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At least 163 records · Page 9Linked to original sources

Teaching resources for dermatology on the WWW--quiz system and dynamic lecture scripts using a HTTP-database demon.

The World Wide Web (WWW) is becoming the major way of acquiring information in all scientific disciplines as well as in business. It is very well suitable for fast distribution and exchange of up to date teaching resources. However, to date most teaching applications on the Web do not use its full power by integrating interactive components. We have set up a computer based training (CBT) framework for Dermatology, which consists of dynamic lecture scripts, case reports, an atlas and a quiz system. All these components heavily rely on an underlying image database that permits the creation of dynamic documents. We used a demon process that keeps the database open and can be accessed using HTTP to achieve better performance and avoid the overhead involved by starting CGI-processes. The result of our evaluation was very encouraging.

Computer Communication Networks↗

[The role of conserved sequences in the regulatory elements of the Antp-like homeobox-containing genes of vertebrates].

By the present time the homeobox genes have been found in the representatives of the main invertebrate and vertebrate taxa. It has been demonstrated that these genes play the key role in the space and time genome expression orchestration in ontogenesis. The autoregulatory and cross-regulatory functional interactions integrate the homeobox genes into the gene networks. We found a correlation in variability of the coding and regulatory regions for vertebrate homeobox genes. The phylogenetic relations of structure and regulatory elements involved into the cross- and autoregulatory connections have been investigated in detail. The comprehensive phylogenetic analysis of the promoter region for these genes compared to results of such analysis of their homeoboxes has revealed two opposed tendencies in evolution of the regulatory elements of genes. The first trend is conservation of many regulatory elements in evolution of vertebrate homeobox genes and the second one is high variability of other non-coding gene regions.

Amino Acid Sequence↗

Effects of acute emotional stress on the brain and autonomic variables.

Under emotional stress (ES) the brain limbic-reticular structures are shown to change first. The integrative interaction of brain structures determines the secondary changes of cardiovascular functions. The effects of ES on autonomic functions are mediated primarily by chemical changes of brain limbic-reticular neurons to neurotransmitters and oligopeptides. Genetic and individual cardiovascular disorders under ES have been demonstrated. Mechanisms of sustained arterial blood hypertension under experimental ES are considered. It has been established that the resistance to ES is strongly dependent on the basic levels of oligopeptides and norepinephrine in the hypothalamus. Additional injections of oligopeptides enhance the resistance to ES.

Acute Disease↗

Electrostatic interactions in an integral membrane protein.

The effects of charge-charge interactions on the midpoint reduction potential (E(m)()) of the primary electron donor (P) in the photosynthetic reaction center of Rhodobacter sphaeroides were investigated by introducing mutations of ionizable amino acids at selected sites. The mutations were designed to alter the electrostatic environment of P, a bacteriochlorophyll dimer, without greatly affecting its structure or molecular orbitals. Two arginine residues at homologous positions in the L and M subunits [residues (L135) and (M164)], Asp (L155), Tyr (L164), and Cys (L247) were changed independently. Arginine (L135) was replaced by Lys, Leu, Gln, or Glu; Arg (M164), by Leu or Glu; Asp (L155), by Asn; Tyr (L164), by Phe; and Cys (L247), by Lys or Asp. The R(L135)E/C(L247)K double mutant also was made. The shift in the E(m)() of P/P(+) was measured in each mutant and was compared with the effect predicted by electrostatics calculations using several different computational approaches. A simple distance-dependent dielectric screening factor reproduced the effects remarkably well. By contrast, microscopic methods that considered the reaction field in the protein and solvent but did not include explicit counterions overestimated the changes in the E(m)() considerably. Including counterions for the charged residues reduced the calculated effects of the mutations in molecular dynamics calculations. The results show that electrostatic interactions of P with ionizable amino acid residues are strongly screened, and suggest that counterions make major contributions to this screening. The screening also could reflect penetration of water or other relaxations not taken into account because of incomplete sampling of configurational space.

Amino Acid Substitution↗

[Structural instability of co-integrates formed during interaction of plasmid R57 with pB322 and RP1. Possible role of IS1 element in the degradation of co-integrates].

