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Sample records for interactions involving ikkg

  1. Modeling Systems Involving Interactions Between Scales

    NASA Astrophysics Data System (ADS)

    Murray, A. B.

    2005-05-01

    When we think of numerical models, `simulation modeling' often comes to mind: The modeler strives to include as many of the processes operating in the system of interest, and in as much detail, as is practical. The goal is typically to make accurate quantitative predictions. However, numerical models can also play an explanatory role. The goal of explaining a poorly understood phenomenon is often best pursued with an `exploratory' model (Murray 2002, 2003), in which a modeler minimizes the processes included and the level of detail, to try to determine what mechanisms-and what aspects of those mechanisms-are essential. These strategies are closely associated with different approaches to modeling processes across temporal and spatial scales. Simulation models often involve `explicit numerical reductionism'-the direct representation of interactions at scales as small as possible. Parameterizing sub-grid-scale processes is often seen as an unfortunate necessity, to be avoided if possible. On the other hand, when devising an exploratory model, a top-down strategy is often employed; an effort is made to represent only the effects that much smaller-scale processes have on the scale of interest. This approach allows investigation of the interactions between the emergent variables and structures that most directly explain many complex behaviors. As a caricature, we don't investigate water-wave phenomena by simulating molecular collisions. In addition, basing a model on processes at much smaller scales than those of the phenomena of interest leads to the concern that model imperfections may propagate up through the scales; that if the small-scale processes are not treated very accurately, the key interactions that emerge at larger scales may not occur as they do in the natural system. However, this risk can be bypassed by basing a model directly on larger-scale interactions, and examining which of these interactions might cause a phenomenon. For this reason, it has been

  2. Van der Waals interactions involving proteins.

    PubMed Central

    Roth, C M; Neal, B L; Lenhoff, A M

    1996-01-01

    Van der Waals (dispersion) forces contribute to interactions of proteins with other molecules or with surfaces, but because of the structural complexity of protein molecules, the magnitude of these effects is usually estimated based on idealized models of the molecular geometry, e.g., spheres or spheroids. The calculations reported here seek to account for both the geometric irregularity of protein molecules and the material properties of the interacting media. Whereas the latter are found to fall in the generally accepted range, the molecular shape is shown to cause the magnitudes of the interactions to differ significantly from those calculated using idealized models, with important consequences. First, the roughness of the molecular surface leads to much lower average interaction energies for both protein-protein and protein-surface cases relative to calculations in which the protein molecule is approximated as a sphere. These results indicate that a form of steric stabilization may be an important effect in protein solutions. Underlying this behavior is appreciable orientational dependence, one reflection of which is that molecules of complementary shape are found to exhibit very strong attractive dispersion interactions. Although this has been widely discussed previously in the context of molecular recognition processes, the broader implications of these phenomena may also be important at larger molecular separations, e.g., in the dynamics of aggregation, precipitation, and crystal growth. Images FIGURE 3 PMID:8789115

  3. Van der Waals Interactions Involving Proteins

    NASA Technical Reports Server (NTRS)

    Roth, Charles M.; Neal, Brian L.; Lenhoff, Abraham M.

    1996-01-01

    Van der Waals (dispersion) forces contribute to interactions of proteins with other molecules or with surfaces, but because of the structural complexity of protein molecules, the magnitude of these effects is usually estimated based on idealized models of the molecular geometry, e.g., spheres or spheroids. The calculations reported here seek to account for both the geometric irregularity of protein molecules and the material properties of the interacting media. Whereas the latter are found to fall in the generally accepted range, the molecular shape is shown to cause the magnitudes of the interactions to differ significantly from those calculated using idealized models. with important consequences. First, the roughness of the molecular surface leads to much lower average interaction energies for both protein-protein and protein-surface cases relative to calculations in which the protein molecule is approximated as a sphere. These results indicate that a form of steric stabilization may be an important effect in protein solutions. Underlying this behavior is appreciable orientational dependence, one reflection of which is that molecules of complementary shape are found to exhibit very strong attractive dispersion interactions. Although this has been widely discussed previously in the context of molecular recognition processes, the broader implications of these phenomena may also be important at larger molecular separations, e.g., in the dynamics of aggregation, precipitation, and crystal growth.

  4. [Mecanisms of pharmacokinetic interactions involving oral anticancer agents].

    PubMed

    Levêque, Dominique; Duval, Céline; Poulat, Charlotte; Palas, Benjamin; El Aatmani, Anne; Dory, Anne; Becker, Guillaume; Gourieux, Bénédicte

    2015-01-01

    Oral anticancer agents and particularly kinase inhibitors are subject to pharmacokinetic drug interactions in relation to absorption and elimination phases. Interacting factors are food, fruit juices, cigarette smoke, acid-reducing agents and inducers/inhibitors. Some anticancer agents are inducers and/or inhibitors and can also perpetrate drug interactions. This review emphasizes the mechanisms of pharmacokinetic drug interactions involving oral anticancer agents. PMID:25609481

  5. Student projects involving novel interaction with large displays.

    PubMed

    Dias, Paulo; Sousa, Tiago; Parracho, Joao; Cardoso, Igor; Monteiro, Andre; Sousa Santos, Beatriz

    2014-01-01

    DETI-Interact is an interactive system that offers information relevant to students in the lobby of the University of Aveiro's Department of Electronics, Telecommunications and Informatics (DETI). The project started in 2009 with a master's thesis addressing interaction with public displays through Android smartphones. Since then, it has evolved considerably; it currently allows gesture interaction based on a Kinect sensor. Meanwhile, it has involved third-year students, master's students, and undergraduate students participating in a research initiation program. PMID:24808202

  6. Physical Interactions Involving Preschoolers and Kindergartners in a Childcare Center

    ERIC Educational Resources Information Center

    Fleck, Bethany; Chavajay, Pablo

    2009-01-01

    This naturalistic observational study described the similarities and differences in physical interactions involving preschoolers and kindergartners within the context of a US childcare facility. It examined patterns of touch involving the children across center and circle activities within the course of their day. Results indicated that…

  7. Lexical Cues of Interaction Involvement in Dyadic Instant Messaging Conversations

    ERIC Educational Resources Information Center

    Nguyen, Duyen T.; Fussell, Susan R.

    2014-01-01

    We explore how people express and interpret lexical cues of interaction involvement in dyadic conversations via instant messaging (IM) in two studies. In Study 1, an experiment with 60 participants, we manipulated level of involvement in a conversation with a distraction task. We examined how participants' uses of verbal cues such as pronouns…

  8. Methods for Mapping of Interaction Networks Involving Membrane Proteins

    SciTech Connect

    Hooker, Brian S.; Bigelow, Diana J.; Lin, Chiann Tso

    2007-11-23

    Numerous approaches have been taken to study protein interactions, such as tagged protein complex isolation followed by mass spectrometry, yeast two-hybrid methods, fluorescence resonance energy transfer, surface plasmon resonance, site-directed mutagenesis, and crystallography. Membrane protein interactions pose significant challenges due to the need to solubilize membranes without disrupting protein-protein interactions. Traditionally, analysis of isolated protein complexes by high-resolution 2D gel electrophoresis has been the main method used to obtain an overall picture of proteome constituents and interactions. However, this method is time consuming, labor intensive, detects only abundant proteins and is not suitable for the coverage required to elucidate large interaction networks. In this review, we discuss the application of various methods to elucidate interactions involving membrane proteins. These techniques include methods for the direct isolation of single complexes or interactors as well as methods for characterization of entire subcellular and cellular interactomes.

  9. Quantifying Engagement: Measuring Player Involvement in Human-Avatar Interactions

    PubMed Central

    Norris, Anne E.; Weger, Harry; Bullinger, Cory; Bowers, Alyssa

    2014-01-01

    This research investigated the merits of using an established system for rating behavioral cues of involvement in human dyadic interactions (i.e., face-to-face conversation) to measure involvement in human-avatar interactions. Gameplay audio-video and self-report data from a Feasibility Trial and Free Choice study of an effective peer resistance skill building simulation game (DRAMA-RAMA™) were used to evaluate reliability and validity of the rating system when applied to human-avatar interactions. The Free Choice study used a revised game prototype that was altered to be more engaging. Both studies involved girls enrolled in a public middle school in Central Florida that served a predominately Hispanic (greater than 80%), low-income student population. Audio-video data were coded by two raters, trained in the rating system. Self-report data were generated using measures of perceived realism, predictability and flow administered immediately after game play. Hypotheses for reliability and validity were supported: Reliability values mirrored those found in the human dyadic interaction literature. Validity was supported by factor analysis, significantly higher levels of involvement in Free Choice as compared to Feasibility Trial players, and correlations between involvement dimension sub scores and self-report measures. Results have implications for the science of both skill-training intervention research and game design. PMID:24748718

  10. Communicative interactions involving plants: information, evolution, and ecology.

    PubMed

    Mescher, Mark C; Pearse, Ian S

    2016-08-01

    The role of information obtained via sensory cues and signals in mediating the interactions of organisms with their biotic and abiotic environments has been a major focus of work on sensory and behavioral ecology. Information-mediated interactions also have important implications for broader ecological patterns emerging at the community and ecosystem levels that are only now beginning to be explored. Given the extent to which plants dominate the sensory landscapes of terrestrial ecosystems, information-mediated interactions involving plants should be a major focus of efforts to elucidate these broader patterns. Here we explore how such efforts might be enhanced by a clear understanding of information itself-a central and potentially unifying concept in biology that has nevertheless been the subject of considerable confusion-and of its relationship to adaptive evolution and ecology. We suggest that information-mediated interactions should be a key focus of efforts to more fully integrate evolutionary biology and ecology. PMID:27421106

  11. Thermodynamic signatures in macromolecular interactions involving conformational flexibility.

    PubMed

    Menzel, Anja; Neumann, Piotr; Schwieger, Christian; Stubbs, Milton T

    2014-07-01

    The energetics of macromolecular interactions are complex, particularly where protein flexibility is involved. Exploiting serendipitous differences in the plasticity of a series of closely related trypsin variants, we analyzed the enthalpic and entropic contributions accompanying interaction with L45K-eglin C. Binding of the four variants show significant differences in released heat, although the affinities vary little, in accordance with the principle of enthalpy-entropy compensation. Binding of the most disordered variant is almost entirely enthalpically driven, with practically no entropy change. As structures of the complexes reveal negligible differences in protein-inhibitor contacts, we conclude that solvent effects contribute significantly to binding affinities. PMID:25003391

  12. Identification of Inhibitors of Biological Interactions Involving Intrinsically Disordered Proteins

    PubMed Central

    Marasco, Daniela; Scognamiglio, Pasqualina Liana

    2015-01-01

    Protein–protein interactions involving disordered partners have unique features and represent prominent targets in drug discovery processes. Intrinsically Disordered Proteins (IDPs) are involved in cellular regulation, signaling and control: they bind to multiple partners and these high-specificity/low-affinity interactions play crucial roles in many human diseases. Disordered regions, terminal tails and flexible linkers are particularly abundant in DNA-binding proteins and play crucial roles in the affinity and specificity of DNA recognizing processes. Protein complexes involving IDPs are short-lived and typically involve short amino acid stretches bearing few “hot spots”, thus the identification of molecules able to modulate them can produce important lead compounds: in this scenario peptides and/or peptidomimetics, deriving from structure-based, combinatorial or protein dissection approaches, can play a key role as hit compounds. Here, we propose a panoramic review of the structural features of IDPs and how they regulate molecular recognition mechanisms focusing attention on recently reported drug-design strategies in the field of IDPs. PMID:25849651

  13. Drug interactions involving cimetidine--mechanisms, documentation, implications.

    PubMed

    Greene, W

    1984-01-01

    In summary, cimetidine is a potent inhibitor of liver microsomal activity, which may also decrease hepatic blood flow. Other effects of the drug include inhibition of gastric secretion and intrinsic toxic properties. These effects, combined with the common use of cimetidine in clinical practice, make the risk of adverse drug interactions a relatively frequent risk in the clinical setting. Although a multitude of interactions with cimetidine has been evaluated, many of these are incompletely described or understood. At the present time, a potentially significant alteration of absorption appears to exist with only ketoconazole, elemental iron, vitamin B12 (long-term therapy), and pancreatic enzyme supplements (increased activity). Significant metabolic inhibition or decreased excretion appears to exist with warfarin, propranolol, theophylline, phenytoin, quinidine, possibly lidocaine and procainamide, and certain benzodiazepines. Other potential, but less well ascertained interactions may involve the narcotic analgesics, caffeine, ethanol, pentobarbital, imipramine, chlormethiazole, and metronidazole. In these settings, the clinician must be aware of interaction potential, and astutely monitor the patient during combination therapy. Other data indicate that concomitant administration of antacids may reduce the absorption of cimetidine, that the drug may protect against the toxic effects of acetaminophen overdose, and that combination with certain other myelosuppressants may carry a significant risk. Thus, in regard to these reports, cimetidine is a drug with complex effects on the absorption, elimination, and toxicity of other drugs. When used in the setting of multiple drug therapy, the clinician must be alert to potentially increased or decreased effects of the drugs mentioned in this review. In addition, one must be aware that other hepatically metabolised agents not mentioned here may be affected by the addition of cimetidine therapy. Because of the therapeutic

  14. Extracellular Paracoccidioides brasiliensis phospholipase B involvement in alveolar macrophage interaction

    PubMed Central

    2010-01-01

    Background Phospholipase B (PLB) has been reported to be one of the virulence factors for human pathogenic fungi and has also been described as necessary for the early events in infection. Based on these data, we investigated the role of PLB in virulence and modulation of the alveolar pulmonary immune response during infection using an in-vitro model of host-pathogen interaction, i.e. Paracoccidioides brasiliensis yeast cells infecting alveolar macrophage (MH-S) cells. Results The effect of PLB was analyzed using the specific inhibitor alexidine dihydrochloride (0.25 μM), and pulmonary surfactant (100 μg mL-1), during 6 hours of co-cultivation of P. brasiliensis and MH-S cells. Alexidine dihydrochloride inhibited PLB activity by 66% and significantly decreased the adhesion and internalization of yeast cells by MH-S cells. Genes involved in phagocytosis (trl2, cd14) and the inflammatory response (nfkb, tnf-α, il-1β) were down-regulated in the presence of this PLB inhibitor. In contrast, PLB activity and internalization of yeast cells significantly increased in the presence of pulmonary surfactant; under this condition, genes such as clec2 and the pro-inflammatory inhibitor (nkrf) were up-regulated. Also, the pulmonary surfactant did not alter cytokine production, while alexidine dihydrochloride decreased the levels of interleukin-10 (IL-10) and increased the levels of IL-12 and tumor necrosis factor-α (TNF-α). In addition, gene expression analysis of plb1, sod3 and icl1 suggests that P. brasiliensis gene re-programming is effective in facilitating adaptation to this inhospitable environment, which mimics the lung-environment interaction. Conclusion P. brasiliensis PLB activity is involved in the process of adhesion and internalization of yeast cells at the MH-S cell surface and may enhance virulence and subsequent down-regulation of macrophage activation. PMID:20843362

  15. Father Involvement in Feeding Interactions with Their Young Children

    PubMed Central

    Guerrero, Alma D.; Chu, Lynna; Franke, Todd; Kuo, Alice A.

    2016-01-01

    Objective To examine the associations of father-child feeding and physical interactions with dietary practices and weight status in children. Methods A nationally representative sample of children, mothers, and fathers who participated in the Early Childhood Longitudinal Study Birth cohort study (N = 2441) was used to explore the relationship of father-child feeding and physical activity interactions with child dietary practices and weight status. Logistic multivariable regression analyses were adjusted for child, father, mother, and socio-demographic characteristics. Results Approximately 40% of fathers reported having a great deal of influence on their preschool child’s nutrition and about 50% reported daily involvement in preparing food for their child and assisting their child with eating. Children had over 2 times the odds of consuming fast food at least once a week if fathers reported eating out with their child a few times a week compared to fathers who reported rarely or never eating out with their child (OR, 2.89; 95% CI, 1.94–4.29), adjusting for all covariates. Whether fathers reported eating out with their children was also significantly associated with children’s sweetened beverage intake. Conclusions Potentially modifiable behaviors that support healthy dietary practices in children may be supported by targeting fathers. PMID:26931754

  16. Formation Mechanism for a Hybrid Supramolecular Network Involving Cooperative Interactions

    NASA Astrophysics Data System (ADS)

    Mura, Manuela; Silly, Fabien; Burlakov, Victor; Castell, Martin R.; Briggs, G. Andrew D.; Kantorovich, Lev N.

    2012-04-01

    A novel mechanism of hybrid assembly of molecules on surfaces is proposed stemming from interactions between molecules and on-surface metal atoms which eventually got trapped inside the network pores. Based on state-of-the-art theoretical calculations, we find that the new mechanism relies on formation of molecule-metal atom pairs which, together with molecules themselves, participate in the assembly growth. Most remarkably, the dissociation of pairs is facilitated by a cooperative interaction involving many molecules. This new mechanism is illustrated on a low coverage Melamine hexagonal network on the Au(111) surface where multiple events of gold atoms trapping via a set of so-called “gate” transitions are found by kinetic Monte Carlo simulations based on transition rates obtained using ab initio density functional theory calculations and the nudged elastic band method. Simulated STM images of gold atoms trapped in the pores of the Melamine network predict that the atoms should appear as bright spots inside Melamine hexagons. No trapping was found at large Melamine coverages, however. These predictions have been supported by preliminary STM experiments which show bright spots inside Melamine hexagons at low Melamine coverages, while empty pores are mostly observed at large coverages. Therefore, we suggest that bright spots sometimes observed in the pores of molecular assemblies on metal surfaces may be attributed to trapped substrate metal atoms. We believe that this type of mechanism could be used for delivering adatom species of desired functionality (e.g., magnetic) into the pores of hydrogen-bonded networks serving as templates for their capture.

  17. Interacting Protein Kinases Involved in the Regulation of Flagellar Length

    PubMed Central

    Erdmann, Maja; Scholz, Anne; Melzer, Inga M.; Schmetz, Christel; Wiese, Martin

    2006-01-01

    A striking difference of the life stages of the protozoan parasite Leishmania is a long flagellum in the insect stage promastigotes and a rudimentary organelle in the mammalian amastigotes. LmxMKK, a mitogen-activated protein (MAP) kinase kinase from Leishmania mexicana, is required for growth of a full-length flagellum. We identified LmxMPK3, a MAP kinase homologue, with a similar expression pattern as LmxMKK being not detectable in amastigotes, up-regulated during the differentiation to promastigotes, constantly expressed in promastigotes, and shut down during the differentiation to amastigotes. LmxMPK3 null mutants resemble the LmxMKK knockouts with flagella reduced to one-fifth of the wild-type length, stumpy cell bodies, and vesicles and membrane fragments in the flagellar pocket. A constitutively activated recombinant LmxMKK activates LmxMPK3 in vitro. Moreover, LmxMKK is likely to be directly involved in the phosphorylation of LmxMPK3 in vivo. Finally, LmxMPK3 is able to phosphorylate LmxMKK, indicating a possible feedback regulation. This is the first time that two interacting components of a signaling cascade have been described in the genus Leishmania. Moreover, we set the stage for the analysis of reversible phosphorylation in flagellar morphogenesis. PMID:16467378

  18. Surface interactions involved in flashover with high density electronegative gases.

    SciTech Connect

    Hodge, Keith Conquest; Warne, Larry Kevin; Jorgenson, Roy Eberhardt; Wallace, Zachariah Red; Lehr, Jane Marie

    2010-01-01

    This report examines the interactions involved with flashover along a surface in high density electronegative gases. The focus is on fast ionization processes rather than the later time ionic drift or thermalization of the discharge. A kinetic simulation of the gas and surface is used to examine electron multiplication and includes gas collision, excitation and ionization, and attachment processes, gas photoionization and surface photoemission processes, as well as surface attachment. These rates are then used in a 1.5D fluid ionization wave (streamer) model to study streamer propagation with and without the surface in air and in SF6. The 1.5D model therefore includes rates for all these processes. To get a better estimate for the behavior of the radius we have studied radial expansion of the streamer in air and in SF6. The focus of the modeling is on voltage and field level changes (with and without a surface) rather than secondary effects, such as, velocities or changes in discharge path. An experiment has been set up to carry out measurements of threshold voltages, streamer velocities, and other discharge characteristics. This setup includes both electrical and photographic diagnostics (streak and framing cameras). We have observed little change in critical field levels (where avalanche multiplication sets in) in the gas alone versus with the surface. Comparisons between model calculations and experimental measurements are in agreement with this. We have examined streamer sustaining fields (field which maintains ionization wave propagation) in the gas and on the surface. Agreement of the gas levels with available literature is good and agreement between experiment and calculation is good also. Model calculations do not indicate much difference between the gas alone versus the surface levels. Experiments have identified differences in velocity between streamers on the surface and in the gas alone (the surface values being larger).

  19. Is Nonverbal Communication Disrupted in Interactions Involving Patients With Schizophrenia?

    PubMed Central

    Lavelle, Mary; Healey, Patrick G.T.; McCabe, Rosemarie

    2013-01-01

    Background: Nonverbal communication is a critical feature of successful social interaction and interpersonal rapport. Social exclusion is a feature of schizophrenia. This experimental study investigated if the undisclosed presence of a patient with schizophrenia in interaction changes nonverbal communication (ie, speaker gesture and listener nodding). Method: 3D motion-capture techniques recorded 20 patient (1 patient, 2 healthy participants) and 20 control (3 healthy participants) interactions. Participants rated their experience of rapport with each interacting partner. Patients’ symptoms, social cognition, and executive functioning were assessed. Four hypotheses were tested: (1) Compared to controls, patients display less speaking gestures and listener nods. (2) Patients’ increased symptom severity and poorer social cognition are associated with patients’ reduced gesture and nods. (3) Patients’ partners compensate for patients’ reduced nonverbal behavior by gesturing more when speaking and nodding more when listening. (4) Patients’ reduced nonverbal behavior, increased symptom severity, and poorer social cognition are associated with others experiencing poorer rapport with the patient. Results: Patients gestured less when speaking. Patients with more negative symptoms nodded less as listeners, while their partners appeared to compensate by gesturing more as speakers. Patients with more negative symptoms also gestured more when speaking, which, alongside increased negative symptoms and poorer social cognition, was associated with others experiencing poorer patient rapport. Conclusions: Patients’ symptoms are associated with the nonverbal behavior of patients and their partners. Patients’ increased negative symptoms and gesture use are associated with poorer interpersonal rapport. This study provides specific evidence about how negative symptoms impact patients’ social interactions. PMID:22941744

  20. Identification of Protein Interactions Involved in Cellular Signaling

    PubMed Central

    Westermarck, Jukka; Ivaska, Johanna; Corthals, Garry L.

    2013-01-01

    Protein-protein interactions drive biological processes. They are critical for all intra- and extracellular functions, and the technologies to analyze them are widely applied throughout the various fields of biological sciences. This study takes an in-depth view of some common principles of cellular regulation and provides a detailed account of approaches required to comprehensively map signaling protein-protein interactions in any particular cellular system or condition. We provide a critical review of the benefits and disadvantages of the yeast two-hybrid method and affinity purification coupled with mass spectrometric procedures for identification of signaling protein-protein interactions. In particular, we emphasize the quantitative and qualitative differences between tandem affinity and one-step purification (such as FLAG and Strep tag) methods. Although applicable to all types of interaction studies, a special section is devoted in this review to aspects that should be considered when attempting to identify signaling protein interactions that often are transient and weak by nature. Finally, we discuss shotgun and quantitative information that can be gleaned by MS-coupled methods for analysis of multiprotein complexes. PMID:23481661

  1. Differential phytosociological interactions involving male and female atriplex bonnevillensis

    USGS Publications Warehouse

    Sinclair, J.; Emlen, J.M.; Rinella, M.; Snelgrove, J.; Freeman, D.C.

    2009-01-01

    Wind-pollinated dioecious plants often exhibit spatial segregation of the sexes. This partial niche separation has most often been explored using abiotic niche axes. However, if the sexes are truly separated in space, then they are apt to encounter different plant species that may heavily affect growth and reproduction. Also, to the extent that their niches differ, the sexes may respond differently to the same co-occurring species. Here we examine interspecific interactions that influence male and female reproductive potential in Atriplex bonnevillensis. Using Emlen's interaction assessment, a technique which assesses species interactions based on cover classes, we show that Salsola species compete significantly with females but not males, while Halogeton glomeratus competes with males but not females. The effect of competition only became apparent when we corrected for site-specific fertility. These results imply that differential competition must be considered when studying dioecious plants that display spatial segregation of the sexes.

  2. Interactions of Dnd proteins involved in bacterial DNA phosphorothioate modification

    PubMed Central

    Xiong, Wei; Zhao, Gong; Yu, Hao; He, Xinyi

    2015-01-01

    DNA phosphorothioation (PT) is the first discovered physiological DNA backbone modification, in which a non-bridging oxygen atom of the phosphodiester bond is replaced with a sulfur atom in Rp (rectus for plane) configuration. PT modification is governed by a highly conserved gene cluster dndA/iscS-dndBCDE that is widespread across bacterial and archaeal species. However, little is known about how these proteins coordinately react with each other to perform oxygen–sulfur swap. We here demonstrated that IscS, DndC, DndD and DndE form a protein complex of which the molecular ratio for four proteins in the complex is approximate 1:1:1:1. DndB here displayed little or weak affinity to the complex and the constructs harboring dndACDE can confer the host in vivo PT modification. Using co-purification and pull down strategy, we demonstrated that the four proteins assemble into a pipeline in collinear to its gene organization, namely, IscS binding to DndC, DndC binding to DndD, and DndD binding to DndE. Moreover, weak interactions between DndE and IscS, DndE and DndC were also identified. PMID:26539172

  3. Human macrophage differentiation involves an interaction between integrins and fibronectin

    SciTech Connect

    Laouar, A.; Chubb, C.B.H.; Collart, F.; Huberman, E.

    1997-03-14

    The authors have examined the role of integrins and extracellular matrix (ECM) proteins in macrophage differentiation of (1) human HL-60 myeloid leukemia cells induced by phorbol 12-myristate 13-acetate (PMA) and (2) human peripheral blood monocytes induced by either PMA or macrophage-colony stimulating factor (M-CSF). Increased {beta}{sub 1} integrin and fibronectin (FN) gene expression was observed in PMA-treated HL-60 cells and PMA- or M-CSF-treated monocytes, even at a time preceding the manifestation of macrophage markers. Treated HL-60 cells and monocytes also released and deposited FN on the culture dishes. An HL-60 cell variant, HL-525, which is deficient in protein kinase C {beta} (PKC{beta}) and resistant to PMA-induced differentiation, failed to express FN after PMA treatment. Restoration of PKC{beta} resulted in PMA-induced FN gene expression and macrophage differentiation. The macrophage phenotype induced in HL-60 cells or monocytes was attenuated by anti-{beta}{sub 1} integrin or anti-FN MAbs. The authors suggest that macrophage differentiation involves activation of PKC and expression of specific integrins and ECM proteins. The stimulated cells, through their integrins, attach and spread on these substrates by binding to the deposited ECM proteins. This attachment and spreading in turn, through integrin signaling, leads to the macrophage phenotype.

  4. Communication Adaptability and Interaction Involvement as Predictors of Cross-Cultural Adjustment.

    ERIC Educational Resources Information Center

    Chen, Guo-Ming

    A study of 142 foreign college students staying in the United States examined the effects of communication adaptability and interaction involvement on cross-cultural adjustment. Further testing was conducted to investigate which of the components of communication adaptability and interaction involvement best predicted the dimensions of…

  5. Technically Speaking: On the Structure and Experience of Interaction Involving Augmentative Alternative Communications

    ERIC Educational Resources Information Center

    Engelke, Christopher Robert

    2013-01-01

    Technically Speaking: On the Structure and Experience of Interaction Involving Augmentative Alternative Communications examines the ways that communication is structured and experienced by looking at interactions involving augmented communicators--people with severe speech disabilities who use forms of assistive technology in order to communicate…

  6. The impact of banners on digital television: the role of program interactivity and product involvement.

    PubMed

    Cauberghe, Verolien; De Pelsmacker, Patrick

    2008-02-01

    In a sample of 281 respondents, the effect of a noninteractive and a medium-interactive television program on recall and brand attitudes for low- and high-involvement products advertised in banners during these programs was investigated. Medium-interactive programs resulted in less product and brand recall and recognition of brands in embedded banner advertisements, but generated more positive brand attitudes than noninteractive programs. These effects were more outspoken for a high-involvement product than for a low-involvement product. The impact of perceived program interactivity on brand attitude is fully mediated program valence and involvement for low-involvement products, but not for high-involvement products, for which perceived program interactivity had a direct impact on brand attitude. PMID:18275319

  7. In vitro and in vivo drug interactions involving human CYP3A.

    PubMed

    Thummel, K E; Wilkinson, G R

    1998-01-01

    Cytochrome P4503A (CYP3A) is importantly involved in the metabolism of many chemically diverse drugs administered to humans. Moreover, its localization in high amounts both in the small intestinal epithelium and liver makes it a major contributor to presystemic elimination following oral drug administration. Drug interactions involving enzyme inhibition or induction are common following the coadministration of two or more CYP3A substrates. Studies using in vitro preparations are useful in identifying such potential interactions and possibly permitting extrapolation of in vitro findings to the likely in vivo situation. Even if accurate quantitative predictions cannot be made, several classes of drugs can be expected to result in a drug interaction based on clinical experience. In many instances, the extent of such drug interactions is sufficiently pronounced to contraindicate the therapeutic use of the involved drugs. PMID:9597161

  8. Development of Inventories for Assessing Parent and Teacher Interaction and Involvement. Final Report.

    ERIC Educational Resources Information Center

    Schaefer, Earl S.; Edgerton, Marianna

    This study was designed to develop a conceptual scheme and brief reliable measures of parent and teacher involvement and interaction, to be given to kindergarteners' parents and teachers at the time of enrollment and again at the end of kindergarten. The inventories provide a framework for an analysis of (1) characteristics of parents and teachers…

  9. Mapping of the Regions Involved in Homotypic Interactions of Tula Hantavirus N Protein

    PubMed Central

    Kaukinen, Pasi; Vaheri, Antti; Plyusnin, Alexander

    2003-01-01

    Hantavirus nucleocapsid (N) protein has been suggested to form homodimers and homotrimers that are further integrated into the nucleocapsid filaments around the viral RNA. Here we report detailed mapping of the regions involved in the homotypic N protein interactions in Tula hantavirus (TULV). Peptide scan screening was used to define the interaction regions, and the mammalian two-hybrid assay was used for the functional analysis of N protein mutants. To study linear regions responsible for N protein interaction(s), we used peptide scanning in which N peptides synthesized on membranes recognize recombinant TULV N protein. The data showed that the N protein bound to membrane-bound peptides comprising amino acids 13 to 30 and 41 to 57 in the N-terminal part and 340 to 379, 391 to 407, and 410 to 419 in the C-terminal part of the molecule. Further mapping of the interaction regions by alanine scanning indicated the importance of basic amino acids along the N protein and especially asparagine-394, histidine-395, and phenyalanine-396 in forming the binding interface. Analysis of truncated mutants in the mammalian two-hybrid assay showed that N-terminal amino acids 1 to 43 are involved in and C-terminal amino acids 393 to 398 (VNHFHL) are absolutely crucial for the homotypic interactions. Furthermore, our data suggested a tail-to-tail and head-to-head binding scheme for the N proteins. PMID:14512541

  10. Focal Adhesion Kinase Is Involved in Rabies Virus Infection through Its Interaction with Viral Phosphoprotein P

    PubMed Central

    Fouquet, Baptiste; Nikolic, Jovan; Larrous, Florence; Bourhy, Hervé; Wirblich, Christoph

    2014-01-01

    ABSTRACT The rabies virus (RABV) phosphoprotein P is a multifunctional protein: it plays an essential role in viral transcription and replication, and in addition, RABV P has been identified as an interferon antagonist. Here, a yeast two-hybrid screen revealed that RABV P interacts with the focal adhesion kinase (FAK). The binding involved the 106-to-131 domain, corresponding to the dimerization domain of P and the C-terminal domain of FAK containing the proline-rich domains PRR2 and PRR3. The P-FAK interaction was confirmed in infected cells by coimmunoprecipitation and colocalization of FAK with P in Negri bodies. By alanine scanning, we identified a single mutation in the P protein that abolishes this interaction. The mutant virus containing a substitution of Ala for Arg in position 109 in P (P.R109A), which did not interact with FAK, is affected at a posttranscriptional step involving protein synthesis and viral RNA replication. Furthermore, FAK depletion inhibited viral protein expression in infected cells. This provides the first evidence of an interaction of RABV with FAK that positively regulates infection. IMPORTANCE Rabies virus exhibits a small genome that encodes a limited number of viral proteins. To maintain efficient virus replication, some of them are multifunctional, such as the phosphoprotein P. We and others have shown that P establishes complex networks of interactions with host cell components. These interactions have revealed much about the role of P and about host-pathogen interactions in infected cells. Here, we identified another cellular partner of P, the focal adhesion kinase (FAK). Our data shed light on the implication of FAK in RABV infection and provide evidence that P-FAK interaction has a proviral function. PMID:25410852

  11. Do Parentese Prosody and Fathers' Involvement in Interacting Facilitate Social Interaction in Infants Who Later Develop Autism?

    PubMed Central

    Cohen, David; Cassel, Raquel S.; Saint-Georges, Catherine; Mahdhaoui, Ammar; Laznik, Marie-Christine; Apicella, Fabio; Muratori, Pietro; Maestro, Sandra; Muratori, Filippo; Chetouani, Mohamed

    2013-01-01

    Background Whether development of autism impacts the interactive process between an infant and his/her parents remains an unexplored issue. Methodology and Principal Findings Using computational analysis taking into account synchronic behaviors and emotional prosody (parentese), we assessed the course of infants' responses to parents' type of speech in home movies from typically developing (TD) infants and infants who will subsequently develop autism aged less than 18 months. Our findings indicate: that parentese was significantly associated with infant responses to parental vocalizations involving orientation towards other people and with infant receptive behaviours; that parents of infants developing autism displayed more intense solicitations that were rich in parentese; that fathers of infants developing autism spoke to their infants more than fathers of TD infants; and that fathers' vocalizations were significantly associated with intersubjective responses and active behaviours in infants who subsequently developed autism. Conclusion The parents of infants who will later develop autism change their interactive pattern of behaviour by both increasing parentese and father's involvement in interacting with infants; both are significantly associated with infant's social responses. We stress the possible therapeutic implications of these findings and its implication for Dean Falk's theory regarding pre-linguistic evolution in early hominins. PMID:23650498

  12. Strigolactone Involvement in Root Development, Response to Abiotic Stress, and Interactions with the Biotic Soil Environment

    PubMed Central

    Kapulnik, Yoram; Koltai, Hinanit

    2014-01-01

    Strigolactones, recently discovered as plant hormones, regulate the development of different plant parts. In the root, they regulate root architecture and affect root hair length and density. Their biosynthesis and exudation increase under low phosphate levels, and they are associated with root responses to these conditions. Their signaling pathway in the plant includes protein interactions and ubiquitin-dependent repressor degradation. In the root, they lead to changes in actin architecture and dynamics as well as localization of the PIN-FORMED auxin transporter in the plasma membrane. Strigolactones are also involved with communication in the rhizosphere. They are necessary for germination of parasitic plant seeds, they enhance hyphal branching of arbuscular mycorrhizal fungi of the Glomus and Gigaspora spp., and they promote rhizobial symbiosis. This review focuses on the role played by strigolactones in root development, their response to nutrient deficiency, and their involvement with plant interactions in the rhizosphere. PMID:25037210

  13. Interactions between copy number and expression level of genes involved in fluconazole resistance in Candida glabrata

    PubMed Central

    Abbes, Salma; Mary, Charles; Sellami, Hayet; Michel-Nguyen, Annie; Ayadi, Ali; Ranque, Stéphane

    2013-01-01

    Objectives: This study aimed to elucidate the relative involvement of drug resistance gene copy number and overexpression in fluconazole resistance in clinical C. glabrata isolates using a population-based approach. Methods: Fluconazole resistance levels were quantified using the minimal inhibitory concentration (MIC) via Etest method. Both gene expression levels and gene copy number of CgCDR1, CgPDH1, CgERG11, and CgSNQ2 were assessed via quantitative real-time PCR. The influence of the main effects and first-level interactions of both the expression level and copy number of these genes on fluconazole resistance levels were analyzed using a multivariate statistical model. Results: Forty-three C. glabrata isolates were collected from 30 patients during in a hospital survey. In the multivariate analysis, C. glabrata fluconazole MICs were independently increased by CgSNQ2 overexpression (p < 10−4) and the interaction between CgPDH1 gene copy number and CgPDH1 expression level (p = 0.038). In contrast, both CgPDH1 overexpression (p = 0.049) and the interaction between CgSNQ2 and CgERG11 expression (p = 0.003) led to a significant decrease in fluconazole MICs. Conclusion: Fluconazole resistance in C. glabrata involves complex interactions between drug resistance gene expression and/or copy number. The population-based multivariate analysis highlighted the involvement of the CgSNQ2 gene in fluconazole resistance and the complex effect of the other genes such as PDH1 for which overexpression was associated with reduced fluconazole resistance levels, while the interaction between PDH1 overexpression and copy number was associated with increased resistance levels. PMID:24273749

  14. Involvement of the carboxyl group in QPs in interaction with succinate dehydrogenase

    SciTech Connect

    Xu, J.; Yu, L.; Yu, C.

    1987-05-01

    Bovine heart mitochondrial succinate-ubiquinone reductase (SQR) can be resolved into two reconstitutively active fractions; soluble succinate dehydrogenase (SDH), and a two-subunit Q-binding protein known as QPs or cytochrome b/sub 560/ fraction. The interaction between SDH and QPs involves both hydrophobic and ionic interactions. The involvement of an amino group in SDH has been established, the participation of a negatively charged group in QPs was then being speculated. Recently, they have used dicyclohexyl carbodiimide (DCCD) to study the involvement of carboxyl group in QPs with respect to interaction with SDH. When isolated QPs was treated with a 300-molar excess of DCCD per mole of protein at pH 6.0 in the presence of 0.2% D-N-gluco-N-methyl-decanamide, more than 80% of the reconstitutive activity of QPs was diminished. The inhibition of QPs by DCCD is pH and detergent concentration dependent. When intact or reconstituted SQR was treated with DCCD, no inhibition was observed, indicating that a carboxyl group in QPs which is essential for interaction with SDH is protected from DCCD modification in the presence of active SDH. No protecting effect was observed when reconstitutively inactive SDH was used, indicating that there is no interaction between reconstitutively inactive SDH and QPs. The (/sup 14/C)-DCCD labeling study showed that the DCCD was incorporated into the smaller subunit of QPs. The modification of QPs by DCCD also caused an alteration of spectral characteristics of cytochrome b/sub 560/.

  15. Genetic Interactions Involving Five or More Genes Contribute to a Complex Trait in Yeast

    PubMed Central

    Taylor, Matthew B.; Ehrenreich, Ian M.

    2014-01-01

    Recent research suggests that genetic interactions involving more than two loci may influence a number of complex traits. How these ‘higher-order’ interactions arise at the genetic and molecular levels remains an open question. To provide insights into this problem, we dissected a colony morphology phenotype that segregates in a yeast cross and results from synthetic higher-order interactions. Using backcrossing and selective sequencing of progeny, we found five loci that collectively produce the trait. We fine-mapped these loci to 22 genes in total and identified a single gene at each locus that caused loss of the phenotype when deleted. Complementation tests or allele replacements provided support for functional variation in these genes, and revealed that pre-existing genetic variants and a spontaneous mutation interact to cause the trait. The causal genes have diverse functions in endocytosis (END3), oxidative stress response (TRR1), RAS-cAMP signalling (IRA2), and transcriptional regulation of multicellular growth (FLO8 and MSS11), and for the most part have not previously been shown to exhibit functional relationships. Further efforts uncovered two additional loci that together can complement the non-causal allele of END3, suggesting that multiple genotypes in the cross can specify the same phenotype. Our work sheds light on the complex genetic and molecular architecture of higher-order interactions, and raises questions about the broader contribution of such interactions to heritable trait variation. PMID:24784154

  16. Structural Insights into Protein-Protein Interactions Involved in Bacterial Cell Wall Biogenesis

    PubMed Central

    Laddomada, Federica; Miyachiro, Mayara M.; Dessen, Andréa

    2016-01-01

    The bacterial cell wall is essential for survival, and proteins that participate in its biosynthesis have been the targets of antibiotic development efforts for decades. The biosynthesis of its main component, the peptidoglycan, involves the coordinated action of proteins that are involved in multi-member complexes which are essential for cell division (the “divisome”) and/or cell wall elongation (the “elongasome”), in the case of rod-shaped cells. Our knowledge regarding these interactions has greatly benefitted from the visualization of different aspects of the bacterial cell wall and its cytoskeleton by cryoelectron microscopy and tomography, as well as genetic and biochemical screens that have complemented information from high resolution crystal structures of protein complexes involved in divisome or elongasome formation. This review summarizes structural and functional aspects of protein complexes involved in the cytoplasmic and membrane-related steps of peptidoglycan biosynthesis, with a particular focus on protein-protein interactions whereby disruption could lead to the development of novel antibacterial strategies. PMID:27136593

  17. Evolution of genes involved in gamete interaction: evidence for positive selection, duplications and losses in vertebrates.

