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At least 523 records · Page 29Linked to original sources

A Bayesian network driven approach to model the transcriptional response to nitric oxide in Saccharomyces cerevisiae.

The transcriptional response to exogenously supplied nitric oxide in Saccharomyces cerevisiae was modeled using an integrated framework of Bayesian network learning and experimental feedback. A Bayesian network learning algorithm was used to generate network models of transcriptional output, followed by model verification and revision through experimentation. Using this framework, we generated a network model of the yeast transcriptional response to nitric oxide and a panel of other environmental signals. We discovered two environmental triggers, the diauxic shift and glucose repression, that affected the observed transcriptional profile. The computational method predicted the transcriptional control of yeast flavohemoglobin YHB1 by glucose repression, which was subsequently experimentally verified. A freely available software application, ExpressionNet, was developed to derive Bayesian network models from a combination of gene expression profile clusters, genetic information and experimental conditions.

Algorithms↗

Multicellular simulation predicts microvascular patterning and in silico tissue assembly.

Remodeling of microvascular networks in mammals is critical for physiological adaptations and therapeutic revascularization. Cellular behaviors such as proliferation, differentiation, and migration are coordinated in these remodeling events via combinations of biochemical and biomechanical signals. We developed a cellular automata (CA) computational simulation that integrates epigenetic stimuli, molecular signals, and cellular behaviors to predict microvascular network patterning events. Over 50 rules obtained from published experimental data govern independent behaviors (including proliferation, differentiation, and migration) of thousands of interacting cells and diffusible growth factors in their tissue environment. From initial network patterns of in vivo blood vessel networks, the model predicts emergent patterning responses to two stimuli: 1) network-wide changes in hemodynamic mechanical stresses, and 2) exogenous focal delivery of an angiogenic growth factor. The CA model predicts comparable increases in vascular density (370+/-29 mm/mm3) 14 days after treatment with exogenous growth factor to that in vivo (480+/-41 mm/mm3) and approximately a twofold increase in contractile vessel lengths 5-10 days after 10% increase in circumferential wall strain, consistent with in vivo results. The CA simulation was thus able to identify a functional patterning module capable of quantitatively predicting vessel network remodeling in response to two important epigenetic stimuli.

Cell Differentiation↗

Learning procedure in a neural control model for the urinary bladder.

A continuous neural network coupled to a dynamical model of the urinary bladder is defined. The neural network is trained to control the bladder model to track a prescribed volume fluctuation, by adjusting weights and time constants. The gradients of the error in the output neurons of the neural network are unknown. Therefore, the learning procedure discussed here minimizes the error functional without using gradient descent.

Animals↗

Signaling pathways from the chloroplast to the nucleus.

Genetic and physiological studies have to-date revealed evidence for five signaling pathways by which the chloroplast exerts retrograde control over nuclear genes. One of these pathways is dependent on product(s) of plastid protein synthesis, for another the signal is singlet oxygen, a third employs chloroplast-generated hydrogen peroxide, a fourth is controlled by the redox state of the photosynthetic electron transport chain, and a fifth involves intermediates and possibly proteins of tetrapyrrole biosynthesis. These five pathways may be part of a complex signaling network that links the functional and physiological state of the chloroplast to the nucleus. Mutants defective in various steps of photosynthesis reveal a surprising diversity in nuclear responses suggesting the existence of a complex signaling network.

Cell Nucleus↗

Optic flow representation in the optic lobes of Diptera: modeling innervation matrices onto collators and their evolutionary implications.

A network model of optic flow processing, based on physiological and anatomical features of motion-processing neurons, is used to investigate the role of small-field motion detectors emulating T5 cells in producing optic flow selective properties in wide-field collator neurons. The imposition of different connectivities can mimic variations observed in comparative studies of lobula plate architecture across the Diptera. The results identify two features that are crucial for optic flow selectivity: the broadness of the spatial patterns of synaptic connections from motion detectors to collators, and the relative contributions of excitatory and inhibitory synaptic outputs. If these two aspects of the innervation matrix are balanced appropriately, the network's sensitivity to perturbations in physiological properties of the small-field motion detectors is dramatically reduced, suggesting that sensory systems can evolve robust mechanisms that do not rely upon precise control of network parameters. These results also suggest that alternative lobula plate architectures observed in insects are consistent in allowing optic flow selective properties in wide-field neurons. The implications for the evolution of optic flow selective neurons are discussed.

