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Results for “Integrative interaction”

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At least 667 records · Page 37Linked to original sources

PubMed1999

Reflection interference contrast microscopy combined with scanning force microscopy verifies the nature of protein-ligand interaction force measurements.

The integration of a stand-alone scanning force microscope (SFM) scanner with a reflection interference contrast microscope (RICM) makes it possible to measure directly the separation distance between the SFM probe and the sample surface. The SFM-RICM combination, when applied to the force measurements between ligand-derivatized SFM probe and a protein receptor-derivatized surface, showed that the anomalous force discontinuities often observed for such interacting pairs were indeed a real behavior characteristic of a particular experimental configuration. Apart from small discrepancies due to transient damping, commercially available cantilevers did behave in an ideal mechanical fashion, thus indicating that protein-ligand unbinding events were occurring at distances much larger than their maximum extended length. This external verification of separation distance requires a closer examination of the physical events occurring upon detachment of the surfaces. An alternative interpretation of such force measurements is proposed here in which the protein and/or ligand immobilization chemistry is called into question.

Biophysical Phenomena↗

PubMed1994

The binding of natural variants of human factor IX to endothelial cells.

The Gla-domain of human factor IX contains a specific element required for the binding of factor IX to an endothelial cell surface protein. We have investigated the dependence of this interaction on the structural integrity of the adjacent hydrophobic stack and epidermal growth factor-like domains. The ability of purified natural variants of human factor IX to compete with wild-type factor IX binding to the endothelial cell surface was used to obtain apparent Ki values of the variants. Our data suggest that the functional integrity of the Gla domain, enabling factor IX to specifically interact with an endothelial cell surface protein, depends on the structural and functional integrity of both the hydrophobic stack domain and the first epidermal growth factor-like domain.

Blotting, Western↗

PubMed1999

Human responses to upright tilt: a window on central autonomic integration.

1. We examined interactions between haemodynamic and autonomic neural oscillations during passive upright tilt, to gain better insight into human autonomic regulatory mechanisms. 2. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in nine healthy young adults. Subjects breathed in time with a metronome at 12 breaths min-1 (0.2 Hz) for 5 min each, in supine, and 20, 40, 60, 70 and 80 deg head-up positions. We performed fast Fourier transform (and autoregressive) power spectral analyses and integrated low-frequency (0.05-0.15 Hz) and respiratory-frequency (0. 15-0.5 Hz) spectral powers. 3. Integrated areas of muscle sympathetic bursts and their low- and respiratory-frequency spectral powers increased directly and significantly with the tilt angle. The centre frequency of low-frequency sympathetic oscillations was constant before and during tilt. Sympathetic bursts occurred more commonly during expiration than inspiration at low tilt angles, but occurred equally in expiration and inspiration at high tilt angles. 4. Systolic and diastolic pressures and their low- and respiratory-frequency spectral powers increased, and R-R intervals and their respiratory-frequency spectral power decreased progressively with the tilt angle. Low-frequency R-R interval spectral power did not change. 5. The cross-spectral phase angle between systolic pressures and R-R intervals remained constant and consistently negative at the low frequency, but shifted progressively from positive to negative at the respiratory frequency during tilt. The arterial baroreflex modulus, calculated from low-frequency cross-spectra, decreased at high tilt angles. 6. Our results document changes of baroreflex responses during upright tilt, which may reflect leftward movement of subjects on their arterial pressure sympathetic and vagal response relations. The intensity, but not the centre frequency of low-frequency cardiovascular rhythms, is modulated by the level of arterial baroreceptor input. Tilt reduces respiratory gating of sympathetic and vagal motoneurone responsiveness to stimulatory inputs for different reasons; during tilt, sympathetic stimulation increases to a level that overwhelms the respiratory gate, and vagal stimulation decreases to a level below that necessary for maximal respiratory gating to occur.

Adult↗

PubMed2003

The use of transepithelial models to examine host-pathogen interactions.

