WorldWideScience

Sample records for neural immune signaling

  1. Innate immune signaling in CLL.

    Science.gov (United States)

    Maus, Marcela V

    2016-01-28

    In this issue of Blood, Wagner et al describe a complex signaling model that explains the mechanism of action of a long-known prognostic marker in chronic lymphocytic leukemia (CLL) and integrates its function with the innate immune system and B-cell receptor signaling.

  2. Neural Membrane Signaling Platforms

    Directory of Open Access Journals (Sweden)

    Ron Wallace

    2010-06-01

    Full Text Available Throughout much of the history of biology, the cell membrane was functionally defined as a semi-permeable barrier separating aqueous compartments, and an anchoring site for proteins. Little attention was devoted to its possible regulatory role in intracellular molecular processes and neuron electrical signaling. This article reviews the history of membrane studies and the current state of the art. Emphasis is placed on natural and artificial membrane studies of electric field effects on molecular organization, especially as these may relate to impulse propagation in neurons. Implications of these studies for new designs in artificial intelligence are briefly examined.

  3. Neural membrane signaling platforms.

    Science.gov (United States)

    Wallace, Ron

    2010-06-10

    Throughout much of the history of biology, the cell membrane was functionally defined as a semi-permeable barrier separating aqueous compartments, and an anchoring site for proteins. Little attention was devoted to its possible regulatory role in intracellular molecular processes and neuron electrical signaling. This article reviews the history of membrane studies and the current state of the art. Emphasis is placed on natural and artificial membrane studies of electric field effects on molecular organization, especially as these may relate to impulse propagation in neurons. Implications of these studies for new designs in artificial intelligence are briefly examined.

  4. [Glutamate signaling and neural plasticity].

    Science.gov (United States)

    Watanabe, Masahiko

    2013-07-01

    Proper functioning of the nervous system relies on the precise formation of neural circuits during development. At birth, neurons have redundant synaptic connections not only to their proper targets but also to other neighboring cells. Then, functional neural circuits are formed during early postnatal development by the selective strengthening of necessary synapses and weakening of surplus connections. Synaptic connections are also modified so that projection fields of active afferents expand at the expense of lesser ones. We have studied the molecular mechanisms underlying these activity-dependent prunings and the plasticity of synaptic circuitry using gene-engineered mice defective in the glutamatergic signaling system. NMDA-type glutamate receptors are critically involved in the establishment of the somatosensory pathway ascending from the brainstem trigeminal nucleus to the somatosensory cortex. Without NMDA receptors, whisker-related patterning fails to develop, whereas lesion-induced plasticity occurs normally during the critical period. In contrast, mice lacking the glutamate transporters GLAST or GLT1 are selectively impaired in the lesion-induced critical plasticity of cortical barrels, although whisker-related patterning itself develops normally. In the developing cerebellum, multiple climbing fibers initially innervating given Purkinje cells are eliminated one by one until mono-innervation is achieved. In this pruning process, P/Q-type Ca2+ channels expressed on Purkinje cells are critically involved by the selective strengthening of single main climbing fibers against other lesser afferents. Therefore, the activation of glutamate receptors that leads to an activity-dependent increase in the intracellular Ca2+ concentration plays a key role in the pruning of immature synaptic circuits into functional circuits. On the other hand, glutamate transporters appear to control activity-dependent plasticity among afferent fields, presumably through adjusting

  5. Cognitive Control Signals for Neural Prosthetics

    National Research Council Canada - National Science Library

    S. Musallam; B. D. Corneil; B. Greger; H. Scherberger; R. A. Andersen

    2004-01-01

    Recent development of neural prosthetics for assisting paralyzed patients has focused on decoding intended hand trajectories from motor cortical neurons and using this signal to control external devices...

  6. Neural network signal understanding for instrumentation

    DEFF Research Database (Denmark)

    Pau, L. F.; Johansen, F. S.

    1990-01-01

    A report is presented on the use of neural signal interpretation theory and techniques for the purpose of classifying the shapes of a set of instrumentation signals, in order to calibrate devices, diagnose anomalies, generate tuning/settings, and interpret the measurement results. Neural signal...... understanding research is surveyed, and the selected implementation and its performance in terms of correct classification rates and robustness to noise are described. Formal results on neural net training time and sensitivity to weights are given. A theory for neural control using functional link nets is given......, and an explanation facility designed to help neural signal understanding is described. The results are compared to those obtained with a knowledge-based signal interpretation system using the same instrument and data...

  7. The performance of immune-based neural network with financial time series prediction

    Directory of Open Access Journals (Sweden)

    Dhiya Al-Jumeily

    2015-12-01

    Full Text Available This paper presents the use of immune-based neural networks that include multilayer perceptron (MLP and functional neural network for the prediction of financial time series signals. Extensive simulations for the prediction of one- and five-steps-ahead of stationary and non-stationary time series were performed which indicate that immune-based neural networks in most cases demonstrated advantages in capturing chaotic movement in the financial signals with an improvement in the profit return and rapid convergence over MLPs.

  8. Sub-meninges Implantation Reduces Immune Response to Neural Implants

    Science.gov (United States)

    Markwardt, Neil T.; Stokol, Jodi; Rennaker, Robert L.

    2013-01-01

    Glial scar formation around neural interfaces inhibits their ability to acquire usable signals from the surrounding neurons. To improve neural recording performance, the inflammatory response and glial scarring must be minimized. Previous work has indicated that meningeally derived cells participate in the immune response, and it is possible that the meninges may grow down around the shank of a neural implant, contributing to the formation of the glial scar. This study examines whether the glial scar can be reduced by placing a neural probe completely below the meninges. Rats were implanted with sets of loose microwire implants placed either completely below the meninges or implanted conventionally with the upper end penetrating the meninges, but not attached to the skull. Histological analysis was performed 4 weeks following surgical implantation to evaluate the glial scar. Our results found that sub-meninges implants showed an average reduction in reactive astrocyte activity of 63% compared to trans-meninges implants. Microglial activity was also reduced for sub-meninges implants. These results suggest that techniques that isolate implants from the meninges offer the potential to reduce the encapsulation response which should improve chronic recording quality and stability. PMID:23370311

  9. Imaging Posture Veils Neural Signals

    Directory of Open Access Journals (Sweden)

    Robert T Thibault

    2016-10-01

    Full Text Available Whereas modern brain imaging often demands holding body positions incongruent with everyday life, posture governs both neural activity and cognitive performance. Humans commonly perform while upright; yet, many neuroimaging methodologies require participants to remain motionless and adhere to non-ecological comportments within a confined space. This inconsistency between ecological postures and imaging constraints undermines the transferability and generalizability of many a neuroimaging assay.Here we highlight the influence of posture on brain function and behavior. Specifically, we challenge the tacit assumption that brain processes and cognitive performance are comparable across a spectrum of positions. We provide an integrative synthesis regarding the increasingly prominent influence of imaging postures on autonomic function, mental capacity, sensory thresholds, and neural activity. Arguing that neuroimagers and cognitive scientists could benefit from considering the influence posture wields on both general functioning and brain activity, we examine existing imaging technologies and the potential of portable and versatile imaging devices (e.g., functional near infrared spectroscopy. Finally, we discuss ways that accounting for posture may help unveil the complex brain processes of everyday cognition.

  10. Hormonal signaling in plant immunity

    NARCIS (Netherlands)

    Caarls, L.

    2016-01-01

    Insect hervivores and pathogens are a major problem in agriculture and therefore, control of these pests and diseases is essential. For this, understanding the plant immune response can be instrumental. The plant hormones salicylic acid (SA) and jasmonic acid (JA) play an essential role in defense

  11. Neural synchronization via potassium signaling

    DEFF Research Database (Denmark)

    Postnov, Dmitry E; Ryazanova, Ludmila S; Mosekilde, Erik

    2006-01-01

    Using a relatively simple model we examine how variations of the extracellular potassium concentration can give rise to synchronization of two nearby pacemaker cells. With the volume of the extracellular space and the rate of potassium diffusion as control parameters, the dual nature...... junctional coupling, potassium signaling gives rise to considerable changes of the cellular response to external stimuli....

  12. Damage signals in the insect immune response

    Directory of Open Access Journals (Sweden)

    Robert eKrautz

    2014-07-01

    Full Text Available Insects and mammals share an ancient innate immune system comprising both humoral and cellular responses. The insect immune system consists of the fat body, which secretes effector molecules into the hemolymph and several classes of hemocytes, which reside in the hemolymph and of protective border epithelia. Key features of wound- and immune responses are shared between insect and mammalian immune systems including the mode of activation by commonly shared microbial (nonself patterns and the recognition of these patterns by dedicated receptors. It is unclear how metazoan parasites in insects, which lack these shared motifs, are recognized. Research in recent years has demonstrated that during entry into the insect host, many eukaryotic pathogens leave traces that alert potential hosts of the damage they have afflicted. In accordance with terminology used in the mammalian immune systems, these signals have been dubbed danger- or damage-associated signals. Damage signals are necessary byproducts generated during entering hosts either by mechanical or proteolytic damage. Here, we briefly review the current stage of knowledge on how wound closure and wound healing during mechanical damage is regulated and how damage-related signals contribute to these processes. We also discuss how sensors of proteolytic activity induce insect innate immune responses. Strikingly damage-associated signals are also released from cells that have aberrant growth, including tumor cells. These signals may induce apoptosis in the damaged cells, the recruitment of immune cells to the aberrant tissue and even activate humoral responses. Thus, this ensures the removal of aberrant cells and compensatory proliferation to replace lost tissue. Several of these pathways may have been co-opted from wound healing and developmental processes.

  13. Reconstruction of periodic signals using neural networks

    Directory of Open Access Journals (Sweden)

    José Danilo Rairán Antolines

    2014-01-01

    Full Text Available In this paper, we reconstruct a periodic signal by using two neural networks. The first network is trained to approximate the period of a signal, and the second network estimates the corresponding coefficients of the signal's Fourier expansion. The reconstruction strategy consists in minimizing the mean-square error via backpro-pagation algorithms over a single neuron with a sine transfer function. Additionally, this paper presents mathematical proof about the quality of the approximation as well as a first modification of the algorithm, which requires less data to reach the same estimation; thus making the algorithm suitable for real-time implementations.

  14. Bacterial Immune Evasion through Manipulation of Host Inhibitory Immune Signaling

    NARCIS (Netherlands)

    Van Avondt, Kristof; van Sorge, Nina M.|info:eu-repo/dai/nl/279926812; Meyaard, Linde|info:eu-repo/dai/nl/13444972X

    An innate immune response is essential for survival of the host upon infection, yet excessive inflammation can result in harmful complications [1]. Inhibitory signaling evolved to limit host responses and prevent inflammatory pathology [2,3]. Given the significance of inhibitory pathways for

  15. TAM receptor signaling in immune homeostasis.

    Science.gov (United States)

    Rothlin, Carla V; Carrera-Silva, Eugenio A; Bosurgi, Lidia; Ghosh, Sourav

    2015-01-01

    The TAM receptor tyrosine kinases (RTKs)-TYRO3, AXL, and MERTK-together with their cognate agonists GAS6 and PROS1 play an essential role in the resolution of inflammation. Deficiencies in TAM signaling have been associated with chronic inflammatory and autoimmune diseases. Three processes regulated by TAM signaling may contribute, either independently or collectively, to immune homeostasis: the negative regulation of the innate immune response, the phagocytosis of apoptotic cells, and the restoration of vascular integrity. Recent studies have also revealed the function of TAMs in infectious diseases and cancer. Here, we review the important milestones in the discovery of these RTKs and their ligands and the studies that underscore the functional importance of this signaling pathway in physiological immune settings and disease.

  16. Neural basis of multisensory looming signals.

    Science.gov (United States)

    Tyll, Sascha; Bonath, Björn; Schoenfeld, Mircea Ariel; Heinze, Hans-Jochen; Ohl, Frank W; Noesselt, Tömme

    2013-01-15

    Approaching or looming signals are often related to extremely relevant environmental events (e.g. threats or collisions) making these signals critical for survival. However, the neural network underlying multisensory looming processing is not yet fully understood. Using functional magnetic resonance imaging (fMRI) we identified the neural correlates of audiovisual looming processing in humans: audiovisual looming (vs. receding) signals enhance fMRI-responses in low-level visual and auditory areas plus multisensory cortex (superior temporal sulcus; plus parietal and frontal structures). When characterizing the fMRI-response profiles for multisensory looming stimuli, we found significant enhancements relative to the mean and maximum of unisensory responses in looming-sensitive visual and auditory cortex plus STS. Superadditive enhancements were observed in visual cortex. Subject-specific region-of-interest analyses further revealed superadditive response profiles within all sensory-specific looming-sensitive structures plus bilateral STS for audiovisual looming vs. summed unisensory looming conditions. Finally, we observed enhanced connectivity of bilateral STS with low-level visual areas in the context of looming processing. This enhanced coupling of STS with unisensory regions might potentially serve to enhance the salience of unisensory stimulus features and is accompanied by superadditive fMRI-responses. We suggest that this preference in neural signaling for looming stimuli effectively informs animals to avoid potential threats or collisions. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Neural reflexes in inflammation and immunity

    National Research Council Canada - National Science Library

    Andersson, Ulf; Tracey, Kevin J

    2012-01-01

    .... Development of advanced neurophysiological and immunological techniques recently enabled the study of reflex neural circuits that maintain immunological homeostasis, and are essential for health in mammals...

  18. Met1-linked Ubiquitination in Immune Signalling

    DEFF Research Database (Denmark)

    Fiil, Berthe Katrine; Gyrd-Hansen, Mads

    2014-01-01

    identification of physiological substrates for Met1-Ub in response to activation of innate immune receptors. These discoveries have significantly advanced our understanding of how non-degradative ubiquitin modifications control pro-inflammatory responses mediated by nuclear factor κB and mitogen......Methionine 1-linked ubiquitin chains (Met1-Ub), or linear ubiquitin, has emerged as a central post-translational modification in innate immune signalling. Molecular machinery that assembles, senses and, more recently, disassembles Met1-Ub has been identified, and technical advances have enabled...

  19. Active voltammetric microsensors with neural signal processing.

    Energy Technology Data Exchange (ETDEWEB)

    Vogt, M. C.

    1998-12-11

    Many industrial and environmental processes, including bioremediation, would benefit from the feedback and control information provided by a local multi-analyte chemical sensor. For most processes, such a sensor would need to be rugged enough to be placed in situ for long-term remote monitoring, and inexpensive enough to be fielded in useful numbers. The multi-analyte capability is difficult to obtain from common passive sensors, but can be provided by an active device that produces a spectrum-type response. Such new active gas microsensor technology has been developed at Argonne National Laboratory. The technology couples an electrocatalytic ceramic-metallic (cermet) microsensor with a voltammetric measurement technique and advanced neural signal processing. It has been demonstrated to be flexible, rugged, and very economical to produce and deploy. Both narrow interest detectors and wide spectrum instruments have been developed around this technology. Much of this technology's strength lies in the active measurement technique employed. The technique involves applying voltammetry to a miniature electrocatalytic cell to produce unique chemical ''signatures'' from the analytes. These signatures are processed with neural pattern recognition algorithms to identify and quantify the components in the analyte. The neural signal processing allows for innovative sampling and analysis strategies to be employed with the microsensor. In most situations, the whole response signature from the voltammogram can be used to identify, classify, and quantify an analyte, without dissecting it into component parts. This allows an instrument to be calibrated once for a specific gas or mixture of gases by simple exposure to a multi-component standard rather than by a series of individual gases. The sampled unknown analytes can vary in composition or in concentration, the calibration, sensing, and processing methods of these active voltammetric microsensors can

  20. Metabolic signals and innate immune activation in obesity and exercise

    National Research Council Canada - National Science Library

    Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

    2015-01-01

    ... being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs...

  1. PIMS Modulates Immune Tolerance by Negatively Regulating Drosophila Innate Immune Signaling

    OpenAIRE

    Lhocine, Nouara; Paulo S. Ribeiro; Buchon, Nicolas; Wepf, Alexander; Wilson, Rebecca; Tenev, Tencho; Lemaitre, Bruno; Gstaiger, Matthias; Meier, Pascal; Leulier, François

    2008-01-01

    Metazoans tolerate commensal-gut microbiota by suppressing immune activation while maintaining the ability to launch rapid and balanced immune reactions to pathogenic bacteria. Little is known about the mechanisms underlying the establishment of this threshold. We report that a recently identified Drosophila immune regulator, which we call PGRP-LC-interacting inhibitor of Imd signaling (PIMS), is required to suppress the Imd innate immune signaling pathway in response to commensal bacteria. p...

  2. Neural signal registration and analysis of axons grown in microchannels

    Science.gov (United States)

    Pigareva, Y.; Malishev, E.; Gladkov, A.; Kolpakov, V.; Bukatin, A.; Mukhina, I.; Kazantsev, V.; Pimashkin, A.

    2016-08-01

    Registration of neuronal bioelectrical signals remains one of the main physical tools to study fundamental mechanisms of signal processing in the brain. Neurons generate spiking patterns which propagate through complex map of neural network connectivity. Extracellular recording of isolated axons grown in microchannels provides amplification of the signal for detailed study of spike propagation. In this study we used neuronal hippocampal cultures grown in microfluidic devices combined with microelectrode arrays to investigate a changes of electrical activity during neural network development. We found that after 5 days in vitro after culture plating the spiking activity appears first in microchannels and on the next 2-3 days appears on the electrodes of overall neural network. We conclude that such approach provides a convenient method to study neural signal processing and functional structure development on a single cell and network level of the neuronal culture.

  3. Using Artificial Neural Networks for ECG Signals Denoising

    Directory of Open Access Journals (Sweden)

    Zoltán Germán-Salló

    2010-12-01

    Full Text Available The authors have investigated some potential applications of artificial neural networks in electrocardiografic (ECG signal prediction. For this, the authors used an adaptive multilayer perceptron structure to predict the signal. The proposed procedure uses an artificial neural network based learning structure to estimate the (n+1th sample from n previous samples To train and adjust the network weights, the backpropagation (BP algorithm was used. In this paper, prediction of ECG signals (as time series using multi-layer feedforward neural networks will be described. The results are evaluated through approximation error which is defined as the difference between the predicted and the original signal.The prediction procedure is carried out (simulated in MATLAB environment, using signals from MIT-BIH arrhythmia database. Preliminary results are encouraging enough to extend the proposed method for other types of data signals.

  4. Hybrid digital signal processing and neural networks applications in PWRs

    Energy Technology Data Exchange (ETDEWEB)

    Eryurek, E.; Upadhyaya, B.R.; Kavaklioglu, K.

    1991-12-31

    Signal validation and plant subsystem tracking in power and process industries require the prediction of one or more state variables. Both heteroassociative and auotassociative neural networks were applied for characterizing relationships among sets of signals. A multi-layer neural network paradigm was applied for sensor and process monitoring in a Pressurized Water Reactor (PWR). This nonlinear interpolation technique was found to be very effective for these applications.

  5. Towards a magnetoresistive platform for neural signal recording

    Science.gov (United States)

    Sharma, P. P.; Gervasoni, G.; Albisetti, E.; D'Ercoli, F.; Monticelli, M.; Moretti, D.; Forte, N.; Rocchi, A.; Ferrari, G.; Baldelli, P.; Sampietro, M.; Benfenati, F.; Bertacco, R.; Petti, D.

    2017-05-01

    A promising strategy to get deeper insight on brain functionalities relies on the investigation of neural activities at the cellular and sub-cellular level. In this framework, methods for recording neuron electrical activity have gained interest over the years. Main technological challenges are associated to finding highly sensitive detection schemes, providing considerable spatial and temporal resolution. Moreover, the possibility to perform non-invasive assays would constitute a noteworthy benefit. In this work, we present a magnetoresistive platform for the detection of the action potential propagation in neural cells. Such platform allows, in perspective, the in vitro recording of neural signals arising from single neurons, neural networks and brain slices.

  6. Neural crest specification: tissues, signals, and transcription factors.

    Science.gov (United States)

    Rogers, C D; Jayasena, C S; Nie, S; Bronner, M E

    2012-01-01

    The neural crest is a transient population of multipotent and migratory cells unique to vertebrate embryos. Initially derived from the borders of the neural plate, these cells undergo an epithelial to mesenchymal transition to leave the central nervous system, migrate extensively in the periphery, and differentiate into numerous diverse derivatives. These include but are not limited to craniofacial cartilage, pigment cells, and peripheral neurons and glia. Attractive for their similarities to stem cells and metastatic cancer cells, neural crest cells are a popular model system for studying cell/tissue interactions and signaling factors that influence cell fate decisions and lineage transitions. In this review, we discuss the mechanisms required for neural crest formation in various vertebrate species, focusing on the importance of signaling factors from adjacent tissues and conserved gene regulatory interactions, which are required for induction and specification of the ectodermal tissue that will become neural crest. Copyright © 2011 Wiley Periodicals, Inc.

  7. Neural Network Enhanced Structure Determination of Osteoporosis, Immune System, and Radiation Repair Proteins Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation will utilize self learning neural network technology to determine the structure of osteoporosis, immune system disease, and excess radiation...

  8. Small-signal neural models and their applications.

    Science.gov (United States)

    Basu, Arindam

    2012-02-01

    This paper introduces the use of the concept of small-signal analysis, commonly used in circuit design, for understanding neural models. We show that neural models, varying in complexity from Hodgkin-Huxley to integrate and fire have similar small-signal models when their corresponding differential equations are close to the same bifurcation with respect to input current. Three applications of small-signal neural models are shown. First, some of the properties of cortical neurons described by Izhikevich are explained intuitively through small-signal analysis. Second, we use small-signal models for deriving parameters for a simple neural model (such as resonate and fire) from a more complicated but biophysically relevant one like Morris-Lecar. We show similarity in the subthreshold behavior of the simple and complicated model when they are close to a Hopf bifurcation and a saddle-node bifurcation. Hence, this is useful to correctly tune simple neural models for large-scale cortical simulations. Finaly, the biasing regime of a silicon ion channel is derived by comparing its small-signal model with a Hodgkin-Huxley-type model.

  9. Neural processing of auditory signals and modular neural control for sound tropism of walking machines

    DEFF Research Database (Denmark)

    Manoonpong, Poramate; Pasemann, Frank; Fischer, Joern

    2005-01-01

    . The parameters of these networks are optimized by an evolutionary algorithm. In addition, a simple modular neural controller then generates the desired different walking patterns such that the machine walks straight, then turns towards a switched-on sound source, and then stops near to it....... and a neural preprocessing system together with a modular neural controller are used to generate a sound tropism of a four-legged walking machine. The neural preprocessing network is acting as a low-pass filter and it is followed by a network which discerns between signals coming from the left or the right...

  10. Trichomoniasis immunity and the involvement of the purinergic signaling

    Directory of Open Access Journals (Sweden)

    Camila Braz Menezes

    2016-08-01

    Full Text Available Innate and adaptive immunity play a significant role in trichomoniasis, the most common non-viral sexually transmitted disease worldwide. In the urogenital tract, innate immunity is accomplished by a defense physical barrier constituted by epithelial cells, mucus, and acidic pH. During infection, immune cells, antimicrobial peptides, cytokines, chemokines, and adaptive immunity evolve in the reproductive tract, and a proinflammatory response is generated to eliminate the invading extracellular pathogen Trichomonas vaginalis. However, the parasite has developed complex evolutionary mechanisms to evade the host immune response through cysteine proteases, phenotypic variation, and molecular mimicry. The purinergic system constitutes a signaling cellular net where nucleotides and nucleosides, enzymes, purinoceptors and transporters are involved in almost all cells and tissues signaling pathways, especially in central and autonomic nervous systems, endocrine, respiratory, cardiac, reproductive, and immune systems, during physiological as well as pathological processes. The involvement of the purinergic system in T. vaginalis biology and infection has been demonstrated and this review highlights the participation of this signaling pathway in the parasite immune evasion strategies. Keywords: Trichomoniasis, Innate immune response, Adaptive immune response, Evasion mechanisms, Purinergic signaling

  11. PIMS modulates immune tolerance by negatively regulating Drosophila innate immune signaling.

    Science.gov (United States)

    Lhocine, Nouara; Ribeiro, Paulo S; Buchon, Nicolas; Wepf, Alexander; Wilson, Rebecca; Tenev, Tencho; Lemaitre, Bruno; Gstaiger, Matthias; Meier, Pascal; Leulier, François

    2008-08-14

    Metazoans tolerate commensal-gut microbiota by suppressing immune activation while maintaining the ability to launch rapid and balanced immune reactions to pathogenic bacteria. Little is known about the mechanisms underlying the establishment of this threshold. We report that a recently identified Drosophila immune regulator, which we call PGRP-LC-interacting inhibitor of Imd signaling (PIMS), is required to suppress the Imd innate immune signaling pathway in response to commensal bacteria. pims expression is Imd (immune deficiency) dependent, and its basal expression relies on the presence of commensal flora. In the absence of PIMS, resident bacteria trigger constitutive expression of antimicrobial peptide genes (AMPs). Moreover, pims mutants hyperactivate AMPs upon infection with Gram-negative bacteria. PIMS interacts with the peptidoglycan recognition protein (PGRP-LC), causing its depletion from the plasma membrane and shutdown of Imd signaling. Therefore, PIMS is required to establish immune tolerance to commensal bacteria and to maintain a balanced Imd response following exposure to bacterial infections.

  12. Automatic Speech Recognition from Neural Signals: A Focused Review.

    Science.gov (United States)

    Herff, Christian; Schultz, Tanja

    2016-01-01

    Speech interfaces have become widely accepted and are nowadays integrated in various real-life applications and devices. They have become a part of our daily life. However, speech interfaces presume the ability to produce intelligible speech, which might be impossible due to either loud environments, bothering bystanders or incapabilities to produce speech (i.e., patients suffering from locked-in syndrome). For these reasons it would be highly desirable to not speak but to simply envision oneself to say words or sentences. Interfaces based on imagined speech would enable fast and natural communication without the need for audible speech and would give a voice to otherwise mute people. This focused review analyzes the potential of different brain imaging techniques to recognize speech from neural signals by applying Automatic Speech Recognition technology. We argue that modalities based on metabolic processes, such as functional Near Infrared Spectroscopy and functional Magnetic Resonance Imaging, are less suited for Automatic Speech Recognition from neural signals due to low temporal resolution but are very useful for the investigation of the underlying neural mechanisms involved in speech processes. In contrast, electrophysiologic activity is fast enough to capture speech processes and is therefor better suited for ASR. Our experimental results indicate the potential of these signals for speech recognition from neural data with a focus on invasively measured brain activity (electrocorticography). As a first example of Automatic Speech Recognition techniques used from neural signals, we discuss the Brain-to-text system.

  13. Automatic Speech Recognition from Neural Signals: A Focused Review

    Directory of Open Access Journals (Sweden)

    Christian Herff

    2016-09-01

    Full Text Available Speech interfaces have become widely accepted and are nowadays integrated in various real-life applications and devices. They have become a part of our daily life. However, speech interfaces presume the ability to produce intelligible speech, which might be impossible due to either loud environments, bothering bystanders or incapabilities to produce speech (i.e.~patients suffering from locked-in syndrome. For these reasons it would be highly desirable to not speak but to simply envision oneself to say words or sentences. Interfaces based on imagined speech would enable fast and natural communication without the need for audible speech and would give a voice to otherwise mute people.This focused review analyzes the potential of different brain imaging techniques to recognize speech from neural signals by applying Automatic Speech Recognition technology. We argue that modalities based on metabolic processes, such as functional Near Infrared Spectroscopy and functional Magnetic Resonance Imaging, are less suited for Automatic Speech Recognition from neural signals due to low temporal resolution but are very useful for the investigation of the underlying neural mechanisms involved in speech processes. In contrast, electrophysiologic activity is fast enough to capture speech processes and is therefor better suited for ASR. Our experimental results indicate the potential of these signals for speech recognition from neural data with a focus on invasively measured brain activity (electrocorticography. As a first example of Automatic Speech Recognition techniques used from neural signals, we discuss the emph{Brain-to-text} system.

  14. Insights into innate immune signalling in controlling cardiac remodelling.

    Science.gov (United States)

    Zhang, Yaxing; Huang, Zan; Li, Hongliang

    2017-11-01

    Canonical innate immune signalling involves complex cascades: multiple germline-encoded pattern recognition receptors rapidly recognize pathogen-associated or damage-associated molecular patterns to induce the production of cytokines, which bind to their corresponding receptors to orchestrate subsequent host defense phases. Inflammation is a healthy response to pathogenic signals, which are typically rapid and specific, and they terminate once the threat has passed. However, excessive activation or suppression of innate immune or inflammatory responses can lead to considerable human suffering, such as cardiac remodelling. Interestingly, recent studies have revealed that innate immune molecules in the parenchymal cells of the heart influence cardiac homeostasis not only by directly regulating innate immune responses but also through reprogrammed signalling pathways, which are independent of conventional innate immune signalling. Elucidating 'innate immune signalling reprogramming' events will help us better understand the functions of innate immune molecules and, moreover, the pathogenesis of cardiac diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  15. Stereo Matching Based on Immune Neural Network in Abdomen Reconstruction

    Directory of Open Access Journals (Sweden)

    Huan Liu

    2015-01-01

    Full Text Available Stereo feature matching is a technique that finds an optimal match in two images from the same entity in the three-dimensional world. The stereo correspondence problem is formulated as an optimization task where an energy function, which represents the constraints on the solution, is to be minimized. A novel intelligent biological network (Bio-Net, which involves the human B-T cells immune system into neural network, is proposed in this study in order to learn the robust relationship between the input feature points and the output matched points. A model from input-output data (left reference point-right target point is established. In the experiments, the abdomen reconstructions for different-shape mannequins are then performed by means of the proposed method. The final results are compared and analyzed, which demonstrate that the proposed approach greatly outperforms the single neural network and the conventional matching algorithm in precise. Particularly, as far as time cost and efficiency, the proposed method exhibits its significant promising and potential for improvement. Hence, it is entirely considered as an effective and feasible alternative option for stereo matching.

  16. Neural Processing of Auditory Signals and Modular Neural Control for Sound Tropism of Walking Machines

    Directory of Open Access Journals (Sweden)

    Hubert Roth

    2008-11-01

    Full Text Available The specialized hairs and slit sensillae of spiders (Cupiennius salei can sense the airflow and auditory signals in a low-frequency range. They provide the sensor information for reactive behavior, like e.g. capturing a prey. In analogy, in this paper a setup is described where two microphones and a neural preprocessing system together with a modular neural controller are used to generate a sound tropism of a four-legged walking machine. The neural preprocessing network is acting as a low-pass filter and it is followed by a network which discerns between signals coming from the left or the right. The parameters of these networks are optimized by an evolutionary algorithm. In addition, a simple modular neural controller then generates the desired different walking patterns such that the machine walks straight, then turns towards a switched-on sound source, and then stops near to it.

  17. Innate immune signalling of the zebrafish embryo

    NARCIS (Netherlands)

    Stockhammer, Oliver W.

    2010-01-01

    In the last decade the study of the innate immune system has gained renewed scientific momentum as a result of the discovery of essential receptor families, such as the Toll-like receptor (TLR) family, that are required for pathogen recognition. These receptors detect specific molecular structures

  18. Signaling in large-scale neural networks

    DEFF Research Database (Denmark)

    Berg, Rune W; Hounsgaard, Jørn

    2009-01-01

    We examine the recent finding that neurons in spinal motor circuits enter a high conductance state during functional network activity. The underlying concomitant increase in random inhibitory and excitatory synaptic activity leads to stochastic signal processing. The possible advantages of this m......We examine the recent finding that neurons in spinal motor circuits enter a high conductance state during functional network activity. The underlying concomitant increase in random inhibitory and excitatory synaptic activity leads to stochastic signal processing. The possible advantages...... of this metabolically costly organization are analyzed by comparing with synaptically less intense networks driven by the intrinsic response properties of the network neurons....

  19. Application of the minimum fuel neural network to music signals

    DEFF Research Database (Denmark)

    Harbo, Anders La-Cour

    2004-01-01

    Finding an optimal representation of a signal in an over-complete dictionary is often quite difficult. Since general results in this field are not very application friendly it truly helps to specify the framework as much as possible. We investigate the method Minimum Fuel Neural Network (MFNN...

  20. Models of Acetylcholine and Dopamine Signals Differentially Improve Neural Representations

    Science.gov (United States)

    Holca-Lamarre, Raphaël; Lücke, Jörg; Obermayer, Klaus

    2017-01-01

    Biological and artificial neural networks (ANNs) represent input signals as patterns of neural activity. In biology, neuromodulators can trigger important reorganizations of these neural representations. For instance, pairing a stimulus with the release of either acetylcholine (ACh) or dopamine (DA) evokes long lasting increases in the responses of neurons to the paired stimulus. The functional roles of ACh and DA in rearranging representations remain largely unknown. Here, we address this question using a Hebbian-learning neural network model. Our aim is both to gain a functional understanding of ACh and DA transmission in shaping biological representations and to explore neuromodulator-inspired learning rules for ANNs. We model the effects of ACh and DA on synaptic plasticity and confirm that stimuli coinciding with greater neuromodulator activation are over represented in the network. We then simulate the physiological release schedules of ACh and DA. We measure the impact of neuromodulator release on the network's representation and on its performance on a classification task. We find that ACh and DA trigger distinct changes in neural representations that both improve performance. The putative ACh signal redistributes neural preferences so that more neurons encode stimulus classes that are challenging for the network. The putative DA signal adapts synaptic weights so that they better match the classes of the task at hand. Our model thus offers a functional explanation for the effects of ACh and DA on cortical representations. Additionally, our learning algorithm yields performances comparable to those of state-of-the-art optimisation methods in multi-layer perceptrons while requiring weaker supervision signals and interacting with synaptically-local weight updates. PMID:28690509

  1. PIMS Modulates Immune Tolerance by Negatively Regulating Drosophila Innate Immune Signaling

    National Research Council Canada - National Science Library

    Lhocine, Nouara; Ribeiro, Paulo S; Buchon, Nicolas; Wepf, Alexander; Wilson, Rebecca; Tenev, Tencho; Lemaitre, Bruno; Gstaiger, Matthias; Meier, Pascal; Leulier, François

    2008-01-01

    .... Little is known about the mechanisms underlying the establishment of this threshold. We report that a recently identified Drosophila immune regulator, which we call PGRP-LC-interacting inhibitor of Imd signaling (PIMS...

  2. Estimating Neural Signal Dynamics in the Human Brain

    Directory of Open Access Journals (Sweden)

    Christopher W Tyler

    2011-06-01

    Full Text Available Although brain imaging methods are highly effective for localizing the effects of neural activation throughout the human brain in terms of the blood oxygenation level dependent (BOLD response, there is currently no way to estimate the underlying neural signal dynamics in generating the BOLD response in each local activation region (except for processes slower than the BOLD time course. Knowledge of the neural signal is critical information if spatial mapping is to progress to the analysis of dynamic information flow through the cortical networks as the brain performs its tasks. We introduce an analytic approach that provides a new level of conceptualization and specificity in the study of brain processing by noninvasive methods. This technique allows us to use brain imaging methods to determine the dynamics of local neural population responses to their native temporal resolution throughout the human brain, with relatively narrow confidence intervals on many response properties. The ability to characterize local neural dynamics in the human brain represents a significant enhancement of brain imaging capabilities, with potential application from general cognitive studies to assessment of neuropathologies.

  3. Use of artificial neural networks in biosensor signal classification

    Directory of Open Access Journals (Sweden)

    Vlastimil Dohnal

    2008-01-01

    Full Text Available Biosensors are analytical devices that transforms chemical information, ranging from the concentration of a specific sample component to total composition analysis, into an analytical signal and that utilizes a biochemical mechanism for the chemical recognition. The complexity of biosensor construction and generation of measured signal requires the development of new method for signal eva­luation and its possible defects recognition. A new method based on artificial neural networks (ANN was developed for recognition of characteristic behavior of signals joined with malfunction of sensor. New algorithm uses unsupervised Kohonen self-organizing neural networks. The work with ANN has two phases – adaptation and prediction. During the adaptation step the classification model is build. Measured data form groups after projection into two-dimensional space based on theirs similarity. After identification of these groups and establishing the connection with signal disorders ANN can be used for evaluation of newly measured signals. This algorithm was successfully applied for 540 signal classification obtained from immobilized acetylcholinesterase biosensor measurement of organophosphate and carbamate pesticides in vegetables, fruits, spices, potatoes and soil samples. From six different signal defects were successfully classified four – low response after substrate addition, equilibration at high values, slow equilibration after substrate addition respectively low sensitivity on syntostigmine.

  4. Signal regulatory proteins in the immune system

    NARCIS (Netherlands)

    van Beek, Ellen M.; Cochrane, Fiona; Barclay, A. Neil; van den Berg, Timo K.

    2005-01-01

    Signal regulatory proteins (SIRPs) constitute a family of transmembrane glycoproteins with extracellular Ig-like domains. Several SIRP family members have thus far been identified on myeloid and other cells in man, mouse, rat, and cattle. In the present study, we provide a description of the SIRP

  5. Music Signal Processing Using Vector Product Neural Networks

    Science.gov (United States)

    Fan, Z. C.; Chan, T. S.; Yang, Y. H.; Jang, J. S. R.

    2017-05-01

    We propose a novel neural network model for music signal processing using vector product neurons and dimensionality transformations. Here, the inputs are first mapped from real values into three-dimensional vectors then fed into a three-dimensional vector product neural network where the inputs, outputs, and weights are all three-dimensional values. Next, the final outputs are mapped back to the reals. Two methods for dimensionality transformation are proposed, one via context windows and the other via spectral coloring. Experimental results on the iKala dataset for blind singing voice separation confirm the efficacy of our model.

  6. Innate Immune Signaling Activated by MDR Bacteria in the Airway

    Science.gov (United States)

    Parker, Dane; Ahn, Danielle; Cohen, Taylor; Prince, Alice

    2015-01-01

    Health care-associated bacterial pneumonias due to multiple-drug resistant (MDR) pathogens are an important public health problem and are major causes of morbidity and mortality worldwide. In addition to antimicrobial resistance, these organisms have adapted to the milieu of the human airway and have acquired resistance to the innate immune clearance mechanisms that normally prevent pneumonia. Given the limited efficacy of antibiotics, bacterial clearance from the airway requires an effective immune response. Understanding how specific airway pathogens initiate and regulate innate immune signaling, and whether this response is excessive, leading to host-induced pathology may guide future immunomodulatory therapy. We will focus on three of the most important causes of health care-associated pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and review the mechanisms through which an inappropriate or damaging innate immune response is stimulated, as well as describe how airway pathogens cause persistent infection by evading immune activation. PMID:26582515

  7. Signaling Mechanisms in Pattern-Triggered Immunity (PTI)

    KAUST Repository

    Bigeard, Jean

    2015-01-01

    In nature, plants constantly have to face pathogen attacks. However, plant disease rarely occurs due to efficient immune systems possessed by the host plants. Pathogens are perceived by two different recognition systems that initiate the so-called pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), both of which are accompanied by a set of induced defenses that usually repel pathogen attacks. Here we discuss the complex network of signaling pathways occurring during PTI, focusing on the involvement of mitogen-activated protein kinases. © 2015 The Author.

  8. Immune challenges and visual signalling in tree frogs

    Science.gov (United States)

    Desprat, Julia L.; Lengagne, Thierry; Mondy, Nathalie

    2017-04-01

    In animals, mate-choice is often based on sexual signals that carry information and help the receiver make the best choice to improve the receiver's fitness. Orange visual sexual signals have been hypothesised to carry immune information because they are often due to carotenoid pigments which are also involved in immunity response. Although many studies have focused on the direct relationships between coloration and immunocompetence, few studies have simultaneously studied immunocompetent response and coloration variation after an immune challenge. We tested this hypothesis on starved and ad libitum-fed males of the European tree frog Hyla arborea. Our results show that male coloration is not a reliable indicator of its immune response capacity in this species. However, after an immune challenge induced by a PHA ( Phaseolus vulgaris phytohaemagglutinin) injection, starved males presented a significant coloration loss and this alteration was related to the immune response intensity. Taken together, these results suggest that the brighter (lighter) coloration may be used as a cue by female to exclude males with a recent immune challenge, due to diseases or parasites for example.

  9. High-Risk Human Papillomavirus Targets Crossroads in Immune Signaling

    Science.gov (United States)

    Tummers, Bart; Van Der Burg, Sjoerd H.

    2015-01-01

    Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review. PMID:26008697

  10. High-Risk Human Papillomavirus Targets Crossroads in Immune Signaling

    Directory of Open Access Journals (Sweden)

    Bart Tummers

    2015-05-01

    Full Text Available Persistent infections with a high-risk type human papillomavirus (hrHPV can progress to cancer. High-risk HPVs infect keratinocytes (KCs and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review.

  11. High-risk human papillomavirus targets crossroads in immune signaling.

    Science.gov (United States)

    Tummers, Bart; Burg, Sjoerd H Van Der

    2015-05-21

    Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review.

  12. Neural systems for choice and valuation with counterfactual learning signals.

    Science.gov (United States)

    Tobia, M J; Guo, R; Schwarze, U; Boehmer, W; Gläscher, J; Finckh, B; Marschner, A; Büchel, C; Obermayer, K; Sommer, T

    2014-04-01

    The purpose of this experiment was to test a computational model of reinforcement learning with and without fictive prediction error (FPE) signals to investigate how counterfactual consequences contribute to acquired representations of action-specific expected value, and to determine the functional neuroanatomy and neuromodulator systems that are involved. 80 male participants underwent dietary depletion of either tryptophan or tyrosine/phenylalanine to manipulate serotonin (5HT) and dopamine (DA), respectively. They completed 80 rounds (240 trials) of a strategic sequential investment task that required accepting interim losses in order to access a lucrative state and maximize long-term gains, while being scanned. We extended the standard Q-learning model by incorporating both counterfactual gains and losses into separate error signals. The FPE model explained the participants' data significantly better than a model that did not include counterfactual learning signals. Expected value from the FPE model was significantly correlated with BOLD signal change in the ventromedial prefrontal cortex (vmPFC) and posterior orbitofrontal cortex (OFC), whereas expected value from the standard model did not predict changes in neural activity. The depletion procedure revealed significantly different neural responses to expected value in the vmPFC, caudate, and dopaminergic midbrain in the vicinity of the substantia nigra (SN). Differences in neural activity were not evident in the standard Q-learning computational model. These findings demonstrate that FPE signals are an important component of valuation for decision making, and that the neural representation of expected value incorporates cortical and subcortical structures via interactions among serotonergic and dopaminergic modulator systems. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Signaling Cascades of Pasteurella multocida Toxin in Immune Evasion

    Science.gov (United States)

    Kubatzky, Katharina F.; Kloos, Bianca; Hildebrand, Dagmar

    2013-01-01

    Pasteurella multocida toxin (PMT) is a protein toxin found in toxigenic strains of Pasteurella multocida. PMT is the causative agent for atrophic rhinitis in pigs, a disease characterized by loss of nasal turbinate bones due to an inhibition of osteoblast function and an increase in osteoclast activity and numbers. Apart from this, PMT acts as a strong mitogen, protects from apoptosis and has an impact on the differentiation and function of immune cells. Many signaling pathways have been elucidated, however, the effect of these signaling cascades as a means to subvert the host’s immune system are just beginning to unravel. PMID:24064721

  14. Multiagent Intrusion Detection Based on Neural Network Detectors and Artificial Immune System

    OpenAIRE

    Vaitsekhovich, L.; Golovko, V; Rubanau, V.

    2009-01-01

    In this article the artificial immune system and neural network techniques for intrusion detection have been addressed. The AIS allows detecting unknown samples of computer attacks. The integration of AIS and neural networks as detectors permits to increase performance of the system security. The detector structure is based on the integration of the different neural networks namely RNN and MLP. The KDD-99 dataset was used for experiments performing. The experimental results show that such int...

  15. DMPD: ITAM-based signaling beyond the adaptive immune response. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16332394 ITAM-based signaling beyond the adaptive immune response. Fodor S, Jakus Z...TAM-based signaling beyond the adaptive immune response. PubmedID 16332394 Title ITAM-based signaling beyond the adaptive

  16. DMPD: IRAK1: a critical signaling mediator of innate immunity. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17890055 IRAK1: a critical signaling mediator of innate immunity. Gottipati S, Rao ...IRAK1: a critical signaling mediator of innate immunity. PubmedID 17890055 Title IRAK1: a critical signaling media

  17. The gateway theory: how regional neural activation creates a gateway for immune cells via an inflammation amplifier.

    Science.gov (United States)

    Ogura, Hideki; Arima, Yasunobu; Kamimura, Daisuke; Murakami, Masaaki

    2013-01-01

    The inflammation amplifier, a nuclear factor-kappa B (NF-kB)feedback loop in non-immune cells including fibroblasts and endothelial cells, describes how NF-kB-mediated transcriptions are enhanced to induce the inflammation in the presence of signal Tranducer and Activator of Transcription 3 (STAT3) activation. It was originally discovered in rheumatoid arthritis and multiple sclerosis mouse models and has since been shown to be associated with various human diseases and disorders including autoimmune diseases, metabolic syndromes, neurodegenerative diseases, and other inflammatory diseases. The amplifier begins with IL-17, which acts as the main signal to express NF-kB-mediated transcriptions, and IL-6, an NF-kB target, which functions as a fuel for the inflammation amplifier. Indeed, other NF-kB targets including various chemokines also act as effector molecules that cause local accumulation of various immune cells and subsequent inflammation. Through extensive studies in the multiple sclerosis model experimental autoimmune encephalomyelitis, we recently demonstrated that regional neural activation induces excess activation of the inflammation amplifier at specific blood vessels in the fifth lumbar cord, creating a gateway for immune cells to enter the central nervous system (CNS). We thus propose the gateway theory to describe how regional neural activation enables immune cells to enter the CNS from the blood and argue that this theory might provide novel therapeutic targets for inflammatory diseases and disorders.

  18. [A telemetery system for neural signal acquiring and processing].

    Science.gov (United States)

    Wang, Min; Song, Yongji; Suen, Jiantao; Zhao, Yiliang; Jia, Aibin; Zhu, Jianping

    2011-02-01

    Recording and extracting characteristic brain signals in freely moving animals is the basic and significant requirement in the study of brain-computer interface (BCI). To record animal's behaving and extract characteristic brain signals simultaneously could help understand the complex behavior of neural ensembles. Here, a system was established to record and analyse extracellular discharge in freely moving rats for the study of BCI. It comprised microelectrode and micro-driver assembly, analog front end (AFE), programmer system on chip (PSoC), wireless communication and the LabVIEW used as the platform for the graphic user interface.

  19. Stochastic resonance with colored noise for neural signal detection.

    Science.gov (United States)

    Duan, Fabing; Chapeau-Blondeau, François; Abbott, Derek

    2014-01-01

    We analyze signal detection with nonlinear test statistics in the presence of colored noise. In the limits of small signal and weak noise correlation, the optimal test statistic and its performance are derived under general conditions, especially concerning the type of noise. We also analyze, for a threshold nonlinearity-a key component of a neural model, the conditions for noise-enhanced performance, establishing that colored noise is superior to white noise for detection. For a parallel array of nonlinear elements, approximating neurons, we demonstrate even broader conditions allowing noise-enhanced detection, via a form of suprathreshold stochastic resonance.

  20. Fate Specification of Neural Plate Border by Canonical Wnt Signaling and Grhl3 is Crucial for Neural Tube Closure.

    Science.gov (United States)

    Kimura-Yoshida, Chiharu; Mochida, Kyoko; Ellwanger, Kristina; Niehrs, Christof; Matsuo, Isao

    2015-06-01

    During primary neurulation, the separation of a single-layered ectodermal sheet into the surface ectoderm (SE) and neural tube specifies SE and neural ectoderm (NE) cell fates. The mechanisms underlying fate specification in conjunction with neural tube closure are poorly understood. Here, by comparing expression profiles between SE and NE lineages, we observed that uncommitted progenitor cells, expressing stem cell markers, are present in the neural plate border/neural fold prior to neural tube closure. Our results also demonstrated that canonical Wnt and its antagonists, DKK1/KREMEN1, progressively specify these progenitors into SE or NE fates in accord with the progress of neural tube closure. Additionally, SE specification of the neural plate border via canonical Wnt signaling is directed by the grainyhead-like 3 (Grhl3) transcription factor. Thus, we propose that the fate specification of uncommitted progenitors in the neural plate border by canonical Wnt signaling and its downstream effector Grhl3 is crucial for neural tube closure. This study implicates that failure in critical genetic factors controlling fate specification of progenitor cells in the neural plate border/neural fold coordinated with neural tube closure may be potential causes of human neural tube defects.

  1. Signalling through C-type lectin receptors: shaping immune responses

    NARCIS (Netherlands)

    Geijtenbeek, Teunis B. H.; Gringhuis, Sonja I.

    2009-01-01

    C-type lectin receptors (CLRs) expressed by dendritic cells are crucial for tailoring immune responses to pathogens. Following pathogen binding, CLRs trigger distinct signalling pathways that induce the expression of specific cytokines which determine T cell polarization fates. Some CLRs can induce

  2. Signalling by the phosphoinositide 3-kinase family in immune cells

    Science.gov (United States)

    Okkenhaug, Klaus

    2015-01-01

    Phosphoinositide 3-kinases control many important aspects of immune cell development, differentiation and function. Mammals have eight PI3K catalytic subunits which are divided into 3 classes based on similarities in structure and function. Specific roles for the class I PI3Ks have been broadly investigated and are relatively well understood as is the function of their corresponding phosphatases. More recently, specific roles for the class II and class III PI3Ks have emerged. Through vertebrate evolution and in parallel with the evolution of adaptive immunity, there has been a dramatic increase not only in the genes for PI3K subunits but also in genes for phosphatases that act on 3-phopshoinositides and on 3-phosphoinositide binding proteins. Our understanding of the PI3Ks in immunity is guided by fundamental discoveries made in simpler model organisms as well as by appreciating new adaptions of this signalling module in mammals in general and immune cells in particular. PMID:23330955

  3. Metabolism-associated danger signal-induced immune response and reverse immune checkpoint-activated CD40(+) monocyte differentiation.

    Science.gov (United States)

    Dai, Jin; Fang, Pu; Saredy, Jason; Xi, Hang; Ramon, Cueto; Yang, William; Choi, Eric T; Ji, Yong; Mao, Wei; Yang, Xiaofeng; Wang, Hong

    2017-07-24

    Adaptive immunity is critical for disease progression and modulates T cell (TC) and antigen-presenting cell (APC) functions. Three signals were initially proposed for adaptive immune activation: signal 1 antigen recognition, signal 2 co-stimulation or co-inhibition, and signal 3 cytokine stimulation. In this article, we propose to term signal 2 as an immune checkpoint, which describes interactions of paired molecules leading to stimulation (stimulatory immune checkpoint) or inhibition (inhibitory immune checkpoint) of an immune response. We classify immune checkpoint into two categories: one-way immune checkpoint for forward signaling towards TC only, and two-way immune checkpoint for both forward and reverse signaling towards TC and APC, respectively. Recently, we and others provided evidence suggesting that metabolic risk factors (RF) activate innate and adaptive immunity, involving the induction of immune checkpoint molecules. We summarize these findings and suggest a novel theory, metabolism-associated danger signal (MADS) recognition, by which metabolic RF activate innate and adaptive immunity. We emphasize that MADS activates the reverse immune checkpoint which leads to APC inflammation in innate and adaptive immunity. Our recent evidence is shown that metabolic RF, such as uremic toxin or hyperhomocysteinemia, induced immune checkpoint molecule CD40 expression in monocytes (MC) and elevated serum soluble CD40 ligand (sCD40L) resulting in CD40(+) MC differentiation. We propose that CD40(+) MC is a novel pro-inflammatory MC subset and a reliable biomarker for chronic kidney disease severity. We summarize that CD40:CD40L immune checkpoint can induce TC and APC activation via forward stimulatory, reverse stimulatory, and TC contact-independent immune checkpoints. Finally, we modeled metabolic RF-induced two-way stimulatory immune checkpoint amplification and discussed potential signaling pathways including AP-1, NF-κB, NFAT, STAT, and DNA methylation and their

  4. Modular and Coordinated Expression of Immune System Regulatory and Signalling Components in the Developing and Adult Nervous System

    Directory of Open Access Journals (Sweden)

    Jimena eMonzon-Sandoval

    2015-08-01

    Full Text Available During development, the nervous system is assembled and sculpted through a concerted series of neurodevelopmental events orchestrated by a complex genetic programme. While neural-specific gene expression plays a critical part in this process, in recent years, a number of immune-related signalling and regulatory components have also been shown to play key physiological roles in the developing and adult nervous system. While the involvement of individual immune-related signalling components in neural functions may reflect their ubiquitous character, it may also reflect a much wider, as yet undescribed, genetic network of immune–related molecules acting as an intrinsic component of the neural-specific regulatory machinery that ultimately shapes the nervous system. In order to gain insights into the scale and wider functional organization of immune-related genetic networks in the nervous system, we examined the large scale pattern of expression of these genes in the brain. Our results show a highly significant correlated expression and transcriptional clustering among immune-related genes in the developing and adult brain, and this correlation was the highest in the brain when compared to muscle, liver, kidney and endothelial cells. We experimentally tested the regulatory clustering of immune system genes by using microarray expression profiling in cultures of dissociated neurons stimulated with the pro-inflammatory cytokine TNF-alpha, and found a highly significant enrichment of immune system-related genes among the resulting differentially expressed genes. Our findings strongly suggest a coherent recruitment of entire immune-related genetic regulatory modules by the neural-specific genetic programme that shapes the nervous system.

  5. Modular and coordinated expression of immune system regulatory and signaling components in the developing and adult nervous system

    Science.gov (United States)

    Monzón-Sandoval, Jimena; Castillo-Morales, Atahualpa; Crampton, Sean; McKelvey, Laura; Nolan, Aoife; O’Keeffe, Gerard; Gutierrez, Humberto

    2015-01-01

    During development, the nervous system (NS) is assembled and sculpted through a concerted series of neurodevelopmental events orchestrated by a complex genetic programme. While neural-specific gene expression plays a critical part in this process, in recent years, a number of immune-related signaling and regulatory components have also been shown to play key physiological roles in the developing and adult NS. While the involvement of individual immune-related signaling components in neural functions may reflect their ubiquitous character, it may also reflect a much wider, as yet undescribed, genetic network of immune–related molecules acting as an intrinsic component of the neural-specific regulatory machinery that ultimately shapes the NS. In order to gain insights into the scale and wider functional organization of immune-related genetic networks in the NS, we examined the large scale pattern of expression of these genes in the brain. Our results show a highly significant correlated expression and transcriptional clustering among immune-related genes in the developing and adult brain, and this correlation was the highest in the brain when compared to muscle, liver, kidney and endothelial cells. We experimentally tested the regulatory clustering of immune system (IS) genes by using microarray expression profiling in cultures of dissociated neurons stimulated with the pro-inflammatory cytokine TNF-alpha, and found a highly significant enrichment of immune system-related genes among the resulting differentially expressed genes. Our findings strongly suggest a coherent recruitment of entire immune-related genetic regulatory modules by the neural-specific genetic programme that shapes the NS. PMID:26379506

  6. Neural crest specification by noncanonical Wnt signaling and PAR-1

    Science.gov (United States)

    Ossipova, Olga; Sokol, Sergei Y.

    2011-01-01

    Neural crest (NC) cells are multipotent progenitors that form at the neural plate border, undergo epithelial-mesenchymal transition and migrate to diverse locations in vertebrate embryos to give rise to many cell types. Multiple signaling factors, including Wnt proteins, operate during early embryonic development to induce the NC cell fate. Whereas the requirement for the Wnt/β-catenin pathway in NC specification has been well established, a similar role for Wnt proteins that do not stabilize β-catenin has remained unclear. Our gain- and loss-of-function experiments implicate Wnt11-like proteins in NC specification in Xenopus embryos. In support of this conclusion, modulation of β-catenin-independent signaling through Dishevelled and Ror2 causes predictable changes in premigratory NC. Morpholino-mediated depletion experiments suggest that Wnt11R, a Wnt protein that is expressed in neuroectoderm adjacent to the NC territory, is required for NC formation. Wnt11-like signals might specify NC by altering the localization and activity of the serine/threonine polarity kinase PAR-1 (also known as microtubule-associated regulatory kinase or MARK), which itself plays an essential role in NC formation. Consistent with this model, PAR-1 RNA rescues NC markers in embryos in which noncanonical Wnt signaling has been blocked. These experiments identify novel roles for Wnt11R and PAR-1 in NC specification and reveal an unexpected connection between morphogenesis and cell fate. PMID:22110058

  7. Lossless Compression Schemes for ECG Signals Using Neural Network Predictors

    Directory of Open Access Journals (Sweden)

    C. Eswaran

    2007-01-01

    Full Text Available This paper presents lossless compression schemes for ECG signals based on neural network predictors and entropy encoders. Decorrelation is achieved by nonlinear prediction in the first stage and encoding of the residues is done by using lossless entropy encoders in the second stage. Different types of lossless encoders, such as Huffman, arithmetic, and runlength encoders, are used. The performances of the proposed neural network predictor-based compression schemes are evaluated using standard distortion and compression efficiency measures. Selected records from MIT-BIH arrhythmia database are used for performance evaluation. The proposed compression schemes are compared with linear predictor-based compression schemes and it is shown that about 11% improvement in compression efficiency can be achieved for neural network predictor-based schemes with the same quality and similar setup. They are also compared with other known ECG compression methods and the experimental results show that superior performances in terms of the distortion parameters of the reconstructed signals can be achieved with the proposed schemes.

  8. Innate immune signaling in defense against intestinal microbes

    Science.gov (United States)

    Kinnebrew, Melissa A.; Pamer, Eric G.

    2015-01-01

    Summary The gastrointestinal system is a common entry point for pathogenic microbes to access the inner environment of the body. Antimicrobial factors produced by the intestinal mucosa limit the translocation of both commensal and pathogenic microbes across the intestinal epithelial cell barrier. The regulation of these host defense mechanisms largely depends on the activation of innate immune receptors by microbial molecules. Under steady-state conditions, the microbiota provides constitutive signals to the innate immune system, which helps to maintain a healthy inflammatory tone within the intestinal mucosa and, thus, enhances resistance to infection with enteric pathogens. During an acute infection, the intestinal epithelial cell barrier is breached, and the detection of microbial molecules in the intestinal lamina propria rapidly stimulates innate immune signaling pathways that coordinate early defense mechanisms. Herein, we review how microbial molecules shed by both commensal and pathogenic microbes direct host defenses at the intestinal mucosa. We highlight the signaling pathways, effector molecules, and cell populations that are activated by microbial molecule recognition and, thereby, are involved in the maintenance of homeostatic levels of host defense and in the early response to acute enteric infection. Finally, we discuss how manipulation of these host defense pathways by stimulating innate immune receptors is a potential therapeutic strategy to prevent or alleviate intestinal disease. PMID:22168416

  9. Neural plasticity in the gastrointestinal tract: chronic inflammation, neurotrophic signals, and hypersensitivity.

    Science.gov (United States)

    Demir, Ihsan Ekin; Schäfer, Karl-Herbert; Tieftrunk, Elke; Friess, Helmut; Ceyhan, Güralp O

    2013-04-01

    Neural plasticity is not only the adaptive response of the central nervous system to learning, structural damage or sensory deprivation, but also an increasingly recognized common feature of the gastrointestinal (GI) nervous system during pathological states. Indeed, nearly all chronic GI disorders exhibit a disease-stage-dependent, structural and functional neuroplasticity. At structural level, GI neuroplasticity usually comprises local tissue hyperinnervation (neural sprouting, neural, and ganglionic hypertrophy) next to hypoinnervated areas, a switch in the neurochemical (neurotransmitter/neuropeptide) code toward preferential expression of neuropeptides which are frequently present in nociceptive neurons (e.g., substance P/SP, calcitonin-gene-related-peptide/CGRP) and of ion channels (TRPV1, TRPA1, PAR2), and concomitant activation of peripheral neural glia. The functional counterpart of these structural alterations is altered neuronal electric activity, leading to organ dysfunction (e.g., impaired motility and secretion), together with reduced sensory thresholds, resulting in hypersensitivity and pain. The present review underlines that neural plasticity in all GI organs, starting from esophagus, stomach, small and large intestine to liver, gallbladder, and pancreas, actually exhibits common phenotypes and mechanisms. Careful appraisal of these GI neuroplastic alterations reveals that--no matter which etiology, i.e., inflammatory, infectious, neoplastic/malignant, or degenerative--neural plasticity in the GI tract primarily occurs in the presence of chronic tissue- and neuro-inflammation. It seems that studying the abundant trophic and activating signals which are generated during this neuro-immune-crosstalk represents the key to understand the remarkable neuroplasticity of the GI tract.

  10. Network modeling reveals prevalent negative regulatory relationships between signaling sectors in Arabidopsis immune signaling.

    Directory of Open Access Journals (Sweden)

    Masanao Sato

    Full Text Available Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways. Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network. The plant immune signaling network, which controls inducible responses to pathogen attack, is such a complex network. We studied the Arabidopsis immune signaling network upon challenge with a strain of the bacterial pathogen Pseudomonas syringae expressing the effector protein AvrRpt2 (Pto DC3000 AvrRpt2. This bacterial strain feeds multiple inputs into the signaling network, allowing many parts of the network to be activated at once. mRNA profiles for 571 immune response genes of 22 Arabidopsis immunity mutants and wild type were collected 6 hours after inoculation with Pto DC3000 AvrRpt2. The mRNA profiles were analyzed as detailed descriptions of changes in the network state resulting from the genetic perturbations. Regulatory relationships among the genes corresponding to the mutations were inferred by recursively applying a non-linear dimensionality reduction procedure to the mRNA profile data. The resulting static network model accurately predicted 23 of 25 regulatory relationships reported in the literature, suggesting that predictions of novel regulatory relationships are also accurate. The network model revealed two striking features: (i the components of the network are highly interconnected; and (ii negative regulatory relationships are common between signaling sectors. Complex regulatory relationships, including a novel negative regulatory relationship between the early microbe-associated molecular pattern-triggered signaling sectors and the salicylic acid sector, were further validated. We propose that prevalent negative regulatory relationships among the signaling sectors make the plant immune signaling network a "sector

  11. The gateway theory: bridging neural and immune interactions in the CNS

    Science.gov (United States)

    Kamimura, Daisuke; Yamada, Moe; Harada, Masaya; Sabharwal, Lavannya; Meng, Jie; Bando, Hidenori; Ogura, Hideki; Atsumi, Toru; Arima, Yasunobu; Murakami, Masaaki

    2013-01-01

    The central nervous system (CNS) is considered an immune-privileged tissue protected by a specific vessel structure, the blood-brain barrier (BBB). Upon infection or traumatic injury in the CNS, the BBB is breached, and various immune cells are recruited to the affected area. In the case of autoimmune diseases in the CNS like multiple sclerosis (MS), autoreactive T cells against some CNS-specific antigens can theoretically attack neurons throughout the CNS. The affected CNS regions in MS patients can be detected as multiple focal plaques in the cerebrum, thoracic cord, and other regions. Vision problems are often associated with the initial phase of MS, suggesting a disturbance in the optic nerves. These observations raise the possibility that there exist specific signals that direct autoreactive T cells past the BBB and into particular sites of the CNS. Using a mouse model of MS, experimental autoimmune encephalomyelitis (EAE), we recently defined the mechanism of the pathogenesis in which regional neural stimulations modulate the status of the blood vessel endothelium to allow the invasion of autoreactive T cells into specific sites of the CNS via the fifth lumbar cord. This gate for autoreactive T cells can be artificially manipulated by removing gravity forces on the hind legs or by electric pulses to the soleus muscles, quadriceps, and triceps of mice, resulting in an accumulation of autoreactive T cells in the intended regions via the activation of regional neurons. Gating blood vessels by regional neural stimulations, a phenomenon we call the gateway theory, has potential therapeutic value not only in preventing autoimmunity, but also in augmenting the effects of cancer immunotherapies. PMID:24194696

  12. Signal Processing in Periodically Forced Gradient Frequency Neural Networks.

    Science.gov (United States)

    Kim, Ji Chul; Large, Edward W

    2015-01-01

    Oscillatory instability at the Hopf bifurcation is a dynamical phenomenon that has been suggested to characterize active non-linear processes observed in the auditory system. Networks of oscillators poised near Hopf bifurcation points and tuned to tonotopically distributed frequencies have been used as models of auditory processing at various levels, but systematic investigation of the dynamical properties of such oscillatory networks is still lacking. Here we provide a dynamical systems analysis of a canonical model for gradient frequency neural networks driven by a periodic signal. We use linear stability analysis to identify various driven behaviors of canonical oscillators for all possible ranges of model and forcing parameters. The analysis shows that canonical oscillators exhibit qualitatively different sets of driven states and transitions for different regimes of model parameters. We classify the parameter regimes into four main categories based on their distinct signal processing capabilities. This analysis will lead to deeper understanding of the diverse behaviors of neural systems under periodic forcing and can inform the design of oscillatory network models of auditory signal processing.

  13. Dual roles for spike signaling in cortical neural populations

    Directory of Open Access Journals (Sweden)

    Dana eBallard

    2011-06-01

    Full Text Available A prominent feature of signaling in cortical neurons is that of randomness in the action potential. The output of a typical pyramidal cell can be well fit with a Poisson model, and variations in the Poisson rate repeatedly have been shown to be correlated with stimuli. However while the rate provides a very useful characterization of neural spike data, it may not be the most fundamental description of the signaling code. Recent data showing γ frequency range multi-cell action potential correlations, together with spike timing dependent plasticity, are spurring a re-examination of the classical model, since precise timing codes imply that the generation of spikes is essentially deterministic. Could the observed Poisson randomness and timing determinism reflect two separate modes of communication, or do they somehow derive from a single process? We investigate in a timing-based model whether the apparent incompatibility between these probabilistic and deterministic observations may be resolved by examining how spikes could be used in the underlying neural circuits. The crucial component of this model draws on dual roles for spike signaling. In learning receptive fields from ensembles of inputs, spikes need to behave probabilistically, whereas for fast signaling of individual stimuli, the spikes need to behave deterministically. Our simulations show that this combination is possible if deterministic signals using γ latency coding are probabilistically routed through different members of a cortical cell population at different times. This model exhibits standard features characteristic of Poisson models such as orientation tuning post-stimulus histograms and exponential interval histograms. In addition it makes testable predictions that follow from the γ latency coding.

  14. Artificial neural network based approach to EEG signal simulation.

    Science.gov (United States)

    Tomasevic, Nikola M; Neskovic, Aleksandar M; Neskovic, Natasa J

    2012-06-01

    In this paper a new approach to the electroencephalogram (EEG) signal simulation based on the artificial neural networks (ANN) is proposed. The aim was to simulate the spontaneous human EEG background activity based solely on the experimentally acquired EEG data. Therefore, an EEG measurement campaign was conducted on a healthy awake adult in order to obtain an adequate ANN training data set. As demonstration of the performance of the ANN based approach, comparisons were made against autoregressive moving average (ARMA) filtering based method. Comprehensive quantitative and qualitative statistical analysis showed clearly that the EEG process obtained by the proposed method was in satisfactory agreement with the one obtained by measurements.

  15. Fault Tolerant Neural Network for ECG Signal Classification Systems

    Directory of Open Access Journals (Sweden)

    MERAH, M.

    2011-08-01

    Full Text Available The aim of this paper is to apply a new robust hardware Artificial Neural Network (ANN for ECG classification systems. This ANN includes a penalization criterion which makes the performances in terms of robustness. Specifically, in this method, the ANN weights are normalized using the auto-prune method. Simulations performed on the MIT ? BIH ECG signals, have shown that significant robustness improvements are obtained regarding potential hardware artificial neuron failures. Moreover, we show that the proposed design achieves better generalization performances, compared to the standard back-propagation algorithm.

  16. Automated embolic signal detection using Deep Convolutional Neural Network.

    Science.gov (United States)

    Sombune, Praotasna; Phienphanich, Phongphan; Phuechpanpaisal, Sutanya; Muengtaweepongsa, Sombat; Ruamthanthong, Anuchit; Tantibundhit, Charturong

    2017-07-01

    This work investigated the potential of Deep Neural Network in detection of cerebral embolic signal (ES) from transcranial Doppler ultrasound (TCD). The resulting system is aimed to couple with TCD devices in diagnosing a risk of stroke in real-time with high accuracy. The Adaptive Gain Control (AGC) approach developed in our previous study is employed to capture suspected ESs in real-time. By using spectrograms of the same TCD signal dataset as that of our previous work as inputs and the same experimental setup, Deep Convolutional Neural Network (CNN), which can learn features while training, was investigated for its ability to bypass the traditional handcrafted feature extraction and selection process. Extracted feature vectors from the suspected ESs are later determined whether they are of an ES, artifact (AF) or normal (NR) interval. The effectiveness of the developed system was evaluated over 19 subjects going under procedures generating emboli. The CNN-based system could achieve in average of 83.0% sensitivity, 80.1% specificity, and 81.4% accuracy, with considerably much less time consumption in development. The certainly growing set of training samples and computational resources will contribute to high performance. Besides having potential use in various clinical ES monitoring settings, continuation of this promising study will benefit developments of wearable applications by leveraging learnable features to serve demographic differentials.

  17. DMPD: Innate immune responses: crosstalk of signaling and regulation of genetranscription. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16753195 Innate immune responses: crosstalk of signaling and regulation of genetranscript...l) (.csml) Show Innate immune responses: crosstalk of signaling and regulation of genetranscription. PubmedI...D 16753195 Title Innate immune responses: crosstalk of signaling and regulation of genetranscript

  18. Neural regulation of innate and adaptive immunity in the gut

    NARCIS (Netherlands)

    Dhawan, S.

    2017-01-01

    This thesis investigates the role of neurotransmitters acetylcholine (ACh) and norepinephrine (NE), in modulating the innate and adaptive immune function in the intestine, during physiological and pathophysiological conditions. Furthermore, this thesis attempts to advance our current understanding

  19. Metabolic signals and innate immune activation in obesity and exercise.

    Science.gov (United States)

    Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

    2015-01-01

    The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities. Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.