Adaptation, Physiological↗

A flexible algorithm for construction of 3-D vessel networks for use in thermal modeling.

A new algorithm for the construction of artificial blood vessel networks is presented. The algorithm produces three-dimensional (3-D) geometrical representations of both arterial and venous networks. The key ingredient of the algorithm is a 3-D potential function defined in the tissue volume. This potential function controls the paths by which points are connected to existing vessels, thereby producing new vessel segments. The potential function has no physiological interpretation, but, by adjustment of parameters governing the potential, it is possible to produce networks that have physiologically meaningful geometrical properties. If desired, the veins can be generated counter current to the arteries. Furthermore, the potential function allows fashioning of the networks to the presence of bone or air cavities. The resulting networks can be used for thermal simulations of hyperthermia treatment.

Algorithms↗

The molecular mechanisms of cardiovascular and renal regulation by endothelin peptides.

In summary, we have seen that endothelins are potent cardiovascular and renal regulatory peptides. Cardiovascular regulation by endothelin requires complex spatial and temporal regulation of endothelin gene expression and the coordinated interplay of numerous signaling pathways. Although the precise physiologic role for endothelin peptides in the cardiovascular and renal systems remains uncertain, two general models can be proposed, as follows. (1) Endothelin appears to act as an autocrine or paracrine hormone involved in long-term (hours to days) regulation of cardiovascular and renal function in normal physiology. Similar regulation occurs in response to other cardiovascular hormones such as angiotensin II, atrial natriuretic peptides, and catecholamines. In this respect it is noteworthy that endothelin also interacts with other hormonal systems that affect cardiovascular status, such as renin-aldosterone and atrial natriuretic peptide (see references 9, 161, 162, and 213-217). (2) Endothelin might also function as a proinflammatory peptide, being locally produced at sites of vascular damage and injury. The fact that endothelin secretion is stimulated by cytokines, growth factors, and transforming growth factor beta is consistent with this role. In addition, the mitogenic actions of endothelin could contribute to vascular remodeling in the inflammatory response. A similar, defensive role has been proposed for other regulatory peptides. Endothelin has also been implicated in the pathogenesis of numerous disorders such as hypertension (see references 28, 56, 168, 184, and 224 through 226), cerebral and myocardial vasospasm (see references 180, 223, and 227 through 233), acute renal failure, and cyclosporine nephrotoxicity. It is clear that the development of specific ECE inhibitors and endothelin receptor antagonists will enable definitive experiments addressing the role of endothelin in normal physiology and the putative role of endothelin in the development of hypertension and other cardiovascular disorders. Further identification and biochemical analysis of signaling networks evoked by endothelin, in conjunction with physiologic studies, should provide a detailed understanding of the complex biologic events regulated by endothelin peptides.

Amino Acid Sequence↗

The hippocampal CA3 network: an in vivo intracellular labeling study.

The intrahippocampal distribution of axon collaterals of individual CA3 pyramidal cells was investigated in the rat. Pyramidal cells in the CA3 region of the hippocampus were physiologically characterized and filled with biocytin in anesthetized animals. Their axonal trees were reconstructed with the aid of a drawing tube. Single CA3 pyramidal cells arborized most extensively in the CA1 region, covering approximately two-thirds of the longitudinal axis of the hippocampus. The total length of axon collaterals in the CA3 region was less than in CA1 and the axon branches tended to cluster in narrow bands (200-800 microns), usually several hundred microns anterior or posterior to the cell body. The majority of the recurrent collaterals of a given neuron remained in the same subfield (CA3a, b, or c) as the parent cell. CA3a neurons innervated predominantly the basal dendrites, whereas neurons located proximal to the hilus (CA3c) terminated predominantly on the apical dendrites of both CA1 and CA3 cells. Two cells, with horizontal dendrites and numerous thorny excrescences at the CA3c-hilus transitional zone, were also labeled and projected to both CA3 and CA1 regions. All CA3 neurons projected some collaterals to the hilar region. Proximal (CA3c) neurons had numerous collaterals in the hilus proper. One CA3c pyramidal cell in the dorsal hippocampus sent an axon collaterals to the inner third of the molecular layer. CA3c pyramidal cells in the ventral hippocampus had extensive projections to the inner third of the dentate molecular layer, as well as numerous collaterals in the hilus, CA3, and CA1 areas, and several axon collaterals penetrated the subiculum. The total projected axon length of a single neuron ranged from 150 to 300 mm. On the basis of the projected axon length and bouton density (mean interbouton distance: 4.7 microns), we estimate that a single CA3 pyramidal cell can make synapses with 30,000-60,000 neurons in the ipsilateral hippocampus. The concentrated distribution of the axon collaterals ("patches") indicates that subpopulations of neurons may receive disproportionately denser innervation, whereas innervation in the rest of the target zones is rather sparse. These observations offer new insights into the physiological organization of the CA3 pyramidal cell network.

