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Testing visual acuity of children using vanishing optotypes.

To test visual acuity in children, we developed a chart constructed so that the mean Fourier transform of the luminance of the figures on the chart at zero spatial frequency is the same as the background luminance. When the eye reaches its limit of resolution, the figures vanish into the gray background of the chart rather than becoming "blurred" as in conventional visual acuity charts. We compared the number of errors in determining the visual acuity of children aged 3-4.5 years using this high-frequency chart and a standard black-and-white high-contrast chart. Significantly fewer errors were found with the high-frequency chart, suggesting that this type of testing may improve the accuracy of visual acuity measurements in children.

Child, Preschool↗

An autosomal dominant granular corneal dystrophy family associated with R555W mutation in the BIGH3 gene.

Autosomal dominant granular corneal dystrophy is a stromal corneal dystrophy characterized by discrete granular opacities that cause recurrent corneal erosion and blurred vision. Four different corneal dystrophies, including granular dystrophy, are caused by mutations of the BIGH3 gene. We report a case of autosomal dominant granular corneal dystrophy in a 45-year-old woman with bilateral blurred vision and recurrent eye pain since adolescence. Numerous diffuse granular opacities were found in the superficial stroma of the cornea. Her 3 sons had a similar history and clinical presentation. Autosomal dominant granular corneal dystrophy was diagnosed. Mutation analysis by single-strand conformation polymorphism and direct sequencing in 2 of the affected family members revealed R555W mutation in the BIGH3 gene. This independent R555W mutation has been previously found in different ethnic populations including Caucasians and Japanese with granular dystrophy of Groenouw type I. These findings indicate the importance of R555 amino acid in the pathogenesis of autosomal dominant granular corneal dystrophy.

Corneal Dystrophies, Hereditary↗

Measuring visual acuity--mesopic or photopic conditions, and high or low contrast letters?

PURPOSE: To develop single-valued wavefront aberration metrics that correlate strongly with visual performance. The purpose of this study is to explore whether photopic high contrast visual acuity (VA) is an appropriate visual performance reference and whether mesopic and/or low contrast testing provides any advantage. METHODS: Subjects from the Texas Investigation of Cataract Optics study (N = 148) ranged in age from 21.6 to 83.8 years and from clear lens to dense nuclear cataract. Visual acuity was measured under four conditions: photopic high (VA(PHC)) and low (VA(PLC)) contrast, mesopic high (VA(MHC)) and low (VA(MLC)) contrast (photopic = 280 cd/m(2), mesopic = 0.75 cd/m(2)). Variables were tested for compliance with normality (-2.00 < skew and kurtosis < 2.00) and transformed if required. Linear regression and Bland-Altman 95% limits of agreement (+/-1.96 SD) were used to examine relationships between VA variables and between VA and wavefront aberration metrics. RESULTS: The two photopic measures VA(PHC) (skew = 2.57, kurtosis = 12.2) and VA(PLC) (1.67, 5.41) were poorly distributed, but the two mesopic measures VA(MHC) (0.88, 1.67) and VA(MLC) (0.29, -0.18) were normally distributed. Strong correlations existed between the (transformed) VA variables (R: 0.53 to 0.84). However, limits of agreement ranged over 0.30 to 0.42 logMAR, whereas retest data suggested a range of 0.15. All four were offered in stepwise multiple linear regression for 30 wavefront metrics: 20 included VA(MLC) alone, two included VA(PLC), two included VA(MHC) and six included both VA(MLC) and VA(MHC); R(2) averaged 25%. CONCLUSION: Although strongly correlated, low contrast and/or mesopic VA testing provides different information. Wave aberration metrics correlates better with VA(MLC) making this the visual performance test of choice.

Adult↗

Caveolin-1 is up-regulated in transdifferentiated lens epithelial cells but minimal in normal human and murine lenses.