    PubMed

    Meslin, Camille; Mugnier, Sylvie; Callebaut, Isabelle; Laurin, Michel; Pascal, Géraldine; Poupon, Anne; Goudet, Ghylène; Monget, Philippe

    2012-01-01

    Genes encoding proteins involved in sperm-egg interaction and fertilization exhibit a particularly fast evolution and may participate in prezygotic species isolation [1], [2]. Some of them (ZP3, ADAM1, ADAM2, ACR and CD9) have individually been shown to evolve under positive selection [3], [4], suggesting a role of positive Darwinian selection on sperm-egg interaction. However, the genes involved in this biological function have not been systematically and exhaustively studied with an evolutionary perspective, in particular across vertebrates with internal and external fertilization. Here we show that 33 genes among the 69 that have been experimentally shown to be involved in fertilization in at least one taxon in vertebrates are under positive selection. Moreover, we identified 17 pseudogenes and 39 genes that have at least one duplicate in one species. For 15 genes, we found neither positive selection, nor gene copies or pseudogenes. Genes of teleosts, especially genes involved in sperm-oolemma fusion, appear to be more frequently under positive selection than genes of birds and eutherians. In contrast, pseudogenization, gene loss and gene gain are more frequent in eutherians. Thus, each of the 19 studied vertebrate species exhibits a unique signature characterized by gene gain and loss, as well as position of amino acids under positive selection. Reflecting these clade-specific signatures, teleosts and eutherian mammals are recovered as clades in a parsimony analysis. Interestingly the same analysis places Xenopus apart from teleosts, with which it shares the primitive external fertilization, and locates it along with amniotes (which share internal fertilization), suggesting that external or internal environmental conditions of germ cell interaction may not be the unique factors that drive the evolution of fertilization genes. Our work should improve our understanding of the fertilization process and on the establishment of reproductive barriers, for example by

  18. Identification of Critical Paraoxonase 1 Residues Involved in High Density Lipoprotein Interaction.

    PubMed

    Gu, Xiaodong; Huang, Ying; Levison, Bruce S; Gerstenecker, Gary; DiDonato, Anthony J; Hazen, Leah B; Lee, Joonsue; Gogonea, Valentin; DiDonato, Joseph A; Hazen, Stanley L

    2016-01-22

    Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated protein with atherosclerosis-protective and systemic anti-oxidant functions. We recently showed that PON1, myeloperoxidase, and HDL bind to one another in vivo forming a functional ternary complex (Huang, Y., Wu, Z., Riwanto, M., Gao, S., Levison, B. S., Gu, X., Fu, X., Wagner, M. A., Besler, C., Gerstenecker, G., Zhang, R., Li, X. M., Didonato, A. J., Gogonea, V., Tang, W. H., et al. (2013) J. Clin. Invest. 123, 3815-3828). However, specific residues on PON1 involved in the HDL-PON1 interaction remain unclear. Unambiguous identification of protein residues involved in docking interactions to lipid surfaces poses considerable methodological challenges. Here we describe a new strategy that uses a novel synthetic photoactivatable and click chemistry-taggable phospholipid probe, which, when incorporated into HDL, was used to identify amino acid residues on PON1 that directly interact with the lipoprotein phospholipid surface. Several specific PON1 residues (Leu-9, Tyr-185, and Tyr-293) were identified through covalent cross-links with the lipid probes using affinity isolation coupled to liquid chromatography with on-line tandem mass spectrometry. Based upon the crystal structure for PON1, the identified residues are all localized in relatively close proximity on the surface of PON1, defining a domain that binds to the HDL lipid surface. Site-specific mutagenesis of the identified PON1 residues (Leu-9, Tyr-185, and Tyr-293), coupled with functional studies, reveals their importance in PON1 binding to HDL and both PON1 catalytic activity and stability. Specifically, the residues identified on PON1 provide important structural insights into the PON1-HDL interaction. More generally, the new photoactivatable and affinity-tagged lipid probe developed herein should prove to be a valuable tool for identifying contact sites supporting protein interactions with lipid interfaces such as found on cell membranes

  19. Ex vivo identification of protein-protein interactions involving the dopamine transporter.

    PubMed

    Hadlock, Gregory C; Nelson, Chad C; Baucum, Anthony J; Hanson, Glen R; Fleckenstein, Annette E

    2011-03-30

    The dopamine (DA) transporter (DAT) is a key regulator of dopaminergic signaling as it mediates the reuptake of extrasynaptic DA and thereby terminates dopaminergic signaling. Emerging evidence indicates that DAT function is influenced through interactions with other proteins. The current report describes a method to identify such interactions following DAT immunoprecipitation from a rat striatal synaptosomal preparation. This subcellular fraction was selected since DAT function is often determined ex vivo by measuring DA uptake in this preparation and few reports investigating DAT-protein interactions have utilized this preparation. Following SDS-PAGE and colloidal Coomassie staining, selected protein bands from a DAT-immunoprecipitate were excised, digested with trypsin, extracted, and analyzed by liquid chromatography tandem mass spectrometry (LC/MS/MS). From the analysis of the tryptic peptides, several proteins were identified including DAT, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) β, CaMKII δ, protein kinase C (PKC) β, and PKC γ. Co-immunoprecipitation of PKC, CaMKII, and protein interacting with C kinase-1 with DAT was confirmed by Western blotting. Thus, the present study highlights a method to immunoprecipitate DAT and to identify co-immunoprecipitating proteins using LC/MS/MS and Western blotting. This method can be utilized to evaluate DAT protein-protein interactions but also to assess interactions involving other synaptic proteins. Ex vivo identification of protein-protein interactions will provide new insight into the function and regulation of a variety of synaptic, membrane-associated proteins, including DAT. PMID:21291912

  20. Banana ethylene response factors are involved in fruit ripening through their interactions with ethylene biosynthesis genes.

    PubMed

    Xiao, Yun-yi; Chen, Jian-ye; Kuang, Jiang-fei; Shan, Wei; Xie, Hui; Jiang, Yue-ming; Lu, Wang-jin

    2013-05-01

    The involvement of ethylene response factor (ERF) transcription factor (TF) in the transcriptional regulation of ethylene biosynthesis genes during fruit ripening remains largely unclear. In this study, 15 ERF genes, designated as MaERF1-MaERF15, were isolated and characterized from banana fruit. These MaERFs were classified into seven of the 12 known ERF families. Subcellular localization showed that MaERF proteins of five different subfamilies preferentially localized to the nucleus. The 15 MaERF genes displayed differential expression patterns and levels in peel and pulp of banana fruit, in association with four different ripening treatments caused by natural, ethylene-induced, 1-methylcyclopropene (1-MCP)-delayed, and combined 1-MCP and ethylene treatments. MaERF9 was upregulated while MaERF11 was downregulated in peel and pulp of banana fruit during ripening or after treatment with ethylene. Furthermore, yeast-one hybrid (Y1H) and transient expression assays showed that the potential repressor MaERF11 bound to MaACS1 and MaACO1 promoters to suppress their activities and that MaERF9 activated MaACO1 promoter activity. Interestingly, protein-protein interaction analysis revealed that MaERF9 and -11 physically interacted with MaACO1. Taken together, these results suggest that MaERFs are involved in banana fruit ripening via transcriptional regulation of or interaction with ethylene biosynthesis genes. PMID:23599278

  1. A Test of the Interactive Effects of Organizational Commitment and Job Involvement on Various Types of Absence.

    ERIC Educational Resources Information Center

    Mathieu, John E.; Kohler, Stacey S.

    1990-01-01

    Examined joint direct and interactive influences of organizational commitment and job involvement on employee absence rates in bus drivers (N=192). Results support hypothesis that commitment and involvement interact as related to drivers' personal absences, but not as related to absences resulting from illness, family obligation, or transportation…

  2. Fe-S Bonded Interactions Involving High and Low Spin State Divalent Fe Atoms

    NASA Astrophysics Data System (ADS)

    Gibbs, G. V.; Cox, D. F.; Rosso, K. M.; Ross, N. L.

    2006-12-01

    Bond critical point and local energy density properties together with the net atomic charges were generated for the theoretical electron density distributions, ρ(r), for a variety of Fe sulfide crystalline materials with high and low spin state divalent Fe atoms in octahedral coordination and high spin state divalent and trivalent Fe atoms in tetrahedral coordination. The value of the electron density, ρ(rc), and the Laplacian, ▽ 2ρ(rc), the local potential energy density, V(rc), and the local electronic energy density, H(rc), at bond critical points, (rc), each increases and the local kinetic energy density, G(rc), decreases as the coordination numbers of the Fe atoms decrease and the shared character of the Fe-S bonds is indicated to increase. The properties of the bonded interactions involving the octahedrally coordinated low spin state divalent Fe atoms in pyrite and marcasite depart substantially from those of the octahedrally coordinated high spin state divalent Fe atoms in troilite, symthite and greigite. The Fe-S bond lengths are shorter and the values of ρ(rc) and ▽ 2ρ(rc), are larger for pyrite and marcasite indicating that the accumulation and local concentration of ρ(r) in the vicinity of rc is greater than those involving the longer, high spin state Fe-S bonded interactions. The net atomic charges conferred on the Fe and S atoms in pyrite and marcasite are also smaller than those calculated for sulfides with high spin state octahedrally coordinate divalent Fe atoms. Collectively, the Fe-S bonded interactions are indicated to be intermediate in character on the basis of their bond indices with the low spin Fe-S bonds being more shared interactions than the high spin state bonded interactions. S-S bond paths exist between each of the surface S atoms of the adjacent layers of FeS6 octahedra in smythite, indicating that the neutral Fe3S4 layers are linked together by S-S bonded interactions. Such interactions not only exist between the S atoms on

  3. Vaccination with proteins involved in tick-pathogen interactions reduces vector infestations and pathogen infection.

    PubMed

    Merino, Octavio; Antunes, Sandra; Mosqueda, Juan; Moreno-Cid, Juan A; Pérez de la Lastra, José M; Rosario-Cruz, Rodrigo; Rodríguez, Sergio; Domingos, Ana; de la Fuente, José

    2013-12-01

    Tick-borne pathogens cause diseases that greatly impact animal health and production worldwide. The ultimate goal of tick vaccines is to protect against tick-borne diseases through the control of vector infestations and reducing pathogen infection and transmission. Tick genetic traits are involved in vector-pathogen interactions and some of these molecules such as Subolesin (SUB) have been shown to protect against vector infestations and pathogen infection. Based on these premises, herein we characterized the efficacy of cattle vaccination with tick proteins involved in vector-pathogen interactions, TROSPA, SILK, and Q38 for the control of cattle tick, Rhipicephalus (Boophilus) microplus infestations and infection with Anaplasma marginale and Babesia bigemina. SUB and adjuvant/saline placebo were used as positive and negative controls, respectively. The results showed that vaccination with Q38, SILK and SUB reduced tick infestations and oviposition with vaccine efficacies of 75% (Q38), 62% (SILK) and 60% (SUB) with respect to ticks fed on placebo control cattle. Vaccination with TROSPA did not have a significant effect on any of the tick parameters analyzed. The results also showed that vaccination with Q38, TROSPA and SUB reduced B. bigemina DNA levels in ticks while vaccination with SILK and SUB resulted in lower A. marginale DNA levels when compared to ticks fed on placebo control cattle. The positive correlation between antigen-specific antibody titers and reduction of tick infestations and pathogen infection strongly suggested that the effect of the vaccine was the result of the antibody response in vaccinated cattle. Vaccination and co-infection with A. marginale and B. bigemina also affected the expression of genes encoding for vaccine antigens in ticks fed on cattle. These results showed that vaccines using tick proteins involved in vector-pathogen interactions could be used for the dual control of tick infestations and pathogen infection. PMID:24084474

  4. Metabolomics of reef benthic interactions reveals a bioactive lipid involved in coral defence.

    PubMed

    Quinn, Robert A; Vermeij, Mark J A; Hartmann, Aaron C; Galtier d'Auriac, Ines; Benler, Sean; Haas, Andreas; Quistad, Steven D; Lim, Yan Wei; Little, Mark; Sandin, Stuart; Smith, Jennifer E; Dorrestein, Pieter C; Rohwer, Forest

    2016-04-27

    Holobionts are assemblages of microbial symbionts and their macrobial host. As extant representatives of some of the oldest macro-organisms, corals and algae are important for understanding how holobionts develop and interact with one another. Using untargeted metabolomics, we show that non-self interactions altered the coral metabolome more than self-interactions (i.e. different or same genus, respectively). Platelet activating factor (PAF) and Lyso-PAF, central inflammatory modulators in mammals, were major lipid components of the coral holobionts. When corals were damaged during competitive interactions with algae, PAF increased along with expression of the gene encoding Lyso-PAF acetyltransferase; the protein responsible for converting Lyso-PAF to PAF. This shows that self and non-self recognition among some of the oldest extant holobionts involve bioactive lipids identical to those in highly derived taxa like humans. This further strengthens the hypothesis that major players of the immune response evolved during the pre-Cambrian. PMID:27122568

  5. Metabolomics of reef benthic interactions reveals a bioactive lipid involved in coral defence

    PubMed Central

    Vermeij, Mark J. A.; Hartmann, Aaron C.; Galtier d'Auriac, Ines; Benler, Sean; Haas, Andreas; Quistad, Steven D.; Lim, Yan Wei; Little, Mark; Sandin, Stuart; Smith, Jennifer E.; Dorrestein, Pieter C.; Rohwer, Forest

    2016-01-01

    Holobionts are assemblages of microbial symbionts and their macrobial host. As extant representatives of some of the oldest macro-organisms, corals and algae are important for understanding how holobionts develop and interact with one another. Using untargeted metabolomics, we show that non-self interactions altered the coral metabolome more than self-interactions (i.e. different or same genus, respectively). Platelet activating factor (PAF) and Lyso-PAF, central inflammatory modulators in mammals, were major lipid components of the coral holobionts. When corals were damaged during competitive interactions with algae, PAF increased along with expression of the gene encoding Lyso-PAF acetyltransferase; the protein responsible for converting Lyso-PAF to PAF. This shows that self and non-self recognition among some of the oldest extant holobionts involve bioactive lipids identical to those in highly derived taxa like humans. This further strengthens the hypothesis that major players of the immune response evolved during the pre-Cambrian. PMID:27122568

  6. Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human cells

    NASA Technical Reports Server (NTRS)

    Wiese, Claudia; Collins, David W.; Albala, Joanna S.; Thompson, Larry H.; Kronenberg, Amy; Schild, David; Chatterjee, A. (Principal Investigator)

    2002-01-01

    Homologous recombinational repair of DNA double-strand breaks and crosslinks in human cells is likely to require Rad51 and the five Rad51 paralogs (XRCC2, XRCC3, Rad51B/Rad51L1, Rad51C/Rad51L2 and Rad51D/Rad51L3), as has been shown in chicken and rodent cells. Previously, we reported on the interactions among these proteins using baculovirus and two- and three-hybrid yeast systems. To test for interactions involving XRCC3 and Rad51C, stable human cell lines have been isolated that express (His)6-tagged versions of XRCC3 or Rad51C. Ni2+-binding experiments demonstrate that XRCC3 and Rad51C interact in human cells. In addition, we find that Rad51C, but not XRCC3, interacts directly or indirectly with Rad51B, Rad51D and XRCC2. These results argue that there are at least two complexes of Rad51 paralogs in human cells (Rad51C-XRCC3 and Rad51B-Rad51C-Rad51D-XRCC2), both containing Rad51C. Moreover, Rad51 is not found in these complexes. X-ray treatment did not alter either the level of any Rad51 paralog or the observed interactions between paralogs. However, the endogenous level of Rad51C is moderately elevated in the XRCC3-overexpressing cell line, suggesting that dimerization between these proteins might help stabilize Rad51C.

  7. Molecular interactions and residues involved in force generation in the T4 viral DNA packaging motor.

    PubMed

    Migliori, Amy D; Smith, Douglas E; Arya, Gaurav

    2014-12-12

    Many viruses utilize molecular motors to package their genomes into preformed capsids. A striking feature of these motors is their ability to generate large forces to drive DNA translocation against entropic, electrostatic, and bending forces resisting DNA confinement. A model based on recently resolved structures of the bacteriophage T4 motor protein gp17 suggests that this motor generates large forces by undergoing a conformational change from an extended to a compact state. This transition is proposed to be driven by electrostatic interactions between complementarily charged residues across the interface between the N- and C-terminal domains of gp17. Here we use atomistic molecular dynamics simulations to investigate in detail the molecular interactions and residues involved in such a compaction transition of gp17. We find that although electrostatic interactions between charged residues contribute significantly to the overall free energy change of compaction, interactions mediated by the uncharged residues are equally if not more important. We identify five charged residues and six uncharged residues at the interface that play a dominant role in the compaction transition and also reveal salt bridging, van der Waals, and solvent hydrogen-bonding interactions mediated by these residues in stabilizing the compact form of gp17. The formation of a salt bridge between Glu309 and Arg494 is found to be particularly crucial, consistent with experiments showing complete abrogation in packaging upon Glu309Lys mutation. The computed contributions of several other residues are also found to correlate well with single-molecule measurements of impairments in DNA translocation activity caused by site-directed mutations. PMID:25311860

  8. MCT Expression and Lactate Influx/Efflux in Tanycytes Involved in Glia-Neuron Metabolic Interaction

    PubMed Central

    Cortés-Campos, Christian; Elizondo, Roberto; Llanos, Paula; Uranga, Romina María; Nualart, Francisco; García, María Angeles

    2011-01-01

    Metabolic interaction via lactate between glial cells and neurons has been proposed as one of the mechanisms involved in hypothalamic glucosensing. We have postulated that hypothalamic glial cells, also known as tanycytes, produce lactate by glycolytic metabolism of glucose. Transfer of lactate to neighboring neurons stimulates ATP synthesis and thus contributes to their activation. Because destruction of third ventricle (III-V) tanycytes is sufficient to alter blood glucose levels and food intake in rats, it is hypothesized that tanycytes are involved in the hypothalamic glucose sensing mechanism. Here, we demonstrate the presence and function of monocarboxylate transporters (MCTs) in tanycytes. Specifically, MCT1 and MCT4 expression as well as their distribution were analyzed in Sprague Dawley rat brain, and we demonstrate that both transporters are expressed in tanycytes. Using primary tanycyte cultures, kinetic analyses and sensitivity to inhibitors were undertaken to confirm that MCT1 and MCT4 were functional for lactate influx. Additionally, physiological concentrations of glucose induced lactate efflux in cultured tanycytes, which was inhibited by classical MCT inhibitors. Because the expression of both MCT1 and MCT4 has been linked to lactate efflux, we propose that tanycytes participate in glucose sensing based on a metabolic interaction with neurons of the arcuate nucleus, which are stimulated by lactate released from MCT1 and MCT4-expressing tanycytes. PMID:21297988

  9. Classical lattice spin models involving singular interactions isotropic in spin space.

    PubMed

    Chamati, Hassan; Romano, Silvano

    2015-07-01

    We address here a few classical lattice spin models, involving n-component unit vectors (n=2,3), associated with a D-dimensional lattice Z(D),D=1,2, and interacting via a pair potential restricted to nearest neighbors and being isotropic in spin space, i.e., defined by a function of the scalar product between the interacting spins. When the potential involves a continuous function of the scalar product, the Mermin-Wagner theorem and its generalizations exclude orientational order at all finite temperatures in the thermodynamic limit, and exclude phase transitions at finite temperatures when D=1; on the other hand, we have considered here some comparatively simple functions of the scalar product which are bounded from below, diverge to +∞ for certain mutual orientations, and are continuous almost everywhere with integrable singularities. Exact solutions are presented for D=1, showing an absence of phase transitions and an absence of orientational order at all finite temperatures in the thermodynamic limit; for D=2, and in the absence of more stringent mathematical results, extensive simulations carried out on some of them point to the absence of orientational order at all finite temperatures and suggest the existence of a Berezinskiĭ-Kosterlitz-Thouless transition. PMID:26274152

  10. Yeast Irc22 Is a Novel Dsk2-Interacting Protein that Is Involved in Salt Tolerance

    PubMed Central

    Ishii, Takashi; Funakoshi, Minoru; Kobayashi, Hideki; Sekiguchi, Takeshi

    2014-01-01

    The yeast ubiquitin-like and ubiquitin-associated protein Dsk2 is one of the ubiquitin receptors that function in the ubiquitin-proteasome pathway. We screened the Dsk2-interacting proteins in Saccharomyces cerevisiae by a two-hybrid assay and identified a novel Dsk2-interacting protein, Irc22, the gene locus of which has previously been described as YEL001C, but the function of which is unknown. IRC22/YEL001C encodes 225 amino acid residues with a calculated molecular weight of 25 kDa. The Irc22 protein was detected in yeast cells. IRC22 was a nonessential gene for yeast growth, and its homologs were found among ascomycetous yeasts. Irc22 interacted with Dsk2 in yeast cells, but not with Rad23 and Ddi1. Ubiquitin-dependent degradation was impaired mildly by over-expression or disruption of IRC22. Compared with the wild-type strain, dsk2Δ exhibited salt sensitivity while irc22Δ exhibited salt tolerance at high temperatures. The salt-tolerant phenotype that was observed in irc22Δ disappeared in the dsk2Δirc22Δ double disruptant, indicating that DSK2 is positively and IRC22 is negatively involved in salt stress tolerance. IRC22 disruption did not affect any responses to DNA damage and oxidative stress when comparing the irc22Δ and wild-type strains. Collectively, these results suggest that Dsk2 and Irc22 are involved in salt stress tolerance in yeast. PMID:24709957

  11. Numerical and Analytical Solutions of Hypersonic Interactions Involving Surface Property Discontinuities

    NASA Technical Reports Server (NTRS)

    Gnoffo, Peter A.; Inger, George R.

    1999-01-01

    The local viscous-inviscid interaction field generated by a wall temperature jump on a flat plate in supersonic flow and on the windside of a Reusable Launch Vehicle in hypersonic flow is studied in detail by both a Navier-Stokes numerical code and an analytical triple-deck model. Treatment of the rapid heat transfer changes both upstream and downstream of the jump is included. Closed form relationships derived from the triple-deck theory are presented. The analytically predicted pressure and heating variations including upstream influence are found to be in generally good agreement with the Computational Fluid Dynamic (CFD) predictions. These analyses not only clarify the interactive physics involved but also are useful in preliminary design of thermal protection systems and as an insertable module to improve CFD code efficiency when applied to such small-scale interaction problems. The analyses only require conditions at the wall and boundary-layer edge which are easily extracted from a baseline, constant wall temperature, CFD solution.

  12. Involvement of budding yeast Rad5 in translesion DNA synthesis through physical interaction with Rev1

    PubMed Central

    Xu, Xin; Lin, Aiyang; Zhou, Cuiyan; Blackwell, Susan R.; Zhang, Yiran; Wang, Zihao; Feng, Qianqian; Guan, Ruifang; Hanna, Michelle D.; Chen, Zhucheng; Xiao, Wei

    2016-01-01

    DNA damage tolerance (DDT) is responsible for genomic stability and cell viability by bypassing the replication block. In Saccharomyces cerevisiae DDT employs two parallel branch pathways to bypass the DNA lesion, namely translesion DNA synthesis (TLS) and error-free lesion bypass, which are mediated by sequential modifications of PCNA. Rad5 has been placed in the error-free branch of DDT because it contains an E3 ligase domain required for PCNA polyubiquitination. Rad5 is a multi-functional protein and may also play a role in TLS, since it interacts with the TLS polymerase Rev1. In this study we mapped the Rev1-interaction domain in Rad5 to the amino acid resolution and demonstrated that Rad5 is indeed involved in TLS possibly through recruitment of Rev1. Genetic analyses show that the dual functions of Rad5 can be separated and reconstituted. Crystal structure analysis of the Rad5–Rev1 interaction reveals a consensus RFF motif in the Rad5 N-terminus that binds to a hydrophobic pocket within the C-terminal domain of Rev1 that is highly conserved in eukaryotes. This study indicates that Rad5 plays a critical role in pathway choice between TLS and error-free DDT. PMID:27001510

  13. Involvement of budding yeast Rad5 in translesion DNA synthesis through physical interaction with Rev1.

    PubMed

    Xu, Xin; Lin, Aiyang; Zhou, Cuiyan; Blackwell, Susan R; Zhang, Yiran; Wang, Zihao; Feng, Qianqian; Guan, Ruifang; Hanna, Michelle D; Chen, Zhucheng; Xiao, Wei

    2016-06-20

    DNA damage tolerance (DDT) is responsible for genomic stability and cell viability by bypassing the replication block. In Saccharomyces cerevisiae DDT employs two parallel branch pathways to bypass the DNA lesion, namely translesion DNA synthesis (TLS) and error-free lesion bypass, which are mediated by sequential modifications of PCNA. Rad5 has been placed in the error-free branch of DDT because it contains an E3 ligase domain required for PCNA polyubiquitination. Rad5 is a multi-functional protein and may also play a role in TLS, since it interacts with the TLS polymerase Rev1. In this study we mapped the Rev1-interaction domain in Rad5 to the amino acid resolution and demonstrated that Rad5 is indeed involved in TLS possibly through recruitment of Rev1. Genetic analyses show that the dual functions of Rad5 can be separated and reconstituted. Crystal structure analysis of the Rad5-Rev1 interaction reveals a consensus RFF motif in the Rad5 N-terminus that binds to a hydrophobic pocket within the C-terminal domain of Rev1 that is highly conserved in eukaryotes. This study indicates that Rad5 plays a critical role in pathway choice between TLS and error-free DDT. PMID:27001510

  14. Interactions involving ozone, Botrytis cinerea, and B. squamosa on onion leaves

    SciTech Connect

    Rist, D.L.

    1983-01-01

    Interactions involving Botrytis cinerea Pers., B. squamosa Walker, and ozone on onion (alium cepae L.) were investigated. Initially, threshold dosages of ozone required to predispose onion leaves to greater infection by B. cinerea and B. squamosa were determined under controlled conditions in an ozone-exposure chamber. Subsequent experiments supported the hypothesis that nutrients leaking out of ozone-injured cells stimulated lesion production by B. cinerea. The electrical conductivity of, and carbohydrate concentration in, dew collected from leaves of onion plants which had been exposed to ozone were greater than the electrical conductivity of, and carbohydrate concentration in, dew collected from leaves of other, non-exposed onion plants. When conidia of B. cinerea were suspended in dew collected from leaves of plants which had been exposed to ozone and the resulting suspension atomized onto leaves of non-exposed plants, more lesions were induced than on leaves of other non-exposed plants inoculated with conidia suspended in dew collected from plants which had not been exposed to ozone. EDU protected onion leaves from ozone-induced predisposition to these fungi under controlled conditions. Experiments designed to detect interaction between B. cinerea and B. squamosa in onion leaf blighting indicated that such interaction did not occur. Leaves were blighted rapidly when inoculated with B. squamosa whether B. cinerea was present or absent.

  15. Involvement of apoptosis in host-parasite interactions in the zebra mussel.

    PubMed

    Minguez, Laëtitia; Brulé, Nelly; Sohm, Bénédicte; Devin, Simon; Giambérini, Laure

    2013-01-01

    The question of whether cell death by apoptosis plays a biological function during infection is key to understanding host-parasite interactions. We investigated the involvement of apoptosis in several host-parasite systems, using zebra mussels Dreissena polymorpha as test organisms and their micro- and macroparasites. As a stress response associated with parasitism, heat shock proteins (Hsp) can be induced. In this protein family, Hsp70 are known to be apoptosis inhibitors. Mussels were diagnosed for their respective infections by standard histological methods; apoptosis was detected using the TUNEL methods on paraffin sections and Hsp70 by immunohistochemistry on cryosections. Circulating hemocytes were the main cells observed in apoptosis whereas infected tissues displayed no or few apoptotic cells. Parasitism by intracellular bacteria Rickettsiales-like and the trematode Bucephalus polymorphus were associated with the inhibition of apoptosis whereas ciliates Ophryoglena spp. or the trematode Phyllodistomum folium did not involve significant differences in apoptosis. Even if some parasites were able to modulate apoptosis in zebra mussels, we did not see evidence of any involvement of Hsp70 on this mechanism. PMID:23785455

  16. Involvement of Apoptosis in Host-Parasite Interactions in the Zebra Mussel

    PubMed Central

    Minguez, Laëtitia; Brulé, Nelly; Sohm, Bénédicte; Devin, Simon; Giambérini, Laure

    2013-01-01

    The question of whether cell death by apoptosis plays a biological function during infection is key to understanding host-parasite interactions. We investigated the involvement of apoptosis in several host-parasite systems, using zebra mussels Dreissena polymorpha as test organisms and their micro- and macroparasites. As a stress response associated with parasitism, heat shock proteins (Hsp) can be induced. In this protein family, Hsp70 are known to be apoptosis inhibitors. Mussels were diagnosed for their respective infections by standard histological methods; apoptosis was detected using the TUNEL methods on paraffin sections and Hsp70 by immunohistochemistry on cryosections. Circulating hemocytes were the main cells observed in apoptosis whereas infected tissues displayed no or few apoptotic cells. Parasitism by intracellular bacteria Rickettsiales-like and the trematode Bucephalus polymorphus were associated with the inhibition of apoptosis whereas ciliates Ophryoglena spp. or the trematode Phyllodistomum folium did not involve significant differences in apoptosis. Even if some parasites were able to modulate apoptosis in zebra mussels, we did not see evidence of any involvement of Hsp70 on this mechanism. PMID:23785455

  17. A Pmk1-interacting gene is involved in appressorium differentiation and plant infection in Magnaporthe oryzae.

    PubMed

    Zhang, Haifeng; Xue, Chaoyang; Kong, Lingan; Li, Guotian; Xu, Jin-Rong

    2011-08-01

    In the rice blast fungus Magnaporthe oryzae, the PMK1 mitogen-activated protein (MAP) kinase gene regulates appressorium formation and infectious growth. Its homologs in many other fungi also play critical roles in fungal development and pathogenicity. However, the targets of this important MAP kinase and its interacting genes are not well characterized. In this study, we constructed two yeast two-hybrid libraries of M. oryzae and screened for Pmk1-interacting proteins. Among the nine Pmk1-interacting clones (PICs) identified, two of them, PIC1 and PIC5, were selected for further characterization. Pic1 has one putative nuclear localization signal and one putative MAP kinase phosphorylation site. Pic5 contains one transmembrane domain and two functionally unknown CTNS (cystinosin/ERS1p repeat) motifs. The interaction of Pmk1 with Pic1 or Pic5 was confirmed by coimmunoprecipitation assays. Targeted gene deletion of PIC1 had no apparent effects on vegetative growth and pathogenicity but resulted in a significant reduction in conidiation and abnormal germ tube differentiation on onion epidermal cells. Deletion of PIC5 led to a reduction in conidiation and hyphal growth. Autolysis of aerial hyphae became visible in cultures older than 4 days. The pic5 mutant was defective in germ tube growth and appressorium differentiation. It was reduced in appressorial penetration and virulence on the plant. Both PIC1 and PIC5 are conserved in filamentous ascomycetes, but none of their orthologs have been functionally characterized. Our data indicate that PIC5 is a novel virulence factor involved in appressorium differentiation and pathogenesis in M. oryzae. PMID:21642506

  18. Mining to find the lipid interaction networks involved in Ovarian Cancers

    PubMed Central

    Kanagasabai, Rajaraman; Narasimhan, Kothandaraman; Low, Hong-Sang; Ang, Wee Tiong; Fernandis, Aaron Z.; Wenk, Markus R.; Choolani, Mahesh A.; Baker, Christopher J. O.

    2009-01-01

    The role of lipids in cancer during the genesis, progression and subsequent metastasis stages is increasingly discussed in the scientific literature. This information is discussed in a wide range of journals making it difficult for researchers to track the latest developments. A comprehensive assessment and translation of the lipidome of ovarian cancer, originating from literature, has yet to be made. We illustrate the deployment of semantic technologies; lipid ontology and text mining, in the aggregation and coordination of lipid literature. We provide the first report on the roles and types of lipids involved in ovarian cancer based on the mining of literature and identify key lipid-protein interactions that may point to potential drug discovery targets. PMID:21347172

  19. Local Area Disadvantage and Gambling Involvement and Disorder: Evidence for Gene-Environment Correlation and Interaction

    PubMed Central

    Slutske, Wendy S.; Deutsch, Arielle R.; Statham, Dixie B.; Martin, Nicholas G.

    2015-01-01

    Previous research has demonstrated that local area characteristics (such as disadvantage and gambling outlet density) and genetic risk factors are associated with gambling involvement and disordered gambling. These two lines of research were brought together in the present study by examining the extent to which genetic contributions to individual differences in gambling involvement and disorder contributed to being exposed to, and were also accentuated by, local area disadvantage. Participants were members of the national community-based Australian Twin Registry who completed a telephone interview in which the past-year frequency of gambling and symptoms of disordered gambling were assessed. Indicators of local area disadvantage were based on census data matched to the participants' postal codes. Univariate biometric model-fitting revealed that exposure to area disadvantage was partially explained by genetic factors. Bivariate biometric model-fitting was conducted to examine the evidence for gene-environment interaction while accounting for gene-environment correlation. These analyses demonstrated that: (a) a small portion of the genetic propensity to gamble was explained by moving to or remaining in a disadvantaged area, and (b) the remaining genetic and unique environmental variation in the frequency of participating in electronic machine gambling (among men and women) and symptoms of disordered gambling (among women) was greater in more disadvantaged localities. As the gambling industry continues to grow, it will be important to take into account the multiple contexts in which problematic gambling behavior can emerge -- from genes to geography -- as well as the ways in which such contexts may interact with each other. PMID:26147321

  20. DUF581 Is Plant Specific FCS-Like Zinc Finger Involved in Protein-Protein Interaction

    PubMed Central

    K, Muhammed Jamsheer; Laxmi, Ashverya

    2014-01-01

    Zinc fingers are a ubiquitous class of protein domain with considerable variation in structure and function. Zf-FCS is a highly diverged group of C2-C2 zinc finger which is present in animals, prokaryotes and viruses, but not in plants. In this study we identified that a plant specific domain of unknown function, DUF581 is a zf-FCS type zinc finger. Based on HMM-HMM comparison and signature motif similarity we named this domain as FCS-Like Zinc finger (FLZ) domain. A genome wide survey identified that FLZ domain containing genes are bryophytic in origin and this gene family is expanded in spermatophytes. Expression analysis of selected FLZ gene family members of A. thaliana identified an overlapping expression pattern suggesting a possible redundancy in their function. Unlike the zf-FCS domain, the FLZ domain found to be highly conserved in sequence and structure. Using a combination of bioinformatic and protein-protein interaction tools, we identified that FLZ domain is involved in protein-protein interaction. PMID:24901469

  1. Salmonella Biofilm Formation on Aspergillus niger Involves Cellulose – Chitin Interactions

    PubMed Central

    Brandl, Maria T.; Carter, Michelle Q.; Parker, Craig T.; Chapman, Matthew R.; Huynh, Steven; Zhou, Yaguang

    2011-01-01

    Salmonella cycles between host and nonhost environments, where it can become an active member of complex microbial communities. The role of fungi in the environmental adaptation of enteric pathogens remains relatively unexplored. We have discovered that S. enterica Typhimurium rapidly attaches to and forms biofilms on the hyphae of the common fungus, Aspergillus niger. Several Salmonella enterica serovars displayed a similar interaction, whereas other bacterial species were unable to bind to the fungus. Bacterial attachment to chitin, a major constituent of fungal cell walls, mirrored this specificity. Pre-incubation of S. Typhimurium with N-acetylglucosamine, the monomeric component of chitin, reduced binding to chitin beads by as much as 727-fold and inhibited attachment to A. niger hyphae considerably. A cellulose-deficient mutant of S. Typhimurium failed to attach to chitin beads and to the fungus. Complementation of this mutant with the cellulose operon restored binding to chitin beads to 79% of that of the parental strain and allowed for attachment and biofilm formation on A. niger, indicating that cellulose is involved in bacterial attachment to the fungus via the chitin component of its cell wall. In contrast to cellulose, S. Typhimurium curli fimbriae were not required for attachment and biofilm development on the hyphae but were critical for its stability. Our results suggest that cellulose–chitin interactions are required for the production of mixed Salmonella-A. niger biofilms, and support the hypothesis that encounters with chitinaceous alternate hosts may contribute to the ecological success of human pathogens. PMID:22003399

  2. Adhesion receptors involved in HSC and early-B cell interactions with bone marrow microenvironment.

    PubMed

    De Grandis, Maria; Lhoumeau, Anne-Catherine; Mancini, Stéphane J C; Aurrand-Lions, Michel

    2016-02-01

    Hematopoiesis takes place in the bone marrow of adult mammals and is the process by which blood cells are replenished every day throughout life. Differentiation of hematopoietic cells occurs in a stepwise manner through intermediates of differentiation that could be phenotypically identified. This has allowed establishing hematopoietic cell classification with hematopoietic stem cells (HSCs) at the top of the hierarchy. HSCs are mostly quiescent and serve as a reservoir for maintenance of lifelong hematopoiesis. Over recent years, it has become increasingly clear that HSC quiescence is not only due to intrinsic properties, but is also mediated by cognate interactions between HSCs and surrounding cells within micro-anatomical sites called “niches”. This hematopoietic/stromal crosstalk model also applies to more mature progenitors such as B cell progenitors, which are thought to reside in distinct “niches”. This prompted many research teams to search for specific molecular mechanisms supporting leuko-stromal crosstalk in the bone marrow and acting at specific stage of differentiation to regulate hematopoietic homeostasis. Here, we review recent data on adhesion mechanisms involved in HSCs and B cell progenitors interactions with surrounding bone marrow stromal cells. PMID:26495446

  3. University Physics Students' Use of Models in Explanations of Phenomena Involving Interaction between Metals and Electromagnetic Radiation.

    ERIC Educational Resources Information Center

    Redfors, Andreas; Ryder, Jim

    2001-01-01

    Examines third year university physics students' use of models when explaining familiar phenomena involving interaction between metals and electromagnetic radiation. Concludes that few students use a single model consistently. (Contains 27 references.) (DDR)

  4. Interaction Involvement in Cross-Culture Computer-Mediated Communication: Examination of a Communication Process in Dyadic Instant Messaging Conversations

    ERIC Educational Resources Information Center

    Nguyen, Thi Thao Duyen

    2013-01-01

    This dissertation explores how participants express and interpret verbal cues of interaction involvement in dyadic conversations via text-based Instant Messaging (IM). Moreover, it seeks to discover differences in the way American participants and Chinese participants use verbal cues when they are highly, or lowly involved. Based on previous…

  5. The different interactions of Colletotrichum gloeosporioides with two strawberry varieties and the involvement of salicylic acid

    PubMed Central

    Zhang, Qing-Yu; Zhang, Li-Qing; Song, Li-Li; Duan, Ke; Li, Na; Wang, Yan-Xiu; Gao, Qing-Hua

    2016-01-01

    The disease symptoms recognized as ‘Anthracnose’ are caused by Colletotrichum spp. and lead to large-scale strawberry (Fragaria×ananassa Duchesne) losses worldwide in terms of both quality and production. Little is known regarding the mechanisms underlying the genetic variations in the strawberry–Colletotrichum spp. interaction. In this work, Colletotrichum gloeosporioides (C. gloeosporioides) infection was characterized in two varieties exhibiting different susceptibilities, and the involvement of salicylic acid (SA) was examined. Light microscopic observation showed that C. gloeosporioides conidia germinated earlier and faster on the leaf surface of the susceptible cultivar compared with the less-susceptible cultivar. Several PR genes were differentially expressed, with higher-amplitude changes observed in the less-susceptible cultivar. The less-susceptible cultivar contained a higher level of basal SA, and the SA levels increased rapidly upon infection, followed by a sharp decrease before the necrotrophic phase. External SA pretreatment reduced susceptibility and elevated the internal SA levels in both varieties, which were sharply reduced in the susceptible cultivar upon inoculation. The less-susceptible cultivar also displayed a more sensitive and marked increase in the transcripts of NB-LRR genes to C. gloeosporioides, and SA pretreatment differentially induced transcript accumulation in the two varieties during infection. Furthermore, SA directly inhibited the germination of C. gloeosporioides conidia; NB-LRR transcript accumulation in response to SA pretreatment was both dose- and cultivar-dependent. The results demonstrate that the less-susceptible cultivar showed reduced conidia germination. The contribution of SA might involve microbial isolate-specific sensitivity to SA, cultivar/tissue-specific SA homeostasis and signaling, and the sensitivity of R genes and the related defense network to SA and pathogens. PMID:27004126

  6. The different interactions of Colletotrichum gloeosporioides with two strawberry varieties and the involvement of salicylic acid.

    PubMed

    Zhang, Qing-Yu; Zhang, Li-Qing; Song, Li-Li; Duan, Ke; Li, Na; Wang, Yan-Xiu; Gao, Qing-Hua

    2016-01-01

    The disease symptoms recognized as 'Anthracnose' are caused by Colletotrichum spp. and lead to large-scale strawberry (Fragaria×ananassa Duchesne) losses worldwide in terms of both quality and production. Little is known regarding the mechanisms underlying the genetic variations in the strawberry-Colletotrichum spp. interaction. In this work, Colletotrichum gloeosporioides (C. gloeosporioides) infection was characterized in two varieties exhibiting different susceptibilities, and the involvement of salicylic acid (SA) was examined. Light microscopic observation showed that C. gloeosporioides conidia germinated earlier and faster on the leaf surface of the susceptible cultivar compared with the less-susceptible cultivar. Several PR genes were differentially expressed, with higher-amplitude changes observed in the less-susceptible cultivar. The less-susceptible cultivar contained a higher level of basal SA, and the SA levels increased rapidly upon infection, followed by a sharp decrease before the necrotrophic phase. External SA pretreatment reduced susceptibility and elevated the internal SA levels in both varieties, which were sharply reduced in the susceptible cultivar upon inoculation. The less-susceptible cultivar also displayed a more sensitive and marked increase in the transcripts of NB-LRR genes to C. gloeosporioides, and SA pretreatment differentially induced transcript accumulation in the two varieties during infection. Furthermore, SA directly inhibited the germination of C. gloeosporioides conidia; NB-LRR transcript accumulation in response to SA pretreatment was both dose- and cultivar-dependent. The results demonstrate that the less-susceptible cultivar showed reduced conidia germination. The contribution of SA might involve microbial isolate-specific sensitivity to SA, cultivar/tissue-specific SA homeostasis and signaling, and the sensitivity of R genes and the related defense network to SA and pathogens. PMID:27004126

  7. Large-scale study of the interactions between proteins involved in type IV pilus biology in Neisseria meningitidis: characterization of a subcomplex involved in pilus assembly.

