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At least 631 records · Page 35Linked to original sources

Base-pair substitutions in avian sarcoma virus U5 and U3 long terminal repeat sequences alter the process of DNA integration in vitro.

We have described a reconstituted avian sarcoma virus (ASV) concerted DNA integration system with specially designed mini-donor DNA containing a supF transcription unit, a supercoiled plasmid acceptor, purified bacterially expressed ASV integrase (IN), and human high-mobility-group protein I(Y). Integration in this system is dependent upon the mini-donor DNA having IN recognition sequences at both ends and upon both ends of the same donor integrating into the acceptor DNA. The integrated DNA product exhibits all of the features associated with integration of viral DNA in vivo (P. Hindmarsh et al., J. Virol., 73:2994-3003, 1999). Individual integrants are isolated from bacteria containing drug-resistant markers with amber mutations. This system was used to evaluate the importance of sequences in the terminal U5 and U3 long terminal repeats at positions 5 and/or 6, adjacent to the conserved CA dinucleotide. Base-pair substitutions introduced at these positions in U5 result in significant reductions in recovered integrants from bacteria, due to increases in one-ended insertion events. Among the recovered integrants from reactions with mutated U5 but not U3 IN recognition sequences were products that contain large deletions in the acceptor DNA. Base-pair substitutions at positions 5 and 6 in U3 mostly reduce the efficiency of integration of the modified donor. Together, these results indicate that sequences directly 5' to the conserved CA dinucleotide are very important for the process of concerted DNA integration. Furthermore, IN interacts with U3 and U5 termini differently, and aberrant end-processing events leading to nonconcerted DNA integration are more common in U5 than in U3.

Avian Sarcoma Viruses↗

Integrated software suite for magnetocardiographic data analysis--a proposal based on an interactive programming environment.

OBJECTIVES: This paper describes an integrated software suite (ISS) for the processing of magnetocardiographic (MCG) recordings obtained with super-conducting multi-channel systems having different characteristics. We aimed to develop a highly flexible suite including toolboxes for current MCG applications, organized consistently with an open architecture that allows function integrations and upgrades with minimal modifications; the suite was designed for the compliance not only of physicists and engineers but also of physicians, who have a different professional profile and are accustomed to retrieve information in different ways. METHODS: The MCG-ISS was designed to work with all common graphical user interface operative systems. MATLAB was chosen as the interactive programming environment (IPE), and the software was developed to achieve usability, interactivity, reliability, modularity, expansibility, interoperability, adaptability and graphics style tailoring. Three users, already experienced in MCG data analysis, have intensively tested MCG-ISS for six months. A great amount of MCG data on normal subjects and patients was used to assess software performances in terms of user compliance and confidence and total analysis time. RESULTS: The proposed suite is an all-in-one analysis tool that succeeded in speeding MCG data analysis up to about 55% with respect to standard reference routines; it consequently enhanced analysis performance and user compliance. CONCLUSIONS: Those results, together with the MCG-ISS advantage of being independent on the acquisition system, suggest that software suites like the proposed one could uphold a wider diffusion of MCG as a diagnostic tool in the clinical setting.

Diagnosis, Computer-Assisted↗

Antagonists of the NMDA receptor-channel complex and motor coordination.

Many structurally different, centrally active antagonists of the NMDA receptor-channel complex induce phencyclidine-like side effects in mammals which include head weaving, body rolling, sniffing and disturbances of motor coordination. The ability of these compounds to cause disturbances of motor coordination correlates directly with their ability to antagonize the NMDA receptor-channel complex in vivo. Although noncompetitive antagonists increase motility in rodents, whereas competitive antagonists do not, both classes of compounds appear to induce schizophrenia-like psychosis in human beings, and cause similar changes in a variety of different biogenic amine neurotransmitter systems in the limbic and motoric areas of the brain. The complex spectrum of behavioural effects observed after the administration of antagonists of the NMDA receptor-channel complex probably reflects the intricate nature of the interaction with positive and negative feedback loops of the motor circuit. Recent research indicates that the site of integration of this interaction could be the striatal medium spiny GABAergic neuron.

