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Relationship of activity in the subthalamic nucleus-globus pallidus network to cortical electroencephalogram.

One of the functions of the excitatory subthalamic nucleus (STN) is to relay cortical activity to other basal ganglia structures. The response of the STN to cortical input is shaped by inhibition from the reciprocally connected globus pallidus (GP). To examine the activity in the STN-GP network in relation to cortical activity, we recorded single and multiple unit activity in STN and/or GP together with cortical electroencephalogram in anesthetized rats during various states of cortical activation. During cortical slow-wave activity (SWA), STN and GP neurons fired bursts of action potentials at frequencies that were similar to those of coincident slow ( approximately 1 Hz) and spindle (7-14 Hz) cortical oscillations. Spontaneous or sensory-driven global activation was associated with a reduction of SWA and a shift in STN-GP activity from burst- to tonic- or irregular-firing. Rhythmic activity in STN and GP neurons was lost when the cortex was inactivated by spreading depression and did not resume until SWA had recovered. Although rhythmic STN-GP activity was correlated with SWA, the phase relationships of activities of neurons within the STN and GP and between the nuclei were variable. Even when neurons displayed synchronous bursting activity, correlations on the millisecond time scale, which might indicate shared synaptic input, were not observed. These data indicate that (1) STN and GP activity is intimately related to cortical activity and hence the sleep-wake cycle; (2) rhythmic oscillatory activity in the STN-GP network in disease states may be driven by the cortex; and (3) activity of the STN-GP network is regulated in space in a complex manner.

Action Potentials↗

Strain-driven mesoscopic reconstruction of the As/Ge(111) surface.

Periodic arrays of large hexagonal tiles (up to 170 A in size) are observed on As/Ge(111) surfaces. First-principles total energy calculations combined with scanning tunneling microscopy reveal a (5-7-5)-ringed structure for the trenches that separate the tiles. We find that trenches form via an exothermic process. The calculated equilibrium trench spacing of approximately 104 A agrees with experiment. Comparison between first-principles calculations and continuum elasticity theory suggests that the observed mesoscopic reconstruction is driven entirely by long-range surface strain relaxation.

Journal Article↗

Receptive field expansion in adult visual cortex is linked to dynamic changes in strength of cortical connections.

1. Receptive field (RF) sizes of neurons in adult primary visual cortex are dynamic, expanding and contracting in response to alternate stimulation outside and within the RF over periods ranging from seconds to minutes. The substrate for this dynamic expansion was shown to lie in cortex, as opposed to subcortical parts of the visual pathway. The present study was designed to examine changes in cortical connection strengths that could underlie this observed plasticity by measuring the changes in cross-correlation histograms between pairs of primary visual cortex neurons that are induced to dynamically change their RF sizes. 2. Visually driven neural activity was recorded from single units in the superficial layers of primary visual cortex in adult cats, with two independent electrodes separated by 0.1-5 mm at their tips, and cross-correlated on-line. The neurons were then conditioned by stimulation with an "artificial scotoma," a field of flashing random dots filling the region of visual space around a blank rectangle enclosing the RFs of the recorded neurons. The neuronal RFs were tested for expansion and their visually driven output again cross-correlated. After this, the neurons were stimulated vigorously through their RF centers to induce the field to collapse, and the visually driven output from the collapsed RFs was again cross-correlated. Cross-correlograms obtained before and after conditioning, and after RF collapse, were normalized by their flanks to control for changes in peak size due solely to fluctuations in spike rate. 3. A total of 37 pairs of neurons that showed distinct cross-correlogram peaks, and whose RF borders were clearly discernible both before and after conditioning, were used in the final analysis. Of these neuron pairs, conditioning led to a clear expansion of RF boundaries in 28 pairs, whereas in 9 pairs the RFs did not expand. RFs that did expand showed no significant shifts in their orientation preference, orientation selectivity, or ocularity. 4. When the RFs of a pair of neurons expanded with conditioning, the area of the associated flank-normalized cross-correlogram peaks also increased (by a factor ranging from 0.84 up to 3.5). Correlograms returned to their preconditioning values when RFs collapsed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Ternary phase diagram of dipalmitoyl-PC/dilauroyl-PC/cholesterol: nanoscopic domain formation driven by cholesterol.