Caveolae are flask-shaped invaginations of the plasma membrane found in many cell types. Caveolae play a role in lipid transport, endocytosis, signal transduction, and cell transformation. Expression of caveolin-1, the principal component of caveolae and a regulator of caveolae-dependent signaling and endocytosis, was investigated in lens epithelial cells and lens fiber cells in wild-type (wt) and SPARC-null mice and normal human donors in vivo and in vitro. RT-PCR, immunofluorescence and immunoblot analyses of human and murine ocular tissues revealed that caveolin-1 was expressed in the corneal epithelium, corneal endothelial cells, and blood vessels of iris, ciliary body and retina, but minimal in the normal lens epithelia or fiber cells of murine and human lens. In contrast, caveolin-1 was significantly up-regulated in mesenchymal-transdifferentiated lens epithelia in SPARC-null cataract lenses. In addition, lens epithelial cells from primary culture or from cultures of immortalized lens epithelial cell lines expressed significant amounts of caveolin-1. The lens epithelial cells expressed epidermal growth factor (EGF) receptor and were responsive to EGF-mediated cell proliferation, but they did not show EGF-dependent caveolin-1 tyrosine phosphorylation. Caveolin-1 might have a role in the process of epithelial-mesenchymal transdifferentiation (EMT) in the lens, the most common cause of vision loss in human secondary cataracts.

Aged↗

Gait and long cane kinematics: a comparison of sighted and visually impaired subjects.

Although visually impaired individuals have used the long cane to increase mobility for many years, few empirical studies have examined the effectiveness of this tool. The purposes of this research were to determine if these cane procedures provide adequate protection for visually impaired individuals and to compare sighted and visually impaired gait mechanics. Seven sighted (four females, three males) and five visually impaired subjects (two females, three males) were videotaped at 60 Hz by two cameras situated at opposite 45 degrees angles to the subjects' frontal plane so that three-dimensional coordinates could be calculated via direct linear transformation. One-way analyses of variance were calculated on 17 variables to determine if there was a significant biomechanical difference between sighted and visually impaired gait at an adjusted alpha = .003. The results showed that for both groups the cane tip touched outside where the foot landed and that the only variable significantly different between the two groups was resultant cane velocity. The major conclusion of this research was that present cane techniques may not provide adequate protection for visually impaired individuals since the purpose of mobility training is to have the person touch the ground with the cane tip at the foot contact positions.

Analysis of Variance↗

Depth and shape from differential perspective in the presence of bending deformations.

It is shown that there exist classes of useful partial solutions to what has become known as the structure from motion problem, that is, the problem of finding the three-dimensional shape as well as the movement in space of objects on the basis of their optical projections in several distinct phases of the movement. The class of solutions treated in this paper is quite different from the usual treatment in that the rigidity condition is relaxed so as to include the important class of bending deformations. For instance, we show a case in which important aspects of shape are obtained for a configuration of seven points, no four of which move in a rigid way, and which can be obtained from only two views. (This violates all requirements of the structure from motion theorem.) We discuss an algorithm that obtains the three-dimensional configuration of a polyhedral vertex up to a relief transformation (a similar transformation to the one that maps object to image space in paraxial optics), in the presence of arbitrary flections of the edges, from the projection and the instantaneous-movement parallax. Such a solution can, for instance, be used to predict side views of the vertex, as is demonstrated for a specific example. The solution can be used in an iterative fashion on triangulations to solve the case of extended curved surfaces suffering arbitrary bendings. The class of bending deformations encompasses all deformations that conserve distances along the surface (but not necessarily through space); thus stretchings are excluded. Practical examples include, e.g., deformations of flexible but nonstretchable shells. Actual numerical examples illustrate the practicability of the method.

Humans↗

The rhodopsin system of the squid.

