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At least 703 records · Page 39Linked to original sources
PubMed2000

Atomic force microscopy of native purple membrane.

Atomic force microscopy (AFM) allows the observation of surface structures of purple membrane (PM) in buffer solution with subnanometer resolution. This offers the possibility to classify the major conformations of the native bacteriorhodopsin (BR) surfaces and to map the variability of individual polypeptide loops connecting transmembrane alpha-helices of BR. The position, the variability and the flexibility of these loops depend on the packing arrangement of BR molecules in the lipid bilayer with significant differences observed between the trigonal and orthorhombic crystal forms. Cleavage of the Schiff base bond leads to a disassembly of the trigonal PM crystal, which is restored by regenerating the bleached PM. The combination of single molecule AFM imaging and single molecule force-spectroscopy provides an unique insight into the interactions between individual BR molecules and the PM, and between secondary structure elements within BR.

Bacteriorhodopsins↗
PubMed1998

Production of G-protein-coupled receptors in yeast.

Yeasts combine the advantages of fast and easy handling with the potential to perform eukaryotic post-translational modifications and are for this reason interesting hosts for heterologous production of G-protein-coupled receptors. The possibility to connect foreign receptors to a yeast internal MAP kinase pathway was used to establish yeast-based systems for high-throughput screening of compound libraries. In addition, yeasts have the potential for high level production of G-protein-coupled receptors. In this field, non-Saccharomyces yeasts seems to be interesting alternatives to S. cerevisiae, as well as to systems based on higher eukaryotic cells.

Animals↗
PubMed2001

A method for the identification of pseudorabies virus protein and angiotensin AT(1A) receptor mRNA expression in the same CNS neurons.

Neurotropic viruses have been used over the last 10 years to map the distribution of chains of synaptically connected neurons in the CNS. The peptide content of infected neurons has been determined in a number of cases immunohistochemically. However, it has been unclear whether specific mRNA can be assessed in virus-infected neurons. We have established a technique which enables the identification of viral protein and mRNA in the same neuron. In the present study pseudorabies virus retrogradely transported from the kidney was localised using immunohistochemistry and mRNA for the angiotensin II AT(1A) receptor was detected by hybridisation histochemistry. Virus protein was visualised using an immunohistochemical procedure with diaminobenzidine as the chromogen and the same sections were exposed to radioactively labelled ((35)S) riboprobes, hybridising the angiotensin II AT(1A) receptor. The combination of these two approaches resulted in the identification of neurons shown to project polysynaptically to the kidney and express AT(1A) mRNA. These data provide neuroanatomical support for previous physiological observations that ablation of the lamina terminalis and administration of losartan, the AT(1) receptor antagonist, blocks the inhibition of renal sympathetic nerve activity following centrally injected Ang II in rats and sheep [5].

Animals↗
PubMed1991

A neural network approach to hippocampal function in classical conditioning.

Hippocampal participation in classical conditioning in terms of Grossberg's (1975) attentional theory is described. According to the present rendition of this theory, pairing of a conditioned stimulus (CS) with an unconditioned stimulus (US) causes both an association of the sensory representation of the CS with the US (conditioned reinforcement learning) and an association of the sensory representation of the CS with the drive representation of the US (incentive motivation learning). Sensory representations compete among themselves for a limited-capacity short-term memory (STM) that is reflected in a long-term memory storage. The STM regulation hypothesis, which proposes that the hippocampus controls incentive motivation, self-excitation, and competition among sensory representations thereby regulating the contents of a limited capacity STM, is introduced. Under the STM regulation hypothesis, nodes and connections in Grossberg's neural network are mapped onto regional hippocampal-cerebellar circuits. The resulting neural model provides (a) a framework for understanding the dynamics of information processing and storage in the hippocampus and cerebellum during classical conditioning of the rabbit's nictitating membrane, (b) principles for understanding the effect of different hippocampal manipulations on classical conditioning, and (c) numerous novel and testable predictions.

Animals↗
PubMedDate not supplied

Specificity of cortico-cortical connections in monkey visual system.

