS Proteins of Mycobacterium tuberculosis Are Ca(2+) Binding Mediators of Host-Pathogen Interaction.

    Science.gov (United States)

    Yeruva, Veena C; Kulkarni, Apoorva; Khandelwal, Radhika; Sharma, Yogendra; Raghunand, Tirumalai R

    2016-08-23

    The phenomenal success of Mycobacterium tuberculosis (M.tb) as a pathogen is primarily based on its ability to modulate host immune responses. The genome of M.tb encodes multiple immunomodulatory proteins, including several members of the multigenic PE_PPE family of which the PE_PGRS proteins are a subset. Curiously, 56 of the 61 PE_PGRS proteins contain multiple copies of the glycine-rich sequence motif GGXGXD/NXUX, a nonapeptide sequence predicted to bind Ca(2+), but the functional significance of these motifs remains a mystery. Here we provide evidence via isothermal titration calorimetry, (45)Ca blotting, fluorescence, and circular dichroism spectroscopy that Ca(2+) binds to the PE_PGRS proteins, PE_PGRS33 (Rv1818c) (10 motifs) and PE_PGRS61 (Rv3653) (one motif). Ca(2+) was observed not to bind to PE_PGRS8 (Rv0742), which lacks nonapeptide motifs. Using recombinant Mycobacterium smegmatis strains expressing Rv1818c and Rv3653 and the THP-1 macrophage model of infection, we show that the two proteins mediate Ca(2+)-dependent upregulation of the anti-inflammatory cytokine IL-10, events critical to the pathogenesis of M.tb. Both Rv1818c and Rv3653 interact with TLR2 in a Ca(2+)-dependent manner, providing a novel mechanistic basis for their immunomodulatory effects. Mutations in the nonapeptide motif of Rv3653 led to compromised Ca(2+) binding, validating the functional criticality of this motif. This study demonstrates for the first time not only their Ca(2+) binding properties but also an essential role for Ca(2+) in the functioning of the M.tb PE_PGRS proteins, opening up the possibility of developing novel anti-tuberculosis therapeutics that inhibit Ca(2+)-PE_PGRS binding.

  4. Interaction of structure-specific and promiscuous G-protein-coupled receptors mediates small-molecule signaling in Caenorhabditis elegans.

    Science.gov (United States)

    Park, Donha; O'Doherty, Inish; Somvanshi, Rishi K; Bethke, Axel; Schroeder, Frank C; Kumar, Ujendra; Riddle, Donald L

    2012-06-19

    A chemically diverse family of small-molecule signals, the ascarosides, control developmental diapause (dauer), olfactory learning, and social behaviors of the nematode model organism, Caenorhabditis elegans. The ascarosides act upstream of conserved signaling pathways, including the insulin, TGF-β, serotonin, and guanylyl cyclase pathways; however, the sensory processes underlying ascaroside function are poorly understood. Because ascarosides often are multifunctional and show strongly synergistic effects, characterization of their receptors will be essential for understanding ascaroside biology and may provide insight into molecular mechanisms that produce synergistic outcomes in small-molecule sensing. Based on DAF-8 immunoprecipitation, we here identify two G-protein-coupled receptors, DAF-37 and DAF-38, which cooperatively mediate ascaroside perception. daf-37 mutants are defective in all responses to ascr#2, one of the most potent dauer-inducing ascarosides, although this mutant responds normally to other ascarosides. In contrast, daf-38 mutants are partially defective in responses to several different ascarosides. Through cell-specific overexpression, we show that DAF-37 regulates dauer when expressed in ASI neurons and adult behavior when expressed in ASK neurons. Using a photoaffinity-labeled ascr#2 probe and amplified luminescence assays (AlphaScreen), we demonstrate that ascr#2 binds to DAF-37. Photobleaching fluorescent energy transfer assays revealed that DAF-37 and DAF-38 form heterodimers, and we show that heterodimerization strongly increases cAMP inhibition in response to ascr#2. These results suggest that that the ascarosides' intricate signaling properties result in part from the interaction of highly structure-specific G-protein-coupled receptors such as DAF-37 with more promiscuous G-protein-coupled receptors such as DAF-38.

  5. Interaction of structure-specific and promiscuous G-protein–coupled receptors mediates small-molecule signaling in Caenorhabditis elegans

    Science.gov (United States)

    Park, Donha; O'Doherty, Inish; Somvanshi, Rishi K.; Bethke, Axel; Schroeder, Frank C.; Kumar, Ujendra; Riddle, Donald L.

    2012-01-01

    A chemically diverse family of small-molecule signals, the ascarosides, control developmental diapause (dauer), olfactory learning, and social behaviors of the nematode model organism, Caenorhabditis elegans. The ascarosides act upstream of conserved signaling pathways, including the insulin, TGF-β, serotonin, and guanylyl cyclase pathways; however, the sensory processes underlying ascaroside function are poorly understood. Because ascarosides often are multifunctional and show strongly synergistic effects, characterization of their receptors will be essential for understanding ascaroside biology and may provide insight into molecular mechanisms that produce synergistic outcomes in small-molecule sensing. Based on DAF-8 immunoprecipitation, we here identify two G-protein–coupled receptors, DAF-37 and DAF-38, which cooperatively mediate ascaroside perception. daf-37 mutants are defective in all responses to ascr#2, one of the most potent dauer-inducing ascarosides, although this mutant responds normally to other ascarosides. In contrast, daf-38 mutants are partially defective in responses to several different ascarosides. Through cell-specific overexpression, we show that DAF-37 regulates dauer when expressed in ASI neurons and adult behavior when expressed in ASK neurons. Using a photoaffinity-labeled ascr#2 probe and amplified luminescence assays (AlphaScreen), we demonstrate that ascr#2 binds to DAF-37. Photobleaching fluorescent energy transfer assays revealed that DAF-37 and DAF-38 form heterodimers, and we show that heterodimerization strongly increases cAMP inhibition in response to ascr#2. These results suggest that that the ascarosides' intricate signaling properties result in part from the interaction of highly structure-specific G-protein–coupled receptors such as DAF-37 with more promiscuous G-protein–coupled receptors such as DAF-38. PMID:22665789

  6. Surface defect mediated magnetic interactions and ferromagnetism in Cr/Co Co-doped ZnO nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Aljawfi, Rezq Naji, E-mail: rizqnaji@yahoo.com [Department of Physics, Aligarh Muslim University, Aligarh 202002 (India); Rahman, F. [Department of Physics, Aligarh Muslim University, Aligarh 202002 (India); Batoo, Khalid Mujasam [King Abdullah Institute for Nanotechnology, King Saud University (Saudi Arabia)

    2013-04-15

    We report the structural and ferromagnetic properties of Zn{sub 0.97−x}Cr{sub x}Co{sub 0.03}O (x=0.0, 0.03, 0.06 and 0.09) nanoparticles (NPs) synthesized through citric–gel route. X-ray diffraction (XRD) and selected area electron diffraction (SAED) results show the single phase nature with hexagonal wurtzite structure, and reveal the incorporation of Cr{sup 3+} and Co{sup 2+} ions into lattice positions of Zn{sup 2+} ions in ZnO lattice. The average size of NPs decreases from ∼24 to 9 nm with increasing Cr dopant concentrations (x). Micro-Raman and X-ray photoelectron spectroscopy (XPS) studies show the presence of oxygen vacancies (V{sub O}) defects. The XPS study shows interaction between Cr–Co dopant and transfer of electrons from Cr (3d) state to unfilled (3d) state of Co. The observed ferromagnetism is intrinsic in nature, and not due to any metallic segregation or impurity phase. The oxygen vacancies mediated the dopant ions interaction, and the ferromagnetism can be elucidated by bound magnetic polaron (BMP) mechanism. - Highlights: ► Nanoparticles Zn{sub 0.97−x}Cr{sub x}Co{sub 0.03}O (x=0.0, 0.03, 0.06 and 0.09) are synthesized through sol–gel route. ► Crystalline structure and single phase character are confirmed by XRD, SEM, TEM, SAED and EDAX techniques. ► Raman and UV–vis spectra reveal the incorporation of Cr and Co into the ZnO lattice structure. ► The oxygen vacancies are observed from XPS and Raman spectra but there is no evidence of Co metallic cluster or CoO. ► The observed ferromagnetism is intrinsic in nature and not due to any metallic Co segregation or cobalt oxide which can be explained by bound magnetic polaron (BMP) theory.

  7. CD47-signal regulatory protein-alpha (SIRP alpha) interactions form a barrier for antibody-mediated tumor cell destruction

    NARCIS (Netherlands)

    Zhao, Xi Wen; van Beek, Ellen M.; Schornagel, Karin; Van der Maaden, Hans; Van Houdt, Michel; Otten, Marielle A.; Finetti, Pascal; Van Egmond, Marjolein; Matozaki, Takashi; Kraal, Georg; Birnbaum, Daniel; van Elsas, Andrea; Kuijpers, Taco W.; Bertucci, Francois; van den Berg, Timo K.

