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Results for “Integrative interaction”

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At least 847 records · Page 47Linked to original sources

PubMed2002

A cell-based bar code reader for high-throughput screening of ion channel-ligand interactions.

This paper presents a microfluidics-patch clamp platform for performing high-throughput screening and rapid characterization of weak-affinity ion channel-ligand interactions. This platform integrates a microfluidic chip consisting of multiple channels entering an open volume with standard patch clamp equipment. The microfluidic chip is placed on a motorized scanning stage and the method relies on the ability to scan rapidly, on the order of milliseconds, a patch-clamped cell across discrete zones of different solutions created in the open volume. Under ideal conditions, this method has the capacity to obtain kinetically resolved patch clamp measurements and dose-response curves of up to 10(3) ligand solutions in a single day.

Animals↗

PubMed2005

Characteristics of dynamic mass redistribution of epidermal growth factor receptor signaling in living cells measured with label-free optical biosensors.

This paper reported the identification of a novel optical signature for epidermal growth factor (EGF) receptor signaling in human epidermoid carcinoma A431 cells mediated by EGF. The optical signature was based on dynamic mass redistribution (DMR) in living cells triggered by EGFR activation, as monitored in real time with resonant waveguide grating biosensors. Analysis of the modulation of the EGF-induced DMR signals by a variety of known modulators provided links of various targets to distinct steps in the cellular responses. Results showed that the dynamic mass redistribution in quiescent A431 cells mediated by EGF required EGFR tyrosine kinase activity, actin polymerization, and dynamin and mainly proceeded through MEK. The DMR signals obtained serve as integrated signatures for interaction networks in the EGFR signaling.

Animals↗

PubMed2004

Altered substrate specificity in flavocytochrome b2: structural insights into the mechanism of L-lactate dehydrogenation.

Flavocytochrome b(2) from Saccharomyces cerevisiae is a l-lactate/cytochrome c oxidoreductase belonging to a large family of 2-hydroxyacid-dependent flavoenzymes. The crystal structure of the enzyme, with pyruvate bound at the active site, has been determined [Xia, Z.-X., and Mathews, F. S. (1990) J. Mol. Biol. 212, 837-863]. The authors indicate that the methyl group of pyruvate is in close contact with Ala198 and Leu230. These two residues are not well-conserved throughout the family of (S)-2-hydroxy acid oxidases/dehydrogenases. Thus, to probe substrate specificity in flavocytochrome b(2), these residues have been substituted by glycine and alanine, respectively. Kinetic studies on the L230A mutant enzyme and the A198G/L230A double mutant enzyme indicate a change in substrate selectivity for the enzyme toward larger (S)-2-hydroxy acids. In particular, the L230A enzyme is more efficient at utilizing (S)-2-hydroxyoctanoate by a factor of 40 as compared to the wild-type enzyme [Daff, S., Manson, F. D. C., Reid, G. A., and Chapman, S. K. (1994) Biochem. J. 301, 829-834], and the A198G/L230A double mutant enzyme is 6-fold more efficient with the aromatic substrate l-mandelate than it is with l-lactate [Sinclair, R., Reid, G. A., and Chapman, S. K. (1998) Biochem. J. 333, 117-120]. To complement these solution studies, we have solved the structure of the A198G/L230A enzyme in complex with pyruvate and as the FMN-sulfite adduct (both to 2.7 A resolution). We have also obtained the structure of the L230A mutant enzyme in complex with phenylglyoxylate (the product of mandelate oxidation) to 3.0 A resolution. These structures reveal the increased active-site volume available for binding larger substrates, while also confirming that the integrity of the interactions important for catalysis is maintained. In addition to this, the mode of binding of the bulky phenylglyoxylate at the active site is in accordance with the operation of a hydride transfer mechanism for substrate oxidation/flavin reduction in flavocytochrome b(2), whereas a mechanism involving the formation of a carbanion intermediate would appear to be sterically prohibited.

Amino Acid Sequence↗

PubMed1998

Cytochrome c-induced increase of motionally restricted lipid in reconstituted cytochrome c oxidase membranes, revealed by spin-label ESR spectroscopy.

