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At least 163 records · Page 9Linked to original sources
PubMed1993

Simulation of stochastic micropopulation models--III. COGNET: an artificial neural network for visual recognition.

COGNET, based on a neural network first described by Fukushima, demonstrates the relationship between connectionist and other micropopulation models. Its success and physiological orientation led to an implementation using the SUMMERS simulation shell. After self-supervised learning, COGNET uses forward and backward propagation of signals to recognize partial and noisy patterns, and to reconstruct the originals. Stochastic features include variable thresholds for neuronal firing and occasional cell death. The successful implementation of COGNET demonstrates the generality of the concepts embodied in SUMMERS, which in turn promotes the reusability of software and facilitates the extension of computational models in biomedical research. COGNET itself forms a framework for building other physiologically oriented neural network models.

Computer Simulation↗
PubMedDate not supplied

Self-assembled extracellular matrix protein networks by microcontact printing.

Physiological patterns of the extracellular matrix protein, laminin-1, were obtained on glass substrates by physisorption-assisted microcontact printing. Besides the well-retained antigenicity confirmed by indirect immunofluorescence assays, we investigated the supramolecular organization of the proteins by atomic force microscopy. We found the characteristic protein self-assembling in polygonal networks with well-defined sub-100 nm quaternary structures of laminin. The formation of these physiological mesh-like protein matrices was obtained by means of one-step soft lithography without any preliminary functionalization of glass, which can be exploited for many possible applications for cell cultures and biomolecular devices.

Coated Materials, Biocompatible↗
PubMedDate not supplied

[Emergence of circadian rhythms in infants before and after birth: evidence for variations by parental influence].

BACKGROUND: Organisms have developed endogenous mechanisms for keeping track of time which allow them to adjust to environmental changes. Entrainment of endogenous rhythms to the day-night cycle is of elementary importance for the regulation of physiological processes. How environmental changes influence the manifestation of circadian rhythms during intrauterine and extrauterine growth depend on complex networking of molecular, physiological and sensory mechanisms. This work reports on development of circadian rhythms in the infant, with particular emphasis on the roles of times cues to which the infant is exposed. SUBJECTS AND METHODS: Activity data of 12 families were continuously recorded during the first 4 months after birth using non-invasive actigraphs. Recordings of parental activity started at the 3rd trimester of pregnancy. Time series analysis was used to investigate the periodic structure of the data. In addition, we review the literature on the ontogenesis of circadian rhythms in humans. RESULTS: During the 3rd trimester, daily variation of physiological functions in the fetus showed a high degree of correspondence with maternal circadian rhythms. Early behaviour of most infants was highly variable between individuals but could be assigned to different entrainment patterns. Good correspondence of mother-infant activity patterns during the early postnatal period, when the infant was not yet entrained to the day-night-cycle, was correlated with the rapid development of an entrained daily pattern in the infant a few weeks later. CONCLUSION: Understanding the emergence of periodic structures at physiological and behavioural level during human ontogenesis will be an asset in the successful intervention and treatment during neonatal care.

Child Development↗
PubMed2003

Novel associated hydrogels for nucleus pulposus replacement.

Hydrogels of poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) blends may provide a material suitable for replacement of the nucleus pulposus of the intervertebral disc. This research examined the stability of these hydrogels under simulated physiological conditions. Polymer dissolution and stability were characterized over 120 days immersion, chemical surface analysis over 56 days immersion, and tensile mechanical behavior over 56 days immersion. Rubber elasticity theory was used by combining mechanical results with swelling data to calculate network characteristics such as the molecular weight between physical crosslinks and density of crosslinks. Properties were examined as a function of PVA/PVP composition as well as PVA molecular weight and PVP molecular weight. Results indicated that PVA/PVP blends prepared with moderate amounts of PVP (0.5-5%) resulted in a polymer network stabilized through interchain hydrogen bonding between hydroxyl groups on PVA chains and carbonyl groups on PVP chains. Most notably, a significant decrease in percentage of polymer mass loss was seen for blends prepared with 143K molecular weight PVA. Surface chemical analysis revealed that PVP unincorporated in the network structure suffered significant dissolution out of the polymer network and into solution. The molecular weight of PVA and PVP were shown to have a significant influence on the blends' network properties. Gels prepared with lower molecular weight PVA resulted in a more stable blend containing a higher density of crosslinks. However, blends prepared with a higher molecular weight PVA showed superior polymer network stability in dissolution studies. The blend that had the best combination of network stability under physiological conditions and a relatively tight, stable, and crosslinked network was prepared with 99% PVA (143K) and 1% PVP (40K). This material is proposed as an implant material for replacement of the degenerated nucleus pulposus.