    2011-01-01

    Monoclonal antibodies are among the most promising therapeutic agents for treating cancer. Therapeutic cancer antibodies bind to tumor cells, turning them into targets for immune-mediated destruction. We show here that this antibody-mediated killing of tumor cells is limited by a mechanism involving

  8. NOD1CARD Might Be Using Multiple Interfaces for RIP2-Mediated CARD-CARD Interaction: Insights from Molecular Dynamics Simulation

    Science.gov (United States)

    Pradhan, Sukanta Kumar; De, Sachinandan

    2017-01-01

    The nucleotide-binding and oligomerization domain (NOD)-containing protein 1 (NOD1) plays the pivotal role in host-pathogen interface of innate immunity and triggers immune signalling pathways for the maturation and release of pro-inflammatory cytokines. Upon the recognition of iE-DAP, NOD1 self-oligomerizes in an ATP-dependent fashion and interacts with adaptor molecule receptor-interacting protein 2 (RIP2) for the propagation of innate immune signalling and initiation of pro-inflammatory immune responses. This interaction (mediated by NOD1 and RIP2) helps in transmitting the downstream signals for the activation of NF-κB signalling pathway, and has been arbitrated by respective caspase-recruitment domains (CARDs). The so-called CARD-CARD interaction still remained contradictory due to inconsistent results. Henceforth, to understand the mode and the nature of the interaction, structural bioinformatics approaches were employed. MD simulation of modelled 1:1 heterodimeric complexes revealed that the type-Ia interface of NOD1CARD and the type-Ib interface of RIP2CARD might be the suitable interfaces for the said interaction. Moreover, we perceived three dynamically stable heterotrimeric complexes with an NOD1:RIP2 ratio of 1:2 (two numbers) and 2:1. Out of which, in the first trimeric complex, a type-I NOD1-RIP2 heterodimer was found interacting with an RIP2CARD using their type-IIa and IIIa interfaces. However, in the second and third heterotrimer, we observed type-I homodimers of NOD1 and RIP2 CARDs were interacting individually with RIP2CARD and NOD1CARD (in type-II and type-III interface), respectively. Overall, this study provides structural and dynamic insights into the NOD1-RIP2 oligomer formation, which will be crucial in understanding the molecular basis of NOD1-mediated CARD-CARD interaction in higher and lower eukaryotes. PMID:28114344

  9. Tumor necrosis factor alpha modulates the dynamics of the plasminogen-mediated early interaction between Bifidobacterium animalis subsp. lactis and human enterocytes.

    Science.gov (United States)

    Centanni, Manuela; Bergmann, Simone; Turroni, Silvia; Hammerschmidt, Sven; Chhatwal, Gursharan Singh; Brigidi, Patrizia; Candela, Marco

    2012-04-01

    The capacity to intervene with the host plasminogen system has recently been considered an important component in the interaction process between Bifidobacterium animalis subsp. lactis and the human host. However, its significance in the bifidobacterial microecology within the human gastrointestinal tract is still an open question. Here we demonstrate that human plasminogen favors the B. animalis subsp. lactis BI07 adhesion to HT29 cells. Prompting the HT29 cell capacity to activate plasminogen, tumor necrosis factor alpha (TNF-α) modulated the plasminogen-mediated bacterium-enterocyte interaction, reducing the bacterial adhesion to the enterocytes and enhancing migration to the luminal compartment.

  10. Orai1 mediates the interaction between STIM1 and hTRPC1 and regulates the mode of activation of hTRPC1-forming Ca2+ channels.

    Science.gov (United States)

    Jardin, Isaac; Lopez, José J; Salido, Gines M; Rosado, Juan A

    2008-09-12

    Orai1 and hTRPC1 have been presented as essential components of store-operated channels mediating highly Ca(2+) selective I(CRAC) and relatively Ca(2+) selective I(SOC), respectively. STIM1 has been proposed to communicate the Ca(2+) content of the intracellular Ca(2+) stores to the plasma membrane store-operated Ca(2+) channels. Here we present evidence for the dynamic interaction between endogenously expressed Orai1 and both STIM1 and hTRPC1 regulated by depletion of the intracellular Ca(2+) stores, using the pharmacological tools thapsigargin plus ionomycin, or by the physiological agonist thrombin, independently of extracellular Ca(2+). In addition we report that Orai1 mediates the communication between STIM1 and hTRPC1, which is essential for the mode of activation of hTRPC1-forming Ca(2+) permeable channels. Electrotransjection of cells with anti-Orai1 antibody, directed toward the C-terminal region that mediates the interaction with STIM1, and stabilization of an actin cortical barrier with jasplakinolide prevented the interaction between STIM1 and hTRPC1. Under these conditions hTRPC1 was no longer involved in store-operated calcium entry but in diacylglycerol-activated non-capacitative Ca(2+) entry. These findings support the functional role of the STIM1-Orai1-hTRPC1 complex in the activation of store-operated Ca(2+) entry.

  11. Nuclear import of cutaneous beta genus HPV8 E7 oncoprotein is mediated by hydrophobic interactions between its zinc-binding domain and FG nucleoporins

    Energy Technology Data Exchange (ETDEWEB)

    Onder, Zeynep; Moroianu, Junona, E-mail: moroianu@bc.edu

    2014-01-20

    We have previously discovered and characterized the nuclear import pathways for the E7 oncoproteins of mucosal alpha genus HPVs, type 16 and 11. Here we investigated the nuclear import of cutaneous beta genus HPV8 E7 protein using confocal microscopy after transfections of HeLa cells with EGFP-8E7 and mutant plasmids and nuclear import assays in digitonin-permeabilized HeLa cells. We determined that HPV8 E7 contains a nuclear localization signal (NLS) within its zinc-binding domain that mediates its nuclear import. Furthermore, we discovered that a mostly hydrophobic patch {sub 65}LRLFV{sub 69} within the zinc-binding domain is essential for the nuclear import and localization of HPV8 E7 via hydrophobic interactions with the FG nucleoporins Nup62 and Nup153. Substitution of the hydrophobic residues within the {sub 65}LRLFV{sub 69} patch to alanines, and not R66A mutation, disrupt the interactions between the 8E7 zinc-binding domain and Nup62 and Nup153 and consequently inhibit nuclear import of HPV8 E7. - Highlights: • HPV8 E7 has a cNLS within its zinc-binding domain that mediates its nuclear import. • Discovery of a hydrophobic patch that is critical for the nuclear import of HPV8 E7. • HPV8 E7 nuclear import is mediated by hydrophobic interactions with FG-Nups, Nup62 and Nup153.

  12. Investigation of cyclooxygenase and signaling pathways involved in human platelet aggregation mediated by synergistic interaction of various agonists.

    Science.gov (United States)

    Khan, Nadia; Farooq, Ahsana Dar; Sadek, Bassem

    2015-01-01

    In the present study, the mechanism(s) of synergistic interaction of various platelet mediators such as arachidonic acid (AA) when combined with 5-hydroxytryptamine (5-HT) or adenosine diphosphate (ADP) on human platelet aggregation were examined. The results demonstrated that 5-HT had no or negligible effect on aggregation but it did potentiate the aggregation response of AA. Similarly, the combination of subeffective concentrations of ADP and AA exhibited noticeable rise in platelet aggregation. Moreover, the observed synergistic effect of AA with 5-HT on platelets was inhibited by different cyclooxygenase (COX) inhibitors, namely ibuprofen and celecoxib, with half maximal inhibitory effect (IC50) values of 18.0 ± 1.8 and 15.6 ± 3.4 μmol/L, respectively. Interestingly, the synergistic effect observed for AA with 5-HT was, also, blocked by the 5-HT receptor blockers cyproheptadine (IC50=22.0 ± 7 μmol/L), ketanserin (IC50=152 ± 23 μmol/L), phospholipase C (PLC) inhibitor (U73122; IC50=6.1 ± 0.8 μmol/L), and mitogen activated protein kinase (MAPK) inhibitor (PD98059; IC50=3.8 ± 0.5 μmol/L). Likewise, the synergism of AA and ADP was, also, attenuated by COX inhibitors (ibuprofen; IC50=20 ± 4 μmol/L and celecoxib; IC50=24 ± 7 μmol/L), PLC inhibitor (U73122; IC50=3.7 ± 0.3 μmol/L), and MAPK inhibitor (PD98059; IC50=2.8 ± 1.1 μmol/L). Our observed data demonstrate that the combination of subthreshold concentrations of agonists amplifies platelet aggregation and that these synergistic effects largely depend on activation of COX/thromboxane A2, receptor-operated Ca(2+) channels, Gq/PLC, and MAPK signaling pathways. Moreover, our data revealed that inhibition of COX pathways by using both selective and/or non-selective COX inhibitors blocks not only AA metabolism and thromboxane A2 formation, but also its binding to Gq receptors and activation of receptor-operated Ca(2+) channels in platelets. Overall, our results show that PLC and MAPK inhibitors proved

  13. Complex Mediation

    DEFF Research Database (Denmark)

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...... that have helped to enrich our understanding of mediated work and the design of computer mediation for such work....