Cytochrome c oxidase isolated from beef heart mitochondria was reconstituted in bilayer membranes of the anionic lipid dimyristoylphosphatidylglycerol (DMPG) with varying enzyme/DMPG ratio. Lipid-protein interactions in the reconstituted membrane complexes were studied in the presence and absence of saturating amounts of bound cytochrome c, by both chemical binding assays and spin-label ESR spectroscopy. The ESR spectra from a phosphatidylglycerol probe spin-labeled on C-14 of the sn-2 chain revealed two distinct lipid populations differing in their rotational mobility. The stoichiometry of lipids that were restricted in their rotational motion by direct interaction with the integral protein was 50-60 lipids/cytochrome c oxidase monomer, in the absence of cytochrome c, independent of the total lipid/protein ratio. Cytochrome c alone did not induce a motionally restricted population in the lipid ESR spectra, when bound to bilayers of negatively charged DMPG alone, in the fluid phase (at 36 degreesC). However, the motionally restricted lipid population associated with reconstituted cytochrome c oxidase/DMPG membranes increased on binding cytochrome c, indicating structural/dynamic changes taking place in the membrane. Depending on the DMPG/cytochrome c oxidase ratio, apparent stoichiometries of up to 115 motionally restricted lipid molecules/cytochrome c oxidase monomer were found, when saturating amounts of cytochrome c were bound. Under these conditions, cytochrome c binds to approximately 9 negatively charged DMPG molecules, independent of the cytochrome c oxidase content in the reconstituted system. A likely explanation for these results is that the surface binding of cytochrome c propagates the motional restriction of the lipid chains beyond the first boundary shell of cytochrome c oxidase, possibly creating microscopic in-plane domains.

Animals↗

PubMed2007

Switching surface chemistry with supramolecular machines.

Tethered supramolecular machines represent a new class of active self-assembled monolayers in which molecular configurations can be reversibly programmed using electrochemical stimuli. We are using these machines to address the chemistry of substrate surfaces for integrated microfluidic systems. Interactions between the tethered tetracationic cyclophane host cyclobis(paraquat-p-phenylene) and dissolved pi-electron-rich guest molecules, such as tetrathiafulvalene, have been reversibly switched by oxidative electrochemistry. The results demonstrate that surface-bound supramolecular machines can be programmed to adsorb or release appropriately designed solution species for manipulating surface chemistry.

Electrochemistry↗

PubMed2004

Cross-notation number priming investigated at different stimulus onset asynchronies in parity and naming tasks.

In this paper, a parity judgment task and a number naming task were used to investigate cross-notational number priming. Primes and targets could be verbal (e.g., seven) or Arabic numbers (e.g., 7), and were always presented in a different notation within the same trial (either a verbal prime and an Arabic target or an Arabic prime and a verbal target). Previous experiments showed that response latencies increase when the distance between prime and target increases (for example, in a naming task, seven is pronounced faster after 6 than after 5). This semantic distance priming effect was the same for Arabic and verbal targets and was the same for within-notation trials as for cross-notation trials. In the present experiments, we wanted to investigate whether the cross-notational priming effect also occurs at SOAs shorter than the ones used in previous experiments. Therefore, we used SOAs of 43, 57, 86, and 115 ms. Semantic distance effects were indeed present at these shorter SOAs: Processing times in the semantic parity judgment task and in the non-semantic naming task increased when the distance between prime and target increased. The results are discussed and integrated within an interactive dual-route model of number processing that postulates that the impact of the semantic and the non-semantic route depends on the task and the notation of the stimuli.

Humans↗

PubMed2006

Task and sex modulate the brain response to emotional incongruity in Asian listeners.

In order to recognize banter or sarcasm in social interactions, listeners must integrate verbal and vocal emotional expressions. Here, we investigated event-related potential correlates of this integration in Asian listeners. We presented emotional words spoken with congruous or incongruous emotional prosody. When listeners classified word meaning as positive or negative and ignored prosody, incongruous trials elicited a larger late positivity than congruous trials in women but not in men. Sex differences were absent when listeners evaluated the congruence between word meaning and emotional prosody. The similarity of these results to those obtained in Western listeners suggests that sex differences in emotional speech processing depend on attentional focus and may reflect culturally independent mechanisms.