Animals↗

Recognition of patient anaesthetic levels: neural network systems, principal components analysis, and canonical discriminant variates.

The goal of this study was to examine the ability of Neural Networks to recognise the levels of anaesthetic state of a patient. Data obtained under different levels of anaesthesia have been modelled for the purpose. It is shown that inferential parameters can be used to recognise the levels of anaesthesia. In addition to demonstrating the ability of neural networks for classification we were interested in understanding the classification strategy discovered by the neural networks. Multivariate data analysis techniques, namely Principal Components Analysis and Canonical Discriminant Variates, were applied to analyse the resultant networks.

Anesthesia↗

Orthogonal arrangement of rhythm-generating microcircuits in the hippocampus.

As a structure involved in learning and memory, the hippocampus functions as a network. The functional differentiation along the longitudinal axis of the hippocampus is poorly demarcated in comparison with the transverse axis. Using patch clamp recordings in conjunction with post hoc anatomy, we have examined the pattern of connectivity and the functional differentiation along the long axis of the hippocampus. Here, we provide anatomical and physiological evidence that the prominent rhythmic network activities of the hippocampus, the behavior-specific gamma and theta oscillations, are seen predominantly along the transverse and longitudinal axes respectively. This orthogonal relationship is the result of the axonal field trajectories and the consequential interaction of the principal cells and major interneuron subtypes involved in generating each rhythm. Thus, the axonal arborization patterns of hippocampal inhibitory cells may represent a structural framework for the spatiotemporal distribution of activity observed within the hippocampus.

Animals↗

Performances of hill-type and neural network muscle models-toward a myosignal-based exoskeleton.

Muscle models are the essential components of any musculoskeletal simulation. In addition, muscle models which are incorporated in neural-based prosthetic and orthotic devices may significantly improve their performance. The aim of the study was to compare the performances of two types of muscle models in terms of predicting the moments developed at the human elbow joint complex based on joint kinematics and neuromuscular activity. The performance evaluation of the muscle models was required to implement them in a powered myosignal-driven exoskeleton (orthotic device). The experimental setup included a passive exoskeleton capable of measuring the joint kinematics and dynamics in addition to the muscle myosignal activity (EMG). Two types of models were developed and analyzed: (i) a Hill-based model and (ii) a neural network. The task, which was selected for evaluating the muscle models performance, was the flexion-extension movement of the forearm with a hand-held weight. For this task the muscle model inputs were the normalized neural activation levels of the four main flexor-extensor muscles of the elbow joint, and the elbow joint angle and angular velocity. Using this inputs, the muscle model predicted the moment applied on the elbow joint during the movement. Results indicated a good performance of the Hill model, although the neural network predictions appeared to be superior. Relative advantages and shortcomings of both approaches were presented and discussed.

Arm↗

Dentate EEG spikes and associated interneuronal population bursts in the hippocampal hilar region of the rat.

1. This paper describes two novel population patterns in the dentate gyrus of the awake rat, termed type 1 and type 2 dentate spikes (DS1, DS2). Their cellular generation and spatial distribution were examined by simultaneous recording of field potentials and unit activity using multiple-site silicon probes and wire electrode arrays. 2. Dentate spikes were large amplitude (2-4 mV), short duration (< 30 ms) field potentials that occurred sparsely during behavioral immobility and slow-wave sleep. Current-source density analysis revealed large sinks in the outer (DS1) and middle (DS2) thirds of the dentate molecular layer, respectively. DS1 and DS2 had similar longitudinal, lateral, and interhemispheric synchrony. 3. Dentate spikes invariably were coupled to synchronous population bursts of putative hilar interneurons. CA3 pyramidal cells, on the other hand were suppressed during dentate spikes. 4. After bilateral removal of the entorhinal cortex, dentate spikes disappeared, whereas sharp wave-associated bursts, reflecting synchronous discharge of the CA3-CA1 network, increased several fold. 5. These physiological characteristics of the dentate spikes suggest that they are triggered by a population burst of layer II stellate cells of the lateral (DS1) and medial (DS2) entorhinal cortex. 6. We suggest that dentate spike-associated synchronized bursts of hilar-region interneurons provide a suppressive effect on the excitability of the CA3-CA1 network in the intact brain.