The conjugative plasmid R57 determines resistance to ampicillin and chloramphenicol. Earlier it was shown that R57 encodes site-specific recA-independent recombinase, which acts in cis and resolves IS1-mediated cointegrates arising in the Escherichia coli recA cells between R57 and pBR322. In the present work the properties of the cointegrates between R57 and pBR322 or RP1 arising in the E. coli rec+ strains were studied. It was found that the cointegrates between R57 and pBR322, obtained by mating of the respective biplasmid donors of E. coli rec+ and the rec+ recipients, lost as a result of deletion a large DNA segment of R57 containing determinant Cmr. The resulting hybrid replicons preserved determinants Apr and Tcr of pBR322 and the R57 conjugative properties and were structurally identical. By using plasmid RP1ts12, which is temperature-sensitive in replication, it was demonstrated that in cells rec+ the cointegrates between R57 and RP1 are extremely unstable. On storage they undergo structural degradation mainly affecting the RP1 replicon. The degradation products of the hydrid complex had lost their RP1 genes but preserved the R57 functional determinants. For elucidation of the observed phenomena the properties of the IS1-mediated cointegrates between pBR322:Tn9 and plasmid pBR3.1--deletion derivative of RP1 were studied. It was found that insertion of IS1 sometimes resulted in formation of unstable cointegrates capable of resolving and loosing determinant Cmr with a high frequency. It was suggested that IS1 encodes the site-specific recombinase responsible for resolution of the IS1-mediated cointegrates and deletion generation. Expression of this recombinase appears to be dependent on structure of the insertion sites. The possible role of IS1 and recombinase encoded by it in resolution and structural instability of the cointegrates between R57 and pBR322 or RP1 is discussed.

Chromosome Mapping↗

Adenosine-dopamine receptor-receptor interactions as an integrative mechanism in the basal ganglia.

Increasing evidence suggests that antagonistic interactions between specific subtypes of adenosine and dopamine receptors in the basal ganglia are involved in the motor depressant effects of adenosine receptor agonists and the motor stimulant effects of adenosine receptor antagonists, such as caffeine. The GABAergic striatopallidal neurons are regulated by interacting adenosine A2A and dopamine D2 receptors. On the other hand, the GABAergic striatonigral and striatoentopeduncular neurons seem to be regulated by interacting adenosine A1 and dopamine D1 receptors. Furthermore, behavioural studies have revealed interactions between adenosine A2A and dopamine D1 receptors that occur at the network level. These adenosine-dopamine receptor-receptor interactions might offer new therapeutic leads for basal ganglia disorders.

Animals↗

The peroxin Pex19p interacts with multiple, integral membrane proteins at the peroxisomal membrane.

Pex19p is a protein required for the early stages of peroxisome biogenesis, but its precise function and site of action are unknown. We tested the interaction between Pex19p and all known Pichia pastoris Pex proteins by the yeast two-hybrid assay. Pex19p interacted with six of seven known integral peroxisomal membrane proteins (iPMPs), and these interactions were confirmed by coimmunoprecipitation. The interactions were not reduced upon inhibition of new protein synthesis, suggesting that they occur with preexisting, and not newly synthesized, pools of iPMPs. By mapping the domains in six iPMPs that interact with Pex19p and the iPMP sequences responsible for targeting to the peroxisome membrane (mPTSs), we found the majority of these sites do not overlap. Coimmunoprecipitation of Pex19p from fractions that contain peroxisomes or cytosol revealed that the interactions between predominantly cytosolic Pex19p and the iPMPs occur in the organelle pellet that contains peroxisomes. These data, taken together, suggest that Pex19p may have a chaperone-like role at the peroxisome membrane and that it is not the receptor for targeting of iPMPs to the peroxisome.

Binding Sites↗

Teaching social skills to students with autism to increase peer interactions in an integrated first-grade classroom.

We investigated the use of social skills groups to facilitate increased social interactions for students with autism and their nonhandicapped peers in an integrated first-grade classroom. Social skills groups consisted of training students and peers in initiating, responding, and keeping interactions going; greeting others and conversing on a variety of topics; giving and accepting compliments; taking turns and sharing; asking for help and helping others; and including others in activities. Training occurred during the first 10 min of 20-min play groups, four times per week. Using a multiple baseline across subjects design, results demonstrated increases in the frequency of, time engaged in, and duration of social interactions, as well as the responsivity of students and peers to each other. Results were maintained when students were monitored and given feedback on social performance in play groups and during follow-up.

Autistic Disorder↗

Immediate effects of mainstreamed settings on the social interactions and social integration of preschool children.

The immediate effects of mainstreamed and specialized settings on the peer interactions of preschool children with and without developmental delays were examined. Mainstreamed and specialized playgroups were established involving unacquainted peers and using a methodology that ensured appropriate matching of child and family characteristics. For each 2-week playgroup, the social and play interactions of each child were observed during a designated free-play period. Peer sociometric ratings also were obtained. Results indicated higher levels of peer interactions in mainstreamed settings for both typically developing children and children with developmental delays. The immediate impact of mainstreamed settings appeared to be attributed to the social demands and higher interaction levels of the former group. Children with developmental delays were not fully accepted nor totally socially integrated based on sociometric measures and behavioral indices of peer preferences. Implications of these findings for developing intervention programs to maximize children's peer-related social competence was discussed.