  14. Alveolar macrophage-epithelial cell interaction following exposure to atmospheric particles induces the release of mediators involved in monocyte mobilization and recruitment

    Directory of Open Access Journals (Sweden)

    Mukae Hiroshi

    2005-08-01

    Full Text Available Abstract Background Studies from our laboratory have shown that human alveolar macrophages (AM and bronchial epithelial cells (HBEC exposed to ambient particles (PM10 in vitro increase their production of inflammatory mediators and that supernatants from PM10-exposed cells shorten the transit time of monocytes through the bone marrow and promote their release into the circulation. Methods The present study concerns co-culture of AM and HBEC exposed to PM10 (EHC-93 and the production of mediators involved in monocyte kinetics measured at both the mRNA and protein levels. The experiments were also designed to determine the role of the adhesive interaction between these cells via the intercellular adhesion molecule (ICAM-1 in the production of these mediators. Results AM/HBEC co-cultures exposed to 100 μg/ml of PM10 for 2 or 24 h increased their levels of granulocyte-macrophage colony-stimulating factor (GM-CSF, M-CSF, macrophage inflammatory protein (MIP-1β, monocyte chemotactic protein (MCP-1, interleukin (IL-6 and ICAM-1 mRNA, compared to exposed AM or HBEC mono-cultures, or control non-exposed co-cultures. The levels of GM-CSF, M-CSF, MIP-1β and IL-6 increased in co-cultured supernatants collected after 24 h exposure compared to control cells (p 10-induced increase in co-culture mRNA expression. Conclusion We conclude that an ICAM-1 independent interaction between AM and HBEC, lung cells that process inhaled particles, increases the production and release of mediators that enhance bone marrow turnover of monocytes and their recruitment into tissues. We speculate that this interaction amplifies PM10-induced lung inflammation and contributes to both the pulmonary and systemic morbidity associated with exposure to air pollution.

  15. Predator effects on a detritus‐based food web are primarily mediated by non‐trophic interactions

    National Research Council Canada - National Science Library

    Majdi, Nabil; Boiché, Anatole; Traunspurger, Walter; Lecerf, Antoine; Rudolf, Volker

    2014-01-01

    .... Multiple lines of evidence suggest that, in detritus‐based food webs, non‐trophic interactions may prevail over purely trophic interactions in determining predator effects on plant litter decomposition...

  16. New insight to structure-function relationship of GalNAc mediated primary interaction between insecticidal Cry1Ac toxin and HaALP receptor of Helicoverpa armigera.

    Science.gov (United States)

    Sengupta, Anindita; Sarkar, Anindya; Priya, Prerna; Ghosh Dastidar, Shubhra; Das, Sampa

    2013-01-01

    Over the last few decades Cry1Ac toxin has been widely used in controlling the insect attack due to its high specificity towards target insects. The pore-forming toxin undergoes a complex mechanism in the insect midgut involving sequential interaction with specific glycosylated receptors in which terminal GalNAc molecule plays a vital role. Recent studies on Cry toxins interactions with specific receptors revealed the importance of several amino acid residues in domain III of Cry1Ac, namely Q509, N510, R511, Y513 and W545, serve as potential binding sites that surround the putative GalNAc binding pocket and mediate the toxin-receptor interaction. In the present study, alanine substitution mutations were generated in the Cry1Ac domain III region and functional significance of those key residues was monitored by insect bioassay on Helicoverpa armigera larvae. In addition, ligand blot analysis and SPR binding assay was performed to monitor the binding characteristics of Cry1Ac wild type and mutant toxins towards HaALP receptor isolated from Helicoverpa armigera. Mutagenesis data revealed that, alanine substitutions in R511, Y513 and W545 substantially impacted the relative affinity towards HaALP receptor and toxicity toward target insect. Furthermore, in silico study of GalNAc-mediated interaction also confirmed the important roles of these residues. This structural analysis will provide a detail insight for evaluating and engineering new generation Cry toxins to address the problem of change in insect behavioral patterns.

  17. Model of the Interplay of Band J-T Effect with Magnetic Order Mediated by Exchange Interaction

    OpenAIRE

    Reddy, G. Gangadhar; Ramakanth, A.; Ghatak, S. K.; Behera, S. N.; Nolting, W.; Rao, T. Venkatappa

    2006-01-01

    A model calculation is presented with the aim to study the interplay between magnetic and structural transitions. The model consists of an orbitally doubly degenerate conduction band and a periodic array of local moments. The band electrons interact with the local spins via the s-f interaction. The interaction of the band electrons with phonons is introduced by including band Jahn-Teller (J-T) interaction. The model Hamiltonian, including the above terms, is solved for the single particle Gre...

  18. Why E-Business Must Evolve beyond Market Orientation: Applying Human Interaction Models to Computer-Mediated Corporate Communications.

    Science.gov (United States)

    Johnston, Kevin McCullough

    2001-01-01

    Considers the design of corporate communications for electronic business and discusses the increasing importance of corporate interaction as companies work in virtual environments. Compares sociological and psychological theories of human interaction and relationship formation with organizational interaction theories of corporate relationship…

  19. The interaction of cytoplasmic poly(A)-binding protein with eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay.

    Science.gov (United States)

    Fatscher, Tobias; Boehm, Volker; Weiche, Benjamin; Gehring, Niels H

    2014-10-01

    Nonsense-mediated mRNA decay (NMD) eliminates different classes of mRNA substrates including transcripts with long 3' UTRs. Current models of NMD suggest that the long physical distance between the poly(A) tail and the termination codon reduces the interaction between cytoplasmic poly(A)-binding protein (PABPC1) and the eukaryotic release factor 3a (eRF3a) during translation termination. In the absence of PABPC1 binding, eRF3a recruits the NMD factor UPF1 to the terminating ribosome, triggering mRNA degradation. Here, we have used the MS2 tethering system to investigate the suppression of NMD by PABPC1. We show that tethering of PABPC1 between the termination codon and a long 3' UTR specifically inhibits NMD-mediated mRNA degradation. Contrary to the current model, tethered PABPC1 mutants unable to interact with eRF3a still efficiently suppress NMD. We find that the interaction of PABPC1 with eukaryotic initiation factor 4G (eIF4G), which mediates the circularization of mRNAs, is essential for NMD inhibition by tethered PABPC1. Furthermore, recruiting either eRF3a or eIF4G in proximity to an upstream termination codon antagonizes NMD. While tethering of an eRF3a mutant unable to interact with PABPC1 fails to suppress NMD, tethered eIF4G inhibits NMD in a PABPC1-independent manner, indicating a sequential arrangement of NMD antagonizing factors. In conclusion, our results establish a previously unrecognized link between translation termination, mRNA circularization, and NMD suppression, thereby suggesting a revised model for the activation of NMD at termination codons upstream of long 3' UTR. © 2014 Fatscher et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  20. Endocytic Recycling Proteins EHD1 and EHD2 Interact with Fer-1-like-5 (Fer1L5) and Mediate Myoblast Fusion*

    Science.gov (United States)

    Posey, Avery D.; Pytel, Peter; Gardikiotes, Konstantina; Demonbreun, Alexis R.; Rainey, Mark; George, Manju; Band, Hamid; McNally, Elizabeth M.

    2011-01-01

    The mammalian ferlins are calcium-sensing, C2 domain-containing proteins involved in vesicle trafficking. Myoferlin and dysferlin regulate myoblast fusion and muscle membrane resealing, respectively. Correspondingly, myoferlin is most highly expressed in singly nucleated myoblasts, whereas dysferlin expression is increased in mature, multinucleated myotubes. Myoferlin also mediates endocytic recycling and participates in trafficking the insulin-like growth factor receptor. We have now characterized a novel member of the ferlin family, Fer1L5, because of its high homology to dysferlin and myoferlin. We found that Fer1L5 protein is expressed in small myotubes that contain only two to four nuclei. We also found that Fer1L5 protein binds directly to the endocytic recycling proteins EHD1 and EHD2 and that the second C2 domain in Fer1L5 mediates this interaction. Reduction of EHD1 and/or EHD2 inhibits myoblast fusion, and EHD2 is required for normal translocation of Fer1L5 to the plasma membrane. The characterization of Fer1L5 and its interaction with EHD1 and EHD2 underscores the complex requirement of ferlin proteins and mediators of endocytic recycling for membrane trafficking events during myotube formation. PMID:21177873

  1. Endocytic recycling proteins EHD1 and EHD2 interact with fer-1-like-5 (Fer1L5) and mediate myoblast fusion.

    Science.gov (United States)

    Posey, Avery D; Pytel, Peter; Gardikiotes, Konstantina; Demonbreun, Alexis R; Rainey, Mark; George, Manju; Band, Hamid; McNally, Elizabeth M

    2011-03-01

    The mammalian ferlins are calcium-sensing, C2 domain-containing proteins involved in vesicle trafficking. Myoferlin and dysferlin regulate myoblast fusion and muscle membrane resealing, respectively. Correspondingly, myoferlin is most highly expressed in singly nucleated myoblasts, whereas dysferlin expression is increased in mature, multinucleated myotubes. Myoferlin also mediates endocytic recycling and participates in trafficking the insulin-like growth factor receptor. We have now characterized a novel member of the ferlin family, Fer1L5, because of its high homology to dysferlin and myoferlin. We found that Fer1L5 protein is expressed in small myotubes that contain only two to four nuclei. We also found that Fer1L5 protein binds directly to the endocytic recycling proteins EHD1 and EHD2 and that the second C2 domain in Fer1L5 mediates this interaction. Reduction of EHD1 and/or EHD2 inhibits myoblast fusion, and EHD2 is required for normal translocation of Fer1L5 to the plasma membrane. The characterization of Fer1L5 and its interaction with EHD1 and EHD2 underscores the complex requirement of ferlin proteins and mediators of endocytic recycling for membrane trafficking events during myotube formation.

  2. Nuclear export signal-interacting protein forms complexes with lamin A/C-Nups to mediate the CRM1-independent nuclear export of large hepatitis delta antigen.