  20. Signal transduction in cells of the immune system in microgravity

    Directory of Open Access Journals (Sweden)

    Huber Kathrin

    2008-10-01

    Full Text Available Abstract Life on Earth developed in the presence and under the constant influence of gravity. Gravity has been present during the entire evolution, from the first organic molecule to mammals and humans. Modern research revealed clearly that gravity is important, probably indispensable for the function of living systems, from unicellular organisms to men. Thus, gravity research is no more or less a fundamental question about the conditions of life on Earth. Since the first space missions and supported thereafter by a multitude of space and ground-based experiments, it is well known that immune cell function is severely suppressed in microgravity, which renders the cells of the immune system an ideal model organism to investigate the influence of gravity on the cellular and molecular level. Here we review the current knowledge about the question, if and how cellular signal transduction depends on the existence of gravity, with special focus on cells of the immune system. Since immune cell function is fundamental to keep the organism under imnological surveillance during the defence against pathogens, to investigate the effects and possible molecular mechanisms of altered gravity is indispensable for long-term space flights to Earth Moon or Mars. Thus, understanding the impact of gravity on cellular functions on Earth will provide not only important informations about the development of life on Earth, but also for therapeutic and preventive strategies to cope successfully with medical problems during space exploration.

  1. How complex are intracellular immune receptor signaling complexes?

    Directory of Open Access Journals (Sweden)

    Vera eBonardi

    2012-10-01

    Full Text Available Nucleotide binding leucine-rich repeat proteins (NLRs are the major class of intracellular immune receptors in plants. NLRs typically function to specifically recognize pathogen effectors and to initiate and control defense responses that severely limit pathogen growth in plants (termed effector triggered immunity, or ETI. Despite numerous reports supporting a central role in innate immunity, the molecular mechanisms driving NLR activation and downstream signaling remain largely elusive. Recent reports shed light on the pre- and post-activation dynamics of a few NLR-containing protein complexes. Recent technological advances in the use of proteomics may enable high-resolution definition of immune protein complexes and possible activation-relevant post-translational modifications of the components in these complexes. In this mini-review, we focus on research aimed at characterizing pre- and post-activation NLR protein complexes and the molecular events that follow activation. We discuss the use of new or improved technologies as tools to unveil the molecular mechanisms that define NLR-mediated pathogen recognition.

  2. Partitioning, repressing and derepressing: dynamic regulations in MLA immune receptor triggered defense signaling.

    Science.gov (United States)

    Chang, Cheng; Zhang, Ling; Shen, Qian-Hua

    2013-10-08

    Plants and animals have evolved intracellular nucleotide-binding domain and leucine-rich repeat-containing immune receptors (NLRs) to perceive non-self and trigger immune responses. Plant NLRs detect strain-specific pathogen effectors and activate immune signaling leading to extensive transcriptional reprogramming and termination of pathogen infection. Here we review the recent findings in barley MLA immune receptor mediated immune responses against the barley powdery mildew fungus. We focus on nucleocytoplasmic partitioning of immune receptor, bifurcation of immune signaling, transcriptional repression and derepression connecting receptor activation to immune responses. We also discuss similar findings from other plant NLRs where appropriate.

  3. An FGF3-BMP Signaling Axis Regulates Caudal Neural Tube Closure, Neural Crest Specification and Anterior-Posterior Axis Extension.

    Science.gov (United States)

    Anderson, Matthew J; Schimmang, Thomas; Lewandoski, Mark

    2016-05-01

    During vertebrate axis extension, adjacent tissue layers undergo profound morphological changes: within the neuroepithelium, neural tube closure and neural crest formation are occurring, while within the paraxial mesoderm somites are segmenting from the presomitic mesoderm (PSM). Little is known about the signals between these tissues that regulate their coordinated morphogenesis. Here, we analyze the posterior axis truncation of mouse Fgf3 null homozygotes and demonstrate that the earliest role of PSM-derived FGF3 is to regulate BMP signals in the adjacent neuroepithelium. FGF3 loss causes elevated BMP signals leading to increased neuroepithelium proliferation, delay in neural tube closure and premature neural crest specification. We demonstrate that elevated BMP4 depletes PSM progenitors in vitro, phenocopying the Fgf3 mutant, suggesting that excessive BMP signals cause the Fgf3 axis defect. To test this in vivo we increased BMP signaling in Fgf3 mutants by removing one copy of Noggin, which encodes a BMP antagonist. In such mutants, all parameters of the Fgf3 phenotype were exacerbated: neural tube closure delay, premature neural crest specification, and premature axis termination. Conversely, genetically decreasing BMP signaling in Fgf3 mutants, via loss of BMP receptor activity, alleviates morphological defects. Aberrant apoptosis is observed in the Fgf3 mutant tailbud. However, we demonstrate that cell death does not cause the Fgf3 phenotype: blocking apoptosis via deletion of pro-apoptotic genes surprisingly increases all Fgf3 defects including causing spina bifida. We demonstrate that this counterintuitive consequence of blocking apoptosis is caused by the increased survival of BMP-producing cells in the neuroepithelium. Thus, we show that FGF3 in the caudal vertebrate embryo regulates BMP signaling in the neuroepithelium, which in turn regulates neural tube closure, neural crest specification and axis termination. Uncovering this FGF3-BMP signaling axis is

  4. Theta signal as the neural signature of social exclusion.

    Science.gov (United States)

    Cristofori, Irene; Moretti, Laura; Harquel, Sylvain; Posada, Andres; Deiana, Gianluca; Isnard, Jean; Mauguière, François; Sirigu, Angela

    2013-10-01

    The feeling of being excluded from a social interaction triggers social pain, a sensation as intense as actual physical pain. Little is known about the neurophysiological underpinnings of social pain. We addressed this issue using intracranial electroencephalography in 15 patients performing a ball game where inclusion and exclusion blocks were alternated. Time-frequency analyses showed an increase in power of theta-band oscillations during exclusion in the anterior insula (AI) and posterior insula, the subgenual anterior cingulate cortex (sACC), and the fusiform "face area" (FFA). Interestingly, the AI showed an initial fast response to exclusion but the signal rapidly faded out. Activity in the sACC gradually increased and remained significant thereafter. This suggests that the AI may signal social pain by detecting emotional distress caused by the exclusion, whereas the sACC may be linked to the learning aspects of social pain. Theta activity in the FFA was time-locked to the observation of a player poised to exclude the participant, suggesting that the FFA encodes the social value of faces. Taken together, our findings suggest that theta activity represents the neural signature of social pain. The time course of this signal varies across regions important for processing emotional features linked to social information.

  5. Signalling crosstalk in light stress and immune reactions in plants.

    Science.gov (United States)

    Trotta, Andrea; Rahikainen, Moona; Konert, Grzegorz; Finazzi, Giovanni; Kangasjärvi, Saijaliisa

    2014-04-19

    The evolutionary history of plants is tightly connected with the evolution of microbial pathogens and herbivores, which use photosynthetic end products as a source of life. In these interactions, plants, as the stationary party, have evolved sophisticated mechanisms to sense, signal and respond to the presence of external stress agents. Chloroplasts are metabolically versatile organelles that carry out fundamental functions in determining appropriate immune reactions in plants. Besides photosynthesis, chloroplasts host key steps in the biosynthesis of amino acids, stress hormones and secondary metabolites, which have a great impact on resistance against pathogens and insect herbivores. Changes in chloroplast redox signalling pathways and reactive oxygen species metabolism also mediate local and systemic signals, which modulate plant resistance to light stress and disease. Moreover, interplay among chloroplastic signalling networks and plasma membrane receptor kinases is emerging as a key mechanism that modulates stress responses in plants. This review highlights the central role of chloroplasts in the signalling crosstalk that essentially determines the outcome of plant-pathogen interactions in plants.

  6. Active random noise control using adaptive learning rate neural networks with an immune feedback law

    Science.gov (United States)

    Sasaki, Minoru; Kuribayashi, Takumi; Ito, Satoshi

    2005-12-01

    In this paper an active random noise control using adaptive learning rate neural networks with an immune feedback law is presented. The adaptive learning rate strategy increases the learning rate by a small constant if the current partial derivative of the objective function with respect to the weight and the exponential average of the previous derivatives have the same sign, otherwise the learning rate is decreased by a proportion of its value. The use of an adaptive learning rate attempts to keep the learning step size as large as possible without leading to oscillation. In the proposed method, because of the immune feedback law change a learning rate of the neural networks individually and adaptively, it is expected that a cost function minimize rapidly and training time is decreased. Numerical simulations and experiments of active random noise control with the transfer function of the error path will be performed, to validate the convergence properties of the adaptive learning rate Neural Networks with the immune feedback law. Control results show that adaptive learning rate Neural Networks control structure can outperform linear controllers and conventional neural network controller for the active random noise control.

  7. Two multichannel integrated circuits for neural recording and signal processing.

    Science.gov (United States)

    Obeid, Iyad; Morizio, James C; Moxon, Karen A; Nicolelis, Miguel A L; Wolf, Patrick D

    2003-02-01

    We have developed, manufactured, and tested two analog CMOS integrated circuit "neurochips" for recording from arrays of densely packed neural electrodes. Device A is a 16-channel buffer consisting of parallel noninverting amplifiers with a gain of 2 V/V. Device B is a 16-channel two-stage analog signal processor with differential amplification and high-pass filtering. It features selectable gains of 250 and 500 V/V as well as reference channel selection. The resulting amplifiers on Device A had a mean gain of 1.99 V/V with an equivalent input noise of 10 microV(rms). Those on Device B had mean gains of 53.4 and 47.4 dB with a high-pass filter pole at 211 Hz and an equivalent input noise of 4.4 microV(rms). Both devices were tested in vivo with electrode arrays implanted in the somatosensory cortex.

  8. Modulation of hippocampal neural plasticity by glucose-related signaling.

    Science.gov (United States)

    Mainardi, Marco; Fusco, Salvatore; Grassi, Claudio

    2015-01-01

    Hormones and peptides involved in glucose homeostasis are emerging as important modulators of neural plasticity. In this regard, increasing evidence shows that molecules such as insulin, insulin-like growth factor-I, glucagon-like peptide-1, and ghrelin impact on the function of the hippocampus, which is a key area for learning and memory. Indeed, all these factors affect fundamental hippocampal properties including synaptic plasticity (i.e., synapse potentiation and depression), structural plasticity (i.e., dynamics of dendritic spines), and adult neurogenesis, thus leading to modifications in cognitive performance. Here, we review the main mechanisms underlying the effects of glucose metabolism on hippocampal physiology. In particular, we discuss the role of these signals in the modulation of cognitive functions and their potential implications in dysmetabolism-related cognitive decline.

  9. Correlated EEG Signals Simulation Based on Artificial Neural Networks.

    Science.gov (United States)

    Tomasevic, Nikola M; Neskovic, Aleksandar M; Neskovic, Natasa J

    2017-08-01

    In recent years, simulation of the human electroencephalogram (EEG) data found its important role in medical domain and neuropsychology. In this paper, a novel approach to simulation of two cross-correlated EEG signals is proposed. The proposed method is based on the principles of artificial neural networks (ANN). Contrary to the existing EEG data simulators, the ANN-based approach was leveraged solely on the experimentally acquired EEG data. More precisely, measured EEG data were utilized to optimize the simulator which consisted of two ANN models (each model responsible for generation of one EEG sequence). In order to acquire the EEG recordings, the measurement campaign was carried out on a healthy awake adult having no cognitive, physical or mental load. For the evaluation of the proposed approach, comprehensive quantitative and qualitative statistical analysis was performed considering probability distribution, correlation properties and spectral characteristics of generated EEG processes. The obtained results clearly indicated the satisfactory agreement with the measurement data.

  10. Modulation of Hippocampal Neural Plasticity by Glucose-Related Signaling

    Directory of Open Access Journals (Sweden)

    Marco Mainardi

    2015-01-01

    Full Text Available Hormones and peptides involved in glucose homeostasis are emerging as important modulators of neural plasticity. In this regard, increasing evidence shows that molecules such as insulin, insulin-like growth factor-I, glucagon-like peptide-1, and ghrelin impact on the function of the hippocampus, which is a key area for learning and memory. Indeed, all these factors affect fundamental hippocampal properties including synaptic plasticity (i.e., synapse potentiation and depression, structural plasticity (i.e., dynamics of dendritic spines, and adult neurogenesis, thus leading to modifications in cognitive performance. Here, we review the main mechanisms underlying the effects of glucose metabolism on hippocampal physiology. In particular, we discuss the role of these signals in the modulation of cognitive functions and their potential implications in dysmetabolism-related cognitive decline.

  11. Acquiring neural signals for developing a perception and cognition model

    Science.gov (United States)

    Li, Wei; Li, Yunyi; Chen, Genshe; Shen, Dan; Blasch, Erik; Pham, Khanh; Lynch, Robert

    2012-06-01

    The understanding of how humans process information, determine salience, and combine seemingly unrelated information is essential to automated processing of large amounts of information that is partially relevant, or of unknown relevance. Recent neurological science research in human perception, and in information science regarding contextbased modeling, provides us with a theoretical basis for using a bottom-up approach for automating the management of large amounts of information in ways directly useful for human operators. However, integration of human intelligence into a game theoretic framework for dynamic and adaptive decision support needs a perception and cognition model. For the purpose of cognitive modeling, we present a brain-computer-interface (BCI) based humanoid robot system to acquire brainwaves during human mental activities of imagining a humanoid robot-walking behavior. We use the neural signals to investigate relationships between complex humanoid robot behaviors and human mental activities for developing the perception and cognition model. The BCI system consists of a data acquisition unit with an electroencephalograph (EEG), a humanoid robot, and a charge couple CCD camera. An EEG electrode cup acquires brainwaves from the skin surface on scalp. The humanoid robot has 20 degrees of freedom (DOFs); 12 DOFs located on hips, knees, and ankles for humanoid robot walking, 6 DOFs on shoulders and arms for arms motion, and 2 DOFs for head yaw and pitch motion. The CCD camera takes video clips of the human subject's hand postures to identify mental activities that are correlated to the robot-walking behaviors. We use the neural signals to investigate relationships between complex humanoid robot behaviors and human mental activities for developing the perception and cognition model.

  12. Novel roles for immune molecules in neural development: Implications for neurodevelopmental disoders

    Directory of Open Access Journals (Sweden)

    Paula A Garay

    2010-09-01

    Full Text Available Although the brain has classically been considered "immune-privileged," current research suggests extensive communication between the nervous and the immune systems in both health and disease. Recent studies demonstrate that immune molecules are present at the right place and time to modulate the development and function of the healthy and diseased CNS. Indeed, immune molecules play integral roles in the CNS throughout neural development, including affecting neurogenesis, neuronal migration, axon guidance, synapse formation, activity-dependent refinement of circuits, and synaptic plasticity. Moreover, the roles of individual immune molecules in the nervous system may change over development. This review focuses on the effects of immune molecules on neuronal connections in the mammalian central nervous system—specifically the roles for MHCI and its receptors, complement, and cytokines on the function, refinement, and plasticity of cortical and hippocampal synapses and their relationship to neurodevelopmental disorders. These functions for immune molecules during neural development suggest that they could also mediate pathological responses to chronic elevations of cytokines in neurodevelopmental disorders, including autism spectrum disorders (ASD and schizophrenia.

  13. Influence of the complex-shape light signal on the neural network

    Science.gov (United States)

    Melnikov, Leonid A.; Novosselova, Anna V.; Blinova, Nadejda V.

    1999-03-01

    The effect of external signals of different shapes (constant, serrated and others) on the ring neural network modeling the visual perception is investigated numerically. New specific features in the dynamics of the neural network, such as the excitation, the swapping and the depression, were observed. The cooperative amplication of the external signal and the memory effect have been observed.

  14. Proceedings of the IEEE 2003 Neural Networks for Signal Processing Workshop

    DEFF Research Database (Denmark)

    Larsen, Jan

    methodology and real-world application domains and is widely entering into everyday solutions adopted by research and industry, going far beyond “traditional” neural networks and academic examples. As reflected in this collection, contemporary neural networks for signal processing combine many ideas from......This proceeding contains refereed papers presented at the thirteenth IEEE Workshop on Neural Networks for Signal Processing (NNSP’2003), held at the Atria-Mercure Conference Center, Toulouse, France, September 17-19, 2003. The Neural Networks for Signal Processing Technical Committee of the IEEE...... Signal Processing Society organized the workshop with sponsorship of the Signal Processing Society and the co-operation of the IEEE Neural Networks Society. The IEEE Press published the previous twelve volumes of the NNSP Workshop proceedings in a hardbound volume. This year, the bound volume...

  15. Disrupted dorsal neural tube BMP signaling in the cilia mutant Arl13bhnn stems from abnormal Shh signaling

    Science.gov (United States)

    Horner, Vanessa L.; Caspary, Tamara

    2011-01-01

    In the embryonic neural tube, multiple signaling pathways work in concert to create functional neuronal circuits in the adult spinal cord. In the ventral neural tube, Sonic hedgehog (Shh) acts as a graded morphogen to specify neurons necessary for movement. In the dorsal neural tube, bone morphogenetic protein (BMP) and Wnt signals cooperate to specify neurons involved in sensation. Several signaling pathways, including Shh, rely on primary cilia in vertebrates. In this study, we used a mouse mutant with abnormal cilia, Arl13bhnn, to study the relationship between cilia, cell signaling, and neural tube patterning. Alr13bhnn mutants have abnormal ventral neural tube patterning due to disrupted Shh signaling; in addition, dorsal patterning defects occur, but the cause of these is unknown. Here we show that the Arl13bhnn dorsal patterning defects result from abnormal BMP signaling. In addition, we find that Wnt ligands are abnormally expressed in Arl13bhnn mutants; surprisingly, however, downstream Wnt signaling is normal. We demonstrate that Arl13b is required non-autonomously for BMP signaling and Wnt ligand expression, indicating that the abnormal Shh signaling environment in Arl13bhnn embryos indirectly causes dorsal defects. PMID:21539826

  16. Neural signalling of food healthiness associated with emotion processing

    Directory of Open Access Journals (Sweden)

    Uwe eHerwig

    2016-02-01

    Full Text Available The ability to differentiate healthy from unhealthy foods is important in order to promote good health. Food, however, may have an emotional connotation, which could be inversely related to healthiness. The neurobiological background of differentiating healthy and unhealthy food and its relations to emotion processing are not yet well understood. We addressed the neural activations, particularly considering the single subject level, when one evaluates a food item to be of a higher, compared to a lower grade of healthiness with a particular view on emotion processing brain regionsThirty-seven healthy subjects underwent functional magnetic resonance imaging while evaluating the healthiness of food presented as photographs with a subsequent rating on a visual analogue scale. We compared individual evaluations of high and low healthiness of food items and also considered gender differences.We found increased activation when food was evaluated to be healthy in the left dorsolateral prefrontal cortex and precuneus in whole brain analyses. In ROI analyses, perceived and rated higher healthiness was associated with lower amygdala activity and higher ventral striatal and orbitofrontal cortex activity. Females exerted a higher activation in midbrain areas when rating food items as being healthy.Our results underline the close relationship between food and emotion processing, which makes sense considering evolutionary aspects. Actively evaluating and deciding whether food is healthy is accompanied by neural signalling associated with reward and self-relevance, which could promote salutary nutrition behaviour. The involved brain regions may be amenable to mechanisms of emotion regulation in the context of psychotherapeutic regulation of food intake.

  17. Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Guang; Li, Yan; Wang, Xiao-yu [Key Laboratory for Regenerative Medicine of The Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632 (China); Han, Zhe [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510224 (China); Chuai, Manli [College of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH (United Kingdom); Wang, Li-jing [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510224 (China); Ho Lee, Kenneth Ka [Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin (Hong Kong); Geng, Jian-guo, E-mail: jgeng@umich.edu [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510224 (China); Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109 (United States); Yang, Xuesong, E-mail: yang_xuesong@126.com [Key Laboratory for Regenerative Medicine of The Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632 (China)

    2013-05-01

    Formation of the neural tube is the morphological hallmark for development of the embryonic central nervous system (CNS). Therefore, neural tube development is a crucial step in the neurulation process. Slit/Robo signaling was initially identified as a chemo-repellent that regulated axon growth cone elongation, but its role in controlling neural tube development is currently unknown. To address this issue, we investigated Slit/Robo1 signaling in the development of chick neCollege of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH, UKural tube and transgenic mice over-expressing Slit2. We disrupted Slit/Robo1 signaling by injecting R5 monoclonal antibodies into HH10 neural tubes to block the Robo1 receptor. This inhibited the normal development of the ventral body curvature and caused the spinal cord to curl up into a S-shape. Next, Slit/Robo1 signaling on one half-side of the chick embryo neural tube was disturbed by electroporation in ovo. We found that the morphology of the neural tube was dramatically abnormal after we interfered with Slit/Robo1 signaling. Furthermore, we established that silencing Robo1 inhibited cell proliferation while over-expressing Robo1 enhanced cell proliferation. We also investigated the effects of altering Slit/Robo1 expression on Sonic Hedgehog (Shh) and Pax7 expression in the developing neural tube. We demonstrated that over-expressing Robo1 down-regulated Shh expression in the ventral neural tube and resulted in the production of fewer HNK-1{sup +} migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug{sup +} pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1{sup +} migrating NCCs but reduced Pax7 expression and fewer Slug{sup +} pre-migratory NCCs were observed. In conclusion, we propose that Slit/Robo1 signaling is involved in regulating neural tube

  18. The relationship between Sonic hedgehog signalling, cilia and neural tube defects

    Science.gov (United States)

    Murdoch, Jennifer N.; Copp, Andrew J.

    2013-01-01

    The Hedgehog signalling pathway is essential for many aspects of normal embryonic development, including formation and patterning of the neural tube. Absence of Shh ligand is associated with the midline defect holoprosencephaly, while increased Shh signalling is associated with exencephaly and spina bifida. To complicate this apparently simple relationship, mutation of proteins required for function of cilia often leads to impaired Shh signalling and to disruption of neural tube closure. In this manuscript, we review the literature on Shh pathway mutants and discuss the relationship between Shh signalling, cilia and neural tube defects. PMID:20544799

  19. Signaling and transcriptional regulation in neural crest specification and migration: lessons from xenopus embryos.

    Science.gov (United States)

    Pegoraro, Caterina; Monsoro-Burq, Anne H

    2013-01-01

    The neural crest is a population of highly migratory and multipotent cells, which arises from the border of the neural plate in vertebrate embryos. In the last few years, the molecular actors of neural crest early development have been intensively studied, notably by using the frog embryo, as a prime model for the analysis of the earliest embryonic inductions. In addition, tremendous progress has been made in understanding the molecular and cellular basis of Xenopus cranial neural crest migration, by combining in vitro and in vivo analysis. In this review, we examine how the action of previously known neural crest-inducing signals [bone morphogenetic protein (BMP), wingless-int (Wnt), fibroblast growth factor (FGF)] is controlled by newly discovered modulators during early neural plate border patterning and neural crest specification. This regulation controls the induction of key transcription factors that cooperate to pattern the premigratory neural crest progenitors. These data are discussed in the perspective of the gene regulatory network that controls neural and neural crest patterning. We then address recent findings on noncanonical Wnt signaling regulation, cell polarization, and collective cell migration which highlight how cranial neural crest cells populate their target tissue, the branchial arches, in vivo. More than ever, the neural crest stands as a powerful and attractive model to decipher complex vertebrate regulatory circuits in vivo. Copyright © 2012 Wiley Periodicals, Inc.

  20. Translating the 'Sugar Code' into Immune and Vascular Signaling Programs.

    Science.gov (United States)

    Cerliani, Juan P; Blidner, Ada G; Toscano, Marta A; Croci, Diego O; Rabinovich, Gabriel A

    2017-04-01

    The vast range and complexity of glycan structures and their dynamic variations in health and disease have presented formidable challenges toward understanding the biological significance of these molecules. Despite these limitations, compelling evidence highlights a major role for galectins, a family of soluble glycan-binding proteins, as endogenous decoders that translate glycan-containing information into a broad spectrum of cellular responses by modulating receptor clustering, reorganization, endocytosis, and signaling. Here, we underscore pioneer findings and recent advances in understanding the biology of galectin-glycan interactions in myeloid, lymphoid, and endothelial compartments, highlighting important pathways by which these multivalent complexes control immune and vascular programs. Implementation of novel glycoanalytical approaches, as well as the use of genetically engineered cell and organism models, have allowed glycans and galectins to be explored across a range of cellular processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Antitumor mechanisms of metformin: Signaling, metabolism, immunity and beyond

    Directory of Open Access Journals (Sweden)

    Ismael Samudio

    2010-08-01

    Full Text Available Metformin is a synthetic biguanide first described in the 1920´s as a side product of the synthesis of N,N-dimethylguanidine. Like otherrelated biguanides, metformin displays antihyperglycemic properties, and has become the most widely prescribed oral antidiabetic medicinearound the world. Intriguing recent evidence suggests that metformin has chemopreventive and direct antitumor properties, and severalongoing clinical studies around the world are using this agent alone or in combination with chemotherapeutic schemes to determineprospectively its safety and efficacy in the treatment of human cancer. Notably, immune activating effects of metformin have recently beendescribed, and may support a notion put forth in the 1950s that this agent possessed antiviral and antimalarial effects. However, how theseeffects may contribute to its observed antitumor effects in retrospective studies has not been discussed. Mechanistically, metformin has beenshown to activate liver kinase B1 (LKB1 and its downstream target AMP-activated kinase (AMPK. The activation of AMPK has beenproposed to mediate metformin´s glucose lowering effect, although recent evidence suggests that this agent can inhibit electron transport inhepatocyte mitochondria resulting in AMPK-independent inhibition of hepatic gluconeogenesis. Likewise, albeit activation of AMPK andthe resulting inhibition of the mammalian target of rapamycin (mTOR signaling have been suggested to mediate the antitumor effects ofmetformin, AMPK-independent growth inhibitory properties of this agent in tumor cells have also been described. Here we present a briefreview of the signaling, metabolic, and immune effects of metformin and discuss how their interplay may orchestrate the antitumor effectsof this agent. In addition, we provide the rationale for a compassionate use study of metformin in combination with metronomic chemotherapy.

  2. Using pulse width modulation for wireless transmission of neural signals in multichannel neural recording systems.

    Science.gov (United States)

    Yin, Ming; Ghovanloo, Maysam

    2009-08-01

    We have used a well-known technique in wireless communication, pulse width modulation (PWM) of time division multiplexed (TDM) signals, within the architecture of a novel wireless integrated neural recording (WINeR) system. We have evaluated the performance of the PWM-based architecture and indicated its accuracy and potential sources of error through detailed theoretical analysis, simulations, and measurements on a setup consisting of a 15-channel WINeR prototype as the transmitter and two types of receivers; an Agilent 89600 vector signal analyzer and a custom wideband receiver, with 36 and 75 MHz of maximum bandwidth, respectively. Furthermore, we present simulation results from a realistic MATLAB-Simulink model of the entire WINeR system to observe the system behavior in response to changes in various parameters. We have concluded that the 15-ch WINeR prototype, which is fabricated in a 0.5- mum standard CMOS process and consumes 4.5 mW from +/-1.5 V supplies, can acquire and wirelessly transmit up to 320 k-samples/s to a 75-MHz receiver with 8.4 bits of resolution, which is equivalent to a wireless data rate of approximately 2.56 Mb/s.

  3. Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function

    NARCIS (Netherlands)

    D.S. Shouval (Dror); R.S. Biswas (Rajat); J.A. Goettel (Jeremy); K. McCann (Katelyn); E. Conaway (Evan); N.S. Redhu (Naresh); I.D. Mascanfroni (Ivan); Z. AlAdham (Ziad); S. Lavoie (Sydney); M. Ibourk (Mouna); D.D. Nguyen (Deanna); J.N. Samsom (Janneke); J.C. Escher (Johanna); R. Somech (Raz); B. Weiss (Batia); R. Beier (Rita); L.S. Conklin (Laurie); C.L. Ebens (Christen); F.G.M.S. Santos (Fernanda); A.R. Ferreira (Alexandre); J.K. Sherlock (Jon); A.K. Bhan (Atul); W. Müller (Werner); J.R. Mora (J. Rodrigo); F.J. Quintana (Francisco); C. Klein (Christoph); A.M. Muise (Aleixo); R.I. Horwitz (Ralph); S.B. Snapper (Scott)

    2014-01-01

    textabstractIntact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on Tcells, was critical for regulating mucosal

  4. Endoplasmic reticulum stress pathway required for immune homeostasis is neurally controlled by arrestin-1.

    Science.gov (United States)

    Singh, Varsha; Aballay, Alejandro

    2012-09-28

    In response to pathogen infection, the host innate immune system activates microbial killing pathways and cellular stress pathways that need to be balanced because insufficient or excessive immune responses have deleterious consequences. Recent studies demonstrate that two G protein-coupled receptors (GPCRs) in the nervous system of Caenorhabditis elegans control immune homeostasis. To investigate further how GPCR signaling controls immune homeostasis at the organismal level, we studied arrestin-1 (ARR-1), which is the only GPCR adaptor protein in C. elegans. The results indicate that ARR-1 is required for GPCR signaling in ASH, ASI, AQR, PQR, and URX neurons, which control the unfolded protein response and a p38 mitogen-activated protein kinase signaling pathway required for innate immunity. ARR-1 activity also controlled immunity through ADF chemosensory and AFD thermosensory neurons that regulate longevity. Furthermore, we found that although ARR-1 played a key role in the control of immunity by AFD thermosensory neurons, it did not control longevity through these cells. However, ARR-1 partially controlled longevity through ADF neurons.

  5. The neural subjective frame: from bodily signals to perceptual consciousness

    Science.gov (United States)

    Park, Hyeong-Dong; Tallon-Baudry, Catherine

    2014-01-01

    The report ‘I saw the stimulus’ operationally defines visual consciousness, but where does the ‘I’ come from? To account for the subjective dimension of perceptual experience, we introduce the concept of the neural subjective frame. The neural subjective frame would be based on the constantly updated neural maps of the internal state of the body and constitute a neural referential from which first person experience can be created. We propose to root the neural subjective frame in the neural representation of visceral information which is transmitted through multiple anatomical pathways to a number of target sites, including posterior insula, ventral anterior cingulate cortex, amygdala and somatosensory cortex. We review existing experimental evidence showing that the processing of external stimuli can interact with visceral function. The neural subjective frame is a low-level building block of subjective experience which is not explicitly experienced by itself which is necessary but not sufficient for perceptual experience. It could also underlie other types of subjective experiences such as self-consciousness and emotional feelings. Because the neural subjective frame is tightly linked to homeostatic regulations involved in vigilance, it could also make a link between state and content consciousness. PMID:24639580

  6. Discrimination of Cylinders with Different Wall Thicknesses using Neural Networks and Simulated Dolphin Sonar Signals

    DEFF Research Database (Denmark)

    Andersen, Lars Nonboe; Au, Whitlow; Larsen, Jan

    1999-01-01

    This paper describes a method integrating neural networks into a system for recognizing underwater objects. The system is based on a combination of simulated dolphin sonar signals, simulated auditory filters and artificial neural networks. The system is tested on a cylinder wall thickness...

  7. Learning ensembles of neural networks by means of a Bayesian artificial immune system.

    Science.gov (United States)

    Castro, Pablo A Dalbem; Von Zuben, Fernando José

    2011-02-01

    In this paper, we apply an immune-inspired approach to design ensembles of heterogeneous neural networks for classification problems. Our proposal, called Bayesian artificial immune system, is an estimation of distribution algorithm that replaces the traditional mutation and cloning operators with a probabilistic model, more specifically a Bayesian network, representing the joint distribution of promising solutions. Among the additional attributes provided by the Bayesian framework inserted into an immune-inspired search algorithm are the automatic control of the population size along the search and the inherent ability to promote and preserve diversity among the candidate solutions. Both are attributes generally absent from alternative estimation of distribution algorithms, and both were shown to be useful attributes when implementing the generation and selection of components of the ensemble, thus leading to high-performance classifiers. Several aspects of the design are illustrated in practical applications, including a comparative analysis with other attempts to synthesize ensembles.

  8. DMPD: Peptidoglycan signaling in innate immunity and inflammatory disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15802263 Peptidoglycan signaling in innate immunity and inflammatory disease. McDon...ald C, Inohara N, Nunez G. J Biol Chem. 2005 May 27;280(21):20177-80. Epub 2005 Mar 31. (.png) (.svg) (.html) (.csml) Show Peptidog...lycan signaling in innate immunity and inflammatory disease. PubmedID 15802263 Title Peptidog

  9. Intelligent Noise Removal from EMG Signal Using Focused Time-Lagged Recurrent Neural Network

    OpenAIRE

    Kale, S. N.; Dudul, S. V.

    2009-01-01

    Electromyography (EMG) signals can be used for clinical/biomedical application and modern human computer interaction. EMG signals acquire noise while traveling through tissue, inherent noise in electronics equipment, ambient noise, and so forth. ANN approach is studied for reduction of noise in EMG signal. In this paper, it is shown that Focused Time-Lagged Recurrent Neural Network (FTLRNN) can elegantly solve to reduce the noise from EMG signal. After rigorous computer simulations, authors d...

  10. Robust Clustering of Acoustic Emission Signals Using Neural Networks and Signal Subspace Projections

    Directory of Open Access Journals (Sweden)

    Vahid Emamian

    2003-03-01

    Full Text Available Acoustic emission-based techniques are being used for the nondestructive inspection of mechanical systems. For reliable automatic fault monitoring related to the generation and propagation of cracks, it is important to identify the transient crack-related signals in the presence of strong time-varying noise and other interference. A prominent difficulty is the inability to differentiate events due to crack growth from noise of various origins. This work presents a novel algorithm for automatic clustering and separation of acoustic emission (AE events based on multiple features extracted from the experimental data. The algorithm consists of two steps. In the first step, the noise is separated from the events of interest and subsequently removed using a combination of covariance analysis, principal component analysis (PCA, and differential time delay estimates. The second step processes the remaining data using a self-organizing map (SOM neural network, which outputs the noise and AE signals into separate neurons. To improve the efficiency of classification, the short-time Fourier transform (STFT is applied to retain the time-frequency features of the remaining events, reducing the dimension of the data. The algorithm is verified with two sets of data, and a correct classification ratio over 95% is achieved.

  11. High-Risk Human Papillomavirus Targets Crossroads in Immune Signaling

    OpenAIRE

    Bart Tummers; van der Burg, Sjoerd H

    2015-01-01

    Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellu...

  12. Neural retina identity is specified by lens-derived BMP signals.

    Science.gov (United States)

    Pandit, Tanushree; Jidigam, Vijay K; Patthey, Cedric; Gunhaga, Lena

    2015-05-15

    The eye has served as a classical model to study cell specification and tissue induction for over a century. Nevertheless, the molecular mechanisms that regulate the induction and maintenance of eye-field cells, and the specification of neural retina cells are poorly understood. Moreover, within the developing anterior forebrain, how prospective eye and telencephalic cells are differentially specified is not well defined. In the present study, we have analyzed these issues by manipulating signaling pathways in intact chick embryo and explant assays. Our results provide evidence that at blastula stages, BMP signals inhibit the acquisition of eye-field character, but from neural tube/optic vesicle stages, BMP signals from the lens are crucial for the maintenance of eye-field character, inhibition of dorsal telencephalic cell identity and specification of neural retina cells. Subsequently, our results provide evidence that a Rax2-positive eye-field state is not sufficient for the progress to a neural retina identity, but requires BMP signals. In addition, our results argue against any essential role of Wnt or FGF signals during the specification of neural retina cells, but provide evidence that Wnt signals together with BMP activity are sufficient to induce cells of retinal pigment epithelial character. We conclude that BMP activity emanating from the lens ectoderm maintains eye-field identity, inhibits telencephalic character and induces neural retina cells. Our findings link the requirement of the lens ectoderm for neural retina specification with the molecular mechanism by which cells in the forebrain become specified as neural retina by BMP activity. © 2015. Published by The Company of Biologists Ltd.

  13. Tetraspanin microdomains in immune cell signalling and malignant disease.

    NARCIS (Netherlands)

    Wright, M.D.; Moseley, G.W.; Spriel, A.B. van

    2004-01-01

    A contemporary goal of researchers in leucocyte signalling has been to uncover how cells physically organize and compartmentalize signalling molecules into efficient, regulated signalling networks. This work has revealed important roles of membrane microdomains that are characterized by their

  14. Effects of social sustainability signals on neural valuation signals and taste-experience of food products

    Directory of Open Access Journals (Sweden)

    Laura eEnax

    2015-09-01

    Full Text Available Value-based decision making occurs when individuals choose between different alternatives and place a value on each alternative and its attributes. Marketing actions frequently manipulate product attributes, by adding e.g., health claims on the packaging. A previous imaging study found that an emblem for organic products increased willingness to pay (WTP and activity in the ventral striatum (VS. The current study investigated neural and behavioral processes underlying the influence of Fair Trade (FT labeling on food valuation and choice. Sustainability is an important product attribute for many consumers, with FT signals being one way to highlight ethically sustainable production. Forty participants valuated products in combination with an FT emblem or no emblem and stated their WTP in a bidding task while in an MRI scanner. After that, participants tasted – objectively identical – chocolates, presented either as FT or as conventionally produced. In the fMRI task, WTP was significantly higher for FT products. FT labeling increased activity in regions important for reward-processing and salience, that is, in the VS, anterior and posterior cingulate, as well as superior frontal gyrus. Subjective value, that is, WTP was correlated with activity in the ventromedial prefrontal cortex (vmPFC. We find that the anterior cingulate, VS and superior frontal gyrus exhibit task-related increases in functional connectivity to the vmPFC when an FT product was evaluated, suggesting a network which alters valuation processes. We also found a significant taste-placebo effect, with higher experienced taste pleasantness and intensity for FT labeled chocolates. Our results reveal a possible neural mechanism underlying valuation processes of certified food products. The results are important in light of understanding current marketing trends as well as designing future interventions that aim at positively influencing food choice.

  15. Effects of social sustainability signaling on neural valuation signals and taste-experience of food products.

    Science.gov (United States)

    Enax, Laura; Krapp, Vanessa; Piehl, Alexandra; Weber, Bernd

    2015-01-01

    Value-based decision making occurs when individuals choose between different alternatives and place a value on each alternative and its attributes. Marketing actions frequently manipulate product attributes, by adding, e.g., health claims on the packaging. A previous imaging study found that an emblem for organic products increased willingness to pay (WTP) and activity in the ventral striatum (VS). The current study investigated neural and behavioral processes underlying the influence of Fair Trade (FT) labeling on food valuation and choice. Sustainability is an important product attribute for many consumers, with FT signals being one way to highlight ethically sustainable production. Forty participants valuated products in combination with an FT emblem or no emblem and stated their WTP in a bidding task while in an MRI scanner. After that, participants tasted-objectively identical-chocolates, presented either as "FT" or as "conventionally produced". In the fMRI task, WTP was significantly higher for FT products. FT labeling increased activity in regions important for reward-processing and salience, that is, in the VS, anterior and posterior cingulate, as well as superior frontal gyrus. Subjective value, that is, WTP was correlated with activity in the ventromedial prefrontal cortex (vmPFC). We find that the anterior cingulate, VS and superior frontal gyrus exhibit task-related increases in functional connectivity to the vmPFC when an FT product was evaluated. Effective connectivity analyses revealed a highly probable directed modulation of the vmPFC by those three regions, suggesting a network which alters valuation processes. We also found a significant taste-placebo effect, with higher experienced taste pleasantness and intensity for FT labeled chocolates. Our results reveal a possible neural mechanism underlying valuation processes of certified food products. The results are important in light of understanding current marketing trends as well as designing

  16. A Decline in Response Variability Improves Neural Signal Detection during Auditory Task Performance.

    Science.gov (United States)

    von Trapp, Gardiner; Buran, Bradley N; Sen, Kamal; Semple, Malcolm N; Sanes, Dan H

    2016-10-26

    The detection of a sensory stimulus arises from a significant change in neural activity, but a sensory neuron's response is rarely identical to successive presentations of the same stimulus. Large trial-to-trial variability would limit the central nervous system's ability to reliably detect a stimulus, presumably affecting perceptual performance. However, if response variability were to decrease while firing rate remained constant, then neural sensitivity could improve. Here, we asked whether engagement in an auditory detection task can modulate response variability, thereby increasing neural sensitivity. We recorded telemetrically from the core auditory cortex of gerbils, both while they engaged in an amplitude-modulation detection task and while they sat quietly listening to the identical stimuli. Using a signal detection theory framework, we found that neural sensitivity was improved during task performance, and this improvement was closely associated with a decrease in response variability. Moreover, units with the greatest change in response variability had absolute neural thresholds most closely aligned with simultaneously measured perceptual thresholds. Our findings suggest that the limitations imposed by response variability diminish during task performance, thereby improving the sensitivity of neural encoding and potentially leading to better perceptual sensitivity. The detection of a sensory stimulus arises from a significant change in neural activity. However, trial-to-trial variability of the neural response may limit perceptual performance. If the neural response to a stimulus is quite variable, then the response on a given trial could be confused with the pattern of neural activity generated when the stimulus is absent. Therefore, a neural mechanism that served to reduce response variability would allow for better stimulus detection. By recording from the cortex of freely moving animals engaged in an auditory detection task, we found that variability

  17. Regulatory mechanisms of innate immune signaling in zebrafish embryos

    NARCIS (Netherlands)

    Kanwal, Zakia

    2012-01-01

    The work presented in this thesis has provided new insights into the mechanisms involved in the regulation of innate immune responses in zebrafish embryos. Furthermore, cell-specific transcriptome profiling studies identified novel marker genes for distinguishing immune cell types, which is highly

  18. Cupping regulates local immunomodulation to activate neural-endocrine-immune worknet.

    Science.gov (United States)

    Guo, Yang; Chen, Bo; Wang, Dong-Qiang; Li, Ming-Yue; Lim, Calista Hui-Min; Guo, Yi; Chen, Zelin

    2017-08-01

    Research on cupping therapy is lacking at home and abroad. However, cupping and acupuncture therapy are both surface stimulation therapies. This paper suggests the mechanism of cupping therapy and proposes that the same mechanism underlies both cupping and acupuncture therapy. The microenvironment is changed when stimulating the surface of the skin, and physical signals transform into biological signals, which also interact with each other in the body. These signalling cascades activate the neuroendocrine-immune system, which produces the therapeutic effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. G-protein-coupled receptor signaling and neural tube closure defects.

    Science.gov (United States)

    Shimada, Issei S; Mukhopadhyay, Saikat

    2017-01-30

    Disruption of the normal mechanisms that mediate neural tube closure can result in neural tube defects (NTDs) with devastating consequences in affected patients. With the advent of next-generation sequencing, we are increasingly detecting mutations in multiple genes in NTD cases. However, our ability to determine which of these genes contribute to the malformation is limited by our understanding of the pathways controlling neural tube closure. G-protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors in humans and have been historically favored as drug targets. Recent studies implicate several GPCRs and downstream signaling pathways in neural tube development and closure. In this review, we will discuss our current understanding of GPCR signaling pathways in pathogenesis of NTDs. Notable examples include the orphan primary cilia-localized GPCR, Gpr161 that regulates the basal suppression machinery of sonic hedgehog pathway by means of activation of cAMP-protein kinase A signaling in the neural tube, and protease-activated receptors that are activated by a local network of membrane-tethered proteases during neural tube closure involving the surface ectoderm. Understanding the role of these GPCR-regulated pathways in neural tube development and closure is essential toward identification of underlying genetic causes to prevent NTDs. Birth Defects Research 109:129-139, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Molecular signaling networks in regulation of immunity and disease

    DEFF Research Database (Denmark)

    Laursen, Janne Marie; Jensen, Stina Rikke; Sørensen, Morten

    The gut microbiota, host tissues, and the immune system form a complex network where extensive crosstalk and molecular interactions substantially impact the overall state of the system. Concomitantly, modulation of host immune function is recurrently a result of the interaction of complex......), plays a crucial role in shaping the nature of the adaptive/memorybased immune response after encountering inflammatory compounds. In the gut, the DC is continuously exposed to microbial and dietary components that are recognized by its innate pattern recognition receptors, and the phenotype developed...... and dynamic microbial communities with the immune cell compartment in the gut, and therefore the interaction between components from different gut bacteria can efficiently shape the phenotype of the immune response. A specialized antigenpresenting cell present at mucosal surfaces, the dendritic cell (DC...

  1. [Resolution of overlapping Raman signals based on an adaptiveI immune algorithm].

    Science.gov (United States)

    Cao, Ling-yan; Cheng, Ming-xiao; Yu, Zheng-wei; Zhao, Tian-qi; Lin, Jin-guo

    2012-05-01

    Raman spectroscopy can be used in situ real-time measurement because it's rapid, and it is helpful to real-time online monitoring of process control. With the complexity of the environment and the characteristics of Raman signal, it is hard to avoid some overlapping spectrum peaks. Based on the advantage of immune algorithm, an immune algorithm (IA) was applied to the overlapping Raman signals of aromatics. With extraction of each single Raman spectrum peak signal from the mixture signals for resolution, Results show that the method is effective to identify the overlapped Raman signal for its fast resolution and accurate quantitative determination with the relative error less than 1%. For the overlapping Raman signals with fluorescence background disturbance, we proposed an adaptive immune algorithm, which is combined with independent component analysis. It can effectively resolve the fluorescence background signal, and it provides a new way for Raman spectra analysis of complex samples.

  2. Dengue vaccine safety signal: Immune enhancement, waning immunity, or chance occurrence?

    Science.gov (United States)

    Gessner, Bradford D; Halsey, Neal

    2017-06-14

    A new dengue vaccine was associated with increased risk of hospitalized virologically-confirmed disease during year 3 of follow-up among children age 2-5years. Among hypotheses to explain this finding, we could not distinguish definitively between antibody dependent enhancement, waning immunity, or chance occurrence. However, any theory must account for the following: (a) the signal occurred mainly because of decreased dengue among controls rather than increased dengue among vaccinees; (b) among 48 data points, a statistically significant increase in hospitalization among vaccinated children occurred for only one age group, during one year, and in one region; (c) cumulative risk was similar for vaccinated vs. control children age 2-5years at the end of year 5 and lower for vaccinated vs. control children among older age groups; (d) the protective effect of vaccine against hospitalization decreased from years 1-2 to years 3-5 of follow-up for all age groups and regions. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  3. Neural signal sampling via the low power wireless pico system.

    Science.gov (United States)

    Cieslewski, Grzegorz; Cheney, David; Gugel, Karl; Sanchez, Justin C; Principe, Jose C

    2006-01-01

    This paper presents a powerful new low power wireless system for sampling multiple channels of neural activity based on Texas Instruments MSP430 microprocessors and Nordic Semiconductor's ultra low power high bandwidth RF transmitters and receivers. The system's development process, component selection, features and test methodology are presented.

  4. Immunization with a Neural-Derived Peptide Protects the Spinal Cord from Apoptosis after Traumatic Injury

    Directory of Open Access Journals (Sweden)

    Roxana Rodríguez-Barrera

    2013-01-01

    Full Text Available Apoptosis is one of the most destructive mechanisms that develop after spinal cord (SC injury. Immunization with neural-derived peptides (INDPs such as A91 has shown to reduce the deleterious proinflammatory response and the amount of harmful compounds produced after SC injury. With the notion that the aforementioned elements are apoptotic inducers, we hypothesized that INDPs would reduce apoptosis after SC injury. In order to test this assumption, adult rats were subjected to SC contusion and immunized either with A91 or phosphate buffered saline (PBS; control group. Seven days after injury, animals were euthanized to evaluate the number of apoptotic cells at the injury site. Apoptosis was evaluated using DAPI and TUNEL techniques; caspase-3 activity was also evaluated. To further elucidate the mechanisms through which A91 exerts this antiapoptotic effects we quantified tumor necrosis factor-alpha (TNF-α. To also demonstrate that the decrease in apoptotic cells correlated with a functional improvement, locomotor recovery was evaluated. Immunization with A91 significantly reduced the number of apoptotic cells and decreased caspase-3 activity and TNF-α concentration. Immunization with A91 also improved the functional recovery of injured rats. The present study shows the beneficial effect of INDPs on preventing apoptosis and provides more evidence on the neuroprotective mechanisms exerted by this strategy.

  5. Comparative evaluation of different wavelet thresholding methods for neural signal processing.

    Science.gov (United States)

    Barabino, Gianluca; Baldazzi, Giulia; Sulas, Eleonora; Carboni, Caterina; Raffo, Luigi; Pani, Danilo

    2017-07-01

    Neural signal decoding is the basis for the development of neuroprosthetic devices and systems. Depending on the part of the nervous system these signals are picked up from, different signal-to-noise ratios (SNR) can be experienced. Wavelet denoising is often adopted due to its capability of reducing, to some extent, the noise falling within the signal spectrum. Several variables influence the denoising quality, but usually the focus in on the selection of the best performing mother wavelet. However, the threshold definition and the way it is applied to the signal have a significant impact on the denoising quality, determining the amount of noise removed and the distortion introduced on the signal. This work presents a comparative analysis of different threshold definition and thresholding mechanisms on neural signals, either largely adopted for neural signal processing or not. In order to evaluate the quality of the denoising in terms of the introduced distortion, which is important when decoding is implemented through spike-sorting algorithms, a synthetic dataset built on real action potentials was used, creating signals with different SNR and characterized by an additive white Gaussian noise (AWGN). The obtained results reveal the superiority of an approach, originally conceived for noisy non-linear time series, over the more typical ones. When compared to the original signal, a correlation above 0.9 was obtained, while in terms of root mean square error (RMSE) an improvement of 13% and 33% was reported with respect to the Minimax and Universal thresholds respectively.

  6. Neural responses to multimodal ostensive signals in 5-month-old infants.

    Directory of Open Access Journals (Sweden)

    Eugenio Parise

    Full Text Available Infants' sensitivity to ostensive signals, such as direct eye contact and infant-directed speech, is well documented in the literature. We investigated how infants interpret such signals by assessing common processing mechanisms devoted to them and by measuring neural responses to their compounds. In Experiment 1, we found that ostensive signals from different modalities display overlapping electrophysiological activity in 5-month-old infants, suggesting that these signals share neural processing mechanisms independently of their modality. In Experiment 2, we found that the activation to ostensive signals from different modalities is not additive to each other, but rather reflects the presence of ostension in either stimulus stream. These data support the thesis that ostensive signals obligatorily indicate to young infants that communication is directed to them.

  7. DMPD: Innate immune sensing of pathogens and danger signals by cell surface Toll-likereceptors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17275324 Innate immune sensing of pathogens and danger signals by cell surface Toll... Show Innate immune sensing of pathogens and danger signals by cell surface Toll-likereceptors. PubmedID 172...75324 Title Innate immune sensing of pathogens and danger signals by cell surface

  8. Computationally efficient locally-recurrent neural networks for online signal processing

    CERN Document Server

    Hussain, A; Shim, I

    1999-01-01

    A general class of computationally efficient locally recurrent networks (CERN) is described for real-time adaptive signal processing. The structure of the CERN is based on linear-in-the- parameters single-hidden-layered feedforward neural networks such as the radial basis function (RBF) network, the Volterra neural network (VNN) and the functionally expanded neural network (FENN), adapted to employ local output feedback. The corresponding learning algorithms are derived and key structural and computational complexity comparisons are made between the CERN and conventional recurrent neural networks. Two case studies are performed involving the real- time adaptive nonlinear prediction of real-world chaotic, highly non- stationary laser time series and an actual speech signal, which show that a recurrent FENN based adaptive CERN predictor can significantly outperform the corresponding feedforward FENN and conventionally employed linear adaptive filtering models. (13 refs).

  9. Nonlinear identification using a B-spline neural network and chaotic immune approaches

    Science.gov (United States)

    dos Santos Coelho, Leandro; Pessôa, Marcelo Wicthoff

    2009-11-01

    One of the important applications of B-spline neural network (BSNN) is to approximate nonlinear functions defined on a compact subset of a Euclidean space in a highly parallel manner. Recently, BSNN, a type of basis function neural network, has received increasing attention and has been applied in the field of nonlinear identification. BSNNs have the potential to "learn" the process model from input-output data or "learn" fault knowledge from past experience. BSNN can be used as function approximators to construct the analytical model for residual generation too. However, BSNN is trained by gradient-based methods that may fall into local minima during the learning procedure. When using feed-forward BSNNs, the quality of approximation depends on the control points (knots) placement of spline functions. This paper describes the application of a modified artificial immune network inspired optimization method - the opt-aiNet - combined with sequences generate by Hénon map to provide a stochastic search to adjust the control points of a BSNN. The numerical results presented here indicate that artificial immune network optimization methods are useful for building good BSNN model for the nonlinear identification of two case studies: (i) the benchmark of Box and Jenkins gas furnace, and (ii) an experimental ball-and-tube system.

  10. Modulation of Hippocampal Neural Plasticity by Glucose-Related Signaling

    OpenAIRE

    Marco Mainardi; Salvatore Fusco; Claudio Grassi

    2015-01-01

    Hormones and peptides involved in glucose homeostasis are emerging as important modulators of neural plasticity. In this regard, increasing evidence shows that molecules such as insulin, insulin-like growth factor-I, glucagon-like peptide-1, and ghrelin impact on the function of the hippocampus, which is a key area for learning and memory. Indeed, all these factors affect fundamental hippocampal properties including synaptic plasticity (i.e., synapse potentiation and depression), structural p...

  11. Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation

    Science.gov (United States)

    Muralidharan, Sujatha; Mandrekar, Pranoti

    2013-01-01

    Extensive research in the past decade has identified innate immune recognition receptors and intracellular signaling pathways that culminate in inflammatory responses. Besides its role in cytoprotection, the importance of cell stress in inflammation and host defense against pathogens is emerging. Recent studies have shown that proteins in cellular stress responses, including the heat shock response, ER stress response, and DNA damage response, interact with and regulate signaling intermediates involved in the activation of innate and adaptive immune responses. The effect of such regulation by cell stress proteins may dictate the inflammatory profile of the immune response during infection and disease. In this review, we describe the regulation of innate immune cell activation by cell stress pathways, present detailed descriptions of the types of stress response proteins and their crosstalk with immune signaling intermediates that are essential in host defense, and illustrate the relevance of these interactions in diseases characteristic of aberrant immune responses, such as chronic inflammatory diseases, autoimmune disorders, and cancer. Understanding the crosstalk between cellular stress proteins and immune signaling may have translational implications for designing more effective regimens to treat immune disorders. PMID:23990626

  12. Dusting the sugar fingerprint: C-type lectin signaling in adaptive immunity

    NARCIS (Netherlands)

    den Dunnen, Jeroen; Gringhuis, Sonja I.; Geijtenbeek, Teunis B. H.

    2010-01-01

    Pathogen recognition by dendritic cells (DCs) is central to the induction of adaptive immunity. Pattern recognition receptors (PRRs) on DCs interact with pathogens, leading to signaling events that dictate adaptive immune responses. It is becoming clear that C-type lectins are important PRRs that

  13. Innate signaling by the C-type lectin DC-SIGN dictates immune responses

    NARCIS (Netherlands)

    Dunnen, den J.; Gringhuis, S.I.; Geijtenbeek, T.B.H.

    2009-01-01

    Effective immune responses depend on the recognition of pathogens by dendritic cells (DCs) through pattern recognition receptors (PRRs). These receptors induce specific signaling pathways that lead to the induction of immune responses against the pathogens. It is becoming evident that C-type lectins

  14. An Artificial Neural Network Based Robot Controller that Uses Rat’s Brain Signals

    Directory of Open Access Journals (Sweden)

    Marsel Mano

    2013-04-01

    Full Text Available Brain machine interface (BMI has been proposed as a novel technique to control prosthetic devices aimed at restoring motor functions in paralyzed patients. In this paper, we propose a neural network based controller that maps rat’s brain signals and transforms them into robot movement. First, the rat is trained to move the robot by pressing the right and left lever in order to get food. Next, we collect brain signals with four implanted electrodes, two in the motor cortex and two in the somatosensory cortex area. The collected data are used to train and evaluate different artificial neural controllers. Trained neural controllers are employed online to map brain signals and transform them into robot motion. Offline and online classification results of rat’s brain signals show that the Radial Basis Function Neural Networks (RBFNN outperforms other neural networks. In addition, online robot control results show that even with a limited number of electrodes, the robot motion generated by RBFNN matched the motion generated by the left and right lever position.

  15. A VLSI field-programmable mixed-signal array to perform neural signal processing and neural modeling in a prosthetic system.

    Science.gov (United States)

    Bamford, Simeon A; Hogri, Roni; Giovannucci, Andrea; Taub, Aryeh H; Herreros, Ivan; Verschure, Paul F M J; Mintz, Matti; Del Giudice, Paolo

    2012-07-01

    A very-large-scale integration field-programmable mixed-signal array specialized for neural signal processing and neural modeling has been designed. This has been fabricated as a core on a chip prototype intended for use in an implantable closed-loop prosthetic system aimed at rehabilitation of the learning of a discrete motor response. The chosen experimental context is cerebellar classical conditioning of the eye-blink response. The programmable system is based on the intimate mixing of switched capacitor analog techniques with low speed digital computation; power saving innovations within this framework are presented. The utility of the system is demonstrated by the implementation of a motor classical conditioning model applied to eye-blink conditioning in real time with associated neural signal processing. Paired conditioned and unconditioned stimuli were repeatedly presented to an anesthetized rat and recordings were taken simultaneously from two precerebellar nuclei. These paired stimuli were detected in real time from this multichannel data. This resulted in the acquisition of a trigger for a well-timed conditioned eye-blink response, and repetition of unpaired trials constructed from the same data led to the extinction of the conditioned response trigger, compatible with natural cerebellar learning in awake animals.

  16. Supramolecular organizing centers (SMOCs) as signaling machines in innate immune activation.

    Science.gov (United States)

    Qiao, Qi; Wu, Hao

    2015-11-01

    Innate immunity offers the first line of defense against infections and other types of danger such as tumorigenesis. Its discovery provides tremendous therapeutic opportunities for numerous human diseases. Delving into the structural basis of signal transduction by innate immune receptors, our lab has recently helped to establish the new paradigm in which innate immune receptors transduce ligand-binding signals through formation of higher-order assemblies containing intracellular adapters, signaling enzymes and their substrates. These large signalosome assemblies may be visible under light microscopy as punctate structures in the µm scale, connecting to the underlying molecular structures in the nm scale. They drive proximity-induced enzyme activation, and provide a mechanism for signaling amplification by nucleated polymerization. These supramolecular signaling complexes also open new questions on their cellular organization and mode of regulation, pose challenges to our methodology, and afford valuable implications in drug discovery against these medically important pathways.

  17. Neural basis of impaired safety signaling in Obsessive Compulsive Disorder.

    Science.gov (United States)

    Apergis-Schoute, Annemieke M; Gillan, Claire M; Fineberg, Naomi A; Fernandez-Egea, Emilio; Sahakian, Barbara J; Robbins, Trevor W

    2017-03-21

    The ability to assign safety to stimuli in the environment is integral to everyday functioning. A key brain region for this evaluation is the ventromedial prefrontal cortex (vmPFC). To investigate the importance of vmPFC safety signaling, we used neuroimaging of Pavlovian fear reversal, a paradigm that involves flexible updating when the contingencies for a threatening (CS+) and safe (CS-) stimulus reverse, in a prototypical disorder of inflexible behavior influenced by anxiety, Obsessive Compulsive Disorder (OCD). Skin conductance responses in OCD patients (n = 43) failed to differentiate during reversal compared with healthy controls (n = 35), although significant differentiation did occur during early conditioning and amygdala BOLD signaling was unaffected in these patients. Increased vmPFC activation (for CS+ > CS-) during early conditioning predicted the degree of generalization in OCD patients during reversal, whereas vmPFC safety signals were absent throughout learning in these patients. Regions of the salience network (dorsal anterior cingulate, insula, and thalamus) showed early learning task-related hyperconnectivity with the vmPFC in OCD, consistent with biased processing of the CS+. Our findings reveal an absence of vmPFC safety signaling in OCD, undermining flexible threat updating and explicit contingency knowledge. Although differential threat learning can occur to some extent in the absence of vmPFC safety signals, effective CS- signaling becomes crucial during conflicting threat and safety cues. These results promote further investigation of vmPFC safety signaling in other anxiety disorders, with potential implications for the development of exposure-based therapies, in which safety signaling is likely to play a key role.

  18. Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function.

    Science.gov (United States)

    Shouval, Dror S; Biswas, Amlan; Goettel, Jeremy A; McCann, Katelyn; Conaway, Evan; Redhu, Naresh S; Mascanfroni, Ivan D; Al Adham, Ziad; Lavoie, Sydney; Ibourk, Mouna; Nguyen, Deanna D; Samsom, Janneke N; Escher, Johanna C; Somech, Raz; Weiss, Batia; Beier, Rita; Conklin, Laurie S; Ebens, Christen L; Santos, Fernanda G M S; Ferreira, Alexandre R; Sherlock, Mary; Bhan, Atul K; Müller, Werner; Mora, J Rodrigo; Quintana, Francisco J; Klein, Christoph; Muise, Aleixo M; Horwitz, Bruce H; Snapper, Scott B

    2014-05-15

    Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on T cells, was critical for regulating mucosal homeostasis. Following wild-type (WT) CD4(+) T cell transfer, Rag2(-/-)Il10rb(-/-) mice developed severe colitis in association with profound defects in generation and function of Treg cells. Moreover, loss of IL-10R signaling impaired the generation and function of anti-inflammatory intestinal and bone-marrow-derived macrophages and their ability to secrete IL-10. Importantly, transfer of WT but not Il10rb(-/-) anti-inflammatory macrophages ameliorated colitis induction by WT CD4(+) T cells in Rag2(-/-)Il10rb(-/-) mice. Similar alterations in the generation and function of anti-inflammatory macrophages were observed in IL-10R-deficient patients with very early onset inflammatory bowel disease. Collectively, our studies define innate immune IL-10R signaling as a key factor regulating mucosal immune homeostasis in mice and humans. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Vesicular signalling and immune modulation as hedonic fingerprints

    DEFF Research Database (Denmark)

    Bisgaard, Christina F; Bak, Steffen; Christensen, Trine

    2012-01-01

    ) differential gel electrophoresis (DIGE) and tandem mass spectrometry (MS/MS). The majority of the proteins we identified were enzymes involved in different metabolic activities. Additional proteins were functionally classified as vesicular proteins and immune system proteins. Rab GDP dissociation inhibitor...

  20. Immune Signaling and Antimicrobial Peptide Expression in Lepidoptera

    Directory of Open Access Journals (Sweden)

    Heidi Goodrich-Blair

    2013-07-01

    Full Text Available Many lepidopteran insects are agricultural pests that affect stored grains, food and fiber crops. These insects have negative ecological and economic impacts since they lower crop yield, and pesticides are expensive and can have off-target effects on beneficial arthropods. A better understanding of lepidopteran immunity will aid in identifying new targets for the development of specific insect pest management compounds. A fundamental aspect of immunity, and therefore a logical target for control, is the induction of antimicrobial peptide (AMP expression. These peptides insert into and disrupt microbial membranes, thereby promoting pathogen clearance and insect survival. Pathways leading to AMP expression have been extensively studied in the dipteran Drosophila melanogaster. However, Diptera are an important group of pollinators and pest management strategies that target their immune systems is not recommended. Recent advances have facilitated investigation of lepidopteran immunity, revealing both conserved and derived characteristics. Although the general pathways leading to AMP expression are conserved, specific components of these pathways, such as recognition proteins have diverged. In this review we highlight how such comparative immunology could aid in developing pest management strategies that are specific to agricultural insect pests.

  1. The essential role of G protein-coupled receptor (GPCR) signaling in regulating T cell immunity.

    Science.gov (United States)

    Wang, Dashan

    2018-02-12

    The aim of this paper is to clarify the critical role of GPCR signaling in T cell immunity. The G protein-coupled receptors (GPCRs) are the most common targets in current pharmaceutical industry, and represent the largest and most versatile family of cell surface communicating molecules. GPCRs can be activated by a diverse array of ligands including neurotransmitters, chemokines as well as sensory stimuli. Therefore, GPCRs are involved in many key cellular and physiological processes, such as sense of light, taste and smell, neurotransmission, metabolism, endocrine and exocrine secretion. In recent years, GPCRs have been found to play an important role in immune system. T cell is an important type of immune cell, which plays a central role in cell-mediated immunity. A variety of GPCRs and their signaling mediators (RGS proteins, GRKs and β-arrestin) have been found to express in T cells and involved T cell-mediated immunity. We will summarize the role of GPCR signaling and their regulatory molecules in T cell activation, homeostasis and function in this article. GPCR signaling plays an important role in T cell activation, homeostasis and function. GPCR signaling is critical in regulating T cell immunity.

  2. miR-34 Modulates Innate Immunity and Ecdysone Signaling in Drosophila

    Science.gov (United States)

    Xiong, Xiao-Peng; Chang, Kung-Yen; Ren, Xingjie; Ni, Jian-Quan; Rana, Tariq M.; Zhou, Rui

    2016-01-01

    microRNAs are endogenous small regulatory RNAs that modulate myriad biological processes by repressing target gene expression in a sequence-specific manner. Here we show that the conserved miRNA miR-34 regulates innate immunity and ecdysone signaling in Drosophila. miR-34 over-expression activates antibacterial innate immunity signaling both in cultured cells and in vivo, and flies over-expressing miR-34 display improved survival and pathogen clearance upon Gram-negative bacterial infection; whereas miR-34 knockout animals are defective in antibacterial defense. In particular, miR-34 achieves its immune-stimulatory function, at least in part, by repressing the two novel target genes Dlg1 and Eip75B. In addition, our study reveals a mutual repression between miR-34 expression and ecdysone signaling, and identifies miR-34 as a node in the intricate interplay between ecdysone signaling and innate immunity. Lastly, we identify cis-regulatory genomic elements and trans-acting transcription factors required for optimal ecdysone-mediated repression of miR-34. Taken together, our study enriches the repertoire of immune-modulating miRNAs in animals, and provides new insights into the interplay between steroid hormone signaling and innate immunity. PMID:27893816

  3. Elevated immune-inflammatory signaling in mood disorders: a new therapeutic target?

    Science.gov (United States)

    McNamara, Robert K; Lotrich, Francis E

    2012-09-01

    Converging translational evidence has implicated elevated immune-inflammatory signaling activity in the pathoetiology of mood disorders, including major depressive disorder and bipolar disorder. This is supported in part by cross-sectional evidence for increased levels of proinflammatory eicosanoids, cytokines and acute-phase proteins during mood episodes, and prospective longitudinal evidence for the emergence of mood symptoms in response to chronic immune-inflammatory activation. In addition, mood-stabilizer and atypical antipsychotic medications downregulate initial components of the immune-inflammatory signaling pathway, and adjunctive treatment with anti-inflammatory agents augment the therapeutic efficacy of antidepressant, mood stabilizer and atypical antipsychotic medications. Potential pathogenic mechanisms linked with elevated immune-inflammatory signaling include perturbations in central serotonin neurotransmission and progressive white matter pathology. Both heritable genetic factors and environmental factors including dietary fatty-acid composition may act in concert to sustain elevated immune-inflammatory signaling. Collectively, these data suggest that elevated immune-inflammatory signaling is a mechanism that is relevant to the pathoetiology of mood disorders, and may therefore represent a new therapeutic target for the development of more effective treatments.

  4. Perlecan is required for FGF-2 signaling in the neural stem cell niche

    Directory of Open Access Journals (Sweden)

    Aurelien Kerever

    2014-03-01

    Full Text Available In the adult subventricular zone (neurogenic niche, neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis.

  5. ERNN: a biologically inspired feedforward neural network to discriminate emotion from EEG signal.

    Science.gov (United States)

    Khosrowabadi, Reza; Quek, Chai; Ang, Kai Keng; Wahab, Abdul

    2014-03-01

    Emotions play an important role in human cognition, perception, decision making, and interaction. This paper presents a six-layer biologically inspired feedforward neural network to discriminate human emotions from EEG. The neural network comprises a shift register memory after spectral filtering for the input layer, and the estimation of coherence between each pair of input signals for the hidden layer. EEG data are collected from 57 healthy participants from eight locations while subjected to audio-visual stimuli. Discrimination of emotions from EEG is investigated based on valence and arousal levels. The accuracy of the proposed neural network is compared with various feature extraction methods and feedforward learning algorithms. The results showed that the highest accuracy is achieved when using the proposed neural network with a type of radial basis function.

  6. A radial basis function neural network based on artificial immune systems for remote sensing image classification

    Science.gov (United States)

    Yan, Qin; Zhong, Yanfei

    2008-12-01

    The radial basis function (RBF) neural network is a powerful method for remote sensing image classification. It has a simple architecture and the learning algorithm corresponds to the solution of a linear regression problem, resulting in a fast training process. The main drawback of this strategy is the requirement of an efficient algorithm to determine the number, position, and dispersion of the RBF. Traditional methods to determine the centers are: randomly choose input vectors from the training data set; vectors obtained from unsupervised clustering algorithms, such as k-means, applied to the input data. These conduce that traditional RBF neural network is sensitive to the center initialization. In this paper, the artificial immune network (aiNet) model, a new computational intelligence based on artificial immune networks (AIN), is applied to obtain appropriate centers for remote sensing image classification. In the aiNet-RBF algorihtm, each input pattern corresonds to an antigenic stimulus, while each RBF candidate center is considered to be an element, or cell, of the immune network model. The steps are as follows: A set of candidate centers is initialized at random, where the initial number of candidates and their positions is not crucial to the performance. Then, the clonal selection principle will control which candidates will be selected and how they will be upadated. Note that the clonal selection principle will be responsible for how the centers will represent the training data set. Finally, the immune network will identify and eliminate or suppress self-recognizing individuals to control the number of candidate centers. After the above learning phase, the aiNet network centers represent internal images of the inuput patterns presented to it. The algorithm output is taken to be the matrix of memory cells' coordinates that represent the final centers to be adopted by the RBF network. The stopping criterion of the proposed algorithm is given by a pre

  7. Processing of signals from an ion-elective electrode array by a neural network

    NARCIS (Netherlands)

    Bos, M.; Bos, A.; van der Linden, W.E.

    1990-01-01

    Neural network software is described for processing the signals of arrays of ion-selective electrodes. The performance of the software was tested in the simultaneous determination of calcium and copper(II) ions in binary mixtures of copper(II) nitrate and calcium chloride and the simultaneous

  8. Reward Motivation Accelerates the Onset of Neural Novelty Signals in Humans to 85 Milliseconds

    National Research Council Canada - National Science Library

    Bunzeck, Nico; Doeller, Christian F; Fuentemilla, Lluis; Dolan, Raymond J; Duzel, Emrah

    2009-01-01

    ... are rewarded [8] . In human recognition memory studies, on the other hand, reward is not used to motivate the detection of novel or familiar items. Remarkably, the possibility that the timing of neural novelty signals might be affected if the discrimination of novel and familiar items is rewarded has not yet been tested. Indeed, novelty proces...

