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At least 739 records · Page 41Linked to original sources
PubMed2001

Neural models for auditory localization based on spectral cues.

In this paper we analyze several auditory localization neural models that are based on head related transfer functions (HRTFs). HRTFs represent the combined directional-spectral response of the pinnae head and torso. The role of HRTFs in such modeling has hitherto been underestimated despite substantial experimental evidence to its relevance in spatial hearing, especially in determining direction of high-frequency sound sources. In the first section we suggest a neural model that links the physiology of binaural processing to a neural network that extracts spectral ratios. These ratios correspond to HRTFs ratios and can provide auditory directional cues. Next, we compare several methods of matching HRTFs ratios using discriminative matching measure (DMM). We consider several solutions to the matching problem from a neural signal processing viewpoint. We compare correlation based approaches with DMM optimization approach and with a non-linear approach based on neural back-propagation algorithm. All three models can be implemented by neural networks. Finally, we include experimental results of simulations that are conducted using these methods. Experiments show that the back-propagation based neural network yields the best results in terms of DMM both for narrow-band and broad band excitation. The back-propagation neural network is also superior in matching noisy HRTF ratio vectors.

Animals↗
PubMedDate not supplied

Molecular mechanisms of transcriptional regulation by nuclear receptors. Perspectives for therapeutic implications.

Nuclear receptors are ligand-regulated transcription factors that evolved from an ancestral orphan receptor into a highly diverse family present throughout the entire animal kingdom. They encompass receptors for steroid and non-steroid hormones, vitamins and metabolic intermediates. These receptors signal through endocrine, paracrine, autocrine and intracrine networks to regulate multiple aspects of animal physiology, including homeostasis, development and reproduction. They exert genomic effects via direct binding as monomers, homo- or heterodimers on cognate DNA elements (hormone response elements). They also participate in signal transduction cross-talk to indirectly modulate other gene expression programmes. By coordinating expression of genetic programmes, nuclear receptors contribute to cell fate-determining processes, thereby shaping and sustaining the organism. All these actions result from one fundamental interaction: receptor binding of a cognate ligand, which induces a major allosteric change in the ligand-binding domain. This conformational alteration is transformed into cascades of protein-protein recognitions, culminating in the establishment of coregulator/cointegrator complexes on gene promoters. Coregulators induce chromatin remodelling and acetylation, thus enabling the targeted recruitment and activation of the basal transcription machinery. This review discusses the molecular infrastructure of nuclear receptor signalling. Emphasis is given to determinants of signalling specificity, especially since they highlight prominent targets for novel drug discovery.

Journal Article↗
PubMed2004

Omentalization of a nonresectable uterine stump abscess in a dog.

One month after ovariohysterectomy, a 2-year-old spayed female Golden Retriever was evaluated because of an extensive uterine stump abscess. Clinical signs included intermittent vomiting, signs of depression, lethargy, and pollakiuria. The dog underwent abdominal surgery; the greatly enlarged uterine stump was tightly adhered to the dorsal surface of the bladder, encompassing the distal portions of the ureters and the bladder's neurovascular supply. En bloc resection of the uterine stump was not considered an acceptable treatment option because of the risk of surgical damage to and subsequent devitalization of the bladder or ureters, urinary incontinence, or urinary tract obstruction. Therefore, the diseased uterine tissue that extended cranial to the bladder was resected, and the remaining abscess cavity was lavaged and packed with omentum. The dog recovered fully from the procedure. The omentum is an effective physiologic drain; its extensive vascular and lymphatic networks absorb fluid and actively promote elimination of infection. Omentalization appears to be an option for surgical management of nonresectable uterine stump abscesses in dogs.

Abdominal Abscess↗
PubMed2003

Frequency modulation of synchronized Ca2+ spikes in cultured hippocampal networks through G-protein-coupled receptors.