A ternary phase diagram is proposed for the hydrated lamellar lipid mixture dipalmitoylphosphatidylcholine/dilauroylphosphatidylcholine/cholesterol (DPPC/DLPC/cholesterol) at room temperature. The entire composition space has been thoroughly mapped by complementary experimental techniques, revealing interesting phase behavior that has not been previously described. Confocal fluorescence microscopy shows a regime of coexisting DPPC-rich ordered and DLPC-rich fluid lamellar phases, having an upper boundary at apparently constant cholesterol mole fraction chi(chol) approximately 0.16. Fluorescence resonance energy transfer experiments confirm the identification and extent of this two-phase regime and, furthermore, reveal a 1-phase regime between chi(chol) approximately 0.16 and 0.25, consisting of ordered and fluid nanoscopic domains. Dipyrene-PC excimer/monomer measurements confirm the new regime between chi(chol) approximately 0.16 and 0.25 and also show that rigidly ordered phases seem to disappear around chi(chol) approximately 0.25. This study should be considered as a step toward a more complete understanding of lateral heterogeneity within biomembranes. Cholesterol may play a role in domain separation on the nanometer scale.

1,2-Dipalmitoylphosphatidylcholine↗

Reconstruction of target speed for the guidance of pursuit eye movements.

We studied how object speed is reconstructed from the responses of motion-selective cells for the generation of a behavior that is tightly linked to the speed of visual motion. In theory, the speed of an object could be estimated either from the speed tuning of the active population of motion-selective cells or from the rate of displacement of activation across the cortical map of visual space. We measured the pursuit eye movements evoked by stimuli containing two conflicting motion components: a local component designed to excite motion-selective cells with a particular speed tuning and a displacement component designed to excite cells with a sequence of spatial receptive fields. Pursuit eye movements were driven primarily by the local-motion component and were affected to only a small degree by the rate of target displacement across visual space. Extracellular single-unit recordings using the same stimuli revealed that the responses of cells in the middle temporal visual area (MT) depended primarily on the local-motion component but were influenced by the displacement component to the same degree as were pursuit eye movements. We conclude that the initiation of pursuit is consistent with a reconstruction of target speed based on the speed tuning of the active population of MT cells.

Acceleration↗

Parametrically forced surface wave with a nonmonotonic dispersion relation.

Surface wave patterns that arise in a mechanically driven ferrofluid system under constant magnetic field are investigated (1) to find out what kind of spatial patterns emerge when the system acquires a nonmonotonic dispersion relation and (2) to compare its surface wave patterns with those produced in the magnetically driven system studied earlier. As the strength of the applied magnetic field increases, the initial subharmonic square lattice formed by the Faraday instability first transforms to rolls, then becomes a rhomboid lattice. The rolls and the rhomboid lattice are found to coexist for a finite range of parameter space forming patterns with mixed domains. Possible underlying mechanisms for the observed rhomboid lattice is discussed. None of the diverse superlattices observed in the magnetically driven ferrofluid system appears in the mechanically driven system studied here.

Journal Article↗

Pleural pressure distribution and its relationship to lung volume and interstitial pressure.