    PubMed

    Georgiadou, Michaella; Castagnini, Marta; Karimova, Gouzel; Ladant, Daniel; Pelicic, Vladimir

    2012-06-01

    The functionally versatile type IV pili (Tfp) are one of the most widespread virulence factors in bacteria. However, despite generating much research interest for decades, the molecular mechanisms underpinning the various aspects of Tfp biology remain poorly understood, mainly because of the complexity of the system. In the human pathogen Neisseria meningitidis for example, 23 proteins are dedicated to Tfp biology, 15 of which are essential for pilus biogenesis. One of the important gaps in our knowledge concerns the topology of this multiprotein machinery. Here we have used a bacterial two-hybrid system to identify and quantify the interactions between 11 Pil proteins from N. meningitidis. We identified 20 different binary interactions, many of which are novel. This represents the most complex interaction network between Pil proteins reported to date and indicates, among other things, that PilE, PilM, PilN and PilO, which are involved in pilus assembly, indeed interact. We focused our efforts on this subset of proteins and used a battery of assays to determine the membrane topology of PilN and PilO, map the interaction domains between PilE, PilM, PilN and PilO, and show that a widely conserved N-terminal motif in PilN is essential for both PilM-PilN interactions and pilus assembly. Finally, we show that PilP (another protein involved in pilus assembly) forms a complex with PilM, PilN and PilO. Taken together, these findings have numerous implications for understanding Tfp biology and provide a useful blueprint for future studies. PMID:22486968

  8. Non-covalent interactions involving halogenated derivatives of capecitabine and thymidylate synthase: a computational approach.

    PubMed

    Rahman, Adhip; Hoque, Mohammad Mazharol; Khan, Mohammad A K; Sarwar, Mohammed G; Halim, Mohammad A

    2016-01-01

    Capecitabine, a fluoropyrimidine prodrug, has been a frequently chosen ligand for the last one and half decades to inhibit thymidylate synthase (TYMS) for treatment of colorectal cancer. TYMS is a key enzyme for de novo synthesis of deoxythymidine monophosphate and subsequent synthesis of DNA. Recent years have also seen the trait of modifying ligands using halogens and trifluoromethyl (-CF3) group to ensure enhanced drug performance. In this study, in silico modification of capecitabine with Cl, Br, I atoms and -CF3 group has been performed. Density functional theory has been employed to optimize the drug molecules and elucidate their thermodynamic and electrical properties such as Gibbs free energy, enthalpy, electronic energy, dipole moment and frontier orbital features (HOMO-LUMO gap, hardness and softness). Flexible and rigid molecular docking have been implemented between drugs and the receptor TYMS. Both inter- and intra-molecular non-covalent interactions involving the amino acid residues of TYMS and the drug molecules are explored in details. The drugs were superimposed on the resolved crystal structure (at 1.9 Å) of ZD1694/dUMP/TYMS system to shed light on similarity of the binding of capecitabine, and its modifiers, to that of ZD1694. Together, these results may provide more insights prior to synthesizing halogen-directed derivatives of capecitabine for anticancer treatment. PMID:27026843

  9. Fluid–structure interaction involving large deformations: 3D simulations and applications to biological systems

    PubMed Central

    Tian, Fang-Bao; Dai, Hu; Luo, Haoxiang; Doyle, James F.; Rousseau, Bernard

    2013-01-01

    Three-dimensional fluid–structure interaction (FSI) involving large deformations of flexible bodies is common in biological systems, but accurate and efficient numerical approaches for modeling such systems are still scarce. In this work, we report a successful case of combining an existing immersed-boundary flow solver with a nonlinear finite-element solid-mechanics solver specifically for three-dimensional FSI simulations. This method represents a significant enhancement from the similar methods that are previously available. Based on the Cartesian grid, the viscous incompressible flow solver can handle boundaries of large displacements with simple mesh generation. The solid-mechanics solver has separate subroutines for analyzing general three-dimensional bodies and thin-walled structures composed of frames, membranes, and plates. Both geometric nonlinearity associated with large displacements and material nonlinearity associated with large strains are incorporated in the solver. The FSI is achieved through a strong coupling and partitioned approach. We perform several validation cases, and the results may be used to expand the currently limited database of FSI benchmark study. Finally, we demonstrate the versatility of the present method by applying it to the aerodynamics of elastic wings of insects and the flow-induced vocal fold vibration. PMID:24415796

  10. Interatomic Coulombic Decay Effects in Theoretical DNA Recombination Systems Involving Protein Interaction Sites

    NASA Astrophysics Data System (ADS)

    Vargas, E. L.; Rivas, D. A.; Duot, A. C.; Hovey, R. T.; Andrianarijaona, V. M.

    2015-03-01

    DNA replication is the basis for all biological reproduction. A strand of DNA will ``unzip'' and bind with a complimentary strand, creating two identical strands. In this study, we are considering how this process is affected by Interatomic Coulombic Decay (ICD), specifically how ICD affects the individual coding proteins' ability to hold together. ICD mainly deals with how the electron returns to its original state after excitation and how this affects its immediate atomic environment, sometimes affecting the connectivity between interaction sites on proteins involved in the DNA coding process. Biological heredity is fundamentally controlled by DNA and its replication therefore it affects every living thing. The small nature of the proteins (within the range of nanometers) makes it a good candidate for research of this scale. Understanding how ICD affects DNA molecules can give us invaluable insight into the human genetic code and the processes behind cell mutations that can lead to cancer. Authors wish to give special thanks to Pacific Union College Student Senate in Angwin, California, for their financial support.

  11. Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing.

    PubMed Central

    Saarialho-Kere, U K; Kovacs, S O; Pentland, A P; Olerud, J E; Welgus, H G; Parks, W C

    1993-01-01

    We reported that interstitial collagenase is produced by keratinocytes at the edge of ulcers in pyogenic granuloma, and in this report, we assessed if production of this metalloproteinase is a common feature of the epidermal response in a variety of wounds. In all samples of chronic ulcers, regardless of etiology, and in incision wounds, collagenase mRNA, localized by in situ hybridization, was prominently expressed by basal keratinocytes bordering the sites of active re-epithelialization indicating that collagenolytic activity is a characteristic response of the epidermis to wounding. No expression of mRNAs for 72- and 92-kD gelatinases or matrilysin was seen in keratinocytes, and no signal for any metalloproteinase was detected in normal epidermis. Immunostaining for type IV collagen showed that collagenase-positive keratinocytes were not in contact with an intact basement membrane and, unlike normal keratinocytes, expressed alpha 5 beta 1 receptors. These observations suggest that cell-matrix interactions influence collagenase expression by epidermal cells. Indeed, as determined by ELISA, primary cultures of human keratinocytes grown on basement membrane proteins (Matrigel; Collaborative Research Inc., Bedford, MA) did not express significant levels of collagenase, whereas cells grown on type I collagen produced markedly increased levels. These results suggest that migrating keratinocytes actively involved in re-epithelialization acquire a collagenolytic phenotype upon contact with the dermal matrix. Images PMID:8254040

  12. Fluid-structure interaction involving large deformations: 3D simulations and applications to biological systems.

    PubMed

    Tian, Fang-Bao; Dai, Hu; Luo, Haoxiang; Doyle, James F; Rousseau, Bernard

    2014-02-01

    Three-dimensional fluid-structure interaction (FSI) involving large deformations of flexible bodies is common in biological systems, but accurate and efficient numerical approaches for modeling such systems are still scarce. In this work, we report a successful case of combining an existing immersed-boundary flow solver with a nonlinear finite-element solid-mechanics solver specifically for three-dimensional FSI simulations. This method represents a significant enhancement from the similar methods that are previously available. Based on the Cartesian grid, the viscous incompressible flow solver can handle boundaries of large displacements with simple mesh generation. The solid-mechanics solver has separate subroutines for analyzing general three-dimensional bodies and thin-walled structures composed of frames, membranes, and plates. Both geometric nonlinearity associated with large displacements and material nonlinearity associated with large strains are incorporated in the solver. The FSI is achieved through a strong coupling and partitioned approach. We perform several validation cases, and the results may be used to expand the currently limited database of FSI benchmark study. Finally, we demonstrate the versatility of the present method by applying it to the aerodynamics of elastic wings of insects and the flow-induced vocal fold vibration. PMID:24415796

  13. Antiretroviral Drug Interactions: Overview of Interactions Involving New and Investigational Agents and the Role of Therapeutic Drug Monitoring for Management

    PubMed Central

    Rathbun, R. Chris; Liedtke, Michelle D.

    2011-01-01

    Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. Interactions between antiretrovirals and medications for other diseases are common due to shared metabolism through cytochrome P450 (CYP450) and uridine diphosphate glucuronosyltransferase (UGT) enzymes and transport by membrane proteins (e.g., p-glycoprotein, organic anion-transporting polypeptide). The clinical significance of antiretroviral drug interactions is reviewed, with a focus on new and investigational agents. An overview of the mechanistic basis for drug interactions and the effect of individual antiretrovirals on CYP450 and UGT isoforms are provided. Interactions between antiretrovirals and medications for other co-morbidities are summarized. The role of therapeutic drug monitoring in the detection and management of antiretroviral drug interactions is also briefly discussed. PMID:24309307

  14. Pharmacokinetic herb-drug interactions (part 2): drug interactions involving popular botanical dietary supplements and their clinical relevance.

    PubMed

    Gurley, Bill J; Fifer, Espero Kim; Gardner, Zoë

    2012-09-01

    In Part 2 of this review, a critical examination of the pertinent scientific literature is undertaken in order to assess the interaction risk that popular dietary supplements may pose when taken concomitantly with conventional medications. Botanicals most likely to produce clinically important herb-drug interactions are those whose phytochemicals act as mechanism-based inhibitors of cytochrome P450 enzyme activity (e.g., Hydrastis canadensis, Piper nigrum, Schisandra chinensis) or function as ligands for orphan nuclear receptors (e.g., Hypericum perforatum). In addition, several external factors unrelated to phytochemical pharmacology can augment the drug interaction potential of botanical supplements. PMID:22565299

  15. Aldrin-induced locomotor activity: possible involvement of the central GABAergic-cholinergic-dopaminergic interaction.

    PubMed

    Jamaluddin, S; Poddar, M K

    2001-01-01

    Aldrin (5 mg/kg/day, p.o.) under nontolerant condition, administered either for a single day or for 12 consecutive days, enhanced locomotor activity (LA) of rats. The increase in LA was greater in rats treated with aldrin for 12 consecutive days than that observed with a single dose. The aim of the present study is to evaluate the involvement of possible interactions of central GABAergic, cholinergic and dopaminergic systems using their agonist(s) and antagonist(s) in the regulation of LA in aldrin nontolerant rats. Administration of either L-DOPA along with carbidopa or bicuculline potentiated aldrin-induced increase in LA under nontolerant condition as well as LA of the control rats. Treatment with muscimol, haloperidol, atropine or physostigmine all decreased the LA of both aldrin nontolerant and control rats. Further, the application of (a) haloperidol along with bicuculline, atropine or physostigmine and (b) physostigmine along with bicuculline or L-DOPA + carbidopa significantly reduced LA but L-DOPA + carbidopa along with atropine or bicuculline increased LA of the control rats. These agonist(s)/antagonist(s)-induced decrease or increase in LA of the control rats were attenuated or potentiated, respectively, when those agonist(s)/antagonist(s) under abovementioned condition were administered to aldrin nontolerant rats. The attenuating or potentiating effects of aldrin on agonist(s)/antagonist(s) (either individually or in different combinations)-induced change in LA were greater in rats treated with aldrin for 12 consecutive days than that observed with a single-dose aldrin treatment. These results suggest that aldrin, under nontolerant condition, reduces central GABAergic activity and increases LA by activating dopaminergic system via inhibition of cholinergic activity. The treatment with aldrin for 12 consecutive days produces greater effect than that caused by a single-day treatment. PMID:11785907

  16. Drug interactions involving antiepileptic drugs: assessment of the consistency among three drug compendia and FDA-approved labels.

    PubMed

    Ekstein, Dana; Tirosh, Matanya; Eyal, Yonatan; Eyal, Sara

    2015-03-01

    Interactions of antiepileptic drugs (AEDs) with other substances may lead to adverse effects and treatment failure. To avoid such interactions, clinicians often rely on drug interaction compendia. Our objective was to compare the concordance for twenty-two AEDs among three drug interaction compendia (Micromedex, Lexi-Interact, and Clinical Pharmacology) and the US Food and Drug Administration-approved product labels. For each AED, the overall concordance among data sources regarding existence of interactions and their classification was poor, with less than twenty percent of interactions listed in all four sources. Concordance among the three drug compendia decreased with the fraction of the drug excreted unchanged and was greater for established inducers of hepatic drug-metabolizing enzymes than for the drugs that are not inducers (R-square=0.83, P<0.01). For interactions classified as contraindications, major, and severe, concordance among the four data sources was, in most cases, less than 30%. Prescribers should be aware of the differences between drug interaction sources of information for both older AEDs and newer AEDs, in particular for those AEDs which are not involved in hepatic enzyme-mediated interactions. PMID:25771206

  17. Mapping of the regions involved in self-interaction of rice stripe virus P3 protein.

    PubMed

    Zhao, S L; Hao, J H; Xue, Y N; Liang, C Y

    2016-03-01

    Rice stripe virus (RSV) protein P3 is a suppressor of RNA silencing in plants. P3 has been shown by biomolecular fluorescence complementation assay to self-interact in planta but the regions responsible for homotypic interaction have not been determined. Here we analyzed the domains for the self-interaction of P3 by using yeast two-hybrid, co-immunoprecipitation and fluorescence experiments. The results showed that P3 was also able to interact with itself in yeast and insect cells. The domain responsible for P3-P3 interaction was mapped to amino acids 15-30 at the N-terminal region of P3. Furthermore, subcellular localization suggested that the homo-oligomerization was the prerequisite for P3 to form larger protein aggregates in the nucleus of insect cell. PMID:26982473

  18. Perspectives of Foster Parents on Interactions and Involvement with K-12 Public Schools in a County in Southern California

    ERIC Educational Resources Information Center

    Stein-Steele, Eric Charles

    2013-01-01

    The purpose of this study was to (a) understand foster parents' perceptions of their parental roles and their involvement in their foster children's academic work; (b) understand their perceptions of their experiences in interacting with their foster children's public school; and (c) provide suggestions to enhance the parent-school…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We provide here a comparative genome analysis of the Pseudomonas fluorescens group, including seven new genomic sequences for plant-associated strains. These strains exhibit a diverse spectrum of traits involved in biological control and other multitrophic interactions with plants, microbes, and ins...

  20. Collaboratives for Wildlife-Wind Turbine Interaction Research: Fostering Multistakeholder Involvement (Poster)

    SciTech Connect

    Sinclair, K.

    2013-04-01

    This poster highlights the various wildlife-wind collaboratives (specific to wildlife-wind turbine interaction research) that currently exist. Examples of collaboratives are included along with contact information, objectives, benefits, and ways to advance the knowledge base.

  1. Design, Utility, and History of the Colorado Adoption Project: Examples Involving Adjustment Interactions1

    PubMed Central

    Rhea, Sally Ann; Bricker, Josh B.; Corley, Robin P.; DeFries, John C.; Wadsworth, Sally J.

    2013-01-01

    This paper describes the Colorado Adoption Project (CAP), a longitudinal study in behavioral development, and discusses how adoption studies may be used to assess genetic and environmental etiologies of individual differences for important developmental outcomes. Previous CAP research on adjustment outcomes in childhood and adolescence which found significant interactions, including gene-environment interactions, is reviewed. New research suggests mediating effects of menarche and religiosity on age at first sex in this predominantly middle-class, Caucasian sample. PMID:23833552

  2. Potential Energy Curves and Collisions Integrals of Air Components. 2; Interactions Involving Ionized Atoms

    NASA Technical Reports Server (NTRS)

    Stallcop, James R.; Partridge, Harry; Levin, Eugene; Langhoff, Stephen R. (Technical Monitor)

    1995-01-01

    Collision integrals are fundamental quantities required to determine the transport properties of the environment surrounding aerospace vehicles in the upper atmosphere. These collision integrals can be determined as a function of temperature from the potential energy curves describing the atomic and molecular collisions. Ab initio calculations provide a practical method of computing the required interaction potentials. In this work we will discuss recent advances in scattering calculations with an emphasis on the accuracy that is obtainable. Results for interactions of the atoms and ionized atoms of nitrogen and oxygen will be reviewed and their application to the determination of transport properties, such as diffusion and viscosity coefficients, will be examined.

  3. Inner Membrane Protein YhcB Interacts with RodZ Involved in Cell Shape Maintenance in Escherichia coli

    PubMed Central

    Li, Gaochi; Hamamoto, Kentaro; Kitakawa, Madoka

    2012-01-01

    Depletion of YhcB, an inner membrane protein of Escherichia coli, inhibited the growth of rodZ deletion mutant showing that the loss of both YhcB and RodZ is synthetically lethal. Furthermore, YhcB was demonstrated to interact with RodZ as well as several other proteins involved in cell shape maintenance and an inner membrane protein YciS of unknown function, using bacterial two-hybrid system. These observations seem to indicate that YhcB is involved in the biogenesis of cell envelope and the maintenance of cell shape together with RodZ.

  4. Host Genes Involved in the Interaction between Aspergillus flavus and Maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aflatoxin contamination caused by Aspergillus flavus is a major concern in maize production. Understanding the complex interrelationships of genes during the A. flavus-maize interaction may be the key to developing strategies to interrupt the aflatoxin contamination process. The A. flavus Genome Seq...

  5. The BARD1/HP1 interaction: Another clue to heterochromatin involvement in homologous recombination

    PubMed Central

    Fukuda, Takayo; Tsuruga, Tomoko; Kuroda, Takako; Takeuchi, Jun; Wu, Wenwen; Ohta, Tomohiko

    2016-01-01

    Chromatin compaction represents a barrier for the repair of DNA double-strand breaks (DSBs). However, heterochromatin components are also required for DSB repair by homologous recombination. The BARD1/HP1 interaction, required for the retention of BRCA1, CTIP, and RAD51 at DSB sites, may play a critical role in the crosstalk between chromatin compaction and DSB repair. PMID:27308582

  6. A Kinesthetic Model Demonstrating Molecular Interactions Involved in Anterior-Posterior Pattern Formation in "Drosophila"

    ERIC Educational Resources Information Center

    Douglas, Kristin R.

    2008-01-01

    Prerequisites for the Developmental Biology course at Augustana College are introductory courses in zoology and cell biology. After introductory courses students appreciate the fact that proteins have three-dimensional structures; however, they often fail to recognize how protein interactions with other cellular components can lead to specific…

  7. Interpreters' Involvement in Multi-Party Interactions: The Nature of Participation as Listener and Speaker

    ERIC Educational Resources Information Center

    Takimoto, Masato

    2012-01-01

    This paper investigates two naturally occurring business interpreting situations where there are a number of participants. Unlike dialogue interpreting situations where there are only two primary interlocutors, the overall interaction shows more complexity in these multi-party situations. This, in turn, means that the interpreters' functions and…

  8. Identification of sequence motifs involved in Dengue virus-host interactions.

    PubMed

    Asnet Mary, J; Paramasivan, R; Shenbagarathai, R

    2016-03-01

    Dengue fever is a rapidly spreading mosquito-borne virus infection, which remains a serious global public health problem. As there is no specific treatment or commercial vaccine available for effective control of the disease, the attempts on developing novel control strategies are underway. Viruses utilize the surface receptor proteins of host to enter into the cells. Though various proteins were said to be receptors of Dengue virus (DENV) using Virus Overlay Protein Binding Assay, the precise interaction between DENV and host is not explored. Understanding the structural features of domain III envelope glycoprotein would help in developing efficient antiviral inhibitors. Therefore, an attempt was made to identify the sequence motifs present in domain III envelope glycoprotein of Dengue virus. Computational analysis revealed that the NGR motif is present in the domain III envelope glycoprotein of DENV-1 and DENV-3. Similarly, DENV-1, DENV-2 and DENV-4 were found to contain Yxxphi motif which is a tyrosine-based sorting signal responsible for the interaction with a mu subunit of adaptor protein complex. High-throughput virtual screening resulted in five compounds as lead molecules based on glide score, which ranges from -4.664 to -6.52 kcal/Mol. This computational prediction provides an additional tool for understanding the virus-host interactions and helps to identify potential targets in the host. Further, experimental evidence is warranted to confirm the virus-host interactions and also inhibitory activity of reported lead compounds. PMID:25905427

  9. Exploring the Impact of Work Satisfaction and Involvement on Marital Interaction When Both Partners are Employed

    ERIC Educational Resources Information Center

    Ridley, Carl A.

    1973-01-01

    The two major conclusions of this study were: (1) teachers and their husbands follow different patterns concerning the job satisfaction-marital adjustment relationship, and (2) teachers and their husbands were more than moderately successful at preventing their job involvement from interfering with their marital adjustment. (Author)

  10. Relationship of Purchasing, Brand, and Self Involvement with Advertising Interactions and Beliefs among Malaysian Students.

    ERIC Educational Resources Information Center

    Ramaprasad, Jyotika

    A study examined Malaysian students' involvement with purchasing, with branded products, and with themselves as well as their responses to and beliefs about advertising, by ethnic group. Subjects, 387 students at a university in Penang, Malaysia, completed questionnaires measuring their responses to advertising. Results indicated a relatively high…

  11. Unique and Interactive Effects of Empathy and Social Status on Involvement in Bullying

    ERIC Educational Resources Information Center

    Caravita, Simona C. S.; Di Blasio, Paola; Salmivalli, Christina

    2009-01-01

    This study investigated the relationships between affective and cognitive empathy, social preference and perceived popularity, and involvement in bullying situations by bullying others or defending the victimized children. The participants were 266 primary and 195 secondary school students. Affective and cognitive empathy, as well as the status…

  12. The Interactive Effects of Perceived Parental Involvement and Personality on Teacher Satisfaction

    ERIC Educational Resources Information Center

    Li, Chung-Kai; Hung, Chia-Hung

    2012-01-01

    Purpose: This study aims to examine the relations between teachers' perception of parental involvement and teacher satisfaction. It further aims to investigate how this relationship may be moderated by interpersonal personality traits. Design/methodology/approach: A questionnaire was conducted; participants were 572 classroom teachers who teach at…

  13. Construction of protein interaction network involved in lung adenocarcinomas using a novel algorithm

    PubMed Central

    Chen, Juan; Yang, Hai-Tao; Li, Zhu; Xu, Ning; Yu, Bo; Xu, Jun-Ping; Zhao, Pei-Ge; Wang, Yan; Zhang, Xiu-Juan; Lin, Dian-Jie

    2016-01-01

    Studies that only assess differentially-expressed (DE) genes do not contain the information required to investigate the mechanisms of diseases. A complete knowledge of all the direct and indirect interactions between proteins may act as a significant benchmark in the process of forming a comprehensive description of cellular mechanisms and functions. The results of protein interaction network studies are often inconsistent and are based on various methods. In the present study, a combined network was constructed using selected gene pairs, following the conversion and combination of the scores of gene pairs that were obtained across multiple approaches by a novel algorithm. Samples from patients with and without lung adenocarcinoma were compared, and the RankProd package was used to identify DE genes. The empirical Bayesian (EB) meta-analysis approach, the search tool for the retrieval of interacting genes/proteins database (STRING), the weighted gene coexpression network analysis (WGCNA) package and the differentially-coexpressed genes and links package (DCGL) were used for network construction. A combined network was also constructed with a novel rank-based algorithm using a combined score. The topological features of the 5 networks were analyzed and compared. A total of 941 DE genes were screened. The topological analysis indicated that the gene interaction network constructed using the WGCNA method was more likely to produce a small-world property, which has a small average shortest path length and a large clustering coefficient, whereas the combined network was confirmed to be a scale-free network. Gene pairs that were identified using the novel combined method were mostly enriched in the cell cycle and p53 signaling pathway. The present study provided a novel perspective to the network-based analysis. Each method has advantages and disadvantages. Compared with single methods, the combined algorithm used in the present study may provide a novel method to

  14. Clinically significant drug–drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review

    PubMed Central

    Kotlinska-Lemieszek, Aleksandra; Klepstad, Pål; Haugen, Dagny Faksvåg

    2015-01-01

    Background Opioids are the most frequently used drugs to treat pain in cancer patients. In some patients, however, opioids can cause adverse effects and drug–drug interactions. No advice concerning the combination of opioids and other drugs is given in the current European guidelines. Objective To identify studies that report clinically significant drug–drug interactions involving opioids used for pain treatment in adult cancer patients. Design and data sources Systematic review with searches in Embase, MEDLINE, and Cochrane Central Register of Controlled Trials from the start of the databases (Embase from 1980) through January 2014. In addition, reference lists of relevant full-text papers were hand-searched. Results Of 901 retrieved papers, 112 were considered as potentially eligible. After full-text reading, 17 were included in the final analysis, together with 15 papers identified through hand-searching of reference lists. All of the 32 included publications were case reports or case series. Clinical manifestations of drug–drug interactions involving opioids were grouped as follows: 1) sedation and respiratory depression, 2) other central nervous system symptoms, 3) impairment of pain control and/or opioid withdrawal, and 4) other symptoms. The most common mechanisms eliciting drug–drug interactions were alteration of opioid metabolism by inhibiting the activity of cytochrome P450 3A4 and pharmacodynamic interactions due to the combined effect on opioid, dopaminergic, cholinergic, and serotonergic activity in the central nervous system. Conclusion Evidence for drug–drug interactions associated with opioids used for pain treatment in cancer patients is very limited. Still, the cases identified in this systematic review give some important suggestions for clinical practice. Physicians prescribing opioids should recognize the risk of drug–drug interactions and if possible avoid polypharmacy. PMID:26396499

  15. Type of hemodialysis and preference for behavioral involvement: interactive effects on adherence in end-stage renal disease.

    PubMed

    Christensen, A J; Smith, T W; Turner, C W; Holman, J M; Gregory, M C

    1990-01-01

    Examined the effects of hemodialysis type (i.e., staff controlled, in center vs. patient controlled, home) and patient preference for behavioral involvement on adherence and emotional adjustment in a sample of 53 patients with end-stage renal disease. Consistent with person x treatment interaction models, higher levels of preference for behavioral involvement were associated with better dietary adherence (i.e., lower serum potassium) for patients receiving dialysis at home but worse dietary adherence for patients receiving treatment in a dialysis center. A similar though weaker patient x treatment type matching pattern was observed for fluid-intake adherence (i.e., interdialytic weight gain). No effects were observed for patients' self-reported depression levels. Possible mechanisms for the interactional effect on adherence are discussed. PMID:2331980

  16. Hsp12p and PAU genes are involved in ecological interactions between natural yeast strains.

    PubMed

    Rivero, Damaríz; Berná, Luisa; Stefanini, Irene; Baruffini, Enrico; Bergerat, Agnes; Csikász-Nagy, Attila; De Filippo, Carlotta; Cavalieri, Duccio

    2015-08-01

    The coexistence of different yeasts in a single vineyard raises the question on how they communicate and why slow growers are not competed out. Genetically modified laboratory strains of Saccharomyces cerevisiae are extensively used to investigate ecological interactions, but little is known about the genes regulating cooperation and competition in ecologically relevant settings. Here, we present evidences of Hsp12p-dependent altruistic and contact-dependent competitive interactions between two natural yeast isolates. Hsp12p is released during cell death for public benefit by a fast-growing strain that also produces a killer toxin to inhibit growth of a slow grower that can enjoy the benefits of released Hsp12p. We also show that the protein Pau5p is essential in the defense against the killer effect. Our results demonstrate that the combined action of Hsp12p, Pau5p and a killer toxin is sufficient to steer a yeast community. PMID:26079802

  17. The effect of diet and opponent size on aggressive interactions involving caribbean crazy ants (Nylanderia fulva).

    PubMed

    Horn, Katherine C; Eubanks, Micky D; Siemann, Evan

    2013-01-01

    Biotic interactions are often important in the establishment and spread of invasive species. In particular, competition between introduced and native species can strongly influence the distribution and spread of exotic species and in some cases competition among introduced species can be important. The Caribbean crazy ant, Nylanderia fulva, was recently introduced to the Gulf Coast of Texas, and appears to be spreading inland. It has been hypothesized that competition with the red imported fire ant, Solenopsis invicta, may be an important factor in the spread of crazy ants. We investigated the potential of interspecific competition among these two introduced ants by measuring interspecific aggression between Caribbean crazy ant workers and workers of Solenopsis invicta. Specifically, we examined the effect of body size and diet on individual-level aggressive interactions among crazy ant workers and fire ants. We found that differences in diet did not alter interactions between crazy ant workers from different nests, but carbohydrate level did play an important role in antagonistic interactions with fire ants: crazy ants on low sugar diets were more aggressive and less likely to be killed in aggressive encounters with fire ants. We found that large fire ants engaged in fewer fights with crazy ants than small fire ants, but fire ant size affected neither fire ant nor crazy ant mortality. Overall, crazy ants experienced higher mortality than fire ants after aggressive encounters. Our findings suggest that fire ant workers might outcompete crazy ant workers on an individual level, providing some biotic resistance to crazy ant range expansion. However, this resistance may be overcome by crazy ants that have a restricted sugar intake, which may occur when crazy ants are excluded from resources by fire ants. PMID:23776702

  18. A Failure to Communicate: MYOSIN RESIDUES INVOLVED IN HYPERTROPHIC CARDIOMYOPATHY AFFECT INTER-DOMAIN INTERACTION.

    PubMed

    Kronert, William A; Melkani, Girish C; Melkani, Anju; Bernstein, Sanford I

    2015-12-01

    Our molecular modeling studies suggest a charge-dependent interaction between residues Glu-497 in the relay domain and Arg-712 in the converter domain of human β-cardiac myosin. To test the significance of this putative interaction, we generated transgenic Drosophila expressing indirect flight muscle myosin with charge reversal mutations in the relay (E496R) or converter (R713E). Each mutation yielded dramatic reductions in myosin Ca-ATPase activity (~80%) as well as in basal (~67%) and actin-activated (~84%) Mg-ATPase activity. E496R myosin-induced in vitro actin-sliding velocity was reduced by 71% and R713E myosin permitted no actin motility. Indirect flight muscles of late pupae from each mutant displayed disrupted myofibril assembly, with adults having severely abnormal myofibrils and no flight ability. To understand the molecular basis of these defects, we constructed a putative compensatory mutant that expresses myosin with both E496R and R713E. Intriguingly, ATPase values were restored to ~73% of wild-type and actin-sliding velocity increased to 40%. The double mutation suppresses myofibril assembly defects in pupal indirect flight muscles and dramatically reduces myofibril disruption in young adults. Although sarcomere organization is not sustained in older flies and flight ability is not restored in homozygotes, young heterozygotes fly well. Our results indicate that this charge-dependent interaction between the myosin relay and converter domains is essential to the mechanochemical cycle and sarcomere assembly. Furthermore, the same inter-domain interaction is disrupted when modeling human β-cardiac myosin heavy chain cardiomyopathy mutations E497D or R712L, implying that abolishing this salt bridge is one cause of the human disease. PMID:26446785

  19. Involvement of two classes of binding sites in the interactions of cyclophilin B with peripheral blood T-lymphocytes.

    PubMed Central

    Denys, A; Allain, F; Carpentier, M; Spik, G

    1998-01-01

    Cyclophilin B (CyPB) is a cyclosporin A (CsA)-binding protein, mainly associated with the secretory pathway, and is released in biological fluids. We recently reported that CyPB specifically binds to T-lymphocytes and promotes enhanced incorporation of CsA. The interactions with cellular binding sites involved, at least in part, the specific N-terminal extension of the protein. In this study, we intended to specify further the nature of the CyPB-binding sites on peripheral blood T-lymphocytes. We first provide evidence that the CyPB binding to heparin-Sepharose is prevented by soluble sulphated glycosaminoglycans (GAG), raising the interesting possibility that such interactions may occur on the T-cell surface. We then characterized CyPB binding to T-cell surface GAG and found that these interactions involved the N-terminal extension of CyPB, but not its conserved CsA-binding domain. In addition, we determined the presence of a second CyPB binding site, which we termed a type I site, in contrast with type II for GAG interactions. The two binding sites exhibit a similar affinity but the expression of the type I site was 3-fold lower. The conclusion that CyPB binding to the type I site is distinct from the interactions with GAG was based on the findings that it was (1) resistant to NaCl wash and GAG-degrading enzyme treatments, (2) reduced in the presence of CsA or cyclophilin C, and (3) unmodified in the presence of either the N-terminal peptide of CyPB or protamine. Finally, we showed that the type I binding sites were involved in an endocytosis process, supporting the hypothesis that they may correspond to a functional receptor for CyPB. PMID:9841882

  20. Coil–globule transition of a polymer involved in excluded-volume interactions with macromolecules

    SciTech Connect

    Odagiri, Kenta; Seki, Kazuhiko

    2015-10-07

    Polymers adopt extended coil and compact globule states according to the balance between entropy and interaction energies. The transition of a polymer between an extended coil state and compact globule state can be induced by changing thermodynamic force such as temperature to alter the energy/entropy balance. Previously, this transition was theoretically studied by taking into account the excluded-volume interaction between monomers of a polymer chain using the partition function. For binary mixtures of a long polymer and short polymers, the coil-globule transition can be induced by changing the concentration of the shorter polymers. Here, we investigate the transition caused by short polymers by generalizing the partition function of the long polymer to include the excluded-volume effect of short polymers. The coil-globule transition is studied as a function of the concentration of mixed polymers by systematically varying Flory’s χ-parameters. We show that the transition is caused by the interplay between the excluded-volume interaction and the dispersion state of short polymers in the solvent. We also reveal that the same results can be obtained by combining the mixing entropy and elastic energy if the volume of a long polymer is properly defined.

  1. Training in Compensatory Strategies Enhances Rapport in Interactions Involving People with Möbius Syndrome

    PubMed Central

    Michael, John; Bogart, Kathleen; Tylén, Kristian; Krueger, Joel; Bech, Morten; Østergaard, John Rosendahl; Fusaroli, Riccardo

    2015-01-01

    In the exploratory study reported here, we tested the efficacy of an intervention designed to train teenagers with Möbius syndrome (MS) to increase the use of alternative communication strategies (e.g., gestures) to compensate for their lack of facial expressivity. Specifically, we expected the intervention to increase the level of rapport experienced in social interactions by our participants. In addition, we aimed to identify the mechanisms responsible for any such increase in rapport. In the study, five teenagers with MS interacted with three naïve participants without MS before the intervention, and with three different naïve participants without MS after the intervention. Rapport was assessed by self-report and by behavioral coders who rated videos of the interactions. Individual non-verbal behavior was assessed via behavioral coders, whereas verbal behavior was automatically extracted from the sound files. Alignment was assessed using cross recurrence quantification analysis and mixed-effects models. The results showed that observer-coded rapport was greater after the intervention, whereas self-reported rapport did not change significantly. Observer-coded gesture and expressivity increased in participants with and without MS, whereas overall linguistic alignment decreased. Fidgeting and repetitiveness of verbal behavior also decreased in both groups. In sum, the intervention may impact non-verbal and verbal behavior in participants with and without MS, increasing rapport as well as overall gesturing, while decreasing alignment. PMID:26500605

  2. Training in Compensatory Strategies Enhances Rapport in Interactions Involving People with Möbius Syndrome.

    PubMed

    Michael, John; Bogart, Kathleen; Tylén, Kristian; Krueger, Joel; Bech, Morten; Østergaard, John Rosendahl; Fusaroli, Riccardo

    2015-01-01

    In the exploratory study reported here, we tested the efficacy of an intervention designed to train teenagers with Möbius syndrome (MS) to increase the use of alternative communication strategies (e.g., gestures) to compensate for their lack of facial expressivity. Specifically, we expected the intervention to increase the level of rapport experienced in social interactions by our participants. In addition, we aimed to identify the mechanisms responsible for any such increase in rapport. In the study, five teenagers with MS interacted with three naïve participants without MS before the intervention, and with three different naïve participants without MS after the intervention. Rapport was assessed by self-report and by behavioral coders who rated videos of the interactions. Individual non-verbal behavior was assessed via behavioral coders, whereas verbal behavior was automatically extracted from the sound files. Alignment was assessed using cross recurrence quantification analysis and mixed-effects models. The results showed that observer-coded rapport was greater after the intervention, whereas self-reported rapport did not change significantly. Observer-coded gesture and expressivity increased in participants with and without MS, whereas overall linguistic alignment decreased. Fidgeting and repetitiveness of verbal behavior also decreased in both groups. In sum, the intervention may impact non-verbal and verbal behavior in participants with and without MS, increasing rapport as well as overall gesturing, while decreasing alignment. PMID:26500605

  3. Biomembrane models and drug-biomembrane interaction studies: Involvement in drug design and development

    PubMed Central

    Pignatello, R.; Musumeci, T.; Basile, L.; Carbone, C.; Puglisi, G.

    2011-01-01

    Contact with many different biological membranes goes along the destiny of a drug after its systemic administration. From the circulating macrophage cells to the vessel endothelium, to more complex absorption barriers, the interaction of a biomolecule with these membranes largely affects its rate and time of biodistribution in the body and at the target sites. Therefore, investigating the phenomena occurring on the cell membranes, as well as their different interaction with drugs in the physiological or pathological conditions, is important to exploit the molecular basis of many diseases and to identify new potential therapeutic strategies. Of course, the complexity of the structure and functions of biological and cell membranes, has pushed researchers toward the proposition and validation of simpler two- and three-dimensional membrane models, whose utility and drawbacks will be discussed. This review also describes the analytical methods used to look at the interactions among bioactive compounds with biological membrane models, with a particular accent on the calorimetric techniques. These studies can be considered as a powerful tool for medicinal chemistry and pharmaceutical technology, in the steps of designing new drugs and optimizing the activity and safety profile of compounds already used in the therapy. PMID:21430952

  4. Transgenerational interactions involving parental age and immune status affect female reproductive success in Drosophila melanogaster

    PubMed Central

    Nystrand, M.; Dowling, D. K.

    2014-01-01

    It is well established that the parental phenotype can influence offspring phenotypic expression, independent of the effects of the offspring's own genotype. Nonetheless, the evolutionary implications of such parental effects remain unclear, partly because previous studies have generally overlooked the potential for interactions between parental sources of non-genetic variance to influence patterns of offspring phenotypic expression. We tested for such interactions, subjecting male and female Drosophila melanogaster of two different age classes to an immune activation challenge or a control treatment. Flies were then crossed in all age and immune status combinations, and the reproductive success of their immune- and control-treated daughters measured. We found that daughters produced by two younger parents exhibited reduced reproductive success relative to those of other parental age combinations. Furthermore, immune-challenged daughters exhibited higher reproductive success when produced by immune-challenged relative to control-treated mothers, a pattern consistent with transgenerational immune priming. Finally, a complex interplay between paternal age and parental immune statuses influenced daughter's reproductive success. These findings demonstrate the dynamic nature of age- and immune-mediated parental effects, traceable to both parents, and regulated by interactions between parents and between parents and offspring. PMID:25253454

  5. Multiple Protein Interactions Involving Proposed Extracellular Loop Domains of the Tight Junction Protein Occludin

    PubMed Central

    Nusrat, Asma; Brown, G. Thomas; Tom, Jeffrey; Drake, Alex; Bui, Tam T.T.; Quan, Cliff; Mrsny, Randall J.

    2005-01-01

    Occludin is a tetraspan integral membrane protein in epithelial and endothelial tight junction (TJ) structures that is projected to have two extracellular loops. We have used peptides emulating central regions of human occludin's first and second loops, termed O-A:101–121 and O-B:210–228, respectively, to examine potential molecular interactions between these two regions of occludin and other TJ proteins. A superficial biophysical assessment of A:101–121 and O-B:210–228 showed them to have dissimilar solution conformation characteristics. Although O-A:101–121 failed to strongly interact with protein components of the human epithelial intestinal cell line T84, O-B:210–228 selectively associated with occludin, claudin-one and the junctional adhesion molecule (JAM)-A. Further, the presence of O-B:210–228, but not O-A:101–121, impeded the recovery of functional TJ structures. A scrambled peptide sequences of O-B:210–228 failed to influence TJ assembly. These studies demonstrate distinct properties for these two extracellular segments of the occludin protein and provide an improved understanding of how specific domains of occludin may interact with proteins present at TJ structures. PMID:15659655

  6. Interactions among stakehoklders involved in return to work after sick leave due to mental disorders: a meta-ethnography.

