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At least 1,567 records · Page 87Linked to original sources
PubMed2005

Increased high-frequency oscillations precede in vitro low-Mg seizures.

PURPOSE: High-frequency oscillations (HFOs) in the range of > or = 80 Hz have been recorded in neocortical and hippocampal brain structures in vitro and in vivo and have been associated with physiologic and epileptiform neuronal population activity. Frequencies in the fast-ripple range (> 200 Hz) are believed to be exclusive to epileptiform activity and have been recorded in vitro, in vivo, and in epilepsy patients. Although the presence of HFOs is well characterized, their temporal evolution in the context of transition to seizure activity is not well understood. METHODS: With an in vitro low-magnesium model of spontaneous seizures, we obtained extracellular field recordings (hippocampal regions CA1 and CA3) of interictal, preictal, and ictal activity. Recordings were subjected to power-frequency analysis, in time, by using a local multiscale Fourier transform. The power spectrum was computed continuously and was quantified for each epileptiform discharge into four frequency ranges spanning subripple, ripple, and two fast-ripple frequency bands. RESULTS: A statistically significant increasing trend was observed in the subripple (0-100 Hz), ripple (100-200 Hz), and fast-ripple 1 (200-300 Hz) frequency bands during the epoch corresponding to the transition to seizure (preictal to ictal). CONCLUSIONS: Temporal patterns of HFOs during epileptiform activity are indicative of dynamic changes in network behavior, and their characterization may offer insights into pathophysiologic processes underlying seizure initiation.

Animals↗
PubMed1998

Capitated risk-bearing managed care systems could improve end-of-life care.

Capitated or salaried managed care systems offer an important opportunity to provide high quality, cost-effective end-of-life care. However, capitated healthcare delivery systems have strong incentives to avoid patient populations in need of such care. Care currently provided at the end of life in fee-for-service practice is commonly deficient, with high rates of avoidable pain and other burdens. Only hospice offers a better track record, yet access to hospice is limited, and length of stay is short. Traditional staff- or group-model managed care plans, with their emphasis on prevention, patient education, cost efficiency, service coordination, and integrated provider networks, present a dynamic set of conditions and organizational structures that would support real change. Advantages derived from managed care systems providing quality end-of-life care include coordinated care across delivery sites, interdisciplinary teams, integrated services, and opportunities to develop innovative care programs, service arrays, utilization controls, and accountability for care standards. We propose a special comprehensive system of managed care, which we call MediCaring, for seriously ill persons nearing the end of life. MediCaring would encompass the best elements of palliative care within a managed care structure: comprehensive, supportive, community-based services that meet personal and medical needs, a focus on patient preferences, symptom management, family counseling, and support. Other programs, such as hospice, have shown that continuity and coordinated care, financed through a capitated payment and directed at a special population, are both feasible and effective. There are obstacles to improving care at the end of life. Managed care systems, like most of medical care, have largely ignored the terminally ill patient. Current financing arrangements make it financially undesirable for insurers to recruit or retain the very sick; very ill patients can be costly over a prolonged time. In addition, inertia and habit inhibit change, and there are few criteria by which to judge whether care at the end-of-life is "good." Nevertheless, capitated or salaried managed care systems committed to enhanced end-of-life care seem well positioned to achieve it if payment reimbursements were revised to encourage this end.

Aged↗
PubMed2007

Temperature compensation through systems biology.

Temperature has a strong influence on most individual biochemical reactions. Despite this, many organisms have the remarkable ability to keep certain physiological fluxes approximately constant over an extended temperature range. In this study, we show how temperature compensation can be considered as a pathway phenomenon rather than the result of a single-enzyme property. Using metabolic control analysis, it is possible to identify reaction networks that exhibit temperature compensation. Because most activation enthalpies are positive, temperature compensation of a flux can occur when certain control coefficients are negative. This can be achieved in networks with branching reactions or if the first irreversible reaction is regulated by a feedback loop. Hierarchical control analysis shows that networks that are dynamic through regulated gene expression or signal transduction may offer additional possibilities to bring the apparent activation enthalpies close to zero and lead to temperature compensation. A calorimetric experiment with yeast provides evidence that such a dynamic temperature adaptation can actually occur.

Gene Expression Regulation↗
PubMed2001

Ecology. Tropical forest diversity--the plot thickens.

