Kinematic analysis of shear displacement as a means for operating mechanotransduction channels in the contact region between adjacent stereocilia of mammalian cochlear hair cells

In sensory hair cells of the cochlea, deflection of the stereociliary bundle results in direct mechanical gating of mechanoelectrical transduction channels, a function generally attributed to the tip link running between the tips of short stereocilia and the sides of adjacent taller ones. However, immunocytochemical experiments indicate that the channels may not be associated with the tip link but occur just below it in a region of contact between the stereocilia. To determine whether transduction channels in this location could be operated during physiologically appropriate deflections as effectively by shear displacement as if they were associated with the tip link, a two dimensional kinematic analysis of relative motion between stereocilia has been performed assuming contact between stereocilia is maintained during deflection. Bundle geometry and dimensions were determined from transmission electron micrographs of hair cells from several frequency locations between 0.27 and 13.00 kHz in the guinea-pig cochlea. The analysis indicates that for a 10 nm deflection of the tallest stereocilia of both inner and outer hair cells, i.e. within the range of the maximum sensitivity of mammalian hair bundles, the average shear displacement in the contact region would be 1.6 nm, but that it increases systematically towards higher frequency regions for outer hair cells. This displacement is comparable in magnitude to tip-link elongation for individual stereociliary pairs.     

Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats . I. Behavioral results

We imaged the horizontal semicircular canal (HSCC) crista and cupula of toadfish, Opsanus tau, by using a) confocal light microscopy of isolated vital HSCC; b) serial sections of fixed, trichrome-stained HSCC; and c) scanning electron microscopy of fixed HSCCs. HSCC were dissections which included an ampulla and an attached canal tube (long and slender canal portion), and, in some cases, a small portion of the utricular wall. Cupulae were seen as multipartite mucus connective tissue shells rising from the crista and extending toward the ampullary roof. They were composed of several refractile bands traversing the cupulae perpendicular to longitudinal fibers extending from the cupular base to its apex. Alcian green-stained cupulae showed an asymmetric alcianphilic, dark, X-shaped structure, indicating that the pillar is rich in mucin and carbohydrate, an interpretation supported by images of trichrome-stained sections. The cupular antrum is devoid of prominent refractile fibers. No tubes or channels were observed in the cupula or antrum of vital preparations. Cupular shell fibers cover the surface of the crista, are roughly parallel, and are associated with a translucent material having a refractive index greater than the surrounding endolymph. Stereocilia were thin, 100-microm-long structures, with little longitudinal curvature, which end with no end bulb. No strands extend from stereocilia to the roof or other portions of the cupular antrum. Gross movements of stereocilia were not seen in mechanically quiescent preparations. Within the cupular antrum, stereocilia were parallel to connective tissue fibers, all embedded in an isotropic gel. This fiber-reinforced gel and cupular matrix are sensitive to N-acetlyneuraminidase and beta-N-acetyl glucosaminidase, and minimally sensitive to beta-N-acetyl hexosaminidase. Connective tissue fibers may serve to stiffen the gel, whose matrix would restrict lateral motion of embedded fibers and stereocilia thereby providing mechanical support for stereocilia.     

Direct tests of muscle cross-bridge theories: predictions of a Brownian dumbbell model for position-dependent cross-bridge lifetimes and step sizes with an optically trapped actin filament

Force and displacement events from a single myosin molecule interacting with an actin filament suspended between optically trapped beads (Finer, J. T., R. M. Simmons, and J. A. Spudich. 1994. Nature. 368:113-119) can be interpreted in terms of a generalized cross-bridge model that includes the effects of Brownian forces on the beads. Steady-state distributions of force and displacement can be obtained directly from a generalized Smoluchowski equation for Brownian motion of the actin-bead "dumbbell," and time series from Monte Carlo simulations of the corresponding Langevin equation. When the frequency spectrum of Brownian motion extends beyond cross-bridge transition rates, the inverse mean lifetimes of force/displacement pulses are given by cross-bridge rate constants averaged over a Boltzmann distribution of Brownian noise. These averaged rate constants reflect the strain-dependence of the rate constants for the stationary filament, most faithfully at high trap stiffness. Hence, measurements of the lifetimes and displacements of single events as a function of the resting position of the dumbbell can provide a direct test of different cross-bridge theories of muscle contraction. Quantitative demonstrations are given for Huxley models with 1) faster binding or 2) slower dissociation at positive cross-bridge strain. Predictions for other models can be inferred from the averaging procedure.     