    PubMed

    Neves, Robson da Fonseca; Nunes, Mônica de Oliveira; Magalhães, Lilian

    2015-11-01

    Mental disorders cause impact in the work environment. Investigations of interaction among stakeholders who are involved in the return to work are scarce. Meta-ethnography serves to synthesize qualitative studies by means of ongoing interpretation and comparison of the ideas presented in the articles. The goal of this study is to present a meta-ethnography of the interactions among the stakeholders involved in the return to work process after leave of absence due to mental disorders. It aims: (1) to investigate the interactions among stakeholders involved in return to work; (2) to identify enablers or obstacles for the return to work. The database search found 619 articles, 16 of which met the inclusion criteria. Analysis of the articles revealed six second-order concepts that resulted in two syntheses. The first is about performance ethos in the return to work, and the second shows return to work as a catalyst of new life styles. Models that favor the worker's performance ethos, as well as a perspective oriented by psychosocial aspects may enable return to work practices after leave of absence due to mental disorders. PMID:26840809

  7. Transcript profiles of maize embryo sacs and preliminary identification of genes involved in the embryo sac–pollen tube interaction

    PubMed Central

    Wang, Shuai Shuai; Wang, Fang; Tan, Su Jian; Wang, Ming Xiu; Sui, Na; Zhang, Xian Sheng

    2014-01-01

    The embryo sac, the female gametophyte of flowering plants, plays important roles in the pollination and fertilization process. Maize (Zea mays L.) is a model monocot, but little is known about the interactions between its embryo sac and the pollen tube. In this study, we compared the transcript profiles of mature embryo sacs, mature embryo sacs 14–16 h after pollination, and mature nucelli. Comparing the transcript profiles of the embryo sacs before and after the entry of the pollen tube, we identified 3467 differentially expressed transcripts (3382 differentially expressed genes; DEGs). The DEGs were grouped into 22 functional categories. Among the DEGs, 221 genes were induced upon the entry of the pollen tube, and many of them encoded proteins involved in RNA binding, processing, and transcription, signaling, miscellaneous enzyme family processes, and lipid metabolism processes. Genes in the DEG dataset were grouped into 17 classes in a gene ontology enrichment analysis. The DEGs included many genes encoding proteins involved in protein amino acid phosphorylation and protein ubiquitination, implying that these processes might play important roles in the embryo sac–pollen tube interaction. Additionally, our analyses indicate that the expression of 112 genes encoding cysteine-rich proteins (CRPs) is induced during pollination and fertilization. The CRPs likely regulate pollen tube guidance and embryo sac development. These results provide important information on the genes involved in the embryo sac–pollen tube interaction in maize. PMID:25566277

  8. Influence of external inputs and asymmetry of connections on information-geometric measures involving up to ten neuronal interactions.

    PubMed

    Nie, Yimin; Fellous, Jean-Marc; Tatsuno, Masami

    2014-10-01

    The investigation of neural interactions is crucial for understanding information processing in the brain. Recently an analysis method based on information geometry (IG) has gained increased attention, and the property of the pairwise IG measure has been studied extensively in relation to the two-neuron interaction. However, little is known about the property of IG measures involving more neuronal interactions. In this study, we systematically investigated the influence of external inputs and the asymmetry of connections on the IG measures in cases ranging from 1-neuron to 10-neuron interactions. First, the analytical relationship between the IG measures and external inputs was derived for a network of 10 neurons with uniform connections. Our results confirmed that the single and pairwise IG measures were good estimators of the mean background input and of the sum of the connection weights, respectively. For the IG measures involving 3 to 10 neuronal interactions, we found that the influence of external inputs was highly nonlinear. Second, by computer simulation, we extended our analytical results to asymmetric connections. For a network of 10 neurons, the simulation showed that the behavior of the IG measures in relation to external inputs was similar to the analytical solution obtained for a uniformly connected network. When the network size was increased to 1000 neurons, the influence of external inputs almost disappeared. This result suggests that all IG measures from 1-neuron to 10-neuron interactions are robust against the influence of external inputs. In addition, we investigated how the strength of asymmetry influenced the IG measures. Computer simulation of a 1000-neuron network showed that all the IG measures were robust against the modulation of the asymmetry of connections. Our results provide further support for an information-geometric approach and will provide useful insights when these IG measures are applied to real experimental spike data. PMID

  9. Bench to Bed Evidences for Pharmacokinetic and Pharmacodynamic Interactions Involving Oseltamivir and Chinese Medicine

    PubMed Central

    Chang, Qi; Wo, Siukwan; Ngai, Karry L. K.; Wang, Xiaoan; Fok, Benny; Ngan, Teresa M.; Wong, Vivian T.; Chan, Thomas Y. K.; Lee, Vincent H. L.; Tomlinson, Brian; Chan, Paul K. S.; Chow, Moses S. S.; Zuo, Zhong

    2014-01-01

    Oseltamivir (OA), an ethyl ester prodrug of oseltamivir carboxylate (OC), is clinically used as a potent and selective inhibitor of neuraminidase. Chinese medicines have been advocated to combine with conventional drug for avian influenza. The current study aims to investigate the potential pharmacokinetic and pharmacodynamic interactions of a Chinese medicine formula, namely, Yin Qiao San and Sang Ju Yin (CMF1), commonly used for anti-influenza in combination with OA in both rat and human, and to reveal the underlined mechanisms. It was found that although Cmax, AUC and urinary recovery of OC, as well as metabolic ratio (AUCOC/AUCOA), were significantly decreased in a dose-dependent manner following combination use of CMF1 and OA in rat studies (P < 0.01), such coadministration in 14 healthy volunteers only resulted in a trend of minor decrease in the related parameters. Further mechanistic studies found that although CMF1 could reduce absorption and metabolism of OA, it appears to enhance viral inhibition of OA (P < 0.01). In summary, although there was potential interaction between OA and CMF1 found in rat studies, its clinical impact was expected to be minimal. The coadministration of OA and CMF1 at the clinical recommended dosages is, therefore, considered to be safe. PMID:24527044

  10. Molecular Players Involved in the Interaction Between Beneficial Bacteria and the Immune System

    PubMed Central

    Hevia, Arancha; Delgado, Susana; Sánchez, Borja; Margolles, Abelardo

    2015-01-01

    The human gastrointestinal tract is a very complex ecosystem, in which there is a continuous interaction between nutrients, host cells, and microorganisms. The gut microbiota comprises trillions of microbes that have been selected during evolution on the basis of their functionality and capacity to survive in, and adapt to, the intestinal environment. Host bacteria and our immune system constantly sense and react to one another. In this regard, commensal microbes contribute to gut homeostasis, whereas the necessary responses are triggered against enteropathogens. Some representatives of our gut microbiota have beneficial effects on human health. Some of the most important roles of these microbes are to help to maintain the integrity of the mucosal barrier, to provide nutrients such as vitamins, or to protect against pathogens. In addition, the interaction between commensal microbiota and the mucosal immune system is crucial for proper immune function. This process is mainly performed via the pattern recognition receptors of epithelial cells, such as Toll-like or Nod-like receptors, which are able to recognize the molecular effectors that are produced by intestinal microbes. These effectors mediate processes that can ameliorate certain inflammatory gut disorders, discriminate between beneficial and pathogenic bacteria, or increase the number of immune cells or their pattern recognition receptors (PRRs). This review intends to summarize the molecular players produced by probiotic bacteria, notably Lactobacillus and Bifidobacterium strains, but also other very promising potential probiotics, which affect the human immune system. PMID:26635753

  11. The immunoglobulin-like domain is involved in interaction of Neuregulin1 with ErbB

    SciTech Connect

    Eto, Ko . E-mail: etoko@gpo.kumamoto-u.ac.jp; Eda, Kazufumi; Kanemoto, Shintaro; Abe, Shin-ichi

    2006-11-17

    Neuregulin1 (NRG1) is a growth factor that signals through the interaction of the epidermal growth factor (EGF)-like domain with ErbB receptors. An immunoglobulin (Ig)-like domain is contained together with EGF-like domain in the ectodomain of some isoforms generated by alternative splicing, but its role in NRG1 signaling remained unclear. In the present study, we identified a novel isoform of NRG1 containing an Ig-like domain conserved among species from adult Xenopus laevis, which is predominantly expressed in the testis and brain. We generated recombinant proteins for the whole ectodomain and EGF-like domain alone of the isoform to compare their effects on cell proliferation, and phosphorylation of and their association with ErbB receptor, demonstrating that the ectodomain had {approx}10{sup 3}-fold higher abilities than the EGF-like domain. Therefore, the Ig-like domain is probably essential for efficient interaction of an EGF-like domain with ErbB receptors.

  12. Surfactant behavior of ionic liquids involving a drug: from molecular interactions to self-assembly.

    PubMed

    Tourné-Péteilh, Corine; Coasne, Benoit; In, Martin; Brevet, David; Devoisselle, Jean-Marie; Vioux, André; Viau, Lydie

    2014-02-11

    Aggregates formed in an aqueous medium by three ionic liquids CnMImIbu made up of 1-alkyl-3-methyl-imidazolium cation (n = 4, 6, 8) and ibuprofenate anion are investigated. Dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), (1)H nuclear magnetic resonance measurements, and atom-scale molecular dynamics simulations are used to shed light on the main interactions governing the formation of the aggregates and their composition. At high concentration, mixed micelles are formed with a composition that depends on the imidazolium alkyl chain length. For the shortest alkyl chain, micelles are mainly composed of ibuprofenate anions with some imidazolium cations intercalated between the anions. Upon increasing the alkyl chain length, the composition of the aggregates gets enriched in imidazolium cations and aggregates of stoichiometric composition are obtained. Attractive interactions between these aggregates led to the formation of larger aggregates. As suggested by molecular simulations, these larger aggregates might constitute the early stage of phase separation. Transitions from micelles to vesicles or ribbons are observed due to dilution effects and changes in the chemical composition of the aggregates. We also show that aggregation can be probed using simple microscopic quantities such as radial distribution functions and average solvation numbers. PMID:24437472

  13. Two domains of the epidermal growth factor receptor are involved in cytoskeletal interactions

    SciTech Connect

    Song Wei; Wu Jing; Ge Gaoxiang; Lin Qishui

    2008-06-13

    Epidermal growth factor receptor can interact directly with F-actin through an actin-binding domain. In the present study, a mutant EGFR, lacking a previously identified actin-binding domain (ABD 1), was still able to bind elements of the cytoskeleton. A second EGFR actin-binding domain (ABD 2) was identified in the region of the receptor that includes Tyr-1148 by a yeast two-hybrid assay. GST fusion proteins comprising ABD 1 or ABD 2 bound actin in vitro and competed for actin-binding with the full-length EGFR. EGFR binding to actin was also studied in intact cells using fluorescence resonance energy transfer (FRET). The localization of the EGFR/actin-binding complex changed after EGF stimulation. Fusion proteins containing mutations in ABD1 or ABD2 did not display a FRET signal. The results lead to the conclusion that the interaction between ABD1 and ABD2 and actin during EGF-induced signal transduction, and thus between EGFR and actin, are important in cell activation.

  14. Molecular Players Involved in the Interaction Between Beneficial Bacteria and the Immune System.

    PubMed

    Hevia, Arancha; Delgado, Susana; Sánchez, Borja; Margolles, Abelardo

    2015-01-01

    The human gastrointestinal tract is a very complex ecosystem, in which there is a continuous interaction between nutrients, host cells, and microorganisms. The gut microbiota comprises trillions of microbes that have been selected during evolution on the basis of their functionality and capacity to survive in, and adapt to, the intestinal environment. Host bacteria and our immune system constantly sense and react to one another. In this regard, commensal microbes contribute to gut homeostasis, whereas the necessary responses are triggered against enteropathogens. Some representatives of our gut microbiota have beneficial effects on human health. Some of the most important roles of these microbes are to help to maintain the integrity of the mucosal barrier, to provide nutrients such as vitamins, or to protect against pathogens. In addition, the interaction between commensal microbiota and the mucosal immune system is crucial for proper immune function. This process is mainly performed via the pattern recognition receptors of epithelial cells, such as Toll-like or Nod-like receptors, which are able to recognize the molecular effectors that are produced by intestinal microbes. These effectors mediate processes that can ameliorate certain inflammatory gut disorders, discriminate between beneficial and pathogenic bacteria, or increase the number of immune cells or their pattern recognition receptors (PRRs). This review intends to summarize the molecular players produced by probiotic bacteria, notably Lactobacillus and Bifidobacterium strains, but also other very promising potential probiotics, which affect the human immune system. PMID:26635753

  15. SMYD1, an SRF-Interacting Partner, Is Involved in Angiogenesis.

    PubMed

    Ye, Xiangli; Qian, Yu; Wang, Qian; Yuan, Wuzhou; Mo, Xiaoyang; Li, Yongqing; Jiang, Zhigang; Xu, Wei; Deng, Yun; Wan, Yongqi; Fan, Xiongwei; Wu, Xiushan; Wang, Yuequn

    2016-01-01

    Previous studies have demonstrated that Smyd1 plays a critical role in cardiomyocyte differentiation, cardiac morphogenesis and myofibril organization. In this study, we uncovered a novel function of Smyd1 in the regulation of endothelial cells (ECs). Our data showed that Smyd1 is expressed in vascular endothelial cells, and knockdown of SMYD1 in endothelial cells impairs EC migration and tube formation. Furthermore, Co-IP and GST pull-down assays demonstrated that SMYD1 is associated with the Serum Response Factor (SRF). EMSA assays further showed that SMYD1 forms a complex with SRF and enhances SRF DNA binding activity. Our studies indicate that SMYD1 serves as an SRF-interacting protein, enhances SRF DNA binding activity, and is required for EC migration and tube formation to regulate angiogenesis. PMID:26799706

  16. Interactive tutorial to improve student understanding of single photon experiments involving a Mach-Zehnder interferometer

    NASA Astrophysics Data System (ADS)

    Marshman, Emily; Singh, Chandralekha

    2016-03-01

    We have developed and evaluated a quantum interactive learning tutorial (QuILT) on a Mach-Zehnder interferometer with single photons to expose upper-level students in quantum mechanics courses to contemporary quantum optics applications. The QuILT strives to help students develop the ability to apply fundamental quantum principles to physical situations in quantum optics and explore the differences between classical and quantum ideas. The QuILT adapts visualization tools to help students build physical intuition about counter-intuitive quantum optics phenomena with single photons including a quantum eraser setup and focuses on helping them integrate qualitative and quantitative understanding. We discuss findings from in-class evaluations.

  17. Bezafibrate-mizoribine interaction: Involvement of organic anion transporters OAT1 and OAT3 in rats.

    PubMed

    Feng, Yuan; Wang, Changyuan; Liu, Qi; Meng, Qiang; Huo, Xiaokui; Liu, Zhihao; Sun, Pengyuan; Yang, Xiaobo; Sun, Huijun; Qin, Jianhua; Liu, Kexin

    2016-01-01

    A patient with rheumatoid arthritis developed rhabdomyolysis while undergoing treatment with mizoribine concomitantly with bezafibrate. The symptoms rapidly disappeared and laboratory test results normalized when she discontinued the two drugs. The purpose of the present study was to elucidate the transporter-mediated molecular pharmacokinetic mechanisms of drug-drug interactions between bezafibrate and mizoribine. Comparing bezafibrate-mizoribine group with bezafibrate group, the Tmax and Cmax of bezafibrate were essentially unchanged in rats. The AUC of bezafibrate was significantly increased and t1/2β was prolonged markedly with an obviously reduction in plasma clearance and cumulative urinary excretion. The changes were similar to oral studies following intravenous co-administration. In rat kidney slices, the uptake of bezafibrate was markedly inhibited by p-aminohippurate, benzylpenicillin and probenecid but not by tetraethyl ammonium. Mizoribine not only decreased the uptake of bezafibrate, but also inhibited the uptake of p-aminohippurate and benzylpenicillin. The uptakes of bezafibrate and mizoribine were significantly higher compared to vector-HEK293 cells. The uptakes of bezafibrate and mizoribine in highest concentration were increased 1.63 and 1.46 folds in hOAT1-transfected cells, 1.43 and 1.24 folds in hOAT3-transfected cells, respectively. The Km values of bezafibrate uptake by hOAT1/3hOAT1-/hOAT3-HEK293 K293 cells were increased 1.68 fold in hOAT1-HEK293 cell and 2.12 fold in hOAT3-HEK293 cell in the presence of mizoribine with no change of Vmax. It indicated that mizoribine could inhibit the uptake of bezafibrate by hOAT1/3-HEK293 cells in a competitive way. In conclusion, OAT1 and OAT3 are the target transporters of drug-drug interactions between bezafibrate and mizoribine in pharmacokinetic aspects. PMID:26474691

  18. Chemical characterization and location of ionic interactions involved in the assembly of the C1 complex of human complement.

    PubMed

    Illy, C; Thielens, N M; Arlaud, G J

    1993-12-01

    The C1 complex of human complement comprises two loosely interacting subunits, C1q and the Ca(2+)-dependent C1s-C1r-C1r-C1s tetramer. With a view to gain information on the nature of the ionic interactions involved in C1 assembly, we have studied the effects of the chemical modifications of charged residues of C1q or the tetramer on their ability to reconstitute the C1 complex. Treatment of C1q with pyridoxal-5'-phosphate, acetic anhydride, and citraconic anhydride, as well as with cyclohexanedione and diethylpyrocarbonate, inhibited its ability to associate with C1s-C1r-C1r-C1s. Treatment of the collagen-like fragments of C1q with the same reagents yielded the same effects. Treatment of C1s-C1r-C1r-C1s with 1-ethyl-3-[-3-(dimethylamino) propyl] carbodiimide also prevented C1 assembly, through modification of acidic amino acids which were shown to be located in C1r. Further studies on the location of the interaction sites within C1q, using ligand-blotting and competition experiments with synthetic peptides, were unsuccessful, suggesting that these sites are contributed to by two or three of the C1q chains. It is concluded that C1 assembly involves interactions between acidic amino acids of C1r and lysine (hydroxylysine) and arginine residues located within the collagen-like region of C1q. Sequence comparison with mannan binding protein, another collagen-like molecule which binds the C1s-C1r-C1r-C1s tetramer, suggests Arg A38, and HyL B32, B65, and C29 of C1q as possible interaction sites. PMID:8136028

  19. A C-code for the double folding interaction potential for reactions involving deformed target nuclei

    NASA Astrophysics Data System (ADS)

    Gontchar, I. I.; Chushnyakova, M. V.

    2013-01-01

    We present a C-code designed to obtain the interaction potential between a spherical projectile nucleus and an axial-symmetrical deformed target nucleus and in particular to find the Coulomb barrier, by using the double folding model (DFM). The program calculates the nucleus-nucleus potential as a function of the distance between the centers of mass of colliding nuclei as well as of the angle between the axis of symmetry of the target nucleus and the beam direction. The most important output parameters are the Coulomb barrier energy and the radius. Since many researchers use a Woods-Saxon profile for the nuclear term of the potential we provide an option in our code for fitting the DFM potential by such a profile near the barrier. Program summaryProgram title: DFMDEF Catalogue identifier: AENI_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AENI_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 2245 No. of bytes in distributed program, including test data, etc.: 215442 Distribution format: tar.gz Programming language: C. Computer: PC, Mac. Operating system: Windows XP (with the GCC-compiler version 2), MacOS, Linux. RAM: 100 MB with average parameters set Classification: 17.9. Nature of problem: The code calculates in a semimicroscopic way the bare interaction potential between a spherical projectile nucleus and a deformed but axially symmetric target nucleus as a function of the center of mass distance as well as of the angle between the axis of symmetry of the target nucleus and the beam direction. The height and the position of the Coulomb barrier are found. The calculated potential is approximated by a conventional Woods-Saxon profile near the barrier. Dependence of the barrier parameters upon the characteristics of the effective NN forces (like, e

  20. AUTONOMY AND RELATEDNESS IN MOTHER-TEEN INTERACTIONS AS PREDICTORS OF INVOLVEMENT IN ADOLESCENT DATING AGGRESSION

    PubMed Central

    Niolon, Phyllis Holditch; Kuperminc, Gabriel P.; Allen, Joseph P.

    2015-01-01

    Objective This multi-method, longitudinal study examines the negotiation of autonomy and relatedness between teens and their mothers as etiologic predictors of perpetration and victimization of dating aggression two years later. Method Observations of 88 mid-adolescents and their mothers discussing a topic of disagreement were coded for each individual’s demonstrations of autonomy and relatedness using a validated coding system. Adolescents self-reported on perpetration and victimization of physical and psychological dating aggression two years later. We hypothesized that mother’s and adolescents’ behaviors supporting autonomy and relatedness would longitudinally predict lower reporting of dating aggression, and that their behaviors inhibiting autonomy and relatedness would predict higher reporting of dating aggression. Results Hypotheses were not supported; main findings were characterized by interactions of sex and risk status with autonomy. Maternal behaviors supporting autonomy predicted higher reports of perpetration and victimization of physical dating aggression for girls, but not for boys. Adolescent behaviors supporting autonomy predicted higher reports of perpetration of physical dating aggression for high-risk adolescents, but not for low-risk adolescents. Conclusions Results indicate that autonomy is a dynamic developmental process, operating differently as a function of social contexts in predicting dating aggression. Examination of these and other developmental processes within parent-child relationships is important in predicting dating aggression, but may depend on social context. PMID:25914852

  1. Macrofaunal involvement in the sublittoral decay of kelp debris: the detritivore community and species interactions

    NASA Astrophysics Data System (ADS)

    Bedford, A. P.; Moore, P. G.

    1984-01-01

    The fauna associated with sea-bed accumulations of decomposing Laminaria saccharina has been studied by year-round SCUBA diving at two sites in the Clyde Sea area. Seasonal changes in density of 64 species are reported. In the autumn, large quantities of kelp are detached by storms. This weed carries with it to the sea bed a large part of its normal fauna. Additional species settle onto the weed from the plankton whilst others migrate onto it from the surrounding sea bed. Peak densities of associated species were recorded in autumn. Litter bag experiments in situ showed that, except during the summer, weed is lost from sea-bed accumulations at a faster rate when macrofaunal animals are excluded. The macrofauna therefore inhibits decomposition. The relative importance of interactive cropping by three macrodetritivores, Psammechinus miliaris (Echinodermata), Platynereis dumerilii (Polychaeta) and Gammarus locusta (Amphipoda) was studied by in situ containment of different species combinations. The presence of Gammarus with Psammechinus resulted in less weed being lost than when Psammechinus was isolated. This is because Gammarus selectively crops rotting weed, retarding frond disintegration by microbes. Platynereis retards microbial colonization of frond tissues ruptured during its feeding by repeated cropping of the same region. Weed would decompose very rapidly were it not for macrofaunal cropping. Macroalgal decay thus differs profoundly from that of vascular plants.

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

    PubMed Central

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

    2014-01-01

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

  3. Sperm whale predator-prey interactions involve chasing and buzzing, but no acoustic stunning.

    PubMed

    Fais, A; Johnson, M; Wilson, M; Aguilar Soto, N; Madsen, P T

    2016-01-01

    The sperm whale carries a hypertrophied nose that generates powerful clicks for long-range echolocation. However, it remains a conundrum how this bizarrely shaped apex predator catches its prey. Several hypotheses have been advanced to propose both active and passive means to acquire prey, including acoustic debilitation of prey with very powerful clicks. Here we test these hypotheses by using sound and movement recording tags in a fine-scale study of buzz sequences to relate the acoustic behaviour of sperm whales with changes in acceleration in their head region during prey capture attempts. We show that in the terminal buzz phase, sperm whales reduce inter-click intervals and estimated source levels by 1-2 orders of magnitude. As a result, received levels at the prey are more than an order of magnitude below levels required for debilitation, precluding acoustic stunning to facilitate prey capture. Rather, buzzing involves high-frequency, low amplitude clicks well suited to provide high-resolution biosonar updates during the last stages of capture. The high temporal resolution helps to guide motor patterns during occasionally prolonged chases in which prey are eventually subdued with the aid of fast jaw movements and/or buccal suction as indicated by acceleration transients (jerks) near the end of buzzes. PMID:27340122

  4. Invasion of insect cells by Spiroplasma citri involves spiralin relocalization and lectin/glycoconjugate-type interactions.

    PubMed

    Duret, Sybille; Batailler, Brigitte; Dubrana, Marie-Pierre; Saillard, Colette; Renaudin, Joël; Béven, Laure; Arricau-Bouvery, Nathalie

    2014-07-01

    Spiroplamas are helical, cell wall-less bacteria belonging to the Class Mollicutes, a group of microorganisms phylogenetically related to low G+C, Gram-positive bacteria. Spiroplasma species are all found associated with arthropods and a few, including Spiroplasma citri are pathogenic to plant. Thus S. citri has the ability to colonize cells of two very distinct hosts, the plant and the insect vector. While spiroplasmal factors involved in transmission by the leafhopper Circulifer haematoceps have been identified, their specific contribution to invasion of insect cells is poorly understood. In this study we provide evidence that the lipoprotein spiralin plays a major role in the very early step of cell invasion. Confocal laser scanning immunomicroscopy revealed a relocalization of spiralin at the contact zone of adhering spiroplasmas. The implication of a role for spiralin in adhesion to insect cells was further supported by adhesion assays showing that a spiralin-less mutant was impaired in adhesion and that recombinant spiralin triggered adhesion of latex beads. We also showed that cytochalasin D induced changes in the surface-exposed glycoconjugates, as inferred from the lectin binding patterns, and specifically improved adhesion of S. citri wild-type but not of the spiralin-less mutant. These results indicate that cytochalasin D exposes insect cell receptors of spiralin that are masked in untreated cells. In addition, competitive adhesion assays with lectins strongly suggest spiralin to exhibit glycoconjugate binding properties similar to that of the Vicia villosa agglutinin (VVA) lectin. PMID:24438161

  5. Sperm whale predator-prey interactions involve chasing and buzzing, but no acoustic stunning

    PubMed Central

    Fais, A.; Johnson, M.; Wilson, M.; Aguilar Soto, N.; Madsen, P. T.

    2016-01-01

    The sperm whale carries a hypertrophied nose that generates powerful clicks for long-range echolocation. However, it remains a conundrum how this bizarrely shaped apex predator catches its prey. Several hypotheses have been advanced to propose both active and passive means to acquire prey, including acoustic debilitation of prey with very powerful clicks. Here we test these hypotheses by using sound and movement recording tags in a fine-scale study of buzz sequences to relate the acoustic behaviour of sperm whales with changes in acceleration in their head region during prey capture attempts. We show that in the terminal buzz phase, sperm whales reduce inter-click intervals and estimated source levels by 1–2 orders of magnitude. As a result, received levels at the prey are more than an order of magnitude below levels required for debilitation, precluding acoustic stunning to facilitate prey capture. Rather, buzzing involves high-frequency, low amplitude clicks well suited to provide high-resolution biosonar updates during the last stages of capture. The high temporal resolution helps to guide motor patterns during occasionally prolonged chases in which prey are eventually subdued with the aid of fast jaw movements and/or buccal suction as indicated by acceleration transients (jerks) near the end of buzzes. PMID:27340122

  6. Animal Models to Study Host-Bacteria Interactions Involved in Periodontitis

    PubMed Central

    Graves, Dana T.; Kang, Jun; Andriankaja, Oelisoa; Wada, Keisuke; Rossa, Carlos

    2013-01-01

    Animal models have distinct advantages because they can mimic cellular complexities that occur in humans in vivo and are often more accurate than in vitro studies that take place on plastic surfaces with limited numbers of cell types present. Furthermore, cause and effect relationships can be established by applying inhibitors or activators or through the use of genetically modified animals. Such gain or loss of function studies are often difficult to achieve in human clinical studies, particularly in obtaining target tissue due to important ethical considerations. Animal models in periodontal disease are particularly important at this point in the development of the scientific basis for understanding the predominant pathological processes. Periodontal disease can be broken down into discrete steps, each of which may be studied separately depending upon the animal model. These steps involve the development of a pathogenic biofilm, invasion of connective tissue by bacteria or their products, induction of a destructive host response in connective tissue and limitation of a repair process that follows tissue breakdown. Animal studies can test hypotheses related to each of these steps, and should be evaluated by their capacity to test a specific hypothesis rather than recapitulating all aspects of periodontal disease. Thus, each of the models described below can be adapted to test discrete components of the pathological process of periodontal disease, but not necessarily all of them. PMID:22142960

  7. Influence of gold(I) complexes involving adenine derivatives on major drug-drug interaction pathway.

    PubMed

    Dvořák, Zdeněk; Novotná, Aneta; Vančo, Ján; Trávníček, Zdeněk

    2013-12-01

    A series of considerably anti-inflammatory active gold(I) mixed-ligand complexes, involving the benzyl-substituted derivatives of N6-benzyladenine (HLn) and triphenylphosphine (PPh3) as ligands and having the general formula [Au(Ln)(PPh3)]·xH2O (1-4; n=1-4 and x=0-1), was evaluated for the ability to influence the expression of CYP1A1/2 and CYP3A4 and transcriptional activity of glucocorticoid (GR) and aryl hydrocarbon (AhR) receptors in primary human hepatocytes and HepG2 cells. In both tests, evaluating the ability of the complexes to modulate the expression of CYP1A1, CYP1A2 and CYP3A4 in primary human hepatocytes and influence the transcriptional activity of AhR and GR in the reporter cell lines, no negative influence on the major drug-metabolizing cytochrome P450 isoenzymes and their signaling pathway (through GR and AhR receptors) was observed. These positive findings revealed another substantial evidence that could lead to utilization of the complexes as effective and relatively safe drugs for the treatment of hard-to-treat inflammation-related diseases, such as rheumatoid arthritis, comparable or even better than clinically used gold-containing drug Auranofin. PMID:24157406

  8. PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome.

    PubMed

    Fu, Alan; Jacobs, Daniel I; Hoffman, Aaron E; Zheng, Tongzhang; Zhu, Yong

    2015-10-01

    Although PIWI-interacting RNAs (piRNAs) account for the largest class of the small non-coding RNA superfamily, virtually nothing is known of their function in human carcinogenesis. Once thought to be expressed solely in the germ line where they safeguard the genome against transposon-induced insertional mutations, piRNAs are now believed to play an active role in somatic gene regulation through sequence-specific histone modification and DNA methylation. In the current study, we investigate the role of piRNA-021285 (piR-021285) in the regulation of the breast cancer methylome. Genotypic screening of a panel of single-nucleotide polymorphism (SNP)-containing piRNAs revealed a significant association between SNP rs1326306 G>T in piR-021285 and increased likelihood for breast cancer in a Connecticut-based population (441 cases and 479 controls). Given nascent but compelling evidence of piRNA-mediated gene-specific methylation in the soma, a genome-wide methylation screen was then carried out using wild type (WT) and variant piR-021285 mimic-transfected MCF7 cells to explore whether the observed association could be attributed in part to piR-021285-induced methylation at cancer-relevant genes. We found significant methylation differences at a number of experimentally implicated breast cancer-related genes, including attenuated 5' untranslated region (UTR)/first exon methylation at the proinvasive ARHGAP11A gene in variant mimic-transfected cells. Follow-up functional analyses revealed both concurrent increased ARHGAP11A mRNA expression and enhanced invasiveness in variant versus WT piR-021285 mimic-transfected breast cancer cell lines. Taken together, our findings demonstrate the first evidence supporting a role of piRNAs, a novel group of non-coding RNA, in human tumorigenesis via a piRNA-mediated epigenetic mechanism, which warrants further confirmation and investigation. PMID:26210741

  9. Human anterior thalamic nuclei are involved in emotion-attention interaction.

    PubMed

    Sun, Lihua; Peräkylä, Jari; Polvivaara, Markus; Öhman, Juha; Peltola, Jukka; Lehtimäki, Kai; Huhtala, Heini; Hartikainen, Kaisa M

    2015-11-01

    Patients treated with deep brain stimulation (DBS) provide an opportunity to study affective processes in humans with "lesion on demand" at key nodes in the limbic circuitries, such as at the anterior thalamic nuclei (ANT). ANT has been suggested to play a role in emotional control with its connection to the orbitofrontal cortex and the anterior cingulate cortex. However, direct evidence for its role in emotional function in human subjects is lacking. Reported side effects of ANT-DBS in the treatment of refractory epilepsy include depression related symptoms. In line with these mood-related clinical side effects, we have previously reported that stimulating the anterior thalamus increased emotional interference in a visual attention task as indicated by prolonged reaction times due to threat-related emotional distractors. We used event-related potentials to investigate potential attentional mechanism behind this behavioural observation. We hypothesized that ANT-DBS leads to greater attention capture by threat-related distractors. We tested this hypothesis using centro-parietal N2-P3 peak-to-peak amplitude as a measure of allocated attentional resources. Six epileptic patients treated with deep brain stimulation at ANT participated in the study. Electroencephalography was recorded while the patients performed a computer based Executive-Reaction Time test with threat-related emotional distractors. During the task, either ANT or a thalamic control location was stimulated, or the stimulation was turned off. Stimulation of ANT was associated with increased centro-parietal N2-P3 amplitude and increased reaction time in the context of threat-related emotional distractors. We conclude that high frequency electric stimulation of ANT leads to greater attentional capture by emotional stimuli. This is the first study to provide direct evidence from human subjects with on-line electric manipulation of ANT for its role in emotion-attention interaction. PMID:26440152

  10. Involvement of NIPSNAP1, a neuropeptide nocistatin-interacting protein, in inflammatory pain

    PubMed Central

    Okamoto, Kazuya; Ohashi, Masaki; Ohno, Kana; Takeuchi, Arisa; Matsuoka, Etsuko; Fujisato, Kyohei; Minami, Toshiaki; Ito, Seiji

    2016-01-01

    Background Chronic pain associated with inflammation is an important clinical problem, and the underlying mechanisms remain poorly understood. 4-Nitrophenylphosphatase domain and nonneuronal SNAP25-like protein homolog (NIPSNAP) 1, an interacting protein with neuropeptide nocistatin, is implicated in the inhibition of tactile pain allodynia. Although nocistatin inhibits some inflammatory pain responses, whether NIPSNAP1 affects inflammatory pain appears to be unclear. Here, we examined the nociceptive behavioral response of NIPSNAP1-deficient mice and the expression of NIPSNAP1 following peripheral inflammation to determine the contribution of NIPSNAP1 to inflammatory pain. Results Nociceptive behavioral response increased in phase II of the formalin test, particularly during the later stage (26–50 min) in NIPSNAP1-deficient mice, although the response during phase I (0–15 min) was not significantly different between the deficient and wild-type mice. Moreover, phosphorylation of extracellular signal-related kinase was enhanced in the spinal dorsal horn of the deficient mice. The prolonged inflammatory pain induced by carrageenan and complete Freund’s adjuvant was exacerbated in NIPSNAP1-deficient mice. NIPSNAP1 mRNA was expressed in small- and medium-sized neurons of the dorsal root ganglion and motor neurons of the spinal cord. In the formalin test, NIPSNAP1 mRNA was slightly increased in dorsal root ganglion but not in the spinal cord. In contrast, NIPSNAP1 mRNA levels in dorsal root ganglion were significantly decreased during 24–48 h after carrageenan injection. Prostaglandin E2, a major mediator of inflammation, stimulated NIPSNAP1 mRNA expression via the cAMP-protein kinase A signaling pathway in isolated dorsal root ganglion cells. Conclusions These results suggest that changes in NIPSNAP1 expression may contribute to the pathogenesis of inflammatory pain. PMID:27030720

  11. SpiE interacts with Corynebacterium glutamicum WhcE and is involved in heat and oxidative stress responses.

    PubMed

    Park, Jung Chul; Park, Joon-Song; Kim, Younhee; Kim, Pil; Kim, Eung Soo; Lee, Heung-Shick

    2016-05-01

    The gene whcE in Corynebacterium glutamicum positively responds to oxidative and heat stress. To search for proteins that interact with WhcE, we employed a two-hybrid system with WhcE as the bait. Sequencing analysis of the isolated clones revealed peptide sequences, one of which showed high sequence identity to a hydrophobe/amphiphile efflux-1 family transporter encoded by NCgl1497. The interaction of the NCgl1497-encoded protein with WhcE in vivo was verified using reporter gene expression by real-time quantitative PCR (RT-qPCR). The WhcE protein strongly interacted with the NCgl1497-encoded protein in the presence of oxidative and heat stress. Furthermore, purified WhcE and NCgl1497-encoded proteins interacted in vitro, especially in the presence of the oxidant diamide, and the protein-protein interaction was disrupted in the presence of the reductant dithiothreitol. In addition, the transcription of NCgl1497 was activated approximately twofold in diamide- or heat-treated cells. To elucidate the function of the NCgl497 gene, an NCgl1497-deleted mutant strain was constructed. The mutant showed decreased viability in the presence of diamide and heat stress. The mutant strain also exhibited reduced transcription of the thioredoxin reductase gene, which is known to be regulated by whcE. Based on the results, NCgl1497 was named spiE (stress protein interacting with WhcE). Collectively, our data suggest that spiE is involved in the whcE-mediated oxidative stress response pathway of C. glutamicum. PMID:26996627

  12. Coordination polymers of Ag(I) based on iminocarbene ligands involving metal-carbon and metal-heteroatom interactions

    NASA Astrophysics Data System (ADS)

    Netalkar, Sandeep P.; Netalkar, Priya P.; Revankar, Vidyanand K.

    2016-03-01

    The reaction of Ag2O with three novel imino-NHC ligands derived from 2-chloroacetophenone with pendant N-donor functional group incorporated by reaction with methoxyamine and 1-methyl/ethyl/n-butyl-substituted imidazoles afforded one-dimensional coordination polymers with [(-NHCarbene)Ag(NHCarbene-)PF6]n formulation involving both carbon-metal and heteroatom-metal interactions, the carbon and heteroatom involved in coordination to silver being from different molecule of the ligand. The complexes as well as the ligands were characterized by spectroscopic methods as well as the solid state structures determined in case of 2a, 3a and complex 5. The iminocarbene ligands serve as non-chelating building block for supramolecular silver assemblies.

  13. Involvement of sulfates from cruzipain, a major antigen of Trypanosoma cruzi, in the interaction with immunomodulatory molecule Siglec-E.

    PubMed

    Ferrero, Maximiliano R; Heins, Anja M; Soprano, Luciana L; Acosta, Diana M; Esteva, Mónica I; Jacobs, Thomas; Duschak, Vilma G

    2016-02-01

    In order to investigate the involvement of sulfated groups in the Trypanosoma cruzi host-parasite relationship, we studied the interaction between the major cysteine proteinase of T. cruzi, cruzipain (Cz), a sulfate-containing sialylated molecule and the sialic acid-binding immunoglobulin like lectin-E (Siglec-E). To this aim, ELISA, indirect immunofluorescence assays and flow cytometry, using mouse Siglec-E-Fc fusion molecules and glycoproteins of parasites, were performed. Competition assays verified that the lectins, Maackia amurensis II (Mal II) and Siglec-E-Fc, compete for the same binding sites. Taking into account that Mal II binding remains unaltered by sulfation, we established this lectin as sialylation degree control. Proteins of an enriched microsomal fraction showed the highest binding to Siglec-E as compared with those from the other parasite subcellular fractions. ELISA assays and the affinity purification of Cz by a Siglec-E column confirmed the interaction between both molecules. The significant decrease in binding of Siglec-E-Fc to Cz and to its C-terminal domain (C-T) after desulfation of these molecules suggests that sulfates contribute to the interaction between Siglec-E-Fc and these glycoproteins. Competitive ELISA assays confirmed the involvement of sulfated epitopes in the affinity between Siglec-E and Cz, probably modified by natural protein environment. Interestingly, data from flow cytometry of untreated and chlorate-treated parasites suggested that sulfates are not primary receptors, but enhance the binding of Siglec-E to trypomastigotic forms. Altogether, our findings support the notion that sulfate-containing sialylated glycoproteins interact with Siglec-E, an ortholog protein of human Siglec-9, and might modulate the immune response of the host, favoring parasitemia and persistence of the parasite. PMID:26047932

  14. Cross-talk between glucocorticoid and retinoic acid signals involving glucocorticoid receptor interaction with the homoeodomain protein Pbx1.

    PubMed Central

    Subramaniam, Nanthakumar; Campión, Javier; Rafter, Ingalill; Okret, Sam

    2003-01-01

    Glucocorticoid (GC) signalling influences the response of the cell to a number of other signals via a mechanism referred to as 'cross-talk'. This cross-talk may act at several levels, including an interaction between the transcription factors involved in the signalling pathways. In the present paper, we demonstrate a novel functional interaction between GC and all- trans -retinoic acid (RA) signalling. We show that, in P19 embryonal carcinoma cells, GCs potentiate RA-induced expression of the murine Hoxb -1 gene through an autoregulatory element, b1-ARE, recognized by the Pbx1 and HOXB1 homoeodomain proteins. The synergistic effect of GC did not involve GC receptor (GR) binding to the b1-ARE, and the GC-GR complex alone was unable to activate transcription via the element. Furthermore, the ability of the GR to transactivate was not required, excluding expression of a GC-induced protein as the mechanism for the GC/RA synergy. Additional transfection experiments showed that the Pbx1/HOXB1 heterodimer was the target for the GC effect. Furthermore, functional dissection of the GR demonstrated that the DNA-binding domain (DBD) of the GR was required for the synergy. A physical interaction between the GR and Pbx1 proteins was demonstrated in vivo by co-immunoprecipitation experiments. These results are compatible with a model in which the GC/RA synergy is mediated by a direct interaction between the GR and Pbx1. On the basis of the ubiquitous expression of both GR and Pbx1, a number of genes regulated by Pbx are likely to be important targets for GC-mediated 'cross-talk'. PMID:12487626

  15. Cross-talk between glucocorticoid and retinoic acid signals involving glucocorticoid receptor interaction with the homoeodomain protein Pbx1.