Animals↗

Improving test ordering in primary care: the added value of a small-group quality improvement strategy compared with classic feedback only.

PURPOSE: We wanted to evaluate the added value of small peer-group quality improvement meetings compared with simple feedback as a strategy to improve test-ordering behavior. Numbers of tests ordered by primary care physicians are increasing, and many of these tests seem to be unnecessary according to established, evidence-based guidelines. METHODS: We enrolled 194 primary care physicians from 27 local primary care practice groups in 5 health care regions (5 diagnostic centers). The study was a cluster randomized trial with randomization at the local physician group level. We evaluated an innovative, multifaceted strategy, combining written comparative feedback, group education on national guidelines, and social influence by peers in quality improvement sessions in small groups. The strategy was aimed at 3 specific clinical topics: cardiovascular issues, upper abdominal complaints, and lower abdominal complaints. The mean number of tests per physician per 6 months at baseline and the physicians' region were used as independent variables, and the mean number of tests per physician per 6 months was the dependent variable. RESULTS: The new strategy was executed in 13 primary care groups, whereas 14 groups received feedback only. For all 3 clinical topics, the decrease in mean total number of tests ordered by physicians in the intervention arm was far more substantial (on average 51 fewer tests per physician per half-year) than the decrease in mean number of tests ordered by physicians in the feedback arm (P = .005). Five tests considered to be inappropriate for the clinical problem of upper abdominal complaints decreased in the intervention arm, with physicians in the feedback arm ordering 13 more tests per 6 months (P = .002). Interdoctor variation in test ordering decreased more in the intervention arm. CONCLUSION: Compared with only disseminating comparative feedback reports to primary care physicians, the new strategy of involving peer interaction and social influence improved the physicians' test-ordering behavior. To be effective, feedback needs to be integrated in an interactive, educational environment.

Abdominal Pain↗

Identification of phospholipid scramblase 1 as a novel interacting molecule with beta -secretase (beta -site amyloid precursor protein (APP) cleaving enzyme (BACE)).

beta-Site amyloid precursor protein (APP)-cleaving enzyme (BACE) is an integral membrane aspartic proteinase responsible for beta-site processing of APP, and its cytoplasmic region composed of 24 amino acid residues has been shown to be involved in the endosomal localization of BACE. With the yeast two-hybrid screening, we found that the cytoplasmic domain of phospholipid scramblase 1 (PLSCR1), a type II integral membrane protein, interacts with the cytoplasmic region of BACE. In cultured cells, BACE and PLSCR1 were colocalized in the Golgi area and in endosomal compartments, whereas they were co-redistributed in late endosome-derived multivesicular bodies when treated with U18666A, suggesting that both proteins share a common trafficking pathway in cells. Co-immunoprecipitation analysis showed that both proteins form a protein complex at an endogenous expression level in the human neuroblastoma SH-SY5Ycells, and the dileucine residue of the BACE tail is also revealed to be essential for the physical interaction with PLSCR1 in vitro and in vivo. Moreover, both BACE and PLSCR1 were localized in a low buoyant lipid microdomain in SH-SY5Y cells. The dileucine-defective BACE mutant was also fractionated into the lipid microdomain, but much less stably than wild-type BACE. Taken together, our current study suggests the functional involvement of PLSCR1 in the intracellular distribution of BACE and/or recruitment of BACE into the detergent-insoluble lipid raft.

Amyloid Precursor Protein Secretases↗

Leukaemia inhibitory factor (LIF): a cytokine of emerging importance in chronic airway inflammation.

Inflammation is a complex set of mechanisms by which tissues respond to an injury. These responses involve the coordinated interaction between the nervous and immune systems. An integral part of this interaction is the release of a variety of cytokines that regulate cellular and molecular responses. Leukaemia Inhibitory Factor (LIF), a member of the IL-6 family of cytokines, has been shown to be an integral component of the interface between nerves and the immune system. However, little is known about this cytokine in the context of normal lung function or indeed, inflammation. Evidence is emerging that this cytokine may play an important role in regulating the neural-immune system interaction during acute inflammatory insult and the subsequent healing and restitution process. However, LIF may act as either a pro- or antiinflammatory cytokine, depending on the cell type and a number of other variables. In this review, the role of LIF in airway inflammation and resolution of inflammation is discussed. In particular, recent work suggesting that LIF is a mediator of bi-directional cross-talk between neural tissue and the immune system is highlighted.