Martingale Approach to Monte Carlo Simulation and Linear Random Vibration

A method is developed for generating samples of the state X of a linear filter driven by Gaussian white noise. The method can also be applied to developed formulas giving the second moment properties of X. The proposed solution is based on two facts. First, the integrals defining the forcing component of X are continuous martingales because their integrands are continuous deterministic functions and their integrators are Brownian motions. Second, a continuous martingale satisfying some additional properties can be time changed to a standard Brownian motion. The proposed Monte Carlo algorithm for generating samples of X calculates samples of this process from samples of a standard Brownian motion defined in a new clock by mapping these samples to the original clock. The algorithm does not use recurrence formulas for generating samples of X and does not approximate the probability law of this process. Examples are presented to illustrate the application of the proposed method. The examples include the Ornstein-Uhlenbeck process and the response of a simple oscillator and multi-degree-of-freedom system to Gaussian white noise.     

Microstructural evolution during liquid phase sintering: Part I. Development of microstructure

During liquid phase sintering, numerous solid-solid particle contacts can be generated by particle motion within the fluid. It is shown that, somewhat surprisingly, Brownian motion can produce such contacts. If such contacts are accompanied by particle adherence, the particles can then subsequently fuse into one (i.e., coalesce) by the liquid state analog of the evaporation-condensation mechanism of sintering. An isolated microstructure will develop if the time for particle coalescence is much less than the time between contacts. A highly skeletal arrangement of particles will form under the converse condition. Using these principles, a “microstructure map” is calculated in which the expected morphology of microstructure (i.e., skeletal or isolated) is related to the solid particle volume fraction, the kinetic and thermodynamic parameters affecting particle coalescence, and the frequency of particle contacts by Brownian motion. Some discussion of the thermodynamic and morphological factors affecting the probability of particle adherence after contact is presented.     

Smooth pursuit eye movements to extraretinal motion signals: deficits in relatives of patients with schizophrenia

BACKGROUND: Although mounting evidence supports the idea that smooth pursuit abnormality marks the genetic liability to schizophrenia, the precise ocular motor mechanism underlying the abnormality remains unknown. Based on recent findings in schizophrenia, we hypothesize that subtle deficits in the ability to hold online and/or use extraretinal motion information underlie the pursuit abnormality in vulnerable individuals. METHODS: The hypothesis was tested in 69 first-degree, biological relatives of probands with schizophrenia; 26 relatives had schizophrenia spectrum personalities (SSP). Subjects recruited from the community (n=71; 29 with SSP), without a known family history of psychosis, constituted the comparison groups. The traditional smooth pursuit gain measure, which is a ratio of smooth pursuit eye velocity in response to both retinal and extraretinal motion signals and the target velocity, was obtained. In addition, newly developed measures of predictive smooth pursuit (ie, in the presence of only extraretinal motion signals) were obtained. The latter measures were evaluated after the current retinal motion signals were made unavailable by briefly making the target invisible. RESULTS: Relatives, particularly those with SSP, showed significantly poorer predictive pursuit response to extraretinal motion signals (F(2,136)=6.51, P<.005), compared with the community subjects. However, the traditional smooth pursuit gain in response to both retinal and extraretinal motion signals was not different between groups. CONCLUSIONS: These results suggest that relatives of patients with schizophrenia, particularly those with SSP, have specific deficits in predictive pursuit based on only extraretinal motion signals. Normal smooth pursuit gain in response to both retinal and extraretinal motion signals is likely due to compensation based on retinal motion information. The latter suggests normal retinal motion processing and smooth pursuit motor output.     