    PubMed

    Subramaniam, Nanthakumar; Campión, Javier; Rafter, Ingalill; Okret, Sam

    2003-03-15

    Glucocorticoid (GC) signalling influences the response of the cell to a number of other signals via a mechanism referred to as 'cross-talk'. This cross-talk may act at several levels, including an interaction between the transcription factors involved in the signalling pathways. In the present paper, we demonstrate a novel functional interaction between GC and all- trans -retinoic acid (RA) signalling. We show that, in P19 embryonal carcinoma cells, GCs potentiate RA-induced expression of the murine Hoxb -1 gene through an autoregulatory element, b1-ARE, recognized by the Pbx1 and HOXB1 homoeodomain proteins. The synergistic effect of GC did not involve GC receptor (GR) binding to the b1-ARE, and the GC-GR complex alone was unable to activate transcription via the element. Furthermore, the ability of the GR to transactivate was not required, excluding expression of a GC-induced protein as the mechanism for the GC/RA synergy. Additional transfection experiments showed that the Pbx1/HOXB1 heterodimer was the target for the GC effect. Furthermore, functional dissection of the GR demonstrated that the DNA-binding domain (DBD) of the GR was required for the synergy. A physical interaction between the GR and Pbx1 proteins was demonstrated in vivo by co-immunoprecipitation experiments. These results are compatible with a model in which the GC/RA synergy is mediated by a direct interaction between the GR and Pbx1. On the basis of the ubiquitous expression of both GR and Pbx1, a number of genes regulated by Pbx are likely to be important targets for GC-mediated 'cross-talk'. PMID:12487626

  16. Molecular Basis of Gene-Gene Interaction: Cyclic Cross-Regulation of Gene Expression and Post-GWAS Gene-Gene Interaction Involved in Atrial Fibrillation

    PubMed Central

    Xu, Chengqi; Zhang, Hongfu; Lu, Qiulun; Chang, Le; Wang, Fan; Wang, Pengxia; Zhang, Rongfeng; Hu, Zhenkun; Song, Qixue; Yang, Xiaowei; Li, Cong; Li, Sisi; Zhao, Yuanyuan; Yang, Qin; Yin, Dan; Wang, Xiaojing; Si, Wenxia; Li, Xiuchun; Xiong, Xin; Wang, Dan; Huang, Yuan; Luo, Chunyan; Li, Jia; Wang, Jingjing; Chen, Jing; Wang, Longfei; Wang, Li; Han, Meng; Ye, Jian; Chen, Feifei; Liu, Jingqiu; Liu, Ying; Wu, Gang; Yang, Bo; Cheng, Xiang; Liao, Yuhua; Wu, Yanxia; Ke, Tie; Chen, Qiuyun; Tu, Xin; Elston, Robert; Rao, Shaoqi; Yang, Yanzong; Xia, Yunlong; Wang, Qing K.

    2015-01-01

    -gene interactions involved in genetics of complex disease traits. PMID:26267381

  17. Analysis of the RelA:CBP/p300 Interaction Reveals Its Involvement in NF-κB-Driven Transcription

    PubMed Central

    Mukherjee, Sulakshana P.; Behar, Marcelo; Birnbaum, Harry A.; Hoffmann, Alexander; Wright, Peter E.; Ghosh, Gourisankar

    2013-01-01

    NF-κB plays a vital role in cellular immune and inflammatory response, survival, and proliferation by regulating the transcription of various genes involved in these processes. To activate transcription, RelA (a prominent NF-κB family member) interacts with transcriptional co-activators like CREB-binding protein (CBP) and its paralog p300 in addition to its cognate κB sites on the promoter/enhancer regions of DNA. The RelA:CBP/p300 complex is comprised of two components—first, DNA binding domain of RelA interacts with the KIX domain of CBP/p300, and second, the transcriptional activation domain (TAD) of RelA binds to the TAZ1 domain of CBP/p300. A phosphorylation event of a well-conserved RelA(Ser276) is prerequisite for the former interaction to occur and is considered a decisive factor for the overall RelA:CBP/p300 interaction. The role of the latter interaction in the transcription of RelA-activated genes remains unclear. Here we provide the solution structure of the latter component of the RelA:CBP complex by NMR spectroscopy. The structure reveals the folding of RelA–TA2 (a section of TAD) upon binding to TAZ1 through its well-conserved hydrophobic sites in a series of grooves on the TAZ1 surface. The structural analysis coupled with the mechanistic studies by mutational and isothermal calorimetric analyses allowed the design of RelA-mutants that selectively abrogated the two distinct components of the RelA:CBP/p300 interaction. Detailed studies of these RelA mutants using cell-based techniques, mathematical modeling, and genome-wide gene expression analysis showed that a major set of the RelA-activated genes, larger than previously believed, is affected by this interaction. We further show how the RelA:CBP/p300 interaction controls the nuclear response of NF-κB through the negative feedback loop of NF-κB pathway. Additionally, chromatin analyses of RelA target gene promoters showed constitutive recruitment of CBP/p300, thus indicating a possible role

  18. The case for multimodal analysis of atypical interaction: questions, answers and gaze in play involving a child with autism.

    PubMed

    Muskett, Tom; Body, Richard

    2013-01-01

    Conversation analysis (CA) continues to accrue interest within clinical linguistics as a methodology that can enable elucidation of structural and sequential orderliness in interactions involving participants who produce ostensibly disordered communication behaviours. However, it can be challenging to apply CA to re-examine clinical phenomena that have initially been defined in terms of linguistics, as a logical starting point for analysis may be to focus primarily on the organisation of language ("talk") in such interactions. In this article, we argue that CA's methodological power can only be fully exploited in this research context when a multimodal analytic orientation is adopted, where due consideration is given to participants' co-ordinated use of multiple semiotic resources including, but not limited to, talk (e.g., gaze, embodied action, object use and so forth). To evidence this argument, a two-layered analysis of unusual question-answer sequences in a play episode involving a child with autism is presented. It is thereby demonstrated that only when the scope of enquiry is broadened to include gaze and other embodied action can an account be generated of orderliness within these sequences. This finding has important implications for CA's application as a research methodology within clinical linguistics. PMID:24067142

  19. Protein-protein interactions involving voltage-gated sodium channels: Post-translational regulation, intracellular trafficking and functional expression.

    PubMed

    Shao, Dongmin; Okuse, Kenji; Djamgoz, Mustafa B A

    2009-07-01

    Voltage-gated sodium channels (VGSCs), classically known to play a central role in excitability and signalling in nerves and muscles, have also been found to be expressed in a range of 'non-excitable' cells, including lymphocytes, fibroblasts and endothelia. VGSC abnormalities are associated with various diseases including epilepsy, long-QT syndrome 3, Brugada syndrome, sudden infant death syndrome and, more recently, various human cancers. Given their pivotal role in a wide range of physiological and pathophysiological processes, regulation of functional VGSC expression has been the subject of intense study. An emerging theme is post-translational regulation and macro-molecular complexing by protein-protein interactions and intracellular trafficking, leading to changes in functional VGSC expression in plasma membrane. This partially involves endoplasmic reticulum associated degradation and ubiquitin-proteasome system. Several proteins have been shown to associate with VGSCs. Here, we review the interactions involving VGSCs and the following proteins: p11, ankyrin, syntrophin, beta-subunit of VGSC, papin, ERM and Nedd4 proteins. Protein kinases A and C, as well as Ca(2+)-calmodulin dependent kinase II that have also been shown to regulate intracellular trafficking of VGSCs by changing the balance of externalization vs. internalization, and an effort is made to separate these effects from the short-term phosphorylation of mature proteins in plasma membrane. Two further modulatory mechanisms are reciprocal interactions with the cytoskeleton and, late-stage, activity-dependent regulation. Thus, the review gives an updated account of the range of post-translational molecular mechanisms regulating functional VGSC expression. However, many details of VGSC subtype-specific regulation and pathophysiological aspects remain unknown and these are highlighted throughout for completeness. PMID:19401147

  20. The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network

    PubMed Central

    Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

    2016-01-01

    Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet

  1. Syndecan 4 Is Involved in Mediating HCV Entry through Interaction with Lipoviral Particle-Associated Apolipoprotein E

    PubMed Central

    Lefèvre, Mathieu; Felmlee, Daniel J.; Parnot, Marie; Baumert, Thomas F.; Schuster, Catherine

    2014-01-01

    Hepatitis C virus (HCV) is a major cause of liver disease worldwide and HCV infection represents a major health problem. HCV associates with host lipoproteins forming host/viral hybrid complexes termed lipoviral particles. Apolipoprotein E (apoE) is a lipoprotein component that interacts with heparan sulfate proteoglycans (HSPG) to mediate hepatic lipoprotein uptake, and may likewise mediate HCV entry. We sought to define the functional regions of apoE with an aim to identify critical apoE binding partners involved in HCV infection. Using adenoviral vectors and siRNA to modulate apoE expression we show a direct correlation of apoE expression and HCV infectivity, whereas no correlation exists with viral protein expression. Mutating the HSPG binding domain (HSPG-BD) of apoE revealed key residues that are critical for mediating HCV infection. Furthermore, a novel synthetic peptide that mimics apoE’s HSPG-BD directly and competitively inhibits HCV infection. Genetic knockdown of the HSPG proteins syndecan (SDC) 1 and 4 revealed that SDC4 principally mediates HCV entry. Our data demonstrate that HCV uses apoE-SDC4 interactions to enter hepatoma cells and establish infection. Targeting apoE-SDC interactions could be an alternative strategy for blocking HCV entry, a critical step in maintaining chronic HCV infection. PMID:24751902

  2. Seasonal phenology of interactions involving short-lived annual plants, a multivoltine herbivore and its endoparasitoid wasp.

    PubMed

    Fei, Minghui; Gols, Rieta; Harvey, Jeffrey A

    2014-01-01

    Spatial-temporal realism is often missing in many studies of multitrophic interactions, which are conducted at a single time frame and/or involving interactions between insects with a single species of plant. In this scenario, an underlying assumption is that the host-plant species is ubiquitous throughout the season and that the insects always interact with it. We studied interactions involving three naturally occurring wild species of cruciferous plants, Brassica rapa, Sinapis arvensis and Brassica nigra, that exhibit different seasonal phenologies, and a multivoltine herbivore, the large cabbage white butterfly, Pieris brassicae, and its gregarious endoparasitoid wasp, Cotesia glomerata. The three plants have very short life cycles. In central Europe, B. rapa grows in early spring, S. arvensis in late spring and early summer, and B. nigra in mid to late summer. P. brassicae generally has three generations per year, and C. glomerata at least two. This means that different generations of the insects must find and exploit different plant species that may differ in quality and which may be found some distance from one another. Insects were either reared on each of the three plant species for three successive generations or shifted between generations from B. rapa to S. arvensis to B. nigra. Development time from neonate to pupation and pupal fresh mass were determined in P. brassicae and egg-to-adult development time and body mass in C. glomerata. Overall, herbivores performed marginally better on S. arvensis and B. nigra plants than on B. rapa plants. Parasitoids performance was closely tailored with that of the host. Irrespective as to whether the insects were shifted to a new plant in successive generations or not, development time of P. brassicae and C. glomerata decreased dramatically over time. Our results show that there were some differences in insect development on different plant species and when transferred from one species to another. However, all three

  3. ZmABA2, an interacting protein of ZmMPK5, is involved in abscisic acid biosynthesis and functions.

    PubMed

    Ma, Fangfang; Ni, Lan; Liu, Libo; Li, Xi; Zhang, Huan; Zhang, Aying; Tan, Mingpu; Jiang, Mingyi

    2016-02-01

    In maize (Zea mays), the mitogen-activated protein kinase ZmMPK5 has been shown to be involved in abscisic acid (ABA)-induced antioxidant defence and to enhance the tolerance of plants to drought, salt stress and oxidative stress. However, the underlying molecular mechanisms are poorly understood. Here, using ZmMPK5 as bait in yeast two-hybrid screening, a protein interacting with ZmMPK5 named ZmABA2, which belongs to a member of the short-chain dehydrogenase/reductase family, was identified. Pull-down assay and bimolecular fluorescence complementation analysis and co-immunoprecipitation test confirmed that ZmMPK5 interacts with ZmABA2 in vitro and in vivo. Phosphorylation of Ser173 in ZmABA2 by ZmMPK5 was shown to increase the activity of ZmABA2 and the protein stability. Various abiotic stimuli induced the expression of ZmABA2 in leaves of maize plants. Pharmacological, biochemical and molecular biology and genetic analyses showed that both ZmMPK5 and ZmABA2 coordinately regulate the content of ABA. Overexpression of ZmABA2 in tobacco plants was found to elevate the content of ABA, regulate seed germination and root growth under drought and salt stress and enhance the tolerance of tobacco plants to drought and salt stress. These results suggest that ZmABA2 is a direct target of ZmMPK5 and is involved in ABA biosynthesis and functions. PMID:26096642

  4. Conformational variety of flexible mono-dentate ligands in coordination compounds: influence of π-involving interactions.

    PubMed

    Khavasi, Hamid Reza; Kavand, Sima

    2016-06-28

    The effect of intermolecular interactions on the conformational variety of flexible mono-dentate ligands in coordination compounds has been investigated through the preparation of two series of mercury(ii) complexes. In this regard, the molecular and structural architecture of eight complexes, [HgCl2(L(amide-Cl))2] (), [HgCl2(L(amide-Br))2] (), [HgBr2(L(amide-Br))2] (), and [HgI2(L(amide-Br))2] (), as the first series and [HgBr2(L(imine-Cl))2] (), [HgBr2(L(imine-Br))2] (), [HgI2(L(imine-Cl))]n (), and [HgI2(L(imine-Br))]n (), as the second series, using two kind of flexible ligands, N-(1-halonaphthalen-4-yl)nicotinamide, L(amide-X), and 4-halo-N-((pyridin-3-yl)methylene)naphthalen-1-amine, L(imine-X), has been studied. Inspection of the packing of these compounds clearly shows the presence of conformational changes in the arrangement of the ligands in each series. Although there are slight differences between the crystal packing of these compounds, it seems that π-involving intermolecular interactions including πnaphπnaph in the first series and πimineπpy/naph in the second series with the cooperation of Hgπpy can lock the ligand conformational variety to a single conformer. PMID:27293034

  5. Rydberg and valence state excitation dynamics: a velocity map imaging study involving the E-V state interaction in HBr.

    PubMed

    Zaouris, Dimitris; Kartakoullis, Andreas; Glodic, Pavle; Samartzis, Peter C; Rafn Hróðmarsson, Helgi; Kvaran, Ágúst

    2015-04-28

    Photoexcitation dynamics of the E((1)Σ(+)) (v' = 0) Rydberg state and the V((1)Σ(+)) (v') ion-pair vibrational states of HBr are investigated by velocity map imaging (VMI). H(+) photoions, produced through a number of vibrational and rotational levels of the two states were imaged and kinetic energy release (KER) and angular distributions were extracted from the data. In agreement with previous work, we found the photodissociation channels forming H*(n = 2) + Br((2)P3/2)/Br*((2)P1/2) to be dominant. Autoionization pathways leading to H(+) + Br((2)P3/2)/Br*((2)P1/2) via either HBr(+)((2)Π3/2) or HBr(+)*((2)Π1/2) formation were also present. The analysis of KER and angular distributions and comparison with rotationally and mass resolved resonance enhanced multiphoton ionization (REMPI) spectra revealed the excitation transition mechanisms and characteristics of states involved as well as the involvement of the E-V state interactions and their v' and J' dependence. PMID:25801122

  6. The involvement of sand disturbance, cannibalism and intra-guild predation in competitive interactions among pit-building antlion larvae.

    PubMed

    Barkae, Erez D; Scharf, Inon; Subach, Aziz; Ovadia, Ofer

    2010-10-01

    Competition in trap-building predators such as antlion larvae is a complex biotic interaction, potentially involving exploitation competition, sand throwing (i.e., interference competition), cannibalism and intra-guild predation. We investigated the short-term behavioral and developmental responses of the strict sit-and-wait antlion predator Myrmeleon hyalinus to sand disturbance (i.e., quantification of the impact of severe sand throwing), and to con- and hetero-specific competition by a larger sit-and-pursue antlion species Lopezus fedtschenkoi. We found that antlions subjected to sand disturbances reduced their pit construction activity and relocated less often. Furthermore, the reduction in pit construction activity was stronger among antlions subjected to disturbances prior to feeding. Almost no death occurred during the sand disturbance experiment, but as expected, disturbances caused reductions in the relative growth rates of antlions. This negative effect was stronger in the group exposed to sand disturbances prior to feeding. The presence of the sit-and-pursue competitor led to reductions both in pit construction and in relocation activities of M. hyalinus. Although the per-capita food supply was identical in both experiments, only 48% of M. hyalinus larvae survived the competition experiment, and this pattern was consistent between the con- and hetero-specific treatments. However, in the presence of hetero-specific competitors, the relative growth rate of surviving larvae was significantly lower than that measured in the presence of con-specific competitors. Our study demonstrates that investigating the different components of complex biotic interactions can markedly improve our understanding of how these different factors interact to influence the behavior and life history of organisms. PMID:20943359

  7. The Endothelin-Integrin Axis Is Involved in Macrophage-induced Breast Cancer Cell Chemotactic Interactions with Endothelial Cells*

    PubMed Central

    Chen, Chia-Chi; Chen, Li-Li; Hsu, Yu-Ting; Liu, Ko-Jiunn; Fan, Chi-Shuan; Huang, Tze-Sing

    2014-01-01

    Elevated macrophage infiltration in tumor tissues is associated with breast cancer metastasis. Cancer cell migration/invasion toward angiogenic microvasculature is a key step in metastatic spread. We therefore studied how macrophages stimulated breast cancer cell interactions with endothelial cells. Macrophages produced cytokines, such as interleukin-8 and tumor necrosis factor-α, to stimulate endothelin (ET) and ET receptor (ETR) expression in breast cancer cells and human umbilical vascular endothelial cells (HUVECs). ET-1 was induced to a greater extent from HUVECs than from breast cancer cells, resulting in a density difference that facilitated cancer cell chemotaxis toward HUVECs. Macrophages also stimulated breast cancer cell adhesion to HUVECs and transendothelial migration, which were repressed by ET-1 antibody or ETR inhibitors. The ET axis induced integrins, such as αV and β1, and their counterligands, such as intercellular adhesion molecule-2 and P-selectin, in breast cancer cells and HUVECs, and antibodies against these integrins efficiently suppressed macrophage-stimulated breast cancer cell interactions with HUVECs. ET-1 induced Ets-like kinase-1 (Elk-1), signal transducer and activator of transcription-3 (STAT-3), and nuclear factor-κB (NF-κB) phosphorylation in breast cancer cells. The use of inhibitors to prevent their phosphorylation or ectopic overexpression of dominant-negative IκBα perturbed ET-1-induced integrin αV and integrin β1 expression. The physical associations of these three transcriptional factors with the gene promoters of the two integrins were furthermore evidenced by a chromatin immunoprecipitation assay. Finally, our mouse orthotopic tumor model revealed an ET axis-mediated lung metastasis of macrophage-stimulated breast cancer cells, suggesting that the ET axis was involved in macrophage-enhanced breast cancer cell endothelial interactions. PMID:24550382

  8. Ligand requirements for involvement of PKCε in synergistic analgesic interactions between spinal μ and δ opioid receptors

    PubMed Central

    Schuster, D J; Metcalf, M D; Kitto, K F; Messing, R O; Fairbanks, C A; Wilcox, G L

    2015-01-01

    BACKGROUND AND PURPOSE We recently found that PKCε was required for spinal analgesic synergy between two GPCRs, δ opioid receptors and α2A adrenoceptors, co-located in the same cellular subpopulation. We sought to determine if co-delivery of μ and δ opioid receptor agonists would similarly result in synergy requiring PKCε. EXPERIMENTAL APPROACH Combinations of μ and δ opioid receptor agonists were co-administered intrathecally by direct lumbar puncture to PKCε-wild-type (PKCε-WT) and -knockout (PKCε-KO) mice. Antinociception was assessed using the hot-water tail-flick assay. Drug interactions were evaluated by isobolographic analysis. KEY RESULTS All agonists produced comparable antinociception in both PKCε-WT and PKCε-KO mice. Of 19 agonist combinations that produced analgesic synergy, only 3 required PKCε for a synergistic interaction. In these three combinations, one of the agonists was morphine, although not all combinations involving morphine required PKCε. Morphine + deltorphin II and morphine + deltorphin I required PKCε for synergy, whereas a similar combination, morphine + deltorphin, did not. Additionally, morphine + oxymorphindole required PKCε for synergy, whereas a similar combination, morphine + oxycodindole, did not. CONCLUSIONS AND IMPLICATIONS We discovered biased agonism for a specific signalling pathway at the level of spinally co-delivered opioid agonists. As the bias is only revealed by an appropriate ligand combination and cannot be accounted for by a single drug, it is likely that the receptors these agonists act on are interacting with each other. Our results support the existence of μ and δ opioid receptor heteromers at the spinal level in vivo. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24827408

  9. Comparative Genomic Analysis Reveals a Diverse Repertoire of Genes Involved in Prokaryote-Eukaryote Interactions within the Pseudovibrio Genus

    PubMed Central

    Romano, Stefano; Fernàndez-Guerra, Antonio; Reen, F. Jerry; Glöckner, Frank O.; Crowley, Susan P.; O'Sullivan, Orla; Cotter, Paul D.; Adams, Claire; Dobson, Alan D. W.; O'Gara, Fergal

    2016-01-01

    Strains of the Pseudovibrio genus have been detected worldwide, mainly as part of bacterial communities associated with marine invertebrates, particularly sponges. This recurrent association has been considered as an indication of a symbiotic relationship between these microbes and their host. Until recently, the availability of only two genomes, belonging to closely related strains, has limited the knowledge on the genomic and physiological features of the genus to a single phylogenetic lineage. Here we present 10 newly sequenced genomes of Pseudovibrio strains isolated from marine sponges from the west coast of Ireland, and including the other two publicly available genomes we performed an extensive comparative genomic analysis. Homogeneity was apparent in terms of both the orthologous genes and the metabolic features shared amongst the 12 strains. At the genomic level, a key physiological difference observed amongst the isolates was the presence only in strain P. axinellae AD2 of genes encoding proteins involved in assimilatory nitrate reduction, which was then proved experimentally. We then focused on studying those systems known to be involved in the interactions with eukaryotic and prokaryotic cells. This analysis revealed that the genus harbors a large diversity of toxin-like proteins, secretion systems and their potential effectors. Their distribution in the genus was not always consistent with the phylogenetic relationship of the strains. Finally, our analyses identified new genomic islands encoding potential toxin-immunity systems, previously unknown in the genus. Our analyses shed new light on the Pseudovibrio genus, indicating a large diversity of both metabolic features and systems for interacting with the host. The diversity in both distribution and abundance of these systems amongst the strains underlines how metabolically and phylogenetically similar bacteria may use different strategies to interact with the host and find a niche within its

  10. Stagonospora nodorum utilizes a sophisticated inverse gene-for-gene system involving proteinaceous host-selective toxins interacting with dominant wheat sensitivity genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Stagonospora nodorum-wheat pathosystem involves a complex of proteinaceous host-selective toxins that interact either directly or indirectly with host sensitivity/susceptibility gene products in an inverse gene-for-gene manner. Compatible interactions among these gene products are highly import...

  11. The interactive effect of job involvement and organizational commitment on job turnover revisited: a note on the mediating role of turnover intention.

    PubMed

    Sjöberg, A; Sverke, M

    2000-09-01

    This study extends previous theoretical and empirical research on Blau and Boal's (1987) model of the interactive effect of job involvement and organizational commitment on employee withdrawal. Using longitudinal data from a survey among the nursing staff of a Swedish emergency hospital (N = 535) and register information on actual turnover, the results showed, in contrast to the statement of the original theoretical model, that turnover intention mediates the additive and multiplicative effects of job involvement and organizational commitment on actual turnover. The study suggests that the proposed involvement by commitment interaction is theoretically justified, and underscores the pertinence of investigating intermediate linkages in turnover research. PMID:11041307

  12. Involvement of de novo ceramide synthesis in pro-inflammatory adipokine secretion and adipocyte-macrophage interaction.

    PubMed

    Hamada, Yoji; Nagasaki, Hiroshi; Fujiya, Atsushi; Seino, Yusuke; Shang, Qing-Long; Suzuki, Takeshi; Hashimoto, Hiroyuki; Oiso, Yutaka

    2014-12-01

    Interaction between adipocytes and macrophages has been suggested to play a central role in the pathogenesis of obesity. Ceramide, a sphingolipid de novo synthesized from palmitate, is known to stimulate pro-inflammatory cytokine secretion from multiple types of cells. To clarify whether de novo synthesized ceramide contributes to cytokine dysregulation in adipocytes and macrophages, we observed cytokine secretion in mature 3T3-L1 adipocytes (L1) and RAW264.7 macrophages (RAW) cultured alone or co-cultured under the suppression of de novo ceramide synthesis. Palmitate enhanced ceramide accumulation and stimulated the expression and secretion of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in L1. The suppression of serine-palmitoyl transferase, a rate-limiting enzyme of de novo ceramide synthesis, by myriocin or siRNA attenuated those palmitate-induced alterations, and a ceramide synthase inhibitor fumonisin B1 showed similar results. In contrast, the inhibitor of sphingosine kinase or a membrane-permeable ceramide analogue augmented the cytokine secretion. Myriocin effects on the palmitate-induced changes were not abrogated by toll-like receptor-4 blockade. Although palmitate stimulated RAW to secrete tumor necrosis factor-α (TNF-α), it did not significantly increase ceramide content, and neither myriocin nor fumonisin B1 attenuated the TNF-α hypersecretion. The co-culture of L1 with RAW markedly augmented IL-6 and MCP-1 levels in media. Myriocin or fumonisin B1 significantly lowered these cytokine levels and suppressed the gene expression of TNF-α and MCP-1 in RAW and of IL-6 and MCP-1 in L1. In conclusion, de novo synthesized ceramide partially mediates the palmitate effects on pro-inflammatory adipokines and is possibly involved in the interaction with macrophages. PMID:25283329

  13. Comparative Genomics of Plant-Associated Pseudomonas spp.: Insights into Diversity and Inheritance of Traits Involved in Multitrophic Interactions

    PubMed Central

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

    2012-01-01

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

  14. COMMD7 as a novel NEMO interacting protein involved in the termination of NF-κB signaling.

    PubMed

    Esposito, Elio; Napolitano, Gennaro; Pescatore, Alessandra; Calculli, Giuseppe; Incoronato, Maria Rosaria; Leonardi, Antonio; Ursini, Matilde Valeria

    2016-01-01

    NEMO/IKKγ is the regulatory subunit of the IκB Kinase (IKK) complex, required for the activation of the NF-κB pathway, which is involved in a variety of key processes, including immunity, inflammation, differentiation, and cell survival. Termination of NF-κB activity on specific -κB responsive genes, which is crucial for the resolution of inflammatory responses, can be achieved by direct degradation of the chromatin-bound NF-κB subunit RelA/p65, a process mediated by a protein complex that contains Copper Metabolism Murr1 Domain 1 (COMMD1). In this study, we identify COMMD7, another member of the COMMDs protein family, as a novel NEMO-interacting protein. We show that COMMD7 exerts an inhibitory effect on NF-κB activation upon TNFα stimulation. COMMD7 interacts with COMMD1 and together they cooperate to down-regulate NF-κB activity. Accordingly, termination of TNFα-induced NF-κB activity on the -κB responsive gene, Icam1, is defective in cells silenced for COMMD7 expression. Furthermore, this impairment is not greatly increased when we silence the expression of both COMMD7 and COMMD1 indicating that the two proteins participate in the same pathway of termination of TNFα-induced NF-κB activity. Importantly, we have demonstrated that COMMD7's binding to NEMO does not interfere with the binding to the IKKs, and that the disruption of the IKK complex through the use of the NBP competitor impairs the termination of NF-κB activity. We propose that an intact IKK complex is required for the termination of NF-κB-dependent transcription and that COMMD7 acts as a scaffold in the IKK-mediated NF-κB termination. PMID:26060140

  15. Cep57 is a Mis12-interacting kinetochore protein involved in kinetochore targeting of Mad1–Mad2

    PubMed Central

    Zhou, Haining; Wang, Tianning; Zheng, Tao; Teng, Junlin; Chen, Jianguo

    2016-01-01

    The spindle assembly checkpoint (SAC) arrests cells in mitosis by sensing unattached kinetochores, until all chromosomes are bi-oriented by spindle microtubules. Kinetochore accumulation of the SAC component Mad1–Mad2 is crucial for SAC activation. However, the mechanism by which Mad1–Mad2 accumulation at kinetochores is regulated is not clear. Here we find that Cep57 is localized to kinetochores in human cells, and binds to Mis12, a KMN (KNL1/Mis12 complex/Ndc80 complex) network component. Cep57 also interacts with Mad1, and depletion of Cep57 results in decreased kinetochore localization of Mad1–Mad2, reduced SAC signalling and increased chromosome segregation errors. We also show that the microtubule-binding activity of Cep57 is involved in the timely removal of Mad1 from kinetochores. Thus, these findings reveal that the KMN network-binding protein Cep57 is a mitotic kinetochore component, and demonstrate the functional connection between the KMN network and the SAC. PMID:26743940

  16. Assessment of cholesteryl ester transfer protein inhibitors for interaction with proteins involved in the immune response to infection.

    PubMed

    Clark, Ronald W; Cunningham, David; Cong, Yang; Subashi, Timothy A; Tkalcevic, George T; Lloyd, David B; Boyd, James G; Chrunyk, Boris A; Karam, George A; Qiu, Xiayang; Wang, Ing-Kae; Francone, Omar L

    2010-05-01

    The CETP inhibitor, torcetrapib, was prematurely terminated from phase 3 clinical trials due to an increase in cardiovascular and noncardiovascular mortality. Because nearly half of the latter deaths involved patients with infection, we have tested torcetrapib and other CETPIs to see if they interfere with lipopolysaccharide binding protein (LBP) or bactericidal/permeability increasing protein (BPI). No effect of these potent CETPIs on LPS binding to either protein was detected. Purified CETP itself bound weakly to LPS with a Kd >or= 25 microM compared with 0.8 and 0.5 nM for LBP and BPI, respectively, and this binding was not blocked by torcetrapib. In whole blood, LPS induced tumor necrosis factor-alpha normally in the presence of torcetrapib. Furthermore, LPS had no effect on CETP activity. We conclude that the sepsis-related mortality of the ILLUMINATE trial was unlikely due to a direct effect of torcetrapib on LBP or BPI function, nor to inhibition of an interaction of CETP with LPS. Instead, we speculate that the negative outcome seen for patients with infections might be related to the changes in plasma lipoprotein composition and metabolism, or alternatively to the known off-target effects of torcetrapib, such as aldosterone elevation, which may have aggravated the effects of sepsis. PMID:19965592

  17. Cep57 is a Mis12-interacting kinetochore protein involved in kinetochore targeting of Mad1-Mad2.

    PubMed

    Zhou, Haining; Wang, Tianning; Zheng, Tao; Teng, Junlin; Chen, Jianguo

    2016-01-01

    The spindle assembly checkpoint (SAC) arrests cells in mitosis by sensing unattached kinetochores, until all chromosomes are bi-oriented by spindle microtubules. Kinetochore accumulation of the SAC component Mad1-Mad2 is crucial for SAC activation. However, the mechanism by which Mad1-Mad2 accumulation at kinetochores is regulated is not clear. Here we find that Cep57 is localized to kinetochores in human cells, and binds to Mis12, a KMN (KNL1/Mis12 complex/Ndc80 complex) network component. Cep57 also interacts with Mad1, and depletion of Cep57 results in decreased kinetochore localization of Mad1-Mad2, reduced SAC signalling and increased chromosome segregation errors. We also show that the microtubule-binding activity of Cep57 is involved in the timely removal of Mad1 from kinetochores. Thus, these findings reveal that the KMN network-binding protein Cep57 is a mitotic kinetochore component, and demonstrate the functional connection between the KMN network and the SAC. PMID:26743940

  18. RNA-protein interactions: involvement of NS3, NS5, and 3' noncoding regions of Japanese encephalitis virus genomic RNA.

    PubMed Central

    Chen, C J; Kuo, M D; Chien, L J; Hsu, S L; Wang, Y M; Lin, J H

    1997-01-01

    The mechanism of replication of the flavivirus Japanese encephalitis virus (JEV) is not well known. The structures at the 3' end of the viral genome are highly conserved among divergent flaviviruses, suggesting that they may function as cis-acting signals for RNA replication and, as such, might specifically bind to cellular or viral proteins. UV cross-linking experiments were performed to identify the proteins that bind with the JEV plus-strand 3' noncoding region (NCR). Two proteins, p71 and p110, from JEV-infected but not from uninfected cell extracts were shown to bind specifically to the plus-strand 3' NCR. The quantities of these binding proteins increased during the course of JEV infection and correlated with the levels of JEV RNA synthesis in cell extracts. UV cross-linking coupled with Western blot and immunoprecipitation analysis showed that the p110 and p71 proteins were JEV NS5 and NS3, respectively, which are proposed as components of the RNA replicase. The putative stem-loop structure present within the plus-strand 3' NCR was required for the binding of these proteins. Furthermore, both proteins could interact with each other and form a protein-protein complex in vivo. These findings suggest that the 3' NCR of JEV genomic RNA may form a replication complex together with NS3 and NS5; this complex may be involved in JEV minus-strand RNA synthesis. PMID:9094618

  19. Signaling by the heavy-metal sensor CusS involves rearranged helical interactions in specific transmembrane regions.

    PubMed

    Fung, Danny Ka Chun; Ma, Yongzheng; Xia, Tingying; Luk, Jakson Chak Hon; Yan, Aixin

    2016-06-01

    Two-component systems (TCSs) play important roles in the adaptation of bacteria to stress. Despite their increasingly well understood mechanistic features, it remains poorly understood how TCSs transduce signals across membranes. Here, we use the E. coli Cu/Ag-responsive CusSR TCS as a model to investigate the roles of CusS transmembrane (TM) residues. Proline scanning of TM1 domain led to identification of the T17P, F18P, and S21P variants, which display higher kinase activities relative to wild type. A single point mutation, V202G, in the adjacent TM2 domain specifically suppresses the hyperactivities of these mutants. Disulfide crosslinking analysis demonstrated that T17 and V202 are situated in close proximity, and Cys residues substituted at those two positions form exclusive intramolecular crosslinks when CusS is in the signaling-inactive state. In the signaling-active variant of CusS, however, only intermolecular crosslinking between the two Cys residues could be observed, suggesting that destabilization of an intramolecular constraint and a subsequent rearrangement of helical interactions in this TM region is involved in the activation of CusS. An analogous TM helical interface in the P. aeruginosa heavy metal sensor kinase CzcS is also observed. Together, these results suggested a conserved transmembrane signal transduction mechanism in the heavy metal sensing TCSs. PMID:26844675

  20. Assessment of cholesteryl ester transfer protein inhibitors for interaction with proteins involved in the immune response to infection[S

    PubMed Central

    Clark, Ronald W.; Cunningham, David; Cong, Yang; Subashi, Timothy A.; Tkalcevic, George T.; Lloyd, David B.; Boyd, James G.; Chrunyk, Boris A.; Karam, George A.; Qiu, Xiayang; Wang, Ing-Kae; Francone, Omar L.

    2010-01-01

    The CETP inhibitor, torcetrapib, was prematurely terminated from phase 3 clinical trials due to an increase in cardiovascular and noncardiovascular mortality. Because nearly half of the latter deaths involved patients with infection, we have tested torcetrapib and other CETPIs to see if they interfere with lipopolysaccharide binding protein (LBP) or bactericidal/permeability increasing protein (BPI). No effect of these potent CETPIs on LPS binding to either protein was detected. Purified CETP itself bound weakly to LPS with a Kd ≥ 25 uM compared with 0.8 and 0.5 nM for LBP and BPI, respectively, and this binding was not blocked by torcetrapib. In whole blood, LPS induced tumor necrosis factor-α normally in the presence of torcetrapib. Furthermore, LPS had no effect on CETP activity. We conclude that the sepsis-related mortality of the ILLUMINATE trial was unlikely due to a direct effect of torcetrapib on LBP or BPI function, nor to inhibition of an interaction of CETP with LPS. Instead, we speculate that the negative outcome seen for patients with infections might be related to the changes in plasma lipoprotein composition and metabolism, or alternatively to the known off-target effects of torcetrapib, such as aldosterone elevation, which may have aggravated the effects of sepsis. PMID:19965592

  1. Involvement of and Interaction between WNT10A and EDA Mutations in Tooth Agenesis Cases in the Chinese Population

    PubMed Central

    Feng, Hailan; Qu, Hong; Song, Shujuan; Bai, Baojing; Zhang, Zhenting

    2013-01-01

    Background Dental agenesis is the most common, often heritable, developmental anomaly in humans. Although WNT10A gene mutations are known to cause rare syndromes associated with tooth agenesis, including onycho-odontodermal dysplasia (OODD), Schöpf-Schulz-Passarge syndrome (SSPS), hypohidrotic ectodermal dysplasia (HED), and more than half of the cases of isolated oligodontia recently, the genotype-phenotype correlations and the mode of inheritance of WNT10A mutations remain unclear. The phenotypic expression with WNT10A mutations shows a high degree of variability, suggesting that other genes might function with WNT10A in regulating ectodermal organ development. Moreover, the involvement of mutations in other genes, such as EDA, which is also associated with HED and isolated tooth agenesis, is not clear. Therefore, we hypothesized that EDA mutations interact with WNT10A mutations to play a role in tooth agenesis. Additionally, EDA, EDAR, and EDARADD encode signaling molecules in the Eda/Edar/NF-κB signaling pathways, we also checked EDAR and EDARADD in this study. Methods WNT10A, EDA, EDAR and EDARADD were sequenced in 88 patients with isolated oligodontia and 26 patients with syndromic tooth agenesis. The structure of two mutated WNT10A and two mutated EDA proteins was analyzed. Results Digenic mutations of both WNT10A and EDA were identified in 2 of 88 (2.27%) isolated oligodontia cases and 4 of 26 (15.38%) syndromic tooth agenesis cases. No mutation in EDAR or EDARADD gene was found. Conclusions WNT10A and EDA digenic mutations could result in oligodontia and syndromic tooth agenesis in the Chinese population. Moreover, our results will greatly expand the genotypic spectrum of tooth agenesis. PMID:24312213

  2. Roles of rifampicin in drug-drug interactions: underlying molecular mechanisms involving the nuclear pregnane X receptor

    PubMed Central

    Chen, Jiezhong; Raymond, Kenneth

    2006-01-01

    Rifampicin, an important drug in the treatment of tuberculosis, is used extensively despite its broad effects on drug-drug interactions, creating serious problems. The clinical importance of such interactions includes autoinduction leading to suboptimal or failed treatment. The concomitantly administered effects of rifampicin on other drugs can result in their altered metabolism or transportation that are metabolised by cytochromes P450 or transported by p-glycoprotein in the gastrointestinal tract and liver. This review paper summarises recent findings with emphases on the molecular mechanisms used to explain these broad drug-drug interactions. In general, rifampicin can act on a pattern: rifampicin activates the nuclear pregnane X receptor that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. This pattern of action may explain many of the rifampicin inducing drug-drug interactions. However, effects through other mechanisms have also been reported and these make any explanation of such drug-drug interactions more complex. PMID:16480505

  3. Examining the interaction of parental involvement and parenting style in predicting adherence in youth with type 1 diabetes

    PubMed Central

    Landers, Sara E.; Friedrich, Elizabeth A.; Jawad, Abbas F.; Miller, Victoria A.

    2016-01-01

    Introduction This study examined whether aspects of parenting style (specifically, warmth, autonomy support, and coercion) moderated the association between parental involvement and adherence in youth with type 1 diabetes. Methods Children ages 8–16 years with type 1 diabetes and a parent completed assessments of parental involvement, parenting style, and adherence. Results Parent autonomy support and coercion were associated with adherence but warmth was not. Child report of more parental involvement was associated with better adherence. Warmth, autonomy support, and coercion were not moderators. Discussion The findings underscore the importance of parental involvement, operationalized as responsibility for diabetes tasks, and parenting style, specifically coercion and autonomy support, for adherence in pediatric chronic illness management. Longitudinal research is needed to better understand how and why dimensions of involvement (e.g., responsibility, monitoring, support) vary over time and whether they impact outcomes differentially. PMID:26866945

  4. [Operation and interaction peculiarities of diagnostic laboratories involved in providing protection from infectious diseases during the XXII Olympic Winter Games and XI Paralympic Winter Games 2014 in Sochi].

    PubMed

    Onishenko, G G; Popova, A Iu; Bragina, I V; Kuz'kin, B P; Ezhlova, E B; Demina, Iu V; Gus'kov, A S; Ivanov, G E; Chikina, L V; Klindukhova, V P; Grechanaia, T V; Tesheva, S Ch; Kulichenko, A N; Efremenko, D B; Manin, E A; Kuznetsova, I V; Parkhomenko, V V; Kulichenko, O A; Rafeenko, G K; Shcherbina, L I; Zavora, D L; Briukhanov, A F; Eldinova, V E; Iunicheva, Iu V; Derliatko, S K; Komarov, N S

    2015-01-01

    The experience of the organization and functioning of the laboratory network during the XXII Olympic Winter Games and XI Paralympic Winter Games of 2014 in Sochi is considered. Efforts to establish an effective system of laboratory support, the order of work and interaction of diagnostic laboratories involved in diseases control of population during the Olympic Games are analyzed. PMID:25842962

  5. From Trust in Automation to Decision Neuroscience: Applying Cognitive Neuroscience Methods to Understand and Improve Interaction Decisions Involved in Human Automation Interaction

    PubMed Central

    Drnec, Kim; Marathe, Amar R.; Lukos, Jamie R.; Metcalfe, Jason S.