Biocompatible Materials↗
PubMed1993

The role of interneurons in controlling the tail-withdrawal reflex in Aplysia: a network model.

1. The contributions of monosynaptic and polysynaptic circuitry to the tail-withdrawal reflex in the marine mollusk Aplysia californica were assessed by the use of physiologically based neural network models. Effects of monosynaptic circuitry were examined by the use of a two-layer network model with four sensory neurons in the input layer and one motor neuron in the output layer. Results of these simulations indicated that the monosynaptic circuit could not account fully for long-duration responses of tail motor neurons elicited by tail stimulation. 2. A three-layer network model was constructed by interposing a layer of two excitatory interneurons between the input and output layers of the two-layer network model. These interneurons had properties mimicking those of the recently described interneuron LP117, receiving excitatory input from pleural sensory neurons and evoking a biphasic excitatory postsynaptic potential (EPSP) in pedal motor neurons (Cleary and Byrne 1993). The three-layer model could account for long-duration responses in motor neurons. 3. Sensory neurons are a known site of plasticity in Aplysia. Synaptic plasticity was incorporated into the three-layer model by altering the magnitudes of conductance changes evoked in motor neurons and interneurons by presynaptic sensory neurons. In these simulations the excitatory interneurons converted an amplitude-coded input into an amplitude- and duration-coded output, allowing the three-layer network to support a large range of output amplitudes and durations. 4. Synaptic plasticity at more than one locus modified dramatically the input-output relationship of the three-layer network model. This feature gave the model redundancy in its plastic properties and points to the possibility of distributed memory in the circuitry mediating withdrawal reflexes in Aplysia. Multiple sites of control over the response of the network would likely allow a more diverse repertoire of responses.

Animals↗
PubMed1998

The significance of an increase in soluble interleukin-2 receptor level in colorectal cancer and its biological regulating role in the physiological switching of the immune response cytokine network from TH1 to TH2 and back.

Current research has still not clarified the biological role of soluble interleukin(IL)-2 receptor (sIL-2R) and the significance of its increase in the serum of colon cancer patients compared to healthy subjects. To address these questions at the immunological level in a group of patients and healthy subjects, we determined the sIL-2R level in the serum and its release from peripheral blood mononuclear cells (PBMC) as a function of tumour necrosis factor (TNF) alpha, IL-1 alpha, IL-1 beta, IL-2, interferon (IFN) gamma, IL-4, IL-6 and IL-10 levels in the serum and PBMC production; and PBMC proliferative responses to IL-2, IL-4 and anti-CD3 monoclonal antibody (CD3), variously combined. The level of sIL-2R in patients' serum was higher than in healthy subjects and correlated with the stage of advancement. Moreover, while in healthy subjects the serum level of sIL-2R was not significantly correlated with other parameters, in patients it was positively related to IL-4, IL-6 and IL-10 serum levels, PBMC IL-4 production and to the PBMC proliferative response to CD3 and CD3 + IL-2; it was negatively correlated to IL-2 serum level and IL-1 beta PBMC release. A negative connection between IFN gamma serum level and the PBMC production of sIL-2R was also found. This suggests that the increase of sIL-2R in the serum of patients, compared to healthy subjects, is involved in the inappropriate expansion of the T helper (TH2) suppressive immune response, which we previously reported. The multivariate statistical method supported the above suggestions and we also found that, in healthy subjects, the up- and down-regulation of sIL-2R in the serum within the physiological ranges seems to have a regulating role in the relationships between TNF alpha, IFN gamma and IL-4, IL-6, contributing to the operation of the cytokine network between TH1 and TH2 cells. However, in patients compared to healthy subjects the increased sIL-2R serum level seems to direct the immune response towards a suppressive type, which may be due to an alteration in the above-mentioned physiological regulating role.

Adult↗
PubMed2003

Impact of aging on hippocampal function: plasticity, network dynamics, and cognition.