    Science.gov (United States)

    Huang, Cheng; Jiang, Jia-Yin; Chang, Shin C; Tsay, Yeou-Guang; Chen, Mei-Ru; Chang, Ming-Fu

    2013-02-01

    Nuclear export is an important process that not only regulates the functions of cellular factors but also facilitates the assembly of viral nucleoprotein complexes. Chromosome region maintenance 1 (CRM1) that mediates the transport of proteins bearing the classical leucine-rich nuclear export signal (NES) is the best-characterized nuclear export receptor. Recently, several CRM1-independent nuclear export pathways were also identified. The nuclear export of the large form of hepatitis delta antigen (HDAg-L), a nucleocapsid protein of hepatitis delta virus (HDV), which contains a CRM1-independent proline-rich NES, is mediated by the host NES-interacting protein (NESI). The mechanism of the NESI protein in mediating nuclear export is still unknown. In this study, NESI was characterized as a highly glycosylated membrane protein. It interacted and colocalized well in the nuclear envelope with lamin A/C and nucleoporins. Importantly, HDAg-L could be coimmunoprecipitated with lamin A/C and nucleoporins. In addition, binding of the cargo HDAg-L to the C terminus of NESI was detected for the wild-type protein but not for the nuclear export-defective HDAg-L carrying a P205A mutation [HDAg-L(P205A)]. Knockdown of lamin A/C effectively reduced the nuclear export of HDAg-L and the assembly of HDV. These data indicate that by forming complexes with lamin A/C and nucleoporins, NESI facilitates the CRM1-independent nuclear export of HDAg-L.

  3. Peer-Mediated Intervention for the Development of Social Interaction Skills in High-Functioning Autism Spectrum Disorder: A Pilot Study

    Science.gov (United States)

    Rodríguez-Medina, Jairo; Martín-Antón, Luis J.; Carbonero, Miguel A.; Ovejero, Anastasio

    2016-01-01

    Autism Spectrum Disorder (ASD) is characterized by difficulties with social interaction and communication, which manifest at school especially in less structured situations such as recess. Recess provides opportunities for relationship with peers in a natural context, for which students with ASD may not be equipped with the necessary skills to use without support. Using a single-case design, we evaluated an intervention applied in recess to improve the social interaction skills of a student with high-functioning ASD mediated by his peers without ASD, in second grade of elementary school. This intervention includes different strategies to initiate the peers without ASD, using direct instruction, modeling, and social reinforcement carried out in the recess setting. After 14 sessions, changes were observed in the rates of initiating and responding to interactions, and a negative trend in the percentage of time that the student maintained low-intensity interactions or was alone. Teachers and family perceived improvements in social skills, more peer acceptance, and increase in the frequency and duration of social interactions. This intervention can help teachers to apply research-based practices to improve some social interaction skills in high-functioning students with autism in inclusive school environments. PMID:28066303

  4. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions...... interaction between a human operator and an artificial actor or agent. We can apply insights from puppetry to develop culturally-aware robots. Here we describe the development of a robotic marionette theatre wherein robotic controllers assume the role of human puppeteers. The system has been built, tested...

  5. Functional interaction between hMYH and hTRADD in the TNF-α-mediated survival and death pathways of HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Vy Tran, An Hue; Hahm, Soo-Hyun; Han, Se Hee [Department of Advanced Technology Fusion, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701 (Korea, Republic of); Chung, Ji Hyung [Department of Applied Bioscience, College of Life Science, CHA University, Gyeonggi-do 463-836 (Korea, Republic of); Park, Geon Tae [Cornell University, Ithaca, NY 14850 (United States); Han, Ye Sun, E-mail: yshan@konkuk.ac.kr [College of Global Integrated Studies, Division of Interdisciplinary Studies, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701 (Korea, Republic of)

    2015-07-15

    Highlights: • We determine the interaction between hMYH and hTRADD. • We examine changes in the level of hMYH–hTRADD interaction under TNF-α treatment. • hTRADD–hMYH association is involved in the nuclear translocation of NFκB. • hTRADD–hMYH complex influences the TNFR1–TRADD association. - Abstract: The tumor necrosis factor (TNF) signaling pathway is a classical immune system pathway that plays a key role in regulating cell survival and apoptosis. The TNF receptor-associated death domain (TRADD) protein is recruited to the death domain of TNF receptor 1 (TNFR1), where it interacts with TNF receptor-associated factor 2 (TRAF2) and receptor-interacting protein (RIP) for the induction of apoptosis, necrosis, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and mitogen-activated protein (MAP) kinase activation. In this study, we found that the human MutY homolog (hMYH) interacted with human TRADD (hTRADD) via the C-terminal domain of hMYH. Moreover, under conditions promoting TNF-α-induced cell death or survival in HeLa cells, this interaction was weakened or enhanced, respectively. The interaction between hMYH and hTRADD was important for signaling pathways mediated by TNF-α. Our results also suggested that the hTRADD–hMYH association was involved in the nuclear translocation of NFκB and formation of the TNFR1–TRADD complex. Thus, this study identified a novel mechanism through which the hMYH–hTRADD interaction may affect the TNF-α signaling pathway. Implications: In HeLa cells, the hTRADD–hMYH interaction functioned in both cell survival and apoptosis pathways following TNF-α stimulation.

  6. Applying Positioning Theory to the Analysis of Classroom Interactions: Mediating Micro-Identities, Macro-Kinds, and Ideologies of Knowing

    Science.gov (United States)

    Anderson, Kate T.

    2009-01-01

    This study contributes to positioning theory by approaching the discursive and material mediation of classroom positioning from an integrated micro-, meso-, and macro-social perspective. I propose an analytic framework that unpacks the lived and ideological resources for positioning and their social and curricular implications for understanding…

  7. Unequally redundant RCD1 and SRO1 mediate stress and developmental responses and interact with transcription factors

    NARCIS (Netherlands)

    Jaspers, P.; Blomster, T.; Brosché, M.; Salojärvi, J.; Ahlfors, R.; Vainonen, J.P.; Reddy, R.A.; Immink, G.H.; Angenent, G.C.; Turck, F.; Overmyer, K.; Kangasjärvi, J.

    2009-01-01

    RADICAL-INDUCED CELL DEATH1 (RCD1) is an important regulator of stress and hormonal and developmental responses in Arabidopsis thaliana. Together with its closest homolog, SIMILAR TO RCD-ONE1 (SRO1), it is the only Arabidopsis protein containing the WWE domain, which is known to mediate protein–prot

  8. On the passage of time : Temporal differences in video-mediated and face-to-face interaction

    NARCIS (Netherlands)

    Kleij, R. van der; Paashuis, R.M.; Schraagen, J.M.C.

    2005-01-01

    This paper examines team work over time in video-mediated non-collocated and traditional face-to-face same-room teams. In a longitudinal between-groups design, 22 three-person teams were tested in 4 1-h test sessions at 2-week intervals. A paper-folding task was designed for the experiment that had

  9. Holocarboxylase synthetase is a chromatin protein and interacts directly with histone H3 to mediate biotinylation of K9 and K18.

    Science.gov (United States)

    Bao, Baolong; Pestinger, Valerie; Hassan, Yousef I; Borgstahl, Gloria E O; Kolar, Carol; Zempleni, Janos

    2011-05-01

    Holocarboxylase synthetase (HCS) mediates the binding of biotin to lysine (K) residues in histones H2A, H3 and H4; HCS knockdown disturbs gene regulation and decreases stress resistance and lifespan in eukaryotes. We tested the hypothesis that HCS interacts physically with histone H3 for subsequent biotinylation. Co-immunoprecipitation experiments were conducted and provided evidence that HCS co-localizes with histone H3 in human cells; physical interactions between HCS and H3 were confirmed using limited proteolysis assays. Yeast two-hybrid (Y2H) studies revealed that the N-terminal and C-terminal domains in HCS participate in H3 binding. Recombinant human HCS was produced and exhibited biological activity, as evidenced by biotinylation of its known substrate, recombinant p67. Recombinant histone H3.2 and synthetic H3-based peptides were also good targets for biotinylation by recombinant HCS (rHCS) in vitro, based on tracing histone-bound biotin with [(3)H]biotin, streptavidin and anti-biotin antibody. Biotinylation site-specific antibodies were generated and revealed that both K9 and K18 in H3 were biotinylated by HCS. Collectively, these studies provide conclusive evidence that HCS interacts directly with histone H3, causing biotinylation of K9 and K18. We speculate that the targeting of HCS to distinct regions in human chromatin is mediated by DNA sequence, biotin, RNA, epigenetic marks or chromatin proteins.

  10. The same periplasmic ExbD residues mediate in vivo interactions between ExbD homodimers and ExbD-TonB heterodimers.

    Science.gov (United States)

    Ollis, Anne A; Postle, Kathleen

    2011-12-01

    The TonB system couples cytoplasmic membrane proton motive force to TonB-gated outer membrane transporters for active transport of nutrients into the periplasm. In Escherichia coli, cytoplasmic membrane proteins ExbB and ExbD promote conformational changes in TonB, which transmits this energy to the transporters. The only known energy-dependent interaction occurs between the periplasmic domains of TonB and ExbD. This study identified sites of in vivo homodimeric interactions within ExbD periplasmic domain residues 92 to 121. ExbD was active as a homodimer (ExbD(2)) but not through all Cys substitution sites, suggesting the existence of conformationally dynamic regions in the ExbD periplasmic domain. A subset of homodimeric interactions could not be modeled on the nuclear magnetic resonance (NMR) structure without significant distortion. Most importantly, the majority of ExbD Cys substitutions that mediated homodimer formation also mediated ExbD-TonB heterodimer formation with TonB A150C. Consistent with the implied competition, ExbD homodimer formation increased in the absence of TonB. Although ExbD D25 was not required for their formation, ExbD dimers interacted in vivo with ExbB. ExbD-TonB interactions required ExbD transmembrane domain residue D25. These results suggested a model where ExbD(2) assembled with ExbB undergoes a transmembrane domain-dependent transition and exchanges partners in localized homodimeric interfaces to form an ExbD(2)-TonB heterotrimer. The findings here were also consistent with our previous hypothesis that ExbD guides the conformation of the TonB periplasmic domain, which itself is conformationally dynamic.

