WorldWideScience

Sample records for neural immune signaling

  1. Neural circuitry and immunity

    Science.gov (United States)

    Pavlov, Valentin A.; Tracey, Kevin J.

    2015-01-01

    Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuroimmune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases defines the emerging field of Bioelectronic Medicine. PMID:26512000

  2. Signal Processing and Neural Network Simulator

    Science.gov (United States)

    Tebbe, Dennis L.; Billhartz, Thomas J.; Doner, John R.; Kraft, Timothy T.

    1995-04-01

    The signal processing and neural network simulator (SPANNS) is a digital signal processing simulator with the capability to invoke neural networks into signal processing chains. This is a generic tool which will greatly facilitate the design and simulation of systems with embedded neural networks. The SPANNS is based on the Signal Processing WorkSystemTM (SPWTM), a commercial-off-the-shelf signal processing simulator. SPW provides a block diagram approach to constructing signal processing simulations. Neural network paradigms implemented in the SPANNS include Backpropagation, Kohonen Feature Map, Outstar, Fully Recurrent, Adaptive Resonance Theory 1, 2, & 3, and Brain State in a Box. The SPANNS was developed by integrating SAIC's Industrial Strength Neural Networks (ISNN) Software into SPW.

  3. Neural Control of the Immune System

    Science.gov (United States)

    Sundman, Eva; Olofsson, Peder S.

    2014-01-01

    Neural reflexes support homeostasis by modulating the function of organ systems. Recent advances in neuroscience and immunology have revealed that neural reflexes also regulate the immune system. Activation of the vagus nerve modulates leukocyte cytokine production and alleviates experimental shock and autoimmune disease, and recent data have…

  4. 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.

  5. Zinc Signals and Immunity.

    Science.gov (United States)

    Maywald, Martina; Wessels, Inga; Rink, Lothar

    2017-10-24

    Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as "zinc waves", and late homeostatic zinc signals regarding prolonged changes in intracellular zinc.

  6. Sub-meninges implantation reduces immune response to neural implants.

    Science.gov (United States)

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

    2013-04-15

    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. Published by Elsevier B.V.

  7. Dynamic decomposition of spatiotemporal neural signals.

    Directory of Open Access Journals (Sweden)

    Luca Ambrogioni

    2017-05-01

    Full Text Available Neural signals are characterized by rich temporal and spatiotemporal dynamics that reflect the organization of cortical networks. Theoretical research has shown how neural networks can operate at different dynamic ranges that correspond to specific types of information processing. Here we present a data analysis framework that uses a linearized model of these dynamic states in order to decompose the measured neural signal into a series of components that capture both rhythmic and non-rhythmic neural activity. The method is based on stochastic differential equations and Gaussian process regression. Through computer simulations and analysis of magnetoencephalographic data, we demonstrate the efficacy of the method in identifying meaningful modulations of oscillatory signals corrupted by structured temporal and spatiotemporal noise. These results suggest that the method is particularly suitable for the analysis and interpretation of complex temporal and spatiotemporal neural signals.

  8. Neural Parallel Engine: A toolbox for massively parallel neural signal processing.

    Science.gov (United States)

    Tam, Wing-Kin; Yang, Zhi

    2018-05-01

    Large-scale neural recordings provide detailed information on neuronal activities and can help elicit the underlying neural mechanisms of the brain. However, the computational burden is also formidable when we try to process the huge data stream generated by such recordings. In this study, we report the development of Neural Parallel Engine (NPE), a toolbox for massively parallel neural signal processing on graphical processing units (GPUs). It offers a selection of the most commonly used routines in neural signal processing such as spike detection and spike sorting, including advanced algorithms such as exponential-component-power-component (EC-PC) spike detection and binary pursuit spike sorting. We also propose a new method for detecting peaks in parallel through a parallel compact operation. Our toolbox is able to offer a 5× to 110× speedup compared with its CPU counterparts depending on the algorithms. A user-friendly MATLAB interface is provided to allow easy integration of the toolbox into existing workflows. Previous efforts on GPU neural signal processing only focus on a few rudimentary algorithms, are not well-optimized and often do not provide a user-friendly programming interface to fit into existing workflows. There is a strong need for a comprehensive toolbox for massively parallel neural signal processing. A new toolbox for massively parallel neural signal processing has been created. It can offer significant speedup in processing signals from large-scale recordings up to thousands of channels. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Estimation of neural energy in microelectrode signals

    Science.gov (United States)

    Gaumond, R. P.; Clement, R.; Silva, R.; Sander, D.

    2004-09-01

    We considered the problem of determining the neural contribution to the signal recorded by an intracortical electrode. We developed a linear least-squares approach to determine the energy fraction of a signal attributable to an arbitrary number of autocorrelation-defined signals buried in noise. Application of the method requires estimation of autocorrelation functions Rap(tgr) characterizing the action potential (AP) waveforms and Rn(tgr) characterizing background noise. This method was applied to the analysis of chronically implanted microelectrode signals from motor cortex of rat. We found that neural (AP) energy consisted of a large-signal component which grows linearly with the number of threshold-detected neural events and a small-signal component unrelated to the count of threshold-detected AP signals. The addition of pseudorandom noise to electrode signals demonstrated the algorithm's effectiveness for a wide range of noise-to-signal energy ratios (0.08 to 39). We suggest, therefore, that the method could be of use in providing a measure of neural response in situations where clearly identified spike waveforms cannot be isolated, or in providing an additional 'background' measure of microelectrode neural activity to supplement the traditional AP spike count.

  10. Neural networks in signal processing

    International Nuclear Information System (INIS)

    Govil, R.

    2000-01-01

    Nuclear Engineering has matured during the last decade. In research and design, control, supervision, maintenance and production, mathematical models and theories are used extensively. In all such applications signal processing is embedded in the process. Artificial Neural Networks (ANN), because of their nonlinear, adaptive nature are well suited to such applications where the classical assumptions of linearity and second order Gaussian noise statistics cannot be made. ANN's can be treated as nonparametric techniques, which can model an underlying process from example data. They can also adopt their model parameters to statistical change with time. Algorithms in the framework of Neural Networks in Signal processing have found new applications potentials in the field of Nuclear Engineering. This paper reviews the fundamentals of Neural Networks in signal processing and their applications in tasks such as recognition/identification and control. The topics covered include dynamic modeling, model based ANN's, statistical learning, eigen structure based processing and generalization structures. (orig.)

  11. A fuzzy neural network for sensor signal estimation

    International Nuclear Information System (INIS)

    Na, Man Gyun

    2000-01-01

    In this work, a fuzzy neural network is used to estimate the relevant sensor signal using other sensor signals. Noise components in input signals into the fuzzy neural network are removed through the wavelet denoising technique. Principal component analysis (PCA) is used to reduce the dimension of an input space without losing a significant amount of information. A lower dimensional input space will also usually reduce the time necessary to train a fuzzy-neural network. Also, the principal component analysis makes easy the selection of the input signals into the fuzzy neural network. The fuzzy neural network parameters are optimized by two learning methods. A genetic algorithm is used to optimize the antecedent parameters of the fuzzy neural network and a least-squares algorithm is used to solve the consequent parameters. The proposed algorithm was verified through the application to the pressurizer water level and the hot-leg flowrate measurements in pressurized water reactors

  12. Role of α7 nicotinic receptor in the immune system and intracellular signaling pathways.

    Science.gov (United States)

    Zdanowski, Robert; Krzyżowska, Małgorzata; Ujazdowska, Dominika; Lewicka, Aneta; Lewicki, Sławomir

    2015-01-01

    Acetylcholine has been well known as one of the most exemplary neurotransmitters. In humans, this versatile molecule and its synthesizing enzyme, choline acetyltransferase, have been found in various non-neural tissues such as the epithelium, endothelium, mesothelium muscle, blood cells and immune cells. The non-neuronal acetylcholine is accompanied by the expression of acetylcholinesterase and nicotinic/muscarinic acetylcholine receptors. Increasing evidence of the non-neuronal acetylcholine system found throughout the last few years has indicated this neurotransmitter as one of the major cellular signaling molecules (associated e.g. with kinases and transcription factors activity). This system is responsible for maintenance and optimization of the cellular function, such as proliferation, differentiation, adhesion, migration, intercellular contact and apoptosis. Additionally, it controls proper activity of immune cells and affects differentiation, antigen presentation or cytokine production (both pro- and anti-inflammatory). The present article reviews recent findings about the non-neuronal cholinergic system in the field of immune system and intracellular signaling pathways.

  13. Recycling signals in the neural crest

    OpenAIRE

    Taneyhill, Lisa A.; Bronner-Fraser, Marianne E.

    2006-01-01

    Vertebrate neural crest cells are multipotent and differentiate into structures that include cartilage and the bones of the face, as well as much of the peripheral nervous system. Understanding how different model vertebrates utilize signaling pathways reiteratively during various stages of neural crest formation and differentiation lends insight into human disorders associated with the neural crest.

  14. Recycling signals in the neural crest.

    Science.gov (United States)

    Taneyhill, Lisa A; Bronner-Fraser, Marianne

    2005-01-01

    Vertebrate neural crest cells are multipotent and differentiate into structures that include cartilage and the bones of the face, as well as much of the peripheral nervous system. Understanding how different model vertebrates utilize signaling pathways reiteratively during various stages of neural crest formation and differentiation lends insight into human disorders associated with the neural crest.

  15. Phytochemicals for taming agitated immune-endocrine-neural axis.

    Science.gov (United States)

    Patel, Seema

    2017-07-01

    Homeostasis of immune-endocrine-neural axis is paramount for human health. If this axis gets agitated due to age, genetic variations, environmental exposures or lifestyle assaults, a cascade of adverse reactions occurs in human body. Cytokines, hormones and neurotransmitters, the effector molecules of this axis behave erratically, leading to a gamut of neural, endocrine, autoimmune, and metabolic diseases. Current panel of drugs can tackle some of them but not in a sustainable, benign way as a myriad of side effects, causal of them have been documented. In this context, phytochemicals, the secondary metabolites of plants seem beneficial. These bioactive constituents encompassing polyphenols, alkaloids, flavonoids, terpenoids, tannins, lignans, stilbenoids (resveratrol), saponins, polysaccharides, glycosides, and lectins etc. have been proven to exert antioxidant, anti-inflammatory, hypolipidemic, hypotensive, antidiabetic, anticancer, immunomodulatory, anti-allergic, analgesic, hepatoprotective, neuroprotective, dermatoprotective, and antimicrobial properties, among a litany of other biological effects. This review presents a holistic perspective of common afflictions resultant of immune-endocrine-neural axis disruption, and the phytochemicals capable of restoring their normalcy and mitigating the ailments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. AKT signaling displays multifaceted functions in neural crest development.

    Science.gov (United States)

    Sittewelle, Méghane; Monsoro-Burq, Anne H

    2018-05-31

    AKT signaling is an essential intracellular pathway controlling cell homeostasis, cell proliferation and survival, as well as cell migration and differentiation in adults. Alterations impacting the AKT pathway are involved in many pathological conditions in human disease. Similarly, during development, multiple transmembrane molecules, such as FGF receptors, PDGF receptors or integrins, activate AKT to control embryonic cell proliferation, migration, differentiation, and also cell fate decisions. While many studies in mouse embryos have clearly implicated AKT signaling in the differentiation of several neural crest derivatives, information on AKT functions during the earliest steps of neural crest development had remained relatively scarce until recently. However, recent studies on known and novel regulators of AKT signaling demonstrate that this pathway plays critical roles throughout the development of neural crest progenitors. Non-mammalian models such as fish and frog embryos have been instrumental to our understanding of AKT functions in neural crest development, both in neural crest progenitors and in the neighboring tissues. This review combines current knowledge acquired from all these different vertebrate animal models to describe the various roles of AKT signaling related to neural crest development in vivo. We first describe the importance of AKT signaling in patterning the tissues involved in neural crest induction, namely the dorsal mesoderm and the ectoderm. We then focus on AKT signaling functions in neural crest migration and differentiation. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. 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. PMID:25594431

  18. Necroptotic signaling in adaptive and innate immunity.

    Science.gov (United States)

    Lu, Jennifer V; Chen, Helen C; Walsh, Craig M

    2014-11-01

    The vertebrate immune system is highly dependent on cell death for efficient responsiveness to microbial pathogens and oncogenically transformed cells. Cell death pathways are vital to the function of many immune cell types during innate, humoral and cellular immune responses. In addition, cell death regulation is imperative for proper adaptive immune self-tolerance and homeostasis. While apoptosis has been found to be involved in several of these roles in immunity, recent data demonstrate that alternative cell death pathways are required. Here, we describe the involvement of a programmed form of cellular necrosis called "necroptosis" in immunity. We consider the signaling pathways that promote necroptosis downstream of death receptors, type I transmembrane proteins of the tumor necrosis factor (TNF) receptor family. The involvement of necroptotic signaling through a "RIPoptosome" assembled in response to innate immune stimuli or genotoxic stress is described. We also characterize the induction of necroptosis following antigenic stimulation in T cells lacking caspase-8 or FADD function. While necroptotic signaling remains poorly understood, it is clear that this pathway is an essential component to effective vertebrate immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Cholinergic signalling in gut immunity

    NARCIS (Netherlands)

    Dhawan, Shobhit; Cailotto, Cathy; Harthoorn, Lucien F.; de Jonge, Wouter J.

    2012-01-01

    The gut immune system shares many signalling molecules and receptors with the autonomic nervous system. A good example is the vagal neurotransmitter acetylcholine (ACh), for which many immune cell types express cholinergic receptors (AChR). In the last decade the vagal nerve has emerged as an

  20. Molecular and Functional Neuroscience in Immunity.

    Science.gov (United States)

    Pavlov, Valentin A; Chavan, Sangeeta S; Tracey, Kevin J

    2018-04-26

    The nervous system regulates immunity and inflammation. The molecular detection of pathogen fragments, cytokines, and other immune molecules by sensory neurons generates immunoregulatory responses through efferent autonomic neuron signaling. The functional organization of this neural control is based on principles of reflex regulation. Reflexes involving the vagus nerve and other nerves have been therapeutically explored in models of inflammatory and autoimmune conditions, and recently in clinical settings. The brain integrates neuro-immune communication, and brain function is altered in diseases characterized by peripheral immune dysregulation and inflammation. Here we review the anatomical and molecular basis of the neural interface with immunity, focusing on peripheral neural control of immune functions and the role of the brain in the model of the immunological homunculus. Clinical advances stemming from this knowledge within the framework of bioelectronic medicine are also briefly outlined.

  1. Roles of Zinc Signaling in the Immune System.

    Science.gov (United States)

    Hojyo, Shintaro; Fukada, Toshiyuki

    2016-01-01

    Zinc (Zn) is an essential micronutrient for basic cell activities such as cell growth, differentiation, and survival. Zn deficiency depresses both innate and adaptive immune responses. However, the precise physiological mechanisms of the Zn-mediated regulation of the immune system have been largely unclear. Zn homeostasis is tightly controlled by the coordinated activity of Zn transporters and metallothioneins, which regulate the transport, distribution, and storage of Zn. There is growing evidence that Zn behaves like a signaling molecule, facilitating the transduction of a variety of signaling cascades in response to extracellular stimuli. In this review, we highlight the emerging functional roles of Zn and Zn transporters in immunity, focusing on how crosstalk between Zn and immune-related signaling guides the normal development and function of immune cells.

  2. Convergent and Divergent Signaling in PAMP-Triggered Immunity and Effector-Triggered Immunity.

    Science.gov (United States)

    Peng, Yujun; van Wersch, Rowan; Zhang, Yuelin

    2018-04-01

    Plants use diverse immune receptors to sense pathogen attacks. Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors localized on the plasma membrane leads to PAMP-triggered immunity (PTI). Detection of pathogen effectors by intracellular or plasma membrane-localized immune receptors results in effector-triggered immunity (ETI). Despite the large variations in the magnitude and duration of immune responses triggered by different PAMPs or pathogen effectors during PTI and ETI, plasma membrane-localized immune receptors activate similar downstream molecular events such as mitogen-activated protein kinase activation, oxidative burst, ion influx, and increased biosynthesis of plant defense hormones, indicating that defense signals initiated at the plasma membrane converge at later points. On the other hand, activation of ETI by immune receptors localized to the nucleus appears to be more directly associated with transcriptional regulation of defense gene expression. Here, we review recent progress in signal transductions downstream of different groups of plant immune receptors, highlighting the converging and diverging molecular events.

  3. 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.

  4. 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

  5. Simultaneous multichannel signal transfers via chaos in a recurrent neural network.

    Science.gov (United States)

    Soma, Ken-ichiro; Mori, Ryota; Sato, Ryuichi; Furumai, Noriyuki; Nara, Shigetoshi

    2015-05-01

    We propose neural network model that demonstrates the phenomenon of signal transfer between separated neuron groups via other chaotic neurons that show no apparent correlations with the input signal. The model is a recurrent neural network in which it is supposed that synchronous behavior between small groups of input and output neurons has been learned as fragments of high-dimensional memory patterns, and depletion of neural connections results in chaotic wandering dynamics. Computer experiments show that when a strong oscillatory signal is applied to an input group in the chaotic regime, the signal is successfully transferred to the corresponding output group, although no correlation is observed between the input signal and the intermediary neurons. Signal transfer is also observed when multiple signals are applied simultaneously to separate input groups belonging to different memory attractors. In this sense simultaneous multichannel communications are realized, and the chaotic neural dynamics acts as a signal transfer medium in which the signal appears to be hidden.

  6. Robo signaling regulates the production of cranial neural crest cells.

    Science.gov (United States)

    Li, Yan; Zhang, Xiao-Tan; Wang, Xiao-Yu; Wang, Guang; Chuai, Manli; Münsterberg, Andrea; Yang, Xuesong

    2017-12-01

    Slit/Robo signaling plays an important role in the guidance of developing neurons in developing embryos. However, it remains obscure whether and how Slit/Robo signaling is involved in the production of cranial neural crest cells. In this study, we examined Robo1 deficient mice to reveal developmental defects of mouse cranial frontal and parietal bones, which are derivatives of cranial neural crest cells. Therefore, we determined the production of HNK1 + cranial neural crest cells in early chick embryo development after knock-down (KD) of Robo1 expression. Detection of markers for pre-migratory and migratory neural crest cells, PAX7 and AP-2α, showed that production of both was affected by Robo1 KD. In addition, we found that the transcription factor slug is responsible for the aberrant delamination/EMT of cranial neural crest cells induced by Robo1 KD, which also led to elevated expression of E- and N-Cadherin. N-Cadherin expression was enhanced when blocking FGF signaling with dominant-negative FGFR1 in half of the neural tube. Taken together, we show that Slit/Robo signaling influences the delamination/EMT of cranial neural crest cells, which is required for cranial bone development. Copyright © 2017. Published by Elsevier Inc.

  7. NMDA Receptor Signaling Is Important for Neural Tube Formation and for Preventing Antiepileptic Drug-Induced Neural Tube Defects.

    Science.gov (United States)

    Sequerra, Eduardo B; Goyal, Raman; Castro, Patricio A; Levin, Jacqueline B; Borodinsky, Laura N

    2018-05-16

    Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that NMDA receptors are important for the formation of the neural tube and that the loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation. SIGNIFICANCE STATEMENT Neural tube defects are one of the most common birth defects. Clinical investigations have determined that the use of antiepileptic drugs during pregnancy increases the incidence of these defects in the offspring by unknown mechanisms. This study discovers that glutamate signaling regulates neural plate cell proliferation and oriented migration and is necessary for neural tube formation. We demonstrate that the widely used antiepileptic drug valproic acid interferes with glutamate signaling and consequently induces neural tube defects, challenging the current hypotheses arguing that they are side effects of this antiepileptic drug that cause the increased incidence of these defects. Understanding the mechanisms of neurotransmitter signaling during neural tube formation may contribute to the identification and development of antiepileptic drugs that are safer during pregnancy. Copyright © 2018 the authors 0270-6474/18/384762-12$15.00/0.

  8. Application of neural networks to signal prediction in nuclear power plant

    International Nuclear Information System (INIS)

    Wan Joo Kim; Soon Heung Chang; Byung Ho Lee

    1993-01-01

    This paper describes the feasibility study of an artificial neural network for signal prediction. The purpose of signal prediction is to estimate the value of undetected next time step signal. As the prediction method, based on the idea of auto regression, a few previous signals are inputs to the artificial neural network and the signal value of next time step is estimated with the outputs of the network. The artificial neural network can be applied to the nonlinear system and answers in short time. The training algorithm is a modified backpropagation model, which can effectively reduce the training time. The target signal of the simulation is the steam generator water level, which is one of the important parameters in nuclear power plants. The simulation result shows that the predicted value follows the real trend well

  9. 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

  10. 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.

  11. Electrocardiogram (ECG Signal Modeling and Noise Reduction Using Hopfield Neural Networks

    Directory of Open Access Journals (Sweden)

    F. Bagheri

    2013-02-01

    Full Text Available The Electrocardiogram (ECG signal is one of the diagnosing approaches to detect heart disease. In this study the Hopfield Neural Network (HNN is applied and proposed for ECG signal modeling and noise reduction. The Hopfield Neural Network (HNN is a recurrent neural network that stores the information in a dynamic stable pattern. This algorithm retrieves a pattern stored in memory in response to the presentation of an incomplete or noisy version of that pattern. Computer simulation results show that this method can successfully model the ECG signal and remove high-frequency noise.

  12. Inter-donor variation in cell subset specific immune signaling responses in healthy individuals.

    Science.gov (United States)

    Longo, Diane M; Louie, Brent; Wang, Ena; Pos, Zoltan; Marincola, Francesco M; Hawtin, Rachael E; Cesano, Alessandra

    2012-01-01

    Single cell network profiling (SCNP) is a multi-parameter flow cytometry based approach that allows for the simultaneous interrogation of intracellular signaling pathways in multiple cell subpopulations within heterogeneous tissues, without the need for individual cell subset isolation. Thus, the technology is extremely well-suited for characterizing the multitude of interconnected signaling pathways and immune cell subpopulations that regulate the function of the immune system. Recently, SCNP was applied to generate a functional map of the healthy human immune cell signaling network by profiling immune signaling pathways downstream of 12 immunomodulators in 7 distinct immune cell subsets within peripheral blood mononuclear cells (PBMCs) from 60 healthy donors. In the study reported here, the degree of inter-donor variation in the magnitude of the immune signaling responses was analyzed. The highest inter-donor differences in immune signaling pathway activity occurred following perturbation of the immune signaling network, rather than in basal signaling. When examining the full panel of immune signaling responses, as one may expect, the overall degree of inter-donor variation was positively correlated (r = 0.727) with the magnitude of node response (i.e. a larger median signaling response was associated with greater inter-donor variation). However, when examining the degree of heterogeneity across cell subpopulations for individual signaling nodes, cell subset specificity in the degree of inter-donor variation was observed for several nodes. For such nodes, relatively weak correlations between inter-donor variation and the magnitude of the response were observed. Further, within the phenotypically distinct subpopulations, a fraction of the immune signaling responses had bimodal response profiles in which (a) only a portion of the cells had elevated phospho-protein levels following modulation and (b) the proportion of responsive cells varied by donor. These data

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

    International Nuclear Information System (INIS)

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

    1991-01-01

    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

  14. 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.

  15. The response of early neural genes to FGF signaling or inhibition of BMP indicate the absence of a conserved neural induction module

    Directory of Open Access Journals (Sweden)

    Rogers Crystal D

    2011-12-01

    Full Text Available Abstract Background The molecular mechanism that initiates the formation of the vertebrate central nervous system has long been debated. Studies in Xenopus and mouse demonstrate that inhibition of BMP signaling is sufficient to induce neural tissue in explants or ES cells respectively, whereas studies in chick argue that instructive FGF signaling is also required for the expression of neural genes. Although additional signals may be involved in neural induction and patterning, here we focus on the roles of BMP inhibition and FGF8a. Results To address the question of necessity and sufficiency of BMP inhibition and FGF signaling, we compared the temporal expression of the five earliest genes expressed in the neuroectoderm and determined their requirements for induction at the onset of neural plate formation in Xenopus. Our results demonstrate that the onset and peak of expression of the genes vary and that they have different regulatory requirements and are therefore unlikely to share a conserved neural induction regulatory module. Even though all require inhibition of BMP for expression, some also require FGF signaling; expression of the early-onset pan-neural genes sox2 and foxd5α requires FGF signaling while other early genes, sox3, geminin and zicr1 are induced by BMP inhibition alone. Conclusions We demonstrate that BMP inhibition and FGF signaling induce neural genes independently of each other. Together our data indicate that although the spatiotemporal expression patterns of early neural genes are similar, the mechanisms involved in their expression are distinct and there are different signaling requirements for the expression of each gene.

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

    KAUST Repository

    Bigeard, Jean; Colcombet, Jean; Hirt, Heribert

    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.

  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 development of a PZT-based microdrive for neural signal recording

    International Nuclear Information System (INIS)

    Park, Sangkyu; Yoon, Euisung; Park, Sukho; Lee, Sukchan; Shin, Hee-sup; Park, Hyunjun; Kim, Byungkyu; Kim, Daesoo; Park, Jongoh

    2008-01-01

    A hand-controlled microdrive has been used to obtain neural signals from rodents such as rats and mice. However, it places severe physical stress on the rodents during its manipulation, and this stress leads to alertness in the mice and low efficiency in obtaining neural signals from the mice. To overcome this issue, we developed a novel microdrive, which allows one to adjust the electrodes by a piezoelectric device (PZT) with high precision. Its mass is light enough to install on the mouse's head. The proposed microdrive has three H-type PZT actuators and their guiding structure. The operation principle of the microdrive is based on the well known inchworm mechanism. When the three PZT actuators are synchronized, linear motion of the electrode is produced along the guiding structure. The electrodes used for the recording of the neural signals from neuron cells were fixed at one of the PZT actuators. Our proposed microdrive has an accuracy of about 400 nm and a long stroke of about 5 mm. In response to formalin-induced pain, single unit activities are robustly measured at the thalamus with electrodes whose vertical depth is adjusted by the microdrive under urethane anesthesia. In addition, the microdrive was efficient in detecting neural signals from mice that were moving freely. Thus, the present study suggests that the PZT-based microdrive could be an alternative for the efficient detection of neural signals from mice during behavioral states without any stress to the mice. (technical note)

  19. Sensor signal analysis by neural networks for surveillance in nuclear reactors

    International Nuclear Information System (INIS)

    Keyvan, S.; Rabelo, L.C.

    1992-01-01

    The application of neural networks as a tool for reactor diagnostics is examined here. Reactor pump signals utilized in a wear-out monitoring system developed for early detection of the degradation of a pump shaft are analyzed as a semi-benchmark test to study the feasibility of neural networks for monitoring and surveillance in nuclear reactors. The Adaptive Resonance Theory (ART 2 and ART 2-A) paradigm of neural networks is applied in this study. The signals are collected signals as well as generated signals simulating the wear progress. The wear-out monitoring system applies noise analysis techniques, and is capable of distinguishing these signals apart and providing a measure of the progress of the degradation. This paper presents the results of the analysis of these data, and provides an evaluation on the performance of ART 2-A and ART 2 for reactor signal analysis. The selection of ART 2 is due to its desired design principles such as unsupervised learning, stability-plasticity, search-direct access, and the match-reset tradeoffs

  20. Weak correlations between hemodynamic signals and ongoing neural activity during the resting state

    Science.gov (United States)

    Winder, Aaron T.; Echagarruga, Christina; Zhang, Qingguang; Drew, Patrick J.

    2017-01-01

    Spontaneous fluctuations in hemodynamic signals in the absence of a task or overt stimulation are used to infer neural activity. We tested this coupling by simultaneously measuring neural activity and changes in cerebral blood volume (CBV) in the somatosensory cortex of awake, head-fixed mice during periods of true rest, and during whisker stimulation and volitional whisking. Here we show that neurovascular coupling was similar across states, and large spontaneous CBV changes in the absence of sensory input were driven by volitional whisker and body movements. Hemodynamic signals during periods of rest were weakly correlated with neural activity. Spontaneous fluctuations in CBV and vessel diameter persisted when local neural spiking and glutamatergic input was blocked, and during blockade of noradrenergic receptors, suggesting a non-neuronal origin for spontaneous CBV fluctuations. Spontaneous hemodynamic signals reflect a combination of behavior, local neural activity, and putatively non-neural processes. PMID:29184204

  1. 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

    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....

  2. Seismic signal auto-detecing from different features by using Convolutional Neural Network

    Science.gov (United States)

    Huang, Y.; Zhou, Y.; Yue, H.; Zhou, S.

    2017-12-01

    We try Convolutional Neural Network to detect some features of seismic data and compare their efficience. The features include whether a signal is seismic signal or noise and the arrival time of P and S phase and each feature correspond to a Convolutional Neural Network. We first use traditional STA/LTA to recongnize some events and then use templete matching to find more events as training set for the Neural Network. To make the training set more various, we add some noise to the seismic data and make some synthetic seismic data and noise. The 3-component raw signal and time-frequancy ananlyze are used as the input data for our neural network. Our Training is performed on GPUs to achieve efficient convergence. Our method improved the precision in comparison with STA/LTA and template matching. We will move to recurrent neural network to see if this kind network is better in detect P and S phase.

  3. Sphingosine-1-Phosphate (S1P) Signaling in Neural Progenitors.

    Science.gov (United States)

    Callihan, Phillip; Alqinyah, Mohammed; Hooks, Shelley B

    2018-01-01

    Sphingosine-1-phosphate (S1P) and its receptors are important in nervous system development. Reliable in vitro human model systems are needed to further define specific roles for S1P signaling in neural development. We have described S1P-regulated signaling, survival, and differentiation in a human embryonic stem cell-derived neuroepithelial progenitor cell line (hNP1) that expresses functional S1P receptors. These cells can be further differentiated to a neuronal cell type and therefore represent a good model system to study the role of S1P signaling in human neural development. The following sections describe in detail the culture and differentiation of hNP1 cells and two assays to measure S1P signaling in these cells.

  4. MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells.

    Science.gov (United States)

    Jones, Russell G; Pearce, Edward J

    2017-05-16

    Tissue-resident immune cells must balance survival in peripheral tissues with the capacity to respond rapidly upon infection or tissue damage, and in turn couple these responses with intrinsic metabolic control and conditions in the tissue microenvironment. The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) is a central integrator of extracellular and intracellular growth signals and cellular metabolism and plays important roles in both innate and adaptive immune responses. This review discusses the function of mTOR signaling in the differentiation and function of tissue-resident immune cells, with focus on the role of mTOR as a metabolic sensor and its impact on metabolic regulation in innate and adaptive immune cells. We also discuss the impact of metabolic constraints in tissues on immune homeostasis and disease, and how manipulating mTOR activity with drugs such as rapamycin can modulate immunity in these contexts. Copyright © 2017. Published by Elsevier Inc.

  5. Nonlinear signal processing using neural networks: Prediction and system modelling

    Energy Technology Data Exchange (ETDEWEB)

    Lapedes, A.; Farber, R.

    1987-06-01

    The backpropagation learning algorithm for neural networks is developed into a formalism for nonlinear signal processing. We illustrate the method by selecting two common topics in signal processing, prediction and system modelling, and show that nonlinear applications can be handled extremely well by using neural networks. The formalism is a natural, nonlinear extension of the linear Least Mean Squares algorithm commonly used in adaptive signal processing. Simulations are presented that document the additional performance achieved by using nonlinear neural networks. First, we demonstrate that the formalism may be used to predict points in a highly chaotic time series with orders of magnitude increase in accuracy over conventional methods including the Linear Predictive Method and the Gabor-Volterra-Weiner Polynomial Method. Deterministic chaos is thought to be involved in many physical situations including the onset of turbulence in fluids, chemical reactions and plasma physics. Secondly, we demonstrate the use of the formalism in nonlinear system modelling by providing a graphic example in which it is clear that the neural network has accurately modelled the nonlinear transfer function. It is interesting to note that the formalism provides explicit, analytic, global, approximations to the nonlinear maps underlying the various time series. Furthermore, the neural net seems to be extremely parsimonious in its requirements for data points from the time series. We show that the neural net is able to perform well because it globally approximates the relevant maps by performing a kind of generalized mode decomposition of the maps. 24 refs., 13 figs.

  6. Vitamin D signaling in intestinal innate immunity and homeostasis.

    Science.gov (United States)

    Dimitrov, Vassil; White, John H

    2017-09-15

    The lumen of the gut hosts a plethora of microorganisms that participate in food assimilation, inactivation of harmful particles and in vitamin synthesis. On the other hand, enteric flora, a number of food antigens, and toxins are capable of triggering immune responses causing inflammation, which, when unresolved, may lead to chronic conditions such as inflammatory bowel disease (IBD). It is important, therefore, to contain the gut bacteria within the lumen, control microbial load and composition, as well as ensure adequate innate and adaptive immune responses to pathogenic threats. There is growing evidence that vitamin D signaling has impacts on all these aspects of intestinal physiology, contributing to healthy enteric homeostasis. VD was first discovered as the curative agent for nutritional rickets, and its classical actions are associated with calcium absorption and bone health. However, vitamin D exhibits a number of extra-skeletal effects, particularly in innate immunity. Notably, it stimulates production of pattern recognition receptors, anti-microbial peptides, and cytokines, which are at the forefront of innate immune responses. They play a role in sensing the microbiota, in preventing excessive bacterial overgrowth, and complement the actions of vitamin D signaling in enhancing intestinal barrier function. Vitamin D also favours tolerogenic rather than inflammogenic T cell differentiation and function. Compromised innate immune function and overactive adaptive immunity, as well as defective intestinal barrier function, have been associated with IBD. Importantly, observational and intervention studies support a beneficial role of vitamin D supplementation in patients with Crohn's disease, a form of IBD. This review summarizes the effects of vitamin D signaling on barrier integrity and innate and adaptive immunity in the gut, as well as on microbial load and composition. Collectively, studies to date reveal that vitamin D signaling has widespread effects

  7. 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.

  8. 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.

  9. Neural redundancy applied to the parity space for signal validation

    International Nuclear Information System (INIS)

    Mol, Antonio Carlos de Abreu; Pereira, Claudio Marcio Nascimento Abreu; Martinez, Aquilino Senra

    2005-01-01

    The objective of signal validation is to provide more reliable information from the plant sensor data The method presented in this work introduces the concept of neural redundancy and applies it to the space parity method [1] to overcome an inherent deficiency of this method - the determination of the best estimative of the redundant measures when they are inconsistent. The concept of neural redundancy consists on the calculation of a redundancy through neural networks based on the time series of the own state variable. Therefore, neural networks, dynamically trained with the time series, will estimate the current value of the own measure, which will be used as referee of the redundant measures in the parity space. For this purpose the neural network should have the capacity to supply the neural redundancy in real time and with maximum error corresponding to the group deviation. The historical series should be enough to allow the estimate of the next value, during transients and at the same time, it should be optimized to facilitate the retraining of the neural network to each acquisition. In order to have the capacity to reproduce the tendency of the time series even under accident condition, the dynamic training of the neural network privileges the recent points of the time series. The tests accomplished with simulated data of a nuclear plant, demonstrated that this method applied on the parity space method improves the signal validation process. (author)

  10. Neural redundancy applied to the parity space for signal validation

    Energy Technology Data Exchange (ETDEWEB)

    Mol, Antonio Carlos de Abreu; Pereira, Claudio Marcio Nascimento Abreu [Instituto de Engenharia Nuclear (IEN), Rio de Janeiro, RJ (Brazil)]. E-mail: cmnap@ien.gov.br; Martinez, Aquilino Senra [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia]. E-mail: aquilino@lmp.br

    2005-07-01

    The objective of signal validation is to provide more reliable information from the plant sensor data The method presented in this work introduces the concept of neural redundancy and applies it to the space parity method [1] to overcome an inherent deficiency of this method - the determination of the best estimative of the redundant measures when they are inconsistent. The concept of neural redundancy consists on the calculation of a redundancy through neural networks based on the time series of the own state variable. Therefore, neural networks, dynamically trained with the time series, will estimate the current value of the own measure, which will be used as referee of the redundant measures in the parity space. For this purpose the neural network should have the capacity to supply the neural redundancy in real time and with maximum error corresponding to the group deviation. The historical series should be enough to allow the estimate of the next value, during transients and at the same time, it should be optimized to facilitate the retraining of the neural network to each acquisition. In order to have the capacity to reproduce the tendency of the time series even under accident condition, the dynamic training of the neural network privileges the recent points of the time series. The tests accomplished with simulated data of a nuclear plant, demonstrated that this method applied on the parity space method improves the signal validation process. (author)

  11. The innate immune signaling in cancer and cardiometabolic diseases: Friends or foes?

    Science.gov (United States)

    Wang, Weijun; Zhang, Yaxing; Yang, Ling; Li, Hongliang

    2017-02-28

    The innate immune system is responsible for sensing pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) by several types of germline-encoded pattern-recognition receptors (PRRs). It has the capacity to help the human body maintain homeostasis under normal conditions. However, in pathological conditions, PAMPs or DAMPs trigger aberrant innate immune and inflammatory responses and thus negatively or positively influence the progression of cancer and cardiometabolic diseases. Interestingly, we found that some elements of innate immune signaling are involved in these diseases partially via immune-independent manners, indicating a deeper understanding of the function of innate immune signaling in these diseases is urgent. In this review, we summarize the primary innate immune signaling pathways and their association with cancer and cardiometabolic diseases, with the aim of providing effective therapies for these diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. High-dimensional analysis of the aging immune system: verification of age-associated differences in immune signaling responses in healthy donors.

    Science.gov (United States)

    Longo, Diane M; Louie, Brent; Ptacek, Jason; Friedland, Greg; Evensen, Erik; Putta, Santosh; Atallah, Michelle; Spellmeyer, David; Wang, Ena; Pos, Zoltan; Marincola, Francesco M; Schaeffer, Andrea; Lukac, Suzanne; Railkar, Radha; Beals, Chan R; Cesano, Alessandra; Carayannopoulos, Leonidas N; Hawtin, Rachael E

    2014-06-21

    Single-cell network profiling (SCNP) is a multiparametric flow cytometry-based approach that simultaneously measures evoked signaling in multiple cell subsets. Previously, using the SCNP approach, age-associated immune signaling responses were identified in a cohort of 60 healthy donors. In the current study, a high-dimensional analysis of intracellular signaling was performed by measuring 24 signaling nodes in 7 distinct immune cell subsets within PBMCs in an independent cohort of 174 healthy donors [144 elderly (>65 yrs); 30 young (25-40 yrs)]. Associations between age and 9 immune signaling responses identified in the previously published 60 donor cohort were confirmed in the current study. Furthermore, within the current study cohort, 48 additional immune signaling responses differed significantly between young and elderly donors. These associations spanned all profiled modulators and immune cell subsets. These results demonstrate that SCNP, a systems-based approach, can capture the complexity of the cellular mechanisms underlying immunological aging. Further, the confirmation of age associations in an independent donor cohort supports the use of SCNP as a tool for identifying reproducible predictive biomarkers in areas such as vaccine response and response to cancer immunotherapies.

  13. CD95-CD95L: can the brain learn from the immune system?

    DEFF Research Database (Denmark)

    Becher, B; Barker, P A; Owens, T

    1998-01-01

    being recognized that CD95 signaling by immune cells mediates effects other than apoptosis, such as cell survival and under inflammatory conditions expression of this protein promotes neural-immune interactions. Both neuroscientists and immunologists can contribute to defining the mechanisms underlying...

