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PubMed2002

Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction.

The extra-enzymic function of cell-surface adenosine deaminase (ADA), an enzyme mainly localized in the cytosol but also found on the cell surface of monocytes, B cells and T cells, has lately been the subject of numerous studies. Cell-surface ADA is able to transduce co-stimulatory signals in T cells via its interaction with CD26, an integral membrane protein that acts as ADA-binding protein. The aim of the present study was to explore whether ADA-CD26 interaction plays a role in the adhesion of lymphocyte cells to human epithelial cells. To meet this aim, different lymphocyte cell lines (Jurkat and CEM T) expressing endogenous, or overexpressing human, CD26 protein were tested in adhesion assays to monolayers of colon adenocarcinoma human epithelial cells, Caco-2, which express high levels of cell-surface ADA. Interestingly, the adhesion of Jurkat and CEM T cells to a monolayer of Caco-2 cells was greatly dependent on CD26. An increase by 50% in the cell-to-cell adhesion was found in cells containing higher levels of CD26. Incubation with an anti-CD26 antibody raised against the ADA-binding site or with exogenous ADA resulted in a significant reduction (50-70%) of T-cell adhesion to monolayers of epithelial cells. The role of ADA-CD26 interaction in the lymphocyte-epithelial cell adhesion appears to be mediated by CD26 molecules that are not interacting with endogenous ADA (ADA-free CD26), since SKW6.4 (B cells) that express more cell-surface ADA showed lower adhesion than T cells. Adhesion stimulated by CD26 and ADA is mediated by T cell lymphocyte function-associated antigen. A role for ADA-CD26 interaction in cell-to-cell adhesion was confirmed further in integrin activation assays. FACS analysis revealed a higher expression of activated integrins on T cell lines in the presence of increasing amounts of exogenous ADA. Taken together, these results suggest that the ADA-CD26 interaction on the cell surface has a role in lymphocyte-epithelial cell adhesion.

Adenosine Deaminase↗

PubMed2006

UniHI: an entry gate to the human protein interactome.

Systematic mapping of protein-protein interactions has become a central task of functional genomics. To map the human interactome, several strategies have recently been pursued. The generated interaction datasets are valuable resources for scientists in biology and medicine. However, comparison reveals limited overlap between different interaction networks. This divergence obstructs usability, as researchers have to interrogate numerous heterogeneous datasets to identify potential interaction partners for proteins of interest. To facilitate direct access through a single entry gate, we have started to integrate currently available human protein interaction data in an easily accessible online database. It is called UniHI (Unified Human Interactome) and is available at http://www.mdc-berlin.de/unihi. At present, it is based on 10 major interaction maps derived by computational and experimental methods. It includes more than 150,000 distinct interactions between more than 17 000 unique human proteins. UniHI provides researchers with a flexible integrated tool for finding and using comprehensive information about the human interactome.

Computer Graphics↗

PubMed1996

A Monte Carlo simulation study of protein-induced heat capacity changes and lipid-induced protein clustering.

Monte Carlo simulations were used to describe the interaction of peripheral and integral proteins with lipids in terms of heat capacity profiles and protein distribution. The simulations were based on a two-state model for the lipid, representing the lipid state as being either gel or fluid. The interaction between neighboring lipids has been taken into account through an unlike nearest neighbor free energy term delta omega, which is a measure of the cooperativity of the lipid transition. Lipid/protein interaction was considered using the experimental observation that the transition midpoints of lipid membranes are shifted upon protein binding, a thermodynamic consequence of different binding constants of protein with fluid or gel lipids. The difference of the binding free energies was used as an additional parameter to describe lipid-protein interaction. The heat capacity profiles of lipid/protein complexes could be well described for both peripheral and integral proteins. Binding of proteins results in a shift and an asymmetric broadening of the melting profile. The model results in a coexistence of gel and fluid lipid domains in the proximity of the thermotropic transition. As a consequence, bound peripheral proteins aggregate in the temperature range of the lipid transition. Integral proteins induce calorimetric melting curves that are qualitatively different from that of peripheral proteins and aggregate in either gel or liquid crystalline lipid phase. The results presented here are in good agreement with calorimetric experiments on lipid-protein complexes and have implementations for the functional control of proteins.

