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At least 397 records · Page 22Linked to original sources

The use of irreversible ligands to inactivate receptor subtypes: 4-DAMP mustard and muscarinic receptors in smooth muscle.

Irreversible ligands are useful tools for investigating the function of receptor subtypes in various physiological processes. The mechanism for alkylation involves the formation of a reversible receptor complex followed by a covalent reaction. The extent of receptor alkylation is determined by the dissociation constant of the reversible complex and the rate constant for conversion to the covalent complex. Selectivity can be achieved if the irreversible ligand exhibits a difference in its dissociation constants for receptor subtypes. Selective alkylation can also be achieved using a selective competitive inhibitor to protect the desired receptor subtype. By using the non-M2-selective irreversible antagonist, 4-DAMP mustard, in combination with the competitive M2-selective antagonist, AF-DX 116, it has been possible to achieve a highly selective inactivation of all non-M2 subtypes of the muscarinic receptors in smooth muscle and has enabled the discovery of the functional role of M2 receptors in smooth muscle.

Animals↗

A simulation analysis on mechanisms of damped oscillation in retinal rod photoreceptor cells.

The different actions of two I(h) channel blockers, zatebradine (UL-FS 49) and ZD7288, on rod photoresponses were analysed by computer simulation using a newly revised ionic current model of the rod photoreceptor, based on Hodgkin-Huxley equations. The model, adjusted to fit the experimental results of amphibian rods, shows that both of the blockers enhance the light-induced membrane hyperpolarization. Our model can also predict a mechanism of a damped oscillation arising during the recovery phase appeared only in the presence of zatebradine which, unlike ZD7288, reduces both I(h) and I(Kv). We suggest that the oscillation can appear due to the alternative activation of voltage-dependent Ca(2+) current (I(Ca)) and calcium-dependent current (I(K(Ca)) and I(Cl(Ca))) when I(Kv) is blocked, with I(K(Ca)) having a stronger effect than I(Cl(Ca)).

Action Potentials↗

Damping and modification of the multiquanta Davydov-like solitons in molecular chains.

Relaxation of the multivibron soliton in molecular chain on lattice vibrations is investigated within the simple microscopic model. It was shown that its dynamics is governed by the nonlinear Schrödinger equation containing damping term. Its appearance is the consequence of the emission and absorption of real phonons arising when soliton velocity approaches the phase speed of sound. Explicit time dependence of the soliton parameters results as a consequence of these perturbations. In particular, soliton amplitude decreases while its width increases.

Nonlinear Dynamics↗

Tonic efferent-induced cochlear damping in roosting and echolocating mustached bats.

The activity of the medial olivocochlear (MOC) efferent system in mustached bats, Pteronotus p. parnellii, was studied by monitoring changes in the mechanical properties of the cochlea. The changing properties were expressed by the decay time (DT) of cochlear microphonic potentials produced by transient-induced ringing (Henson et al., 1995). Tape-recorded roost noise (biosonar and communication sounds) produced sudden, marked decreases in DT when presented to the contralateral ear of animals adapted to the quiet. When the animals were first removed from their roosts the DT was relatively short (1.2-1.5 ms) but this gradually lengthened by about 0.5-1.0 ms as they rested in a quiet chamber. The time required to reach a stable, quiet-adapted state after noise exposure varied with SPL and exposure time; in many experiments recovery was in the range of 90-120 min. When quiet-adapted bats were isolated and allowed to fly and echolocate for 20 min, the DTs measured within a few minutes after the end of the flight were also short and only slowly returned to longer preflight values. The administration of a single dose of gentamicin, which blocks MOC effects, greatly reduced the amount of suppression (damping) observed after periods of noise and echolocation sound exposure. We conclude that tonic MOC activity is induced by the natural vocalizations and roost noise and this activity probably regulates and protects the highly resonant cochlear partition.

Adaptation, Physiological↗

Stimulated production of vowel-like LX-waveforms and spectral damping in the absence of phonation.