  9. Neural cell adhesion molecule induces intracellular signaling via multiple mechanisms of Ca2+ homeostasis

    DEFF Research Database (Denmark)

    Kiryushko, Darya; Korshunova, Irina; Berezin, Vladimir

    2006-01-01

    The neural cell adhesion molecule (NCAM) plays a pivotal role in the development of the nervous system, promoting neuronal differentiation via homophilic (NCAM-NCAM) as well as heterophilic (NCAM-fibroblast growth factor receptor [FGFR]) interactions. NCAM-induced intracellular signaling has been...

  10. Analysis of Stiffened Penstock External Pressure Stability Based on Immune Algorithm and Neural Network

    Directory of Open Access Journals (Sweden)

    Wensheng Dong

    2014-01-01

    Full Text Available The critical external pressure stability calculation of stiffened penstock in the hydroelectric power station is very important work for penstock design. At present, different assumptions and boundary simplification are adopted by different calculation methods which sometimes cause huge differences too. In this paper, we present an immune based artificial neural network model via the model and stability theory of elastic ring, we study effects of some factors (such as pipe diameter, pipe wall thickness, sectional size of stiffening ring, and spacing between stiffening rings on penstock critical external pressure during huge thin-wall procedure of penstock. The results reveal that the variation of diameter and wall thickness can lead to sharp variation of penstock external pressure bearing capacity and then give the change interval of it. This paper presents an optimizing design method to optimize sectional size and spacing of stiffening rings and to determine penstock bearing capacity coordinate with the bearing capacity of stiffening rings and penstock external pressure stability coordinate with its strength safety. As a practical example, the simulation results illustrate that the method presented in this paper is available and can efficiently overcome inherent defects of BP neural network.

  11. Semantic Congruence Accelerates the Onset of the Neural Signals of Successful Memory Encoding.

    Science.gov (United States)

    Packard, Pau A; Rodríguez-Fornells, Antoni; Bunzeck, Nico; Nicolás, Berta; de Diego-Balaguer, Ruth; Fuentemilla, Lluís

    2017-01-11

    As the stream of experience unfolds, our memory system rapidly transforms current inputs into long-lasting meaningful memories. A putative neural mechanism that strongly influences how input elements are transformed into meaningful memory codes relies on the ability to integrate them with existing structures of knowledge or schemas. However, it is not yet clear whether schema-related integration neural mechanisms occur during online encoding. In the current investigation, we examined the encoding-dependent nature of this phenomenon in humans. We showed that actively integrating words with congruent semantic information provided by a category cue enhances memory for words and increases false recall. The memory effect of such active integration with congruent information was robust, even with an interference task occurring right after each encoding word list. In addition, via electroencephalography, we show in 2 separate studies that the onset of the neural signals of successful encoding appeared early (∼400 ms) during the encoding of congruent words. That the neural signals of successful encoding of congruent and incongruent information followed similarly ∼200 ms later suggests that this earlier neural response contributed to memory formation. We propose that the encoding of events that are congruent with readily available contextual semantics can trigger an accelerated onset of the neural mechanisms, supporting the integration of semantic information with the event input. This faster onset would result in a long-lasting and meaningful memory trace for the event but, at the same time, make it difficult to distinguish it from plausible but never encoded events (i.e., related false memories). Conceptual or schema congruence has a strong influence on long-term memory. However, the question of whether schema-related integration neural mechanisms occur during online encoding has yet to be clarified. We investigated the neural mechanisms reflecting how the active

  12. A four-channel microelectronic system for neural signal regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Xie Shushan; Wang Zhigong; Li Wenyuan [Institute of RF- and OE-ICs, Southeast University, Nanjing 210096 (China); Lue Xiaoying; Pan Haixian, E-mail: zgwang@seu.edu.c [State Key Laboratory of Bio-Electronics, Southeast University, Nanjing 210096 (China)

    2009-12-15

    This paper presents a microelectronic system which is capable of making a signal record and functional electric stimulation of an injured spinal cord. As a requirement of implantable engineering for the regeneration microelectronic system, the system is of low noise, low power, small size and high performance. A front-end circuit and two high performance OPAs (operational amplifiers) have been designed for the system with different functions, and the two OPAs are a low-noise low-power two-stage OPA and a constant-g{sub m} RTR input and output OPA. The system has been realized in CSMC 0.5-{mu}m CMOS technology. The test results show that the system satisfies the demands of neuron signal regeneration. (semiconductor integrated circuits)

  13. Ebola Virus Altered Innate and Adaptive Immune Response Signalling Pathways: Implications for Novel Therapeutic Approaches.

    Science.gov (United States)

    Kumar, Anoop

    2016-01-01

    Ebola virus (EBOV) arise attention for their impressive lethality by the poor immune response and high inflammatory reaction in the patients. It causes a severe hemorrhagic fever with case fatality rates of up to 90%. The mechanism underlying this lethal outcome is poorly understood. In 2014, a major outbreak of Ebola virus spread amongst several African countries, including Leone, Sierra, and Guinea. Although infections only occur frequently in Central Africa, but the virus has the potential to spread globally. Presently, there is no vaccine or treatment is available to counteract Ebola virus infections due to poor understanding of its interaction with the immune system. Accumulating evidence indicates that the virus actively alters both innate and adaptive immune responses and triggers harmful inflammatory responses. In the literature, some reports have shown that alteration of immune signaling pathways could be due to the ability of EBOV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. On the other hand, some reports have demonstrated that EBOV, VP35 proteins act as interferon antagonists. So, how the Ebola virus altered the innate and adaptive immune response signaling pathways is still an open question for the researcher to be explored. Thus, in this review, I try to summarize the mechanisms of the alteration of innate and adaptive immune response signaling pathways by Ebola virus which will be helpful for designing effective drugs or vaccines against this lethal infection. Further, potential targets, current treatment and novel therapeutic approaches have also been discussed.

  14. Transforming Musical Signals through a Genre Classifying Convolutional Neural Network

    Science.gov (United States)

    Geng, S.; Ren, G.; Ogihara, M.

    2017-05-01

    Convolutional neural networks (CNNs) have been successfully applied on both discriminative and generative modeling for music-related tasks. For a particular task, the trained CNN contains information representing the decision making or the abstracting process. One can hope to manipulate existing music based on this 'informed' network and create music with new features corresponding to the knowledge obtained by the network. In this paper, we propose a method to utilize the stored information from a CNN trained on musical genre classification task. The network was composed of three convolutional layers, and was trained to classify five-second song clips into five different genres. After training, randomly selected clips were modified by maximizing the sum of outputs from the network layers. In addition to the potential of such CNNs to produce interesting audio transformation, more information about the network and the original music could be obtained from the analysis of the generated features since these features indicate how the network 'understands' the music.

  15. FGF signalling regulates chromatin organisation during neural differentiation via mechanisms that can be uncoupled from transcription.

    Directory of Open Access Journals (Sweden)

    Nishal S Patel

    Full Text Available Changes in higher order chromatin organisation have been linked to transcriptional regulation; however, little is known about how such organisation alters during embryonic development or how it is regulated by extrinsic signals. Here we analyse changes in chromatin organisation as neural differentiation progresses, exploiting the clear spatial separation of the temporal events of differentiation along the elongating body axis of the mouse embryo. Combining fluorescence in situ hybridisation with super-resolution structured illumination microscopy, we show that chromatin around key differentiation gene loci Pax6 and Irx3 undergoes both decompaction and displacement towards the nuclear centre coincident with transcriptional onset. Conversely, down-regulation of Fgf8 as neural differentiation commences correlates with a more peripheral nuclear position of this locus. During normal neural differentiation, fibroblast growth factor (FGF signalling is repressed by retinoic acid, and this vitamin A derivative is further required for transcription of neural genes. We show here that exposure to retinoic acid or inhibition of FGF signalling promotes precocious decompaction and central nuclear positioning of differentiation gene loci. Using the Raldh2 mutant as a model for retinoid deficiency, we further find that such changes in higher order chromatin organisation are dependent on retinoid signalling. In this retinoid deficient condition, FGF signalling persists ectopically in the elongating body, and importantly, we find that inhibiting FGF receptor (FGFR signalling in Raldh2-/- embryos does not rescue differentiation gene transcription, but does elicit both chromatin decompaction and nuclear position change. These findings demonstrate that regulation of higher order chromatin organisation during differentiation in the embryo can be uncoupled from the machinery that promotes transcription and, for the first time, identify FGF as an extrinsic signal that

  16. Deep convolutional neural network for the automated detection and diagnosis of seizure using EEG signals.

    Science.gov (United States)

    Acharya, U Rajendra; Oh, Shu Lih; Hagiwara, Yuki; Tan, Jen Hong; Adeli, Hojjat

    2017-09-27

    An encephalogram (EEG) is a commonly used ancillary test to aide in the diagnosis of epilepsy. The EEG signal contains information about the electrical activity of the brain. Traditionally, neurologists employ direct visual inspection to identify epileptiform abnormalities. This technique can be time-consuming, limited by technical artifact, provides variable results secondary to reader expertise level, and is limited in identifying abnormalities. Therefore, it is essential to develop a computer-aided diagnosis (CAD) system to automatically distinguish the class of these EEG signals using machine learning techniques. This is the first study to employ the convolutional neural network (CNN) for analysis of EEG signals. In this work, a 13-layer deep convolutional neural network (CNN) algorithm is implemented to detect normal, preictal, and seizure classes. The proposed technique achieved an accuracy, specificity, and sensitivity of 88.67%, 90.00% and 95.00%, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Astrocytic Calcium Waves Signal Brain Injury to Neural Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Anna Kraft

    2017-03-01

    Full Text Available Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48 hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather than by diffusible factors or hypoxia. Using a newly established in vitro system we show that calcium waves induced in an astrocytic monolayer spread to neural stem and progenitor cells and increase their self-renewal as well as migratory behavior. These changes are due to an upregulation of the Notch signaling pathway. This introduces the concept of propagating astrocytic calcium waves transmitting brain injury signals over long distances.

  18. Dectin-1-Syk-CARD9 Signaling Pathway in TB Immunity

    Directory of Open Access Journals (Sweden)

    Matthew Wagener

    2018-02-01

    Full Text Available One of the first steps toward mounting an effective immune response to Mycobacterium tuberculosis (Mtb is recognition of the pathogen through pattern-recognition receptors (PRRs expressed by innate immune cells. Activation of the PRR Dectin-1 by an unknown mycobacterial ligand triggers an intracellular signaling cascade involving numerous proteins, including spleen tyrosine kinase, protein kinase C-delta, and caspase recruitment domain family member 9, some of which have been shown to influence host immune response to TB infection. Here, we review the role of Dectin-1 signaling pathway in anti-mycobacterial immunity and discuss its contribution in the control of Mtb infection, and potential applications in TB vaccine adjuvanticity.

  19. Effect of signal noise on the learning capability of an artificial neural network

    Science.gov (United States)

    Vega, J. J.; Reynoso, R.; Calvet, H. Carrillo

    2009-07-01

    Digital Pulse Shape Analysis (DPSA) by artificial neural networks (ANN) is becoming an important tool to extract relevant information from digitized signals in different areas. In this paper, we present a systematic evidence of how the concomitant noise that distorts the signals or patterns to be identified by an ANN set limits to its learning capability. Also, we present evidence that explains overtraining as a competition between the relevant pattern features, on the one side, against the signal noise, on the other side, as the main cause defining the shape of the error surface in weight space and, consequently, determining the steepest descent path that controls the ANN adaptation process.

  20. Effect of signal noise on the learning capability of an artificial neural network

    Energy Technology Data Exchange (ETDEWEB)

    Vega, J.J. [Departamento del Acelerador, Gerencia de Ciencias Ambientales, Instituto Nacional de Investigaciones Nucleares, Apartado Postal 18-1027, Mexico D.F. 11801 (Mexico)], E-mail: jjvc@nuclear.inin.mx; Reynoso, R. [Departamento del Acelerador, Gerencia de Ciencias Ambientales, Instituto Nacional de Investigaciones Nucleares, Apartado Postal 18-1027, Mexico D.F. 11801 (Mexico); Calvet, H. Carrillo [Laboratorio de Dinamica no Lineal, Facultad de Ciencias, Universidad Nacional Autonoma de Mexico, Mexico D.F. 04510 (Mexico)

    2009-07-21

    Digital Pulse Shape Analysis (DPSA) by artificial neural networks (ANN) is becoming an important tool to extract relevant information from digitized signals in different areas. In this paper, we present a systematic evidence of how the concomitant noise that distorts the signals or patterns to be identified by an ANN set limits to its learning capability. Also, we present evidence that explains overtraining as a competition between the relevant pattern features, on the one side, against the signal noise, on the other side, as the main cause defining the shape of the error surface in weight space and, consequently, determining the steepest descent path that controls the ANN adaptation process.

  1. Neural Network Based Recognition of Signal Patterns in Application to Automatic Testing of Rails

    Directory of Open Access Journals (Sweden)

    Tomasz Ciszewski

    2006-01-01

    Full Text Available The paper describes the application of neural network for recognition of signal patterns in measuring data gathered by the railroad ultrasound testing car. Digital conversion of the measuring signal allows to store and process large quantities of data. The elaboration of smart, effective and automatic procedures recognizing the obtained patterns on the basisof measured signal amplitude has been presented. The test shows only two classes of pattern recognition. In authors’ opinion if we deliver big enough quantity of training data, presented method is applicable to a system that recognizes many classes.

  2. The role of innate immune signaling in the pathogenesis of atopic dermatitis and consequences for treatments.

    Science.gov (United States)

    Skabytska, Yuliya; Kaesler, Susanne; Volz, Thomas; Biedermann, Tilo

    2016-01-01

    The skin is the largest organ at the interface between the environment and the host. Consequently, the skin plays a central role in mounting effective host defense. In addition to pathogens, the microbiota and the host immune system are in permanent contact and communication via the skin. Consequences of this permanent interaction are a unique and partly symbiotic relationship, a tight interdependence between these partners, and also a functional "setting the clock," in which, in the healthy steady state, an induction of protective responses to pathogens is guaranteed. At the same time, commensal microbes contribute to the alertness of the immune system and to the maintenance of immune tolerance. Atopic dermatitis (AD) is a chronic inflammatory skin disease based on a complex genetic trait with defects in cutaneous barrier, in stabilizing skin integrity. Most of AD patients develop deviated innate and adaptive immune responses. As a result, increased susceptibility to cutaneous infection is found in AD patients, and the interactions between these microbes and the skin participate in the development of chronic cutaneous inflammation. The role of the adaptive immune system was characterized in much detail, less though the contribution of innate immunity to AD pathogenesis. It is rather recent evidence that demonstrates a dominant role of components of the innate immune system not only for protecting from microbial invasion but also by orchestrating chronic skin inflammation. In this review we discuss the role of innate immune signaling and consecutive immune networks important for the pathogenesis and management of AD.

  3. Quantitative dynamic imaging of immune cell signalling using lentiviral gene transfer.

    Science.gov (United States)

    Bagnall, J; Boddington, C; Boyd, J; Brignall, R; Rowe, W; Jones, N A; Schmidt, L; Spiller, D G; White, M R H; Paszek, P

    2015-06-01

    Live-cell imaging of fluorescent fusion proteins has transformed our understanding of mammalian cell signalling and function. However, some cellular systems such as immune cells are unsuitable or refractory to many existing transgene delivery methods thus limiting systematic analyses. Here, a flexible lentiviral gene transfer platform for dynamic time-lapse imaging has been developed and validated with single-molecule spectroscopy, mathematical modelling and transcriptomics and used for analysis of a set of inflammation-related signalling networks. Time-lapse imaging of nuclear factor kappa B (NF-κB), signal transducer and activator of transcription (STATs) and nuclear factor of activated T-cells (NFAT) in mammalian immune cell lines provided evidence for heterogeneous temporal encoding of inflammatory signals. In particular, the absolute quantification of single-cell responses over time via fluorescent correlation spectroscopy (FCS) showed that NF-κB p65 activation in response to tumour necrosis factor α (TNFα) was differentially encoded in variable amplitude of nuclear translocation between immune and non-immune cells. The absolute number of activated molecules was dictated in part by the cell size, suggesting a morphology-dependent regulatory mechanism. The developed platform will enable further absolute quantitative analyses of the dynamic interactions between signalling networks, in and between individual cells, allowing better integration with mathematical models of signalling networks.

  4. OTULIN Restricts Met1-Linked Ubiquitination to Control Innate Immune Signaling

    DEFF Research Database (Denmark)

    Fiil, Berthe Katrine; Damgaard, Rune Busk; Wagner, Sebastian Alexander

    2013-01-01

    Conjugation of Met1-linked polyubiquitin (Met1-Ub) by the linear ubiquitin chain assembly complex (LUBAC) is an important regulatory modification in innate immune signaling. So far, only few Met1-Ub substrates have been described, and the regulatory mechanisms have remained elusive. We recently...... spontaneously accumulated Met1-Ub on LUBAC components, and NOD2 or TNFR1 stimulation led to extensive Met1-Ub accumulation on receptor complex components. We propose that OTULIN restricts Met1-Ub formation after immune receptor stimulation to prevent unwarranted proinflammatory signaling....

  5. Radial glial neural progenitors regulate nascent brain vascular network stabilization via inhibition of Wnt signaling.

    Directory of Open Access Journals (Sweden)

    Shang Ma

    Full Text Available The cerebral cortex performs complex cognitive functions at the expense of tremendous energy consumption. Blood vessels in the brain are known to form stereotypic patterns that facilitate efficient oxygen and nutrient delivery. Yet little is known about how vessel development in the brain is normally regulated. Radial glial neural progenitors are well known for their central role in orchestrating brain neurogenesis. Here we show that, in the late embryonic cortex, radial glial neural progenitors also play a key role in brain angiogenesis, by interacting with nascent blood vessels and regulating vessel stabilization via modulation of canonical Wnt signaling. We find that ablation of radial glia results in vessel regression, concomitant with ectopic activation of Wnt signaling in endothelial cells. Direct activation of Wnt signaling also results in similar vessel regression, while attenuation of Wnt signaling substantially suppresses regression. Radial glial ablation and ectopic Wnt pathway activation leads to elevated endothelial expression of matrix metalloproteinases, while inhibition of metalloproteinase activity significantly suppresses vessel regression. These results thus reveal a previously unrecognized role of radial glial progenitors in stabilizing nascent brain vascular network and provide novel insights into the molecular cascades through which target neural tissues regulate vessel stabilization and patterning during development and throughout life.

  6. A low power multichannel analog front end for portable neural signal recordings.

    Science.gov (United States)

    Obeid, Iyad; Nicolelis, Miguel A L; Wolf, Patrick D

    2004-02-15

    We present the design and testing of a 16-channel analog amplifier for processing neural signals. Each channel has the following features: (1) variable gain (70-94 dB), (2) four high pass Bessel filter poles (f(-3 dB)=445 Hz), (3) five low pass Bessel filter poles (f(-3 dB)=6.6 kHz), and (4) differential amplification with a user selectable reference channel to reject common mode background biological noise. Processed signals are time division multiplexed and sampled by an on-board 12-bit analog to digital converter at up to 62.5k samples/s per channel. The board is powered by two low dropout voltage regulators which may be supplied by a single battery. The board measures 8.1 cm x 9.9 cm, weighs 50 g, and consumes up to 130 mW. Its low input-referred noise (1.0 microV(RMS)) makes it possible to process low amplitude neural signals; the board was successfully tested in vivo to process cortically derived extracellular action potentials in primates. Signals processed by this board were compared to those generated by a commercially available system and were found to be nearly identical. Background noise generated by mastication was substantially attenuated by the selectable reference circuit. The described circuit is light weight and low power and is used as a component of a wearable multichannel neural telemetry system.

  7. Global and local missions of cAMP signaling in neural plasticity, learning, and memory.

    Science.gov (United States)

    Lee, Daewoo

    2015-01-01

    The fruit fly Drosophila melanogaster has been a popular model to study cAMP signaling and resultant behaviors due to its powerful genetic approaches. All molecular components (AC, PDE, PKA, CREB, etc) essential for cAMP signaling have been identified in the fly. Among them, adenylyl cyclase (AC) gene rutabaga and phosphodiesterase (PDE) gene dunce have been intensively studied to understand the role of cAMP signaling. Interestingly, these two mutant genes were originally identified on the basis of associative learning deficits. This commentary summarizes findings on the role of cAMP in Drosophila neuronal excitability, synaptic plasticity and memory. It mainly focuses on two distinct mechanisms (global versus local) regulating excitatory and inhibitory synaptic plasticity related to cAMP homeostasis. This dual regulatory role of cAMP is to increase the strength of excitatory neural circuits on one hand, but to act locally on postsynaptic GABA receptors to decrease inhibitory synaptic plasticity on the other. Thus the action of cAMP could result in a global increase in the neural circuit excitability and memory. Implications of this cAMP signaling related to drug discovery for neural diseases are also described.

  8. Global Synchronization Measurement of Multivariate Neural Signals with Massively Parallel Nonlinear Interdependence Analysis.

    Science.gov (United States)

    Chen, Dan; Li, Xiaoli; Cui, Dong; Wang, Lizhe; Lu, Dongchuan

    2014-01-01

    The estimation of synchronization amongst multiple brain regions is a critical issue in understanding brain functions. There is a lack of an appropriate approach which is capable of 1) measuring the direction and strength of synchronization of activities of multiple brain regions, and 2) adapting to the quickly increasing sizes and scales of neural signals. Nonlinear Interdependence (NLI) analysis is an effective method for measuring synchronization direction and strength of bivariate neural signal. However, the method currently does not directly apply in handling multivariate signal. Its application in practice has also long been largely hampered by the ultra-high complexity of NLI algorithms. Aiming at these problems, this study 1) extends the conventional NLI to quantify the global synchronization of multivariate neural signals, and 2) develops a parallelized NLI method with general-purpose computing on the graphics processing unit (GPGPU), namely, G-NLI. The approach performs synchronization measurement in a massively parallel manner. The G-NLI has improved the runtime performance by more than 1000 times comparing to the original sequential NLI. Meanwhile, the G-NLI was employed to analyze 10-channel local field potential (LFP) recordings from a patient suffering from temporal lobe epilepsy. The results demonstrate that the proposed G-NLI method can support real-time global synchronization measurement and it could be successful in localization of epileptic focus.

  9. Intrinsic lens potential of neural retina inhibited by Notch signaling as the cause of lens transdifferentiation.

    Science.gov (United States)

    Iida, Hideaki; Ishii, Yasuo; Kondoh, Hisato

    2017-01-15

    Embryonic neural retinas of avians produce lenses under spreading culture conditions. This phenomenon has been regarded as a paradigm of transdifferentiation due to the overt change in cell type. Here we elucidated the underlying mechanisms. Retina-to-lens transdifferentiation occurs in spreading cultures, suggesting that it is triggered by altered cell-cell interactions. Thus, we tested the involvement of Notch signaling based on its role in retinal neurogenesis. Starting from E8 retina, a small number of crystallin-expressing lens cells began to develop after 20 days in control spreading cultures. By contrast, addition of Notch signal inhibitors to cultures after day 2 strongly promoted lens development beginning at day 11, and a 10-fold increase in δ-crystallin expression level. After Notch signal inhibition, transcription factor genes that regulate the early stage of eye development, Prox1 and Pitx3, were sequentially activated. These observations indicate that the lens differentiation potential is intrinsic to the neural retina, and this potential is repressed by Notch signaling during normal embryogenesis. Therefore, Notch suppression leads to lens transdifferentiation by disinhibiting the neural retina-intrinsic program of lens development. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Human Age Recognition by Electrocardiogram Signal Based on Artificial Neural Network

    Science.gov (United States)

    Dasgupta, Hirak

    2016-12-01

    The objective of this work is to make a neural network function approximation model to detect human age from the electrocardiogram (ECG) signal. The input vectors of the neural network are the Katz fractal dimension of the ECG signal, frequencies in the QRS complex, male or female (represented by numeric constant) and the average of successive R-R peak distance of a particular ECG signal. The QRS complex has been detected by short time Fourier transform algorithm. The successive R peak has been detected by, first cutting the signal into periods by auto-correlation method and then finding the absolute of the highest point in each period. The neural network used in this problem consists of two layers, with Sigmoid neuron in the input and linear neuron in the output layer. The result shows the mean of errors as -0.49, 1.03, 0.79 years and the standard deviation of errors as 1.81, 1.77, 2.70 years during training, cross validation and testing with unknown data sets, respectively.

  11. Ultra-low-power and robust digital-signal-processing hardware for implantable neural interface microsystems.

    Science.gov (United States)

    Narasimhan, S; Chiel, H J; Bhunia, S

    2011-04-01

    Implantable microsystems for monitoring or manipulating brain activity typically require on-chip real-time processing of multichannel neural data using ultra low-power, miniaturized electronics. In this paper, we propose an integrated-circuit/architecture-level hardware design framework for neural signal processing that exploits the nature of the signal-processing algorithm. First, we consider different power reduction techniques and compare the energy efficiency between the ultra-low frequency subthreshold and conventional superthreshold design. We show that the superthreshold design operating at a much higher frequency can achieve comparable energy dissipation by taking advantage of extensive power gating. It also provides significantly higher robustness of operation and yield under large process variations. Next, we propose an architecture level preferential design approach for further energy reduction by isolating the critical computation blocks (with respect to the quality of the output signal) and assigning them higher delay margins compared to the noncritical ones. Possible delay failures under parameter variations are confined to the noncritical components, allowing graceful degradation in quality under voltage scaling. Simulation results using prerecorded neural data from the sea-slug (Aplysia californica) show that the application of the proposed design approach can lead to significant improvement in total energy, without compromising the output signal quality under process variations, compared to conventional design approaches.

  12. Wireless transmission of neural signals using entropy and mutual information compression.

    Science.gov (United States)

    Craciun, Stefan; Cheney, David; Gugel, Karl; Sanchez, Justin C; Principe, Jose C

    2011-02-01

    Two of the most critical tasks when designing a portable wireless neural recording system are to limit power consumption and to efficiently use the limited bandwidth. It is known that for most wireless devices the majority of power is consumed by the wireless transmitter and it often represents the bottleneck of the overall design. This paper compares two compression techniques that take advantage of the sparseness of the neural spikes in neural recordings using an information theoretic formalism to enhance the well-established vector quantization (VQ) algorithm. The two discriminative VQ algorithms are applied to neuronal recordings proving their ability to accurately reconstruct action potential (AP) regions of the neuronal signal while compressing background activity without using thresholds. The two operational modes presented offer distinct characteristics to lossy compression. The first approach requires no preprocessing or prior knowledge of the signal while the second requires a training set of spikes to obtain AP templates. The compression algorithms are implemented on an on-board digital signal processor (DSP) and results show that power consumption is decreased while the bandwidth is more efficiently utilized. The compression algorithms have been tested in real time on a hardware platform (PICO DSP ) enhanced with the DSP which runs the algorithm before sending the compressed data to a wireless transmitter. The compression ratios obtained range from 70:1 and 40:1 depending on the signal to noise ratio (SNR) of the input signal. The spike sorting accuracy in the reconstructed data is 95% compatible to the original neural data.

  13. Quality-on-Demand Compression of EEG Signals for Telemedicine Applications Using Neural Network Predictors

    Directory of Open Access Journals (Sweden)

    N. Sriraam

    2011-01-01

    Full Text Available A telemedicine system using communication and information technology to deliver medical signals such as ECG, EEG for long distance medical services has become reality. In either the urgent treatment or ordinary healthcare, it is necessary to compress these signals for the efficient use of bandwidth. This paper discusses a quality on demand compression of EEG signals using neural network predictors for telemedicine applications. The objective is to obtain a greater compression gains at a low bit rate while preserving the clinical information content. A two-stage compression scheme with a predictor and an entropy encoder is used. The residue signals obtained after prediction is first thresholded using various levels of thresholds and are further quantized and then encoded using an arithmetic encoder. Three neural network models, single-layer and multi-layer perceptrons and Elman network are used and the results are compared with linear predictors such as FIR filters and AR modeling. The fidelity of the reconstructed EEG signal is assessed quantitatively using parameters such as PRD, SNR, cross correlation and power spectral density. It is found from the results that the quality of the reconstructed signal is preserved at a low PRD thereby yielding better compression results compared to results obtained using lossless scheme.

  14. Quality-on-Demand Compression of EEG Signals for Telemedicine Applications Using Neural Network Predictors.

    Science.gov (United States)

    Sriraam, N

    2011-01-01

    A telemedicine system using communication and information technology to deliver medical signals such as ECG, EEG for long distance medical services has become reality. In either the urgent treatment or ordinary healthcare, it is necessary to compress these signals for the efficient use of bandwidth. This paper discusses a quality on demand compression of EEG signals using neural network predictors for telemedicine applications. The objective is to obtain a greater compression gains at a low bit rate while preserving the clinical information content. A two-stage compression scheme with a predictor and an entropy encoder is used. The residue signals obtained after prediction is first thresholded using various levels of thresholds and are further quantized and then encoded using an arithmetic encoder. Three neural network models, single-layer and multi-layer perceptrons and Elman network are used and the results are compared with linear predictors such as FIR filters and AR modeling. The fidelity of the reconstructed EEG signal is assessed quantitatively using parameters such as PRD, SNR, cross correlation and power spectral density. It is found from the results that the quality of the reconstructed signal is preserved at a low PRD thereby yielding better compression results compared to results obtained using lossless scheme.

  15. Comparison of MLP neural network and neuro-fuzzy system in transcranial Doppler signals recorded from the cerebral vessels.

    Science.gov (United States)

    Hardalaç, Firat

    2008-04-01

    Transcranial Doppler signals recorded from cerebral vessels of 110 patients were transferred to a personal computer by using a 16 bit sound card. Spectral analyses of Transcranial Doppler signals were performed for determining the Multi Layer Perceptron (MLP) neural network and neuro Ankara-fuzzy system inputs. In order to do a good interpretation and rapid diagnosis, FFT parameters of Transcranial Doppler signals classified using MLP neural network and neuro-fuzzy system. Our findings demonstrated that 92% correct classification rate was obtained from MLP neural network, and 86% correct classification rate was obtained from neuro-fuzzy system.

  16. Global exponential stability and dissipativity of generalized neural networks with time-varying delay signals.

    Science.gov (United States)

    Manivannan, R; Samidurai, R; Cao, Jinde; Alsaedi, Ahmed; Alsaadi, Fuad E

    2017-03-01

    This paper investigates the problems of exponential stability and dissipativity of generalized neural networks (GNNs) with time-varying delay signals. By constructing a novel Lyapunov-Krasovskii functionals (LKFs) with triple integral terms that contain more advantages of the state vectors of the neural networks, and the upper bound on the time-varying delay signals are formulated. We employ a new integral inequality technique (IIT), free-matrix-based (FMB) integral inequality approach, and Wirtinger double integral inequality (WDII) technique together with the reciprocally convex combination (RCC) approach to bound the time derivative of the LKFs. An improved exponential stability and strictly (Q,S,R)-γ-dissipative conditions of the addressed systems are represented by the linear matrix inequalities (LMIs). Finally, four interesting numerical examples are developed to verify the usefulness of the proposed method with a practical application to a biological network. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Defective ALK5 signaling in the neural crest leads to increased postmigratory neural crest cell apoptosis and severe outflow tract defects

    Directory of Open Access Journals (Sweden)

    Sucov Henry M

    2006-11-01

    Full Text Available Abstract Background Congenital cardiovascular diseases are the most common form of birth defects in humans. A substantial portion of these defects has been associated with inappropriate induction, migration, differentiation and patterning of pluripotent cardiac neural crest stem cells. While TGF-β-superfamily signaling has been strongly implicated in neural crest cell development, the detailed molecular signaling mechanisms in vivo are still poorly understood. Results We deleted the TGF-β type I receptor Alk5 specifically in the mouse neural crest cell lineage. Failure in signaling via ALK5 leads to severe cardiovascular and pharyngeal defects, including inappropriate remodeling of pharyngeal arch arteries, abnormal aortic sac development, failure in pharyngeal organ migration and persistent truncus arteriosus. While ALK5 is not required for neural crest cell migration, our results demonstrate that it plays an important role in the survival of post-migratory cardiac neural crest cells. Conclusion Our results demonstrate that ALK5-mediated signaling in neural crest cells plays an essential cell-autonomous role in the pharyngeal and cardiac outflow tract development.

  18. Signalling through the Type 1 Insulin-Like Growth Factor Receptor (IGF1R Interacts with Canonical Wnt Signalling to Promote Neural Proliferation in Developing Brain

    Directory of Open Access Journals (Sweden)

    Qichen Hu

    2012-05-01

    Full Text Available Signalling through the IGF1R [type 1 IGF (insulin-like growth factor receptor] and canonical Wnt signalling are two signalling pathways that play critical roles in regulating neural cell generation and growth. To determine whether the signalling through the IGF1R can interact with the canonical Wnt signalling pathway in neural cells in vivo, we studied mutant mice with altered IGF signalling. We found that in mice with blunted IGF1R expression specifically in nestin-expressing neural cells (IGF1RNestin–KO mice the abundance of neural β-catenin was significantly reduced. Blunting IGF1R expression also markedly decreased: (i the activity of a LacZ (β-galactosidase reporter transgene that responds to Wnt nuclear signalling (LacZTCF reporter transgene and (ii the number of proliferating neural precursors. In contrast, overexpressing IGF-I (insulin-like growth factor I in brain markedly increased the activity of the LacZTCF reporter transgene. Consistently, IGF-I treatment also markedly increased the activity of the LacZTCF reporter transgene in embryonic neuron cultures that are derived from LacZTCF Tg (transgenic mice. Importantly, increasing the abundance of β-catenin in IGF1RNestin–KO embryonic brains by suppressing the activity of GSK3β (glycogen synthase kinase-3β significantly alleviated the phenotypic changes induced by IGF1R deficiency. These phenotypic changes includes: (i retarded brain growth, (ii reduced precursor proliferation and (iii decreased neuronal number. Our current data, consistent with our previous study of cultured oligodendrocytes, strongly support the concept that IGF signalling interacts with canonical Wnt signalling in the developing brain to promote neural proliferation. The interaction of IGF and canonical Wnt signalling plays an important role in normal brain development by promoting neural precursor proliferation.

  19. Reconfigurable embedded system architecture for next-generation Neural Signal Processing.

    Science.gov (United States)

    Balasubramanian, Karthikeyan; Obeid, Iyad

    2010-01-01

    This work presents a new architectural framework for next generation Neural Signal Processing (NSP). The essential features of the NSP hardware platform include scalability, reconfigurability, real-time processing ability and data storage. This proposed framework has been implemented in a proof-of-concept NSP prototype using an embedded system architecture synthesized in a Xilinx(®)Virtex(®)5 development board. The prototype includes a threshold-based spike detector and a fuzzy logic-based spike sorter.

  20. Immune response and insulin signalling alter mosquito feeding behaviour to enhance malaria transmission potential.

    Science.gov (United States)

    Cator, Lauren J; Pietri, Jose E; Murdock, Courtney C; Ohm, Johanna R; Lewis, Edwin E; Read, Andrew F; Luckhart, Shirley; Thomas, Matthew B

    2015-07-08

    Malaria parasites alter mosquito feeding behaviour in a way that enhances parasite transmission. This is widely considered a prime example of manipulation of host behaviour to increase onward transmission, but transient immune challenge in the absence of parasites can induce the same behavioural phenotype. Here, we show that alterations in feeding behaviour depend on the timing and dose of immune challenge relative to blood ingestion and that these changes are functionally linked to changes in insulin signalling in the mosquito gut. These results suggest that altered phenotypes derive from insulin signalling-dependent host resource allocation among immunity, blood feeding, and reproduction in a manner that is not specific to malaria parasite infection. We measured large increases in mosquito survival and subsequent transmission potential when feeding patterns are altered. Leveraging these changes in physiology, behaviour and life history could promote effective and sustainable control of female mosquitoes responsible for transmission.

  1. Steroid Hormone Signaling Is Essential to Regulate Innate Immune Cells and Fight Bacterial Infection in Drosophila

    Science.gov (United States)

    Regan, Jennifer C.; Brandão, Ana S.; Leitão, Alexandre B.; Mantas Dias, Ângela Raquel; Sucena, Élio; Jacinto, António; Zaidman-Rémy, Anna

    2013-01-01

    Coupling immunity and development is essential to ensure survival despite changing internal conditions in the organism. Drosophila metamorphosis represents a striking example of drastic and systemic physiological changes that need to be integrated with the innate immune system. However, nothing is known about the mechanisms that coordinate development and immune cell activity in the transition from larva to adult. Here, we reveal that regulation of macrophage-like cells (hemocytes) by the steroid hormone ecdysone is essential for an effective innate immune response over metamorphosis. Although it is generally accepted that steroid hormones impact immunity in mammals, their action on monocytes (e.g. macrophages and neutrophils) is still not well understood. Here in a simpler model system, we used an approach that allows in vivo, cell autonomous analysis of hormonal regulation of innate immune cells, by combining genetic manipulation with flow cytometry, high-resolution time-lapse imaging and tissue-specific transcriptomic analysis. We show that in response to ecdysone, hemocytes rapidly upregulate actin dynamics, motility and phagocytosis of apoptotic corpses, and acquire the ability to chemotax to damaged epithelia. Most importantly, individuals lacking ecdysone-activated hemocytes are defective in bacterial phagocytosis and are fatally susceptible to infection by bacteria ingested at larval stages, despite the normal systemic and local production of antimicrobial peptides. This decrease in survival is comparable to the one observed in pupae lacking immune cells altogether, indicating that ecdysone-regulation is essential for hemocyte immune functions and survival after infection. Microarray analysis of hemocytes revealed a large set of genes regulated at metamorphosis by EcR signaling, among which many are known to function in cell motility, cell shape or phagocytosis. This study demonstrates an important role for steroid hormone regulation of immunity in vivo in

  2. Steroid hormone signaling is essential to regulate innate immune cells and fight bacterial infection in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jennifer C Regan

    2013-10-01

    Full Text Available Coupling immunity and development is essential to ensure survival despite changing internal conditions in the organism. Drosophila metamorphosis represents a striking example of drastic and systemic physiological changes that need to be integrated with the innate immune system. However, nothing is known about the mechanisms that coordinate development and immune cell activity in the transition from larva to adult. Here, we reveal that regulation of macrophage-like cells (hemocytes by the steroid hormone ecdysone is essential for an effective innate immune response over metamorphosis. Although it is generally accepted that steroid hormones impact immunity in mammals, their action on monocytes (e.g. macrophages and neutrophils is still not well understood. Here in a simpler model system, we used an approach that allows in vivo, cell autonomous analysis of hormonal regulation of innate immune cells, by combining genetic manipulation with flow cytometry, high-resolution time-lapse imaging and tissue-specific transcriptomic analysis. We show that in response to ecdysone, hemocytes rapidly upregulate actin dynamics, motility and phagocytosis of apoptotic corpses, and acquire the ability to chemotax to damaged epithelia. Most importantly, individuals lacking ecdysone-activated hemocytes are defective in bacterial phagocytosis and are fatally susceptible to infection by bacteria ingested at larval stages, despite the normal systemic and local production of antimicrobial peptides. This decrease in survival is comparable to the one observed in pupae lacking immune cells altogether, indicating that ecdysone-regulation is essential for hemocyte immune functions and survival after infection. Microarray analysis of hemocytes revealed a large set of genes regulated at metamorphosis by EcR signaling, among which many are known to function in cell motility, cell shape or phagocytosis. This study demonstrates an important role for steroid hormone regulation of

  3. Purinergic signaling and infection by Leishmania: A new approach to evasion of the immune response

    Directory of Open Access Journals (Sweden)

    Amanda Braga de Figueiredo

    2016-08-01

    Full Text Available Infection by protozoan parasites is part of the most common Tropical Neglected Diseases. In the case of leishmaniasis, several millions of people are at risk of contracting the disease. In spite of innumerous studies that elucidated the immune response capable of killing the parasite, the understanding of the evasion mechanisms utilized by the parasite to survive within the very cell responsible for its destruction is still incomplete. In this review, we offer a new approach to the control of the immune response against the parasite. The ability of the parasite to modulate the levels of extracellular ATP and adenosine either by directly acting on the levels of these molecules or by inducing the expression of CD39 and CD73 on the infected cell may influence the magnitude of the immune response against the parasite contributing to its growth and survival. Keywords: Leishmania, Innate response, Immune evasion, Purinergic signaling

  4. GDSL LIPASE1 Modulates Plant Immunity through Feedback Regulation of Ethylene Signaling1[W

    Science.gov (United States)

    Kim, Hye Gi; Kwon, Sun Jae; Jang, Young Jin; Nam, Myung Hee; Chung, Joo Hee; Na, Yun-Cheol; Guo, Hongwei; Park, Ohkmae K.

    2013-01-01

    Ethylene is a key signal in the regulation of plant defense responses. It is required for the expression and function of GDSL LIPASE1 (GLIP1) in Arabidopsis (Arabidopsis thaliana), which plays an important role in plant immunity. Here, we explore molecular mechanisms underlying the relationship between GLIP1 and ethylene signaling by an epistatic analysis of ethylene response mutants and GLIP1-overexpressing (35S:GLIP1) plants. We show that GLIP1 expression is regulated by ethylene signaling components and, further, that GLIP1 expression or application of petiole exudates from 35S:GLIP1 plants affects ethylene signaling both positively and negatively, leading to ETHYLENE RESPONSE FACTOR1 activation and ETHYLENE INSENSITIVE3 (EIN3) down-regulation, respectively. Additionally, 35S:GLIP1 plants or their exudates increase the expression of the salicylic acid biosynthesis gene SALICYLIC ACID INDUCTION-DEFICIENT2, known to be inhibited by EIN3 and EIN3-LIKE1. These results suggest that GLIP1 regulates plant immunity through positive and negative feedback regulation of ethylene signaling, and this is mediated by its activity to accumulate a systemic signal(s) in the phloem. We propose a model explaining how GLIP1 regulates the fine-tuning of ethylene signaling and ethylene-salicylic acid cross talk. PMID:24170202

  5. Detecting and Predicting Muscle Fatigue during Typing By SEMG Signal Processing and Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    Elham Ghoochani

    2011-03-01

    Full Text Available Introduction: Repetitive strain injuries are one of the most prevalent problems in occupational diseases. Repetition, vibration and bad postures of the extremities are physical risk factors related to work that can cause chronic musculoskeletal disorders. Repetitive work on a computer with low level contraction requires the posture to be maintained for a long time, which can cause muscle fatigue. Muscle fatigue in shoulders and neck is one of the most prevalent problems reported with computer users especially during typing. Surface electromyography (SEMG signals are used for detecting muscle fatigue as a non-invasive method. Material and Methods: Nine healthy females volunteered for signal recoding during typing. EMG signals were recorded from the trapezius muscle, which is subjected to muscle fatigue during typing.  After signal analysis and feature extraction, detecting and predicting muscle fatigue was performed by using the MLP artificial neural network. Results: Recorded signals were analyzed in time and frequency domains for feature extraction. Results of classification showed that the MLP neural network can detect and predict muscle fatigue during typing with 80.79 % ± 1.04% accuracy. Conclusion: Intelligent classification and prediction of muscle fatigue can have many applications in human factors engineering (ergonomics, rehabilitation engineering and biofeedback equipment for mitigating the injuries of repetitive works.

  6. EEG signal classification using PSO trained RBF neural network for epilepsy identification

    Directory of Open Access Journals (Sweden)

    Sandeep Kumar Satapathy

    Full Text Available The electroencephalogram (EEG is a low amplitude signal generated in the brain, as a result of information flow during the communication of several neurons. Hence, careful analysis of these signals could be useful in understanding many human brain disorder diseases. One such disease topic is epileptic seizure identification, which can be identified via a classification process of the EEG signal after preprocessing with the discrete wavelet transform (DWT. To classify the EEG signal, we used a radial basis function neural network (RBFNN. As shown herein, the network can be trained to optimize the mean square error (MSE by using a modified particle swarm optimization (PSO algorithm. The key idea behind the modification of PSO is to introduce a method to overcome the problem of slow searching in and around the global optimum solution. The effectiveness of this procedure was verified by an experimental analysis on a benchmark dataset which is publicly available. The result of our experimental analysis revealed that the improvement in the algorithm is significant with respect to RBF trained by gradient descent and canonical PSO. Here, two classes of EEG signals were considered: the first being an epileptic and the other being non-epileptic. The proposed method produced a maximum accuracy of 99% as compared to the other techniques. Keywords: Electroencephalography, Radial basis function neural network, Particle swarm optimization, Discrete wavelet transform, Machine learning

  7. Genetic algorithm for the optimization of features and neural networks in ECG signals classification.

    Science.gov (United States)

    Li, Hongqiang; Yuan, Danyang; Ma, Xiangdong; Cui, Dianyin; Cao, Lu

    2017-01-31

    Feature extraction and classification of electrocardiogram (ECG) signals are necessary for the automatic diagnosis of cardiac diseases. In this study, a novel method based on genetic algorithm-back propagation neural network (GA-BPNN) for classifying ECG signals with feature extraction using wavelet packet decomposition (WPD) is proposed. WPD combined with the statistical method is utilized to extract the effective features of ECG signals. The statistical features of the wavelet packet coefficients are calculated as the feature sets. GA is employed to decrease the dimensions of the feature sets and to optimize the weights and biases of the back propagation neural network (BPNN). Thereafter, the optimized BPNN classifier is applied to classify six types of ECG signals. In addition, an experimental platform is constructed for ECG signal acquisition to supply the ECG data for verifying the effectiveness of the proposed method. The GA-BPNN method with the MIT-BIH arrhythmia database achieved a dimension reduction of nearly 50% and produced good classification results with an accuracy of 97.78%. The experimental results based on the established acquisition platform indicated that the GA-BPNN method achieved a high classification accuracy of 99.33% and could be efficiently applied in the automatic identification of cardiac arrhythmias.

  8. Genetic algorithm for the optimization of features and neural networks in ECG signals classification

    Science.gov (United States)

    Li, Hongqiang; Yuan, Danyang; Ma, Xiangdong; Cui, Dianyin; Cao, Lu

    2017-01-01

    Feature extraction and classification of electrocardiogram (ECG) signals are necessary for the automatic diagnosis of cardiac diseases. In this study, a novel method based on genetic algorithm-back propagation neural network (GA-BPNN) for classifying ECG signals with feature extraction using wavelet packet decomposition (WPD) is proposed. WPD combined with the statistical method is utilized to extract the effective features of ECG signals. The statistical features of the wavelet packet coefficients are calculated as the feature sets. GA is employed to decrease the dimensions of the feature sets and to optimize the weights and biases of the back propagation neural network (BPNN). Thereafter, the optimized BPNN classifier is applied to classify six types of ECG signals. In addition, an experimental platform is constructed for ECG signal acquisition to supply the ECG data for verifying the effectiveness of the proposed method. The GA-BPNN method with the MIT-BIH arrhythmia database achieved a dimension reduction of nearly 50% and produced good classification results with an accuracy of 97.78%. The experimental results based on the established acquisition platform indicated that the GA-BPNN method achieved a high classification accuracy of 99.33% and could be efficiently applied in the automatic identification of cardiac arrhythmias.

  9. DAMP signaling is a key pathway inducing immune modulation after brain injury.

    Science.gov (United States)

    Liesz, Arthur; Dalpke, Alexander; Mracsko, Eva; Antoine, Daniel J; Roth, Stefan; Zhou, Wei; Yang, Huan; Na, Shin-Young; Akhisaroglu, Mustafa; Fleming, Thomas; Eigenbrod, Tatjana; Nawroth, Peter P; Tracey, Kevin J; Veltkamp, Roland

    2015-01-14

    Acute brain lesions induce profound alterations of the peripheral immune response comprising the opposing phenomena of early immune activation and subsequent immunosuppression. The mechanisms underlying this brain-immune signaling are largely unknown. We used animal models for experimental brain ischemia as a paradigm of acute brain lesions and additionally investigated a large cohort of stroke patients. We analyzed release of HMGB1 isoforms by mass spectrometry and investigated its inflammatory potency and signaling pathways by immunological in vivo and in vitro techniques. Features of the complex behavioral sickness behavior syndrome were characterized by homecage behavior analysis. HMGB1 downstream signaling, particularly with RAGE, was studied in various transgenic animal models and by pharmacological blockade. Our results indicate that the cytokine-inducing, fully reduced isoform of HMGB1 was released from the ischemic brain in the hyperacute phase of stroke in mice and patients. Cytokines secreted in the periphery in response to brain injury induced sickness behavior, which could be abrogated by inhibition of the HMGB1-RAGE pathway or direct cytokine neutralization. Subsequently, HMGB1-release induced bone marrow egress and splenic proliferation of bone marrow-derived suppressor cells, inhibiting the adaptive immune responses in vivo and vitro. Furthermore, HMGB1-RAGE signaling resulted in functional exhaustion of mature monocytes and lymphopenia, the hallmarks of immune suppression after extensive ischemia. This study introduces the HMGB1-RAGE-mediated pathway as a key mechanism explaining the complex postischemic brain-immune interactions. Copyright © 2015 the authors 0270-6474/15/350583-16$15.00/0.

  10. H. pylori exploits and manipulates innate and adaptive immune cell signaling pathways to establish persistent infection

    Directory of Open Access Journals (Sweden)

    Arnold Isabelle C

    2011-11-01

    Full Text Available Abstract Persistent infection with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes carriers to a high gastric cancer risk, but has also been linked to protection from allergic, chronic inflammatory and autoimmune diseases. In the course of tens of thousands of years of co-existence with its human host, H. pylori has evolved elaborate adaptations that allow it to persist in the hostile environment of the stomach in the face of a vigorous innate and adaptive immune response. For this review, we have identified several key immune cell types and signaling pathways that appear to be preferentially targeted by the bacteria to establish and maintain persistent infection. We explore the mechanisms that allow the bacteria to avoid detection by innate immune cells via their pattern recognition receptors, to escape T-cell mediated adaptive immunity, and to reprogram the immune system towards tolerance rather than immunity. The implications of the immunomodulatory properties of the bacteria for the prevention of allergic and auto-immune diseases in chronically infected individuals are also discussed.

  11. A probablistic neural network classification system for signal and image processing

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, B. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    The Acoustical Heart Valve Analysis Package is a system for signal and image processing and classification. It is being developed in both Matlab and C, to provide an interactive, interpreted environment, and has been optimized for large scale matrix operations. It has been used successfully to classify acoustic signals from implanted prosthetic heart valves in human patients, and will be integrated into a commercial Heart Valve Screening Center. The system uses several standard signal processing algorithms, as well as supervised learning techniques using the probabilistic neural network (PNN). Although currently used for the acoustic heart valve application, the algorithms and modular design allow it to be used for other applications, as well. We will describe the signal classification system, and show results from a set of test valves.

  12. RBF neural network prediction on weak electrical signals in Aloe vera var. chinensis

    Science.gov (United States)

    Wang, Lanzhou; Zhao, Jiayin; Wang, Miao

    2008-10-01

    A Gaussian radial base function (RBF) neural network forecast on signals in the Aloe vera var. chinensis by the wavelet soft-threshold denoised as the time series and using the delayed input window chosen at 50, is set up to forecast backward. There was the maximum amplitude at 310.45μV, minimum -75.15μV, average value -2.69μV and Aloe vera var. chinensis respectively. The electrical signal in Aloe vera var. chinensis is a sort of weak, unstable and low frequency signals. A result showed that it is feasible to forecast plant electrical signals for the timing by the RBF. The forecast data can be used as the preferences for the intelligent autocontrol system based on the adaptive characteristic of plants to achieve the energy saving on the agricultural production in the plastic lookum or greenhouse.

  13. Cancellation of artifacts in ECG signals using a normalized adaptive neural filter.

    Science.gov (United States)

    Wu, Yunfeng; Rangayyan, Rangaraj M; Ng, Sin-Chun

    2007-01-01

    Denoising electrocardiographic (ECG) signals is an essential procedure prior to their analysis. In this paper, we present a normalized adaptive neural filter (NANF) for cancellation of artifacts in ECG signals. The normalized filter coefficients are updated by the steepest-descent algorithm; the adaptation process is designed to minimize the difference between second-order estimated output values and the desired artifact-free ECG signals. Empirical results with benchmark data show that the adaptive artifact canceller that includes the NANF can effectively remove muscle-contraction artifacts and high-frequency noise in ambulatory ECG recordings, leading to a high signal-to-noise ratio. Moreover, the performance of the NANF in terms of the root-mean-squared error, normalized correlation coefficient, and filtered artifact entropy is significantly better than that of the popular least-mean-square (LMS) filter.

  14. Embryonic requirements for ErbB signaling in neural crest development and adult pigment pattern formation

    Science.gov (United States)

    Budi, Erine H.; Patterson, Larissa B.; Parichy, David M.

    2009-01-01

    SUMMARY Vertebrate pigment cells are derived from neural crest cells and are a useful system for studying neural crest-derived traits during post-embryonic development. In zebrafish, neural crest-derived melanophores differentiate during embryogenesis to produce stripes in the early larva. Dramatic changes to the pigment pattern occur subsequently during the larva-to-adult transformation, or metamorphosis. At this time, embryonic melanophores are replaced by newly differentiating metamorphic melanophores that form the adult stripes. Mutants with normal embryonic/early larval pigment patterns but defective adult patterns identify factors required uniquely to establish, maintain, or recruit the latent precursors to metamorphic melanophores. We show that one such mutant, picasso, lacks most metamorphic melanophores and results from mutations in the ErbB gene erbb3b, encoding an EGFR-like receptor tyrosine kinase. To identify critical periods for ErbB activities, we treated fish with pharmacological ErbB inhibitors and also knocked-down erbb3b by morpholino injection. These analyses reveal an embryonic critical period for ErbB signaling in promoting later pigment pattern metamorphosis, despite the normal patterning of embryonic/early larval melanophores. We further demonstrate a peak requirement during neural crest migration that correlates with early defects in neural crest pathfinding and peripheral ganglion formation. Finally, we show that erbb3b activities are both autonomous and non-autonomous to the metamorphic melanophore lineage. These data identify a very early, embryonic, requirement for erbb3b in the development of much later metamorphic melanophores, and suggest complex modes by which ErbB signals promote adult pigment pattern development. PMID:18508863

  15. Ectopic expression of the immune adaptor protein CD3zeta in neural stem/progenitor cells disrupts cell-fate specification.

    Science.gov (United States)

    Angibaud, Julie; Baudouin, Stéphane J; Louveau, Antoine; Nerrière-Daguin, Véronique; Bonnamain, Virginie; Csaba, Zsolt; Dournaud, Pascal; Naveilhan, Philippe; Noraz, Nelly; Pellier-Monnin, Véronique; Boudin, Hélène

    2012-02-01

    Immune signaling and neuroinflammatory mediators have recently emerged as influential variables that regulate neural precursor/stem cell (NPC) behavior and function. In this study, we investigated whether the signaling adaptor protein CD3ζ, a transmembrane protein involved in T cell differentiation and function and recently shown to regulate neuronal development in the central nervous system (CNS), may have a role in NPC differentiation. We analyzed the expression profile of CD3ζ in embryonic rat brain during neurogenic periods and in neurosphere-derived neural cells, and we investigated the action of CD3ζ on cell differentiation. We found that CD3ζ expression coincided with neuronal commitment, but its forced expression in NPCs prevented the production of neurons and oligodendrocytes, but not astroglial cells. This blockade of neuronal differentiation was operated through an ITAM-independent mechanism, but required the Asp36 of the CD3ζ transmembrane domain involved in membrane receptor interaction. Together, our findings show that ectopic CD3ζ expression in NPCs impaired their normal cell-fate specification and suggest that variations of CD3ζ expression in the developing CNS might result in neurodevelopmental anomalies.

  16. Cell-type-specific modulation of innate immune signalling by vitamin D in human mononuclear phagocytes.

    Science.gov (United States)

    Kundu, Rhiannon; Theodoraki, Aikaterini; Haas, Carolin T; Zhang, Yanjing; Chain, Benjamin; Kriston-Vizi, Janos; Noursadeghi, Mahdad; Khoo, Bernard

    2017-01-01

    Vitamin D is widely reported to inhibit innate immune signalling and dendritic cell (DC) maturation as a potential immunoregulatory mechanism. It is not known whether vitamin D has global or gene-specific effects on transcriptional responses downstream of innate immune stimulation, or whether vitamin D inhibition of innate immune signalling is common to different cells. We confirmed vitamin D inhibition of nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signalling in monocyte-derived DC (MDDC) stimulated with lipopolysaccharide (LPS). This was associated with global but modest attenuation of LPS-induced transcriptional changes at genome-wide level. Surprisingly, vitamin D did not inhibit innate immune NF-κB activation in monocyte-derived macrophages. Consistent with our findings in MDDC, ex vivo vitamin D treatment of primary peripheral blood myeloid DC also led to significant inhibition of LPS-inducible NF-κB activation. Unexpectedly, in the same samples, vitamin D enhanced activation of both NF-κB and MAPK signalling in primary peripheral blood monocytes. In a cross-sectional clinical cohort, we found no relationship between peripheral blood vitamin D levels and LPS-inducible activation of NF-κB and MAPK pathways in monocytes of myeloid DC. Remarkably, however, in vivo supplementation of people with vitamin D deficiency in this clinical cohort also enhanced LPS-inducible MAPK signalling in peripheral blood monocytes. Therefore, we report that vitamin D differentially modulates the molecular response to innate immune stimulation in monocytes, macrophages and dendritic cells. These results are of importance in the design of studies on vitamin D supplementation in infectious and immunological diseases. © 2016 The Authors. Immunology Published by John Wiley & Sons Ltd.

  17. Disease-causing mutations in the XIAP BIR2 domain impair NOD2-dependent immune signalling

    DEFF Research Database (Denmark)

    Damgaard, Rune Busk; Fiil, Berthe Katrine; Speckmann, Carsten

    2013-01-01

    X-linked Inhibitor of Apoptosis (XIAP) is an essential ubiquitin ligase for pro-inflammatory signalling downstream of the nucleotide-binding oligomerization domain containing (NOD)-1 and -2 pattern recognition receptors. Mutations in XIAP cause X-linked lymphoproliferative syndrome type-2 (XLP2...... that the RIPK2 binding site in XIAP overlaps with the BIR2 IBM-binding pocket and find that a bivalent Smac mimetic compound (SMC) potently antagonises XIAP function downstream of NOD2 to limit signalling. These findings suggest that impaired immune signalling in response to NOD1/2 stimulation is a general...

  18. Intra-day signal instabilities affect decoding performance in an intracortical neural interface system

    Science.gov (United States)

    Perge, János A.; Homer, Mark L.; Malik, Wasim Q.; Cash, Sydney; Eskandar, Emad; Friehs, Gerhard; Donoghue, John P.; Hochberg, Leigh R.

    2013-06-01

    Objective. Motor neural interface systems (NIS) aim to convert neural signals into motor prosthetic or assistive device control, allowing people with paralysis to regain movement or control over their immediate environment. Effector or prosthetic control can degrade if the relationship between recorded neural signals and intended motor behavior changes. Therefore, characterizing both biological and technological sources of signal variability is important for a reliable NIS. Approach. To address the frequency and causes of neural signal variability in a spike-based NIS, we analyzed within-day fluctuations in spiking activity and action potential amplitude recorded with silicon microelectrode arrays implanted in the motor cortex of three people with tetraplegia (BrainGate pilot clinical trial, IDE). Main results. 84% of the recorded units showed a statistically significant change in apparent firing rate (3.8 ± 8.71 Hz or 49% of the mean rate) across several-minute epochs of tasks performed on a single session, and 74% of the units showed a significant change in spike amplitude (3.7 ± 6.5 µV or 5.5% of mean spike amplitude). 40% of the recording sessions showed a significant correlation in the occurrence of amplitude changes across electrodes, suggesting array micro-movement. Despite the relatively frequent amplitude changes, only 15% of the observed within-day rate changes originated from recording artifacts such as spike amplitude change or electrical noise, while 85% of the rate changes most likely emerged from physiological mechanisms. Computer simulations confirmed that systematic rate changes of individual neurons could produce a directional ‘bias’ in the decoded neural cursor movements. Instability in apparent neuronal spike rates indeed yielded a directional bias in 56% of all performance assessments in participant cursor control (n = 2 participants, 108 and 20 assessments over two years), resulting in suboptimal performance in these sessions

  19. Respiratory signal prediction based on adaptive boosting and multi-layer perceptron neural network

    Science.gov (United States)

    Sun, W. Z.; Jiang, M. Y.; Ren, L.; Dang, J.; You, T.; Yin, F.-F.

    2017-09-01

    To improve the prediction accuracy of respiratory signals using adaptive boosting and multi-layer perceptron neural network (ADMLP-NN) for gated treatment of moving target in radiation therapy. The respiratory signals acquired using a real-time position management (RPM) device from 138 previous 4DCT scans were retrospectively used in this study. The ADMLP-NN was composed of several artificial neural networks (ANNs) which were used as weaker predictors to compose a stronger predictor. The respiratory signal was initially smoothed using a Savitzky-Golay finite impulse response smoothing filter (S-G filter). Then, several similar multi-layer perceptron neural networks (MLP-NNs) were configured to estimate future respiratory signal position from its previous positions. Finally, an adaptive boosting (Adaboost) decision algorithm was used to set weights for each MLP-NN based on the sample prediction error of each MLP-NN. Two prediction methods, MLP-NN and ADMLP-NN (MLP-NN plus adaptive boosting), were evaluated by calculating correlation coefficient and root-mean-square-error between true and predicted signals. For predicting 500 ms ahead of prediction, average correlation coefficients were improved from 0.83 (MLP-NN method) to 0.89 (ADMLP-NN method). The average of root-mean-square-error (relative unit) for 500 ms ahead of prediction using ADMLP-NN were reduced by 27.9%, compared to those using MLP-NN. The preliminary results demonstrate that the ADMLP-NN respiratory prediction method is more accurate than the MLP-NN method and can improve the respiration prediction accuracy.

  20. Innate immune signalling at the intestinal epithelium in homeostasis and disease

    Science.gov (United States)

    Pott, Johanna; Hornef, Mathias

    2012-01-01

    The intestinal epithelium—which constitutes the interface between the enteric microbiota and host tissues—actively contributes to the maintenance of mucosal homeostasis and defends against pathogenic microbes. The recognition of conserved microbial products by cytosolic or transmembrane pattern recognition receptors in epithelial cells initiates signal transduction and influences effector cell function. However, the signalling pathways, effector molecules and regulatory mechanisms involved are not yet fully understood, and the functional outcome is poorly defined. This review analyses the complex and dynamic role of intestinal epithelial innate immune recognition and signalling, on the basis of results in intestinal epithelial cell-specific transgene or gene-deficient animals. This approach identifies specific epithelial cell functions within the diverse cellular composition of the mucosal tissue, in the presence of the complex and dynamic gut microbiota. These insights have thus provided a more comprehensive understanding of the role of the intestinal epithelium in innate immunity during homeostasis and disease. PMID:22801555

  1. Plant immune and growth receptors share common signalling components but localise to distinct plasma membrane nanodomains.

    Science.gov (United States)

    Bücherl, Christoph A; Jarsch, Iris K; Schudoma, Christian; Segonzac, Cécile; Mbengue, Malick; Robatzek, Silke; MacLean, Daniel; Ott, Thomas; Zipfel, Cyril

    2017-03-06

    Cell surface receptors govern a multitude of signalling pathways in multicellular organisms. In plants, prominent examples are the receptor kinases FLS2 and BRI1, which activate immunity and steroid-mediated growth, respectively. Intriguingly, despite inducing distinct signalling outputs, both receptors employ common downstream signalling components, which exist in plasma membrane (PM)-localised protein complexes. An important question is thus how these receptor complexes maintain signalling specificity. Live-cell imaging revealed that FLS2 and BRI1 form PM nanoclusters. Using single-particle tracking we could discriminate both cluster populations and we observed spatiotemporal separation between immune and growth signalling platforms. This finding was confirmed by visualising FLS2 and BRI1 within distinct PM nanodomains marked by specific remorin proteins and differential co-localisation with the cytoskeleton. Our results thus suggest that signalling specificity between these pathways may be explained by the spatial separation of FLS2 and BRI1 with their associated signalling components within dedicated PM nanodomains.

  2. ER-mediated control for abundance, quality, and signaling of transmembrane immune receptors in plants

    Directory of Open Access Journals (Sweden)

    Nico eTintor

    2014-02-01

    Full Text Available Plants recognize a wide range of microbes with cell-surface and intracellular immune receptors. Transmembrane pattern recognition receptors (PRRs initiate immune responses upon recognition of cognate ligands characteristic of microbes or aberrant cellular states, designated microbe-associated molecular patterns (MAMPs or danger-associated molecular patterns (DAMPs, respectively. Pattern-triggered immunity (PTI provides a first line of defense that restricts the invasion and propagation of both adapted and non-adapted pathogens. Receptor kinases (RKs and receptor-like proteins (RLPs with an extracellular leucine-rich repeat (LRR or lysine-motif (LysM domain are extensively used as PRRs. The correct folding of the extracellular domain of these receptors is under quality control (QC in the endoplasmic reticulum (ER, which thus provides a critical step in plant immunity. Genetic and structural insight suggests that ERQC regulates not only the abundance and quality of transmembrane receptors but also affects signal sorting between multi-branched pathways downstream of the receptor. However, ERQC dysfunction can also positively stimulate plant immunity, possibly through cell death and DAMP signaling pathways.

  3. Signaling Circuits and Regulation of Immune Suppression by Ovarian Tumor-Associated Macrophages

    Directory of Open Access Journals (Sweden)

    Martin J. Cannon

    2015-05-01

    Full Text Available The barriers presented by immune suppression in the ovarian tumor microenvironment present one of the biggest challenges to development of successful tumor vaccine strategies for prevention of disease recurrence and progression following primary surgery and chemotherapy. New insights gained over the last decade have revealed multiple mechanisms of immune regulation, with ovarian tumor-associated macrophages/DC likely to fulfill a central role in creating a highly immunosuppressive milieu that supports disease progression and blocks anti-tumor immunity. This review provides an appraisal of some of the key signaling pathways that may contribute to immune suppression in ovarian cancer, with a particular focus on the potential involvement of the c-KIT/PI3K/AKT, wnt/β-catenin, IL-6/STAT3 and AhR signaling pathways in regulation of indoleamine 2,3-dioxygenase expression in tumor-associated macrophages. Knowledge of intercellular and intracellular circuits that shape immune suppression may afford insights for development of adjuvant treatments that alleviate immunosuppression in the tumor microenvironment and enhance the clinical efficacy of ovarian tumor vaccines.

  4. DMPD: Glucocorticoids and the innate immune system: crosstalk with the toll-likereceptor signaling network. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17576036 Glucocorticoids and the innate immune system: crosstalk with the toll-like...07 May 13. (.png) (.svg) (.html) (.csml) Show Glucocorticoids and the innate immune system: crosstalk with t...he toll-likereceptor signaling network. PubmedID 17576036 Title Glucocorticoids and the innate immune syst...em: crosstalk with the toll-likereceptor signaling network. Authors Chinenov Y, Rog

  5. Social discounting involves modulation of neural value signals by temporoparietal junction

    Science.gov (United States)

    Strombach, Tina; Weber, Bernd; Hangebrauk, Zsofia; Kenning, Peter; Karipidis, Iliana I.; Tobler, Philippe N.; Kalenscher, Tobias

    2015-01-01

    Most people are generous, but not toward everyone alike: generosity usually declines with social distance between individuals, a phenomenon called social discounting. Despite the pervasiveness of social discounting, social distance between actors has been surprisingly neglected in economic theory and neuroscientific research. We used functional magnetic resonance imaging (fMRI) to study the neural basis of this process to understand the neural underpinnings of social decision making. Participants chose between selfish and generous alternatives, yielding either a large reward for the participant alone, or smaller rewards for the participant and another individual at a particular social distance. We found that generous choices engaged the temporoparietal junction (TPJ). In particular, the TPJ activity was scaled to the social-distance–dependent conflict between selfish and generous motives during prosocial choice, consistent with ideas that the TPJ promotes generosity by facilitating overcoming egoism bias. Based on functional coupling data, we propose and provide evidence for a biologically plausible neural model according to which the TPJ supports social discounting by modulating basic neural value signals in the ventromedial prefrontal cortex to incorporate social-distance–dependent other-regarding preferences into an otherwise exclusively own-reward value representation. PMID:25605887

  6. Enhancement of signal sensitivity in a heterogeneous neural network refined from synaptic plasticity

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiumin; Small, Michael, E-mail: ensmall@polyu.edu.h, E-mail: 07901216r@eie.polyu.edu.h [Department of Electronic and Information Engineering, Hong Kong Polytechnic University, Hung Hom, Kowloon (Hong Kong)

    2010-08-15

    Long-term synaptic plasticity induced by neural activity is of great importance in informing the formation of neural connectivity and the development of the nervous system. It is reasonable to consider self-organized neural networks instead of prior imposition of a specific topology. In this paper, we propose a novel network evolved from two stages of the learning process, which are respectively guided by two experimentally observed synaptic plasticity rules, i.e. the spike-timing-dependent plasticity (STDP) mechanism and the burst-timing-dependent plasticity (BTDP) mechanism. Due to the existence of heterogeneity in neurons that exhibit different degrees of excitability, a two-level hierarchical structure is obtained after the synaptic refinement. This self-organized network shows higher sensitivity to afferent current injection compared with alternative archetypal networks with different neural connectivity. Statistical analysis also demonstrates that it has the small-world properties of small shortest path length and high clustering coefficients. Thus the selectively refined connectivity enhances the ability of neuronal communications and improves the efficiency of signal transmission in the network.