Biophysical Phenomena↗

PubMed2001

ISYS: a decentralized, component-based approach to the integration of heterogeneous bioinformatics resources.

MOTIVATION: Heterogeneity of databases and software resources continues to hamper the integration of biological information. Top-down solutions are not feasible for the full-scale problem of integration across biological species and data types. Bottom-up solutions so far have not integrated, in a maximally flexible way, dynamic and interactive graphical-user-interface components with data repositories and analysis tools. RESULTS: We present a component-based approach that relies on a generalized platform for component integration. The platform enables independently-developed components to synchronize their behavior and exchange services, without direct knowledge of one another. An interface-based data model allows the exchange of information with minimal component interdependency. From these interactions an integrated system results, which we call ISYSf1.gif" BORDER="0">. By allowing services to be discovered dynamically based on selected objects, ISYS encourages a kind of exploratory navigation that we believe to be well-suited for applications in genomic research.

Arabidopsis↗

PubMed2005

Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity.

Dendritic cells (DCs) regulate various aspects of innate immunity, including natural killer (NK) cell function. Here we define the mechanisms involved in DC-NK cell interactions during viral infection. NK cells were efficiently activated by murine cytomegalovirus (MCMV)-infected CD11b(+) DCs. NK cell cytotoxicity required interferon-alpha and interactions between the NKG2D activating receptor and NKG2D ligand, whereas the production of interferon-gamma by NK cells relied mainly on DC-derived interleukin 18. Although Toll-like receptor 9 contributes to antiviral immunity, we found that signaling pathways independent of Toll-like receptor 9 were important in generating immune responses to MCMV, including the production of interferon-alpha and the induction of NK cell cytotoxicity. Notably, adoptive transfer of MCMV-activated CD11b(+) DCs resulted in improved control of MCMV infection, indicating that these cells participate in controlling viral replication in vivo.

Animals↗

PubMed2003

Depth variation bias and interaction with gain setting in ultrasonic tissue characterization by integrated backscatter analysis.

Integrated backscatter signal (IBS) has been proposed as a tool to measure cardiac fibrosis. To overcome problems associated with machine settings and attenuation of the chest wall, IBS has been expressed in relation to posterior pericardium, as a variation across cardiac cycle, or both. Depth of the reflecting structure has never been considered as a source of variability. Accordingly, we studied the effect of structure depth on IBS and examined its interaction with gain setting. Backscatter signals were recorded from plastic phantoms containing identical structures set at increasing depth and in 1 healthy volunteer using silicone spacers to modify depth, on a wide range of gain settings. In the phantom, IBS signal linearly decreased with increasing depth and nonlinearly increased with increasing gain (all r(2) > 0.97). In the healthy volunteer, results from septum were very similar to the phantom experiment. Values of septal IBS were adjusted using multiple regression coefficients for gain and depth from the phantom experiment and resulted in a near-complete offset of effect of depth and gain on septal IBS (P = not significant for both gain and depth). These assumptions were also used to compare IBS analysis between hypertensive patients and patients with hypertrophic cardiomyopathy. Thus, depth and its relation with gain should be taken into account and might be almost fully predicted. Using appropriate regression modeling may allow analysis in optimal imaging conditions, tolerating between-patient comparisons even in limited diastolic frames.

Cardiomyopathy, Hypertrophic↗

PubMed2006

Alternate interfaces may mediate homomeric and heteromeric assembly in the transmembrane domains of SNARE proteins.