Animals↗

Root growth maintenance during water deficits: physiology to functional genomics.

Progress in understanding the network of mechanisms involved in maize primary root growth maintenance under water deficits is reviewed. These include the adjustment of growth zone dimensions, turgor maintenance by osmotic adjustment, and enhanced cell wall loosening. The role of the hormone abscisic acid (ABA) in maintaining root growth under water deficits is also addressed. The research has taken advantage of kinematic analysis, i.e. characterization of spatial and temporal patterns of cell expansion within the root growth zone. This approach revealed different growth responses to water deficits and ABA deficiency in distinct regions of the root tip. In the apical 3 mm region, elongation is maintained at well-watered rates under severe water deficit, although only in ABA-sufficient roots, whereas the region from 3-7 mm from the apex exhibits maximum elongation in well-watered roots, but progressive inhibition of elongation in roots under water deficit. This knowledge has greatly facilitated discovery of the mechanisms involved in regulating the responses. The spatial resolution with which this system has been characterized and the physiological knowledge gained to date provide a unique and powerful underpinning for functional genomics studies. Characterization of water deficit-induced changes in transcript populations and cell wall protein profiles within the growth zone of the maize primary root is in progress. Initial results from EST and unigene analyses in the tips of well-watered and water-stressed roots highlight the strength of the kinematic approach to transcript profiling.

Adaptation, Physiological↗

Inflammatory mediators regulate interleukin-8 production by cultured gestational tissues: evidence for a cytokine network at the chorio-decidual interface.

The physiology of parturition, and the pathophysiology of preterm labor, is incompletely understood. Infection of gestational tissues may account for a significant proportion of women who experience preterm labor. Interleukin-8 (IL-8), or neutrophil-activating protein (NAP-1), is a potent chemotactic and activating factor for neutrophils and has been implicated in the pathogenesis of inflammatory injury to skin and lung, but has yet to be described in gestational tissues. Cultured chorion and decidual cells obtained from normal human pregnancies were used to evaluate whether these tissues produce IL-8 basally and in response to inflammatory cytokines. As measured by specific IL-8 RIA, chorion and decidual cells produce IL-8 constitutively and in response to IL-1 beta and tumor necrosis factor. Cotreatment of chorion cells or decidual cells with IL-1 beta and actinomycin D or cycloheximide abrogated IL-8 production. Northern blot analysis confirmed that IL-1 beta stimulation of chorion and decidual cells resulted in increased IL-8 messenger RNA expression. Our data support the concept that a complex cytokine network between maternal and fetal gestational tissues exists, and that activation of inflammatory cytokine production in these tissues, including IL-8, likely contributes to the pathophysiology of infection-induced preterm labor.

Blotting, Northern↗

Chronic alpha 1-adrenergic blockade stimulates terminal and arcade arteriolar development.

The arteriolar network undergoes structural adaptation in several physiological and pathological conditions, including exercise, maturation, hypertension, and reduced tissue perfusion due to arterial ligation. Although many physical and biochemical stimuli for arteriolar adaptation have been proposed, the individual contributions of these specific stimuli have yet to be elucidated. We tested the hypothesis that hemodynamic stress is an important determinant of growth and remodeling in the arteriolar network. An immunofluorescence, dual-labeling technique for the smooth muscle (SM) contractile proteins SM alpha-actin and SM myosin heavy chain (MHC) was used to assess terminal and arcade arteriolar (AA) remodeling in the rat gracilis muscle arteriolar network in response to chronic vasodilation, a stimulus that elevates circumferential wall stress levels in the arterioles and capillaries. SM alpha-actin, a marker of SM from the earliest stages of differentiation, was used to delineate the terminal and AAs. SM-MHC, a marker of SM in later stages of differentiation, was used to assess the relative maturity state of SM in terminal arteriolar endings. Mean percentage of SM-MHC negative terminal arteriolar endings per muscle, a measure of terminal arteriolar development, increased from 37.6 to 56.0% after 1 wk of prazosin treatment and from 36.3 to 57.6% after 2 wk of treatment. Mean number of AA segments with diameters < 15 microns increased more than threefold from 1.25 to 5.25 after 2 wk, consistent with the formation of new AA segments by the anastomoses of small-diameter terminal arterioles. Because arteriolar remodeling proceeded in a network pattern that has been shown to be consistent with a circumferential wall stress-growth rule and inconsistent with a wall shear stress-growth rule, the experimental results suggest that circumferential wall stress is a stimulus for arteriolar network remodeling.