Animals↗

Low-temperature transport in Heisenberg chains.

A technique to determine accurately transport properties of integrable and nonintegrable quantum-spin chains at finite temperatures by quantum Monte Carlo is presented. The reduction of the Drude weight by interactions in the integrable gapless regime is evaluated. Evidence for the absence of Drude weight in the gapless regime of a nonintegrable system with longer-ranged interactions is presented. We estimate the effect of the nonintegrability on the transport properties and compare with recent experiments on one-dimensional quantum-spin chains.

Journal Article↗

An evaluation of satisfaction with telemedicine among health-care professionals.

A survey was conducted among non-doctor health-care professionals in six rural counties in Missouri. The purpose of the survey was to establish baseline data to evaluate the effect of changes in the health-care sector, especially technology changes, on the job satisfaction, career satisfaction, relationships and communication activities of health professionals. The survey included three rural counties in which integrated telecommunication and interactive video telemedicine services were being installed, but before significant activities had begun, and three comparator counties without substantial integrated telecommunications infrastructure and telemedicine services. During a one-month study period, 1108 questionnaires were distributed. The total response rate was 50.1% (n = 555). Of the respondents, 30.3% indicated that technology in health-care was having a large effect on their work, although only 18.2% indicated that telemedicine and telecommunications were having a large effect. No systematic differences were found among the health professionals in the two communities at the time telemedicine equipment was being installed.

Health Knowledge, Attitudes, Practice↗

Wigner-Dyson statistics for a class of integrable models.

We construct an ensemble of second-quantized Hamiltonians with two bosonic degrees of freedom, whose members display with probability one Gaussian orthogonal ensemble (GOE) or Gaussian unitary ensemble (GUE) statistics. Nevertheless, these Hamiltonians have a second integral of motion, namely, the boson number, and thus are integrable. To construct this ensemble we use some "reverse engineering" starting from the fact that n bosons in a two-level system with random interactions have an integrable classical limit by the old Heisenberg association of boson operators to actions and angles. By choosing an n-body random interaction and degenerate levels we end up with GOE or GUE Hamiltonians. Ergodicity of these ensembles completes the example.

Journal Article↗

Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.

Inwardly rectifying K(+) (Kir) channels are important regulators of resting membrane potential and cell excitability. The activity of Kir channels is critically dependent on the integrity of channel interactions with phosphatidylinositol 4,5-bisphosphate (PIP(2)). Here we identify and characterize channel-PIP(2) interactions that are conserved among Kir family members. We find basic residues that interact with PIP(2), two of which have been associated with Andersen's and Bartter's syndromes. We show that several naturally occurring mutants decrease channel-PIP(2) interactions, leading to disease.

Amino Acid Sequence↗

Phosphorylation of ankyrin down-regulates its cooperative interaction with spectrin and protein 3.

Ankyrin mediates the primary attachment between beta spectrin and protein 3. Ankyrin and spectrin interact in a positively cooperative fashion such that ankyrin binding increases the extent of spectrin tetramer and oligomer formation (Giorgi and Morrow: submitted, 1988). This cooperative interaction is enhanced by the cytoplasmic domain of protein 3, which is prepared as a 45-41-kDa fragment generated by chymotryptic digestion of erythrocyte membranes. Using sensitive isotope-ratio methods and nondenaturing PAGE, we now demonstrate directly (1) the enhanced affinity of ankyrin for spectrin oligomers compared to spectrin dimers; (2) a selective stimulation of the affinity of ankyrin for spectrin oligomer by the 43-kDa cytoplasmic domain of protein 3; and (3) a selective reduction in the affinity of ankyrin for spectrin tetramer and oligomer after its phosphorylation by the erythrocyte cAMP-independent membrane kinase. The phosphorylation of ankyrin does not affect its binding to spectrin dimer. Ankyrin also enhances the rate of interconversion between dimer-tetramer-oligomer by 2-3-fold at 30 degrees C, and in the presence of the 43-kDa fragment, ankyrin stimulates the rate of oligomer interconversions by nearly 40-fold at this temperature. These results demonstrate a long-range cooperative interaction between an integral membrane protein and the peripheral cytoskeleton and indicate that this linkage may be regulated by covalent protein phosphorylation. Such interactions may be of general importance in nonerythroid cells.