The mechanics of the pleural space has long been controversial. We summarize recent research pertaining to pleural mechanics within the following conceptual framework, which is still not universally accepted. Pleural pressure, the force acting to inflate the lung within the thorax, is generated by the opposing elastic recoils of the lung and chest wall and the forces generated by respiratory muscles. The spatial variation of pleural pressure is a result of complex force interactions among the lung and other structures that make up the thorax. Gravity contributes one of the forces that act on these structures, and regional lung expansion and pleural pressure distribution change with changes in body orientation. Forces are transmitted directly between the chest wall and the lung through a very thin but continuous pleural liquid space. The pressure in pleural liquid equals the pressure acting to expand the lung. Pleural liquid is not in hydrostatic equilibrium, and viscous flow of pleural liquid is driven by the combined effect of the gravitational force acting on the liquid and the pressure distribution imposed by the surrounding structures. The dynamics of pleural liquid are considered an integral part of a continual microvascular filtration into the pleural space. Similar concepts apply to the pulmonary interstitium. Regional differences in lung volume expansion also result in regional differences in interstitial pressure within the lung parenchyma and thus affect regional lung fluid filtration.

Body Fluids↗

Antagonistic effects of perilymphatic calcium and magnesium on the activity of single cochlear afferent neurons.

The dependence of the spontaneous and sound driven activity of single cochlear nerve fibers on the calcium and magnesium content of the perilymph was studied by perfusion of the perilymphatic space. It was possible to study these effects under steady-state conditions by continuously perfusing scala tympani at low rates while simultaneously recording from units in the chinchilla auditory nerve. Preparations were stable for many hours. As previously reported [Robertson and Johnstone (1979) Pflügers Arch. 380, 7-12], perfusion with solutions containing elevated concentrations of magnesium reduces both the spontaneous and driven activity. When calcium was eliminated from the perfusate, activity was completely abolished for stimuli with sound pressure levels below 100 dB. During partial blocks, a relatively frequency-independent threshold elevation was seen for frequencies well below the characteristic frequency (CF) of the unit, with greater elevations closer to CF. When the threshold elevation at CF was 30-40 dB, the width of the 'tip' portion of the tuning curve was reduced, resembling that of naturally-occurring units with low spontaneous rates of discharge. These effects are similar to that of raising the criterion for response during threshold measurement and are probably related to a frequency-dependent nonlinearity exhibited by the motion of the basilar membrane. The dynamic range for the growth of average rate with level was increased and saturation was shifted to higher stimulus levels during elevated magnesium perfusion. Raising the calcium content of the perfusate increased both spontaneous and driven rates, even in the saturated portion of the rate-intensity plot. Under these conditions, the response of the unit may more directly correspond to the intracellular potential of the presynaptic hair cell. It is argued that the primary site of divalent cation interaction is in the control of transmitter release. Inner hair cells of the mammalian cochlea apparently do not release transmitter in the absence of a calcium influx. The size of the pool of 'readily-available' transmitter appears to be influenced by divalent cations. Even though this synapse is probably specialized for the transmission of auditory signals, the mechanism of synaptic transmission is probably not fundamentally different from that of other well-characterized synapses.

Animals↗

Thyroid-associated eye disease.