When the primate primary visual cortex, area 17, is stained for the mitochondrial enzyme cytochrome oxidase, it shows a striking polka-dot pattern (cytochrome oxidase blobs). Area 18, the second visual area, shows a cytochrome-oxidase pattern of coarse alternating thick and thin stripes running perpendicular to the 17-18 border and separated by lighter (interstripe) regions. Here we show that the thin cytochrome oxidase stripes, and possibly also the thick stripes, in area 18 receive projections specifically from the blobs in area 17, and that the interstripe regions of 18 receive projections from the interblob matrix of area 17. This indicates a specificity of cortico-cortical connections far exceeding the demands of topographical mapping. Together with our physiological results, it suggests that within the pathway from area 17 to area 18 different kinds of information may be handled separately and in parallel.

Animals↗
PubMed2002

Magnetic resonance imaging of the rat Harderian gland.

The intra-orbital lacrimal gland (Harderian gland, or HG) of the female rat was studied by magnetic resonance imaging (MRI) to evaluate whether MRI can be used to visualize the gland in vivo and localized-1H-spectroscopy detect its lipid content. The results were correlated with post-mortem anatomical sections, and with light and electron microscopy. On MRI, HG presented as a mass located between the ocular bulb and the orbit. In strongly T2W sequences the secretory structures had a reduced signal while intraparenchymal connective tissue was visible. T2-quantitative maps values of HG (60.12 +/- 8.15 ms, mean +/- SD) were different from other tissues (i.e. muscular tissue, T2 = 44.79 +/- 3.43 ms and olfactory bulb, T2 = 79.26 +/- 4.25 ms). In contrast-enhanced-MRI, HG had a signal-intensity-drop of 0.074 +/- 0.072 (mean +/- SD), after injection of AMI-25, significantly different from the muscle (0.17 +/- 0.10). Localized MRI spectra gave a large part of the signal originating from fat protons, but with a significant percentage from water protons. At light and electron microscopy the lipid deposition appeared to be composed of low-density material filling a large part of the cytoplasm, and the porphyrin aggregates were easily recognizable. The data demonstrate that an in vivo study of the HG was feasible and that high-field MRI allowed analysis of the gross anatomy detecting the lipid content of the gland.

Animals↗
PubMed2005

Topographic variability of the esophageal left atrial relation influencing ablation lines in patients with atrial fibrillation.

UNLABELLED: Topography of the esophagus in atrial fibrillation ablation. INTRODUCTION: The close anatomic relationship of the posterior wall of the left atrium (LA) and the thermosensitive esophagus creates a potential hazard in catheter ablation procedures. METHODS AND RESULTS: In 30 patients (pts) with atrial fibrillation (AF) undergoing catheter ablation, we prospectively studied the course and contact of the esophagus in relation to LA and the topographic proximity to ablation lines encircling the right-sided and left-sided pulmonary veins (PV) as well as to the posterior line connecting the encircling lines using the electromagnetic mapping system for reconstruction of LA and for tagging of the esophagus. This new technique of anatomic tagging of the esophagus was validated against the CT scan as a standard imaging procedure. The esophageal course was highly variable, extending from courses in direct vicinity to the left- or right-sided PV as well as in the midportion of the posterior LA. In order to avoid energy application in direct proximity to the esophagus, adjustments of the left and right PV encircling lines were necessary in 14/30 pts (47%) and 3/30 (10%). In 30 pts (100%), the mid- to inferior areas of the posterior LA revealed contact with the esophagus. Therefore, posterior and inferior linear ablation lines were abandoned and shifted to superior in 29 pts (97%). CONCLUSIONS: Anatomic tagging of esophagus revealed a highly variable proximity to different areas of the posterior LA suggesting individual adjustment of encircling and linear ablation lines in AF ablation procedures to avoid the life threatening complication of esophagus perforation.

Atrial Fibrillation↗
PubMed2005

Population dynamics simulations of functional model proteins.

