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At least 397 records · Page 22Linked to original sources

Quantification of acute neurotoxic effects of trimethyltin using neuronal networks cultured on microelectrode arrays.

We used spontaneously active monolayer networks in vitro, cultured on thin film microelectrode arrays as experimental platforms for the determination of trimethyltin chloride (TMT) toxicity. Two different tissues of the mouse CNS (spinal cord and auditory cortex) exhibited characteristic and dose-dependent changes of their electrophysiological activity patterns after treatment with TMT, a standard neurotoxicant. Spinal cord networks began to respond to TMT at 1-2 microM and shut off activity at 4-7 microM. Auditory cortex cultures started to respond at 2-3 microM and shut off activity at 7-8 microM. Repeated applications of low doses of TMT always influenced the electrical activity in a reversible manner, with no overt cytotoxic effects. The inhibitory concentrations for a 50% reduction of activity (IC ) were 1.5+/-0.5 microM (spinal cord) and 4.3+/-0.9 microM (auditory cortex) indicating a relatively low interculture variability within one tissue type. The non-overlapping IC50 range for cortical and spinal cord cultures may suggest tissue specificity for network responses to TMT. Shut-off concentrations were found to be within a factor of two of the lethal concentrations reported for mice in vivo. Action potential amplitude and shape did not change even when complete cessation of activity was approached, suggesting that acute TMT applications did not affect neuronal metabolism that would lead to a lowering of membrane potentials. Our results suggest that spontaneously active monolayer networks in vitro are suitable for toxicological investigations since network activity can be influenced in a dose-dependent manner. These properties allow the development of neurotoxicity biosensors based on physiological responses of spontaneously active networks.

Action Potentials↗

Age matters: collagen birefringence of superficial articular cartilage is increased in young guinea-pigs but decreased in older animals after identical physiological type of joint loading.

OBJECTIVE: To compare responses of the collagen network and glycosaminoglycans (GAGs) of articular cartilage to physiological type of joint loading in young growing and adult mature guinea-pigs. DESIGN: 10- and 44-week-old guinea-pigs were accustomed to treadmill running for 3 weeks. Thereafter the animals ran 2500 m/day, 5 days a week, for 15 weeks. Articular cartilage specimens from knee joints were collected at 28 and 62 weeks. Osteoarthritis (OA) prevalence and severity was evaluated by aid of light microscopy. The degree of collagen fibril network organization and content was analyzed with quantitative polarized light microscopy. The local concentration of GAGs was determined from cartilage sections with digital densitometry after safranin-O staining. RESULTS: In the young guinea-pigs, running increased up to 24% the optical retardation of polarized light by collagen in the superficial articular cartilage of femur, indicating either a higher degree of fibril assembly and organization or increased amount of collagen, or both. In contrast, in the adult mature animals the optical retardation decreased almost 50% after joint loading (P< 0.01-0.001). Running did not increase cartilage fibrillation. Significant changes in GAG content of cartilage were not found either in the young or adult mature runners. CONCLUSIONS: Increased birefringence of the superficial articular cartilage after joint loading in young guinea-pigs can be interpreted to be a sign of improved and decreased birefringence in older animals a sign of worsened property of the collagen network. It can be suggested therefore that joint loading strengthened the collagen network in the young runners. It can be hypothesized further that with time the inferior property of the collagen network predisposes the older runners to earlier OA than in controls.

Aging↗

A generalized higher-order correlation analysis framework for multi-omics network inference.

Multiple -omics (genomics, proteomics, etc.) profiles are commonly generated to gain insight into a disease or physiological system. Constructing multi-omics networks with respect to the trait(s) of interest provides an opportunity to understand relationships between molecular features but integration is challenging due to multiple data sets with high dimensionality. One approach is to use canonical correlation to integrate one or two omics types and a single trait of interest. However, these types of methods may be limited due to (1) not accounting for higher-order correlations existing among features, (2) computational inefficiency when extending to more than two omics data when using a penalty term-based sparsity method, and (3) lack of flexibility for focusing on specific correlations (e.g., omics-to-phenotype correlation versus omics-to-omics correlations). In this work, we have developed a novel multi-omics network analysis pipeline called Sparse Generalized Tensor Canonical Correlation Analysis Network Inference (SGTCCA-Net) that can effectively overcome these limitations. We also introduce an implementation to improve the summarization of networks for downstream analyses. Simulation and real-data experiments demonstrate the effectiveness of our novel method for inferring omics networks and features of interest.