  14. Neural network committees for finger joint angle estimation from surface EMG signals

    Directory of Open Access Journals (Sweden)

    Reddy Narender P

    2009-01-01

    Full Text Available Abstract Background In virtual reality (VR systems, the user's finger and hand positions are sensed and used to control the virtual environments. Direct biocontrol of VR environments using surface electromyography (SEMG signals may be more synergistic and unconstraining to the user. The purpose of the present investigation was to develop a technique to predict the finger joint angle from the surface EMG measurements of the extensor muscle using neural network models. Methodology SEMG together with the actual joint angle measurements were obtained while the subject was performing flexion-extension rotation of the index finger at three speeds. Several neural networks were trained to predict the joint angle from the parameters extracted from the SEMG signals. The best networks were selected to form six committees. The neural network committees were evaluated using data from new subjects. Results There was hysteresis in the measured SMEG signals during the flexion-extension cycle. However, neural network committees were able to predict the joint angle with reasonable accuracy. RMS errors ranged from 0.085 ± 0.036 for fast speed finger-extension to 0.147 ± 0.026 for slow speed finger extension, and from 0.098 ± 0.023 for the fast speed finger flexion to 0.163 ± 0.054 for slow speed finger flexion. Conclusion Although hysteresis was observed in the measured SEMG signals, the committees of neural networks were able to predict the finger joint angle from SEMG signals.

  15. Hepatocyte growth factor/scatter factor-MET signaling in neural crest-derived melanocyte development.

    Science.gov (United States)

    Kos, L; Aronzon, A; Takayama, H; Maina, F; Ponzetto, C; Merlino, G; Pavan, W

    1999-02-01

    The mechanisms governing development of neural crest-derived melanocytes, and how alterations in these pathways lead to hypopigmentation disorders, are not completely understood. Hepatocyte growth factor/scatter factor (HGF/SF) signaling through the tyrosine-kinase receptor, MET, is capable of promoting the proliferation, increasing the motility, and maintaining high tyrosinase activity and melanin synthesis of melanocytes in vitro. In addition, transgenic mice that ubiquitously overexpress HGF/SF demonstrate hyperpigmentation in the skin and leptomenigenes and develop melanomas. To investigate whether HGF/ SF-MET signaling is involved in the development of neural crest-derived melanocytes, transgenic embryos, ubiquitously overexpressing HGF/SF, were analyzed. In HGF/SF transgenic embryos, the distribution of melanoblasts along the characteristic migratory pathway was not affected. However, additional ectopically localized melanoblasts were also observed in the dorsal root ganglia and neural tube, as early as 11.5 days post coitus (p.c.). We utilized an in vitro neural crest culture assay to further explore the role of HGF/SF-MET signaling in neural crest development. HGF/SF added to neural crest cultures increased melanoblast number, permitted differentiation into pigmented melanocytes, promoted melanoblast survival, and could replace mast-cell growth factor/Steel factor (MGF) in explant cultures. To examine whether HGF/SF-MET signaling is required for the proper development of melanocytes, embryos with a targeted Met null mutation (Met-/-) were analysed. In Met-/- embryos, melanoblast number and location were not overtly affected up to 14 days p.c. These results demonstrate that HGF/SF-MET signaling influences, but is not required for, the initial development of neural crest-derived melanocytes in vivo and in vitro.

  16. 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.

  17. Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures

    International Nuclear Information System (INIS)

    Hirsch, Cordula; Campano, Louise M.; Woehrle, Simon; Hecht, Andreas

    2007-01-01

    Canonical Wnt signaling triggers the formation of heterodimeric transcription factor complexes consisting of β-catenin and T cell factors, and thereby controls the execution of specific genetic programs. During the expansion and neurogenic phases of embryonic neural development canonical Wnt signaling initially controls proliferation of neural progenitor cells, and later neuronal differentiation. Whether Wnt growth factors affect neural progenitor cells postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling on neural progenitors isolated from cerebral cortices of newborn mice. Expression profiling of pathway components revealed that these cells are fully equipped to respond to Wnt signals. However, Wnt pathway activation affected only a subset of neonatal progenitors and elicited a limited increase in proliferation and neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway activation only transiently stimulated S-phase entry but did not support long-term proliferation of progenitor cultures. The dampened nature of the Wnt response correlates with the predominant expression of inhibitory pathway components and the rapid actuation of negative feedback mechanisms. Interestingly, in differentiating cell cultures activation of canonical Wnt signaling reduced Hes1 and Hes5 expression suggesting that during postnatal neural development, Wnt/β-catenin signaling enhances neurogenesis from progenitor cells by interfering with Notch pathway activity

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

    Directory of Open Access Journals (Sweden)

    Ankush Gosain

    Full Text Available 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

  19. Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma.

    Science.gov (United States)

    Liu, W Robert; Shipp, Margaret A

    2017-11-23

    Classical Hodgkin lymphoma (cHL) is an unusual B-cell-derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number-dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor-positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade. © 2017 by The American Society of Hematology.

  20. Met1-linked Ubiquitination in Immune Signalling

    DEFF Research Database (Denmark)

    Fiil, Berthe Katrine; Gyrd-Hansen, Mads

    2014-01-01

    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...... 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...

  1. 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.

  2. Detecting modulated signals in modulated noise: (II) neural thresholds in the songbird forebrain.

    Science.gov (United States)

    Bee, Mark A; Buschermöhle, Michael; Klump, Georg M

    2007-10-01

    Sounds in the real world fluctuate in amplitude. The vertebrate auditory system exploits patterns of amplitude fluctuations to improve signal detection in noise. One experimental paradigm demonstrating these general effects has been used in psychophysical studies of 'comodulation detection difference' (CDD). The CDD effect refers to the fact that thresholds for detecting a modulated, narrowband noise signal are lower when the envelopes of flanking bands of modulated noise are comodulated with each other, but fluctuate independently of the signal compared with conditions in which the envelopes of the signal and flanking bands are all comodulated. Here, we report results from a study of the neural correlates of CDD in European starlings (Sturnus vulgaris). We manipulated: (i) the envelope correlations between a narrowband noise signal and a masker comprised of six flanking bands of noise; (ii) the signal onset delay relative to masker onset; (iii) signal duration; and (iv) masker spectrum level. Masked detection thresholds were determined from neural responses using signal detection theory. Across conditions, the magnitude of neural CDD ranged between 2 and 8 dB, which is similar to that reported in a companion psychophysical study of starlings [U. Langemann & G.M. Klump (2007) Eur. J. Neurosci., 26, 1969-1978]. We found little evidence to suggest that neural CDD resulted from the across-channel processing of auditory grouping cues related to common envelope fluctuations and synchronous onsets between the signal and flanking bands. We discuss a within-channel model of peripheral processing that explains many of our results.

  3. A digitally assisted, signal folding neural recording amplifier.

    Science.gov (United States)

    Chen, Yi; Basu, Arindam; Liu, Lei; Zou, Xiaodan; Rajkumar, Ramamoorthy; Dawe, Gavin Stewart; Je, Minkyu

    2014-08-01

    A novel signal folding and reconstruction scheme for neural recording applications that exploits the 1/f(n) characteristics of neural signals is described in this paper. The amplified output is 'folded' into a predefined range of voltages by using comparison and reset circuits along with the core amplifier. After this output signal is digitized and transmitted, a reconstruction algorithm can be applied in the digital domain to recover the amplified signal from the folded waveform. This scheme enables the use of an analog-to-digital convertor with less number of bits for the same effective dynamic range. It also reduces the transmission data rate of the recording chip. Both of these features allow power and area savings at the system level. Other advantages of the proposed topology are increased reliability due to the removal of pseudo-resistors, lower harmonic distortion and low-voltage operation. An analysis of the reconstruction error introduced by this scheme is presented along with a behavioral model to provide a quick estimate of the post reconstruction dynamic range. Measurement results from two different core amplifier designs in 65 nm and 180 nm CMOS processes are presented to prove the generality of the proposed scheme in the neural recording applications. Operating from a 1 V power supply, the amplifier in 180 nm CMOS has a gain of 54.2 dB, bandwidth of 5.7 kHz, input referred noise of 3.8 μVrms and power dissipation of 2.52 μW leading to a NEF of 3.1 in spike band. It exhibits a dynamic range of 66 dB and maximum SNDR of 43 dB in LFP band. It also reduces system level power (by reducing the number of bits in the ADC by 2) as well as data rate to 80% of a conventional design. In vivo measurements validate the ability of this amplifier to simultaneously record spike and LFP signals.

  4. Model for neural signaling leap statistics

    International Nuclear Information System (INIS)

    Chevrollier, Martine; Oria, Marcos

    2011-01-01

    We present a simple model for neural signaling leaps in the brain considering only the thermodynamic (Nernst) potential in neuron cells and brain temperature. We numerically simulated connections between arbitrarily localized neurons and analyzed the frequency distribution of the distances reached. We observed qualitative change between Normal statistics (with T 37.5 0 C, awaken regime) and Levy statistics (T = 35.5 0 C, sleeping period), characterized by rare events of long range connections.

  5. Model for neural signaling leap statistics

    Science.gov (United States)

    Chevrollier, Martine; Oriá, Marcos

    2011-03-01

    We present a simple model for neural signaling leaps in the brain considering only the thermodynamic (Nernst) potential in neuron cells and brain temperature. We numerically simulated connections between arbitrarily localized neurons and analyzed the frequency distribution of the distances reached. We observed qualitative change between Normal statistics (with T = 37.5°C, awaken regime) and Lévy statistics (T = 35.5°C, sleeping period), characterized by rare events of long range connections.

  6. Neural signal processing for identifying failed fuel rods in nuclear reactors

    International Nuclear Information System (INIS)

    Seixas, Jose M. de; Soares Filho, William; Pereira, Wagner C.A.; Teles, Claudio C.B.

    2002-01-01

    Ultrasonic pulses were used for automatic detection of failed nuclear fuel rods. For experimental tests of the proposed method, an assembly prototype of 16 x 16 rods was built by using genuine rods but without fuel inside (just air). Some rods were partially filled with water to simulate cracked rods. Using neural signal processing on the received echoes of the emitted ultrasonic pulses, a detection efficiency of 97% was obtained. Neural detection is shown to outperform other classical discriminating methods and can also reveal important features of the signal structure of the received echoes. (author)

  7. 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 genetran...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 o

  8. 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.

  9. SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

    Science.gov (United States)

    Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

    2013-04-30

    The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

  10. ETOH inhibits embryonic neural stem/precursor cell proliferation via PLD signaling

    International Nuclear Information System (INIS)

    Fujita, Yuko; Hiroyama, Masami; Sanbe, Atsushi; Yamauchi, Junji; Murase, Shoko; Tanoue, Akito

    2008-01-01

    While a mother's excessive alcohol consumption during pregnancy is known to have adverse effects on fetal neural development, little is known about the underlying mechanism of these effects. In order to investigate these mechanisms, we investigated the toxic effect of ethanol (ETOH) on neural stem/precursor cell (NSC) proliferation. In cultures of NSCs, phospholipase D (PLD) is activated following stimulation with epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2). Exposure of NSCs to ETOH suppresses cell proliferation, while it has no effect on cell death. Phosphatidic acid (PA), which is a signaling messenger produced by PLD, reverses ETOH inhibition of NSC proliferation. Blocking the PLD signal by 1-butanol suppresses the proliferation. ETOH-induced suppression of NSC proliferation and the protective effect of PA for ETOH-induced suppression are mediated through extracellular signal-regulated kinase signaling. These results indicate that exposure to ETOH impairs NSC proliferation by altering the PLD signaling pathway

  11. Applications of autoassociative neural networks for signal validation in accident management

    International Nuclear Information System (INIS)

    Fantoni, P.; Mazzola, A.

    1994-01-01

    The OECD Halden Reactor Project has been working for several years with computer based systems for determination on plant status including early fault detection and signal validation. The method here presented explores the possibility to use a neural network approach to validate important process signals during normal and abnormal plant conditions. In BWR plants, signal validation has two important applications: reliable thermal limits calculation and reliable inputs to other computerized systems that support the operator during accident scenarious. This work shows how a properly trained autoassociative neural network can promptly detect faulty process signal measurements and produce a best estimate of the actual process value. Noise has been artificially added to the input to evaluate the network ability to respond in a very low signal to noise ratio environment. Training and test datasets have been simulated by the real time transient simulator code APROS. Future development addresses the validation of the model through the use of real data from the plant. (author). 5 refs, 17 figs

  12. Model for neural signaling leap statistics

    Energy Technology Data Exchange (ETDEWEB)

    Chevrollier, Martine; Oria, Marcos, E-mail: oria@otica.ufpb.br [Laboratorio de Fisica Atomica e Lasers Departamento de Fisica, Universidade Federal da ParaIba Caixa Postal 5086 58051-900 Joao Pessoa, Paraiba (Brazil)

    2011-03-01

    We present a simple model for neural signaling leaps in the brain considering only the thermodynamic (Nernst) potential in neuron cells and brain temperature. We numerically simulated connections between arbitrarily localized neurons and analyzed the frequency distribution of the distances reached. We observed qualitative change between Normal statistics (with T 37.5{sup 0}C, awaken regime) and Levy statistics (T = 35.5{sup 0}C, sleeping period), characterized by rare events of long range connections.

  13. Notch signaling patterns neurogenic ectoderm and regulates the asymmetric division of neural progenitors in sea urchin embryos.

    Science.gov (United States)

    Mellott, Dan O; Thisdelle, Jordan; Burke, Robert D

    2017-10-01

    We have examined regulation of neurogenesis by Delta/Notch signaling in sea urchin embryos. At gastrulation, neural progenitors enter S phase coincident with expression of Sp-SoxC. We used a BAC containing GFP knocked into the Sp-SoxC locus to label neural progenitors. Live imaging and immunolocalizations indicate that Sp-SoxC-expressing cells divide to produce pairs of adjacent cells expressing GFP. Over an interval of about 6 h, one cell fragments, undergoes apoptosis and expresses high levels of activated Caspase3. A Notch reporter indicates that Notch signaling is activated in cells adjacent to cells expressing Sp-SoxC. Inhibition of γ-secretase, injection of Sp-Delta morpholinos or CRISPR/Cas9-induced mutation of Sp-Delta results in supernumerary neural progenitors and neurons. Interfering with Notch signaling increases neural progenitor recruitment and pairs of neural progenitors. Thus, Notch signaling restricts the number of neural progenitors recruited and regulates the fate of progeny of the asymmetric division. We propose a model in which localized signaling converts ectodermal and ciliary band cells to neural progenitors that divide asymmetrically to produce a neural precursor and an apoptotic cell. © 2017. Published by The Company of Biologists Ltd.

  14. Are innate immune signaling pathways in plants and animals conserved?

    Science.gov (United States)

    Ausubel, Frederick M

    2005-10-01

    Although adaptive immunity is unique to vertebrates, the innate immune response seems to have ancient origins. Common features of innate immunity in vertebrates, invertebrate animals and plants include defined receptors for microbe-associated molecules, conserved mitogen-associated protein kinase signaling cascades and the production of antimicrobial peptides. It is commonly reported that these similarities in innate immunity represent a process of divergent evolution from an ancient unicellular eukaryote that pre-dated the divergence of the plant and animal kingdoms. However, at present, data suggest that the seemingly analogous regulatory modules used in plant and animal innate immunity are a consequence of convergent evolution and reflect inherent constraints on how an innate immune system can be constructed.

  15. 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 mediator

  16. Characterization of Radar Signals Using Neural Networks

    Science.gov (United States)

    1990-12-01

    e***e*e*eeeeeeeeeeeesseeeeeese*eee*e*e************s /* Function Name: load.input.ptterns Number: 4.1 /* Description: This function determines wether ...XSE.last.layer Number: 8.5 */ /* Description: The function determines wether to backpropate the *f /* parameter by the sigmoidal or linear update...Sigmoidal Function," Mathematics of Control, Signals and Systems, 2:303-314 (March 1989). 6. Dayhoff, Judith E. Neural Network Architectures. New York: Van

  17. Application of neural computing paradigms for signal validation

    International Nuclear Information System (INIS)

    Upadhyaya, B.R.; Eryurek, E.; Mathai, G.

    1989-01-01

    Signal validation and process monitoring problems often require the prediction of one or more process variables in a system. The feasibility of applying neural network paradigms to relate one variable with a set of other related variables is studied. The backpropagation network (BPN) is applied to develop models of signals from both a commercial power plant and the EBR-II. Modification of the BPN algorithm is studied with emphasis on the speed of network training and the accuracy of prediction. The prediction of process variables in a Westinghouse PWR is presented in this paper

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

    Science.gov (United States)

    Wang, Dashan

    2018-06-01

    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.

  19. DMPD: Regulation of innate immunity by suppressor of cytokine signaling (SOCS)proteins. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18406369 Regulation of innate immunity by suppressor of cytokine signaling (SOCS)proteins...svg) (.html) (.csml) Show Regulation of innate immunity by suppressor of cytokine signaling (SOCS)proteins. ...PubmedID 18406369 Title Regulation of innate immunity by suppressor of cytokine signaling (SOCS)proteins

  20. Using neural networks to enhance the Higgs boson signal at hadron colliders

    International Nuclear Information System (INIS)

    Field, R.D.; Kanev, Y.; Tayebnejad, M.; Griffin, P.A.

    1995-01-01

    Neural networks are used to help distinguish the ZZ → ell + ell - -jet-jet signal produced by the decay of a 400 GeV Higgs boson at a proton-proton collider energy of 15 TeV from the ''ordinary'' QCD Z + jets background. The ideal case where only one event at a time enters the detector (no pile-up) and the case of multiple interactions per beam crossing (pile-up) are examined. In both cases, when used in conjunction with the standard cuts, neural networks provide an additional signal to background enhancement

  1. Analysing 21cm signal with artificial neural network

    Science.gov (United States)

    Shimabukuro, Hayato; a Semelin, Benoit

    2018-05-01

    The 21cm signal at epoch of reionization (EoR) should be observed within next decade. We expect that cosmic 21cm signal at the EoR provides us both cosmological and astrophysical information. In order to extract fruitful information from observation data, we need to develop inversion method. For such a method, we introduce artificial neural network (ANN) which is one of the machine learning techniques. We apply the ANN to inversion problem to constrain astrophysical parameters from 21cm power spectrum. We train the architecture of the neural network with 70 training datasets and apply it to 54 test datasets with different value of parameters. We find that the quality of the parameter reconstruction depends on the sensitivity of the power spectrum to the different parameter sets at a given redshift and also find that the accuracy of reconstruction is improved by increasing the number of given redshifts. We conclude that the ANN is viable inversion method whose main strength is that they require a sparse extrapolation of the parameter space and thus should be usable with full simulation.

  2. 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.

  3. Multiple-failure signal validation in nuclear power plants using artificial neural networks

    International Nuclear Information System (INIS)

    Fantoni, P.F.; Mazzola, A.

    1996-01-01

    The possibility of using a neural network to validate process signals during normal and abnormal plant conditions is explored. In boiling water reactor plants, signal validation is used to generate reliable thermal limits calculation and to supply reliable inputs to other computerized systems that support the operator during accident scenarios. The way that autoassociative neural networks can promptly detect faulty process signal measurements and produce a best estimate of the actual process values even in multifailure situations is shown. A method was developed to train the network for multiple sensor-failure detection, based on a random failure simulation algorithm. Noise was artificially added to the input to evaluate the network's ability to respond in a very low signal-to-noise ratio environment. Training and test data sets were simulated by the real-time transient simulator code APROS

  4. Reconstruction of Micropattern Detector Signals using Convolutional Neural Networks

    Science.gov (United States)

    Flekova, L.; Schott, M.

    2017-10-01

    Micropattern gaseous detector (MPGD) technologies, such as GEMs or MicroMegas, are particularly suitable for precision tracking and triggering in high rate environments. Given their relatively low production costs, MPGDs are an exemplary candidate for the next generation of particle detectors. Having acknowledged these advantages, both the ATLAS and CMS collaborations at the LHC are exploiting these new technologies for their detector upgrade programs in the coming years. When MPGDs are utilized for triggering purposes, the measured signals need to be precisely reconstructed within less than 200 ns, which can be achieved by the usage of FPGAs. In this work, we present a novel approach to identify reconstructed signals, their timing and the corresponding spatial position on the detector. In particular, we study the effect of noise and dead readout strips on the reconstruction performance. Our approach leverages the potential of convolutional neural network (CNNs), which have recently manifested an outstanding performance in a range of modeling tasks. The proposed neural network architecture of our CNN is designed simply enough, so that it can be modeled directly by an FPGA and thus provide precise information on reconstructed signals already in trigger level.

  5. Neural Crest-Derived Mesenchymal Cells Require Wnt Signaling for Their Development and Drive Invagination of the Telencephalic Midline

    Science.gov (United States)

    Choe, Youngshik; Zarbalis, Konstantinos S.; Pleasure, Samuel J.

    2014-01-01

    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. PMID:24516524

  6. 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.

  7. Anomalous Signal Detection in ELF Band Electromagnetic Wave using Multi-layer Neural Network with Wavelet Decomposition

    Science.gov (United States)

    Itai, Akitoshi; Yasukawa, Hiroshi; Takumi, Ichi; Hata, Masayasu

    It is well known that electromagnetic waves radiated from the earth's crust are useful for predicting earthquakes. We analyze the electromagnetic waves received at the extremely low frequency band of 223Hz. These observed signals contain the seismic radiation from the earth's crust, but also include several undesired signals. Our research focuses on the signal detection technique to identify an anomalous signal corresponding to the seismic radiation in the observed signal. Conventional anomalous signal detections lack a wide applicability due to their assumptions, e.g. the digital data have to be observed at the same time or the same sensor. In order to overcome the limitation related to the observed signal, we proposed the anomalous signals detection based on a multi-layer neural network which is trained by digital data observed during a span of a day. In the neural network approach, training data do not need to be recorded at the same place or the same time. However, some noises, which have a large amplitude, are detected as the anomalous signal. This paper develops a multi-layer neural network to decrease the false detection of the anomalous signal from the electromagnetic wave. The training data for the proposed network is the decomposed signal of the observed signal during several days, since the seismic radiations are often recorded from several days to a couple of weeks. Results show that the proposed neural network is useful to achieve the accurate detection of the anomalous signal that indicates seismic activity.

  8. Development of protective autoimmunity by immunization with a neural-derived peptide is ineffective in severe spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Susana Martiñón

    Full Text Available Protective autoimmunity (PA is a physiological response to central nervous system trauma that has demonstrated to promote neuroprotection after spinal cord injury (SCI. To reach its beneficial effect, PA should be boosted by immunizing with neural constituents or neural-derived peptides such as A91. Immunizing with A91 has shown to promote neuroprotection after SCI and its use has proven to be feasible in a clinical setting. The broad applications of neural-derived peptides make it important to determine the main features of this anti-A91 response. For this purpose, adult Sprague-Dawley rats were subjected to a spinal cord contusion (SCC; moderate or severe or a spinal cord transection (SCT; complete or incomplete. Immediately after injury, animals were immunized with PBS or A91. Motor recovery, T cell-specific response against A91 and the levels of IL-4, IFN-γ and brain-derived neurotrophic factor (BDNF released by A91-specific T (T(A91 cells were evaluated. Rats with moderate SCC, presented a better motor recovery after A91 immunization. Animals with moderate SCC or incomplete SCT showed significant T cell proliferation against A91 that was characterized chiefly by the predominant production of IL-4 and the release of BDNF. In contrast, immunization with A91 did not promote a better motor recovery in animals with severe SCC or complete SCT. In fact, T cell proliferation against A91 was diminished in these animals. The present results suggest that the effective development of PA and, consequently, the beneficial effects of immunizing with A91 significantly depend on the severity of SCI. This could mainly be attributed to the lack of T(A91 cells which predominantly showed to have a Th2 phenotype capable of producing BDNF, further promoting neuroprotection.

  9. Explaining neural signals in human visual cortex with an associative learning model.

    Science.gov (United States)

    Jiang, Jiefeng; Schmajuk, Nestor; Egner, Tobias

    2012-08-01

    "Predictive coding" models posit a key role for associative learning in visual cognition, viewing perceptual inference as a process of matching (learned) top-down predictions (or expectations) against bottom-up sensory evidence. At the neural level, these models propose that each region along the visual processing hierarchy entails one set of processing units encoding predictions of bottom-up input, and another set computing mismatches (prediction error or surprise) between predictions and evidence. This contrasts with traditional views of visual neurons operating purely as bottom-up feature detectors. In support of the predictive coding hypothesis, a recent human neuroimaging study (Egner, Monti, & Summerfield, 2010) showed that neural population responses to expected and unexpected face and house stimuli in the "fusiform face area" (FFA) could be well-described as a summation of hypothetical face-expectation and -surprise signals, but not by feature detector responses. Here, we used computer simulations to test whether these imaging data could be formally explained within the broader framework of a mathematical neural network model of associative learning (Schmajuk, Gray, & Lam, 1996). Results show that FFA responses could be fit very closely by model variables coding for conditional predictions (and their violations) of stimuli that unconditionally activate the FFA. These data document that neural population signals in the ventral visual stream that deviate from classic feature detection responses can formally be explained by associative prediction and surprise signals.

  10. A preferential design approach for energy-efficient and robust implantable neural signal processing hardware.

    Science.gov (United States)

    Narasimhan, Seetharam; Chiel, Hillel J; Bhunia, Swarup

    2009-01-01

    For implantable neural interface applications, it is important to compress data and analyze spike patterns across multiple channels in real time. Such a computational task for online neural data processing requires an innovative circuit-architecture level design approach for low-power, robust and area-efficient hardware implementation. Conventional microprocessor or Digital Signal Processing (DSP) chips would dissipate too much power and are too large in size for an implantable system. In this paper, we propose a novel hardware design approach, referred to as "Preferential Design" that exploits the nature of the neural signal processing algorithm to achieve a low-voltage, robust and area-efficient implementation using nanoscale process technology. The basic idea is to isolate the critical components with respect to system performance and design them more conservatively compared to the noncritical ones. This allows aggressive voltage scaling for low power operation while ensuring robustness and area efficiency. We have applied the proposed approach to a neural signal processing algorithm using the Discrete Wavelet Transform (DWT) and observed significant improvement in power and robustness over conventional design.

  11. Functional comparison of innate immune signaling pathways in primates.

    Directory of Open Access Journals (Sweden)

    Luis B Barreiro

    2010-12-01

    Full Text Available Humans respond differently than other primates to a large number of infections. Differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. Consistent with that notion, genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates, suggesting that immune responses evolve rapidly, yet providing only indirect evidence for possible inter-species functional differences. To directly compare immune responses among primates, we stimulated primary monocytes from humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS and studied the ensuing time-course regulatory responses. We find that, while the universal Toll-like receptor response is mostly conserved across primates, the regulatory response associated with viral infections is often lineage-specific, probably reflecting rapid host-virus mutual adaptation cycles. Additionally, human-specific immune responses are enriched for genes involved in apoptosis, as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. Finally, we find that chimpanzee-specific immune signaling pathways are enriched for HIV-interacting genes. Put together, our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases.

  12. Enhancing the top-quark signal at Fermilab Tevatron using neural nets

    International Nuclear Information System (INIS)

    Ametller, L.; Garrido, L.; Talavera, P.

    1994-01-01

    We show, in agreement with previous studies, that neural nets can be useful for top-quark analysis at the Fermilab Tevatron. The main features of t bar t and background events in a mixed sample are projected on a single output, which controls the efficiency, purity, and statistical significance of the t bar t signal. We consider a feed-forward multilayer neural net for the CDF reported top-quark mass, using six kinematical variables as inputs. Our main results are based on the exhaustive comparison of the neural net performances with those obtainable from the standard experimental analysis, by imposing different sets of linear cuts over the same variables, showing how the neural net approach improves the standard analysis results

  13. Neural signal processing and closed-loop control algorithm design for an implanted neural recording and stimulation system.

    Science.gov (United States)

    Hamilton, Lei; McConley, Marc; Angermueller, Kai; Goldberg, David; Corba, Massimiliano; Kim, Louis; Moran, James; Parks, Philip D; Sang Chin; Widge, Alik S; Dougherty, Darin D; Eskandar, Emad N

    2015-08-01

    A fully autonomous intracranial device is built to continually record neural activities in different parts of the brain, process these sampled signals, decode features that correlate to behaviors and neuropsychiatric states, and use these features to deliver brain stimulation in a closed-loop fashion. In this paper, we describe the sampling and stimulation aspects of such a device. We first describe the signal processing algorithms of two unsupervised spike sorting methods. Next, we describe the LFP time-frequency analysis and feature derivation from the two spike sorting methods. Spike sorting includes a novel approach to constructing a dictionary learning algorithm in a Compressed Sensing (CS) framework. We present a joint prediction scheme to determine the class of neural spikes in the dictionary learning framework; and, the second approach is a modified OSort algorithm which is implemented in a distributed system optimized for power efficiency. Furthermore, sorted spikes and time-frequency analysis of LFP signals can be used to generate derived features (including cross-frequency coupling, spike-field coupling). We then show how these derived features can be used in the design and development of novel decode and closed-loop control algorithms that are optimized to apply deep brain stimulation based on a patient's neuropsychiatric state. For the control algorithm, we define the state vector as representative of a patient's impulsivity, avoidance, inhibition, etc. Controller parameters are optimized to apply stimulation based on the state vector's current state as well as its historical values. The overall algorithm and software design for our implantable neural recording and stimulation system uses an innovative, adaptable, and reprogrammable architecture that enables advancement of the state-of-the-art in closed-loop neural control while also meeting the challenges of system power constraints and concurrent development with ongoing scientific research designed

  14. Filtering and spectral processing of 1-D signals using cellular neural networks

    NARCIS (Netherlands)

    Moreira-Tamayo, O.; Pineda de Gyvez, J.

    1996-01-01

    This paper presents cellular neural networks (CNN) for one-dimensional discrete signal processing. Although CNN has been extensively used in image processing applications, little has been done for 1-dimensional signal processing. We propose a novel CNN architecture to carry out these tasks. This

  15. Serotonergic Chemosensory Neurons Modify the C. elegans Immune Response by Regulating G-Protein Signaling in Epithelial Cells

    Science.gov (United States)

    Anderson, Alexandra; Laurenson-Schafer, Henry; Partridge, Frederick A.; Hodgkin, Jonathan; McMullan, Rachel

    2013-01-01

    The nervous and immune systems influence each other, allowing animals to rapidly protect themselves from changes in their internal and external environment. However, the complex nature of these systems in mammals makes it difficult to determine how neuronal signaling influences the immune response. Here we show that serotonin, synthesized in Caenorhabditis elegans chemosensory neurons, modulates the immune response. Serotonin released from these cells acts, directly or indirectly, to regulate G-protein signaling in epithelial cells. Signaling in these cells is required for the immune response to infection by the natural pathogen Microbacterium nematophilum. Here we show that serotonin signaling suppresses the innate immune response and limits the rate of pathogen clearance. We show that C. elegans uses classical neurotransmitters to alter the immune response. Serotonin released from sensory neurons may function to modify the immune system in response to changes in the animal's external environment such as the availability, or quality, of food. PMID:24348250

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Uriel Trahtemberg

    2017-10-01

    Full Text Available 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 × 108 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

  18. Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis.

    Science.gov (United States)

    Carucci, Nicoletta; Cacci, Emanuele; Nisi, Paola S; Licursi, Valerio; Paul, Yu-Lee; Biagioni, Stefano; Negri, Rodolfo; Rugg-Gunn, Peter J; Lupo, Giuseppe

    2017-04-01

    During vertebrate neural development, positional information is largely specified by extracellular morphogens. Their distribution, however, is very dynamic due to the multiple roles played by the same signals in the developing and adult neural tissue. This suggests that neural progenitors are able to modify their competence to respond to morphogen signalling and autonomously maintain positional identities after their initial specification. In this work, we take advantage of in vitro culture systems of mouse neural stem/progenitor cells (NSPCs) to show that NSPCs isolated from rostral or caudal regions of the mouse neural tube are differentially responsive to retinoic acid (RA), a pivotal morphogen for the specification of posterior neural fates. Hoxb genes are among the best known RA direct targets in the neural tissue, yet we found that RA could promote their transcription only in caudal but not in rostral NSPCs. Correlating with these effects, key RA-responsive regulatory regions in the Hoxb cluster displayed opposite enrichment of activating or repressing histone marks in rostral and caudal NSPCs. Finally, RA was able to strengthen Hoxb chromatin activation in caudal NSPCs, but was ineffective on the repressed Hoxb chromatin of rostral NSPCs. These results suggest that the response of NSPCs to morphogen signalling across the rostrocaudal axis of the neural tube may be gated by the epigenetic configuration of target patterning genes, allowing long-term maintenance of intrinsic positional values in spite of continuously changing extrinsic signals.

  19. Irrational exuberance and neural crash warning signals during endogenous experimental market bubbles.

    Science.gov (United States)

    Smith, Alec; Lohrenz, Terry; King, Justin; Montague, P Read; Camerer, Colin F

    2014-07-22

    Groups of humans routinely misassign value to complex future events, especially in settings involving the exchange of resources. If properly structured, experimental markets can act as excellent probes of human group-level valuation mechanisms during pathological overvaluations--price bubbles. The connection between the behavioral and neural underpinnings of such phenomena has been absent, in part due to a lack of enabling technology. We used a multisubject functional MRI paradigm to measure neural activity in human subjects participating in experimental asset markets in which endogenous price bubbles formed and crashed. Although many ideas exist about how and why such bubbles may form and how to identify them, our experiment provided a window on the connection between neural responses and behavioral acts (buying and selling) that created the bubbles. We show that aggregate neural activity in the nucleus accumbens (NAcc) tracks the price bubble and that NAcc activity aggregated within a market predicts future price changes and crashes. Furthermore, the lowest-earning subjects express a stronger tendency to buy as a function of measured NAcc activity. Conversely, we report a signal in the anterior insular cortex in the highest earners that precedes the impending price peak, is associated with a higher propensity to sell in high earners, and that may represent a neural early warning signal in these subjects. Such markets could be a model system to understand neural and behavior mechanisms in other settings where emergent group-level activity exhibits mistaken belief or valuation.

  20. Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway.

    Science.gov (United States)

    Troutwine, B R; Ghezzi, A; Pietrzykowski, A Z; Atkinson, N S

    2016-04-01

    A growing body of evidence has shown that alcohol alters the activity of the innate immune system and that changes in innate immune system activity can influence alcohol-related behaviors. Here, we show that the Toll innate immune signaling pathway modulates the level of alcohol resistance in Drosophila. In humans, a low level of response to alcohol is correlated with increased risk of developing an alcohol use disorder. The Toll signaling pathway was originally discovered in, and has been extensively studied in Drosophila. The Toll pathway is a major regulator of innate immunity in Drosophila, and mammalian Toll-like receptor signaling has been implicated in alcohol responses. Here, we use Drosophila-specific genetic tools to test eight genes in the Toll signaling pathway for effects on the level of response to ethanol. We show that increasing the activity of the pathway increases ethanol resistance whereas decreasing the pathway activity reduces ethanol resistance. Furthermore, we show that gene products known to be outputs of innate immune signaling are rapidly induced following ethanol exposure. The interaction between the Toll signaling pathway and ethanol is rooted in the natural history of Drosophila melanogaster. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  1. Signal-independent timescale analysis (SITA) and its application for neural coding during reaching and walking.

    Science.gov (United States)

    Zacksenhouse, Miriam; Lebedev, Mikhail A; Nicolelis, Miguel A L

    2014-01-01

    What are the relevant timescales of neural encoding in the brain? This question is commonly investigated with respect to well-defined stimuli or actions. However, neurons often encode multiple signals, including hidden or internal, which are not experimentally controlled, and thus excluded from such analysis. Here we consider all rate modulations as the signal, and define the rate-modulations signal-to-noise ratio (RM-SNR) as the ratio between the variance of the rate and the variance of the neuronal noise. As the bin-width increases, RM-SNR increases while the update rate decreases. This tradeoff is captured by the ratio of RM-SNR to bin-width, and its variations with the bin-width reveal the timescales of neural activity. Theoretical analysis and simulations elucidate how the interactions between the recovery properties of the unit and the spectral content of the encoded signals shape this ratio and determine the timescales of neural coding. The resulting signal-independent timescale analysis (SITA) is applied to investigate timescales of neural activity recorded from the motor cortex of monkeys during: (i) reaching experiments with Brain-Machine Interface (BMI), and (ii) locomotion experiments at different speeds. Interestingly, the timescales during BMI experiments did not change significantly with the control mode or training. During locomotion, the analysis identified units whose timescale varied consistently with the experimentally controlled speed of walking, though the specific timescale reflected also the recovery properties of the unit. Thus, the proposed method, SITA, characterizes the timescales of neural encoding and how they are affected by the motor task, while accounting for all rate modulations.

  2. 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

  3. Xanomeline suppresses excessive pro-inflammatory cytokine responses through neural signal-mediated pathways and improves survival in lethal inflammation

    Science.gov (United States)

    Rosas-Ballina, Mauricio; Ferrer, Sergio Valdés; Dancho, Meghan; Ochani, Mahendar; Katz, David; Cheng, Kai Fan; Olofsson, Peder S.; Chavan, Sangeeta S.; Al-Abed, Yousef; Tracey, Kevin J.; Pavlov, Valentin A.

    2014-01-01

    Inflammatory conditions characterized by excessive immune cell activation and cytokine release, are associated with bidirectional immune system-brain communication, underlying sickness behavior and other physiological responses. The vagus nerve has an important role in this communication by conveying sensory information to the brain, and brain-derived immunoregulatory signals that suppress peripheral cytokine levels and inflammation. Brain muscarinic acetylcholine receptor (mAChR)-mediated cholinergic signaling has been implicated in this regulation. However, the possibility of controlling inflammation by peripheral administration of centrally-acting mAChR agonists is unexplored. To provide insight we used the centrally-acting M1 mAChR agonist xanomeline, previously developed in the context of Alzheimer’s disease and schizophrenia. Intraperitoneal administration of xanomeline significantly suppressed serum and splenic TNF levels, alleviated sickness behavior, and increased survival during lethal murine endotoxemia. The anti-inflammatory effects of xanomeline were brain mAChR-mediated and required intact vagus nerve and splenic nerve signaling. The anti-inflammatory efficacy of xanomeline was retained for at least 20h, associated with alterations in splenic lymphocyte, and dendritic cell proportions, and decreased splenocyte responsiveness to endotoxin. These results highlight an important role of the M1 mAChR in a neural circuitry to spleen in which brain cholinergic activation lowers peripheral pro-inflammatory cytokines to levels favoring survival. The therapeutic efficacy of xanomeline was also manifested by significantly improved survival in preclinical settings of severe sepsis. These findings are of interest for strategizing novel therapeutic approaches in inflammatory diseases. PMID:25063706

  4. 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.