Squid rhodopsin (lambda(max) 493 mmicro)-like vertebrate rhodopsins-contains a retinene chromophore linked to a protein, opsin. Light transforms rhodopsin to lumi- and metarhodopsin. However, whereas vertebrate metarhodopsin at physiological temperatures decomposes into retinene and opsin, squid metarhodopsin is stable. Light also converts squid metarhodopsin to rhodopsin. Rhodopsin is therefore regenerated from metarhodopsin in the light. Irradiation of rhodopsin or metarhodopsin produces a steady state by promoting the reactions, See PDF for Equation Squid rhodopsin contains neo-b (11-cis) retinene; metarhodopsin all-trans retinene. The interconversion of rhodopsin and metarhodopsin involves only the stereoisomerization of their chromophores. Squid metarhodopsin is a pH indicator, red (lambda(max) 500 mmicro) near neutrality, yellow (lambda(max) 380 mmicro) in alkaline solution. The two forms-acid and alkaline metarhodopsin-are interconverted according to the equation, Alkaline metarhodopsin + H(+) right harpoon over left harpoonacid metarhodopsin, with pK 7.7. In both forms, retinene is attached to opsin at the same site as in rhodopsin. However, metarhodopsin decomposes more readily than rhodopsin into retinene and opsin. The opsins apparently fit the shape of the neo-b chromophore. When light isomerizes the chromophore to the all-trans configuration, squid opsin accepts the all-trans chromophore, while vertebrate opsins do not and hence release all-trans retinene. Light triggers vision by affecting directly the shape of the retinene chromophore. This changes its relationship with opsin, so initiating a train of chemical reactions.

Animals↗

Semicircular canal contributions to the three-dimensional vestibuloocular reflex: a model-based approach.

1. We studied the contribution of the individual semicircular canals to the generation of horizontal and torsional eye movements in cynomolgus monkeys. Eye movements were elicited by sinusoidal rotation about a vertical (gravitational) axis at 0.2 Hz with the animals tilted in various attitudes of static forward or backward pitch. The gains of the horizontal and torsional components of the vestibuloocular reflex (VOR) were measured for each tilt position. The gains as a function of tilt position were fit with sinusoidal functions, and spatial gains and phases were determined. After control responses were recorded, the semicircular canals were plugged, animals were allowed to adapt, and the test procedure was repeated. Animals were prepared with only the anterior and posterior canals intact [vertical canal (VC) animals], with only the lateral canals intact [lateral canal (LC) animal], and with only one anterior and the contralateral posterior canals intact [right anterior and left posterior canal (RALP) animals; left anterior and right posterior canal (LARP) animals]. 2. In normal animals, the gain of the horizontal (yaw axis) velocity of the compensatory eye movements decreased as they were pitched forward or backward, and a torsional velocity appeared, reversing phase at the peak of the horizontal gain. After the anterior and posterior canals were plugged (LC animal), the horizontal component was reduced when the animal was tilted backward; the gain was zero with about -60 degrees of backward tilt. The spatial phase of the torsional component had the same characteristics. This is consistent with the fact that both responses were produced by the lateral canals, which from our results are tilted between 28 and 39 degrees above the horizontal stereotaxic plane. 3. After both lateral canals were plugged (VC animals), horizontal velocity was reduced in the upright position but increased as the animals were pitched backward relative to the axis of rotation. Torsional velocities, which were zero in the upright position in the normal animal, were now 180 degrees out of phase with the horizontal velocity. The peak values of the horizontal and torsional components were significantly shifted from the normal data and were closely aligned with each other, reaching peak values at approximately -56 degrees pitched back (-53 degrees horizontal, -58 degrees torsional). The same was true for the LARP and RALP animals; the peak values were at -59 degrees pitched back (-55 degrees horizontal, -62 degrees torsional). Likewise, in the LC animal the peak yaw and roll gains occurred at about the same angle of forward tilt, 35 degrees (30 degrees horizontal, 39 degrees torsional). Thus, in each case, the canal plugging had transformed the VOR from a compensatory to a direction-fixed response with regard to the head. Therefore there was no adaptation of the response planes of the individual canals after plugging. 4. The data were compared with eye velocity predictions of a model based on the geometric organization of the canals and their relation to a head coordinate frame. The model used the normal to the canal planes to form a nonorthogonal coordinate basis for representing eye velocity. An analysis of variance was used to define the goodness of fit of model predictions to the data. Model predictions and experimental data agreed closely for both normal animals and for the animals with canal lesions. Moreover, if horizontal and roll components from the LC and VC animals were combined, the summation overlay the response of the normal monkeys and the predictions of the model. In addition, a combination of the RALP and LARP animals predicted the response of the lateral-canal-plugged (VC) animals. 5. When operated animals were tested in light, the gains, peak values, and spatial phases of horizontal and roll eye velocity returned to the preoperative values, regardless of the type of surgery performed. This indicates that vision compensated for the lack o

Animals↗

Corresponding chromaticities for different states of adaptation to complex visual fields.