Genomics↗

Information in full and reduced data sets of electrical impedance spectra from various skin conditions, compared using a holographic neural network.

Information relating to patho-physiological events in living tissues, including skin, should be found in the beta-dispersion frequency range of the electrical impedance. For intact skin, the alpha-dispersion is strongly influenced by the condition of the stratum corneum, particularly its hydration. For intact skin, these dispersions are not well separated: in a Nyquist plot, most of the relatively small beta-dispersion will be hidden behind the upper-frequency end of the alpha-dispersion arc. In the study, information obtained with a set of four indices, claimed to extract most of the information in the pertinent frequency interval, is compared with the full information measured at 31 frequencies, between 1 kHz and 1 MHz, for irritant and allergic contact reactions and nodular basal cell carcinomas, using a holographic neural network that appears to be useful for model-independent evaluation of the consequences of data-reduction procedures. Cole parameters should be avoided in the beta-range for intact skin. The indices are well supported, as long as differences from a reference site are used, and it seems that they can serve as the basis for differential diagnostics even as absolute values, although more information may be extracted from the complete spectrum.

Diagnosis, Differential↗

Understanding regulatory networks and engineering for enhanced drought tolerance in plants.

Drought stress is one of the major limitations to crop productivity. To develop crop plants with enhanced tolerance of drought stress, a basic understanding of physiological, biochemical and gene regulatory networks is essential. Various functional genomics tools have helped to advance our understanding of stress signal perception and transduction, and of the associated molecular regulatory network. These tools have revealed several stress-inducible genes and various transcription factors that regulate the drought-stress-inducible systems. Translational genomics of these candidate genes using model plants provided encouraging results, but the field testing of transgenic crop plants for better performance and yield is still minimal. Better understanding of the specific roles of various metabolites in crop stress tolerance will give rise to a strategy for the metabolic engineering of crop tolerance of drought.

Adaptation, Physiological↗

The EGF receptor as central transducer of heterologous signalling systems.

The cross-talk between heterologous signalling systems of the cell represents a new dimension of complexity in the molecular communication network that governs a great variety of physiological processes. In pathophysiologically transformed cells, key elements of this network could offer unique opportunities for pharmacological intervention. In this article, the current state of knowledge regarding the role of epidermal growth factor (EGF) in such a network is described and the recent advances made in the elucidation of the mechanism underlying EGF receptor transactivation are discussed.

Animals↗

Steroid hormones and excitability in the mammalian brain.

Adrenocortical and gonadal steroid hormones can pass the blood-brain barrier and bind to intracellular receptors in the brain. In addition to steroid hormones binding to intracellular steroid receptors, metabolites of these steroids and steroid hormones produced in the brain (neurosteroids) are thought to bind to membrane recognition sites. Actions mediated by the intracellular receptors are generally delayed in onset and are of prolonged duration, whereas the hormones binding to membrane recognition sites induce fast effects. Both fast and delayed actions by steroid hormones potentially alter the electrical properties of neuronal membranes and thus the firing patterns of neurons carrying receptors for the hormones. We here review the fast and delayed actions by steroid hormones on single cell electrical properties in the mammalian nervous system. In general, fast effects by corticosteroids-presumably mediated by membrane receptors-induce inhibitory effects on cellular firing, although regional differences seem to exist. Delayed effects by corticosteroid hormones via mineralocorticoid receptors serve to maintain or enhance fast transmission in the brain, while modulatory inputs are suppressed. By contrast, corticosteroids acting through glucocorticoid receptors suppress transmission carried by amino acids, particularly when the activity is elevated in comparison to resting level; modulatory inputs are enhanced. Prolonged activation of glucocorticoid receptors can implicate the integrity of neuronal circuits by allowing considerable influx of calcium ions during depolarization. Of the gonadal hormones, estradiol mainly exerts excitatory actions, in both a rapid and a delayed mode. Progesterone on the other hand is predominantly inhibitory, usually with a short delay in onset. The effect of androgens on neuronal excitability has not yet been studied in great detail. Finally, neurosteroids and A-ring reduced steroids in general induce rapid effects on firing patterns, probably by acting on ligand gated ion channels. The diverse actions of steroid hormones on single cell activity have consequences for the excitability in local circuits in which these cells participate. This is illustrated in this review for two processes that depend on circuit rather than single cell function, i.e., long term potentiation and epilepsy. The diverging character of steroid hormones with regard to the time frame, space, and nature of their effects is also reflected in the functional processes that are linked to the activity of the networks responding to steroids. In this way steroid hormones add an essentially new aspect to the regulation of functional processes in the brain, during physiological conditions but also when networks are implicated during diseases and disorders. Future research on steroid modulation of cellular excitability will gain considerably from attempts to either link the changed excitability to the underlying molecular events or study the effects on cellular activity in close connection with behavioral functions.