  5. 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

  6. Calcium signaling mediates five types of cell morphological changes to form neural rosettes.

    Science.gov (United States)

    Hříbková, Hana; Grabiec, Marta; Klemová, Dobromila; Slaninová, Iva; Sun, Yuh-Man

    2018-02-12

    Neural rosette formation is a critical morphogenetic process during neural development, whereby neural stem cells are enclosed in rosette niches to equipoise proliferation and differentiation. How neural rosettes form and provide a regulatory micro-environment remains to be elucidated. We employed the human embryonic stem cell-based neural rosette system to investigate the structural development and function of neural rosettes. Our study shows that neural rosette formation consists of five types of morphological change: intercalation, constriction, polarization, elongation and lumen formation. Ca 2+ signaling plays a pivotal role in the five steps by regulating the actions of the cytoskeletal complexes, actin, myosin II and tubulin during intercalation, constriction and elongation. These, in turn, control the polarizing elements, ZO-1, PARD3 and β-catenin during polarization and lumen production for neural rosette formation. We further demonstrate that the dismantlement of neural rosettes, mediated by the destruction of cytoskeletal elements, promotes neurogenesis and astrogenesis prematurely, indicating that an intact rosette structure is essential for orderly neural development. © 2018. Published by The Company of Biologists Ltd.

  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. Signal-Independent Timescale Analysis (SITA and its Application for Neural Coding during Reaching and Walking

    Directory of Open Access Journals (Sweden)

    Miriam eZacksenhouse

    2014-08-01

    Full Text Available What are the relevant timescales of neural encoding in the brain? This question is commonly investigated with respect to well-defined stimuli or actions. However, neurons often encode multiple signals, including hidden or internal, which are not experimentally controlled, and thus excluded from such analysis. Here we consider all rate modulations as the signal, and define the rate-modulations signal-to-noise ratio (RM-SNR as the ratio between the variance of the rate and the variance of the neuronal noise. As the bin-width increases, RM-SNR increases while the update rate decreases. This tradeoff is captured by the ratio of RM-SNR to bin-width, and its variations with the bin-width reveal the timescales of neural activity. Theoretical analysis and simulations elucidate how the interactions between the recovery properties of the unit and the spectral content of the encoded signals shape this ratio and determine the timescales of neural coding. The resulting signal-independent timescale analysis (SITA is applied to investigate timescales of neural activity recorded from the motor cortex of monkeys during: (i reaching experiments with Brain-Machine Interface (BMI, and (ii locomotion experiments at different speeds. Interestingly, the timescales during BMI experiments did not change significantly with the control mode or training. During locomotion, the analysis identified units whose timescale varied consistently with the experimentally controlled speed of walking, though the specific timescale reflected also the recovery properties of the unit. Thus, the proposed method, SITA, characterizes the timescales of neural encoding and how they are affected by the motor task, while accounting for all rate modulations.

  9. 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

  10. Active voltammetric microsensors with neural signal processing

    Science.gov (United States)

    Vogt, Michael C.; Skubal, Laura R.

    1999-02-01

    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 detect, recognize, and

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

    Directory of Open Access Journals (Sweden)

    Daewoo eLee

    2015-08-01

    Full Text Available 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.

  12. miR-342-5p Regulates Neural Stem Cell Proliferation and Differentiation Downstream to Notch Signaling in Mice

    Directory of Open Access Journals (Sweden)

    Fang Gao

    2017-04-01

    Full Text Available Summary: Notch signaling is critically involved in neural development, but the downstream effectors remain incompletely understood. In this study, we cultured neurospheres from Nestin-Cre-mediated conditional Rbp-j knockout (Rbp-j cKO and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, miR-342-5p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted. Consistently, the promoter of the miR-342-5p host gene, the Ena-vasodilator stimulated phosphoprotein-like (Evl, was negatively regulated by Notch signaling, probably through HES5. Transfection of miR-342-5p promoted the differentiation of neural stem cells (NSCs into intermediate neural progenitors (INPs in vitro and reduced the stemness of NSCs in vivo. Furthermore, miR-342-5p inhibited the differentiation of neural stem/intermediate progenitor cells into astrocytes, likely mediated by targeting GFAP directly. Our results indicated that miR-342-5p could function as a downstream effector of Notch signaling to regulate the differentiation of NSCs into INPs and astrocytes commitment. : In this article, Han and colleagues show that miR-342-5p acts as a downstream effector of Notch signaling in the mouse CNS. Notch signal inhibits miR-342-5p expression by regulating its host gene Evl. And with attenuated Notch signal in NSCs, miR-342-5p is upregulated to promote NSCs transition into INPs, and to inhibit astrocyte commitment by targeting GFAP. Keywords: neural stem cells, intermediate neural progenitors, Notch, RBP-J, neuron, glia, miR-342-5p

  13. Immunomodulation of enteric neural function in irritable bowel syndrome.

    Science.gov (United States)

    O'Malley, Dervla

    2015-06-28

    Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder which is characterised by symptoms such as bloating, altered bowel habit and visceral pain. It's generally accepted that miscommunication between the brain and gut underlies the changes in motility, absorpto-secretory function and pain sensitivity associated with IBS. However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. Anecdotally, IBS patients have noted that periods of stress can result in symptom flares and many patients exhibit co-morbid stress-related mood disorders such as anxiety and depression. However, in addition to psychosocial stressors, infection-related stress has also been linked with the initiation, persistence and severity of symptom flares. Indeed, prior gastrointestinal infection is one of the strongest predictors of developing IBS. Despite a lack of overt morphological inflammation, the importance of immune factors in the pathophysiology of IBS is gaining acceptance. Subtle changes in the numbers of mucosal immune cell infiltrates and elevated levels of circulating pro-inflammatory cytokines have been reproducibly demonstrated in IBS populations. Moreover, these immune mediators directly affect neural signalling. An exciting new area of research is the role of luminal microbiota in the modulation of neuro-immune signalling, resulting in local changes in gastrointestinal function and alterations in central neural functioning. Progress in this area has begun to unravel some of the complexities of neuroimmune and neuroendocrine interactions and how these molecular exchanges contribute to GI dysfunction.

  14. PANP is a novel O-glycosylated PILR{alpha} ligand expressed in neural tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kogure, Amane [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); Shiratori, Ikuo [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Wang, Jing [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); Lanier, Lewis L. [Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143 (United States); Arase, Hisashi, E-mail: arase@biken.osaka-u.ac.jp [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); JST CREST, Saitama 332-0012 (Japan)

    2011-02-18

    Research highlights: {yields} A Novel molecule, PANP, was identified to be a PILR{alpha} ligand. {yields} Sialylated O-glycan structures on PANP were required for PILR{alpha} recognition. {yields} Transcription of PANP was mainly observed in neural tissues. {yields} PANP seems to be involved in immune regulation as a ligand for PILR{alpha}. -- Abstract: PILR{alpha} is an immune inhibitory receptor possessing an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain enabling it to deliver inhibitory signals. Binding of PILR{alpha} to its ligand CD99 is involved in immune regulation; however, whether there are other PILR{alpha} ligands in addition to CD99 is not known. Here, we report that a novel molecule, PILR-associating neural protein (PANP), acts as an additional ligand for PILR{alpha}. Transcription of PANP was mainly observed in neural tissues. PILR{alpha}-Ig fusion protein bound cells transfected with PANP and the transfectants stimulated PILR{alpha} reporter cells. Specific O-glycan structures on PANP were found to be required for PILR recognition of this ligand. These results suggest that PANP is involved in immune regulation as a ligand of the PILR{alpha}.

  15. Genetic deletion of Rnd3 in neural stem cells promotes proliferation via upregulation of Notch signaling.

    Science.gov (United States)

    Dong, Huimin; Lin, Xi; Li, Yuntao; Hu, Ronghua; Xu, Yang; Guo, Xiaojie; La, Qiong; Wang, Shun; Fang, Congcong; Guo, Junli; Li, Qi; Mao, Shanping; Liu, Baohui

    2017-10-31

    Rnd3, a Rho GTPase, is involved in the inhibition of actin cytoskeleton dynamics through the Rho kinase-dependent signaling pathway. We previously demonstrated that mice with genetic deletion of Rnd3 developed a markedly larger brain compared with wild-type mice. Here, we demonstrate that Rnd3 knockout mice developed an enlarged subventricular zone, and we identify a novel role for Rnd3 as an inhibitor of Notch signaling in neural stem cells. Rnd3 deficiency, both in vivo and in vitro , resulted in increased levels of Notch intracellular domain protein. This led to enhanced Notch signaling and promotion of aberrant neural stem cell growth, thereby resulting in a larger subventricular zone and a markedly larger brain. Inhibition of Notch activity abrogated this aberrant neural stem cell growth.

  16. 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

  17. [A wavelet neural network algorithm of EEG signals data compression and spikes recognition].

    Science.gov (United States)

    Zhang, Y; Liu, A; Yu, K

    1999-06-01

    A novel method of EEG signals compression representation and epileptiform spikes recognition based on wavelet neural network and its algorithm is presented. The wavelet network not only can compress data effectively but also can recover original signal. In addition, the characters of the spikes and the spike-slow rhythm are auto-detected from the time-frequency isoline of EEG signal. This method is well worth using in the field of the electrophysiological signal processing and time-frequency analyzing.

  18. An input feature selection method applied to fuzzy neural networks for signal esitmation

    International Nuclear Information System (INIS)

    Na, Man Gyun; Sim, Young Rok

    2001-01-01

    It is well known that the performance of a fuzzy neural networks strongly depends on the input features selected for its training. In its applications to sensor signal estimation, there are a large number of input variables related with an output. As the number of input variables increases, the training time of fuzzy neural networks required increases exponentially. Thus, it is essential to reduce the number of inputs to a fuzzy neural networks and to select the optimum number of mutually independent inputs that are able to clearly define the input-output mapping. In this work, principal component analysis (PAC), genetic algorithms (GA) and probability theory are combined to select new important input features. A proposed feature selection method is applied to the signal estimation of the steam generator water level, the hot-leg flowrate, the pressurizer water level and the pressurizer pressure sensors in pressurized water reactors and compared with other input feature selection methods

  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. Application of artificial neural network to search for gravitational-wave signals associated with short gamma-ray bursts

    International Nuclear Information System (INIS)

    Kim, Kyungmin; Lee, Hyun Kyu; Harry, Ian W; Hodge, Kari A; Kim, Young-Min; Lee, Chang-Hwan; Oh, John J; Oh, Sang Hoon; Son, Edwin J

    2015-01-01

    We apply a machine learning algorithm, the artificial neural network, to the search for gravitational-wave signals associated with short gamma-ray bursts (GRBs). The multi-dimensional samples consisting of data corresponding to the statistical and physical quantities from the coherent search pipeline are fed into the artificial neural network to distinguish simulated gravitational-wave signals from background noise artifacts. Our result shows that the data classification efficiency at a fixed false alarm probability (FAP) is improved by the artificial neural network in comparison to the conventional detection statistic. Specifically, the distance at 50% detection probability at a fixed false positive rate is increased about 8%–14% for the considered waveform models. We also evaluate a few seconds of the gravitational-wave data segment using the trained networks and obtain the FAP. We suggest that the artificial neural network can be a complementary method to the conventional detection statistic for identifying gravitational-wave signals related to the short GRBs. (paper)

  1. 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

  2. Innate immune receptor Toll-like receptor 4 signalling in neuropsychiatric diseases.

    Science.gov (United States)

    García Bueno, B; Caso, J R; Madrigal, J L M; Leza, J C

    2016-05-01

    The innate immunity is a stereotyped first line of defense against pathogens and unspecified damage signals. One of main actors of innate immunity are the Toll-like receptors (TLRs), and one of the better characterized members of this family is TLR-4, that it is mainly activated by Gram-negative bacteria lipopolysaccharide. In brain, TLR-4 organizes innate immune responses against infections or cellular damage, but also possesses other physiological functions. In the last years, some evidences suggest a role of TLR-4 in stress and stress-related neuropsychiatric diseases. Peripheral and brain TLR-4 activation triggers sickness behavior, and its expression is a risk factor of depression. Some elements of the TLR-4 signaling pathway are up-regulated in peripheral samples and brain post-mortem tissue from depressed and suicidal patients. The "leaky gut" hypothesis of neuropsychiatric diseases is based on the existence of an increase of the intestinal permeability which results in bacterial translocation able to activate TLR-4. Enhanced peripheral TLR-4 expression/activity has been described in subjects diagnosed with schizophrenia, bipolar disorder and in autistic children. A role for TLR-4 in drugs abuse has been also proposed. The therapeutic potential of pharmacological/genetic modulation of TLRs signaling pathways in neuropsychiatry is promising, but a great preclinical/clinical scientific effort is still needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Cannabinoids and Innate Immunity: Taking a Toll on Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Eric J. Downer

    2011-01-01

    Full Text Available The biologically active components of cannabis have therapeutic potential in neuroinflammatory disorders due to their anti-inflammatory propensity. Cannabinoids influence immune function in both the peripheral and the central nervous system (CNS, and the components of the cannabinoid system, the cannabinoid receptors and their endogenous ligands (endocannabinoids, have been detected on immune cells as well as in brain glia. Neuroinflammation is the complex innate immune response of neural tissue to control infection and eliminate pathogens, and Toll-like receptors (TLRs, a major family of pattern recognition receptors (PRRs that mediate innate immunity, have emerged as players in the neuroinflammatory processes underpinning various CNS diseases. This review will highlight evidence that cannabinoids interact with the immune system by impacting TLR-mediated signaling events, which may provide cues for devising novel therapeutic approaches for cannabinoid ligands.

  4. Recurrent neural network approach to quantum signal: coherent state restoration for continuous-variable quantum key distribution

    Science.gov (United States)

    Lu, Weizhao; Huang, Chunhui; Hou, Kun; Shi, Liting; Zhao, Huihui; Li, Zhengmei; Qiu, Jianfeng

    2018-05-01

    In continuous-variable quantum key distribution (CV-QKD), weak signal carrying information transmits from Alice to Bob; during this process it is easily influenced by unknown noise which reduces signal-to-noise ratio, and strongly impacts reliability and stability of the communication. Recurrent quantum neural network (RQNN) is an artificial neural network model which can perform stochastic filtering without any prior knowledge of the signal and noise. In this paper, a modified RQNN algorithm with expectation maximization algorithm is proposed to process the signal in CV-QKD, which follows the basic rule of quantum mechanics. After RQNN, noise power decreases about 15 dBm, coherent signal recognition rate of RQNN is 96%, quantum bit error rate (QBER) drops to 4%, which is 6.9% lower than original QBER, and channel capacity is notably enlarged.

  5. Convergence of neuro-endocrine-immune pathways in the pathophysiology of irritable bowel syndrome.

    Science.gov (United States)

    Buckley, Maria M; O'Mahony, Siobhain M; O'Malley, Dervla

    2014-07-21

    Disordered signalling between the brain and the gut are generally accepted to underlie the functional bowel disorder, irritable bowel syndrome (IBS). However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. This common gastrointestinal disorder is characterised by alterations in bowel habit such as diarrhoea and/or constipation, bloating and abdominal pain, and symptom exacerbation has been linked with periods of stress, both psychosocial and infection-related. Indeed, a high level of comorbidity exists between IBS and stress-related mood disorders such as anxiety and depression. Moreover, studies have observed alterations in autonomic output and neuro-endocrine signalling in IBS patients. Accumulating evidence indicates that a maladaptive stress response, probably mediated by the stress hormone, corticotropin-releasing factor contributes to the initiation, persistence and severity of symptom flares. Other risk factors for developing IBS include a positive family history, childhood trauma, dietary factors and prior gastrointestinal infection. An emerging role has been attributed to the importance of immune factors in the pathophysiology of IBS with evidence of altered cytokine profiles and increased levels of mucosal immune cells. These factors have also been shown to have direct effects on neural signalling. This review discusses how pathological changes in neural, immune and endocrine pathways, and communication between these systems, contribute to symptom flares in IBS.

  6. Brain Region-Dependent Rejection of Neural Precursor Cell Transplants

    Directory of Open Access Journals (Sweden)

    Nina Fainstein

    2018-04-01

    Full Text Available The concept of CNS as an immune-privileged site has been challenged by the occurrence of immune surveillance and allogeneic graft rejection in the brain. Here we examined whether the immune response to allogeneic neural grafts is determined by the site of implantation in the CNS. Dramatic regional differences were observed between immune responses to allogeneic neural precursor/stem cell (NPC grafts in the striatum vs. the hippocampus. Striatal grafts were heavily infiltrated with IBA-1+ microglia/macrophages and CD3+ T cells and completely rejected. In contrast, hippocampal grafts exhibited milder IBA-1+ cell infiltration, were not penetrated efficiently by CD3+ cells, and survived efficiently for at least 2 months. To evaluate whether the hippocampal protective effect is universal, astrocytes were then transplanted. Allogeneic astrocyte grafts elicited a vigorous rejection process from the hippocampus. CD200, a major immune-inhibitory signal, plays an important role in protecting grafts from rejection. Indeed, CD200 knock out NPC grafts were rejected more efficiently than wild type NPCs from the striatum. However, lack of CD200 expression did not elicit NPC graft rejection from the hippocampus. In conclusion, the hippocampus has partial immune-privilege properties that are restricted to NPCs and are CD200-independent. The unique hippocampal milieu may be protective for allogeneic NPC grafts, through host-graft interactions enabling sustained immune-regulatory properties of transplanted NPCs. These findings have implications for providing adequate immunosuppression in clinical translation of cell therapy.

  7. Retinoic acid signaling in B-cells is essential for oral immunization and microflora composition

    Science.gov (United States)

    Pantazi, Eirini; Marks, Ellen; Stolarczyk, Emilie; Lycke, Nils; Noelle, Randolph J.; Elgueta, Raul

    2015-01-01

    Retinoic acid (RA)3 is a critical regulator of the intestinal adaptive immune response. However, the intrinsic impact of RA on B cell differentiation in the regulation of gut humoral immunity in vivo has never been directly shown. To address this issue, we have been able to generate a mouse model where B-cells specifically express a dominant negative receptor α for RA. Here, we show that the silencing of RA signaling in B-cells reduces the numbers of IgA+ antibody secreting cells (ASC) both in vitro and in vivo, suggesting that RA has a direct effect on IgA plasma cell (PC) differentiation. Moreover, the lack of RA signaling in B-cells abrogates Ag-specific IgA responses after oral immunization and affects the microbiota composition. In conclusion, these results suggest that RA signaling in B-cells through the RA receptor α is important to generate an effective gut humoral response and to maintain a normal microbiota composition. PMID:26163586

  8. 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

  9. 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

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

    DEFF Research Database (Denmark)

    Harbo, Anders La-Cour

    2004-01-01

    ) for finding sparse representations of music signals. This method is a set of two ordinary differential equations. We argue that the most important parameter for optimal use of this method is the discretization step size, and we demonstrate that this can be a priori determined. This significantly speeds up......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...

  11. Forecast of TEXT plasma disruptions using soft X rays as input signal in a neural network

    International Nuclear Information System (INIS)

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

    1999-01-01

    A feedforward neural network with two hidden layers is used to forecast major and minor disruptive instabilities in TEXT tokamak discharges. Using the experimental data of soft X ray signals as input data, the neural network is trained with one disruptive plasma discharge, and a different disruptive discharge is used for validation. After being properly trained, the networks, with the same set of weights, are used to forecast disruptions in two other plasma discharges. It is observed that the neural network is able to predict the occurrence of a disruption more than 3 ms in advance. This time interval is almost 3 times longer than the one already obtained previously when a magnetic signal from a Mirnov coil was used to feed the neural networks. Visually no indication of an upcoming disruption is seen from the experimental data this far back from the time of disruption. Finally, by observing the predictive behaviour of the network for the disruptive discharges analysed and comparing the soft X ray data with the corresponding magnetic experimental signal, it is conjectured about where inside the plasma column the disruption first started. (author)

  12. TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke

    Directory of Open Access Journals (Sweden)

    Buckwalter Marion S

    2010-10-01

    Full Text Available Abstract Background TGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging. Methods We performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia. Results TGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes. Conclusions We found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial

  13. TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke.

    Science.gov (United States)

    Doyle, Kristian P; Cekanaviciute, Egle; Mamer, Lauren E; Buckwalter, Marion S

    2010-10-11

    TGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging. We performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia. TGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes. We found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial scar formation and the immune response to stroke.

  14. Immune evasion of porcine enteric coronaviruses and viral modulation of antiviral innate signaling.

    Science.gov (United States)

    Zhang, Qingzhan; Yoo, Dongwan

    2016-12-02

    Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) are emerged and reemerging viruses in pigs, and together with transmissible gastroenteritis virus (TGEV), pose significant economic concerns to the swine industry. These viruses infect epithelial cells of the small intestine and cause watery diarrhea, dehydration, and a high mortality in neonatal piglets. Type I interferons (IFN-α/β) are major antiviral cytokines forming host innate immunity, and in turn, these enteric coronaviruses have evolved to modulate the host innate immune signaling during infection. Accumulating evidence however suggests that IFN induction and signaling in the intestinal epithelial cells differ from other epithelial cells, largely due to distinct features of the gut epithelial mucosal surface and commensal microflora, and it appears that type III interferon (IFN-λ) plays a key role to maintain the antiviral state in the gut. This review describes the recent understanding on the immune evasion strategies of porcine enteric coronaviruses and the role of different types of IFNs for intestinal antiviral innate immunity. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Detection of directional eye movements based on the electrooculogram signals through an artificial neural network

    International Nuclear Information System (INIS)

    Erkaymaz, Hande; Ozer, Mahmut; Orak, İlhami Muharrem

    2015-01-01

    The electrooculogram signals are very important at extracting information about detection of directional eye movements. Therefore, in this study, we propose a new intelligent detection model involving an artificial neural network for the eye movements based on the electrooculogram signals. In addition to conventional eye movements, our model also involves the detection of tic and blinking of an eye. We extract only two features from the electrooculogram signals, and use them as inputs for a feed-forwarded artificial neural network. We develop a new approach to compute these two features, which we call it as a movement range. The results suggest that the proposed model have a potential to become a new tool to determine the directional eye movements accurately

  16. The COP9 signalosome converts temporal hormone signaling to spatial restriction on neural competence.

    Directory of Open Access Journals (Sweden)

    Yi-Chun Huang

    2014-11-01

    Full Text Available During development, neural competence is conferred and maintained by integrating spatial and temporal regulations. The Drosophila sensory bristles that detect mechanical and chemical stimulations are arranged in stereotypical positions. The anterior wing margin (AWM is arrayed with neuron-innervated sensory bristles, while posterior wing margin (PWM bristles are non-innervated. We found that the COP9 signalosome (CSN suppresses the neural competence of non-innervated bristles at the PWM. In CSN mutants, PWM bristles are transformed into neuron-innervated, which is attributed to sustained expression of the neural-determining factor Senseless (Sens. The CSN suppresses Sens through repression of the ecdysone signaling target gene broad (br that encodes the BR-Z1 transcription factor to activate sens expression. Strikingly, CSN suppression of BR-Z1 is initiated at the prepupa-to-pupa transition, leading to Sens downregulation, and termination of the neural competence of PWM bristles. The role of ecdysone signaling to repress br after the prepupa-to-pupa transition is distinct from its conventional role in activation, and requires CSN deneddylating activity and multiple cullins, the major substrates of deneddylation. Several CSN subunits physically associate with ecdysone receptors to represses br at the transcriptional level. We propose a model in which nuclear hormone receptors cooperate with the deneddylation machinery to temporally shutdown downstream target gene expression, conferring a spatial restriction on neural competence at the PWM.

  17. 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.

  18. Pulse-coupled neural nets: translation, rotation, scale, distortion, and intensity signal invariance for images.

    Science.gov (United States)

    Johnson, J L

    1994-09-10

    The linking-field neural network model of Eckhorn et al. [Neural Comput. 2, 293-307 (1990)] was introduced to explain the experimentally observed synchronous activity among neural assemblies in the cat cortex induced by feature-dependent visual activity. The model produces synchronous bursts of pulses from neurons with similar activity, effectively grouping them by phase and pulse frequency. It gives a basic new function: grouping by similarity. The synchronous bursts are obtained in the limit of strong linking strengths. The linking-field model in the limit of moderate-to-weak linking characterized by few if any multiple bursts is investigated. In this limit dynamic, locally periodic traveling waves exist whose time signal encodes the geometrical structure of a two-dimensional input image. The signal can be made insensitive to translation, scale, rotation, distortion, and intensity. The waves transmit information beyond the physical interconnect distance. The model is implemented in an optical hybrid demonstration system. Results of the simulations and the optical system are presented.

  19. 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.

  20. Noise in Neural Networks: Thresholds, Hysteresis, and Neuromodulation of Signal-To-Noise

    Science.gov (United States)

    Keeler, James D.; Pichler, Elgar E.; Ross, John

    1989-03-01

    We study a neural-network model including Gaussian noise, higher-order neuronal interactions, and neuromodulation. For a first-order network, there is a threshold in the noise level (phase transition) above which the network displays only disorganized behavior and critical slowing down near the noise threshold. The network can tolerate more noise if it has higher-order feedback interactions, which also lead to hysteresis and multistability in the network dynamics. The signal-to-noise ratio can be adjusted in a biological neural network by neuromodulators such as norepinephrine. Comparisons are made to experimental results and further investigations are suggested to test the effects of hysteresis and neuromodulation in pattern recognition and learning. We propose that norepinephrine may ``quench'' the neural patterns of activity to enhance the ability to learn details.

  1. 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.

  2. 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.

  3. ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

    Science.gov (United States)

    Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

    2010-01-01

    SUMMARY The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identified as substrates for ADAM13. ADAM13 upregulates canonical Wnt signaling and early expression of the transcription factor snail2, whereas EfnB1 inhibits the canonical Wnt pathway and snail2 expression. We propose that by cleaving class B Efns, ADAM13 promotes canonical Wnt signaling and early CNC induction. PMID:20708595

  4. Predictable information in neural signals during resting state is reduced in autism spectrum disorder.

    Science.gov (United States)

    Brodski-Guerniero, Alla; Naumer, Marcus J; Moliadze, Vera; Chan, Jason; Althen, Heike; Ferreira-Santos, Fernando; Lizier, Joseph T; Schlitt, Sabine; Kitzerow, Janina; Schütz, Magdalena; Langer, Anne; Kaiser, Jochen; Freitag, Christine M; Wibral, Michael

    2018-04-04

    The neurophysiological underpinnings of the nonsocial symptoms of autism spectrum disorder (ASD) which include sensory and perceptual atypicalities remain poorly understood. Well-known accounts of less dominant top-down influences and more dominant bottom-up processes compete to explain these characteristics. These accounts have been recently embedded in the popular framework of predictive coding theory. To differentiate between competing accounts, we studied altered information dynamics in ASD by quantifying predictable information in neural signals. Predictable information in neural signals measures the amount of stored information that is used for the next time step of a neural process. Thus, predictable information limits the (prior) information which might be available for other brain areas, for example, to build predictions for upcoming sensory information. We studied predictable information in neural signals based on resting-state magnetoencephalography (MEG) recordings of 19 ASD patients and 19 neurotypical controls aged between 14 and 27 years. Using whole-brain beamformer source analysis, we found reduced predictable information in ASD patients across the whole brain, but in particular in posterior regions of the default mode network. In these regions, epoch-by-epoch predictable information was positively correlated with source power in the alpha and beta frequency range as well as autocorrelation decay time. Predictable information in precuneus and cerebellum was negatively associated with nonsocial symptom severity, indicating a relevance of the analysis of predictable information for clinical research in ASD. Our findings are compatible with the assumption that use or precision of prior knowledge is reduced in ASD patients. © 2018 Wiley Periodicals, Inc.

  5. 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.

  6. A Plant Phytosulfokine Peptide Initiates Auxin-Dependent Immunity through Cytosolic Ca2+ Signaling in Tomato.

    Science.gov (United States)

    Zhang, Huan; Hu, Zhangjian; Lei, Cui; Zheng, Chenfei; Wang, Jiao; Shao, Shujun; Li, Xin; Xia, Xiaojian; Cai, Xinzhong; Zhou, Jie; Zhou, Yanhong; Yu, Jingquan; Foyer, Christine H; Shi, Kai

    2018-03-01

    Phytosulfokine (PSK) is a disulfated pentapeptide that is an important signaling molecule. Although it has recently been implicated in plant defenses to pathogen infection, the mechanisms involved remain poorly understood. Using surface plasmon resonance and gene silencing approaches, we showed that the tomato ( Solanum lycopersicum ) PSK receptor PSKR1, rather than PSKR2, functioned as the major PSK receptor in immune responses. Silencing of PSK signaling genes rendered tomato more susceptible to infection by the economically important necrotrophic pathogen Botrytis cinerea Analysis of tomato mutants defective in either defense hormone biosynthesis or signaling demonstrated that PSK-induced immunity required auxin biosynthesis and associated defense pathways. Here, using aequorin-expressing tomato plants, we provide evidence that PSK perception by tomato PSKR1 elevated cytosolic [Ca 2+ ], leading to auxin-dependent immune responses via enhanced binding activity between calmodulins and the auxin biosynthetic YUCs. Thus, our data demonstrate that PSK acts as a damage-associated molecular pattern and is perceived mainly by PSKR1, which increases cytosolic [Ca 2+ ] and activates auxin-mediated pathways that enhance immunity of tomato plants to B. cinerea . © 2018 American Society of Plant Biologists. All rights reserved.

  7. 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

  8. The role of innate signaling in the homeostasis of tolerance and immunity in the intestine.

    Science.gov (United States)

    Wells, Jerry M; Loonen, Linda M P; Karczewski, Jurgen M

    2010-01-01

    In the intestine innate recognition of microbes is achieved through pattern recognition receptor (PRR) families expressed in immune cells and different cell lineages of the intestinal epithelium. Toll-like receptor (TLR) and nucleotide-binding and oligomerization domain-like receptor (NLR) families are emerging as key mediators of immunity through their role as maturation factors of immune cells and triggers for the production of cytokines and chemokines and antimicrobial factors. At the mucosal surface chronic activation of the immune system is avoided through the epithelial production of a glycocalyx, steady-state production of antimicrobial factors as well as the selective expression and localization of PRRs. Additionally, the polarization of epithelial TLR signaling and suppression of NF-kappaB activation by luminal commensals appears to contribute to the homeostasis of tolerance and immunity. Several studies have demonstrated that TLR signaling in epithelial cells contributes to a range of homeostatic mechanisms including proliferation, wound healing, epithelial integrity, and regulation of mucosal immune functions. The intestinal epithelium appears to have uniquely evolved to maintain mucosal tolerance and immunity, and future efforts to further understand the molecular mechanisms of intestinal homeostasis may have a major impact on human health. Copyright 2009 Elsevier GmbH. All rights reserved.

  9. The Notch Signaling Pathway Is Balancing Type 1 Innate Lymphoid Cell Immune Functions

    Directory of Open Access Journals (Sweden)

    Thibaut Perchet

    2018-06-01

    Full Text Available The Notch pathway is one of the canonical signaling pathways implicated in the development of various solid tumors. During carcinogenesis, the Notch pathway dysregulation induces tumor expression of Notch receptor ligands participating to escape the immune surveillance. The Notch pathway conditions both the development and the functional regulation of lymphoid subsets. Its importance on T cell subset polarization has been documented contrary to its action on innate lymphoid cells (ILC. We aim to analyze the effect of the Notch pathway on type 1 ILC polarization and functions after disruption of the RBPJk-dependent Notch signaling cascade. Indeed, type 1 ILC comprises conventional NK (cNK cells and type 1 helper innate lymphoid cells (ILC1 that share Notch-related functional characteristics such as the IFNg secretion downstream of T-bet expression. cNK cells have strong antitumor properties. However, data are controversial concerning ILC1 functions during carcinogenesis with models showing antitumoral capacities and others reporting ILC1 inability to control tumor growth. Using various mouse models of Notch signaling pathway depletion, we analyze the effects of its absence on type 1 ILC differentiation and cytotoxic functions. We also provide clues into its role in the maintenance of immune homeostasis in tissues. We show that modulating the Notch pathway is not only acting on tumor-specific T cell activity but also on ILC immune subset functions. Hence, our study uncovers the intrinsic Notch signaling pathway in ILC1/cNK populations and their response in case of abnormal Notch ligand expression. This study help evaluating the possible side effects mediated by immune cells different from T cells, in case of multivalent forms of the Notch receptor ligand delta 1 treatments. In definitive, it should help determining the best novel combination of therapeutic strategies in case of solid tumors.

  10. High-resolution mass spectrometry driven discovery of peptidic danger signals in insect immunity.

    Directory of Open Access Journals (Sweden)

    Arton Berisha

    Full Text Available The 'danger model' is an alternative concept for immune response postulating that the immune system reacts to entities that do damage (danger associated molecular patterns, DAMP and not only to entities that are foreign (pathogen-associated molecular patterns, PAMP as proposed by classical immunology concepts. In this study we used Galleria mellonella to validate the danger model in insects. Hemolymph of G. mellonella was digested with thermolysin (as a representative for virulence-associated metalloproteinases produced by humanpathogens followed by chromatographic fractionation. Immune-stimulatory activity was tested by measuring lysozyme activity with the lytic zone assays against Micrococcus luteus cell wall components. Peptides were analyzed by nano-scale liquid chromatography coupled to high-resolution Fourier transform mass spectrometers. Addressing the lack of a genome sequence we complemented the rudimentary NCBI protein database with a recently established transcriptome and de novo sequencing methods for peptide identification. This approach led to identification of 127 peptides, 9 of which were identified in bioactive fractions. Detailed MS/MS experiments in comparison with synthetic analogues confirmed the amino acid sequence of all 9 peptides. To test the potential of these putative danger signals to induce immune responses we injected the synthetic analogues into G. mellonella and monitored the anti-bacterial activity against living Micrococcus luteus. Six out of 9 peptides identified in the bioactive fractions exhibited immune-stimulatory activity when injected. Hence, we provide evidence that small peptides resulting from thermolysin-mediated digestion of hemolymph proteins function as endogenous danger signals which can set the immune system into alarm. Consequently, our study indicates that the danger model also plays a role in insect immunity.

  11. The molecular mechanisms of signaling by cooperative assembly formation in innate immunity pathways.

    Science.gov (United States)

    Vajjhala, Parimala R; Ve, Thomas; Bentham, Adam; Stacey, Katryn J; Kobe, Bostjan

    2017-06-01

    The innate immune system is the first line of defense against infection and responses are initiated by pattern recognition receptors (PRRs) that detect pathogen-associated molecular patterns (PAMPs). PRRs also detect endogenous danger-associated molecular patterns (DAMPs) that are released by damaged or dying cells. The major PRRs include the Toll-like receptor (TLR) family members, the nucleotide binding and oligomerization domain, leucine-rich repeat containing (NLR) family, the PYHIN (ALR) family, the RIG-1-like receptors (RLRs), C-type lectin receptors (CLRs) and the oligoadenylate synthase (OAS)-like receptors and the related protein cyclic GMP-AMP synthase (cGAS). The different PRRs activate specific signaling pathways to collectively elicit responses including the induction of cytokine expression, processing of pro-inflammatory cytokines and cell-death responses. These responses control a pathogenic infection, initiate tissue repair and stimulate the adaptive immune system. A central theme of many innate immune signaling pathways is the clustering of activated PRRs followed by sequential recruitment and oligomerization of adaptors and downstream effector enzymes, to form higher-order arrangements that amplify the response and provide a scaffold for proximity-induced activation of the effector enzymes. Underlying the formation of these complexes are co-operative assembly mechanisms, whereby association of preceding components increases the affinity for downstream components. This ensures a rapid immune response to a low-level stimulus. Structural and biochemical studies have given key insights into the assembly of these complexes. Here we review the current understanding of assembly of immune signaling complexes, including inflammasomes initiated by NLR and PYHIN receptors, the myddosomes initiated by TLRs, and the MAVS CARD filament initiated by RIG-1. We highlight the co-operative assembly mechanisms during assembly of each of these complexes. Copyright

  12. Partially flexible MEMS neural probe composed of polyimide and sucrose gel for reducing brain damage during and after implantation

    International Nuclear Information System (INIS)

    Jeon, Myounggun; Yoon, Eui-Sung; Cho, Il-Joo; Cho, Jeiwon; Jung, Dahee; Kim, Yun Kyung; Shin, Sehyun

    2014-01-01

    This paper presents a flexible microelectromechanical systems (MEMS) neural probe that minimizes neuron damage and immune response, suitable for chronic recording applications. MEMS neural probes with various features such as high electrode densities have been actively investigated for neuron stimulation and recording to study brain functions. However, successful recording of neural signals in chronic application using rigid silicon probes still remains challenging because of cell death and macrophages accumulated around the electrodes over time from continuous brain movement. Thus, in this paper, we propose a new flexible MEMS neural probe that consists of two segments: a polyimide-based, flexible segment for connection and a rigid segment composed of thin silicon for insertion. While the flexible connection segment is designed to reduce the long-term chronic neuron damage, the thin insertion segment is designed to minimize the brain damage during the insertion process. The proposed flexible neural probe was successfully fabricated using the MEMS process on a silicon on insulator wafer. For a successful insertion, a biodegradable sucrose gel is coated on the flexible segment to temporarily increase the probe stiffness to prevent buckling. After the insertion, the sucrose gel dissolves inside the brain exposing the polyimide probe. By performing an insertion test, we confirm that the flexible probe has enough stiffness. In addition, by monitoring immune responses and brain histology, we successfully demonstrate that the proposed flexible neural probe incurs fivefold less neural damage than that incurred by a conventional silicon neural probe. Therefore, the presented flexible neural probe is a promising candidate for recording stable neural signals for long-time chronic applications. (paper)

  13. 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

    2018-01-15

    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 110:63-71, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Genomic DISC1 Disruption in hiPSCs Alters Wnt Signaling and Neural Cell Fate

    Directory of Open Access Journals (Sweden)

    Priya Srikanth

    2015-09-01

    Full Text Available Genetic and clinical association studies have identified disrupted in schizophrenia 1 (DISC1 as a candidate risk gene for major mental illness. DISC1 is interrupted by a balanced chr(1;11 translocation in a Scottish family in which the translocation predisposes to psychiatric disorders. We investigate the consequences of DISC1 interruption in human neural cells using TALENs or CRISPR-Cas9 to target the DISC1 locus. We show that disruption of DISC1 near the site of the translocation results in decreased DISC1 protein levels because of nonsense-mediated decay of long splice variants. This results in an increased level of canonical Wnt signaling in neural progenitor cells and altered expression of fate markers such as Foxg1 and Tbr2. These gene expression changes are rescued by antagonizing Wnt signaling in a critical developmental window, supporting the hypothesis that DISC1-dependent suppression of basal Wnt signaling influences the distribution of cell types generated during cortical development.