Synchronized spontaneous Ca2+ spikes in networked neurons represent periodic burst firing of action potentials, which are believed to play a major role in the development and plasticity of neuronal circuitry. How these network activities are shaped and modulated by extrinsic factors during development, however, remains to be studied. Here we report that synchronized Ca2+ spikes among cultured hippocampal neurons can be modulated by two small factors that act on G-protein-coupled receptors (GPCRs): the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) and the chemokine SDF-1 (stromal cell-derived factor-1). PACAP effectively increases the frequency of the synchronized Ca2+ spikes when applied acutely; the PACAP potentiation of Ca2+ spikes requires the activation of the PACAP-specific PAC1 GPCRs and is mediated by the activation of cAMP signaling pathway. SDF-1, on the other hand, significantly reduces the frequency of these Ca2+ spikes through the activation of its specific GPCR CXCR4; the inhibitory action of SDF-1 is mediated by the inhibition of cAMP pathway through the Gi component of GPCRs. Taken together, these results demonstrate that synchronized neuronal network activity can be effectively modulated by physiologically and developmentally relevant small factors that act on GPCRs to target the cAMP pathway. Such modulation of neuronal activity through GPCRs may represent a significant mechanism that underlies the neuronal plasticity during neural development and functioning.

Action Potentials↗
PubMed1985

Musical empathy (Einfuhling).

In this paper an "alpha-effect" is defined as a plethysmograph amplitude increase to the hearing of music concurrently with strong affinity for music, pleasurable feeling and reported empathy. Based on this definition a hypothetical model of empathy to music is formulated and the psychophysiological alpha-effect mechanism is related to the processes of empathy and cognitive attribution. In order to understand the psychophysiological mechanism of the alpha-effect, a network is proposed made up of several physiological processes with feedback circuits and feedback circuits at both the sensory and physiological level, and at the cognitive and psychological level. It was aimed also to give a theoretical account of the efficacy of music and to explicate the underlying psychophysiological mechanisms of that efficacy. The model may also help clinical psychologists who want to use music as a therapeutic tool in arranging optimal programs suited to the individual needs, experience, and background of a patient.

Alpha Rhythm↗
PubMed1996

Mechanisms of action of intravenous immune globulin in immune-mediated diseases.

Intravenous immune globulin (IVIG) exhibits a number of immunomodulatory properties that are mediated by the Fe portion of IgG and by the spectrum of variable (V) regions contained in the immune globulin preparations. Five predominant and non-exclusive mechanisms of action have been proposed to account for the immunomodulatory effects of IVIG in immune-mediated diseases: (i) functional blockade of Fc receptors on splenic macrophages; (ii) inhibition of complement-mediated damage, an effect that is dependent on the ability of IgG to bind C3b and C4b and thus reduce the number of activated complement fragments that may deposit on target surfaces of complement activation; (iii) modulation of the production of cytokines and cytokine antagonists; (iv) neutralization of circulating autoantibodies by complementary (e.g. anti-idiotypic) antibodies in IVIG, a mechanism that accounts for the rapid decrease in titre of circulating autoantibodies that is often observed within hours following the infusion of IVIG; (v) selection of immune repertoires, a complex set of effects that may be observed in individuals receiving IVIG far beyond the half-life of the infused immunoglobulin and that is directly relevant to the ability of IVIG to, for example, suppress autoantibody-producing clones in patients with antibody-mediated autoimmune disease and modulate graft versus host disease (GVHD). IVIG has been shown to downregulate or activate B-cell clones expressing surface IgG that is complementary (anti-idiotypic) to V regions of antibodies present in IVIG. IVIG has been shown also to interact with surface molecules of T cells that are essential to immune regulation, such as the alpha beta TCR, CD5, CD4, non-polymorphic determinants of MHC class I molecules and adhesion molecules of T and B cells. The complex interactions of IVIG with functional molecules of cells of the immune system are relevant to its therapeutic effects in T cell- as well as B cell-mediated diseases and indeed, to our understanding of the physiological role of normal IgG and antibody networks in controlling autoreactivity in healthy individuals.