In order to probe the fundamental principles that govern protein evolution, we use a minimalist model of proteins to provide a mapping from genotype to phenotype. The model is based on physically realistic forces of protein folding and includes an explicit definition of protein function. Thus, we can find the fitness of a sequence from its ability to fold to a stable structure and perform a function. We study the fitness landscapes of these functional model proteins, that is, the set of all sequences mapped on to their corresponding fitnesses and connected to their one mutant neighbors. Through population dynamics simulations we directly study the influence of the nature of the fitness landscape on evolution. Populations are observed to move to a steady state, the distribution of which can often be predicted prior to the population dynamics simulations from the nature of the fitness landscape and a quantity analogous to a partition function. In this paper, we develop a scheme for predicting the steady-state population on a fitness landscape, based on the nature of the fitness landscape, thereby obviating the need for explicit population dynamics simulations and providing some insight into the impact on molecular evolution of the nature of fitness landscapes. Poor predictions are indicative of fitness landscapes that consist of a series of weakly connected sublandscapes.

Computer Simulation↗
PubMed1973

F-deformations and f-tractions.

Let M(n) be a compact, connected topological manifold and F a continuous mapping of M(n) into R that is "topologically nondegenerate" in the sense of (Morse, M. (1959) J. d'Analyse Math., 7, 189-208). Let c be a value of F and set F(c) = {pinM(n)|F(p) </= c}. The topological critical points of F on F(c) are finite in number and can be related to the invariants of the homology groups of F(c) as in the differentiable case. F-Deformations and F-tractions make this possible. F-Tractions are here defined and replace retracting deformations used in the differentiable case. The final relations will serve as a model for similar relations between critical extremals of Weierstrass integrals on Riemannian manifolds.

Journal Article↗
PubMed2003

Transcranial magnetic stimulation as an investigative tool in the study of visual function.

Transcranial magnetic stimulation (TMS) is a novel and powerful probe to study the relationship between human brain function and behavior. TMS is being widely used to investigate memory, language, attention, learning, and motor function and is even being utilized therapeutically in the treatment of depression. Some of the earliest applications of TMS have been directed toward the investigation of human visual perception. For example, a strong TMS pulse delivered to the occipital cortex in a sighted or even blind individual can evoke the sensation of perceiving light (visual phosphenes). TMS can also be used to suppress visual perception and investigate the timing of visual information processing. Furthermore, the functional connectivity between different brain areas can be mapped using TMS, thus establishing a causal link between visual cortical function and visual perception. The present article is meant as an overview of the technique of TMS and a review of the literature as it pertains to the study of visual function. The application of TMS in the diagnosis as well as possible therapeutic use in various visual disorders is also discussed.

Electromagnetic Fields↗
PubMed2001

Low-resolution data analysis for low-density lipoprotein particle.

The knowledge of the molecular structure of LDL, a large lipoprotein complex, is of great interest for medical investigations. Currently available LDL crystals do not diffract to high resolution and do not allow the application of standard crystallographic techniques. Additional difficulties arise because of a very dense crystal packing and the presence of several components with quite different mean densities. Several ab initio phasing methods previously reported by the authors have been successfully applied to find a crystallographic image of LDL at a resolution of 27 A. The most promising results have been obtained using direct phasing with a connectivity analysis of the electron-density maps. The current image makes it possible to discern a single particle covered by a layer of relatively high density that is asymmetrically distributed on the particle surface. It shows a partition of high and low densities inside the particle and, in particular, strips of varying density in the lipid core.

Crystallography, X-Ray↗
PubMed1990

Spontaneous Activity as a Determinant of Axonal Connections.