Electrical impedance 'LX' waveforms measured across the neck at the thyroid level during phonation are known to be correlated with vocal fold movement. Changes in vocal fold contact are thought to be the cause of this phenomenon though emerging applications in radiotherapy indicate that changes in the configuration of both fold and neck tissues are correlated with LX waveform shape. In this paper it is shown that a two-stage tissue damping model with controlled bandpass and passive low pass components is consistent with evidence from gradually degraded, controlled phonation. In particular it is shown that an externally applied stimulus to the vertebral processes of the neck can produce similar impedance waveforms in the absence of phonation and hence no controlled fold contact. It is postulated that this is initial evidence suggesting that both pressure waves and vocal fold contact components contribute to the production of the classical 'LX' waveform.

Electric Impedance↗

Oculomotor localization relies on a damped representation of saccadic eye displacement in human and nonhuman primates.

The oculomotor system has long been thought to rely on an accurate representation of eye displacement or position in a successful attempt to reconcile a stationary target's retinal instability (caused by motion of the eyes) with its corresponding spatial invariance. This is in stark contrast to perceptual localization, which has been shown to rely on a sluggish representation of eye displacement, achieving only partial compensation for the retinal displacement caused by saccadic eye movements. Recent studies, however, have begun to case doubt on the belief that the oculomotor system possess a signal of eye displacement superior to that of the perceptual system. To verify this, five humans and one monkey (Macaca nemestrina) served as subjects in this study of oculomotor localization abilities. Subjects were instructed to make eye movements, as accurately as possible, to the locations of three successive visual stimuli. Presentation of the third stimulus (2-ms duration) was timed so that it fell before, during, or after the subject's saccade from the first stimulus to the second. Localization errors in each subject (human and nonhuman) were consistent with the hypothesis that the oculomotor system has access to only a damped representation of eye displacement--a representation similar to that found in perceptual localization studies.

Animals↗

Temperature-activated interfacial friction damping in carbon nanotube polymer composites.

Effect of temperature on interfacial sliding in single-walled carbon nanotube polycarbonate composites is investigated experimentally. We show that interfacial slip at the tube-polymer interfaces can be activated at relatively low dynamic strain levels ( approximately 0.35%) by raising temperature to approximately 90 degrees C. We attribute this to increased mobility of the polymer chain backbones at elevated temperatures and thermal relaxation of the radial compressive stresses at the tube-polymer interfaces. These results show the potential of polymer nanocomposites as high-temperature damping materials for vibration and acoustic suppression in a variety of dynamic systems.

Motion↗

Radiation damping compensation of selective pulses in water-protein exchange spectroscopy.

The observation of nuclear Overhauser effects (NOEs) between bound water and biological macromolecules such as proteins and nucleic acids can be improved by inverting the water resonance selectively while compensating for radiation damping effects. The efficiency of inversion, the offset profiles, and the appearance of 2D NOE-NOESY spectra can be improved in comparison with earlier methods.

Nuclear Magnetic Resonance, Biomolecular↗

Damping characteristics of bone-to-implant interfaces. A clinical study with the Periotest device.

The Periotest device was used to evaluate the damping characteristics of different bone-to-implant interfaces of Brånemark implants. Implant and abutment lengths were found to have a significant influence on Periotest value (PTV). There was no statistical difference between PTVs of implants located in the anterior and posterior areas of the same jaw at abutment connection. No differences were found between PTVs of standard and self-tapping implants. PTVs at abutment connection were highly influenced by the bone quality. The contact with two corticals, one at each extremity of the implant, was of a greater influence in the maxillary than in the mandibular jaw, indicating a firmer anchorage between the bi-cortical implants and the surrounding bone. A progressive decrease of PTVs over time was observed, significant up to 5 years of loading.

Adult↗

Horses damp the spring in their step.

The muscular work of galloping in horses is halved by storing and returning elastic strain energy in spring-like muscle-tendon units.These make the legs act like a child's pogo stick that is tuned to stretch and recoil at 2.5 strides per second. This mechanism is optimized by unique musculoskeletal adaptations: the digital flexor muscles have extremely short fibres and significant passive properties, whereas the tendons are very long and span several joints. Length change occurs by a stretching of the spring-like digital flexor tendons rather than through energetically expensive length changes in the muscle. Despite being apparently redundant for such a mechanism, the muscle fibres in the digital flexors are well developed. Here we show that the mechanical arrangement of the elastic leg permits it to vibrate at a higher frequency of 30-40 Hz that could cause fatigue damage to tendon and bone. Furthermore, we show that the digital flexor muscles have minimal ability to contribute to or regulate significantly the 2.5-Hz cycle of movement, but are ideally arranged to damp these high-frequency oscillations in the limb.