Anion Exchange Protein 1, Erythrocyte↗

Biosynthesis of the dystonia-associated AAA+ ATPase torsinA at the endoplasmic reticulum.

TorsinA is a widely expressed AAA(+) (ATPases associated with various cellular activities) ATPase of unknown function. Previous studies have described torsinA as a type II protein with a cleavable signal sequence, a single membrane spanning domain, and its C-terminus located in the ER (endoplasmic reticulum) lumen. However, in the present study we show that torsinA is not in fact an integral membrane protein. Instead we find that the mature protein associates peripherally with the ER membrane, most likely through an interaction with an integral membrane protein. Consistent with this model, we provide evidence that the signal peptidase complex cleaves the signal sequence of torsinA, and we show that the region previously suggested to form a transmembrane domain is translocated into the lumen of the ER. The finding that torsinA is a peripheral, and not an integral membrane protein as previously thought, has important implications for understanding the function of this novel ATPase.

Adenosine Triphosphatases↗

Architecture of basic building blocks in protein and domain structural interaction networks.

MOTIVATION: The structural interaction of proteins and their domains in networks is one of the most basic molecular mechanisms for biological cells. Topological analysis of such networks can provide an understanding of and solutions for predicting properties of proteins and their evolution in terms of domains. A single paradigm for the analysis of interactions at different layers, such as domain and protein layers, is needed. RESULTS: Applying a colored vertex graph model, we integrated two basic interaction layers under a unified model: (1) structural domains and (2) their protein/complex networks. We identified four basic and distinct elements in the model that explains protein interactions at the domain level. We searched for motifs in the networks to detect their topological characteristics using a pruning strategy and a hash table for rapid detection. We obtained the following results: first, compared with a random distribution, a substantial part of the protein interactions could be explained by domain-level structural interaction information. Second, there were distinct kinds of protein interaction patterns classified by specific and distinguishable numbers of domains. The intermolecular domain interaction was the most dominant protein interaction pattern. Third, despite the coverage of the protein interaction information differing among species, the similarity of their networks indicated shared architectures of protein interaction network in living organisms. Remarkably, there were only a few basic architectures in the model (>10 for a 4-node network topology), and we propose that most biological combinations of domains into proteins and complexes can be explained by a small number of key topological motifs. CONTACT: doheon@kaist.ac.kr.

Animals↗

[Relation of social integration and personality].

This study aims at describing personality characteristics in three groups of children with different levels of social integration. The three groups were virtually 'confused' with the type of school the children attended at. The first group attended the kind of special school which is shanty towns typical. The second group attended usual State primary schools located in low-income popular areas, and the third group, the same type of school located, however, in medium to high-income residential areas. The Holtzman Inkblot Technique was administered to 120 children (boys and girls), ranging from 8 to 13-year-old's. Triple variance analyses were performed to study the influence of age, sex, social integration, and their interaction among the different personality variables. It was found that the three groups differentiated according to their level of social integration, with different personality traits.

Adolescent↗

Integrated prediction of the helical membrane protein interactome in yeast.

At least a quarter of all genes in most genomes contain putative transmembrane (TM) helices, and helical membrane protein interactions are a major component of the overall cellular interactome. However, current experimental techniques for large-scale detection of protein-protein interactions are biased against membrane proteins. Here, we define protein-protein interaction broadly as co-complexation, and develop a weighted-voting procedure to predict interactions among yeast helical membrane proteins by optimally combining evidence based on diverse genome-wide information such as sequence, function, localization, abundance, regulation, and phenotype. We use logistic regression to simultaneously optimize the weights of all evidence sources for best discrimination based on a set of known helical membrane protein interactions. The resulting integrated classifier not only significantly outperforms classifiers based on any single genomic feature, but also does better than a benchmark Naïve Bayes classifier (using a simplifying assumption of conditional independence among features). Finally, we apply the optimized classifier genome-wide, and construct a comprehensive map of predicted helical membrane protein interactome in yeast. This can serve as a guide for prioritizing further experimental validation efforts.