Adjuvants, Immunologic↗
PubMed1996

Neuroimmune mechanisms in health and disease: 1. Health.

A novel scientific discipline that examines the complex interdependence of the neural, endocrine and immune systems in health and disease has emerged in recent years. In health, the neuroimmunoregulatory network is fundamental to host defence and to the transfer of immunity to offspring; the network also plays important roles in intestinal physiology and in tissue regeneration, healing and reproduction. The proliferation of lymphocytes in primary lymphoid organs (bone marrow, bursa of Fabricius [in birds] and thymus) and in secondary lymphoid organs (spleen, lymph nodes and mucosal lymphoid tissue) depends on prolactin and growth hormone. These hormones allow immune cells to respond to antigen and to soluble mediators, called cytokines. Immune-derived cytokines are capable of inducing fever and of altering neuro-transmitter activity in the brain and hormone secretion by the pituitary gland. The activation of the hypothalamus-pituitary-adrenal axis by cytokines leads to immunosuppression. Lymphoid organs are innervated, and tissue mast cells respond to neurologic stimuli. In general, acetylcholine and substance P exert immunostimulatory and proinflammatory effects, whereas epinephrine and somatostatin are immunosuppressive and anti-inflammatory. In this article, the authors predict that novel approaches to immunomodulation will be possible by altering the level or efficacy of immunoregulatory hormones and neurotransmitters.

Humans↗
PubMed1997

Physiology and pathology of tau protein kinases in relation to Alzheimer's disease.

Alzheimer's disease (AD) is characterized by neuronal cell death and two kinds of deposits, neurofibrillary tangles (NFT) and senile plaques. The main component of NFT is paired helical filaments (PHF), which mainly consist of hyperphosphorylated tau protein. Tau protein kinases I and II were found as candidate enzymes responsible for hyperphosphorylation of tau to induce the formation of PHF. Since prior phosphorylation of tau by TPKII strongly enhanced the action of TPKI, it was thought that TPKII was involved in the formation of PHF-tau in concert with TPKI. After cloning, TPKI was found to be identical with glycogen synthase kinase 3 beta (GSK3 beta), while TPKII consists of a novel 23 kDa protein activator and a catalytic subunit that is identical with cyclin-dependent kinase 5 (CDK5). The phosphorylation sites on tau by TPKI and TPKII could account for the most, but not all, of the major phosphorylation sites of fetal tau and PHF-tau. An antibody for a site specifically phosphorylated by TPKI (Ser413) could identify all three neurofibrillary lesions in the AD brain, and double staining for either TPKI or TPKII and NFT in the brain of Down's syndrome patients clearly demonstrated that TPKI and TPKII are both associated with NFT in vivo, suggesting that the level of TPKI or TPKII is elevated in AD brain by some mechanism. On the other hand, the levels of both TPKs change developmentally, being high in the neonatal period when the phosphorylation of fetal tau proceeds actively, suggesting that the TPKI/TPKII cooperative system has an important physiological role in the formation of neural networks. In AD brain, aberrant accumulation of amyloid-beta protein (A beta) occurs ahead of the accumulation of PHF in NFT. When a primary culture of embryonic rat hippocampus was treated with 20 microM A beta, induction of TPKI, extensive phosphorylation of tau and then programmed cell death were observed, indicating that TPKI induced by A beta phosphorylates tau, followed by disruption of axonal transportation and finally cell death. By using a yeast two hybrid system, TPKI was found to interact with pyruvate dehydrogenase (PDH), which is a key enzyme in the glycolytic pathway. PDH was phosphorylated in vitro by TPKI to reduce the activity converting pyruvate into acetyl-CoA, which is required for acetylcholine synthesis. In a primary culture of rat hippocampal cells treated with A beta, PDH was inactivated in inverse relation to the activation of TPKI, resulting in accumulation of pyruvate or lactate, energy failure induced by the disturbance of glucose metabolism, and a shortage of acetylcholine owing to deficiency of acetyl-CoA, all of which are characteristic of AD brain. In cholinergic neurons such as those of the septum, non-aggregated A beta, specifically A beta (1-42), not A beta (1-40), caused a shortage of acetylcholine by activation of TPKI and inactivation of PDH without cell death.