Many pathogens must overcome an epithelial barrier in order to establish an infection. Unsurprisingly, such pathogens have evolved different mechanisms to overcome this obstacle, targeting specific epithelial structures or functions. These include disruption of epithelial barrier function, transcytosing from the apical to the basolateral membrane domain or inducing cell movement such as neutrophil recruitment. When studying these processes in vivo, animal models often fail to mimic the disease observed in humans and present a complex system in which many variables cannot be controlled. Therefore, in vitro transepithelial models that permit the study of a relevant biological surface have been developed, to integrate not only interactions between bacteria and epithelial cells but also, under certain conditions, to integrate a third cell type, such as neutrophils or dendritic cells. Such models are particularly useful for studying the bacteria-host relationship as it would occur in the microenvironment of the human epithelium and have enhanced our understanding of the unique strategies by which pathogenic bacteria exploit host cells to overcome the initial epithelial hurdle.

Animals↗

PubMed2002

Self-organized pattern formation: experimental dissection of motion detection and motion integration by variation of attentional spread.

The formation of global motion patterns depends on the stimulus activation of local motion detectors as well as integrative excitatory and/or inhibitory interactions among the activated detectors. The counterphase row-of-elements [Vis. Res. 34 (1994) 1843] is an ideal stimulus for examining the relationship between the activational/energizing effect of the stimulus and interaction among the activated detectors. This is because the formation of the alternative unidirectional and oscillatory motion patterns for this stimulus requires the stimulation of local motion detectors, but there is no information in the stimulus that specifies either of the patterns. Their formation depends instead on the relative contributions of excitatory and inhibitory interactions to detector activation; the temporal patterns are self-organized. Broadly spread attention affects motion integration by changing the balance of excitatory versus inhibitory interactions, increasing the perception of unidirectional compared with oscillatory motion. (It likewise increases the perception of group compared with element motion for the Ternus stimulus.) There is, however, little if any effect of attentional spread on the luminance contrast required for the perception of single-element motion. The results indicate that the balance of integrative excitatory and/or inhibitory detector interactions can be modified by the perceiver's spread of attention, and further, that such changes need not be mediated by changes in the local, stimulus activation of the detectors.

Adult↗

PubMed2000

Psychoactive cannabinoids and membrane signaling.

THC-like psychoactive cannabinoids permeate the lipid bilayer of the membrane, altering its physicochemical properties and activating phospholipases. As a result, an increased production of arachidonic acid occurs with its cascade of eicosanoids, including prostaglandins. In addition, THC and its psychoactive derivatives bind within the membrane in a stereospecific fashion, to a transmembrane G protein coupled receptor (GPCR) for which THC has a much higher affinity than the natural ligands, arachidonylethanolamide (AEA) and 2-arachidonyglycerol (2-AG). These natural lipid ligands may be considered signaling molecules which are generated in the membrane lipid bilayer. THC alters the physicochemical disposition of the lipid bilayer and interacts with the integral membrane protein receptors through alteration of the boundary lipid. This effect is distinct from the mechanism resulting from its persistent binding to a G protein coupled transmembrane receptor. THC does not interact directly with neurotransmitter receptors but alters their pharmacological response in an allosteric fashion. It is proposed that the binding of AEA and 2-AG to the G protein coupled transmembrane receptor possesses a physiological function which is to regulate the signaling between boundary lipids and membrane receptors in response to extracellular signals. AEA and 2-AG are eicosanoid signaling molecules which modulate the activity of G protein coupled transmembrane receptors. AEA and 2-AG should not be identified with synthetic ligand molecules dubbed 'endogenous cannabinoids' which are 'xenobiotics' with no physiological regulating function. THC deregulates persistently a basic signaling mechanism of the membrane lipid bilayer and of its integrated receptors with resulting impairment of cellular function of brain, heart and male gonads. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

PubMed2005

Systematic interpretation of genetic interactions using protein networks.

