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Results for “Integrative interaction”

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At least 865 records · Page 48Linked to original sources

PubMed1980

Charge selectivity at the lipid-protein interface of membranous Na,K-ATPase.

Lipid interactions with the integral membrane protein Na,K-ATPase (ATP phosphohydrolase, EC 3.6.1.3) purified from the electric organ of Electrophorus electricus were studied by spin labeling. A protein-associated component (boundary layer) in equilibrium with the fluid bilayer is clearly evident in the electron spin resonance spectra. The influence of charge on this equilibrium was determined by varying the head group of the lipid while maintaining the chain length and the position of the label constant. The lipid spin labels were 14-proxylstearylmethyl phosphate and the corresponding dimethylphosphate, alcohol, and quaternary amine. By using a pairwise spectral analysis, as well as a conventional spectral analysis, the binding affinity was found to decrease in the order of negative greater than neutral greater than positive charges. The fraction bound decreased from about 0.57 for the negatively charged phosphate to 0.25 for the positively charged quaternary amine. The amount of each bound lipid was nearly constant over the temperature range investigated (5-35 degrees C). High salt concentrations reversibly abolished the selectivity between the labels, confirming the role of charge in the binding equilibria.

Animals↗

PubMed2004

On the transcriptional regulation of methicillin resistance: MecI repressor in complex with its operator.

Bacterial resistance to antibiotics poses a serious worldwide public health problem due to the high morbidity and mortality caused by infectious diseases. Most hospital-onset infections are associated with methicillin-resistant Staphylococcus aureus (MRSA) strains that have acquired multiple drug resistance to beta-lactam antibiotics. In a response to antimicrobial stress, nearly all clinical MRSA isolates produce beta-lactamase (BlaZ) and a penicillin-binding protein with low affinity for beta-lactam antibiotics (PBP2a, also known as PBP2' or MecA). Both effectors are regulated by homologous signal transduction systems consisting of a sensor/transducer and a transcriptional repressor. MecI (methicillin repressor) blocks mecA but also blaZ transcription and that of itself and the co-transcribed sensor/transducer. The structure of MecI in complex with a cognate operator double-stranded DNA reveals a homodimeric arrangement with a novel C-terminal spiral staircase dimerization domain responsible for dimer integrity. Each protomer interacts with the DNA major groove through a winged helix DNA-binding domain and specifically recognizes the nucleotide sequence 5'-Gua-Thy-Ade-X-Thy-3'. This results in an unusual convex bending of the DNA helix. The structure of this first molecular determinant of methicillin resistance in complex with its target DNA provides insights into its regulatory mechanism and paves the way for new antimicrobial strategies against MRSA.

Amino Acid Sequence↗

PubMed2006

The SWI/SNF chromatin-remodeling complex is a cofactor for Tat transactivation of the HIV promoter.

Tat is a critical viral transactivator essential for human immunodeficiency virus (HIV) gene expression. Activation involves binding to an RNA stem-loop structure and recruitment of the positive transcription elongation factor b. Tat also induces the remodeling of a single nucleosome in the HIV promoter. However, the mechanism of this remodeling has remained unclear. Knockdown of INI-1 and BRG-1, two components of the SWI/SNF chromatin-remodeling complex, suppressed Tat-mediated transactivation. Cells lacking INI-1 (G401 and MON) or BRG-1 (C33A) exhibited defective transactivation by Tat that was restored upon INI-1 and BRG-1 expression, respectively. Tat was co-immunoprecipitated with several SWI/SNF subunits, including INI-1, BRG-1, and beta-actin. The SWI/SNF complex interacted with the integrated HIV promoter in a Tat-dependent manner. We also found that INI-1 and BRG-1 synergized with the p300 acetyltransferase to activate the HIV promoter. This synergism depended on the acetyltransferase activity of p300 and on Tat Lys(50) and Lys(51). In conclusion, Tat-mediated activation of the HIV promoter requires the SWI/SNF complex in synergy with the coactivator p300.

Cell Line↗

PubMed2005

Exploring trial-by-trial modulations of the Simon effect.