    2016-01-01

    Human automation interaction (HAI) systems have thus far failed to live up to expectations mainly because human users do not always interact with the automation appropriately. Trust in automation (TiA) has been considered a central influence on the way a human user interacts with an automation; if TiA is too high there will be overuse, if TiA is too low there will be disuse. However, even though extensive research into TiA has identified specific HAI behaviors, or trust outcomes, a unique mapping between trust states and trust outcomes has yet to be clearly identified. Interaction behaviors have been intensely studied in the domain of HAI and TiA and this has led to a reframing of the issues of problems with HAI in terms of reliance and compliance. We find the behaviorally defined terms reliance and compliance to be useful in their functionality for application in real-world situations. However, we note that once an inappropriate interaction behavior has occurred it is too late to mitigate it. We therefore take a step back and look at the interaction decision that precedes the behavior. We note that the decision neuroscience community has revealed that decisions are fairly stereotyped processes accompanied by measurable psychophysiological correlates. Two literatures were therefore reviewed. TiA literature was extensively reviewed in order to understand the relationship between TiA and trust outcomes, as well as to identify gaps in current knowledge. We note that an interaction decision precedes an interaction behavior and believe that we can leverage knowledge of the psychophysiological correlates of decisions to improve joint system performance. As we believe that understanding the interaction decision will be critical to the eventual mitigation of inappropriate interaction behavior, we reviewed the decision making literature and provide a synopsis of the state of the art understanding of the decision process from a decision neuroscience perspective. We forward

  6. The interaction between the Hepatitis C proteins NS4B and NS5A is involved in viral replication

    PubMed Central

    David, Naama; Yaffe, Yakey; Hagoel, Lior; Elazar, Menashe; Glenn, Jeffrey S.; Hirschberg, Koret; Sklan, Ella H.

    2015-01-01

    Hepatitis C virus (HCV) replicates in membrane associated, highly ordered replication complexes (RCs). These complexes include viral and host proteins necessary for viral RNA genome replication. The interaction network among viral and host proteins underlying the formation of these RCs is yet to be thoroughly characterized. Here, we investigated the association between NS4B and NS5A, two critical RC components. We characterized the interaction between these proteins using fluorescence resonance energy transfer and a mammalian two-hybrid system. Specific tryptophan residues within the C-terminal domain (CTD) of NS4B were shown to mediate this interaction. Domain I of NS5A, was sufficient to mediate its interaction with NS4B. Mutations in the NS4B CTD tryptophan residues abolished viral replication. Moreover, one of these mutations also affected NS5A hyperphosphorylation. These findings provide new insights into the importance of the NS4B–NS5A interaction and serve as a starting point for studying the complex interactions between the replicase subunits. PMID:25462354

  7. Cell interactions involved in development of the bilaterally symmetrical intestinal valve cells during embryogenesis in Caenorhabditis elegans.

    PubMed

    Bowerman, B; Tax, F E; Thomas, J H; Priess, J R

    1992-12-01

    We describe two different cell interactions that appear to be required for the proper development of a pair of bilaterally symmetrical cells in Caenorhabditis elegans called the intestinal valve cells. Previous experiments have shown that at the beginning of the 4-cell stage of embryogenesis, two sister blastomeres called ABa and ABp are equivalent in development potential. We show that cell interactions between ABp and a neighboring 4-cell-stage blastomere called P2 distinguish the fates of ABa and ABp by inducing descendants of ABp to produce the intestinal valve cells, a cell type not made by ABa. A second cell interaction appears to occur later in embryogenesis when two bilaterally symmetrical descendants of ABp, which both have the potential to produce valve cells, contact each other; production of the valve cells subsequently becomes limited to only one of the two descendants. This second interaction does not occur properly if the two symmetrical descendants of ABp are prevented from contacting each other. Thus the development of the intestinal valve cells appears to require both an early cell interaction that establishes a bilaterally symmetrical pattern of cell fate and a later interaction that breaks the symmetrical cell fate pattern by restricting to only one of two cells the ability to produce a pair of valve cells. PMID:1295733

  8. A mammalian germ cell-specific RNA-binding protein interacts with ubiquitously expressed proteins involved in splice site selection

    NASA Astrophysics Data System (ADS)

    Elliott, David J.; Bourgeois, Cyril F.; Klink, Albrecht; Stévenin, James; Cooke, Howard J.

    2000-05-01

    RNA-binding motif (RBM) genes are found on all mammalian Y chromosomes and are implicated in spermatogenesis. Within human germ cells, RBM protein shows a similar nuclear distribution to components of the pre-mRNA splicing machinery. To address the function of RBM, we have used protein-protein interaction assays to test for possible physical interactions between these proteins. We find that RBM protein directly interacts with members of the SR family of splicing factors and, in addition, strongly interacts with itself. We have mapped the protein domains responsible for mediating these interactions and expressed the mouse RBM interaction region as a bacterial fusion protein. This fusion protein can pull-down several functionally active SR protein species from cell extracts. Depletion and add-back experiments indicate that these SR proteins are the only splicing factors bound by RBM which are required for the splicing of a panel of pre-mRNAs. Our results suggest that RBM protein is an evolutionarily conserved mammalian splicing regulator which operates as a germ cell-specific cofactor for more ubiquitously expressed pre-mRNA splicing activators.

  9. Gene-Gene and Gene-Environment Interactions Involving HLA-DRB1, PTPN22, and Smoking in Two Subsets of Rheumatoid Arthritis

    PubMed Central

    Källberg, Henrik; Padyukov, Leonid; Plenge, Robert M.; Rönnelid, Johan; Gregersen, Peter K.; van der Helm-van Mil, Annette H. M.; Toes, Rene E. M.; Huizinga, Tom W.; Klareskog, Lars; Alfredsson, Lars

    2007-01-01

    Gene-gene and gene-environment interactions are key features in the development of rheumatoid arthritis (RA) and other complex diseases. The aim of this study was to use and compare three different definitions of interaction between the two major genetic risk factors of RA—the HLA-DRB1 shared epitope (SE) alleles and the PTPN22 R620W allele—in three large case-control studies: the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, the North American RA Consortium (NARAC) study, and the Dutch Leiden Early Arthritis Clinic study (in total, 1,977 cases and 2,405 controls). The EIRA study was also used to analyze interactions between smoking and the two genes. “Interaction” was defined either as a departure from additivity, as interaction in a multiplicative model, or in terms of linkage disequilibrium—for example, deviation from independence of penetrance of two unlinked loci. Consistent interaction, defined as departure from additivity, between HLA-DRB1 SE alleles and the A allele of PTPN22 R620W was seen in all three studies regarding anti-CCP–positive RA. Testing for multiplicative interactions demonstrated an interaction between the two genes only when the three studies were pooled. The linkage disequilibrium approach indicated a gene-gene interaction in EIRA and NARAC, as well as in the pooled analysis. No interaction was seen between smoking and PTPN22 R620W. A new pattern of interactions is described between the two major known genetic risk factors and the major environmental risk factor concerning the risk of developing anti-CCP–positive RA. The data extend the basis for a pathogenetic hypothesis for RA involving genetic and environmental factors. The study also raises and illustrates principal questions concerning ways to define interactions in complex diseases. PMID:17436241

  10. Herb-drug, food-drug, nutrient-drug, and drug-drug interactions: mechanisms involved and their medical implications.

    PubMed

    Sørensen, Janina Maria

    2002-06-01

    Adverse drug reactions (ADRs) and iatrogenic diseases have been identified as significant factors responsible for patient morbidity and mortality. Significant studies on drug metabolism in humans have been published during the last few years, offering a deeper comprehension of the mechanisms underlying adverse drug reactions and interactions. More understanding of these mechanisms, and of recent advances in laboratory technology, can help to evaluate potential drug interactions when drugs are prescribed concurrently. Increasing knowledge of interindividual variation in drug breakdown capacity and recent findings concerning the influence of environment, diet, nutrients, and herbal products can be used to reduce ADRs and iatrogenic diseases. Reviewed data suggest that drug treatment should be increasingly custom tailored to suit the individual patient and that appropriately co-prescribed diet and herbal remedies, could increase drug efficacy and lessen drug toxicity. This review focuses mainly on recently published research material. The cytochrome p450 enzymes, their role in metabolism, and their mechanisms of action are reviewed, and their role in drug-drug interactions are discussed. Drug-food and drug-herb interactions have garnered attention. Interdisciplinary communication among medical herbalists, medical doctors, and dietetic experts needs to be improved and encouraged. Internet resources for obtaining current information regarding drug-drug, drug-herb, and drug-nutrient interactions are provided. PMID:12165187

  11. Direct interaction between nucleosome assembly protein 1 and the papillomavirus E2 proteins involved in activation of transcription.

    PubMed

    Rehtanz, Manuela; Schmidt, Hanns-Martin; Warthorst, Ursula; Steger, Gertrud

    2004-03-01

    Using a yeast two-hybrid screen, we identified human nucleosome assembly protein 1 (hNAP-1) as a protein interacting with the activation domain of the transcriptional activator encoded by papillomaviruses (PVs), the E2 protein. We show that the interaction between E2 and hNAP-1 is direct and not merely mediated by the transcriptional coactivator p300, which is bound by both proteins. Coexpression of hNAP-1 strongly enhances activation by E2, indicating a functional interaction as well. E2 binds to at least two separate domains within hNAP-1, one within the C terminus and an internal domain. The binding of E2 to hNAP-1 is necessary for cooperativity between the factors. Moreover, the N-terminal 91 amino acids are crucial for the transcriptional activity of hNAP-1, since deletion mutants lacking this N-terminal portion fail to cooperate with E2. We provide evidence that hNAP-1, E2, and p300 can form a ternary complex efficient in the activation of transcription. We also show that p53 directly interacts with hNAP-1, indicating that transcriptional activators in addition to PV E2 interact with hNAP-1. These results suggest that the binding of sequence-specific DNA binding proteins to hNAP-1 may be an important step contributing to the activation of transcription. PMID:14966293

  12. The role of residue stability in transient protein-protein interactions involved in enzymatic phosphate hydrolysis. A computational study.

    PubMed

    Bonet, Jaume; Caltabiano, Gianluigi; Khan, Abdul Kareem; Johnston, Michael A; Corbí, Carles; Gómez, Alex; Rovira, Xavier; Teyra, Joan; Villà-Freixa, Jordi

    2006-04-01

    Finding why protein-protein interactions (PPIs) are so specific can provide a valuable tool in a variety of fields. Statistical surveys of so-called transient complexes (like those relevant for signal transduction mechanisms) have shown a tendency of polar residues to participate in the interaction region. Following this scheme, residues in the unbound partners have to compete between interacting with water or interacting with other residues of the protein. On the other hand, several works have shown that the notion of active site electrostatic preorganization can be used to interpret the high efficiency in enzyme reactions. This preorganization can be related to the instability of the residues important for catalysis. In some enzymes, in addition, conformational changes upon binding to other proteins lead to an increase in the activity of the enzymatic partner. In this article the linear response approximation version of the semimacroscopic protein dipoles Langevin dipoles (PDLD/S-LRA) model is used to evaluate the stability of several residues in two phosphate hydrolysis enzymes upon complexation with their activating partners. In particular, the residues relevant for PPI and for phosphate hydrolysis in the CDK2/Cyclin A and Ras/GAP complexes are analyzed. We find that the evaluation of the stability of residues in these systems can be used to identify not only active site regions but it can also be used as a guide to locate "hot spots" for PPIs. We also show that conformational changes play a major role in positioning interfacing residues in a proper "energetic" orientation, ready to interact with the residues in the partner protein surface. Thus, we extend the preorganization theory to PPIs, extrapolating the results we obtained from the above-mentioned complexes to a more general case. We conclude that the correlation between stability of a residue in the surface and the likelihood that it participates in the interaction can be a general fact for transient

  13. The uses of overlap: carer-child interaction involving a nine-year-old boy with auditory neuropathy.

    PubMed

    Anstey, Julie; Wells, Bill

    2013-01-01

    The subject of this single case study, Ricky, is a nine-year-old boy with a profound hearing loss arising from auditory neuropathy. Despite cochlear implantation at the age of two, his receptive language skills remain very restricted and his speech is unintelligible. Techniques of interactional linguistics are used to analyse recordings of Ricky and his mother during shared book reading. Both participants display competences in managing turn-taking and overlapping talk that enable them to progress the book-reading activity, to talk spontaneously on topically related matters and also to handle issues of phonetic and linguistic repair. Instances of both competitive and non-competitive overlap reveal that Ricky has access to interactionally important prosodic skills. The study thus reinforces the need, when assessing a child's potential to understand and use spoken language, to examine the child's talk from an interactional perspective. It further indicates that overlapping talk is not necessarily a problem; indeed it can be part of a solution to issues of interpersonal understanding that routinely arise in the course of talk-in-interaction. PMID:23848368

  14. Peer Interactions in a Computer Lab: Reflections on Results of a Case Study Involving Web-Based Dynamic Geometry Sketches

    ERIC Educational Resources Information Center

    Sinclair, Margaret P.

    2005-01-01

    A case study, originally set up to identify and describe some benefits and limitations of using dynamic web-based geometry sketches, provided an opportunity to examine peer interactions in a lab. Since classes were held in a computer lab, teachers and pairs faced the challenges of working and communicating in a lab environment. Research has shown…

  15. NuMA localization, stability, and function in spindle orientation involve 4.1 and Cdk1 interactions

    PubMed Central

    Seldin, Lindsey; Poulson, Nicholas D.; Foote, Henry P.; Lechler, Terry

    2013-01-01

    The epidermis is a multilayered epithelium that requires asymmetric divisions for stratification. A conserved cortical protein complex, including LGN, nuclear mitotic apparatus (NuMA), and dynein/dynactin, plays a key role in establishing proper spindle orientation during asymmetric divisions. The requirements for the cortical recruitment of these proteins, however, remain unclear. In this work, we show that NuMA is required to recruit dynactin to the cell cortex of keratinocytes. NuMA's cortical recruitment requires LGN; however, LGN interactions are not sufficient for this localization. Using fluorescence recovery after photobleaching, we find that the 4.1-binding domain of NuMA is important for stabilizing its interaction with the cell cortex. This is functionally important, as loss of 4.1/NuMA interaction results in spindle orientation defects, using two distinct assays. Furthermore, we observe an increase in cortical NuMA localization as cells enter anaphase. Inhibition of Cdk1 or mutation of a single residue in NuMA mimics this effect. NuMA's anaphase localization is independent of LGN and 4.1 interactions, revealing two distinct mechanisms responsible for NuMA cortical recruitment at different stages of mitosis. This work highlights the complexity of NuMA localization and reveals the importance of NuMA cortical stability for productive force generation during spindle orientation. PMID:24109598

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

    PubMed

    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. PMID:23775788

  17. Nucleolin Interacts with US11 Protein of Herpes Simplex Virus 1 and Is Involved in Its Trafficking

    PubMed Central

    Greco, Anna; Arata, Loredana; Soler, Eric; Gaume, Xavier; Couté, Yohann; Hacot, Sabine; Callé, Aleth; Monier, Karine; Epstein, Alberto L.; Sanchez, Jean-Charles; Bouvet, Philippe

    2012-01-01

    Herpes simplex virus type 1 (HSV-1) infection induces profound nucleolar modifications at the functional and organizational levels, including nucleolar invasion by several viral proteins. One of these proteins is US11, which exhibits several different functions and displays both cytoplasmic localization and clear nucleolar localization very similar to that of the major multifunctional nucleolar protein nucleolin. To determine whether US11 interacts with nucleolin, we purified US11 protein partners by coimmunoprecipitations using a tagged protein, Flag-US11. From extracts of cells expressing Flag-US11 protein, we copurified a protein of about 100 kDa that was further identified as nucleolin. In vitro studies have demonstrated that nucleolin interacts with US11 and that the C-terminal domain of US11, which is required for US11 nucleolar accumulation, is sufficient for interaction with nucleolin. This association was confirmed in HSV-1-infected cells. We found an increase in the nucleolar accumulation of US11 in nucleolin-depleted cells, thereby revealing that nucleolin could play a role in US11 nucleocytoplasmic trafficking through one-way directional transport out of the nucleolus. Since nucleolin is required for HSV-1 nuclear egress, the interaction of US11 with nucleolin may participate in the outcome of infection. PMID:22130536

  18. Nucleolin interacts with US11 protein of herpes simplex virus 1 and is involved in its trafficking.

    PubMed

    Greco, Anna; Arata, Loredana; Soler, Eric; Gaume, Xavier; Couté, Yohann; Hacot, Sabine; Callé, Aleth; Monier, Karine; Epstein, Alberto L; Sanchez, Jean-Charles; Bouvet, Philippe; Diaz, Jean-Jacques

    2012-02-01

    Herpes simplex virus type 1 (HSV-1) infection induces profound nucleolar modifications at the functional and organizational levels, including nucleolar invasion by several viral proteins. One of these proteins is US11, which exhibits several different functions and displays both cytoplasmic localization and clear nucleolar localization very similar to that of the major multifunctional nucleolar protein nucleolin. To determine whether US11 interacts with nucleolin, we purified US11 protein partners by coimmunoprecipitations using a tagged protein, Flag-US11. From extracts of cells expressing Flag-US11 protein, we copurified a protein of about 100 kDa that was further identified as nucleolin. In vitro studies have demonstrated that nucleolin interacts with US11 and that the C-terminal domain of US11, which is required for US11 nucleolar accumulation, is sufficient for interaction with nucleolin. This association was confirmed in HSV-1-infected cells. We found an increase in the nucleolar accumulation of US11 in nucleolin-depleted cells, thereby revealing that nucleolin could play a role in US11 nucleocytoplasmic trafficking through one-way directional transport out of the nucleolus. Since nucleolin is required for HSV-1 nuclear egress, the interaction of US11 with nucleolin may participate in the outcome of infection. PMID:22130536

  19. Chromatin Insulator Factors Involved in Long-Range DNA Interactions and Their Role in the Folding of the Drosophila Genome

    PubMed Central

    Dejardin, Stephanie; Allemand, Frederic; Gamot, Adrien; Labesse, Gilles; Cuvier, Olivier; Nègre, Nicolas; Cohen-Gonsaud, Martin; Margeat, Emmanuel; Nöllmann, Marcelo

    2014-01-01

    Chromatin insulators are genetic elements implicated in the organization of chromatin and the regulation of transcription. In Drosophila, different insulator types were characterized by their locus-specific composition of insulator proteins and co-factors. Insulators mediate specific long-range DNA contacts required for the three dimensional organization of the interphase nucleus and for transcription regulation, but the mechanisms underlying the formation of these contacts is currently unknown. Here, we investigate the molecular associations between different components of insulator complexes (BEAF32, CP190 and Chromator) by biochemical and biophysical means, and develop a novel single-molecule assay to determine what factors are necessary and essential for the formation of long-range DNA interactions. We show that BEAF32 is able to bind DNA specifically and with high affinity, but not to bridge long-range interactions (LRI). In contrast, we show that CP190 and Chromator are able to mediate LRI between specifically-bound BEAF32 nucleoprotein complexes in vitro. This ability of CP190 and Chromator to establish LRI requires specific contacts between BEAF32 and their C-terminal domains, and dimerization through their N-terminal domains. In particular, the BTB/POZ domains of CP190 form a strict homodimer, and its C-terminal domain interacts with several insulator binding proteins. We propose a general model for insulator function in which BEAF32/dCTCF/Su(HW) provide DNA specificity (first layer proteins) whereas CP190/Chromator are responsible for the physical interactions required for long-range contacts (second layer). This network of organized, multi-layer interactions could explain the different activities of insulators as chromatin barriers, enhancer blockers, and transcriptional regulators, and suggest a general mechanism for how insulators may shape the organization of higher-order chromatin during cell division. PMID:25165871

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

    PubMed Central

    Zhang, Yuan; Li, Jingyun; Wang, Chengshuo; Zhang, Luo

    2015-01-01

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

  1. The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence

    PubMed Central

    Burla, Romina; Carcuro, Mariateresa; Torre, Mattia La; Fratini, Federica; Crescenzi, Marco; D'Apice, Maria Rosaria; Spitalieri, Paola; Raffa, Grazia Daniela; Astrologo, Letizia; Lattanzi, Giovanna; Cundari, Enrico; Raimondo, Domenico; Biroccio, Annamaria; Gatti, Maurizio

    2016-01-01

    AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just like lamins. Double immunostaining revealed that AKTIP partially co-localizes with lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle poles and at the midbody of late telophase cells similar to lamin B1. AKTIP-depleted cells show senescence-associated markers and recapitulate several aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP is a new player in lamin-related processes, including those that govern nuclear architecture, telomere homeostasis and cellular senescence. PMID:27512140

  2. The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence.

    PubMed

    Burla, Romina; Carcuro, Mariateresa; Torre, Mattia La; Fratini, Federica; Crescenzi, Marco; D'Apice, Maria Rosaria; Spitalieri, Paola; Raffa, Grazia Daniela; Astrologo, Letizia; Lattanzi, Giovanna; Cundari, Enrico; Raimondo, Domenico; Biroccio, Annamaria; Gatti, Maurizio; Saggio, Isabella

    2016-08-01

    AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just like lamins. Double immunostaining revealed that AKTIP partially co-localizes with lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle poles and at the midbody of late telophase cells similar to lamin B1. AKTIP-depleted cells show senescence-associated markers and recapitulate several aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP is a new player in lamin-related processes, including those that govern nuclear architecture, telomere homeostasis and cellular senescence. PMID:27512140

  3. Mexican American Mothers and Fathers’ Prenatal Attitudes and Father Prenatal Involvement: Links to Mother-Infant Interaction and Father Engagement

    PubMed Central

    Cabrera, Natasha J.; Shannon, Jacqueline; Mitchell, Stephanie; West, Jerry

    2010-01-01

    The present study examines the associations between Mexican American mothers’ and fathers’ pregnancy intentions, fathers’ participation in prenatal activities and mother-infant interactions and father engagement with 9 month-old infants in a nationally representative sample of 735 infants and their parents participating in the Early Childhood Longitudinal Study – Birth Cohort. After controlling for a host of variables, multiple regressions revealed that when mothers wanted the pregnancy, fathers engaged in more literacy and caregiving activities than when mothers did not want the pregnancy. When couples disagreed about wanting the pregnancy, fathers engaged in more literacy activities and showed more warmth than when they agreed. Relationship quality significantly moderated the effects of parents’ wantedness on mother-infant interactions and fathers’ engagement in literacy activities. PMID:20300483

  4. Upstream Stimulatory Factor 2, a Novel FoxA1-Interacting Protein, Is Involved in Prostate-Specific Gene Expression

    PubMed Central

    Sun, Qian; Yu, Xiuping; Degraff, David J.; Matusik, Robert J.

    2009-01-01

    The forkhead protein A1 (FoxA1) is critical for the androgenic regulation of prostate-specific promoters. Prostate tissue rescued from FoxA1 knockout mice exhibits abnormal prostate development, typified by the absence of expression of differentiation markers and inability to engage in secretion. Chromatin immunoprecipitation and coimmunoprecipitation studies revealed that FoxA1 is one of the earliest transcription factors that binds to prostate-specific promoters, and that a direct protein-protein interaction occurs between FoxA1 and androgen receptor. Interestingly, evidence of the interaction of FoxA1 with other transcription factors is lacking. The upstream stimulatory factor 2 (USF2), an E-box-binding transcription factor of the basic-helix-loop-helix-leucine-zipper family, binds to a consensus DNA sequence similar to FoxA1. Our in vitro and in vivo studies demonstrate the binding of USF2 to prostate-specific gene promoters including the probasin promoter, spermine-binding protein promoter, and prostate-specific antigen core enhancer. Furthermore, we show a direct physical interaction between FoxA1 and USF2 through the use of immunoprecipitation and glutathione-S-transferase pull-down assays. This interaction is mediated via the forkhead DNA-binding domain of FoxA1 and the DNA-binding domain of USF2. In summary, these data indicate that USF2 is one of the components of the FoxA1/androgen receptor transcriptional protein complex that contributes to the expression of androgen-regulated and prostate-specific genes. PMID:19846536

  5. OLDER ADULTS CATCH UP TO YOUNGER ADULTS ON A LEARNING AND MEMORY TASK THAT INVOLVES COLLABORATIVE SOCIAL INTERACTION

    PubMed Central

    Derksen, B.J.; Duff, M.C.; Weldon, K.; Zhang, J.; Zamba, G.; Tranel, D.; Denburg, N.L.

    2014-01-01

    Learning and memory abilities tend to decline as people age. The current study examines the question of whether a learning situation that emphasizes collaborative social interaction might help older persons overcome age-related learning and memory changes and thus perform similarly to younger persons. Younger and Older participants (n = 34 in each group) completed the Barrier Task, a game-like social interaction where partners work together to develop labels for a set of abstract tangrams. Participants were also administered standard clinical neuropsychological measures of memory, on which the Older group showed expected inferiority to the Younger group. On the Barrier Task, the Older group performed less well than the Younger group early on, but as the task progressed, the performance of the Older group caught up and became statistically indistinguishable from that of the Younger group. These results can be taken to suggest that a learning milieu characterized by collaborative social interaction can attenuate some of the typical memory disadvantages associated with being older. PMID:24841619

  6. The Chaperonin Containing TCP1 Complex (CCT/TRiC) Is Involved in Mediating Sperm-Oocyte Interaction

    PubMed Central

    Dun, Matthew D.; Smith, Nathan D.; Baker, Mark A.; Lin, Minjie; Aitken, R. John; Nixon, Brett

    2011-01-01

    Sperm-oocyte interactions are among the most remarkable processes in cell biology. These cellular recognition events are initiated by an exquisitely specific adhesion of free-swimming spermatozoa to the zona pellucida, an acellular matrix that surrounds the ovulated oocyte. Decades of research focusing on this interaction have led to the establishment of a widely held paradigm that the zona pellucida receptor is a single molecular entity that is constitutively expressed on the sperm cell surface. In contrast, we have employed the techniques of blue native-polyacrylamide gel electrophoresis, far Western blotting, and proximity ligation to secure the first direct evidence in support of a novel hypothesis that zona binding is mediated by multimeric sperm receptor complex(es). Furthermore, we show that one such multimeric association, comprising the chaperonin-containing TCP1 complex (CCT/TRiC) and a zona-binding protein, zona pellucida-binding protein 2, is present on the surface of capacitated spermatozoa and could account for the zona binding activity of these cells. Collectively, these data provide an important biochemical insight into the molecular basis of sperm-zona pellucida interaction and a plausible explanation for how spermatozoa gain their ability to fertilize. PMID:21880732

  7. Characterization of an Additional Binding Surface on the p97 N-Terminal Domain Involved in Bipartite Cofactor Interactions.

    PubMed

    Hänzelmann, Petra; Schindelin, Hermann

    2016-01-01

    The type II AAA ATPase p97 interacts with a large number of cofactors that regulate its function by recruiting it to different cellular pathways. Most of the cofactors interact with the N-terminal (N) domain of p97, either via ubiquitin-like domains or short linear binding motifs. While some linear binding motifs form α helices, another group features short stretches of unstructured hydrophobic sequences as found in the so-called SHP (BS1, binding segment 1) motif. Here we present the crystal structure of a SHP-binding motif in complex with p97, which reveals a so far uncharacterized binding site on the p97 N domain that is different from the conserved binding surface of all other known p97 cofactors. This finding explains how cofactors like UFD1/NPL4 and p47 can utilize a bipartite binding mechanism to interact simultaneously with the same p97 monomer via their ubiquitin-like domain and SHP motif. PMID:26712280

  8. Structural and Functional Characterization of CRM1-Nup214 Interactions Reveals Multiple FG-Binding Sites Involved in Nuclear Export.

    PubMed

    Port, Sarah A; Monecke, Thomas; Dickmanns, Achim; Spillner, Christiane; Hofele, Romina; Urlaub, Henning; Ficner, Ralf; Kehlenbach, Ralph H

    2015-10-27

    CRM1 is the major nuclear export receptor. During translocation through the nuclear pore, transport complexes transiently interact with phenylalanine-glycine (FG) repeats of multiple nucleoporins. On the cytoplasmic side of the nuclear pore, CRM1 tightly interacts with the nucleoporin Nup214. Here, we present the crystal structure of a 117-amino-acid FG-repeat-containing fragment of Nup214, in complex with CRM1, Snurportin 1, and RanGTP at 2.85 Å resolution. The structure reveals eight binding sites for Nup214 FG motifs on CRM1, with intervening stretches that are loosely attached to the transport receptor. Nup214 binds to N- and C-terminal regions of CRM1, thereby clamping CRM1 in a closed conformation and stabilizing the export complex. The role of conserved hydrophobic pockets for the recognition of FG motifs was analyzed in biochemical and cell-based assays. Comparative studies with RanBP3 and Nup62 shed light on specificities of CRM1-nucleoporin binding, which serves as a paradigm for transport receptor-nucleoporin interactions. PMID:26489467

  9. NMR identification of the binding surfaces involved in the Salmonella and Shigella Type III secretion tip-translocon protein-protein interactions.

    PubMed

    McShan, Andrew C; Kaur, Kawaljit; Chatterjee, Srirupa; Knight, Kevin M; De Guzman, Roberto N

    2016-08-01

    The type III secretion system (T3SS) is essential for the pathogenesis of many bacteria including Salmonella and Shigella, which together are responsible for millions of deaths worldwide each year. The structural component of the T3SS consists of the needle apparatus, which is assembled in part by the protein-protein interaction between the tip and the translocon. The atomic detail of the interaction between the tip and the translocon proteins is currently unknown. Here, we used NMR methods to identify that the N-terminal domain of the Salmonella SipB translocon protein interacts with the SipD tip protein at a surface at the distal region of the tip formed by the mixed α/β domain and a portion of its coiled-coil domain. Likewise, the Shigella IpaB translocon protein and the IpaD tip protein interact with each other using similar surfaces identified for the Salmonella homologs. Furthermore, removal of the extreme N-terminal residues of the translocon protein, previously thought to be important for the interaction, had little change on the binding surface. Finally, mutations at the binding surface of SipD reduced invasion of Salmonella into human intestinal epithelial cells. Together, these results reveal the binding surfaces involved in the tip-translocon protein-protein interaction and advance our understanding of the assembly of the T3SS needle apparatus. Proteins 2016; 84:1097-1107. © 2016 Wiley Periodicals, Inc. PMID:27093649

  10. Investigation of scattering processes in quantum few-body systems involving long-range interaction by the complex-rotation method

    SciTech Connect

    Volkov, M. V.; Elander, N.; Yakovlev, S. L. Yarevsky, E. A.

    2013-02-15

    The complex-rotation method adapted to solving the multichannel scattering problem in the two-body system where the interaction potential contains the long-range Coulomb components is described. The scattering problem is reformulated as the problem of solving a nonhomogeneous Schroedinger equation in which the nonhomogeneous term involves a Coulomb potential cut off at large distances. The incident wave appearing in the nonhomogeneous term is a solution of the Schroedinger equation with longrange Coulomb interaction. This formulation is free from approximations associated with a direct cutoff of Coulomb interaction at large distances. The efficiency of this formalism is demonstrated by considering the example of solving scattering problems in the {alpha}-{alpha} and p-p systems.

  11. Functional analysis of Abp1p-interacting proteins involved in endocytosis of the MCC component in Aspergillus oryzae.

    PubMed

    Matsuo, Kento; Higuchi, Yujiro; Kikuma, Takashi; Arioka, Manabu; Kitamoto, Katsuhiko

    2013-07-01

    We have investigated the functions of three endocytosis-related proteins in the filamentous fungus Aspergillus oryzae. Yeast two-hybrid screening using the endocytic marker protein AoAbp1 (A.oryzae homolog of Saccharomyces cerevisiae Abp1p) as a bait identified four interacting proteins named Aip (AoAbp1 interacting proteins). In mature hyphae, EGFP (enhanced green fluorescent protein) fused to Aips colocalized with AoAbp1 at the hyphal tip region and the plasma membrane, suggesting that Aips function in endocytosis. aipA is a putative AAA ATPase and its function has been dissected (Higuchi et al., 2011). aipB, the homolog of A. nidulans myoA, encodes an essential class I myosin and its conditional mutant showed a germination defect. aipC and aipD do not contain any recognizable domains except some proline-rich regions which may interact with two SH3 (Src homology 3) domains of AoAbp1. Neither aipC nor aipD disruptants showed any defects in their growth, but the aipC disruptant formed less conidia compared with the control strain. In addition, the aipC disruptant was resistant to the triazole antifungal drugs that inhibit ergosterol biosynthesis. Although no aip disruptants showed any defects in the uptake of the fluorescent dye FM4-64, the endocytosis of the arginine permease AoCan1, one of the MCC (membrane compartment of Can1p) components, was delayed in both aipC and aipD disruptants. In A. oryzae, AoCan1 localized mainly at the plasma membrane in the basal region of hyphae, suggesting that different endocytic mechanisms exist in apical and basal regions of highly polarized cells. PMID:23597630

  12. A network of interdependent molecular interactions describes a higher order Nrd1-Nab3 complex involved in yeast transcription termination.

    PubMed

    Loya, Travis J; O'Rourke, Thomas W; Degtyareva, Natalya; Reines, Daniel

    2013-11-22

    Nab3 and Nrd1 are yeast heterogeneous nuclear ribonucleoprotein (hnRNP)-like proteins that heterodimerize and bind RNA. Genetic and biochemical evidence reveals that they are integral to the termination of transcription of short non-coding RNAs by RNA polymerase II. Here we define a Nab3 mutation (nab3Δ134) that removes an essential part of the protein's C terminus but nevertheless can rescue, in trans, the phenotype resulting from a mutation in the RNA recognition motif of Nab3. This low complexity region of Nab3 appears intrinsically unstructured and can form a hydrogel in vitro. These data support a model in which multiple Nrd1-Nab3 heterodimers polymerize onto substrate RNA to effect termination, allowing complementation of one mutant Nab3 molecule by another lacking a different function. The self-association property of Nab3 adds to the previously documented interactions between these hnRNP-like proteins, RNA polymerase II, and the nascent transcript, leading to a network of nucleoprotein interactions that define a higher order Nrd1-Nab3 complex. This was underscored from the synthetic phenotypes of yeast strains with pairwise combinations of Nrd1 and Nab3 mutations known to affect their distinct biochemical activities. The mutations included a Nab3 self-association defect, a Nab3-Nrd1 heterodimerization defect, a Nrd1-polymerase II binding defect, and an Nab3-RNA recognition motif mutation. Although no single mutation was lethal, cells with any two mutations were not viable for four such pairings, and a fifth displayed a synthetic growth defect. These data strengthen the idea that a multiplicity of interactions is needed to assemble a higher order Nrd1-Nab3 complex that coats specific nascent RNAs in preparation for termination. PMID:24100036

  13. A lattice Boltzmann-finite element model for two-dimensional fluid-structure interaction problems involving shallow waters

    NASA Astrophysics Data System (ADS)

    De Rosis, Alessandro

    2014-03-01

    In this paper, a numerical method for the modeling of shallow waters interacting with slender elastic structures is presented. The fluid domain is modeled through the lattice Boltzmann method, while the solid domain is idealized by corotational beam finite elements undergoing large displacements. Structure dynamics is predicted by using the time discontinuous Galerkin method and the fluid-structure interface conditions are handled by the Immersed Boundary method. An explicit coupling strategy to combine the adopted numerical methods is proposed and its effectiveness is tested by computing the error in terms of the energy that is artificially introduced at the fluid-solid interface.

  14. SNF2H interacts with XRCC1 and is involved in repair of H2O2-induced DNA damage.

    PubMed

    Kubota, Yoshiko; Shimizu, Shinji; Yasuhira, Shinji; Horiuchi, Saburo

    2016-07-01

    The protein XRCC1 has no inherent enzymatic activity, and is believed to function in base excision repair as a dedicated scaffold component that coordinates other DNA repair factors. Repair foci clearly represent the recruitment and accumulation of DNA repair factors at sites of damage; however, uncertainties remain regarding their organization in the context of nuclear architecture and their biological significance. Here we identified the chromatin remodeling factor SNF2H/SMARCA5 as a novel binding partner of XRCC1, with their interaction dependent on the casein kinase 2-mediated constitutive phosphorylation of XRCC1. The proficiency of repairing H2O2-induced damage was strongly impaired by SNF2H knock-down, and similar impairment was observed with knock-down of both XRCC1 and SNF2H simultaneously, suggesting their role in a common repair pathway. Most SNF2H exists in the nuclear matrix fraction, forming salt extraction-resistant foci-like structures in unchallenged nuclei. Remarkably, damage-induced formation of both PAR and XRCC1 foci depended on SNF2H, and the PAR and XRCC1 foci co-localized with the SNF2H foci. We propose a model in which a base excision repair complex containing damaged chromatin is recruited to specific locations in the nuclear matrix for repair, with this recruitment mediated by XRCC1-SNF2H interaction. PMID:27268481

  15. An Armadillo Motif in Ufd3 Interacts with Cdc48 and is Involved in Ubiquitin Homeostasis and Protein Degradation

    SciTech Connect

    Zhao, G.; Li, G; Schindelin, H; Lennarz, W

    2009-01-01

    The yeast AAA-ATPase Cdc48 and the ubiquitin fusion degradation (UFD) proteins play important, evolutionarily conserved roles in ubiquitin dependent protein degradation. The N-terminal domain of Cdc48 interacts with substrate-recruiting cofactors, whereas the C terminus of Cdc48 binds to proteins such as Ufd3 that process substrates. Ufd3 is essential for efficient protein degradation and for maintaining cellular ubiquitin levels. This protein contains an N-terminal WD40 domain, a central ubiquitin-binding domain, and a C-terminal Cdc48-binding PUL domain. The crystal structure of the PUL domain reveals an Armadillo repeat with high structural similarity to importin-a, and the Cdc48-binding site could be mapped to the concave surface of the PUL domain by biochemical studies. Alterations of the Cdc48 binding site of Ufd3 by site-directed mutagenesis resulted in a depletion of cellular ubiquitin pools and reduced activity of the ubiquitin fusion degradation pathway. Therefore, our data provide direct evidence that the functions of Ufd3 in ubiquitin homeostasis and protein degradation depend on its interaction with the C terminus of Cdc48.

  16. Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: involvement of transforming growth factor beta1.

    PubMed

    Gohongi, T; Fukumura, D; Boucher, Y; Yun, C O; Soff, G A; Compton, C; Todoroki, T; Jain, R K

    1999-10-01

    Angiogenesis inhibitors produced by a primary tumor can create a systemic anti-angiogenic environment and maintain metastatic tumor cells in a state of dormancy. We show here that the gallbladder microenvironment modulates the production of transforming growth factor (TGF)-beta1, a multifunctional cytokine that functions as an endogenous anti-angiogenic and anti-tumor factor in a cranial window preparation. We found that a wide variety of human gallbladder tumors express TGF-beta1 irrespective of histologic type. We implanted a gel impregnated with basic fibroblast growth factor or Mz-ChA-2 tumor in the cranial windows of mice without tumors or mice with subcutaneous or gallbladder tumors to study angiogenesis and tumor growth at a secondary site. Angiogenesis, leukocyte-endothelial interaction in vessels and tumor growth in the cranial window were substantially inhibited in mice with gallbladder tumors. The concentration of TGF-beta1 in the plasma of mice with gallbladder tumors was 300% higher than that in the plasma of mice without tumors or with subcutaneous tumors. In contrast, there was no difference in the plasma levels of other anti- and pro-angiogenic factors. Treatment with neutralizing antibody against TGF-beta1 reversed both angiogenesis suppression and inhibition of leukocyte rolling induced by gallbladder tumors. TGF-beta1 also inhibited Mz-ChA-2 tumor cell proliferation. Our results indicate that the production of anti-angiogenesis/proliferation factors is regulated by tumor-host interactions. PMID:10502827

  17. Interspecific interactions involving Neoseiulus californicus (Acari: Phytoseiidae) and Agistemus brasiliensis (Acari: Stigmaeidae) as predators of Brevipalpus phoenicis (Acari: Tenuipalpidae).

    PubMed

    da Silva, Marcos Zatti; Sato, Mário Eidi; de Oliveira, Carlos Amadeu Leite; Nicastro, Roberto Lomba

    2015-03-01

    Brevipalpus phoenicis (Geijskes) is associated with the transmission of Citrus leprosis which is considered the main viral disease for the Brazilian citrus production. Mites of the families Stigmaeidae and Phytoseiidae coexist in various agricultural crops, often promoting the biological control of pest mites. The aim of this work was to study the interactions of Neoseiulus californicus (McGregor) (Phytoseiidae) and Agistemus brasiliensis Matioli, Ueckermann & Oliveira (Stigmaeidae), in the presence or absence of B. phoenicis. Two experiments were carried out. In the first, a N. californicus female was placed in each leaf disc arena, with eggs of B. phoenicis and A. brasiliensis as food sources. In the second, an A. brasiliensis female was placed in each arena, with eggs of B. phoenicis and N. californicus as food sources. Adults of both predators were able to consume both types of eggs available as food sources, but they fed on considerably higher proportions of B. phoenicis than on eggs of the predator. Eggs of A. brasiliensis were not a suitable food source for N. californicus, which produced only 0.1 egg per female per day when only eggs of that species were present in the experimental unit. The results suggest that eggs of N. californicus were a suitable food source for A. brasiliensis, which oviposited 1.12 eggs per day, when only eggs of N. californicus were provided to the stigmaeid mite. The possible interactions among N. californicus, A. brasiliensis and B. phoenicis in citrus orchards are discussed. PMID:25524512

  18. Interaction of 2-aminopyrimidine with σ- and π-acceptors involving chemical reactions via initial charge transfer complexation

    NASA Astrophysics Data System (ADS)

    Rabie, U. M.; Abou-El-Wafa, M. H.; Mohamed, R. A.