Animals↗

CRE-mediated gene transcription in neocortical neuronal plasticity during the developmental critical period.

Neuronal activity-dependent processes are believed to mediate the formation of synaptic connections during neocortical development, but the underlying intracellular mechanisms are not known. In the visual system, altering the pattern of visually driven neuronal activity by monocular deprivation induces cortical synaptic rearrangement during a postnatal developmental window, the critical period. Here, using transgenic mice carrying a CRE-lacZ reporter, we demonstrate that a calcium- and cAMP-regulated signaling pathway is activated following monocular deprivation. We find that monocular deprivation leads to an induction of CRE-mediated lacZ expression in the visual cortex preceding the onset of physiologic plasticity, and this induction is dramatically downregulated following the end of the critical period. These results suggest that CRE-dependent coordinate regulation of a network of genes may control physiologic plasticity during postnatal neocortical development.

Aging↗

Neuronal plasticity of interrelated cerebellar and cortical networks.

The comprehension of the cerebellar physiology is rapidly changing in particular because of the demonstration of the cerebellar importance on cognition. In the present paper, recent data on cerebro cerebellar interactions is reviewed, particularly focusing on cerebellar influences over the neurophysiology of primary motor and primary sensory cortices. The cerebellar role in implicit learning and in sensory data processing is analysed and discussed. It is proposed that the cerebellum could control cortical plastic changes by modulating cortical excitability in a discrete topographic manner and that this mechanism could induce the coupling between significant sensory inputs and definite motor outputs considered as the neurobiological substrate for implicit learning.

Afferent Pathways↗

Computerized detection of breast cancer with artificial intelligence and thermograms.

This paper shows the concurrent use of thermography and artificial neural networks (ANN) for the diagnosis of breast cancer, a disease that is growing in prominence in women all over the world. It has been reported that breast thermography itself could detect breast cancer up to 10 years earlier than the conventional golden methods such as mammography, in particular in the younger patient. However, the accuracy of thermography is dependent on many factors such as the symmetry of the breasts' temperature and temperature stability. A woman's body temperature is known to be stable in certain periods after menstruation and it was found that the accuracy of thermography in women whose thermal images are taken in a suitable period (5th - 12th and 21st day of menstruation) is higher (80%) than the total population of patients (73%). The stability of the body temperature will depend on physiological state. This paper examines the use of ANN to complement the infrared heat radiating from the surface of the body with other physiological data. Four backpropagation neural networks were developed and trained using the results from the Singapore General Hospital patients' physiological data and thermographs. Owing to the inaccuracies found in thermography and the low population size gathered for this project, the networks developed could only accurately diagnose about 61.54% of the breast cancer cases. Nevertheless, the basic neural network framework has been established and it has great potential for future development of an intelligent breast cancer diagnosis system. This would be especially useful to the teenagers and young adults who are unsuitable for mammography at a young age. An intelligent breast thermography-neural network will be able to give an accurate diagnosis of breast cancer and can make a positive impact on breast disease detection.

Adult↗

Speech recognition by an artificial neural network using findings on the afferent auditory system.

An artificial neural network which uses anatomical and physiological findings on the afferent pathway from the ear to the cortex is presented and the roles of the constituent functions in recognition of continuous speech are examined. The network deals with successive spectra of speech sounds by a cascade of several neural layers: lateral excitation layer (LEL), lateral inhibition layer (LIL), and a pile of feature detection layers (FDL's). These layers are shown to be effective for recognizing spoken words. Namely, first, LEL reduces the distortion of sound spectrum caused by the pitch of speech sounds. Next, LIL emphasizes the major energy peaks of sound spectrum, the formants. Last, FDL's detect syllables and words in successive formants, where two functions, time-delay and strong adaptation, play important roles: time-delay makes it possible to retain the pattern of formant changes for a period to detect spoken words successively; strong adaptation contributes to removing the time-warp of formant changes. Digital computer simulations show that the network detect isolated syllables, isolated words, and connected words in continuous speech, while reproducing the fundamental responses found in the auditory system such as ON, OFF, ON-OFF, and SUSTAINED patterns.