  11. The Same Periplasmic ExbD Residues Mediate In Vivo Interactions between ExbD Homodimers and ExbD-TonB Heterodimers ▿ †

    Science.gov (United States)

    Ollis, Anne A.; Postle, Kathleen

    2011-01-01

    The TonB system couples cytoplasmic membrane proton motive force to TonB-gated outer membrane transporters for active transport of nutrients into the periplasm. In Escherichia coli, cytoplasmic membrane proteins ExbB and ExbD promote conformational changes in TonB, which transmits this energy to the transporters. The only known energy-dependent interaction occurs between the periplasmic domains of TonB and ExbD. This study identified sites of in vivo homodimeric interactions within ExbD periplasmic domain residues 92 to 121. ExbD was active as a homodimer (ExbD2) but not through all Cys substitution sites, suggesting the existence of conformationally dynamic regions in the ExbD periplasmic domain. A subset of homodimeric interactions could not be modeled on the nuclear magnetic resonance (NMR) structure without significant distortion. Most importantly, the majority of ExbD Cys substitutions that mediated homodimer formation also mediated ExbD-TonB heterodimer formation with TonB A150C. Consistent with the implied competition, ExbD homodimer formation increased in the absence of TonB. Although ExbD D25 was not required for their formation, ExbD dimers interacted in vivo with ExbB. ExbD-TonB interactions required ExbD transmembrane domain residue D25. These results suggested a model where ExbD2 assembled with ExbB undergoes a transmembrane domain-dependent transition and exchanges partners in localized homodimeric interfaces to form an ExbD2-TonB heterotrimer. The findings here were also consistent with our previous hypothesis that ExbD guides the conformation of the TonB periplasmic domain, which itself is conformationally dynamic. PMID:21984795

  12. Tomato 14-3-3 protein TFT7 interacts with a MAP kinase kinase to regulate immunity-associated programmed cell death mediated by diverse disease resistance proteins.

    Science.gov (United States)

    Oh, Chang-Sik; Martin, Gregory B

    2011-04-22

    Programmed cell death (PCD) associated with immunity is triggered when a plant disease resistance (R) protein recognizes a corresponding pathogen virulence protein. In tomato, detection by the host Pto kinase of the Pseudomonas syringae proteins AvrPto or AvrPtoB causes localized PCD. Previously, we reported that both MAPKKKα (mitogen-activated protein kinase kinase kinase) and the tomato 14-3-3 protein 7 (TFT7) positively regulate Pto-mediated PCD in tomato and Nicotiana benthamiana. In addition, in contrast to MAPKKKα, TFT7 is required for PCD mediated by four other R proteins. Here we investigate why TFT7 is required for PCD induced by diverse R proteins in plants. We discovered that a MAPKK, SlMKK2, which acts downstream of SlMAPKKKα, also interacts with TFT7 in plant cells. Gene silencing experiments revealed that the orthologous genes of both SlMKK2 and TFT7 in N. benthamiana are required for PCD mediated by the same set of R proteins. SlMKK2 and its orthologs contain a 14-3-3 binding site in their N terminus, and Thr(33) in this site is required for interaction with TFT7 in vivo. Like the structurally similar human 14-3-3ε protein, TFT7 forms a homodimer in vivo. Because TFT7 interacts with both SlMAPKKKα and SlMKK2 and also forms a homodimer, we propose that TFT7 may coordinately recruit these client proteins for efficient signal transfer, leading to PCD induction.

  13. OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Wenbin [Department of Biotechnology, Jinan University, Guangzhou 510632 (China); Zhou, You [Minerva Foundation Institute for Medical Research, Helsinki (Finland); Li, Jiwei [Department of Biotechnology, Jinan University, Guangzhou 510632 (China); Mysore, Raghavendra [Minerva Foundation Institute for Medical Research, Helsinki (Finland); Luo, Wei; Li, Shiqian [Department of Biotechnology, Jinan University, Guangzhou 510632 (China); Chang, Mau-Sun [Institute of Biochemical Sciences, National Taiwan University, No. 1, Taipei, Taiwan (China); Olkkonen, Vesa M. [Minerva Foundation Institute for Medical Research, Helsinki (Finland); Yan, Daoguang, E-mail: tydg@jnu.edu.cn [Department of Biotechnology, Jinan University, Guangzhou 510632 (China)

    2014-04-01

    We earlier identified OSBP-related protein 8 (ORP8) as an endoplasmic reticulum/nuclear envelope oxysterol-binding protein implicated in cellular lipid homeostasis, migration, and organization of the microtubule cytoskeleton. Here, a yeast two-hybrid screen identified Homo sapiens sperm associated antigen 5 (SPAG5)/Astrin as interaction partner of ORP8. The putative interaction was further confirmed by pull-down and co-immunoprecipitation assays. ORP8 did not colocalize with kinetochore-associated SPAG5 in mitotic HepG2 or HuH7 cells, but overexpressed ORP8 was capable of recruiting SPAG5 onto endoplasmic reticulum membranes in interphase cells. In our experiments, 25-hydroxycholesterol (25OHC) retarded the HepG2 cell cycle, causing accumulation in G2/M phase; ORP8 overexpression resulted in the same phenotype. Importantly, ORP8 knock-down dramatically inhibited the oxysterol effect on HepG2 cell cycle, suggesting a mediating role of ORP8. Furthermore, knock-down of SPAG5 significantly reduced the effects of both ORP8 overexpression and 25OHC on the cell cycle, placing SPAG5 downstream of the two cell-cycle interfering factors. Taken together, the present results suggest that ORP8 may via SPAG5 mediate oxysterol interference of the HepG2 cell cycle. - Highlights: • The oxysterol-binding protein ORP8 was found to interact with the mitotic regulator SPAG5/Astrin. • Treatment of HepG2 cells with 25-hydroxycholesterol caused cell cycle retardation in G2/M. • ORP8 overexpression caused a similar G2/M accumulation, and ORP8 knock-down reversed the 25-hydroxycholesterol effect. • Reduction of cellular of SPAG5/Astrin reversed the cell cycle effects of both 25-hydroxycholesterol and ORP8 overexpression. • Our results suggest that ORP8 mediates via SPAG5/Astrin the oxysterol interference of HepG2 cell cycle.

  14. Interaction among two subpopulations of Ehrlich ascites tumor in vivo: evidence of a contact mediated immune response

    DEFF Research Database (Denmark)

    Aabo, K; Vindeløv, L L; Skovsgaard, T

    1987-01-01

    Clonal interaction among two subpopulations of Ehrlich ascites carcinoma was studied during in vivo growth in immune competent N/D mice in which the cell lines had been propagated for several years as ascites tumors. A growth inhibitory interaction by a subcutaneously slow growing subpopulation (E1...

  15. Designing Smart Artifacts for Adaptive Mediation of Social Viscosity: Triadic Actor-Network Enactments as a Basis for Interaction Design

    Science.gov (United States)

    Salamanca, Juan

    2012-01-01

    With the advent of ubiquitous computing, interaction design has broadened its object of inquiry into how smart computational artifacts inconspicuously act in people's everyday lives. Although user-centered design approaches remains useful for exploring how people cope with interactive systems, they cannot explain how this new breed of…

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed by these r......Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed......-immune traits to assess its applicability to complex traits in general. We find that genes in loci associated to height and lipid levels assemble into significantly connected networks but did not detect excess connectivity among Type 2 Diabetes (T2D) loci beyond chance. Taken together, our results constitute...

  17. LyGDI, a novel SHIP-interacting protein, is a negative regulator of FcγR-mediated phagocytosis.

    Science.gov (United States)

    Mehta, Payal; Wavreille, Anne-Sophie; Justiniano, Steven E; Marsh, Rachel L; Yu, Jianhua; Burry, Richard W; Jarjoura, David; Eubank, Timothy; Caligiuri, Michael A; Butchar, Jonathan P; Tridandapani, Susheela

    2011-01-01

    SHIP and SHIP-2 are inositol phosphatases that regulate FcγR-mediated phagocytosis through catalytic as well as non-catalytic mechanisms. In this study we have used two-dimensional fluorescence difference gel electrophoresis (DIGE) analysis to identify downstream signaling proteins that uniquely associate with SHIP or SHIP-2 upon FcγR clustering in human monocytes. We identified LyGDI as a binding partner of SHIP, associating inducibly with the SHIP/Grb2/Shc complex. Immunodepletion and competition experiments with recombinant SHIP domains revealed that Grb2 and the proline-rich domain of SHIP were necessary for SHIP-LyGDI association. Functional studies in primary human monocytes showed that LyGDI sequesters Rac in the cytosol, preventing it from localizing to the membrane. Consistent with this, suppression of LyGDI expression resulted in significantly enhanced FcγR-mediated phagocytosis.