Aging is associated with specific impairments of learning and memory, some of which are similar to those caused by hippocampal damage. Studies of the effects of aging on hippocampal anatomy, physiology, plasticity, and network dynamics may lead to a better understanding of age-related cognitive deficits. Anatomical and electrophysiological studies indicate that the hippocampus of the aged rat sustains a loss of synapses in the dentate gyrus, a loss of functional synapses in area CA1, a decrease in the NMDA-receptor-mediated response at perforant path synapses onto dentate gyrus granule cells, and an alteration of Ca(2+) regulation in area CA1. These changes may contribute to the observed age-related impairments of synaptic plasticity, which include deficits in the induction and maintenance of long-term potentiation (LTP) and lower thresholds for depotentiation and long-term depression (LTD). This shift in the balance of LTP and LTD could, in turn, impair the encoding of memories and enhance the erasure of memories, and therefore contribute to cognitive deficits experienced by many aged mammals. Altered synaptic plasticity may also change the dynamic interactions among cells in hippocampal networks, causing deficits in the storage and retrieval of information about the spatial organization of the environment. Further studies of the aged hippocampus will not only lead to treatments for age-related cognitive impairments, but may also clarify the mechanisms of learning in adult mammals.

Aged↗
PubMed2005

Learning in ex-vivo developing networks of cortical neurons.

This contribution describes the use of multi-site interaction with large cortical networks in the study of learning. The general physiological properties of the network are described, and the concept of learning is mapped to the experimental network preparation. Learning is then analyzed in terms of exploration (defined as changes in the configuration of associations within the biological network) and recognition (the stabilization of "worthy" associations).

Animals↗
PubMed2005

Alteration of the perceived path of a non-pursued target during smooth pursuit: analysis by a neural network model.

During pursuit of a circularly moving target, the perceived movement of a second circularly moving target is altered. The perceived movement of the non-pursued target is different from both its real movement path and its retinal path. In the present paper this phenomenon is studied using a physiologically based neural network model. Simulation results were compared to psychophysical findings in human subjects. Model simulations enabled us to suggest an explanation for this phenomenon in terms of underlying physiological mechanisms and to estimate the contribution of the efferent eye-movement signal to the perceptual process.

Adult↗
PubMed2006

The brain as a system of nested but partially overlapping networks. Heuristic relevance of the model for brain physiology and pathology.

A new model of the brain organization is proposed. The model is based on the assumption that a global molecular network enmeshes the entire central nervous system. Thus, brain extra-cellular and intra-cellular molecular networks are proposed to communicate at the level of special plasma membrane regions (e.g., the lipid rafts) where horizontal molecular networks can represent input/output regions allowing the cell to have informational exchanges with the extracellular environment. Furthermore, some "pervasive signals" such as field potentials, pressure waves and thermal gradients that affect large parts of the brain cellular and molecular networks are discussed. Finally, at least two learning paradigms are analyzed taking into account the possible role of Volume Transmission: the so-called model of "temporal difference learning" and the "Turing B-unorganised machine". The relevance of this new view of brain organization for a deeper understanding of some neurophysiological and neuropathological aspects of its function is briefly discussed.

Animals↗
PubMed1996

Postnatal remodeling of the leptomeningeal vascular network as assessed by intravital fluorescence video-microscopy in the rat.

An intriguing characteristic of the ontogenic development of the cerebral vasculature is the rapid differentiation of the neonatal leptomeningeal vascular plexus into the mature, adult network form. The physiological and cellular mechanisms of this cerebrovascular remodeling process are unclear. The objective of this work was to determine and correlate changes in vascular density, network pattern and flow velocity in leptomeningeal microvessels of the rat during postnatal development in vivo. To this end, microvascular diameter, segment length, and vascular density of reconstructed leptomeningeal networks were measured from video-recordings of the microcirculation visualized through a cranial window in 0-15-day-old Sprague-Dawley rats. The velocity of erythrocytes in the microvessels was measured by frame to frame tracking of fluorescently labeled red blood cells. We found that surface vascular density (total vessel length per area), node density and segment density (object per area) decreased significantly by the second week after birth. Anastomosing vascular polygons, characteristic to newborn networks, became less numerous and larger in diameter during the postnatal 2-week period, indicating progressive rarefaction of the networks. Vessel diameter and red cell velocity showed transient increases at 1.5 weeks. The velocity/diameter ratio (V/D), an index of wall shear rate, increased by the age of 1.5 weeks and remained unchanged afterwards. There was a negative correlation between V/D and diameter at 1 week; this relationship was reversed to a positive correlation at 2 weeks. We conclude that postnatal remodeling of the leptomeningeal vascular network is associated with rarefaction and an adaptation of vessel caliber to wall shear rate. These changes may contribute to arterio-venous differentiation and redistribution of blood flow from the superficial to the intracortical vasculature in the developing brain.

Animals↗
PubMed1995

Mathematic modelling of the enteric nervous network. 5. Excitation propagation in a planar neural network.