  15. 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

  16. Effects of PM2.5 exposure on the Notch signaling pathway and immune imbalance in chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    Gu, Xing-yu; Chu, Xu; Zeng, Xiao-Li; Bao, Hai-Rong; Liu, Xiao-Ju

    2017-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is associated with T lymphocytes subset (Th1/Th2, Th17/Treg) imbalance. Notch signaling pathway plays a key role in the development of the adaptive immunity. The immune disorder induced by fine particulate matter (PM2.5) is related to COPD. The aim of this study was to investigate the mechanism by which PM2.5 influences the Notch signaling pathway leading to worsening immune disorder and accelerating COPD development. A COPD mouse model was established by cigarette smoke exposure. PM2.5 exposure was performed by aerosol inhalation. γ-secretase inhibitor (GSI) was given using intraperitoneal injection. Splenic T lymphocytes were purified using a density gradient centrifugation method. CD4 + T lymphocyte subsets (Th1/Th2, Th17/Treg) were detected using flow cytometry. mRNA and proteins of Notch1/2/3/4, Hes1/5, and Hey1 were detected using RT-PCR and Western blot. Serum INF-γ, IL-4, IL-17 and IL-10 concentrations were measured using ELISA. The results showed that in COPD mice Th1% and Th17%, Th1/Th2 and Th17/Treg were increased, and the levels of mRNA and protein in Notch1/2/3/4, Hes1/5, and Hey1 and serum INF-γ and IL-17 concentrations were significantly increased, and Th2%, Treg%, and serum IL-4 and IL-10 concentrations were significantly decreased. COPD Mice have Th1- and Th17-mediated immune disorder, and the Notch signaling pathway is in an overactivated state. PM2.5 promotes the overactivation of the Notch signaling pathway and aggravates the immune disorder of COPD. GSI can partially inhibit the activation of the Notch signaling pathway and alleviate the immune disorder under basal state and the immune disorder of COPD caused by PM2.5. This result suggests that PM2.5 is involved in the immune disorder of mice with COPD by affecting the Notch signaling pathway and that PM2.5 aggravates COPD. - Highlights: • The COPD mice demonstrated Th1 and Th17 dominant immune imbalance. • PM2.5 aggravates the Th1/Th2 and Th

  17. Danger Signals Activating the Immune Response after Trauma

    Directory of Open Access Journals (Sweden)

    Stefanie Hirsiger

    2012-01-01

    Full Text Available Sterile injury can cause a systemic inflammatory response syndrome (SIRS that resembles the host response during sepsis. The inflammatory response following trauma comprises various systems of the human body which are cross-linked with each other within a highly complex network of inflammation. Endogenous danger signals (danger-associated molecular patterns; DAMPs; alarmins as well as exogenous pathogen-associated molecular patterns (PAMPs play a crucial role in the initiation of the immune response. With popularization of the “danger theory,” numerous DAMPs and PAMPs and their corresponding pathogen-recognition receptors have been identified. In this paper, we highlight the role of the DAMPs high-mobility group box protein 1 (HMGB1, interleukin-1α (IL-1α, and interleukin-33 (IL-33 as unique dual-function mediators as well as mitochondrial danger signals released upon cellular trauma and necrosis.

  18. 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

  19. Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity

    Directory of Open Access Journals (Sweden)

    Stephan Menzel

    2018-03-01

    Full Text Available Adenosine triphosphate (ATP and nicotinamide adenine dinucleotide (NAD+ are released as danger signals from cells during infection and sterile inflammation. In the extracellular compartment ATP is converted by CD39, CD73, and other ecto-enzymes into metabolites that modulate the activity of T cells and macrophages. While ATP mediates pro-inflammatory signals via P2X7 and other P2 receptors, adenosine triggers anti-inflammatory signaling via the adenosine 2a receptor (Adora2a and other P1 receptors. The latter also plays a role in maintaining an immunosuppressive tumor microenvironment. NAD+ is converted by CD38, CD203 and other ecto-enzymes to the Ca2+ mobilizing messengers cyclic ADP-ribose and ADP-ribose, and to adenosine. Recent findings on the roles of CD38, CD39, CD73, CD203, P2X7, and Adora2a in inflammation and immunity underscore the potential of these proteins as drug targets. However, available small molecule inhibitors often lack specificity and mediate unwanted off-target toxicity. Nanobodies – single domain antibodies derived from heavy chain antibodies that naturally occur in camelids – display a propensity to bind functional epitopes not accessible to conventional antibodies. Like conventional antibodies, nanobodies and nanobody-based biologics are highly specific and have well-understood, tunable in vivo pharmacodynamics with little if any toxicity. Nanobodies thus represent attractive alternatives to small molecule inhibitors for modulating purinergic signaling in inflammation and immunity. Here we review recent progress made in developing nanobodies against key targets of purinergic signaling.

  20. Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity.

    Science.gov (United States)

    Menzel, Stephan; Schwarz, Nicole; Haag, Friedrich; Koch-Nolte, Friedrich

    2018-01-01

    Adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD + ) are released as danger signals from cells during infection and sterile inflammation. In the extracellular compartment ATP is converted by CD39, CD73, and other ecto-enzymes into metabolites that modulate the activity of T cells and macrophages. While ATP mediates pro-inflammatory signals via P2X7 and other P2 receptors, adenosine triggers anti-inflammatory signaling via the adenosine 2a receptor (Adora2a) and other P1 receptors. The latter also plays a role in maintaining an immunosuppressive tumor microenvironment. NAD + is converted by CD38, CD203 and other ecto-enzymes to the Ca 2+ mobilizing messengers cyclic ADP-ribose and ADP-ribose, and to adenosine. Recent findings on the roles of CD38, CD39, CD73, CD203, P2X7, and Adora2a in inflammation and immunity underscore the potential of these proteins as drug targets. However, available small molecule inhibitors often lack specificity and mediate unwanted off-target toxicity. Nanobodies - single domain antibodies derived from heavy chain antibodies that naturally occur in camelids - display a propensity to bind functional epitopes not accessible to conventional antibodies. Like conventional antibodies, nanobodies and nanobody-based biologics are highly specific and have well-understood, tunable in vivo pharmacodynamics with little if any toxicity. Nanobodies thus represent attractive alternatives to small molecule inhibitors for modulating purinergic signaling in inflammation and immunity. Here we review recent progress made in developing nanobodies against key targets of purinergic signaling.

  1. Dangerous mating systems: signal complexity, signal content and neural capacity in spiders.

    Science.gov (United States)

    Herberstein, M E; Wignall, A E; Hebets, E A; Schneider, J M

    2014-10-01

    Spiders are highly efficient predators in possession of exquisite sensory capacities for ambushing prey, combined with machinery for launching rapid and determined attacks. As a consequence, any sexually motivated approach carries a risk of ending up as prey rather than as a mate. Sexual selection has shaped courtship to effectively communicate the presence, identity, motivation and/or quality of potential mates, which help ameliorate these risks. Spiders communicate this information via several sensory channels, including mechanical (e.g. vibrational), visual and/or chemical, with examples of multimodal signalling beginning to emerge in the literature. The diverse environments that spiders inhabit have further shaped courtship content and form. While our understanding of spider neurobiology remains in its infancy, recent studies are highlighting the unique and considerable capacities of spiders to process and respond to complex sexual signals. As a result, the dangerous mating systems of spiders are providing important insights into how ecology shapes the evolution of communication systems, with future work offering the potential to link this complex communication with its neural processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Lunatic fringe-mediated Notch signaling regulates adult hippocampal neural stem cell maintenance.

    Science.gov (United States)

    Semerci, Fatih; Choi, William Tin-Shing; Bajic, Aleksandar; Thakkar, Aarohi; Encinas, Juan Manuel; Depreux, Frederic; Segil, Neil; Groves, Andrew K; Maletic-Savatic, Mirjana

    2017-07-12

    Hippocampal neural stem cells (NSCs) integrate inputs from multiple sources to balance quiescence and activation. Notch signaling plays a key role during this process. Here, we report that Lunatic fringe ( Lfng), a key modifier of the Notch receptor, is selectively expressed in NSCs. Further, Lfng in NSCs and Notch ligands Delta1 and Jagged1, expressed by their progeny, together influence NSC recruitment, cell cycle duration, and terminal fate. We propose a new model in which Lfng-mediated Notch signaling enables direct communication between a NSC and its descendants, so that progeny can send feedback signals to the 'mother' cell to modify its cell cycle status. Lfng-mediated Notch signaling appears to be a key factor governing NSC quiescence, division, and fate.

  3. SUMO-, MAPK- and resistance protein-signaling converge at transcription complexes that regulate plant innate immunity

    NARCIS (Netherlands)

    Burg, van den H.A.; Takken, F.L.W.

    2010-01-01

    Upon pathogen perception plant innate immune receptors activate various signaling pathways that trigger host defenses. PAMP-triggered defense signaling requires mitogen-activated protein kinase (MAPK) pathways, which modulate the activity of transcription factors through phosphorylation. Here, we

  4. SUMO-, MAPK-, and resistance protein-signaling converge at transcription complexes that regulate plant innate immunity

    NARCIS (Netherlands)

    van den Burg, H.A.; Takken, F.L.W.

    2010-01-01

    Upon pathogen perception plant innate immune receptors activate various signaling pathways that trigger host defenses. PAMP-triggered defense signaling requires mitogen-activated protein kinase (MAPK) pathways, which modulate the activity of transcription factors through phosphorylation. Here, we

  5. 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

  6. Semaphorin7A and its receptors: pleiotropic regulators of immune cell function, bone homeostasis, and neural development.

    Science.gov (United States)

    Jongbloets, Bart C; Ramakers, Geert M J; Pasterkamp, R Jeroen

    2013-03-01

    Semaphorins form a large, evolutionary conserved family of cellular guidance signals. The semaphorin family contains several secreted and transmembrane proteins, but only one GPI-anchored member, Semaphorin7A (Sema7A). Although originally identified in immune cells, as CDw108, Sema7A displays widespread expression outside the immune system. It is therefore not surprising that accumulating evidence supports roles for this protein in a wide variety of biological processes in different organ systems and in disease. Well-characterized biological effects of Sema7A include those during bone and immune cell regulation, neuron migration and neurite growth. These effects are mediated by two receptors, plexinC1 and integrins. However, most of what is known today about Sema7A signaling concerns Sema7A-integrin interactions. Here, we review our current knowledge of Sema7A function and signaling in different organ systems, highlighting commonalities between the cellular effects and signaling pathways activated by Sema7A in different cell types. Furthermore, we discuss a potential role for Sema7A in disease and provide directions for further research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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...... difference experiment and demonstrates high accuracy for small wall thickness differences. Results from the experiment are compared with results obtained by a false killer whale (pseudorca crassidens)....

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

    International Nuclear Information System (INIS)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C.; Ballestas, Mary E.; Elmets, Craig A.; Robbins, David J.; Matalon, Sadis; Deshane, Jessy S.; Afaq, Farrukh; Bickers, David R.; Athar, Mohammad

    2013-01-01

    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

  13. 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.

  14. 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

  15. Linear ubiquitination signals in adaptive immune responses.

    Science.gov (United States)

    Ikeda, Fumiyo

    2015-07-01

    Ubiquitin can form eight different linkage types of chains using the intrinsic Met 1 residue or one of the seven intrinsic Lys residues. Each linkage type of ubiquitin chain has a distinct three-dimensional topology, functioning as a tag to attract specific signaling molecules, which are so-called ubiquitin readers, and regulates various biological functions. Ubiquitin chains linked via Met 1 in a head-to-tail manner are called linear ubiquitin chains. Linear ubiquitination plays an important role in the regulation of cellular signaling, including the best-characterized tumor necrosis factor (TNF)-induced canonical nuclear factor-κB (NF-κB) pathway. Linear ubiquitin chains are specifically generated by an E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) and hydrolyzed by a deubiquitinase (DUB) called ovarian tumor (OTU) DUB with linear linkage specificity (OTULIN). LUBAC linearly ubiquitinates critical molecules in the TNF pathway, such as NEMO and RIPK1. The linear ubiquitin chains are then recognized by the ubiquitin readers, including NEMO, which control the TNF pathway. Accumulating evidence indicates an importance of the LUBAC complex in the regulation of apoptosis, development, and inflammation in mice. In this article, I focus on the role of linear ubiquitin chains in adaptive immune responses with an emphasis on the TNF-induced signaling pathways. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Neural network-based sensor signal accelerator.

    Energy Technology Data Exchange (ETDEWEB)

    Vogt, M. C.

    2000-10-16

    A strategy has been developed to computationally accelerate the response time of a generic electronic sensor. The strategy can be deployed as an algorithm in a control system or as a physical interface (on an embedded microcontroller) between a slower responding external sensor and a higher-speed control system. Optional code implementations are available to adjust algorithm performance when computational capability is limited. In one option, the actual sensor signal can be sampled at the slower rate with adaptive linear neural networks predicting the sensor's future output and interpolating intermediate synthetic output values. In another option, a synchronized collection of predictors sequentially controls the corresponding synthetic output voltage. Error is adaptively corrected in both options. The core strategy has been demonstrated with automotive oxygen sensor data. A prototype interface device is under construction. The response speed increase afforded by this strategy could greatly offset the cost of developing a replacement sensor with a faster physical response time.

  17. 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

  18. Small leucine rich proteoglycan family regulates multiple signalling pathways in neural development and maintenance.

    Science.gov (United States)

    Dellett, Margaret; Hu, Wanzhou; Papadaki, Vasiliki; Ohnuma, Shin-ichi

    2012-04-01

    The small leucine-rich repeat proteoglycan (SLRPs) family of proteins currently consists of five classes, based on their structural composition and chromosomal location. As biologically active components of the extracellular matrix (ECM), SLRPs were known to bind to various collagens, having a role in regulating fibril assembly, organization and degradation. More recently, as a function of their diverse proteins cores and glycosaminoglycan side chains, SLRPs have been shown to be able to bind various cell surface receptors, growth factors, cytokines and other ECM components resulting in the ability to influence various cellular functions. Their involvement in several signaling pathways such as Wnt, transforming growth factor-β and epidermal growth factor receptor also highlights their role as matricellular proteins. SLRP family members are expressed during neural development and in adult neural tissues, including ocular tissues. This review focuses on describing SLRP family members involvement in neural development with a brief summary of their role in non-neural ocular tissues and in response to neural injury. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

  19. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Libregts, Sten F.W.M.; Nolte, Martijn A., E-mail: m.nolte@sanquin.nl

    2014-12-10

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function.

  20. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    International Nuclear Information System (INIS)

    Libregts, Sten F.W.M.; Nolte, Martijn A.

    2014-01-01

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function

  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. Orphan nuclear receptor TLX activates Wnt/β-catenin signalling to stimulate neural stem cell proliferation and self-renewal

    Science.gov (United States)

    Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T.; Gage, Fred H.; Evans, Ronald M.; Shi, Yanhong

    2010-01-01

    The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/β-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/β-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active β-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a β-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active β-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active β-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active β-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/β-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode. PMID:20010817

  3. Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal.

    Science.gov (United States)

    Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T; Gage, Fred H; Evans, Ronald M; Shi, Yanhong

    2010-01-01

    The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/beta-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/beta-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active beta-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a beta-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active beta-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active beta-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active beta-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/beta-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode.

  4. Molecular Pathways for Immune Recognition of Preproinsulin Signal Peptide in Type 1 Diabetes.

    Science.gov (United States)

    Kronenberg-Versteeg, Deborah; Eichmann, Martin; Russell, Mark A; de Ru, Arnoud; Hehn, Beate; Yusuf, Norkhairin; van Veelen, Peter A; Richardson, Sarah J; Morgan, Noel G; Lemberg, Marius K; Peakman, Mark

    2018-04-01

    The signal peptide region of preproinsulin (PPI) contains epitopes targeted by HLA-A-restricted (HLA-A0201, A2402) cytotoxic T cells as part of the pathogenesis of β-cell destruction in type 1 diabetes. We extended the discovery of the PPI epitope to disease-associated HLA-B*1801 and HLA-B*3906 (risk) and HLA-A*1101 and HLA-B*3801 (protective) alleles, revealing that four of six alleles present epitopes derived from the signal peptide region. During cotranslational translocation of PPI, its signal peptide is cleaved and retained within the endoplasmic reticulum (ER) membrane, implying it is processed for immune recognition outside of the canonical proteasome-directed pathway. Using in vitro translocation assays with specific inhibitors and gene knockout in PPI-expressing target cells, we show that PPI signal peptide antigen processing requires signal peptide peptidase (SPP). The intramembrane protease SPP generates cytoplasm-proximal epitopes, which are transporter associated with antigen processing (TAP), ER-luminal epitopes, which are TAP independent, each presented by different HLA class I molecules and N-terminal trimmed by ER aminopeptidase 1 for optimal presentation. In vivo, TAP expression is significantly upregulated and correlated with HLA class I hyperexpression in insulin-containing islets of patients with type 1 diabetes. Thus, PPI signal peptide epitopes are processed by SPP and loaded for HLA-guided immune recognition via pathways that are enhanced during disease pathogenesis. © 2018 by the American Diabetes Association.

  5. 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.

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

    International Nuclear Information System (INIS)

    Li Xiumin; Small, Michael

    2010-01-01

    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. Signaling by myeloid C-type lectin receptors in immunity and homeostasis.

    Science.gov (United States)

    Sancho, David; Reis e Sousa, Caetano

    2012-01-01

    Myeloid cells are key drivers of physiological responses to pathogen invasion or tissue damage. Members of the C-type lectin receptor (CLR) family stand out among the specialized receptors utilized by myeloid cells to orchestrate these responses. CLR ligands include carbohydrate, protein, and lipid components of both pathogens and self, which variably trigger endocytic, phagocytic, proinflammatory, or anti-inflammatory reactions. These varied outcomes rely on a versatile system for CLR signaling that includes tyrosine-based motifs that recruit kinases, phosphatases, or endocytic adaptors as well as nontyrosine-based signals that modulate the activation of other pathways or couple to the uptake machinery. Here, we review the signaling properties of myeloid CLRs and how they impact the role of myeloid cells in innate and adaptive immunity.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

    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.

  9. 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.

  10. ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

    OpenAIRE

    Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

    2010-01-01

    The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identif...

  11. Colorectal cancer cells suppress CD4+ T cells immunity through canonical Wnt signaling.

    Science.gov (United States)

    Sun, Xuan; Liu, Suoning; Wang, Daguang; Zhang, Yang; Li, Wei; Guo, Yuchen; Zhang, Hua; Suo, Jian

    2017-02-28

    Understanding how colorectal cancer escapes from immunosurveillance and immune attack is important for developing novel immunotherapies for colorectal cancer. In this study we evaluated the role of canonical Wnt signaling in the regulation of T cell function in a mouse colorectal cancer model. We found that colorectal cancer cells expressed abundant Wnt ligands, and intratumoral T cells expressed various Frizzled proteins. Meanwhile, both active β-catenin and total β-catenin were elevated in intratumoral T cells. In vitro study indicated that colorectal cancer cells suppressed IFN-γ expression and increased IL-17a expression in activated CD4+ T cells. However, the cytotoxic activity of CD8+ T cells was not altered by colorectal cancer cells. To further evaluate the importance of Wnt signaling for CD4+ T cell-mediated cancer immunity, β-catenin expression was enforced in CD4+ T cells using lentiviral transduction. In an adoptive transfer model, enforced expression of β-catenin in intratumoral CD4+ T cells increased IL-17a expression, enhanced proliferation and inhibited apoptosis of colorectal cancer cells. Taken together, our study disclosed a new mechanism by which colorectal cancer impairs T cell immunity.

  12. 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.

  13. Impact of the Innate Immune Response in the Actions of Ethanol on the Central Nervous System.

    Science.gov (United States)

    Montesinos, Jorge; Alfonso-Loeches, Silvia; Guerri, Consuelo

    2016-11-01

    The innate immune response in the central nervous system (CNS) participates in both synaptic plasticity and neural damage. Emerging evidence from human and animal studies supports the role of the neuroimmune system response in many actions of ethanol (EtOH) on the CNS. Research studies have shown that alcohol stimulates brain immune cells, microglia, and astrocytes, by activating innate immune receptors Toll-like receptors (TLRs) and NOD-like receptors (inflammasome NLRs) triggering signaling pathways, which culminate in the production of pro-inflammatory cytokines and chemokines that lead to neuroinflammation. This review focuses on evidence that indicates the participation of TLRs and the inflammasome NLRs signaling response in many effects of EtOH on the CNS, such as neuroinflammation associated with brain damage, cognitive and behavioral dysfunction, and adolescent brain development alterations. It also reviews findings that indicate the role of TLR4-dependent signaling immune molecules in alcohol consumption, reward, and addiction. The research data suggest that overactivation of TLR4 or NLRs increases pro-inflammatory cytokines and mediators to cause neural damage in the cerebral cortex and hippocampus, while modest TLR4 activation, along with the generation of certain cytokines and chemokines in specific brain areas (e.g., amygdala, ventral tegmental area), modulate neurotransmission, alcohol drinking, and alcohol rewards. Elimination of TLR4 and NLRP3 abolishes many neuroimmune effects of EtOH. Despite much progress being made in this area, there are some research gaps and unanswered questions that this review discusses. Finally, potential therapies that target neuroimmune pathways to treat neuropathological and behavioral consequences of alcohol abuse are also evaluated. Copyright © 2016 by the Research Society on Alcoholism.

  14. Cutting Edge: Retinoic Acid Signaling in B Cells Is Essential for Oral Immunization and Microflora Composition.

    Science.gov (United States)

    Pantazi, Eirini; Marks, Ellen; Stolarczyk, Emilie; Lycke, Nils; Noelle, Randolph J; Elgueta, Raul

    2015-08-15

    Retinoic acid (RA) is a critical regulator of the intestinal adaptive immune response. However, the intrinsic impact of RA on B cell differentiation in the regulation of gut humoral immunity in vivo has never been directly shown. To address this issue, we have been able to generate a mouse model where B cells specifically express a dominant-negative receptor α for RA. In this study, we show that the silencing of RA signaling in B cells reduces the numbers of IgA(+) Ab-secreting cells both in vitro and in vivo, suggesting that RA has a direct effect on IgA plasma cell differentiation. Moreover, the lack of RA signaling in B cells abrogates Ag-specific IgA responses after oral immunization and affects the microbiota composition. In conclusion, these results suggest that RA signaling in B cells through the RA receptor α is important to generate an effective gut humoral response and to maintain a normal microbiota composition. Copyright © 2015 by The American Association of Immunologists, Inc.

  15. Neural induction in Xenopus: requirement for ectodermal and endomesodermal signals via Chordin, Noggin, beta-Catenin, and Cerberus.

    Directory of Open Access Journals (Sweden)

    Hiroki Kuroda

    2004-05-01

    Full Text Available The origin of the signals that induce the differentiation of the central nervous system (CNS is a long-standing question in vertebrate embryology. Here we show that Xenopus neural induction starts earlier than previously thought, at the blastula stage, and requires the combined activity of two distinct signaling centers. One is the well-known Nieuwkoop center, located in dorsal-vegetal cells, which expresses Nodal-related endomesodermal inducers. The other is a blastula Chordin- and Noggin-expressing (BCNE center located in dorsal animal cells that contains both prospective neuroectoderm and Spemann organizer precursor cells. Both centers are downstream of the early beta-Catenin signal. Molecular analyses demonstrated that the BCNE center was distinct from the Nieuwkoop center, and that the Nieuwkoop center expressed the secreted protein Cerberus (Cer. We found that explanted blastula dorsal animal cap cells that have not yet contacted a mesodermal substratum can, when cultured in saline solution, express definitive neural markers and differentiate histologically into CNS tissue. Transplantation experiments showed that the BCNE region was required for brain formation, even though it lacked CNS-inducing activity when transplanted ventrally. Cell-lineage studies demonstrated that BCNE cells give rise to a large part of the brain and retina and, in more posterior regions of the embryo, to floor plate and notochord. Loss-of-function experiments with antisense morpholino oligos (MO showed that the CNS that forms in mesoderm-less Xenopus embryos (generated by injection with Cerberus-Short [CerS] mRNA required Chordin (Chd, Noggin (Nog, and their upstream regulator beta-Catenin. When mesoderm involution was prevented in dorsal marginal-zone explants, the anterior neural tissue formed in ectoderm was derived from BCNE cells and had a complete requirement for Chd. By injecting Chd morpholino oligos (Chd-MO into prospective neuroectoderm and Cerberus

  16. Micro Aerial Vehicle (MAV Flapping Motion Control Using an Immune Network with Different Immune Factors

    Directory of Open Access Journals (Sweden)

    Liguo Weng

    2013-08-01

    Full Text Available This paper proposes a novel Neural-Immunology/Memory Network to address the problem of motion control for flapping-wing Micro Aerial Vehicles (MAVs. This network is inspired by the human memory system as well as the immune system, and it is effective in attenuating the system errors and other lumped system uncertainties. In contrast to most existing Neural Networks, the convergence of this proposed Neural-Immunology/Memory Network can be theoretically proven. Both analyses and simulations that are based on different immune factors show that the proposed control method is effective in dealing with external disturbances, system nonlinearities, uncertainties and parameter variations.

  17. Abdominal pain in Irritable Bowel Syndrome: a review of putative psychological, neural and neuro-immune mechanisms.

    Science.gov (United States)

    Elsenbruch, Sigrid

    2011-03-01

    Chronic abdominal pain is a common symptom of great clinical significance in several areas of medicine. In many cases no organic cause can be established resulting in the classification as functional gastrointestinal disorder. Irritable Bowel Syndrome (IBS) is the most common of these conditions and is considered an important public health problem because it can be disabling and constitutes a major social and economic burden given the lack of effective treatments. IBS aetiology is most likely multi-factorial involving biological, psychological and social factors. Visceral hyperalgesia (or hypersensitivity) and visceral hypervigilance, which could be mediated by peripheral, spinal, and/or central pathways, constitute key concepts in current research on pathophysiological mechanisms of visceral hyperalgesia. The role of central nervous system mechanisms along the "brain-gut axis" is increasingly appreciated, owing to accumulating evidence from brain imaging studies that neural processing of visceral stimuli is altered in IBS together with long-standing knowledge regarding the contribution of stress and negative emotions to symptom frequency and severity. At the same time, there is also growing evidence suggesting that peripheral immune mechanisms and disturbed neuro-immune communication could play a role in the pathophysiology of visceral hyperalgesia. This review presents recent advances in research on the pathophysiology of visceral hyperalgesia in IBS, with a focus on the role of stress and anxiety in central and peripheral response to visceral pain stimuli. Together, these findings support that in addition to lower pain thresholds displayed by a significant proportion of patients, the evaluation of pain appears to be altered in IBS. This may be attributable to affective disturbances, negative emotions in anticipation of or during visceral stimulation, and altered pain-related expectations and learning processes. Disturbed "top-down" emotional and cognitive pain

  18. 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.

  19. [Zinc signaling : a novel regulatory system on bone homeostasis, and immune and allergic responses].

    Science.gov (United States)

    Fukada, Toshiyuki; Nishida, Keigo; Yamasaki, Satoru; Hojyo, Shintaro

    2012-11-01

    Zinc (Zn) is an essential trace element that is required for proliferation, differentiation, and variety of cellular functions, and unbalanced homeostasis of Zn ion (Zn(2 + )) results in health problems such as abnormal bone formation and immunodeficiency. Recent studies have shed light on important roles of Zn(2 + )as a signaling mediator, called Zn signal. Zn(2 + )homeostasis is regulated through Zn transporters and cation channels. Advances of genetic and molecular approaches have revealed that Zn signal regulates mammalian physiology and pathogenesis. We will address that Zn signal undoubtedly contributes to our health, by highlighting it in bone homeostasis and immune regulation, and discuss that the "Zn signal axis" selectively controls intracellular signal transduction to fine-tune cellular functions.

  20. Cyclic GMP-AMP as an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA.

    Science.gov (United States)

    Kato, Kazuki; Omura, Hiroki; Ishitani, Ryuichiro; Nureki, Osamu

    2017-06-20

    The innate immune system functions as the first line of defense against invading bacteria and viruses. In this context, the cGAS/STING [cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase/STING] signaling axis perceives the nonself DNA associated with bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. In this pathway, the noncanonical cyclic dinucleotide 2',3'-cyclic GMP-AMP (2',3'-cGAMP) functions as a second messenger for signal transduction: 2',3'-cGAMP is produced by the enzyme cGAS upon its recognition of double-stranded DNA, and then the 2',3'-cGAMP is recognized by the receptor STING to induce the phosphorylation of downstream factors, including TBK1 (TANK binding kinase 1) and IRF3 (interferon regulatory factor 3). Numerous crystal structures of the components of this cGAS/STING signaling axis have been reported and these clarify the structural basis for their signal transduction mechanisms. In this review, we summarize recent progress made in the structural dissection of this signaling pathway and indicate possible directions of forthcoming research.

  1. In vivo monitoring of glial scar proliferation on chronically implanted neural electrodes by fiber optical coherence tomography

    Science.gov (United States)

    Xie, Yijing; Martini, Nadja; Hassler, Christina; Kirch, Robert D.; Stieglitz, Thomas; Seifert, Andreas; Hofmann, Ulrich G.

    2014-01-01

    In neural prosthetics and stereotactic neurosurgery, intracortical electrodes are often utilized for delivering therapeutic electrical pulses, and recording neural electrophysiological signals. Unfortunately, neuroinflammation impairs the neuron-electrode-interface by developing a compact glial encapsulation around the implants in long term. At present, analyzing this immune reaction is only feasible with post-mortem histology; currently no means for specific in vivo monitoring exist and most applicable imaging modalities can not provide information in deep brain regions. Optical coherence tomography (OCT) is a well established imaging modality for in vivo studies, providing cellular resolution and up to 1.2 mm imaging depth in brain tissue. A fiber based spectral domain OCT was shown to be capable of minimally invasive brain imaging. In the present study, we propose to use a fiber based spectral domain OCT to monitor the progression of the tissue's immune response through scar encapsulation progress in a rat animal model. A fine fiber catheter was implanted in rat brain together with a flexible polyimide microelectrode in sight both of which acts as a foreign body and induces the brain tissue immune reaction. OCT signals were collected from animals up to 12 weeks after implantation and thus gliotic scarring in vivo monitored for that time. Preliminary data showed a significant enhancement of the OCT backscattering signal during the first 3 weeks after implantation, and increased attenuation factor of the sampled tissue due to the glial scar formation. PMID:25191264

  2. EEG signal classification based on artificial neural networks and amplitude spectra features

    Science.gov (United States)

    Chojnowski, K.; FrÄ czek, J.

    BCI (called Brain-Computer Interface) is an interface that allows direct communication between human brain and an external device. It bases on EEG signal collection, processing and classification. In this paper a complete BCI system is presented which classifies EEG signal using artificial neural networks. For this purpose we used a multi-layered perceptron architecture trained with the RProp algorithm. Furthermore a simple multi-threaded method for automatic network structure optimizing was shown. We presented the results of our system in the opening and closing eyes recognition task. We also showed how our system could be used for controlling devices basing on imaginary hand movements.

  3. Immune-Modulating Perspectives for Low Frequency Electromagnetic Fields in Innate Immunity

    Directory of Open Access Journals (Sweden)

    Maria Manuela Rosado

    2018-03-01

    Full Text Available In recent years, the effects of electromagnetic fields (EMFs on the immune system have received a considerable interest, not only to investigate possible negative health impact but also to explore the possibility to favorably modulate immune responses. To generate beneficial responses, the immune system should eradicate pathogens while “respecting” the organism and tolerating irrelevant antigens. According to the current view, damage-associated molecules released by infected or injured cells, or secreted by innate immune cells generate danger signals activating an immune response. These signals are also relevant to the subsequent activation of homeostatic mechanisms that control the immune response in pro- or anti-inflammatory reactions, a feature that allows modulation by therapeutic treatments. In the present review, we describe and discuss the effects of extremely low frequency (ELF-EMF and pulsed EMF on cell signals and factors relevant to the activation of danger signals and innate immunity cells. By discussing the EMF modulating effects on cell functions, we envisage the use of EMF as a therapeutic agent to regulate immune responses associated with wound healing.

  4. Immune Homeostasis in Epithelial Cells: Evidence and Role of Inflammasome Signaling Reviewed.

    Science.gov (United States)

    Peeters, Paul M; Wouters, Emiel F; Reynaert, Niki L

    2015-01-01

    The epithelium regulates the interaction between the noxious xenogenous, as well as the microbial environment and the immune system, not only by providing a barrier but also by expressing a number of immunoregulatory membrane receptors, and intracellular danger sensors and their downstream effectors. Amongst these are a number of inflammasome sensor subtypes, which have been initially characterized in myeloid cells and described to be activated upon assembly into multiprotein complexes by microbial and environmental triggers. This review compiles a vast amount of literature that supports a pivotal role for inflammasomes in the various epithelial barriers of the human body as essential factors maintaining immune signaling and homeostasis.

  5. 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.

  6. Neural Correlates of Success and Failure Signals During Neurofeedback Learning.

    Science.gov (United States)

    Radua, Joaquim; Stoica, Teodora; Scheinost, Dustin; Pittenger, Christopher; Hampson, Michelle

    2018-05-15

    Feedback-driven learning, observed across phylogeny and of clear adaptive value, is frequently operationalized in simple operant conditioning paradigms, but it can be much more complex, driven by abstract representations of success and failure. This study investigates the neural processes involved in processing success and failure during feedback learning, which are not well understood. Data analyzed were acquired during a multisession neurofeedback experiment in which ten participants were presented with, and instructed to modulate, the activity of their orbitofrontal cortex with the aim of decreasing their anxiety. We assessed the regional blood-oxygenation-level-dependent response to the individualized neurofeedback signals of success and failure across twelve functional runs acquired in two different magnetic resonance sessions in each of ten individuals. Neurofeedback signals of failure correlated early during learning with deactivation in the precuneus/posterior cingulate and neurofeedback signals of success correlated later during learning with deactivation in the medial prefrontal/anterior cingulate cortex. The intensity of the latter deactivations predicted the efficacy of the neurofeedback intervention in the reduction of anxiety. These findings indicate a role for regulation of the default mode network during feedback learning, and suggest a higher sensitivity to signals of failure during the early feedback learning and to signals of success subsequently. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. 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

  8. 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...nd the innate immune system: crosstalk with the toll-likereceptor signaling network. Authors Chinenov Y, Rog

  9. Neural network signal understanding for instrumentation

    DEFF Research Database (Denmark)

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

    1990-01-01

    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...

  10. Characterisation of eddy current signals using different types of artificial neural networks

    International Nuclear Information System (INIS)

    Shyamsunder, M.T.; Rajagopalan, C.; Jayakumar, T.; Kalyanasundaram, P.; Baldev Raj; Ray, K.K.

    1996-01-01

    Eddy current testing is one of the important techniques in nondestructive testing. Automated characterisation of eddy current signals (ECS), either in the form of lissajous patterns (figure-of-eight) or individual voltage vs. time signals is an area of growing interest. This is particularly relevant in environments where the signal-to-noise ratio (SNR) of ECS are very poor. Intelligent, timely and precise interpretation of resulting data, is the key for improving the efficiency of NDT and E. A comprehensive study has been undertaken by the authors for the characterisation of ECS having poor SNR, using three types of artificial neural networks (ANNs). The types of ANNs used in this study are [a] the error-back propagation model, [b] the binary Hopfield model and [c] the Kohonen's self-organising maps model. Eddy current signals, acquired from different types of defects such as holes and notches on stainless steel type 316 sheets were used in this study. (author)

  11. 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.

  12. 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.

  13. 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 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 sinensis haemocytes, revealing the involvement of the TLR13-MyD88-NF-κB 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.

  14. A low-power current-reuse dual-band analog front-end for multi-channel neural signal recording.

    Science.gov (United States)

    Sepehrian, H; Gosselin, B

    2014-01-01

    Thoroughly studying the brain activity of freely moving subjects requires miniature data acquisition systems to measure and wirelessly transmit neural signals in real time. In this application, it is mandatory to simultaneously record the bioelectrical activity of a large number of neurons to gain a better knowledge of brain functions. However, due to limitations in transferring the entire raw data to a remote base station, employing dedicated data reduction techniques to extract the relevant part of neural signals is critical to decrease the amount of data to transfer. In this work, we present a new dual-band neural amplifier to separate the neuronal spike signals (SPK) and the local field potential (LFP) simultaneously in the analog domain, immediately after the pre-amplification stage. By separating these two bands right after the pre-amplification stage, it is possible to process LFP and SPK separately. As a result, the required dynamic range of the entire channel, which is determined by the signal-to-noise ratio of the SPK signal of larger bandwidth, can be relaxed. In this design, a new current-reuse low-power low-noise amplifier and a new dual-band filter that separates SPK and LFP while saving capacitors and pseudo resistors. A four-channel dual-band (SPK, LFP) analog front-end capable of simultaneously separating SPK and LFP is implemented in a TSMC 0.18 μm technology. Simulation results present a total power consumption per channel of 3.1 μw for an input referred noise of 3.28 μV and a NEF for 2.07. The cutoff frequency of the LFP band is fc=280 Hz, and fL=725 Hz and fL=11.2 KHz for SPK, with 36 dB gain for LFP band 46 dB gain for SPK band.

  15. 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.

  16. 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.

  17. 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.

  18. Adaptation in the innate immune system and heterologous innate immunity.

    Science.gov (United States)

    Martin, Stefan F

    2014-11-01

    The innate immune system recognizes deviation from homeostasis caused by infectious or non-infectious assaults. The threshold for its activation seems to be established by a calibration process that includes sensing of microbial molecular patterns from commensal bacteria and of endogenous signals. It is becoming increasingly clear that adaptive features, a hallmark of the adaptive immune system, can also be identified in the innate immune system. Such adaptations can result in the manifestation of a primed state of immune and tissue cells with a decreased activation threshold. This keeps the system poised to react quickly. Moreover, the fact that the innate immune system recognizes a wide variety of danger signals via pattern recognition receptors that often activate the same signaling pathways allows for heterologous innate immune stimulation. This implies that, for example, the innate immune response to an infection can be modified by co-infections or other innate stimuli. This "design feature" of the innate immune system has many implications for our understanding of individual susceptibility to diseases or responsiveness to therapies and vaccinations. In this article, adaptive features of the innate immune system as well as heterologous innate immunity and their implications are discussed.

  19. Interleukin-36 cytokines may overcome microbial immune evasion strategies that inhibit interleukin-1 family signaling.

    Science.gov (United States)

    Jensen, Liselotte E

    2017-08-15

    Pathogens deploy immune evasion strategies to successfully establish infections within their hosts. Naturally, the host responds by acquiring mechanisms to counter these strategies. There is increasing evidence that the three interleukin-36 (IL-36) cytokines, IL-36α, IL-36β and IL-36γ, play important roles in host immunity. With a focus on the skin as a target for microbial and viral invasion, the current knowledge of IL-36 functions is reviewed. Furthermore, the hypothesis that the IL-36s have evolved to counteract virulence factors is presented using viruses as an example. The IL-36s are related to IL-1α, IL-1β, IL-18, and IL-33. Numerous viruses affecting the skin have developed immune evasion strategies that neutralize IL-1α, IL-1β, or IL-18 signaling or combinations of these pathways. Through small differences in activation mechanisms and receptor utilization, it is possible that IL-36 signaling may proceed unhindered in the presence of these viral inhibitors. Thus, one physiological function of the IL-36s may be to counteract microbial immune evasion. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  20. Patterns of cortical oscillations organize neural activity into whole-brain functional networks evident in the fMRI BOLD signal

    Directory of Open Access Journals (Sweden)

    Jennifer C Whitman

    2013-03-01

    Full Text Available Recent findings from electrophysiology and multimodal neuroimaging have elucidated the relationship between patterns of cortical oscillations evident in EEG / MEG and the functional brain networks evident in the BOLD signal. Much of the existing literature emphasized how high-frequency cortical oscillations are thought to coordinate neural activity locally, while low-frequency oscillations play a role in coordinating activity between more distant brain regions. However, the assignment of different frequencies to different spatial scales is an oversimplification. A more informative approach is to explore the arrangements by which these low- and high-frequency oscillations work in concert, coordinating neural activity into whole-brain functional networks. When relating such networks to the BOLD signal, we must consider how the patterns of cortical oscillations change at the same speed as cognitive states, which often last less than a second. Consequently, the slower BOLD signal may often reflect the summed neural activity of several transient network configurations. This temporal mismatch can be circumvented if we use spatial maps to assess correspondence between oscillatory networks and BOLD networks.