  7. Toll-like receptors (TLRs) in aquatic animals: signaling pathways, expressions and immune responses.

    Science.gov (United States)

    Rauta, Pradipta R; Samanta, Mrinal; Dash, Hirak R; Nayak, Bismita; Das, Surajit

    2014-01-01

    The innate system's recognition of non-self and danger signals is mediated by a limited number of germ-line encoded pattern recognition receptors (PRRs) that recognize pathogen associated molecular patterns (PAMPs). Toll-like receptors (TLRs) are single, non-catalytic, membrane-spanning PRRs present in invertebrates and vertebrates. They act by specifically recognizing PAMPs of a variety of microbes and activate signaling cascades to induce innate immunity. A large number of TLRs have been identified in various aquatic animals of phyla Cnidaria, Annelida, Mollusca, Arthropoda, Echinodermata and Chordata. TLRs of aquatic and warm-blooded higher animals exhibit some distinctive features due to their diverse evolutionary lineages. However, majority of them share conserve signaling pathways in pathogen recognition and innate immunity. Functional analysis of novel TLRs in aquatic animals is very important in understanding the comparative immunology between warm-blooded and aquatic animals. In additions to innate immunity, recent reports have highlighted the additional roles of TLRs in adaptive immunity. Therefore, vaccines against many critical diseases of aquatic animals may be made more effective by supplementing TLR activators which will stimulate dendritic cells. This article describes updated information of TLRs in aquatic animals and their structural and functional relationship with warm-blooded animals. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Quantitative Evaluation of Stomatal Cytoskeletal Patterns during the Activation of Immune Signaling in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Masaki Shimono

    Full Text Available Historically viewed as primarily functioning in the regulation of gas and water vapor exchange, it is now evident that stomata serve an important role in plant immunity. Indeed, in addition to classically defined functions related to cell architecture and movement, the actin cytoskeleton has emerged as a central component of the plant immune system, underpinning not only processes related to cell shape and movement, but also receptor activation and signaling. Using high resolution quantitative imaging techniques, the temporal and spatial changes in the actin microfilament array during diurnal cycling of stomatal guard cells has revealed a highly orchestrated transition from random arrays to ordered bundled filaments. While recent studies have demonstrated that plant stomata close in response to pathogen infection, an evaluation of stimulus-induced changes in actin cytoskeletal dynamics during immune activation in the guard cell, as well as the relationship of these changes to the function of the actin cytoskeleton and stomatal aperture, remains undefined. In the current study, we employed quantitative cell imaging and hierarchical clustering analyses to define the response of the guard cell actin cytoskeleton to pathogen infection and the elicitation of immune signaling. Using this approach, we demonstrate that stomatal-localized actin filaments respond rapidly, and specifically, to both bacterial phytopathogens and purified pathogen elicitors. Notably, we demonstrate that higher order temporal and spatial changes in the filament array show distinct patterns of organization during immune activation, and that changes in the naïve diurnal oscillations of guard cell actin filaments are perturbed by pathogens, and that these changes parallel pathogen-induced stomatal gating. The data presented herein demonstrate the application of a highly tractable and quantifiable method to assign transitions in actin filament organization to the activation of

  9. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

    Science.gov (United States)

    Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

    2017-06-07

    Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

  10. Altered neural reward and loss processing and prediction error signalling in depression

    Science.gov (United States)

    Ubl, Bettina; Kuehner, Christine; Kirsch, Peter; Ruttorf, Michaela

    2015-01-01

    Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression. PMID:25567763

  11. The contribution of type I interferon signaling to immunity induced by alphavirus replicon vaccines.

    Science.gov (United States)

    Thompson, Joseph M; Whitmore, Alan C; Staats, Herman F; Johnston, Robert

    2008-09-15

    The type I interferon (IFN) system is critical for protecting the mammalian host from numerous virus infections and plays a key role in shaping the antiviral adaptive immune response. In this report, the importance of type I IFN signaling was assessed in a mouse model of alphavirus-induced humoral immune induction. Venezuelan equine encephalitis virus replicon particles (VRP) expressing the hemagglutinin (HA) gene from influenza virus (HA-VRP) were used to vaccinate both wildtype (wt) and IFN alpha/beta receptor knockout (RKO) mice. HA-VRP vaccination induced equivalent levels of flu-specific systemic IgG, mucosal IgG, and systemic IgA antibodies in both wt and IFN RKO mice. In contrast, HA-VRP vaccination of IFN RKO mice failed to induce significant levels of flu-specific mucosal IgA antibodies at multiple mucosal surfaces. In the VRP adjuvant system, co-delivery of null VRP with ovalbumin (OVA) protein significantly increased the levels of OVA-specific serum IgG, fecal IgG, and fecal IgA antibodies in both wt and RKO mice, suggesting that type I IFN signaling plays a less significant role in the VRP adjuvant effect. Taken together, these results suggest that (1) at least in regard to IFN signaling, the mechanisms which regulate alphavirus-induced immunity differ when VRP are utilized as expression vectors as opposed to adjuvants, and (2) type I IFN signaling is required for the induction of mucosal IgA antibodies directed against VRP-expressed antigen. These results shed new light on the regulatory networks which promote immune induction, and specifically mucosal immune induction, with alphavirus vaccine vectors.

  12. Vitamin D Signaling in the Bovine Immune System: A Model for Understanding Human Vitamin D Requirements

    Directory of Open Access Journals (Sweden)

    Corwin D. Nelson

    2012-03-01

    Full Text Available The endocrine physiology of vitamin D in cattle has been rigorously investigated and has yielded information on vitamin D requirements, endocrine function in health and disease, general metabolism, and maintenance of calcium homeostasis in cattle. These results are relevant to human vitamin D endocrinology. The current debate regarding vitamin D requirements is centered on the requirements for proper intracrine and paracrine vitamin D signaling. Studies in adult and young cattle can provide valuable insight for understanding vitamin D requirements as they relate to innate and adaptive immune responses during infectious disease. In cattle, toll-like receptor recognition activates intracrine and paracrine vitamin D signaling mechanism in the immune system that regulates innate and adaptive immune responses in the presence of adequate 25-hydroxyvitamin D. Furthermore, experiments with mastitis in dairy cattle have provided in vivo evidence for the intracrine vitamin D signaling mechanism in macrophages as well as vitamin D mediated suppression of infection. Epidemiological evidence indicates that circulating concentrations above 32 ng/mL of 25-hydroxyvitamin D are necessary for optimal vitamin D signaling in the immune system, but experimental evidence is lacking for that value. Experiments in cattle can provide that evidence as circulating 25-hydroxyvitamin D concentrations can be experimentally manipulated within ranges that are normal for humans and cattle. Additionally, young and adult cattle can be experimentally infected with bacteria and viruses associated with significant diseases in both cattle and humans. Utilizing the bovine model to further delineate the immunomodulatory role of vitamin D will provide potentially valuable insights into the vitamin D requirements of both humans and cattle, especially as they relate to immune response capacity and infectious disease resistance.

  13. Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses.

    Science.gov (United States)

    Chiurchiù, Valerio; Leuti, Alessandro; Maccarrone, Mauro

    2015-06-01

    The concept of the central nervous system (CNS) as an immune-privileged site, essentially due to the presence of the blood brain barrier, appears to be overly simplistic. Indeed, within healthy CNS immune activities are permitted and are required for neuronal function and host defense, not only due to the presence of the resident innate immune cells of the brain, but also by virtue of a complex cross-talk of the CNS with peripheral immune cells. Nonetheless, long-standing and persisting neuroinflammatory responses are most often detrimental and characterize several neuroinflammatory diseases, including multiple sclerosis, Alzheimer's disease and amyotrophic lateral sclerosis. A growing body of evidence suggests that Cannabis sativa-derived phytocannabinoids, as well as synthetic cannabinoids, are endowed with significant immunoregulatory and anti-inflammatory properties, both in peripheral tissues and in the CNS, through the activation of cannabinoid receptors. In this review, the immunomodulatory effects of cannabinoid signaling on the most relevant brain immune cells will be discussed. In addition, the impact of cannabinoid regulation on the overall integration of the manifold brain immune responses will also be highlighted, along with the implication of these compounds as potential agents for the management of neuroinflammatory disorders.

  14. The CD47-SIRPα signaling axis as an innate immune checkpoint in cancer.

    Science.gov (United States)

    Matlung, Hanke L; Szilagyi, Katka; Barclay, Neil A; van den Berg, Timo K

    2017-03-01

    Immune checkpoint inhibitors, including those targeting CTLA-4/B7 and the PD-1/PD-L1 inhibitory pathways, are now available for clinical use in cancer patients, with other interesting checkpoint inhibitors being currently in development. Most of these have the purpose to promote adaptive T cell-mediated immunity against cancer. Here, we review another checkpoint acting to potentiate the activity of innate immune cells towards cancer. This innate immune checkpoint is composed of what has become known as the 'don't-eat me' signal CD47, which is a protein broadly expressed on normal cells and often overexpressed on cancer cells, and its counter-receptor, the myeloid inhibitory immunoreceptor SIRPα. Blocking CD47-SIRPα interactions has been shown to promote the destruction of cancer cells by phagocytes, including macrophages and neutrophils. Furthermore, there is growing evidence that targeting of the CD47-SIRPα axis may also promote antigen-presenting cell function and thereby stimulate adaptive T cell-mediated anti-cancer immunity. The development of CD47-SIRPα checkpoint inhibitors and the potential side effects that these may have are discussed. Collectively, this identifies the CD47-SIRPα axis as a promising innate immune checkpoint in cancer, and with data of the first clinical studies with CD47-SIRPα checkpoint inhibitors expected within the coming years, this is an exciting and rapidly developing field. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Integration of Signals along Orthogonal Axes of the Vertebrate Neural Tube Controls Progenitor Competence and Increases Cell Diversity

    Science.gov (United States)

    Sasai, Noriaki; Kutejova, Eva; Briscoe, James

    2014-01-01

    A relatively small number of signals are responsible for the variety and pattern of cell types generated in developing embryos. In part this is achieved by exploiting differences in the concentration or duration of signaling to increase cellular diversity. In addition, however, changes in cellular competence—temporal shifts in the response of cells to a signal—contribute to the array of cell types generated. Here we investigate how these two mechanisms are combined in the vertebrate neural tube to increase the range of cell types and deliver spatial control over their location. We provide evidence that FGF signaling emanating from the posterior of the embryo controls a change in competence of neural progenitors to Shh and BMP, the two morphogens that are responsible for patterning the ventral and dorsal regions of the neural tube, respectively. Newly generated neural progenitors are exposed to FGF signaling, and this maintains the expression of the Nk1-class transcription factor Nkx1.2. Ventrally, this acts in combination with the Shh-induced transcription factor FoxA2 to specify floor plate cells and dorsally in combination with BMP signaling to induce neural crest cells. As development progresses, the intersection of FGF with BMP and Shh signals is interrupted by axis elongation, resulting in the loss of Nkx1.2 expression and allowing the induction of ventral and dorsal interneuron progenitors by Shh and BMP signaling to supervene. Hence a similar mechanism increases cell type diversity at both dorsal and ventral poles of the neural tube. Together these data reveal that tissue morphogenesis produces changes in the coincidence of signals acting along orthogonal axes of the neural tube and this is used to define spatial and temporal transitions in the competence of cells to interpret morphogen signaling. PMID:25026549

  16. Infection of goats with goatpox virus triggers host antiviral defense through activation of innate immune signaling.

    Science.gov (United States)

    Zeng, Xiancheng; Wang, Song; Chi, Xiaojuan; Chen, Shi-long; Huang, Shile; Lin, Qunqun; Xie, Baogui; Chen, Ji-Long

    2016-02-01

    Goatpox, caused by goatpox virus (GTPV), is one of the most serious infectious diseases associated with high morbidity and mortality in goats. However, little is known about involvement of host innate immunity during the GTPV infection. For this, goats were experimentally infected with GTPV. The results showed that GTPV infection significantly induced mRNA expression of type I interferon (IFN)-α and IFN-β in peripheral blood lymphocytes, spleen and lung. In addition, GTPV infection enhanced expression of several inflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-18; and tumor necrosis factor-α (TNF-α). Strikingly, infection with GTPV activated signal transducers and activators of transcription 3 (STAT3), a critical cytokine signaling molecule. Interestingly, the virus infection induced expression of suppressor of cytokine signaling (SOCS)-1. Importantly, the infection resulted in an increased expression of some critical interferon-stimulated genes, such as interferon-induced transmembrane protein (IFITM) 1, IFITM3, interferon stimulated gene (ISG) 15 and ISG20. Furthermore, we found that infection with GTPV up-regulated expression of Toll-like receptor (TLR) 2 and TLR9. These results revealed that GTPV infection activated host innate immune signaling and thereby triggered antiviral innate immunity. The findings provide novel insights into complex mechanisms underlying GTPV-host interaction and pathogenesis of GTPV. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Feature reconstruction of LFP signals based on PLSR in the neural information decoding study.

    Science.gov (United States)

    Yonghui Dong; Zhigang Shang; Mengmeng Li; Xinyu Liu; Hong Wan

    2017-07-01

    To solve the problems of Signal-to-Noise Ratio (SNR) and multicollinearity when the Local Field Potential (LFP) signals is used for the decoding of animal motion intention, a feature reconstruction of LFP signals based on partial least squares regression (PLSR) in the neural information decoding study is proposed in this paper. Firstly, the feature information of LFP coding band is extracted based on wavelet transform. Then the PLSR model is constructed by the extracted LFP coding features. According to the multicollinearity characteristics among the coding features, several latent variables which contribute greatly to the steering behavior are obtained, and the new LFP coding features are reconstructed. Finally, the K-Nearest Neighbor (KNN) method is used to classify the reconstructed coding features to verify the decoding performance. The results show that the proposed method can achieve the highest accuracy compared to the other three methods and the decoding effect of the proposed method is robust.

  18. Employment and comparison of different Artificial Neural Networks for epilepsy diagnosis from EEG signals.

    Science.gov (United States)

    Sezer, Esma; Işik, Hakan; Saracoğlu, Esra

    2012-02-01

    In this study, it has been intended to analyze Electroencephalography (EEG) signals by Wavelet Transform (WT) for diagnosis of epilepsy, to employ various Artificial Neural Networks (ANNs) for the signals' automatic classification. Furthermore, carrying out a performance comparison has been aimed. Three EEG signals have been decomposed into frequency sub bands by WT and the feature vectors have been extracted from these sub bands. In order to reduce the sizes of the extracted feature vectors, Principal Component Analysis (PCA) method has been applied when necessary and these feature vectors have been classified by five different ANNs as either epileptic or healthy. The performance evaluation has been carried out by conducting ROC analysis for the used ANN models that and their comparisons have also been included.

  19. Accelerometer signal-based human activity recognition using augmented autoregressive model coefficients and artificial neural nets.

    Science.gov (United States)

    Khan, A M; Lee, Y K; Kim, T S

    2008-01-01

    Automatic recognition of human activities is one of the important and challenging research areas in proactive and ubiquitous computing. In this work, we present some preliminary results of recognizing human activities using augmented features extracted from the activity signals measured using a single triaxial accelerometer sensor and artificial neural nets. The features include autoregressive (AR) modeling coefficients of activity signals, signal magnitude areas (SMA), and title angles (TA). We have recognized four human activities using AR coefficients (ARC) only, ARC with SMA, and ARC with SMA and TA. With the last augmented features, we have achieved the recognition rate above 99% for all four activities including lying, standing, walking, and running. With our proposed technique, real time recognition of some human activities is possible.

  20. Neural crest-derived mesenchymal cells require Wnt signaling for their development and drive invagination of the telencephalic midline.

    Directory of Open Access Journals (Sweden)

    Youngshik Choe

    Full Text Available Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis.

  1. A short receptor downregulates JAK/STAT signalling to control the Drosophila cellular immune response.

    Directory of Open Access Journals (Sweden)

    Rami Makki

    2010-08-01

    Full Text Available The posterior signalling centre (PSC, a small group of specialised cells, controls hemocyte (blood cell homeostasis in the Drosophila larval hematopoietic organ, the lymph gland. This role of the PSC is very reminiscent of the "niche," the micro-environment of hematopoietic stem cells in vertebrates. We have recently shown that the PSC acts in a non-cell-autonomous manner to maintain janus tyrosine kinase/signal transducers and activators of transcription (JAK/STAT signalling in hematopoietic progenitors (prohemocytes, thereby preserving the multipotent character necessary for their differentiation into lamellocytes, a cryptic and dedicated immune cell type required to fight specific immune threats such as wasp parasitism. In this report, on the basis of a knock out generated by homologous recombination, we show that a short type I cytokine-related receptor CG14225/Latran is required for switching off JAK/STAT signalling in prohemocytes. This is a prerequisite to massive differentiation of lamellocytes upon wasp parasitisation. In vivo and cell culture assays indicate that Latran forms heteromers with Domeless, the Drosophila type I cytokine signalling receptor related to mammalian GP130, and antagonises Domeless activity in a dose-dependent manner. Our analysis further shows that a primary immune response to wasp parasitism is a strong decrease in cytokine mRNA levels in the lymph gland, followed by an increase in the latran/domeless ratio. We propose that this sequence of events culminates in the complete inhibition of residual JAK/STAT signalling by Latran. JAK/STAT activity has been associated with several human diseases including leukaemia while knock-out studies in mice point to a central role of this pathway in hematopoiesis and regulation of immune functions. The specific function of Drosophila Latran is, to our knowledge, the first in vivo example of a role for a nonsignalling receptor in controlling a dedicated immune response, and

  2. Vehicle Signal Analysis Using Artificial Neural Networks for a Bridge Weigh-in-Motion System.

    Science.gov (United States)

    Kim, Sungkon; Lee, Jungwhee; Park, Min-Seok; Jo, Byung-Wan

    2009-01-01

    This paper describes the procedures for development of signal analysis algorithms using artificial neural networks for Bridge Weigh-in-Motion (B-WIM) systems. Through the analysis procedure, the extraction of information concerning heavy traffic vehicles such as weight, speed, and number of axles from the time domain strain data of the B-WIM system was attempted. As one of the several possible pattern recognition techniques, an Artificial Neural Network (ANN) was employed since it could effectively include dynamic effects and bridge-vehicle interactions. A number of vehicle traveling experiments with sufficient load cases were executed on two different types of bridges, a simply supported pre-stressed concrete girder bridge and a cable-stayed bridge. Different types of WIM systems such as high-speed WIM or low-speed WIM were also utilized during the experiments for cross-checking and to validate the performance of the developed algorithms.

  3. Vehicle Signal Analysis Using Artificial Neural Networks for a Bridge Weigh-in-Motion System

    Directory of Open Access Journals (Sweden)

    Min-Seok Park

    2009-10-01

    Full Text Available This paper describes the procedures for development of signal analysis algorithms using artificial neural networks for Bridge Weigh-in-Motion (B-WIM systems. Through the analysis procedure, the extraction of information concerning heavy traffic vehicles such as weight, speed, and number of axles from the time domain strain data of the B-WIM system was attempted. As one of the several possible pattern recognition techniques, an Artificial Neural Network (ANN was employed since it could effectively include dynamic effects and bridge-vehicle interactions. A number of vehicle traveling experiments with sufficient load cases were executed on two different types of bridges, a simply supported pre-stressed concrete girder bridge and a cable-stayed bridge. Different types of WIM systems such as high-speed WIM or low-speed WIM were also utilized during the experiments for cross-checking and to validate the performance of the developed algorithms.

  4. Hybrid fuzzy logic committee neural networks for recognition of swallow acceleration signals.

    Science.gov (United States)

    Das, A; Reddy, N P; Narayanan, J

    2001-02-01

    Biological signals are complex and often require intelligent systems for recognition of characteristic signals. In order to improve the reliability of the recognition or automated diagnostic systems, hybrid fuzzy logic committee neural networks were developed and the system was used for recognition of swallow acceleration signals from artifacts. Two sets of fuzzy logic-committee networks (FCN) each consisting of seven member networks were developed, trained and evaluated. The FCN-I was used to recognize dysphagic swallow from artifacts, and the second committee FCN-II was used to recognize normal swallow from artifacts. Several networks were trained and the best seven were recruited into each committee. Acceleration signals from the throat were bandpass filtered, and several parameters were extracted and fed to the fuzzy logic block of either FCN-I or FCN-II. The fuzzified membership values were fed to the committee of neural networks which provided the signal classification. A majority opinion of the member networks was used to arrive at the final decision. Evaluation results revealed that FCN correctly identified 16 out of 16 artifacts and 31 out of 33 dysphagic swallows. In two cases, the decision was ambiguous due to the lack of a majority opinion. FCN-II correctly identified 24 out of 24 normal swallows, and 28 out of 29 artifacts. In one case, the decision was ambiguous due to the lack of a majority opinion. The present hybrid intelligent system consisting of fuzzy logic and committee networks provides a reliable tool for recognition and classification of acceleration signals due to swallowing.

  5. Modeling fMRI signals can provide insights into neural processing in the cerebral cortex

    Science.gov (United States)

    Sharifian, Fariba; Heikkinen, Hanna; Vigário, Ricardo

    2015-01-01

    Every stimulus or task activates multiple areas in the mammalian cortex. These distributed activations can be measured with functional magnetic resonance imaging (fMRI), which has the best spatial resolution among the noninvasive brain imaging methods. Unfortunately, the relationship between the fMRI activations and distributed cortical processing has remained unclear, both because the coupling between neural and fMRI activations has remained poorly understood and because fMRI voxels are too large to directly sense the local neural events. To get an idea of the local processing given the macroscopic data, we need models to simulate the neural activity and to provide output that can be compared with fMRI data. Such models can describe neural mechanisms as mathematical functions between input and output in a specific system, with little correspondence to physiological mechanisms. Alternatively, models can be biomimetic, including biological details with straightforward correspondence to experimental data. After careful balancing between complexity, computational efficiency, and realism, a biomimetic simulation should be able to provide insight into how biological structures or functions contribute to actual data processing as well as to promote theory-driven neuroscience experiments. This review analyzes the requirements for validating system-level computational models with fMRI. In particular, we study mesoscopic biomimetic models, which include a limited set of details from real-life networks and enable system-level simulations of neural mass action. In addition, we discuss how recent developments in neurophysiology and biophysics may significantly advance the modelling of fMRI signals. PMID:25972586

  6. Larger Neural Responses Produce BOLD Signals That Begin Earlier in Time

    Directory of Open Access Journals (Sweden)

    Serena eThompson

    2014-06-01

    Full Text Available Functional MRI analyses commonly rely on the assumption that the temporal dynamics of hemodynamic response functions (HRFs are independent of the amplitude of the neural signals that give rise to them. The validity of this assumption is particularly important for techniques that use fMRI to resolve sub-second timing distinctions between responses, in order to make inferences about the ordering of neural processes. Whether or not the detailed shape of the HRF is independent of neural response amplitude remains an open question, however. We performed experiments in which we measured responses in primary visual cortex (V1 to large, contrast-reversing checkerboards at a range of contrast levels, which should produce varying amounts of neural activity. Ten subjects (ages 22-52 were studied in each of two experiments using 3 Tesla scanners. We used rapid, 250 msec, temporal sampling (repetition time, or TR and both short and long inter-stimulus interval (ISI stimulus presentations. We tested for a systematic relationship between the onset of the HRF and its amplitude across conditions, and found a strong negative correlation between the two measures when stimuli were separated in time (long- and medium-ISI experiments, but not the short-ISI experiment. Thus, stimuli that produce larger neural responses, as indexed by HRF amplitude, also produced HRFs with shorter onsets. The relationship between amplitude and latency was strongest in voxels with lowest mean-normalized variance (i.e., parenchymal voxels. The onset differences observed in the longer-ISI experiments are likely attributable to mechanisms of neurovascular coupling, since they are substantially larger than reported differences in the onset of action potentials in V1 as a function of response amplitude.

  7. Apoptotic Cells Induced Signaling for Immune Homeostasis in Macrophages and Dendritic Cells.

    Science.gov (United States)

    Trahtemberg, Uriel; Mevorach, Dror

    2017-01-01

    Inefficient and abnormal clearance of apoptotic cells (efferocytosis) contributes to systemic autoimmune disease in humans and mice, and inefficient chromosomal DNA degradation by DNAse II leads to systemic polyarthritis and a cytokine storm. By contrast, efficient clearance allows immune homeostasis, generally leads to a non-inflammatory state for both macrophages and dendritic cells (DCs), and contributes to maintenance of peripheral tolerance. As many as 3 × 10(8) cells undergo apoptosis every hour in our bodies, and one of the primary "eat me" signals expressed by apoptotic cells is phosphatidylserine (PtdSer). Apoptotic cells themselves are major contributors to the "anti-inflammatory" nature of the engulfment process, some by secreting thrombospondin-1 (TSP-1) or adenosine monophosphate and possibly other immune modulating "calm-down" signals that interact with macrophages and DCs. Apoptotic cells also produce "find me" and "tolerate me" signals to attract and immune modulate macrophages and DCs that express specific receptors for some of these signals. Neither macrophages nor DCs are uniform, and each cell type may variably express membrane proteins that function as receptors for PtdSer or for opsonins like complement or opsonins that bind to PtdSer, such as protein S and growth arrest-specific 6. Macrophages and DCs also express scavenger receptors, CD36, and integrins that function via bridging molecules such as TSP-1 or milk fat globule-EGF factor 8 protein and that differentially engage in various multi-ligand interactions between apoptotic cells and phagocytes. In this review, we describe the anti-inflammatory and pro-homeostatic nature of apoptotic cell interaction with the immune system. We do not review some forms of immunogenic cell death. We summarize the known apoptotic cell signaling events in macrophages and DCs that are related to toll-like receptors, nuclear factor kappa B, inflammasome, the lipid-activated nuclear receptors, Tyro3, Axl

  8. Nucleic acid sensing and innate immunity: signaling pathways controlling viral pathogenesis and autoimmunity

    Science.gov (United States)

    Ahlers, Laura R. H.; Goodman, Alan G.

    2016-01-01

    Innate immunity refers to the body’s initial response to curb infection upon exposure to invading organisms. While the detection of pathogen-associated molecules is an ancient form of host defense, if dysfunctional, autoimmune disease may result. The innate immune response during pathogenic infection is initiated through the activation of receptors recognizing conserved molecular patterns, such as nucleic acids from a virus’ genome or replicative cycle. Additionally, the host’s own nucleic acids are capable of activating an immune response. Therefore, it follows that the nucleic acid-sensing pathways must be tightly controlled to avoid an autoimmune response from recognition of self, yet still be unimpeded to respond to viral infections. In this review, we will describe the nucleic acid sensing pathways and how they respond to virus infection. Moreover, we will discuss autoimmune diseases that develop when these pathways fail to signal properly and identify knowledge gaps that are prime for interrogation. PMID:27857881

  9. Neural Mechanisms for Acoustic Signal Detection under Strong Masking in an Insect.

    Science.gov (United States)

    Kostarakos, Konstantinos; Römer, Heiner

    2015-07-22

    produces an extremely noisy sound, yet the second species still detects its own song. Using intracellular recording techniques we identified two neural mechanisms underlying the surprising behavioral signal detection at the level of single identified interneurons. These neural mechanisms for signal detection are likely to be important for other sensory modalities as well, where noise in the communication channel creates similar problems. Also, they may be used for the development of algorithms for the filtering of specific signals in technical microphones or hearing aids. Copyright © 2015 Kostarakos and Römer.

  10. Impaired Cellular Immunity in the Murine Neural Crest Conditional Deletion of Endothelin Receptor-B Model of Hirschsprung’s Disease

    Science.gov (United States)

    Gosain, Ankush; Barlow-Anacker, Amanda J.; Erickson, Chris S.; Pierre, Joseph F.; Heneghan, Aaron F.; Epstein, Miles L.; Kudsk, Kenneth A.

    2015-01-01

    Hirschsprung’s disease (HSCR) is characterized by aganglionosis from failure of neural crest cell (NCC) migration to the distal hindgut. Up to 40% of HSCR patients suffer Hirschsprung’s-associated enterocolitis (HAEC), with an incidence that is unchanged from the pre-operative to the post-operative state. Recent reports indicate that signaling pathways involved in NCC migration may also be involved in the development of secondary lymphoid organs. We hypothesize that gastrointestinal (GI) mucosal immune defects occur in HSCR that may contribute to enterocolitis. EdnrB was deleted from the neural crest (EdnrBNCC-/-) resulting in mutants with defective NCC migration, distal colonic aganglionosis and the development of enterocolitis. The mucosal immune apparatus of these mice was interrogated at post-natal day (P) 21–24, prior to histological signs of enterocolitis. We found that EdnrBNCC-/- display lymphopenia of their Peyer’s Patches, the major inductive site of GI mucosal immunity. EdnrBNCC-/- Peyer’s Patches demonstrate decreased B-lymphocytes, specifically IgM+IgDhi (Mature) B-lymphocytes, which are normally activated and produce IgA following antigen presentation. EdnrBNCC-/- animals demonstrate decreased small intestinal secretory IgA, but unchanged nasal and bronchial airway secretory IgA, indicating a gut-specific defect in IgA production or secretion. In the spleen, which is the primary source of IgA-producing Mature B-lymphocytes, EdnrBNCC-/- animals display decreased B-lymphocytes, but an increase in Mature B-lymphocytes. EdnrBNCC-/- spleens are also small and show altered architecture, with decreased red pulp and a paucity of B-lymphocytes in the germinal centers and marginal zone. Taken together, these findings suggest impaired GI mucosal immunity in EdnrBNCC-/- animals, with the spleen as a potential site of the defect. These findings build upon the growing body of literature that suggests that intestinal defects in HSCR are not restricted to

  11. AUTOMATIC RECOGNITION OF BOTH INTER AND INTRA CLASSES OF DIGITAL MODULATED SIGNALS USING ARTIFICIAL NEURAL NETWORK

    Directory of Open Access Journals (Sweden)

    JIDE JULIUS POPOOLA

    2014-04-01

    Full Text Available In radio communication systems, signal modulation format recognition is a significant characteristic used in radio signal monitoring and identification. Over the past few decades, modulation formats have become increasingly complex, which has led to the problem of how to accurately and promptly recognize a modulation format. In addressing these challenges, the development of automatic modulation recognition systems that can classify a radio signal’s modulation format has received worldwide attention. Decision-theoretic methods and pattern recognition solutions are the two typical automatic modulation recognition approaches. While decision-theoretic approaches use probabilistic or likelihood functions, pattern recognition uses feature-based methods. This study applies the pattern recognition approach based on statistical parameters, using an artificial neural network to classify five different digital modulation formats. The paper deals with automatic recognition of both inter-and intra-classes of digitally modulated signals in contrast to most of the existing algorithms in literature that deal with either inter-class or intra-class modulation format recognition. The results of this study show that accurate and prompt modulation recognition is possible beyond the lower bound of 5 dB commonly acclaimed in literature. The other significant contribution of this paper is the usage of the Python programming language which reduces computational complexity that characterizes other automatic modulation recognition classifiers developed using the conventional MATLAB neural network toolbox.

  12. Astrocytic Calcium Waves Signal Brain Injury to Neural Stem and Progenitor Cells.

    Science.gov (United States)

    Kraft, Anna; Jubal, Eduardo Rosales; von Laer, Ruth; Döring, Claudia; Rocha, Adriana; Grebbin, Moyo; Zenke, Martin; Kettenmann, Helmut; Stroh, Albrecht; Momma, Stefan

    2017-03-14

    Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ) to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48 hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather than by diffusible factors or hypoxia. Using a newly established in vitro system we show that calcium waves induced in an astrocytic monolayer spread to neural stem and progenitor cells and increase their self-renewal as well as migratory behavior. These changes are due to an upregulation of the Notch signaling pathway. This introduces the concept of propagating astrocytic calcium waves transmitting brain injury signals over long distances. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Analysis of the Human Mucosal Response to Cholera Reveals Sustained Activation of Innate Immune Signaling Pathways.

    Science.gov (United States)

    Bourque, Daniel L; Bhuiyan, Taufiqur Rahman; Genereux, Diane P; Rashu, Rasheduzzaman; Ellis, Crystal N; Chowdhury, Fahima; Khan, Ashraful I; Haq Alam, Nur; Lazina Hossain, Anik Paul; Mayo-Smith, Leslie M; Charles, Richelle C; Weil, Ana A; LaRocque, Regina C; Calderwood, Stephen B; Ryan, Edward T; Karlsson, Elinor K; Qadri, Firdausi; Harris, Jason B

    2017-11-13

    To better understand the innate immune response to Vibrio cholerae infection, we tracked gene expression in the duodenal mucosa of eleven Bangladeshi adults with cholera, using biopsies obtained immediately after rehydration and at 30 and 180 days later. We identified differentially expressed genes and performed an analysis to predict differentially regulated pathways and upstream regulators. During acute cholera, there was a broad increase in the expression of genes associated with innate immunity, including activation of the NF-κB, MAPK, and TLR-mediated signaling pathways, which unexpectedly persisted even 30 days after infection. Focusing on early differences in gene expression, we identified 37 genes that were differentially expressed on days 2 and 30 across eleven participants. These genes included the endosomal toll like receptor, TLR8, which was expressed in lamina propria cells. Underscoring a potential role for endosomal TLR-mediated signaling in vivo, our pathway analysis found that IRF7 and interferons β1 and α2 were among the top upstream regulators activated during cholera. Among innate immune effectors, we found that DUOX2, an NADPH-oxidase involved in the maintenance of intestinal homeostasis, was upregulated in intestinal epithelial cells during cholera. Notably, the observed increases in DUOX2 and TLR8 expression were also modeled in vitro when stimulating Caco-2 or THP-1 cells, respectively, with live V. cholerae but not with heat killed organisms or cholera toxin alone. These previously unidentified features of the innate immune response to V. cholerae extend our understanding mucosal immune signaling pathways and effectors activated in vivo following cholera. Copyright © 2017 American Society for Microbiology.

  14. Clemastine causes immune suppression through inhibition of extracellular signal-regulated kinase-dependent proinflammatory cytokines.

    Science.gov (United States)

    Johansen, Pål; Weiss, Andreas; Bünter, Antonia; Waeckerle-Men, Ying; Fettelschoss, Antonia; Odermatt, Bernhard; Kündig, Thomas M

    2011-12-01

    Antihistamines are considered safe and used worldwide against allergy, pruritus, nausea, and cough and as sleeping aids. Nonetheless, a growing number of reports suggest that antihistamines also have immunoregulatory functions. We examined the extent and by what potential mechanisms histamine-1-receptor (H1R) antagonists exert immune suppressive effects. Immune suppression by antihistamines and immunosuppressants was tested in mice infected with Listeria monocytogenes. Potential modes of action were studied in vitro by using murine and human cells. We also tested whether injection of clemastine in healthy volunteers affected the activation of peripheral macrophages and monocytes. Finally, therapeutic application of clemastine-mediated immune suppression was tested in a murine model of sepsis. Clemastine and desloratadine strongly reduced innate responses to Listeria monocytogenes in mice as did dexamethasone. The immune suppression was MyD88 independent and characterized by inhibition of the mitogen-activated protein kinase-extracellular signal-regulated kinase signaling pathway, leading to overall impaired innate immunity with reduced TNF-α and IL-6 production. Surprisingly, the observed effects were H1R independent as demonstrated in H1R-deficient mice. Moreover, in a double-blind placebo-controlled clinical trial, 1 intravenous administration of clemastine reduced the TNF-α secretion potential of peripheral blood macrophages and monocytes. This inhibition could be exploited to treat sepsis in mice. The safety profile of antihistamines may need to be revisited. However, antihistamine-mediated immune suppression may also be exploited and find applications in the treatment of inflammatory diseases. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  15. Cullin-RING Ubiquitin Ligases in Salicylic Acid-Mediated Plant Immune Signaling

    Directory of Open Access Journals (Sweden)

    James J. Furniss

    2015-03-01

    Full Text Available Plant immune responses against biotrophic pathogens are regulated by the signaling hormone salicylic acid (SA. SA establishes immunity by regulating a variety of cellular processes, including programmed cell death (PCD to isolate and kill invading pathogens, and development of systemic acquired resistance (SAR which provides long-lasting, broad-spectrum resistance throughout the plant. Central to these processes is post-translational modification of SA-regulated signaling proteins by ubiquitination, i.e. the covalent addition of small ubiquitin proteins. Emerging evidence indicates SA-induced protein ubiquitination is largely orchestrated by Cullin-RING ligases (CRLs, which recruit specific substrates for ubiquitination using interchangeable adaptors. Ligation of ubiquitin chains interlinked at lysine 48 leads to substrate degradation by the 26S proteasome. Here we discuss how CRL-mediated degradation of both nucleotide-binding/leucine-rich repeat domain containing (NLR immune receptors and SA-induced transcription regulators are critical for functional PCD and SAR responses, respectively. By placing these recent findings in context of knowledge gained in other eukaryotic model species, we highlight potential alternative roles for processive ubiquitination in regulating the activity of SA-mediated immune responses.

  16. Barley MLA immune receptors directly interfere with antagonistically acting transcription factors to initiate disease resistance signaling.

    Science.gov (United States)

    Chang, Cheng; Yu, Deshui; Jiao, Jian; Jing, Shaojuan; Schulze-Lefert, Paul; Shen, Qian-Hua

    2013-03-01

    The nucleotide binding domain and Leucine-rich repeat (NLR)-containing proteins in plants and animals mediate pathogen sensing inside host cells and mount innate immune responses against microbial pathogens. The barley (Hordeum vulgare) mildew A (MLA) locus encodes coiled-coil (CC)-type NLRs mediating disease resistance against the powdery mildew pathogen Blumeria graminis. Here, we report direct interactions between MLA and two antagonistically acting transcription factors, MYB6 and WRKY1. The N-terminal CC signaling domain of MLA interacts with MYB6 to stimulate its DNA binding activity. MYB6 functions as a positive regulator of basal and MLA-mediated immunity responses to B. graminis. MYB6 DNA binding is antagonized by direct association with WRKY1 repressor, which in turn also interacts with the MLA CC domain. The activated form of full-length MLA10 receptor is needed to release MYB6 activator from WRKY1 repression and to stimulate MYB6-dependent gene expression. This implies that, while sequestered by the WRKY1 repressor in the presence of the resting immune receptor, MYB6 acts as an immediate and positive postactivation signaling component of the active state of MLA during transcriptional reprogramming for innate immune responses.

  17. Light acclimation, retrograde signalling, cell death and immune defences in plants.

    Science.gov (United States)

    Karpiński, Stanisław; Szechyńska-Hebda, Magdalena; Wituszyńska, Weronika; Burdiak, Paweł

    2013-04-01

    This review confronts the classical view of plant immune defence and light acclimation with recently published data. Earlier findings have linked plant immune defences to nucleotide-binding site leucine-rich repeat (NBS-LRR)-dependent recognition of pathogen effectors and to the role of plasma membrane-localized NADPH-dependent oxidoreductase (AtRbohD), reactive oxygen species (ROS) and salicylic acid (SA). However, recent results suggest that plant immune defence also depends on the absorption of excessive light energy and photorespiration. Rapid changes in light intensity and quality often cause the absorption of energy, which is in excess of that required for photosynthesis. Such excessive light energy is considered to be a factor triggering photoinhibition and disturbance in ROS/hormonal homeostasis, which leads to cell death in foliar tissues. We highlight here the tight crosstalk between ROS- and SA-dependent pathways leading to light acclimation, and defence responses leading to pathogen resistance. We also show that LESION SIMULATING DISEASE 1 (LSD1) regulates and integrates these processes. Moreover, we discuss the role of plastid-nucleus signal transduction, photorespiration, photoelectrochemical signalling and 'light memory' in the regulation of acclimation and immune defence responses. All of these results suggest that plants have evolved a genetic system that simultaneously regulates systemic acquired resistance (SAR), cell death and systemic acquired acclimation (SAA). © 2012 Blackwell Publishing Ltd.

  18. NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma

    Science.gov (United States)

    Daley, Donnele; Mani, Vishnu R.; Mohan, Navyatha; Akkad, Neha; Savadkar, Shivraj; Lee, Ki Buom; Torres-Hernandez, Alejandro; Aykut, Berk; Diskin, Brian; Wang, Wei; Farooq, Mohammad S.; Mahmud, Arif I.; Werba, Gregor; Morales, Eduardo J.; Lall, Sarah; Rubin, Amanda G.; Berman, Matthew E.; Hundeyin, Mautin

    2017-01-01

    The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the differentiation of CD4+ T cells into tumor-promoting T helper type 2 cell (Th2 cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell polarization and cytotoxic CD8+ T cell activation. The suppressive effects of NLRP3 signaling were IL-10 dependent. Pharmacological inhibition or deletion of NLRP3, ASC (apoptosis-associated speck-like protein containing a CARD complex), or caspase-1 protected against PDA and was associated with immunogenic reprogramming of innate and adaptive immunity within the TME. Similarly, transfer of PDA-entrained macrophages or T cells from NLRP3−/− hosts was protective. These data suggest that targeting NLRP3 holds the promise for the immunotherapy of PDA. PMID:28442553

  19. TRPM2 channel-mediated ROS-sensitive Ca2+ signaling mechanisms in immune cells

    Directory of Open Access Journals (Sweden)

    Sharifah eSyed Mortadza

    2015-08-01

    Full Text Available Transient receptor potential melastatin 2 (TRPM2 proteins form Ca2+-permeable cationic channels that are potently activated by reactive oxygen species (ROS. ROS are produced during immune responses as signaling molecules as well as anti-microbial agents. ROS-sensitive TRPM2 channels are widely expressed in cells of the immune system and located on the cell surface as a Ca2+ influx pathway in macrophages, monocytes, neutrophils, lymphocytes and microglia but preferentially within the lysosomal membranes as a Ca2+ release mechanism in dendritic cells; ROS activation of the TRPM2 channels, regardless of the subcellular location, results in an increase in the intracellular Ca2+ concentrations. Recent studies have revealed that TRPM2-mediated ROS-sensitive Ca2+ signaling mechanisms play a crucial role in a number of processes and functions in immune cells. This mini-review discusses the recent advances in revelation of the various roles the TRPM2 channels have in immune cell functions and the implications in inflammatory diseases.

  20. Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections.

    Directory of Open Access Journals (Sweden)

    Sine K Kratholm

    Full Text Available Interleukin (IL -21 is produced by Natural Killer T (NKT cells and CD4(+ T cells and is produced in response to virus infections, where IL-21 has been shown to be essential in adaptive immune responses. Cells from the innate immune system such as Natural Killer (NK cells and macrophages are also important in immune protection against virus. These cells express the IL-21 receptor (IL-21R and respond to IL-21 with increased cytotoxicity and cytokine production. Currently, however it is not known whether IL-21 plays a significant role in innate immune responses to virus infections. The purpose of this study was to investigate the role of IL-21 and IL-21R in the innate immune response to a virus infection. We used C57BL/6 wild type (WT and IL-21R knock out (KO mice in a murine vaginal Herpes Simplex Virus type 2 (HSV-2 infection model to show that IL-21 - IL-21R signalling is indeed important in innate immune responses against HSV-2. We found that the IL-21R was expressed in the vaginal epithelium in uninfected (u.i WT mice, and expression increased early after HSV-2 infection. IL-21R KO mice exhibited increased vaginal viral titers on day 2 and 3 post infection (p.i. and subsequently developed significantly higher disease scores and a lower survival rate compared to WT mice. In addition, WT mice infected with HSV-2 receiving intra-vaginal pre-treatment with murine recombinant IL-21 (mIL-21 had decreased vaginal viral titers on day 2 p.i., significantly lower disease scores, and a higher survival rate compared to infected untreated WT controls. Collectively our data demonstrate the novel finding that the IL-21R plays a critical role in regulating innate immune responses against HSV-2 infection.

  1. Investigations of Escherichia coli promoter sequences with artificial neural networks: new signals discovered upstream of the transcriptional startpoint

    DEFF Research Database (Denmark)

    Pedersen, Anders Gorm; Engelbrecht, Jacob

    1995-01-01

    We present a novel method for using the learning ability of a neural network as a measure of information in local regions of input data. Using the method to analyze Escherichia coli promoters, we discover all previously described signals, and furthermore find new signals that are regularly spaced...

  2. Real-time neural signals of perceptual priming with unfamiliar geometric shapes.

    Science.gov (United States)

    Voss, Joel L; Paller, Ken A

    2010-07-07

    Perceptual priming is a type of item-specific implicit memory that is distinct from explicit memory. Neural signals of the processing responsible for perceptual priming can be difficult to isolate due to concurrent conceptual processing and explicit recognition. We successfully identified neural correlates of perceptual priming by using minimally meaningful, difficult-to-recognize, kaleidoscope images. Human participants were required to quickly indicate the number of colors present in each stimulus, and priming was shown by faster and more accurate visual discriminations for repeated compared with initial presentations. Electroencephalographic responses linked with this differential perceptual fluency were identified as negative potentials 100-300 ms poststimulus onset. Furthermore, different potentials recorded during initial presentations were indicative of perceptual learning, in that their amplitude predicted the magnitude of later priming. These electrophysiological findings show that the degree of perceptual learning engaged upon first encountering a novel visual stimulus predicts the degree of perceptual fluency experienced when the stimulus is processed a second time. It is thus possible to isolate multiple neural processing stages relevant to perceptual priming by using real-time measures of relevant neurophysiological activity in conjunction with experimental circumstances that limit the contaminating influences of other neurocognitive events.

  3. Immune signal transduction in leishmaniasis from natural to artificial systems: role of feedback loop insertion.

    Science.gov (United States)

    Mol, Milsee; Patole, Milind S; Singh, Shailza

    2014-01-01

    Modulated immune signal (CD14-TLR and TNF) in leishmaniasis can be linked to EGFR pathway involved in wound healing, through crosstalk points. This signaling network can be further linked to a synthetic gene circuit acting as a positive feedback loop to elicit a synchronized intercellular communication among the immune cells which may contribute to a better understanding of signaling dynamics in leishmaniasis. Network reconstruction with positive feedback loop, simulation (ODE 15s solver) and sensitivity analysis of CD14-TLR, TNF and EGFR was done in SimBiology (MATLAB 7.11.1). Cytoscape and adjacency matrix were used to calculate network topology. PCA was extracted by using sensitivity coefficient in MATLAB. Model reduction was done using time, flux and sensitivity score. Network has five crosstalk points: NIK, IκB-NFκB and MKK (4/7, 3/6, 1/2) which show high flux and sensitivity. PI3K in EGFR pathway shows high flux and sensitivity. PCA score was high for cytoplasmic ERK1/2, PI3K, Atk, STAT1/3 and nuclear JNK. Of the 125 parameters, 20% are crucial as deduced by model reduction. EGFR can be linked to CD14-TLR and TNF through the MAPK crosstalk points. These pathways may be controlled through Ras and Raf that lie upstream of signaling components ERK ½ (c) and JNK (n) that have a high PCA score via a synthetic gene circuit for activating cell-cell communication to elicit an inflammatory response. Also a disease resolving effect may be achieved through PI3K in the EGFR pathway. The reconstructed signaling network can be linked to a gene circuit with a positive feedback loop, for cell-cell communication resulting in synchronized response in the immune cell population, for disease resolving effect in leishmaniasis. © 2013 Elsevier B.V. All rights reserved.

  4. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Robbins, David J. [Department of Surgery, Molecular Oncology Program, Miller School of Medicine, University of Miami, Miami (United States); Matalon, Sadis [Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S. [Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Afaq, Farrukh [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Bickers, David R. [Department of Dermatology, Columbia University Medical Center, New York (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

    2013-11-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions.

  5. Modulation Classification of Satellite Communication Signals Using Cumulants and Neural Networks

    Science.gov (United States)

    Smith, Aaron; Evans, Michael; Downey, Joseph

    2017-01-01

    National Aeronautics and Space Administration (NASA)'s future communication architecture is evaluating cognitive technologies and increased system intelligence. These technologies are expected to reduce the operational complexity of the network, increase science data return, and reduce interference to self and others. In order to increase situational awareness, signal classification algorithms could be applied to identify users and distinguish sources of interference. A significant amount of previous work has been done in the area of automatic signal classification for military and commercial applications. As a preliminary step, we seek to develop a system with the ability to discern signals typically encountered in satellite communication. Proposed is an automatic modulation classifier which utilizes higher order statistics (cumulants) and an estimate of the signal-to-noise ratio. These features are extracted from baseband symbols and then processed by a neural network for classification. The modulation types considered are phase-shift keying (PSK), amplitude and phase-shift keying (APSK),and quadrature amplitude modulation (QAM). Physical layer properties specific to the Digital Video Broadcasting - Satellite- Second Generation (DVB-S2) standard, such as pilots and variable ring ratios, are also considered. This paper will provide simulation results of a candidate modulation classifier, and performance will be evaluated over a range of signal-to-noise ratios, frequency offsets, and nonlinear amplifier distortions.

  6. Encoding physiological signals as images for affective state recognition using convolutional neural networks.

    Science.gov (United States)

    Guangliang Yu; Xiang Li; Dawei Song; Xiaozhao Zhao; Peng Zhang; Yuexian Hou; Bin Hu

    2016-08-01

    Affective state recognition based on multiple modalities of physiological signals has been a hot research topic. Traditional methods require designing hand-crafted features based on domain knowledge, which is time-consuming and has not achieved a satisfactory performance. On the other hand, conducting classification on raw signals directly can also cause some problems, such as the interference of noise and the curse of dimensionality. To address these problems, we propose a novel approach that encodes different modalities of data as images and use convolutional neural networks (CNN) to perform the affective state recognition task. We validate our aproach on the DECAF dataset in comparison with two state-of-the-art methods, i.e., the Support Vector Machines (SVM) and Random Forest (RF). Experimental results show that our aproach outperforms the baselines by 5% to 9%.

  7. Immunization

    Science.gov (United States)

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  8. Classification of seismic signals at Villarrica volcano (Chile) using neural networks and genetic algorithms

    Science.gov (United States)

    Curilem, Gloria; Vergara, Jorge; Fuentealba, Gustavo; Acuña, Gonzalo; Chacón, Max

    2009-02-01

    Each volcano has its own unique seismic activity. The aim of this work is to construct a system able to classify seismic signals for the Villarrica volcano, one of the most active volcanoes in South America. Since seismic signals are the result of particular processes inside the volcano's structure, they can be used to forecast volcanic activity. This paper describes the different kinds of seismic signals recorded at the Villarrica volcano and their significance. Three kind of signals were considered as most representative of this volcano's activity: the long-period, the tremor, and the energetic tremor signals. A classifier is implemented to read the seismic registers at 30-second intervals, extract the most relevant features of each interval, and classify them into one of the three kinds of signals considered as most representative of this particular volcano. To do so, 1033 different kinds of 30-s signals were extracted and classified by a human expert. A feature extraction process was applied to obtain the main characteristics of each of them. This process was developed using criteria which have been shown by others to effectively classify seismic signals, based on the experience of a human expert. The classifier was implemented with a Multi-Layer Perceptron (MLP) artificial neural network whose architecture and training process were optimized by means of a genetic algorithm. This technique searched for the most adequate MLP configuration to improve the classification performance, optimizing the number of hidden neurons, the transfer functions of the neurons, and the training algorithm. The optimization process also performed a feature selection to reduce the number of signal features, optimizing the number of network inputs. The results show that the optimized classifier reaches more than 93% exactitude. identifying the signals of each kind. The amplitude of the signals is the most important feature for its classification, followed by its frequency content. The

  9. Ectonucleotidases as regulators of purinergic signaling in thrombosis, inflammation, and immunity.

    Science.gov (United States)

    Deaglio, Silvia; Robson, Simon C

    2011-01-01

    Evolving studies in models of transplant rejection, inflammatory bowel disease, and cancer, among others, have implicated purinergic signaling in clinical manifestations of vascular injury and thrombophilia, inflammation, and immune disturbance. Within the vasculature, spatial and temporal expression of CD39 nucleoside triphosphate diphosphohydrolase (NTPDase) family members together with CD73 ecto-5'-nucleotidase control platelet activation, thrombus size, and stability. This is achieved by closely regulated phosphohydrolytic activities to scavenge extracellular nucleotides, maintain P2-receptor integrity, and coordinate adenosinergic signaling responses. The CD38/CD157 family of extracellular NADases degrades NAD(+) and generates Ca(2+)-active metabolites, including cyclic ADP ribose and ADP ribose. These mediators regulate leukocyte adhesion and chemotaxis. These mechanisms are crucial in vascular homeostasis, hemostasis, thrombogenesis, and during inflammation. There has been recent interest in ectonucleotidase expression by immune cells. CD39 expression identifies Langerhans-type dendritic cells and efficiently distinguishes T regulatory cells from other resting or activated T cells. CD39, together with CD73 in mice, serves as an integral component of the suppressive machinery of T cells. Purinergic responses also impact generation of T helper-type 17 cells. Further, CD38 and changes in NAD(+) availability modulate ADP ribosylation of the cytolytic P2X7 receptor that deletes T regulatory cells. Expression of CD39, CD73, and CD38 ectonucleotidases on either endothelial or immune cells allows for homeostatic integration and control of vascular inflammatory and immune cell reactions at sites of injury. Ongoing development of therapeutic strategies targeting these and other ectonucleotidases offers promise for the management of vascular thrombosis, disordered inflammation, and aberrant immune reactivity. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Rabconnectin-3a regulates vesicle endocytosis and canonical Wnt signaling in zebrafish neural crest migration.

    Directory of Open Access Journals (Sweden)

    Adam M Tuttle

    2014-05-01

    Full Text Available Cell migration requires dynamic regulation of cell-cell signaling and cell adhesion. Both of these processes involve endocytosis, lysosomal degradation, and recycling of ligand-receptor complexes and cell adhesion molecules from the plasma membrane. Neural crest (NC cells in vertebrates are highly migratory cells, which undergo an epithelial-mesenchymal transition (EMT to leave the neural epithelium and migrate throughout the body to give rise to many different derivatives. Here we show that the v-ATPase interacting protein, Rabconnectin-3a (Rbc3a, controls intracellular trafficking events and Wnt signaling during NC migration. In zebrafish embryos deficient in Rbc3a, or its associated v-ATPase subunit Atp6v0a1, many NC cells fail to migrate and misregulate expression of cadherins. Surprisingly, endosomes in Rbc3a- and Atp6v0a1-deficient NC cells remain immature but still acidify. Rbc3a loss-of-function initially downregulates several canonical Wnt targets involved in EMT, but later Frizzled-7 accumulates at NC cell membranes, and nuclear B-catenin levels increase. Presumably due to this later Wnt signaling increase, Rbc3a-deficient NC cells that fail to migrate become pigment progenitors. We propose that Rbc3a and Atp6v0a1 promote endosomal maturation to coordinate Wnt signaling and intracellular trafficking of Wnt receptors and cadherins required for NC migration and cell fate determination. Our results suggest that different v-ATPases and associated proteins may play cell-type-specific functions in intracellular trafficking in many contexts.

  11. Extruded Bread Classification on the Basis of Acoustic Emission Signal With Application of Artificial Neural Networks

    Science.gov (United States)

    Świetlicka, Izabela; Muszyński, Siemowit; Marzec, Agata

    2015-04-01

    The presented work covers the problem of developing a method of extruded bread classification with the application of artificial neural networks. Extruded flat graham, corn, and rye breads differening in water activity were used. The breads were subjected to the compression test with simultaneous registration of acoustic signal. The amplitude-time records were analyzed both in time and frequency domains. Acoustic emission signal parameters: single energy, counts, amplitude, and duration acoustic emission were determined for the breads in four water activities: initial (0.362 for rye, 0.377 for corn, and 0.371 for graham bread), 0.432, 0.529, and 0.648. For classification and the clustering process, radial basis function, and self-organizing maps (Kohonen network) were used. Artificial neural networks were examined with respect to their ability to classify or to cluster samples according to the bread type, water activity value, and both of them. The best examination results were achieved by the radial basis function network in classification according to water activity (88%), while the self-organizing maps network yielded 81% during bread type clustering.

  12. A potential neural substrate for processing functional classes of complex acoustic signals.

    Directory of Open Access Journals (Sweden)

    Isabelle George

    Full Text Available Categorization is essential to all cognitive processes, but identifying the neural substrates underlying categorization processes is a real challenge. Among animals that have been shown to be able of categorization, songbirds are particularly interesting because they provide researchers with clear examples of categories of acoustic signals allowing different levels of recognition, and they possess a system of specialized brain structures found only in birds that learn to sing: the song system. Moreover, an avian brain nucleus that is analogous to the mammalian secondary auditory cortex (the caudo-medial nidopallium, or NCM has recently emerged as a plausible site for sensory representation of birdsong, and appears as a well positioned brain region for categorization of songs. Hence, we tested responses in this non-primary, associative area to clear and distinct classes of songs with different functions and social values, and for a possible correspondence between these responses and the functional aspects of songs, in a highly social songbird species: the European starling. Our results clearly show differential neuronal responses to the ethologically defined classes of songs, both in the number of neurons responding, and in the response magnitude of these neurons. Most importantly, these differential responses corresponded to the functional classes of songs, with increasing activation from non-specific to species-specific and from species-specific to individual-specific sounds. These data therefore suggest a potential neural substrate for sorting natural communication signals into categories, and for individual vocal recognition of same-species members. Given the many parallels that exist between birdsong and speech, these results may contribute to a better understanding of the neural bases of speech.

  13. Immunizations

    Science.gov (United States)

    ... Why Exercise Is Wise Are Detox Diets Safe? Immunizations KidsHealth > For Teens > Immunizations Print A A A What's in this article? ... fault if you don't have all the immunizations (vaccinations) you need. Shots that doctors recommend today ...

  14. Transfer functions for protein signal transduction: application to a model of striatal neural plasticity.

    Directory of Open Access Journals (Sweden)

    Gabriele Scheler

    Full Text Available We present a novel formulation for biochemical reaction networks in the context of protein signal transduction. The model consists of input-output transfer functions, which are derived from differential equations, using stable equilibria. We select a set of "source" species, which are interpreted as input signals. Signals are transmitted to all other species in the system (the "target" species with a specific delay and with a specific transmission strength. The delay is computed as the maximal reaction time until a stable equilibrium for the target species is reached, in the context of all other reactions in the system. The transmission strength is the concentration change of the target species. The computed input-output transfer functions can be stored in a matrix, fitted with parameters, and even recalled to build dynamical models on the basis of state changes. By separating the temporal and the magnitudinal domain we can greatly simplify the computational model, circumventing typical problems of complex dynamical systems. The transfer function transformation of biochemical reaction systems can be applied to mass-action kinetic models of signal transduction. The paper shows that this approach yields significant novel insights while remaining a fully testable and executable dynamical model for signal transduction. In particular we can deconstruct the complex system into local transfer functions between individual species. As an example, we examine modularity and signal integration using a published model of striatal neural plasticity. The modularizations that emerge correspond to a known biological distinction between calcium-dependent and cAMP-dependent pathways. Remarkably, we found that overall interconnectedness depends on the magnitude of inputs, with higher connectivity at low input concentrations and significant modularization at moderate to high input concentrations. This general result, which directly follows from the properties of

  15. Compound developmental eye disorders following inactivation of TGFβ signaling in neural-crest stem cells

    Directory of Open Access Journals (Sweden)

    Suter Ueli

    2005-12-01

    Full Text Available Abstract Background Development of the eye depends partly on the periocular mesenchyme derived from the neural crest (NC, but the fate of NC cells in mammalian eye development and the signals coordinating the formation of ocular structures are poorly understood. Results Here we reveal distinct NC contributions to both anterior and posterior mesenchymal eye structures and show that TGFβ signaling in these cells is crucial for normal eye development. In the anterior eye, TGFβ2 released from the lens is required for the expression of transcription factors Pitx2 and Foxc1 in the NC-derived cornea and in the chamber-angle structures of the eye that control intraocular pressure. TGFβ enhances Foxc1 and induces Pitx2 expression in cell cultures. As in patients carrying mutations in PITX2 and FOXC1, TGFβ signal inactivation in NC cells leads to ocular defects characteristic of the human disorder Axenfeld-Rieger's anomaly. In the posterior eye, NC cell-specific inactivation of TGFβ signaling results in a condition reminiscent of the human disorder persistent hyperplastic primary vitreous. As a secondary effect, retinal patterning is also disturbed in mutant mice. Conclusion In the developing eye the lens acts as a TGFβ signaling center that controls the development of eye structures derived from the NC. Defective TGFβ signal transduction interferes with NC-cell differentiation and survival anterior to the lens and with normal tissue morphogenesis and patterning posterior to the lens. The similarity to developmental eye disorders in humans suggests that defective TGFβ signal modulation in ocular NC derivatives contributes to the pathophysiology of these diseases.

  16. A neural network method for identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Engelbrecht, Jacob; Brunak, Søren

    1997-01-01

    We have developed a new method for the identication of signal peptides and their cleavage sites based on neural networks trained on separate sets of prokaryotic and eukaryotic sequences. The method performs signicantly better than previous prediction schemes, and can easily be applied to genome......-wide data sets. Discrimination between cleaved signal peptides and uncleaved N-terminal signal-anchor sequences is also possible, though with lower precision....

  17. USP9X deubiquitylating enzyme maintains RAPTOR protein levels, mTORC1 signalling and proliferation in neural progenitors.

    Science.gov (United States)

    Bridges, Caitlin R; Tan, Men-Chee; Premarathne, Susitha; Nanayakkara, Devathri; Bellette, Bernadette; Zencak, Dusan; Domingo, Deepti; Gecz, Jozef; Murtaza, Mariyam; Jolly, Lachlan A; Wood, Stephen A

    2017-03-24

    USP9X, is highly expressed in neural progenitors and, essential for neural development in mice. In humans, mutations in USP9X are associated with neurodevelopmental disorders. To understand USP9X's role in neural progenitors, we studied the effects of altering its expression in both the human neural progenitor cell line, ReNcell VM, as well as neural stem and progenitor cells derived from Nestin-cre conditionally deleted Usp9x mice. Decreasing USP9X resulted in ReNcell VM cells arresting in G0 cell cycle phase, with a concomitant decrease in mTORC1 signalling, a major regulator of G0/G1 cell cycle progression. Decreased mTORC1 signalling was also observed in Usp9x-null neurospheres and embryonic mouse brains. Further analyses revealed, (i) the canonical mTORC1 protein, RAPTOR, physically associates with Usp9x in embryonic brains, (ii) RAPTOR protein level is directly proportional to USP9X, in both loss- and gain-of-function experiments in cultured cells and, (iii) USP9X deubiquitlyating activity opposes the proteasomal degradation of RAPTOR. EdU incorporation assays confirmed Usp9x maintains the proliferation of neural progenitors similar to Raptor-null and rapamycin-treated neurospheres. Interestingly, loss of Usp9x increased the number of sphere-forming cells consistent with enhanced neural stem cell self-renewal. To our knowledge, USP9X is the first deubiquitylating enzyme shown to stabilize RAPTOR.

  18. Implementing eigenvector methods/probabilistic neural networks for analysis of EEG signals.

    Science.gov (United States)

    Ubeyli, Elif Derya

    2008-11-01

    A new approach based on the implementation of probabilistic neural network (PNN) is presented for classification of electroencephalogram (EEG) signals. In practical applications of pattern recognition, there are often diverse features extracted from raw data which needs recognizing. Because of the importance of making the right decision, the present work is carried out for searching better classification procedures for the EEG signals. Decision making was performed in two stages: feature extraction by eigenvector methods and classification using the classifiers trained on the extracted features. The aim of the study is classification of the EEG signals by the combination of eigenvector methods and the PNN. The purpose is to determine an optimum classification scheme for this problem and also to infer clues about the extracted features. The present research demonstrated that the power levels of the power spectral density (PSD) estimates obtained by the eigenvector methods are the features which well represent the EEG signals and the PNN trained on these features achieved high classification accuracies.

  19. SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis

    Science.gov (United States)

    Li, Jingyuan; Huang, Xiaofeng; Xu, Xun; Mayo, Julie; Bringas, Pablo; Jiang, Rulang; Wang, Songling; Chai, Yang

    2011-01-01

    TGFβ/BMP signaling regulates the fate of multipotential cranial neural crest (CNC) cells during tooth and jawbone formation as these cells differentiate into odontoblasts and osteoblasts, respectively. The functional significance of SMAD4, the common mediator of TGFβ/BMP signaling, in regulating the fate of CNC cells remains unclear. In this study, we investigated the mechanism of SMAD4 in regulating the fate of CNC-derived dental mesenchymal cells through tissue-specific inactivation of Smad4. Ablation of Smad4 results in defects in odontoblast differentiation and dentin formation. Moreover, ectopic bone-like structures replaced normal dentin in the teeth of Osr2-IresCre;Smad4fl/fl mice. Despite the lack of dentin, enamel formation appeared unaffected in Osr2-IresCre;Smad4fl/fl mice, challenging the paradigm that the initiation of enamel development depends on normal dentin formation. At the molecular level, loss of Smad4 results in downregulation of the WNT pathway inhibitors Dkk1 and Sfrp1 and in the upregulation of canonical WNT signaling, including increased β-catenin activity. More importantly, inhibition of the upregulated canonical WNT pathway in Osr2-IresCre;Smad4fl/fl dental mesenchyme in vitro partially rescued the CNC cell fate change. Taken together, our study demonstrates that SMAD4 plays a crucial role in regulating the interplay between TGFβ/BMP and WNT signaling to ensure the proper CNC cell fate decision during organogenesis. PMID:21490069

  20. Real-Time Neural Signals Decoding onto Off-the-Shelf DSP Processors for Neuroprosthetic Applications.

    Science.gov (United States)

    Pani, Danilo; Barabino, Gianluca; Citi, Luca; Meloni, Paolo; Raspopovic, Stanisa; Micera, Silvestro; Raffo, Luigi

    2016-09-01

    The control of upper limb neuroprostheses through the peripheral nervous system (PNS) can allow restoring motor functions in amputees. At present, the important aspect of the real-time implementation of neural decoding algorithms on embedded systems has been often overlooked, notwithstanding the impact that limited hardware resources have on the efficiency/effectiveness of any given algorithm. Present study is addressing the optimization of a template matching based algorithm for PNS signals decoding that is a milestone for its real-time, full implementation onto a floating-point digital signal processor (DSP). The proposed optimized real-time algorithm achieves up to 96% of correct classification on real PNS signals acquired through LIFE electrodes on animals, and can correctly sort spikes of a synthetic cortical dataset with sufficiently uncorrelated spike morphologies (93% average correct classification) comparably to the results obtained with top spike sorter (94% on average on the same dataset). The power consumption enables more than 24 h processing at the maximum load, and latency model has been derived to enable a fair performance assessment. The final embodiment demonstrates the real-time performance onto a low-power off-the-shelf DSP, opening to experiments exploiting the efferent signals to control a motor neuroprosthesis.

  1. Electromagnetic field effects on cells of the immune system: The role of calcium signaling

    Energy Technology Data Exchange (ETDEWEB)

    Walleczek, J. (Lawrence Berkeley Lab., CA (United States))

    1992-10-01

    During the past decade considerable evidence has accumulated demonstrating that nonthermal exposures of cells of the immune system to extremely low-frequency (ELF) electromagnetic fields (< 300 Hz) can elicit cellular changes that might be relevant to in vivo immune activity. A similar responsiveness to nonionizing electromagnetic energy in this frequency range has also been documented for tissues of the neuroendocrine and musculoskeletal system. However, knowledge about the underlying biological mechanisms by which such fields can induce cellular changes is still very limited. It is generally believed that the cell membrane and Ca[sup 2+]-regulated activity is involved in bioactive ELF field coupling to living systems. This article begins with a short review of the current state of knowledge concerning the effects of nonthermal levels of ELF electromagnetic fields on the biochemistry and activity of immune cells and then closely examines new results that suggest a role for Ca[sup 2+] in the induction of these cellular field effects. Based on these findings it is proposed that membrane-mediated Ca[sup 2+] in the induction of these cellular field effects. Based on these findings it is proposed that membrane-mediated Ca[sup 2+] signaling processes are involved in the mediation of field effects on the immune system. 69 refs., 2 tabs.

  2. Electromagnetic field effects on cells of the immune system: The role of calcium signalling

    Energy Technology Data Exchange (ETDEWEB)

    Walleczek, J.

    1991-07-01

    During the past decade considerable evidence has accumulated demonstrating the exposures of cells of the immune system to relatively weak extremely-low-frequency (ELF) electromagnetic fields (< 300 Hz) can elicit cellular changes which might be relevant to in-vivo immune activity. However, knowledge about the underlying biological mechanisms by which weak fields induce cellular changes is still very limited. It is generally believed that the cell membrane and Ca{sup 2+} regulated activity is involved in bioactive ELF field-coupling to living systems. This article begins with a short review of the current state of knowledge concerning the effects of nonthermal levels of ELF electromagnetic fields on the biochemistry and activity of immune cells, and then closely examines new results which suggest a role for Ca{sup 2+} in the induction of these cellular field effects. Based on these findings it is proposed that membrane-mediated Ca{sup 2+} signalling processes are involved in the mediation of field effects on the immune system. 64 refs., 2 tabs.

  3. HIF-mediated innate immune responses: cell signaling and therapeutic implications

    Directory of Open Access Journals (Sweden)

    Harris AJ

    2014-05-01

    Full Text Available Alison J Harris, AA Roger Thompson, Moira KB Whyte, Sarah R Walmsley Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield, UK Abstract: Leukocytes recruited to infected, damaged, or inflamed tissues during an immune response must adapt to oxygen levels much lower than those in the circulation. Hypoxia inducible factors (HIFs are key mediators of cellular responses to hypoxia and, as in other cell types, HIFs are critical for the upregulation of glycolysis, which enables innate immune cells to produce adenosine triphosphate anaerobically. An increasing body of evidence demonstrates that hypoxia also regulates many other innate immunological functions, including cell migration, apoptosis, phagocytosis of pathogens, antigen presentation and production of cytokines, chemokines, and angiogenic and antimicrobial factors. Many of these functions are mediated by HIFs, which are not only stabilized posttranslationally by hypoxia, but also transcriptionally upregulated by inflammatory signals. Here, we review the role of HIFs in the responses of innate immune cells to hypoxia, both in vitro and in vivo, with a particular focus on myeloid cells, on which the majority of studies have so far been carried out. Keywords: hypoxia, neutrophils, monocytes, macrophages

  4. Estrogen receptor signal in regulation of B cell activation during diverse immune responses.

    Science.gov (United States)

    Asaba, Josaine; Bandyopadhyay, Mausumi; Kindy, Mark; Dasgupta, Subhajit

    2015-11-01

    The role of signalling through oestrogen receptors (ERs) in the regulation of B cell activation is an area of growing importance not only in terms protective immunity but also in the determination of the mechanisms of the onset of autoimmune disorders and cancers. The mode of signalling action of this single chain nuclear receptor protein molecule depends on its ability to bind to the promoters of Pax5, HOXC4 and apolipoprotein B RNA-editing enzyme activation-induced cytidine deaminase (AID) genes. ER-mediated transcriptional regulation induces class switch recombination of the immunoglobulin heavy chain variable (VH) to DH-JH genes and somatic hypermutation in developing B cells. The mode of action of ER is associated with BCR-signal pathways that involve the regulator proteins BAFF and APRIL. Additionally, the plasma membrane-bound G protein-coupled oestrogen receptor-1 (GEPR1) directs diverse cell signalling events in B cells that involve the MAPK pathways. These signals are immensely important during progenitor and precursor B cell activation. We have focused our goals on the medicinal aspects of ER-signalling mechanisms and their effects on polyclonal B cell activation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Dendritic Cells Coordinate Innate Immunity via MyD88 Signaling to Control Listeria monocytogenes Infection

    Directory of Open Access Journals (Sweden)

    Catharina Arnold-Schrauf

    2014-02-01

    Full Text Available Listeria monocytogenes (LM, a facultative intracellular Gram-positive pathogen, can cause life-threatening infections in humans. In mice, the signaling cascade downstream of the myeloid differentiation factor 88 (MyD88 is essential for proper innate immune activation against LM, as MyD88-deficient mice succumb early to infection. Here, we show that MyD88 signaling in dendritic cells (DCs is sufficient to mediate the protective innate response, including the production of proinflammatory cytokines, neutrophil infiltration, bacterial clearance, and full protection from lethal infection. We also demonstrate that MyD88 signaling by DCs controls the infection rates of CD8α+ cDCs and thus limits the spread of LM to the T cell areas. Furthermore, in mice expressing MyD88 in DCs, inflammatory monocytes, which are required for bacterial clearance, are activated independently of intrinsic MyD88 signaling. In conclusion, CD11c+ conventional DCs critically integrate pathogen-derived signals via MyD88 signaling during early infection with LM in vivo.