Adult↗

PubMed1995

Structure of serum response factor core bound to DNA.

The human serum response factor is a transcription factor belonging to the MADS domain protein family with members characterized from the plant and animal kingdoms. The X-ray crystal structure of the serum response factor core in a specific-recognition DNA complex shows that the functions of DNA binding, dimerization and accessory-factor interaction are compactly integrated into a novel protein unit. The intrinsic and induced conformation of the serum response element DNA is the principal DNA feature recognized in the specific complex.

Amino Acid Sequence↗

PubMed2002

Obesity and immunocompetence.

The increasing worldwide prevalence of obesity is a major health problem since excessive body weight constitutes a risk factor in a number of chronic diseases. It has been reported that obese individuals are more susceptible to infection than lean subjects; however, the underlying factors are not fully understood. Limited and often controversial information exists comparing immunocompetence in obese and nonobese subjects as well as the cellular and molecular mechanisms involved, although much evidence supports a link between adipose tissue metabolism and immunocompetent cell functions. The complexity and heterogeneity of nutritional status and immune system interactions require an integral study of the immunocompetent cells, their subsets and products, as well as specific and non-specific inducer/regulatory systems in situations of human obesity. Additional research is needed to determine the clinical implications of these alterations on immunity and whether various interventions such as weight loss, exercise or nutrient supplementation could help to ameliorate them.

Adipose Tissue↗

PubMed2001

Application of electron spin resonance for investigating peptide-lipid interactions, and correlation with thermodynamics.

Peptide-lipid interactions can be investigated with spin-labelled lipid probes by using electron spin resonance (ESR) methods that have been developed for studying lipid-protein interactions with both integral and peripheral membrane proteins and also with surface-binding proteins that additionally penetrate the membrane. This approach has the advantage that a direct comparison can be made with the databank of ESR results from the various types of membrane protein. The appropriateness of the peptides as models for membrane proteins, or for their specific segments, can then be assessed. Further, differences in behaviour can be readily identified, as for example in the case of surface-active cytolytic or fusogenic peptides. Comparison with thermodynamic predictions for membrane insertion provides a useful adjunct to the spin-label method.

Amino Acid Sequence↗

PubMed1997

Interaction among preschoolers with and without disabilities: effects of across-the-day peer intervention.

We examined the effects of a peer-mediated intervention package that taught typically developing children to be more aware of communicative attempts to classmates with disabilities, to use a small set of facilitative strategies ("Stay, play, talk"), and to distribute strategy use across the school day. A multiple baseline design across subjects was instituted with two cohorts of preschool children. Following baseline observations, a total of 8 target children with moderate development disabilities were eventually paired with trained peers who received "buddy training." One trained peer were taught facilitative strategies and encouraged to use them during classroom activities, consistent improvements in social interaction on the part of the trained peers and target children were demonstrated. Similar or more frequent interactions were demonstrated when trained peers were reassigned to different target children during generalization probes. In addition, treatment effects were revealed when comparing sequential analyses applied to the specific communicative behaviors across experimental conditions, in changes in target children's sociometric ratings, and in social validity judgments of videotapes from before and after treatment. This peer intervention approach has promise for improving the communicative interaction and social integration of children with disabilities attending inclusive preschools.

Child↗

PubMed2002

Effects of iloprost on adhesion molecules and F1 + 2 in peripheral ischemia.