  1. 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.

  2. 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.

  3. 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...

  4. Signaling mechanisms underlying the robustness and tunability of the plant immune network

    Science.gov (United States)

    Kim, Yungil; Tsuda, Kenichi; Igarashi, Daisuke; Hillmer, Rachel A.; Sakakibara, Hitoshi; Myers, Chad L.; Katagiri, Fumiaki

    2014-01-01

    Summary How does robust and tunable behavior emerge in a complex biological network? We sought to understand this for the signaling network controlling pattern-triggered immunity (PTI) in Arabidopsis. A dynamic network model containing four major signaling sectors, the jasmonate, ethylene, PAD4, and salicylate sectors, which together explain up to 80% of the PTI level, was built using data for dynamic sector activities and PTI levels under exhaustive combinatorial sector perturbations. Our regularized multiple regression model had a high level of predictive power and captured known and unexpected signal flows in the network. The sole inhibitory sector in the model, the ethylene sector, was central to the network robustness via its inhibition of the jasmonate sector. The model's multiple input sites linked specific signal input patterns varying in strength and timing to different network response patterns, indicating a mechanism enabling tunability. PMID:24439900

  5. Development of a signal-analysis algorithm for the ZEUS transition-radiation detector under application of a neural network

    International Nuclear Information System (INIS)

    Wollschlaeger, U.

    1992-07-01

    The aim of this thesis consisted in the development of a procedure for the analysis of the data of the transition-radiation detector at ZEUS. For this a neural network was applied and first studied, which results concerning the separation power between electron an pions can be reached by this procedure. It was shown that neural nets yield within the error limits as well results as standard algorithms (total charge, cluster analysis). At an electron efficiency of 90% pion contaminations in the range 1%-2% were reached. Furthermore it could be confirmed that neural networks can be considered for the here present application field as robust in relatively insensitive against external perturbations. For the application in the experiment beside the separation power also the time-behaviour is of importance. The requirement to keep dead-times small didn't allow the application of standard method. By a simulation the time availabel for the signal analysis was estimated. For the testing of the processing time in a neural network subsequently the corresponding algorithm was implemented into an assembler code for the digital signal processor DSP56001. (orig./HSI) [de

  6. Deep Learning Neural Networks and Bayesian Neural Networks in Data Analysis

    Directory of Open Access Journals (Sweden)

    Chernoded Andrey

    2017-01-01

    Full Text Available Most of the modern analyses in high energy physics use signal-versus-background classification techniques of machine learning methods and neural networks in particular. Deep learning neural network is the most promising modern technique to separate signal and background and now days can be widely and successfully implemented as a part of physical analysis. In this article we compare Deep learning and Bayesian neural networks application as a classifiers in an instance of top quark analysis.

  7. 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.

  8. Real-time classification of signals from three-component seismic sensors using neural nets

    Science.gov (United States)

    Bowman, B. C.; Dowla, F.

    1992-05-01

    Adaptive seismic data acquisition systems with capabilities of signal discrimination and event classification are important in treaty monitoring, proliferation, and earthquake early detection systems. Potential applications include monitoring underground chemical explosions, as well as other military, cultural, and natural activities where characteristics of signals change rapidly and without warning. In these applications, the ability to detect and interpret events rapidly without falling behind the influx of the data is critical. We developed a system for real-time data acquisition, analysis, learning, and classification of recorded events employing some of the latest technology in computer hardware, software, and artificial neural networks methods. The system is able to train dynamically, and updates its knowledge based on new data. The software is modular and hardware-independent; i.e., the front-end instrumentation is transparent to the analysis system. The software is designed to take advantage of the multiprocessing environment of the Unix operating system. The Unix System V shared memory and static RAM protocols for data access and the semaphore mechanism for interprocess communications were used. As the three-component sensor detects a seismic signal, it is displayed graphically on a color monitor using X11/Xlib graphics with interactive screening capabilities. For interesting events, the triaxial signal polarization is computed, a fast Fourier Transform (FFT) algorithm is applied, and the normalized power spectrum is transmitted to a backpropagation neural network for event classification. The system is currently capable of handling three data channels with a sampling rate of 500 Hz, which covers the bandwidth of most seismic events. The system has been tested in laboratory setting with artificial events generated in the vicinity of a three-component sensor.

  9. 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.

  10. Single-cell network profiling of peripheral blood mononuclear cells from healthy donors reveals age- and race-associated differences in immune signaling pathway activation.

    Science.gov (United States)

    Longo, Diane M; Louie, Brent; Putta, Santosh; Evensen, Erik; Ptacek, Jason; Cordeiro, James; Wang, Ena; Pos, Zoltan; Hawtin, Rachael E; Marincola, Francesco M; Cesano, Alessandra

    2012-02-15

    A greater understanding of the function of the human immune system at the single-cell level in healthy individuals is critical for discerning aberrant cellular behavior that occurs in settings such as autoimmunity, immunosenescence, and cancer. To achieve this goal, a systems-level approach capable of capturing the response of the interdependent immune cell types to external stimuli is required. In this study, an extensive characterization of signaling responses in multiple immune cell subpopulations within PBMCs from a cohort of 60 healthy donors was performed using single-cell network profiling (SCNP). SCNP is a multiparametric flow cytometry-based approach that enables the simultaneous measurement of basal and evoked signaling in multiple cell subsets within heterogeneous populations. In addition to establishing the interindividual degree of variation within a broad panel of immune signaling responses, the possible association of any observed variation with demographic variables including age and race was investigated. Using half of the donors as a training set, multiple age- and race-associated variations in signaling responses in discrete cell subsets were identified, and several were subsequently confirmed in the remaining samples (test set). Such associations may provide insight into age-related immune alterations associated with high infection rates and diminished protection following vaccination and into the basis for ethnic differences in autoimmune disease incidence and treatment response. SCNP allowed for the generation of a functional map of healthy immune cell signaling responses that can provide clinically relevant information regarding both the mechanisms underlying immune pathological conditions and the selection and effect of therapeutics.

  11. Regulation of adult neural progenitor cell functions by purinergic signaling.

    Science.gov (United States)

    Tang, Yong; Illes, Peter

    2017-02-01

    Extracellular purines are signaling molecules in the neurogenic niches of the brain and spinal cord, where they activate cell surface purinoceptors at embryonic neural stem cells (NSCs) and adult neural progenitor cells (NPCs). Although mRNA and protein are expressed at NSCs/NPCs for almost all subtypes of the nucleotide-sensitive P2X/P2Y, and the nucleoside-sensitive adenosine receptors, only a few of those have acquired functional significance. ATP is sequentially degraded by ecto-nucleotidases to ADP, AMP, and adenosine with agonistic properties for distinct receptor-classes. Nucleotides/nucleosides facilitate or inhibit NSC/NPC proliferation, migration and differentiation. The most ubiquitous effect of all agonists (especially of ATP and ADP) appears to be the facilitation of cell proliferation, usually through P2Y1Rs and sometimes through P2X7Rs. However, usually P2X7R activation causes necrosis/apoptosis of NPCs. Differentiation can be initiated by P2Y2R-activation or P2X7R-blockade. A key element in the transduction mechanism of either receptor is the increase of the intracellular free Ca 2+ concentration, which may arise due to its release from intracellular storage sites (G protein-coupling; P2Y) or due to its passage through the receptor-channel itself from the extracellular space (ATP-gated ion channel; P2X). Further research is needed to clarify how purinergic signaling controls NSC/NPC fate and how the balance between the quiescent and activated states is established with fine and dynamic regulation. GLIA 2017;65:213-230. © 2016 Wiley Periodicals, Inc.

  12. 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.

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

    International Nuclear Information System (INIS)

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

    1998-02-01

    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

  14. Introduction to Artificial Neural Networks

    DEFF Research Database (Denmark)

    Larsen, Jan

    1999-01-01

    The note addresses introduction to signal analysis and classification based on artificial feed-forward neural networks.......The note addresses introduction to signal analysis and classification based on artificial feed-forward neural networks....

  15. 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.

  16. Phenothiourea sensitizes zebrafish cranial neural crest and extraocular muscle development to changes in retinoic acid and IGF signaling.

    Directory of Open Access Journals (Sweden)

    Brenda L Bohnsack

    Full Text Available 1-Phenyl 2-thiourea (PTU is a tyrosinase inhibitor commonly used to block pigmentation and aid visualization of zebrafish development. At the standard concentration of 0.003% (200 µM, PTU inhibits melanogenesis and reportedly has minimal other effects on zebrafish embryogenesis. We found that 0.003% PTU altered retinoic acid and insulin-like growth factor (IGF regulation of neural crest and mesodermal components of craniofacial development. Reduction of retinoic acid synthesis by the pan-aldehyde dehydrogenase inhibitor diethylbenzaldehyde, only when combined with 0.003% PTU, resulted in extraocular muscle disorganization. PTU also decreased retinoic acid-induced teratogenic effects on pharyngeal arch and jaw cartilage despite morphologically normal appearing PTU-treated controls. Furthermore, 0.003% PTU in combination with inhibition of IGF signaling through either morpholino knockdown or pharmacologic inhibition of tyrosine kinase receptor phosphorylation, disrupted jaw development and extraocular muscle organization. PTU in and of itself inhibited neural crest development at higher concentrations (0.03% and had the greatest inhibitory effect when added prior to 22 hours post fertilization (hpf. Addition of 0.003% PTU between 4 and 20 hpf decreased thyroxine (T4 in thyroid follicles in the nasopharynx of 96 hpf embryos. Treatment with exogenous triiodothyronine (T3 and T4 improved, but did not completely rescue, PTU-induced neural crest defects. Thus, PTU should be used with caution when studying zebrafish embryogenesis as it alters the threshold of different signaling pathways important during craniofacial development. The effects of PTU on neural crest development are partially caused by thyroid hormone signaling.

  17. 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.

  18. 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.

  19. 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.

  20. The adaptor molecule RIAM integrates signaling events critical for integrin-mediated control of immune function and cancer progression.

    Science.gov (United States)

    Patsoukis, Nikolaos; Bardhan, Kankana; Weaver, Jessica D; Sari, Duygu; Torres-Gomez, Alvaro; Li, Lequn; Strauss, Laura; Lafuente, Esther M; Boussiotis, Vassiliki A

    2017-08-22

    Lymphocyte activation requires adhesion to antigen-presenting cells. This is a critical event linking innate and adaptive immunity. Lymphocyte adhesion is accomplished through LFA-1, which must be activated by a process referred to as inside-out integrin signaling. Among the few signaling molecules that have been implicated in inside-out integrin activation in hematopoietic cells are the small guanosine triphosphatase (GTPase) Rap1 and its downstream effector Rap1-interacting molecule (RIAM), a multidomain protein that defined the Mig10-RIAM-lamellipodin (MRL) class of adaptor molecules. Through its various domains, RIAM is a critical node of signal integration for activation of T cells, recruits monomeric and polymerized actin to drive actin remodeling and cytoskeletal reorganization, and promotes inside-out integrin signaling in T cells. As a regulator of inside-out integrin activation, RIAM affects multiple functions of innate and adaptive immunity. The effects of RIAM on cytoskeletal reorganization and integrin activation have implications in cell migration and trafficking of cancer cells. We provide an overview of the structure and interactions of RIAM, and we discuss the implications of RIAM functions in innate and adaptive immunity and cancer. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  1. Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling.

    Science.gov (United States)

    Zhu, Wanqu; Yao, Xiao; Liang, Yan; Liang, Dan; Song, Lu; Jing, Naihe; Li, Jinsong; Wang, Gang

    2015-02-01

    Unraveling the mechanisms underlying early neural differentiation of embryonic stem cells (ESCs) is crucial to developing cell-based therapies of neurodegenerative diseases. Neural fate acquisition is proposed to be controlled by a 'default' mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of murine ESCs. Unexpectedly, we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23 depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of two other Mediator subunits, Med1 and Med15, did not alter the neural differentiation of ESCs. Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23 depletion attenuated BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1, which is involved in Bmp4 promoter-enhancer communication. Interestingly, med23 knockdown in zebrafish embryos also enhanced neural development at early embryogenesis, which could be reversed by co-injection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination. © 2015. Published by The Company of Biologists Ltd.

  2. 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

  3. Using Pulse Width Modulation for Wireless Transmission of Neural Signals in Multichannel Neural Recording Systems

    Science.gov (United States)

    Yin, Ming; Ghovanloo, Maysam

    2013-01-01

    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-μm 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 ~ 2.26 Mb/s. PMID:19497823

  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. 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.

  6. A negative modulatory role for rho and rho-associated kinase signaling in delamination of neural crest cells

    Directory of Open Access Journals (Sweden)

    Kalcheim Chaya

    2008-10-01

    Full Text Available Abstract 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.

  7. 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.

  8. Air pollution and children: neural and tight junction antibodies and combustion metals, the role of barrier breakdown and brain immunity in neurodegeneration.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Vojdani, Aristo; Blaurock-Busch, Eleonore; Busch, Yvette; Friedle, Albrecht; Franco-Lira, Maricela; Sarathi-Mukherjee, Partha; Martínez-Aguirre, Xavier; Park, Su-Bin; Torres-Jardón, Ricardo; D'Angiulli, Amedeo

    2015-01-01

    Millions of children are exposed to concentrations of air pollutants, including fine particulate matter (PM2.5), above safety standards. In the Mexico City Metropolitan Area (MCMA) megacity, children show an early brain imbalance in oxidative stress, inflammation, innate and adaptive immune response-associated genes, and blood-brain barrier breakdown. We investigated serum and cerebrospinal fluid (CSF) antibodies to neural and tight junction proteins and environmental pollutants in 139 children ages 11.91 ± 4.2 y with high versus low air pollution exposures. We also measured metals in serum and CSF. MCMA children showed significantly higher serum actin IgG, occludin/zonulin 1 IgA, IgG, myelin oligodendrocyte glycoprotein IgG and IgM (p < 0.01), myelin basic protein IgA and IgG, S-100 IgG and IgM, and cerebellar IgG (p < 0.001). Serum IgG antibodies to formaldehyde, benzene, and bisphenol A, and concentrations of Ni and Cd were significantly higher in exposed children (p < 0.001). CSF MBP antibodies and nickel concentrations were higher in MCMA children (p = 0.03). Air pollution exposure damages epithelial and endothelial barriers and is a robust trigger of tight junction and neural antibodies. Cryptic 'self' tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology hallmarks present in megacity children. The major factor determining the impact of neural antibodies is the integrity of the blood-brain barrier. Defining the air pollution linkage of the brain/immune system interactions and damage to physical and immunological barriers with short and long term neural detrimental effects to children's brains ought to be of pressing importance for public health.

  9. Application of complex discrete wavelet transform in classification of Doppler signals using complex-valued artificial neural network.

    Science.gov (United States)

    Ceylan, Murat; Ceylan, Rahime; Ozbay, Yüksel; Kara, Sadik

    2008-09-01

    In biomedical signal classification, due to the huge amount of data, to compress the biomedical waveform data is vital. This paper presents two different structures formed using feature extraction algorithms to decrease size of feature set in training and test data. The proposed structures, named as wavelet transform-complex-valued artificial neural network (WT-CVANN) and complex wavelet transform-complex-valued artificial neural network (CWT-CVANN), use real and complex discrete wavelet transform for feature extraction. The aim of using wavelet transform is to compress data and to reduce training time of network without decreasing accuracy rate. In this study, the presented structures were applied to the problem of classification in carotid arterial Doppler ultrasound signals. Carotid arterial Doppler ultrasound signals were acquired from left carotid arteries of 38 patients and 40 healthy volunteers. The patient group included 22 males and 16 females with an established diagnosis of the early phase of atherosclerosis through coronary or aortofemoropopliteal (lower extremity) angiographies (mean age, 59 years; range, 48-72 years). Healthy volunteers were young non-smokers who seem to not bear any risk of atherosclerosis, including 28 males and 12 females (mean age, 23 years; range, 19-27 years). Sensitivity, specificity and average detection rate were calculated for comparison, after training and test phases of all structures finished. These parameters have demonstrated that training times of CVANN and real-valued artificial neural network (RVANN) were reduced using feature extraction algorithms without decreasing accuracy rate in accordance to our aim.

  10. Transmission of wireless neural signals through a 0.18 µm CMOS low-power amplifier.

    Science.gov (United States)

    Gazziro, M; Braga, C F R; Moreira, D A; Carvalho, A C P L F; Rodrigues, J F; Navarro, J S; Ardila, J C M; Mioni, D P; Pessatti, M; Fabbro, P; Freewin, C; Saddow, S E

    2015-01-01

    In the field of Brain Machine Interfaces (BMI) researchers still are not able to produce clinically viable solutions that meet the requirements of long-term operation without the use of wires or batteries. Another problem is neural compatibility with the electrode probes. One of the possible ways of approaching these problems is the use of semiconductor biocompatible materials (silicon carbide) combined with an integrated circuit designed to operate with low power consumption. This paper describes a low-power neural signal amplifier chip, named Cortex, fabricated using 0.18 μm CMOS process technology with all electronics integrated in an area of 0.40 mm(2). The chip has 4 channels, total power consumption of only 144 μW, and is impedance matched to silicon carbide biocompatible electrodes.

  11. Notch1 Signaling Regulates the Th17/Treg Immune Imbalance in Patients with Psoriasis Vulgaris.

    Science.gov (United States)

    Ma, Lei; Xue, HaiBo; Gao, Tianqin; Gao, MeiLan; Zhang, YuJie

    2018-01-01

    To evaluate the regulating effect of Notch1 signaling on Th17/Treg immune imbalance in psoriasis vulgaris (PV). Notch1, Hes-1, ROR γ t, Foxp3, IL-17, and IL-10 mRNA expression, as well as Th17 and Treg cell percentages in peripheral CD4 + T cells, were detected by real-time quantitative RT-PCR and flow cytometry, and serum concentrations of IL-17 and IL-10 were detected by ELISA in 36 PV patients and 32 healthy controls. Additionally, CD4 + T cells from 12 PV patients were treated with γ -secretase inhibitor DAPT, and the above indexes were measured. PV patients presented distinct Th17/Treg immune imbalance and highly expressed Notch1 and Hes-1 mRNA levels, which were positively correlated with psoriasis area and severity index (PASI) and the ratios of Th17/Treg and ROR γ t/Foxp3. DAPT treatment resulted in the obvious downregulation of Th17 cell percentage in cocultured CD4 + T cells, ROR γ t and IL-17 mRNA levels, and IL-17 concentration in cell-free supernatant from cocultured CD4 + T cells of PV patients in a dose-dependent manner, while there was no significant influence on Treg cell percentage, Foxp3, and IL-10 expression, therefore leading to the recovery of Th17/Treg immune imbalance. Notch1 signaling may contribute to the pathogenesis of PV by regulating Th17/Treg immune imbalance.

  12. 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.

  13. Beta1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance

    DEFF Research Database (Denmark)

    Campos, Lia S; Leone, Dino P; Relvas, Joao B

    2004-01-01

    , signalling is required for neural stem cell maintenance, as assessed by neurosphere formation, and inhibition or genetic ablation of beta1 integrin using cre/lox technology reduces the level of MAPK activity. We conclude that integrins are therefore an important part of the signalling mechanisms that control......The emerging evidence that stem cells develop in specialised niches highlights the potential role of environmental factors in their regulation. Here we examine the role of beta1 integrin/extracellular matrix interactions in neural stem cells. We find high levels of beta1 integrin expression...... in the stem-cell containing regions of the embryonic CNS, with associated expression of the laminin alpha2 chain. Expression levels of laminin alpha2 are reduced in the postnatal CNS, but a population of cells expressing high levels of beta1 remains. Using neurospheres - aggregate cultures, derived from...

  14. 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.

  15. Toll-like Receptor 4: Innate Immune Regulator of Neuroimmune and Neuroendocrine interactions in Stress and Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Jiajun eLiu

    2014-09-01

    Full Text Available Major depressive disorder (MDD poses one of the highest disease burdens worldwide. Yet, current treatments targeting serotonergic and noradrenaline reuptake systems are insufficient to provide long-term relief from depressive symptoms in most patients, indicating the need for new treatment targets. Having the ability to influence behaviour similar to depressive symptoms, as well as communicate with neuronal and neuroendocrine systems, the innate immune system is a strong candidate for MDD treatments. Given the complex nature of immune signalling, the main question becomes: What is the role of the innate immune system in MDD?The current review presents evidence that toll-like receptor 4 (TLR4, via driving both peripheral and central immune responses, can interact with serotonergic neurotransmission and cause neuroendocrine disturbances, thus integrating with widely observed hallmarks of MDD. Additionally, through describing the multi-directional communication between immune, neural and endocrine systems in stress, TLR4 – related mechanisms can mediate stress-induced adaptations, which are necessary for the development of MDD. Therefore, apart from exogenous pathogenic mechanisms, TLR4 is involved in immune changes as a result of endogenous stress signals, playing an integral part in the pathophysiology, and could be a potential target for pharmacological treatments to improve current interventions for MDD.

  16. 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.

  17. Sympathetic neural modulation of the immune system

    International Nuclear Information System (INIS)

    Madden, K.S.

    1989-01-01

    One route by which the central nervous system communicates with lymphoid organs in the periphery is through the sympathetic nervous system (SNS). To study SNS regulation of immune activity in vivo, selective removal of peripheral noradrenergic nerve fibers was achieved by administration of the neurotoxic drug, 6-hydroxydopamine (6-OHDA), to adult mice. To assess SNS influence on lymphocyte proliferation in vitro, uptake of 125 iododeoxyuridine ( 125 IUdR), a DNA precursor, was measured following 6-OHDA treatment. Sympathectomy prior to epicutaneous immunization with TNCB did not alter draining lymph nodes (LN) cell proliferation, whereas 6-OHDA treatment before footpad immunization with KLH reduced DNA synthesis in popliteal LN by 50%. In mice which were not deliberately immunized, sympathectomy stimulated 125 IUdR uptake inguinal and axillary LN, spleen, and bone marrow. In vitro, these LN and spleen cells exhibited decreased proliferation responses to the T cell mitogen, concanavalin A (Con A), whereas lipopolysaccharide (LPS)-stimulated IgG secretion was enhanced. Studies examining 51 Cr-labeled lymphocyte trafficking to LN suggested that altered cell migration may play a part in sympathectomy-induced changes in LN cell function

  18. Neural computation and the computational theory of cognition.

    Science.gov (United States)

    Piccinini, Gualtiero; Bahar, Sonya

    2013-04-01

    We begin by distinguishing computationalism from a number of other theses that are sometimes conflated with it. We also distinguish between several important kinds of computation: computation in a generic sense, digital computation, and analog computation. Then, we defend a weak version of computationalism-neural processes are computations in the generic sense. After that, we reject on empirical grounds the common assimilation of neural computation to either analog or digital computation, concluding that neural computation is sui generis. Analog computation requires continuous signals; digital computation requires strings of digits. But current neuroscientific evidence indicates that typical neural signals, such as spike trains, are graded like continuous signals but are constituted by discrete functional elements (spikes); thus, typical neural signals are neither continuous signals nor strings of digits. It follows that neural computation is sui generis. Finally, we highlight three important consequences of a proper understanding of neural computation for the theory of cognition. First, understanding neural computation requires a specially designed mathematical theory (or theories) rather than the mathematical theories of analog or digital computation. Second, several popular views about neural computation turn out to be incorrect. Third, computational theories of cognition that rely on non-neural notions of computation ought to be replaced or reinterpreted in terms of neural computation. Copyright © 2012 Cognitive Science Society, Inc.

  19. Neural signal for counteracting pre-action bias in the centromedian thalamic nucleus

    Directory of Open Access Journals (Sweden)

    Takafumi eMinamimoto

    2014-01-01

    Full Text Available Most of our daily actions are selected and executed involuntarily under familiar situations by the guidance of internal drives, such as motivation. The behavioral tendency or biasing towards one over others reflects the action-selection process in advance of action execution (i.e., pre-action bias. Facing unexpected situations, however, pre-action bias should be withdrawn and replaced by an alternative that is suitable for the situation (i.e., counteracting bias. To understand the neural mechanism for the counteracting process, we studied the neural activity of the thalamic centromedian (CM nucleus in monkeys performing GO-NOGO task with asymmetrical or symmetrical reward conditions. The monkeys reacted to GO signal faster in large-reward condition, indicating behavioral bias toward large reward. In contrast, they responded slowly in small-reward condition, suggesting a conflict between internal drive and external demand. We found that neurons in the CM nucleus exhibited phasic burst discharges after GO and NOGO instructions especially when they were associated with small reward. The small-reward preference was positively correlated with the strength of behavioral bias toward large reward. The small-reward preference disappeared when only NOGO action was requested. The timing of activation predicted the timing of action opposed to bias. These results suggest that CM signals the discrepancy between internal pre-action bias and external demand, and mediates the counteracting process — resetting behavioral bias and leading to execution of opposing action.

  20. The Neural Border: Induction, Specification and Maturation of the territory that generates Neural Crest cells.

    Science.gov (United States)

    Pla, Patrick; Monsoro-Burq, Anne H

    2018-05-28

    The neural crest is induced at the edge between the neural plate and the nonneural ectoderm, in an area called the neural (plate) border, during gastrulation and neurulation. In recent years, many studies have explored how this domain is patterned, and how the neural crest is induced within this territory, that also participates to the prospective dorsal neural tube, the dorsalmost nonneural ectoderm, as well as placode derivatives in the anterior area. This review highlights the tissue interactions, the cell-cell signaling and the molecular mechanisms involved in this dynamic spatiotemporal patterning, resulting in the induction of the premigratory neural crest. Collectively, these studies allow building a complex neural border and early neural crest gene regulatory network, mostly composed by transcriptional regulations but also, more recently, including novel signaling interactions. Copyright © 2018. Published by Elsevier Inc.

  1. Adrenergic Signaling: A Targetable Checkpoint Limiting Development of the Antitumor Immune Response

    Science.gov (United States)

    Qiao, Guanxi; Chen, Minhui; Bucsek, Mark J.; Repasky, Elizabeth A.; Hylander, Bonnie L.

    2018-01-01

    An immune response must be tightly controlled so that it will be commensurate with the level of response needed to protect the organism without damaging normal tissue. The roles of cytokines and chemokines in orchestrating these processes are well known, but although stress has long been thought to also affect immune responses, the underlying mechanisms were not as well understood. Recently, the role of nerves and, specifically, the sympathetic nervous system, in regulating immune responses is being revealed. Generally, an acute stress response is beneficial but chronic stress is detrimental because it suppresses the activities of effector immune cells while increasing the activities of immunosuppressive cells. In this review, we first discuss the underlying biology of adrenergic signaling in cells of both the innate and adaptive immune system. We then focus on the effects of chronic adrenergic stress in promoting tumor growth, giving examples of effects on tumor cells and immune cells, explaining the methods commonly used to induce stress in preclinical mouse models. We highlight how this relates to our observations that mandated housing conditions impose baseline chronic stress on mouse models, which is sufficient to cause chronic immunosuppression. This problem is not commonly recognized, but it has been shown to impact conclusions of several studies of mouse physiology and mouse models of disease. Moreover, the fact that preclinical mouse models are chronically immunosuppressed has critical ramifications for analysis of any experiments with an immune component. Our group has found that reducing adrenergic stress by housing mice at thermoneutrality or treating mice housed at cooler temperatures with β-blockers reverses immunosuppression and significantly improves responses to checkpoint inhibitor immunotherapy. These observations are clinically relevant because there are numerous retrospective epidemiological studies concluding that cancer patients who were

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

    Directory of Open Access Journals (Sweden)

    S. N. Kale

    2009-01-01

    Full Text Available 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 developed an optimal FTLRNN model, which removes the noise from the EMG signal. Results show that the proposed optimal FTLRNN model has an MSE (Mean Square Error as low as 0.000067 and 0.000048, correlation coefficient as high as 0.99950 and 0.99939 for noise signal and EMG signal, respectively, when validated on the test dataset. It is also noticed that the output of the estimated FTLRNN model closely follows the real one. This network is indeed robust as EMG signal tolerates the noise variance from 0.1 to 0.4 for uniform noise and 0.30 for Gaussian noise. It is clear that the training of the network is independent of specific partitioning of dataset. It is seen that the performance of the proposed FTLRNN model clearly outperforms the best Multilayer perceptron (MLP and Radial Basis Function NN (RBF models. The simple NN model such as the FTLRNN with single-hidden layer can be employed to remove noise from EMG signal.

  3. Neuroendocrine signaling modulates specific neural networks relevant to migraine.

    Science.gov (United States)

    Martins-Oliveira, Margarida; Akerman, Simon; Holland, Philip R; Hoffmann, Jan R; Tavares, Isaura; Goadsby, Peter J

    2017-05-01

    Migraine is a disabling brain disorder involving abnormal trigeminovascular activation and sensitization. Fasting or skipping meals is considered a migraine trigger and altered fasting glucose and insulin levels have been observed in migraineurs. Therefore peptides involved in appetite and glucose regulation including insulin, glucagon and leptin could potentially influence migraine neurobiology. We aimed to determine the effect of insulin (10U·kg -1 ), glucagon (100μg·200μl -1 ) and leptin (0.3, 1 and 3mg·kg -1 ) signaling on trigeminovascular nociceptive processing at the level of the trigeminocervical-complex and hypothalamus. Male rats were anesthetized and prepared for craniovascular stimulation. In vivo electrophysiology was used to determine changes in trigeminocervical neuronal responses to dural electrical stimulation, and phosphorylated extracellular signal-regulated kinases 1 and 2 (pERK1/2) immunohistochemistry to determine trigeminocervical and hypothalamic neural activity; both in response to intravenous administration of insulin, glucagon, leptin or vehicle control in combination with blood glucose analysis. Blood glucose levels were significantly decreased by insulin (pneuronal firing in the trigeminocervical-complex was significantly inhibited by insulin (pmetabolic homeostasis may occur through disturbed glucose regulation and a transient hypothalamic dysfunction. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Immune regulation and CNS autoimmune disease

    DEFF Research Database (Denmark)

    Antel, J P; Owens, T

    1999-01-01

    The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity...... and duration of the tissue directed injury. Convergence of research, involving direct manipulation of specific cells and molecular mediators in animal models and in vitro analysis of human immune and neural cells and tissues, is providing increasing insight into the role of these immune regulatory functions...

  5. Andrographolide Promotes Neural Differentiation of Rat Adipose Tissue-Derived Stromal Cells through Wnt/β-Catenin Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yan Liang

    2017-01-01

    Full Text Available Adipose tissue-derived stromal cells (ADSCs are a high-yield source of pluripotent stem cells for use in cell-based therapies. We explored the effect of andrographolide (ANDRO, one of the ingredients of the medicinal herb extract on the neural differentiation of rat ADSCs and associated molecular mechanisms. We observed that rat ADSCs were small and spindle-shaped and expressed multiple stem cell markers including nestin. They were multipotent as evidenced by adipogenic, osteogenic, chondrogenic, and neural differentiation under appropriate conditions. The proportion of cells exhibiting neural-like morphology was higher, and neurites developed faster in the ANDRO group than in the control group in the same neural differentiation medium. Expression levels of the neural lineage markers MAP2, tau, GFAP, and β-tubulin III were higher in the ANDRO group. ANDRO induced a concentration-dependent increase in Wnt/β-catenin signaling as evidenced by the enhanced expression of nuclear β-catenin and the inhibited form of GSK-3β (pSer9. Thus, this study shows for the first time how by enhancing the neural differentiation of ADSCs we expect that ANDRO pretreatment may increase the efficacy of adult stem cell transplantation in nervous system diseases, but more exploration is needed.

  6. The neonicotinoid insecticide Clothianidin adversely affects immune signaling in a human cell line.

    Science.gov (United States)

    Di Prisco, Gennaro; Iannaccone, Marco; Ianniello, Flora; Ferrara, Rosalba; Caprio, Emilio; Pennacchio, Francesco; Capparelli, Rosanna

    2017-10-18

    Clothianidin is a widely used neonicotinoid insecticide, which is a potent agonist of the nicotinic acetylcholine receptor in insects. This neurotoxic compound has a negative impact on insect immunity, as it down-regulates the activation of the transcription factor NF-κB. Given the evolutionary conserved role of NF-κB in the modulation of the immune response in the animal kingdom, here we want to assess any effect of Clothianidin on vertebrate defense barriers. In presence of this neonicotinoid insecticide, a pro-inflammatory challenge with LPS on the human monocytic cell line THP-1 results both in a reduced production of the cytokine TNF-α and in a down-regulation of a reporter gene under control of NF-κB promoter. This finding is corroborated by a significant impact of Clothianidin on the transcription levels of different immune genes, characterized by a core disruption of TRAF4 and TRAF6 that negatively influences NF-κB signaling. Moreover, exposure to Clothianidin concurrently induces a remarkable up-regulation of NGFR, which supports the occurrence of functional ties between the immune and nervous systems. These results suggest a potential risk of immunotoxicity that neonicotinoids may have on vertebrates, which needs to be carefully assessed at the organism level.

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

    Science.gov (United States)

    Vanni, Simo; Sharifian, Fariba; Heikkinen, Hanna; Vigário, Ricardo

    2015-08-01

    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. Copyright © 2015 the American Physiological Society.

  8. CXXC5 is a novel BMP4-regulated modulator of Wnt signaling in neural stem cells

    Czech Academy of Sciences Publication Activity Database

    Andersson, T.; Södersten, E.; Duckworth, J.K.; Cascante, A.; Fritz, N.; Sacchetti, P.; Červenka, I.; Bryja, Vítězslav; Hermanson, O.

    2008-01-01

    Roč. 284, č. 6 (2008), s. 3672-3681 ISSN 0021-9258 Grant - others:GA AV ČR(CZ) KJB501630801 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : Wnt signaling * CXXC5 * neural stem cells Subject RIV: BO - Biophysics Impact factor: 5.520, year: 2008

  9. Spatio-temporal Model of Endogenous ROS and Raft-Dependent WNT/Beta-Catenin Signaling Driving Cell Fate Commitment in Human Neural Progenitor Cells

    Science.gov (United States)

    Haack, Fiete; Lemcke, Heiko; Ewald, Roland; Rharass, Tareck; Uhrmacher, Adelinde M.

    2015-01-01

    Canonical WNT/β-catenin signaling is a central pathway in embryonic development, but it is also connected to a number of cancers and developmental disorders. Here we apply a combined in-vitro and in-silico approach to investigate the spatio-temporal regulation of WNT/β-catenin signaling during the early neural differentiation process of human neural progenitors cells (hNPCs), which form a new prospect for replacement therapies in the context of neurodegenerative diseases. Experimental measurements indicate a second signal mechanism, in addition to canonical WNT signaling, being involved in the regulation of nuclear β-catenin levels during the cell fate commitment phase of neural differentiation. We find that the biphasic activation of β-catenin signaling observed experimentally can only be explained through a model that combines Reactive Oxygen Species (ROS) and raft dependent WNT/β-catenin signaling. Accordingly after initiation of differentiation endogenous ROS activates DVL in a redox-dependent manner leading to a transient activation of down-stream β-catenin signaling, followed by continuous auto/paracrine WNT signaling, which crucially depends on lipid rafts. Our simulation studies further illustrate the elaborate spatio-temporal regulation of DVL, which, depending on its concentration and localization, may either act as direct inducer of the transient ROS/β-catenin signal or as amplifier during continuous auto-/parcrine WNT/β-catenin signaling. In addition we provide the first stochastic computational model of WNT/β-catenin signaling that combines membrane-related and intracellular processes, including lipid rafts/receptor dynamics as well as WNT- and ROS-dependent β-catenin activation. The model’s predictive ability is demonstrated under a wide range of varying conditions for in-vitro and in-silico reference data sets. Our in-silico approach is realized in a multi-level rule-based language, that facilitates the extension and modification of the

  10. 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

  11. Activin/Nodal Signaling Supports Retinal Progenitor Specification in a Narrow Time Window during Pluripotent Stem Cell Neuralization

    Directory of Open Access Journals (Sweden)

    Michele Bertacchi

    2015-10-01

    Full Text Available Retinal progenitors are initially found in the anterior neural plate region known as the eye field, whereas neighboring areas undertake telencephalic or hypothalamic development. Eye field cells become specified by switching on a network of eye field transcription factors, but the extracellular cues activating this network remain unclear. In this study, we used chemically defined media to induce in vitro differentiation of mouse embryonic stem cells (ESCs toward eye field fates. Inhibition of Wnt/β-catenin signaling was sufficient to drive ESCs to telencephalic, but not retinal, fates. Instead, retinal progenitors could be generated from competent differentiating mouse ESCs by activation of Activin/Nodal signaling within a narrow temporal window corresponding to the emergence of primitive anterior neural progenitors. Activin also promoted eye field gene expression in differentiating human ESCs. Our results reveal insights into the mechanisms of eye field specification and open new avenues toward the generation of retinal progenitors for translational medicine.

  12. 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

  13. 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.

  14. Neural Signaling of Food Healthiness Associated with Emotion Processing.

    Science.gov (United States)

    Herwig, Uwe; Dhum, Matthias; Hittmeyer, Anna; Opialla, Sarah; Scherpiet, Sigrid; Keller, Carmen; Brühl, Annette B; Siegrist, Michael

    2016-01-01

    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 regions. Thirty-seven healthy subjects underwent functional magnetic resonance imaging while evaluating the healthiness of food presented as photographs with a subsequent rating on a visual analog 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 signaling associated with reward and self-relevance, which could promote salutary nutrition behavior. The involved brain regions may be amenable to mechanisms of emotion regulation in the context of psychotherapeutic regulation of food intake.

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

    International Nuclear Information System (INIS)

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

    2001-01-01

    A feed-forward neural network is used to forecast major and minor disruptions in TEXT tokamak discharges. Using the experimental data of soft X-ray signals as input data, the neural net is trained with one disruptive plasma discharge, while a different disruptive discharge is used for validation. After proper training, the net works with the same set of weights, it is then used to forecast disruptions in two other different plasma discharges. It is observed that the neural net is capable of predicting the onset of a disruption up to 3.12 ms in advance. From what we observe in the predictive behavior of our network, speculations are made whether the disruption triggering mechanism is associated with an increase in the m=2 magnetic island, that disturbs the central part of the plasma column afterwards, or the initial perturbation has first occurred in the central part of the plasma column and then the m=2 MHD mode is destabilized. (author)

  16. Implantable neurotechnologies: a review of integrated circuit neural amplifiers.

    Science.gov (United States)

    Ng, Kian Ann; Greenwald, Elliot; Xu, Yong Ping; Thakor, Nitish V

    2016-01-01

    Neural signal recording is critical in modern day neuroscience research and emerging neural prosthesis programs. Neural recording requires the use of precise, low-noise amplifier systems to acquire and condition the weak neural signals that are transduced through electrode interfaces. Neural amplifiers and amplifier-based systems are available commercially or can be designed in-house and fabricated using integrated circuit (IC) technologies, resulting in very large-scale integration or application-specific integrated circuit solutions. IC-based neural amplifiers are now used to acquire untethered/portable neural recordings, as they meet the requirements of a miniaturized form factor, light weight and low power consumption. Furthermore, such miniaturized and low-power IC neural amplifiers are now being used in emerging implantable neural prosthesis technologies. This review focuses on neural amplifier-based devices and is presented in two interrelated parts. First, neural signal recording is reviewed, and practical challenges are highlighted. Current amplifier designs with increased functionality and performance and without penalties in chip size and power are featured. Second, applications of IC-based neural amplifiers in basic science experiments (e.g., cortical studies using animal models), neural prostheses (e.g., brain/nerve machine interfaces) and treatment of neuronal diseases (e.g., DBS for treatment of epilepsy) are highlighted. The review concludes with future outlooks of this technology and important challenges with regard to neural signal amplification.