While each of his or her two eyes was independently adapted to a different illuminant in viewing a complex visual field, each of a number of observers matched a series of test colors seen by one eye with a juxtaposed variable stimulus seen by the other eye. The 2 degrees test and matching stimuli were located centrally in the complex adapting field, which subtended an angle of 31 degrees X 24 degrees. In making the matches, the observer viewed the test and matching stimuli for a series of brief intervals (approximately 1 sec) while viewing the complex adapting field with normal eye movements. Nine experiments were performed with different pairs of illuminants and different illuminances ranging from that of an average living room to that of a scene illuminated with hazy sunlight. In three other experiments each of the observer's two eyes was adapted to a different illuminance of D55. The amount of adaptation was more nearly complete at high levels of illuminance than at low levels, and the proportional amount of adaptation was less for the "blue" receptors. When adaptation coefficients were determined from the actual adaptation differences (e.g., from corresponding tristimulus values for matching neutrals) rather than from the adapting illuminants, a linear von Kries transformation based on experimentally determined visual primaries gave corresponding chromaticities that were in good agreement with the results obtained in each of the chromatic-adaptation experiments, except at the lowest illuminances. The results of the experiments in which each eye was adapted to different levels of the same illuminant indicated again that adaptation to the different levels was incomplete, the proportional amount of adaptation being less at low illuminances and for the "blue" receptors. This caused a change in chromatic adaptation with the level of illuminance even when the chromaticities of the adapting lights were equal. The results of these experiments also indicated that higher purities are needed in order to produce the same absolute color appearances at low levels of illuminance.

Color↗

Stereopsis, vertical disparity and relief transformations.

The pattern of retinal binocular disparities acquired by a fixating visual system depends on both the depth structure of the scene and the viewing geometry. This paper treats the problem of interpreting the disparity pattern in terms of scene structure without relying on estimates of fixation position from eye movement control and proprioception mechanisms. We propose a sequential decomposition of this interpretation process into disparity correction, which is used to compute three-dimensional structure up to a relief transformation, and disparity normalization, which is used to resolve the relief ambiguity to obtain metric structure. We point out that the disparity normalization stage can often be omitted, since relief transformations preserve important properties such as depth ordering and coplanarity. Based on this framework we analyse three previously proposed computational models of disparity processing; the Mayhew and Longuet-Higgins model, the deformation model and the polar angle disparity model. We show how these models are related, and argue that none of them can account satisfactorily for available psychophysical data. We therefore propose an alternative model, regional disparity correction. Using this model we derive predictions for a number of experiments based on vertical disparity manipulations, and compare them to available experimental data. The paper is concluded with a summary and a discussion of the possible architectures and mechanisms underling stereopsis in the human visual system.

Convergence, Ocular↗

Curvature of visual space under vertical eye rotation: implications for spatial vision and visuomotor control.

Most models of spatial vision and visuomotor control reconstruct visual space by adding a vector representing the site of retinal stimulation to another vector representing gaze angle. However, this scheme fails to account for the curvatures in retinal projection produced by rotatory displacements in eye orientation. In particular, our simulations demonstrate that even simple vertical eye rotation changes the curvature of horizontal retinal projections with respect to eye-fixed retinal landmarks. We confirmed the existence of such curvatures by measuring target direction in eye coordinates in which the retinotopic representation of horizontally displaced targets curved obliquely as a function of vertical eye orientation. We then asked subjects to point (open loop) toward briefly flashed targets at various points along these lines of curvature. The vector-addition model predicted errors in pointing trajectory as a function of eye orientation. In contrast, with only minor exceptions, actual subjects showed no such errors, showing a complete neural compensation for the eye position-dependent geometry of retinal curvatures. Rather than bolstering the traditional model with additional corrective mechanisms for these nonlinear effects, we suggest that the complete geometry of retinal projection can be decoded through a single multiplicative comparison with three-dimensional eye orientation. Moreover, because the visuomotor transformation for pointing involves specific parietal and frontal cortical processes, our experiment implicates specific regions of cortex in such nonlinear transformations.