Membrane Proteins↗

A probabilistic functional network of yeast genes.

A conceptual framework for integrating diverse functional genomics data was developed by reinterpreting experiments to provide numerical likelihoods that genes are functionally linked. This allows direct comparison and integration of different classes of data. The resulting probabilistic gene network estimates the functional coupling between genes. Within this framework, we reconstructed an extensive, high-quality functional gene network for Saccharomyces cerevisiae, consisting of 4681 (approximately 81%) of the known yeast genes linked by approximately 34,000 probabilistic linkages comparable in accuracy to small-scale interaction assays. The integrated linkages distinguish true from false-positive interactions in earlier data sets; new interactions emerge from genes' network contexts, as shown for genes in chromatin modification and ribosome biogenesis.

Bayes Theorem↗

Integrin-matrix interactions in the cerebral microvasculature.

The integrity of all organ systems requires faithful interaction between its component cells and the extracellular matrix (ECM). In the central nervous system (CNS), matrix adhesion receptors are uniquely expressed by the cells comprising the microvascular compartment, and by neurons and their supporting glial cells. Cells within the cerebral microvasculature express both the integrin and dystroglycan families of matrix adhesion receptors. However, the functional significance of these receptors is only now being explored. Capillaries of the cerebral microvasculature consist of the luminal endothelium, which is separated from circumferential astrocyte end-feet by the intervening ECM of the basal lamina. Endothelial cells and astrocytes cooperate to generate and maintain the basal lamina and the unique barrier functions of the endothelium. Integrins and the dystroglycan complex are found on the matrix-proximate faces of both endothelial cells and astrocyte end-feet. Pericytes rest against the basal lamina. In the extravascular compartment, select integrins are expressed on neurons, microglial cells, and oligodendroglia. Significant alterations in both cellular adhesion receptors and their ligands occur under the conditions of focal cerebral ischemia, multiple sclerosis (MS) and the modeled condition experimental autoimmune encephalomyelitis (EAE), certain tumors of the CNS, and arteriovenous malformations (AVMs). The changes in matrix adhesion receptor expression in these conditions support their functional significance in the normal state. We propose that matrix adhesion receptors are essential for the maintenance of the integrity of the blood-brain permeability barrier, and that modulation of these receptors contribute to alterations in the barrier during brain injury. This review examines current information about cell adhesion receptor expression within the cerebral microvasculature and surrounding tissue, and their potential roles during the vascular responses to local injury.

Animals↗

Integration of the Lorentz-Dirac equation: Interaction of an intense laser pulse with high-energy electrons.

Usually the motion of an electron under the influence of electromagnetic fields is influenced to a small extent by radiation damping. With the advent of high power high irradiance lasers it has become possible to generate focused laser irradiances where electrons interacting with the laser become highly relativistic over very short time and spatial scales. By focusing petawatt class lasers to very small spot sizes the amount of radiation emitted by electrons can become very large. Resultingly, the damping of the electron motion by the emission of this radiation can become large. In order to study this problem a code is written to solve a set of equations describing the evolution of a strong electromagnetic wave interacting with a single electron. Usually the equation of motion of an electron including radiation damping under the influence of electromagnetic fields is derived from the Lorentz-Dirac equation treating the damping as a perturbation. We use this equation to integrate forward in time and use the Lorentz-Dirac equation to integrate backward in time. We show that for very short wavelength electromagnetic radiation deep in the quantum regime at high irradiances differences between the perturbation equation and Lorentz-Dirac can be seen. However, for electron motion in the classical regime the differences are negligible. For electron motion in the classical regime the first order damping equation is found to be very adequate.

Journal Article↗