To investigate the role of spontaneous retinal activity in map refinement, we studied goldfish kept in darkness during regeneration of a cut optic nerve. In one experiment, such fish (with lenses ablated to blur vision) were maintained for 70 days in stroboscopic light, diurnal light, or total darkness interrupted daily by 15 minutes of stroboscopic light. The retinotectal projection was then assessed for retinotopy by standard methods, using retrograde transport of wheat germ agglutinin-horseradish peroxidase. As in previous work, significantly more refinement was found in diurnal than in stroboscopic light. In darkness, refinement was as complete as in diurnal light. In a second experiment, similar fish were kept in stroboscopic light for 63 days. Some were then assessed to confirm that refinement had been delayed, while others were transferred to darkness or diurnal light for assessment later. After 7 days in either environment, no further refinement was seen; but after 21 days, substantial and significant refinement has occurred in both. Thus the effects of darkness and diurnal light were indistinguishable, and very different from those of stroboscopic light and (in previous studies) tetrodotoxin. Map refinement is evidently activity-dependent but not experience-dependent, and can effectively use the correlated spontaneous firing of neighbouring ganglion cells as its basis. Locally correlated spontaneous activity, which appears also to drive eye- and class-specific axon segregation in mammals, occurs widely in the nervous system. It could potentially generate systematic interconnection patterns even between neuronal populations without an overtly topographic organization.

Journal Article↗
PubMed1992

The Critical Period for Experience-dependent Plasticity in a System of Binocular Visual Connections in Xenopus laevis: Its Extension by Dark-rearing.

Following surgical rotation of an eye, the Xenopus 'intertectal' system is capable of a vision-dependent alteration of its connectivity, that restores spatial registration of binocular maps on the optic tectum. In the preceding paper (Keating and Grant, Eur. J. Neurosci., 4, 27 - 36, 1992), we reported that this capacity undergoes a progressive, age-dependent restriction during a critical period around the time of metamorphosis, so that rotations produced in animals aged >/=3 months postmetamorphosis normally evoke no such alteration of the system. Here we examine whether this restriction is rigidly age-dependent or whether vision can influence its profile. We report that in animals dark-reared from embryonic stage 35 through the critical period to 3 months, 1 year or even 2 years after metamorphosis, rotations instituted at those ages now result in intertectal reorganization if a period of normal vision is allowed after the operation. Similarly, intertectal alteration was also seen in animals eye-rotated at larval stage 58, then dark-reared just for the duration of the critical period, and subsequently returned, at 3 months of age, to a normal visual environment. We conclude, therefore, that the normal developmental restriction in the plasticity of the Xenopus intertectal system is not strictly age-dependent, but that vision contributes to the process by activating the underlying plasticity mechanisms.

Journal Article↗
PubMed1998

The effect of abdominal wall morphology on ultrasonic pulse distortion. Part II. Simulations.

Wavefront propagation through the abdominal wall was simulated using a finite-difference time-domain implementation of the linearized wave propagation equations for a lossless, inhomogeneous, two-dimensional fluid as well as a simplified straight-ray model for a two-dimensional absorbing medium. Scanned images of six human abdominal wall cross sections provided the data for the propagation media in the simulations. The images were mapped into regions of fat, muscle, and connective tissue, each of which was assigned uniform sound speed, density, and absorption values. Propagation was simulated through each whole specimen as well as through each fat layer and muscle layer individually. Wavefronts computed by the finite-difference method contained arrival time, energy level, and wave shape distortion similar to that in measurements. Straight-ray simulations produced arrival time fluctuations similar to measurements but produced much smaller energy level fluctuations. These simulations confirm that both fat and muscle produce significant wavefront distortion and that distortion produced by fat sections differs from that produced by muscle sections. Spatial correlation of distortion with tissue composition suggests that most major arrival time fluctuations are caused by propagation through large-scale inhomogeneities such as fatty regions within muscle layers, while most amplitude and waveform variations are the result of scattering from smaller inhomogeneities such as septa within the subcutaneous fat. Additional finite-difference simulations performed using uniform-layer models of the abdominal wall indicate that wavefront distortion is primarily caused by tissue structures and inhomogeneities rather than by refraction at layer interfaces or by variations in layer thicknesses.

Abdominal Muscles↗
PubMed1967

Behavioral acts elicited by stimulation of single, identifiable brain cells.