Actins↗

The excitatory neuronal network of rat layer 4 barrel cortex.

Sensory whiskers are mapped to rodent layer 4 somatosensory cortex as discrete units termed barrels, which can be visualized at high resolution in living brain slices. Both anatomical and physiological properties of the layer 4 neuronal network can thus be investigated in the context of the functional boundaries of this sensory map. Large-scale confinement of neuronal arbors to single barrels was suggested by restricted lateral diffusion of DiI across septa between barrels. Morphological analysis of dendritic and axonal arborizations of individual excitatory neurons showed that neuronal processes remain within the barrel of origin through polarization toward the center of the barrel. Functionally, the large-scale properties of the neuronal network were investigated through mapping the spatial extent of field EPSPs, which were found to attenuate at barrel borders. This ensemble property of a layer 4 barrel was further investigated by analyzing the connectivity of pairs of excitatory neurons with respect to the locations of the somata. Approximately one-third of the excitatory neurons within the same barrel were synaptically coupled. At the septum between adjacent barrels the connectivity dropped rapidly, and very few connections were found between neurons located in adjacent barrels. Each layer 4 barrel is thus composed of an excitatory neuronal network, which to a first order approximation, acts independently of its neighbors.

Animals↗

A computer-assisted personalized approach in an undergraduate plant physiology class

We used Computer-Assisted Personalized Approach (CAPA), a networked teaching and learning tool that generates computer individualized homework problem sets, in our large-enrollment introductory plant physiology course. We saw significant improvement in student examination performance with regular homework assignments, with CAPA being an effective and efficient substitute for hand-graded homework. Using CAPA, each student received a printed set of similar but individualized problems of a conceptual (qualitative) and/or quantitative nature with quality graphics. Because each set of problems is unique, students were encouraged to work together to clarify concepts but were required to do their own work for credit. Students could enter answers multiple times without penalty, and they were able to obtain immediate feedback and hints until the due date. These features increased student time on task, allowing higher course standards and student achievement in a diverse student population. CAPA handles routine tasks such as grading, recording, summarizing, and posting grades. In anonymous surveys, students indicated an overwhelming preference for homework in CAPA format, citing several features such as immediate feedback, multiple tries, and on-line accessibility as reasons for their preference. We wrote and used more than 170 problems on 17 topics in introductory plant physiology, cataloging them in a computer library for general access. Representative problems are compared and discussed.

Journal Article↗

Activity-based sleep-wake identification in infants.

Actigraphy offers one of the best-known alternatives to polysomnography for sleep-wake identification. The advantages of actigraphy include high accuracy, simplicity of use and low intrusiveness. These features allow the use of actigraphy for determining sleep-wake states in such highly sensitive groups as infants. This study utilizes a motion sensor (accelerometer) for a dual purpose: to determine an infant's position in the crib and to identify sleep-wake states. The accelerometer was positioned over the sacral region on the infant's diaper, unlike commonly used attachment to an ankle. Opposed to broadly used discriminant analysis, this study utilized logistic regression and neural networks as predictors. The accuracy of predicted sleep-wake states was established in comparison to the sleep-wake states recorded by technicians in a polysomnograph study. Both statistical and neural predictors of this study provide an accuracy of approximately 77-92% which is comparable to similar studies achieving prediction rates of 85-95%, thus validating the suggested methodology. The results support the use of body motion as a simple and reliable method for determining sleep-wake states in infants. Nonlinear mapping capabilities of the neural network benefit the accuracy of sleep-wake state identification. Utilization of the accelerometer for the dual purpose allows us to minimize intrusiveness of home infant monitors.

Female↗