Graves' ophthalmopathy (GO) is thought to result from a complex interplay of genetic and environmental factors. Various genes, including those coding for HLA, may determine a patient's susceptibility to the disease and its severity, but in addition, numerous and often unknown environmental factors may determine its course. Once established, the chronic inflammatory process within the orbital tissues appears to take on a momentum of its own. Based upon our current state of knowledge, we propose the working scheme shown in Fig. 1 for the pathogenesis of GO: Against the background of a permissive immunogenetic milieu, circulating T cells in patients with Graves' Disease (GD), directed against certain antigens on thyroid follicular cells, recognize antigenic epitopes that are shared by tissues contained in the orbital space. Here, preadipocytes and fibroblasts most likely act as target and effector cells of the orbital immune process. This includes preadipocyte fibroblasts present in the perimysium of extraocular muscles, which do not appear to be immunologically or metabolically different from those located in the orbital connective tissue. Differentiation of orbital preadipocyte fibroblasts into mature adipocytes expressing increased levels of TSHR may be driven by stimulation with circulating or locally produced cytokines or effectors. To date, it is still unknown how autoreactive T cells escape deletion by the immune system and become directed against a self-antigen that is presented by cells residing in the thyroid gland and in certain extrathyroidal locations. Mimicry of a host antigen by a microorganism or presentation of an altered self-antigen may promote proliferation and expansion of autoreactive T cell clones. T cell recruitment into the orbital tissues is facilitated by certain chemokines and cytokines, which help to attract T cells by stimulating the expression of several adhesion molecules (e.g. ICAM-1, VCAM-1, CD44) in vascular endothelium and connective tissue cells. Adhesion molecules are known to be important for a variety of interactions between immunocompetent cells, connective tissue cells and extracellular matrix components. In addition, these molecules play a central role in lymphocyte activation and localization, facilitating antigen recognition, T cell costimulation, and various effector-target cell functions at the inflammatory sites, many of which result in amplification of the cellular immune process in active GO. Analysis of variable region genes of T cell antigen receptors in orbital T cells of patients with active GO has revealed limited variability of TcR V gene usage, suggesting that antigen-driven selection and/or expansion of specific T cells may occur during the early stages of GO. T cells and macrophages populate the orbital space and release a number of cytokines (most likely a Th-1-type spectrum) into the surrounding tissues. Cytokines, oxygen free radicals and fibrogenic growth factors, released both from infiltrating inflammatory and residential cells, act upon orbital preadipocytes in a paracrine and autocrine manner to stimulate adipogenesis, fibroblast proliferation, glycosaminoglycan synthesis, and the expression of immunomodulatory molecules. Smoking, a well-known aggravating factor in GO with an uncertain mode of action, may aggravate tissue hypoxia and exert important immunomodulatory effects. Finally, the long-held hypothesis of a thyroid cross-reactive antigen within the orbital tissues has recently gained significant support from an animal model of ophthalmopathy, and from in vitro and ex vivo studies. If confirmed by immunological studies, these data may well explain the localized infiltration of the orbital tissues by autoreactive lymphocytes that share intriguing molecular features with intrathyroidal lymphocytes. Local release of certain cytokines, TSHR-directed autoantibodies, or other factors might further enhance adipogenesis, glycosaminoglycan synthesis and expression of

Adipocytes↗

The International Space Station human life sciences experiment implementation process.

The selection, definition, and development phases of a Life Sciences flight research experiment has been consistent throughout the past decade. The implementation process, however, has changed significantly within the past two years. This change is driven primarily by the shift from highly integrated, dedicated research missions on platforms with well defined processes to self contained experiments with stand alone operations on platforms which are being concurrently designed. For experiments manifested on the International Space Station (ISS) and/or on short duration missions, the more modular, streamlined, and independent the individual experiment is, the more likely it is to be successfully implemented before the ISS assembly is completed. During the assembly phase of the ISS, science operations are lower in priority than the construction of the station. After the station has been completed, it is expected that more resources will be available to perform research. The complexity of implementing investigations increases with the logistics needed to perform the experiment. Examples of logistics issues include- hardware unique to the experiment; large up and down mass and volume needs; access to crew and hardware during the ascent or descent phases; maintenance of hardware and supplies with a limited shelf life,- baseline data collection schedules with lengthy sessions or sessions close to the launch or landing; onboard stowage availability, particularly cold stowage; and extensive training where highly proficient skills must be maintained. As the ISS processes become better defined, experiment implementation will meet new challenges due to distributed management, on-orbit resource sharing, and adjustments to crew availability pre- and post-increment.

Biological Science Disciplines↗

Multiple dynamic transitions in an anisotropic Heisenberg ferromagnet driven by polarized magnetic field.

A uniaxially (along the Z axis) anisotropic Heisenberg ferromagnet, in the presence of time-dependent (but uniform over space) magnetic field, is studied by Monte Carlo simulation. The time-dependent magnetic field was taken as elliptically polarized where the resultant field vector rotates in the X-Z plane. The system is cooled (in the presence of the elliptically polarized magnetic field) from high temperature. As the temperature decreases, it was found that in the low anisotropy limit the system undergoes three successive dynamical phase transitions. These three dynamic transitions were confirmed by studying the temperature variation of dynamic "specific heat." The temperature variation of dynamic specific heat shows three peaks indicating three dynamic transition points.