  18. LyGDI, a novel SHIP-interacting protein, is a negative regulator of FcγR-mediated phagocytosis.

    Directory of Open Access Journals (Sweden)

    Payal Mehta

    Full Text Available SHIP and SHIP-2 are inositol phosphatases that regulate FcγR-mediated phagocytosis through catalytic as well as non-catalytic mechanisms. In this study we have used two-dimensional fluorescence difference gel electrophoresis (DIGE analysis to identify downstream signaling proteins that uniquely associate with SHIP or SHIP-2 upon FcγR clustering in human monocytes. We identified LyGDI as a binding partner of SHIP, associating inducibly with the SHIP/Grb2/Shc complex. Immunodepletion and competition experiments with recombinant SHIP domains revealed that Grb2 and the proline-rich domain of SHIP were necessary for SHIP-LyGDI association. Functional studies in primary human monocytes showed that LyGDI sequesters Rac in the cytosol, preventing it from localizing to the membrane. Consistent with this, suppression of LyGDI expression resulted in significantly enhanced FcγR-mediated phagocytosis.

  19. Sucrose Production Mediated by Lipid Metabolism Suppresses the Physical Interaction of Peroxisomes and Oil Bodies during Germination of Arabidopsis thaliana.

    Science.gov (United States)

    Cui, Songkui; Hayashi, Yasuko; Otomo, Masayoshi; Mano, Shoji; Oikawa, Kazusato; Hayashi, Makoto; Nishimura, Mikio

    2016-09-16

    Physical interaction between organelles is a flexible event and essential for cells to adapt rapidly to environmental stimuli. Germinating plants utilize oil bodies and peroxisomes to mobilize storage lipids for the generation of sucrose as the main energy source. Although membrane interaction between oil bodies and peroxisomes has been widely observed, its underlying molecular mechanism is largely unknown. Here we present genetic evidence for control of the physical interaction between oil bodies and peroxisomes. We identified alleles of the sdp1 mutant altered in oil body morphology. This mutant accumulates bigger and more oil body aggregates compared with the wild type and showed defects in lipid mobilization during germination. SUGAR DEPENDENT 1 (SDP1) encodes major triacylglycerol lipase in Arabidopsis Interestingly, sdp1 seedlings show enhanced physical interaction between oil bodies and peroxisomes compared with the wild type, whereas exogenous sucrose supplementation greatly suppresses the interaction. The same phenomenon occurs in the peroxisomal defective 1 (ped1) mutant, defective in lipid mobilization because of impaired peroxisomal β-oxidation, indicating that sucrose production is a key factor for oil body-peroxisomal dissociation. Peroxisomal dissociation and subsequent release from oil bodies is dependent on actin filaments. We also show that a peroxisomal ATP binding cassette transporter, PED3, is the potential anchor protein to the membranes of these organelles. Our results provide novel components linking lipid metabolism and oil body-peroxisome interaction whereby sucrose may act as a negative signal for the interaction of oil bodies and peroxisomes to fine-tune lipolysis.

  20. 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.

  1. Interactions

    DEFF Research Database (Denmark)

    The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists...... such as Lorentz and Einstein as well as mathematicians such as Poincare, Minkowski, Hilbert and Weyl contributed to this development. They created the new physical theories and the mathematical disciplines that play such paramount roles in their mathematical formulations. These physicists and mathematicians were...

  2. Entecavir interacts with influx transporters hOAT1, hCNT2, hCNT3, but not with hOCT2: the potential for renal transporter-mediated cytotoxicity and drug-drug interactions

    Directory of Open Access Journals (Sweden)

    František eTrejtnar

    2016-01-01

    Full Text Available Entecavir (ETV is one of the most potent agents for the treatment of the hepatitis B viral infection. The drug is principally eliminated by the kidney. The goal of this study was to investigate the potential of ETV to interact in vitro with the renal SLC transporters hOAT1, hOCT2, hCNT2 and hCNT3. Potential drug-drug interactions of ETV at the renal transporters with antiviral drugs known to be excreted by the kidney (adefovir, tenofovir, cidofovir as well as transporter-dependent cytotoxicity were also examined. Interactions with the selected transporters along with cytotoxicity were studied in several transiently-transfected cellular models using specific substrates and inhibitors. ETV was found to be both a substrate and inhibitor of hOAT1 (IC50 = 175.3 µM, hCNT2 (IC50 = 241.9 µM and hCNT3 (IC50 = 278.4 µM transporters, although it interacted with the transporters with relatively low affinities. ETV inhibited the cellular uptake of adefovir, tenofovir and cidofovir by hOAT1; however, effective inhibition was shown at ETV concentrations exceeding therapeutic levels. In comparison with adefovir, tenofovir and cidofovir, ETV displayed no transporter-mediated cytotoxicity in cells transfected with hOAT1, hCNT2, and hCNT3. No significant interaction of ETV with hOCT2 was detected. The study demonstrates interactions of ETV with several human renal transporters. For the first time, an interaction of ETV with the hCNTs was proved. We show that the potency of ETV to cause nephrotoxicity and/or clinically significant drug-drug interactions related to the tested transporters is considerably lower than that of adefovir, tenofovir and cidofovir.

  3. Inositol hexakisphosphate (IP6) generated by IP5K mediates cullin-COP9 signalosome interactions and CRL function

    National Research Council Canada - National Science Library

    Paul C. Scherer; Yan Ding; Zhiqing Liu; Jing Xu; Haibin Mao; James C. Barrow; Ning Wei; Ning Zheng; Solomon H. Snyder; Feng Rao

    2016-01-01

    .... We now report that inositol hexakisphosphate (IP6) is a major physiologic determinant of the CRL-CSN interface, which includes a hitherto unidentified electrostatic interaction between the N-terminal acidic tail of CSN subunit 2 (CSN2...

  4. The TRAPP subunit Trs130p interacts with the GAP Gyp6p to mediate Ypt6p dynamics at the late Golgi

    Directory of Open Access Journals (Sweden)

    Stephanie eBrunet

    2016-05-01

    Full Text Available Small GTPases of the Rab superfamily participate in virtually all vesicle-mediated trafficking events. Cycling between an active GTP-bound form and an inactive GDP-bound form is accomplished in conjunction with guanine nucleotide exchange factors (GEFs and GTPase activating proteins (GAPs, respectively. Rab cascades have been described in which an effector of an activated Rab is a GEF for a downstream Rab, thus ensuring activation of a pathway in an ordered fashion. Much less is known concerning crosstalk between GEFs and GAPs although regulation between these factors could also contribute to the overall physiology of a cell. Here we demonstrate that a subunit of the TRAPP II multisubunit tethering factor, a GEF for the GTPase Ypt1p, participates in the recruitment of Gyp6p, a GAP for the GTPase Ypt6p, to Golgi membranes. The extreme carboxy-terminal portion of the TRAPP II subunit Trs130p is required for the interaction between TRAPP II and Gyp6p. We further demonstrate that TRAPP II mutants, but not a TRAPP III mutant, display a defect in Gyp6p interaction. A consequence of this defective interaction is the enhanced localization of Ypt6p at late Golgi membranes. Although a ypt31/32 mutant also resulted in an enhanced localization of Gyp6p at the late Golgi, the effect was not as dramatic as that seen for TRAPP II mutants, nor was Ypt31/32 detected in the same TRAPP II purification that detected Gyp6p. We propose that the interaction between TRAPP II and Gyp6p represents a parallel mechanism in addition to that mediated by Ypt31/32 for the recruitment of a GAP to the appropriate membrane, and is a novel example of crosstalk between a Rab GAP and GEF.

  5. Randomized controlled trial of primary care pediatric parenting programs: effect on reduced media exposure in infants, mediated through enhanced parent-child interaction.

    Science.gov (United States)

    Mendelsohn, Alan L; Dreyer, Benard P; Brockmeyer, Carolyn A; Berkule-Silberman, Samantha B; Huberman, Harris S; Tomopoulos, Suzy

    2011-01-01

    To determine whether pediatric primary care-based programs to enhance parenting and early child development reduce media exposure and whether enhanced parenting mediates the effects. Randomized controlled trial. Urban public hospital pediatric primary care clinic. A total of 410 mother-newborn dyads enrolled after childbirth. Patients were randomly assigned to 1 of 2 interventions, the Video Interaction Project (VIP) and Building Blocks (BB) interventions, or to a control group. The VIP intervention comprised 1-on-1 sessions with a child development specialist who facilitated interactions in play and shared reading through review of videotapes made of the parent and child on primary care visit days; learning materials and parenting pamphlets were also provided. The BB intervention mailed parenting materials, including age-specific newsletters suggesting activities to facilitate interactions, learning materials, and parent-completed developmental questionnaires (Ages and Stages questionnaires). Electronic media exposure in the home using a 24-hour recall diary. The mean (SD) exposure at 6 months was 146.5 (125.0) min/d. Exposure to VIP was associated with reduced total duration of media exposure compared with the BB and control groups (mean [SD] min/d for VIP, 131.6 [118.7]; BB, 151.2 [116.7]; control, 155.4 [138.7]; P = .009). Enhanced parent-child interactions were found to partially mediate relations between VIP and media exposure for families with a ninth grade or higher literacy level (Sobel statistic = 2.49; P = .01). Pediatric primary care may represent an important venue for addressing the public health problem of media exposure in young children at a population level. clinicaltrials.gov Identifier: NCT00212576.