  17. 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.

  18. 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.

  19. Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity

    Science.gov (United States)

    Cai, Chenxu; Liu, Guangao; Wang, Yuande; Du, Juan; Lin, Xin; Yang, Meixiang

    2017-01-01

    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. PMID:28049627

  20. 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 (T FH ) cell differentiation. Intriguingly, the deletion of SFRs completely rescued the severe defect in T FH 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 T FH cells. Thus, our current study revises our understanding of the mechanisms underlying T cell defects in patients with XLP. © 2017 Chen et al.

  1. Supervised Learning with Complex-valued Neural Networks

    CERN Document Server

    Suresh, Sundaram; Savitha, Ramasamy

    2013-01-01

    Recent advancements in the field of telecommunications, medical imaging and signal processing deal with signals that are inherently time varying, nonlinear and complex-valued. The time varying, nonlinear characteristics of these signals can be effectively analyzed using artificial neural networks.  Furthermore, to efficiently preserve the physical characteristics of these complex-valued signals, it is important to develop complex-valued neural networks and derive their learning algorithms to represent these signals at every step of the learning process. This monograph comprises a collection of new supervised learning algorithms along with novel architectures for complex-valued neural networks. The concepts of meta-cognition equipped with a self-regulated learning have been known to be the best human learning strategy. In this monograph, the principles of meta-cognition have been introduced for complex-valued neural networks in both the batch and sequential learning modes. For applications where the computati...

  2. Integrating Artificial Immune, Neural and Endrocine Systems in Autonomous Sailing Robots

    Science.gov (United States)

    2010-09-24

    system - Development of an adaptive hormone system capable of changing operation and control of the neural network depending on changing enviromental ...and control of the neural network depending on changing enviromental conditions • First basic design of the MOOP and a simple neural-endocrine based

  3. Neural reflex pathways in intestinal inflammation: hypotheses to viable therapy

    NARCIS (Netherlands)

    Willemze, Rose A.; Luyer, Misha D.; Buurman, Wim A.; de Jonge, Wouter J.

    2015-01-01

    Studies in neuroscience and immunology have clarified much of the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. As with other organs, intestinal immune responses and the development of immunity seems to be modulated by neural reflexes.

  4. Immune function of a Rab-related protein by modulating the JAK-STAT signaling pathway in the silkworm, Bombyx mori.

    Science.gov (United States)

    Chen, Chen; Eldein, Salah; Zhou, Xiaosan; Sun, Yu; Gao, Jin; Sun, Yuxuan; Liu, Chaoliang; Wang, Lei

    2018-01-01

    The Rab-family GTPases mainly regulate intracellular vesicle transport, and play important roles in the innate immune response in invertebrates. However, the function and signal transduction of Rab proteins in immune reactions remain unclear in silkworms. In this study, we analyzed a Rab-related protein of silkworm Bombyx mori (BmRABRP) by raising antibodies against its bacterially expressed recombinant form. Tissue distribution analysis showed that BmRABRP mRNA and protein were high expressed in the Malpighian tubule and fat body, respectively. However, among the different stages, only the fourth instar larvae and pupae showed significant BmRABRP levels. After challenge with four pathogenic microorganisms (Escherichia coli, BmNPV, Beauveria bassiana, Micrococcus luteus), the expression of BmRABRP mRNA in the fat body was significantly upregulated. In contrast, the BmRABRP protein was significantly upregulated after infection with BmNPV, while it was downregulated by E. coli, B. bassiana, and M. luteus. A specific dsRNA was used to explore the immune function and relationship between BmRABRP and the JAK-STAT signaling pathway. After BmRABRP gene interference, significant reduction in the number of nodules and increased mortality suggested that BmRABRP plays an important role in silkworm's response to bacterial challenge. In addition, four key genes (BmHOP, BmSTAT, BmSOCS2, and BmSOCS6) of the JAK-STAT signaling pathway showed significantly altered expressions after BmRABRP silencing. BmHOP and BmSOCS6 expressions were significantly decreased, while BmSTAT and BmSOCS2 were significantly upregulated. Our results suggested that BmRABRP is involved in the innate immune response against pathogenic microorganisms through the JAK-STAT signaling pathway in silkworm. © 2017 Wiley Periodicals, Inc.

  5. 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.

  6. 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...

  7. Neural network approach to the prediction of seismic events based on low-frequency signal monitoring of the Kuril-Kamchatka and Japanese regions

    Directory of Open Access Journals (Sweden)

    Irina Popova

    2013-08-01

    Full Text Available Very-low-frequency/ low-frequency (VLF/LF sub-ionospheric radiowave monitoring has been widely used in recent years to analyze earthquake preparatory processes. The connection between earthquakes with M ≥5.5 and nighttime disturbances of signal amplitude and phase has been established. Thus, it is possible to use nighttime anomalies of VLF/LF signals as earthquake precursors. Here, we propose a method for estimation of the VLF/LF signal sensitivity to seismic processes using a neural network approach. We apply the error back-propagation technique based on a three-level perceptron to predict a seismic event. The back-propagation technique involves two main stages to solve the problem; namely, network training, and recognition (the prediction itself. To train a neural network, we first create a so-called ‘training set’. The ‘teacher’ specifies the correspondence between the chosen input and the output data. In the present case, a representative database includes both the LF data received over three years of monitoring at the station in Petropavlovsk-Kamchatsky (2005-2007, and the seismicity parameters of the Kuril-Kamchatka and Japanese regions. At the first stage, the neural network established the relationship between the characteristic features of the LF signal (the mean and dispersion of a phase and an amplitude at nighttime for a few days before a seismic event and the corresponding level of correlation with a seismic event, or the absence of a seismic event. For the second stage, the trained neural network was applied to predict seismic events from the LF data using twelve time intervals in 2004, 2005, 2006 and 2007. The results of the prediction are discussed.

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

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    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.

  9. 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.

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

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    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.

  11. 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.

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

    Science.gov (United States)

    Park, Hyeong-Dong; Tallon-Baudry, Catherine

    2014-05-05

    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.

  13. 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

  14. Ras-dva1 small GTPase regulates telencephalon development in Xenopus laevis embryos by controlling Fgf8 and Agr signaling at the anterior border of the neural plate

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    Maria B. Tereshina

    2014-07-01

    Full Text Available We previously found that the small GTPase Ras-dva1 is essential for the telencephalic development in Xenopus laevis because Ras-dva1 controls the Fgf8-mediated induction of FoxG1 expression, a key telencephalic regulator. In this report, we show, however, that Ras-dva1 and FoxG1 are expressed in different groups of cells; whereas Ras-dva1 is expressed in the outer layer of the anterior neural fold, FoxG1 and Fgf8 are activated in the inner layer from which the telencephalon is derived. We resolve this paradox by demonstrating that Ras-dva1 is involved in the transduction of Fgf8 signal received by cells in the outer layer, which in turn send a feedback signal that stimulates FoxG1 expression in the inner layer. We show that this feedback signal is transmitted by secreted Agr proteins, the expression of which is activated in the outer layer by mediation of Ras-dva1 and the homeodomain transcription factor Otx2. In turn, Agrs are essential for maintaining Fgf8 and FoxG1 expression in cells at the anterior neural plate border. Our finding reveals a novel feedback loop mechanism based on the exchange of Fgf8 and Agr signaling between neural and non-neural compartments at the anterior margin of the neural plate and demonstrates a key role of Ras-dva1 in this mechanism.

  15. Reconstruction of gastric slow wave from finger photoplethysmographic signal using radial basis function neural network.

    Science.gov (United States)

    Mohamed Yacin, S; Srinivasa Chakravarthy, V; Manivannan, M

    2011-11-01

    Extraction of extra-cardiac information from photoplethysmography (PPG) signal is a challenging research problem with significant clinical applications. In this study, radial basis function neural network (RBFNN) is used to reconstruct the gastric myoelectric activity (GMA) slow wave from finger PPG signal. Finger PPG and GMA (measured using Electrogastrogram, EGG) signals were acquired simultaneously at the sampling rate of 100 Hz from ten healthy subjects. Discrete wavelet transform (DWT) was used to extract slow wave (0-0.1953 Hz) component from the finger PPG signal; this slow wave PPG was used to reconstruct EGG. A RBFNN is trained on signals obtained from six subjects in both fasting and postprandial conditions. The trained network is tested on data obtained from the remaining four subjects. In the earlier study, we have shown the presence of GMA information in finger PPG signal using DWT and cross-correlation method. In this study, we explicitly reconstruct gastric slow wave from finger PPG signal by the proposed RBFNN-based method. It was found that the network-reconstructed slow wave provided significantly higher (P wave than the correlation obtained (≈0.7) between the PPG slow wave from DWT and the EEG slow wave. Our results showed that a simple finger PPG signal can be used to reconstruct gastric slow wave using RBFNN method.

  16. 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

  17. Epstein-Barr virus large tegument protein BPLF1 contributes to innate immune evasion through interference with toll-like receptor signaling.

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    Michiel van Gent

    2014-02-01

    Full Text Available Viral infection triggers an early host response through activation of pattern recognition receptors, including Toll-like receptors (TLR. TLR signaling cascades induce production of type I interferons and proinflammatory cytokines involved in establishing an anti-viral state as well as in orchestrating ensuing adaptive immunity. To allow infection, replication, and persistence, (herpesviruses employ ingenious strategies to evade host immunity. The human gamma-herpesvirus Epstein-Barr virus (EBV is a large, enveloped DNA virus persistently carried by more than 90% of adults worldwide. It is the causative agent of infectious mononucleosis and is associated with several malignant tumors. EBV activates TLRs, including TLR2, TLR3, and TLR9. Interestingly, both the expression of and signaling by TLRs is attenuated during productive EBV infection. Ubiquitination plays an important role in regulating TLR signaling and is controlled by ubiquitin ligases and deubiquitinases (DUBs. The EBV genome encodes three proteins reported to exert in vitro deubiquitinase activity. Using active site-directed probes, we show that one of these putative DUBs, the conserved herpesvirus large tegument protein BPLF1, acts as a functional DUB in EBV-producing B cells. The BPLF1 enzyme is expressed during the late phase of lytic EBV infection and is incorporated into viral particles. The N-terminal part of the large BPLF1 protein contains the catalytic site for DUB activity and suppresses TLR-mediated activation of NF-κB at, or downstream of, the TRAF6 signaling intermediate. A catalytically inactive mutant of this EBV protein did not reduce NF-κB activation, indicating that DUB activity is essential for attenuating TLR signal transduction. Our combined results show that EBV employs deubiquitination of signaling intermediates in the TLR cascade as a mechanism to counteract innate anti-viral immunity of infected hosts.

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

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    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.

  19. 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.

  20. Transmission of innate immune signaling by packaging of cGAMP in viral particles.

    Science.gov (United States)

    Gentili, Matteo; Kowal, Joanna; Tkach, Mercedes; Satoh, Takeshi; Lahaye, Xavier; Conrad, Cécile; Boyron, Marilyn; Lombard, Bérangère; Durand, Sylvère; Kroemer, Guido; Loew, Damarys; Dalod, Marc; Théry, Clotilde; Manel, Nicolas

    2015-09-11

    Infected cells detect viruses through a variety of receptors that initiate cell-intrinsic innate defense responses. Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) is a cytosolic sensor for many DNA viruses and HIV-1. In response to cytosolic viral DNA, cGAS synthesizes the second messenger 2'3'-cyclic GMP-AMP (cGAMP), which activates antiviral signaling pathways. We show that in cells producing virus, cGAS-synthesized cGAMP can be packaged in viral particles and extracellular vesicles. Viral particles efficiently delivered cGAMP to target cells. cGAMP transfer by viral particles to dendritic cells activated innate immunity and antiviral defenses. Finally, we show that cell-free murine cytomegalovirus and Modified Vaccinia Ankara virus contained cGAMP. Thus, transfer of cGAMP by viruses may represent a defense mechanism to propagate immune responses to uninfected target cells. Copyright © 2015, American Association for the Advancement of Science.

  1. 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.

  2. The Hippo Pathway: Immunity and Cancer.

    Science.gov (United States)

    Taha, Zaid; J Janse van Rensburg, Helena; Yang, Xiaolong

    2018-03-28

    Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work.

  3. Approaches Mediating Oxytocin Regulation of the Immune System.

    Science.gov (United States)

    Li, Tong; Wang, Ping; Wang, Stephani C; Wang, Yu-Feng

    2016-01-01

    The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo-neurohypophysial system (HNS) emerged as an important component of neuroendocrine-immune network, wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus, their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic, and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic-pituitary-immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly its relationship with other hypothalamic-pituitary-immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of the immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine-immune network.

  4. Recent Advances in Neural Recording Microsystems

    Directory of Open Access Journals (Sweden)

    Benoit Gosselin

    2011-04-01

    Full Text Available The accelerating pace of research in neuroscience has created a considerable demand for neural interfacing microsystems capable of monitoring the activity of large groups of neurons. These emerging tools have revealed a tremendous potential for the advancement of knowledge in brain research and for the development of useful clinical applications. They can extract the relevant control signals directly from the brain enabling individuals with severe disabilities to communicate their intentions to other devices, like computers or various prostheses. Such microsystems are self-contained devices composed of a neural probe attached with an integrated circuit for extracting neural signals from multiple channels, and transferring the data outside the body. The greatest challenge facing development of such emerging devices into viable clinical systems involves addressing their small form factor and low-power consumption constraints, while providing superior resolution. In this paper, we survey the recent progress in the design and the implementation of multi-channel neural recording Microsystems, with particular emphasis on the design of recording and telemetry electronics. An overview of the numerous neural signal modalities is given and the existing microsystem topologies are covered. We present energy-efficient sensory circuits to retrieve weak signals from neural probes and we compare them. We cover data management and smart power scheduling approaches, and we review advances in low-power telemetry. Finally, we conclude by summarizing the remaining challenges and by highlighting the emerging trends in the field.

  5. Frequency-difference-dependent stochastic resonance in neural systems

    Science.gov (United States)

    Guo, Daqing; Perc, Matjaž; Zhang, Yangsong; Xu, Peng; Yao, Dezhong

    2017-08-01

    Biological neurons receive multiple noisy oscillatory signals, and their dynamical response to the superposition of these signals is of fundamental importance for information processing in the brain. Here we study the response of neural systems to the weak envelope modulation signal, which is superimposed by two periodic signals with different frequencies. We show that stochastic resonance occurs at the beat frequency in neural systems at the single-neuron as well as the population level. The performance of this frequency-difference-dependent stochastic resonance is influenced by both the beat frequency and the two forcing frequencies. Compared to a single neuron, a population of neurons is more efficient in detecting the information carried by the weak envelope modulation signal at the beat frequency. Furthermore, an appropriate fine-tuning of the excitation-inhibition balance can further optimize the response of a neural ensemble to the superimposed signal. Our results thus introduce and provide insights into the generation and modulation mechanism of the frequency-difference-dependent stochastic resonance in neural systems.

  6. 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.

  7. Bioelectric signal classification using a recurrent probabilistic neural network with time-series discriminant component analysis.

    Science.gov (United States)

    Hayashi, Hideaki; Shima, Keisuke; Shibanoki, Taro; Kurita, Yuichi; Tsuji, Toshio

    2013-01-01

    This paper outlines a probabilistic neural network developed on the basis of time-series discriminant component analysis (TSDCA) that can be used to classify high-dimensional time-series patterns. TSDCA involves the compression of high-dimensional time series into a lower-dimensional space using a set of orthogonal transformations and the calculation of posterior probabilities based on a continuous-density hidden Markov model that incorporates a Gaussian mixture model expressed in the reduced-dimensional space. The analysis can be incorporated into a neural network so that parameters can be obtained appropriately as network coefficients according to backpropagation-through-time-based training algorithm. The network is considered to enable high-accuracy classification of high-dimensional time-series patterns and to reduce the computation time taken for network training. In the experiments conducted during the study, the validity of the proposed network was demonstrated for EEG signals.

  8. 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

  9. Electroacupuncture in the repair of spinal cord injury: inhibiting the Notch signaling pathway and promoting neural stem cell proliferation

    Directory of Open Access Journals (Sweden)

    Xin Geng

    2015-01-01

    Full Text Available Electroacupuncture for the treatment of spinal cord injury has a good clinical curative effect, but the underlying mechanism is unclear. In our experiments, the spinal cord of adult Sprague-Dawley rats was clamped for 60 seconds. Dazhui (GV14 and Mingmen (GV4 acupoints of rats were subjected to electroacupuncture. Enzyme-linked immunosorbent assay revealed that the expression of serum inflammatory factors was apparently downregulated in rat models of spinal cord injury after electroacupuncture. Hematoxylin-eosin staining and immunohistochemistry results demonstrated that electroacupuncture contributed to the proliferation of neural stem cells in rat injured spinal cord, and suppressed their differentiation into astrocytes. Real-time quantitative PCR and western blot assays showed that electroacupuncture inhibited activation of the Notch signaling pathway induced by spinal cord injury. These findings indicate that electroacupuncture repaired the injured spinal cord by suppressing the Notch signaling pathway and promoting the proliferation of endogenous neural stem cells.

  10. A fast, robust algorithm for power line interference cancellation in neural recording

    Science.gov (United States)

    Keshtkaran, Mohammad Reza; Yang, Zhi

    2014-04-01

    Objective. Power line interference may severely corrupt neural recordings at 50/60 Hz and harmonic frequencies. The interference is usually non-stationary and can vary in frequency, amplitude and phase. To retrieve the gamma-band oscillations at the contaminated frequencies, it is desired to remove the interference without compromising the actual neural signals at the interference frequency bands. In this paper, we present a robust and computationally efficient algorithm for removing power line interference from neural recordings. Approach. The algorithm includes four steps. First, an adaptive notch filter is used to estimate the fundamental frequency of the interference. Subsequently, based on the estimated frequency, harmonics are generated by using discrete-time oscillators, and then the amplitude and phase of each harmonic are estimated by using a modified recursive least squares algorithm. Finally, the estimated interference is subtracted from the recorded data. Main results. The algorithm does not require any reference signal, and can track the frequency, phase and amplitude of each harmonic. When benchmarked with other popular approaches, our algorithm performs better in terms of noise immunity, convergence speed and output signal-to-noise ratio (SNR). While minimally affecting the signal bands of interest, the algorithm consistently yields fast convergence (30 dB) in different conditions of interference strengths (input SNR from -30 to 30 dB), power line frequencies (45-65 Hz) and phase and amplitude drifts. In addition, the algorithm features a straightforward parameter adjustment since the parameters are independent of the input SNR, input signal power and the sampling rate. A hardware prototype was fabricated in a 65 nm CMOS process and tested. Software implementation of the algorithm has been made available for open access at https://github.com/mrezak/removePLI. Significance. The proposed algorithm features a highly robust operation, fast adaptation to

  11. 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

  12. Mechanisms and pathways of innate immune activation and regulation in health and cancer.

    Science.gov (United States)

    Cui, Jun; Chen, Yongjun; Wang, Helen Y; Wang, Rong-Fu

    2014-01-01

    Research on innate immune signaling and regulation has recently focused on pathogen recognition receptors (PRRs) and their signaling pathways. Members of PRRs sense diverse microbial invasions or danger signals, and initiate innate immune signaling pathways, leading to proinflammatory cytokines production, which, in turn, instructs adaptive immune response development. Despite the diverse functions employed by innate immune signaling to respond to a variety of different pathogens, the innate immune response must be tightly regulated. Otherwise, aberrant, uncontrolled immune responses will lead to harmful, or even fatal, consequences. Therefore, it is essential to better discern innate immune signaling and many regulators, controlling various signaling pathways, have been identified. In this review, we focus on the recent advances in our understanding of the activation and regulation of innate immune signaling in the host response to pathogens and cancer.

  13. 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.

  14. An artificial neural network model of energy expenditure using nonintegrated acceleration signals.

    Science.gov (United States)

    Rothney, Megan P; Neumann, Megan; Béziat, Ashley; Chen, Kong Y

    2007-10-01

    Accelerometers are a promising tool for characterizing physical activity patterns in free living. The major limitation in their widespread use to date has been a lack of precision in estimating energy expenditure (EE), which may be attributed to the oversimplified time-integrated acceleration signals and subsequent use of linear regression models for EE estimation. In this study, we collected biaxial raw (32 Hz) acceleration signals at the hip to develop a relationship between acceleration and minute-to-minute EE in 102 healthy adults using EE data collected for nearly 24 h in a room calorimeter as the reference standard. From each 1 min of acceleration data, we extracted 10 signal characteristics (features) that we felt had the potential to characterize EE intensity. Using these data, we developed a feed-forward/back-propagation artificial neural network (ANN) model with one hidden layer (12 x 20 x 1 nodes). Results of the ANN were compared with estimations using the ActiGraph monitor, a uniaxial accelerometer, and the IDEEA monitor, an array of five accelerometers. After training and validation (leave-one-subject out) were completed, the ANN showed significantly reduced mean absolute errors (0.29 +/- 0.10 kcal/min), mean squared errors (0.23 +/- 0.14 kcal(2)/min(2)), and difference in total EE (21 +/- 115 kcal/day), compared with both the IDEEA (P types under free-living conditions.

  15. SIGNALING MECHANISMS IN SEPSIS-INDUCED IMMUNE DYSFUNCTION

    OpenAIRE

    Hasan, Zirak

    2013-01-01

    Sepsis and subsequent organ failure remain the major cause of mortality in intensive care units in spite of significant research efforts. The lung is the most vulnerable organ affected by early hyper-inflammatory immune response in septic patients. On the other hand, the septic insult induces immune dysfunction in later phases of sepsis which in turn increases susceptibility to infections. The aim of this thesis was to investigate early and late inflammatory mechanisms in abdominal sepsis ind...

  16. The vagal innervation of the gut and immune homeostasis

    NARCIS (Netherlands)

    Matteoli, Gianluca; Boeckxstaens, Guy E.

    2013-01-01

    The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. Recently, in animal models of sepsis, the vagus nerve (VN) has been proposed to play a crucial role in the regulation of the immune response, also referred to as the

  17. Innate immune responses: Crosstalk of signaling and regulation of gene transcription

    International Nuclear Information System (INIS)

    Zhong Bo; Tien Po; Shu Hongbing

    2006-01-01

    Innate immune responses to pathogens such as bacteria and viruses are triggered by recognition of specific structures of invading pathogens called pathogen-associated molecular patterns (PAMPs) by cellular pattern recognition receptors (PRRs) that are located at plasma membrane or inside cells. Stimulation of different PAMPs activates Toll-like receptor (TLR)-dependent and -independent signaling pathways that lead to activation of transcription factors nuclear factor-κB (NF-κB), interferon regulatory factor 3/7 (IRF3/7) and/or activator protein-1 (AP-1), which collaborate to induce transcription of a large number of downstream genes. This review focuses on the rapid progress that has recently improved our understanding of the crosstalk among the pathways and the precise regulation of transcription of the downstream genes

  18. MAVS dimer is a crucial signaling component of innate immunity and the target of hepatitis C virus NS3/4A protease.

    Science.gov (United States)

    Baril, Martin; Racine, Marie-Eve; Penin, François; Lamarre, Daniel

    2009-02-01

    The mitochondrial antiviral signaling (MAVS) protein plays a central role in innate antiviral immunity. Upon recognition of a virus, intracellular receptors of the RIG-I-like helicase family interact with MAVS to trigger a signaling cascade. In this study, we investigate the requirement of the MAVS structure for enabling its signaling by structure-function analyses and resonance energy transfer approaches in live cells. We now report the essential role of the MAVS oligomer in signal transduction and map the transmembrane domain as the main determinant of dimerization. A combination of mutagenesis and computational methods identified a cluster of residues making favorable van der Waals interactions at the MAVS dimer interface. We also correlated the activation of IRF3 and NF-kappaB with MAVS oligomerization rather than its mitochondrial localization. Finally, we demonstrated that MAVS oligomerization is disrupted upon expression of HCV NS3/4A protease, suggesting a mechanism for the loss of antiviral signaling. Altogether, our data suggest that the MAVS oligomer is essential in the formation of a multiprotein membrane-associated signaling complex and enables downstream activation of IRF3 and NF-kappaB in antiviral innate immunity.

  19. 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.

  20. 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.

  1. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease.

    Science.gov (United States)

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD.

  2. Modulation of IL-33/ST2-TIR and TLR signalling pathway by fingolimod and analogues in immune cells.

    Science.gov (United States)

    Rüger, K; Ottenlinger, F; Schröder, M; Zivković, A; Stark, H; Pfeilschifter, J M; Radeke, H H

    2014-12-01

    For the immune modulatory drug fingolimod (FTY720), lymphocyte sequestration has been extensively studied and accepted as mode of action. Further, direct effects on immune cell signalling are incompletely understood. Herein, we used the parent drug and newly synthesized analogues to investigate their effects on dendritic cell (DC) calcium signalling and on Th1, Th2 and Th17 responses. DC calcium signalling was determined with a single cell-based confocal assay and IL-33/ST2-TIR Th2-like response with ST2-transduced EL4-6.1 thymoma cells. The Th1/Th17 responses were examined with a LPS/TLR-enhanced antigen presentation assay with OVA-TCRtg CD4 and CD8 spleen cells. Our results revealed a comparable influence of fingolimod and S1P on intracellular calcium level in DC, while an oxy-derivative of fingolimod exhibited an EC50 of 3.3 nm, being 14 times more potent than FTY720-P. The IL-33/ST2-TIR Th2-like response in ST2-EL4 cells was inhibited by fingolimod and analogues at varying degrees. Using the OVA-TCRtg LPS/TLR-enhanced spleen cell assay, we found that fingolimod inhibited both IL-17 and IFN-γ production. In contrast, fingolimod phosphate failed to decrease Th1 cytokines. Interestingly, the effects of the parent compound fingolimod were modulated by the PP2A inhibitor okadaic acid, thus suggesting PP2A as relevant intracellular target. These studies describe detailed immune-modulating properties of fingolimod, including interference with a prototypical Th2 response via IL-33/ST2-TIR. Moreover, differential effects of fingolimod versus its phosphorylated derivative on TLR-activated and antigen-dependent Th1 activation suggest PP2A as an additional target of fingolimod immune therapy. Together with the analogues tested, these data may guide the development of more specific fingolimod derivatives. © 2014 John Wiley & Sons Ltd.

  3. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees.

    Science.gov (United States)

    Di Prisco, Gennaro; Cavaliere, Valeria; Annoscia, Desiderato; Varricchio, Paola; Caprio, Emilio; Nazzi, Francesco; Gargiulo, Giuseppe; Pennacchio, Francesco

    2013-11-12

    Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture.

  4. The role of immune mechanisms in Tourette syndrome.

    Science.gov (United States)

    Martino, Davide; Zis, Panagiotis; Buttiglione, Maura

    2015-08-18

    Tourette syndrome (TS) is a childhood-onset tic disorder associated with abnormal development of brain networks involved in the sensory and motor processing. An involvement of immune mechanisms in its pathophysiology has been proposed. Animal models based on active immunization with bacterial or viral mimics, direct injection of cytokines or patients' serum anti-neuronal antibodies, and transgenic approaches replicated stereotyped behaviors observed in human TS. A crucial role of microglia in the neural-immune crosstalk within TS and related disorders has been proposed by animal models and confirmed by recent post mortem studies. With analogy to autism, genetic and early life environmental factors could foster the involvement of immune mechanisms to the abnormal developmental trajectories postulated in TS, as well as lead to systemic immune dysregulation in this condition. Clinical studies demonstrate an association between TS and immune responses to pathogens like group A Streptococcus (GAS), although their role as risk-modifiers is still undefined. Overactivity of immune responses at a systemic level is suggested by clinical studies exploring cytokine and immunoglobulin levels, immune cell subpopulations, and gene expression profiling of peripheral lymphocytes. The involvement of autoantibodies, on the other hand, remains uncertain and warrants more work using live cell-based approaches. Overall, a body of evidence supports the hypothesis that disease mechanisms in TS, like other neurodevelopmental illnesses (e.g. autism), may involve dysfunctional neural-immune cross-talk, ultimately leading to altered maturation of brain pathways controlling different behavioral domains and, possibly, differences in organising immune and stress responses. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses.

    Science.gov (United States)

    Baril, Martin; Es-Saad, Salwa; Chatel-Chaix, Laurent; Fink, Karin; Pham, Tram; Raymond, Valérie-Ann; Audette, Karine; Guenier, Anne-Sophie; Duchaine, Jean; Servant, Marc; Bilodeau, Marc; Cohen, Eric; Grandvaux, Nathalie; Lamarre, Daniel

    2013-01-01

    To identify new regulators of antiviral innate immunity, we completed the first genome-wide gene silencing screen assessing the transcriptional response at the interferon-β (IFNB1) promoter following Sendai virus (SeV) infection. We now report a novel link between WNT signaling pathway and the modulation of retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)-dependent innate immune responses. Here we show that secretion of WNT2B and WNT9B and stabilization of β-catenin (CTNNB1) upon virus infection negatively regulate expression of representative inducible genes IFNB1, IFIT1 and TNF in a CTNNB1-dependent effector mechanism. The antiviral response is drastically reduced by glycogen synthase kinase 3 (GSK3) inhibitors but restored in CTNNB1 knockdown cells. The findings confirm a novel regulation of antiviral innate immunity by a canonical-like WNT/CTNNB1 signaling pathway. The study identifies novel avenues for broad-spectrum antiviral targets and preventing immune-mediated diseases upon viral infection.

  6. Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses.

    Directory of Open Access Journals (Sweden)

    Martin Baril

    Full Text Available To identify new regulators of antiviral innate immunity, we completed the first genome-wide gene silencing screen assessing the transcriptional response at the interferon-β (IFNB1 promoter following Sendai virus (SeV infection. We now report a novel link between WNT signaling pathway and the modulation of retinoic acid-inducible gene I (RIG-I-like receptor (RLR-dependent innate immune responses. Here we show that secretion of WNT2B and WNT9B and stabilization of β-catenin (CTNNB1 upon virus infection negatively regulate expression of representative inducible genes IFNB1, IFIT1 and TNF in a CTNNB1-dependent effector mechanism. The antiviral response is drastically reduced by glycogen synthase kinase 3 (GSK3 inhibitors but restored in CTNNB1 knockdown cells. The findings confirm a novel regulation of antiviral innate immunity by a canonical-like WNT/CTNNB1 signaling pathway. The study identifies novel avenues for broad-spectrum antiviral targets and preventing immune-mediated diseases upon viral infection.

  7. Serotonin, neural markers and memory

    Directory of Open Access Journals (Sweden)

    Alfredo eMeneses

    2015-07-01

    Full Text Available Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals’ species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 receptors as well as SERT (serotonin transporter seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence

  8. 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.

  9. An Implantable Mixed Analog/Digital Neural Stimulator Circuit

    DEFF Research Database (Denmark)

    Gudnason, Gunnar; Bruun, Erik; Haugland, Morten

    1999-01-01

    This paper describes a chip for a multichannel neural stimulator for functional electrical stimulation. The chip performs all the signal processing required in an implanted neural stimulator. The power and signal transmission to the stimulator is carried out via an inductive link. From the signals...... electrical stimulation is to restore various bodily functions (e.g. motor functions) in patients who have lost them due to injury or disease....

  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. A multi-channel low-power system-on-chip for single-unit recording and narrowband wireless transmission of neural signal.

    Science.gov (United States)

    Bonfanti, A; Ceravolo, M; Zambra, G; Gusmeroli, R; Spinelli, A S; Lacaita, A L; Angotzi, G N; Baranauskas, G; Fadiga, L

    2010-01-01

    This paper reports a multi-channel neural recording system-on-chip (SoC) with digital data compression and wireless telemetry. The circuit consists of a 16 amplifiers, an analog time division multiplexer, an 8-bit SAR AD converter, a digital signal processor (DSP) and a wireless narrowband 400-MHz binary FSK transmitter. Even though only 16 amplifiers are present in our current die version, the whole system is designed to work with 64 channels demonstrating the feasibility of a digital processing and narrowband wireless transmission of 64 neural recording channels. A digital data compression, based on the detection of action potentials and storage of correspondent waveforms, allows the use of a 1.25-Mbit/s binary FSK wireless transmission. This moderate bit-rate and a low frequency deviation, Manchester-coded modulation are crucial for exploiting a narrowband wireless link and an efficient embeddable antenna. The chip is realized in a 0.35- εm CMOS process with a power consumption of 105 εW per channel (269 εW per channel with an extended transmission range of 4 m) and an area of 3.1 × 2.7 mm(2). The transmitted signal is captured by a digital TV tuner and demodulated by a wideband phase-locked loop (PLL), and then sent to a PC via an FPGA module. The system has been tested for electrical specifications and its functionality verified in in-vivo neural recording experiments.

  12. A role for chemokine signaling in neural crest cell migration and craniofacial development

    Science.gov (United States)

    Killian, Eugenia C. Olesnicky; Birkholz, Denise A.; Artinger, Kristin Bruk

    2009-01-01

    Neural crest cells (NCCs) are a unique population of multipotent cells that migrate along defined pathways throughout the embryo and give rise to many diverse cell types including pigment cells, craniofacial cartilage and the peripheral nervous system (PNS). Aberrant migration of NCCs results in a wide variety of congenital birth defects including craniofacial abnormalities. The chemokine Sdf1 and its receptors, Cxcr4 and Cxcr7, have been identified as key components in the regulation of cell migration in a variety of tissues. Here we describe a novel role for the zebrafish chemokine receptor Cxcr4a in the development and migration of cranial NCCs (CNCCs). We find that loss of Cxcr4a, but not Cxcr7b results in aberrant CNCC migration, defects in the neurocranium, as well as cranial ganglia dismorphogenesis. Moreover, overexpression of either Sdf1b or Cxcr4a causes aberrant CNCC migration and results in ectopic craniofacial cartilages. We propose a model in which Sdf1b signaling from the pharyngeal arch endoderm and optic stalk to Cxcr4a expressing CNCCs is important for both the proper condensation of the CNCCs into pharyngeal arches and the subsequent patterning and morphogenesis of the neural crest derived tissues. PMID:19576198

  13. Gaseous 3-pentanol primes plant immunity against a bacterial speck pathogen, Pseudomonas syringae pv. tomato via salicylic acid and jasmonic acid-dependent signaling pathways in Arabidopsis.

    Science.gov (United States)

    Song, Geun C; Choi, Hye K; Ryu, Choong-Min

    2015-01-01

    3-Pentanol is an active organic compound produced by plants and is a component of emitted insect sex pheromones. A previous study reported that drench application of 3-pentanol elicited plant immunity against microbial pathogens and an insect pest in crop plants. Here, we evaluated whether 3-pentanol and the derivatives 1-pentanol and 2-pentanol induced plant systemic resistance using the in vitro I-plate system. Exposure of Arabidopsis seedlings to 10 μM and 100 nM 3-pentanol evaporate elicited an immune response to Pseudomonas syringae pv. tomato DC3000. We performed quantitative real-time PCR to investigate the 3-pentanol-mediated Arabidopsis immune responses by determining Pathogenesis-Related (PR) gene expression levels associated with defense signaling through salicylic acid (SA), jasmonic acid (JA), and ethylene signaling pathways. The results show that exposure to 3-pentanol and subsequent pathogen challenge upregulated PDF1.2 and PR1 expression. Selected Arabidopsis mutants confirmed that the 3-pentanol-mediated immune response involved SA and JA signaling pathways and the NPR1 gene. Taken together, this study indicates that gaseous 3-pentanol triggers induced resistance in Arabidopsis by priming SA and JA signaling pathways. To our knowledge, this is the first report that a volatile compound of an insect sex pheromone triggers plant systemic resistance against a bacterial pathogen.

  14. Gaseous 3-pentanol primes plant immunity against a bacterial speck pathogen, Pseudomonas syringae pv. tomato via salicylic acid and jasmonic acid-dependent signaling pathways in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Geun Cheol eSong

    2015-10-01

    Full Text Available 3-Pentanol is an active organic compound produced by plants and is a component of emitted insect sex pheromones. A previous study reported that drench application of 3-pentanol elicited plant immunity against microbial pathogens and an insect pest in crop plants. Here, we evaluated whether 3-pentanol and the derivatives 1-pentanol and 2-pentanol induced plant systemic resistance using the in vitro I-plate system. Exposure of Arabidopsis seedlings to 10 M and 100 nM 3-pentanol evaporate elicited an immune response to Pseudomonas syringae pv. tomato DC3000. We performed quantitative real-time PCR to investigate the 3-pentanol-mediated Arabidopsis immune responses by determining Pathogenesis-Related (PR gene expression levels associated with defense signaling through SA, JA, and ethylene signaling pathways. The results show that exposure to 3-pentanol and subsequent pathogen challenge upregulated PDF1.2 and PR1 expression. Selected Arabidopsis mutants confirmed that the 3-pentanol-mediated immune response involved salicylic acid (SA and jasmonic acid (JA signaling pathways and the NPR1 gene. Taken together, this study indicates that gaseous 3-pentanol triggers induced resistance in Arabidopsis by priming SA and JA signaling pathways. To our knowledge, this is the first report that a volatile compound of an insect sex pheromone triggers plant systemic resistance against a bacterial pathogen.

  15. NeuroMEMS: Neural Probe Microtechnologies

    Directory of Open Access Journals (Sweden)

    Sam Musallam

    2008-10-01

    Full Text Available Neural probe technologies have already had a significant positive effect on our understanding of the brain by revealing the functioning of networks of biological neurons. Probes are implanted in different areas of the brain to record and/or stimulate specific sites in the brain. Neural probes are currently used in many clinical settings for diagnosis of brain diseases such as seizers, epilepsy, migraine, Alzheimer’s, and dementia. We find these devices assisting paralyzed patients by allowing them to operate computers or robots using their neural activity. In recent years, probe technologies were assisted by rapid advancements in microfabrication and microelectronic technologies and thus are enabling highly functional and robust neural probes which are opening new and exciting avenues in neural sciences and brain machine interfaces. With a wide variety of probes that have been designed, fabricated, and tested to date, this review aims to provide an overview of the advances and recent progress in the microfabrication techniques of neural probes. In addition, we aim to highlight the challenges faced in developing and implementing ultralong multi-site recording probes that are needed to monitor neural activity from deeper regions in the brain. Finally, we review techniques that can improve the biocompatibility of the neural probes to minimize the immune response and encourage neural growth around the electrodes for long term implantation studies.