  6. Novel Mutation of LRP6 Identified in Chinese Han Population Links Canonical WNT Signaling to Neural Tube Defects.

    Science.gov (United States)

    Shi, Zhiwen; Yang, Xueyan; Li, Bin-Bin; Chen, Shuxia; Yang, Luming; Cheng, Liangping; Zhang, Ting; Wang, Hongyan; Zheng, Yufang

    2017-09-29

    Neural tube defects (NTDs), the second most frequent cause of human congenital abnormalities, are debilitating birth defects due to failure of neural tube closure. It has been shown that noncanonical WNT/planar cell polarity (PCP) signaling is required for convergent extension (CE), the initiation step of neural tube closure (NTC). But the effect of canonical WNT//β-catenin signaling during NTC is still elusive. LRP6 (low density lipoprotein receptor related proteins 6) was identified as a co-receptor for WNT/β-catenin signaling, but recent studies showed that it also can mediate WNT/PCP signaling. In this study, we screened mutations in the LRP6 gene in 343 NTDs and 215 ethnically matched normal controls of Chinese Han population. Three rare missense mutations (c.1514A>G, p.Y505C); c.2984A>G, p.D995G; and c.4280C>A, p.P1427Q) of the LRP6 gene were identified in Chinese NTD patients. The Y505C mutation is a loss-of-function mutation on both WNT/β-catenin and PCP signaling. The D995G mutation only partially lost inhibition on PCP signaling without affecting WNT/β-catenin signaling. The P1427Q mutation dramatically increased WNT/β-catenin signaling but only mildly loss of inhibition on PCP signaling. All three mutations failed to rescue CE defects caused by lrp6 morpholino oligos knockdown in zebrafish. Of interest, when overexpressed, D995G did not induce any defects, but Y505C and P1427Q caused more severe CE defects in zebrafish. Our results suggested that over-active canonical WNT signaling induced by gain-of-function mutation in LRP6 could also contribute to human NTDs, and a balanced WNT/β-catenin and PCP signaling is probably required for proper neural tube development. Birth Defects Research, 2017.© 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Phosphorylation of Sox9 is required for neural crest delamination and is regulated downstream of BMP and canonical Wnt signaling.

    Science.gov (United States)

    Liu, Jessica A J; Wu, Ming-Hoi; Yan, Carol H; Chau, Bolton K H; So, Henry; Ng, Alvis; Chan, Alan; Cheah, Kathryn S E; Briscoe, James; Cheung, Martin

    2013-02-19

    Coordination of neural crest cell (NCC) induction and delamination is orchestrated by several transcription factors. Among these, Sry-related HMG box-9 (Sox9) and Snail2 have been implicated in both the induction of NCC identity and, together with phoshorylation, NCC delamination. How phosphorylation effects this function has not been clear. Here we show, in the developing chick neural tube, that phosphorylation of Sox9 on S64 and S181 facilitates its SUMOylation, and the phosphorylated forms of Sox9 are essential for trunk neural crest delamination. Both phosphorylation and to a lesser extent SUMOylation, of Sox9 are required to cooperate with Snail2 to promote delamination. Moreover, bone morphogenetic protein and canonical Wnt signaling induce phosphorylation of Sox9, thereby connecting extracellular signals with the delamination of NCCs. Together the data suggest a model in which extracellular signals initiate phosphorylation of Sox9 and its cooperation with Snail2 to induce NCC delamination.

  8. Lymphovascular and neural regulation of metastasis: Shared tumour signalling pathways and novel therapeutic approaches

    Science.gov (United States)

    Le, C.P.; Karnezis, T.; Achen, M. G.; Stacker, S.A.; Sloan, E.K.

    2014-01-01

    The progression of cancer is supported by a wide variety of non-neoplastic cell types which make up the tumour stroma, including immune cells, endothelial cells, cancer-associated fibroblasts and nerve fibres. These host cells contribute molecular signals that enhance primary tumour growth and provide physical avenues for metastatic dissemination. This article provides an overview of the role of blood vessels, lymphatic vessels and nerve fibres in the tumour microenvironment, and highlights the interconnected molecular signalling pathways that control their development and activation in cancer. Further the review highlights the known pharmacological agents which target these pathways and discusses the potential therapeutic uses of drugs that target angiogenesis, lymphangiogenesis and stress response pathways in the different stages of cancer care. PMID:24267548

  9. IL-1β Signaling Promotes CNS-Intrinsic Immune Control of West Nile Virus Infection

    Science.gov (United States)

    Ramos, Hilario J.; Lanteri, Marion C.; Blahnik, Gabriele; Negash, Amina; Suthar, Mehul S.; Brassil, Margaret M.; Sodhi, Khushbu; Treuting, Piper M.; Busch, Michael P.; Norris, Philip J.; Gale, Michael

    2012-01-01

    West Nile virus (WNV) is an emerging flavivirus capable of infecting the central nervous system (CNS) and mediating neuronal cell death and tissue destruction. The processes that promote inflammation and encephalitis within the CNS are important for control of WNV disease but, how inflammatory signaling pathways operate to control CNS infection is not defined. Here, we identify IL-1β signaling and the NLRP3 inflammasome as key host restriction factors involved in viral control and CNS disease associated with WNV infection. Individuals presenting with acute WNV infection displayed elevated levels of IL-1β in their plasma over the course of infection, suggesting a role for IL-1β in WNV immunity. Indeed, we found that in a mouse model of infection, WNV induced the acute production of IL-1β in vivo, and that animals lacking the IL-1 receptor or components involved in inflammasome signaling complex exhibited increased susceptibility to WNV pathogenesis. This outcome associated with increased accumulation of virus within the CNS but not peripheral tissues and was further associated with altered kinetics and magnitude of inflammation, reduced quality of the effector CD8+ T cell response and reduced anti-viral activity within the CNS. Importantly, we found that WNV infection triggers production of IL-1β from cortical neurons. Furthermore, we found that IL-1β signaling synergizes with type I IFN to suppress WNV replication in neurons, thus implicating antiviral activity of IL-1β within neurons and control of virus replication within the CNS. Our studies thus define the NLRP3 inflammasome pathway and IL-1β signaling as key features controlling WNV infection and immunity in the CNS, and reveal a novel role for IL-1β in antiviral action that restricts virus replication in neurons. PMID:23209411

  10. Intracellular B Lymphocyte Signalling and the Regulation of Humoral Immunity and Autoimmunity.

    Science.gov (United States)

    Taher, Taher E; Bystrom, Jonas; Ong, Voon H; Isenberg, David A; Renaudineau, Yves; Abraham, David J; Mageed, Rizgar A

    2017-04-29

    B lymphocytes are critical for effective immunity; they produce antibodies and cytokines, present antigens to T lymphocytes and regulate immune responses. However, because of the inherent randomness in the process of generating their vast repertoire of antigen-specific receptors, B cells can also cause diseases through recognizing and reacting to self. Therefore, B lymphocyte selection and responses require tight regulation at multiple levels and at all stages of their development and activation to avoid diseases. Indeed, newly generated B lymphocytes undergo rigorous tolerance mechanisms in the bone marrow and, subsequently, in the periphery after their migration. Furthermore, activation of mature B cells is regulated through controlled expression of co-stimulatory receptors and intracellular signalling thresholds. All these regulatory events determine whether and how B lymphocytes respond to antigens, by undergoing apoptosis or proliferation. However, defects that alter regulated co-stimulatory receptor expression or intracellular signalling thresholds can lead to diseases. For example, autoimmune diseases can result from altered regulation of B cell responses leading to the emergence of high-affinity autoreactive B cells, autoantibody production and tissue damage. The exact cause(s) of defective B cell responses in autoimmune diseases remains unknown. However, there is evidence that defects or mutations in genes that encode individual intracellular signalling proteins lead to autoimmune diseases, thus confirming that defects in intracellular pathways mediate autoimmune diseases. This review provides a synopsis of current knowledge of signalling proteins and pathways that regulate B lymphocyte responses and how defects in these could promote autoimmune diseases. Most of the evidence comes from studies of mouse models of disease and from genetically engineered mice. Some, however, also come from studying B lymphocytes from patients and from genome-wide association

  11. A study on a robot arm driven by three-dimensional trajectories predicted from non-invasive neural signals.

    Science.gov (United States)

    Kim, Yoon Jae; Park, Sung Woo; Yeom, Hong Gi; Bang, Moon Suk; Kim, June Sic; Chung, Chun Kee; Kim, Sungwan

    2015-08-20

    A brain-machine interface (BMI) should be able to help people with disabilities by replacing their lost motor functions. To replace lost functions, robot arms have been developed that are controlled by invasive neural signals. Although invasive neural signals have a high spatial resolution, non-invasive neural signals are valuable because they provide an interface without surgery. Thus, various researchers have developed robot arms driven by non-invasive neural signals. However, robot arm control based on the imagined trajectory of a human hand can be more intuitive for patients. In this study, therefore, an integrated robot arm-gripper system (IRAGS) that is driven by three-dimensional (3D) hand trajectories predicted from non-invasive neural signals was developed and verified. The IRAGS was developed by integrating a six-degree of freedom robot arm and adaptive robot gripper. The system was used to perform reaching and grasping motions for verification. The non-invasive neural signals, magnetoencephalography (MEG) and electroencephalography (EEG), were obtained to control the system. The 3D trajectories were predicted by multiple linear regressions. A target sphere was placed at the terminal point of the real trajectories, and the system was commanded to grasp the target at the terminal point of the predicted trajectories. The average correlation coefficient between the predicted and real trajectories in the MEG case was [Formula: see text] ([Formula: see text]). In the EEG case, it was [Formula: see text] ([Formula: see text]). The success rates in grasping the target plastic sphere were 18.75 and 7.50 % with MEG and EEG, respectively. The success rates of touching the target were 52.50 and 58.75 % respectively. A robot arm driven by 3D trajectories predicted from non-invasive neural signals was implemented, and reaching and grasping motions were performed. In most cases, the robot closely approached the target, but the success rate was not very high because

  12. Lipid motif of a bacterial antigen mediates immune responses via TLR2 signaling.

    Directory of Open Access Journals (Sweden)

    Amit A Lugade

    Full Text Available The cross-talk between the innate and the adaptive immune system is facilitated by the initial interaction of antigen with dendritic cells. As DCs express a large array of TLRs, evidence has accumulated that engagement of these molecules contributes to the activation of adaptive immunity. We have evaluated the immunostimulatory role of the highly-conserved outer membrane lipoprotein P6 from non-typeable Haemophilus influenzae (NTHI to determine whether the presence of the lipid motif plays a critical role on its immunogenicity. We undertook a systematic analysis of the role that the lipid motif plays in the activation of DCs and the subsequent stimulation of antigen-specific T and B cells. To facilitate our studies, recombinant P6 protein that lacked the lipid motif was generated. Mice immunized with non-lipidated rP6 were unable to elicit high titers of anti-P6 Ig. Expression of the lipid motif on P6 was also required for proliferation and cytokine secretion by antigen-specific T cells. Upregulation of T cell costimulatory molecules was abrogated in DCs exposed to non-lipidated rP6 and in TLR2(-/- DCs exposed to native P6, thereby resulting in diminished adaptive immune responses. Absence of either the lipid motif on the antigen or TLR2 expression resulted in diminished cytokine production from stimulated DCs. Collectively, our data suggest that the lipid motif of the lipoprotein antigen is essential for triggering TLR2 signaling and effective stimulation of APCs. Our studies establish the pivotal role of a bacterial lipid motif on activating both innate and adaptive immune responses to an otherwise poorly immunogenic protein antigen.

  13. A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution.

    Science.gov (United States)

    Crawford, Michael A; Broadhurst, C Leigh; Guest, Martin; Nagar, Atulya; Wang, Yiqun; Ghebremeskel, Kebreab; Schmidt, Walter F

    2013-01-01

    Six hundred million years ago, the fossil record displays the sudden appearance of intracellular detail and the 32 phyla. The "Cambrian Explosion" marks the onset of dominant aerobic life. Fossil intracellular structures are so similar to extant organisms that they were likely made with similar membrane lipids and proteins, which together provided for organisation and specialisation. While amino acids could be synthesised over 4 billion years ago, only oxidative metabolism allows for the synthesis of highly unsaturated fatty acids, thus producing novel lipid molecular species for specialised cell membranes. Docosahexaenoic acid (DHA) provided the core for the development of the photoreceptor, and conversion of photons into electricity stimulated the evolution of the nervous system and brain. Since then, DHA has been conserved as the principle acyl component of photoreceptor synaptic and neuronal signalling membranes in the cephalopods, fish, amphibian, reptiles, birds, mammals and humans. This extreme conservation in electrical signalling membranes despite great genomic change suggests it was DHA dictating to DNA rather than the generally accepted other way around. We offer a theoretical explanation based on the quantum mechanical properties of DHA for such extreme conservation. The unique molecular structure of DHA allows for quantum transfer and communication of π-electrons, which explains the precise depolarisation of retinal membranes and the cohesive, organised neural signalling which characterises higher intelligence. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. EEG signal classification method based on fractal features and neural network.

    Science.gov (United States)

    Phothisonothai, Montri; Nakagawa, Masahiro

    2008-01-01

    In this paper, we propose a method to classify electroencephalogram (EEG) signal recorded from left- and right-hand movement imaginations. Three subjects (two males and one female) are volunteered to participate in the experiment. We use a technique of complexity measure based on fractal analysis to reveal feature patterns in the EEG signal. Effective algorithm, namely, detrended fluctuation analysis (DFA) has been selected to estimate embedded fractal dimension (FD) values between relaxing and imaging states of the recorded EEG signal. To show the waveform of FDs, we use a windowing-based method or called time-dependent fractal dimension (TDFD) and the Kullback-Leibler (K-L) divergence. Two feature parameters; K-L divergence and different expected values are proposed to be input variables of the classifier. Finally, featured data are classified by a three-layer feed-forward neural network based on a simple backpropagation algorithm. Experimental results can be considerably applied in a brain-computer interface (BCI) application and show that the proposed method is more effective than the conventional method by improving average classification rates of 87.5% and 88.3% for left- and right-hand movement imagery tasks, respectively.

  15. Classification of Human Emotion from Deap EEG Signal Using Hybrid Improved Neural Networks with Cuckoo Search

    Directory of Open Access Journals (Sweden)

    M. Sreeshakthy

    2016-01-01

    Full Text Available Department of Computer Science and Engineering,Anna University Regional Centre, Coimbatore, Indiam.sribtechit@gmail.comJ. PreethiDepartment of Computer Science and EngineeringAnna University Regional Centre, Coimbatore, Indiapreethi17j@yahoo.comEmotions are very important in human decision handling, interaction and cognitive process. In this paper describes that recognize the human emotions from DEAP EEG dataset with different kind of methods. Audio – video based stimuli is used to extract the emotions. EEG signal is divided into different bands using discrete wavelet transformation with db8 wavelet function for further process. Statistical and energy based features are extracted from the bands, based on the features emotions are classified with feed forward neural network with weight optimized algorithm like PSO. Before that the particular band has to be selected based on the training performance of neural networks and then the emotions are classified. In this experimental result describes that the gamma and alpha bands are provides the accurate classification result with average classification rate of 90.3% of using NNRBF, 90.325% of using PNN, 96.3% of using PSO trained NN, 98.1 of using Cuckoo trained NN. At last the emotions are classified into two different groups like valence and arousal. Based on that identifies the person normal and abnormal behavioral using classified emotion.

  16. Spectral properties of multiple myoelectric signals: New insights into the neural origin of muscle synergies.

    Science.gov (United States)

    Frère, Julien

    2017-07-04

    It is still unclear if muscle synergies reflect neural strategies or mirror the underlying mechanical constraints. Therefore, this study aimed to verify the consistency of muscle groupings between the synergies based on the linear envelope (LE) of muscle activities and those incorporating the time-frequency (TF) features of the electromyographic (EMG) signals. Twelve healthy participants performed six 20-m walking trials at a comfort and fast self-selected speed, while the activity of eleven lower limb muscles was recorded by means of surface EMG. Wavelet-transformed EMG was used to obtain the TF pattern and muscle synergies were extracted by non-negative matrix factorization. When five muscle synergies were extracted, both methods defined similar muscle groupings whatever the walking speed. When accounting the reconstruction level of the initial dataset, a new TF synergy emerged. This new synergy dissociated the activity of the rectus femoris from those of the vastii muscles (synergy #1) and from the one of the tensor fascia latae (synergy #5). Overall, extracting TF muscle synergies supports the neural origin of muscle synergies and provides an opportunity to distinguish between prescriptive and descriptive muscle synergies. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Immune regulatory neural stem/precursor cells protect from central nervous system autoimmunity by restraining dendritic cell function.

    Directory of Open Access Journals (Sweden)

    Stefano Pluchino

    Full Text Available BACKGROUND: The systemic injection of neural stem/precursor cells (NPCs provides remarkable amelioration of the clinico-pathological features of experimental autoimmune encephalomyelitis (EAE. This is dependent on the capacity of transplanted NPCs to engage concurrent mechanisms of action within specific microenvironments in vivo. Among a wide range of therapeutic actions alternative to cell replacement, neuroprotective and immune modulatory capacities of transplanted NPCs have been described. However, lacking is a detailed understanding of the mechanisms by which NPCs exert their therapeutic plasticity. This study was designed to identify the first candidate that exemplifies and sustains the immune modulatory capacity of transplanted NPCs. METHODOLOGY/PRINCIPAL FINDINGS: To achieve the exclusive targeting of the peripheral immune system, SJL mice with PLP-induced EAE were injected subcutaneously with NPCs and the treatment commenced prior to disease onset. NPC-injected EAE mice showed significant clinical improvement, as compared to controls. Exogenous NPCs lacking the expression of major neural antigens were reliably (and for long-term found at the level of draining lymph nodes, while establishing sophisticated anatomical interactions with lymph node cells. Importantly, injected NPCs were never found in organs other than lymph nodes, including the brain and the spinal cord. Draining lymph nodes from transplanted mice showed focal up-regulation of major developmental stem cell regulators, such as BMP-4, Noggin and Sonic hedgehog. In lymph nodes, injected NPCs hampered the activation of myeloid dendritic cells (DCs and steadily restrained the expansion of antigen-specific encephalitogenic T cells. Both ex vivo and in vitro experiments identified a novel highly NPC-specific-BMP-4-dependent-mechanism hindering the DC maturation. CONCLUSION/SIGNIFICANCE: The study described herein, identifies the first member of the TGF beta/BMP family of stem cell

  18. AUTOMATIC SEGMENTATION OF BROADCAST AUDIO SIGNALS USING AUTO ASSOCIATIVE NEURAL NETWORKS

    Directory of Open Access Journals (Sweden)

    P. Dhanalakshmi

    2010-12-01

    Full Text Available In this paper, we describe automatic segmentation methods for audio broadcast data. Today, digital audio applications are part of our everyday lives. Since there are more and more digital audio databases in place these days, the importance of effective management for audio databases have become prominent. Broadcast audio data is recorded from the Television which comprises of various categories of audio signals. Efficient algorithms for segmenting the audio broadcast data into predefined categories are proposed. Audio features namely Linear prediction coefficients (LPC, Linear prediction cepstral coefficients, and Mel frequency cepstral coefficients (MFCC are extracted to characterize the audio data. Auto Associative Neural Networks are used to segment the audio data into predefined categories using the extracted features. Experimental results indicate that the proposed algorithms can produce satisfactory results.

  19. A low-noise low-power amplifier for implantable device for neural signal acquisition.

    Science.gov (United States)

    Li, Ming-Ze; Tang, Kea-Tiong

    2009-01-01

    This paper presents a low-noise low-power amplifier for implantable device for neural signal acquisition. By operating MOS transistors in the subthreshold region, smaller low-frequency noise and lower power consumption can be achieved. A low power, low-noise common-drain buffer and a low-noise, high-linearity, low pass filter are used for high frequency noise filtering. Post-layout simulation shows the input referred noise of the system is 2.19microVrms from 10Hz to 10 KHz, power consumption is 55.8microW, and the NEF is 2.53. The amplifier was fabricated using a TSMC 0.18microm 1P6M CMOS process. Simulation results show that this low-noise, low-power amplifier is suitable for implantable device applications.

  20. Modulation of Innate Immune Signalling by Lipid-Mediated MAVS Transmembrane Domain Oligomerization.

    Directory of Open Access Journals (Sweden)

    Luis Nobre

    Full Text Available RIG-I-like receptors detect viral RNA in infected cells and promote oligomerization of the outer mitochondrial membrane protein MAVS to induce innate immunity to viral infection through type I interferon production. Mitochondrial reactive oxygen species (mROS have been shown to enhance anti-viral MAVS signalling, but the mechanisms have remained obscure. Using a biochemical oligomerization-reporter fused to the transmembrane domain of MAVS, we found that mROS inducers promoted lipid-dependent MAVS transmembrane domain oligomerization in the plane of the outer mitochondrial membrane. These events were mirrored by Sendai virus infection, which similarly induced lipid peroxidation and promoted lipid-dependent MAVS transmembrane domain oligomerization. Our observations point to a role for mROS-induced changes in lipid bilayer properties in modulating antiviral innate signalling by favouring the oligomerization of MAVS transmembrane domain in the outer-mitochondrial membrane.

  1. G-protein-coupled receptors and localized signaling in the primary cilium during ventral neural tube patterning.

    Science.gov (United States)

    Hwang, Sun-Hee; Mukhopadhyay, Saikat

    2015-01-01

    The primary cilium is critical in sonic hedgehog (Shh)-dependent ventral patterning of the vertebrate neural tube. Most mutants that cause disruption of the cilium result in decreased Shh signaling in the neural tube. In contrast, mutations in the intraflagellar complex A (IFT-A) and the tubby family protein, Tulp3, result in increased Shh signaling in the neural tube. Proteomic analysis of Tulp3-binding proteins first pointed to the role of the IFT-A complex in trafficking Tulp3 into the cilia. Tulp3 directs trafficking of rhodopsin family G-protein-coupled receptors (GPCRs) to the cilia, suggesting the role of a GPCR in mediating the paradoxical effects of the Tulp3/IFT-A complex in causing increased Shh signaling. Gpr161 has recently been identified as a Tulp3/IFT-A-regulated GPCR that localizes to the primary cilium. A null knock-out mouse model of Gpr161 phenocopies Tulp3 and IFT-A mutants, and causes increased Shh signaling throughout the neural tube. In the absence of Shh, the bifunctional Gli transcription factors are proteolytically processed into repressor forms in a protein kinase A (PKA) -dependent and cilium-dependent manner. Gpr161 activity results in increased cAMP levels in a Gαs -coupled manner, and determines processing of Gli3. Shh signaling also results in removal of Gpr161 from the cilia, suggesting that Gpr161 functions in a positive feedback loop in the Shh pathway. As PKA-null and Gαs mutant embryos also exhibit increased Shh signaling in the neural tube, Gpr161 is a strong candidate for a GPCR that regulates ciliary cAMP levels, and activates PKA in close proximity to the cilia. © 2014 Wiley Periodicals, Inc.

  2. Decoding neural events from fMRI BOLD signal: A comparison of existing approaches and development of a new algorithm

    Science.gov (United States)

    Bush, Keith; Cisler, Josh

    2013-01-01

    Neuroimaging methodology predominantly relies on the blood oxygenation level dependent (BOLD) signal. While the BOLD signal is a valid measure of neuronal activity, variance in fluctuations of the BOLD signal are not only due to fluctuations in neural activity. Thus, a remaining problem in neuroimaging analyses is developing methods that ensure specific inferences about neural activity that are not confounded by unrelated sources of noise in the BOLD signal. Here, we develop and test a new algorithm for performing semi-blind (i.e., no knowledge of stimulus timings) deconvolution of the BOLD signal that treats the neural event as an observable, but intermediate, probabilistic representation of the system’s state. We test and compare this new algorithm against three other recent deconvolution algorithms under varied levels of autocorrelated and Gaussian noise, hemodynamic response function (HRF) misspecification, and observation sampling rate (i.e., TR). Further, we compare the algorithms’ performance using two models to simulate BOLD data: a convolution of neural events with a known (or misspecified) HRF versus a biophysically accurate balloon model of hemodynamics. We also examine the algorithms’ performance on real task data. The results demonstrated good performance of all algorithms, though the new algorithm generally outperformed the others (3.0% improvement) under simulated resting state experimental conditions exhibiting multiple, realistic confounding factors (as well as 10.3% improvement on a real Stroop task). The simulations also demonstrate that the greatest negative influence on deconvolution accuracy is observation sampling rate. Practical and theoretical implications of these results for improving inferences about neural activity from fMRI BOLD signal are discussed. PMID:23602664

  3. Optimization of neural network architecture for classification of radar jamming FM signals

    Science.gov (United States)

    Soto, Alberto; Mendoza, Ariadna; Flores, Benjamin C.

    2017-05-01

    The purpose of this study is to investigate several artificial Neural Network (NN) architectures in order to design a cognitive radar system capable of optimally distinguishing linear Frequency-Modulated (FM) signals from bandlimited Additive White Gaussian Noise (AWGN). The goal is to create a theoretical framework to determine an optimal NN architecture to achieve a Probability of Detection (PD) of 95% or higher and a Probability of False Alarm (PFA) of 1.5% or lower at 5 dB Signal to Noise Ratio (SNR). Literature research reveals that the frequency-domain power spectral densities characterize a signal more efficiently than its time-domain counterparts. Therefore, the input data is preprocessed by calculating the magnitude square of the Discrete Fourier Transform of the digitally sampled bandlimited AWGN and linear FM signals to populate a matrix containing N number of samples and M number of spectra. This matrix is used as input for the NN, and the spectra are divided as follows: 70% for training, 15% for validation, and 15% for testing. The study begins by experimentally deducing the optimal number of hidden neurons (1-40 neurons), then the optimal number of hidden layers (1-5 layers), and lastly, the most efficient learning algorithm. The training algorithms examined are: Resilient Backpropagation, Scaled Conjugate Gradient, Conjugate Gradient with Powell/Beale Restarts, Polak-Ribiére Conjugate Gradient, and Variable Learning Rate Backpropagation. We determine that an architecture with ten hidden neurons (or higher), one hidden layer, and a Scaled Conjugate Gradient for training algorithm encapsulates an optimal architecture for our application.

  4. Cross-regulations between N-metabolism and Nitric Oxide (NO signaling during plant immunity

    Directory of Open Access Journals (Sweden)

    Elise eThalineau

    2016-04-01

    Full Text Available Plants are sessile organisms that have evolved a complex immune system which helps them cope with pathogen attacks. However, the capacity of a plant to mobilize different defense responses is strongly affected by its physiological status. Nitrogen (N is a major nutrient that can play an important role in plant immunity by increasing or decreasing plant resistance to pathogens. Although no general rule can be drawn about the effect of N availability and quality on the fate of plant/pathogen interactions, plants’ capacity to acquire, assimilate, allocate N, and maintain amino acid homeostasis appears to partly mediate the effects of N on plant defense. Nitric oxide (NO, one of the products of N metabolism, plays an important role in plant immunity signaling. NO is generated in part through Nitrate Reductase (NR, a key enzyme involved in nitrate assimilation, and its production depends on levels of nitrate/nitrite, NR substrate/product, as well as on L-arginine and polyamine levels. Cross-regulation between NO signaling and N supply/metabolism has been evidenced. NO production can be affected by N supply, and conversely NO appears to regulate nitrate transport and assimilation. Based on this knowledge, we hypothesized that N availability partly controls plant resistance to pathogens by controlling NO homeostasis. Using the Medicago truncatula/Aphanomyces euteiches pathosystem, we showed that NO homeostasis is important for resistance to this oomycete and that N availability impacts NO homeostasis by affecting S-nitrosothiol (SNO levels and S-nitrosoglutathione reductase activity in roots. These results could therefore explain the increased resistance we noted in N-deprived as compared to N-replete M. truncatula seedlings. They open onto new perspectives for the studies of N/plant defense interactions.

  5. Cross-Regulation between N Metabolism and Nitric Oxide (NO) Signaling during Plant Immunity.

    Science.gov (United States)

    Thalineau, Elise; Truong, Hoai-Nam; Berger, Antoine; Fournier, Carine; Boscari, Alexandre; Wendehenne, David; Jeandroz, Sylvain

    2016-01-01

    Plants are sessile organisms that have evolved a complex immune system which helps them cope with pathogen attacks. However, the capacity of a plant to mobilize different defense responses is strongly affected by its physiological status. Nitrogen (N) is a major nutrient that can play an important role in plant immunity by increasing or decreasing plant resistance to pathogens. Although no general rule can be drawn about the effect of N availability and quality on the fate of plant/pathogen interactions, plants' capacity to acquire, assimilate, allocate N, and maintain amino acid homeostasis appears to partly mediate the effects of N on plant defense. Nitric oxide (NO), one of the products of N metabolism, plays an important role in plant immunity signaling. NO is generated in part through Nitrate Reductase (NR), a key enzyme involved in nitrate assimilation, and its production depends on levels of nitrate/nitrite, NR substrate/product, as well as on L-arginine and polyamine levels. Cross-regulation between NO signaling and N supply/metabolism has been evidenced. NO production can be affected by N supply, and conversely NO appears to regulate nitrate transport and assimilation. Based on this knowledge, we hypothesized that N availability partly controls plant resistance to pathogens by controlling NO homeostasis. Using the Medicago truncatula/Aphanomyces euteiches pathosystem, we showed that NO homeostasis is important for resistance to this oomycete and that N availability impacts NO homeostasis by affecting S-nitrosothiol (SNO) levels and S-nitrosoglutathione reductase activity in roots. These results could therefore explain the increased resistance we noted in N-deprived as compared to N-replete M. truncatula seedlings. They open onto new perspectives for the studies of N/plant defense interactions.

  6. Targeting Cannabinoid Signaling in the Immune System: “High”-ly Exciting Questions, Possibilities, and Challenges

    Directory of Open Access Journals (Sweden)

    Attila Oláh

    2017-11-01

    Full Text Available It is well known that certain active ingredients of the plants of Cannabis genus, i.e., the “phytocannabinoids” [pCBs; e.g., (−-trans-Δ9-tetrahydrocannabinol (THC, (−-cannabidiol, etc.] can influence a wide array of biological processes, and the human body is able to produce endogenous analogs of these substances [“endocannabinoids” (eCB, e.g., arachidonoylethanolamine (anandamide, AEA, 2-arachidonoylglycerol (2-AG, etc.]. These ligands, together with multiple receptors (e.g., CB1 and CB2 cannabinoid receptors, etc., and a complex enzyme and transporter apparatus involved in the synthesis and degradation of the ligands constitute the endocannabinoid system (ECS, a recently emerging regulator of several physiological processes. The ECS is widely expressed in the human body, including several members of the innate and adaptive immune system, where eCBs, as well as several pCBs were shown to deeply influence immune functions thereby regulating inflammation, autoimmunity, antitumor, as well as antipathogen immune responses, etc. Based on this knowledge, many in vitro and in vivo studies aimed at exploiting the putative therapeutic potential of cannabinoid signaling in inflammation-accompanied diseases (e.g., multiple sclerosis or in organ transplantation, and to dissect the complex immunological effects of medical and “recreational” marijuana consumption. Thus, the objective of the current article is (i to summarize the most recent findings of the field; (ii to highlight the putative therapeutic potential of targeting cannabinoid signaling; (iii to identify open questions and key challenges; and (iv to suggest promising future directions for cannabinoid-based drug development.

  7. The Raf Kinase Inhibitor Sorafenib Inhibits JAK-STAT Signal Transduction in Human Immune Cells.

    Science.gov (United States)

    Martin del Campo, Sara E; Levine, Kala M; Mundy-Bosse, Bethany L; Grignol, Valerie P; Fairchild, Ene T; Campbell, Amanda R; Trikha, Prashant; Mace, Thomas A; Paul, Bonnie K; Jaime-Ramirez, Alena Cristina; Markowitz, Joseph; Kondadasula, Sri Vidya; Guenterberg, Kristan D; McClory, Susan; Karpa, Volodymyr I; Pan, Xueliang; Olencki, Thomas E; Monk, J Paul; Mortazavi, Amir; Tridandapani, Susheela; Lesinski, Gregory B; Byrd, John C; Caligiuri, Michael A; Shah, Manisha H; Carson, William E

    2015-09-01

    Sorafenib is an oral multikinase inhibitor that was originally developed as a Raf kinase inhibitor. We hypothesized that sorafenib would also have inhibitory effects on cytokine signaling pathways in immune cells. PBMCs from normal donors were treated with varying concentrations of sorafenib and stimulated with IFN-α or IL-2. Phosphorylation of STAT1 and STAT5 was measured by flow cytometry and confirmed by immunoblot analysis. Changes in IFN-α- and IL-2-stimulated gene expression were measured by quantitative PCR, and changes in cytokine production were evaluated by ELISA. Cryopreserved PBMCs were obtained from cancer patients before and after receiving 400 mg sorafenib twice daily. Patient PBMCs were thawed, stimulated with IL-2 or IFN-α, and evaluated for phosphorylation of STAT1 and STAT5. Pretreatment of PBMCs with 10 μM sorafenib decreased STAT1 and STAT5 phosphorylation after treatment with IFN-α or IL-2. This inhibitory effect was observed in PBMCs from healthy donors over a range of concentrations of sorafenib (5-20 μM), IL-2 (2-24 nM), and IFN-α (10(1)-10(6) U/ml). This effect was observed in immune cell subsets, including T cells, B cells, NK cells, regulatory T cells, and myeloid-derived suppressor cells. Pretreatment with sorafenib also inhibited PBMC expression of IFN-α- and IL-2-regulated genes and inhibited NK cell production of IFN-γ, RANTES, MIP1-α, and MIG in response to IFN-α stimulation. PBMCs from patients receiving sorafenib therapy showed decreased responsiveness to IL-2 and IFN-α treatment. Sorafenib is a Raf kinase inhibitor that could have off-target effects on cytokine-induced signal transduction in immune effector cells. Copyright © 2015 by The American Association of Immunologists, Inc.

  8. Fatty acid–induced gut-brain signaling attenuates neural and behavioral effects of sad emotion in humans

    OpenAIRE

    Van Oudenhove, Lukas; Mckie, Shane; Lassman, Daniel; Uddin, Bilal; Paine, Peter; Coen, Steven; Gregory, Lloyd; Tack, Jan; Aziz, Qasim

    2011-01-01

    Although a relationship between emotional state and feeding behavior is known to exist, the interactions between signaling initiated by stimuli in the gut and exteroceptively generated emotions remain incompletely understood. Here, we investigated the interaction between nutrient-induced gut-brain signaling and sad emotion induced by musical and visual cues at the behavioral and neural level in healthy nonobese subjects undergoing functional magnetic resonance imaging. Subjects received an in...

  9. The receptor kinase CERK1 has dual functions in symbiosis and immunity signalling.

    Science.gov (United States)

    Zhang, Xiaowei; Dong, Wentao; Sun, Jongho; Feng, Feng; Deng, Yiwen; He, Zuhua; Oldroyd, Giles E D; Wang, Ertao

    2015-01-01

    The establishment of symbiotic interactions between mycorrhizal fungi, rhizobial bacteria and their legume hosts involves a common symbiosis signalling pathway. This signalling pathway is activated by Nod factors produced by rhizobia and these are recognised by the Nod factor receptors NFR1/LYK3 and NFR5/NFP. Mycorrhizal fungi produce lipochitooligosaccharides (LCOs) similar to Nod factors, as well as short-chain chitin oligomers (CO4/5), implying commonalities in signalling during mycorrhizal and rhizobial associations. Here we show that NFR1/LYK3, but not NFR5/NFP, is required for the establishment of the mycorrhizal interaction in legumes. NFR1/LYK3 is necessary for the recognition of mycorrhizal fungi and the activation of the symbiosis signalling pathway leading to induction of calcium oscillations and gene expression. Chitin oligosaccharides also act as microbe associated molecular patterns that promote plant immunity via similar LysM receptor-like kinases. CERK1 in rice has the highest homology to NFR1 and we show that this gene is also necessary for the establishment of the mycorrhizal interaction as well as for resistance to the rice blast fungus. Our results demonstrate that NFR1/LYK3/OsCERK1 represents a common receptor for chitooligosaccharide-based signals produced by mycorrhizal fungi, rhizobial bacteria (in legumes) and fungal pathogens. It would appear that mycorrhizal recognition has been conserved in multiple receptors across plant species, but additional diversification in certain plant species has defined other signals that this class of receptors can perceive. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  10. Immune challenge and satiety-related activation of both distinct and overlapping neuronal populations in the brainstem indicate parallel pathways for viscerosensory signaling.

    Science.gov (United States)

    Gaykema, Ronald P A; Daniels, Teresa E; Shapiro, Nathan J; Thacker, Gregory C; Park, Su-Mi; Goehler, Lisa E

    2009-10-19

    Caudal brainstem viscerosensory nuclei convey information about the body's internal state to forebrain regions implicated in feeding behavior and responses to immune challenge, and may modulate ingestive behavior following immune activation. Illness-induced appetite loss might be attributed to accentuated "satiety" pathways, activation of a distinct "danger channel" separate from satiety pathways, or both. To evaluate neural substrates that could mediate the effects of illness on ingestive behavior, we analyzed the pattern and phenotypes of medullary neurons responsive to consumption of a preferred food, sweetened milk, and to intraperitoneal lipopolysaccharide challenge that reduced sweetened milk intake. Brainstem sections were stained for c-Fos, dopamine beta-hydroxylase, phenylethanolamine-N-methyltransferase, and glucagon-like peptide-1 (GLP-1) immunoreactivity. Sweetened milk intake activated many neurons throughout the nucleus of the solitary tract (NTS), including A2 noradrenergic neurons in the caudal half of the NTS. LPS challenge activated a similar population of neurons in the NTS, in addition to rostral C2 adrenergic and mid-level A2 noradrenergic neurons in the NTS, many C1 and A1 neurons in the ventrolateral medulla, and in GLP-1 neurons in the dorsal medullary reticular nucleus. Increased numbers of activated GLP-1 neurons in the NTS were only associated with sweetened milk ingestion. Evidence for parallel processing was reflected in the parabrachial nucleus, where sweetened milk intake resulted in activation of the inner external lateral, ventrolateral and central medial portions, whereas LPS challenge induced c-Fos expression in the outer external lateral portions. Thus, signals generated in response to potentially dangerous physiological conditions seem to be propagated via specific populations of catecholaminergic neurons in the NTS and VLM, and likely include a pathway through the external lateral PBN. The data indicate that immune challenge

  11. Lingo-1 shRNA and Notch signaling inhibitor DAPT promote differentiation of neural stem/progenitor cells into neurons.

    Science.gov (United States)

    Wang, Jue; Ye, Zhizhong; Zheng, Shuhui; Chen, Luming; Wan, Yong; Deng, Yubin; Yang, Ruirui

    2016-03-01

    Determination of the exogenous factors that regulate differentiation of neural stem/progenitor cells into neurons, oligodendrocytes and astrocytes is an important step in the clinical therapy of spinal cord injury (SCI). The Notch pathway inhibits the differentiation of neural stem/progenitor cells and Lingo-1 is a strong negative regulator for myelination and axon growth. While Lingo-1 shRNA and N-[N-(3, 5-difluorophenacetyl)-1-alanyl]-S-Phenylglycinet-butylester (DAPT), a Notch pathway inhibitor, have been used separately to help repair SCI, the results have been unsatisfactory. Here we investigated and elucidated the preliminary mechanism for the effect of Lingo-1 shRNA and DAPT on neural stem/progenitor cells differentiation. We found that neural stem/progenitor cells from E14 rat embryos expressed Nestin, Sox-2 and Lingo-1, and we optimized the transduction of neural stem/progenitor cells using lentiviral vectors encoding Lingo-1 shRNA. The addition of DAPT decreased the expression of Notch intracellular domain (NICD) as well as the downstream genes Hes1 and Hes5. Expression of NeuN, CNPase and GFAP in DAPT treated cells and expression of NeuN in Lingo-1 shRNA treated cells confirmed differentiation of neural stem/progenitor cells into neurons, oligodendrocytes and astrocytes. These results revealed that while Lingo-1 shRNA and Notch signaling inhibitor DAPT both promoted differentiation of neural stem cells into neurons, only DAPT was capable of driving neural stem/progenitor cells differentiation into oligodendrocytes and astrocytes. Since we were able to show that both Lingo-1 shRNA and DAPT could drive neural stem/progenitor cells differentiation, our data might aid the development of more effective SCI therapies using Lingo-1 shRNA and DAPT. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Analysis of acoustic emission signals at austempering of steels using neural networks

    Science.gov (United States)

    Łazarska, Malgorzata; Wozniak, Tadeusz Z.; Ranachowski, Zbigniew; Trafarski, Andrzej; Domek, Grzegorz

    2017-05-01

    Bearing steel 100CrMnSi6-4 and tool steel C105U were used to carry out this research with the steels being austempered to obtain a martensitic-bainitic structure. During the process quite a large number of acoustic emissions (AE) were observed. These signals were then analysed using neural networks resulting in the identification of three groups of events of: high, medium and low energy and in addition their spectral characteristics were plotted. The results were presented in the form of diagrams of AE incidence as a function of time. It was demonstrated that complex transformations of austenite into martensite and bainite occurred when austempering bearing steel at 160 °C and tool steel at 130 °C respectively. The selected temperatures of isothermal quenching of the tested steels were within the area near to MS temperature, which affected the complex course of phase transition. The high activity of AE is a typical occurrence for martensitic transformation and this is the transformation mechanism that induces the generation of AE signals of higher energy in the first stage of transition. In the second stage of transformation, the initially nucleated martensite accelerates the occurrence of the next bainitic transformation.

  13. Classification of a Driver's cognitive workload levels using artificial neural network on ECG signals.

    Science.gov (United States)

    Tjolleng, Amir; Jung, Kihyo; Hong, Wongi; Lee, Wonsup; Lee, Baekhee; You, Heecheon; Son, Joonwoo; Park, Seikwon

    2017-03-01

    An artificial neural network (ANN) model was developed in the present study to classify the level of a driver's cognitive workload based on electrocardiography (ECG). ECG signals were measured on 15 male participants while they performed a simulated driving task as a primary task with/without an N-back task as a secondary task. Three time-domain ECG measures (mean inter-beat interval (IBI), standard deviation of IBIs, and root mean squared difference of adjacent IBIs) and three frequencydomain ECG measures (power in low frequency, power in high frequency, and ratio of power in low and high frequencies) were calculated. To compensate for individual differences in heart response during the driving tasks, a three-step data processing procedure was performed to ECG signals of each participant: (1) selection of two most sensitive ECG measures, (2) definition of three (low, medium, and high) cognitive workload levels, and (3) normalization of the selected ECG measures. An ANN model was constructed using a feed-forward network and scaled conjugate gradient as a back-propagation learning rule. The accuracy of the ANN classification model was found satisfactory for learning data (95%) and testing data (82%). Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Nogo Receptor Signaling Restricts Adult Neural Plasticity by Limiting Synaptic AMPA Receptor Delivery.

    Science.gov (United States)

    Jitsuki, Susumu; Nakajima, Waki; Takemoto, Kiwamu; Sano, Akane; Tada, Hirobumi; Takahashi-Jitsuki, Aoi; Takahashi, Takuya

    2016-01-01

    Experience-dependent plasticity is limited in the adult brain, and its molecular and cellular mechanisms are poorly understood. Removal of the myelin-inhibiting signaling protein, Nogo receptor (NgR1), restores adult neural plasticity. Here we found that, in NgR1-deficient mice, whisker experience-driven synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) insertion in the barrel cortex, which is normally complete by 2 weeks after birth, lasts into adulthood. In vivo live imaging by two-photon microscopy revealed more AMPAR on the surface of spines in the adult barrel cortex of NgR1-deficient than on those of wild-type (WT) mice. Furthermore, we observed that whisker stimulation produced new spines in the adult barrel cortex of mutant but not WT mice, and that the newly synthesized spines contained surface AMPAR. These results suggest that Nogo signaling limits plasticity by restricting synaptic AMPAR delivery in coordination with anatomical plasticity. © The Author 2015. Published by Oxford University Press.

  15. Depression and treatment response: dynamic interplay of signaling pathways and altered neural processes.

    Science.gov (United States)

    Duric, Vanja; Duman, Ronald S

    2013-01-01

    Since the 1960s, when the first tricyclic and monoamine oxidase inhibitor antidepressant drugs were introduced, most of the ensuing agents were designed to target similar brain pathways that elevate serotonin and/or norepinephrine signaling. Fifty years later, the main goal of the current depression research is to develop faster-acting, more effective therapeutic agents with fewer side effects, as currently available antidepressants are plagued by delayed therapeutic onset and low response rates. Clinical and basic science research studies have made significant progress towards deciphering the pathophysiological events within the brain involved in development, maintenance, and treatment of major depressive disorder. Imaging and postmortem brain studies in depressed human subjects, in combination with animal behavioral models of depression, have identified a number of different cellular events, intracellular signaling pathways, proteins, and target genes that are modulated by stress and are potentially vital mediators of antidepressant action. In this review, we focus on several neural mechanisms, primarily within the hippocampus and prefrontal cortex, which have recently been implicated in depression and treatment response.

  16. A search for protein biomarkers links olfactory signal transduction to social immunity.

    Science.gov (United States)

    Guarna, Maria Marta; Melathopoulos, Andony P; Huxter, Elizabeth; Iovinella, Immacolata; Parker, Robert; Stoynov, Nikolay; Tam, Amy; Moon, Kyung-Mee; Chan, Queenie W T; Pelosi, Paolo; White, Rick; Pernal, Stephen F; Foster, Leonard J

    2015-02-08

    The Western honey bee (Apis mellifera L.) is a critical component of human agriculture through its pollination activities. For years, beekeepers have controlled deadly pathogens such as Paenibacillus larvae, Nosema spp. and Varroa destructor with antibiotics and pesticides but widespread chemical resistance is appearing and most beekeepers would prefer to eliminate or reduce the use of in-hive chemicals. While such treatments are likely to still be needed, an alternate management strategy is to identify and select bees with heritable traits that allow them to resist mites and diseases. Breeding such bees is difficult as the tests involved to identify disease-resistance are complicated, time-consuming, expensive and can misidentify desirable genotypes. Additionally, we do not yet fully understand the mechanisms behind social immunity. Here we have set out to discover the molecular mechanism behind hygienic behavior (HB), a trait known to confer disease resistance in bees. After confirming that HB could be selectively bred for, we correlated measurements of this behavior with protein expression over a period of three years, at two geographically distinct sites, using several hundred bee colonies. By correlating the expression patterns of individual proteins with HB scores, we identified seven putative biomarkers of HB that survived stringent control for multiple hypothesis testing. Intriguingly, these proteins were all involved in semiochemical sensing (odorant binding proteins), nerve signal transmission or signal decay, indicative of the series of events required to respond to an olfactory signal from dead or diseased larvae. We then used recombinant versions of two odorant-binding proteins to identify the classes of ligands that these proteins might be helping bees detect. Our data suggest that neurosensory detection of odors emitted by dead or diseased larvae is the likely mechanism behind a complex and important social immunity behavior that allows bees to co

  17. Estrogen Stimulates Proliferation and Differentiation of Neural Stem/Progenitor Cells through Different Signal Transduction Pathways

    Directory of Open Access Journals (Sweden)

    Makiko Okada

    2010-10-01

    Full Text Available Our previous study indicated that both 17β-estradiol (E2, known to be an endogenous estrogen, and bisphenol A (BPA, known to be a xenoestrogen, could positively influence the proliferation or differentiation of neural stem/progenitor cells (NS/PCs. The aim of the present study was to identify the signal transduction pathways for estrogenic activities promoting proliferation and differentiation of NS/PCs via well known nuclear estrogen receptors (ERs or putative membrane-associated ERs. NS/PCs were cultured from the telencephalon of 15-day-old rat embryos. In order to confirm the involvement of nuclear ERs for estrogenic activities, their specific antagonist, ICI-182,780, was used. The presence of putative membrane-associated ER was functionally examined as to whether E2 can activate rapid intracellular signaling mechanism. In order to confirm the involvement of membrane-associated ERs for estrogenic activities, a cell-impermeable E2, bovine serum albumin-conjugated E2 (E2-BSA was used. We showed that E2 could rapidly activate extracellular signal-regulated kinases 1/2 (ERK 1/2, which was not inhibited by ICI-182,780. ICI-182,780 abrogated the stimulatory effect of these estrogens (E2 and BPA on the proliferation of NS/PCs, but not their effect on the differentiation of the NS/PCs into oligodendroglia. Furthermore, E2-BSA mimicked the activity of differentiation from NS/PCs into oligodendroglia, but not the activity of proliferation. Our study suggests that (1 the estrogen induced proliferation of NS/PCs is mediated via nuclear ERs; (2 the oligodendroglial generation from NS/PCs is likely to be stimulated via putative membrane‑associated ERs.

  18. G-protein coupled receptor signaling architecture of mammalian immune cells.

    Directory of Open Access Journals (Sweden)

    Natalia Polouliakh

    Full Text Available A series of recent studies on large-scale networks of signaling and metabolic systems revealed that a certain network structure often called "bow-tie network" are observed. In signaling systems, bow-tie network takes a form with diverse and redundant inputs and outputs connected via a small numbers of core molecules. While arguments have been made that such network architecture enhances robustness and evolvability of biological systems, its functional role at a cellular level remains obscure. A hypothesis was proposed that such a network function as a stimuli-reaction classifier where dynamics of core molecules dictate downstream transcriptional activities, hence physiological responses against stimuli. In this study, we examined whether such hypothesis can be verified using experimental data from Alliance for Cellular Signaling (AfCS that comprehensively measured GPCR related ligands response for B-cell and macrophage. In a GPCR signaling system, cAMP and Ca2+ act as core molecules. Stimuli-response for 32 ligands to B-Cells and 23 ligands to macrophages has been measured. We found that ligands with correlated changes of cAMP and Ca2+ tend to cluster closely together within the hyperspaces of both cell types and they induced genes involved in the same cellular processes. It was found that ligands inducing cAMP synthesis activate genes involved in cell growth and proliferation; cAMP and Ca2+ molecules that increased together form a feedback loop and induce immune cells to migrate and adhere together. In contrast, ligands without a core molecules response are scattered throughout the hyperspace and do not share clusters. G-protein coupling receptors together with immune response specific receptors were found in cAMP and Ca2+ activated clusters. Analyses have been done on the original software applicable for discovering 'bow-tie' network architectures within the complex network of intracellular signaling where ab initio clustering has been

  19. Inhibitory control and trait aggression: neural and behavioral insights using the emotional stop signal task.

    Science.gov (United States)

    Pawliczek, Christina M; Derntl, Birgit; Kellermann, Thilo; Kohn, Nils; Gur, Ruben C; Habel, Ute

    2013-10-01

    Deficits in response inhibition and heightened impulsivity have been linked to psychiatric disorders and aggression. They have been investigated in clinical groups as well as individuals with trait characteristics, yielding insights into the underlying neural and behavioral mechanisms of response inhibition and impulsivity. The motor inhibition tasks employed in most studies, however, have lacked an emotional component, which is crucial given that both response inhibition and impulsivity attain salience within a socio-emotional context. For this fMRI study, we selected a group with high trait aggression (HA, n=17) and one with low trait aggression (LA, n=16) from 550 males who had completed an Aggression Questionnaire. Neural activation was compared to an emotional version (including angry and neutral faces) of the stop signal task. Behavioral results revealed impaired response inhibition in HA, associated with higher motor impulsivity. This was accompanied by attenuated activation in brain regions involved in response inhibition, including the pre-supplementary motor area (SMA) and motor cortex. Together, these findings offer evidence that a reduced inhibition capacity is present in HA. Notably, response inhibition improved during anger trials in both groups, suggesting a facilitation effect through heightened activation in the related brain regions. In both groups, inclusion of the anger stimuli enhanced the activation of the motor and somatosensory areas, which modulate executive control, and of limbic regions including the amygdala. In summary, the investigation of response inhibition in individuals with high and low trait characteristics affords useful insights into the underlying distinct processing mechanisms. It can contribute to the investigation of trait markers in a clinical context without having to deal with the complex mechanisms of a clinical disorder itself. In contrast, the mechanisms of emotional response inhibition did not differ between groups

  20. Improved Neural Signal Classification in a Rapid Serial Visual Presentation Task Using Active Learning.

    Science.gov (United States)

    Marathe, Amar R; Lawhern, Vernon J; Wu, Dongrui; Slayback, David; Lance, Brent J

    2016-03-01

    The application space for brain-computer interface (BCI) technologies is rapidly expanding with improvements in technology. However, most real-time BCIs require extensive individualized calibration prior to use, and systems often have to be recalibrated to account for changes in the neural signals due to a variety of factors including changes in human state, the surrounding environment, and task conditions. Novel approaches to reduce calibration time or effort will dramatically improve the usability of BCI systems. Active Learning (AL) is an iterative semi-supervised learning technique for learning in situations in which data may be abundant, but labels for the data are difficult or expensive to obtain. In this paper, we apply AL to a simulated BCI system for target identification using data from a rapid serial visual presentation (RSVP) paradigm to minimize the amount of training samples needed to initially calibrate a neural classifier. Our results show AL can produce similar overall classification accuracy with significantly less labeled data (in some cases less than 20%) when compared to alternative calibration approaches. In fact, AL classification performance matches performance of 10-fold cross-validation (CV) in over 70% of subjects when training with less than 50% of the data. To our knowledge, this is the first work to demonstrate the use of AL for offline electroencephalography (EEG) calibration in a simulated BCI paradigm. While AL itself is not often amenable for use in real-time systems, this work opens the door to alternative AL-like systems that are more amenable for BCI applications and thus enables future efforts for developing highly adaptive BCI systems.

  1. Mechanisms of Immune Signaling in Colitis-Associated CancerSummary

    Directory of Open Access Journals (Sweden)

    Maximilian J. Waldner

    2015-01-01

    Full Text Available The inflammatory bowel diseases ulcerative colitis and Crohn’s disease are associated with an increased risk for the development of colorectal cancer. During recent years, several immune signaling pathways have been linked to colitis-associated cancer (CAC, largely owing to the availability of suitable preclinical models. Among these, chronic intestinal inflammation has been shown to support tumor initiation through oxidative stress–induced mutations. A proinflammatory microenvironment that develops, possibly as a result of defective intestinal barrier function and host–microbial interactions, enables tumor promotion. Several molecular pathways such as tumor necrosis factor/nuclear factor-κB or interleukin 6/signal transducer and activator of transcription 3 signaling have been identified as important contributors to CAC development and could be promising therapeutic targets for the prevention and treatment of CAC. Keywords: Colorectal Cancer, Crohn's Disease, Cytokines, Inflammatory Bowel Disease, Interleukin-6, Tumor Necrosis Factor Alpha, Ulcerative Colitis

  2. Weak signal detection and propagation in diluted feed-forward neural network with recurrent excitation and inhibition

    Science.gov (United States)

    Wang, Jiang; Han, Ruixue; Wei, Xilei; Qin, Yingmei; Yu, Haitao; Deng, Bin

    2016-12-01

    Reliable signal propagation across distributed brain areas provides the basis for neural circuit function. Modeling studies on cortical circuits have shown that multilayered feed-forward networks (FFNs), if strongly and/or densely connected, can enable robust signal propagation. However, cortical networks are typically neither densely connected nor have strong synapses. This paper investigates under which conditions spiking activity can be propagated reliably across diluted FFNs. Extending previous works, we model each layer as a recurrent sub-network constituting both excitatory (E) and inhibitory (I) neurons and consider the effect of interactions between local excitation and inhibition on signal propagation. It is shown that elevation of cellular excitation-inhibition (EI) balance in the local sub-networks (layers) softens the requirement for dense/strong anatomical connections and thereby promotes weak signal propagation in weakly connected networks. By means of iterated maps, we show how elevated local excitability state compensates for the decreased gain of synchrony transfer function that is due to sparse long-range connectivity. Finally, we report that modulations of EI balance and background activity provide a mechanism for selectively gating and routing neural signal. Our results highlight the essential role of intrinsic network states in neural computation.

  3. Two major gate-keepers in the self-renewal of neural stem cells: Erk1/2 and PLCγ1 in FGFR signaling

    Directory of Open Access Journals (Sweden)

    Lee Jin-A

    2009-06-01

    Full Text Available Abstract Neural stem cells are undifferentiated precursor cells that proliferate, self-renew, and give rise to neuronal and glial lineages. Understanding the molecular mechanisms underlying their self-renewal is an important aspect in neural stem cell biology. The regulation mechanisms governing self-renewal of neural stem cells and the signaling pathways responsible for the proliferation and maintenance of adult stem cells remain largely unknown. In this issue of Molecular Brain [Ma DK et al. Molecular genetic analysis of FGFR1 signaling reveals distinct roles of MAPK and PLCγ1 activation for self-renewal of adult neural stem cells. Molecular Brain 2009, 2:16], characterized the different roles of MAPK and PLCγ1 in FGFR1 signaling in the self-renewal of neural stem cells. These novel findings provide insights into basic neural stem cell biology and clinical applications of potential stem-cell-based therapy.

  4. La protéine CG4572 de Drosophile et la propagation du signal ARNi immun antiviral

    OpenAIRE

    Karlikow, Margot

    2015-01-01

    During viral infection, cell survival will depend on adequately giving, receiving and processing information to establish an efficient antiviral immune response. Cellular communication is therefore essential to allow the propagation of immune signals that will confer protection to the entire organism.The major antiviral defense in insects is the RNA interference (RNAi) mechanism that is activated by detection of viral double-stranded RNA (dsRNA). The antiviral RNAi mechanism can be divided in...

  5. Diagnosis of epilepsy from electroencephalography signals using multilayer perceptron and Elman Artificial Neural Networks and Wavelet Transform.

    Science.gov (United States)

    Işik, Hakan; Sezer, Esma

    2012-02-01

    In this study, it has been intended to perform an automatic classification of Electroencephalography (EEG) signals via Artificial Neural Networks (ANN) and to investigate these signals using Wavelet Transform (WT) for diagnosing epilepsy syndrome. EEG signals have been decomposed into frequency sub-bands using WT and a set of feature vectors which were extracted from the sub-bands. Dimensions of these feature vectors have been reduced via Principal Component Analysis (PCA) method and then classified as epileptic or healthy using Multilayer Perceptron (MLP) and ELMAN ANN. Performance evaluation of the used ANN models have been carried out by performing Receiver Operation Characteristic (ROC) analysis.

  6. STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats.

    Science.gov (United States)

    Tang, Qing-Ping; Shen, Qin; Wu, Li-Xiang; Feng, Xiang-Ling; Liu, Hui; Wu, Bei; Huang, Xiao-Song; Wang, Gai-Qing; Li, Zhong-Hao; Liu, Zun-Jing

    2016-07-01

    Willed-movement training has been demonstrated to be a promising approach to increase motor performance and neural plasticity in ischemic rats. However, little is known regarding the molecular signals that are involved in neural plasticity following willed-movement training. To investigate the potential signals related to neural plasticity following willed-movement training, littermate rats were randomly assigned into three groups: middle cerebral artery occlusion, environmental modification, and willed-movement training. The infarct volume was measured 18 d after occlusion of the right middle cerebral artery. Reverse transcription-polymerase chain reaction (PCR) and immunofluorescence staining were used to detect the changes in the signal transducer and activator of transcription 3 (STAT3) mRNA and protein, respectively. A chromatin immunoprecipitation was used to investigate whether STAT3 bound to plasticity-related genes, such as brain-derived neurotrophic factor (BDNF), synaptophysin, and protein interacting with C kinase 1 (PICK1). In this study, we demonstrated that STAT3 mRNA and protein were markedly increased following 15-d willed-movement training in the ischemic hemispheres of the treated rats. STAT3 bound to BDNF, PICK1, and synaptophysin promoters in the neocortical cells of rats. These data suggest that the increased STAT3 levels after willed-movement training might play critical roles in the neural plasticity by directly regulating plasticity-related genes.

  7. Integrated analysis of genetic, behavioral, and biochemical data implicates neural stem cell-induced changes in immunity, neurotransmission and mitochondrial function in Dementia with Lewy Body mice.

    Science.gov (United States)

    Lakatos, Anita; Goldberg, Natalie R S; Blurton-Jones, Mathew

    2017-03-10

    We previously demonstrated that transplantation of murine neural stem cells (NSCs) can improve motor and cognitive function in a transgenic model of Dementia with Lewy Bodies (DLB). These benefits occurred without changes in human α-synuclein pathology and were mediated in part by stem cell-induced elevation of brain-derived neurotrophic factor (BDNF). However, instrastriatal NSC transplantation likely alters the brain microenvironment via multiple mechanisms that may synergize to promote cognitive and motor recovery. The underlying neurobiology that mediates such restoration no doubt involves numerous genes acting in concert to modulate signaling within and between host brain cells and transplanted NSCs. In order to identify functionally connected gene networks and additional mechanisms that may contribute to stem cell-induced benefits, we performed weighted gene co-expression network analysis (WGCNA) on striatal tissue isolated from NSC- and vehicle-injected wild-type and DLB mice. Combining continuous behavioral and biochemical data with genome wide expression via network analysis proved to be a powerful approach; revealing significant alterations in immune response, neurotransmission, and mitochondria function. Taken together, these data shed further light on the gene network and biological processes that underlie the therapeutic effects of NSC transplantation on α-synuclein induced cognitive and motor impairments, thereby highlighting additional therapeutic targets for synucleinopathies.

  8. GPS low noise amplifier with high immunity to wireless jamming signals and power control option

    Directory of Open Access Journals (Sweden)

    H. Schulz

    2004-01-01

    Full Text Available A SiGe GPS low noise amplifier with power control option and high immunity to wireless jamming signals is presented. These novel features applied to Atmel’s ATR0610 GPS LNA allow significant power saving at the radio interface while meeting the out-of-band linearity requirements. The results show the noise figure less than 2.1 dB, including the embedded pre-select filter, and out-of-band IIP3 above +8 dBm in the frequency range between 1.8GHz and 2 GHz with 3mA current consumption. The GPS system performance shows GPS sensitivity below -141 dBm with 5 ms integration interval.

  9. NOD2-RIP2-Mediated Signaling Helps Shape Adaptive Immunity in Visceral Leishmaniasis.

    Science.gov (United States)

    Nascimento, Manuela S L; Ferreira, Marcela D; Quirino, Gustavo F S; Maruyama, Sandra R; Krishnaswamy, Jayendra K; Liu, Dong; Berlink, Jonilson; Fonseca, Denise M; Zamboni, Dario S; Carregaro, Vanessa; Almeida, Roque P; Cunha, Thiago M; Eisenbarth, Stephanie S; Silva, João S

    2016-12-01

    Interferon γ (IFN-γ) and interleukin 17A (IL-17A)-producing cells are described to be related to the protection against Leishmania infantum infection. How the immune system coordinates the balance between T-helper type 1 (Th1) and 17 (Th17) responses during visceral leishmaniasis (VL) is still unknown. Here, we combined transcriptional profiling, using RNA sequencing analysis of human samples, with an experimental model to show that Th17-related genes are suppressed and that Th1 signature genes are induced during human VL. The high amount of Th1 cells in VL was dependent on the NOD2-RIP2 signaling in dendritic cells, which was crucial for interleukin 12 production through the phosphorylation of MAPK. On the other hand, this pathway inhibits Th17 cells by limiting interleukin 23 production. As a consequence, Nod2(-/-) and Rip2(-/-) mice showed defects in Th1 responses and higher parasite loads as compared to WT mice. Together, the data demonstrate that the NOD2-RIP2 pathway is activated in murine and human VL and plays a role in shaping adaptive immunity toward a Th1 profile. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  10. TLR4 signalling in pulmonary stromal cells is critical for inflammation and immunity in the airways.

    Science.gov (United States)

    Perros, Frederic; Lambrecht, Bart N; Hammad, Hamida

    2011-09-24

    Inflammation of the airways, which is often associated with life-threatening infection by Gram-negative bacteria or presence of endotoxin in the bioaerosol, is still a major cause of severe airway diseases. Moreover, inhaled endotoxin may play an important role in the development and progression of airway inflammation in asthma. Pathologic changes induced by endotoxin inhalation include bronchospasm, airflow obstruction, recruitment of inflammatory cells, injury of the alveolar epithelium, and disruption of pulmonary capillary integrity leading to protein rich fluid leak in the alveolar space. Mammalian Toll-like receptors (TLRs) are important signalling receptors in innate host defense. Among these receptors, TLR4 plays a critical role in the response to endotoxin. Lungs are a complex compartmentalized organ with separate barriers, namely the alveolar-capillary barrier, the microvascular endothelium, and the alveolar epithelium. An emerging theme in the field of lung immunology is that structural cells (SCs) of the airways such as epithelial cells (ECs), endothelial cells, fibroblasts and other stromal cells produce activating cytokines that determine the quantity and quality of the lung immune response. This review focuses on the role of TLR4 in the innate and adaptive immune functions of the pulmonary SCs.

  11. Immune characteristics study of AG490, a signal pathway inhibitor, in EAE model mice

    Directory of Open Access Journals (Sweden)

    Zhihua Zhao

    2017-02-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease characterized by demyelination, axonal damage and progressive neurologic dysfunction in central nervous system (CNS. Many evidences show that B cells play an important role in the pathogenesis of MS. Follicular helper T cells (Tfh secrete IL-21 to prompt the proliferation and differentiation of B cells in germinal center (GC through clonal proliferation, somatic hypermutation, antibody class switching, antibody affinity maturation process. AG490 is a synthetic inhibitor to JAK-STAT signal pathway, which has been studied in inflammatory, tumor and autoimmune diseases. In the present study, the experimental mice were divided into 3 groups, vehicle group and AG490 group were given MOG35-55 to induce EAE model, from the third day after immunization, the mice were given vehicle or AG490 by intraperitoneal injection every other day. All mice were assessed clinical scores after immunization. On twentieth day, all mice were sacrificed, HE staining and solochrome cyanine staining were performed to evaluate inflammatory cells infiltration and demyelination, spleen sections were stained with PNA-FITC to analyze the difference in germinal center. Compared with vehicle group, the incidence of AG490 group was deceased, onset time was delayed, the severity was significantly reduced. The inflammatory cells and demyelination in AG490 group were lower than those in vehicle group. Immunofluorescence showed the fluorescence intensity of AG490 group was significantly lower than in the vehicle group, but higher than that of control group.

  12. Noni (Morinda citrifolia L.) fruit juice reverses age-related decline in neural-immune interactions in the spleens of old F344 rats.

    Science.gov (United States)

    Pratap, Uday P; Hima, Lalgi; Priyanka, Hannah P; ThyagaRajan, Srinivasan

    2017-02-23

    Various parts of the tropical plant, Morinda citrifolia L. (Noni), have been widely used in traditional medicine in South and Southeast Asia for several centuries. The therapeutic effects of the noni are believed to be mediated through several phytochemicals such as anthraquinones, iridoid, fatty acid glycosides, alcohols, etc. The aim of the study is to investigate the effects of Morinda citrifolia fruit juice (noni fruit juice; NFJ) on neural-immune interactions through the involvement of intracellular signaling pathways both in vitro and in vivo in the splenic lymphocytes of young and old male F344 rats. In the in vitro study, splenocytes from young and old F344 rats were isolated and treated with 0.0001-1% concentrations of NFJ for a period of 24h, while in the in vivo study, old F344 rats were orally administered (5ml/kg body weight) with NFJ (5%, 10% and 20%) twice daily for 60 days. After the treatment period, concanavalin A (Con A)-induced lymphocyte proliferation, cytokines (IL-2, IFN-γ, IL-6, and TNF-α) production, expression of tyrosine hydroxylase (p-TH), nerve growth factor (NGF), m-TOR, IκB-α, p-NF-κB (p50 and p65), p-ERK, p-Akt, p-CREB and lipid peroxidation, protein carbonyl formation, nitric oxide (NO) production were examined in the splenocytes. In vitro NFJ incubation of splenic lymphocytes increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and expression of p-ERK, p-Akt, and p-CREB in young and old rats. In vivo treatment of old rats with NFJ increased lymphoproliferation, IL-2 and IFN-γ production, the expression of p-TH, NGF, and NO production, and suppressed IL-6 production, lipid peroxidation, protein carbonyl formation, and the expression of IκB-α and p-NF-κB (p50) in the splenocytes. Taken together, these results suggest that Morinda citrifolia fruit juice enhanced neural-immune interactions and cell survival pathways while inhibiting inflammatory processes that may be useful in the treatment of age

  13. Dynamics of BMP and Hes1/Hairy1 signaling in the dorsal neural tube underlies the transition from neural crest to definitive roof plate.