By stimulation of and recording from all of the nerve trunks and from over 50 of the large nerve cell bodies in the isolated brain of the nudibranch Tritonia gilberti a map of the axonal paths and synaptic connections has been constructed. The nervous correlates of sensory and motor activities can be monitored in single cells of the intact animal. Similarly, discrete responses in local muscles of the body wall and complex behavioral sequences such as turning and swimming are triggered by stimulation of single identifiable units.

Animals↗
PubMedDate not supplied

Motion planning with complete knowledge using a colored SOM.

The motion planning problem requires that a collision-free path be determined for a robot moving amidst a fixed set of obstacles. Most neural network approaches to this problem are for the situation in which only local knowledge about the configuration space is available. The main goal of the paper is to show that neural networks are also suitable tools in situations with complete knowledge of the configuration space. In this paper we present an approach that combines a neural network and deterministic techniques. We define a colored version of Kohonen's self-organizing map that consists of two different classes of nodes. The network is presented with random configurations of the robot and, from this information, it constructs a road map of possible motions in the work space. The map is a growing network, and different nodes are used to approximate boundaries of obstacles and the Voronoi diagram of the obstacles, respectively. In a second phase, the positions of the two kinds of nodes are combined to obtain the road map. In this way a number of typical problems with small obstacles and passages are avoided, and the required number of nodes for a given accuracy is within reasonable limits. This road map is searched to find a motion connecting the given source and goal configurations of the robot. The algorithm is simple and general; the only specific computation that is required is a check for intersection of two polygons. We implemented the algorithm for planar robots allowing both translation and rotation and experiments show that compared to conventional techniques it performs well, even for difficult motion planning scenes.

Algorithms↗
PubMed2004

Spatial expression of the kallikrein-kinin system during nephrogenesis.

During nephrogenesis, new nephrons are induced in the periphery of the kidney, while maturing nephrons occupy a deeper position in the renal cortex. This centrifugal pattern of maturation is characterized by nephron patterning, establishment of proximal-distal segment identity, tubular and glomerular growth and differentiation, and acquisition of specialized functions. All of these processes are coordinated in time and space with renal vasculogenesis, glomerulogenesis and regional hemodynamic changes. The end-result ensures that tubular structure and function are tightly coordinated with glomerular filtration during normal kidney development. To achieve this delicate task of glomerulotubular balance, the developing kidney produces growth factors and vasoactive hormones that act in a paracrine manner to regulate nephrovascular growth, differentiation and physiological functions. One such paracrine system is the kallikrein-kinin system (KKS), which generates bradykinin (BK) from the cleavage of kininogen by kallikrein. BK activates a G-protein coupled receptor, B2R, to regulate renal blood flow and salt and water excretion. The developing kidney expresses an endogenous KKS. Expression of the KKS components and B2R is intimately coordinated with the terminal differentiation of the distal nephron. Kallikrein marks the onset of connecting tubule development, whereas kininogen and B2R map to the developing ureteric bud branches and maturing collecting ducts.Gene targeting studies indicate that the fetal KKS plays an important role in the maintenance of terminal epithelial cell differentiation.

Animals↗
PubMed1996

HB Gouda [alpha 72(EF1)His-->Gln], a new silent alpha chain variant.

We describe a new alpha chain mutant accidentally found in a diabetic patient. The propositus is being treated for diabetes mellitus II with 4% glycated hemoglobin (Hb A1C). The variant, named Hb Gouda, is not detectable by starch gel electrophoresis but appears as a shoulder before the Hb A fraction during the chromatographic separation of Hb A1C. The hematological analysis revealed normal parameters with a normal serum iron value. No anomalies were reported in connection with Hb Gouda. The tryptic peptide map and sequencing of the alpha T-9 peptide revealed the substitution of a histidine by a glutamine at position 72. By selective amplification and sequencing of both the alpha genes, we have assigned the new mutation to the alpha 2 gene. Position 72 of the alpha chain is a moderately conserved site located between two non-conserved amino acids. This site is not involved in heme, dimer or tetramer contacts, or in Bohr effect or in 2,3-diphosphoglycerate binding.

Amino Acid Sequence↗