The present study investigates sequential modulations of the Simon effect. The Simon effect involves faster responses to spatially corresponding than to noncorresponding stimuli, even when stimulus position is irrelevant. Recently, the Simon effect has been shown to decrease or to disappear after noncorresponding predecessor trials. Possible explanations for these sequential modulations include (a) the gating of position-based response activation (conflict monitoring), (b) repetition or alternation effects, and (c) the interaction between feature integration (binding) processes and stimulus-response (S-R) correspondence. Three experiments tested different predictions of these models by comparing Simon effects after neutral trials with those after corresponding and noncorresponding trials, respectively, and by varying the stimulus-onset asynchrony (SOA) between and within experiments. Experiments 1 and 2 revealed large Simon effects after corresponding trials, intermediate Simon effects after neutral trials, and small (or no) Simon effects after noncorresponding trials. Moreover, some systematic effects of S-R repetitions and S-R alternations were observed. Finally, the sequential modulations were maximal at short SOAs and decreased with increasing SOA, but still occurred at an SOA of 6 seconds. The results seem to exclude repetition or alternation effects as the main cause of sequential modulations of the Simon effect, but both conflict monitoring and binding may contribute to these effects.

Adolescent↗

PubMed2001

The short arm of the laminin gamma2 chain plays a pivotal role in the incorporation of laminin 5 into the extracellular matrix and in cell adhesion.

Laminin 5 is a basement membrane component that actively promotes adhesion and migration of epithelial cells. Laminin 5 undergoes extracellular proteolysis of the gamma2 chain that removes the NH(2)-terminal short arm of the polypeptide and reduces the size of laminin 5 from 440 to 400 kD. The functional consequence of this event remains obscure, although lines of evidence indicate that cleavage of the gamma2 chain potently stimulated scattering and migration of keratinocytes and cancer cells. To define the biological role of the gamma2 chain short arm, we expressed mutated gamma2 cDNAs into immortalized gamma2-null keratinocytes. By immunofluorescence and immunohistochemical studies, cell detachment, and adhesion assays, we found that the gamma2 short arm drives deposition of laminin 5 into the extracellular matrix (ECM) and sustains cell adhesion. Our results demonstrate that the unprocessed 440-kD form of laminin 5 is a biologically active adhesion ligand, and that the gamma2 globular domain IV is involved in intermolecular interactions that mediate integration of laminin 5 in the ECM and cell attachment.

Basement Membrane↗

PubMed1999

Division of labor among the alpha6beta4 integrin, beta1 integrins, and an E3 laminin receptor to signal morphogenesis and beta-casein expression in mammary epithelial cells.

Contact of cultured mammary epithelial cells with the basement membrane protein laminin induces multiple responses, including cell shape changes, growth arrest, and, in the presence of prolactin, transcription of the milk protein beta-casein. We sought to identify the specific laminin receptor(s) mediating the multiple cell responses to laminin. Using assays with clonal mammary epithelial cells, we reveal distinct functions for the alpha6beta4 integrin, beta1 integrins, and an E3 laminin receptor. Signals from laminin for beta-casein expression were inhibited in the presence of function-blocking antibodies against both the alpha6 and beta1 integrin subunits and by the laminin E3 fragment. The alpha6-blocking antibody perturbed signals mediated by the alpha6beta4 integrin, and the beta1-blocking antibody perturbed signals mediated by another integrin, the alpha subunit(s) of which remains to be determined. Neither alpha6- nor beta1-blocking antibodies perturbed the cell shape changes resulting from cell exposure to laminin. However, the E3 laminin fragment and heparin both inhibited cell shape changes induced by laminin, thereby implicating an E3 laminin receptor in this function. These results elucidate the multiplicity of cell-extracellular matrix interactions required to integrate cell structure and signaling and ultimately permit normal cell function.

Animals↗

PubMed2000

MPSA: integrated system for multiple protein sequence analysis with client/server capabilities.

UNLABELLED: MPSA is a stand-alone software intended to protein sequence analysis with a high integration level and Web clients/server capabilities. It provides many methods and tools, which are integrated into an interactive graphical user interface. It is available for most Unix/Linux and non-Unix systems. MPSA is able to connect to a Web server (e.g. http://pbil.ibcp.fr/NPSA) in order to perform large-scale sequence comparison on up-to-date databanks. AVAILABILITY: Free to academic http://www.ibcp.fr/mpsa/ CONTACT: c.blanchet@ibcp.fr

Computing Methodologies↗

PubMed1999

Role of the essential yeast protein PSU1 in p6anscriptional enhancement by the ligand-dependent activation function AF-2 of nuclear receptors.