Also see the archival list of Science's Compass: Enhanced Perspectives ECOLOGY:Enhanced: Tropical Forest Diversity--The Plot Thickens David F. R. P. Burslem, Nancy C. Garwood, Sean C. Thomas Ecologists have long pondered why tropical forests contain such a huge number of species and what factors might be responsible for maintaining this diversity. In a Perspective, Burslem and colleagues discuss unique data sets from the forest dynamics plots (FDP) network, which shed light on the factors responsible for tropical forest diversity. D. F. R. P. Burslem is in the Department of Plant and Soil Science, University of Aberdeen, Aberdeen AB24 3UU, UK. E-mail: d.burslem@abdn.ac.uk. N. C. Garwood is in the Department of Botany, Natural History Museum, London SW7 5BD, UK. E-mail: ncg@nhm.ac.uk. S. C. Thomas is in the Faculty of Forestry, University of Toronto, Toronto M5S 3B3, Canada. E-mail: sc.thomas@utoronto.ca

Ecosystem↗
PubMed2006

Requirement for coronin 1 in T lymphocyte trafficking and cellular homeostasis.

The evolutionarily conserved actin-related protein (Arp2/3) complex is a key component of actin filament networks that is dynamically regulated by nucleation-promoting and inhibitory factors. Although much is known about actin assembly, the physiologic functions of inhibitory proteins are unclear. We generated coronin 1-/- mice and found that coronin 1 exerted an inhibitory effect on cellular steady-state F-actin formation via an Arp2/3-dependent mechanism. Whereas coronin 1 was required for chemokine-mediated migration, it was dispensable for T cell antigen receptor functions in T cells. Moreover, actin dynamics, through a mitochondrial pathway, was linked to lymphocyte homeostasis.

Actin-Related Protein 2-3 Complex↗
PubMed1999

Linking spontaneous activity of single cortical neurons and the underlying functional architecture.

The relation between the activity of a single neocortical neuron and the dynamics of the network in which it is embedded was explored by single-unit recordings and real-time optical imaging. The firing rate of a spontaneously active single neuron strongly depends on the instantaneous spatial pattern of ongoing population activity in a large cortical area. Very similar spatial patterns of population activity were observed both when the neuron fired spontaneously and when it was driven by its optimal stimulus. The evoked patterns could be used to reconstruct the spontaneous activity of single neurons.

Action Potentials↗
PubMed2001

Polarized entry of uropathogenic Afa/Dr diffusely adhering Escherichia coli strain IH11128 into human epithelial cells: evidence for alpha5beta1 integrin recognition and subsequent internalization through a pathway involving caveolae and dynamic unstable microtubules.

Afa/Dr diffusely adhering Escherichia coli strain IH11128 bacteria basolaterally entered polarized epithelial cells by a CD55- and CD66e-independent mechanism through interaction with the alpha5beta1 integrin and a pathway involving caveolae and dynamic microtubules (MTs). IH11128 invasion within HeLa cells was dramatically decreased after the cells were treated with the cholesterol-extracting drug methyl-beta-cyclodextrin or the caveola-disrupting drug filipin. Disassembly of the dynamically unstable MT network by the compound 201-F resulted in a total abolition of IH11128 entry. In apically infected polarized fully differentiated Caco-2/TC7 cells, no IH11128 entry was observed. The entry of bacteria into apically IH11128-infected fully differentiated Caco-2/TC7 cells was greatly enhanced by treating cells with Ca2+-free medium supplemented with EGTA, a procedure that disrupts intercellular junctions and thus exposes the basolateral surface to bacteria. Basally infected fully differentiated polarized Caco-2/TC7 cells grown on inverted inserts mounted in chamber culture showed a highly significant level of intracellular IH11128 bacteria compared with cells subjected to the apical route of infection. No expression of CD55 and CD66e, the receptors for the Afa/Dr adhesins, was found at the basolateral domains of these cells. Consistent with the hypothesis that a cell-to-cell adhesion molecule acts as a receptor for polarized IH11128 entry, an antibody blockade using anti-alpha5beta1 integrin polyclonal antibody completely abolished bacterial entry. Experiments conducted with the laboratory strain E. coli K-12 EC901 carrying the recombinant plasmid pBJN406, which expresses Dr hemagglutinin, demonstrated that the dra operon is involved in polarized entry of IH11128 bacteria. Examined as a function of cell differentiation, the number of internalized bacteria decreased dramatically beyond cell confluency. Surviving intracellular IH11128 bacteria residing intracellularly had no effect on the functional differentiation of Caco-2/TC7 cells.