BACKGROUND: Iloprost has beneficial effects on microcirculation by preventing platelet and leukocyte reciprocal activation, which is known to lead to endothelial damage and acute thrombosis. This drug also reduces inflammatory system activation by decreasing alpha M beta 2 integrin expression on the phagocyte membrane, might have a role in the protection and restoration of endothelial integrity and might interact with coagulation cascade activation. DESIGN: Forty patients were enrolled: 29 with systemic sclerosis (SSc) and 11 with peripheral artery disease (PAD). Iloprost was administered for 5 days in the first group and for 21 days in second group of patients. To ascertain whether iloprost modifies the parameters of endothelial and coagulation cascade activations, the plasma concentrations of S-ICAM-1 and F1 + 2 were detected in patients at baseline, after 5 days and, in PAD patients only, after 21 days of iloprost therapy. S-ICAM-1 is the endothelial counter receptor for alpha M beta 2 integrin and is a marker of endothelial cell activation; and F1 + 2 is a marker of coagulation cascade activation. RESULTS: After infusion of iloprost a significant decrease of S-ICAM-1 was observed in both the SSc (P < 0.002) and PAD patients (P < 0.004). Similarly, a significant decrease of F1 + 2 was observed in the SSc (P < 0.0004) and PAD patients (P < 0.003). CONCLUSIONS: The study provides evidence that iloprost reduces endothelial cells and coagulation cascade activations. Both of these mechanisms are responsible for improvement in microvascular functional capacity and for the long-term clinical benefit observed. After iloprost infusion, the SSc patients showed marked reductions in F1 + 2 and S-ICAM-1 concentrations that were statistically more significant relative to the PAD patients.

Adult↗

PubMed1999

Molecular characterization of Escherichia coli FtsE and FtsX.

The genes ftsE and ftsX are organized in one operon together with ftsY. FtsY codes for the receptor of the signal recognition particle (SRP) that functions in targeting a subset of inner membrane proteins. We have found no indications for a structural relationship between FtsE/X and FtsY. Evidence is presented that FtsE and FtsX form a complex in the inner membrane that bears the characteristics of an ATP-binding cassette (ABC)-type transporter. FtsE is a hydrophilic nucleotide-binding protein that has a tendency to dimerize and associates with the inner membrane through an interaction with the integral membrane protein FtsX. An FtsE null mutant showed filamentous growth and appeared viable on high salt medium only, indicating a role for FtsE in cell division and/or salt transport.

ATP-Binding Cassette Transporters↗

PubMed1998

[Development of a surgical simulator for interventions of the paranasal sinuses. Technical principles and initial prototype].

BACKGROUND: Traditional training methods for surgeons include anatomical studies on human cadavers. Limited availability and ethical problems led to the consideration of alternatives. The surgeon's level of training could be significantly increased by a interactive training system trough computer graphics and virtual reality (VR). METHODS: Two main issues addressed are the 3-D reconstruction process and 3-D interaction to guide the surgical instruments. To provide the virtual environment, a realistic representation of the region of interest with all relevant anatomical parts is required. This model has to be suitable for computer simulation, while preserving as accurately as possible important anatomic features. Therefore the concept of creating a 3-D representation semi-automatically was developed. Textures derived from endoscopic images are superimposed on the virtual anatomic structures and provide better realism. RESULTS: Intuitive handling of the surgical instruments is ensured by using the tracking technique. The system allows navigation via a virtual camera and interaction with the virtual anatomical structures. Currently the use of a force feedback system and the simulation of deformations of tissues is critical. CONCLUSIONS: The VR based simulation system offers an alternative to conventional training methods. The future role of surgical simulation depends on overcoming the current drawbacks to provide greater interactive realism: the integration of a force feedback system to simulate the resistance of anatomical structures and the simulation of tissue deformations--both currently under development.

Artificial Intelligence↗

PubMed2004

Structure of inhomogeneous polymer solutions: a density functional approach.

The structure of polymer solutions confined between surfaces is studied using a density functional theory where the polymer molecules have been modeled as a pearl necklace of freely jointed hard spheres and the solvent as hard spheres. The present theory uses the concept of universality of the free energy density functional to obtain the first-order direct correlation function of the nonuniform system from that of the corresponding uniform system, calculated through the Verlet-modified type bridge function. The uniform bulk fluid direct correlation function required as input has been calculated from the reference interaction site model integral equation theory using the Percus-Yevick closure relation. The calculated results on the density profiles of the polymer as well as the solvent are shown to compare well with computer simulation results.

Journal Article↗

PubMedDate not supplied

The importance of nurse caring behaviors as perceived by patients receiving care at an emergency department.