The fusion of a vesicle to a target membrane is mediated by temporally and spatially regulated interactions within a set of evolutionarily conserved proteins. Integral to proper fusion is the interaction between proteins originating on both vesicle and target membranes to form a protein bridge between the two membranes, known as the SNARE complex. This protein complex includes the single-pass transmembrane helix proteins: syntaxin and synaptobrevin. Experimental data and amino acid sequence analysis suggest that an interface of interaction is conserved between the transmembrane regions of the two proteins. However, conflicting reports have been presented on the role of the synaptobrevin transmembrane domain in mediating important protein-protein interactions. To address this question, a thermodynamic study was carried out to determine quantitatively the self-association propensities of the transmembrane domains of synaptobrevin and syntaxin. Our results show that the transmembrane domain of synaptobrevin has only a modest ability to self-associate, whereas the transmembrane domain of syntaxin is able to form stable homodimers. Nevertheless, by a single amino acid substitution, synaptobrevin can be driven to dimerize with the same affinity as syntaxin. Furthermore, crosslinking studies show that dimerization of synaptobrevin is promoted by oxidizing agents. Despite the presence of a conserved cysteine residue in the same location as in synaptobrevin, syntaxin dimerization is not promoted by oxidization. This analysis suggests that subtle yet distinct differences are present between the two transmembrane dimer interfaces. A syntaxin/synaptobrevin heterodimer is able to form under oxidizing conditions, and we propose that the interface of interaction for the heterodimer may resemble the homodimer interface formed by the synaptobrevin transmembrane domain. Computational analysis of the transmembrane sequences of syntaxin and synaptobrevin reveal structural models that correlate with the experimental data. These data may provide insight into the role of transmembrane segments in the mechanism of vesicle fusion.

Animals↗

PubMed2000

The mechanism of interaction between visual flow and eye velocity signals for heading perception.

A translating eye receives a radial pattern of motion that is centered on the direction of heading. If the eye is rotating and translating, visual and extraretinal signals help to cancel the rotation and to perceive heading correctly. This involves (1) an interaction between visual and eye movement signals and (2) a motion template stage that analyzes the pattern of visual motion. Early interaction leads to motion templates that integrate head-centered motion signals in the visual field. Integration of retinal motion signals leads to late interaction. Here, we show that retinal flow limits precision of heading. This result argues against an early, vector subtraction type of interaction, but is consistent with a late, gain field type of interaction with eye velocity signals and neurophysiological findings in area MST of the monkey.

Eye Movements↗

PubMed2006

PIANA: protein interactions and network analysis.

UNLABELLED: We present a software framework and tool called Protein Interactions And Network Analysis (PIANA) that facilitates working with protein interaction networks by (1) integrating data from multiple sources, (2) providing a library that handles graph-related tasks and (3) automating the analysis of protein-protein interaction networks. PIANA can also be used as a stand-alone application to create protein interaction networks and perform tasks such as predicting protein interactions and helping to identify spots in a 2D electrophoresis gel. AVAILABILITY: PIANA is under the GNU GPL. Source code, database and detailed documentation may be freely downloaded from http://sbi.imim.es/piana.

Computer Graphics↗

PubMedDate not supplied

Multisensory interaction in saccadic reaction time: a time-window-of-integration model.

Saccadic reaction time to visual targets tends to be faster when stimuli from another modality (in particular, audition and touch) are presented in close temporal or spatial proximity even when subjects are instructed to ignore the accessory input (focused attention task). Multisensory interaction effects measured in neural structures involved in saccade generation (in particular, the superior colliculus) have demonstrated a similar spatio-temporal dependence. Neural network models of multisensory spatial integration have been shown to generate convergence of the visual, auditory, and tactile reference frames and the sensorimotor coordinate transformations necessary for coordinated head and eye movements. However, because these models do not capture the temporal coincidences critical for multisensory integration to occur, they cannot easily predict multisensory effects observed in behavioral data such as saccadic reaction times. This article proposes a quantitative stochastic framework, the time-window-of-integration model, to account for the temporal rules of multisensory integration. Saccadic responses collected from a visual-tactile focused attention task are shown to be consistent with the time-window-of-integration model predictions.

Adaptation, Physiological↗

PubMed1996

Contour integration with colour and luminance contrast.