Journal Article↗

Entropy-driven genome organization.

DNA and RNA polymerases active on bacterial and human genomes in the crowded environment of a cell are modeled as beads spaced along a string. Aggregation of the large polymerizing complexes increases the entropy of the system through an increase in entropy of the many small crowding molecules; this occurs despite the entropic costs of looping the intervening DNA. Results of a quantitative cost/benefit analysis are consistent with observations that active polymerases cluster into replication and transcription "factories" in both pro- and eukaryotes. We conclude that the second law of thermodynamics acts through nonspecific entropic forces between engaged polymerases to drive the self-organization of genomes into loops containing several thousands (and sometimes millions) of basepairs.

Computer Simulation↗

Apoplasmic and Protoplasmic Water Transport through the Parenchyma of the Potato Storage Organ.

Stationary volume fluxes through living and denatured parenchyma slices of the potato (Solanum tuberosum L.) storage organ were studied to estimate the hydraulic conductivity of the cell wall and to evaluate the significance of water transport through protoplasts, cell walls, and intercellular spaces. Slices were placed between liquid compartments, steady-state fluxes induced by pressure or concentration gradients of low- and high-molecular-mass osmotica were measured, and water transport pathways were distinguished on the basis of their difference in limiting pore size. The protoplasts were the dominating route for osmotically driven water transport through living slices, even in the case of a polymer osmoticum that is excluded from cell walls. The specific hydraulic conductivity of the cell wall matrix is too small to allow a significant contribution of the narrow cell wall bypass to water flow through the living tissue. This conclusion is based on (a) ultrafilter coefficients of denatured parenchyma slices, (b) the absence of a significant difference between ultrafilter coefficients of the living tissue slices for osmotica with low and high cell wall reflection coefficients, and (c) the absence of a significant interaction (solvent drag) between apoplasmic permeation of mannitol and the water flux caused by a concentration difference of excluded polyethylene glycol. Liquid-filled intercellular spaces were the dominating pathways for pressure-driven volume fluxes through the parenchyma tissue.

Journal Article↗

On the population dynamics of the malaria vector.

A deterministic differential equation model for the population dynamics of the human malaria vector is derived and studied. Conditions for the existence and stability of a non-zero steady state vector population density are derived. These reveal that a threshold parameter, the vectorial basic reproduction number, exist and the vector can established itself in the community if and only if this parameter exceeds unity. When a non-zero steady state population density exists, it can be stable but it can also be driven to instability via a Hopf Bifurcation to periodic solutions, as a parameter is varied in parameter space. By considering a special case, an asymptotic perturbation analysis is used to derive the amplitude of the oscillating solutions for the full non-linear system. The present modelling exercise and results show that it is possible to study the population dynamics of disease vectors, and hence oscillatory behaviour as it is often observed in most indirectly transmitted infectious diseases of humans, without recourse to external seasonal forcing.

Animals↗

Single-coordinate-driving method for molecular docking: application to modeling of guest inclusion in cyclodextrin.

An extension of the computer program CICADA has been developed that allows us to use the single-coordinate-driving (SCD) method for flexible molecular docking. The docking procedure is composed of three independent space rotations, three independent translations, and the torsions selected by the user. One of the coordinates is driven; the other coordinates are relaxed. This procedure follows low-energy wells on the potential energy surface of the entire system. The program allows us to dock more than one ligand molecule to the receptor. We ran two test examples, docking N,N-dimethylformamide into alpha-cyclodextrin and R-phenoxypropionic acid into beta-cyclodextrin. The test examples showed that the SCD approach is able to overcome high-energy barriers and to cover the entire box within which the search is performed. The limitations of molecular dynamics docking in comparison with our approach also are discussed. The philosophy of the newly developed approach is not only to find the best dock for the receptor-ligand(s) system, but also to describe all the important binding modes and provide a good starting point for studying the dynamics within the cavity during the docking process.