Alzheimer Disease↗
PubMed1986

Modelling study of spinal generators structure; the role of alpha motoneurons, Renshaw cells and Ia interneurons in locomotion.

The properties of a model system composed of nets of motoneurons, Ia interneurons and Renshaw cells corresponding to the set of muscles driving one joint were analyzed from the point of view of their participation in locomotion control, i.e., generation of signals driving individual muscles. The model was constructed of neuron-like analog elements. The relations between the structure of the system, its control by tonic and phasic inputs and the properties of the generated signals were examined. The pattern of activity of motoneuron-like elements was considered to reflect the physiological pattern of muscle activity during locomotion. The network modelled in this way was an adjustable system, i.e., the parameters of the generated pattern could be varied by both tonic and phasic signals. A phasic signal acting on a background of moderate tonic signals seemed to enable a broader adjustment of the parameters of the generated pattern than tonic signals only. The best correspondence between generated and physiological patterns was obtained when the Renshaw cells were additionally and selectively inhibited by tonic signals.

Animals↗
PubMed2006

Analysis of nighttime activity and daytime pain in patients with chronic back pain using a self-organizing map neural network.

There may be a relationship between sleep and pain in patients with chronic back pain. We collected day-time pain and nighttime activity data from 18 patients diagnosed with chronic back pain. The patients were followed for 6 days and 5 nights. Pain levels were collected every 90 min between 0800 hours and 2,200 hours using a computerized electronic diary. Activity levels were collected using a wrist accelerometer (Actiwatch AW-64). The Actiwatch sampled activity counts every 1 min. Patients were asked to wear the Actiwatch on their non-dominant arm. The pain level measurements were interpolated using cubic splines. A mean pain level was calculated for each period 0800 hours to 2,200 hours as well as for the 6-day period. The difference between the mean pain levels for the 6-day period and each 0800 hours to 2,200 hours period was calculated for each patient. Nighttime activity data were analyzed using the Actiwatch Sleep Analysis software. Correlations were calculated between the Actiwatch Sleep Analysis variables and the mean pain level differences for each patient and period. The correlation analysis was performed with SPSS 7.5. We were unable to show any significant relationships.A different approach to analyze the data was used. A Self-Organizing Map (SOM) Neural Network was trained using the original nighttime activity level time series from 10 randomly selected patients. Recall was then performed on all the activity level data. Correlations were calculated between the pain level variance for the 6-day period for each patient and the corresponding difference in the SOM output coordinates. The correlation was found to be r = 0.73, p < 0.01). We conclude that daytime pain levels are not directly correlated with sleep in the following night and that sleep is not directly correlated with daytime pain levels on the following day in this group of patients. There appears to be a correlation between the difference in nighttime activity levels and patterns and the daytime pain variance. Patients who experience large fluctuations in daytime pain levels also show a higher variability in their nighttime activity levels and patterns. Even though we were unable to show a direct relationship between daytime pain and sleep, it may be reasonable to assume that better pain control resulting in less daytime pain fluctuations can provide more stable nighttime activity levels and patterns in this limited group of patients. By using a neural network model, we were able to extract information from the nighttime activity levels even though a traditional statistical analysis was unsuccessful.

Back Pain↗
PubMed1992

Artificial neural networks in bioprocess state estimation.