Nuclear receptors (NRs) can function as ligandinducible transregulators in both mammalian and yeast cells, indicating that important features of transcriptional control have been conserved throughout evolution. We report here the isolation and characterization of an essential yeast protein of unknown function, PSU1, which exhibits properties expected for a co-activator/mediator of the ligand-dependent activation function AF-2 present in the ligand-binding domain (LBD, region E) of NRs. PSU1 interacts in a ligand-dependent manner with the LBD of several NRs, including retinoic acid (RARalpha), retinoid X (RXRalpha), thyroid hormone (TRalpha), vitamin D3 (VDR) and oestrogen (ERalpha) receptors. Importantly, both in yeast and in vitro, these interactions require the integrity of the AF-2 activating domain. When tethered to a heterologous DNA-binding domain, PSU1 can activate transcription on its own. By using yeast reporter cells that express PSU1 conditionally, we show that PSU1 is required for transactivation by the AF-2 of ERalpha. Taken together these data suggest that in yeast, PSU1 is involved in ligand-dependent transactivation by NRs. Sequence analysis revealed that in addition to a highly conserved motif found in a family of MutT-related proteins, PSU1 contains several alpha-helical leucine-rich motifs sharing the consensus sequence LLxPhiL (x, any amino acid; Phi, hydrophobic amino acid) in regions that elicit either transactivation or NR-binding activity.

Amino Acid Sequence↗

PubMed2026

Adaptive deletion of functional duplicate genes in Drosophila.

Gene deletion is traditionally viewed as a nonadaptive mechanism that eliminates functional redundancy, yet emerging evidence indicates that it disproportionately affects tissue-specific duplicates with unique functions. Here, we test whether gene deletion preferentially removes weakly constrained, degenerating duplicates or instead eliminates functionally active duplicates through an adaptive process. To identify the evolutionary and functional factors that determine which duplicates are lost, we systematically analyzed 100 gene deletion events in Drosophila by integrating sequence, expression, interaction, and structural data. We uncovered a strong bias toward the loss of younger child copies among functionally unique duplicates, whereas no such bias was observed for redundant duplicates. Contrary to expectations under relaxed constraint, deleted functionally unique genes evolve more slowly, show higher expression, engage in more protein-protein interactions, and do not exhibit elevated structural divergence or intrinsic disorder relative to redundant duplicates. When compared with single-copy genes, deleted functionally unique genes display similar evolutionary rates, slightly lower expression, greater network connectivity, comparable structural divergence, and lower intrinsic disorder. These patterns suggest that deletion frequently affects functionally active rather than degenerate genes. Collectively, our results support the hypothesis that gene deletion in Drosophila can represent an adaptive process acting on transiently functional duplicates, potentially driven by either genome streamlining or context-dependent deleterious effects.

evolution↗

PubMed2006

Identification of loci affecting flavour volatile emissions in tomato fruits.

Fresh tomato fruit flavour is the sum of the interaction between sugars, acids, and a set of approximately 30 volatile compounds synthesized from a diverse set of precursors, including amino acids, lipids, and carotenoids. Some of these volatiles impart desirable qualities while others are negatively perceived. As a first step to identify the genes responsible for the synthesis of flavour-related chemicals, an attempt was made to identify loci that influence the chemical composition of ripe fruits. A genetically diverse but well-defined Solanum pennellii IL population was used. Because S. pennellii is a small green-fruited species, this population exhibits great biochemical diversity and is a rich source of genes affecting both fruit development and chemical composition. This population was used to identify multiple loci affecting the composition of chemicals related to flavour. Twenty-five loci were identified that are significantly altered in one or more of 23 different volatiles and four were altered in citric acid content. It was further shown that emissions of carotenoid-derived volatiles were directly correlated with the fruit carotenoid content. Linked molecular markers should be useful for breeding programmes aimed at improving fruit flavour. In the longer term, the genes responsible for controlling the levels of these chemicals will be important tools for understanding the complex interactions that ultimately integrate to provide the unique flavour of a tomato.

Carotenoids↗

PubMed1998

Functional association of poly(ADP-ribose) polymerase with DNA polymerase alpha-primase complex: a link between DNA strand break detection and DNA replication.