Child, Preschool↗

TRAIT: A Comprehensive Database for T-cell Receptor-antigen Interactions.

Comprehensive and integrated resources on interactions between T-cell receptors (TCRs) and antigens are still lacking for adoptive T-cell-based immunotherapies, highlighting a significant gap that must be addressed to fully understand the mechanisms of antigen recognition by T cells. In this study, we present the T-cell receptor-antigen interaction database (TRAIT), a comprehensive database that profiles the interactions between TCRs and antigens. TRAIT stands out due to its comprehensive description of TCR-antigen interactions by integrating sequences, structures, and affinities. It provides millions of experimentally validated TCR-antigen pairs, resulting in an exhaustive landscape of antigen-specific TCRs. Notably, TRAIT emphasizes single-cell omics as a major reliable data source for TCR-antigen interactions and includes millions of reliable non-interactive TCRs. Additionally, it thoroughly demonstrates the interactions between mutations of TCRs and antigens, thereby benefiting affinity optimization of engineered TCRs as well as vaccine design. TCRs on clinical trials are innovatively provided. With the significant efforts made toward elucidating the complex interactions between TCRs and antigens, TRAIT is expected to ultimately contribute superior algorithms and substantial advancements in the field of T-cell-based immunotherapies. TRAIT is freely accessible at https://pgx.zju.edu.cn/traitdb.

Receptors, Antigen, T-Cell↗

An integrated addition and interaction model for assessing toxicity of chemical mixtures.

The high propensity for simultaneous exposure to multiple environmental chemicals necessitates the development and use of models that provide insight into the toxicity of chemical mixtures. In this study, we developed a mathematical model that combines concepts of concentration addition, response addition, and toxicokinetic chemical interaction to assess toxicity of chemical mixtures. A ternary mixture of acetylcholinesterase inhibiting organophosphates (malathion and parathion) and the P450 inhibitor piperonyl butoxide was used to model toxicity. Concentration-response curves were generated for individual chemicals as well as for mixtures of the chemicals using acute toxicity tests with Daphnia magna. The toxicity of binary combinations of malathion and parathion adhered to the principles of concentration addition. The contribution of piperonyl butoxide to mixture toxicity was integrated using a model for response addition. Piperonyl butoxide also modified the toxicity of the organophosphates by inhibiting their metabolic activation. The antagonistic effects of piperonyl butoxide towards the organophosphates were quantified as coefficients of interactions (K-functions) and incorporated into the mixture model. Finally, toxicity of the ternary mixture was modeled at 30 different mixture formulations using three additive models that assumed no interaction (concentration addition, response addition, and integrated addition) and using the integrated addition and interaction (IAI) model. Toxicity of the 30 mixtures was then experimentally determined and compared to model results. Only the IAI model accurately predicted the toxicity of the mixtures. The IAI model holds promise as a means for assessing hazard of complex chemical mixtures.

Acetylcholinesterase↗

Collinear interactions and contour integration.

The visibility of a local target is influenced by the global configuration of the stimulus. Collinear configurations are a specific case in which facilitation or suppression of the target has been found to be dependent on the contrast threshold of the target. The role of collinear interactions in perceptual grouping, especially in contour integration, is still controversial. In the current study, the role of collinear interactions in noise was investigated using experimental conditions similar to those utilized in studies of contour integration. The contrast detection paradigm in the presence of similar Gabor elements presented in the background was used. The results show that contrast detection threshold of the target alone is increased (suppression) when it is embedded in randomly oriented background elements. However, when the target is flanked by two collinear Gabor elements, the target is facilitated even at higher target contrast levels. Facilitation is not found for orthogonal configurations. The results suggest that the response to a local element in a contour is modified by lateral facilitative and suppressive inputs from elements comprising the smooth contour and randomly oriented background elements, respectively. Thus, detection of elements along a contour should be considered as integration of global neuronal activity rather than as the output of local and individual neurons.

Contrast Sensitivity↗

Quantum phase transitions in the interacting boson model: integrability, level repulsion, and level crossing.

We study the quantum phase transition mechanisms that arise in the interacting boson model. We show that the second-order nature of the phase transition from U(5) to O(6) may be attributed to quantum integrability, whereas all the first-order phase transitions of the model are due to level repulsion with one singular point of level crossing. We propose a model Hamiltonian with a true first-order phase transition for finite systems due to level crossings.

Journal Article↗

Integrated fluid handling system for biomolecular interaction analysis.