A mathematical model of the enteric nervous system (Auerbach's plexus) as a planar neural network has been developed, based on the actual morphological data of its organization. The network is composed of excitatory (cholinergic) and inhibitory (adrenergic) neurones interconnected by polysynaptic channels, formed of the geometrically non-uniform unmyelinated nerve axons. The synaptic zones are modelled as a three-compartment open pharmacokinetics system, i.e., presynaptic terminal, synaptic cleft and postsynaptic membrane where the pharmacokinetic mechanisms of electrochemical coupling are considered. All the chemical reactions of transformation of acetylcholine and adrenaline within them are described by first order Michaelis-Menten kinetics. The propagation of the electrical impulse along the pathways and in the vicinity of the nerve terminal is described by the modified Hodgkin-Huxley equations. The results of numerical simulation of the propagation of excitation within the neuronal chain, inhibitory feedback circuit, and a planar neuronal network under normal physiological conditions and after treatment with cholinergic/adrenergic agonists and antagonists are presented. The model predicts the dose-dependent influence of pharmacological agents on the neural network function.

Action Potentials↗
PubMed2004

The HUPO PSI's molecular interaction format--a community standard for the representation of protein interaction data.

A major goal of proteomics is the complete description of the protein interaction network underlying cell physiology. A large number of small scale and, more recently, large-scale experiments have contributed to expanding our understanding of the nature of the interaction network. However, the necessary data integration across experiments is currently hampered by the fragmentation of publicly available protein interaction data, which exists in different formats in databases, on authors' websites or sometimes only in print publications. Here, we propose a community standard data model for the representation and exchange of protein interaction data. This data model has been jointly developed by members of the Proteomics Standards Initiative (PSI), a work group of the Human Proteome Organization (HUPO), and is supported by major protein interaction data providers, in particular the Biomolecular Interaction Network Database (BIND), Cellzome (Heidelberg, Germany), the Database of Interacting Proteins (DIP), Dana Farber Cancer Institute (Boston, MA, USA), the Human Protein Reference Database (HPRD), Hybrigenics (Paris, France), the European Bioinformatics Institute's (EMBL-EBI, Hinxton, UK) IntAct, the Molecular Interactions (MINT, Rome, Italy) database, the Protein-Protein Interaction Database (PPID, Edinburgh, UK) and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING, EMBL, Heidelberg, Germany).

Database Management Systems↗
PubMedDate not supplied

Physiologically realistic formation of autoassociative memory in networks with theta/gamma oscillations: role of fast NMDA channels.

Recordings from brain regions involved in memory function show dual oscillations in which each cycle of a low-frequency theta oscillation (5-8 Hz) is subdivided into about seven subcycles by high frequency gamma oscillations (20-60 Hz). It has been proposed (Lisman and Idiart 1995) that such networks are a multiplexed short-term memory (STM) buffer that can actively maintain about seven memories, a capability of human STM. A memory is encoded by a subset of principal neurons that fire synchronously in a particular gamma subcycle. Firing is maintained by a membrane process intrinsic to each cell. We now extend this model by incorporating recurrent connections with modifiable synapses to store long-term memory (LTM). The repetition provided by STM gradually modifies synapses in a physiologically realistic way. Because different memories are active in different gamma subcycles, the formation of autoassociative LTM requires that synaptic modification depend on N-methyl-D-aspartate (NMDA) channels having a time constant of deactivation that is of the same order as the duration of a gamma subcycle (15-50 msec). Many types of NMDA channels have longer time constants (150 msec), as for instance those found in the hippocampus, but both fast and slow NMDA channels are present in cortex. This is the first proposal for the special role of these fast NMDA channels. The STM for novel items must depend on activity-dependent changes intrinsic to neurons rather than recurrent connections, which have not developed the required selectivity. Because these intrinsic mechanisms are not error-correcting, STM will become slowly corrupted by noise. This limits the accuracy with which LTM can become encoded after a single presentation. Accurate encoding of items in LTM can be achieved by multiple presentations, provided different memory items are presented in a varied interleaved order. Our results indicate that a limited memory-capacity STM model can be integrated in the same network with a high-capacity LTM model.

Association↗
PubMed2002

Can we discover novel pathways using metabolomic analysis?

Metabolomic analysis aims at the identification and quantitation of all metabolites in a given biological sample. Current data acquisition and network analysis strategies are classified on the basis of pathway elucidation and characteristics of theoretical networks. The development of metabolomic methods and tools is progressing rapidly, but an understanding of the resulting data is limited owing to a fundamental lack of biochemical and physiological knowledge about network organization in plants.