Genetic interaction analysis,in which two mutations have a combined effect not exhibited by either mutation alone, is a powerful and widespread tool for establishing functional linkages between genes. In the yeast Saccharomyces cerevisiae, ongoing screens have generated >4,800 such genetic interaction data. We demonstrate that by combining these data with information on protein-protein, prote in-DNA or metabolic networks, it is possible to uncover physical mechanisms behind many of the observed genetic effects. Using a probabilistic model, we found that 1,922 genetic interactions are significantly associated with either between- or within-pathway explanations encoded in the physical networks, covering approximately 40% of known genetic interactions. These models predict new functions for 343 proteins and suggest that between-pathway explanations are better than within-pathway explanations at interpreting genetic interactions identified in systematic screens. This study provides a road map for how genetic and physical interactions can be integrated to reveal pathway organization and function.

Algorithms↗

PubMed2004

Structure of short polymers at interfaces: a combined simulation and theoretical study.

The structure of polymers confined between surfaces is studied using computer simulation and a density functional approach. The simple model system considers the polymer molecule as a pearl necklace of freely jointed hard spheres, having attractions among the beads, confined between attractive surfaces. This approach uses the universality of the free-energy functional to obtain the self-consistent field required in the single chain simulation. The second-order direct correlation function for the uniform bulk fluid required as input has been calculated from the reference interaction site model integral equation theory using mean spherical approximation. The theoretical results are shown to compare well with the Monte Carlo simulation results for varying densities, chain lengths, and with different attractive interaction parameters. The simulation results on the conformational properties give important indications regarding the behavior of chains as they approach the surfaces.

Journal Article↗

PubMed2005

High-order discretization schemes for biochemical applications of boundary element solvation and variational electrostatic projection methods.

A series of high-order surface element discretization schemes for variational boundary element methods are introduced. The surface elements are chosen in accord with angular quadrature rules for integration of spherical harmonics. Surface element interactions are modeled by Coulomb integrals between spherical Gaussian functions with exponents chosen to reproduce the exact variational energy and Gauss's law for a point charge in a spherical cavity. The present work allows high-order surface element expansions to be made for variational methods such as the conductorlike screening model for solvation and the variational electrostatic projection method for generalized solvent boundary potentials in molecular simulations.

Algorithms↗

PubMed2003

Visualization and analysis of protein interactions.

SUMMARY: We have developed a new program called InterViewer for drawing large-scale protein interaction networks in three-dimensional space. Unique features of InterViewer include (1) it is much faster than other recent implementations of drawing algorithms; (2) it can be used not only for visualizing protein interactions but also for analyzing them interactively; and (3) it provides an integrated framework for querying protein interaction databases and directly visualizes the query results. AVAILABILITY: http://wilab.inha.ac.kr/protein/

Algorithms↗

PubMed2025

AQuA Tools: clear and reliable BEDPE operations for 3D genomics.

MOTIVATION: The genome interacts with itself within the volume of the cell nucleus to process information. These interactions mediate signal integration, gene regulation, and cell identity. The identification of new therapeutic targets from non-coding disease-associated variants relies critically on correctly assigning variants to genes through 3D interactions. Experimental techniques in 3D genomics, such as HiC and HiChIP, allow the mapping of interactions through sequencing. Bioinformatics for 3D genomics contends primarily with contact matrices that contain interaction frequencies for all possible element pairs, and BEDPE files that store element pairs that interact. Whereas the tools available for processing linear genomic data are mature, operating on contact matrices and BEDPE files remains cumbersome, opaque, and error-prone, as researchers have had to shoehorn tools originally designed for linear data. A genome arithmetic designed from the ground up for 3D genomics does not yet exist. RESULTS: We present AQuA Tools, a suite of shell- and R-based command-line tools that provide a set of core operations on contact matrices and BEDPE files motivated by key questions in population genetics, cancer research, and precision medicine. We have designed our core operations to be clear, reliable, intuitive and versatile. Core operations can be chained together along with standard UNIX commands. Our goal is to make AQuA Tools easy for the novice to learn and the go-to choice for power users. We hope our tools will motivate more researchers to use 3D genomic data in their projects. AVAILABILITY AND IMPLEMENTATION: We provide and maintain AQuA Tools at https://github.com/axiotl/aqua-tools.

Genomics↗

PubMed2006

Sodium/calcium exchanger: influence of metabolic regulation on ion carrier interactions.