  16. 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

  17. Artificial immune system algorithm in VLSI circuit configuration

    Science.gov (United States)

    Mansor, Mohd. Asyraf; Sathasivam, Saratha; Kasihmuddin, Mohd Shareduwan Mohd

    2017-08-01

    In artificial intelligence, the artificial immune system is a robust bio-inspired heuristic method, extensively used in solving many constraint optimization problems, anomaly detection, and pattern recognition. This paper discusses the implementation and performance of artificial immune system (AIS) algorithm integrated with Hopfield neural networks for VLSI circuit configuration based on 3-Satisfiability problems. Specifically, we emphasized on the clonal selection technique in our binary artificial immune system algorithm. We restrict our logic construction to 3-Satisfiability (3-SAT) clauses in order to outfit with the transistor configuration in VLSI circuit. The core impetus of this research is to find an ideal hybrid model to assist in the VLSI circuit configuration. In this paper, we compared the artificial immune system (AIS) algorithm (HNN-3SATAIS) with the brute force algorithm incorporated with Hopfield neural network (HNN-3SATBF). Microsoft Visual C++ 2013 was used as a platform for training, simulating and validating the performances of the proposed network. The results depict that the HNN-3SATAIS outperformed HNN-3SATBF in terms of circuit accuracy and CPU time. Thus, HNN-3SATAIS can be used to detect an early error in the VLSI circuit design.

  18. Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.

    Science.gov (United States)

    Trovato, Maria; D'Armiento, Maria; Lavra, Luca; Ulivieri, Alessandra; Dominici, Roberto; Vitarelli, Enrica; Grosso, Maddalena; Vecchione, Raffaella; Barresi, Gaetano; Sciacchitano, Salvatore

    2007-02-01

    Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

  19. Ectopic cross-talk between thyroid and retinoic acid signaling: A possible etiology for spinal neural tube defects.

    Science.gov (United States)

    Li, Huili; Bai, Baoling; Zhang, Qin; Bao, Yihua; Guo, Jin; Chen, Shuyuan; Miao, Chunyue; Liu, Xiaozhen; Zhang, Ting

    2015-12-01

    Previous studies have highlighted the connections between neural tube defects (NTDs) and both thyroid hormones (TH) and vitamin A. However, whether the two hormonal signaling pathways interact in NTDs has remained unclear. We measured the expression levels of TH signaling genes in human fetuses with spinal NTDs associated with maternal hyperthyroidism as well as levels of retinoic acid (RA) signaling genes in mouse fetuses exposed to an overdose of RA using NanoString or real-time PCR on spinal cord tissues. Interactions between the two signaling pathways were detected by ChIP assays. The data revealed attenuated DIO2/DIO3 switching in fetuses with NTDs born to hyperthyroid mothers. The promoters of the RA signaling genes CRABP1 and RARB were ectopically occupied by increased RXRG and RXRB but displayed decreased levels of inhibitory histone modifications, suggesting that elevated TH signaling abnormally stimulates RA signaling genes. Conversely, in the mouse model, the observed decrease in Dio3 expression could be explained by increased levels of inhibitory histone modifications in the Dio3 promoter region, suggesting that overactive RA signaling may ectopically derepress TH signaling. This study thus raises in vivo a possible abnormal cross-promotion between two different hormonal signals through their common RXRs and the subsequent recruitment of histone modifications, prompting further investigation into their involvement in the etiology of spinal NTDs. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. High speed digital interfacing for a neural data acquisition system

    Directory of Open Access Journals (Sweden)

    Bahr Andreas

    2016-09-01

    Full Text Available Diseases like schizophrenia and genetic epilepsy are supposed to be caused by disorders in the early development of the brain. For the further investigation of these relationships a custom designed application specific integrated circuit (ASIC was developed that is optimized for the recording from neonatal mice [Bahr A, Abu-Saleh L, Schroeder D, Krautschneider W. 16 Channel Neural Recording Integrated Circuit with SPI Interface and Error Correction Coding. Proc. 9th BIOSTEC 2016. Biodevices: Rome, Italy, 2016; 1: 263; Bahr A, Abu-Saleh L, Schroeder D, Krautschneider W. Development of a neural recording mixed signal integrated circuit for biomedical signal acquisition. Biomed Eng Biomed Tech Abstracts 2015; 60(S1: 298–299; Bahr A, Abu-Saleh L, Schroeder D, Krautschneider WH. 16 Channel Neural Recording Mixed Signal ASIC. CDNLive EMEA 2015 Conference Proceedings, 2015.]. To enable the live display of the neural signals a multichannel neural data acquisition system with live display functionality is presented. It implements a high speed data transmission from the ASIC to a computer with a live display functionality. The system has been successfully implemented and was used in a neural recording of a head-fixed mouse.

  1. Molecular signaling networks in regulation of immunity and disease

    DEFF Research Database (Denmark)

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

    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......), 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...... in the DC during activation is of profound importance for the state of immune response and thereby also affects the inflammatory and metabolic status in tissues. We have shown that specific fermentation products from gut bacteria have distinct immunoregulatory effects that effectively inhibit...

  2. Honest sexual signaling in turtles: experimental evidence of a trade-off between immune response and coloration in red-eared sliders Trachemys scripta elegans.

    Science.gov (United States)

    Ibáñez, Alejandro; Polo-Cavia, Nuria; López, Pilar; Martín, José

    2014-10-01

    Sexual signals can be evolutionarily stable if they are honest and condition dependent or costly to the signaler. One possible cost is the existence of a trade-off between maintaining the immune system and the elaboration of ornaments. This hypothesis has been experimentally tested in some groups of animals but not in others such as turtles. We experimentally challenged the immune system of female red-eared sliders Trachemys scripta elegans, with a bacterial antigen (lipopolysaccharide (LPS)) without pathogenic effects to explore whether the immune activation affected visual colorful ornaments of the head. The LPS injection altered the reflectance patterns of color ornaments. In comparison to the control animals, the yellow chin stripes of injected animals exhibited (1) reduced brightness, (2) lower long wavelength (>470 nm) reflectance, and (3) lower values for carotenoid chroma. The postorbital patches of injected individuals also showed reduced very long wavelength (>570 nm) reflectance but did not change in carotenoid chroma. Thus, experimental turtles showed darker and less "yellowish" chin stripes and less "reddish" postorbital patches at the end of the experiment, whereas control turtles did not change their coloration. This is the first experimental evidence supporting the existence of a trade-off between the immune system and the expression of visual ornaments in turtles. We suggest that this trade-off may allow turtles to honestly signal individual quality via characteristics of coloration, which may have an important role in intersexual selection processes.

  3. Honest sexual signaling in turtles: experimental evidence of a trade-off between immune response and coloration in red-eared sliders Trachemys scripta elegans

    Science.gov (United States)

    Ibáñez, Alejandro; Polo-Cavia, Nuria; López, Pilar; Martín, José

    2014-10-01

    Sexual signals can be evolutionarily stable if they are honest and condition dependent or costly to the signaler. One possible cost is the existence of a trade-off between maintaining the immune system and the elaboration of ornaments. This hypothesis has been experimentally tested in some groups of animals but not in others such as turtles. We experimentally challenged the immune system of female red-eared sliders Trachemys scripta elegans, with a bacterial antigen (lipopolysaccharide (LPS)) without pathogenic effects to explore whether the immune activation affected visual colorful ornaments of the head. The LPS injection altered the reflectance patterns of color ornaments. In comparison to the control animals, the yellow chin stripes of injected animals exhibited (1) reduced brightness, (2) lower long wavelength (>470 nm) reflectance, and (3) lower values for carotenoid chroma. The postorbital patches of injected individuals also showed reduced very long wavelength (>570 nm) reflectance but did not change in carotenoid chroma. Thus, experimental turtles showed darker and less "yellowish" chin stripes and less "reddish" postorbital patches at the end of the experiment, whereas control turtles did not change their coloration. This is the first experimental evidence supporting the existence of a trade-off between the immune system and the expression of visual ornaments in turtles. We suggest that this trade-off may allow turtles to honestly signal individual quality via characteristics of coloration, which may have an important role in intersexual selection processes.

  4. Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection

    Directory of Open Access Journals (Sweden)

    Vidlak Debbie

    2012-06-01

    Full Text Available Abstract Although IL-17A (commonly referred to as IL-17 has been implicated in the pathogenesis of central nervous system (CNS autoimmune disease, its role during CNS bacterial infections remains unclear. To evaluate the broader impact of IL-17 family members in the context of CNS infection, we utilized IL-17 receptor (IL-17R knockout (KO mice that lack the ability to respond to IL-17, IL-17F and IL-17E (IL-25. In this article, we demonstrate that IL-17R signaling regulates bacterial clearance as well as natural killer T (NKT cell and gamma-delta (γδ T cell infiltrates during Staphylococcus aureus-induced brain abscess formation. Specifically, when compared with wild-type (WT animals, IL-17R KO mice exhibited elevated bacterial burdens at days 7 and 14 following S. aureus infection. Additionally, IL-17R KO animals displayed elevated neutrophil chemokine production, revealing the ability to compensate for the lack of IL-17R activity. Despite these differences, innate immune cell recruitment into brain abscesses was similar in IL-17R KO and WT mice, whereas IL-17R signaling exerted a greater influence on adaptive immune cell recruitment. In particular, γδ T cell influx was increased in IL-17R KO mice at day 7 post-infection. In addition, NK1.1high infiltrates were absent in brain abscesses of IL-17R KO animals and, surprisingly, were rarely detected in the livers of uninfected IL-17R KO mice. Although IL-17 is a key regulator of neutrophils in other infection models, our data implicate an important role for IL-17R signaling in regulating adaptive immunity during CNS bacterial infection.

  5. Nuclear reactor pump diagnostics via noise analysis/artificial neural networks

    International Nuclear Information System (INIS)

    Keyvan, S.; Rabelo, L.C.

    1991-01-01

    A feasibility study is performed on the utilization of artificial neural networks as a tool for reactor diagnostics. Reactor pump signals utilized in a wear-out monitoring system developed for early detection of degradation of pump shaft are analyzed as a semi-benchmark test to study the feasibility of neural networks for pattern recognition. The Adaptive Resonance Theory (ART 2) paradigm of artificial neural networks is applied in this study. The signals are collected signals as well as generated signals simulating the wear progress. The wear-out monitoring system applies noise analysis techniques, and is capable of distinguishing between these signals and providing a measure of the progress of the degradation. This paper presents the results of the analysis of these data via the ART 2 paradigm

  6. Tumor necrosis factor α triggers proliferation of adult neural stem cells via IKK/NF-κB signaling

    Directory of Open Access Journals (Sweden)

    Kaltschmidt Christian

    2006-09-01

    Full Text Available Abstract Background Brain inflammation has been recognized as a complex phenomenon with numerous related aspects. In addition to the very well-described neurodegenerative effect of inflammation, several studies suggest that inflammatory signals exert a potentially positive influence on neural stem cell proliferation, migration and differentiation. Tumor necrosis factor alpha (TNF-α is one of the best-characterized mediators of inflammation. To date, conclusions about the action of TNF on neural stem or progenitor cells (NSCs, NPCs have been conflicting. TNF seems to activate NSC proliferation and to inhibit their differentiation into NPCs. The purpose of the present study was to analyze the molecular signal transduction mechanisms induced by TNF and resulting in NSC proliferation. Results Here we describe for the first time the TNF-mediated signal transduction cascade in neural stem cells (NSCs that results in increased proliferation. Moreover, we demonstrate IKK-α/β-dependent proliferation and markedly up-regulated cyclin D1 expression after TNF treatment. The significant increase in proliferation in TNF-treated cells was indicated by increased neurosphere volume, increased bromodeoxyuridin (BrdU incorporation and a higher total cell number. Furthermore, TNF strongly activated nuclear factor-kappa B (NF-κB as measured by reporter gene assays and by an activity-specific antibody. Proliferation of control and TNF-treated NSCs was strongly inhibited by expression of the NF-κB super-repressor IκB-AA1. Pharmacological blockade of IκB ubiquitin ligase activity led to comparable decreases in NF-κB activity and proliferation. In addition, IKK-β gene product knock-down via siRNA led to diminished NF-κB activity, attenuated cyclin D1 expression and finally decreased proliferation. In contrast, TGFβ-activated kinase 1 (TAK-1 is partially dispensable for TNF-mediated and endogenous proliferation. Understanding stem cell proliferation is crucial

  7. Classification Technique for Ultrasonic Weld Inspection Signals using a Neural Network based on 2-dimensional fourier Transform and Principle Component Analysis

    International Nuclear Information System (INIS)

    Kim, Jae Joon

    2004-01-01

    Neural network-based signal classification systems are increasingly used in the analysis of large volumes of data obtained in NDE applications. Ultrasonic inspection methods on the other hand are commonly used in the nondestructive evaluation of welds to detect flaws. An important characteristic of ultrasonic inspection is the ability to identify the type of discontinuity that gives rise to a peculiar signal. Standard techniques rely on differences in individual A-scans to classify the signals. This paper proposes an ultrasonic signal classification technique based on the information tying in the neighboring signals. The approach is based on a 2-dimensional Fourier transform and the principal component analysis to generate a reduced dimensional feature vector for classification. Results of applying the technique to data obtained from the inspection of actual steel welds are presented

  8. Network properties of robust immunity in plants.

    Directory of Open Access Journals (Sweden)

    Kenichi Tsuda

    2009-12-01

    Full Text Available Two modes of plant immunity against biotrophic pathogens, Effector Triggered Immunity (ETI and Pattern-Triggered Immunity (PTI, are triggered by recognition of pathogen effectors and Microbe-Associated Molecular Patterns (MAMPs, respectively. Although the jasmonic acid (JA/ethylene (ET and salicylic acid (SA signaling sectors are generally antagonistic and important for immunity against necrotrophic and biotrophic pathogens, respectively, their precise roles and interactions in ETI and PTI have not been clear. We constructed an Arabidopsis dde2/ein2/pad4/sid2-quadruple mutant. DDE2, EIN2, and SID2 are essential components of the JA, ET, and SA sectors, respectively. The pad4 mutation affects the SA sector and a poorly characterized sector. Although the ETI triggered by the bacterial effector AvrRpt2 (AvrRpt2-ETI and the PTI triggered by the bacterial MAMP flg22 (flg22-PTI were largely intact in plants with mutations in any one of these genes, they were mostly abolished in the quadruple mutant. For the purposes of this study, AvrRpt2-ETI and flg22-PTI were measured as relative growth of Pseudomonas syringae bacteria within leaves. Immunity to the necrotrophic fungal pathogen Alternaria brassicicola was also severely compromised in the quadruple mutant. Quantitative measurements of the immunity levels in all combinatorial mutants and wild type allowed us to estimate the effects of the wild-type genes and their interactions on the immunity by fitting a mixed general linear model. This signaling allocation analysis showed that, contrary to current ideas, each of the JA, ET, and SA signaling sectors can positively contribute to immunity against both biotrophic and necrotrophic pathogens. The analysis also revealed that while flg22-PTI and AvrRpt2-ETI use a highly overlapping signaling network, the way they use the common network is very different: synergistic relationships among the signaling sectors are evident in PTI, which may amplify the signal

  9. Immune Regulation of RAW264.7 Cells In Vitro by Flavonoids from Astragalus complanatus via Activating the NF-κB Signalling Pathway

    Directory of Open Access Journals (Sweden)

    Yu Li

    2018-01-01

    Full Text Available The current study aimed at investigating the effects of flavonoids from Astragalus complanatus (FAC on the proliferation, the contents, and gene expression levels of cytokines, secretion of surface stimulating factors, cell cycle, and the expression level of the NF-κB signalling pathway in RAW264.7 cells. Our results revealed that compared with control group, the contents of IL-6, IL-1β, TNF-α, and NO and the mRNA expression levels of IL-6, IL-1β, TNF-α, and iNOS in FAC-treated groups significantly increased (p<0.01. Moreover, FAC induced macrophage activation to release the above-mentioned mediators partly involved in NF-κB/MAPK signalling pathways. Therefore, FAC regulates immune function in RAW264.7 cells via activating the NF-κB signalling pathway. FAC could be applicable for agriculture, drug research, and food industry as a potent immune-modulatory agent.

  10. Dlx proteins position the neural plate border and determine adjacent cell fates.

    Science.gov (United States)

    Woda, Juliana M; Pastagia, Julie; Mercola, Mark; Artinger, Kristin Bruk

    2003-01-01

    The lateral border of the neural plate is a major source of signals that induce primary neurons, neural crest cells and cranial placodes as well as provide patterning cues to mesodermal structures such as somites and heart. Whereas secreted BMP, FGF and Wnt proteins influence the differentiation of neural and non-neural ectoderm, we show here that members of the Dlx family of transcription factors position the border between neural and non-neural ectoderm and are required for the specification of adjacent cell fates. Inhibition of endogenous Dlx activity in Xenopus embryos with an EnR-Dlx homeodomain fusion protein expands the neural plate into non-neural ectoderm tissue whereas ectopic activation of Dlx target genes inhibits neural plate differentiation. Importantly, the stereotypic pattern of border cell fates in the adjacent ectoderm is re-established only under conditions where the expanded neural plate abuts Dlx-positive non-neural ectoderm. Experiments in which presumptive neural plate was grafted to ventral ectoderm reiterate induction of neural crest and placodal lineages and also demonstrate that Dlx activity is required in non-neural ectoderm for the production of signals needed for induction of these cells. We propose that Dlx proteins regulate intercellular signaling across the interface between neural and non-neural ectoderm that is critical for inducing and patterning adjacent cell fates.

  11. Tcf3 represses Wnt-β-catenin signaling and maintains neural stem cell population during neocortical development.

    Directory of Open Access Journals (Sweden)

    Atsushi Kuwahara

    Full Text Available During mouse neocortical development, the Wnt-β-catenin signaling pathway plays essential roles in various phenomena including neuronal differentiation and proliferation of neural precursor cells (NPCs. Production of the appropriate number of neurons without depletion of the NPC population requires precise regulation of the balance between differentiation and maintenance of NPCs. However, the mechanism that suppresses Wnt signaling to prevent premature neuronal differentiation of NPCs is poorly understood. We now show that the HMG box transcription factor Tcf3 (also known as Tcf7l1 contributes to this mechanism. Tcf3 is highly expressed in undifferentiated NPCs in the mouse neocortex, and its expression is reduced in intermediate neuronal progenitors (INPs committed to the neuronal fate. We found Tcf3 to be a repressor of Wnt signaling in neocortical NPCs in a reporter gene assay. Tcf3 bound to the promoter of the proneural bHLH gene Neurogenin1 (Neurog1 and repressed its expression. Consistent with this, Tcf3 repressed neuronal differentiation and increased the self-renewal activity of NPCs. We also found that Wnt signal stimulation reduces the level of Tcf3, and increases those of Tcf1 (also known as Tcf7 and Lef1, positive mediators of Wnt signaling, in NPCs. Together, these results suggest that Tcf3 antagonizes Wnt signaling in NPCs, thereby maintaining their undifferentiated state in the neocortex and that Wnt signaling promotes the transition from Tcf3-mediated repression to Tcf1/Lef1-mediated enhancement of Wnt signaling, constituting a positive feedback loop that facilitates neuronal differentiation.

  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. A theory of how active behavior stabilises neural activity: Neural gain modulation by closed-loop environmental feedback.

    Directory of Open Access Journals (Sweden)

    Christopher L Buckley

    2018-01-01

    Full Text Available During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input. We support this theory with modeling and data analysis in two vertebrate systems. First, in a model of rodent whisking we show that negative feedback mediated by whisking vibrissa can suppress coherent neural fluctuations and neural responses to sensory input in the barrel cortex. We argue this suppression provides an appealing account of a brain state transition (a marked change in global brain activity coincident with the onset of whisking in rodents. Moreover, this mechanism suggests a novel signal detection mechanism that selectively accentuates active, rather than passive, whisker touch signals. This mechanism is consistent with a predictive coding strategy that is sensitive to the consequences of motor actions rather than the difference between the predicted and actual sensory input. We further support the theory by re-analysing previously published two-photon data recorded in zebrafish larvae performing closed-loop optomotor behaviour in a virtual swim simulator. We show, as predicted by this theory, that the degree to which each cell contributes in linking sensory and motor signals well explains how much its neural fluctuations are suppressed by closed-loop optomotor behaviour. More generally we argue that our results

  14. A theory of how active behavior stabilises neural activity: Neural gain modulation by closed-loop environmental feedback.

    Science.gov (United States)

    Buckley, Christopher L; Toyoizumi, Taro

    2018-01-01

    During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input. We support this theory with modeling and data analysis in two vertebrate systems. First, in a model of rodent whisking we show that negative feedback mediated by whisking vibrissa can suppress coherent neural fluctuations and neural responses to sensory input in the barrel cortex. We argue this suppression provides an appealing account of a brain state transition (a marked change in global brain activity) coincident with the onset of whisking in rodents. Moreover, this mechanism suggests a novel signal detection mechanism that selectively accentuates active, rather than passive, whisker touch signals. This mechanism is consistent with a predictive coding strategy that is sensitive to the consequences of motor actions rather than the difference between the predicted and actual sensory input. We further support the theory by re-analysing previously published two-photon data recorded in zebrafish larvae performing closed-loop optomotor behaviour in a virtual swim simulator. We show, as predicted by this theory, that the degree to which each cell contributes in linking sensory and motor signals well explains how much its neural fluctuations are suppressed by closed-loop optomotor behaviour. More generally we argue that our results demonstrate the dependence

  15. Noise Analysis studies with neural networks

    International Nuclear Information System (INIS)

    Seker, S.; Ciftcioglu, O.

    1996-01-01

    Noise analysis studies with neural network are aimed. Stochastic signals at the input of the network are used to obtain an algorithmic multivariate stochastic signal modeling. To this end, lattice modeling of a stochastic signal is performed to obtain backward residual noise sources which are uncorrelated among themselves. There are applied together with an additional input to the network to obtain an algorithmic model which is used for signal detection for early failure in plant monitoring. The additional input provides the information to the network to minimize the difference between the signal and the network's one-step-ahead prediction. A stochastic algorithm is used for training where the errors reflecting the measurement error during the training are also modelled so that fast and consistent convergence of network's weights is obtained. The lattice structure coupled to neural network investigated with measured signals from an actual power plant. (authors)

  16. Improved prediction of signal peptides: SignalP 3.0

    DEFF Research Database (Denmark)

    Bendtsen, Jannick Dyrløv; Nielsen, Henrik; von Heijne, G.

    2004-01-01

    We describe improvements of the currently most popular method for prediction of classically secreted proteins, SignalP. SignalP consists of two different predictors based on neural network and hidden Markov model algorithms, where both components have been updated. Motivated by the idea that the ...

  17. Neural Networks

    International Nuclear Information System (INIS)

    Smith, Patrick I.

    2003-01-01

    Physicists use large detectors to measure particles created in high-energy collisions at particle accelerators. These detectors typically produce signals indicating either where ionization occurs along the path of the particle, or where energy is deposited by the particle. The data produced by these signals is fed into pattern recognition programs to try to identify what particles were produced, and to measure the energy and direction of these particles. Ideally, there are many techniques used in this pattern recognition software. One technique, neural networks, is particularly suitable for identifying what type of particle caused by a set of energy deposits. Neural networks can derive meaning from complicated or imprecise data, extract patterns, and detect trends that are too complex to be noticed by either humans or other computer related processes. To assist in the advancement of this technology, Physicists use a tool kit to experiment with several neural network techniques. The goal of this research is interface a neural network tool kit into Java Analysis Studio (JAS3), an application that allows data to be analyzed from any experiment. As the final result, a physicist will have the ability to train, test, and implement a neural network with the desired output while using JAS3 to analyze the results or output. Before an implementation of a neural network can take place, a firm understanding of what a neural network is and how it works is beneficial. A neural network is an artificial representation of the human brain that tries to simulate the learning process [5]. It is also important to think of the word artificial in that definition as computer programs that use calculations during the learning process. In short, a neural network learns by representative examples. Perhaps the easiest way to describe the way neural networks learn is to explain how the human brain functions. The human brain contains billions of neural cells that are responsible for processing

  18. Retrieving infinite numbers of patterns in a spin-glass model of immune networks

    Science.gov (United States)

    Agliari, E.; Annibale, A.; Barra, A.; Coolen, A. C. C.; Tantari, D.

    2017-01-01

    The similarity between neural and (adaptive) immune networks has been known for decades, but so far we did not understand the mechanism that allows the immune system, unlike associative neural networks, to recall and execute a large number of memorized defense strategies in parallel. The explanation turns out to lie in the network topology. Neurons interact typically with a large number of other neurons, whereas interactions among lymphocytes in immune networks are very specific, and described by graphs with finite connectivity. In this paper we use replica techniques to solve a statistical mechanical immune network model with “coordinator branches” (T-cells) and “effector branches” (B-cells), and show how the finite connectivity enables the coordinators to manage an extensive number of effectors simultaneously, even above the percolation threshold (where clonal cross-talk is not negligible). A consequence of its underlying topological sparsity is that the adaptive immune system exhibits only weak ergodicity breaking, so that also spontaneous switch-like effects as bi-stabilities are present: the latter may play a significant role in the maintenance of immune homeostasis.

  19. Immune regulation by microbiome metabolites.

    Science.gov (United States)

    Kim, Chang H

    2018-03-22

    Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite-specific receptors such as P2X 7 , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets. Microbial metabolites and their receptors form an extensive array of signals to respond to changes in nutrition, health and immunological status. As a consequence, microbial metabolite signals contribute to nutrient harvest from diet, and regulate host metabolism and the immune system. Importantly, microbial metabolites bidirectionally function to promote both tolerance and immunity to effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects of microbial metabolites have been observed as well. Key immune-regulatory functions of the metabolites, generated from carbohydrates, proteins and bile acids, are reviewed in this article. © 2018 John Wiley & Sons Ltd.

  20. Eddy Current Flaw Characterization Using Neural Networks

    International Nuclear Information System (INIS)

    Song, S. J.; Park, H. J.; Shin, Y. K.

    1998-01-01

    Determination of location, shape and size of a flaw from its eddy current testing signal is one of the fundamental issues in eddy current nondestructive evaluation of steam generator tubes. Here, we propose an approach to this problem; an inversion of eddy current flaw signal using neural networks trained by finite element model-based synthetic signatures. Total 216 eddy current signals from four different types of axisymmetric flaws in tubes are generated by finite element models of which the accuracy is experimentally validated. From each simulated signature, total 24 eddy current features are extracted and among them 13 features are finally selected for flaw characterization. Based on these features, probabilistic neural networks discriminate flaws into four different types according to the location and the shape, and successively back propagation neural networks determine the size parameters of the discriminated flaw

  1. Polyclonal immune responses to antigens associated with cancer signaling pathways and new strategies to enhance cancer vaccines.

    Science.gov (United States)

    Clay, Timothy M; Osada, Takuya; Hartman, Zachary C; Hobeika, Amy; Devi, Gayathri; Morse, Michael A; Lyerly, H Kim

    2011-04-01

    Aberrant signaling pathways are a hallmark of cancer. A variety of strategies for inhibiting signaling pathways have been developed, but monoclonal antibodies against receptor tyrosine kinases have been among the most successful. A challenge for these therapies is therapeutic unresponsiveness and acquired resistance due to mutations in the receptors, upregulation of alternate growth and survival pathways, or inadequate function of the monoclonal antibodies. Vaccines are able to induce polyclonal responses that can have a multitude of affects against the target molecule. We began to explore therapeutic vaccine development to antigens associated with these signaling pathways. We provide an illustrative example in developing therapeutic cancer vaccines inducing polyclonal adaptive immune responses targeting the ErbB family member HER2. Further, we will discuss new strategies to augment the clinical efficacy of cancer vaccines by enhancing vaccine immunogenicity and reversing the immunosuppressive tumor microenvironment.

  2. Neural networks and applications tutorial

    Science.gov (United States)

    Guyon, I.

    1991-09-01

    The importance of neural networks has grown dramatically during this decade. While only a few years ago they were primarily of academic interest, now dozens of companies and many universities are investigating the potential use of these systems and products are beginning to appear. The idea of building a machine whose architecture is inspired by that of the brain has roots which go far back in history. Nowadays, technological advances of computers and the availability of custom integrated circuits, permit simulations of hundreds or even thousands of neurons. In conjunction, the growing interest in learning machines, non-linear dynamics and parallel computation spurred renewed attention in artificial neural networks. Many tentative applications have been proposed, including decision systems (associative memories, classifiers, data compressors and optimizers), or parametric models for signal processing purposes (system identification, automatic control, noise canceling, etc.). While they do not always outperform standard methods, neural network approaches are already used in some real world applications for pattern recognition and signal processing tasks. The tutorial is divided into six lectures, that where presented at the Third Graduate Summer Course on Computational Physics (September 3-7, 1990) on Parallel Architectures and Applications, organized by the European Physical Society: (1) Introduction: machine learning and biological computation. (2) Adaptive artificial neurons (perceptron, ADALINE, sigmoid units, etc.): learning rules and implementations. (3) Neural network systems: architectures, learning algorithms. (4) Applications: pattern recognition, signal processing, etc. (5) Elements of learning theory: how to build networks which generalize. (6) A case study: a neural network for on-line recognition of handwritten alphanumeric characters.

  3. Neural Global Pattern Similarity Underlies True and False Memories.

    Science.gov (United States)

    Ye, Zhifang; Zhu, Bi; Zhuang, Liping; Lu, Zhonglin; Chen, Chuansheng; Xue, Gui

    2016-06-22

    The neural processes giving rise to human memory strength signals remain poorly understood. Inspired by formal computational models that posit a central role of global matching in memory strength, we tested a novel hypothesis that the strengths of both true and false memories arise from the global similarity of an item's neural activation pattern during retrieval to that of all the studied items during encoding (i.e., the encoding-retrieval neural global pattern similarity [ER-nGPS]). We revealed multiple ER-nGPS signals that carried distinct information and contributed differentially to true and false memories: Whereas the ER-nGPS in the parietal regions reflected semantic similarity and was scaled with the recognition strengths of both true and false memories, ER-nGPS in the visual cortex contributed solely to true memory. Moreover, ER-nGPS differences between the parietal and visual cortices were correlated with frontal monitoring processes. By combining computational and neuroimaging approaches, our results advance a mechanistic understanding of memory strength in recognition. What neural processes give rise to memory strength signals, and lead to our conscious feelings of familiarity? Using fMRI, we found that the memory strength of a given item depends not only on how it was encoded during learning, but also on the similarity of its neural representation with other studied items. The global neural matching signal, mainly in the parietal lobule, could account for the memory strengths of both studied and unstudied items. Interestingly, a different global matching signal, originated from the visual cortex, could distinguish true from false memories. The findings reveal multiple neural mechanisms underlying the memory strengths of events registered in the brain. Copyright © 2016 the authors 0270-6474/16/366792-11$15.00/0.

  4. Molecular Mechanisms Underlying β-Adrenergic Receptor-Mediated Cross-Talk between Sympathetic Neurons and Immune Cells

    Directory of Open Access Journals (Sweden)

    Dianne Lorton

    2015-03-01

    Full Text Available Cross-talk between the sympathetic nervous system (SNS and immune system is vital for health and well-being. Infection, tissue injury and inflammation raise firing rates of sympathetic nerves, increasing their release of norepinephrine (NE in lymphoid organs and tissues. NE stimulation of β2-adrenergic receptors (ARs in immune cells activates the cAMP-protein kinase A (PKA intracellular signaling pathway, a pathway that interfaces with other signaling pathways that regulate proliferation, differentiation, maturation and effector functions in immune cells. Immune–SNS cross-talk is required to maintain homeostasis under normal conditions, to develop an immune response of appropriate magnitude after injury or immune challenge, and subsequently restore homeostasis. Typically, β2-AR-induced cAMP is immunosuppressive. However, many studies report actions of β2-AR stimulation in immune cells that are inconsistent with typical cAMP–PKA signal transduction. Research during the last decade in non-immune organs, has unveiled novel alternative signaling mechanisms induced by β2-AR activation, such as a signaling switch from cAMP–PKA to mitogen-activated protein kinase (MAPK pathways. If alternative signaling occurs in immune cells, it may explain inconsistent findings of sympathetic regulation of immune function. Here, we review β2-AR signaling, assess the available evidence for alternative signaling in immune cells, and provide insight into the circumstances necessary for “signal switching” in immune cells.

  5. Polarity-specific high-level information propagation in neural networks.

    Science.gov (United States)

    Lin, Yen-Nan; Chang, Po-Yen; Hsiao, Pao-Yueh; Lo, Chung-Chuan

    2014-01-01

    Analyzing the connectome of a nervous system provides valuable information about the functions of its subsystems. Although much has been learned about the architectures of neural networks in various organisms by applying analytical tools developed for general networks, two distinct and functionally important properties of neural networks are often overlooked. First, neural networks are endowed with polarity at the circuit level: Information enters a neural network at input neurons, propagates through interneurons, and leaves via output neurons. Second, many functions of nervous systems are implemented by signal propagation through high-level pathways involving multiple and often recurrent connections rather than by the shortest paths between nodes. In the present study, we analyzed two neural networks: the somatic nervous system of Caenorhabditis elegans (C. elegans) and the partial central complex network of Drosophila, in light of these properties. Specifically, we quantified high-level propagation in the vertical and horizontal directions: the former characterizes how signals propagate from specific input nodes to specific output nodes and the latter characterizes how a signal from a specific input node is shared by all output nodes. We found that the two neural networks are characterized by very efficient vertical and horizontal propagation. In comparison, classic small-world networks show a trade-off between vertical and horizontal propagation; increasing the rewiring probability improves the efficiency of horizontal propagation but worsens the efficiency of vertical propagation. Our result provides insights into how the complex functions of natural neural networks may arise from a design that allows them to efficiently transform and combine input signals.

  6. Proposal of a model of mammalian neural induction

    Science.gov (United States)

    Levine, Ariel J.; Brivanlou, Ali H.

    2009-01-01

    How does the vertebrate embryo make a nervous system? This complex question has been at the center of developmental biology for many years. The earliest step in this process – the induction of neural tissue – is intimately linked to patterning of the entire early embryo, and the molecular and embryological basis these processes are beginning to emerge. Here, we analyze classic and cutting-edge findings on neural induction in the mouse. We find that data from genetics, tissue explants, tissue grafting, and molecular marker expression support a coherent framework for mammalian neural induction. In this model, the gastrula organizer of the mouse embryo inhibits BMP signaling to allow neural tissue to form as a default fate – in the absence of instructive signals. The first neural tissue induced is anterior and subsequent neural tissue is posteriorized to form the midbrain, hindbrain, and spinal cord. The anterior visceral endoderm protects the pre-specified anterior neural fate from similar posteriorization, allowing formation of forebrain. This model is very similar to the default model of neural induction in the frog, thus bridging the evolutionary gap between amphibians and mammals. PMID:17585896

  7. Applying Statistical and Complex Network Methods to Explore the Key Signaling Molecules of Acupuncture Regulating Neuroendocrine-Immune Network

    Directory of Open Access Journals (Sweden)

    Kuo Zhang

    2018-01-01

    Full Text Available The mechanisms of acupuncture are still unclear. In order to reveal the regulatory effect of manual acupuncture (MA on the neuroendocrine-immune (NEI network and identify the key signaling molecules during MA modulating NEI network, we used a rat complete Freund’s adjuvant (CFA model to observe the analgesic and anti-inflammatory effect of MA, and, what is more, we used statistical and complex network methods to analyze the data about the expression of 55 common signaling molecules of NEI network in ST36 (Zusanli acupoint, and serum and hind foot pad tissue. The results indicate that MA had significant analgesic, anti-inflammatory effects on CFA rats; the key signaling molecules may play a key role during MA regulating NEI network, but further research is needed.

  8. GYF-21, an Epoxide 2-(2-Phenethyl-Chromone Derivative, Suppresses Innate and Adaptive Immunity via Inhibiting STAT1/3 and NF-κB Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Ran Guo

    2017-05-01

    Full Text Available Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system characterized by demyelinating plaques and axonal loss. Inhibition on over activation of innate and adaptive immunity provides a rationale strategy for treatment of multiple sclerosis. In the present study, we investigated the inhibitory effects of GYF-21, an epoxide 2-(2-phenethyl-chromone derivative isolated from Chinese agarwood, on innate and adaptive immunity for revealing its potential to treat multiple sclerosis. The results showed that GYF-21 markedly inhibited the activation of microglia, and dendritic cells as well as neutrophils, all of which play important roles in innate immunity. Furthermore, GYF-21 significantly suppressed adaptive immunity via inhibiting the differentiation of naive CD4+ T cells into T helper 1 (Th1 and T helper 17 (Th17 cells, and suppressing the activation, proliferation, and IFN-γ secretion of CD8+ T cells. The mechanism study showed that GYF-21 evidently inhibited the activation of STAT1/3 and NF-κB signaling pathways in microglia. In conclusion, we demonstrated that GYF-21 can significantly inhibit innate and adaptive immunity via suppressing STAT1/3 and NF-κB signaling pathways, and has potential to be developed into therapeutic drug for multiple sclerosis.

  9. 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.

  10. Linear ubiquitination in immunity.

    Science.gov (United States)

    Shimizu, Yutaka; Taraborrelli, Lucia; Walczak, Henning

    2015-07-01

    Linear ubiquitination is a post-translational protein modification recently discovered to be crucial for innate and adaptive immune signaling. The function of linear ubiquitin chains is regulated at multiple levels: generation, recognition, and removal. These chains are generated by the linear ubiquitin chain assembly complex (LUBAC), the only known ubiquitin E3 capable of forming the linear ubiquitin linkage de novo. LUBAC is not only relevant for activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) in various signaling pathways, but importantly, it also regulates cell death downstream of immune receptors capable of inducing this response. Recognition of the linear ubiquitin linkage is specifically mediated by certain ubiquitin receptors, which is crucial for translation into the intended signaling outputs. LUBAC deficiency results in attenuated gene activation and increased cell death, causing pathologic conditions in both, mice, and humans. Removal of ubiquitin chains is mediated by deubiquitinases (DUBs). Two of them, OTULIN and CYLD, are constitutively associated with LUBAC. Here, we review the current knowledge on linear ubiquitination in immune signaling pathways and the biochemical mechanisms as to how linear polyubiquitin exerts its functions distinctly from those of other ubiquitin linkage types. © 2015 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

  11. Distribution network fault section identification and fault location using artificial neural network

    DEFF Research Database (Denmark)

    Dashtdar, Masoud; Dashti, Rahman; Shaker, Hamid Reza

    2018-01-01

    In this paper, a method for fault location in power distribution network is presented. The proposed method uses artificial neural network. In order to train the neural network, a series of specific characteristic are extracted from the recorded fault signals in relay. These characteristics...... components of the sequences as well as three-phase signals could be obtained using statistics to extract the hidden features inside them and present them separately to train the neural network. Also, since the obtained inputs for the training of the neural network strongly depend on the fault angle, fault...... resistance, and fault location, the training data should be selected such that these differences are properly presented so that the neural network does not face any issues for identification. Therefore, selecting the signal processing function, data spectrum and subsequently, statistical parameters...

  12. Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells.