Acoustic Stimulation↗

Wiring diagrams of MAPK regulation by MEKK1, 2, and 3.

Mitogen-activated protein kinase (MAPK) pathways are activated by a plethora of stimuli. The literature is filled with papers describing the activation of different MAPKs by almost any stimulus or insult imaginable to cells. In this review, we use signal transduction wiring diagrams to illustrate putative upstream regulators for the MAPK kinase kinases, MEKK1, 2, and 3. Targeted gene disruption of MEKK1, 2, or 3 defined phenotypes for each MEKK associated with loss of specific MAPK regulation. Genetic analysis of MEKK function clearly defines specific components of the wiring diagram that require MEKK1, 2, or 3 for physiological responses. We propose that signal transduction network wiring diagrams are valuable tools for hypothesis building and filtering physiologically relevant phenotypic responses from less connected protein relations in the regulation of MAPK pathways.

Animals↗

Breast cancer lymphedema: pathophysiology and risk reduction guidelines.

PURPOSE/OBJECTIVES: To review the normal physiology of the blood capillary-interstitial-lymphatic vessel interface, describe the pathophysiology of lymphedema secondary to treatment for breast cancer, and summarize the physiologic bases of the current National Lymphedema Network (NLN) risk reduction guidelines. DATA SOURCES: Journal articles, anatomy and physiology textbooks, published research data, and Web sites. DATA SYNTHESIS: Lymphedema occurring after treatment for breast cancer significantly affects physical, psychological, and sexual functioning. About 28% of breast cancer survivors develop lymphedema. When arterial capillary filtration exceeds lymphatic transport capacity, lymphedema occurs. NLN risk reduction guidelines may decrease lymphedema risk. CONCLUSION: Lymphedema is chronic and disfiguring. Most NLN risk reduction guidelines, although not evidence-based, are based on sound physiologic principles. Evidence-based research of the effectiveness of NLN risk reduction guidelines is indicated. IMPLICATIONS FOR NURSING: Until evidence-based research contradicts NLN's risk reduction guidelines, nurses should inform patients with breast cancer about their risk for lymphedema, guidelines to reduce that risk, and the physiologic rationale for the guidelines.

Adult↗

Neural dynamics in cortical networks--precision of joint-spiking events.

Electrophysiological studies of cortical function on the basis of multiple single-neuron recordings reveal neuronal interactions which depend on stimulus context and behavioural events. These interactions exhibit dynamics on different time scales, with time constants down to the millisecond range. Mechanisms underlying such dynamic organization of the cortical network were investigated by experimental and theoretical approaches. We review some recent results from these studies, concentrating on the occurrence of precise joint-spiking events in cortical activity, both in physiological and in model neural networks. These findings suggest that a combinatorial neural code, based on rapid associations of groups of neurons co-ordinating their activity at the single spike level, is biologically feasible.

Action Potentials↗

Modeling mortality in the intensive care unit: comparing the performance of a back-propagation, associative-learning neural network with multivariate logistic regression.

The objective of this study was to compare and contrast two techniques of modeling mortality in a 30 bed multi-disciplinary ICU; neural networks and logistic regression. Fifteen physiological variables were recorded on day 3 for 422 consecutive patients whose duration of stay was over 72 hours. Two separate models were built using each technique. First, logistic and neural network models were constructed on the complete 422 patient dataset and discrimination was compared. Second, the database was randomly divided into a 284 patient developmental dataset and a 138 patient validation dataset. The developmental dataset was used to construct logistic and neural net models and the predictive power of these models was verified on the validation dataset. On the complete dataset, the neural network clearly outperformed the logistic model (sensitivity and specificity of 1 and .997 vs. .525 and .966, area under ROC curve .9993 vs. .9259), while both performed equally well on the validation dataset (area under ROC of .82). The excellent performance of the neural net on the complete dataset reveals that the problem is classifiable. Since our dataset only contained 40 mortality events, it is highly likely that the validation dataset was not representative of the developmental dataset, which led to a decreased predictive performance by both the neural net and the logistic regression models. Theoretically, given an extensive dataset, the neural network should be able to perform mortality prediction with a sensitivity and a specificity approaching 95%. Clinically, this would be an extremely important achievement.(ABSTRACT TRUNCATED AT 250 WORDS)

Hospital Mortality↗

Olfactory associative discrimination: a model for studying modifications of synaptic efficacy in neuronal networks supporting long-term memory.