The Na(+)/Ca(2+) exchanger's family of membrane transporters is widely distributed in cells and tissues of the animal kingdom and constitutes one of the most important mechanisms for extruding Ca(2+) from the cell. Two basic properties characterize them. 1) Their activity is not predicted by thermodynamic parameters of classical electrogenic countertransporters (dependence on ionic gradients and membrane potential), but is markedly regulated by transported (Na(+) and Ca(2+)) and nontransported ionic species (protons and other monovalent cations). These modulations take place at specific sites in the exchanger protein located at extra-, intra-, and transmembrane protein domains. 2) Exchange activity is also regulated by the metabolic state of the cell. The mammalian and invertebrate preparations share MgATP in that role; the squid has an additional compound, phosphoarginine. This review emphasizes the interrelationships between ionic and metabolic modulations of Na(+)/Ca(2+) exchange, focusing mainly in two preparations where most of the studies have been carried out: the mammalian heart and the squid giant axon. A surprising fact that emerges when comparing the MgATP-related pathways in these two systems is that although they are different (phosphatidylinositol bisphosphate in the cardiac and a soluble cytosolic regulatory protein in the squid), their final target effects are essentially similar: Na(+)-Ca(2+)-H(+) interactions with the exchanger. A model integrating both ionic and metabolic interactions in the regulation of the exchanger is discussed in detail as well as its relevance in cellular Ca(i)(2+) homeostasis.

Animals↗

PubMed1978

Cell-factor interaction and factor-dependant long-term growth of human T-progenitor cells.

Specific cell-factor interactions provide a basic mechanism for differentiation of myeloid and lymphoid cells. Evidence at the present time indicates that factor-producing cells, factor and factor-responding cells are integrated into an interacting network to produce various specific differentiatied functions. To elucidate the mechanisms of such interactions in the differentiation of T lymphocyte, a systematic study was carried out to characterize a liquid suspension culture system for T progenitor cells from human peripheral blood or bone marrow. T progenitor cells were assayed either by their membrane properties or by their ability to form colonies in semisolid media. T lymphocyte growth stimulators (TL-GS) were isolated from phytohemagglutin (PHA)-stimulated human T lymphocyte conditioned medium. TL-GS were capable of selectively supporting growth for four months or longer of T progenitor cells. This system should facilitate the study of cell-factor interactions mediating the proliferation and differentiation of T lymphocytes.

Cell Differentiation↗

PubMed2000

Dentists' judgment strategies on prophylactic removal of mandibular third molars.

The number of molars selected for prophylactic removal varies widely among general dental practitioners and oral surgeons. To understand the basis for such variations, we investigated two hypotheses: (1) Individual judgment strategies will differ concerning the use of cues (items of information), and (2) few dentists will integrate the cues according to evidence in the literature. To analyze 30 general dental practitioners' (GDPs) and 10 oral surgeons' use of cues in the judgment preceding the treatment decision, we used the Brunwik's lens as a conceptual model. The cues were the patient's age, and the angular position and the degree of impaction of the molar. The clinical situation was simulated by written case descriptions. The proportion of variation explained by the cues and their combinations (total model) varied between 61% and 100% and between 4% and 76% as main effects. Two GDPs and one oral surgeon integrated the cues additively, i.e., any of the cues is independent of the other cues in the judgment. In general, the dentists integrated the cues interactively, i.e., the impact of one cue depends on the levels of some other cues. Even though most variations in judgments were accounted for by the cues, the dentists did not integrate the cues according to evidence in the literature and lacked insight into their decision-making thought processes.

Adult↗

PubMed1994

Integrity promoting care of demented patients: patterns of interaction during morning care.

Video-recorded morning care sessions (n = 49) of demented nursing home patients (n = 5), were analyzed before, as well as after, training of the staff in integrity promoting care. A phenomenological-hermeneutic analysis was performed based on the Erikson theory of "eight stages of man" and musical notations were used for the analysis of courses of events. The analysis revealed five main patterns of interaction; positive, negative, intermediate, negative/intermediate turned into positive by the patient, and negative/intermediate turned into positive by the caregiver. Before the training, negative and intermediate patterns dominated (58%), while positive patterns dominated (84%) after the training. The positive patterns of interaction were characterized by the caregiver communicating with the patient as a competent partner, showing humanity, respect and support. The activity was carried out in intimacy. This led to the patient displaying more and more ability.