Adult↗

[The pathogenesis and treatment of corneal disorders].

In this 21 st century, it is predicted that blindness caused by corneal disorders which are difficult to prevent or treat will increase. It is important to study the pathogenesis, prevention, and treatment of these corneal disorders. Two corneal disorders, keratoconus and corneal dystrophy, were investigated to elucidate the pathogenesis by using molecular biological or molecular genetic techniques. Corneal transplantation is performed to restore vision of patients with corneal disorders, but the condition of the donor corneal endothelium is the key to maintaining transparency of the grafted cornea. We investigated the function or cell cycle mechanism of corneal endothelium at the level of the gene, and we also studied induced genes of endothelial cells during preservation of donor corneas. 1. Keratoconus: We searched for keratoconus patients with questionnaires sent to 141 hospitals in the 23 Wards of Tokyo. The incidence of patients was estimated to be 12.4 x 10(-5) for males and 6.7 x 10(-5) for females. The male/female ratio was 1.7: 1.0. The number of male patients was low when compared with studies reported 17 years ago. Rupture of Descemet's membrane in males was significantly higher than in females. Genesis of incidence: Apoptosis-related gene expression in thinning of the cornea was analyzed with cDNA microarrays, using mRNA isolated from cultured keratocytes of normal human corneas and keratoconus corneas. The expression of tumor necrosis factor alpha-induced protein 6(TNFAIP 6) was more enhanced, while insulin growth factor binding protein 5(IGFBP 5) was less expressed in keratoconus patients. 2. Corneal dystrophy: In corneal dystrophy related to four candidate genes such as transforming growth factor beta-induced(TGFBI) gene, membrane component 1 surface maker 1(M 1 S 1) gene, carbohydrate sulfotransferase gene 6(CHST 6), and collagen type VIII alpha-2(COL8 A 2) gene, 208 Japanese and 42 Vietnamese families were analyzed for the gene mutation and studied for the frequency of gene mutation and differences of clinical features. About 80% of Japanese with corneal dystrophies had mutation of the TGFBI gene and about 70% of them had Avellino corneal dystrophy. However, in Vietnamese patients, mutations were found in both the TGFBI gene (lattice corneal dystrophy; the phenotype gene was His 626 Arg) and in the CHST gene. The difference in frequency in gene mutations was significant between the two nationalities. Moreover, a novel corneal dystrophy associated with Asp 123 His mutation in TGFBI gene was found in one Vietnamese family. 3. Corneal endothelial cell: 1) gene expression: We performed random sequence and homology research analysis of 1,000 clones from a rabbit corneal endothelial cDNA library. Forty-five genes, including collagen type VIII alpha-1, were listed for the frequently observed cDNA in the library. 2) gene transfection: One of the causes of a growth-arrested state in human corneal endothelium was thought to be the presence of transforming growth factor-beta (TGF-beta) in aqueous humor. The transfection of Smad 7 gene, which blocks the signal, showed proliferation of the endothelial cells in the presence of aqueous humor. This suggests that there may be a possible practical application for using gene transfection with a non-viral DNA vector or with an adenovirus vector.

Adolescent↗

Repeatability of subjective refraction in myopic and keratoconic subjects: results of vector analysis.

This paper evaluates the repeatability of refraction in keratoconus patients and normal myopes, using representations of spherocylindrical power that are theoretically valid. Data consist of test-retest refraction data from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study and similar data from normal myopes. Dioptric powers are transformed to an orthogonal vector representation of dioptric power. The metric of change is the dioptric difference between test and retest. The median difference between test and retest in keratoconus patients is four to six times larger than in normal myopes. Refraction over a rigid contact lens on a keratoconic cornea improves repeatability but remains approximately twice as large as in normal myopes. The methods demonstrated here possess advantages over previous methods and provide a more valid comparison between test and retest and between different subject groups. The repeatability of refraction in keratoconus patients is substantially worse than in normal myopes.