  6. Association between SAP and FynT: Inducible SH3 domain-mediated interaction controlled by engagement of the SLAM receptor.

    Science.gov (United States)

    Chen, Riyan; Latour, Sylvain; Shi, Xiaochu; Veillette, André

    2006-08-01

    SAP is an intracellular adaptor molecule composed almost exclusively of an SH2 domain. It is mutated in patients with X-linked lymphoproliferative disease, a human immunodeficiency. Several immune abnormalities were also identified in SAP-deficient mice. By way of its SH2 domain, SAP interacts with tyrosine-based motifs in the cytoplasmic domain of SLAM family receptors. SAP promotes SLAM family receptor-induced protein tyrosine phosphorylation, due to its capacity to recruit the Src-related kinase FynT. This unusual property relies on the existence of a second binding surface in the SAP SH2 domain, centered on arginine 78 of SAP, that binds directly to the FynT SH3 domain. Herein, we wanted to further understand the mechanisms controlling the interaction between SLAM-SAP and FynT. Our experiments showed that, unlike conventional associations mediated by SH3 domains, the interaction of the FynT SH3 domain with SLAM-SAP was strictly inducible. It was absolutely dependent on engagement of SLAM by extracellular ligands. We obtained evidence that this inducibility was not due to increased binding of SLAM to SAP following SLAM engagement. Furthermore, it could occur independently of any appreciable SLAM-dependent biochemical signal. In fact, our data indicated that the induced association of the FynT SH3 domain with SLAM-SAP was triggered by a change in the conformation of SLAM-associated SAP caused by SLAM engagement. Together, these data elucidate further the events initiating SLAM-SAP signaling in immune cells. Moreover, they identify a strictly inducible interaction mediated by an SH3 domain.

  7. New insight to structure-function relationship of GalNAc mediated primary interaction between insecticidal Cry1Ac toxin and HaALP receptor of Helicoverpa armigera.

    Directory of Open Access Journals (Sweden)

    Anindita Sengupta

    Full Text Available Over the last few decades Cry1Ac toxin has been widely used in controlling the insect attack due to its high specificity towards target insects. The pore-forming toxin undergoes a complex mechanism in the insect midgut involving sequential interaction with specific glycosylated receptors in which terminal GalNAc molecule plays a vital role. Recent studies on Cry toxins interactions with specific receptors revealed the importance of several amino acid residues in domain III of Cry1Ac, namely Q509, N510, R511, Y513 and W545, serve as potential binding sites that surround the putative GalNAc binding pocket and mediate the toxin-receptor interaction. In the present study, alanine substitution mutations were generated in the Cry1Ac domain III region and functional significance of those key residues was monitored by insect bioassay on Helicoverpa armigera larvae. In addition, ligand blot analysis and SPR binding assay was performed to monitor the binding characteristics of Cry1Ac wild type and mutant toxins towards HaALP receptor isolated from Helicoverpa armigera. Mutagenesis data revealed that, alanine substitutions in R511, Y513 and W545 substantially impacted the relative affinity towards HaALP receptor and toxicity toward target insect. Furthermore, in silico study of GalNAc-mediated interaction also confirmed the important roles of these residues. This structural analysis will provide a detail insight for evaluating and engineering new generation Cry toxins to address the problem of change in insect behavioral patterns.

  8. Long-term Effects of Parents' Education on Children's Educational and Occupational Success: Mediation by Family Interactions, Child Aggression, and Teenage Aspirations.

    Science.gov (United States)

    Dubow, Eric F; Boxer, Paul; Huesmann, L Rowell

    2009-07-01

    We examine the prediction of individuals' educational and occupational success at age 48 from contextual and personal variables assessed during their middle childhood and late adolescence. We focus particularly on the predictive role of the parents' educational level during middle childhood, controlling for other indices of socioeconomic status and children's IQ, and the mediating roles of negative family interactions, childhood behavior, and late adolescent aspirations. Data come from the Columbia County Longitudinal Study, which began in 1960 when all 856 third graders in a semi-rural county in New York State were interviewed along with their parents; participants were reinterviewed at ages 19, 30, and 48 (Eron et al, 1971; Huesmann et al., 2002). Parents' educational level when the child was 8 years old significantly predicted educational and occupational success for the child 40 years later. Structural models showed that parental educational level had no direct effects on child educational level or occupational prestige at age 48 but had significant indirect effects that were independent of the other predictor variables' effects. These indirect effects were mediated through age 19 educational aspirations and age 19 educational level. These results provide strong support for the unique predictive role of parental education on adult outcomes 40 years later and underscore the developmental importance of mediators of parent education effects such as late adolescent achievement and achievement-related aspirations.

  9. Nutrient overlap, genetic relatedness and spatial origin influence interaction-mediated shifts in inhibitory phenotype among Streptomyces spp.

    Science.gov (United States)

    Vaz Jauri, Patricia; Kinkel, Linda L

    2014-10-01

    Chemical communication among kin bacteria modulates diverse activities. Despite the general consensus that signaling among non-kin organisms is likely to influence microbial behavior, there is limited information on the potential for microbial interactions to alter microbial phenotypes in natural habitats. We explored patterns of interaction that alter inhibitory phenotypes among Streptomyces isolates from distinct communities. Shifts in inhibition in response to the presence of a partner were evaluated for 861 isolate combinations, and were considered in relation to nutrient use, 16S sequence, inhibition phenotype and community origin. The frequency of inhibition-shifting interactions was significantly higher among isolates from the same (0.40) than from different (0.33) communities, suggesting local selection for inhibition-shifting interactions. Communities varied in the frequency with which Streptomyces isolates responded to a partner but not in the frequency with which isolates induced changes in partners. Streptomyces isolates were more likely to exhibit increased inhibition of a target bacterium in response to isolates that compete for the same nutrients, are closely-related or are strongly inhibited by their antibiotics. This work documents a high frequency of interactions among Streptomyces that shift the capacity of Streptomyces to inhibit other microbes, and suggests significant potential for such interactions to shape microbial community dynamics.

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

    Directory of Open Access Journals (Sweden)

    Nurmi ePangesti

    2013-10-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

  12. OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle.

    Science.gov (United States)

    Zhong, Wenbin; Zhou, You; Li, Jiwei; Mysore, Raghavendra; Luo, Wei; Li, Shiqian; Chang, Mau-Sun; Olkkonen, Vesa M; Yan, Daoguang

    2014-04-01

    We earlier identified OSBP-related protein 8 (ORP8) as an endoplasmic reticulum/nuclear envelope oxysterol-binding protein implicated in cellular lipid homeostasis, migration, and organization of the microtubule cytoskeleton. Here, a yeast two-hybrid screen identified Homo sapiens sperm associated antigen 5 (SPAG5)/Astrin as interaction partner of ORP8. The putative interaction was further confirmed by pull-down and co-immunoprecipitation assays. ORP8 did not colocalize with kinetochore-associated SPAG5 in mitotic HepG2 or HuH7 cells, but overexpressed ORP8 was capable of recruiting SPAG5 onto endoplasmic reticulum membranes in interphase cells. In our experiments, 25-hydroxycholesterol (25OHC) retarded the HepG2 cell cycle, causing accumulation in G2/M phase; ORP8 overexpression resulted in the same phenotype. Importantly, ORP8 knock-down dramatically inhibited the oxysterol effect on HepG2 cell cycle, suggesting a mediating role of ORP8. Furthermore, knock-down of SPAG5 significantly reduced the effects of both ORP8 overexpression and 25OHC on the cell cycle, placing SPAG5 downstream of the two cell-cycle interfering factors. Taken together, the present results suggest that ORP8 may via SPAG5 mediate oxysterol interference of the HepG2 cell cycle.

  13. TRAF6 mediates IL-1β/LPS-induced suppression of TGF-β signaling through its interaction with the type III TGF-β receptor.

    Directory of Open Access Journals (Sweden)

    Seunghwan Lim

    Full Text Available Transforming growth factor-β1 (TGF-β1 is an important anti-inflammatory cytokine that modulates and resolves inflammatory responses. Recent studies have demonstrated that inflammation enhances neoplastic risk and potentiates tumor progression. In the evolution of cancer, pro-inflammatory cytokines such as IL-1β must overcome the anti-inflammatory effects of TGF-β to boost pro-inflammatory responses in epithelial cells. Here we show that IL-1β or Lipopolysaccharide (LPS suppresses TGF-β-induced anti-inflammatory signaling in a NF-κB-independent manner. TRAF6, a key molecule in IL-1β signaling, mediates this suppressive effect through interaction with the type III TGF-β receptor (TβRIII, which is TGF-β-dependent and requires type I TGF-β receptor (TβRI kinase activity. TβRI phosphorylates TβRIII at residue S829, which promotes the TRAF6/TβRIII interaction and consequent sequestration of TβRIII from the TβRII/TβRI complex. Our data indicate that IL-1β enhances the pro-inflammatory response by suppressing TGF-β signaling through TRAF6-mediated sequestration of TβRIII, which may be an important contributor to the early stages of tumor progression.