Baths↗

PubMed2004

Integrated Population Pharmacokinetic Model of both cyclophosphamide and thiotepa suggesting a mutual drug-drug interaction.

PURPOSE/AIMS: Cyclophosphamide (CP) and thiotepa (TT) are frequently administered simultaneously in high-dose chemotherapy regimens. The prodrug CP shows strong autoinduction resulting in increased formation of its activated metabolite 4-hydroxycyclophosphamide (4OHCP). TT inhibits this bioactivation of CP. Previously, we successfully modelled CP bioactivation and the effect of TT on the autoinduction. Recently we suggested that CP may also induce the conversion of TT in to its metabolite tepa (T). The aim of the current study was to investigate whether the influence of CP on TT metabolism can be described with a population pharmacokinetic model and whether this interaction can be incorporated in an integrated model describing both CP and TT pharmacokinetics. METHODS: Plasma samples were collected from 49 patients receiving 86 courses of a combination of high-dose CP (4000 or 6000 mg/m2), TT (320 or 480 mg/m2) and carboplatin (1067 or 1600 mg/m2) given in short infusions during four consecutive days. For each patient, approximately 20 plasma samples were available per course. Concentrations of CP, 4OHCP, TT and T were determined using GC and HPLC. Kinetic data were processed using NONMEM. RESULTS: The pharmacokinetics of TT and T were described with a two-compartment model. TT was eliminated through a non-inducible and an inducible pathway, the latter resulting information of T (ClindTT = 12.4 l/hr, ClnonindTT = 17.0 l/hr). Induction of TT metabolism was mediated by a hypothetical amount of enzyme, different from that involved in CP induction, whose amount increased with time in the presence of CP. The amount of enzyme followed a zero-order formation and a decrease with a first-order elimination rate constant of 0.0343 hr(-1) (t1/2 = 20 hr). This model was significantly better than a model lacking the induction by CP. The model was successfully incorporated into the previously published pharmacokinetic model for CP, and resulted in comparable parameter estimates for this compound and its metabolite 4OHCP. CONCLUSION: The pharmacokinetics of TT, when administered in combination with CP, were successfully described. The model confirms induction of TT metabolism with time and it appears likely that CP is responsible for this phenomenon. The existence of a mutual pharmacokinetic interaction between CP and TT, as described in our integrated model, may be relevant in clinical practice.

Adolescent↗

PubMed2006

The social distribution of risk at work: acute injuries and physical assaults among healthcare workers working in a long-term care facility.

The roles of informal social ties in affecting healthcare workers' risk of injury and assault were investigated in a long-term care facility for the elderly in the US. The original hypothesis was that nurses and healthcare assistants who integrated more with their coworkers would have lower risk. A crude measure of familiarity and social integration with coworkers was constructed from staff attendance records. This variable, which indicates working a floor and shift one has routinely worked on in the past, was associated with a moderate increase in risk of being injured after controlling for lifting demands and a fairly strong increased risk of being assaulted after controlling for resident combativeness. An interaction between social integration and job title was found. The primary associations were in the opposite direction of what was expected. The results suggest that social forces among healthcare workers shape the distribution of risk among workers in a manner more complex than some theories of social integration have suggested. New hypotheses are proposed to explore how social norms and expectations affect the way workers interact with each other and shape the distribution of risk among workgroup members.

Adult↗

PubMed2001

Metabolic modeling of microbial strains in silico.

The large volume of genome-scale data that is being produced and made available in databases on the World Wide Web is demanding the development of integrated mathematical models of cellular processes. The analysis of reconstructed metabolic networks as systems leads to the development of an in silico or computer representation of collections of cellular metabolic constituents, their interactions and their integrated function as a whole. The use of quantitative analysis methods to generate testable hypotheses and drive experimentation at a whole-genome level signals the advent of a systemic modeling approach to cellular and molecular biology.

Genome↗