In this study, we consider how colour contrast can be used to integrate form and how it interacts with luminance contrast in the task. The performance of form integration was assessed by measuring the detection of a winding "contour" of aligned gabor elements embedded in a background of randomly oriented gabors, using both luminance and isoluminant (red/green) contrast. Performance on the task improves with gabor element contrast, and identical performance for colour and luminance contour detection is achieved at high screen contrasts, showing that colour is able to support a complex form integration task. In a second experiment, we investigate whether colour and luminance contrast can be combined in contour integration by measuring the detection of a path with alternating isoluminant colour and luminance elements. We find that contour detection uses both colour and luminance information cooperatively, but performance is much poorer than would be expected from a single common contour integration process which fails to distinguish the two types of contrast. This suggests that there are specific contour integration processes for colour and luminance. In a third experiment, we measure the effects of variations in colour and luminance contrast on contour detection using elements that combine colour and luminance contrast. We find that varying the colour contrast of elements tends to worsen the detection of a luminance contour, as do luminance contrast variations for colour contour detection. These results suggest no special role for colour in integrating contours, and are discussed with regard to their ecological significance.

Algorithms↗

PubMed1982

Cytosolic protein binding to band-3 protein inhibits endocytosis of isolated human erythrocyte membranes.

Recent studies of haemoglobin binding to the cytoplasmic side of the erythrocyte membrane have shown that the predominant high-affinity interaction occurs with the major integral membrane protein known as band-3 protein and that this interaction may occur within the intact erythrocyte in a manner regulated by cell pH. We report here that haemoglobin and glyceraldehyde 3-phosphate dehydrogenase binding to band-3 protein in isolated membranes can inhibit endocytosis during vesiculation in vitro. The specificity of this effect was demonstrated by showing that myoglobin, which has an affinity for the membrane fully one to two orders of magnitude lower than that for haemoglobin, does not inhibit endocytosis.

Anion Exchange Protein 1, Erythrocyte↗

PubMed2005

[Dermis collagens: beyond their structural properties].

The extracellular matrix is a complex network composed of macromolecules such as collagens, proteoglycans and elastin that strongly interact with each other and with cells to maintain the structural integrity of many tissues. These interactions also sustain important cell programs such as migration, proliferation, differentiation and apoptosis. The skin, and more specifically the dermis, contains an extreme diversity of macromolecules that reflects the importance of the composition and organization of the matrix components in providing physical properties and function of the tissues. The most abundant matrix components are the collagens that form a super-family of 27 different members which are divided into different subgroups. The fibrillar collagens, types I, III and V, the FACIT collagens, types XII, XIV and XVI, and collagen VI are all expressed in the collagen-rich dermis. Although the structural features of these collagens are now well characterized, their functions remain elusive. Mutations in human collagen genes give rise to numerous connective tissue diseases including dermis disorders. For example, clinical manifestations in the classical Elhers-Danlos syndrome caused by collagen V gene mutations occur predominantly in the dermis. However, the genotype-phenotype relationship is not clearly established as well as the relation between the distribution and the function of the collagens in dermis. There is no doubt that the ongoing and future work using in vivo approaches will provide new cues regarding the function of collagens in dermis.

ADAM Proteins↗

PubMed2004

The Database of Interacting Proteins: 2004 update.

The Database of Interacting Proteins (http://dip.doe-mbi.ucla.edu) aims to integrate the diverse body of experimental evidence on protein-protein interactions into a single, easily accessible online database. Because the reliability of experimental evidence varies widely, methods of quality assessment have been developed and utilized to identify the most reliable subset of the interactions. This CORE set can be used as a reference when evaluating the reliability of high-throughput protein-protein interaction data sets, for development of prediction methods, as well as in the studies of the properties of protein interaction networks.

Animals↗

PubMed1976

The role of histocompatibility gene products in lymphocyte triggering and differentiation.

Studies performed both in vivo and in vitro have demonstrated that genetic restrictions exist in the development of optimal cell-cell interactions in the immune system. Thus, in mice, the presence or absence of gene identities in the I region of the H-2 complex determines the capacity of lymphoid cells to interact. These cell interaction or CI genes appear to code for cell surface molecules integrally involved in regulatory cell interactions. Analysis of biologically active thymus-derived (T) cell factors capable of regulating differentiation events in other lymphoid cells indicates that such factors are around 40,000-50,000 daltons in mass, bear determinants coded for by I region genes, and consist of two covalently or noncovalently linked components--a heavy glycoprotein of around 40,000 daltons and a lighter protein of around 12,000 daltons. Preliminary evidence suggests that the latter component may be beta2-microglobulin.