Adult↗

Metric 3D reconstruction and texture acquisition of surfaces of revolution from a single uncalibrated view.

Image analysis and computer vision can be effectively employed to recover the three-dimensional structure of imaged objects, together with their surface properties. In this paper, we address the problem of metric reconstruction and texture acquisition from a single uncalibrated view of a surface of revolution (SOR). Geometric constraints induced in the image by the symmetry properties of the SOR structure are exploited to perform self-calibration of a natural camera, 3D metric reconstruction, and texture acquisition. By exploiting the analogy with the geometry of single axis motion, we demonstrate that the imaged apparent contour and the visible segments of two imaged cross sections in a single SOR view provide enough information for these tasks. Original contributions of the paper are: single view self-calibration and reconstruction based on planar rectification, previously developed for planar surfaces, has been extended to deal also with the SOR class of curved surfaces; self-calibration is obtained by estimating both camera focal length (one parameter) and principal point (two parameters) from three independent linear constraints for the SOR fixed entities; the invariant-based description of the SOR scaling function has been extended from affine to perspective projection. The solution proposed exploits both the geometric and topological properties of the transformation that relates the apparent contour to the SOR scaling function. Therefore, with this method, a metric localization of the SOR occluded parts can be made, so as to cope with them correctly. For the reconstruction of textured SORs, texture acquisition is performed without requiring the estimation of external camera calibration parameters, but only using internal camera parameters obtained from self-calibration.

Algorithms↗

Learning viewpoint invariant object representations using a temporal coherence principle.

Invariant object recognition is arguably one of the major challenges for contemporary machine vision systems. In contrast, the mammalian visual system performs this task virtually effortlessly. How can we exploit our knowledge on the biological system to improve artificial systems? Our understanding of the mammalian early visual system has been augmented by the discovery that general coding principles could explain many aspects of neuronal response properties. How can such schemes be transferred to system level performance? In the present study we train cells on a particular variant of the general principle of temporal coherence, the "stability" objective. These cells are trained on unlabeled real-world images without a teaching signal. We show that after training, the cells form a representation that is largely independent of the viewpoint from which the stimulus is looked at. This finding includes generalization to previously unseen viewpoints. The achieved representation is better suited for view-point invariant object classification than the cells' input patterns. This property to facilitate view-point invariant classification is maintained even if training and classification take place in the presence of an--also unlabeled--distractor object. In summary, here we show that unsupervised learning using a general coding principle facilitates the classification of real-world objects, that are not segmented from the background and undergo complex, non-isomorphic, transformations.

Action Potentials↗

Bioinorganic and bioorganic studies of liver alcohol dehydrogenase.

Liver alcohol dehydrogenase (E.C.1.1.1.1) is an NAD(+)/NADH dependent enzyme with a broad substrate specificity being active on an assortment of primary and secondary alcohols. It catalyzes the reversible oxidation of a wide variety of alcohols to the corresponding aldehydes and ketones as well as the oxidation of certain aldehydes to their related carboxylic acids. Although the bioinorganic and bioorganic aspects of the enzymatic mechanism, as well as the structures of various ternary complexes, have been extensively studied, the kinetic significance of certain intermediates has not been fully evaluated. Nevertheless, the availability of computer-assisted programs for kinetic simulation and molecular modeling make it possible to describe the biochemical mechanism more completely. Although the true physiological substrates of this zinc metalloenzyme are unknown, alcohol dehydrogenase effectively catalyzes not only the interconversion of all-trans-retinol and all-trans-retinal but also the oxidation of all-trans-retinal to the corresponding retinoic acid. Retinal and related vitamin A derivatives play fundamental roles in many physiological processes, most notably the vision process. Furthermore, retinoic acid is used in dermatology as well as in the prevention and treatment of different types of cancer. The enzyme-NAD(+)-retinol complex has an apparent pK(a) value of 7.2 and loses a proton rapidly. Proton inventory modeling suggests that the transition state for the hydride transfer step has a partial negative charge on the oxygen of retinoxide. Spectral evidence for an intermediate such as E-NAD(+)-retinoxide was obtained with enzyme that has cobalt(II) substituted for the active site zinc(II). Biophysical considerations of water in these biological processes coupled with the inverse solvent isotope effect lead to the conclusion that the zinc-bound alkoxide makes a strong hydrogen bond with the hydroxyl group of Ser48 and is thus activated for hydride transfer. Moderate pressure accelerates enzyme action indicative of a negative volume of activation. The data with retinol is discussed in terms of enzyme stability, mechanism, adaptation to extreme conditions, as well as water affinities of substrates and inhibitors. Our data concern all-trans, 9-cis, 11-cis, and 13-cis retinols as well as the corresponding retinals. In all cases the enzyme utilizes an approximately ordered mechanism for retinol-retinal interconversion and for retinal-retinoic acid transformation.