An integrated fluid handling system used for multichannel biomolecular interaction analysis is described. Reactions between biological molecules are monitored in real time by measuring changes in the angular position where surface plasmon resonance occurs at a biospecific active surface. The adsorption efficiency of the analyte onto the biospecific active surface is up to approximately 3%, due to the low channel height, 50 microns, in the flow cell. When a large part of the total biospecific active surface for surface plasmon resonance probing (approximately 0.15 mm2) is used, the sensitivity is high. Sample sizes in the order of 1-50 microL can be injected. The sample zone dispersion is minimized by the low dead volume in the system (approximately 0.4 microL) accomplished by using integrated sample loops and thin conduits. An asset of this integration is the low reagent consumption. The sensor chip with the biospecific active surface is reusable and easily exchanged. Experimental results obtained with a theophylline monoclonal antibody as the analyte are compared with a theoretical model. The standard deviation for the repeatability is approximately 5% typically with 50 microL of 250 pM analyte, and the assay time is 10 min. The detection limit is approximately 10 pg of the analyte on the probed spot of the surface. Possible improvements of the sensitivity and detection limit are discussed.

Antibodies, Monoclonal↗

Integrative radiation carcinogenesis: interactions between cell and tissue responses to DNA damage.

Tissue function requires coordinated multicellular behavior as a consequence of diverse signals integrated through the tissue microenvironment; importantly, these cell-cell and cell-microenvironment interactions also actively suppress cancer. Ionizing radiation (IR) elicits a well-defined cellular response to DNA damage that mediates the fate of the individual cell, concomitantly with a less well-characterized overarching tissue stress response that coordinates the response of multiple cell types via microenvironment signaling. We have now shown that these programs to reestablish homeostasis intersect via mutual regulation by transforming growth factor beta1 (TGF beta 1), which acts as an extracellular sensor and signal of stress. In this review, the concept that this type of functional integration of cell and tissue stress response programs is essential to cancer suppression will be discussed. Our experiments using IR, and several recent studies that experimentally manipulate stromal TGF beta, show that disruption of microenvironment signaling actively promotes malignant progression. Understanding the dynamic interactions between tissue and cell stress responses will be necessary for an accurate assessment of cancer risk and may also provide targets for prevention.

Animals↗

Bves modulates epithelial integrity through an interaction at the tight junction.

We first identified Bves (blood vessel/epicardial substance) as a transmembrane protein that localized to the lateral compartment of the epithelial epicardium. Bves traffics to sites of cell-cell contact in cultured epicardial cells and promotes adhesion following transfection into non-adherent fibroblastic L-cells, reminiscent of a cell adhesion molecule. Currently, no function for Bves in relation to epithelial cell adhesion has been identified. We hypothesize that Bves plays a role at cell junctions to establish and/or modulate cell adhesion or cell-cell interactions in epithelial cell types. In this study, we demonstrate that Bves regulates epithelial integrity and that this function may be associated with a role at the tight junction (TJ). We report that Bves localizes with ZO-1 and occludin, markers of the TJ, in polarized epithelial cell lines and in vivo. We find that the behavior of Bves following low Ca2+ challenge or TPA treatment mimics that observed for ZO-1 and is distinct from adherens junction proteins such as E-cadherin. Furthermore, GST pull-down experiments show an interaction between ZO-1 and the intracellular C-terminal tail of Bves. Finally, we demonstrate that Bves modulates tight junction integrity, as indicated by the loss of transepithelial resistance and junction protein localization at the membrane following Bves knock-down in cultured cells. This study is the first to identify a function for Bves in epithelia and supports the hypothesis that Bves contributes to establishment and/or maintenance of epithelial cell integrity.

Animals↗

A graphical user interaction model for integrating complex clinical applications: a pilot study.

We have developed and implemented a multi-faceted, graphical user interaction model for an advanced clinical information system. This paper describes a classification scheme for applications used by clinicians in their daily work, discusses the way clinicians interact with these applications, and the issues that arise during these user interactions. Through its emphasis on support for application interoperation, the graphical user interface that implements the model presents a single, consistent, context to the user, and thereby helps maintain patient safety and ensure ease of use.

Computer Graphics↗

STRING 7--recent developments in the integration and prediction of protein interactions.

Information on protein-protein interactions is still mostly limited to a small number of model organisms, and originates from a wide variety of experimental and computational techniques. The database and online resource STRING generalizes access to protein interaction data, by integrating known and predicted interactions from a variety of sources. The underlying infrastructure includes a consistent body of completely sequenced genomes and exhaustive orthology classifications, based on which interaction evidence is transferred between organisms. Although primarily developed for protein interaction analysis, the resource has also been successfully applied to comparative genomics, phylogenetics and network studies, which are all facilitated by programmatic access to the database backend and the availability of compact download files. As of release 7, STRING has almost doubled to 373 distinct organisms, and contains more than 1.5 million proteins for which associations have been pre-computed. Novel features include AJAX-based web-navigation, inclusion of additional resources such as BioGRID, and detailed protein domain annotation. STRING is available at http://string.embl.de/

Databases, Protein↗