Animals↗

PubMed2002

Enhancement of visual perception by crossmodal visuo-auditory interaction.

Neurophysiological studies have shown in animals that a sudden sound enhanced perceptual processing of subsequent visual stimuli. In the present study, we explored the possibility that such enhancement also exists in humans and can be explained through crossmodal integration effects, whereby the interaction occurs at the level of bimodal neurons. Subjects were required to detect visual stimuli in a unimodal visual condition or in crossmodal audio-visual conditions. The spatial and the temporal proximity of multisensory stimuli were systematically varied. An enhancement of the perceptual sensitivity (d') for luminance detection was found when the audiovisual stimuli followed a rather clear spatial and temporal rule, governing multisensory integration at the neuronal level.

Adult↗

PubMed2003

Epigenetic interactions between Arabidopsis transgenes: characterization in light of transgene integration sites.

The stochastic variability of expression that is a characteristic of eukaryotic nuclear transgenes is often attributed to epigenetic mechanisms that are triggered by repetitive transgene locus structures and influenced by chromosomal position effects. In order to address the contribution of chromosomal position effects in the context of a fully sequenced genome, a novel set of transgene loci was established in the compact genome of Arabidopsis thaliana. Transgenes expressing GFP-tagged or GUS-tagged fusion proteins of Arabidopsis COP1 collectively displayed three types of gene silencing, which are distinguished by their developmental timing, gene dosage dependence, (post)transcriptional control, and extent of endogene co-suppression. Subsequently, the heritability of epistatic interactions between allelic and non-allelic transgene loci was investigated in light of both intrinsic transgene features, in particular T-DNA copy number per locus, and chromosomal insertion sites. The notion that chromosomal flanking sequences underlie the ability of transgenes to function as masters or targets of epigenetically heritable trans-silencing interactions was generally not favored by our data. Moreover, among single T-DNA loci at different chromosomal locations the great majority showed homozygosity-dependent posttranscriptional silencing. However, spontaneous silencing (in cis) may be promoted by a pericentromeric location. Instead, intrinsic transgene features correlated with all major aspects of silencing behavior tested.

Arabidopsis↗

PubMed2006

Nonlinear interaction between shunting and adaptation controls a switch between integration and coincidence detection in pyramidal neurons.

The membrane conductance of a pyramidal neuron in vivo is substantially increased by background synaptic input. Increased membrane conductance, or shunting, does not simply reduce neuronal excitability. Recordings from hippocampal pyramidal neurons using dynamic clamp revealed that adaptation caused complete cessation of spiking in the high conductance state, whereas repetitive spiking could persist despite adaptation in the low conductance state. This behavior was reproduced in a phase plane model and was explained by a shunting-induced increase in voltage threshold. The increase in threshold allows greater activation of the M current (I(M)) at subthreshold potentials and reduces the minimum adaptation required to stabilize the system; in contrast, activation of the afterhyperpolarization current is unaffected by the increase in threshold and therefore remains unable to stop repetitive spiking. The nonlinear interaction between shunting and I(M) has other important consequences. First, timing of spikes elicited by brief stimuli is more precise when background spikes elicited by sustained input are prohibited, as occurs exclusively with I(M)-mediated adaptation in the high conductance state. Second, activation of I(M) at subthreshold potentials, which is increased in the high conductance state, hyperpolarizes average membrane potential away from voltage threshold, allowing only large, rapid fluctuations to reach threshold and elicit spikes. These results suggest that the shift from a low to high conductance state in a pyramidal neuron is accompanied by a switch from encoding time-averaged input with firing rate to encoding transient inputs with precisely timed spikes, in effect, switching the operational mode from integration to coincidence detection.

Action Potentials↗