Chromatography↗
PubMed1999

Effect of capping protein, CapZ, on the length of actin filaments and mechanical properties of actin filament networks.

We report on how physiological concentrations of capping protein shorten actin filaments and on the remarkably fluid nature of solutions of such short filaments even at the high concentrations that exist in cells. We measured the lengths of actin filaments formed by spontaneous polymerization of highly purified actin monomers by fluorescence microscopy after labeling with rhodamine-phalloidin. The length distributions are exponential with a mean of about 7 microm (2600 subunits). As observed previously with less quantitative assays, copolymerization with the actin capping protein, CapZ, reduces the length of the filaments. At cellular concentrations of capping protein, one filament forms for each molecule of capping protein and the population of filaments is uniformly short. Using CapZ to vary the length of actin filaments, we measured how their mechanical properties depend on length. The stiffness (elastic modulus) of actin filament networks depends steeply on the length, with long filaments contributing far out of proportion to their numbers to the stiffness. Even at physiological concentrations (300 microM), networks of filaments limited to lengths observed in cells with a 1 to 500 molar ratio of CapZ are more fluid and much less elastic than lower concentrations of longer actin filaments. Thus the high concentration of short actin filaments in cells must be crosslinked to produce the observed stiffness of the cortex.

Actins↗
PubMed2003

Role of endogenous cannabinoids in synaptic signaling.

Research of cannabinoid actions was boosted in the 1990s by remarkable discoveries including identification of endogenous compounds with cannabimimetic activity (endocannabinoids) and the cloning of their molecular targets, the CB1 and CB2 receptors. Although the existence of an endogenous cannabinoid signaling system has been established for a decade, its physiological roles have just begun to unfold. In addition, the behavioral effects of exogenous cannabinoids such as delta-9-tetrahydrocannabinol, the major active compound of hashish and marijuana, await explanation at the cellular and network levels. Recent physiological, pharmacological, and high-resolution anatomical studies provided evidence that the major physiological effect of cannabinoids is the regulation of neurotransmitter release via activation of presynaptic CB1 receptors located on distinct types of axon terminals throughout the brain. Subsequent discoveries shed light on the functional consequences of this localization by demonstrating the involvement of endocannabinoids in retrograde signaling at GABAergic and glutamatergic synapses. In this review, we aim to synthesize recent progress in our understanding of the physiological roles of endocannabinoids in the brain. First, the synthetic pathways of endocannabinoids are discussed, along with the putative mechanisms of their release, uptake, and degradation. The fine-grain anatomical distribution of the neuronal cannabinoid receptor CB1 is described in most brain areas, emphasizing its general presynaptic localization and role in controlling neurotransmitter release. Finally, the possible functions of endocannabinoids as retrograde synaptic signal molecules are discussed in relation to synaptic plasticity and network activity patterns.

Animals↗
PubMed2006

Structural investigation of cold activity and regulation of aspartate carbamoyltransferase from the extreme psychrophilic bacterium Moritella profunda.

Aspartate carbamoyltransferase (EC 2.1.3.2) is extensively studied as a model for cooperativity and allosteric regulation. The structure of the Escherichia coli enzyme has been thoroughly analyzed by X-ray crystallography, and recently the crystal structures of two hyperthermophilic ATCases of the same structural class have been characterized. We here report the detailed functional and structural investigation of the ATCase from the psychrophilic deep sea bacterium Moritella profunda. Our analysis indicates that the enzyme conforms to the E. coli model in that two allosteric states exist that are influenced by similar homotropic interactions. The heterotropic properties differ in that CTP and UTP inhibit the holoenzyme, but ATP seems to exhibit a dual regulatory pattern, activating the enzyme at low concentrations and inhibiting it in the mM range. The crystal structure of the unliganded M. profunda ATCase shows resemblance to a more extreme T state reported previously for an E. coli ATCase mutant. A detailed molecular analysis reveals potential features of adaptation to cold activity and cold regulation. Moreover, M. profunda ATCase presents similarities with certain mutants of E. coli ATCase altered in their kinetic properties or temperature relationships. Finally, structural and functional comparison of ATCases across the full physiological temperature range agrees with an important, but fundamentally different role for electrostatics in protein adaptation at both extremes, i.e. an increased stability through the formation of ion pairs and ion pair networks at high physiological temperatures, and an increased flexibility through enhanced protein solvation at low temperatures.

Amino Acid Sequence↗