The application of artificial neural networks to the estimation and prediction of bioprocess variables is presented in this paper. A neural network methodology is discussed, which uses environmental and physiological information available from on-line sensors, to estimate concentration of species in the bioreactor. Two case studies are presented, both based on the ethanol production by Zymomonas mobilis. An efficient optimization algorithm which reduces the number of iterations required for convergence is proposed. Results are presented for different training sets and different training methodologies. It is shown that the neural network estimator provides good on-line bioprocess state estimations.

Biomedical Engineering↗
PubMed2004

Reproductive ground plan may mediate colony-level selection effects on individual foraging behavior in honey bees.

The colony-level phenotype of an insect society emerges from interactions between large numbers of individuals that may differ considerably in their morphology, physiology, and behavior. The proximate and ultimate mechanisms that allow this complex integrated system to form are not fully known, and understanding the evolution of social life strategies is a major topic in systems biology. In solitary insects, behavior, sensory tuning, and reproductive physiology are linked. These associations are controlled in part by pleiotropic networks that organize the sequential expression of phases in the reproductive cycle. Here we explore whether similar associations give rise to different behavioral phenotypes in a eusocial worker caste. We document that the pleiotropic genetic network that controls foraging behavior in functionally sterile honey bee workers (Apis mellifera) has a reproductive component. Associations between behavior, physiology, and sensory tuning in workers with different foraging strategies indicate that the underlying genetic architectures were designed to control a reproductive cycle. Genetic circuits that make up the regulatory "ground plan" of a reproductive strategy may provide powerful building blocks for social life. We suggest that exploitation of this ground plan plays a fundamental role in the evolution of social insect societies.

Animals↗
PubMed2006

Functional arrangement of rat diaphragmatic initial lymphatic network.

Fluid and solute flux between the pleural and peritoneal cavities, although never documented under physiological conditions, might play a relevant role in pathological conditions associated with the development of ascitis and pleural effusion and/or in the processes of tumor dissemination. To verify whether a pleuroperitoneal flux might take place through the diaphragmatic lymphatic network, the transdiaphragmatic pressure gradient (Delta P(TD)) was measured in five spontaneously breathing anesthetized rats. Delta P(TD) was -1.93 cmH2O (SD 0.59) and -3.1 cmH2O (SD 0.82) at end expiration and at end inspiration, respectively, indicating the existence of a pressure gradient directed from the abdominal to the pleural cavity. Morphometrical analysis of the diaphragmatic lymphatic network was performed in the excised diaphragm of three additional rats euthanized with an anesthesia overdose. Optical and electron microscopy revealed that lymphatic submesothelial lacunae and lymphatic capillaries among the skeletal muscles fibers show the ultrastructural features of the so-called initial lymphatic vessels, namely, a discontinuous basal lamina and anchoring filaments linking the outer surface of the endothelial cells to connective tissue or to muscle fibers. Primary unidirectional valves in the wall of the initial lymphatics allow entrance of serosal fluid into the lymphatic network preventing fluid backflow, while unidirectional intraluminar valves in the transverse vessels convey lymph centripetally toward central collecting ducts. The complexity and anatomical arrangement of the two valves system suggests that, despite the existence of a favorable Delta P(TD), in the physiological condition no fluid bulk flow takes place between the pleural and peritoneal cavity through the diaphragmatic lymphatic network.

Animals↗
PubMed2007

Realistically coupled neural mass models can generate EEG rhythms.

We study the generation of EEG rhythms by means of realistically coupled neural mass models. Previous neural mass models were used to model cortical voxels and the thalamus. Interactions between voxels of the same and other cortical areas and with the thalamus were taken into account. Voxels within the same cortical area were coupled (short-range connections) with both excitatory and inhibitory connections, while coupling between areas (long-range connections) was considered to be excitatory only. Short-range connection strengths were modeled by using a connectivity function depending on the distance between voxels. Coupling strength parameters between areas were defined from empirical anatomical data employing the information obtained from probabilistic paths, which were tracked by water diffusion imaging techniques and used to quantify white matter tracts in the brain. Each cortical voxel was then described by a set of 16 random differential equations, while the thalamus was described by a set of 12 random differential equations. Thus, for analyzing the neuronal dynamics emerging from the interaction of several areas, a large system of differential equations needs to be solved. The sparseness of the estimated anatomical connectivity matrix reduces the number of connection parameters substantially, making the solution of this system faster. Simulations of human brain rhythms were carried out in order to test the model. Physiologically plausible results were obtained based on this anatomically constrained neural mass model.