Poly(ADP-ribose) polymerase (PARP) is an element of the DNA damage surveillance network evolved by eukaryotic cells to cope with numerous environmental and endogenous genotoxic agents. PARP has been found to be involved in vivo in both cell proliferation and base excision repair of DNA. In this study the interaction between PARP and the DNA polymerase alpha-primase tetramer has been examined. We provide evidence that in proliferating cells: (i) PARP is physically associated with the catalytic subunit of the DNA polymerase alpha-primase tetramer, an association confirmed by confocal microscopy, demonstrating that both enzymes are co-localized at the nuclear periphery of HeLa cells; (ii) this interaction requires the integrity of the second zinc finger of PARP and is maximal during the S and G2/M phases of the cell cycle; (iii) PARP-deficient cells derived from PARP knock-out mice exhibited reduced DNA polymerase activity, compared with the parental cells, a reduction accentuated following exposure to sublethal doses of methylmethanesulfonate. Altogether, the present results strongly suggest that PARP participates in a DNA damage survey mechanism implying its nick-sensor function as part of the control of replication fork progression when breaks are present in the template.

Animals↗

PubMed2006

Absolute enrichment: gene set enrichment analysis for homeostatic systems.

The Gene Set Enrichment Analysis (GSEA) identifies sets of genes that are differentially regulated in one direction. Many homeostatic systems will include one limb that is upregulated in response to a downregulation of another limb and vice versa. Such patterns are poorly captured by the standard formulation of GSEA. We describe a technique to identify groups of genes (which sometimes can be pathways) that include both up- and down-regulated components. This approach lends insights into the feedback mechanisms that may operate, especially when integrated with protein interaction databases.

Algorithms↗

PubMedDate not supplied

Role of biosurfactant and ion channel-forming activities of syringomycin in transmembrane ion flux: a model for the mechanism of action in the plant-pathogen interaction.

Syringomycin is a necrosis-inducing lipopeptide toxin synthesized and secreted by the phytopathogen, Pseudomonas syringae pv. syringae. Although small quantities of syringomycin are known to activate a cascade of physiological events in plasma membranes, the mechanism of action of the phytotoxin has never been fully characterized. The objective of this study was to test the hypothesis that the primary mode of action of syringomycin is to form transmembrane pores that are permeable to cations. Accordingly, direct measurement of ion fluxes were performed using artificial bilayers. The hemolytic properties and surface activity of HPLC-purified syringomycin were quantified by use of an erythrocyte lysis assay and by the drop weight method. Assays were performed using syringomycin form SRE alone or a mixture containing all forms of the phytotoxin. At a threshold concentration of 500 ng/ml, syringomycin induced hemolysis by forming ion channels in membranes. Osmotic protection studies indicated a channel radius of between 0.6 and 1 nm. The ion channel-forming activity was insensitive and permeable to both monovalent and divalent cations, suggesting that syringomycin causes lysis of erythrocytes by colloid osmotic lysis. In addition, syringomycin, like other lipopeptide antibiotics, is a potent biosurfactant capable of lowering the interfacial tension of water to 31 mN/m. The critical micellar concentration of syringomycin was calculated to be 1.25 mg/ml and the gamma CMC was 33 mN/m. A model is presented depicting the mechanism of action of syringomycin in the plant-pathogen interaction. The model integrates known effects of the toxin on ion flux in plasma membranes with formation of ion channels and the consequential cascade of effects associated with cellular signalling.

Amino Acid Sequence↗

PubMed2002

The serum and glucocorticoid-inducible kinase SGK1 and the Na+/H+ exchange regulating factor NHERF2 synergize to stimulate the renal outer medullary K+ channel ROMK1.

Mineralocorticoids stimulate Na(+) reabsorption and K(+) secretion in principal cells of connecting tubule and collecting duct. The involved ion channels are ENaC and ROMK1, respectively. In Xenopus oocytes, the serum and glucocorticoid-sensitive kinase SGK1 has been shown to increase ENaC activity by enhancing its abundance in the plasma membrane. With the same method, ROMK1 appeared to be insensitive to regulation by SGK1. On the other hand, ROMK1 has been shown to colocalize with NHERF2, a protein mediating targeting and trafficking of transport proteins into the cell membrane. The present study has been performed to test whether NHERF2 is required for regulation of ROMK1 by SGK1. Coexpression of neither NHERF2 nor SGK1 with ROMK1 increases ROMK1 activity. However, coexpression of NHERF2 and SGK1 together with ROMK1 markedly increases K(+) channel activity. The combined effect of SGK1 and NHERF2 does not significantly alter the I/V relation of the channel but increases the abundance of the channel in the membrane and decreases the decay of channel activity after inhibition of vesicle insertion with brefeldin. Coexpression of NHERF2 and SGK1 does not modify cytosolic pH but leads to a slight shift of pK(a) of ROMK1 to more acidic values. In conclusion, NHERF2 and SGK1 interact to enhance ROMK1 activity in large part by enhancing the abundance of channel protein within the cell membrane. This interaction allows the integration of genomic regulation and activation of SGK1 and NHERF2 in the control of ROMK1 activity and renal K(+) excretion.