    2007-12-01

    Interaction of 2-aminopyrimidine (AP) with iodine as a typical σ-type acceptor and with a typical π-type acceptor, 2,3,5,6-tetrachloro-1,4-benzoquinone, p-chloranil (CHL) have been studied spectrophotometrically. Electronic absorption spectra of the system AP-I 2 in several organic solvents of different polarities have performed clear charge transfer (CT) band(s). Formation constants ( KCT) and molar absorption coefficients ( ɛCT) and thermodynamic properties, Δ H, Δ S, and Δ G, of this system in various organic solvents were determined and discussed. Interaction of AP with the π-acceptor has shown unique behaviors. Chemical reaction has occurred via prior or initial formation of the outer-sphere CT complex followed by formation of the corresponding anion radicals, CHL rad - , as intermediates. UV-vis, 1H NMR, Mass, and FT-IR spectra in addition to the elemental analysis were used to confirm the proposed occurrence of the chemical reaction and to investigate the synthesized solid products.

  19. Optimization of photosynthesis by multiple metabolic pathways involving interorganelle interactions: resource sharing and ROS maintenance as the bases.

    PubMed

    Sunil, Bobba; Talla, Sai K; Aswani, Vetcha; Raghavendra, Agepati S

    2013-11-01

    The bioenergetic processes of photosynthesis and respiration are mutually beneficial. Their interaction extends to photorespiration, which is linked to optimize photosynthesis. The interplay of these three pathways is facilitated by two major phenomena: sharing of energy/metabolite resources and maintenance of optimal levels of reactive oxygen species (ROS). The resource sharing among different compartments of plant cells is based on the production/utilization of reducing equivalents (NADPH, NADH) and ATP as well as on the metabolite exchange. The responsibility of generating the cellular requirements of ATP and NAD(P)H is mostly by the chloroplasts and mitochondria. In turn, besides the chloroplasts, the mitochondria, cytosol and peroxisomes are common sinks for reduced equivalents. Transporters located in membranes ensure the coordinated movement of metabolites across the cellular compartments. The present review emphasizes the beneficial interactions among photosynthesis, dark respiration and photorespiration, in relation to metabolism of C, N and S. Since the bioenergetic reactions tend to generate ROS, the cells modulate chloroplast and mitochondrial reactions, so as to ensure that the ROS levels do not rise to toxic levels. The patterns of minimization of ROS production and scavenging of excess ROS in intracellular compartments are highlighted. Some of the emerging developments are pointed out, such as model plants, orientation/movement of organelles and metabolomics. PMID:23881384

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

    PubMed

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

    2016-04-01

    Exposure to environmental hazards has been associated with diseases in humans. The identification of single nucleotide polymorphisms (SNPs) in human populations exposed to different environmental hazards, is vital for detecting the genetic risks of some important human diseases. Several studies in this field have been conducted on glutathione S-transferases (GSTs), a phase II detoxification superfamily, to investigate its role in the occurrence of diseases. Human GSTs consist of cytosolic and microsomal superfamilies that are further divided into subfamilies. Based on scientific search engines and a review of the literature, we have found a large amount of published articles on human GST super- and subfamilies that have greatly assisted in our efforts to examine their role in health and disease. Because of its polymorphic variations in relation to environmental hazards such as air pollutants, cigarette smoke, pesticides, heavy metals, carcinogens, pharmaceutical drugs, and xenobiotics, GST is considered as a significant biomarker. This review examines the studies on gene-environment interactions related to various diseases with respect to single nucleotide polymorphisms (SNPs) found in the GST superfamily. Overall, it can be concluded that interactions between GST genes and environmental factors play an important role in human diseases. PMID:27043589

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

    PubMed Central

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

    2016-01-01

    Exposure to environmental hazards has been associated with diseases in humans. The identification of single nucleotide polymorphisms (SNPs) in human populations exposed to different environmental hazards, is vital for detecting the genetic risks of some important human diseases. Several studies in this field have been conducted on glutathione S-transferases (GSTs), a phase II detoxification superfamily, to investigate its role in the occurrence of diseases. Human GSTs consist of cytosolic and microsomal superfamilies that are further divided into subfamilies. Based on scientific search engines and a review of the literature, we have found a large amount of published articles on human GST super- and subfamilies that have greatly assisted in our efforts to examine their role in health and disease. Because of its polymorphic variations in relation to environmental hazards such as air pollutants, cigarette smoke, pesticides, heavy metals, carcinogens, pharmaceutical drugs, and xenobiotics, GST is considered as a significant biomarker. This review examines the studies on gene-environment interactions related to various diseases with respect to single nucleotide polymorphisms (SNPs) found in the GST superfamily. Overall, it can be concluded that interactions between GST genes and environmental factors play an important role in human diseases. PMID:27043589

  2. Intermolecular interactions involving C-H bonds, 3, Structure and energetics of the interaction between CH{sub 4} and CN{sup {minus}}

    SciTech Connect

    Novoa, J.J.; Whangbo, Myung-Hwan; Williams, J.M.

    1991-12-31

    On the basis of SCF and single reference MP2 calculations, the full potential energy surface of the interaction between CH{sub 4} and CN{sup {minus}} was studied using extended basis sets of up to near Hartree-Fock limit quality. Colinear arrangements C-N{sup {minus}}{hor_ellipsis}H-CH{sub 3} and N-C{sup {minus}}{hor_ellipsis}H-CH{sub 3} are found to be the only two energy minima. The binding energies of these two structures are calculated to be 2.5 and 2.1 kcal/mol, respectively, at the MP2 level. The full vibrational analyses of two structures show a red shift of about 30 cm{sup {minus}1} for the v{sub s} C-H stretching.

  3. Identification of critical residues in Hepatitis E virus macro domain involved in its interaction with viral methyltransferase and ORF3 proteins.

    PubMed

    Anang, Saumya; Subramani, Chandru; Nair, Vidya P; Kaul, Sheetal; Kaushik, Nidhi; Sharma, Chandresh; Tiwari, Ashutosh; Ranjith-Kumar, C T; Surjit, Milan

    2016-01-01

    Hepatitis E virus (HEV) is a major cause of hepatitis in normal and organ transplant individuals. HEV open reading frame-1 encodes a polypeptide comprising of the viral nonstructural proteins as well as domains of unknown function such as the macro domain (X-domain), V, DUF3729 and Y. The macro domain proteins are ubiquitously present from prokaryotes to human and in many positive-strand RNA viruses, playing important roles in multiple cellular processes. Towards understanding the function of the HEV macro domain, we characterized its interaction partners among other HEV encoded proteins. Here, we report that the HEV X-domain directly interacts with the viral methyltransferase and the ORF3 proteins. ORF3 association with the X-domain was mediated through two independent motifs, located within its N-terminal 35aa (amino acids) and C-terminal 63-123aa. Methyltransferase interaction domain was mapped to N-terminal 30-90aa. The X-domain interacted with both ORF3 and methyltransferase through its C-terminal region, involving 66(th),67(th) isoleucine and 101(st),102(nd) leucine, conserved across HEV genotypes. Furthermore, ORF3 and methyltransferase competed with each other for associating with the X-domain. These findings provide molecular understanding of the interaction between the HEV macro domain, methyltransferase and ORF3, suggesting an important role of the macro domain in the life cycle of HEV. PMID:27113483

  4. Identification of critical residues in Hepatitis E virus macro domain involved in its interaction with viral methyltransferase and ORF3 proteins

    PubMed Central

    Anang, Saumya; Subramani, Chandru; Nair, Vidya P.; Kaul, Sheetal; Kaushik, Nidhi; Sharma, Chandresh; Tiwari, Ashutosh; Ranjith-Kumar, CT; Surjit, Milan

    2016-01-01

    Hepatitis E virus (HEV) is a major cause of hepatitis in normal and organ transplant individuals. HEV open reading frame-1 encodes a polypeptide comprising of the viral nonstructural proteins as well as domains of unknown function such as the macro domain (X-domain), V, DUF3729 and Y. The macro domain proteins are ubiquitously present from prokaryotes to human and in many positive-strand RNA viruses, playing important roles in multiple cellular processes. Towards understanding the function of the HEV macro domain, we characterized its interaction partners among other HEV encoded proteins. Here, we report that the HEV X-domain directly interacts with the viral methyltransferase and the ORF3 proteins. ORF3 association with the X-domain was mediated through two independent motifs, located within its N-terminal 35aa (amino acids) and C-terminal 63-123aa. Methyltransferase interaction domain was mapped to N-terminal 30-90aa. The X-domain interacted with both ORF3 and methyltransferase through its C-terminal region, involving 66th,67th isoleucine and 101st,102nd leucine, conserved across HEV genotypes. Furthermore, ORF3 and methyltransferase competed with each other for associating with the X-domain. These findings provide molecular understanding of the interaction between the HEV macro domain, methyltransferase and ORF3, suggesting an important role of the macro domain in the life cycle of HEV. PMID:27113483

  5. Interaction between the antisense and target RNAs involved in the regulation of IncB plasmid replication.

    PubMed Central

    Siemering, K R; Praszkier, J; Pittard, A J

    1993-01-01

    Physical analysis of RNA I, the small antisense RNA which regulates the replication of IncB miniplasmid pMU720, showed that it is a highly structured molecule containing an imperfectly paired stem closed by a 6-base hairpin loop. Mutational studies revealed that a 3-base sequence in the hairpin loop is critical to the interaction between RNA I and its complementary target in the RepA mRNA (RNA II). Furthermore, a 2-base interior loop in the upper stem was found to play an important role in facilitating effective binding between RNA I and RNA II. From these analyses, a model describing the molecular mechanism of binding between RNA I and RNA II is proposed. Images PMID:7684039

  6. Scale up issues involved with the ceramic waste form : ceramic-container interactions and ceramic cracking quantification.

    SciTech Connect

    Bateman, K. J.; DiSanto, T.; Goff, K. M.; Johnson, S. G.; O'Holleran, T.; Riley, W. P., Jr.

    1999-05-03

    Argonne National Laboratory is developing a process for the conditioning of spent nuclear fuel to prepare the material for final disposal. Two waste streams will result from the treatment process, a stainless steel based form and a ceramic based form. The ceramic waste form will be enclosed in a stainless steel container. In order to assess the performance of the ceramic waste form in a repository two factors must be examined, the surface area increases caused by waste form cracking and any ceramic/canister interactions that may release toxic material. The results indicate that the surface area increases are less than the High Level Waste glass and any toxic releases are below regulatory limits.

  7. Proteomic analysis of ACTN4-interacting proteins reveals it's a putative involvement in mRNA metabolism

    SciTech Connect

    Khotin, Mikhail; Turoverova, Lidia; Aksenova, Vasilisa; Department of Genetics, St. Petersburg State University, Universitetskaya nab., 7 Barlev, Nikolai; Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN ; Borutinskaite, Veronika Viktorija; Department of Developmental Biology, Institute of Biochemistry, LT-08662 Vilnius ; Vener, Alexander; Bajenova, Olga; Pinaev, George P.; Tentler, Dmitri

    2010-06-25

    Alpha-actinin 4 (ACTN4) is an actin-binding protein. In the cytoplasm, ACTN4 participates in structural organisation of the cytoskeleton via cross-linking of actin filaments. Nuclear localisation of ACTN4 has also been reported, but no clear role in the nucleus has been established. In this report, we describe the identification of proteins associated with ACTN4 in the nucleus. A combination of two-dimensional gel electrophoresis (2D-GE) and MALDI-TOF mass-spectrometry revealed a large number of ACTN4-bound proteins that are involved in various aspects of mRNA processing and transport. The association of ACTN4 with different ribonucleoproteins suggests that a major function of nuclear ACTN4 may be regulation of mRNA metabolism and signaling.

  8. Polyamine biosynthesis inhibitors alter protein-protein interactions involving estrogen receptor in MCF-7 breast cancer cells.

    PubMed

    Thomas, T; Shah, N; Klinge, C M; Faaland, C A; Adihkarakunnathu, S; Gallo, M A; Thomas, T J

    1999-04-01

    We investigated the effects of polyamine biosynthesis inhibition on the estrogenic signaling pathway of MCF-7 breast cancer cells using a protein-protein interaction system. Estrogen receptor (ER) linked to glutathione-S-transferase (GST) was used to examine the effects of two polyamine biosynthesis inhibitors, difluoromethylornithine (DFMO) and CGP 48664. ER was specifically associated with a 45 kDa protein in control cells. In cells treated with estradiol, nine proteins were associated with ER. Cells treated with polyamine biosynthesis inhibitors in the absence of estradiol retained the binding of their ER with a 45 kDa protein and the ER also showed low-affinity interactions with a number of cellular proteins; however, these associations were decreased by the presence of estradiol and the inhibitors. When samples from the estradiol+DFMO treatment group were incubated with spermidine prior to GST-ER pull down assay, an increased association of several proteins with ER was detected. The intensity of the ER-associated 45 kDa protein increased by 10-fold in the presence of 1000 microM spermidine. These results indicate a specific role for spermidine in ER association of proteins. Western blot analysis of samples eluted from GST-ER showed the presence of chicken ovalbumin upstream promoter-transcription factor, an orphan nuclear receptor, and the endogenous full-length ER. These results show that multiple proteins associate with ER and that the binding of some of these proteins is highly sensitive to intracellular polyamine concentrations. Overall, our results indicate the importance of the polyamine pathway in the gene regulatory function of estradiol in breast cancer cells. PMID:10194516

  9. Cauliflower mosaic virus gene VI product N-terminus contains regions involved in resistance-breakage, self-association and interactions with movement protein

    PubMed Central

    Hapiak, Michael; Li, Yongzhong; Agama, Keli; Swade, Shaddy; Okenka, Genevieve; Falk, Jessica; Khandekar, Sushant; Raikhy, Gaurav; Anderson, Alisha; Pollock, Justin; Zellner, Wendy; Schoelz, James; Leisner, Scott M.

    2008-01-01

    Cauliflower mosaic virus (CaMV) gene VI encodes a multifunctional protein (P6) involved in the translation of viral RNA, the formation of inclusion bodies, and the determination of host range. Arabidopsis thaliana ecotype Tsu-0 prevents the systemic spread of most CaMV isolates, including CM1841. However, CaMV isolate W260 overcomes this resistance. In this paper, the N-terminal 110 amino acids of P6 (termed D1) were identified as the resistance-breaking region. D1 also bound full-length P6. Furthermore, binding of W260 D1 to P6 induced higher β-galactosidase activity and better leucine-independent growth in the yeast two-hybrid system than its CM1841 counterpart. Thus, W260 may evade Tsu-0 resistance by mediating P6 self-association in a manner different from that of CM1841. Because Tsu-0 resistance prevents virus movement, interaction of P6 with P1 (CaMV movement protein) was investigated. Both yeast two-hybrid analyses and maltose-binding protein pull-down experiments show that P6 interacts with P1. Although neither half of P1 interacts with P6, the N-terminus of P6 binds P1. Interestingly, D1 by itself does not interact with P1, indicating that different portions of the P6 N-terminus are involved in different activities. The P1-P6 interactions suggest a role for P6 in virus transport, possibly by regulating P1 tubule formation or the assembly of movement complexes. PMID:18851998

  10. Variants of SCARB1 and VDR Involved in Complex Genetic Interactions May Be Implicated in the Genetic Susceptibility to Clear Cell Renal Cell Carcinoma.

    PubMed

    Pośpiech, Ewelina; Ligęza, Janusz; Wilk, Wacław; Gołas, Aniela; Jaszczyński, Janusz; Stelmach, Andrzej; Ryś, Janusz; Blecharczyk, Aleksandra; Wojas-Pelc, Anna; Jura, Jolanta; Branicki, Wojciech

    2015-01-01

    The current data are still inconclusive in terms of a genetic component involved in the susceptibility to renal cell carcinoma. Our aim was to evaluate 40 selected candidate polymorphisms for potential association with clear cell renal cell carcinoma (ccRCC) based on independent group of 167 patients and 200 healthy controls. The obtained data were searched for independent effects of particular polymorphisms as well as haplotypes and genetic interactions. Association testing implied position rs4765623 in the SCARB1 gene (OR = 1.688, 95% CI: 1.104-2.582, P = 0.016) and a haplotype in VDR comprising positions rs739837, rs731236, rs7975232, and rs1544410 (P = 0.012) to be the risk factors in the studied population. The study detected several epistatic effects contributing to the genetic susceptibility to ccRCC. Variation in GNAS1 was implicated in a strong synergistic interaction with BIRC5. This effect was part of a model suggested by multifactor dimensionality reduction method including also a synergy between GNAS1 and SCARB1 (P = 0.036). Significance of GNAS1-SCARB1 interaction was further confirmed by logistic regression (P = 0.041), which also indicated involvement of SCARB1 in additional interaction with EPAS1 (P = 0.008) as well as revealing interactions between GNAS1 and EPAS1 (P = 0.016), GNAS1 and MC1R (P = 0.031), GNAS1 and VDR (P = 0.032), and MC1R and VDR (P = 0.035). PMID:25945350

  11. Involvement of the Carboxyl-Terminal Region of the Yeast Peroxisomal Half ABC Transporter Pxa2p in Its Interaction with Pxa1p and in Transporter Function

    PubMed Central

    Chuang, Cheng-Yi; Chen, Ling-Yun; Fu, Ru-Huei; Chen, Shih-Ming; Ho, Ming-Hua; Huang, Jie-Mau; Hsu, Chia-Chi; Wang, Chien-Cheng; Chen, Meng-Shian; Tsai, Rong-Tzong

    2014-01-01

    Background The peroxisome is a single membrane-bound organelle in eukaryotic cells involved in lipid metabolism, including β-oxidation of fatty acids. The human genetic disorder X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene (encoding ALDP, a peroxisomal half ATP-binding cassette [ABC] transporter). This disease is characterized by defective peroxisomal β-oxidation and a large accumulation of very long-chain fatty acids in brain white matter, adrenal cortex, and testis. ALDP forms a homodimer proposed to be the functional transporter, whereas the peroxisomal transporter in yeast is a heterodimer comprising two half ABC transporters, Pxa1p and Pxa2p, both orthologs of human ALDP. While the carboxyl-terminal domain of ALDP is engaged in dimerization, it remains unknown whether the same region is involved in the interaction between Pxa1p and Pxa2p. Methods/Principal Findings Using a yeast two-hybrid assay, we found that the carboxyl-terminal region (CT) of Pxa2p, but not of Pxa1p, is required for their interaction. Further analysis indicated that the central part of the CT (designated CT2) of Pxa2p was indispensable for its interaction with the carboxyl terminally truncated Pxa1_NBD. An interaction between the CT of Pxa2p and Pxa1_NBD was not detected, but could be identified in the presence of Pxa2_NBD-CT1. A single mutation of two conserved residues (aligned with X-ALD-associated mutations at the same positions in ALDP) in the CT2 of the Pxa2_NBD-CT protein impaired its interaction with Pxa1_NBD or Pxa1_NBD-CT, resulting in a mutant protein that exhibited a proteinase K digestion profile different from that of the wild-type protein. Functional analysis of these mutant proteins on oleate plates indicated that they were defective in transporter function. Conclusions/Significance The CT of Pxa2p is involved in its interaction with Pxa1p and in transporter function. This concept may be applied to human ALDP studies, helping to establish

  12. TEF30 Interacts with Photosystem II Monomers and Is Involved in the Repair of Photodamaged Photosystem II in Chlamydomonas reinhardtii.

    PubMed

    Muranaka, Ligia Segatto; Rütgers, Mark; Bujaldon, Sandrine; Heublein, Anja; Geimer, Stefan; Wollman, Francis-André; Schroda, Michael

    2016-02-01

    The remarkable capability of photosystem II (PSII) to oxidize water comes along with its vulnerability to oxidative damage. Accordingly, organisms harboring PSII have developed strategies to protect PSII from oxidative damage and to repair damaged PSII. Here, we report on the characterization of the THYLAKOID ENRICHED FRACTION30 (TEF30) protein in Chlamydomonas reinhardtii, which is conserved in the green lineage and induced by high light. Fractionation studies revealed that TEF30 is associated with the stromal side of thylakoid membranes. By using blue native/Deriphat-polyacrylamide gel electrophoresis, sucrose density gradients, and isolated PSII particles, we found TEF30 to quantitatively interact with monomeric PSII complexes. Electron microscopy images revealed significantly reduced thylakoid membrane stacking in TEF30-underexpressing cells when compared with control cells. Biophysical and immunological data point to an impaired PSII repair cycle in TEF30-underexpressing cells and a reduced ability to form PSII supercomplexes after high-light exposure. Taken together, our data suggest potential roles for TEF30 in facilitating the incorporation of a new D1 protein and/or the reintegration of CP43 into repaired PSII monomers, protecting repaired PSII monomers from undergoing repeated repair cycles or facilitating the migration of repaired PSII monomers back to stacked regions for supercomplex reassembly. PMID:26644506

  13. RANK-RANKL interactions are involved in cell adhesion-mediated drug resistance in multiple myeloma cell lines.

    PubMed

    Tsubaki, Masanobu; Takeda, Tomoya; Yoshizumi, Misako; Ueda, Emi; Itoh, Tatsuki; Imano, Motohiro; Satou, Takao; Nishida, Shozo

    2016-07-01

    Interaction between multiple myeloma (MM) cells and the bone marrow microenvironment plays a critical role in MM pathogenesis and the development of drug resistance. Recently, it has been reported that MM cells express the receptor activator of nuclear factor-κB (NF-κB) (RANK). However, the role of the RANK/RANK ligand (RANKL) system in drug resistance remains unclear. In this study, we demonstrated a novel function of the RANK/RANKL system in promoting drug resistance in MM. We found that RANKL treatment induced drug resistance in RANK-expressing but not RANK-negative cell lines. RANKL stimulation of RANK-expressing cells increased multidrug resistance protein 1 (MDR1), breast cancer resistance protein (BCRP), and lung resistance protein 1 (LRP1) expression and decreased Bim expression through various signaling molecules. RNA silencing of Bim expression induced drug resistance, but the RANKL-mediated drug resistance could not be overcome through the RNA silencing of MDR1, BCRP, and LRP1 expression. These results indicate that the RANK/RANKL system induces chemoresistance through the activation of multiple signal transduction pathways and by decreasing Bim expression in RANK-positive MM cells. These findings may prove to be useful in the development of cell adhesion-mediated drug resistance inhibitors in RANK-positive MM cells. PMID:26762414

  14. Bounce-resonance wave-particle interactions involving energetic ions and 2nd-harmonic ULF waves

    NASA Astrophysics Data System (ADS)

    Rankin, Robert; Sydorenko, Dmytro; Wang, Chengrui

    2016-07-01

    Multi-point observations from Cluster show clear evidence of acceleration of H+ and O+ ions by large azimuthal mode number ULF waves. In this paper we present a quantitative comparison between these observations and results from a numerical model. The methodology consists of large-scale test-particle simulations of bounce-resonance wave-particle interactions in fields of second harmonic standing ULF waves. The ULF waves are specified using a recently developed three-dimensional model that can take dipolar and compressed dipole magnetic field configurations. Our test particle simulations confirm the theoretical treatment of bounce-resonance developed by Southwood and Kivelson, including the resonance condition that must be satisfied, as well as a phase change of Pi in the energy spectrum. We also find strong nonlinear behaviour for m-numbers between 40-100, and for azimuthal electric field strengths of a few tens of millivolts per metre. The test-particle simulations are able to reproduce energy-dispersed ion signatures observed by Cluster, opening the possibility to more fully understand the inter-relationship between ULF waves and ion energization and transport in the inner magnetosphere.

  15. Tax is involved in up-regulation of HMGB1 expression levels by interaction with C/EBP.

    PubMed

    Zhang, Chen-Guang; Wang, Hui; Niu, Zhi-Guo; Zhang, Jing-Jing; Yin, Ming-Mei; Gao, Zhi-Tao; Hu, Li-Hua

    2013-01-01

    The high mobility group box 1 (HMGB1) protein is a multifunctional cytokine-like molecule that plays an important role in the pathogenesis of tumors. In this study, real-time polymerase chain reactions and Western blot assays indicated that HMGB1 transcriptional activity and protein level are increased in Tax+-T cells (TaxP). To clarify the mechanisms, a series of HMGB1 deletion reporter plasmids (pHLuc1 to pHLuc6) were transfected into Tax--T cells (TaxN, Jurkat) and Tax+-T cells (TaxP). We found that promoter activity in Tax+-T cells to be higher than that in Tax--T cells, indicating a significant increase in pHLuc6. Bay11-7082 (NF-κB inhibitor) treatment did not block the enhancing effect. Chromatin immunoprecipitation assays revealed that Tax was retained on a HMGB1 promoter fragment encompassing -1163 to -975. Bioinformatics analysis showed six characteristic cis-elements for CdxA, AP-1, AML-1a, USF, v-Myb, and C/EBP in the fragment in question. Mutation of cis- elements for C/EBP reduced significant HMGB1 promoter activity induced by Tax. These findings indicate that Tax enhances the expression of HMGB1 gene at the transcriptional level, possibly by interacting with C/EBP. PMID:23534754

  16. Functional groups of sialic acids involved in binding to siglecs (sialoadhesins) deduced from interactions with synthetic analogues.

    PubMed

    Kelm, S; Brossmer, R; Isecke, R; Gross, H J; Strenge, K; Schauer, R

    1998-08-01

    The siglecs, formerly called sialoadhesins, are a family of I-type lectins binding to sialic acids on the cell surface. Five members of this family have been identified: sialoadhesin, myelin-associated glycoprotein (MAG), Schwann cell myelin protein (SMP), CD22 and CD33. We have investigated the relevance of substituents at position C-9 and in the N-acetyl group of N-acetylneuraminic acid, using a series of synthetic sialic-acid analogues either on resialylated human erythrocytes or as free alpha-glycosides in hapten inhibition. All five siglecs require the hydroxy group at C-9 for binding, suggesting hydrogen bonding of this substituent with the binding site. Remarkable differences were found among the proteins in their specificity for modifications of the N-acetyl group. Whereas sialoadhesin, MAG and SMP do not tolerate a hydroxy group as in N-glycolylneuraminic acid, they bind to halogenated acetyl residues. In the case of MAG, N-fluoroacetylneuraminic acid is bound about 17-fold better than N-acetylneuraminic acid. In contrast, human and murine CD22 both show good affinity for N-glycolylneuraminic acid, but only human CD22 bound the halogenated compounds. In conclusion, our data indicate that interactions of the hydroxy group at position 9 and the N-acyl substituent contribute significantly to the binding strength. PMID:9738906

  17. MPG1 Encodes a Fungal Hydrophobin Involved in Surface Interactions during Infection-Related Development of Magnaporthe grisea.

    PubMed Central

    Talbot, N. J.; Kershaw, M. J.; Wakley, G. E.; De Vries, OMH.; Wessels, JGH.; Hamer, J. E.

    1996-01-01

    The rice blast fungus expresses a pathogenicity gene, MPG1, during appressorium formation, disease symptom development, and conidiation. The MPG1 gene sequence predicts a small protein belonging to a family of fungal proteins designated hydrophobins. Using random ascospore analysis and genetic complementation, we showed that MPG1 is necessary for infection-related development of Magnaporthe grisea on rice leaves and for full pathogenicity toward susceptible rice cultivars. The protein product of MPG1 appears to interact with hydrophobic surfaces, where it may act as a developmental sensor for appressorium formation. Ultrastructural studies revealed that MPG1 directs formation of a rodlet layer on conidia composed of interwoven ~5-nm rodlets, which contributes to their surface hydrophobicity. Using combined genetic and biochemical approaches, we identified a 15-kD secreted protein with characteristics that establish it as a class I hydrophobin. The protein is able to form detergent-insoluble high molecular mass complexes, is soluble in trifluoroacetic acid, and exhibits mobility shifts after treatment with performic acid. The production of this protein is directed by MPG1. PMID:12239409

  18. Structural and functional characterization of interactions involving the Tfb1 subunit of TFIIH and the NER factor Rad2

    PubMed Central

    Lafrance-Vanasse, Julien; Arseneault, Geneviève; Cappadocia, Laurent; Chen, Hung-Ta; Legault, Pascale; Omichinski, James G.

    2012-01-01

    The general transcription factor IIH (TFIIH) plays crucial roles in transcription as part of the pre-initiation complex (PIC) and in DNA repair as part of the nucleotide excision repair (NER) machinery. During NER, TFIIH recruits the 3′-endonuclease Rad2 to damaged DNA. In this manuscript, we functionally and structurally characterized the interaction between the Tfb1 subunit of TFIIH and Rad2. We show that deletion of either the PH domain of Tfb1 (Tfb1PH) or several segments of the Rad2 spacer region yield yeast with enhanced sensitivity to UV irradiation. Isothermal titration calorimetry studies demonstrate that two acidic segments of the Rad2 spacer bind to Tfb1PH with nanomolar affinity. Structure determination of a Rad2–Tfb1PH complex indicates that Rad2 binds to TFIIH using a similar motif as TFIIEα uses to bind TFIIH in the PIC. Together, these results provide a mechanistic bridge between the role of TFIIH in transcription and DNA repair. PMID:22373916

  19. Structural and functional characterization of interactions involving the Tfb1 subunit of TFIIH and the NER factor Rad2.

    PubMed

    Lafrance-Vanasse, Julien; Arseneault, Geneviève; Cappadocia, Laurent; Chen, Hung-Ta; Legault, Pascale; Omichinski, James G

    2012-07-01

    The general transcription factor IIH (TFIIH) plays crucial roles in transcription as part of the pre-initiation complex (PIC) and in DNA repair as part of the nucleotide excision repair (NER) machinery. During NER, TFIIH recruits the 3'-endonuclease Rad2 to damaged DNA. In this manuscript, we functionally and structurally characterized the interaction between the Tfb1 subunit of TFIIH and Rad2. We show that deletion of either the PH domain of Tfb1 (Tfb1PH) or several segments of the Rad2 spacer region yield yeast with enhanced sensitivity to UV irradiation. Isothermal titration calorimetry studies demonstrate that two acidic segments of the Rad2 spacer bind to Tfb1PH with nanomolar affinity. Structure determination of a Rad2-Tfb1PH complex indicates that Rad2 binds to TFIIH using a similar motif as TFIIEα uses to bind TFIIH in the PIC. Together, these results provide a mechanistic bridge between the role of TFIIH in transcription and DNA repair. PMID:22373916

  20. Cardiolipin synthetase is involved in antagonistic interaction (reverse CAMP phenomenon) of Mycoplasma species with Staphylococcus aureus beta-hemolysis.

    PubMed

    Kornspan, Jonathan D; Rottem, Shlomo; Nir-Paz, Ran

    2014-05-01

    Mycoplasma hyorhinis has been implicated in a variety of swine diseases. However, little is known about the hemolytic capabilities of Mycoplasma species in general or M. hyorhinis in particular. In this study, we show that M. hyorhinis possesses beta-hemolytic activity which may be involved in the invasion process. M. hyorhinis also possesses antagonistic cooperativity (reverse CAMP phenomenon) with Staphylococcus aureus beta-hemolysis, resulting in the protection of erythrocytes from the beta-hemolytic activity of S. aureus (reverse CAMP). The reversed CAMP phenomenon has been attributed to phospholipase D (PLD) activity. In silico analysis of the M. hyorhinis genome revealed the absence of the pld gene but the presence of the cls gene encoding cardiolipin synthetase, which contains two PLD active domains. The transformation of Mycoplasma gallisepticum that has neither the cls gene nor the reverse CAMP phenomenon with the cls gene from M. hyorhinis resulted in the reverse CAMP phenomenon, suggesting for the first time that reverse CAMP can be induced by cardiolipin synthetase. PMID:24599982

  1. Interaction Network and Localization of Brucella abortus Membrane Proteins Involved in the Synthesis, Transport, and Succinylation of Cyclic β-1,2-Glucans

    PubMed Central

    Guidolin, Leticia S.; Morrone Seijo, Susana M.; Guaimas, Francisco F.

    2015-01-01

    ABSTRACT Cyclic β-1,2-glucans (CβG) are periplasmic homopolysaccharides that play an important role in the virulence and interaction of Brucella with the host. Once synthesized in the cytoplasm by the CβG synthase (Cgs), CβG are transported to the periplasm by the CβG transporter (Cgt) and succinylated by the CβG modifier enzyme (Cgm). Here, we used a bacterial two-hybrid system and coimmunoprecipitation techniques to study the interaction network between these three integral inner membrane proteins. Our results indicate that Cgs, Cgt, and Cgm can form both homotypic and heterotypic interactions. Analyses carried out with Cgs mutants revealed that the N-terminal region of the protein (Cgs region 1 to 418) is required to sustain the interactions with Cgt and Cgm as well as with itself. We demonstrated by single-cell fluorescence analysis that in Brucella, Cgs and Cgt are focally distributed in the membrane, particularly at the cell poles, whereas Cgm is mostly distributed throughout the membrane with a slight accumulation at the poles colocalizing with the other partners. In summary, our results demonstrate that Cgs, Cgt, and Cgm form a membrane-associated biosynthetic complex. We propose that the formation of a membrane complex could serve as a mechanism to ensure the fidelity of CβG biosynthesis by coordinating their synthesis with the transport and modification. IMPORTANCE In this study, we analyzed the interaction and localization of the proteins involved in the synthesis, transport, and modification of Brucella abortus cyclic β-1,2-glucans (CβG), which play an important role in the virulence and interaction of Brucella with the host. We demonstrate that these proteins interact, forming a complex located mainly at the cell poles; this is the first experimental evidence of the existence of a multienzymatic complex involved in the metabolism of osmoregulated periplasmic glucans in bacteria and argues for another example of pole differentiation in Brucella

  2. Interaction of mechanisms involving epoxyeicosatrienoic acids, adenosine receptors, and metabotropic glutamate receptors in neurovascular coupling in rat whisker barrel cortex

    PubMed Central

    Shi, Yanrong; Liu, Xiaoguang; Gebremedhin, Debebe; Falck, John R; Harder, David R; Koehler, Raymond C

    2008-01-01

    Adenosine, astrocyte metabotropic glutamate receptors (mGluRs), and epoxyeicosatrienoic acids (EETs) have been implicated in neurovascular coupling. Although A2A and A2B receptors mediate cerebral vasodilation to adenosine, the role of each receptor in the cerebral blood flow (CBF) response to neural activation remains to be fully elucidated. In addition, adenosine can amplify astrocyte calcium, which may increase arachidonic acid metabolites such as EETs. The interaction of these pathways was investigated by determining if combined treatment with antagonists exerted an additive inhibitory effect on the CBF response. During whisker stimulation of anesthetized rats, the increase in cortical CBF was reduced by approximately half after individual administration of A2B, mGluR and EET antagonists and EET synthesis inhibitors. Combining treatment of either a mGluR antagonist, an EET antagonist, or an EET synthesis inhibitor with an A2B receptor antagonist did not produce an additional decrement in the CBF response. Likewise, the CBF response also remained reduced by ~50% when an EET antagonist was combined with an mGluR antagonist or an mGluR antagonist plus an A2B receptor antagonist. In contrast, A2A and A3 receptor antagonists had no effect on the CBF response to whisker stimulation. We conclude that (1) adenosine A2B receptors, rather than A2A or A3 receptors, play a significant role in coupling cortical CBF to neuronal activity, and (2) the adenosine A2B receptor, mGluR, and EETs signaling pathways are not functionally additive, consistent with the possibility of astrocytic mGluR and adenosine A2B receptor linkage to the synthesis and release of vasodilatory EETs. PMID:17519974

  3. Expression of genes involved in the embryo-maternal interaction in the early-pregnant canine uterus.

    PubMed

    Kautz, E; Gram, A; Aslan, S; Ay, S S; Selçuk, M; Kanca, H; Koldaş, E; Akal, E; Karakaş, K; Findik, M; Boos, A; Kowalewski, M P

    2014-05-01

    Although there is no acute luteolytic mechanism in the absence of pregnancy in the bitch, a precise and well-timed embryo-maternal interaction seems to be required for the initiation and maintenance of gestation. As only limited information is available about these processes in dogs, in this study, the uterine expression of possible decidualization markers was investigated during the pre-implantation stage (days 10-12) of pregnancy and in the corresponding nonpregnant controls. In addition, the expression of selected genes associated with blastocyst development and/or implantation was investigated in embryos flushed from the uteri of bitches used for this study (unhatched and hatched blastocysts). There was an upregulated expression of prolactin receptor (PRLR) and IGF2 observed pre-implantation. The expression of PRL and of IGF1 was unaffected, and neither was the expression of progesterone- or estrogen receptor β (ESR2). In contrast, (ESR1) levels were elevated during early pregnancy. Prostaglandin (PG)-system revealed upregulated expression of PGE2-synthase and its receptors, PTGER2 and PTGER4, and of the PG-transporter. Elevated levels of AKR1C3 mRNA, but not the protein itself, were noted. Expression of prostaglandin-endoperoxide synthase 2 (PTGS2) remained unaffected. Most of the transcripts were predominantly localized to the uterine epithelial cells, myometrium and, to a lesser extent, to the uterine stroma. PGES (PTGES) mRNA was abundantly expressed in both groups of embryos and appeared higher in the hatched ones. The expression level of IGF2 mRNA appeared higher than that of IGF1 mRNA in hatched embryos. In unhatched embryos IGF1, IGF2, and PTGS2 mRNA levels were below the detection limit. PMID:24481956

  4. Evolution of the syntrophic interaction between Desulfovibrio vulgaris and Methanosarcina barkeri: involvement of an ancient horizontal gene transfer

    SciTech Connect

    Scholten, Johannes C.; Culley, David E.; Brockman, Fred J.; Wu, Gang; Zhang, Weiwen

    2007-01-05

    The sulfate reducing bacteria Desulfovibrio vulgaris and the methanogenic archaea Methanosarcina barkeri can grow syntrophically on lactate. In this study, three functionally unknown genes of D. vulgaris, DVU2103, DVU2104 and DVU2108, were found to be up-regulated 2-4 fold following the lifestyle shift from syntroph to sulfatereducer; moreover, none of these genes were regulated when D. vulgaris was grown alone in various pure culture conditions. These results suggest that these genes may play roles related to the lifestyle change of D. vulgaris from syntroph to sulfate reducer. This hypothesis is further supported by phylogenomic analyses showing that homologies of these genes were only narrowly present in several groups of bacteria, most of which are restricted to a syntrophic life-style, such as Pelobacter carbinolicus, Syntrophobacter fumaroxidans, Syntrophomonas wolfei and Syntrophus aciditrophicus. Phylogenetic analysis showed that the genes tended to be clustered with archaeal genera, and they were rooted on archaeal species in the phylogenetic trees, suggesting that they originated from an archaeal methanogen and were horizontally transferred to a common ancestor of delta- Proteobacteria, Clostridia and Thermotogae. While lost in most species during evolution, these genes appear to have been retained in bacteria capable of syntrophic relationships, probably due to their providing a selective advantage. In addition, no significant bias in codon and amino acid usages was detected between these genes and the rest of the D. vulgaris genome, suggesting these gene transfers may have occurred early in the evolutionary history so that sufficient time has elapsed to allow an adaptation to the codon and amino acid usages of D. vulgaris. This report provides novel insights into the origin and evolution of bacterial genes involved in the syntrophic lifestyle.

  5. A JAZ Protein in Astragalus sinicus Interacts with a Leghemoglobin through the TIFY Domain and Is Involved in Nodule Development and Nitrogen Fixation

    PubMed Central

    Li, Yixing; Xu, Meng; Wang, Ning; Li, Youguo

    2015-01-01

    Leghemoglobins (Lbs) play an important role in legumes-rhizobia symbiosis. Lbs bind O2 and protect nitrogenase activity from damage by O2 in nodules, therefore, they are regarded as a marker of active nitrogen fixation in nodules. Additionally, Lbs are involved in the nitric oxide (NO) signaling pathway, acting as a NO scavenger during nodule development and nitrogen fixation. However, regulators responsible for Lb expression and modulation of Lb activity have not been characterized. In our previous work, a Jasmonate-Zim-domain (JAZ) protein interacting with a Lb (AsB2510) in Astragalus sinicus was identified and designated AsJAZ1. In this study, the interaction between AsJAZ1 and AsB2510 was verified using a yeast two-hybrid system and in vitro Glutathione S-transferase (GST) pull-down assays, resulting in identification of the interaction domain as a TIFY (previously known as zinc-finger protein expressed in inflorescence meristem, ZIM) domain. TIFY domain is named after the most conserved amino acids within the domain. Bimolecular fluorescence complementation (BiFC) was used to confirm the interaction between AsJAZ1 and AsB2510 in tobacco cells, demonstrating that AsJAZ1-AsB2510 interaction was localized to the cell membrane and cytoplasm. Furthermore, the expression patterns and the symbiotic phenotypes of AsJAZ1 were investigated. Knockdown of AsJAZ1 expression via RNA interference led to decreased number of nodules, abnormal development of bacteroids, accumulation of poly-x-hydroxybutyrate (PHB) and loss of nitrogenase activity. Taken together, our results suggest that AsJAZ1 interacts with AsB2510 and participates in nodule development and nitrogen fixation. Our results provide novel insights into the functions of Lbs or JAZ proteins during legume-rhizobia symbiosis. PMID:26460857

  6. A JAZ Protein in Astragalus sinicus Interacts with a Leghemoglobin through the TIFY Domain and Is Involved in Nodule Development and Nitrogen Fixation.