Carbohydrate Conformation↗

A double-dissociation of English past-tense production revealed by event-related potentials and low-resolution electromagnetic tomography (LORETA).

OBJECTIVES: Evidence of systematic double-dissociations of neural activity associated with the generation of regular and irregular past tense in healthy individuals may prove decisive in distinguishing between single- and dual-route models of morphological processing, because the former (connectionist models of morphological processing) have only been able to simulate double-dissociations of past-tense morphology as low-probability phenomena. METHODS: Twenty-eight channel event-related potentials (ERPs) were recorded in response to past-tense production and subsequently analyzed using a 3-stage strategy. RESULTS: A data-driven algorithm temporally segmented the ERPs into 16 distinct epochs of stable field configuration (microstates). A space-oriented brain electric field analysis determined that one of those epochs, 288-321 ms after the verb stem presentation, showed significant differences between the regular and irregular verb conditions. As a further test of these results, a novel source localization technique that computes 3-dimensional distribution of cortical current density in the Talairach brain atlas--low-resolution electromagnetic tomography--found in the above microstate more activity for regulars in the right prefrontal and right temporal areas and for irregulars in the left temporal areas and the anterior cingulate cortex, which can be taken as evidence of systematic double-dissociation. CONCLUSIONS: The present results achieved with a source localization technique provide evidence of a two-way compartmentalization of neural activity corresponding to regular and irregular past tense, thus corroborating the dual-mechanism character of verb morphology.

Adult↗

Mechanism of proton entry into the cytoplasmic section of the proton-conducting channel of bacteriorhodopsin.

Bacteriorhodopsin is the light-driven proton-pumping protein of Halobacterium salinarum that extracts protons from the well-buffered cytoplasmic space within the time limits set by the photocycle turnover. The specific mechanism of the proton uptake by the cytoplasmic surface of the protein was investigated in this study by the laser-induced proton pulse technique. The purple membrane preparations were labeled by fluorescein at two residues (36 or 38) of the cytoplasmic surface of the protein, sites that are close to the orifice of the proton-conducting channel. The membranes were pulsed by protons discharged from photoexcited pyranine [Nachliel, E., Gutman, M., Kiryati, S., and Dencher, N.A. (1996) Proc. Nat Acad. Sci. U.S.A. 93, 10747-10752). The reaction of the discharged protons with the pyranine anion and the fluorescein was measured with sub-microsecond resolution. The experimental signals were reconstructed through numeric integration of differential rate equations which quantitated the rates of all proton transfer reactions between all reactants present in the system. The interaction of protons with the orifice of the cytoplasmic channel is enhanced by the exposed carboxylates of the protein. A cluster of three carboxylates acts as a strong proton attractor site while one carboxylate, identified as D36, acts as a mediator that delivers the proton to the channel. The combination of these reactions render the surface of the protein with properties of a proton-collecting antenna. The size of the collecting area is less than that of the protein's surface.

Bacteriorhodopsins↗

Semiconductor and thermoluminescent dosimetry of pulsed soft X ray plasma sources.

A multichannel detection system having a dynamic range of approximately 1 x 10(-9) Gy --20 Gy was developed with the use of commercially produced Si-photodiodes and TLDs for accurate measurement of X ray energy emitted from plasma-focus facility and from laser-produced plasmas. The proof of linearity of the employed detectors accomplished by a comparison of their responses to a broad band spectrum of X rays emitted from plasmas, is reported. It is demonstrated that TLDs irradiated with no protective filter show an incorrect response due to overloading in the sub-keV range and repopulation of dosimetric peaks induced by the UV radiation. The measurement of the power of undesirable secondary X ray sources driven by the primary plasma inside the interaction chamber was performed on the basis of analysis of space dependence of X ray intensity with respect to the assumed r(-2) decrease in the intensity far away from the plasma.

Hot Temperature↗