Animals↗

PubMed2005

Sound-induced flash illusion as an optimal percept.

Recently, it has been shown that visual perception can be radically altered by signals of other modalities. For example, when a single flash is accompanied by multiple auditory beeps, it is often perceived as multiple flashes. This effect is known as the sound-induced flash illusion. In order to investigate the principles underlying this illusion, we developed an ideal observer (derived using Bayes' rule), and compared human judgements with those of the ideal observer for this task. The human observer's performance was highly consistent with that of the ideal observer in all conditions ranging from no interaction, to partial integration, to complete integration, suggesting that the rule used by the nervous system to decide when and how to combine auditory and visual signals is statistically optimal. Our findings show that the sound-induced flash illusion is an epiphenomenon of this general, statistically optimal strategy.

Acoustic Stimulation↗

PubMed2005

Robustness mechanisms in primate societies: a perturbation study.

Conflict management mechanisms have a direct, critical effect on system robustness because they mitigate conflict intensity and help repair damaged relationships. However, robustness mechanisms can also have indirect effects on system integrity by facilitating interactions among components. We explore the indirect role that conflict management mechanisms play in the maintenance of social system robustness, using a perturbation technique to 'knockout' components responsible for effective conflict management. We explore the effects of knockout on pigtailed macaque (Macaca nemestrina) social organization, using a captive group of 84 individuals. This system is ideal in addressing this question because there is heterogeneity in performance of conflict management. Consequently, conflict managers can be easily removed without disrupting other control structures. We find that powerful conflict managers are essential in maintaining social order for the benefit of all members of society. We show that knockout of components responsible for conflict management results in system destabilization by significantly increasing mean levels of conflict and aggression, decreasing socio-positive interaction and decreasing the operation of repair mechanisms.

Aggression↗

PubMed2005

Building messaging substrates for Web and Grid applications.

Grid application frameworks have increasingly aligned themselves with the developments in Web services. Web services are currently the most popular infrastructure based on service-oriented architecture (SOA) paradigm. There are three core areas within the SOA framework: (i) a set of capabilities that are remotely accessible, (ii) communications using messages and (iii) metadata pertaining to the aforementioned capabilities. In this paper, we focus on issues related to the messaging substrate hosting these services; we base these discussions on the NARADABROKERING system. We outline strategies to leverage capabilities available within the substrate without the need to make any changes to the service implementations themselves. We also identify the set of services needed to build Grids of Grids. Finally, we discuss another technology, HPSEARCH, which facilitates the administration of the substrate and the deployment of applications via a scripting interface. These issues have direct relevance to scientific Grid applications, which need to go beyond remote procedure calls in client-server interactions to support integrated distributed applications that couple databases, high performance computing codes and visualization codes.

Computer Simulation↗

PubMed2006

Disentangling information flow in the Ras-cAMP signaling network.

The perturbation of signal-transduction molecules elicits genomic-expression effects that are typically neither restricted to a small set of genes nor uniform. Instead there are broad, varied, and complex changes in expression across the genome. These observations suggest that signal transduction is not mediated by isolated pathways of information flow to distinct groups of genes in the genome. Rather, multiple entangled paths of information flow influence overlapping sets of genes. Using the Ras-cAMP pathway in Saccharomyces cerevisiae as a model system, we perturbed key pathway elements and collected genomic-expression data. Singular value decomposition was applied to separate the genome-wide transcriptional response into weighted expression components exhibited by overlapping groups of genes. Molecular interaction data were integrated to connect gene groups to perturbed signaling elements. The resulting series of linked subnetworks maps multiple putative pathways of information flow through a dense signaling network, and provides a set of testable hypotheses for complex gene-expression effects across the genome.

Cyclic AMP↗