Paradoxical rest

Paradoxical absence of motion in a rotating pattern is reported. The effect requires that the motion of the paradoxically stationary figure be underspecified by local motion signals, and that the paradoxically stationary figure be well segregated. This is consistent with proposals that figural segregation affects the integration of local motion signals.     

Distal separation of chick cochlear hair cell stereocilia: analysis of contact-constraint models

One model often used in the study of hair bundle micromechanics assumes simple geometric relationships between hair displacements, constrained by contact between neighboring hairs at their distal tips. Recent observations of hair bundle motion provided the opportunity to evaluate the contact-constraint model against measured displacements for the tallest and shortest sensory hairs. A contact-constraint model was developed based on the geometry of a single column of stereocilia. The model used morphological data from chick hair bundles for which displacement data in the excitatory and inhibitory directions were also available. For each hair bundle, a unique sensory hair radius was determined so that the calculated resting bundle morphology matched the measured values. The model was then evaluated against the displacement data for each hair bundle. In each case, the model underestimated the excitatory displacement of the shortest hairs. Failure of the model to accurately predict bundle motion raises the possibility of a distal separation between the hairs at rest. It is suggested that tip links pull the hairs through this separation during excitatory deflections. Perhaps at damaging levels of displacement, the hairs suddenly come into contact, tip-link tension dramatically increases, and the tip-links are fractured.     

Discrimination of coherent motion when local motion varies in speed and direction.

Random-dot cinematograms (RDCs) consist of multiple local motion signals that can vary in direction and speed. These local motion signals can result in coherent motion: the percept of an overall direction and speed of motion in an RDC. Thresholds were obtained for discriminating differences in the strength of coherent motion. Observers were found to easily discriminate the strength of coherent motion on the basis of the elements' direction or speed under optimal conditions. However, a nonreciprocal relation was evident when this discrimination was performed under nonoptimal conditions. Discrimination of coherent motion that was based on the elements' direction was unaffected, but discrimination that was based on speed was impaired. Results indicate that humans are sensitive to small differences in coherent motion strength and suggest that the visual system processes direction and speed information nonreciprocally. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural mechanisms for forming a perceptual decision

Cognitive and behavioral responses to environmental stimuli depend on an evaluation of sensory signals within the cerebral cortex. The mechanism by which this occurs in a specific visual task was investigated with a combination of physiological and psychophysical techniques. Rhesus monkeys discriminated among eight possible directions of motion while directional signals were manipulated in visual area MT. One directional signal was generated by a visual stimulus and a second signal was introduced by electrically stimulating neurons that encoded a specific direction of motion. The decisions made by the monkeys in response to the two signals allowed a distinction to be made between two possible mechanisms for interpreting directional signals in MT. The monkeys tended to cast decisions in favor of one or the other signal, indicating that the signals exerted independent effects on performance and that an interactive mechanism such as vector averaging of the two signals was not operative. Thus, the data suggest a mechanism in which monkeys chose the direction encoded by the largest signal in the representation of motion direction, a "winner-take-all" decision process.     

A stochastic theory of grain growth

A stochastic theory of normal grain growth is proposed. The model is based on the concept that the migration of kinks and ledges should cause a Brownian motion of the grain boundary. This motion results in a drift of the grain size distribution to larger sizes. The kinetics of grain growth is thus related to the kinetics of kinks and ledges; specifically, via the rates of nucleation, recombination and sink annihilation. A variety of growth exponents are obtained from a scaling analysis, but only one universal grain size distribution is applicable in all cases. The specific predictions of this model are in total agreement with the recent computer simulations of domain growth, and are consistent with experimental observations of normal grain growth.     

Separation techniques

The past two years have seen continued development of capillary electrophoresis methods. The separation performance of flowable sieving media now equals, and in some respects exceeds, that provided by gels. The application of microfabrication techniques to separation science is gaining pace. There is a continuing trend towards miniaturization and integration of separation with preparative or analytical steps. Innovative separation methods based on microfabrication technology include electrophoresis in purpose-designed molecular sieves, dielectric, trapping using microelectrodes, and force-free motion in Brownian ratchets.     

Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells

The mouse shaker-1 locus, Myo7a, encodes myosin VIIA and mutations in the orthologous gene in humans cause Usher syndrome type 1B or non-syndromic deafness. Myo7a is expressed very early in sensory hair cell development in the inner ear. We describe the effects of three mutations on cochlear hair cell development and function. In the Myo7a816SB and Myo7a6J mutants, stereocilia grow and form rows of graded heights as normal, but the bundles become progressively more disorganised. Most of these mutants show no gross electrophysiological responses, but some did show evidence of hair cell depolarisation despite the disorganisation of their bundles. In contrast, the original shaker-1 mutants, Myo7ash1, had normal early development of stereocilia bundles, but still showed abnormal cochlear responses. These findings suggest that myosin VIIA is required for normal stereocilia bundle organisation and has a role in the function of cochlear hair cells.     

Two motion systems with common and separate pathways for color and luminance

We present psychological experiments that reveal two motion systems, a specific and an unspecific one. The specific system prevails at medium to high temporal frequencies. It comprises at least two separate motion pathways that are selective for color and for luminance and that do not interact until after the motion signal is extracted separately in each. By contrast, the unspecific system prevails at low temporal frequencies and it combines color and luminance signals at an earlier stage, before motion extraction. The successful implementation of an efficient and accurate technique for assessing equiluminance corroborates further the main findings. These results offer a general framework for understanding the nature of interactions between color and luminance signals in motion perception and suggest that previously proposed dichotomies in motion processing may be encompassed by the specific/unspecific dichotomy proposed here.     

Diffusion coefficient and molecular weight of type 5 adenovirus by photon-correlation spectroscopy

The technique of photon-correlation spectroscopy (intensity fluctuation spectroscopy) is applied to light scatter from type 5 adenovirus undergoing Brownian motion in solution and the translation diffusion coefficient (D20,w) measured to be 0,367 +/- 0.003 Fick units. Using Svedberg's equation with previously determined parameters, a molecular weight of 165 - 10(6) +/- 5 - 10(6) is obtained.     

Grouping inhibits motion fading by giving rise to virtual trackable features.

After prolonged viewing of a slowly drifting or rotating pattern under strict fixation, the pattern appears to slow down and then momentarily stop. The authors show that grouping can slow down the process of "motion fading," suggesting that cortical configural form analysis interacts with the computation of motion signals during motion fading. The authors determined that grouping slows motion fading because it can give rise to trackable features, such as virtual contour terminators not present in the image, that possess stronger motion signals than would occur in the absence of such trackable features. That a continuously rotating stimulus will eventually be perceived to stop, despite the presence of such trackable features, suggests that the motion-from-form system itself can be fatigued. The finding that stationary form can remain visible even after the motion signal has faded suggests that the neural bases of motion visibility and form visibility arise from different neuronal populations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional and idling rotatory motion within F1-ATPase

ATP synthase mediates proton flow through its membrane portion, F0, which drives the synthesis of ATP in its headpiece, F1. The F1-portion contains a hexagonal array of three subunits alpha and three beta encircling a central subunit gamma, that in turn interacts with a smaller epsilon and with F0. Recently we reported that the application of polarized absorption recovery after photobleaching showed the ATP-driven rotation of gamma over at least two, if not three, beta. Here we extend probes of such rotation aided by a new theory for assessing continuous versus stepped, Brownian versus unidirectional molecular motion. The observed relaxation of the absorption anisotropy is fully compatible with a unidirectional and stepping rotation of gamma over three equidistantly spaced angular positions in the hexagon formed by the alternating subunits alpha and beta. The results strongly support a rotational catalysis with equal participation of all three catalytic sites. In addition we report a limited rotation of gamma without added nucleotides, perhaps idling and of Brownian nature, that covers only a narrow angular domain.