Adhesins, Bacterial↗
PubMed2005

The association of caveolae, actin, and the dystrophin-glycoprotein complex: a role in smooth muscle phenotype and function?

Smooth muscle cells exhibit phenotypic and mechanical plasticity. During maturation, signalling pathways controlling actin dynamics modulate contractile apparatus-associated gene transcription and contractile apparatus remodelling resulting from length change. Differentiated myocytes accumulate abundant caveolae that evolve from the structural association of lipid rafts with caveolin-1, a protein with domains that confer unique functional properties. Caveolae and caveolin-1 modulate and participate in receptor-mediated signalling, and thus contribute to functional diversity of phenotypically similar myocytes. In mature smooth muscle, caveolae are partitioned into discrete linear domains aligned with structural proteins that tether actin to the extracellular matrix. Caveolin-1 binds with beta-dystroglycan, a subunit of the dystrophin glycoprotein complex (DGC), and with filamin, an actin binding protein that organizes cortical actin, to which integrins and focal adhesion complexes are anchored. The DGC is linked to the actin cytoskeleton by a dystrophin subunit and is a receptor for extracellular laminin. Thus, caveolae and caveolin-associated signalling proteins and receptors are linked via structural proteins to a dynamic filamentous actin network. Despite development of transgenic models to investigate caveolins and membrane-associated actin-linking proteins in skeletal and cardiac muscle function, only superficial understanding of this association in smooth muscle phenotype and function has emerged.

Actins↗
PubMed2003

Spatial and temporal control of differentiation and cell cycle progression in Caulobacter crescentus.

The dimorphic and intrinsically asymmetric bacterium Caulobacter crescentus has become an important model organism to study the bacterial cell cycle, cell polarity, and polar differentiation. A multifaceted regulatory network orchestrates the precise coordination between the development of polar organelles and the cell cycle. One master response regulator, CtrA, directly controls the initiation of chromosome replication as well as several aspects of polar morphogenesis and cell division. CtrA activity is temporally and spatially regulated by multiple partially redundant control mechanisms, such as transcription, phosphorylation, and targeted proteolysis. A multicomponent signal transduction network upstream CtrA, containing histidine kinases CckA, PleC, DivJ, and DivL and the essential response regulator DivK, contributes to the control of CtrA activity in response to cell cycle and developmental cues. An intriguing feature of this signaling network is the dynamic cell cycle-dependent polar localization of its components, which is believed to have a novel regulatory function.

Bacterial Proteins↗
PubMed2004

Light-directed electrical stimulation of neurons cultured on silicon wafers.

Dissociated neurons cultured in vitro can serve as a model system for studying the dynamics of neural networks. Such studies depend on techniques for stimulating patterns of neural activity. We show a technique for extracellular stimulation of dissociated neurons cultured on silicon wafers. When the silicon surface is reverse biased, electrical current can be generated near any neuron by pulsing a laser. Complex spatiotemporal stimulation patterns can be produced by directing a single beam with an acousto-optic deflector. The technique can generate a stimulating current at any location in the culture. This contrasts with multielectrode arrays (MEAs), which can stimulate only at fixed electrode locations. To characterize reliability and spatial selectivity of stimulation, we used intracellular (patch-clamp) recordings to monitor the effect of targeted laser pulses on cultured hippocampal neurons. Action potentials could be stimulated with submillisecond precision and 100-micron spatial resolution at rates exceeding 100 Hz. Optimal control parameters for stimulation are discussed.

Animals↗
PubMed2005

Temporal correlations in stochastic models of double bursting during simulated locomotion.

The output of the spinal central pattern generator for locomotion falls into two broad categories: alternation between antagonistic muscles and double bursting within muscles acting on multiple joints. We first model an alternating half-center and then present two different models of double bursting. The first double-bursting model consists of a central clock with an explicit one-to-one mapping between interneuron activity and model output. The second double-bursting model consists of a half-center with an added feedback neuron. Models are built using rate-coded leaky integrator neurons with slow self-inhibition. Structure-function relationships are explored by the addition of noise. The interaction of noise with the dynamics of each network creates a unique pattern of correlation between phases of the simulated cycle. The effects of noise can be explained by perturbation of deterministic versions of the networks. Three basic results were obtained: slow self-inhibitory currents lead to correlations between parts of the step cycle that are separated in time and network relative; model outputs are most sensitive to perturbations presented just before competitive switches in network activity, and clock-like models possess substantial symmetries within the correlation structure of burst durations, whereas the correlation structure of feedback models are asymmetric. Our models suggest that variability in burst length durations can be analyzed to make inferences about the structure of the spinal networks for locomotion. In particular, correlation patterns within double-bursting outputs may yield important clues regarding the interaction between more central, clock-like networks and feedback from more peripheral interneurons.