    Science.gov (United States)

    Nitzan, Erez; Avraham, Oshri; Kahane, Nitza; Ofek, Shai; Kumar, Deepak; Kalcheim, Chaya

    2016-03-24

    The dorsal midline region of the neural tube that results from closure of the neural folds is generally termed the roof plate (RP). However, this domain is highly dynamic and complex, and is first transiently inhabited by prospective neural crest (NC) cells that sequentially emigrate from the neuroepithelium. It only later becomes the definitive RP, the dorsal midline cells of the spinal cord. We previously showed that at the trunk level of the axis, prospective RP progenitors originate ventral to the premigratory NC and progressively reach the dorsal midline following NC emigration. However, the molecular mechanisms underlying the end of NC production and formation of the definitive RP remain virtually unknown. Based on distinctive cellular and molecular traits, we have defined an initial NC and a subsequent RP stage, allowing us to investigate the mechanisms responsible for the transition between the two phases. We demonstrate that in spite of the constant production of BMP4 in the dorsal tube at both stages, RP progenitors only transiently respond to the ligand and lose competence shortly before they arrive at their final location. In addition, exposure of dorsal tube cells at the NC stage to high levels of BMP signaling induces premature RP traits, such as Hes1/Hairy1, while concomitantly inhibiting NC production. Reciprocally, early inhibition of BMP signaling prevents Hairy1 mRNA expression at the RP stage altogether, suggesting that BMP is both necessary and sufficient for the development of this RP-specific trait. Furthermore, when Hes1/Hairy1 is misexpressed at the NC stage, it inhibits BMP signaling and downregulates BMPR1A/Alk3 mRNA expression, transcription of BMP targets such as Foxd3, cell-cycle progression, and NC emigration. Reciprocally, Foxd3 inhibits Hairy1, suggesting that repressive cross-interactions at the level of, and downstream from, BMP ensure the temporal separation between both lineages. Together, our data suggest that BMP signaling is

  14. Analysing the 21 cm signal from the epoch of reionization with artificial neural networks

    Science.gov (United States)

    Shimabukuro, Hayato; Semelin, Benoit

    2017-07-01

    The 21 cm signal from the epoch of reionization should be observed within the next decade. While a simple statistical detection is expected with Square Kilometre Array (SKA) pathfinders, the SKA will hopefully produce a full 3D mapping of the signal. To extract from the observed data constraints on the parameters describing the underlying astrophysical processes, inversion methods must be developed. For example, the Markov Chain Monte Carlo method has been successfully applied. Here, we test another possible inversion method: artificial neural networks (ANNs). We produce a training set that consists of 70 individual samples. Each sample is made of the 21 cm power spectrum at different redshifts produced with the 21cmFast code plus the value of three parameters used in the seminumerical simulations that describe astrophysical processes. Using this set, we train the network to minimize the error between the parameter values it produces as an output and the true values. We explore the impact of the architecture of the network on the quality of the training. Then we test the trained network on the new set of 54 test samples with different values of the parameters. We find that the quality of the parameter reconstruction depends on the sensitivity of the power spectrum to the different parameters at a given redshift, that including thermal noise and sample variance decreases the quality of the reconstruction and that using the power spectrum at several redshifts as an input to the ANN improves the quality of the reconstruction. We conclude that ANNs are a viable inversion method whose main strength is that they require a sparse exploration of the parameter space and thus should be usable with full numerical simulations.

  15. With a little help from my friends: androgens tap BDNF signaling pathways to alter neural circuits.

    Science.gov (United States)

    Ottem, E N; Bailey, D J; Jordan, C L; Breedlove, S M

    2013-06-03

    Gonadal androgens are critical for the development and maintenance of sexually dimorphic regions of the male nervous system, which is critical for male-specific behavior and physiological functioning. In rodents, the motoneurons of the spinal nucleus of the bulbocavernosus (SNB) provide a useful example of a neural system dependent on androgen. Unless rescued by perinatal androgens, the SNB motoneurons will undergo apoptotic cell death. In adulthood, SNB motoneurons remain dependent on androgen, as castration leads to somal atrophy and dendritic retraction. In a second vertebrate model, the zebra finch, androgens are critical for the development of several brain nuclei involved in song production in males. Androgen deprivation during a critical period during postnatal development disrupts song acquisition and dimorphic size-associated nuclei. Mechanisms by which androgens exert masculinizing effects in each model system remain elusive. Recent studies suggest that brain-derived neurotrophic factor (BDNF) may play a role in androgen-dependent masculinization and maintenance of both SNB motoneurons and song nuclei of birds. This review aims to summarize studies demonstrating that BDNF signaling via its tyrosine receptor kinase (TrkB) receptor may work cooperatively with androgens to maintain somal and dendritic morphology of SNB motoneurons. We further describe studies that suggest the cellular origin of BDNF is of particular importance in androgen-dependent regulation of SNB motoneurons. We review evidence that androgens and BDNF may synergistically influence song development and plasticity in bird species. Finally, we provide hypothetical models of mechanisms that may underlie androgen- and BDNF-dependent signaling pathways. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Serotonin 2A Receptor Signaling Underlies LSD-induced Alteration of the Neural Response to Dynamic Changes in Music.

    Science.gov (United States)

    Barrett, Frederick S; Preller, Katrin H; Herdener, Marcus; Janata, Petr; Vollenweider, Franz X

    2017-09-28

    Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing. This suggests a critical role of 5HT2A receptor signaling in supporting the neural tracking of dynamic tonal structure in music, as well as in supporting the associated increases in emotionality, connectedness, and meaningfulness in response to music that are commonly observed after the administration of LSD and other psychedelics. Together, these findings inform the neuropsychopharmacology of music perception and cognition, meaningful music listening experiences, and altered perception of music during psychedelic experiences. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. The effects of life stress and neural learning signals on fluid intelligence.

    Science.gov (United States)

    Friedel, Eva; Schlagenhauf, Florian; Beck, Anne; Dolan, Raymond J; Huys, Quentin J M; Rapp, Michael A; Heinz, Andreas

    2015-02-01

    Fluid intelligence (fluid IQ), defined as the capacity for rapid problem solving and behavioral adaptation, is known to be modulated by learning and experience. Both stressful life events (SLES) and neural correlates of learning [specifically, a key mediator of adaptive learning in the brain, namely the ventral striatal representation of prediction errors (PE)] have been shown to be associated with individual differences in fluid IQ. Here, we examine the interaction between adaptive learning signals (using a well-characterized probabilistic reversal learning task in combination with fMRI) and SLES on fluid IQ measures. We find that the correlation between ventral striatal BOLD PE and fluid IQ, which we have previously reported, is quantitatively modulated by the amount of reported SLES. Thus, after experiencing adversity, basic neuronal learning signatures appear to align more closely with a general measure of flexible learning (fluid IQ), a finding complementing studies on the effects of acute stress on learning. The results suggest that an understanding of the neurobiological correlates of trait variables like fluid IQ needs to take socioemotional influences such as chronic stress into account.

  18. Bearings Fault Diagnosis Based on Convolutional Neural Networks with 2-D Representation of Vibration Signals as Input

    Directory of Open Access Journals (Sweden)

    Zhang Wei

    2017-01-01

    Full Text Available Periodic vibration signals captured by the accelerometers carry rich information for bearing fault diagnosis. Existing methods mostly rely on hand-crafted time-consuming preprocessing of data to acquire suitable features. In this paper, we use an easy and effective method to transform the 1-D temporal vibration signal into a 2-D image. With the signal image, convolutional Neural Network (CNN is used to train the raw vibration data. As powerful feature extractor and classifier for image recognition, CNN can learn to acquire features most suitable for the classification task by being trained. With the image format of vibration signals, the neuron in fully-connected layer of CNN can see farther and capture the periodic feature of signals. According to the results of the experiments, when fed in enough training samples, the proposed method outperforms other common methods. The proposed method can also be applied to solve intelligent diagnosis problems of other machine systems.

  19. Hierarchical signaling transduction of the immune and muscle cell crosstalk in muscle regeneration.

    Science.gov (United States)

    Yang, Wenjun; Hu, Ping

    2017-08-24

    The muscle regeneration is a complicated bioprocess that involved in many cell types, including necrotic muscle cells, satellite cells, mesenchymal cells, pericytes, immune cells, and other cell types present at the injury site. Immune cells involved in both innate and adaptive immune responses regulate the progress of muscle regeneration. In this review, we discussed the roles of different immune cells in muscle regeneration. The immune cells regulate muscle regeneration through cytokine production, cell-cell contacts, and general immune environment regulation. We also describe the current known mechanism of how immune cells regulating muscle regeneration. Copyright © 2017. Published by Elsevier Inc.

  20. Expression profiling of autism candidate genes during human brain development implicates central immune signaling pathways.

    Directory of Open Access Journals (Sweden)

    Mark N Ziats

    Full Text Available The Autism Spectrum Disorders (ASD represent a clinically heterogeneous set of conditions with strong hereditary components. Despite substantial efforts to uncover the genetic basis of ASD, the genomic etiology appears complex and a clear understanding of the molecular mechanisms underlying Autism remains elusive. We hypothesized that focusing gene interaction networks on ASD-implicated genes that are highly expressed in the developing brain may reveal core mechanisms that are otherwise obscured by the genomic heterogeneity of the disorder. Here we report an in silico study of the gene expression profile from ASD-implicated genes in the unaffected developing human brain. By implementing a biologically relevant approach, we identified a subset of highly expressed ASD-candidate genes from which interactome networks were derived. Strikingly, immune signaling through NFκB, Tnf, and Jnk was central to ASD networks at multiple levels of our analysis, and cell-type specific expression suggested glia--in addition to neurons--deserve consideration. This work provides integrated genomic evidence that ASD-implicated genes may converge on central cytokine signaling pathways.

  1. Expression profiling of autism candidate genes during human brain development implicates central immune signaling pathways.

    Science.gov (United States)

    Ziats, Mark N; Rennert, Owen M

    2011-01-01

    The Autism Spectrum Disorders (ASD) represent a clinically heterogeneous set of conditions with strong hereditary components. Despite substantial efforts to uncover the genetic basis of ASD, the genomic etiology appears complex and a clear understanding of the molecular mechanisms underlying Autism remains elusive. We hypothesized that focusing gene interaction networks on ASD-implicated genes that are highly expressed in the developing brain may reveal core mechanisms that are otherwise obscured by the genomic heterogeneity of the disorder. Here we report an in silico study of the gene expression profile from ASD-implicated genes in the unaffected developing human brain. By implementing a biologically relevant approach, we identified a subset of highly expressed ASD-candidate genes from which interactome networks were derived. Strikingly, immune signaling through NFκB, Tnf, and Jnk was central to ASD networks at multiple levels of our analysis, and cell-type specific expression suggested glia--in addition to neurons--deserve consideration. This work provides integrated genomic evidence that ASD-implicated genes may converge on central cytokine signaling pathways.

  2. Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential.

    Science.gov (United States)

    Aoki, Masayo; Aoki, Hiroaki; Ramanathan, Rajesh; Hait, Nitai C; Takabe, Kazuaki

    2016-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cell processes. It is produced by the phosphorylation of sphingosine by sphingosine kinases (SphKs) and exported out of cells via transporters such as spinster homolog 2 (Spns2). S1P regulates diverse physiological processes by binding to specific G protein-binding receptors, S1P receptors (S1PRs) 1-5, through a process coined as "inside-out signaling." The S1P concentration gradient between various tissues promotes S1PR1-dependent migration of T cells from secondary lymphoid organs into the lymphatic and blood circulation. S1P suppresses T cell egress from and promotes retention in inflamed peripheral tissues. S1PR1 in T and B cells as well as Spns2 in endothelial cells contributes to lymphocyte trafficking. FTY720 (Fingolimod) is a functional antagonist of S1PRs that induces systemic lymphopenia by suppression of lymphocyte egress from lymphoid organs. In this review, we summarize previous findings and new discoveries about the importance of S1P and S1PR signaling in the recruitment of immune cells and lymphocyte retention in inflamed tissues. We also discuss the role of S1P-S1PR1 axis in inflammatory diseases and wound healing.

  3. Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Masayo Aoki

    2016-01-01

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid metabolite involved in many critical cell processes. It is produced by the phosphorylation of sphingosine by sphingosine kinases (SphKs and exported out of cells via transporters such as spinster homolog 2 (Spns2. S1P regulates diverse physiological processes by binding to specific G protein-binding receptors, S1P receptors (S1PRs 1–5, through a process coined as “inside-out signaling.” The S1P concentration gradient between various tissues promotes S1PR1-dependent migration of T cells from secondary lymphoid organs into the lymphatic and blood circulation. S1P suppresses T cell egress from and promotes retention in inflamed peripheral tissues. S1PR1 in T and B cells as well as Spns2 in endothelial cells contributes to lymphocyte trafficking. FTY720 (Fingolimod is a functional antagonist of S1PRs that induces systemic lymphopenia by suppression of lymphocyte egress from lymphoid organs. In this review, we summarize previous findings and new discoveries about the importance of S1P and S1PR signaling in the recruitment of immune cells and lymphocyte retention in inflamed tissues. We also discuss the role of S1P-S1PR1 axis in inflammatory diseases and wound healing.

  4. Lymphotropic Virions Affect Chemokine Receptor-Mediated Neural Signaling and Apoptosis: Implications for Human Immunodeficiency Virus Type 1-Associated Dementia

    Science.gov (United States)

    Zheng, Jialin; Ghorpade, Anuja; Niemann, Douglas; Cotter, Robin L.; Thylin, Michael R.; Epstein, Leon; Swartz, Jennifer M.; Shepard, Robin B.; Liu, Xiaojuan; Nukuna, Adeline; Gendelman, Howard E.

    1999-01-01

    Chemokine receptors pivotal for human immunodeficiency virus type 1 (HIV-1) infection in lymphocytes and macrophages (CCR3, CCR5, and CXCR4) are expressed on neural cells (microglia, astrocytes, and/or neurons). It is these cells which are damaged during progressive HIV-1 infection of the central nervous system. We theorize that viral coreceptors could effect neural cell damage during HIV-1-associated dementia (HAD) without simultaneously affecting viral replication. To these ends, we studied the ability of diverse viral strains to affect intracellular signaling and apoptosis of neurons, astrocytes, and monocyte-derived macrophages. Inhibition of cyclic AMP, activation of inositol 1,4,5-trisphosphate, and apoptosis were induced by diverse HIV-1 strains, principally in neurons. Virions from T-cell-tropic (T-tropic) strains (MN, IIIB, and Lai) produced the most significant alterations in signaling of neurons and astrocytes. The HIV-1 envelope glycoprotein, gp120, induced markedly less neural damage than purified virions. Macrophage-tropic (M-tropic) strains (ADA, JR-FL, Bal, MS-CSF, and DJV) produced the least neural damage, while 89.6, a dual-tropic HIV-1 strain, elicited intermediate neural cell damage. All T-tropic strain-mediated neuronal impairments were blocked by the CXCR4 antibody, 12G5. In contrast, the M-tropic strains were only partially blocked by 12G5. CXCR4-mediated neuronal apoptosis was confirmed in pure populations of rat cerebellar granule neurons and was blocked by HA1004, an inhibitor of calcium/calmodulin-dependent protein kinase II, protein kinase A, and protein kinase C. Taken together, these results suggest that progeny HIV-1 virions can influence neuronal signal transduction and apoptosis. This process occurs, in part, through CXCR4 and is independent of CD4 binding. T-tropic viruses that traffic in and out of the brain during progressive HIV-1 disease may play an important role in HAD neuropathogenesis. PMID:10482576

  5. Investigating the effect of traditional Persian music on ECG signals in young women using wavelet transform and neural networks.

    Science.gov (United States)

    Abedi, Behzad; Abbasi, Ataollah; Goshvarpour, Atefeh

    2017-05-01

    In the past few decades, several studies have reported the physiological effects of listening to music. The physiological effects of different music types on different people are different. In the present study, we aimed to examine the effects of listening to traditional Persian music on electrocardiogram (ECG) signals in young women. Twenty-two healthy females participated in this study. ECG signals were recorded under two conditions: rest and music. For each ECG signal, 20 morphological and wavelet-based features were selected. Artificial neural network (ANN) and probabilistic neural network (PNN) classifiers were used for the classification of ECG signals during and before listening to music. Collected data were separated into two data sets: train and test. Classification accuracies of 88% and 97% were achieved in train data sets using ANN and PNN, respectively. In addition, the test data set was employed for evaluating the classifiers, and classification rates of 84% and 93% were obtained using ANN and PNN, respectively. The present study investigated the effect of music on ECG signals based on wavelet transform and morphological features. The results obtained here can provide a good understanding on the effects of music on ECG signals to researchers.

  6. Forcast of TEXT plasma disruptions using soft X-rays as input signal in a neural network

    Energy Technology Data Exchange (ETDEWEB)

    Vannucci, A.; Oliveira, K.A.; Tajima, T.

    1998-03-03

    A feed-forward neural network with two hidden layers is used in this work to forecast major and minor disruptive instabilities in TEXT discharges. Using soft X-ray signals as input data, the neural net is trained with one disruptive plasma pulse, and a different disruptive discharge is used for validation. After being properly trained the networks, with the same set of weights. is then used to forecast disruptions in two others different plasma pulses. It is observed that the neural net is able to predict the incoming of a disruption more than 3 ms in advance. This time interval is almost three times longer than the one already obtained previously when magnetic signal from a Mirnov coil was used to feed the neural networks with. To our own eye we fail to see any indication of an upcoming disruption from the experimental data this far back from the time of disruption. Finally, from what we observe in the predictive behavior of our network, speculations are made whether the disruption triggering mechanism would be associated to an increase of the m = 2 magnetic island, that disturbs the central part of the plasma column afterwards or, in face of the results from this work, the initial perturbation would have occurred first in the central part of the plasma column, within the q = 1 magnetic surface, and then the m = 2 MHD mode would be destabilized afterwards.

  7. Human papillomavirus type 16 E6 and NFX1-123 mislocalize immune signaling proteins and downregulate immune gene expression in keratinocytes.

    Directory of Open Access Journals (Sweden)

    Justine Levan

    Full Text Available Human papillomavirus (HPV is the most prevalent sexually transmitted infection, affecting an estimated 11% of the world's population. The high-risk HPV types (HR HPV account for approximately 5% of the global burden of cancer and thus cause high morbidity and mortality. Although it is known that persistent infection with HR HPV is the greatest risk factor for developing HPV-associated cancer, and that the HPV early proteins E6 and E7 dysregulate immune detection by its host cells, the mechanisms of immune evasion by HR HPV are not well understood. Previous work in the laboratory identified the endogenous cytoplasmic host protein NFX1-123 as a binding partner of the HR HPV type 16 oncoprotein E6 (16E6. Together NFX1-123 and 16E6 affect cellular growth, differentiation, and immortalization genes and pathways. In a whole genome microarray, human foreskin keratinocytes (HFKs stably expressing 16E6 and overexpressing NFX1-123 showed a diverse set of innate immune genes downregulated two-fold or more when compared to 16E6 cells with endogenous NFX1-123. We demonstrated that 16E6 and NFX1-123 decreased expression of pro-inflammatory cytokines and interferon-stimulated genes (ISGs in 16E6 HFKs at the mRNA and protein level. Knock down of NFX1-123 in 16E6 HFKs resulted in a derepression of innate immune genes, pointing to the requirement of NFX1-123 for immune regulation in the context of 16E6. Studies using immunofluorescent microscopy revealed that 16E6 and NFX1-123 disturbed the normal localization of signaling proteins involved in initiating the immune response. This study identifies NFX1-123 as a critical host protein partner through which 16E6 is able to subvert the immune response and in turn permit a long-lived HR HPV infection.

  8. Human papillomavirus type 16 E6 and NFX1-123 mislocalize immune signaling proteins and downregulate immune gene expression in keratinocytes.

    Science.gov (United States)

    Levan, Justine; Vliet-Gregg, Portia A; Robinson, Kristin L; Katzenellenbogen, Rachel A

    2017-01-01

    Human papillomavirus (HPV) is the most prevalent sexually transmitted infection, affecting an estimated 11% of the world's population. The high-risk HPV types (HR HPV) account for approximately 5% of the global burden of cancer and thus cause high morbidity and mortality. Although it is known that persistent infection with HR HPV is the greatest risk factor for developing HPV-associated cancer, and that the HPV early proteins E6 and E7 dysregulate immune detection by its host cells, the mechanisms of immune evasion by HR HPV are not well understood. Previous work in the laboratory identified the endogenous cytoplasmic host protein NFX1-123 as a binding partner of the HR HPV type 16 oncoprotein E6 (16E6). Together NFX1-123 and 16E6 affect cellular growth, differentiation, and immortalization genes and pathways. In a whole genome microarray, human foreskin keratinocytes (HFKs) stably expressing 16E6 and overexpressing NFX1-123 showed a diverse set of innate immune genes downregulated two-fold or more when compared to 16E6 cells with endogenous NFX1-123. We demonstrated that 16E6 and NFX1-123 decreased expression of pro-inflammatory cytokines and interferon-stimulated genes (ISGs) in 16E6 HFKs at the mRNA and protein level. Knock down of NFX1-123 in 16E6 HFKs resulted in a derepression of innate immune genes, pointing to the requirement of NFX1-123 for immune regulation in the context of 16E6. Studies using immunofluorescent microscopy revealed that 16E6 and NFX1-123 disturbed the normal localization of signaling proteins involved in initiating the immune response. This study identifies NFX1-123 as a critical host protein partner through which 16E6 is able to subvert the immune response and in turn permit a long-lived HR HPV infection.

  9. Multiphoton minimal inertia scanning for fast acquisition of neural activity signals.

    Science.gov (United States)

    Schuck, Renaud; Go, Mary Ann; Garasto, Stefania; Reynolds, Stephanie; Dragotti, Pier Luigi; Schultz, Simon

    2017-11-13

    Multi-photon laser scanning microscopy provides a powerful tool for monitoring the spatiotemporal dynamics of neural circuit activity. It is, however, intrinsically a point scanning technique. Standard raster scanning enables imaging at subcellular resolution; however, acquisition rates are limited by the size of the field of view to be scanned. Recently developed scanning strategies such as Travelling Salesman Scanning (TSS) have been developed to maximize cellular sampling rate by scanning only select regions in the field of view corresponding to locations of interest such as somata. However, such strategies are not optimized for the mechanical properties of galvanometric scanners. We thus aimed to develop a new scanning algorithm which produces minimal inertia trajectories, and compare its performance with existing scanning algorithms. Approach: We describe here the Adaptive Spiral Scanning (SSA) algorithm, which fits a set of near-circular trajectories to the cellular distribution to avoid inertial drifts of galvanometer position. We compare its performance to raster scanning and TSS in terms of cellular sampling frequency and signal-to-noise ratio (SNR). Main Results: Using surrogate neuron spatial position data, we show that SSA acquisition rates are an order of magnitude higher than those for raster scanning and generally exceed those achieved by TSS for neural densities comparable with those found in the cortex. We show that this result also holds true for in vitro hippocampal mouse brain slices bath loaded with the synthetic calcium dye Cal-520 AM. The ability of TSS to "park" the laser on each neuron along the scanning trajectory, however, enables higher SNR than SSA when all targets are precisely scanned. Raster scanning has the highest SNR but at a substantial cost in number of cells scanned. To understand the impact of sampling rate and SNR on functional calcium imaging, we used the Crame ́r-Rao Bound on evoked calcium traces recorded

  10. Development of Filtered Bispectrum for EEG Signal Feature Extraction in Automatic Emotion Recognition Using Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    Prima Dewi Purnamasari

    2017-05-01

    Full Text Available The development of automatic emotion detection systems has recently gained significant attention due to the growing possibility of their implementation in several applications, including affective computing and various fields within biomedical engineering. Use of the electroencephalograph (EEG signal is preferred over facial expression, as people cannot control the EEG signal generated by their brain; the EEG ensures a stronger reliability in the psychological signal. However, because of its uniqueness between individuals and its vulnerability to noise, use of EEG signals can be rather complicated. In this paper, we propose a methodology to conduct EEG-based emotion recognition by using a filtered bispectrum as the feature extraction subsystem and an artificial neural network (ANN as the classifier. The bispectrum is theoretically superior to the power spectrum because it can identify phase coupling between the nonlinear process components of the EEG signal. In the feature extraction process, to extract the information contained in the bispectrum matrices, a 3D pyramid filter is used for sampling and quantifying the bispectrum value. Experiment results show that the mean percentage of the bispectrum value from 5 × 5 non-overlapped 3D pyramid filters produces the highest recognition rate. We found that reducing the number of EEG channels down to only eight in the frontal area of the brain does not significantly affect the recognition rate, and the number of data samples used in the training process is then increased to improve the recognition rate of the system. We have also utilized a probabilistic neural network (PNN as another classifier and compared its recognition rate with that of the back-propagation neural network (BPNN, and the results show that the PNN produces a comparable recognition rate and lower computational costs. Our research shows that the extracted bispectrum values of an EEG signal using 3D filtering as a feature extraction

  11. Exploring the Neuroimmunopharmacology of Opioids: An Integrative Review of Mechanisms of Central Immune Signaling and Their Implications for Opioid Analgesia

    Science.gov (United States)

    Shavit, Yehuda; Grace, Peter M.; Rice, Kenner C.; Maier, Steven F.; Watkins, Linda R.

    2011-01-01

    Vastly stimulated by the discovery of opioid receptors in the early 1970s, preclinical and clinical research was directed at the study of stereoselective neuronal actions of opioids, especially those played in their crucial analgesic role. However, during the past decade, a new appreciation of the non-neuronal actions of opioids has emerged from preclinical research, with specific appreciation for the nonclassic and nonstereoselective sites of action. Opioid activity at Toll-like receptors, newly recognized innate immune pattern recognition receptors, adds substantially to this unfolding story. It is now apparent from molecular and rodent data that these newly identified signaling events significantly modify the pharmacodynamics of opioids by eliciting proinflammatory reactivity from glia, the immunocompetent cells of the central nervous system. These central immune signaling events, including the release of cytokines and chemokines and the associated disruption of glutamate homeostasis, cause elevated neuronal excitability, which subsequently decreases opioid analgesic efficacy and leads to heightened pain states. This review will examine the current preclinical literature of opioid-induced central immune signaling mediated by classic and nonclassic opioid receptors. A unification of the preclinical pharmacology, neuroscience, and immunology of opioids now provides new insights into common mechanisms of chronic pain, naive tolerance, analgesic tolerance, opioid-induced hyperalgesia, and allodynia. Novel pharmacological targets for future drug development are discussed in the hope that disease-modifying chronic pain treatments arising from the appreciation of opioid-induced central immune signaling may become practical. PMID:21752874

  12. Innate Control of Adaptive Immunity: Beyond the Three-Signal Paradigm.

    Science.gov (United States)

    Jain, Aakanksha; Pasare, Chandrashekhar

    2017-05-15

    Activation of cells in the adaptive immune system is a highly orchestrated process dictated by multiples cues from the innate immune system. Although the fundamental principles of innate control of adaptive immunity are well established, it is not fully understood how innate cells integrate qualitative pathogenic information to generate tailored protective adaptive immune responses. In this review, we discuss complexities involved in the innate control of adaptive immunity that extend beyond TCR engagement, costimulation, and priming cytokine production but are critical for the generation of protective T cell immunity. Copyright © 2017 by The American Association of Immunologists, Inc.

  13. Regulation of MyD88-Dependent Signaling Events by S Nitrosylation Retards Toll-Like Receptor Signal Transduction and Initiation of Acute-Phase Immune Responses▿

    OpenAIRE

    Into, Takeshi; Inomata, Megumi; Nakashima, Misako; Shibata, Ken-ichiro; Häcker, Hans; Matsushita, Kenji

    2007-01-01

    Nitric oxide (NO) has been thought to regulate the immune system through S nitrosylation of the transcriptional factor NF-κB. However, regulatory effects of NO on innate immune responses are unclear. Here, we report that NO has a capability to control Toll-like receptor-mediated signaling through S nitrosylation. We found that the adaptor protein MyD88 was primarily S nitrosylated, depending on the presence of endothelial NO synthase (eNOS). S nitrosylation at a particular cysteine residue wi...

  14. Yeast product supplementation modulated humoral and mucosal immunity and uterine inflammatory signals in transition dairy cows.

    Science.gov (United States)

    Yuan, K; Mendonça, L G D; Hulbert, L E; Mamedova, L K; Muckey, M B; Shen, Y; Elrod, C C; Bradford, B J

    2015-05-01

    ) in the uterine samples, reflecting greater abundance of these transcripts collected on d 7 compared with d 42. A quadratic dose effect was detected for IL-6, indicating that 30 and 60g/d doses decreased uterine IL-6 mRNA. The mRNA abundance of MPO and ELANE was increased linearly by YC-EHY. Supplementation with YC-EHY enhanced measures of humoral and mucosal immunity and modulated uterine inflammatory signals and mammary gland health in transition dairy cows. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori) challenged by Beauveria bassiana.

    Science.gov (United States)

    Geng, Tao; Lv, Ding-Ding; Huang, Yu-Xia; Hou, Cheng-Xiang; Qin, Guang-Xing; Guo, Xi-Jie

    2016-12-20

    Innate immunity was critical in insects defensive system and able to be induced by Janus kinase/signal transducer and activator of transcription cascade transduction (JAK/STAT) signaling pathway. Currently, it had been identified many JAK/STAT signaling pathway-related genes in silkworm, but little function was known on insect innate immunity. To explore the roles of JAK/STAT pathway in antifungal immune response in silkworm (Bombyx mori) against Beauveria bassiana infection, the expression patterns of B. mori C-type lectin 5 (BmCTL5) and genes encoding 6 components of JAK/STAT signaling pathway in silkworm challenged by B. bassiana were analyzed using quantitative real time PCR. Meanwhile the activation of JAK/STAT signaling pathway by various pathogenic micro-organisms and the affect of JAK/STAT signaling pathway inhibitors on antifungal activity in silkworm hemolymph was also detected. Moreover, RNAi assay of BmCTL5 and the affect on expression levels of signaling factors were also analyzed. We found that JAK/STAT pathway could be obviously activated in silkworm challenged with B. bassiana and had no response to bacteria and B. mori cytoplasmic polyhedrosis virus (BmCPV). However, the temporal expression patterns of JAK/STAT signaling pathway related genes were significantly different. B. mori downstream receptor kinase (BmDRK) might be a positive regulator of JAK/STAT signaling pathway in silkworm against B. bassiana infection. Moreover, antifungal activity assay showed that the suppression of JAK/STAT signaling pathway by inhibitors could significantly inhibit the antifungal activity in hemolymph and resulted in increased sensitivity of silkworm to B. bassiana infection, indicating that JAK/STAT signaling pathway might be involved in the synthesis and secretion of antifungal substances. The results of RNAi assays suggested that BmCTL5 might be one pattern recognition receptors for JAK/STAT signaling pathway in silkworm. These findings yield insights for better

  16. Network intrusion detection based on a general regression neural network optimized by an improved artificial immune algorithm.

    Science.gov (United States)

    Wu, Jianfa; Peng, Dahao; Li, Zhuping; Zhao, Li; Ling, Huanzhang

    2015-01-01

    To effectively and accurately detect and classify network intrusion data, this paper introduces a general regression neural network (GRNN) based on the artificial immune algorithm with elitist strategies (AIAE). The elitist archive and elitist crossover were combined with the artificial immune algorithm (AIA) to produce the AIAE-GRNN algorithm, with the aim of improving its adaptivity and accuracy. In this paper, the mean square errors (MSEs) were considered the affinity function. The AIAE was used to optimize the smooth factors of the GRNN; then, the optimal smooth factor was solved and substituted into the trained GRNN. Thus, the intrusive data were classified. The paper selected a GRNN that was separately optimized using a genetic algorithm (GA), particle swarm optimization (PSO), and fuzzy C-mean clustering (FCM) to enable a comparison of these approaches. As shown in the results, the AIAE-GRNN achieves a higher classification accuracy than PSO-GRNN, but the running time of AIAE-GRNN is long, which was proved first. FCM and GA-GRNN were eliminated because of their deficiencies in terms of accuracy and convergence. To improve the running speed, the paper adopted principal component analysis (PCA) to reduce the dimensions of the intrusive data. With the reduction in dimensionality, the PCA-AIAE-GRNN decreases in accuracy less and has better convergence than the PCA-PSO-GRNN, and the running speed of the PCA-AIAE-GRNN was relatively improved. The experimental results show that the AIAE-GRNN has a higher robustness and accuracy than the other algorithms considered and can thus be used to classify the intrusive data.

  17. Network intrusion detection based on a general regression neural network optimized by an improved artificial immune algorithm.

    Directory of Open Access Journals (Sweden)

    Jianfa Wu

    Full Text Available To effectively and accurately detect and classify network intrusion data, this paper introduces a general regression neural network (GRNN based on the artificial immune algorithm with elitist strategies (AIAE. The elitist archive and elitist crossover were combined with the artificial immune algorithm (AIA to produce the AIAE-GRNN algorithm, with the aim of improving its adaptivity and accuracy. In this paper, the mean square errors (MSEs were considered the affinity function. The AIAE was used to optimize the smooth factors of the GRNN; then, the optimal smooth factor was solved and substituted into the trained GRNN. Thus, the intrusive data were classified. The paper selected a GRNN that was separately optimized using a genetic algorithm (GA, particle swarm optimization (PSO, and fuzzy C-mean clustering (FCM to enable a comparison of these approaches. As shown in the results, the AIAE-GRNN achieves a higher classification accuracy than PSO-GRNN, but the running time of AIAE-GRNN is long, which was proved first. FCM and GA-GRNN were eliminated because of their deficiencies in terms of accuracy and convergence. To improve the running speed, the paper adopted principal component analysis (PCA to reduce the dimensions of the intrusive data. With the reduction in dimensionality, the PCA-AIAE-GRNN decreases in accuracy less and has better convergence than the PCA-PSO-GRNN, and the running speed of the PCA-AIAE-GRNN was relatively improved. The experimental results show that the AIAE-GRNN has a higher robustness and accuracy than the other algorithms considered and can thus be used to classify the intrusive data.

  18. Radiation-induced glioblastoma signaling cascade regulates viability, apoptosis and differentiation of neural stem cells (NSC).

    Science.gov (United States)

    Ivanov, Vladimir N; Hei, Tom K

    2014-12-01

    Ionizing radiation alone or in combination with chemotherapy is the main treatment modality for brain tumors including glioblastoma. Adult neurons and astrocytes demonstrate substantial radioresistance; in contrast, human neural stem cells (NSC) are highly sensitive to radiation via induction of apoptosis. Irradiation of tumor cells has the potential risk of affecting the viability and function of NSC. In this study, we have evaluated the effects of irradiated glioblastoma cells on viability, proliferation and differentiation potential of non-irradiated (bystander) NSC through radiation-induced signaling cascades. Using media transfer experiments, we demonstrated significant effects of the U87MG glioblastoma secretome after gamma-irradiation on apoptosis in non-irradiated NSC. Addition of anti-TRAIL antibody to the transferred media partially suppressed apoptosis in NSC. Furthermore, we observed a dramatic increase in the production and secretion of IL8, TGFβ1 and IL6 by irradiated glioblastoma cells, which could promote glioblastoma cell survival and modify the effects of death factors in bystander NSC. While differentiation of NSC into neurons and astrocytes occurred efficiently with the corresponding differentiation media, pretreatment of NSC for 8 h with medium from irradiated glioblastoma cells selectively suppressed the differentiation of NSC into neurons, but not into astrocytes. Exogenous IL8 and TGFβ1 increased NSC/NPC survival, but also suppressed neuronal differentiation. On the other hand, IL6 was known to positively affect survival and differentiation of astrocyte progenitors. We established a U87MG neurosphere culture that was substantially enriched by SOX2(+) and CD133(+) glioma stem-like cells (GSC). Gamma-irradiation up-regulated apoptotic death in GSC via the FasL/Fas pathway. Media transfer experiments from irradiated GSC to non-targeted NSC again demonstrated induction of apoptosis and suppression of neuronal differentiation of NSC. In

  19. A Fully Integrated Wireless Compressed Sensing Neural Signal Acquisition System for Chronic Recording and Brain Machine Interface.

    Science.gov (United States)

    Liu, Xilin; Zhang, Milin; Xiong, Tao; Richardson, Andrew G; Lucas, Timothy H; Chin, Peter S; Etienne-Cummings, Ralph; Tran, Trac D; Van der Spiegel, Jan

    2016-07-18

    Reliable, multi-channel neural recording is critical to the neuroscience research and clinical treatment. However, most hardware development of fully integrated, multi-channel wireless neural recorders to-date, is still in the proof-of-concept stage. To be ready for practical use, the trade-offs between performance, power consumption, device size, robustness, and compatibility need to be carefully taken into account. This paper presents an optimized wireless compressed sensing neural signal recording system. The system takes advantages of both custom integrated circuits and universal compatible wireless solutions. The proposed system includes an implantable wireless system-on-chip (SoC) and an external wireless relay. The SoC integrates 16-channel low-noise neural amplifiers, programmable filters and gain stages, a SAR ADC, a real-time compressed sensing module, and a near field wireless power and data transmission link. The external relay integrates a 32 bit low-power microcontroller with Bluetooth 4.0 wireless module, a programming interface, and an inductive charging unit. The SoC achieves high signal recording quality with minimized power consumption, while reducing the risk of infection from through-skin connectors. The external relay maximizes the compatibility and programmability. The proposed compressed sensing module is highly configurable, featuring a SNDR of 9.78 dB with a compression ratio of 8×. The SoC has been fabricated in a 180 nm standard CMOS technology, occupying 2.1 mm × 0.6 mm silicon area. A pre-implantable system has been assembled to demonstrate the proposed paradigm. The developed system has been successfully used for long-term wireless neural recording in freely behaving rhesus monkey.

  20. A system of recurrent neural networks for modularising, parameterising and dynamic analysis of cell signalling networks.

    Science.gov (United States)

    Samarasinghe, S; Ling, H

    In this paper, we show how to extend our previously proposed novel continuous time Recurrent Neural Networks (RNN) approach that retains the advantage of continuous dynamics offered by Ordinary Differential Equations (ODE) while enabling parameter estimation through adaptation, to larger signalling networks using a modular approach. Specifically, the signalling network is decomposed into several sub-models based on important temporal events in the network. Each sub-model is represented by the proposed RNN and trained using data generated from the corresponding ODE model. Trained sub-models are assembled into a whole system RNN which is then subjected to systems dynamics and sensitivity analyses. The concept is illustrated by application to G1/S transition in cell cycle using Iwamoto et al. (2008) ODE model. We decomposed the G1/S network into 3 sub-models: (i) E2F transcription factor release; (ii) E2F and CycE positive feedback loop for elevating cyclin levels; and (iii) E2F and CycA negative feedback to degrade E2F. The trained sub-models accurately represented system dynamics and parameters were in good agreement with the ODE model. The whole system RNN however revealed couple of parameters contributing to compounding errors due to feedback and required refinement to sub-model 2. These related to the reversible reaction between CycE/CDK2 and p27, its inhibitor. The revised whole system RNN model very accurately matched dynamics of the ODE system. Local sensitivity analysis of the whole system model further revealed the most dominant influence of the above two parameters in perturbing G1/S transition, giving support to a recent hypothesis that the release of inhibitor p27 from Cyc/CDK complex triggers cell cycle stage transition. To make the model useful in a practical setting, we modified each RNN sub-model with a time relay switch to facilitate larger interval input data (≈20min) (original model used data for 30s or less) and retrained them that produced

  1. The Neural Feedback Response to Error As a Teaching Signal for the Motor Learning System

    Science.gov (United States)

    Shadmehr, Reza

    2016-01-01

    When we experience an error during a movement, we update our motor commands to partially correct for this error on the next trial. How does experience of error produce the improvement in the subsequent motor commands? During the course of an erroneous reaching movement, proprioceptive and visual sensory pathways not only sense the error, but also engage feedback mechanisms, resulting in corrective motor responses that continue until the hand arrives at its goal. One possibility is that this feedback response is co-opted by the learning system and used as a template to improve performance on the next attempt. Here we used electromyography (EMG) to compare neural correlates of learning and feedback to test the hypothesis that the feedback response to error acts as a template for learning. We designed a task in which mixtures of error-clamp and force-field perturbation trials were used to deconstruct EMG time courses into error-feedback and learning components. We observed that the error-feedback response was composed of excitation of some muscles, and inhibition of others, producing a complex activation/deactivation pattern during the reach. Despite this complexity, across muscles the learning response was consistently a scaled version of the error-feedback response, but shifted 125 ms earlier in time. Across people, individuals who produced a greater feedback response to error, also learned more from error. This suggests that the feedback response to error serves as a teaching signal for the brain. Individuals who learn faster have a better teacher in their feedback control system. SIGNIFICANCE STATEMENT Our sensory organs transduce errors in behavior. To improve performance, we must generate better motor commands. How does the nervous system transform an error in sensory coordinates into better motor commands in muscle coordinates? Here we show that when an error occurs during a movement, the reflexes transform the sensory representation of error into motor

  2. Agonist-Evoked Ca2+ Signaling in Enteric Glia Drives Neural Programs That Regulate Intestinal Motility in MiceSummary

    Directory of Open Access Journals (Sweden)

    Jonathon L. McClain

    2015-11-01

    Full Text Available Background & Aims: Gastrointestinal motility is regulated by enteric neural circuitry that includes enteric neurons and glia. Enteric glia monitor synaptic activity and exhibit responses to neurotransmitters that are encoded by intracellular calcium (Ca2+ signaling. What role evoked glial responses play in the neural regulation of gut motility is unknown. We tested how evoking Ca2+ signaling in enteric glia affects the neural control of intestinal motility. Methods: We used a novel chemogenetic mouse model that expresses the designer receptor hM3Dq under the transcriptional control of the glial fibrillary acidic protein (GFAP promoter (GFAP::hM3Dq mice to selectively trigger glial Ca2+ signaling. We used in situ Ca2+ imaging and immunohistochemistry to validate this model, and we assessed gut motility by measuring pellet output and composition, colonic bead expulsion time, small intestinal transit time, total gut transit time, colonic migrating motor complex (CMMC recordings, and muscle tension recordings. Results: Expression of the hM3Dq receptor is confined to GFAP-positive enteric glia in the intestines of GFAP::hM3Dq mice. In these mice, application of the hM3Dq agonist clozapine-N-oxide (CNO selectively triggers intracellular Ca2+ responses in enteric glia. Glial activation drove neurogenic contractions in the ileum and colon but had no effect on neurogenic relaxations. CNO enhanced the amplitude and frequency of CMMCs in ex vivo preparations of the colon, and CNO increased colonic motility in vivo. CNO had no effect on the composition of fecal matter, small intestinal transit, or whole gut transit. Conclusions: Glial excitability encoded by intracellular Ca2+ signaling functions to modulate excitatory enteric circuits. Selectively triggering glial Ca2+ signaling might be a novel strategy to improve gut function in motility disorders. Keywords: Autonomic, Chemogenetic, Enteric Nervous System, Intestine, Gut

  3. Neural mechanisms underlying the effects of face-based affective signals on memory for faces: a tentative model.

    Science.gov (United States)

    Tsukiura, Takashi

    2012-01-01

    In our daily lives, we form some impressions of other people. Although those impressions are affected by many factors, face-based affective signals such as facial expression, facial attractiveness, or trustworthiness are important. Previous psychological studies have demonstrated the impact of facial impressions on remembering other people, but little is known about the neural mechanisms underlying this psychological process. The purpose of this article is to review recent functional MRI (fMRI) studies to investigate the effects of face-based affective signals including facial expression, facial attractiveness, and trustworthiness on memory for faces, and to propose a tentative concept for understanding this affective-cognitive interaction. On the basis of the aforementioned research, three brain regions are potentially involved in the processing of face-based affective signals. The first candidate is the amygdala, where activity is generally modulated by both affectively positive and negative signals from faces. Activity in the orbitofrontal cortex (OFC), as the second candidate, increases as a function of perceived positive signals from faces; whereas activity in the insular cortex, as the third candidate, reflects a function of face-based negative signals. In addition, neuroscientific studies have reported that the three regions are functionally connected to the memory-related hippocampal regions. These findings suggest that the effects of face-based affective signals on memory for faces could be modulated by interactions between the regions associated with the processing of face-based affective signals and the hippocampus as a memory-related region.

  4. A negative modulatory role for rho and rho-associated kinase signaling in delamination of neural crest cells

    Science.gov (United States)

    Groysman, Maya; Shoval, Irit; Kalcheim, Chaya

    2008-01-01

    Background Neural crest progenitors arise as epithelial cells and then undergo a process of epithelial to mesenchymal transition that precedes the generation of cellular motility and subsequent migration. We aim at understanding the underlying molecular network. Along this line, possible roles of Rho GTPases that act as molecular switches to control a variety of signal transduction pathways remain virtually unexplored, as are putative interactions between Rho proteins and additional known components of this cascade. Results We investigated the role of Rho/Rock signaling in neural crest delamination. Active RhoA and RhoB are expressed in the membrane of epithelial progenitors and are downregulated upon delamination. In vivo loss-of-function of RhoA or RhoB or of overall Rho signaling by C3 transferase enhanced and/or triggered premature crest delamination yet had no effect on cell specification. Consistently, treatment of explanted neural primordia with membrane-permeable C3 or with the Rock inhibitor Y27632 both accelerated and enhanced crest emigration without affecting cell proliferation. These treatments altered neural crest morphology by reducing stress fibers, focal adhesions and downregulating membrane-bound N-cadherin. Reciprocally, activation of endogenous Rho by lysophosphatidic acid inhibited emigration while enhancing the above. Since delamination is triggered by BMP and requires G1/S transition, we examined their relationship with Rho. Blocking Rho/Rock function rescued crest emigration upon treatment with noggin or with the G1/S inhibitor mimosine. In the latter condition, cells emigrated while arrested at G1. Conversely, BMP4 was unable to rescue cell emigration when endogenous Rho activity was enhanced by lysophosphatidic acid. Conclusion Rho-GTPases, through Rock, act downstream of BMP and of G1/S transition to negatively regulate crest delamination by modifying cytoskeleton assembly and intercellular adhesion. PMID:18945340

  5. Long-term stability of neural prosthetic control signals from silicon cortical arrays in rhesus macaque motor cortex

    Science.gov (United States)

    Chestek, Cynthia A.; Gilja, Vikash; Nuyujukian, Paul; Foster, Justin D.; Fan, Joline M.; Kaufman, Matthew T.; Churchland, Mark M.; Rivera-Alvidrez, Zuley; Cunningham, John P.; Ryu, Stephen I.; Shenoy, Krishna V.

    2011-08-01

    Cortically-controlled prosthetic systems aim to help disabled patients by translating neural signals from the brain into control signals for guiding prosthetic devices. Recent reports have demonstrated reasonably high levels of performance and control of computer cursors and prosthetic limbs, but to achieve true clinical viability, the long-term operation of these systems must be better understood. In particular, the quality and stability of the electrically-recorded neural signals require further characterization. Here, we quantify action potential changes and offline neural decoder performance over 382 days of recording from four intracortical arrays in three animals. Action potential amplitude decreased by 2.4% per month on average over the course of 9.4, 10.4, and 31.7 months in three animals. During most time periods, decoder performance was not well correlated with action potential amplitude (p > 0.05 for three of four arrays). In two arrays from one animal, action potential amplitude declined by an average of 37% over the first 2 months after implant. However, when using simple threshold-crossing events rather than well-isolated action potentials, no corresponding performance loss was observed during this time using an offline decoder. One of these arrays was effectively used for online prosthetic experiments over the following year. Substantial short-term variations in waveforms were quantified using a wireless system for contiguous recording in one animal, and compared within and between days for all three animals. Overall, this study suggests that action potential amplitude declines more slowly than previously supposed, and performance can be maintained over the course of multiple years when decoding from threshold-crossing events rather than isolated action potentials. This suggests that neural prosthetic systems may provide high performance over multiple years in human clinical trials.

  6. IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection.

    Directory of Open Access Journals (Sweden)

    Ismail Sebina

    2016-11-01

    Full Text Available Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations for this have focused on antigenic variation by Plasmodium, but have considered less whether host production of parasite-specific antibody is sub-optimal. In particular, it is unclear whether host immune factors might limit antibody responses. Here, we explored the effect of Type I Interferon signalling via IFNAR1 on CD4+ T-cell and B-cell responses in two non-lethal murine models of malaria, P. chabaudi chabaudi AS (PcAS and P. yoelii 17XNL (Py17XNL infection. Firstly, we demonstrated that CD4+ T-cells and ICOS-signalling were crucial for generating germinal centre (GC B-cells, plasmablasts and parasite-specific antibodies, and likewise that T follicular helper (Tfh cell responses relied on B cells. Next, we found that IFNAR1-signalling impeded the resolution of non-lethal blood-stage infection, which was associated with impaired production of parasite-specific IgM and several IgG sub-classes. Consistent with this, GC B-cell formation, Ig-class switching, plasmablast and Tfh differentiation were all impaired by IFNAR1-signalling. IFNAR1-signalling proceeded via conventional dendritic cells, and acted early by limiting activation, proliferation and ICOS expression by CD4+ T-cells, by restricting the localization of activated CD4+ T-cells adjacent to and within B-cell areas of the spleen, and by simultaneously suppressing Th1 and Tfh responses. Finally, IFNAR1-deficiency accelerated humoral immune responses and parasite control by boosting ICOS-signalling. Thus, we provide evidence of a host innate cytokine response that impedes the onset of humoral immunity during experimental malaria.

  7. IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection.

    Science.gov (United States)

    Sebina, Ismail; James, Kylie R; Soon, Megan S F; Fogg, Lily G; Best, Shannon E; Labastida Rivera, Fabian de; Montes de Oca, Marcela; Amante, Fiona H; Thomas, Bryce S; Beattie, Lynette; Souza-Fonseca-Guimaraes, Fernando; Smyth, Mark J; Hertzog, Paul J; Hill, Geoffrey R; Hutloff, Andreas; Engwerda, Christian R; Haque, Ashraful

    2016-11-01

    Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations for this have focused on antigenic variation by Plasmodium, but have considered less whether host production of parasite-specific antibody is sub-optimal. In particular, it is unclear whether host immune factors might limit antibody responses. Here, we explored the effect of Type I Interferon signalling via IFNAR1 on CD4+ T-cell and B-cell responses in two non-lethal murine models of malaria, P. chabaudi chabaudi AS (PcAS) and P. yoelii 17XNL (Py17XNL) infection. Firstly, we demonstrated that CD4+ T-cells and ICOS-signalling were crucial for generating germinal centre (GC) B-cells, plasmablasts and parasite-specific antibodies, and likewise that T follicular helper (Tfh) cell responses relied on B cells. Next, we found that IFNAR1-signalling impeded the resolution of non-lethal blood-stage infection, which was associated with impaired production of parasite-specific IgM and several IgG sub-classes. Consistent with this, GC B-cell formation, Ig-class switching, plasmablast and Tfh differentiation were all impaired by IFNAR1-signalling. IFNAR1-signalling proceeded via conventional dendritic cells, and acted early by limiting activation, proliferation and ICOS expression by CD4+ T-cells, by restricting the localization of activated CD4+ T-cells adjacent to and within B-cell areas of the spleen, and by simultaneously suppressing Th1 and Tfh responses. Finally, IFNAR1-deficiency accelerated humoral immune responses and parasite control by boosting ICOS-signalling. Thus, we provide evidence of a host innate cytokine response that impedes the onset of humoral immunity during experimental malaria.

  8. Effects of traffic noise on tree frog stress levels, immunity, and color signaling.

    Science.gov (United States)

    Troïanowski, Mathieu; Mondy, Nathalie; Dumet, Adeline; Arcanjo, Caroline; Lengagne, Thierry

    2017-10-01

    During the last decade, many studies have focused on the detrimental effects of noise pollution on acoustic communication. Surprisingly, although it is known that noise exposure strongly influences health in humans, studies on wildlife remain scarce. In order to gain insight into the consequences of traffic noise exposure, we experimentally manipulated traffic noise exposure as well as the endocrine status of animals to investigate physiological and phenotypic consequences of noise pollution in an anuran species. We showed that noise exposure increased stress hormone level and induced an immunosuppressive effect. In addition, both traffic noise exposure and stress hormone application negatively impacted H. arborea vocal sac coloration. Moreover, our results suggest profound changes in sexual selection processes because the best quality males with initial attractive vocal sac coloration were the most impacted by noise. Hence, our study suggests that the recent increases in anthropogenic noise worldwide might affect a broader range of animal species than previously thought, because of alteration of visual signals and immunity. Generalizing these results to other taxa is crucial for the conservation of biodiversity in an increasingly noisy world. © 2017 Society for Conservation Biology.

  9. Photosynthetic light reactions--an adjustable hub in basic production and plant immunity signaling.

    Science.gov (United States)

    Kangasjärvi, Saijaliisa; Tikkanen, Mikko; Durian, Guido; Aro, Eva-Mari

    2014-08-01

    Photosynthetic efficiency is a key trait that influences the sustainable utilization of plants for energy and nutrition. By now, extensive research on photosynthetic processes has underscored important structural and functional relationships among photosynthetic thylakoid membrane protein complexes, and their roles in determining the productivity and stress resistance of plants. Photosystem II photoinhibition-repair cycle, for example, has arisen vital in protecting also Photosystem I against light-induced damage. Availability of highly sophisticated genetic, biochemical and biophysical tools has greatly expanded the catalog of components that carry out photoprotective functions in plants. On thylakoid membranes, these components encompass a network of overlapping systems that allow delicate regulation of linear and cyclic electron transfer pathways, balancing of excitation energy distribution between the two photosystems and dissipation of excess light energy in the antenna system as heat. An increasing number of reports indicate that the above mentioned mechanisms also mediate important functions in the regulation of biotic stress responses in plants. Particularly the handling of excitation energy in the light harvesting II antenna complexes appears central to plant immunity signaling. Comprehensive understanding of the underlying mechanisms and regulatory cross-talk, however, still remain elusive. This review highlights the current understanding of components that regulate the function of photosynthetic light reactions and directly or indirectly also modulate disease resistance in higher plants. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. Planar polarization of Vangl2 in the vertebrate neural plate is controlled by Wnt and Myosin II signaling

    Directory of Open Access Journals (Sweden)

    Olga Ossipova

    2015-07-01

    Full Text Available The vertebrate neural tube forms as a result of complex morphogenetic movements, which require the functions of several core planar cell polarity (PCP proteins, including Vangl2 and Prickle. Despite the importance of these proteins for neurulation, their subcellular localization and the mode of action have remained largely unknown. Here we describe the anteroposterior planar cell polarity (AP-PCP of the cells in the Xenopus neural plate. At the neural midline, the Vangl2 protein is enriched at anterior cell edges and that this localization is directed by Prickle, a Vangl2-interacting protein. Our further analysis is consistent with the model, in which Vangl2 AP-PCP is established in the neural plate as a consequence of Wnt-dependent phosphorylation. Additionally, we uncover feedback regulation of Vangl2 polarity by Myosin II, reiterating a role for mechanical forces in PCP. These observations indicate that both Wnt signaling and Myosin II activity regulate cell polarity and cell behaviors during vertebrate neurulation.

  11. Assessing the user experience of older adults using a neural network trained to recognize emotions from brain signals.

    Science.gov (United States)

    Meza-Kubo, Victoria; Morán, Alberto L; Carrillo, Ivan; Galindo, Gilberto; García-Canseco, Eloisa

    2016-08-01

    The use of Ambient Assisted Living (AAL) technologies as a means to cope with problems that arise due to an increasing and aging population is becoming usual. AAL technologies are used to prevent, cure and improve the wellness and health conditions of the elderly. However, their adoption and use by older adults is still a major challenge. User Experience (UX) evaluations aim at aiding on this task, by identifying the experience that a user has while interacting with an AAL technology under particular conditions. This may help designing better products and improve user engagement and adoption of AAL solutions. However, evaluating the UX of AAL technologies is a difficult task, due to the inherent limitations of their subjects and of the evaluation methods. In this study, we validated the feasibility of assessing the UX of older adults while they use a cognitive stimulation application using a neural network trained to recognize pleasant and unpleasant emotions from electroencephalography (EEG) signals by contrasting our results with those of additional self-report and qualitative analysis UX evaluations. Our study results provide evidence about the feasibility of assessing the UX of older adults using a neural network that take as input the EEG signals; the classification accuracy of our neural network ranges from 60.87% to 82.61%. As future work we will conduct additional UX evaluation studies using the three different methods, in order to appropriately validate these results. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. A Hardware-Efficient Scalable Spike Sorting Neural Signal Processor Module for Implantable High-Channel-Count Brain Machine Interfaces.

    Science.gov (United States)

    Yang, Yuning; Boling, Sam; Mason, Andrew J

    2017-08-01

    Next-generation brain machine interfaces demand a high-channel-count neural recording system to wirelessly monitor activities of thousands of neurons. A hardware efficient neural signal processor (NSP) is greatly desirable to ease the data bandwidth bottleneck for a fully implantable wireless neural recording system. This paper demonstrates a complete multichannel spike sorting NSP module that incorporates all of the necessary spike detector, feature extractor, and spike classifier blocks. To meet high-channel-count and implantability demands, each block was designed to be highly hardware efficient and scalable while sharing resources efficiently among multiple channels. To process multiple channels in parallel, scalability analysis was performed, and the utilization of each block was optimized according to its input data statistics and the power, area and/or speed of each block. Based on this analysis, a prototype 32-channel spike sorting NSP scalable module was designed and tested on an FPGA using synthesized datasets over a wide range of signal to noise ratios. The design was mapped to 130 nm CMOS to achieve 0.75 μW power and 0.023 mm2 area consumptions per channel based on post synthesis simulation results, which permits scalability of digital processing to 690 channels on a 4×4 mm2 electrode array.

  13. Fatty acid-induced gut-brain signaling attenuates neural and behavioral effects of sad emotion in humans.

    Science.gov (United States)

    Van Oudenhove, Lukas; McKie, Shane; Lassman, Daniel; Uddin, Bilal; Paine, Peter; Coen, Steven; Gregory, Lloyd; Tack, Jan; Aziz, Qasim

    2011-08-01

    Although a relationship between emotional state and feeding behavior is known to exist, the interactions between signaling initiated by stimuli in the gut and exteroceptively generated emotions remain incompletely understood. Here, we investigated the interaction between nutrient-induced gut-brain signaling and sad emotion induced by musical and visual cues at the behavioral and neural level in healthy nonobese subjects undergoing functional magnetic resonance imaging. Subjects received an intragastric infusion of fatty acid solution or saline during neutral or sad emotion induction and rated sensations of hunger, fullness, and mood. We found an interaction between fatty acid infusion and emotion induction both in the behavioral readouts (hunger, mood) and at the level of neural activity in multiple pre-hypothesized regions of interest. Specifically, the behavioral and neural responses to sad emotion induction were attenuated by fatty acid infusion. These findings increase our understanding of the interplay among emotions, hunger, food intake, and meal-induced sensations in health, which may have important implications for a wide range of disorders, including obesity, eating disorders, and depression.

  14. Dual small-molecule targeting of SMAD signaling stimulates human induced pluripotent stem cells toward neural lineages.

    Directory of Open Access Journals (Sweden)

    Methichit Wattanapanitch

    Full Text Available Incurable neurological disorders such as Parkinson's disease (PD, Huntington's disease (HD, and Alzheimer's disease (AD are very common and can be life-threatening because of their progressive disease symptoms with limited treatment options. To provide an alternative renewable cell source for cell-based transplantation and as study models for neurological diseases, we generated induced pluripotent stem cells (iPSCs from human dermal fibroblasts (HDFs and then differentiated them into neural progenitor cells (NPCs and mature neurons by dual SMAD signaling inhibitors. Reprogramming efficiency was improved by supplementing the histone deacethylase inhibitor, valproic acid (VPA, and inhibitor of p160-Rho associated coiled-coil kinase (ROCK, Y-27632, after retroviral transduction. We obtained a number of iPS colonies that shared similar characteristics with human embryonic stem cells in terms of their morphology, cell surface antigens, pluripotency-associated gene and protein expressions as well as their in vitro and in vivo differentiation potentials. After treatment with Noggin and SB431542, inhibitors of the SMAD signaling pathway, HDF-iPSCs demonstrated rapid and efficient differentiation into neural lineages. Six days after neural induction, neuroepithelial cells (NEPCs were observed in the adherent monolayer culture, which had the ability to differentiate further into NPCs and neurons, as characterized by their morphology and the expression of neuron-specific transcripts and proteins. We propose that our study may be applied to generate neurological disease patient-specific iPSCs allowing better understanding of disease pathogenesis and drug sensitivity assays.

  15. Electroencephalogram Signals Processing for the Diagnosis of Petit mal and Grand mal Epilepsies Using an Artificial Neural Network

    Directory of Open Access Journals (Sweden)

    M. R. Arab

    2010-04-01

    Full Text Available In this study, a novel wavelet transform‐neural network method is presented. The presented method is used for theclassification of grand mal (clonic stage and petit mal (absence epilepsies into healthy, ictal and interictal (EEGs. Preprocessingis included to remove an artifact occurred by blinking and a wandering baseline (electrodes movement as well as an eyeballmovement artifact using the Discrete Wavelet Transformation (DWT. Denoising EEG signals from the AC power supplyfrequency with a suitable notch filter is another job of preprocessing. The preprocessing enhanced speed and accuracy of theprocessing stage (wavelet transform and neural network. The EEGs signals are categorized into normal and petit mal and clonicepilepsy by an expert neurologist. The categorization is confirmed by the Fast Fourier Transform (FFT analysis. The datasetincludes waves such as sharp, spike and spike‐slow wave. Through the Countinous Wavelet Transform (CWT of EEG records,transient features are accurately captured and separated and used as classifier input. We introduce a two‐stage classifier basedon the Learning Vector Quantization (LVQ neural network localized in both time and frequency contexts. The particularcoefficients of the Continuous Wavelet Transform (CWT are networks. The simulation results are very promising and theaccuracy of the proposed method obtained is of about 80%.

  16. Quantitative and kinetic profile of Wnt/β-catenin signaling components during human neural progenitor cell differentiation.

    Science.gov (United States)

    Mazemondet, Orianne; Hubner, Rayk; Frahm, Jana; Koczan, Dirk; Bader, Benjamin M; Weiss, Dieter G; Uhrmacher, Adelinde M; Frech, Moritz J; Rolfs, Arndt; Luo, Jiankai

    2011-12-01

    ReNcell VM is an immortalized human neural progenitor cell line with the ability to differentiate in vitro into astrocytes and neurons, in which the Wnt/β-catenin pathway is known to be involved. However, little is known about kinetic changes of this pathway in human neural progenitor cell differentiation. In the present study, we provide a quantitative profile of Wnt/β-catenin pathway dynamics showing its spatio-temporal regulation during ReNcell VM cell differentiation. We show first that T-cell factor dependent transcription can be activated by stabilized β-catenin. Furthermore, endogenous Wnt ligands, pathway receptors and signaling molecules are temporally controlled, demonstrating changes related to differentiation stages. During the first three hours of differentiation the signaling molecules LRP6, Dvl2 and β-catenin are spatio-temporally regulated between distinct cellular compartments. From 24 h onward, components of the Wnt/β-catenin pathway are strongly activated and regulated as shown by mRNA up-regulation of Wnt ligands (Wnt5a and Wnt7a), receptors including Frizzled-2, -3, -6, -7, and -9, and co-receptors, and target genes including Axin2. This detailed temporal profile of the Wnt/β-catenin pathway is a first step to understand, control and to orientate, in vitro, human neural progenitor cell differentiation.

  17. CONCEPTION OF USE VIBROACOUSTIC SIGNALS AND NEURAL NETWORKS FOR DIAGNOSING OF CHOSEN ELEMENTS OF INTERNAL COMBUSTION ENGINES IN CAR VEHICLES

    Directory of Open Access Journals (Sweden)

    Piotr CZECH

    2014-03-01

    Full Text Available Currently used diagnostics systems are not always efficient and do not give straightforward results which allow for the assessment of the technological condition of the engine or for the identification of the possible damages in their early stages of development. Growing requirements concerning durability, reliability, reduction of costs to minimum and decrease of negative influence on the natural environment are the reasons why there is a need to acquire information about the technological condition of each of the elements of a vehicle during its exploitation. One of the possibilities to achieve information about technological condition of a vehicle are vibroacoustic phenomena. Symptoms of defects, achieved as a result of advanced methods of vibroacoustic signals processing can serve as models which can be used during construction of intelligent diagnostic system based on artificial neural networks. The work presents conception of use artificial neural networks in the task of combustion engines diagnosis.

  18. [Retinoic acid signal pathway regulation of zebra fish tooth development through manipulation of the differentiation of neural crest].

    Science.gov (United States)

    Liu, Xin; Huang, Xing; Xu, Zhiyun; Yang, Deqin

    2016-04-01

    To investigate the mechanism of retinoic acid (RA) signal in dental evolution, RA is used to explore the influence of the mechanism on neural crest's migration during the early stage of zebra fish embryos. We divided embryos of wild type and transgenic line zebra fish into three groups. 1 x 10(-7) to 6 x 10(-7) mol x L(-1) RA and 1 x 10(-7) mo x L(-1) 4-diethylaminobenzaldehyde (DEAB) were added into egg water at 24 hpf for 9 h. Dimethyl sulfoxid (DMSO) with the concentration was used as control group. Then, antisense probes of dlx2a, dlx2b, and barxl were formulated to perform whole-mount in situ hybridization to check the expressions of the genes in 48 hpf to 72 hpf embryos. We observed fluorescence of transgenic line in 4 dpf embryos. We obtained three mRNA probes successfully. Compared with DMSO control group, a low concentration (1 x 10(-7) mol x L(-1)) of RA could up-regulate the expression of mRNA (barx1, dlx2a) in neural crest. Obvious migration trend was observed toward the pharyngeal arch in which teeth adhered. Transgenic fish had spreading fluorescence tendency in pharyngeal arch. However, a high concentration (4 x 10(-7) mol x L(-1)) of RA malformed the embryos and killed them after treatment. One third of the embryos of middle concentration (3 x 10(-7) mo x L(-1)) exhibited delayed development. DEAB resulted in neural crest dysplasia. The expression of barxl and dlx2a were suppressed, and the appearance of dlx2b in tooth was delayed. RA signal pathway can regulate the progenitors of tooth by controlling the growth of the neural crest and manipulating tooth development

  19. The Blomia tropicalis allergen Blo t 7 stimulates innate immune signaling pathways through TLR2.

    Science.gov (United States)

    Soongrung, Tewarit; Mongkorntanyatipa, Karntichar; Peepim, Termsri; Buaklin, Arun; Le Mignon, Maxime; Malainual, Nat; Nony, Emmanuel; Jacquet, Alain

    2018-01-22

    Although the house dust mite species Blomia tropicalis is a leading cause of allergic diseases in tropical and subtropical regions, the identification and characterization of the allergenic proteins remains incomplete. We aimed to characterize a recombinant form of Blo t 7 (rBlo t 7) in terms of IgE reactivity, lipid binding activity and ability to stimulate innate immunity. The mature Blo t 7 cDNA was cloned by PCR methods for the expression of a secreted form of the allergen in P. pastoris. The IgE reactivity to purified rBlo t 7 as well as the potential cross-reactivity with Der p 7 were determined by ELISA. The lipid binding capacity of rBlo t 7 was assayed using fluorescent lipid probes. The stimulation of TLR2 signaling pathway by rBlo t 7 was examined in cell activation and reporter assays. The amplified mature Blo t 7 cDNA revealed the presence of a 60 base pair insertion compared with the reference sequence registered in the GENBANK database. Multiple protein sequence alignments of group 7 mite allergens confirmed that this longer deduced amino acid sequence was the authentic Blo t 7 polypeptide chain. Analysis of IgE reactivity can classify rBlo t 7 as an intermediate B. tropicalis allergen which displayed weak cross-reactivity with Der p 7. Purified rBlo t 7 was shown to bind selectively the naturally fluorescent lipid probe cis-parinaric (cPNA) with a dissociation constant of 2 μM. The group 7 Blomia allergen stimulated the TLR2-, NF-kB- and MAPK-dependent production of IL-8 and GM-CSF in respiratory epithelial cells. Through its propensity to transport fatty acids/lipids and to stimulate TLR2 signaling pathways in airway epithelial cells, Blo t 7 can represent a key allergen for the initiation of the B. tropicalis-induced airway inflammation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Grapevine immune signaling network in response to drought stress as revealed by transcriptomic analysis.

    Science.gov (United States)

    Haider, Muhammad S; Kurjogi, Mahantesh M; Khalil-Ur-Rehman, M; Fiaz, Muhammad; Pervaiz, Tariq; Jiu, Songtao; Haifeng, Jia; Chen, Wang; Fang, Jinggui

    2017-12-01

    Drought is a ubiquitous abiotic factor that severely impedes growth and development of horticulture crops. The challenge postured by global climate change is the evolution of drought-tolerant cultivars that could cope with concurrent stress. Hence, in this study, biochemical, physiological and transcriptome analysis were investigated in drought-treated grapevine leaves. The results revealed that photosynthetic activity and reducing sugars were significantly diminished which were positively correlated with low stomatal conductance and CO2 exchange in drought-stressed leaves. Further, the activities of superoxide dismutase, peroxidase, and catalase were significantly actuated in the drought-responsive grapevine leaves. Similarly, the levels of abscisic acid and jasmonic acid were also significantly increased in the drought-stressed leaves. In transcriptome analysis, 12,451 differentially-expressed genes (DEGs) were annotated, out of which 8021 DEGs were up-regulated and 4430 DEGs were down-regulated in response to drought stress. In addition, the genes encoding pathogen-associated molecular pattern (PAMP) triggered immunity (PTI), including calcium signals, protein phosphatase 2C, calcineurin B-like proteins, MAPKs, and phosphorylation (FLS2 and MEKK1) cascades were up-regulated in response to drought stress. Several genes related to plant-pathogen interaction pathway (RPM1, PBS1, RPS5, RIN4, MIN7, PR1, and WRKYs) were also found up-regulated in response to drought stress. Overall the results of present study showed the dynamic interaction of DEG in grapevine physiology which provides the premise for selection of defense-related genes against drought stress for subsequent grapevine breeding programs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Dysregulated brain immunity and neurotrophin signaling in Rett syndrome and autism spectrum disorders.

    Science.gov (United States)

    Theoharides, Theoharis C; Athanassiou, Marianna; Panagiotidou, Smaro; Doyle, Robert

    2015-02-15

    Rett syndrome is a neurodevelopmental disorder, which occurs in about 1:15,000 females and presents with neurologic and communication defects. It is transmitted as an X-linked dominant linked to mutations of the methyl-CpG-binding protein (MeCP2), a gene transcription suppressor, but its definitive pathogenesis is unknown thus hindering development of effective treatments. Almost half of children with Rett syndrome also have behavioral symptoms consistent with those of autism spectrum disorders (ASDs). PubMed was searched (2005-2014) using the terms: allergy, atopy, brain, brain-derived neurotrophic factor (BDNF), corticotropin-releasing hormone (CRH), cytokines, gene mutations, inflammation, mast cells (MCs), microglia, mitochondria, neurotensin (NT), neurotrophins, seizures, stress, and treatment. There are a number of intriguing differences and similarities between Rett syndrome and ASDs. Rett syndrome occurs in females, while ASDs more often in males, and the former has neurologic disabilities unlike ASDs. There is evidence of dysregulated immune system early in life in both conditions. Lack of microglial phagocytosis and decreased levels of BDNF appear to distinguish Rett syndrome from ASDs, in which there is instead microglia activation and/or proliferation and possibly defective BDNF signaling. Moreover, brain mast cell (MC) activation and focal inflammation may be more prominent in ASDs than Rett syndrome. The flavonoid luteolin blocks microglia and MC activation, provides BDNF-like activity, reverses Rett phenotype in mouse models, and has a significant benefit in children with ASDs. Appropriate formulations of luteolin or other natural molecules may be useful in the treatment of Rett syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Characterization of Japanese flounder (Paralichthys olivaceus) Caspase1 involved in extracellular ATP-mediated immune signaling in fish.