This review summarizes research that correlates behavioral performance and cellular physiology leading to modifications in the neuronal networks supporting long-term memory in the mammalian brain. Rats were trained in an olfactory associative discrimination task in which natural odors were replaced by mimetic olfactory stimulations. Olfactory learning induced synaptic modifications that affected behavioral performance along the central olfactory pathways. Starting with an early increase in monosynaptic efficacy in the dentate gyrus on the first session, a polysynaptic modification appeared later on in this hippocampal network, when rats began to make associations between cues and rewards. Therefore, only when rats made consistent associations did a long-term potentiation in the synapses of the piriform cortex pyramidal neurons appear. These modifications may correspond to the long-term storage of the meaning of the cue-reward association in a specific cortical area. Based on these cumulative results, a hypothesis is proposed to account for how, when, and where synaptic modifications in neural networks are required to constitute long-term memory.

Animals↗

Detection of hemodynamic changes in clinical monitoring by time-delay neural networks.

Small changes that occur in a patient's physiology over long periods of time are difficult to detect, yet they can lead to catastrophic outcomes. Detecting such changes is even more difficult in intensive care unit (ICU) environments where clinicians are bombarded by a barrage of complex monitoring signals from various devices. Early detection accompanied by appropriate intervention can lead to improvement in patient care. Neural networks can be used as the basis for an intelligent early warning system. We developed time-delay neural networks (TDNN) for classifying and detecting hemodynamic changes. A matrix of physiological parameters were extracted from raw signals collected during cardiovascular experiments in mongrel dogs. These matrices represented several episodes of stable, decreasing, and increasing cardiac filling in normal, exerted, and heart failure conditions. The TDNN were trained with these matrices and subsequently tested to predict unseen cases. The TDNN perform remarkably not only in identifying all hemodynamic conditions, but also in quickly detecting their changes. On average, the networks were able to detect the hemodynamic changes in less than 1 s after the onset. Based on the results of this pilot investigation, the use of this form of TDNN to successfully predict hemodynamic conditions appears to be promising.

Animals↗

Persistent synchronized bursting activity in cortical tissues with low magnesium concentration: a modeling study.

We explore the mechanism of synchronized bursting activity with frequency of approximately 10 Hz that appears in cortical tissues at low extracellular magnesium concentration [Mg2+]o. We hypothesize that this activity is persistent, namely coexists with the quiescent state and depends on slow N-methyl-D-aspartate (NMDA) conductances. To explore this hypothesis, we construct and investigate a conductance-based model of excitatory cortical networks. Population bursting activity can persist for physiological values of the NMDA decay time constant (approximately 100 ms). Neurons are synchronized at the time scale of bursts but not of single spikes. A reduced model of a cell coupled to itself can encompass most of this highly synchronized network behavior and is analyzed using the fast-slow method. Synchronized bursts appear for intermediate values of the NMDA conductance g(NMDA) if NMDA conductances are not too fast. Regular spiking activity appears for larger g(NMDA). If the single cell is a conditional burster, persistent synchronized bursts become more robust. Weakly synchronized states appear for zero AMPA conductance g(AMPA). Enhancing g(AMPA) increases both synchrony and the number of spikes within bursts and decreases the bursting frequency. Too strong g(AMPA), however, prevents the activity because it enhances neuronal intrinsic adaptation. When [Mg2+]o is increased, higher g(NMDA) values are needed to maintain bursting activity. Bursting frequency decreases with [Mg2+]o, and the network is silent with physiological [Mg2+]o. Inhibition weakly decreases the bursting frequency if inhibitory cells receive enough NMDA-mediated excitation. This study explains the importance of conditional bursters in layer V in supporting epileptiform activity at low [Mg2+]o.

Action Potentials↗