Brain Mapping↗
PubMed2006

Calcium signaling networks channel plant K+ uptake.

Potassium channel function is fundamental to many physiological processes in plants. In this issue of Cell, identify a protein complex in Arabidopsis consisting of a potassium channel, a protein kinase, and a calcium sensor. This study reveals that plants cope with limited soil potassium by coupling potassium channel activation to a cellular calcium signaling network.

Arabidopsis↗
PubMed1995

Neural networks: a bridge between neuroscience and psychology.

Between the anatomy and physiology of neurons on the one hand, and the study of perception and personality on the other, there is a vast gap in our understanding. Although, today, most neuroscientists say it is axiomatic that the phenomena of mind result from the operation of the brain, they could not tell you how.

Aphasia↗
PubMed2003

Tissue-specific gene expression and ecdysone-regulated genomic networks in Drosophila.

During insect metamorphosis, each tissue displays a unique physiological and morphological response to the steroid hormone 20-hydroxyecdysone (ecdysone). We assayed gene expression in five tissues during metamorphosis onset. Larval-specific tissues display major changes in genome-wide expression profiles, whereas tissues that survive into adulthood display few changes. In one larval tissue, the salivary gland, we used a computational approach to identify a regulatory motif and a cognate transcription factor involved in regulating a set of coexpressed genes. During the metamorphosis of another tissue, the midgut, genes encoding factors from the hedgehog, Notch, EGF, dpp, and wingless pathways are activated by the ecdysone regulatory network. Mutation of the ecdysone receptor abolishes their induction. Cell cycle genes are also activated during the initiation of midgut metamorphosis, and they are also dependent on ecdysone signaling. These results establish multiple new connections between the ecdysone regulatory network and other well-studied regulatory networks.

Amino Acid Sequence↗
PubMed2006

Predicting essential components of signal transduction networks: a dynamic model of guard cell abscisic acid signaling.

Plants both lose water and take in carbon dioxide through microscopic stomatal pores, each of which is regulated by a surrounding pair of guard cells. During drought, the plant hormone abscisic acid (ABA) inhibits stomatal opening and promotes stomatal closure, thereby promoting water conservation. Dozens of cellular components have been identified to function in ABA regulation of guard cell volume and thus of stomatal aperture, but a dynamic description is still not available for this complex process. Here we synthesize experimental results into a consistent guard cell signal transduction network for ABA-induced stomatal closure, and develop a dynamic model of this process. Our model captures the regulation of more than 40 identified network components, and accords well with previous experimental results at both the pathway and whole-cell physiological level. By simulating gene disruptions and pharmacological interventions we find that the network is robust against a significant fraction of possible perturbations. Our analysis reveals the novel predictions that the disruption of membrane depolarizability, anion efflux, actin cytoskeleton reorganization, cytosolic pH increase, the phosphatidic acid pathway, or K(+) efflux through slowly activating K(+) channels at the plasma membrane lead to the strongest reduction in ABA responsiveness. Initial experimental analysis assessing ABA-induced stomatal closure in the presence of cytosolic pH clamp imposed by the weak acid butyrate is consistent with model prediction. Simulations of stomatal response as derived from our model provide an efficient tool for the identification of candidate manipulations that have the best chance of conferring increased drought stress tolerance and for the prioritization of future wet bench analyses. Our method can be readily applied to other biological signaling networks to identify key regulatory components in systems where quantitative information is limited.

Abscisic Acid↗