    Science.gov (United States)

    Li, Shuo; Peng, Weijiao; Li, Jiafang; Hao, Gaixiang; Geng, Xuyun; Sun, Jinsheng

    2017-08-01

    Caspase1 is a member of inflammatory Caspases that play important roles in the innate immune system. Although several teleost caspase1 genes have been identified, their partner proteins and implication in extracellular ATP-mediated immune signaling in fish are still very limited. Here we identified and characterized a caspase1 gene, named JfCaspase1, from Japanese flounder Paralichthys olivaceus. JfCaspase1 mRNA was constitutively expressed in all examined normal tissues with high expression in skin and gills and moderate expression in the enriched Japanese flounder head kidney macrophages (HKMs) and peripheral blood leukocytes (PBLs). JfCaspase1 was initially down-regulated but significantly up-regulated at the later stage upon LPS and poly(I:C) challenges in the HKMs. JfCaspase1 was also up-regulated in the Japanese flounder immune-related tissues including head kidney, gill and spleen by bacterial challenge with Edwardsiella tarda. JfCaspase1 protein is comprised of 384 amino acid residues with a calculated molecular mass of 43.75 kDa and is phylogenetically close to fish Caspase1 proteins. JfCaspase1 was co-immunopercipitated with Japanese flounder apoptosis-associated speck-like protein (ASC) when co-expressed in HeLa cells, suggesting that there is a potential interaction between the two proteins. In addition, we showed that extracellular ATP, a potent signaling molecule in activating innate immune response, rapidly up-regulates JfCaspase1 expression and enhances its enzymatic activity both in the HKMs and PBLs. Our findings indicated that the inflammatory JfCaspase1 interacted with ASC protein is implicated in the extracellular ATP-mediated immune signaling in fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Activation of STING-Dependent Innate Immune Signaling By S-Phase-Specific DNA Damage in Breast Cancer.

    Science.gov (United States)

    Parkes, Eileen E; Walker, Steven M; Taggart, Laura E; McCabe, Nuala; Knight, Laura A; Wilkinson, Richard; McCloskey, Karen D; Buckley, Niamh E; Savage, Kienan I; Salto-Tellez, Manuel; McQuaid, Stephen; Harte, Mary T; Mullan, Paul B; Harkin, D Paul; Kennedy, Richard D

    2017-01-01

    Previously we identified a DNA damage response-deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling. In this study, we address the mechanism of this immune response and its possible clinical significance. We used immunohistochemistry (IHC) to characterize immune infiltration in 184 breast cancer samples, of which 65 were within the DDRD subtype. Isogenic cell lines, which represent DDRD-positive and -negative, were used to study the effects of chemokine release on peripheral blood mononuclear cell (PBMC) migration and the mechanism of immune signaling activation. Finally, we studied the association between the DDRD subtype and expression of the immune-checkpoint protein PD-L1 as detected by IHC. All statistical tests were two-sided. We found that DDRD breast tumors were associated with CD4+ and CD8+ lymphocytic infiltration (Fisher's exact test P activation of the viral response cGAS/STING/TBK1/IRF3 pathway. Importantly, this pathway was activated in a cell cycle-specific manner. Finally, we demonstrated that S-phase DNA damage activated expression of PD-L1 in a STING-dependent manner. We propose a novel mechanism of immune infiltration in DDRD tumors, independent of neoantigen production. Activation of this pathway and associated PD-L1 expression may explain the paradoxical lack of T-cell-mediated cytotoxicity observed in DDRD tumors. We provide a rationale for exploration of DDRD in the stratification of patients for immune checkpoint-based therapies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Pax3 and Hippo Signaling Coordinate Melanocyte Gene Expression in Neural Crest

    Directory of Open Access Journals (Sweden)

    Lauren J. Manderfield

    2014-12-01

    Full Text Available Loss of Pax3, a developmentally regulated transcription factor expressed in premigratory neural crest, results in severe developmental defects and embryonic lethality. Although Pax3 mutations produce profound phenotypes, the intrinsic transcriptional activation exhibited by Pax3 is surprisingly modest. We postulated the existence of transcriptional coactivators that function with Pax3 to mediate developmental functions. A high-throughput screen identified the Hippo effector proteins Taz and Yap65 as Pax3 coactivators. Synergistic coactivation of target genes by Pax3-Taz/Yap65 requires DNA binding by Pax3, is Tead independent, and is regulated by Hippo kinases Mst1 and Lats2. In vivo, Pax3 and Yap65 colocalize in the nucleus of neural crest progenitors in the dorsal neural tube. Neural crest deletion of Taz and Yap65 results in embryo-lethal neural crest defects and decreased expression of the Pax3 target gene, Mitf. These results suggest that Pax3 activity is regulated by the Hippo pathway and that Pax factors are Hippo effectors.

  5. Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling

    KAUST Repository

    Zeis, T.

    2015-04-01

    Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction. To investigate possible underlying mechanisms we analyzed the molecular alterations in histopathological normal appearing cortical gray matter (NAGM) in MS. By performing a differential gene expression analysis of NAGM of control and MS cases we identified reduced transcription of astrocyte specific genes involved in the astrocyte–neuron lactate shuttle (ANLS) and the glutamate–glutamine cycle (GGC). Additional quantitative immunohistochemical analysis demonstrating a CX43 loss in MS NAGM confirmed a crucial involvement of astrocytes and emphasizes their importance in MS pathogenesis. Concurrently, a Toll-like/IL-1β signaling expression signature was detected in MS NAGM, indicating that immune-related signaling might be responsible for the downregulation of ANLS and GGC gene expression in MS NAGM. Indeed, challenging astrocytes with immune stimuli such as IL-1β and LPS reduced their ANLS and GGC gene expression in vitro. The detected upregulation of IL1B in MS NAGM suggests inflammasome priming. For this reason, astrocyte cultures were treated with ATP and ATP/LPS as for inflammasome activation. This treatment led to a reduction of ANLS and GGC gene expression in a comparable manner. To investigate potential sources for ANLS and GGC downregulation in MS NAGM, we first performed an adjuvant-driven stimulation of the peripheral immune system in C57Bl/6 mice in vivo. This led to similar gene expression changes in spinal cord demonstrating that peripheral immune signals might be one source for astrocytic gene expression changes in the brain. IL1B upregulation in MS NAGM itself points to a possible endogenous signaling process leading to ANLS and GGC downregulation. This is supported by our findings that, among others

  6. Adenosine signaling promotes neuronal, catecholaminergic differentiation of primary neural crest cells and CNS-derived CAD cells.

    Science.gov (United States)

    Bilodeau, Matthew L; Ji, Ming; Paris, Maryline; Andrisani, Ourania M

    2005-07-01

    In neural crest (NC) cultures cAMP signaling is an instructive signal in catecholaminergic, sympathoadrenal cell development. However, the extracellular signals activating the cAMP pathway during NC cell development have not been identified. We demonstrate that in avian NC cultures, evidenced by tyrosine hydroxylase expression and catecholamine biosynthesis, adenosine and not adrenergic signaling, together with BMP2, promotes sympathoadrenal cell development. In NC cultures, addition of the adenosine receptor agonist NECA in the presence of BMP2 promotes sympathoadrenal cell development, whereas the antagonist CGS 15943 or the adenosine degrading enzyme adenosine deaminase (ADA) suppresses TH expression. Importantly, NC cells express A2A and A2B receptors which couple with Gsalpha increasing intracellular cAMP. Employing the CNS-derived catecholaminergic CAD cell line, we also demonstrate that neuronal differentiation mediated by serum withdrawal is further enhanced by treatment with IBMX, a cAMP-elevating agent, or the adenosine receptor agonist NECA, acting via cAMP. By contrast, the adenosine receptor antagonist CGS 15943 or the adenosine degrading enzyme ADA inhibits CAD cell neuronal differentiation mediated by serum withdrawal. These results support that adenosine is a physiological signal in neuronal differentiation of the CNS-derived catecholaminergic CAD cell line and suggest that adenosine signaling is involved in NC cell development in vivo.

  7. A High-Performance Lossless Compression Scheme for EEG Signals Using Wavelet Transform and Neural Network Predictors

    Directory of Open Access Journals (Sweden)

    N. Sriraam

    2012-01-01

    Full Text Available Developments of new classes of efficient compression algorithms, software systems, and hardware for data intensive applications in today's digital health care systems provide timely and meaningful solutions in response to exponentially growing patient information data complexity and associated analysis requirements. Of the different 1D medical signals, electroencephalography (EEG data is of great importance to the neurologist for detecting brain-related disorders. The volume of digitized EEG data generated and preserved for future reference exceeds the capacity of recent developments in digital storage and communication media and hence there is a need for an efficient compression system. This paper presents a new and efficient high performance lossless EEG compression using wavelet transform and neural network predictors. The coefficients generated from the EEG signal by integer wavelet transform are used to train the neural network predictors. The error residues are further encoded using a combinational entropy encoder, Lempel-Ziv-arithmetic encoder. Also a new context-based error modeling is also investigated to improve the compression efficiency. A compression ratio of 2.99 (with compression efficiency of 67% is achieved with the proposed scheme with less encoding time thereby providing diagnostic reliability for lossless transmission as well as recovery of EEG signals for telemedicine applications.

  8. Barley MLA Immune Receptors Directly Interfere with Antagonistically Acting Transcription Factors to Initiate Disease Resistance Signaling[C][W

    Science.gov (United States)

    Chang, Cheng; Yu, Deshui; Jiao, Jian; Jing, Shaojuan; Schulze-Lefert, Paul; Shen, Qian-Hua

    2013-01-01

    The nucleotide binding domain and Leucine-rich repeat (NLR)–containing proteins in plants and animals mediate pathogen sensing inside host cells and mount innate immune responses against microbial pathogens. The barley (Hordeum vulgare) mildew A (MLA) locus encodes coiled-coil (CC)–type NLRs mediating disease resistance against the powdery mildew pathogen Blumeria graminis. Here, we report direct interactions between MLA and two antagonistically acting transcription factors, MYB6 and WRKY1. The N-terminal CC signaling domain of MLA interacts with MYB6 to stimulate its DNA binding activity. MYB6 functions as a positive regulator of basal and MLA-mediated immunity responses to B. graminis. MYB6 DNA binding is antagonized by direct association with WRKY1 repressor, which in turn also interacts with the MLA CC domain. The activated form of full-length MLA10 receptor is needed to release MYB6 activator from WRKY1 repression and to stimulate MYB6-dependent gene expression. This implies that, while sequestered by the WRKY1 repressor in the presence of the resting immune receptor, MYB6 acts as an immediate and positive postactivation signaling component of the active state of MLA during transcriptional reprogramming for innate immune responses. PMID:23532068

  9. Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis

    OpenAIRE

    Tian, Lei; Wen, Qi; Dang, Xiaoqian; You, Wulin; Fan, Lihong; WANG, KUNZHENG

    2014-01-01

    Background Femoral head osteonecrosis is frequently observed in patients treated with excessive corticosteroids. The objective of the current study was to establish a rat model to investigate the disruption of immune response in steroid-induced femoral head osteonecrosis via Toll-like receptor 4 (TLR4) signaling pathway. Methods Male SD rats were divided into the treatment group (group A) and the model group (group B) consisting of 24 rats each, and were injected intramuscularly with 20 mg/kg...

  10. A signal pre-processing algorithm designed for the needs of hardware implementation of neural classifiers used in condition monitoring

    DEFF Research Database (Denmark)

    Dabrowski, Dariusz; Hashemiyan, Zahra; Adamczyk, Jan

    2015-01-01

    Gearboxes have a significant influence on the durability and reliability of a power transmission system. Currently, extensive research studies are being carried out to increase the reliability of gearboxes working in the energy industry, especially with a focus on planetary gears in wind turbines...... is to estimate the features of a vibration signal that are related to failures, e.g. misalignment and unbalance. These features can serve as the components of an input vector for a neural classifier. The approach proposed here has several important benefits: it is resistant to small speed fluctuations up to 7...

  11. A Flexible Terminal Approach to Sampled-Data Exponentially Synchronization of Markovian Neural Networks With Time-Varying Delayed Signals.

    Science.gov (United States)

    Cheng, Jun; Park, Ju H; Karimi, Hamid Reza; Shen, Hao

    2017-08-02

    This paper investigates the problem of sampled-data (SD) exponentially synchronization for a class of Markovian neural networks with time-varying delayed signals. Based on the tunable parameter and convex combination computational method, a new approach named flexible terminal approach is proposed to reduce the conservatism of delay-dependent synchronization criteria. The SD subject to stochastic sampling period is introduced to exhibit the general phenomena of reality. Novel exponential synchronization criterion are derived by utilizing uniform Lyapunov-Krasovskii functional and suitable integral inequality. Finally, numerical examples are provided to show the usefulness and advantages of the proposed design procedure.

  12. Titanium dioxide nanoparticles stimulate sea urchin immune cell phagocytic activity involving TLR/p38 MAPK-mediated signalling pathway

    Science.gov (United States)

    Pinsino, Annalisa; Russo, Roberta; Bonaventura, Rosa; Brunelli, Andrea; Marcomini, Antonio; Matranga, Valeria

    2015-01-01

    Titanium dioxide nanoparticles (TiO2NPs) are one of the most widespread-engineered particles in use for drug delivery, cosmetics, and electronics. However, TiO2NP safety is still an open issue, even for ethical reasons. In this work, we investigated the sea urchin Paracentrotus lividus immune cell model as a proxy to humans, to elucidate a potential pathway that can be involved in the persistent TiO2NP-immune cell interaction in vivo. Morphology, phagocytic ability, changes in activation/inactivation of a few mitogen-activated protein kinases (p38 MAPK, ERK), variations of other key proteins triggering immune response (Toll-like receptor 4-like, Heat shock protein 70, Interleukin-6) and modifications in the expression of related immune response genes were investigated. Our findings indicate that TiO2NPs influence the signal transduction downstream targets of p38 MAPK without eliciting an inflammatory response or other harmful effects on biological functions. We strongly recommend sea urchin immune cells as a new powerful model for nano-safety/nano-toxicity investigations without the ethical normative issue. PMID:26412401

  13. Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3: implications for immune evasion.

    Directory of Open Access Journals (Sweden)

    Haifeng Wang

    Full Text Available Viral infection leads to induction of pattern-recognition receptor signaling, which leads to interferon regulatory factor (IRF activation and ultimately interferon (IFN production. To establish infection, many viruses have strategies to evade the innate immunity. For the hepatitis B virus (HBV, which causes chronic infection in the liver, the evasion strategy remains uncertain. We now show that HBV polymerase (Pol blocks IRF signaling, indicating that HBV Pol is the viral molecule that effectively counteracts host innate immune response. In particular, HBV Pol inhibits TANK-binding kinase 1 (TBK1/IkappaB kinase-epsilon (IKKepsilon, the effector kinases of IRF signaling. Intriguingly, HBV Pol inhibits TBK1/IKKepsilon activity by disrupting the interaction between IKKepsilon and DDX3 DEAD box RNA helicase, which was recently shown to augment TBK1/IKKepsilon activity. This unexpected role of HBV Pol may explain how HBV evades innate immune response in the early phase of the infection. A therapeutic implication of this work is that a strategy to interfere with the HBV Pol-DDX3 interaction might lead to the resolution of life-long persistent infection.

  14. Characterization of Apoptosis Signaling Cascades During the Differentiation Process of Human Neural ReNcell VM Progenitor Cells In Vitro.

    Science.gov (United States)

    Jaeger, Alexandra; Fröhlich, Michael; Klum, Susanne; Lantow, Margareta; Viergutz, Torsten; Weiss, Dieter G; Kriehuber, Ralf

    2015-11-01

    Apoptosis is an essential physiological process accompanying the development of the central nervous system and human neurogenesis. However, the time scale and the underlying molecular mechanisms are yet poorly understood. Due to this fact, we investigated the functionality and general inducibility of apoptosis in the human neural ReNcell VM progenitor cell line during differentiation and also after exposure to staurosporine (STS) and ultraviolet B (UVB) irradiation. Transmission light microscopy, flow cytometry, and Western-/Immunoblot analysis were performed to compare proliferating and differentiating, in addition to STS- and UVB-treated cells. In particular, from 24 to 72 h post-initiation of differentiation, G0/G1 cell cycle arrest, increased loss of apoptotic cells, activation of pro-apoptotic BAX, Caspase-3, and cleavage of its substrate PARP were observed during cell differentiation and, to a higher extent, after treatment with STS and UVB. We conclude that redundant or defective cells are eliminated by apoptosis, while otherwise fully differentiated cells were less responsive to apoptosis induction by STS than proliferating cells, likely as a result of reduced APAF-1 expression, and increased levels of BCL-2. These data provide the evidence that apoptotic mechanisms in the neural ReNcell VM progenitor cell line are not only functional, but also inducible by external stimuli like growth factor withdrawal or treatment with STS and UVB, which marks this cell line as a suitable model to investigate apoptosis signaling pathways in respect to the differentiation processes of human neural progenitor cells in vitro.

  15. Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis.

    Science.gov (United States)

    Tian, Lei; Wen, Qi; Dang, Xiaoqian; You, Wulin; Fan, Lihong; Wang, Kunzheng

    2014-01-15

    Femoral head osteonecrosis is frequently observed in patients treated with excessive corticosteroids. The objective of the current study was to establish a rat model to investigate the disruption of immune response in steroid-induced femoral head osteonecrosis via Toll-like receptor 4 (TLR4) signaling pathway. Male SD rats were divided into the treatment group (group A) and the model group (group B) consisting of 24 rats each, and were injected intramuscularly with 20 mg/kg methylprednisolone (MP) for 8 weeks, once a week. The rats in group A were injected intravenously with 7.5 mg/kg TAK242 before each MP administration. A control group (group N) consisted of 12 rats were received saline injection. All animals were sacrificed 8, 10 and 12 weeks from the first MP injection, respectively. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase (TRAP) in serum was tested. The signaling molecules including TLR4, MyD88, NF-κB p65 and MCP-1 were detected by immunohistochemistry, quantitative real-time PCR and Western blot. Femoral head osteonecrosis was observed in the model rats, and the concentration of TRAP and positive staining of all signaling molecules increased significantly in group B compared with that in group A and group N. Compare with the control group, the mRNA expressions and protein levels of all signaling molecules were enhanced significantly in group B, but no significant in group A. Corticosteroids can induce femoral head osteonecrosis by disturbing the immune response via TLR4 signaling pathway. These findings suggest that the disruption of immune response play a role in the pathogenesis of osteonecrosis.

  16. The Sustained Effect of Emotional Signals on Neural Processing in 12-Month-Olds

    Science.gov (United States)

    Leventon, Jacqueline S.; Bauer, Patricia J.

    2013-01-01

    Around the end of the first year of life, infants develop a social referencing ability -- using emotional information from others to guide their own behavior. Much research on social referencing has focused on changes in behavior in response to emotional information. The present study was an investigation of the changes in neural responses that…

  17. MEG and fMRI fusion for nonlinear estimation of neural and BOLD signal changes

    Directory of Open Access Journals (Sweden)

    Sergey M Plis

    2010-11-01

    Full Text Available The combined analysis of MEG/EEG and functional MRI measurements can lead to improvement in the description of the dynamical and spatial properties of brain activity. In this paper we empirically demonstrate this improvement using simulated and recorded task related MEG and fMRI activity. Neural activity estimates were derived using a dynamic Bayesian network with continuous real valued parameters by means of a sequential Monte Carlo technique. In synthetic data, we show that MEG and fMRI fusion improves estimation of the indirectly observed neural activity and smooths tracking of the BOLD response. In recordings of task related neural activity the combination of MEG and fMRI produces a result with greater SNR, that confirms the expectation arising from the nature of the experiment. The highly nonlinear model of the BOLD response poses a difficult inference problem for neural activity estimation; computational requirements are also high due to the time and space complexity. We show that joint analysis of the data improves the system's behavior by stabilizing the differential equations system and by requiring fewer computational resources.

  18. Targeting cFMS signaling to restore immune function and eradicate HIV reservoirs

    Science.gov (United States)

    Gerngross, Lindsey

    While combination anti-retroviral therapy (cART) has improved the length and quality of life of individuals living with HIV-1 infection, the prevalence of HIV-associated neurocognitive disorders (HAND) has increased and remains a significant clinical concern. The neuropathogenesis of HAND is not completely understood, however, latent HIV infection in the central nervous system (CNS) and chronic neuroinflammation are believed to play a prominent role. CNS-associated macrophages and resident microglia are significant contributors to CNS inflammation and constitute the chief reservoir of HIV-1 infection in the CNS. Previous studies from our lab suggest monocyte/macrophage invasion of the CNS in HIV may be driven by altered monocyte/macrophage homeostasis. We have reported expansion of a monocyte subset (CD14+CD16 +CD163+) in peripheral blood of HIV+ patients that is phenotypically similar to macrophages/microglia that accumulate in the CNS as seen in post-mortem tissue. The factors driving the expansion of this monocyte subset are unknown, however, signaling through cFMS, a type III receptor tyrosine kinase (RTK), may play a role. Macrophage-colony stimulating factor (M-CSF), a ligand of cFMS, has been shown to be elevated in the cerebral spinal fluid (CSF) of individuals with the most severe form of HAND, HIV-associated dementia (HAD). M-CSF promotes a Macrophage-2-like phenotype and increases CD16 and CD163 expression in cultured monocytes. M-CSF has also been shown to increase the susceptibility of macrophages to HIV infection and enhance virus production. These findings, in addition to the known function of M-CSF in promoting macrophage survival, supports a role for M-CSF in the development and maintenance of macrophage viral reservoirs in tissues where these cells accumulate, including the CNS. Interestingly, a second ligand for cFMS, IL-34, was recently identified and reported to share some functions with M-CSF, suggesting that both ligands may contribute to HIV

  19. Sample Entropy Analysis of EEG Signals via Artificial Neural Networks to Model Patients’ Consciousness Level Based on Anesthesiologists Experience

    Directory of Open Access Journals (Sweden)

    George J. A. Jiang

    2015-01-01

    Full Text Available Electroencephalogram (EEG signals, as it can express the human brain’s activities and reflect awareness, have been widely used in many research and medical equipment to build a noninvasive monitoring index to the depth of anesthesia (DOA. Bispectral (BIS index monitor is one of the famous and important indicators for anesthesiologists primarily using EEG signals when assessing the DOA. In this study, an attempt is made to build a new indicator using EEG signals to provide a more valuable reference to the DOA for clinical researchers. The EEG signals are collected from patients under anesthetic surgery which are filtered using multivariate empirical mode decomposition (MEMD method and analyzed using sample entropy (SampEn analysis. The calculated signals from SampEn are utilized to train an artificial neural network (ANN model through using expert assessment of consciousness level (EACL which is assessed by experienced anesthesiologists as the target to train, validate, and test the ANN. The results that are achieved using the proposed system are compared to BIS index. The proposed system results show that it is not only having similar characteristic to BIS index but also more close to experienced anesthesiologists which illustrates the consciousness level and reflects the DOA successfully.

  20. Augmented BMPRIA-mediated BMP signaling in cranial neural crest lineage leads to cleft palate formation and delayed tooth differentiation.

    Directory of Open Access Journals (Sweden)

    Lu Li

    Full Text Available The importance of BMP receptor Ia (BMPRIa mediated signaling in the development of craniofacial organs, including the tooth and palate, has been well illuminated in several mouse models of loss of function, and by its mutations associated with juvenile polyposis syndrome and facial defects in humans. In this study, we took a gain-of-function approach to further address the role of BMPR-IA-mediated signaling in the mesenchymal compartment during tooth and palate development. We generated transgenic mice expressing a constitutively active form of BmprIa (caBmprIa in cranial neural crest (CNC cells that contributes to the dental and palatal mesenchyme. Mice bearing enhanced BMPRIa-mediated signaling in CNC cells exhibit complete cleft palate and delayed odontogenic differentiation. We showed that the cleft palate defect in the transgenic animals is attributed to an altered cell proliferation rate in the anterior palatal mesenchyme and to the delayed palatal elevation in the posterior portion associated with ectopic cartilage formation. Despite enhanced activity of BMP signaling in the dental mesenchyme, tooth development and patterning in transgenic mice appeared normal except delayed odontogenic differentiation. These data support the hypothesis that a finely tuned level of BMPRIa-mediated signaling is essential for normal palate and tooth development.

  1. SU-F-E-09: Respiratory Signal Prediction Based On Multi-Layer Perceptron Neural Network Using Adjustable Training Samples

    Energy Technology Data Exchange (ETDEWEB)

    Sun, W; Jiang, M; Yin, F [Duke University Medical Center, Durham, NC (United States)

    2016-06-15

    Purpose: Dynamic tracking of moving organs, such as lung and liver tumors, under radiation therapy requires prediction of organ motions prior to delivery. The shift of moving organ may change a lot due to huge transform of respiration at different periods. This study aims to reduce the influence of that changes using adjustable training signals and multi-layer perceptron neural network (ASMLP). Methods: Respiratory signals obtained using a Real-time Position Management(RPM) device were used for this study. The ASMLP uses two multi-layer perceptron neural networks(MLPs) to infer respiration position alternately and the training sample will be updated with time. Firstly, a Savitzky-Golay finite impulse response smoothing filter was established to smooth the respiratory signal. Secondly, two same MLPs were developed to estimate respiratory position from its previous positions separately. Weights and thresholds were updated to minimize network errors according to Leverberg-Marquart optimization algorithm through backward propagation method. Finally, MLP 1 was used to predict 120∼150s respiration position using 0∼120s training signals. At the same time, MLP 2 was trained using 30∼150s training signals. Then MLP is used to predict 150∼180s training signals according to 30∼150s training signals. The respiration position is predicted as this way until it was finished. Results: In this experiment, the two methods were used to predict 2.5 minute respiratory signals. For predicting 1s ahead of response time, correlation coefficient was improved from 0.8250(MLP method) to 0.8856(ASMLP method). Besides, a 30% improvement of mean absolute error between MLP(0.1798 on average) and ASMLP(0.1267 on average) was achieved. For predicting 2s ahead of response time, correlation coefficient was improved from 0.61415 to 0.7098.Mean absolute error of MLP method(0.3111 on average) was reduced by 35% using ASMLP method(0.2020 on average). Conclusion: The preliminary results

  2. I can't wait! Neural reward signals in impulsive individuals exaggerate the difference between immediate and future rewards.

    Science.gov (United States)

    Schmidt, Barbara; Holroyd, Clay B; Debener, Stefan; Hewig, Johannes

    2017-03-01

    Waiting for rewards is difficult, and highly impulsive individuals with low self-control have an especially hard time with it. Here, we investigated whether neural responses to rewards in a delayed gratification task predict impulsivity and self-control. The EEG was recorded from participants engaged in a guessing game in which on each trial they could win either a large or small reward, paid either now or after 6 months. Ratings confirmed that participants preferred immediate, large rewards over small, delayed rewards. Electrophysiological reward signals reflecting the difference between immediate and future rewards predicted self-report measures of impulsivity and self-control. Further, these signals were highly reliable across two sessions over a 1-week interval, showing high temporal stability like stable personality traits. These results suggest that greater valuation of immediate rewards causes impulsive individuals to redirect control away from delayed rewards, indicating why it is so hard for them to wait. © 2016 Society for Psychophysiological Research.

  3. Mutations in FLS2 Ser-938 Dissect Signaling Activation in FLS2-Mediated Arabidopsis Immunity

    Science.gov (United States)

    Cao, Yangrong; Aceti, David J.; Sabat, Grzegorz; Song, Junqi; Makino, Shin-ichi; Fox, Brian G.; Bent, Andrew F.

    2013-01-01

    FLAGELLIN-SENSING 2 (FLS2) is a leucine-rich repeat/transmembrane domain/protein kinase (LRR-RLK) that is the plant receptor for bacterial flagellin or the flagellin-derived flg22 peptide. Previous work has shown that after flg22 binding, FLS2 releases BIK1 kinase and homologs and associates with BAK1 kinase, and that FLS2 kinase activity is critical for FLS2 function. However, the detailed mechanisms for activation of FLS2 signaling remain unclear. The present study initially identified multiple FLS2 in vitro phosphorylation sites and found that Serine-938 is important for FLS2 function in vivo. FLS2-mediated immune responses are abolished in transgenic plants expressing FLS2S938A, while the acidic phosphomimic mutants FLS2S938D and FLS2S938E conferred responses similar to wild-type FLS2. FLS2-BAK1 association and FLS2-BIK1 disassociation after flg22 exposure still occur with FLS2S938A, demonstrating that flg22-induced BIK1 release and BAK1 binding are not sufficient for FLS2 activity, and that Ser-938 controls other aspects of FLS2 activity. Purified BIK1 still phosphorylated purified FLS2S938A and FLS2S938D mutant kinase domains in vitro. Phosphorylation of BIK1 and homologs after flg22 exposure was disrupted in transgenic Arabidopsis thaliana plants expressing FLS2S938A or FLS2D997A (a kinase catalytic site mutant), but was normally induced in FLS2S938D plants. BIK1 association with FLS2 required a kinase-active FLS2, but FLS2-BAK1 association did not. Hence FLS2-BIK1 dissociation and FLS2-BAK1 association are not sufficient for FLS2-mediated defense activation, but the proposed FLS2 phosphorylation site Ser-938 and FLS2 kinase activity are needed both for overall defense activation and for appropriate flg22-stimulated phosphorylation of BIK1 and homologs. PMID:23637603

  4. A CMOS power-efficient low-noise current-mode front-end amplifier for neural signal recording.

    Science.gov (United States)

    Wu, Chung-Yu; Chen, Wei-Ming; Kuo, Liang-Ting

    2013-04-01

    In this paper, a new current-mode front-end amplifier (CMFEA) for neural signal recording systems is proposed. In the proposed CMFEA, a current-mode preamplifier with an active feedback loop operated at very low frequency is designed as the first gain stage to bypass any dc offset current generated by the electrode-tissue interface and to achieve a low high-pass cutoff frequency below 0.5 Hz. No reset signal or ultra-large pseudo resistor is required. The current-mode preamplifier has low dc operation current to enhance low-noise performance and decrease power consumption. A programmable current gain stage is adopted to provide adjustable gain for adaptive signal scaling. A following current-mode filter is designed to adjust the low-pass cutoff frequency for different neural signals. The proposed CMFEA is designed and fabricated in 0.18-μm CMOS technology and the area of the core circuit is 0.076 mm(2). The measured high-pass cutoff frequency is as low as 0.3 Hz and the low-pass cutoff frequency is adjustable from 1 kHz to 10 kHz. The measured maximum current gain is 55.9 dB. The measured input-referred current noise density is 153 fA /√Hz , and the power consumption is 13 μW at 1-V power supply. The fabricated CMFEA has been successfully applied to the animal test for recording the seizure ECoG of Long-Evan rats.

  5. CYLD Limits Lys63- and Met1-Linked Ubiquitin at Receptor Complexes to Regulate Innate Immune Signaling

    Directory of Open Access Journals (Sweden)

    Matous Hrdinka

    2016-03-01

    Full Text Available Innate immune signaling relies on the deposition of non-degradative polyubiquitin at receptor-signaling complexes, but how these ubiquitin modifications are regulated by deubiquitinases remains incompletely understood. Met1-linked ubiquitin (Met1-Ub is assembled by the linear ubiquitin assembly complex (LUBAC, and this is counteracted by the Met1-Ub-specific deubiquitinase OTULIN, which binds to the catalytic LUBAC subunit HOIP. In this study, we report that HOIP also interacts with the deubiquitinase CYLD but that CYLD does not regulate ubiquitination of LUBAC components. Instead, CYLD limits extension of Lys63-Ub and Met1-Ub conjugated to RIPK2 to restrict signaling and cytokine production. Accordingly, Met1-Ub and Lys63-Ub were individually required for productive NOD2 signaling. Our study thus suggests that LUBAC, through its associated deubiquitinases, coordinates the deposition of not only Met1-Ub but also Lys63-Ub to ensure an appropriate response to innate immune receptor activation.

  6. Cross-regulation between n metabolism and nitric oxide (no) signaling during plant immunity

    OpenAIRE

    Thalineau, Elise; Truong, Hoai-Nam; Berger, Antoine; Fournier, Carine; Boscari, Alexandre; Wendehenne, David; Jeandroz, Sylvain

    2016-01-01

    Plants are sessile organisms that have evolved a complex immune system which helps them cope with pathogen attacks. However, the capacity of a plant to mobilize different defense responses is strongly affected by its physiological status. Nitrogen (N) is a major nutrient that can play an important role in plant immunity by increasing or decreasing plant resistance to pathogens. Although no general rule can be drawn about the effect of N availability and quality on the fate of plant/pathogen i...

  7. Simulation of signal flow in 3D reconstructions of an anatomically realistic neural network in rat vibrissal cortex.

    Science.gov (United States)

    Lang, Stefan; Dercksen, Vincent J; Sakmann, Bert; Oberlaender, Marcel

    2011-11-01

    The three-dimensional (3D) structure of neural circuits represents an essential constraint for information flow in the brain. Methods to directly monitor streams of excitation, at subcellular and millisecond resolution, are at present lacking. Here, we describe a pipeline of tools that allow investigating information flow by simulating electrical signals that propagate through anatomically realistic models of average neural networks. The pipeline comprises three blocks. First, we review tools that allow fast and automated acquisition of 3D anatomical data, such as neuron soma distributions or reconstructions of dendrites and axons from in vivo labeled cells. Second, we introduce NeuroNet, a tool for assembling the 3D structure and wiring of average neural networks. Finally, we introduce a simulation framework, NeuroDUNE, to investigate structure-function relationships within networks of full-compartmental neuron models at subcellular, cellular and network levels. We illustrate the pipeline by simulations of a reconstructed excitatory network formed between the thalamus and spiny stellate neurons in layer 4 (L4ss) of a cortical barrel column in rat vibrissal cortex. Exciting the ensemble of L4ss neurons with realistic input from an ensemble of thalamic neurons revealed that the location-specific thalamocortical connectivity may result in location-specific spiking of cortical cells. Specifically, a radial decay in spiking probability toward the column borders could be a general feature of signal flow in a barrel column. Our simulations provide insights of how anatomical parameters, such as the subcellular organization of synapses, may constrain spiking responses at the cellular and network levels. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Multiple excitatory and inhibitory neural signals converge to fine-tune Caenorhabditis elegans feeding to food availability

    Science.gov (United States)

    Dallière, Nicolas; Bhatla, Nikhil; Luedtke, Zara; Ma, Dengke K.; Woolman, Jonathan; Walker, Robert J.; Holden-Dye, Lindy; O’Connor, Vincent

    2016-01-01

    How an animal matches feeding to food availability is a key question for energy homeostasis. We addressed this in the nematode Caenorhabditis elegans, which couples feeding to the presence of its food (bacteria) by regulating pharyngeal activity (pumping). We scored pumping in the presence of food and over an extended time course of food deprivation in wild-type and mutant worms to determine the neural substrates of adaptive behavior. Removal of food initially suppressed pumping but after 2 h this was accompanied by intermittent periods of high activity. We show pumping is fine-tuned by context-specific neural mechanisms and highlight a key role for inhibitory glutamatergic and excitatory cholinergic/peptidergic drives in the absence of food. Additionally, the synaptic protein UNC-31 [calcium-activated protein for secretion (CAPS)] acts through an inhibitory pathway not explained by previously identified contributions of UNC-31/CAPS to neuropeptide or glutamate transmission. Pumping was unaffected by laser ablation of connectivity between the pharyngeal and central nervous system indicating signals are either humoral or intrinsic to the enteric system. This framework in which control is mediated through finely tuned excitatory and inhibitory drives resonates with mammalian hypothalamic control of feeding and suggests that fundamental regulation of this basic animal behavior may be conserved through evolution from nematode to human.—Dallière, N., Bhatla, N., Luedtke, Z., Ma, D. K., Woolman, J., Walker, R. J., Holden-Dye, L., O’Connor, V. Multiple excitatory and inhibitory neural signals converge to fine-tune Caenorhabditis elegans feeding to food availability. PMID:26514165

  9. Neural network activation during a stop-signal task discriminates cocaine-dependent from non-drug-abusing men.

    Science.gov (United States)

    Elton, Amanda; Young, Jonathan; Smitherman, Sonet; Gross, Robin E; Mletzko, Tanja; Kilts, Clinton D

    2014-05-01

    Cocaine dependence is defined by a loss of inhibitory control over drug-use behaviors, mirrored by measurable impairments in laboratory tasks of inhibitory control. The current study tested the hypothesis that deficits in multiple subprocesses of behavioral control are associated with reliable neural-processing alterations that define cocaine addiction. While undergoing functional magnetic resonance imaging (fMRI), 38 cocaine-dependent men and 27 healthy control men performed a stop-signal task of motor inhibition. An independent component analysis on fMRI time courses identified task-related neural networks attributed to motor, visual, cognitive and affective processes. The statistical associations of these components with five different stop-signal task conditions were selected for use in a linear discriminant analysis to define a classifier for cocaine addiction from a subsample of 26 cocaine-dependent men and 18 controls. Leave-one-out cross-validation accurately classified 89.5% (39/44; chance accuracy = 26/44 = 59.1%) of subjects with 84.6% (22/26) sensitivity and 94.4% (17/18) specificity. The remaining 12 cocaine-dependent and 9 control men formed an independent test sample, for which accuracy of the classifier was 81.9% (17/21; chance accuracy = 12/21 = 57.1%) with 75% (9/12) sensitivity and 88.9% (8/9) specificity. The cocaine addiction classification score was significantly correlated with a measure of impulsiveness as well as the duration of cocaine use for cocaine-dependent men. The results of this study support the ability of a pattern of multiple neural network alterations associated with inhibitory motor control to define a binary classifier for cocaine addiction. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  10. Canonical Wnt/β-catenin signaling is required for maintenance but not activation of Pitx2 expression in neural crest during eye development.

    Science.gov (United States)

    Zacharias, Amanda L; Gage, Philip J

    2010-12-01

    Pitx2 is a paired-like homeodomain gene that acts as a key regulator of eye development. Despite its significance, upstream regulation of Pitx2 expression during eye development remains incompletely understood. We use neural crest-specific ablation of Ctnnb1 to demonstrate that canonical Wnt signaling is not required for initial activation of Pitx2 in neural crest. However, canonical Wnt signaling is subsequently required to maintain Pitx2 expression in the neural crest. Eye development in Ctnnb1-null mice appears grossly normal early but significant phenotypes emerge following loss of Pitx2 expression. LEF-1 and β-catenin bind Pitx2 promoter sequences in ocular neural crest, indicating a likely direct effect of canonical Wnt signaling on Pitx2 expression. Combining our data with previous reports, we propose a model wherein a sequential code of retinoic acid followed by canonical Wnt signaling are required for activation and maintenance of Pitx2 expression, respectively. Other key transcription factors in the neural crest, including Foxc1, do not require intact canonical Wnt signaling. Copyright © 2010 Wiley-Liss, Inc.

  11. Hop-on hop-off: importin-a-guided tours to the nucleus in innate immune signaling

    Directory of Open Access Journals (Sweden)

    Lennart eWirthmueller

    2013-05-01

    Full Text Available Nuclear translocation of immune regulatory proteins and signal transducers is an essential process in animal and plant defense signaling against pathogenic microbes. Import of proteins containing a nuclear localization signal (NLS into the nucleus is mediated by nuclear transport receptors (NTRs termed importins, typically dimers of a cargo-binding alpha-subunit and a beta-subunit that mediates translocation through the nuclear pore complex (NPC. Here, we review recent reports of importin-alpha cargo specificity and mutant phenotypes in plant- and animal-microbe interactions. Using homology modeling of the NLS-binding cleft of nine predicted Arabidopsis alpha-importins and analyses of their gene expression patterns, we discuss functional redundancy and specialization within this transport receptor family. In addition, we consider how pathogen effector proteins that promote infection by manipulating host cell nuclear processes might compete with endogenous cargo proteins for nuclear uptake.

  12. Disrupting morphosyntactic and lexical semantic processing has opposite effects on the sample entropy of neural signals.

    Science.gov (United States)

    Fonseca, André; Boboeva, Vezha; Brederoo, Sanne; Baggio, Giosuè

    2015-04-16

    Converging evidence in neuroscience suggests that syntax and semantics are dissociable in brain space and time. However, it is possible that partly disjoint cortical networks, operating in successive time frames, still perform similar types of neural computations. To test the alternative hypothesis, we collected EEG data while participants read sentences containing lexical semantic or morphosyntactic anomalies, resulting in N400 and P600 effects, respectively. Next, we reconstructed phase space trajectories from EEG time series, and we measured the complexity of the resulting dynamical orbits using sample entropy - an index of the rate at which the system generates or loses information over time. Disrupting morphosyntactic or lexical semantic processing had opposite effects on sample entropy: it increased in the N400 window for semantic anomalies, and it decreased in the P600 window for morphosyntactic anomalies. These findings point to a fundamental divergence in the neural computations supporting meaning and grammar in language. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Classification of Human Emotions from EEG Signals using Statistical Features and Neural Network

    OpenAIRE

    Chai Tong Yuen; Woo San San; Tan Ching Seong; Mohamed Rizon

    2009-01-01

    A statistical based system for human emotions classification by using electroencephalogram (EEG) is proposed in this paper. The data used in this study is acquired using EEG and the emotions are elicited from six human subjects under the effect of emotion stimuli. This paper also proposed an emotion stimulation experiment using visual stimuli. From the EEG data, a total of six statistical features are computed and back-propagation neural network is applied for the classification of human emot...

  14. “Eating” Cancer cells by blocking CD47 signaling: Cancer therapy by targeting the innate immune checkpoint

    Directory of Open Access Journals (Sweden)

    Yi-Rong Xiang

    2017-01-01

    Full Text Available Differing from the adaptive immune checkpoint mediated by programmed cell death-1 (PD-1 PD-1-ligand or CTLA-4, the CD47 and signal regulatory protein α (SIRPα axis is emerging as a novel innate immune checkpoint of the immune cells of myeloid lineage. A balance should be established between the dual signals, the “Don't eat me signal” of CD47-SIRPα and the “Eat me signal” of calreticulin/low-density lipoprotein receptor-related protein. The enhanced expression of CD47 molecule has been found in many cancer tissues, including malignant blood tumors (acute myeloid leukemia and solid tumors. A therapeutic value could be achieved by counteracting the expression of CD47 in cancer cells. In the recent years, great progress has been made to develop anticancer therapies by targeting CD47 (e.g., anti-CD47 antibody, in various types of cancer. However, there are a few challenges, like “antigen sink” in the clinical translation of CD47-mediated anticancer therapies, the attention to which is crucial.

  15. Calcium-mediated repression of β-catenin and its transcriptional signaling mediates neural crest cell death in an avian model of fetal alcohol syndrome.

    Science.gov (United States)

    Flentke, George R; Garic, Ana; Amberger, Ed; Hernandez, Marcos; Smith, Susan M

    2011-07-01

    Fetal alcohol syndrome (FAS) is a common birth defect in many societies. Affected individuals have neurodevelopmental disabilities and a distinctive craniofacial dysmorphology. These latter deficits originate during early development from the ethanol-mediated apoptotic depletion of cranial facial progenitors, a population known as the neural crest. We showed previously that this apoptosis is caused because acute ethanol exposure activates G-protein-dependent intracellular calcium within cranial neural crest progenitors, and this calcium transient initiates the cell death. The dysregulated signals that reside downstream of ethanol's calcium transient and effect neural crest death are unknown. Here we show that ethanol's repression of the transcriptional effector β-catenin causes the neural crest losses. Clinically relevant ethanol concentrations (22-78 mM) rapidly deplete nuclear β-catenin from neural crest progenitors, with accompanying losses of β-catenin transcriptional activity and downstream genes that govern neural crest induction, expansion, and survival. Using forced expression studies, we show that β-catenin loss of function (via dominant-negative T cell transcription factor [TCF]) recapitulates ethanol's effects on neural crest apoptosis, whereas β-catenin gain-of-function in ethanol's presence preserves neural crest survival. Blockade of ethanol's calcium transient using Bapta-AM normalizes β-catenin activity and prevents the neural crest losses, whereas ionomycin treatment is sufficient to destabilize β-catenin. We propose that ethanol's repression of β-catenin causes the neural crest losses in this model of FAS. β-Catenin is a novel target for ethanol's teratogenicity. β-Catenin/Wnt signals participate in many developmental events and its rapid and persistent dysregulation by ethanol may explain why the latter is such a potent teratogen. Copyright © 2011 Wiley-Liss, Inc.

  16. The Calcium-Mediated Repression of β-Catenin and Its Transcriptional Signaling Mediates Neural Crest Cell Death in an Avian Model of Fetal Alcohol Syndrome

    Science.gov (United States)

    Flentke, George R.; Garic, Ana; Amberger, Ed; Hernandez, Marcos; Smith, Susan M.

    2016-01-01

    Fetal Alcohol Syndrome (FAS) is a common birth defect in many societies. Affected individuals have neurodevelopmental disabilities and a distinctive craniofacial dysmorphology. These latter deficits originate during early development from the ethanol-mediated apoptotic depletion of cranial facial progenitors, a population known as the neural crest. We showed previously that this apoptosis is caused because acute ethanol exposure activates a G protein-dependent intracellular calcium within cranial neural crest progenitors, and this calcium transient initiates the cell death. The dysregulated signals that reside downstream of ethanol’s calcium transient and effect neural crest death are unknown. Here we show that ethanol’s repression of the transcriptional effector β-catenin causes the neural crest losses. Clinically-relevant ethanol concentrations (22–78 mM) rapidly deplete nuclear β-catenin from neural crest progenitors, with accompanying losses of β-catenin transcriptional activity and downstream genes that govern neural crest induction, expansion and survival. Using forced expression studies we show that β-catenin loss of function (via dominant-negative TCF) recapitulates ethanol’s effects on neural crest apoptosis, whereas β-catenin gain-of-function in ethanol’s presence preserves neural crest survival. Blockade of ethanol’s calcium transient using Bapta-AM normalizes β-catenin activity and prevents the neural crest losses, whereas ionomycin treatment is sufficient to destabilize β-catenin. We propose that ethanol’s repression of β-catenin causes the neural crest losses in this model of FAS. β-Catenin is a novel target for ethanol’s teratogenicity. β-Catenin/Wnt signals participate in many developmental events and its rapid and persistent dysregulation by ethanol may explain why the latter is such a potent teratogen. PMID:21630427

  17. Simultaneous in vivo recording of local brain temperature and electrophysiological signals with a novel neural probe

    Science.gov (United States)

    Fekete, Z.; Csernai, M.; Kocsis, K.; Horváth, Á. C.; Pongrácz, A.; Barthó, P.

    2017-06-01

    Objective. Temperature is an important factor for neural function both in normal and pathological states, nevertheless, simultaneous monitoring of local brain temperature and neuronal activity has not yet been undertaken. Approach. In our work, we propose an implantable, calibrated multimodal biosensor that facilitates the complex investigation of thermal changes in both cortical and deep brain regions, which records multiunit activity of neuronal populations in mice. The fabricated neural probe contains four electrical recording sites and a platinum temperature sensor filament integrated on the same probe shaft within a distance of 30 µm from the closest recording site. The feasibility of the simultaneous functionality is presented in in vivo studies. The probe was tested in the thalamus of anesthetized mice while manipulating the core temperature of the animals. Main results. We obtained multiunit and local field recordings along with measurement of local brain temperature with accuracy of 0.14 °C. Brain temperature generally followed core body temperature, but also showed superimposed fluctuations corresponding to epochs of increased local neural activity. With the application of higher currents, we increased the local temperature by several degrees without observable tissue damage between 34-39 °C. Significance. The proposed multifunctional tool is envisioned to broaden our knowledge on the role of the thermal modulation of neuronal activity in both cortical and deeper brain regions.

  18. Adjuvant-active aqueous extracts from Artemisia rupestris L. improve immune responses through TLR4 signaling pathway.

    Science.gov (United States)

    Zhang, Ailian; Yang, Yu; Wang, Yan; Zhao, Gan; Yang, Xiumei; Wang, Danyang; Wang, Bin

    2017-02-15

    Activating innate immunity by an adjuvant is required in vaccine development. The study aims to investigate adjuvant effects of aqueous extracts of Artemisia rupestris L. (AEAR) in vivo and in vitro. ICR mice were subcutaneously administered with antigen and AEAR at various doses to evaluate their immune responses of antibodies, dendritic cells (DCs), regulatory T cells (Treg), splenic lymphocyte, and cytokine. The evaluation results showed that AEAR could largely increase titers of antigen-specific antibodies (IgG, IgG 1 , and IgG 2a ) and T cell proliferation. AEAR also increased expression of IFN-γ in CD8 + T cells as well as IL-4 and INF-γ expression in CD4 + T cells. Expression levels of MHC-II, CD40, CD80, and CD86 on DCs were significantly elevated, whereas the Treg frequency was significantly decreased. AEAR (200μg) showed remarkable adjuvant activity. Furthermore, AEAR enhanced MHC-II, CD40, CD80, and CD86 expression as well as the yields of TNF-α and IL-12 on DCs through toll-like receptor4 (TLR4) in vitro. Those results indicated that AEAR could serve as an efficacious immune stimulator for vaccines because it significantly enhanced specific immune responses by promoting DCs maturation and reduced Treg through TLR4 signaling pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Estimation of Potential Interference Immunity of Radio Reception with Spatial Signal Processing in Mutipath Radio-Communication Channels. Part II. Meter and Decimeter Ranges

    Science.gov (United States)

    Lvov, A. V.; Metelev, S. L.

    2016-11-01

    We propose simulation models for estimating the interference immunity of radio reception using the spatial processing of signals in the airborne and ground-based communication channels of the meter and decimeter wavelength ranges. The ultimate achievable interference immunity under various radio-wave propagation conditions is studied.

  20. Deletion of the Innate Immune NLRP3 Receptor Abolishes Cardiac Ischemic Preconditioning and Is Associated with Decreased Il-6/STAT3 Signaling

    NARCIS (Netherlands)

    Zuurbier, Coert J.; Jong, Willeke M. C.; Eerbeek, Otto; Koeman, Anneke; Pulskens, Wilco P.; Butter, Loes M.; Leemans, Jaklien C.; Hollmann, Markus W.

    2012-01-01

    Objective: Recent studies indicate that the innate immune system is not only triggered by exogenous pathogens and pollutants, but also by endogenous danger signals released during ischemia and necrosis. As triggers for the innate immune NLRP3 inflammasome protein complex appear to overlap with those

  1. Deletion of the innate immune NLRP3 receptor abolishes cardiac ischemic preconditioning and is associated with decreased Il-6/STAT3 signaling

    NARCIS (Netherlands)

    Zuurbier, C.J.; Jong, W.M.; Eerbeek, O.; Koeman, A.; Pulskens, W.P.C.; Butter, L.M.; Leemans, J.C.; Hollmann, M.W.

    2012-01-01

    OBJECTIVE: Recent studies indicate that the innate immune system is not only triggered by exogenous pathogens and pollutants, but also by endogenous danger signals released during ischemia and necrosis. As triggers for the innate immune NLRP3 inflammasome protein complex appear to overlap with those

  2. KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington's disease patients

    Science.gov (United States)

    Quinti, Luisa; Dayalan Naidu, Sharadha; Träger, Ulrike; Chen, Xiqun; Kegel-Gleason, Kimberly; Llères, David; Connolly, Colúm; Chopra, Vanita; Low, Cho; Moniot, Sébastien; Sapp, Ellen; Tousley, Adelaide R.; Vodicka, Petr; Van Kanegan, Michael J.; Kaltenbach, Linda S.; Crawford, Lisa A.; Fuszard, Matthew; Higgins, Maureen; Miller, James R. C.; Farmer, Ruth E.; Potluri, Vijay; Samajdar, Susanta; Meisel, Lisa; Zhang, Ningzhe; Snyder, Andrew; Stein, Ross; Hersch, Steven M.; Ellerby, Lisa M.; Schwarzschild, Michael A.; Steegborn, Clemens; Leavitt, Blair R.; Degterev, Alexei; Tabrizi, Sarah J.; Lo, Donald C.; DiFiglia, Marian; Thompson, Leslie M.; Dinkova-Kostova, Albena T.; Kazantsev, Aleksey G.

    2017-01-01

    The activity of the transcription factor nuclear factor-erythroid 2 p45-derived factor 2 (NRF2) is orchestrated and amplified through enhanced transcription of antioxidant and antiinflammatory target genes. The present study has characterized a triazole-containing inducer of NRF2 and elucidated the mechanism by which this molecule activates NRF2 signaling. In a highly selective manner, the compound covalently modifies a critical stress-sensor cysteine (C151) of the E3 ligase substrate adaptor protein Kelch-like ECH-associated protein 1 (KEAP1), the primary negative regulator of NRF2. We further used this inducer to probe the functional consequences of selective activation of NRF2 signaling in Huntington's disease (HD) mouse and human model systems. Surprisingly, we discovered a muted NRF2 activation response in human HD neural stem cells, which was restored by genetic correction of the disease-causing mutation. In contrast, selective activation of NRF2 signaling potently repressed the release of the proinflammatory cytokine IL-6 in primary mouse HD and WT microglia and astrocytes. Moreover, in primary monocytes from HD patients and healthy subjects, NRF2 induction repressed expression of the proinflammatory cytokines IL-1, IL-6, IL-8, and TNFα. Together, our results demonstrate a multifaceted protective potential of NRF2 signaling in key cell types relevant to HD pathology. PMID:28533375

  3. Regulation of Toll-like receptor 4-mediated immune responses through Pasteurella multocida toxin-induced G protein signalling

    Directory of Open Access Journals (Sweden)

    Hildebrand Dagmar

    2012-08-01

    Full Text Available Abstract Background Lipopolysaccharide (LPS-triggered Toll-like receptor (TLR 4-signalling belongs to the key innate defence mechanisms upon infection with Gram-negative bacteria and triggers the subsequent activation of adaptive immunity. There is an active crosstalk between TLR4-mediated and other signalling cascades to secure an effective immune response, but also to prevent excessive inflammation. Many pathogens induce signalling cascades via secreted factors that interfere with TLR signalling to modify and presumably escape the host response. In this context heterotrimeric G proteins and their coupled receptors have been recognized as major cellular targets. Toxigenic strains of Gram-negative Pasteurella multocida produce a toxin (PMT that constitutively activates the heterotrimeric G proteins Gαq, Gα13 and Gαi independently of G protein-coupled receptors through deamidation. PMT is known to induce signalling events involved in cell proliferation, cell survival and cytoskeleton rearrangement. Results Here we show that the activation of heterotrimeric G proteins through PMT suppresses LPS-stimulated IL-12p40 production and eventually impairs the T cell-activating ability of LPS-treated monocytes. This inhibition of TLR4-induced IL-12p40 expression is mediated by Gαi-triggered signalling as well as by Gβγ-dependent activation of PI3kinase and JNK. Taken together we propose the following model: LPS stimulates TLR4-mediated activation of the NFĸB-pathway and thereby the production of TNF-α, IL-6 and IL-12p40. PMT inhibits the production of IL-12p40 by Gαi-mediated inhibition of adenylate cyclase and cAMP accumulation and by Gβγ-mediated activation of PI3kinase and JNK activation. Conclusions On the basis of the experiments with PMT this study gives an example of a pathogen-induced interaction between G protein-mediated and TLR4-triggered signalling and illustrates how a bacterial toxin is able to interfere with the host’s immune

  4. The obtaining of statistical characteristics of informative features of signals in the Autonomous information systems using neural networks

    Directory of Open Access Journals (Sweden)

    V. K. Hohlov

    2014-01-01

    Full Text Available The article studies a neural network approach to obtain the statistical characteristics of the input vector implementations of signal and noise at ill-conditioned matrices of correlation moments to solve the problems to select and reduce the vector dimensions of informative features at detection and recognition of signals and noise based on regression methods.A scientific novelty is determined by applying neural network algorithms for the efficient solution of problems to select the informative features and determine the parameters of regression algorithms in terms of the degeneracy or ill-conditioned data with unknown expectation and covariance matrices.The article proposes to use a single-layer neural network with no zero weights and activation functions to calculate the initial regression characteristics and the mean-square value error of multiple initial regression representations, which are necessary to justify the selection of informative features, reduce a dimension of sign vectors and implement the regression algorithms. It is shown that when excluding direct links between the inputs and their corresponding neurons, in the training network the weight coefficients of neuron inputs are the coefficients of initial multiple regression, the error meansquare value of multiple initial regression representations is calculated at the outputs of neurons. The article considers conditionality of the problem to calculate the matrix that is inverse one for matrix of correlation moments. It defines a condition number, which characterizes the relative error of stated task.The problem concerning the matrix condition of the correlation moment of informative signal features and noise arises when solving the problem to find the multiple coefficients of initial regression (MCIR and the residual mean-square values of the multiple regression representations. For obtaining the MCIR and finding the residual mean-square values the matrix of correlation moments of

  5. Immunobiotic Bifidobacteria Strains Modulate Rotavirus Immune Response in Porcine Intestinal Epitheliocytes via Pattern Recognition Receptor Signaling.

    Directory of Open Access Journals (Sweden)

    Takamasa Ishizuka

    Full Text Available In this work, we aimed to characterize the antiviral response of an originally established porcine intestinal epithelial cell line (PIE cells by evaluating the molecular innate immune response to rotavirus (RVs. In addition, we aimed to select immunomodulatory bacteria with antiviral capabilities. PIE cells were inoculated with RVs isolated from different host species and the infective titers and the molecular innate immune response were evaluated. In addition, the protection against RVs infection and the modulation of immune response by different lactic acid bacteria (LAB strains was studied. The RVs strains OSU (porcine and UK (bovine effectively infected PIE cells. Our results also showed that RVs infection in PIE cells triggered TLR3-, RIG-I- and MDA-5-mediated immune responses with activation of IRF3 and NF-κB, induction of IFN-β and up-regulation of the interferon stimulated genes MxA and RNase L. Among the LAB strains tested, Bifidobacterium infantis MCC12 and B. breve MCC1274 significantly reduced RVs titers in infected PIE cells. The beneficial effects of both bifidobacteria were associated with reduction of A20 expression, and improvements of IRF-3 activation, IFN-β production, and MxA and RNase L expressions. These results indicate the value of PIE cells for studying RVs molecular innate immune response in pigs and for the selection of beneficial bacteria with antiviral capabilities.

  6. Development of an ex Vivo Method for Multi-unit Recording of Microbiota-Colonic-Neural Signaling in Real Time

    Directory of Open Access Journals (Sweden)

    Maria M. Buckley

    2018-02-01

    Full Text Available Background and Objectives: Bidirectional signaling between the gastrointestinal tract and the brain is vital for maintaining whole-body homeostasis. Moreover, emerging evidence implicates vagal afferent signaling in the modulation of host physiology by microbes, which are most abundant in the colon. This study aims to optimize and advance dissection and recording techniques to facilitate real-time recordings of afferent neural signals originating in the distal colon.New Protocol: This paper describes a dissection technique, which facilitates extracellular electrophysiological recordings from visceral pelvic, spinal and vagal afferent neurons in response to stimulation of the distal colon.Examples of Application: Focal application of 75 mM KCl to a section of distal colon with exposed submucosal or myenteric nerve cell bodies and sensory nerve endings evoked activity in the superior mesenteric plexus and the vagal nerve. Noradrenaline stimulated nerve activity in the superior mesenteric plexus, whereas application of carbachol stimulated vagal nerve activity. Exposure of an ex vivo section of distal colon with an intact colonic mucosa to peptidoglycan, but not lipopolysaccharide, evoked vagal nerve firing.Discussion: Previous studies have recorded vagal signaling evoked by bacteria in the small intestine. The technical advances of this dissection and recording technique facilitates recording of afferent nerve signals evoked in extrinsic sensory pathways by neuromodulatory reagents applied to the distal colon. Moreover, we have demonstrated vagal afferent activation evoked by bacterial products applied to the distal colonic mucosa. This protocol may contribute to our understanding of functional bowel disorders where gut-brain communication is dysfunctional, and facilitate real-time interrogation of microbiota-gut-brain signaling.

  7. Characterization of cellular immune response and innate immune signaling in human and nonhuman primate primary mononuclear cells exposed to Burkholderia mallei.

    Science.gov (United States)

    Alam, Shahabuddin; Amemiya, Kei; Bernhards, Robert C; Ulrich, Robert G; Waag, David M; Saikh, Kamal U

    2015-01-01

    Burkholderia pseudomallei infection causes melioidosis and is often characterized by severe sepsis. Although rare in humans, Burkholderia mallei has caused infections in laboratory workers, and the early innate cellular response to B. mallei in human and nonhuman primates has not been characterized. In this study, we examined the primary cellular immune response to B. mallei in PBMC cultures of non-human primates (NHPs), Chlorocebus aethiops (African Green Monkeys), Macaca fascicularis (Cynomolgus macaque), and Macaca mulatta (Rhesus macaque) and humans. Our results demonstrated that B. mallei elicited strong primary pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, and IL-6) equivalent to the levels of B. pseudomallei in primary PBMC cultures of NHPs and humans. When we examined IL-1β and other cytokine responses by comparison to Escherichia coli LPS, African Green Monkeys appears to be most responsive to B. mallei than Cynomolgus or Rhesus. Characterization of the immune signaling mechanism for cellular response was conducted by using a ligand induced cell-based reporter assay, and our results demonstrated that MyD88 mediated signaling contributed to the B. mallei and B. pseudomallei induced pro-inflammatory responses. Notably, the induced reporter activity with B. mallei, B. pseudomallei, or purified LPS from these pathogens was inhibited and cytokine production was attenuated by a MyD88 inhibitor. Together, these results show that in the scenario of severe hyper-inflammatory responses to B. mallei infection, MyD88 targeted therapeutic intervention may be a successful strategy for therapy. Published by Elsevier Ltd.

  8. Implications of central immune signaling caused by drugs of abuse: mechanisms, mediators and new therapeutic approaches for prediction and treatment of drug dependence.

    Science.gov (United States)

    Coller, Janet K; Hutchinson, Mark R

    2012-05-01

    In the past two decades a trickle of manuscripts examining the non-neuronal central nervous system immune consequences of the drugs of abuse has now swollen to a significant body of work. Initially, these studies reported associative evidence of central nervous system proinflammation resulting from exposure to the drugs of abuse demonstrating key implications for neurotoxicity and disease progression associated with, for example, HIV infection. However, more recently this drug-induced activation of central immune signaling is now understood to contribute substantially to the pharmacodynamic actions of the drugs of abuse, by enhancing the engagement of classical mesolimbic dopamine reward pathways and withdrawal centers. This review will highlight the key in vivo animal, human, biological and molecular evidence of these central immune signaling actions of opioids, alcohol, cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). Excitingly, this new appreciation of central immune signaling activity of drugs of abuse provides novel therapeutic interventions and opportunities to identify 'at risk' individuals through the use of immunogenetics. Discussion will also cover the evidence of modulation of this signaling by existing clinical and pre-clinical drug candidates, and novel pharmacological targets. Finally, following examination of the breadth of central immune signaling actions of the drugs of abuse highlighted here, the current known common immune signaling components will be outlined and their impact on established addiction neurocircuitry discussed, thereby synthesizing a common neuroimmune hypothesis of addiction. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. On the saliva proteome of the Eastern European house mouse (Mus musculus musculus) focusing on sexual signalling and immunity.

    Science.gov (United States)

    Stopka, Pavel; Kuntová, Barbora; Klempt, Petr; Havrdová, Leona; Černá, Martina; Stopková, Romana

    2016-08-31

    Chemical communication is mediated by sex-biased signals abundantly present in the urine, saliva and tears. Because most studies concentrated on the urinary signals, we aimed to determine the saliva proteome in wild Mus musculus musculus, to extend the knowledge on potential roles of saliva in chemical communication. We performed the gel-free quantitative LC-MS/MS analyses of saliva and identified 633 proteins with 134 (21%) of them being sexually dimorphic. They include proteins that protect and transport volatile organic compounds in their beta barrel including LCN lipocalins, major urinary proteins (MUPs), and odorant binding proteins (OBPs). To our surprise, the saliva proteome contains one MUP that is female biased (MUP8) and the two protein pheromones MUP20 (or 'Darcin') and ESP1 in individuals of both sex. Thus, contrary to previous assumptions, our findings reveal that these proteins cannot function as male-unique signals. Our study also demonstrates that many olfactory proteins (e.g. LCNs, and OBPs) are not expressed by submandibular glands but are produced elsewhere-in nasal and lacrimal tissues, and potentially also in other oro-facial glands. We have also detected abundant proteins that are involved in wound healing, immune and non-immune responses to pathogens, thus corroborating that saliva has important protective roles.

  10. Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity.

    Science.gov (United States)

    Chen, Shasha; Cai, Chenxu; Li, Zehua; Liu, Guangao; Wang, Yuande; Blonska, Marzenna; Li, Dan; Du, Juan; Lin, Xin; Yang, Meixiang; Dong, Zhongjun

    2017-02-01

    Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) mutations in X-linked lymphoproliferative disease (XLP) lead to defective NKT cell development and impaired humoral immunity. Because of the redundancy of SLAM family receptors (SFRs) and the complexity of SAP actions, how SFRs and SAP mediate these processes remains elusive. Here, we examined NKT cell development and humoral immunity in mice completely deficient in SFR. We found that SFR deficiency severely impaired NKT cell development. In contrast to SAP deficiency, SFR deficiency caused no apparent defect in follicular helper T (TFH) cell differentiation. Intriguingly, the deletion of SFRs completely rescued the severe defect in TFH cell generation caused by SAP deficiency, whereas SFR deletion had a minimal effect on the defective NKT cell development in SAP-deficient mice. These findings suggest that SAP-dependent activating SFR signaling is essential for NKT cell selection; however, SFR signaling is inhibitory in SAP-deficient TFH cells. Thus, our current study revises our understanding of the mechanisms underlying T cell defects in patients with XLP. © 2017 Chen et al.

  11. HIV-1-infected and immune-activated macrophages induce astrocytic differentiation of human cortical neural progenitor cells via the STAT3 pathway.

    Directory of Open Access Journals (Sweden)

    Hui Peng

    Full Text Available Diminished adult neurogenesis is considered a potential mechanism in the pathogenesis of HIV-1-associated dementia (HAD. In HAD, HIV-1-infected and immune-activated brain mononuclear phagocytes (MP; perivascular macrophages and microglia drive central nervous system (CNS inflammation and may alter normal neurogenesis. We previously demonstrated HIV-1-infected and lipopolysaccharide (LPS activated monocyte-derived macrophages (MDM inhibit human neural progenitor cell (NPC neurogenesis, while enhancing astrogliogenesis through the secretion of the inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α, in vitro and in vivo. Here we further test the hypothesis that HIV-1-infected/activated MDM promote NPC astrogliogenesis via activation of the transcription factor signal transducer and activator of transcription 3 (STAT3, a critical factor for astrogliogenesis. Our results show that LPS-activated MDM-conditioned medium (LPS-MCM and HIV-infected/LPS-activated MDM-conditioned medium (LPS+HIV-MCM induced Janus kinase 1 (Jak1 and STAT3 activation. Induction of the Jak-STAT3 activation correlated with increased glia fibrillary acidic protein (GFAP expression, demonstrating an induction of astrogliogenesis. Moreover, STAT3-targeting siRNA (siSTAT3 decreased MCM-induced STAT3 activation and NPC astrogliogenesis. Furthermore, inflammatory cytokines (including IL-6, IL-1β and TNF-α produced by LPS-activated and/or HIV-1-infected MDM may contribute to MCM-induced STAT3 activation and astrocytic differentiation. These observations were confirmed in severe combined immunodeficient (SCID mice with HIV-1 encephalitis (HIVE. In HIVE mice, siRNA control (without target sequence, sicon pre-transfected NPCs injected with HIV-1-infected MDM showed more astrocytic differentiation and less neuronal differentiation of NPCs as compared to NPC injection alone. siSTAT3 abrogated HIV-1-infected MDM-induced astrogliogenesis of injected NPCs. Collectively, these

  12. Acquired Immune Resistance Follows Complete Tumor Regression without Loss of Target Antigens or IFN gamma Signaling

    DEFF Research Database (Denmark)

    Donia, Marco; Harbst, Katja; van Buuren, Marit

    2017-01-01

    Cancer immunotherapy can result in durable tumor regressions in some patients. However, patients who initially respond often experience tumor progression. Here, we report mechanistic evidence of tumoral immune escape in an exemplary clinical case: a patient with metastatic melanoma who developed...... disease recurrence following an initial, unequivocal radiologic complete regression after T-cell-based immunotherapy. Functional cytotoxic T-cell responses, including responses to one mutant neoantigen, were amplified effectively with therapy and generated durable immunologic memory. However, these immune...... radiologic regression. Personalized studies to uncover mechanisms leading to disease recurrence within each individual patient are warranted....

  13. Detecting causal interdependence in simulated neural signals based on pairwise and multivariate analysis.

    Science.gov (United States)

    Yang, C; Le Bouquin Jeannes, R; Faucon, G; Wendling, F

    2010-01-01

    Our objective is to analyze EEG signals recorded with depth electrodes during seizures in patients with drug-resistant epilepsy. Usually, different phases are observed during the seizure process, including a fast onset activity (FOA). We aim to determine how cerebral structures get involved during this FOA, in particular whether some structure can "drive" some other structures. This paper focuses on a linear Granger causality based measure to detect causal relation of interdependence in multivariate signals generated by a physiology-based model of coupled neuronal populations. When coupling between signals exists, statistical analysis supports the relevance of this index for characterizing the information flow and its direction among neuronal populations.

  14. Improved exponential convergence result for generalized neural networks including interval time-varying delayed signals.