BACKGROUND: Increased workload at the emergency department (ED) and the shortage of nurses may leave some patients without proper care. The importance of patients' perceptions of caring is vital when organizing nursing practice under such circumstances. PURPOSE: The purpose of the study was to identify which nurse caring behaviors are perceived by patients in an ED as important indicators of caring. The nurse caring behaviors were categorized in terms of relative importance with respect to demographic variables and perceived illness. Watson's theory of caring was used as a theoretic framework for this quantitative and descriptive study. METHOD: A 61-item questionnaire designed on the basis of Cronin and Harrison's Caring Behaviors Assessment tool, which reflected the 10 carative factors of Watson's theory, was mailed to 300 ED patients. The response rate was 60.7%. RESULTS: Results showed that subjects scored the items "Know what they are doing", "Know when it is necessary to call the doctor", "Know how to give shots, IVs, etc.", and "Know how to handle equipment" as the most important nurse caring behaviors. The subscale "human needs assistance" was ranked highest. CONCLUSION: In line with several previous studies, subjects considered clinical competence to be the most important nurse caring behavior, which further emphasizes the notion of caring as a moral stance integral to all interactions with patients.

Clinical Competence↗

PubMed2001

Reduction of inflammatory response in composite flap transfer by local stress conditioning-induced heat-shock protein 32.

BACKGROUND: The failure of composite flaps despite anastomotic patency is thought to be mediated by the inflammatory response within the microvasculature, which results from unavoidable surgical trauma and transfer-related ischemia-reperfusion. Evidence suggests that stress conditioning may improve flap survival; however, the molecular mechanisms of protection are far from being clear. Therefore, we analyzed whether stress conditioning-induced heat-shock protein 32 is effective to prevent the inflammatory response in transferred osteomyocutaneous flaps. METHODS: In a rat model, leukocyte-endothelial cell interaction and endothelial integrity disruption as early indicators of the inflammatory response were quantitatively analyzed in muscle, subcuticular tissue, and periosteum of microvascularly transferred osteomyocutaneous flaps by using intravital fluorescence microscopy. Twenty-four hours before flap transfer, stress conditioning was induced by local heating of the left hindlimb up to 42.5 degrees C for 30 minutes. In additional animals, stress conditioning-induced activity of heat-shock protein 32 was inhibited by tin protoporphyrin-IX. Unconditioned flaps served as controls. RESULTS: In all tissues analyzed, control flaps showed significant leukocyte adherence in postcapillary venules, increased intercellular adhesion molecule-1 (ICAM-1) expression, and endothelial integrity disruption, but a lack of heat-shock protein 32. In contrast, stress conditioning induced marked heat-shock protein 32 expression, which was associated with a significant reduction (P <.05) of leukocyte adherence, ICAM-1 expression, and endothelial hyperpermeability. The inhibition of heat-shock protein 32 by tin protoporphyrin-IX completely abolished the stress conditioning-induced amelioration of the inflammatory response in all tissues analyzed. CONCLUSIONS: Stress conditioning by local heat-shock priming reduces the inflammatory response in osteomyocutaneous flaps. The protective effect is predominantly mediated by the induction of heat-shock protein 32.

Animals↗

PubMed1997

Local and global representations of velocity: transparency, opponency, and global direction perception.

Human subjects can perceive global motion or motions in displays containing diverse local motions, implying representation of velocity at multiple scales. The phenomena of flexible global direction judgments, and especially of motion transparency, also raise the issue of whether the representation of velocity at any one scale is single-valued or multi-valued. A new performance-based measure of transparency confirms that the visual system represents directional information for each component of a transparent display. However, results with the locally paired random-dot display introduced by Qian et al, show that representations of multiple velocities do not coexist at the finest spatial scale of motion analysis. Functionally distinct scales of motion processing may be associated with (i) local motion detectors which show a strong winner-take-all interaction; (ii) spatial integration of local signals to disambiguate velocity; (iii) selection of reliable velocity signals as proposed in the model of Nowlan and Sejnowski; (iv) object-based or surface-based representations that are not necessarily organised in a fixed spatial matrix. These possibilities are discussed in relation to the neurobiological organisation of the visual motion pathway.

Form Perception↗