Animals↗
PubMed2000

Spike-driven synaptic plasticity: theory, simulation, VLSI implementation.

We present a model for spike-driven dynamics of a plastic synapse, suited for aVLSI implementation. The synaptic device behaves as a capacitor on short timescales and preserves the memory of two stable states (efficacies) on long timescales. The transitions (LTP/LTD) are stochastic because both the number and the distribution of neural spikes in any finite (stimulation) interval fluctuate, even at fixed pre- and postsynaptic spike rates. The dynamics of the single synapse is studied analytically by extending the solution to a classic problem in queuing theory (Takacs process). The model of the synapse is implemented in aVLSI and consists of only 18 transistors. It is also directly simulated. The simulations indicate that LTP/LTD probabilities versus rates are robust to fluctuations of the electronic parameters in a wide range of rates. The solutions for these probabilities are in very good agreement with both the simulations and measurements. Moreover, the probabilities are readily manipulable by variations of the chip's parameters, even in ranges where they are very small. The tests of the electronic device cover the range from spontaneous activity (3-4 Hz) to stimulus-driven rates (50 Hz). Low transition probabilities can be maintained in all ranges, even though the intrinsic time constants of the device are short (approximately 100 ms). Synaptic transitions are triggered by elevated presynaptic rates: for low presynaptic rates, there are essentially no transitions. The synaptic device can preserve its memory for years in the absence of stimulation. Stochasticity of learning is a result of the variability of interspike intervals; noise is a feature of the distributed dynamics of the network. The fact that the synapse is binary on long timescales solves the stability problem of synaptic efficacies in the absence of stimulation. Yet stochastic learning theory ensures that it does not affect the collective behavior of the network, if the transition probabilities are low and LTP is balanced against LTD.

Action Potentials↗
PubMed2000

[Natural organic compounds that affect to microtubule functions: syntheses and structure-activity relationships of combretastatins, curacin A and their analogs as the colchicine-site ligands on tubulin].

Microtubules (MT) are cylindrical polymers of the protein tubulin (TN) alpha, beta-heterodimer, and are known to be the main component of spindles in mitotic apparatus of eucaryotic cells. MT are also involved in many other basic and essential cell functions. There are a number of natural and synthetic compounds that interfere with MT function to cause the mitotic arrest of eucaryotic cells. Such antimitotic agents show a broad biological activity, and can be used for medicinal and agrochemical purposes. On the other hand, they are important also as the biochemical tools for understanding the dynamics of MT network. Most of such antimitotic agents, with a few exceptions, bind to beta-TN. Among them, colchicine (CLC), vinblastine and taxol have played major roles in practical uses as well as in biochemical studies of MT functions. They all bind to beta-TN but their binding sites are different. We have worked on a variety of antimitotic agents that bind to either of colchicine-site, vinblastine-site and taxol-site, in discovery, structures, biological actions and/or interactions with TN. In this paper, the results of our studies on CLC-site ligands were summarized; (1) synthetic analogs of combretastatin A-4 (CBS A-4), isolated as a cytotoxic compound produced by a species of South African tree Combretum caffrum, (2) curacin A (CU-A), a cytotoxic metabolite of a marine cyanobacteria Lyngbya majuscula, and its related compounds. Interactions of these compounds with TN were studied and structure-activity relationships of these two classes of compounds were discussed.

Bibenzyls↗
PubMed2005

Improved fingerprint identification with supervised filtering enhancement.

An important step in the fingerprint identification system is the reliable extraction of distinct features from fingerprint images. Identification performance is directly related to the enhancement of fingerprint images during or after the enrollment phase. Among the various enhancement algorithms, artificial-intelligence-based feature-extraction techniques are attractive owing to their adaptive learning properties. We present a new supervised filtering technique that is based on a dynamic neural-network approach to develop a robust fingerprint enhancement algorithm. For pattern matching, a joint transform correlation (JTC) algorithm has been incorporated that offers high processing speed for real-time applications. Because the fringe-adjusted JTC algorithm has been found to yield a significantly better correlation output compared with alternate JTCs, we used this algorithm for the identification process. Test results are presented to verify the effectiveness of the proposed algorithm.

Algorithms↗
PubMed2007

Identification of phosphorylated proteins.