    Science.gov (United States)

    Rajchakit, G; Saravanakumar, R; Ahn, Choon Ki; Karimi, Hamid Reza

    2017-02-01

    This article examines the exponential stability analysis problem of generalized neural networks (GNNs) including interval time-varying delayed states. A new improved exponential stability criterion is presented by establishing a proper Lyapunov-Krasovskii functional (LKF) and employing new analysis theory. The improved reciprocally convex combination (RCC) and weighted integral inequality (WII) techniques are utilized to obtain new sufficient conditions to ascertain the exponential stability result of such delayed GNNs. The superiority of the obtained results is clearly demonstrated by numerical examples. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Application of Polynomial Neural Networks to Classification of Acoustic Warfare Signals

    Science.gov (United States)

    1993-04-01

    fcf’𔄁IC nf20 uqe o.’ C eouinq thil b4𔃺*e to yWash’nOntq .1u0tos Svverl’ t. O’at r ;0, rl’ -f’ Of 0ly ,"non s *( O no 4’ W~c’mt 1)$ ’T .c~qOuQ~O ’ llno...Report NOSC TD 1855, Naval Ocean Systems Center, San Diego, May, 1990. [34] Ghosh, J., L. Deuser, and S. Beck, "A neural network based hybrid system

  16. A low-power, low-noise neural-signal amplifier circuit in 90-nm CMOS.

    Science.gov (United States)

    Zarifi, M H; Frounchi, J; Farshchi, S; Judy, J W

    2008-01-01

    A fully-differential low-power low-noise preamplifier for biopotential and neural-recording applications is presented. This design, which has been simulated in a standard 90-nm CMOS process, consumes 30 microW from a 3-V power supply. The simulated integrated input-referred noise is 2.3 microV over 0.1 Hz to 20 kHz. The amplifier also provides an output swing of +/- 0.9 V with a THD of less than 0.1%

  17. Advanced microarray analysis highlights modified neuro-immune signaling in nucleated blood cells from Parkinson's disease patients.

    Science.gov (United States)

    Soreq, Lilach; Israel, Zvi; Bergman, Hagai; Soreq, Hermona

    2008-09-15

    Laboratory tests for Parkinson's disease (PD) were recently extended to microarray analyses of nucleated blood cells. Here, we report the use of statistical and gene ontology tools to re-examine these microarray data. Distribution plots and PCA mapping enabled removal of several outliers out of the 105 analyzed PD and control samples, which improved the discriminative power for PD blood cells compared to healthy and neurological disease controls. Combined with gene ontology tests, our findings point at neuro-immune signaling-related transcripts as distinctly expressed early in PD progress and call for exploiting microarray tests also for follow-up of PD treatment efficacy.

  18. Adaptive and innate immune reactions regulating mast cell activation: from receptor-mediated signaling to responses

    DEFF Research Database (Denmark)

    Tkaczyk, Christine; Jensen, Bettina M; Iwaki, Shoko

    2006-01-01

    In this article, we have described studies that have demonstrated that mast cells can be activated as a consequence of adaptive and innate immune reactions and that these responses can be modified by ligands for other receptors expressed on the surface of mast cells. These various stimuli...

  19. Milling tool wear diagnosis by feed motor current signal using an artificial neural network

    Energy Technology Data Exchange (ETDEWEB)

    Khajavi, Mehrdad Nouri; Nasernia, Ebrahim; Rostaghi, Mostafa [Dept. of Mechanical Engineering, Shahid Rajaee Teacher Training University, Tehran (Iran, Islamic Republic of)

    2016-11-15

    In this paper, a Multi-layer perceptron (MLP) neural network was used to predict tool wear in face milling. For this purpose, a series of experiments was conducted using a milling machine on a CK45 work piece. Tool wear was measured by an optical microscope. To improve the accuracy and reliability of the monitoring system, tool wear state was classified into five groups, namely, no wear, slight wear, normal wear, severe wear and broken tool. Experiments were conducted with the aforementioned tool wear states, and different machining conditions and data were extracted. An increase in current amplitude was observed as the tool wear increased. Furthermore, effects of parameters such as tool wear, feed, and cut depth on motor current consumption were analyzed. Considering the complexity of the wear state classification, a multi-layer neural network was used. The root mean square of motor current, feed, cut depth, and tool rpm were chosen as the input and amount of flank wear as the output of MLP. Results showed good performance of the designed tool wear monitoring system.

  20. Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function.

    Science.gov (United States)

    Subramaniam, Karuna; Hooker, Christine I; Biagianti, Bruno; Fisher, Melissa; Nagarajan, Srikantan; Vinogradov, Sophia

    2015-01-01

    Amotivation in schizophrenia is a central predictor of poor functioning, and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy comparison (HC) participants, reward anticipation is associated with activity in frontal-striatal networks. By contrast, schizophrenia (SZ) participants show hypoactivation within these frontal-striatal networks during this motivated anticipatory brain state. Here, we examined neural activation in SZ and HC participants during the anticipatory phase of stimuli that predicted immediate upcoming reward and punishment, and during the feedback/outcome phase, in relation to trait measures of hedonic pleasure and real-world functional capacity. SZ patients showed hypoactivation in ventral striatum during reward anticipation. Additionally, we found distinct differences between HC and SZ groups in their association between reward-related immediate anticipatory neural activity and their reported experience of pleasure. HC participants recruited reward-related regions in striatum that significantly correlated with subjective consummatory pleasure, while SZ patients revealed activation in attention-related regions, such as the IPL, which correlated with consummatory pleasure and functional capacity. These findings may suggest that SZ patients activate compensatory attention processes during anticipation of immediate upcoming rewards, which likely contribute to their functional capacity in daily life.

  1. Neural Correlates of Visual Spatial Attention in Electrocorticographic (ECoG Signals in Humans

    Directory of Open Access Journals (Sweden)

    Aysegul eGunduz

    2011-09-01

    Full Text Available Attention is a cognitive selection mechanism that allocates the limited processing resources of the brain to the sensory streams most relevant to our immediate goals, thereby enhancing responsiveness and behavioral performance. The underlying neural mechanisms of orienting attention are distributedacross a widespread cortical network. While aspects of this network have been extensively studied, details about the electrophysiological dynamics of this network are scarce. In this study, we investigated attentional networks using electrocorticographic (ECoG recordings from the surface ofthe brain, which combine broad spatial coverage with high temporal resolution, in five human subjects. ECoG was recorded when subjects covertly attended to a spatial location and responded to contrast changes in the presence of distractors in a modified Posner cueing task. ECoG amplitudes in the alpha, beta and gamma bands identified neural changes associated with covert attention and motor preparation/execution in the different stages of the task. The results show that attentional engagement was primarily associated with ECoG activity in the visual, prefrontal, premotor, and parietal cortices. Motor preparation/execution was associated with ECoG activity in premotor/sensorimotor cortices. In summary, our results illustrate rich and distributed cortical dynamics that are associated with orienting attention and the subsequent motor preparation and execution. These findings are largely consistent with and expand on primate studies using intracortical recordings and human functional neuroimaging studies.

  2. Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function

    Directory of Open Access Journals (Sweden)

    Karuna Subramaniam

    2015-01-01

    Full Text Available Amotivation in schizophrenia is a central predictor of poor functioning, and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy comparison (HC participants, reward anticipation is associated with activity in frontal–striatal networks. By contrast, schizophrenia (SZ participants show hypoactivation within these frontal–striatal networks during this motivated anticipatory brain state. Here, we examined neural activation in SZ and HC participants during the anticipatory phase of stimuli that predicted immediate upcoming reward and punishment, and during the feedback/outcome phase, in relation to trait measures of hedonic pleasure and real-world functional capacity. SZ patients showed hypoactivation in ventral striatum during reward anticipation. Additionally, we found distinct differences between HC and SZ groups in their association between reward-related immediate anticipatory neural activity and their reported experience of pleasure. HC participants recruited reward-related regions in striatum that significantly correlated with subjective consummatory pleasure, while SZ patients revealed activation in attention-related regions, such as the IPL, which correlated with consummatory pleasure and functional capacity. These findings may suggest that SZ patients activate compensatory attention processes during anticipation of immediate upcoming rewards, which likely contribute to their functional capacity in daily life.

  3. Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function

    Science.gov (United States)

    Subramaniam, Karuna; Hooker, Christine I.; Biagianti, Bruno; Fisher, Melissa; Nagarajan, Srikantan; Vinogradov, Sophia

    2015-01-01

    Amotivation in schizophrenia is a central predictor of poor functioning, and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy comparison (HC) participants, reward anticipation is associated with activity in frontal–striatal networks. By contrast, schizophrenia (SZ) participants show hypoactivation within these frontal–striatal networks during this motivated anticipatory brain state. Here, we examined neural activation in SZ and HC participants during the anticipatory phase of stimuli that predicted immediate upcoming reward and punishment, and during the feedback/outcome phase, in relation to trait measures of hedonic pleasure and real-world functional capacity. SZ patients showed hypoactivation in ventral striatum during reward anticipation. Additionally, we found distinct differences between HC and SZ groups in their association between reward-related immediate anticipatory neural activity and their reported experience of pleasure. HC participants recruited reward-related regions in striatum that significantly correlated with subjective consummatory pleasure, while SZ patients revealed activation in attention-related regions, such as the IPL, which correlated with consummatory pleasure and functional capacity. These findings may suggest that SZ patients activate compensatory attention processes during anticipation of immediate upcoming rewards, which likely contribute to their functional capacity in daily life. PMID:26413478

  4. Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling

    Directory of Open Access Journals (Sweden)

    Bruno Pereira Carreira

    2014-10-01

    Full Text Available Neuroinflammation is characterized by activation of microglial cells, followed by production of nitric oxide (NO, which may have different outcomes on neurogenesis, favoring or inhibiting this process. In the present study, we investigated how the inflammatory mediator NO can affect proliferation of neural stem cells (NSC, and explored possible mechanisms underlying this effect. We investigated which mechanisms are involved in the regulation of NSC proliferation following treatment with an inflammatory stimulus (LPS plus IFN-γ, using a culture system of subventricular zone (SVZ-derived NSC mixed with microglia cells obtained from wild-type mice (iNOS+/+ or from iNOS knockout mice (iNOS-/-. We found an impairment of NSC cell proliferation in iNOS+/+ mixed cultures, which was not observed in iNOS-/- mixed cultures. Furthermore, the increased release of NO by activated iNOS+/+ microglial cells decreased the activation of the ERK/MAPK signaling pathway, which was concomitant with an enhanced nitration of the EGF receptor. Preventing nitrogen reactive species formation with MnTBAP, a scavenger of peroxynitrite, or using the peroxynitrite degradation catalyst FeTMPyP, cell proliferation and ERK signaling were restored to basal levels in iNOS+/+ mixed cultures. Moreover, exposure to the NO donor NOC-18 (100 µM, for 48 h, inhibited SVZ-derived NSC proliferation. Regarding the antiproliferative effect of NO, we found that NOC-18 caused the impairment of signaling through the ERK/MAPK pathway, which may be related to increased nitration of the EGF receptor in NSC. Using MnTBAP nitration was prevented, maintaining ERK signaling, rescuing NSC proliferation. We show that NO from inflammatory origin leads to a decreased function of the EGF receptor, which compromised proliferation of NSC. We also demonstrated that NO-mediated nitration of the EGF receptor caused a decrease in its phosphorylation, thus preventing regular proliferation signaling through the

  5. R-Peak Detection using Daubechies Wavelet and ECG Signal Classification using Radial Basis Function Neural Network

    Science.gov (United States)

    Rai, H. M.; Trivedi, A.; Chatterjee, K.; Shukla, S.

    2014-01-01

    This paper employed the Daubechies wavelet transform (WT) for R-peak detection and radial basis function neural network (RBFNN) to classify the electrocardiogram (ECG) signals. Five types of ECG beats: normal beat, paced beat, left bundle branch block (LBBB) beat, right bundle branch block (RBBB) beat and premature ventricular contraction (PVC) were classified. 500 QRS complexes were arbitrarily extracted from 26 records in Massachusetts Institute of Technology-Beth Israel Hospital (MIT-BIH) arrhythmia database, which are available on Physionet website. Each and every QRS complex was represented by 21 points from p1 to p21 and these QRS complexes of each record were categorized according to types of beats. The system performance was computed using four types of parameter evaluation metrics: sensitivity, positive predictivity, specificity and classification error rate. The experimental result shows that the average values of sensitivity, positive predictivity, specificity and classification error rate are 99.8%, 99.60%, 99.90% and 0.12%, respectively with RBFNN classifier. The overall accuracy achieved for back propagation neural network (BPNN), multilayered perceptron (MLP), support vector machine (SVM) and RBFNN classifiers are 97.2%, 98.8%, 99% and 99.6%, respectively. The accuracy levels and processing time of RBFNN is higher than or comparable with BPNN, MLP and SVM classifiers.

  6. Multiple excitatory and inhibitory neural signals converge to fine-tune Caenorhabditis elegans feeding to food availability.

    Science.gov (United States)

    Dallière, Nicolas; Bhatla, Nikhil; Luedtke, Zara; Ma, Dengke K; Woolman, Jonathan; Walker, Robert J; Holden-Dye, Lindy; O'Connor, Vincent

    2016-02-01

    How an animal matches feeding to food availability is a key question for energy homeostasis. We addressed this in the nematode Caenorhabditis elegans, which couples feeding to the presence of its food (bacteria) by regulating pharyngeal activity (pumping). We scored pumping in the presence of food and over an extended time course of food deprivation in wild-type and mutant worms to determine the neural substrates of adaptive behavior. Removal of food initially suppressed pumping but after 2 h this was accompanied by intermittent periods of high activity. We show pumping is fine-tuned by context-specific neural mechanisms and highlight a key role for inhibitory glutamatergic and excitatory cholinergic/peptidergic drives in the absence of food. Additionally, the synaptic protein UNC-31 [calcium-activated protein for secretion (CAPS)] acts through an inhibitory pathway not explained by previously identified contributions of UNC-31/CAPS to neuropeptide or glutamate transmission. Pumping was unaffected by laser ablation of connectivity between the pharyngeal and central nervous system indicating signals are either humoral or intrinsic to the enteric system. This framework in which control is mediated through finely tuned excitatory and inhibitory drives resonates with mammalian hypothalamic control of feeding and suggests that fundamental regulation of this basic animal behavior may be conserved through evolution from nematode to human. © FASEB.

  7. E3D hand movement velocity reconstruction using power spectral density of EEG signals and neural network.

    Science.gov (United States)

    Korik, A; Siddique, N; Sosnik, R; Coyle, D

    2015-08-01

    Three dimensional (3D) limb motion trajectory is predictable with a non-invasive brain-computer interface (BCI). To date, most non-invasive motion trajectory prediction BCIs use potential values of electroencephalographic (EEG) signals as the input to a multiple linear regression (mLR) based kinetic data estimator. We investigated the possible improvement in accuracy of 3D hand movement prediction (i.e., the correlation of registered and reconstructed hand velocities) by replacing raw EEG potentials with spectrum power values of specific EEG bands. We also investigated if a non-linear neural network based estimator outperformed the mLR approach. The spectrum power model provided significantly higher accuracy (R~0.60) compared to the similar EEG potentials based approach (R~0.45). Additionally, when replacing the mLR based kinetic data estimation module with a feed-forward neural network (NN) we found the NN based spectrum power model provided higher accuracy (R~0.70) compared to the similar mLR based approach (R~0.60).

  8. States versus rewards: dissociable neural prediction error signals underlying model-based and model-free reinforcement learning.

    Science.gov (United States)

    Gläscher, Jan; Daw, Nathaniel; Dayan, Peter; O'Doherty, John P

    2010-05-27

    Reinforcement learning (RL) uses sequential experience with situations ("states") and outcomes to assess actions. Whereas model-free RL uses this experience directly, in the form of a reward prediction error (RPE), model-based RL uses it indirectly, building a model of the state transition and outcome structure of the environment, and evaluating actions by searching this model. A state prediction error (SPE) plays a central role, reporting discrepancies between the current model and the observed state transitions. Using functional magnetic resonance imaging in humans solving a probabilistic Markov decision task, we found the neural signature of an SPE in the intraparietal sulcus and lateral prefrontal cortex, in addition to the previously well-characterized RPE in the ventral striatum. This finding supports the existence of two unique forms of learning signal in humans, which may form the basis of distinct computational strategies for guiding behavior. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Fault Diagnosis System of Induction Motors Based on Neural Network and Genetic Algorithm Using Stator Current Signals

    Directory of Open Access Journals (Sweden)

    Tian Han

    2006-01-01

    Full Text Available This paper proposes an online fault diagnosis system for induction motors through the combination of discrete wavelet transform (DWT, feature extraction, genetic algorithm (GA, and neural network (ANN techniques. The wavelet transform improves the signal-to-noise ratio during a preprocessing. Features are extracted from motor stator current, while reducing data transfers and making online application available. GA is used to select the most significant features from the whole feature database and optimize the ANN structure parameter. Optimized ANN is trained and tested by the selected features of the measurement data of stator current. The combination of advanced techniques reduces the learning time and increases the diagnosis accuracy. The efficiency of the proposed system is demonstrated through motor faults of electrical and mechanical origins on the induction motors. The results of the test indicate that the proposed system is promising for the real-time application.

  10. Homeostatic NF-κB Signaling in Steady-State Migratory Dendritic Cells Regulates Immune Homeostasis and Tolerance.

    Science.gov (United States)

    Baratin, Myriam; Foray, Chloe; Demaria, Olivier; Habbeddine, Mohamed; Pollet, Emeline; Maurizio, Julien; Verthuy, Christophe; Davanture, Suzel; Azukizawa, Hiroaki; Flores-Langarica, Adriana; Dalod, Marc; Lawrence, Toby

    2015-04-21

    Migratory non-lymphoid tissue dendritic cells (NLT-DCs) transport antigens to lymph nodes (LNs) and are required for protective immune responses in the context of inflammation and to promote tolerance to self-antigens in steady-state. However, the molecular mechanisms that elicit steady-state NLT-DC maturation and migration are unknown. By comparing the transcriptome of NLT-DCs in the skin with their migratory counterparts in draining LNs, we have identified a novel NF-κB-regulated gene network specific to migratory DCs. We show that targeted deletion of IKKβ in DCs, a major activator of NF-κB, prevents NLT-DC accumulation in LNs and compromises regulatory T cell conversion in vivo. This was associated with impaired tolerance and autoimmunity. NF-κB is generally considered the prototypical pro-inflammatory transcription factor, but this study describes a role for NF-κB signaling in DCs for immune homeostasis and tolerance that could have implications in autoimmune diseases and immunity. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Classification of EMG signals using artificial neural networks for virtual hand prosthesis control.

    Science.gov (United States)

    Mattioli, Fernando E R; Lamounier, Edgard A; Cardoso, Alexandre; Soares, Alcimar B; Andrade, Adriano O

    2011-01-01

    Computer-based training systems have been widely studied in the field of human rehabilitation. In health applications, Virtual Reality presents itself as an appropriate tool to simulate training environments without exposing the patients to risks. In particular, virtual prosthetic devices have been used to reduce the great mental effort needed by patients fitted with myoelectric prosthesis, during the training stage. In this paper, the application of Virtual Reality in a hand prosthesis training system is presented. To achieve this, the possibility of exploring Neural Networks in a real-time classification system is discussed. The classification technique used in this work resulted in a 95% success rate when discriminating 4 different hand movements.

  12. The Interplay between Radioresistant Caco-2 Cells and the Immune System Increases Epithelial Layer Permeability and Alters Signaling Protein Spectrum

    Science.gov (United States)

    Morini, Jacopo; Babini, Gabriele; Barbieri, Sofia; Baiocco, Giorgio; Ottolenghi, Andrea

    2017-01-01

    Colorectal cancer is one of the most frequent type of cancer, with a higher incidence in the developed countries. Colorectal cancer is usually managed with both surgeries, chemotherapy and radiotherapy. Radiotherapy has the well-known advantage of targeting the tumor, minimizing normal tissue exposure. Nevertheless, during radiation treatment, exposure of healthy tissues is of great concern, in particular because of the effects on the intestinal barrier functions and on cells belonging to the immune system. The functional role of intestinal barrier in avoiding paracellular trafficking and controlling bacterial spread from gut it is well known and it is due to the presence of tight junction complexes. However, intestinal barrier is fundamental in participating to the interplay with immune system, especially considering the gut-associated lymphoid tissue. Until few years ago, radiotherapy was considered to bear only a depressive action on the immune system. However, it is now recognized that the release of pro-inflammatory signals and phenotypic changes in tumoral cells due to ionizing radiation could trigger the immune system against the tumor. In this work, we address how intestinal barrier functions are perturbed by X-ray doses in the range 0–10 Gy, focusing on the interplay between tumoral cells and the immune system. To this aim, we adopted a coculture model in which Caco-2 cells can be grown in presence/absence of peripheral blood mononuclear cells (PBMC). We focused our attention on changes in the proliferation, trans-epithelial electrical resistance (TEER), cytokine release, and proteins of the junctional complexes. Our results indicate a high radioresistance of Caco-2 in the investigated dose range, and an increased permeability of the tumoral cell layer due to the presence of PBMC. This is found to be correlated with activation of PBMC, inhibiting the apoptotic pathway, with the enhancement of cytokine release and with variation of tight junction

  13. Estimating complicated baselines in analytical signals using the iterative training of Bayesian regularized artificial neural networks.

    Science.gov (United States)

    Mani-Varnosfaderani, Ahmad; Kanginejad, Atefeh; Gilany, Kambiz; Valadkhani, Abolfazl

    2016-10-12

    The present work deals with the development of a new baseline correction method based on the comparative learning capabilities of artificial neural networks. The developed method uses the Bayes probability theorem for prevention of the occurrence of the over-fitting and finding a generalized baseline. The developed method has been applied on simulated and real metabolomic gas-chromatography (GC) and Raman data sets. The results revealed that the proposed method can be used to handle different types of baselines with cave, convex, curvelinear, triangular and sinusoidal patterns. For further evaluation of the performances of this method, it has been compared with benchmarking baseline correction methods such as corner-cutting (CC), morphological weighted penalized least squares (MPLS), adaptive iteratively-reweighted penalized least squares (airPLS) and iterative polynomial fitting (iPF). In order to compare the methods, the projected difference resolution (PDR) criterion has been calculated for the data before and after the baseline correction procedure. The calculated values of PDR after the baseline correction using iBRANN, airPLS, MPLS, iPF and CC algorithms for the GC metabolomic data were 4.18, 3.64, 3.88, 1.88 and 3.08, respectively. The obtained results in this work demonstrated that the developed iterative Bayesian regularized neural network (iBRANN) method in this work thoroughly detects the baselines and is superior over the CC, MPLS, airPLS and iPF techniques. A graphical user interface has been developed for the suggested algorithm and can be used for easy implementation of the iBRANN algorithm for the correction of different chromatography, NMR and Raman data sets. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation.

    Science.gov (United States)

    Webber, Emily S; Mankin, David E; Cromwell, Howard C

    2016-01-01

    The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats (Rattus norvegicus) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.

  15. Francisella subverts innate immune signaling: Focus on PI3K/Akt

    Directory of Open Access Journals (Sweden)

    Thomas John Cremer

    2011-02-01

    Full Text Available Intracellular bacterial pathogens exploit host cells as a part of their lifecycle, and they do so by manipulating host cell signaling events. Many such bacteria are known to produce effector proteins that promote cell invasion, alter membrane trafficking and disrupt signaling cascades. This review highlights recent advances in our understanding of signaling pathways involved in host cell responses to Francisella tularensis, a facultative Gram-negative intracellular pathogen that causes tularemia. We highlight several key pathways that are targeted by Francisella, with a focus on the PI3K/Akt pathway. Lastly, we discuss the emerging role of microRNAs, specifically miR-155, as a key regulator of host signaling and defense.

  16. EGFR signaling enhances aerobic glycolysis in triple negative breast cancer cells to promote tumor growth and immune escape

    Science.gov (United States)

    Lim, Seung-Oe; Li, Chia-Wei; Xia, Weiya; Lee, Heng-Huan; Chang, Shih-Shin; Shen, Jia; Hsu, Jennifer L.; Raftery, Dan; Djukovic, Danijel; Gu, Haiwei; Chang, Wei-Chao; Wang, Hung-Ling; Chen, Mong-Liang; Huo, Longfei; Chen, Chung-Hsuan; Wu, Yun; Sahin, Aysegul; Hanash, Samir M.; Hortobagyi, Gabriel N.; Hung, Mien-Chie

    2016-01-01

    Oncogenic signaling reprograms cancer cell metabolism to augment the production of glycolytic metabolites in favor of tumor growth. The ability of cancer cells to evade immunosurveillance and the role of metabolic regulators in T cell functions suggest that oncogene-induced metabolic reprogramming may be linked to immune escape. Epidermal growth factor (EGF) signaling, frequently dysregulated in triple-negative breast cancer (TNBC), is also associated with increased glycolysis. Here, we demonstrated in TNBC cells that EGF signaling activates the first step in glycolysis, but impedes the last step, leading to an accumulation of metabolic intermediates in this pathway. Furthermore, we showed that one of these intermediates, fructose 1,6 bisphosphate (F1,6BP), directly binds to and enhances the activity of the EGF receptor (EGFR), thereby increasing lactate excretion which leads to inhibition of local cytotoxic T cell activity. Notably, combining the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) with the EGFR inhibitor gefitinib effectively suppressed TNBC cell proliferation and tumor growth. Our results illustrate how jointly targeting the EGFR/F1,6BP signaling axis may offer an immediately applicable therapeutic strategy to treat TNBC. PMID:26759242

  17. EGFR Signaling Enhances Aerobic Glycolysis in Triple-Negative Breast Cancer Cells to Promote Tumor Growth and Immune Escape.

    Science.gov (United States)

    Lim, Seung-Oe; Li, Chia-Wei; Xia, Weiya; Lee, Heng-Huan; Chang, Shih-Shin; Shen, Jia; Hsu, Jennifer L; Raftery, Daniel; Djukovic, Danijel; Gu, Haiwei; Chang, Wei-Chao; Wang, Hung-Ling; Chen, Mong-Liang; Huo, Longfei; Chen, Chung-Hsuan; Wu, Yun; Sahin, Aysegul; Hanash, Samir M; Hortobagyi, Gabriel N; Hung, Mien-Chie

    2016-03-01

    Oncogenic signaling reprograms cancer cell metabolism to augment the production of glycolytic metabolites in favor of tumor growth. The ability of cancer cells to evade immunosurveillance and the role of metabolic regulators in T-cell functions suggest that oncogene-induced metabolic reprogramming may be linked to immune escape. EGF signaling, frequently dysregulated in triple-negative breast cancer (TNBC), is also associated with increased glycolysis. Here, we demonstrated in TNBC cells that EGF signaling activates the first step in glycolysis, but impedes the last step, leading to an accumulation of metabolic intermediates in this pathway. Furthermore, we showed that one of these intermediates, fructose 1,6 bisphosphate (F1,6BP), directly binds to and enhances the activity of the EGFR, thereby increasing lactate excretion, which leads to inhibition of local cytotoxic T-cell activity. Notably, combining the glycolysis inhibitor 2-deoxy-d-glucose with the EGFR inhibitor gefitinib effectively suppressed TNBC cell proliferation and tumor growth. Our results illustrate how jointly targeting the EGFR/F1,6BP signaling axis may offer an immediately applicable therapeutic strategy to treat TNBC. ©2016 American Association for Cancer Research.

  18. Multi-scale quantitative precipitation forecasting using nonlinear and nonstationary teleconnection signals and artificial neural network models

    Science.gov (United States)

    Chang, Ni-Bin; Yang, Y. Jeffrey; Imen, Sanaz; Mullon, Lee

    2017-05-01

    Global sea surface temperature (SST) anomalies are observed to have a significant effect on terrestrial precipitation patterns throughout the United States. SST variations have been correlated with terrestrial precipitation via ocean-atmospheric interactions known as climate teleconnections. This study demonstrates how the scale effect could affect the forecasting accuracy with or without the inclusion of those newly discovered unknown teleconnection signals between Adirondack precipitation and SST anomaly in the Atlantic and Pacific oceans. Unique SST regions of both known and unknown telecommunication signals were extracted from the wavelet analysis and used as input variables in an artificial neural network (ANN) forecasting model. Monthly and seasonal scales were considered with respect to a host of long-term (30-year) nonlinear and nonstationary teleconnection signals detected locally at the study site of Adirondack. Similar intra-annual time-lag effects of SST on precipitation variability are salient at both time scales. Sensitivity analysis of four scenarios reveals that more improvements of the forecasting accuracy of the ANN model can be observed by including both known and unknown teleconnection patterns at both time scales, although such improvements are not salient. Research findings also highlight the importance of choosing the forecasting model at the seasonal scale to predict more accurate peak values and global trends of terrestrial precipitation in response to teleconnection signals. The scale shift from monthly to seasonal may improve results by 17% and 17 mm/day in terms of R squared and root of mean square error values, respectively, if both known and unknown SST regions are considered for forecasting.

  19. Neural cross-correlation and signal decorrelation: insights into coding of auditory space.

    Science.gov (United States)

    Saberi, Kourosh; Petrosyan, Agavni

    2005-07-07

    The auditory systems of humans and many other species use the difference in the time of arrival of acoustic signals at the two ears to compute the lateral position of sound sources. This computation is assumed to initially occur in an assembly of neurons organized along a frequency-by-delay surface. Mathematically, the computations are equivalent to a two-dimensional cross-correlation of the input signals at the two ears, with the position of the peak activity along this surface designating the position of the source in space. In this study, partially correlated signals to the two ears are used to probe the mechanisms for encoding spatial cues in stationary or dynamic (moving) signals. It is demonstrated that a cross-correlation model of the auditory periphery coupled with statistical decision theory can predict the patterns of performance by human subjects for both stationary and motion stimuli as a function of stimulus decorrelation. Implications of these findings for the existence of a unique cortical motion system are discussed.

  20. A hardware model of the auditory periphery to transduce acoustic signals into neural activity

    Directory of Open Access Journals (Sweden)

    Takashi eTateno

    2013-11-01

    Full Text Available To improve the performance of cochlear implants, we have integrated a microdevice into a model of the auditory periphery with the goal of creating a microprocessor. We constructed an artificial peripheral auditory system using a hybrid model in which polyvinylidene difluoride was used as a piezoelectric sensor to convert mechanical stimuli into electric signals. To produce frequency selectivity, the slit on a stainless steel base plate was designed such that the local resonance frequency of the membrane over the slit reflected the transfer function. In the acoustic sensor, electric signals were generated based on the piezoelectric effect from local stress in the membrane. The electrodes on the resonating plate produced relatively large electric output signals. The signals were fed into a computer model that mimicked some functions of inner hair cells, inner hair cell–auditory nerve synapses, and auditory nerve fibers. In general, the responses of the model to pure-tone burst and complex stimuli accurately represented the discharge rates of high-spontaneous-rate auditory nerve fibers across a range of frequencies greater than 1 kHz and middle to high sound pressure levels. Thus, the model provides a tool to understand information processing in the peripheral auditory system and a basic design for connecting artificial acoustic sensors to the peripheral auditory nervous system. Finally, we discuss the need for stimulus control with an appropriate model of the auditory periphery based on auditory brainstem responses that were electrically evoked by different temporal pulse patterns with the same pulse number.

  1. Stochastic resonance can enhance information transmission of supra-threshold neural signals.

    Science.gov (United States)

    Kawaguchi, Minato; Mino, Hiroyuki; Momose, Keiko; Durand, Dominique M

    2009-01-01

    Stochastic resonance (SR) has been shown to improve detection of sub-threshold signals with additive uncor-related background noise, not only in a single hippocampal CA1 neuron model, but in a population of hippocampal CA1 neuron models (Array-Enhanced Stochastic Resonance; AESR). However, most of the information in the CNS is transmitted through supra-threshold signals and the effect of stochastic resonance in neurons on these signals is unknown. Therefore, we investigate through computer simulations whether information transmission of supra-threshold input signal can be improved by uncorrelated noise in a population of hippocampal CA1 neuron models by supra-threshold stochastic resonance (SSR). The mutual information was estimated as an index of information transmission via total and noise entropies from the inter-spike interval (ISI) histograms of the spike trains generated by gathering each of spike trains in a population of hippocampal CA1 neuron models at N = 1, 2, 4, 10, 20 and 50. It was shown that the mutual information was maximized at a specific amplitude of uncorrelated noise, i.e., a typical curve of SR was observed when the number of neurons was greater than 10 with SSR. However, SSR did not affect the information transfer with a small number of neurons. In conclusion, SSR may play an important role in processing information such as memory formation in a population of hippocampal neurons.

  2. Immune-Stimulatory Effects of Althaea rosea Flower Extracts through the MAPK Signaling Pathway in RAW264.7 Cells

    Directory of Open Access Journals (Sweden)

    Yon-Suk Kim

    2017-04-01

    Full Text Available Althaea rosea (Linn. is a medicinal plant from China and Korea that has been traditionally used to control inflammation, to stop bedwetting and as a mouthwash in cases of bleeding gums. Its flowers are employed medicinally for their emollient, demulcent and diuretic properties, which make them useful in chest complaints. Furthermore, a flower extract decoction is used to improve blood circulation, for the treatment of constipation, dysmenorrhoea, haemorrhages, etc. However, the possible mechanisms of the immune-stimulatory effect remains to be elucidated. Therefore, we investigated the role of Althaea rosea flower (ARF extracts in the immune-stimulatory effect of macrophages and the underlying mechanisms of action. ARF water extract (ARFW could dose-dependently increase NO production and cytokines (IL-6 and TNF-α. We also found that ARFW significantly increased the expression of iNOS and COX-2 proteins in RAW264.7 cells. Consistent with these results, MAPK protein (JNK, ERK, p38 expression levels were induced after treatment with ARFW. Additionally, ARFW showed a marked increase in the phosphorylation level of IκBα and subsequent IκBα degradation allowing NF-κB nuclear translocation. These results suggest that the immune-stimulatory effect of A. rosea flower extracts is mediated through the translocation of NF-κB p65 subunit into the nucleus from the cytoplasm and subsequent activation of pro-inflammatory cytokines (IL-6 and TNF-α and other mediators (iNOS and COX-2, which occurs mainly through MAPK signalling pathway. Thus, we suggest that ARFW could be considered as a potential therapeutic agent useful in the development of immune-stimulatory compounds.

  3. EEG Signals Analysis Using Multiscale Entropy for Depth of Anesthesia Monitoring during Surgery through Artificial Neural Networks.

    Science.gov (United States)

    Liu, Quan; Chen, Yi-Feng; Fan, Shou-Zen; Abbod, Maysam F; Shieh, Jiann-Shing

    2015-01-01

    In order to build a reliable index to monitor the depth of anesthesia (DOA), many algorithms have been proposed in recent years, one of which is sample entropy (SampEn), a commonly used and important tool to measure the regularity of data series. However, SampEn only estimates the complexity of signals on one time scale. In this study, a new approach is introduced using multiscale entropy (MSE) considering the structure information over different time scales. The entropy values over different time scales calculated through MSE are applied as the input data to train an artificial neural network (ANN) model using bispectral index (BIS) or expert assessment of conscious level (EACL) as the target. To test the performance of the new index's sensitivity to artifacts, we compared the results before and after filtration by multivariate empirical mode decomposition (MEMD). The new approach via ANN is utilized in real EEG signals collected from 26 patients before and after filtering by MEMD, respectively; the results show that is a higher correlation between index from the proposed approach and the gold standard compared with SampEn. Moreover, the proposed approach is more structurally robust to noise and artifacts which indicates that it can be used for monitoring the DOA more accurately.

  4. The classification of oximetry signals using Bayesian neural networks to assist in the detection of obstructive sleep apnoea syndrome.

    Science.gov (United States)

    Marcos, J V; Hornero, R; Alvarez, D; Nabney, I T; Del Campo, F; Zamarrón, C

    2010-03-01

    In the present study, multilayer perceptron (MLP) neural networks were applied to help in the diagnosis of obstructive sleep apnoea syndrome (OSAS). Oxygen saturation (SaO(2)) recordings from nocturnal pulse oximetry were used for this purpose. We performed time and spectral analysis of these signals to extract 14 features related to OSAS. The performance of two different MLP classifiers was compared: maximum likelihood (ML) and Bayesian (BY) MLP networks. A total of 187 subjects suspected of suffering from OSAS took part in the study. Their SaO(2) signals were divided into a training set with 74 recordings and a test set with 113 recordings. BY-MLP networks achieved the best performance on the test set with 85.58% accuracy (87.76% sensitivity and 82.39% specificity). These results were substantially better than those provided by ML-MLP networks, which were affected by overfitting and achieved an accuracy of 76.81% (86.42% sensitivity and 62.83% specificity). Our results suggest that the Bayesian framework is preferred to implement our MLP classifiers. The proposed BY-MLP networks could be used for early OSAS detection. They could contribute to overcome the difficulties of nocturnal polysomnography (PSG) and thus reduce the demand for these studies.

  5. Noncanonical transforming growth factor β (TGFβ) signaling in cranial neural crest cells causes tongue muscle developmental defects.

    Science.gov (United States)

    Iwata, Jun-ichi; Suzuki, Akiko; Pelikan, Richard C; Ho, Thach-Vu; Chai, Yang

    2013-10-11

    Microglossia is a congenital birth defect in humans and adversely impacts quality of life. In vertebrates, tongue muscle derives from the cranial mesoderm, whereas tendons and connective tissues in the craniofacial region originate from cranial neural crest (CNC) cells. Loss of transforming growth factor β (TGFβ) type II receptor in CNC cells in mice (Tgfbr2(fl/fl);Wnt1-Cre) causes microglossia due to a failure of cell-cell communication between cranial mesoderm and CNC cells during tongue development. However, it is still unclear how TGFβ signaling in CNC cells regulates the fate of mesoderm-derived myoblasts during tongue development. Here we show that activation of the cytoplasmic and nuclear tyrosine kinase 1 (ABL1) cascade in Tgfbr2(fl/fl);Wnt1-Cre mice results in a failure of CNC-derived cell differentiation followed by a disruption of TGFβ-mediated induction of growth factors and reduction of myogenic cell proliferation and differentiation activities. Among the affected growth factors, the addition of fibroblast growth factor 4 (FGF4) and neutralizing antibody for follistatin (FST; an antagonist of bone morphogenetic protein (BMP)) could most efficiently restore cell proliferation, differentiation, and organization of muscle cells in the tongue of Tgfbr2(fl/fl);Wnt1-Cre mice. Thus, our data indicate that CNC-derived fibroblasts regulate the fate of mesoderm-derived myoblasts through TGFβ-mediated regulation of FGF and BMP signaling during tongue development.

  6. Disruption of CXCR4 signaling in pharyngeal neural crest cells causes DiGeorge syndrome-like malformations.

    Science.gov (United States)

    Escot, Sophie; Blavet, Cédrine; Faure, Emilie; Zaffran, Stéphane; Duband, Jean-Loup; Fournier-Thibault, Claire

    2016-02-15

    DiGeorge syndrome (DGS) is a congenital disease causing cardiac outflow tract anomalies, craniofacial dysmorphogenesis, thymus hypoplasia, and mental disorders. It results from defective development of neural crest cells (NCs) that colonize the pharyngeal arches and contribute to lower jaw, neck and heart tissues. Although TBX1 has been identified as the main gene accounting for the defects observed in human patients and mouse models, the molecular mechanisms underlying DGS etiology are poorly identified. The recent demonstrations that the SDF1/CXCR4 axis is implicated in NC chemotactic guidance and impaired in cortical interneurons of mouse DGS models prompted us to search for genetic interactions between Tbx1, Sdf1 (Cxcl12) and Cxcr4 in pharyngeal NCs and to investigate the effect of altering CXCR4 signaling on the ontogeny of their derivatives, which are affected in DGS. Here, we provide evidence that Cxcr4 and Sdf1 are genetically downstream of Tbx1 during pharyngeal NC development and that reduction of CXCR4 signaling causes misrouting of pharyngeal NCs in chick and dramatic morphological alterations in the mandibular skeleton, thymus and cranial sensory ganglia. Our results therefore support the possibility of a pivotal role for the SDF1/CXCR4 axis in DGS etiology. © 2016. Published by The Company of Biologists Ltd.

  7. SEMICONDUCTOR INTEGRATED CIRCUITS: A four-channel microelectronic system for neural signal regeneration

    Science.gov (United States)

    Shushan, Xie; Zhigong, Wang; Xiaoying, Lü; Wenyuan, Li; Haixian, Pan

    2009-12-01

    This paper presents a microelectronic system which is capable of making a signal record and functional electric stimulation of an injured spinal cord. As a requirement of implantable engineering for the regeneration microelectronic system, the system is of low noise, low power, small size and high performance. A front-end circuit and two high performance OPAs (operational amplifiers) have been designed for the system with different functions, and the two OPAs are a low-noise low-power two-stage OPA and a constant-gm RTR input and output OPA. The system has been realized in CSMC 0.5-μm CMOS technology. The test results show that the system satisfies the demands of neuron signal regeneration.

  8. Simplest relationship between local field potential and intracellular signals in layered neural tissue.

    Science.gov (United States)

    Chizhov, Anton V; Sanchez-Aguilera, Alberto; Rodrigues, Serafim; de la Prida, Liset Menendez

    2015-12-01

    The relationship between the extracellularly measured electric field potential resulting from synaptic activity in an ensemble of neurons and intracellular signals in these neurons is an important but still open question. Based on a model neuron with a cylindrical dendrite and lumped soma, we derive a formula that substantiates a proportionality between the local field potential and the total somatic transmembrane current that emerges from the difference between the somatic and dendritic membrane potentials. The formula is tested by intra- and extracellular recordings of evoked synaptic responses in hippocampal slices. Additionally, the contribution of different membrane currents to the field potential is demonstrated in a two-population mean-field model. Our formalism, which allows for a simple estimation of unknown dendritic currents directly from somatic measurements, provides an interpretation of the local field potential in terms of intracellularly measurable synaptic signals. It is also applicable to the study of cortical activity using two-compartment neuronal population models.

  9. Feature Selection and Classification of Electroencephalographic Signals: An Artificial Neural Network and Genetic Algorithm Based Approach.

    Science.gov (United States)

    Erguzel, Turker Tekin; Ozekes, Serhat; Tan, Oguz; Gultekin, Selahattin

    2015-10-01

    Feature selection is an important step in many pattern recognition systems aiming to overcome the so-called curse of dimensionality. In this study, an optimized classification method was tested in 147 patients with major depressive disorder (MDD) treated with repetitive transcranial magnetic stimulation (rTMS). The performance of the combination of a genetic algorithm (GA) and a back-propagation (BP) neural network (BPNN) was evaluated using 6-channel pre-rTMS electroencephalographic (EEG) patterns of theta and delta frequency bands. The GA was first used to eliminate the redundant and less discriminant features to maximize classification performance. The BPNN was then applied to test the performance of the feature subset. Finally, classification performance using the subset was evaluated using 6-fold cross-validation. Although the slow bands of the frontal electrodes are widely used to collect EEG data for patients with MDD and provide quite satisfactory classification results, the outcomes of the proposed approach indicate noticeably increased overall accuracy of 89.12% and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.904 using the reduced feature set. © EEG and Clinical Neuroscience Society (ECNS) 2014.

  10. Measurement of neural signals from inexpensive, wireless and dry EEG systems.

    Science.gov (United States)

    Grummett, T S; Leibbrandt, R E; Lewis, T W; DeLosAngeles, D; Powers, D M W; Willoughby, J O; Pope, K J; Fitzgibbon, S P

    2015-07-01

    Electroencephalography (EEG) is challenged by high cost, immobility of equipment and the use of inconvenient conductive gels. We compared EEG recordings obtained from three systems that are inexpensive, wireless, and/or dry (no gel), against recordings made with a traditional, research-grade EEG system, in order to investigate the ability of these 'non-traditional' systems to produce recordings of comparable quality to a research-grade system. The systems compared were: Emotiv EPOC (inexpensive and wireless), B-Alert (wireless), g.Sahara (dry) and g.HIamp (research-grade). We compared the ability of the systems to demonstrate five well-studied neural phenomena: (1) enhanced alpha activity with eyes closed versus open; (2) visual steady-state response (VSSR); (3) mismatch negativity; (4) P300; and (5) event-related desynchronization/synchronization. All systems measured significant alpha augmentation with eye closure, and were able to measure VSSRs (although these were smaller with g.Sahara). The B-Alert and g.Sahara were able to measure the three time-locked phenomena equivalently to the g.HIamp. The Emotiv EPOC did not have suitably located electrodes for two of the tasks and synchronization considerations meant that data from the time-locked tasks were not assessed. The results show that inexpensive, wireless, or dry systems may be suitable for experimental studies using EEG, depending on the research paradigm, and within the constraints imposed by their limited electrode placement and number.

  11. Experimental and Computational Studies of Cortical Neural Network Properties Through Signal Processing

    Science.gov (United States)

    Clawson, Wesley Patrick

    Previous studies, both theoretical and experimental, of network level dynamics in the cerebral cortex show evidence for a statistical phenomenon called criticality; a phenomenon originally studied in the context of phase transitions in physical systems and that is associated with favorable information processing in the context of the brain. The focus of this thesis is to expand upon past results with new experimentation and modeling to show a relationship between criticality and the ability to detect and discriminate sensory input. A line of theoretical work predicts maximal sensory discrimination as a functional benefit of criticality, which can then be characterized using mutual information between sensory input, visual stimulus, and neural response,. The primary finding of our experiments in the visual cortex in turtles and neuronal network modeling confirms this theoretical prediction. We show that sensory discrimination is maximized when visual cortex operates near criticality. In addition to presenting this primary finding in detail, this thesis will also address our preliminary results on change-point-detection in experimentally measured cortical dynamics.

  12. Tyrosine-610 in the Receptor Kinase BAK1 Does Not Play a Major Role in Brassinosteroid Signaling or Innate Immunity

    Directory of Open Access Journals (Sweden)

    Vijayata Singh

    2017-08-01

    Full Text Available The plasma membrane-localized BRI1-ASSOCIATED KINASE1 (BAK1 functions as a co-receptor with several receptor kinases including the brassinosteroid (BR receptor BRASSINOSTEROID-INSENSITIVE 1 (BRI1, which is involved in growth, and the receptors for bacterial flagellin and EF-Tu, FLAGELLIN-SENSING 2 (FLS2 and EF-TU RECEPTOR (EFR, respectively, which are involved in immunity. BAK1 is a dual specificity protein kinase that can autophosphorylate on serine, threonine and tyrosine residues. It was previously reported that phosphorylation of Tyr-610 in the carboxy-terminal domain of BAK1 is required for its function in BR signaling and immunity. However, the functional role of Tyr-610 in vivo has recently come under scrutiny. Therefore, we have generated new BAK1 (Y610F transgenic plants for functional studies. We first produced transgenic Arabidopsis lines expressing BAK1 (Y610F-Flag in the homozygous bak1-4 bkk1-1 double null background. In a complementary approach, we expressed untagged BAK1 and BAK1 (Y610F in the bak1-4 null mutant. Neither BAK1 (Y610F transgenic line had any obvious growth phenotype when compared to wild-type BAK1 expressed in the same background. In addition, the BAK1 (Y610F-Flag plants responded similarly to plants expressing BAK1-Flag in terms of brassinolide (BL inhibition of root elongation, and there were only minor changes in gene expression between the two transgenic lines as monitored by microarray analysis and quantitative real-time PCR. In terms of plant immunity, there were no significant differences between plants expressing BAK1 (Y610F-Flag and BAK1-Flag in the growth of the non-pathogenic hrpA- mutant of Pseudomonas syringae pv. tomato DC3000. Furthermore, untagged BAK1 (Y610F transgenic plants were as responsive as plants expressing BAK1 (in the bak1-4 background and wild-type Col-0 plants toward treatment with the EF-Tu- and flagellin-derived peptide epitopes elf18- and flg22, respectively, as measured by reactive

  13. E3 Ubiquitin Ligases Pellinos as Regulators of Pattern Recognition Receptor Signaling and Immune responses

    Science.gov (United States)

    Medvedev, Andrei E.; Murphy, Michael; Zhou, Hao; Li, Xiaoxia

    2015-01-01

    SUMMARY Pellinos are a family of E3 ubiquitin ligases discovered for their role in catalyzing K63-linked polyubiquitination of Pelle, an IL-1 receptor-associated kinase homologue in the Drosophila Toll pathway. Subsequent studies have revealed the central and non-redundant roles of mammalian Pellino-1, Pellino-2 and Pelino-3 in signaling pathways emanating from IL-1 receptors, Toll-like receptors, NOD-like receptors, T- and B-cell receptors. While Pellinos ability to interact with many signaling intermediates suggested their scaffolding roles, recent findings in mice expressing ligase-inactive Pellinos demonstrated the importance of Pellino ubiquitin ligase activity. Cell-specific functions of Pellinos have emerged, e.g., Pellino-1 being a negative regulator in T-lymphocytes and a positive regulator in myeloid cells, and details of molecular regulation of receptor signaling by various members of the Pellino family have been revealed. In this review, we have summarized current information about Pellino-mediated regulation of signaling by pattern recognition receptors, T-cell and B-cell receptors and TNF receptors, and discuss Pellino’s role in sepsis and infectious diseases, as well as in autoimmune, inflammatory and allergic disorders. We also provide our perspective on the potential of targeting Pellinos with peptide- or small molecule-based drug compounds as a new therapeutic approach for septic shock and autoimmune pathologies. PMID:26085210

  14. The TLR13-MyD88-NF-κB signalling pathway of Cyclina sinensis plays vital roles in innate immune responses.

    Science.gov (United States)

    Ren, Yipeng; Ding, Dan; Pan, Baoping; Bu, Wenjun

    2017-11-01

    Toll-like receptors, the best known pattern recognition receptors, play important roles in recognizing non-self molecules and binding pathogen-associated molecular patterns in the innate immune system. In the present research, the cDNA and protein characterization of the TLR signalling pathway genes including IRAK4, TRAK6 and IKKα (named CsIRAK4, CsTRAF6 and CsIKKα, respectively) with the typical motifs from Cyclina sinensis showed significant similarity with their homologues from other shellfish. Furthermore, the mRNA transcripts of these three genes are ubiquitously expressed in all tissues tested and are dominantly expressed in C. sinensis haemocytes (P signalling pathway in the innate immune responses of C. sinensis by RNA interference and immune challenges. The results suggested the mRNA expression patterns of CsMyD88, CsIRAK4, CsTRAF6, CsIKKα, CsIκB, CsNF-κB, CsC-LYZ and CsAMP were all down-regulated (P signalling pathway in innate immunity by positively adjusting internal signalling factors and immune-related genes. In summary, a TLR13-MyD88-NF-κB signalling pathway exists and plays vital roles in innate immune responses in C. sinensis. These findings collectively lay the foundation for studying the functional characterization of internal signalling factors and establishing a regulatory network for the TLR signalling pathway in molluscs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Identification of grass carp IL-10 receptor subunits: functional evidence for IL-10 signaling in teleost immunity.

    Science.gov (United States)

    Wei, He; Wang, Xinyan; Zhang, Anying; Du, Linyong; Zhou, Hong

    2014-08-01

    Although the functions of teleost IL-10 have been preliminarily determined, functional evidence for its receptor signaling is lacking. Particularly, the identity of fish IL-10 receptor 2 (IL-10R2) is ambiguous. Cytokine receptor family member b4 (CRFB4) and CRFB5 are likely the ortholog of mammalian IL-10R2. In this study, grass carp CRFB4 (gcCRFB4) and gcCRFB5 cDNAs were isolated and characterized. The relatively high expression levels of grass carp IL10 receptor 1 (gcIL-10R1), gcCRFB4 and gcCRFB5 in immune tissues and cells implied their importance in fish immunity. Accordingly, gcIL-10R1, gcCRFB4 and gcCRFB5 were overexpressed in a grass carp kidney cell line to identify the IL-10 receptor subunits upon grass carp IL-10 (gcIL-10) treatment. Results showed that gcIL-10R1 was essential for gcIL-10 stimulation on STAT3 activation and grass carp suppressor of cytokine signaling 3 (gcSOCS3) promoter activity, and also indicated that gcCRFB4 but not gcCRFB5 might be the ortholog of mammalian IL-10R2. Furthermore, mutation of a putative STAT3-binding element in gcSOCS3 promoter attenuated the stimulation of gcIL-10 on gcSOCS3 promoter activity, indicating that gcIL-10 may modulate gcSOCS3 transcription at least partly via STAT3 activation. This notion was further supported by our observation that gcIL-10 was able to induce STAT3 phosphorylation and STAT3 inhibitor could abolish the upregulation of gcSOCS3 mRNA expression by gcIL-10 in grass carp head kidney leukocytes. Taken together, this study for the first time functionally characterized the teleost IL-10 receptor subunits and clarified the conservation of fish IL-10 signaling during evolution, thus laying the ground for further understanding the critical immune events led by IL-10 in teleost. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. AKT signaling mediates IGF-I survival actions on otic neural progenitors.

    Directory of Open Access Journals (Sweden)

    Maria R Aburto

    Full Text Available BACKGROUND: Otic neurons and sensory cells derive from common progenitors whose transition into mature cells requires the coordination of cell survival, proliferation and differentiation programmes. Neurotrophic support and survival of post-mitotic otic neurons have been intensively studied, but the bases underlying the regulation of programmed cell death in immature proliferative otic neuroblasts remains poorly understood. The protein kinase AKT acts as a node, playing a critical role in controlling cell survival and cell cycle progression. AKT is activated by trophic factors, including insulin-like growth factor I (IGF-I, through the generation of the lipidic second messenger phosphatidylinositol 3-phosphate by phosphatidylinositol 3-kinase (PI3K. Here we have investigated the role of IGF-dependent activation of the PI3K-AKT pathway in maintenance of otic neuroblasts. METHODOLOGY/PRINCIPAL FINDINGS: By using a combination of organotypic cultures of chicken (Gallus gallus otic vesicles and acoustic-vestibular ganglia, Western blotting, immunohistochemistry and in situ hybridization, we show that IGF-I-activation of AKT protects neural progenitors from programmed cell death. IGF-I maintains otic neuroblasts in an undifferentiated and proliferative state, which is characterised by the upregulation of the forkhead box M1 (FoxM1 transcription factor. By contrast, our results indicate that post-mitotic p27(Kip-positive neurons become IGF-I independent as they extend their neuronal processes. Neurons gradually reduce their expression of the Igf1r, while they increase that of the neurotrophin receptor, TrkC. CONCLUSIONS/SIGNIFICANCE: Proliferative otic neuroblasts are dependent on the activation of the PI3K-AKT pathway by IGF-I for survival during the otic neuronal progenitor phase of early inner ear development.

  17. Continuous neural identifier for uncertain nonlinear systems with time delays in the input signal.

    Science.gov (United States)

    Alfaro-Ponce, M; Argüelles, A; Chairez, I

    2014-12-01

    Time-delay systems have been successfully used to represent the complexity of some dynamic systems. Time-delay is often used for modeling many real systems. Among others, biological and chemical plants have been described using time-delay terms with better results than those models that have not consider them. However, getting those models represented a challenge and sometimes the results were not so satisfactory. Non-parametric modeling offered an alternative to obtain suitable and usable models. Continuous neural networks (CNN) have been considered as a real alternative to provide models over uncertain non-parametric systems. This article introduces the design of a specific class of non-parametric model for uncertain time-delay system based on CNN considering the so-called delayed learning laws analysis. The convergence analysis as well as the learning laws were produced by means of a Lyapunov-Krasovskii functional. Three examples were developed to demonstrate the effectiveness of the modeling process forced by the identifier proposed in this study. The first example was a simple nonlinear model used as benchmark example. The second example regarded the human immunodeficiency virus dynamic behavior is used to show the performance of the suggested non-parametric identifier based on CNN for no fictitious neither academic models. Finally, a third example describing the evolution of hepatitis B virus served to test the identifier presented in this study and was also useful to provide evidence of its superior performance against a non-delayed identifier based on CNN. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's disease.

    Science.gov (United States)

    Mutez, Eugénie; Nkiliza, Aurore; Belarbi, Karim; de Broucker, Amélie; Vanbesien-Mailliot, Christel; Bleuse, Séverine; Duflot, Aurélie; Comptdaer, Thomas; Semaille, Pierre; Blervaque, Renaud; Hot, David; Leprêtre, Frederic; Figeac, Martin; Destée, Alain; Chartier-Harlin, Marie-Christine

    2014-03-01

    The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is a common genetic cause of Parkinson's disease (PD). Although patients with sporadic PD and individuals with LRRK2-linked PD display the classical PD phenotype, it is not known whether or not the same biological pathways are deregulated in each context. By using transcriptome profiling, we investigated the deregulation of various biological pathways in a total of 47 peripheral blood mononuclear cell (PBMC) samples from patients with sporadic PD, patients heterozygous for the LRRK2 G2019S mutation compared to healthy controls. We found that the deregulation patterns were indeed similar in PBMCs obtained from patients with sporadic PD and from LRRK2 G2019S carriers, with dysfunctions in mitochondrial pathways, cell survival signaling, cancerization, endocytosis signaling and iron metabolism. Analysis of our PBMC data and other publicly available transcriptome datasets (for whole blood samples) showed that deregulation of the immune system, endocytosis and eukaryotic initiation factor 2 (EIF2) signaling are the main features of transcriptome profiles in PD (since they are also present in the transcriptome of dopaminergic neurons from patients). Transcriptome analysis of PBMCs is thus valuable for (i) characterizing the pathophysiological pathways shared by genetic and sporadic forms of PD and (ii) identifying potential biomarkers and therapeutic targets. This minimally invasive approach opens up tremendous perspectives for better diagnosis and therapy of neurodegenerative diseases because it can be applied from the earliest stages of the disease onwards. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Lithium promotes neural precursor cell proliferation: evidence for the involvement of the non-canonical GSK-3β-NF-AT signaling

    Directory of Open Access Journals (Sweden)

    Qu Zhaoxia

    2011-05-01

    Full Text Available Abstract Lithium, a drug that has long been used to treat bipolar disorder and some other human pathogenesis, has recently been shown to stimulate neural precursor growth. However, the involved mechanism is not clear. Here, we show that lithium induces proliferation but not survival of neural precursor cells. Mechanistic studies suggest that the effect of lithium mainly involved activation of the transcription factor NF-AT and specific induction of a subset of proliferation-related genes. While NF-AT inactivation by specific inhibition of its upstream activator calcineurin antagonized the effect of lithium on the proliferation of neural precursor cells, specific inhibition of the NF-AT inhibitor GSK-3β, similar to lithium treatment, promoted neural precursor cell proliferation. One important function of lithium appeared to increase inhibitory phosphorylation of GSK-3β, leading to GSK-3β suppression and subsequent NF-AT activation. Moreover, lithium-induced proliferation of neural precursor cells was independent of its role in inositol depletion. These findings not only provide mechanistic insights into the clinical effects of lithium, but also suggest an alternative therapeutic strategy for bipolar disorder and other neural diseases by targeting the non-canonical GSK-3β-NF-AT signaling.

  20. Three Tctn proteins are functionally conserved in the regulation of neural tube patterning and Gli3 processing but not ciliogenesis and Hedgehog signaling in the mouse.

    Science.gov (United States)

    Wang, Chengbing; Li, Jia; Meng, Qing; Wang, Baolin

    2017-10-01

    Tctn1, Tctn2, and Tctn3 are membrane proteins that localize at the transition zone of primary cilia. Tctn1 and Tctn2 mutations have been reported in both humans and mice, but Tctn3 mutations have been reported only in humans. It is also not clear whether the three Tctn proteins are functionally conserved with respect to ciliogenesis and Hedgehog (Hh) signaling. In the present study, we report that loss of Tctn3 gene function in mice results in a decrease in ciliogenesis and Hh signaling. Consistent with this, Tctn3 mutant mice exhibit holoprosencephaly and randomized heart looping and lack the floor plate in the neural tube, the phenotypes similar to those of Tctn1 and Tctn2 mutants. We also show that overexpression of Tctn3, but not Tctn1 or Tctn2, can rescue ciliogenesis in Tctn3 mutant cells. Similarly, replacement of Tctn3 with Tctn1 or Tctn2 in the Tctn3 gene locus results in reduced ciliogenesis and Hh signaling, holoprosencephaly, and randomized heart looping. Surprisingly, however, the neural tube patterning and the proteolytic processing of Gli3 (a transcription regulator for Hh signaling) into a repressor, both of which are usually impaired in ciliary gene mutants, are normal. These results suggest that Tctn1, Tctn2, and Tctn3 are functionally divergent with respect to their role in ciliogenesis and Hh signaling but conserved in neural tube patterning and Gli3 processing. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. SOX1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch

    Energy Technology Data Exchange (ETDEWEB)

    Genethliou, Nicholas; Panayiotou, Elena [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus); Panayi, Helen; Orford, Michael; Mean, Richard; Lapathitis, George; Gill, Herman; Raoof, Sahir [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Gasperi, Rita De; Elder, Gregory [James J. Peters VA Medical Center, Research and Development (3F22), 130 West Kingsbridge Road, Bronx, NY 10468 (United States); Kessaris, Nicoletta; Richardson, William D. [Wolfson Institute for Biomedical Research and Research Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT (United Kingdom); Malas, Stavros, E-mail: smalas@cing.ac.cy [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus)

    2009-12-25

    During neural development the transition from neurogenesis to gliogenesis, known as the neuron-glial ({Nu}/G) fate switch, requires the coordinated function of patterning factors, pro-glial factors and Notch signalling. How this process is coordinated in the embryonic spinal cord is poorly understood. Here, we demonstrate that during the N/G fate switch in the ventral spinal cord (vSC) SOX1 links the function of neural patterning and Notch signalling. We show that, SOX1 expression in the vSC is regulated by PAX6, NKX2.2 and Notch signalling in a domain-specific manner. We further show that SOX1 regulates the expression of Hes1 and that loss of Sox1 leads to enhanced production of oligodendrocyte precursors from the pMN. Finally, we show that Notch signalling functions upstream of SOX1 during this fate switch and is independently required for the acquisition of the glial fate perse by regulating Nuclear Factor I A expression in a PAX6/SOX1/HES1/HES5-independent manner. These data integrate functional roles of neural patterning factors, Notch signalling and SOX1 during gliogenesis.

  2. Distinct steps of neural induction revealed by Asterix, Obelix and TrkC, genes induced by different signals from the organizer.

    Directory of Open Access Journals (Sweden)

    Sonia Pinho

    2011-04-01

    Full Text Available The amniote organizer (Hensen's node can induce a complete nervous system when grafted into a peripheral region of a host embryo. Although BMP inhibition has been implicated in neural induction, non-neural cells cannot respond to BMP antagonists unless previously exposed to a node graft for at least 5 hours before BMP inhibitors. To define signals and responses during the first 5 hours of node signals, a differential screen was conducted. Here we describe three early response genes: two of them, Asterix and Obelix, encode previously undescribed proteins of unknown function but Obelix appears to be a nuclear RNA-binding protein. The third is TrkC, a neurotrophin receptor. All three genes are induced by a node graft within 4-5 hours but they differ in the extent to which they are inducible by FGF: FGF is both necessary and sufficient to induce Asterix, sufficient but not necessary to induce Obelix and neither sufficient nor necessary for induction of TrkC. These genes are also not induced by retinoic acid, Noggin, Chordin, Dkk1, Cerberus, HGF/SF, Somatostatin or ionomycin-mediated Calcium entry. Comparison of the expression and regulation of these genes with other early neural markers reveals three distinct "epochs", or temporal waves, of gene expression accompanying neural induction by a grafted organizer, which are mirrored by specific stages of normal neural plate development. The results are consistent with neural induction being a cascade of responses elicited by different signals, culminating in the formation of a patterned nervous system.

  3. Neural coding merges sex and habitat chemosensory signals in an insect herbivore.

    Science.gov (United States)

    Trona, Federica; Anfora, Gianfranco; Balkenius, Anna; Bengtsson, Marie; Tasin, Marco; Knight, Alan; Janz, Niklas; Witzgall, Peter; Ignell, Rickard

    2013-06-07

    Understanding the processing of odour mixtures is a focus in olfaction research. Through a neuroethological approach, we demonstrate that different odour types, sex and habitat cues are coded together in an insect herbivore. Stronger flight attraction of codling moth males, Cydia pomonella, to blends of female sex pheromone and plant odour, compared with single compounds, was corroborated by functional imaging of the olfactory centres in the insect brain, the antennal lobes (ALs). The macroglomerular complex (MGC) in the AL, which is dedicated to pheromone perception, showed an enhanced response to blends of pheromone and plant signals, whereas the response in glomeruli surrounding the MGC was suppressed. Intracellular recordings from AL projection neurons that transmit odour information to higher brain centres, confirmed this synergistic interaction in the MGC. These findings underscore that, in nature, sex pheromone and plant odours are perceived as an ensemble. That mating and habitat cues are coded as blends in the MGC of the AL highlights the dual role of plant signals in habitat selection and in premating sexual communication. It suggests that the MGC is a common target for sexual and natural selection in moths, facilitating ecological speciation.

  4. Inhibition of CXCL12 signaling attenuates the postischemic immune response and improves functional recovery after stroke

    DEFF Research Database (Denmark)

    Ruscher, Karsten; Kuric, Enida; Liu, Yawei

    2013-01-01

    cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after transient MCAO (tMCAO). Rats treated with the specific CXCL12 receptor antagonist 1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1......After stroke, brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental stroke. We show here that rats housed in EE after......,4,8,11-tetrazacyclo-tetradecan (AMD3100) showed improved recovery compared with saline-treated rats after tMCAO, without a concomitant reduction in infarct size. This was accompanied by a reduction of infiltrating immune cells in the ischemic hemisphere, particularly cluster of differentiation 3-positive (CD3...

  5. Ascorbic acid alters cell fate commitment of human neural progenitors in a WNT/β-catenin/ROS signaling dependent manner.

    Science.gov (United States)

    Rharass, Tareck; Lantow, Margareta; Gbankoto, Adam; Weiss, Dieter G; Panáková, Daniela; Lucas, Stéphanie

    2017-10-16

    Improving the neuronal yield from in vitro cultivated neural progenitor cells (NPCs) is an essential challenge in transplantation therapy in neurological disorders. In this regard, Ascorbic acid (AA) is widely used to expand neurogenesis from NPCs in cultures although the mechanisms of its action remain unclear. Neurogenesis from NPCs is regulated by the redox-sensitive WNT/β-catenin signaling pathway. We therefore aimed to investigate how AA interacts with this pathway and potentiates neurogenesis. Effects of 200 μM AA were compared with the pro-neurogenic reagent and WNT/β-catenin signaling agonist lithium chloride (LiCl), and molecules with antioxidant activities i.e. N-acetyl-L-cysteine (NAC) and ruthenium red (RuR), in differentiating neural progenitor ReNcell VM cells. Cells were supplemented with reagents for two periods of treatment: a full period encompassing the whole differentiation process versus an early short period that is restricted to the cell fate commitment stage. Intracellular redox balance and reactive oxygen species (ROS) metabolism were examined by flow cytometry using redox and ROS sensors. Confocal microscopy was performed to assess cell viability, neuronal yield, and levels of two proteins: Nucleoredoxin (NXN) and the WNT/β-catenin signaling component Dishevelled 2 (DVL2). TUBB3 and MYC gene responses were evaluated by quantitative real-time PCR. DVL2-NXN complex dissociation was measured by fluorescence resonance energy transfer (FRET). In contrast to NAC which predictably exhibited an antioxidant effect, AA treatment enhanced ROS metabolism with no cytotoxic induction. Both drugs altered ROS levels only at the early stage of the differentiation as no changes were held beyond the neuronal fate commitment stage. FRET studies showed that AA treatment accelerated the redox-dependent release of the initial pool of DVL2 from its sequestration by NXN, while RuR treatment hampered the dissociation of the two proteins. Accordingly, AA

  6. Modulation of immune signaling, bacterial clearance, and corneal integrity by toll-like receptors during streptococcus pneumoniae keratitis.

    Science.gov (United States)

    Tullos, Nathan A; Thompson, Hilary W; Taylor, Sidney D; Sanders, Melissa; Norcross, Erin W; Tolo, Isaiah; Moore, Quincy; Marquart, Mary E

    2013-10-01

    Bacterial keratitis, without effective antimicrobial treatment, leads to poor patient prognosis. Even after bacterial clearance, the host inflammatory response can contribute to corneal damage. Though Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial keratitis, the role of host innate immunity during pneumococcal keratitis is not well characterized. This study investigated the role of Toll-like receptors (TLRs) during pneumococcal keratitis. C57BL/6, as well as TLR2(-/-) and TLR4(-/-) mice, were infected with S. pneumoniae, and infected corneas were examined for 21 days. Quantitative real-time reverse-transcriptase polymerase chain reaction was performed using primers for genes involved in the inflammatory response and TLR signaling. Bacterial survival and leukocyte invasion were examined over a 72-h period. The corneal expression of TLR2, TLR4, and other inflammatory genes was increased at 72 h post-infection (p.i.) compared to uninfected C57BL/6 scratch controls. TLR2(-/-) mice showed a significant increase in bacterial survival at 24 h p.i. likely due to decreased neutrophil infiltration; however, after Day 5 p.i. observed clinical scores of TLR2(-/-) and C57BL/6 mice were not significantly different. In contrast, permanent corneal damage was observed for TLR4(-/-) mice over 21 days. Initially, both TLR(-/-) mouse strains exhibited lower expression levels in many immune genes, but returned to similar or elevated levels compared to C57BL/6 mice by 72 h p.i. TLR2 and TLR4 are involved in the response to pneumococcal keratitis and TLR2 may aid in bacterial clearance by recruitment of neutrophils to the cornea, whereas TLR4 may be necessary to modulate the immune response to limit cellular damage.

  7. Decidual vascular endothelial cells promote maternal-fetal immune tolerance by inducing regulatory T cells through canonical Notch1 signaling.

    Science.gov (United States)

    Yao, Yanyi; Song, Jieping; Wang, Weipeng; Liu, Nian

    2016-05-01

    Adaptation of the maternal immune response to accommodate the semiallogeneic fetus is necessary for pregnancy success. However, the mechanisms by which the fetus avoids rejection despite expression of paternal alloantigens remain incompletely understood. Regulatory T cells (Treg cells) are pivotal for maintaining immune homeostasis, preventing autoimmune disease and fetus rejection. In this study, we found that maternal decidual vascular endothelial cells (DVECs) sustained Foxp3 expression in resting Treg cells in vitro. Moreover, under in vitro Treg cell induction condition with agonistic antibodies and transforming growth factor (TGF)-β, DVECs promoted Treg cell differentiation from non-Treg conventional T cells. Consistent with the promotion of Treg cell maintenance and differentiation, Treg cell-associated gene expression such as TGF-β, Epstein-Barr-induced gene-3, CD39 and glucocorticoid-induced tumor necrosis factor receptor was also increased in the presence of DVECs. Further study revealed that DVECs expressed Notch ligands such as Jagged-1, Delta-like protein 1 (DLL-1) and DLL-4, while Treg cells expressed Notch1 on their surface. The effects of DVECs on Treg cells was inhibited by siRNA-induced knockdown of expression of Jagged-1 a