  14. Rack1 Mediates the Interaction of P-Glycoprotein with Anxa2 and Regulates Migration and Invasion of Multidrug-Resistant Breast Cancer Cells

    Science.gov (United States)

    Yang, Yi; Wu, Na; Wang, Zhiyong; Zhang, Fei; Tian, Ran; Ji, Wei; Ren, Xiubao; Niu, Ruifang

    2016-01-01

    The emergence of multidrug resistance is always associated with more rapid tumor recurrence and metastasis. P-glycoprotein (P-gp), which is a well-known multidrug-efflux transporter, confers enhanced invasion ability in drug-resistant cells. Previous studies have shown that P-gp probably exerts its tumor-promoting function via protein-protein interaction. These interactions were implicated in the activation of intracellular signal transduction. We previously showed that P-gp binds to Anxa2 and promotes the invasiveness of multidrug-resistant (MDR) breast cancer cells through regulation of Anxa2 phosphorylation. However, the accurate mechanism remains unclear. In the present study, a co-immunoprecipitation coupled with liquid chromatography tandem mass spectrometry-based interactomic approach was performed to screen P-gp binding proteins. We identified Rack1 as a novel P-gp binding protein. Knockdown of Rack1 significantly inhibited proliferation and invasion of MDR cancer cells. Mechanistic studies demonstrated that Rack1 functioned as a scaffold protein that mediated the binding of P-gp to Anxa2 and Src. We showed that Rack1 regulated P-gp activity, which was necessary for adriamycin-induced P-gp-mediated phosphorylation of Anxa2 and Erk1/2. Overall, the findings in this study augment novel insights to the understanding of the mechanism employed by P-gp for promoting migration and invasion of MDR cancer cells. PMID:27754360

  15. Evaluating the effects of pollinator-mediated interactions using pollen transfer networks: evidence of widespread facilitation in south Andean plant communities.

    Science.gov (United States)

    Tur, C; Sáez, A; Traveset, A; Aizen, M A

    2016-05-01

    Information about the relative importance of competitive or facilitative pollinator-mediated interactions in a multi-species context is limited. We studied interspecific pollen transfer (IPT) networks to evaluate quantity and quality effects of pollinator sharing among plant species on three high-Andean communities at 1600, 1800 and 2000 m a.s.l. To estimate the sign of the effects (positive, neutral or negative), the relation between conspecific and heterospecific pollen deposited on stigmas was analysed with GLMMs. Network analyses showed that communities were characterised by the presence of pollen hub-donors and receptors. We inferred that facilitative and neutral pollinator-mediated interactions among plants prevailed over competition. Thus, the benefits from pollinator sharing seem to outweigh the costs (i.e. heterospecific deposition and conspecific pollen loss). The largest proportion of facilitated species was found at the highest elevation community, suggesting that under unfavourable conditions for the pollination service and at lower plant densities facilitation can be more common.

  16. Interaction of glucocorticoid receptor (GR) with estrogen receptor (ER) α and activator protein 1 (AP1) in dexamethasone-mediated interference of ERα activity.

    Science.gov (United States)

    Karmakar, Sudipan; Jin, Yetao; Nagaich, Akhilesh K

    2013-08-16

    The role of glucocorticoids in the inhibition of estrogen (17-β-estradiol (E2))-regulated estrogen receptor (ER)-positive breast cancer cell proliferation is well established. We and others have seen that synthetic glucocorticoid dexamethasone (Dex) antagonizes E2-stimulated endogenous ERα target gene expression. However, how glucocorticoids negatively regulate the ERα signaling pathway is still poorly understood. ChIP studies using ERα- and glucocorticoid receptor (GR)-positive MCF-7 cells revealed that GR occupies several ERα-binding regions (EBRs) in cells treated with E2 and Dex simultaneously. Interestingly, there was little or no GR loading to these regions when cells were treated with E2 or Dex alone. The E2+Dex-dependent GR recruitment is associated with the displacement of ERα and steroid receptor coactivator-3 from the target EBRs leading to the repression of ERα-mediated transcriptional activation. The recruitment of GR to EBRs requires assistance from ERα and FOXA1 and is facilitated by AP1 binding within the EBRs. The GR binding to EBRs is mediated via direct protein-protein interaction between the GR DNA-binding domain and ERα. Limited mutational analyses indicate that arginine 488 located within the C-terminal zinc finger domain of the GR DNA-binding domain plays a critical role in stabilizing this interaction. Together, the results of this study unravel a novel mechanism involved in glucocorticoid inhibition of ERα transcriptional activity and E2-mediated cell proliferation and thus establish a foundation for future exploitation of the GR signaling pathway in the treatment of ER-positive breast cancer.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  18. SATB1 Mediates Long-Range Chromatin Interactions: A Dual Regulator of Anti-Apoptotic BCL2 and Pro-Apoptotic NOXA Genes.

    Science.gov (United States)

    Yang, Yin; Wang, Zongdan; Sun, Luan; Shao, Lipei; Yang, Nan; Yu, Dawei; Zhang, Xin; Han, Xiao; Sun, Yujie

    2015-01-01

    Aberrant expression of special AT-rich binding protein 1 (SATB1), a global genomic organizer, has been associated with various cancers, which raises the question of how higher-order chromatin structure contributes to carcinogenesis. Disruption of apoptosis is one of the hallmarks of cancer. We previously demonstrated that SATB1 mediated specific long-range chromosomal interactions between the mbr enhancer located within 3'-UTR of the BCL2 gene and the promoter to regulate BCL2 expression during early apoptosis. In the present study, we used chromosome conformation capture (3C) assays and molecular analyses to further investigate the function of the SATB1-mediated higher-order chromatin structure in co-regulation of the anti-apoptotic BCL2 gene and the pro-apoptotic NOXA gene located 3.4Mb downstream on Chromosome 18. We demonstrated that the mbr enhancer spatially juxtaposed the promoters of BCL2 and NOXA genes through SATB1-mediated chromatin-loop in Jurkat cells. Decreased SATB1 levels switched the mbr-BCL2 loop to mbr-NOXA loop, and thus changed expression of these two genes. The SATB1-mediated dynamic switch of the chromatin loop structures was essential for the cooperative expression of the BCL2 and NOXA genes in apoptosis. Notably, the role of SATB1 was specific, since inhibition of SATB1 degradation by caspase-6 inhibitor or caspase-6-resistant SATB1 mutant reversed expression of BCL-2 and NOXA in response to apoptotic stimulation. This study reveals the critical role of SATB1-organized higher-order chromatin structure in regulating the dynamic equilibrium of apoptosis-controlling genes with antagonistic functions and suggests that aberrant SATB1 expression might contribute to cancer development by disrupting the co-regulated genes in apoptosis pathways.

  19. The pituitary mediates the anxiolytic-like effects of the vasopressin V1B receptor antagonist, SSR149415, in a social interaction test in rats.

    Science.gov (United States)

    Shimazaki, Toshiharu; Iijima, Michihiko; Chaki, Shigeyuki

    2006-08-14

    A vasopressin V(1B) receptor antagonist has been shown to exhibit anxiolytic effects in a variety of animal models of anxiety. In the present study, we examined the involvement of the pituitary in the anxiolytic effects of a vasopressin V(1B) receptor antagonist by conducting a social interaction test in rats. In the sham-operated rats, both the vasopressin V(1B) receptor antagonist SSR149415 and the benzodiazepine chlordiazepoxide significantly increased the social behavior of a pair of unfamiliar rats, and the blood adrenocorticotropic hormone levels were markedly increased during the social interaction test. Hypophysectomy also increased the length of time that the animals engaged in social behavior to the same extent as that observed after treatment of the sham-operated rats with anxiolytics. However, while chlordiazepoxide further increased the duration of social interaction in the hypophysectomized rats, the anxiolytic effects of SSR149415 was no longer observed in these animals. These results suggest that the anxiolytic effects of the vasopressin V(1B) receptor antagonist in the social interaction test are mediated through blockade of the vasopressin V(1B) receptor in the pituitary.

  20. Enhancement of TGF-β-induced Smad3 activity by c-Abl-mediated tyrosine phosphorylation of its coactivator SKI-interacting protein (SKIP).

    Science.gov (United States)

    Kuki, Kazumasa; Yamaguchi, Noritaka; Iwasawa, Shuto; Takakura, Yuki; Aoyama, Kazumasa; Yuki, Ryuzaburo; Nakayama, Yuji; Kuga, Takahisa; Hashimoto, Yuuki; Tomonaga, Takeshi; Yamaguchi, Naoto

    2017-08-26

    c-Abl is a non-receptor-type tyrosine kinase that plays an important role in cell proliferation, migration, apoptosis, and fibrosis. Furthermore, although c-Abl is involved in transforming growth factor-β (TGF-β) signaling, its molecular functions in TGF-β signaling are not fully understood. Here, we found that c-Abl phosphorylates SKI-interacting protein (SKIP), a nuclear cofactor of the transcription factor Smad3. The c-Abl inhibitor imatinib suppressed TGF-β-induced expression of Smad3 targets as well as SKIP/Smad3 interaction. TGF-β-stimulation induced tyrosine phosphorylation of SKIP, and this phosphorylation was suppressed by imatinib. Tyr(292), Tyr(430), and Tyr(433) residues in SKIP were shown to be involved in c-Abl-mediated phosphorylation. Phosphomimetic glutamic acid substitution at Tyr(292) in SKIP enhanced, whereas its phospho-dead phenylalanine substitution attenuated TGF-β-induced SKIP/Smad3 interaction. Moreover, the phosphomimetic mutant of SKIP augmented transcriptional activity of Smad3. Taken together, these results suggest that c-Abl phosphorylates SKIP mainly at Tyr(292) and promotes SKIP/Smad3 interaction for the full activation of TGF-β/Smad3 signaling. Copyright © 2017 Elsevier Inc. All rights reserved.