Reversible protein phosphorylation is crucially involved in all aspects of plant cell physiology. The highly challenging task of revealing and characterizing the dynamic protein phosphorylation networks in plants has only recently begun to become feasible, owing to application of dedicated proteomics and mass spectrometry techniques. The experimental methodology that identified most of the presently known proteins phosphorylated in vivo is based on protein cleavage with trypsin, following chromatographic enrichment of phosphorylated peptides and mass spectrometric fragmentation and sequencing of these phosphopeptides. This procedure is most efficient when it is limited to the tryptic digestion of proteins in distinct isolated fractions or compartments of plant cells. Immobilized metal affinity chromatography (IMAC) is most useful for phosphopeptide enrichment after methylation of the peptides in the complex protein digests. The following tandem mass spectrometry of the isolated phosphopeptides results in both identification of phosphorylated proteins and mapping of the in vivo phosphorylation sites. The relative quantitation of the extent of phosphorylation at individual protein modification sites may be accomplished by either stable isotope labeling technique or dedicated liquid chromatography-mass spectrometry measurements.

Cell Fractionation↗
PubMed2005

Mesocortical dopamine neurons operate in distinct temporal domains using multimodal signaling.

In vivo extracellular recording studies have traditionally shown that dopamine (DA) transiently inhibits prefrontal cortex (PFC) neurons, yet recent biophysical measurements in vitro indicate that DA enhances the evoked excitability of PFC neurons for prolonged periods. Moreover, although DA neurons apparently encode stimulus salience by transient alterations in firing, the temporal properties of the PFC DA signal associated with various behaviors is often extraordinarily prolonged. The present study used in vivo electrophysiological and electrochemical measures to show that the mesocortical system produces a fast non-DA-mediated postsynaptic response in the PFC that appears to be initiated by glutamate. In contrast, short burst stimulation of mesocortical DA neurons that produced transient (<4 s) DA release in the PFC caused a simultaneous reduction in spontaneous firing (consistent with extracellular in vivo recordings) and a form of DA-induced potentiation in which evoked firing was increased for tens of minutes (consistent with in vitro measurements). We suggest that the mesocortical system might transmit fast signals about reward or salience via corelease of glutamate, whereas the simultaneous prolonged DA-mediated modulation of firing biases the long-term processing dynamics of PFC networks.

Action Potentials↗
PubMed2005

Changes of internal state are expressed in coherent shifts of neuromuscular activity in Aplysia feeding behavior.

The multitasking central pattern generator (CPG) that drives consummatory feeding behaviors of Aplysia can produce ingestive, egestive, and intermediate motor programs. External stimuli trigger the programs but, remarkably, do not directly specify which type of program is produced. Rather, recent work has proposed, the type of program is determined by the internal network state of the CPG that has developed in response to the previous history of the stimulation. Here we have tested a key prediction of this network-state hypothesis. If the network state has a real existence and governs real functional behavior, changes in the state should be seen as coherent, coordinated changes along many dimensions of interneuron and motor neuron activity, muscle contraction, and ultimately movement, that underlie functional behavior. In reduced neuromuscular preparations, we elicited repetitive motor programs by continued stimulation of the esophageal nerve while recording the firing of motor neurons B8, B15, B16, B4/5, and B48, and contractions of the accessory radula closer and I7-I10 muscles that respectively close and open the animal's food-grasping organ, the radula. Using sonomicrometric techniques, we similarly recorded the movement of the radula in the complete buccal mass. Successive esophageal nerve programs indeed exhibited clear progressive changes in motor neuron firing, muscle contractions, and the phasing of radula movements within each cycle, from an initially intermediate or even ingestive character to a strongly egestive character. We conclude that the Aplysia feeding CPG really has a coherent internal network state whose dynamics are likely to be reflected in the real behavior of the animal.

Animals↗
PubMed2004

[The pathways of the vaccine in nineteenth and twentieth-century Portuguese India].

The article explores the vicissitudes of the nineteenth-century introduction of the smallpox vaccine into Portugal's Indian colony of Goa. The choice to use smallpox vaccines instead of inoculation evinces local social dynamics and power networks that cannot be reduced to a colonizer-colonized duality but that interact with scientific issues and techniques imported from Europe and adopted locally. Official documents issued by health- service physicians and other administrative authorities reveal the actors involved in the fate of the smallpox vaccine, raising hypotheses about the motives (involving social, economic, technical, and political factors) that shaped their discourse and actions.

Colonialism↗