Alcohol Dehydrogenase↗

Signalling states of photoactivated rhodopsin.

In microseconds after photoexcitation, rhodopsin forms the Meta I intermediate from lumirhodopsin. In this conversion, contacts between retinal and the apoprotein are formed, which result in a defined arrangement of donor and acceptor groups for proton translocations. A system of protonation-dependent coupled equilibria is now adopted, comprising Meta intermediates I, II and III, and their isospectral subforms. Some Meta states were identified as signalling states, in which the receptor interacts with transducin (Gt), rhodopsin kinase (RK) and arrestin. The binding of Gt or arrestin shifts the equilibrium to Meta II, while RK does not, indicating exposure of the RK binding site(s) before Meta II is formed. On contact with the activated receptor, each signalling protein responds with a conformational change, which transforms it into a functionally active state. The bell-shaped pH/rate profiles which are seen for the activation of both the G protein and the receptor kinase, indicate the necessary protonation and deprotonation of groups with different pKa. The right wing of the profile reflects the formation of the protonated subconformation (termed MIIb) of Meta II. For the interaction with Gt, recent work suggests a 'sequential fit' mechanism, involving the recognition of the C-terminal peptide of the Gt alpha subunit and of the farnesylated C-terminus of the gamma subunit. Isolated peptides derived from these portions of the G protein mimic the left wing of the pH/rate profile. We discuss the sequential fit as a time-ordered sequence of microscopic recognition and conformational interlocking in the interaction with the G protein.

Animals↗

Frequency flows and the time-frequency dynamics of multivariate phase synchronization in brain signals.

The quantification of phase synchrony between brain signals is of crucial importance for the study of large-scale interactions in the brain. Current methods are based on the estimation of the stability of the phase difference between pairs of signals over a time window, within successive frequency bands. This paper introduces a new approach to study the dynamics of brain synchronies, Frequency Flows Analysis (FFA). It allows direct tracking and characterization of the nonstationary time-frequency dynamics of phase synchrony among groups of signals. It is based on the use of the one-to-one relationship between frequency locking and phase synchrony, which applies when the concept of phase synchrony is not taken in an extended 'statistical' sense of a bias in the distribution of phase differences, but in the sense of a continuous phase difference conservation during a short period of time. In such a case, phase synchrony implies identical instantaneous frequencies among synchronized signals, with possible time varying frequencies of synchronization. In this framework, synchronous groups of signals or neural assemblies can be identified as belonging to common frequency flows, and the problem of studying synchronization becomes the problem of tracking frequency flows. We use the ridges of the analytic wavelet transforms of the signals of interest in order to estimate maps of instantaneous frequencies and reveal sustained periods of common instantaneous frequency among groups of signal. FFA is shown to track complex dynamics of synchrony in coupled oscillator models, reveal the time-frequency and spatial dynamics of synchrony convergence and divergence in epileptic seizures, and in MEG data the large-scale ongoing dynamics of synchrony correlated with conscious perception during binocular rivalry.

Adult↗