Animals↗

Intranasal exposure to a damp building mould, Stachybotrys chartarum, induces lung inflammation in mice by satratoxin-independent mechanisms.

BACKGROUND: Stachybotrys chartarum is a damp building mould and a potent toxin producer that has been related to serious cases of respiratory health problems. However, the direct link between exposure and health symptoms has not been established. OBJECTIVE: To examine the mechanism by which exposure to spores of satratoxin producing and non-producing S. chartarum strains induce inflammatory responses in murine lungs. METHODS: BALB/c mice were intranasally exposed for 3 weeks to spores of a satratoxin-producing and a non-producing S. chartarum strain. Inflammatory cell infiltration was characterized from bronchoalveolar lavage (BAL) fluid. Cytokine and chemokine mRNA expression in lung tissue was measured with real-time PCR. Bronchial responsiveness to methacholine (MCh) was determined by whole-body plethysmography and serum antibody levels by ELISA. RESULTS: A dose-dependent increase in monocytes, neutrophils and lymphocytes was observed in BAL fluid after intranasal (i.n.) instillation of S. chartarum spores. There was no difference in the BAL between exposure to the satratoxin-producing and the non-producing strains. Infiltration of inflammatory cells was associated with an induction of pro-inflammatory cytokine (IL-1beta, IL-6 and TNF-alpha) and chemokine (CCL3/MIP-1alpha, CCL4/MIP-1beta and CCL2/MCP-1) mRNA levels in the lungs. Interestingly, CXCL5/LIX was the only chemokine that showed significantly higher mRNA levels after exposure to the satratoxin-producing strain compared with the non-producing strain. MCh-induced bronchial responsiveness was not altered significantly after mould instillation. Moreover, no significant increase in total or specific IgE, IgG2a and IgG1 antibody levels were found after S. chartarum exposure. CONCLUSION: These results indicate that lung inflammation induced by i.n. instillations of S. chartarum spores is regulated by the induction of pro-inflammatory cytokines and leucocyte-attracting chemokines. The data also imply that S. chartarum-derived components, other than satratoxins, are mediating the development of this inflammatory response.

Administration, Intranasal↗

Ecological basis for biocontrol of damping-off disease by pseudomonas fluorescens 54/96

Pseudomonas fluorescens 54/96, originally isolated from the rhizosphere of sugar beet, has been shown to be commercially effective in field trials for the suppression of a number of fungal diseases of seedlings. In vitro and microcosm-based assays revealed that both the timing and method of application of bacteria were important for effective control of Pythium ultimum, the causative agent of damping-off disease. Following transposon mutagenesis (Tn5lac), mutants deficient for the suppression of Pythium ultimum infections of peas were isolated. Three major classes of insertional mutants of Ps. fluorescens 54/96 were identified which either inhibited sporulation, reduced mycelial growth or affected the regulation of bacterial metabolic activity. Evaluation of the metabolic capability of pathogen and antagonist revealed evidence for direct competition, as both the fungus and bacterium had similar sole carbon source nutrient utilization profiles. Further comparisons of the activity of the transposon mutants indicated that although the mechanisms of disease control were multifactorial, the most significant factor was the prevention of rapid spore germination in the presence of pea seeds.

Journal Article↗

Damping of persistent oscillations of quadratic optical solitons.

We investigate the dynamics of optical soliton formation in media with quadratic nonlinearity under conditions of long-living oscillations produced by the soliton's internal modes. We compare the predictions of the second-order perturbation approach, combining it with the energy conservation law, with the direct numerical simulations using the transparent boundary conditions. We demonstrate that these two approaches correlate well and describe the nonlinear radiation damping of the internal modes.

Journal Article↗

Complex dynamics and multistability in a damped harmonic oscillator with delayed negative feedback.

A center manifold reduction and numerical calculations are used to demonstrate the presence of limit cycles, two-tori, and multistability in the damped harmonic oscillator with delayed negative feedback. This model is the prototype of a mechanical system operating with delayed feedback. Complex dynamics are thus seen to arise in very plausible and commonly occurring mechanical and neuromechanical feedback systems. (c) 1995 American Institute of Physics.