    PubMed

    Li, Yixing; Xu, Meng; Wang, Ning; Li, Youguo

    2015-01-01

    Leghemoglobins (Lbs) play an important role in legumes-rhizobia symbiosis. Lbs bind O2 and protect nitrogenase activity from damage by O2 in nodules, therefore, they are regarded as a marker of active nitrogen fixation in nodules. Additionally, Lbs are involved in the nitric oxide (NO) signaling pathway, acting as a NO scavenger during nodule development and nitrogen fixation. However, regulators responsible for Lb expression and modulation of Lb activity have not been characterized. In our previous work, a Jasmonate-Zim-domain (JAZ) protein interacting with a Lb (AsB2510) in Astragalus sinicus was identified and designated AsJAZ1. In this study, the interaction between AsJAZ1 and AsB2510 was verified using a yeast two-hybrid system and in vitro Glutathione S-transferase (GST) pull-down assays, resulting in identification of the interaction domain as a TIFY (previously known as zinc-finger protein expressed in inflorescence meristem, ZIM) domain. TIFY domain is named after the most conserved amino acids within the domain. Bimolecular fluorescence complementation (BiFC) was used to confirm the interaction between AsJAZ1 and AsB2510 in tobacco cells, demonstrating that AsJAZ1-AsB2510 interaction was localized to the cell membrane and cytoplasm. Furthermore, the expression patterns and the symbiotic phenotypes of AsJAZ1 were investigated. Knockdown of AsJAZ1 expression via RNA interference led to decreased number of nodules, abnormal development of bacteroids, accumulation of poly-x-hydroxybutyrate (PHB) and loss of nitrogenase activity. Taken together, our results suggest that AsJAZ1 interacts with AsB2510 and participates in nodule development and nitrogen fixation. Our results provide novel insights into the functions of Lbs or JAZ proteins during legume-rhizobia symbiosis. PMID:26460857

  7. How Accurate Are the Minnesota Density Functionals for Noncovalent Interactions, Isomerization Energies, Thermochemistry, and Barrier Heights Involving Molecules Composed of Main-Group Elements?

    PubMed

    Mardirossian, Narbe; Head-Gordon, Martin

    2016-09-13

    The 14 Minnesota density functionals published between the years 2005 and early 2016 are benchmarked on a comprehensive database of 4986 data points (84 data sets) involving molecules composed of main-group elements. The database includes noncovalent interactions, isomerization energies, thermochemistry, and barrier heights, as well as equilibrium bond lengths and equilibrium binding energies of noncovalent dimers. Additionally, the sensitivity of the Minnesota density functionals to the choice of basis set and integration grid is explored for both noncovalent interactions and thermochemistry. Overall, the main strength of the hybrid Minnesota density functionals is that the best ones provide very good performance for thermochemistry (e.g., M06-2X), barrier heights (e.g., M08-HX, M08-SO, MN15), and systems heavily characterized by self-interaction error (e.g., M06-2X, M08-HX, M08-SO, MN15), while the main weakness is that none of them are state-of-the-art for the full spectrum of noncovalent interactions and isomerization energies (although M06-2X is recommended from the 10 hybrid Minnesota functionals). Similarly, the main strength of the local Minnesota density functionals is that the best ones provide very good performance for thermochemistry (e.g., MN15-L), barrier heights (e.g., MN12-L), and systems heavily characterized by self-interaction error (e.g., MN12-L and MN15-L), while the main weakness is that none of them are state-of-the-art for the full spectrum of noncovalent interactions and isomerization energies (although M06-L is clearly the best from the four local Minnesota functionals). As an overall guide, M06-2X and MN15 are perhaps the most broadly useful hybrid Minnesota functionals, while M06-L and MN15-L are perhaps the most broadly useful local Minnesota functionals, although each has different strengths and weaknesses. PMID:27537680

  8. Involvement of cyan and ester groups in surface interactions of aerosil-cyanophenyl alkyl benzoate systems with high silica density: Infrared investigations

    NASA Astrophysics Data System (ADS)

    Frunza, Ligia; Frunza, Stefan; Zgura, Irina; Beica, Traian; Gheorghe, Nicoleta; Ganea, Paul; Stoenescu, Daniel; Dinescu, Adrian; Schönhals, Andreas

    2010-04-01

    Composites prepared from aerosil A380 and liquid crystals (LCs) of 4- n-alkyl-4'-cyanophenyl benzoate type, with four to six carbon atoms in the alkyl chain were investigated by infrared spectroscopy. Their high silica content (of 2-7 g aerosil/1 g of LC) was given by thermogravimetric investigations and allows the observation of a rather thin LC layer on the silica particles. Several surface species onto the external surface of the grains were demonstrated. Arguments are given that monomer and dimer species are present in the bulk cyanophenyl benzoate materials while bulk-like species along with hydrogen-bonded ones coexist in the so-called surface layer of the composites. The main interaction of LC molecules with the aerosil surface is by hydrogen bonding taking place with the involvement of the cyan group. There is a contribution of ester carbonyl group to these surface interactions but this cannot be well quantified.

  9. Co-conservation of rRNA tetraloop sequences and helix length suggests involvement of the tetraloops in higher-order interactions

    NASA Technical Reports Server (NTRS)

    Hedenstierna, K. O.; Siefert, J. L.; Fox, G. E.; Murgola, E. J.

    2000-01-01

    Terminal loops containing four nucleotides (tetraloops) are common in structural RNAs, and they frequently conform to one of three sequence motifs, GNRA, UNCG, or CUUG. Here we compare available sequences and secondary structures for rRNAs from bacteria, and we show that helices capped by phylogenetically conserved GNRA loops display a strong tendency to be of conserved length. The simplest interpretation of this correlation is that the conserved GNRA loops are involved in higher-order interactions, intramolecular or intermolecular, resulting in a selective pressure for maintaining the lengths of these helices. A small number of conserved UNCG loops were also found to be associated with conserved length helices, consistent with the possibility that this type of tetraloop also takes part in higher-order interactions.

  10. Arabidopsis ATG8-INTERACTING PROTEIN1 Is Involved in Autophagy-Dependent Vesicular Trafficking of Plastid Proteins to the Vacuole[W][OPEN

    PubMed Central

    Michaeli, Simon; Honig, Arik; Levanony, Hanna; Peled-Zehavi, Hadas; Galili, Gad

    2014-01-01

    Selective autophagy has been extensively studied in various organisms, but knowledge regarding its functions in plants, particularly in organelle turnover, is limited. We have recently discovered ATG8-INTERACTING PROTEIN1 (ATI1) from Arabidopsis thaliana and showed that following carbon starvation it is localized on endoplasmic reticulum (ER)-associated bodies that are subsequently transported to the vacuole. Here, we show that following carbon starvation ATI1 is also located on bodies associating with plastids, which are distinct from the ER ATI bodies and are detected mainly in senescing cells that exhibit plastid degradation. Additionally, these plastid-localized bodies contain a stroma protein marker as cargo and were observed budding and detaching from plastids. ATI1 interacts with plastid-localized proteins and was further shown to be required for the turnover of one of them, as a representative. ATI1 on the plastid bodies also interacts with ATG8f, which apparently leads to the targeting of the plastid bodies to the vacuole by a process that requires functional autophagy. Finally, we show that ATI1 is involved in Arabidopsis salt stress tolerance. Taken together, our results implicate ATI1 in autophagic plastid-to-vacuole trafficking through its ability to interact with both plastid proteins and ATG8 of the core autophagy machinery. PMID:25281689

  11. Calmodulin activation of an endoplasmic reticulum-located calcium pump involves an interaction with the N-terminal autoinhibitory domain

    NASA Technical Reports Server (NTRS)

    Hwang, I.; Harper, J. F.; Liang, F.; Sze, H.

    2000-01-01

    To investigate how calmodulin regulates a unique subfamily of Ca(2+) pumps found in plants, we examined the kinetic properties of isoform ACA2 identified in Arabidopsis. A recombinant ACA2 was expressed in a yeast K616 mutant deficient in two endogenous Ca(2+) pumps. Orthovanadate-sensitive (45)Ca(2+) transport into vesicles isolated from transformants demonstrated that ACA2 is a Ca(2+) pump. Ca(2+) pumping by the full-length protein (ACA2-1) was 4- to 10-fold lower than that of the N-terminal truncated ACA2-2 (Delta2-80), indicating that the N-terminal domain normally acts to inhibit the pump. An inhibitory sequence (IC(50) = 4 microM) was localized to a region within valine-20 to leucine-44, because a peptide corresponding to this sequence lowered the V(max) and increased the K(m) for Ca(2+) of the constitutively active ACA2-2 to values comparable to the full-length pump. The peptide also blocked the activity (IC(50) = 7 microM) of a Ca(2+) pump (AtECA1) belonging to a second family of Ca(2+) pumps. This inhibitory sequence appears to overlap with a calmodulin-binding site in ACA2, previously mapped between aspartate-19 and arginine-36 (J.F. Harper, B. Hong, I. Hwang, H.Q. Guo, R. Stoddard, J.F. Huang, M.G. Palmgren, H. Sze inverted question mark1998 J Biol Chem 273: 1099-1106). These results support a model in which the pump is kept "unactivated" by an intramolecular interaction between an autoinhibitory sequence located between residues 20 and 44 and a site in the Ca(2+) pump core that is highly conserved between different Ca(2+) pump families. Results further support a model in which activation occurs as a result of Ca(2+)-induced binding of calmodulin to a site overlapping or immediately adjacent to the autoinhibitory sequence.

  12. Investigation of cyclooxygenase and signaling pathways involved in human platelet aggregation mediated by synergistic interaction of various agonists

    PubMed Central

    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 Ca2+ 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 Ca2+ channels in platelets. Overall, our results show that PLC and MAPK inhibitors proved to inhibit the

  13. Investigation of cyclooxygenase and signaling pathways involved in human platelet aggregation mediated by synergistic interaction of various agonists.

    PubMed

    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

  14. Strong ferromagnetic exchange interactions in hinge-like Dy(O2Cu)2 complexes involving double oxygen bridges.

    PubMed

    Ida, Yumi; Ghosh, Soumavo; Ghosh, Ashutosh; Nojiri, Hiroyuki; Ishida, Takayuki

    2015-10-01

    Two trinuclear isomeric compounds, [{(Cu(II)(salpn))(Me(CO)Me)}2Dy(III)(NO3)3] (1) and [{Cu(II)(salpn)}2Dy(III)(H2O)(NO3)3]·MeOH (2), along with one polymeric compound, {[{Cu(II)(salpn)}2Dy(III)(NO3)3bpy]·MeOH·H2O}n (3), were synthesized using a metalloligand, [Cu(II)(salpn)], where H2salpn and bpy stand for N,N'-bis(salicylidene)-1,3-propanediamine and 4,4'-bipyridine, respectively. Compounds 1 and 2 were selectively prepared with two solvents: the less polar acetone led to the exclusive crystallization of 1 with a transoid trinuclear architecture, while more polar solvent methanol provided sole construction of 2 with a cisoid trinuclear architecture. Compound 3 was prepared from 1 or 2 after bpy was introduced as a bridge. The Dy and Cu ions are doubly bridged with oxygen atoms, and the core DyO2Cu skeletons are characterized by different "butterfly angles" of 140.9(1)°, 147.1(19)°, and 142.4(2)° for 1, 2, and 3, respectively. We have examined the molecular structures and magnetic properties of 1-3 using high-frequency electron paramagnetic resonance (HF-EPR), magnetization, and magnetic susceptibility techniques. These compounds showed slow magnetization reversal in the measurements of alternating current magnetic susceptibility. We analyzed EPR frequency-field diagrams using an effective spin-Hamiltonian including only one doublet of Dy sublevels and found that the exchange couplings are ferromagnetic in all compounds. The exchange coupling parameters JDy-Cu of 1, 2, and 3 were determined as 2.25 ± 0.05, 1.82 ± 0.04, and 1.79 ± 0.04 K, respectively. These values are larger than those found in previous research using EPR analysis on [Cu(II)(L(A))(C3H6O)Dy(III)(NO3)3] (H2L(A) = N,N'-bis(3-methoxysalicylidene)-1,3-diamino-2,2-dimethylpropane) and [Dy(III)L(B)2(NO3)2{Cu(II)(CH3OH)}2](NO3)(CH3OH) (H2L(B) = 2,6-bis(acetylaceto)pyridine). The present result shows an advantage of doubly oxygen-bridged motifs to built strong ferromagnetic interactions between

  15. Identification of regions interacting with ovo{sup D} mutations: Potential new genes involved in germline sex determination or differentiation in Drosophila melanogaster

    SciTech Connect

    Pauli, D.; Oliver, B.; Mahowald, A.P.

    1995-02-01

    Only a few Drosophila melanogaster germline sex determination genes are known, and there have been no systematic screens to identify new genes involved in this important biological process. The ovarian phenotypes produced by females mutant for dominant alleles of the ovo gene are modified in flies with altered doses of other loci involved in germline sex determination in Drosophila (Sex-lethal{sup +}, snas fille{sup +} and ovarian tumor{sup +}). This observation constitutes the basis for a screen to identify additional genes required for proper establishment of germline sexual identity. We tested 300 deletions, which together cover {approximately}58% of the euchromatic portion of the genome, for genetic interactions with ovo{sup D}. Hemizygosity for more than a dozen small regions show interactions that either partially suppress or enhance the ovarian phenotypes of females mutant for one or more of the three dominant ovo mutations. These regions probably contain genes whose products act in developmental heirarchies that include ovo{sup +} protein. 40 refs, 7 figs., 5 tabs.

  16. The Interaction between Rice ERF3 and WOX11 Promotes Crown Root Development by Regulating Gene Expression Involved in Cytokinin Signaling.

    PubMed

    Zhao, Yu; Cheng, Saifeng; Song, Yaling; Huang, Yulan; Zhou, Shaoli; Liu, Xiaoyun; Zhou, Dao-Xiu

    2015-09-01

    Crown roots are the main components of the fibrous root system in rice (Oryza sativa). WOX11, a WUSCHEL-related homeobox gene specifically expressed in the emerging crown root meristem, is a key regulator in crown root development. However, the nature of WOX11 function in crown root development has remained elusive. Here, we identified a rice AP2/ERF protein, ERF3, which interacts with WOX11 and was expressed in crown root initials and during crown root growth. Functional analysis revealed that ERF3 was essential for crown root development and acts in auxin- and cytokinin-responsive gene expression. Downregulation of ERF3 in wox11 mutants produced a more severe root phenotype. Also, increased expression of ERF3 could partially complement wox11, indicating that the two genes functioned cooperatively to regulate crown root development. ERF3 and WOX11 shared a common target, the cytokinin-responsive gene RR2. The expression of ERF3 and WOX11 only partially overlapped, underlining a spatio-temporal control of RR2 expression and crown root development. Furthermore, ERF3-regulated RR2 expression was involved in crown root initiation, while the ERF3/WOX11 interaction likely repressed RR2 during crown root elongation. These results define a mechanism regulating gene expression involved in cytokinin signaling during different stages of crown root development in rice. PMID:26307379

  17. Traf2- and Nck-interacting kinase (TNIK) is involved in the anti-cancer mechanism of dovitinib in human multiple myeloma IM-9 cells.

    PubMed

    Chon, Hae Jung; Lee, Yura; Bae, Kyoung Jun; Byun, Byung Jin; Kim, Soon Ae; Kim, Jiyeon

    2016-07-01

    Traf2- and Nck-interacting kinase (TNIK) is a member of the germinal center kinase family. TNIK was first identified as a kinase that is involved in regulating cytoskeletal organization in many types of cells, and it was recently proposed as a novel therapeutic target in several types of human cancers. Although previous studies suggest that TNIK plays a pivotal role in cancer cell survival and prognosis, its function in hematological cancer cell survival has not been investigated. Here we investigated the relationship between TNIK function and cell viability in multiple myeloma IM-9 cells using TNIK small interfering RNA (siRNA) transfection and dovitinib treatment. Treatment of IM-9 cells with TNIK siRNA and dovitinib treatment reduced cell proliferation. The ATP competing kinase assay and western blot analysis showed that dovitinib strongly inhibited both the interaction of TNIK with ATP (K i, 13 nM) and the activation of Wnt signaling effectors such as β-catenin and TCF4. Dovitinib also induced caspase-dependent apoptosis in IM-9 cells without significant cytotoxicity in PBMCs. Our results provide new evidence that TNIK may be involved in the proliferation of multiple myeloma IM-9 cells and in the anti-cancer activity of dovitinib via inhibition of the endogenous Wnt signaling pathway. PMID:26995282

  18. The Interaction between Rice ERF3 and WOX11 Promotes Crown Root Development by Regulating Gene Expression Involved in Cytokinin Signaling[OPEN

    PubMed Central

    Song, Yaling; Huang, Yulan

    2015-01-01

    Crown roots are the main components of the fibrous root system in rice (Oryza sativa). WOX11, a WUSCHEL-related homeobox gene specifically expressed in the emerging crown root meristem, is a key regulator in crown root development. However, the nature of WOX11 function in crown root development has remained elusive. Here, we identified a rice AP2/ERF protein, ERF3, which interacts with WOX11 and was expressed in crown root initials and during crown root growth. Functional analysis revealed that ERF3 was essential for crown root development and acts in auxin- and cytokinin-responsive gene expression. Downregulation of ERF3 in wox11 mutants produced a more severe root phenotype. Also, increased expression of ERF3 could partially complement wox11, indicating that the two genes functioned cooperatively to regulate crown root development. ERF3 and WOX11 shared a common target, the cytokinin-responsive gene RR2. The expression of ERF3 and WOX11 only partially overlapped, underlining a spatio-temporal control of RR2 expression and crown root development. Furthermore, ERF3-regulated RR2 expression was involved in crown root initiation, while the ERF3/WOX11 interaction likely repressed RR2 during crown root elongation. These results define a mechanism regulating gene expression involved in cytokinin signaling during different stages of crown root development in rice. PMID:26307379

  19. AFM analysis of the multiple types of molecular interactions involved in rituximab lymphoma therapy on patient tumor cells and NK cells.

    PubMed

    Li, Mi; Xiao, Xiubin; Zhang, Weijing; Liu, Lianqing; Xi, Ning; Wang, Yuechao

    2014-08-01

    Rituximab is a monoclonal antibody drug approved for the treatment of patients with lymphomas. Rituximab's main killing mechanism is antibody-dependent cellular cytotoxicity (ADCC). During ADCC, rituximab's fragment antigen binding (Fab) region binds to the CD20 antigen on the tumor cell and its fragment crystallizable (Fc) region binds to the Fc receptor (FcR) on the natural killer (NK) cells. In this study, two types of molecular interactions (CD20-rituximab, FcR-rituximab) involved in ADCC were measured simultaneously on cells prepared from biopsy specimens of lymphoma patients by utilizing atomic force microscopy (AFM) with functionalized tips carrying rituximab. NK cells were detected by specific NKp46 fluorescent labeling and tumor cells were detected by specific ROR1 fluorescent labeling. Based on the fluorescence recognition, the binding affinity and distribution of FcRs on NK cells, and CD20 on tumor cells, were quantitatively measured and mapped. The binding affinity and distribution of FcRs (on NK cells) and CD20 (on tumor cells) were associated with rituximab clinical efficacy. The experimental results provide a new approach to simultaneously quantify the multiple types of molecular interactions involved in rituximab ADCC mechanism on patient biopsy cells, which is of potential clinical significance to predict rituximab efficacy for personalized medicine. PMID:25117605

  20. Identification of the cytochrome P450 enzymes involved in the metabolism of cisapride: in vitro studies of potential co-medication interactions

    PubMed Central

    Bohets, H; Lavrijsen, K; Hendrickx, J; van Houdt, J; van Genechten, V; Verboven, P; Meuldermans, W; Heykants, J

    2000-01-01

    Cisapride is a prokinetic drug that is widely used to facilitate gastrointestinal tract motility.Structurally, cisapride is a substituted piperidinyl benzamide that interacts with 5-hydroxytryptamine-4 receptors and which is largely without central depressant or antidopaminergic side-effects.The aims of this study were to investigate the metabolism of cisapride in human liver microsomes and to determine which cytochrome P-450 (CYP) isoenzyme(s) are involved in cisapride biotransformation. Additionally, the effects of various drugs on the metabolism of cisapride were investigated.The major in vitro metabolite of cisapride was formed by oxidative N-dealkylation at the piperidine nitrogen, leading to the production of norcisapride.By using competitive inhibition data, correlation studies and heterologous expression systems, it was demonstrated that CYP3A4 was the major CYP involved. CYP2A6 also contributed to the metabolism of cisapride, albeit to a much lesser extent.The mean apparent Km against cisapride was 8.6±3.5 μM (n=3). The peak plasma levels of cisapride under normal clinical practice are approximately 0.17 μM; therefore it is unlikely that cisapride would inhibit the metabolism of co-administered drugs.In this in vitro study the inhibitory effects of 44 drugs were tested for any effect on cisapride biotransformation. In conclusion, 34 of the drugs are unlikely to have a clinically relevant interaction; however, the antidepressant nefazodone, the macrolide antibiotic troleandomycin, the HIV-1 protease inhibitors ritonavir and indinavir and the calcium channel blocker mibefradil inhibited the metabolism of cisapride and these interactions are likely to be of clinical relevance. Furthermore, the antimycotics ketoconazole, miconazole, hydroxy-itraconazole, itraconazole and fluconazole, when administered orally or intravenously, would inhibit cisapride metabolism. PMID:10780971

  1. Gene network and familial analyses uncover a gene network involving Tbx5/Osr1/Pcsk6 interaction in the second heart field for atrial septation.

    PubMed

    Zhang, Ke K; Xiang, Menglan; Zhou, Lun; Liu, Jielin; Curry, Nathan; Heine Suñer, Damian; Garcia-Pavia, Pablo; Zhang, Xiaohua; Wang, Qin; Xie, Linglin

    2016-03-15

    Atrial septal defects (ASDs) are a common human congenital heart disease (CHD) that can be induced by genetic abnormalities. Our previous studies have demonstrated a genetic interaction between Tbx5 and Osr1 in the second heart field (SHF) for atrial septation. We hypothesized that Osr1 and Tbx5 share a common signaling networking and downstream targets for atrial septation. To identify this molecular networks, we acquired the RNA-Seq transcriptome data from the posterior SHF of wild-type, Tbx5(+/) (-), Osr1(+/-), Osr1(-/-) and Tbx5(+/-)/Osr1(+/-) mutant embryos. Gene set analysis was used to identify the Kyoto Encyclopedia of Genes and Genomes pathways that were affected by the doses of Tbx5 and Osr1. A gene network module involving Tbx5 and Osr1 was identified using a non-parametric distance metric, distance correlation. A subset of 10 core genes and gene-gene interactions in the network module were validated by gene expression alterations in posterior second heart field (pSHF) of Tbx5 and Osr1 transgenic mouse embryos, a time-course gene expression change during P19CL6 cell differentiation. Pcsk6 was one of the network module genes that were linked to Tbx5. We validated the direct regulation of Tbx5 on Pcsk6 using immunohistochemical staining of pSHF, ChIP-quantitative polymerase chain reaction and luciferase reporter assay. Importantly, we identified Pcsk6 as a novel gene associated with ASD via a human genotyping study of an ASD family. In summary, our study implicated a gene network involving Tbx5, Osr1 and Pcsk6 interaction in SHF for atrial septation, providing a molecular framework for understanding the role of Tbx5 in CHD ontogeny. PMID:26744331

  2. Comparative Transcriptome Analysis of Adipose Tissues Reveals that ECM-Receptor Interaction Is Involved in the Depot-Specific Adipogenesis in Cattle.

    PubMed

    Lee, Hyun-Jeong; Jang, Mi; Kim, Hyeongmin; Kwak, Woori; Park, Woncheoul; Hwang, Jae Yeon; Lee, Chang-Kyu; Jang, Gul Won; Park, Mi Na; Kim, Hyeong-Cheol; Jeong, Jin Young; Seo, Kang Seok; Kim, Heebal; Cho, Seoae; Lee, Bo-Young

    2013-01-01

    Adipocytes mainly function as energy storage and endocrine cells. Adipose tissues showed the biological and genetic difference based on their depots. The difference of adipocytes between depots might be influenced by the inherent genetic programing for adipogenesis. We used RNA-seq technique to investigate the transcriptomes in 3 adipose tissues of omental (O), subcutaneous (S) and intramuscular (I) fats in cattle. Sequence reads were obtained from Illumina HiSeq2000 and mapped to the bovine genome using Tophat2. Differentially expressed genes (DEG) between adipose tissues were detected by EdgeR. We identified 5797, 2156, and 5455 DEGs in the comparison between OI, OS, and IS respectively and also found 5657 DEGs in the comparison between the intramuscular and the combined omental and subcutaneous fats (C) (FDR<0.01). Depot specifically up- and down- regulated DEGs were 853 in S, 48 in I, and 979 in O. The numbers of DEGs and functional annotation studies suggested that I had the different genetic profile compared to other two adipose tissues. In I, DEGs involved in the developmental process (eg. EGR2, FAS, and KLF7) were up-regulated and those in the immune system process were down-regulated. Many DEGs from the adipose tissues were enriched in the various GO terms of developmental process and KEGG pathway analysis showed that the ECM-receptor interaction was one of commonly enriched pathways in all of the 3 adipose tissues and also functioned as a sub-pathway of other enriched pathways. However, genes involved in the ECM-receptor interaction were differentially regulated depending on the depots. Collagens, main ECM constituents, were significantly up-regulated in S and integrins, transmembrane receptors, were up-regulated in I. Different laminins were up-regulated in the different depots. This comparative transcriptome analysis of three adipose tissues suggested that the interactions between ECM components and transmembrane receptors of fat cells depend on the

  3. Identification of domains on the extrinsic 23 kDa protein possibly involved in electrostatic interaction with the extrinsic 33 kDa protein in spinach photosystem II.

    PubMed

    Tohri, Akihiko; Dohmae, Naoshi; Suzuki, Takehiro; Ohta, Hisataka; Inoue, Yasunori; Enami, Isao

    2004-03-01

    To elucidate the domains on the extrinsic 23 kDa protein involved in electrostatic interaction with the extrinsic 33 kDa protein in spinach photosystem II, we modified amino or carboxyl groups of the 23 kDa protein to uncharged methyl ester groups with N-succinimidyl propionate or glycine methyl ester in the presence of a water-soluble carbodiimide, respectively. The N-succinimidyl propionate-modified 23 kDa protein did not bind to the 33 kDa protein associated with PSII membranes, whereas the glycine methyl ester-modified 23 kDa protein completely bound. This indicates that positive charges on the 23 kDa protein are important for electrostatic interaction with the 33 kDa protein associated with the PSII membranes. Mapping of the N-succinimidyl propionate-modified sites of the 23 kDa protein was performed using Staphylococcus V8 protease digestion of the modified protein followed by determination of the mass of the resultant peptide fragments with MALDI-TOF MS. The results showed that six domains (Lys11-Lys14, Lys27-Lys38, Lys40, Lys90-Lys96, Lys143-Lys152, Lys166-Lys174) were modified with N-succinimidyl propionate. In these domains, Lys11, Lys13, Lys33, Lys38, Lys143, Lys166, Lys170 and Lys174 were wholly conserved in the 23 kDa protein from 12 species of higher plants. These positively charged lysyl residues on the 23 kDa protein may be involved in electrostatic interactions with the negatively charged carboxyl groups on the 33 kDa protein, the latter has been suggested to be important for the 23 kDa binding [Bricker, T.M. & Frankel, L.K. (2003) Biochemistry42, 2056-2061]. PMID:15009208

  4. Comparative Transcriptome Analysis of Adipose Tissues Reveals that ECM-Receptor Interaction Is Involved in the Depot-Specific Adipogenesis in Cattle

    PubMed Central

    Lee, Hyun-Jeong; Jang, Mi; Kim, Hyeongmin; Kwak, Woori; Park, WonCheoul; Hwang, Jae Yeon; Lee, Chang-Kyu; Jang, Gul Won; Park, Mi Na; Kim, Hyeong-Cheol; Jeong, Jin Young; Seo, Kang Seok; Kim, Heebal; Cho, Seoae; Lee, Bo-Young

    2013-01-01

    Adipocytes mainly function as energy storage and endocrine cells. Adipose tissues showed the biological and genetic difference based on their depots. The difference of adipocytes between depots might be influenced by the inherent genetic programing for adipogenesis. We used RNA-seq technique to investigate the transcriptomes in 3 adipose tissues of omental (O), subcutaneous (S) and intramuscular (I) fats in cattle. Sequence reads were obtained from Illumina HiSeq2000 and mapped to the bovine genome using Tophat2. Differentially expressed genes (DEG) between adipose tissues were detected by EdgeR. We identified 5797, 2156, and 5455 DEGs in the comparison between OI, OS, and IS respectively and also found 5657 DEGs in the comparison between the intramuscular and the combined omental and subcutaneous fats (C) (FDR<0.01). Depot specifically up- and down- regulated DEGs were 853 in S, 48 in I, and 979 in O. The numbers of DEGs and functional annotation studies suggested that I had the different genetic profile compared to other two adipose tissues. In I, DEGs involved in the developmental process (eg. EGR2, FAS, and KLF7) were up-regulated and those in the immune system process were down-regulated. Many DEGs from the adipose tissues were enriched in the various GO terms of developmental process and KEGG pathway analysis showed that the ECM-receptor interaction was one of commonly enriched pathways in all of the 3 adipose tissues and also functioned as a sub-pathway of other enriched pathways. However, genes involved in the ECM-receptor interaction were differentially regulated depending on the depots. Collagens, main ECM constituents, were significantly up-regulated in S and integrins, transmembrane receptors, were up-regulated in I. Different laminins were up-regulated in the different depots. This comparative transcriptome analysis of three adipose tissues suggested that the interactions between ECM components and transmembrane receptors of fat cells depend on the

  5. GUN1 Controls Accumulation of the Plastid Ribosomal Protein S1 at the Protein Level and Interacts with Proteins Involved in Plastid Protein Homeostasis.

    PubMed

    Tadini, Luca; Pesaresi, Paolo; Kleine, Tatjana; Rossi, Fabio; Guljamow, Arthur; Sommer, Frederik; Mühlhaus, Timo; Schroda, Michael; Masiero, Simona; Pribil, Mathias; Rothbart, Maxi; Hedtke, Boris; Grimm, Bernhard; Leister, Dario

    2016-03-01

    Developmental or metabolic changes in chloroplasts can have profound effects on the rest of the plant cell. Such intracellular responses are associated with signals that originate in chloroplasts and convey information on their physiological status to the nucleus, which leads to large-scale changes in gene expression (retrograde signaling). A screen designed to identify components of retrograde signaling resulted in the discovery of the so-called genomes uncoupled (gun) mutants. Genetic evidence suggests that the chloroplast protein GUN1 integrates signals derived from perturbations in plastid redox state, plastid gene expression, and tetrapyrrole biosynthesis (TPB) in Arabidopsis (Arabidopsis thaliana) seedlings, exerting biogenic control of chloroplast functions. However, the molecular mechanism by which GUN1 integrates retrograde signaling in the chloroplast is unclear. Here we show that GUN1 also operates in adult plants, contributing to operational control of chloroplasts. The gun1 mutation genetically interacts with mutations of genes for the chloroplast ribosomal proteins S1 (PRPS1) and L11. Analysis of gun1 prps1 lines indicates that GUN1 controls PRPS1 accumulation at the protein level. The GUN1 protein physically interacts with proteins involved in chloroplast protein homeostasis based on coimmunoprecipitation experiments. Furthermore, yeast two-hybrid and bimolecular fluorescence complementation experiments suggest that GUN1 might transiently interact with several TPB enzymes, including Mg-chelatase subunit D (CHLD) and two other TPB enzymes known to activate retrograde signaling. Moreover, the association of PRPS1 and CHLD with protein complexes is modulated by GUN1. These findings allow us to speculate that retrograde signaling might involve GUN1-dependent formation of protein complexes. PMID:26823545

  6. A reversible Renilla luciferase protein complementation assay for rapid identification of protein-protein interactions reveals the existence of an interaction network involved in xyloglucan biosynthesis in the plant Golgi apparatus.

    PubMed

    Lund, Christian H; Bromley, Jennifer R; Stenbæk, Anne; Rasmussen, Randi E; Scheller, Henrik V; Sakuragi, Yumiko

    2015-01-01

    A growing body of evidence suggests that protein-protein interactions (PPIs) occur amongst glycosyltransferases (GTs) required for plant glycan biosynthesis (e.g. cell wall polysaccharides and N-glycans) in the Golgi apparatus, and may control the functions of these enzymes. However, identification of PPIs in the endomembrane system in a relatively fast and simple fashion is technically challenging, hampering the progress in understanding the functional coordination of the enzymes in Golgi glycan biosynthesis. To solve the challenges, we adapted and streamlined a reversible Renilla luciferase protein complementation assay (Rluc-PCA), originally reported for use in human cells, for transient expression in Nicotiana benthamiana. We tested Rluc-PCA and successfully identified luminescence complementation amongst Golgi-localizing GTs known to form a heterodimer (GAUT1 and GAUT7) and those which homooligomerize (ARAD1). In contrast, no interaction was shown between negative controls (e.g. GAUT7, ARAD1, IRX9). Rluc-PCA was used to investigate PPIs amongst Golgi-localizing GTs involved in biosynthesis of hemicelluloses. Although no PPI was identified among six GTs involved in xylan biosynthesis, Rluc-PCA confirmed three previously proposed interactions and identified seven novel PPIs amongst GTs involved in xyloglucan biosynthesis. Notably, three of the novel PPIs were confirmed by a yeast-based split-ubiquitin assay. Finally, Gateway-enabled expression vectors were generated, allowing rapid construction of fusion proteins to the Rluc reporters and epitope tags. Our results show that Rluc-PCA coupled with transient expression in N. benthamiana is a fast and versatile method suitable for analysis of PPIs between Golgi resident proteins in an easy and mid-throughput fashion in planta. PMID:25326916

  7. A reversible Renilla luciferase protein complementation assay for rapid identification of protein-protein interactions reveals the existence of an interaction network involved in xyloglucan biosynthesis in the plant Golgi apparatus

    SciTech Connect

    Lund, C. H.; Bromley, J. R.; Stenbaek, A.; Rasmussen, R. E.; Scheller, H. V.; Sakuragi, Y.

    2014-10-18

    A growing body of evidence suggests that protein–protein interactions (PPIs) occur amongst glycosyltransferases (GTs) required for plant glycan biosynthesis (e.g. cell wall polysaccharides and N-glycans) in the Golgi apparatus, and may control the functions of these enzymes. However, identification of PPIs in the endomembrane system in a relatively fast and simple fashion is technically challenging, hampering the progress in understanding the functional coordination of the enzymes in Golgi glycan biosynthesis. To solve the challenges, we adapted and streamlined a reversible Renilla luciferase protein complementation assay (Rluc-PCA), originally reported for use in human cells, for transient expression in Nicotiana benthamiana. We tested Rluc-PCA and successfully identified luminescence complementation amongst Golgi-localizing GTs known to form a heterodimer (GAUT1 and GAUT7) and those which homooligomerize (ARAD1). In contrast, no interaction was shown between negative controls (e.g. GAUT7, ARAD1, IRX9). Rluc-PCA was used to investigate PPIs amongst Golgi-localizing GTs involved in biosynthesis of hemicelluloses. Although no PPI was identified among six GTs involved in xylan biosynthesis, Rluc-PCA confirmed three previously proposed interactions and identified seven novel PPIs amongst GTs involved in xyloglucan biosynthesis. Notably, three of the novel PPIs were confirmed by a yeast-based split-ubiquitin assay. Finally, Gateway-enabled expression vectors were generated, allowing rapid construction of fusion proteins to the Rluc reporters and epitope tags. In conclusion, our results show that Rluc-PCA coupled with transient expression in N. benthamiana is a fast and versatile method suitable for analysis of PPIs between Golgi resident proteins in an easy and mid-throughput fashion in planta.

  8. A reversible Renilla luciferase protein complementation assay for rapid identification of protein-protein interactions reveals the existence of an interaction network involved in xyloglucan biosynthesis in the plant Golgi apparatus

    DOE PAGESBeta

    Lund, C. H.; Bromley, J. R.; Stenbaek, A.; Rasmussen, R. E.; Scheller, H. V.; Sakuragi, Y.

    2014-10-18

    A growing body of evidence suggests that protein–protein interactions (PPIs) occur amongst glycosyltransferases (GTs) required for plant glycan biosynthesis (e.g. cell wall polysaccharides and N-glycans) in the Golgi apparatus, and may control the functions of these enzymes. However, identification of PPIs in the endomembrane system in a relatively fast and simple fashion is technically challenging, hampering the progress in understanding the functional coordination of the enzymes in Golgi glycan biosynthesis. To solve the challenges, we adapted and streamlined a reversible Renilla luciferase protein complementation assay (Rluc-PCA), originally reported for use in human cells, for transient expression in Nicotiana benthamiana. Wemore » tested Rluc-PCA and successfully identified luminescence complementation amongst Golgi-localizing GTs known to form a heterodimer (GAUT1 and GAUT7) and those which homooligomerize (ARAD1). In contrast, no interaction was shown between negative controls (e.g. GAUT7, ARAD1, IRX9). Rluc-PCA was used to investigate PPIs amongst Golgi-localizing GTs involved in biosynthesis of hemicelluloses. Although no PPI was identified among six GTs involved in xylan biosynthesis, Rluc-PCA confirmed three previously proposed interactions and identified seven novel PPIs amongst GTs involved in xyloglucan biosynthesis. Notably, three of the novel PPIs were confirmed by a yeast-based split-ubiquitin assay. Finally, Gateway-enabled expression vectors were generated, allowing rapid construction of fusion proteins to the Rluc reporters and epitope tags. In conclusion, our results show that Rluc-PCA coupled with transient expression in N. benthamiana is a fast and versatile method suitable for analysis of PPIs between Golgi resident proteins in an easy and mid-throughput fashion in planta.« less

  9. Involvement of UDP-glucuronosyltransferases UGT1A9 and UGT2B7 in ethanol glucuronidation, and interactions with common drugs of abuse.

    PubMed

    Al Saabi, Alaa; Allorge, Delphine; Sauvage, François-Ludovic; Tournel, Gilles; Gaulier, Jean-Michel; Marquet, Pierre; Picard, Nicolas

    2013-03-01

    Ethyl glucuronide (EtG) determination is increasingly used in clinical and forensic toxicology to document ethanol consumption. The enzymes involved in EtG production, as well as potential interactions with common drugs of abuse, have not been extensively studied. Activities of human liver (HLM), kidney (HKM), and intestinal (HIM) microsomes, as well as of 12 major human recombinant UDP-glucuronosyltransferases (UGTs), toward ethanol (50 and 500 mM) were evaluated in vitro using liquid chromatography-tandem mass spectrometry. Enzyme kinetic parameters were determined for pooled microsomes and recombinant UGTs with significant activity. Individual contributions of UGTs were estimated using the relative activity factor approach, proposed for scaling activities obtained with cDNA-expressed enzymes to HLM. Interaction of morphine, codeine, lorazepam, oxazepam, nicotine, cotinine, cannabinol, and cannabidiol (5, 10, 15 mg/l) with ethanol (1.15, 4.6, 11.5 g/l; i.e., 25, 100, 250 mM) glucuronidation was assessed using pooled HLM. Ethanol glucuronidation intrinsic clearance (Cl(int)) was 4 and 12.7 times higher for HLM than for HKM and HIM, respectively. All recombinant UGTs, except UGT1A1, 1A6, and 1A10, produced EtG in detectable amounts. UGT1A9 and 2B7 were the most active enzymes, each accounting for 17 and 33% of HLM Cl(int), respectively. Only cannabinol and cannabidiol significantly affected ethanol glucuronidation. Cannabinol increased ethanol glucuronidation in a concentration-dependent manner, whereas cannabidiol significantly inhibited EtG formation in a noncompetitive manner (IC(50) = 1.17 mg/l; inhibition constant (K(i)) = 3.1 mg/l). UGT1A9 and 2B7 are the main enzymes involved in ethanol glucuronidation. In addition, our results suggest that cannabinol and cannabidiol could significantly alter ethanol glucuronidation. PMID:23230132

  10. Brain Innate Immunity in the Regulation of Neuroinflammation: Therapeutic Strategies by Modulating CD200-CD200R Interaction Involve the Cannabinoid System

    PubMed Central

    Hernangómez, Miriam; Carrillo-Salinas, Francisco J; Mecha, Miriam; Correa, Fernando; Mestre, Leyre; Loría, Frida; Feliú, Ana; Docagne, Fabian; Guaza, Carmen

    2014-01-01

    The central nervous system (CNS) innate immune response includes an arsenal of molecules and receptors expressed by professional phagocytes, glial cells and neurons that is involved in host defence and clearance of toxic and dangerous cell debris. However, any uncontrolled innate immune responses within the CNS are widely recognized as playing a major role in the development of autoimmune disorders and neurodegeneration, with multiple sclerosis (MS) Alzheimer's disease (AD) being primary examples. Hence, it is important to identify the key regulatory mechanisms involved in the control of CNS innate immunity and which could be harnessed to explore novel therapeutic avenues. Neuroimmune regulatory proteins (NIReg) such as CD95L, CD200, CD47, sialic acid, complement regulatory proteins (CD55, CD46, fH, C3a), HMGB1, may control the adverse immune responses in health and diseases. In the absence of these regulators, when neurons die by apoptosis, become infected or damaged, microglia and infiltrating immune cells are free to cause injury as well as an adverse inflammatory response in acute and chronic settings. We will herein provide new emphasis on the role of the pair CD200-CD200R in MS and its experimental models: experimental autoimmune encephalomyelitis (EAE) and Theiler’s virus induced demyelinating disease (TMEV-IDD). The interest of the cannabinoid system as inhibitor of inflammation prompt us to introduce our findings about the role of endocannabinoids (eCBs) in promoting CD200-CD200 receptor (CD200R) interaction and the benefits caused in TMEV-IDD. Finally, we also review the current data on CD200-CD200R interaction in AD, as well as, in the aging brain. PMID:24588829