Journal Article↗

Abnormal IR effects of Pt nanostructured surfaces upon CO chemisorption due to interaction and electron-hole damping.

The abnormal IR effects (AIREs) characterized by a positive-going peak of platinum (Pt) nanostructured surface generated in a square-wave potential treatment upon CO molecule chemisorption was observed and analyzed with a consideration of the interparticle interaction and electron-hole damping between nanoislands and CO molecules. A theoretical simulation shows that the islanded nanostructured Pt surfaces, which gives rise to interparticle interaction, coupling with electron-hole mechanism, may contribute to the origins of positive-going peak (AIREs) observed by in situ Fourier transformation IR (FTIR) experiments.

Journal Article↗

Time-dependent barrier passage of a non-Ohmic damping system.

We consider a particle passing over the saddle point of an inverse harmonic potential, which is described by a generalized Langevin equation with a non-Ohmic damping of power exponent delta. The time-dependent passing probability and transmission coefficient are obtained analytically by using the reaction flux method. It is shown that the overshooting phenomenon for the passing probability appears in the regime 0<delta<1 and the backflow recrossing over the saddle point is observed, where a nonmonotonous time dependence of the passage probability is detected. The long memory aspect of friction is at the origin of this behavior. Thus the steady transmission coefficient is also a nonmonotonous function of delta.

Journal Article↗

Xeroderma pigmentosum variant cells are less likely than normal cells to incorporate dAMP opposite photoproducts during replication of UV-irradiated plasmids.

Xeroderma pigmentosum (XP) variant patients show the clinical characteristics of the disease, with increased frequencies of skin cancer, but their cells have a normal, or nearly normal, rate of nucleotide excision repair of UV-induced DNA damage and are only slightly more sensitive than normal cells to the cytotoxic effect of UV radiation. However, they are significantly more sensitive to its mutagenic effect. To examine the mechanisms responsible for this hypermutability, we transfected an XP variant cell line with a UV-irradiated (at 254 nm) shuttle vector carrying the supF gene as a target for mutations, allowed replication of the plasmid, determined the frequency and spectrum of mutations induced, and compared the results with those obtained previously when irradiated plasmids carrying the same target gene replicated in a normal cell line [Bredberg, A., Kraemer, K. H. & Seidman, M. M. (1986) Proc. Natl. Acad. Sci. USA 83, 8273-8277]. The frequency of mutants increased linearly with dose, but with a slope 5 times steeper than that seen with normal cells. Sequence analysis of the supF gene showed that 52 of 53 independent mutants generated in the XP variant cells contained base substitutions, with 62 of 64 of the substitutions involving a dipyrimidine. Twenty-eight percent of the mutations involved A.T base pairs, with the majority found at position 136, the middle of a run of three A.T base pairs. (In the normal cells, this value was only 11%.) If the rate of excision of lesions from supF in the two cell lines is equal, our data suggest that XP variant cells are less likely than normal cells to incorporate dAMP opposite bases involved in photo-products. If such incorporation also occurs during replication of chromosomal DNA, this could account for the hypermutability of XP variant cells with UV irradiation.

Bacterial Proteins↗

Viscous Boundary-Layer Damping of r-Modes in Neutron Stars.

Recent work has raised the exciting possibility that r-modes (Rossby waves) in rotating neutron star cores might be strong gravitational-wave sources. We estimate the effect of a solid crust on their viscous damping rate and show that the dissipation rate in the viscous boundary layer between the oscillating fluid and the nearly static crust is more than 105 times higher than that from the shear throughout the interior. This increases the minimum frequency for the onset of the gravitational r-mode instability to at least 500 Hz when the core temperature is less than 1010 K. It eliminates the conflict between the r-mode instability and the accretion-driven spin-up scenario for millisecond radio pulsars and makes it unlikely that the r-mode instability is active in accreting neutron stars. For newborn neutron stars, the formation of a solid crust shortly after birth affects their gravitational-wave spin-down and hence their detectability by ground-based interferometric gravitational-wave detectors.

Journal Article↗