    Science.gov (United States)

    Gaya, Mauro; Barral, Patricia; Burbage, Marianne; Aggarwal, Shweta; Montaner, Beatriz; Warren Navia, Andrew; Aid, Malika; Tsui, Carlson; Maldonado, Paula; Nair, Usha; Ghneim, Khader; Fallon, Padraic G; Sekaly, Rafick-Pierre; Barouch, Dan H; Shalek, Alex K; Bruckbauer, Andreas; Strid, Jessica; Batista, Facundo D

    2018-01-25

    B cells constitute an essential line of defense from pathogenic infections through the generation of class-switched antibody-secreting cells (ASCs) in germinal centers. Although this process is known to be regulated by follicular helper T (TfH) cells, the mechanism by which B cells initially seed germinal center reactions remains elusive. We found that NKT cells, a population of innate-like T lymphocytes, are critical for the induction of B cell immunity upon viral infection. The positioning of NKT cells at the interfollicular areas of lymph nodes facilitates both their direct priming by resident macrophages and the localized delivery of innate signals to antigen-experienced B cells. Indeed, NKT cells secrete an early wave of IL-4 and constitute up to 70% of the total IL-4-producing cells during the initial stages of infection. Importantly, the requirement of this innate immunity arm appears to be evolutionarily conserved because early NKT and IL-4 gene signatures also positively correlate with the levels of neutralizing antibodies in Zika-virus-infected macaques. In conclusion, our data support a model wherein a pre-TfH wave of IL-4 secreted by interfollicular NKT cells triggers the seeding of germinal center cells and serves as an innate link between viral infection and B cell immunity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Folic Acid supplementation stimulates notch signaling and cell proliferation in embryonic neural stem cells.

    Science.gov (United States)

    Liu, Huan; Huang, Guo-Wei; Zhang, Xu-Mei; Ren, Da-Lin; X Wilson, John

    2010-09-01

    The present study investigated the effect of folic acid supplementation on the Notch signaling pathway and cell proliferation in rat embryonic neural stem cells (NSCs). The NSCs were isolated from E14-16 rat brain and grown as neurospheres in serum-free suspension culture. Individual cultures were assigned to one of 3 treatment groups that differed according to the concentration of folic acid in the medium: Control (baseline folic acid concentration of 4 mg/l), low folic acid supplementation (4 mg/l above baseline, Folate-L) and high folic acid supplementation (40 mg/l above baseline, Folate-H). NSCs were identified by their expression of immunoreactive nestin and proliferating cells by incorporation of 5'bromo-2'deoxyuridine. Cell proliferation was also assessed by methyl thiazolyl tetrazolium assay. Notch signaling was analyzed by real-time PCR and western blot analyses of the expression of Notch1 and hairy and enhancer of split 5 (Hes5). Supplementation of NSCs with folic acid increased the mRNA and protein expression levels of Notch1 and Hes5. Folic acid supplementation also stimulated NSC proliferation dose-dependently. Embryonic NSCs respond to folic acid supplementation with increased Notch signaling and cell proliferation. This mechanism may mediate the effects of folic acid supplementation on neurogenesis in the embryonic nervous system.

  14. Study on Magneto-Hydro-Dynamics Disturbance Signal Feature Classification Using Improved S-Transform Algorithm and Radial Basis Function Neural Network

    Directory of Open Access Journals (Sweden)

    Nan YU

    2014-09-01

    Full Text Available The interference signal in magneto-hydro-dynamics (MHD may be the disturbance from the power supply, the equipment itself, or the electromagnetic radiation. Interference signal mixed in normal signal, brings difficulties for signal analysis and processing. Recently proposed S-Transform algorithm combines advantages of short time Fourier transform and wavelet transform. It uses Fourier kernel and wavelet like Gauss window whose width is inversely proportional to the frequency. Therefore, S-Transform algorithm not only preserves the phase information of the signals but also has variable resolution like wavelet transform. This paper proposes a new method to establish a MHD signal classifier using S-transform algorithm and radial basis function neural network (RBFNN. Because RBFNN centers ascertained by k-means clustering algorithm probably are the local optimum, this paper analyzes the characteristics of k-means clustering algorithm and proposes an improved k-means clustering algorithm called GCW (Group-cluster-weight k-means clustering algorithm to improve the centers distribution. The experiment results show that the improvement greatly enhances the RBFNN performance.

  15. High-Density Stretchable Electrode Grids for Chronic Neural Recording.

    Science.gov (United States)

    Tybrandt, Klas; Khodagholy, Dion; Dielacher, Bernd; Stauffer, Flurin; Renz, Aline F; Buzsáki, György; Vörös, János

    2018-04-01

    Electrical interfacing with neural tissue is key to advancing diagnosis and therapies for neurological disorders, as well as providing detailed information about neural signals. A challenge for creating long-term stable interfaces between electronics and neural tissue is the huge mechanical mismatch between the systems. So far, materials and fabrication processes have restricted the development of soft electrode grids able to combine high performance, long-term stability, and high electrode density, aspects all essential for neural interfacing. Here, this challenge is addressed by developing a soft, high-density, stretchable electrode grid based on an inert, high-performance composite material comprising gold-coated titanium dioxide nanowires embedded in a silicone matrix. The developed grid can resolve high spatiotemporal neural signals from the surface of the cortex in freely moving rats with stable neural recording quality and preserved electrode signal coherence during 3 months of implantation. Due to its flexible and stretchable nature, it is possible to minimize the size of the craniotomy required for placement, further reducing the level of invasiveness. The material and device technology presented herein have potential for a wide range of emerging biomedical applications. © 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Modulation of learning and memory by cytokines: signaling mechanisms and long term consequences.

    Science.gov (United States)

    Donzis, Elissa J; Tronson, Natalie C

    2014-11-01

    This review describes the role of cytokines and their downstream signaling cascades on the modulation of learning and memory. Immune proteins are required for many key neural processes and dysregulation of these functions by systemic inflammation can result in impairments of memory that persist long after the resolution of inflammation. Recent research has demonstrated that manipulations of individual cytokines can modulate learning, memory, and synaptic plasticity. The many conflicting findings, however, have prevented a clear understanding of the precise role of cytokines in memory. Given the complexity of inflammatory signaling, understanding its modulatory role requires a shift in focus from single cytokines to a network of cytokine interactions and elucidation of the cytokine-dependent intracellular signaling cascades. Finally, we propose that whereas signal transduction and transcription may mediate short-term modulation of memory, long-lasting cellular and molecular mechanisms such as epigenetic modifications and altered neurogenesis may be required for the long lasting impact of inflammation on memory and cognition. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. 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.

  18. Beneficial role of noise in artificial neural networks

    International Nuclear Information System (INIS)

    Monterola, Christopher; Saloma, Caesar; Zapotocky, Martin

    2008-01-01

    We demonstrate enhancement of neural networks efficacy to recognize frequency encoded signals and/or to categorize spatial patterns of neural activity as a result of noise addition. For temporal information recovery, noise directly added to the receiving neurons allow instantaneous improvement of signal-to-noise ratio [Monterola and Saloma, Phys. Rev. Lett. 2002]. For spatial patterns however, recurrence is necessary to extend and homogenize the operating range of a feed-forward neural network [Monterola and Zapotocky, Phys. Rev. E 2005]. Finally, using the size of the basin of attraction of the networks learned patterns (dynamical fixed points), a procedure for estimating the optimal noise is demonstrated

  19. Mapping and signaling of neural pathways involved in the regulation of hydromineral homeostasis

    Directory of Open Access Journals (Sweden)

    J. Antunes-Rodrigues

    2013-04-01

    Full Text Available Several forebrain and brainstem neurochemical circuitries interact with peripheral neural and humoral signals to collaboratively maintain both the volume and osmolality of extracellular fluids. Although much progress has been made over the past decades in the understanding of complex mechanisms underlying neuroendocrine control of hydromineral homeostasis, several issues still remain to be clarified. The use of techniques such as molecular biology, neuronal tracing, electrophysiology, immunohistochemistry, and microinfusions has significantly improved our ability to identify neuronal phenotypes and their signals, including those related to neuron-glia interactions. Accordingly, neurons have been shown to produce and release a large number of chemical mediators (neurotransmitters, neurohormones and neuromodulators into the interstitial space, which include not only classic neurotransmitters, such as acetylcholine, amines (noradrenaline, serotonin and amino acids (glutamate, GABA, but also gaseous (nitric oxide, carbon monoxide and hydrogen sulfide and lipid-derived (endocannabinoids mediators. This efferent response, initiated within the neuronal environment, recruits several peripheral effectors, such as hormones (glucocorticoids, angiotensin II, estrogen, which in turn modulate central nervous system responsiveness to systemic challenges. Therefore, in this review, we shall evaluate in an integrated manner the physiological control of body fluid homeostasis from the molecular aspects to the systemic and integrated responses.

  20. Automatic sleep stage classification based on EEG signals by using neural networks and wavelet packet coefficients.

    Science.gov (United States)

    Ebrahimi, Farideh; Mikaeili, Mohammad; Estrada, Edson; Nazeran, Homer

    2008-01-01

    Currently in the world there is an alarming number of people who suffer from sleep disorders. A number of biomedical signals, such as EEG, EMG, ECG and EOG are used in sleep labs among others for diagnosis and treatment of sleep related disorders. The usual method for sleep stage classification is visual inspection by a sleep specialist. This is a very time consuming and laborious exercise. Automatic sleep stage classification can facilitate this process. The definition of sleep stages and the sleep literature show that EEG signals are similar in Stage 1 of non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. Therefore, in this work an attempt was made to classify four sleep stages consisting of Awake, Stage 1 + REM, Stage 2 and Slow Wave Stage based on the EEG signal alone. Wavelet packet coefficients and artificial neural networks were deployed for this purpose. Seven all night recordings from Physionet database were used in the study. The results demonstrated that these four sleep stages could be automatically discriminated from each other with a specificity of 94.4 +/- 4.5%, a of sensitivity 84.2+3.9% and an accuracy of 93.0 +/- 4.0%.

  1. An Improved Neural Network Training Algorithm for Wi-Fi Fingerprinting Positioning

    Directory of Open Access Journals (Sweden)

    Esmond Mok

    2013-09-01

    Full Text Available Ubiquitous positioning provides continuous positional information in both indoor and outdoor environments for a wide spectrum of location based service (LBS applications. With the rapid development of the low-cost and high speed data communication, Wi-Fi networks in many metropolitan cities, strength of signals propagated from the Wi-Fi access points (APs namely received signal strength (RSS have been cleverly adopted for indoor positioning. In this paper, a Wi-Fi positioning algorithm based on neural network modeling of Wi-Fi signal patterns is proposed. This algorithm is based on the correlation between the initial parameter setting for neural network training and output of the mean square error to obtain better modeling of the nonlinear highly complex Wi-Fi signal power propagation surface. The test results show that this neural network based data processing algorithm can significantly improve the neural network training surface to achieve the highest possible accuracy of the Wi-Fi fingerprinting positioning method.

  2. A Chip for an Implantable Neural Stimulator

    DEFF Research Database (Denmark)

    Gudnason, Gunnar; Bruun, Erik; Haugland, Morten

    2000-01-01

    This paper describes a chip for a multichannel neural stimulator for functional electrical stimulation (FES). The purpose of FES is to restore muscular control in disabled patients. The chip performs all the signal processing required in an implanted neural stimulator. The power and digital data...

  3. Extracts of Porphyra tenera (Nori Seaweed) Activate the Immune Response in Mouse RAW264.7 Macrophages via NF-κB Signaling.

    Science.gov (United States)

    Song, Ji-Hye; Kang, Hee-Bum; Park, Seung-Ho; Jeong, Ji-Hoon; Park, Jeongjin; You, Yanghee; Lee, Yoo-Hyun; Lee, Jeongmin; Kim, Eungpil; Choi, Kyung-Chul; Jun, Woojin

    2017-12-01

    Porphyra tenera, also known as nori, is a red algal species of seaweed. It is cultivated in Asia for culinary purposes. We report that P. tenera extract (PTE) enhances the immune response in mouse macrophages. We found that P. tenera extract regulates the NF-κB IκB kinase (IKK) signaling pathway, and we assessed the expression and translocation of p65, a subunit of NF-κB, in RAW264.7 mouse macrophage cells after treatment with PTE. We also investigated the effects of 10% ethanol PTE (PTE10) in RAW264.7 cells. The production of IL-10, IL-6, TNF-α, and IFN-γ was induced by PTE treatment of the macrophages, and PTE also enhanced p-IκB and p-AKT. PTE10 showed no cytotoxicity at 10-20 μg/mL in RAW264.7 cells. PTE10, in fact, increased cell viability at 24 h, stimulated macrophage cells, and induced the phosphorylation of Akt. Akt stimulates IKK activity through the phosphorylation of IKKα and enhances immune activity through the activation of NF-κB. In this study, NF-κB activation was induced by increasing p-NF-κB and p-IKK. A subunit of NF-κB, p65, was located in the nucleus and increased the expression of various cytokines. PTE thus enhanced the immune response through IκB-α immunostimulation signaling in RAW264.7 cells. PTE10 has potential therefore for development of future treatments requiring immune system stimulation.

  4. Immune Modulation of NYVAC-Based HIV Vaccines by Combined Deletion of Viral Genes that Act on Several Signalling Pathways

    Directory of Open Access Journals (Sweden)

    Carmen Elena Gómez

    2017-12-01

    Full Text Available An HIV-1 vaccine continues to be a major target to halt the AIDS pandemic. The limited efficacy of the RV144 phase III clinical trial with the canarypox virus-based vector ALVAC and a gp120 protein component led to the conclusion that improved immune responses to HIV antigens are needed for a more effective vaccine. In non-human primates, the New York vaccinia virus (NYVAC poxvirus vector has a broader immunogenicity profile than ALVAC and has been tested in clinical trials. We therefore analysed the HIV immune advantage of NYVAC after removing viral genes that act on several signalling pathways (Toll-like receptors—TLR—interferon, cytokines/chemokines, as well as genes of unknown immune function. We generated a series of NYVAC deletion mutants and studied immune behaviour (T and B cell to HIV antigens and to the NYVAC vector in mice. Our results showed that combined deletion of selected vaccinia virus (VACV genes is a valuable strategy for improving the immunogenicity of NYVAC-based vaccine candidates. These immune responses were differentially modulated, positive or negative, depending on the combination of gene deletions. The deletions also led to enhanced antigen- or vector-specific cellular and humoral responses. These findings will facilitate the development of optimal NYVAC-based vaccines for HIV and other diseases.

  5. DNA Damage Response and Immune Defence: Links and Mechanisms

    Directory of Open Access Journals (Sweden)

    Björn Schumacher

    2016-08-01

    Full Text Available DNA damage plays a causal role in numerous human pathologies including cancer, premature aging and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signalling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signalling. We highlight evidence gained into (i which molecular and cellular pathways of DDR activate immune signalling, (ii how DNA damage drives chronic inflammation, and (iii how chronic inflammation causes DNA damage and pathology in humans.

  6. Aryl hydrocarbon receptor signaling modulates antiviral immune responses: ligand metabolism rather than chemical source is the stronger predictor of outcome.

    Science.gov (United States)

    Boule, Lisbeth A; Burke, Catherine G; Jin, Guang-Bi; Lawrence, B Paige

    2018-01-29

    The aryl hydrocarbon receptor (AHR) offers a compelling target to modulate the immune system. AHR agonists alter adaptive immune responses, but the consequences differ across studies. We report here the comparison of four agents representing different sources of AHR ligands in mice infected with influenza A virus (IAV): TCDD, prototype exogenous AHR agonist; PCB126, pollutant with documented human exposure; ITE, novel pharmaceutical; and FICZ, degradation product of tryptophan. All four compounds diminished virus-specific IgM levels and increased the proportion of regulatory T cells. TCDD, PCB126 and ITE, but not FICZ, reduced virus-specific IgG levels and CD8 + T cell responses. Similarly, ITE, PCB126, and TCDD reduced Th1 and Tfh cells, whereas FICZ increased their frequency. In Cyp1a1-deficient mice, all compounds, including FICZ, reduced the response to IAV. Conditional Ahr knockout mice revealed that all four compounds require AHR within hematopoietic cells. Thus, differences in the immune response to IAV likely reflect variances in quality, magnitude, and duration of AHR signaling. This indicates that binding affinity and metabolism may be stronger predictors of immune effects than a compound's source of origin, and that harnessing AHR will require finding a balance between dampening immune-mediated pathologies and maintaining sufficient host defenses against infection.

  7. mTOR at the Transmitting and Receiving Ends in Tumor Immunity.

    Science.gov (United States)

    Guri, Yakir; Nordmann, Thierry M; Roszik, Jason

    2018-01-01

    Cancer is a complex disease and a leading cause of death worldwide. Immunity is critical for cancer control. Cancer cells exhibit high mutational rates and therefore altered self or neo-antigens, eliciting an immune response to promote tumor eradication. Failure to mount a proper immune response leads to cancer progression. mTOR signaling controls cellular metabolism, immune cell differentiation, and effector function. Deregulated mTOR signaling in cancer cells modulates the tumor microenvironment, thereby affecting tumor immunity and possibly promoting carcinogenesis.

  8. Metallothioneins: Emerging Modulators in Immunity and Infection

    Directory of Open Access Journals (Sweden)

    Kavitha Subramanian Vignesh

    2017-10-01

    Full Text Available Metallothioneins (MTs are a family of metal-binding proteins virtually expressed in all organisms including prokaryotes, lower eukaryotes, invertebrates and mammals. These proteins regulate homeostasis of zinc (Zn and copper (Cu, mitigate heavy metal poisoning, and alleviate superoxide stress. In recent years, MTs have emerged as an important, yet largely underappreciated, component of the immune system. Innate and adaptive immune cells regulate MTs in response to stress stimuli, cytokine signals and microbial challenge. Modulation of MTs in these cells in turn regulates metal ion release, transport and distribution, cellular redox status, enzyme function and cell signaling. While it is well established that the host strictly regulates availability of metal ions during microbial pathogenesis, we are only recently beginning to unravel the interplay between metal-regulatory pathways and immunological defenses. In this perspective, investigation of mechanisms that leverage the potential of MTs to orchestrate inflammatory responses and antimicrobial defenses has gained momentum. The purpose of this review, therefore, is to illumine the role of MTs in immune regulation. We discuss the mechanisms of MT induction and signaling in immune cells and explore the therapeutic potential of the MT-Zn axis in bolstering immune defenses against pathogens.

  9. Neuro-immune interactions in inflammatory bowel disease and irritable bowel syndrome: Future therapeutic targets

    NARCIS (Netherlands)

    Kraneveld, A.D.; Rijnierse, A.; Nijkamp, F.P.; Garssen, J.

    2008-01-01

    The gastro-intestinal tract is well known for its largest neural network outside the central nervous system and for the most extensive immune system in the body. Research in neurogastroenterology implicates the involvement of both enteric nervous system and immune system in symptoms of inflammatory

  10. Neuro-immune interactions in inflammatory bowel disease and irritable bowel syndrome : Future therapeutic targets

    NARCIS (Netherlands)

    Kraneveld, A.D.|info:eu-repo/dai/nl/126612838; Rijnierse, A.|info:eu-repo/dai/nl/304830224; Nijkamp, F.P.|info:eu-repo/dai/nl/067668852; Garssen, J.|info:eu-repo/dai/nl/086369962

    2008-01-01

    The gastro-intestinal tract is well known for its largest neural network outside the central nervous system and for the most extensive immune system in the body. Research in neurogastroenterology implicates the involvement of both enteric nervous system and immune system in symptoms of inflammatory

  11. A Quantitative RNAi Screen for JNK Modifiers Identifies Pvr as a Novel Regulator of Drosophila Immune Signaling

    Science.gov (United States)

    Bond, David; Foley, Edan

    2009-01-01

    Drosophila melanogaster responds to gram-negative bacterial challenges through the IMD pathway, a signal transduction cassette that is driven by the coordinated activities of JNK, NF-κB and caspase modules. While many modifiers of NF-κB activity were identified in cell culture and in vivo assays, the regulatory apparatus that determines JNK inputs into the IMD pathway is relatively unexplored. In this manuscript, we present the first quantitative screen of the entire genome of Drosophila for novel regulators of JNK activity in the IMD pathway. We identified a large number of gene products that negatively or positively impact on JNK activation in the IMD pathway. In particular, we identified the Pvr receptor tyrosine kinase as a potent inhibitor of JNK activation. In a series of in vivo and cell culture assays, we demonstrated that activation of the IMD pathway drives JNK-dependent expression of the Pvr ligands, Pvf2 and Pvf3, which in turn act through the Pvr/ERK MAP kinase pathway to attenuate the JNK and NF-κB arms of the IMD pathway. Our data illuminate a poorly understood arm of a critical and evolutionarily conserved innate immune response. Furthermore, given the pleiotropic involvement of JNK in eukaryotic cell biology, we believe that many of the novel regulators identified in this screen are of interest beyond immune signaling. PMID:19893628

  12. 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

  13. Dynamic neural network-based methods for compensation of nonlinear effects in multimode communication lines

    Science.gov (United States)

    Sidelnikov, O. S.; Redyuk, A. A.; Sygletos, S.

    2017-12-01

    We consider neural network-based schemes of digital signal processing. It is shown that the use of a dynamic neural network-based scheme of signal processing ensures an increase in the optical signal transmission quality in comparison with that provided by other methods for nonlinear distortion compensation.

  14. Defective chemokine signal integration in leukocytes lacking activator of G protein signaling 3 (AGS3).

    Science.gov (United States)

    Branham-O'Connor, Melissa; Robichaux, William G; Zhang, Xian-Kui; Cho, Hyeseon; Kehrl, John H; Lanier, Stephen M; Blumer, Joe B

    2014-04-11

    Activator of G-protein signaling 3 (AGS3, gene name G-protein signaling modulator-1, Gpsm1), an accessory protein for G-protein signaling, has functional roles in the kidney and CNS. Here we show that AGS3 is expressed in spleen, thymus, and bone marrow-derived dendritic cells, and is up-regulated upon leukocyte activation. We explored the role of AGS3 in immune cell function by characterizing chemokine receptor signaling in leukocytes from mice lacking AGS3. No obvious differences in lymphocyte subsets were observed. Interestingly, however, AGS3-null B and T lymphocytes and bone marrow-derived dendritic cells exhibited significant chemotactic defects as well as reductions in chemokine-stimulated calcium mobilization and altered ERK and Akt activation. These studies indicate a role for AGS3 in the regulation of G-protein signaling in the immune system, providing unexpected venues for the potential development of therapeutic agents that modulate immune function by targeting these regulatory mechanisms.

  15. Augmented Indian hedgehog signaling in cranial neural crest cells leads to craniofacial abnormalities and dysplastic temporomandibular joint in mice.

    Science.gov (United States)

    Yang, Ling; Gu, Shuping; Ye, Wenduo; Song, Yingnan; Chen, YiPing

    2016-04-01

    Extensive studies have pinpointed the crucial role of Indian hedgehog (Ihh) signaling in the development of the appendicular skeleton and the essential function of Ihh in the formation of the temporomandibular joint (TMJ). In this study, we have investigated the effect of augmented Ihh signaling in TMJ development. We took a transgenic gain-of-function approach by overexpressing Ihh in the cranial neural crest (CNC) cells using a conditional Ihh transgenic allele and the Wnt1-Cre allele. We found that Wnt1-Cre-mediated tissue-specific overexpression of Ihh in the CNC lineage caused severe craniofacial abnormalities, including cleft lip/palate, encephalocele, anophthalmos, micrognathia, and defective TMJ development. In the mutant TMJ, the glenoid fossa was completely absent, whereas the condyle and the articular disc appeared relatively normal with slightly delayed chondrocyte differentiation. Our findings thus demonstrate that augmented Ihh signaling is detrimental to craniofacial development, and that finely tuned Ihh signaling is critical for TMJ formation. Our results also provide additional evidence that the development of the condyle and articular disc is independent of the glenoid fossa.

  16. Wnt/Yes-Associated Protein Interactions During Neural Tissue Patterning of Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Bejoy, Julie; Song, Liqing; Zhou, Yi; Li, Yan

    2018-04-01

    Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain-like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests. However, the interactions between Wnt and YAP expression for neural lineage commitment of hiPSCs remain poorly explored. The objective of this study is to investigate the effects of Wnt signaling and YAP expression on the cellular population in three-dimensional (3D) neural spheroids derived from hiPSCs. In this study, Wnt signaling was activated using CHIR99021 for 3D neural spheroids derived from human iPSK3 cells through embryoid body formation. Our results indicate that Wnt activation induces nuclear localization of YAP and upregulates the expression of HOXB4, the marker for hindbrain/spinal cord. By contrast, the cells exhibit more rostral forebrain neural identity (expression of TBR1) without Wnt activation. Cytochalasin D was then used to induce cytoplasmic YAP and the results showed the decreased HOXB4 expression. In addition, the incorporation of microparticles in the neural spheroids was investigated for the perturbation of neural patterning. This study may indicate the bidirectional interactions of Wnt signaling and YAP expression during neural tissue patterning, which have the significance in neurological disease modeling, drug screening, and neural tissue regeneration.

  17. mTOR at the Transmitting and Receiving Ends in Tumor Immunity

    Directory of Open Access Journals (Sweden)

    Yakir Guri

    2018-03-01

    Full Text Available Cancer is a complex disease and a leading cause of death worldwide. Immunity is critical for cancer control. Cancer cells exhibit high mutational rates and therefore altered self or neo-antigens, eliciting an immune response to promote tumor eradication. Failure to mount a proper immune response leads to cancer progression. mTOR signaling controls cellular metabolism, immune cell differentiation, and effector function. Deregulated mTOR signaling in cancer cells modulates the tumor microenvironment, thereby affecting tumor immunity and possibly promoting carcinogenesis.

  18. Curcumin increased the differentiation rate of neurons in neural stem cells via wnt signaling in vitro study.

    Science.gov (United States)

    Chen, Fei; Wang, Haoxiang; Xiang, Xin; Yuan, Jichao; Chu, Weihua; Xue, Xingsen; Zhu, Haitao; Ge, Hongfei; Zou, Mingming; Feng, Hua; Lin, Jiangkai

    2014-12-01

    The objective of the present study was to clarify the relationship between the neuroprotective effects of curcumin and the classical wnt signaling pathway. Using Sprague-Dawley rats at a gestational age of 14.5 d, we isolated neural stem cells from the anterior two-thirds of the fetal rat brain. The neural stem cells were passaged three times using the half media replacement method and identified using cellular immunofluorescence. After passaging for three generations, we cultured cells in media without basic fibroblast growth factor and epidermal growth factor. Then we treated cells in five different ways, including a blank control group, a group treated with IWR1 (10 μmol/L), a group treated with curcumin (500 nmol/L), a group treated with IWR1 + curcumin, and a group treated with dimethyl sulfoxide (10 μmol/L). We then measured the protein and RNA expression levels for wnt3a and β-catenin using Western blotting and Reverse transcription-polymerase chain reaction (RT-PCR). Western-blotting: after the third generation of cells had been treated for 72 h, we observed that wnt3a and β-catenin expression was significantly increased in the group receiving 500 nmol/L curcumin but not in the other groups. Furthermore, cells in the IWR1-treated group showed decreased wnt3a and β-catenin expression, and wnt3a and β-catenin was also decreased in the IWR1 + 500 nmol/L curcumin group. No obvious change was observed in the dimethyl sulfoxide group. RT-PCR showed similar changes to those observed with the Western blotting experiments. Our study suggests that curcumin can activate the wnt signaling pathway, which provides evidence that curcumin exhibits a neuroprotective effect through the classical wnt signaling pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Mechanisms Underlying the Immune Response Generated by an Oral Vibrio cholerae Vaccine

    Directory of Open Access Journals (Sweden)

    Danylo Sirskyj

    2016-07-01

    Full Text Available Mechanistic details underlying the resulting protective immune response generated by mucosal vaccines remain largely unknown. We investigated the involvement of Toll-like receptor signaling in the induction of humoral immune responses following oral immunization with Dukoral, comparing wild type mice with TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. Although all groups generated similar levels of IgG antibodies, the proliferation of CD4+ T-cells in response to V. cholerae was shown to be mediated via MyD88/TLR signaling, and independently of Trif signaling. The results demonstrate differential requirements for generation of immune responses. These results also suggest that TLR pathways may be modulators of the quality of immune response elicited by the Dukoral vaccine. Determining the critical signaling pathways involved in the induction of immune response to this vaccine would be beneficial, and could contribute to more precisely-designed versions of other oral vaccines in the future.

  20. Low-dimensional recurrent neural network-based Kalman filter for speech enhancement.

    Science.gov (United States)

    Xia, Youshen; Wang, Jun

    2015-07-01

    This paper proposes a new recurrent neural network-based Kalman filter for speech enhancement, based on a noise-constrained least squares estimate. The parameters of speech signal modeled as autoregressive process are first estimated by using the proposed recurrent neural network and the speech signal is then recovered from Kalman filtering. The proposed recurrent neural network is globally asymptomatically stable to the noise-constrained estimate. Because the noise-constrained estimate has a robust performance against non-Gaussian noise, the proposed recurrent neural network-based speech enhancement algorithm can minimize the estimation error of Kalman filter parameters in non-Gaussian noise. Furthermore, having a low-dimensional model feature, the proposed neural network-based speech enhancement algorithm has a much faster speed than two existing recurrent neural networks-based speech enhancement algorithms. Simulation results show that the proposed recurrent neural network-based speech enhancement algorithm can produce a good performance with fast computation and noise reduction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Anti-synthetase syndrome associated with anti PL-12 and anti-Signal recognition particle antibodies and a necrotizing auto-immune myositis.

    Science.gov (United States)

    Malkan, Ashish; Cappelen-Smith, Cecilia; Beran, Roy; Griffith, Neil; Toong, Catherine; Wang, Min-Xia; Cordato, Dennis

    2015-02-01

    We report a 37-year-old woman with a 2 month history of proximal muscle weakness and extremely high creatine kinase (21,808 U/L) due to necrotizing auto-immune myositis (NAM) in association with anti-synthetase syndrome. Myositis-specific auto-immune antibody panel was positive for anti-Signal recognition particle and anti-PL-12. CT scan of the chest confirmed interstitial lung disease. Prednisolone, intravenous immunoglobulin and cyclophosphamide therapy was given with gradual improvement. This patient is notable for the unusual combination of NAM and anti-synthetase syndrome with the rare finding of two myositis-specific autoantibodies, which directed testing for associated extramuscular features and management with more aggressive immunotherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Zinc as a Gatekeeper of Immune Function

    Directory of Open Access Journals (Sweden)

    Inga Wessels

    2017-11-01

    Full Text Available After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14, zinc “exporters” (ZnT 1–10, and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function.

  3. All-trans retinoic acid promotes neural lineage entry by pluripotent embryonic stem cells via multiple pathways

    Directory of Open Access Journals (Sweden)

    Fang Bo

    2009-07-01

    Full Text Available Abstract Background All-trans retinoic acid (RA is one of the most important morphogens with pleiotropic actions. Its embryonic distribution correlates with neural differentiation in the developing central nervous system. To explore the precise effects of RA on neural differentiation of mouse embryonic stem cells (ESCs, we detected expression of RA nuclear receptors and RA-metabolizing enzymes in mouse ESCs and investigated the roles of RA in adherent monolayer culture. Results Upon addition of RA, cell differentiation was directed rapidly and exclusively into the neural lineage. Conversely, pharmacological interference with RA signaling suppressed this neural differentiation. Inhibition of fibroblast growth factor (FGF signaling did not suppress significantly neural differentiation in RA-treated cultures. Pharmacological interference with extracellular signal-regulated kinase (ERK pathway or activation of Wnt pathway effectively blocked the RA-promoted neural specification. ERK phosphorylation was enhanced in RA-treated cultures at the early stage of differentiation. Conclusion RA can promote neural lineage entry by ESCs in adherent monolayer culture systems. This effect depends on RA signaling and its crosstalk with the ERK and Wnt pathways.

  4. Complex-Valued Neural Networks

    CERN Document Server

    Hirose, Akira

    2012-01-01

    This book is the second enlarged and revised edition of the first successful monograph on complex-valued neural networks (CVNNs) published in 2006, which lends itself to graduate and undergraduate courses in electrical engineering, informatics, control engineering, mechanics, robotics, bioengineering, and other relevant fields. In the second edition the recent trends in CVNNs research are included, resulting in e.g. almost a doubled number of references. The parametron invented in 1954 is also referred to with discussion on analogy and disparity. Also various additional arguments on the advantages of the complex-valued neural networks enhancing the difference to real-valued neural networks are given in various sections. The book is useful for those beginning their studies, for instance, in adaptive signal processing for highly functional sensing and imaging, control in unknown and changing environment, robotics inspired by human neural systems, and brain-like information processing, as well as interdisciplina...

  5. Neem leaf glycoprotein prophylaxis transduces immune dependent stop signal for tumor angiogenic switch within tumor microenvironment.

    Directory of Open Access Journals (Sweden)

    Saptak Banerjee

    Full Text Available We have reported that prophylactic as well as therapeutic administration of neem leaf glycoprotein (NLGP induces significant restriction of solid tumor growth in mice. Here, we investigate whether the effect of such pretreatment (25µg/mice; weekly, 4 times benefits regulation of tumor angiogenesis, an obligate factor for tumor progression. We show that NLGP pretreatment results in vascular normalization in melanoma and carcinoma bearing mice along with downregulation of CD31, VEGF and VEGFR2. NLGP pretreatment facilitates profound infiltration of CD8+ T cells within tumor parenchyma, which subsequently regulates VEGF-VEGFR2 signaling in CD31+ vascular endothelial cells to prevent aberrant neovascularization. Pericyte stabilization, VEGF dependent inhibition of VEC proliferation and subsequent vascular normalization are also experienced. Studies in immune compromised mice confirmed that these vascular and intratumoral changes in angiogenic profile are dependent upon active adoptive immunity particularly those mediated by CD8+ T cells. Accumulated evidences suggest that NLGP regulated immunomodulation is active in tumor growth restriction and normalization of tumor angiogenesis as well, thereby, signifying its clinical translation.

  6. ACTIVATION OF GENES CONTROLLING THE IMMUNE SIGNALING PATHWAYS: DIFFERENTIAL INDIVIDUAL SENSITIVITY OF HUMAN BLOOD CELLS FOR INTERFERON PREPARATIONS AND IFN INDUCERS

    Directory of Open Access Journals (Sweden)

    T. M. Sokolova

    2015-01-01

    Full Text Available We have studied dose effects of several Interferon (IFN inducers, i.e., Genfaxon (beta-1 IFN, Cycloferon and Immunomax upon expression of six genes controlling the signaling in immune pathways (TLR3, TLR4, RIG1, IRF3, IPS, B2M, by means of real-time RT-PCR, being tested with blood cells from three humans. It is revealed that individual cell samples showed different sensitivity to these drugs, probably, due to constitutive levels of TLR3 and TLR4 gene expression and possible connections with their immune pathology. Genfaxon at a dose of 104 ME produced potent stimulation of TLR3, TLR4, IRF3 and B2M genes in two persons. Immunomax, at a dose 0,5 unit, exhibited same effect in one case only (with Epstein-Barr virus infection. Cycloferon stimulated gene expression at much lower levels than Genfaxon in any cases. We have shown a reverse correlation between sensitivity of the cells to Immunomax, and constitutive TLR3 and TLR4 expression. The stimulatory effects of Immunomax were maximal in a person with very low TLR3/4 gene expression. Immunomax boosted the genes from several signaling pathways, including TLR3, TLR4, but genes of RIG/IPS pathway showed higher activation. Cycloferon induced gene transcription of IRF3 and B2M-receptor to higher degree, than expression of TLR3 and TLR4 genes. Hence, our data concerning Genfaxon, Immunomax and Cycloferon confirm their IFN-inducing effects upon human blood cells. The RT-PCR-based evaluation of gene expression related to signaling immune pathways in blood cell populations will enable rapid and highly specific quantitation of IFN and IFN-inducer drugs activities, thus avoiding their biological testing in long-term cell cultures. 

  7. Immune inhibitory receptors in viral infection and cancer

    NARCIS (Netherlands)

    Karnam, G.

    2014-01-01

    We are protected from external and internal dangers by our immune system. Immune responses need to be balanced to prevent uncontrolled inflammation and/or autoimmunity. Cell growth inhibition, apoptosis, and down regulation of receptor signals are all part of the inhibitory tools used by the immune

  8. Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN

    Science.gov (United States)

    Ono, Daisuke; Honma, Sato; Honma, Ken-ichi

    2016-01-01

    The suprachiasmatic nucleus (SCN) is the site of the master circadian clock in mammals. The SCN neural network plays a critical role in expressing the tissue-level circadian rhythm. Previously, we demonstrated postnatal changes in the SCN network in mice, in which the clock gene products CRYPTOCHROMES (CRYs) are involved. Here, we show that vasoactive intestinal polypeptide (VIP) signaling is essential for the tissue-level circadian PER2::LUC rhythm in the neonatal SCN of CRY double-deficient mice (Cry1,2−/−). VIP and arginine vasopressin (AVP) signaling showed redundancy in expressing the tissue-level circadian rhythm in the SCN. AVP synthesis was significantly attenuated in the Cry1,2−/− SCN, which contributes to aperiodicity in the adult mice together with an attenuation of VIP signaling as a natural process of ontogeny. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by AVP and VIP signaling, depending on the postnatal period. PMID:27626074

  9. Antitumor Immunity Is Controlled by Tetraspanin Proteins

    Directory of Open Access Journals (Sweden)

    Fleur Schaper

    2018-05-01

    Full Text Available Antitumor immunity is shaped by the different types of immune cells that are present in the tumor microenvironment (TME. In particular, environmental signals (for instance, soluble factors or cell–cell contact transmitted through the plasma membrane determine whether immune cells are activated or inhibited. Tetraspanin proteins are emerging as central building blocks of the plasma membrane by their capacity to cluster immune receptors, enzymes, and signaling molecules into the tetraspanin web. Whereas some tetraspanins (CD81, CD151, CD9 are widely and broadly expressed, others (CD53, CD37, Tssc6 have an expression pattern restricted to hematopoietic cells. Studies using genetic mouse models have identified important immunological functions of these tetraspanins on different leukocyte subsets, and as such, may be involved in the immune response against tumors. While multiple studies have been performed with regards to deciphering the function of tetraspanins on cancer cells, the effect of tetraspanins on immune cells in the antitumor response remains understudied. In this review, we will focus on tetraspanins expressed by immune cells and discuss their potential role in antitumor immunity. New insights in tetraspanin function in the TME and possible prognostic and therapeutic roles of tetraspanins will be discussed.

  10. 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.

  11. Threonine modulates immune response, antioxidant status and gene expressions of antioxidant enzymes and antioxidant-immune-cytokine-related signaling molecules in juvenile blunt snout bream (Megalobrama amblycephala).

    Science.gov (United States)

    Habte-Tsion, Habte-Michael; Ren, Mingchun; Liu, Bo; Ge, Xianping; Xie, Jun; Chen, Ruli

    2016-04-01

    A 9-week feeding trial was conducted to investigate the effects of graded dietary threonine (Thr) levels (0.58-2.58%) on the hematological parameters, immune response, antioxidant status and hepatopancreatic gene expression of antioxidant enzymes and antioxidant-immune-cytokine-related signaling molecules in juvenile blunt snout bream. For this purpose, 3 tanks were randomly arranged and assigned to each experimental diet. Fish were fed with their respective diet to apparent satiation 4 times daily. The results indicated that white blood cell, red blood cell and haemoglobin significantly responded to graded dietary Thr levels, while hematocrit didn't. Complement components (C3 and C4), total iron-binding capacity (TIBC), immunoglobulin M (IgM), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) increased with increasing dietary Thr levels up to 1.58-2.08% and thereafter tended to decrease. Dietary Thr regulated the gene expressions of Cu/Zn-SOD, Mn-SOD and CAT, GPx1, glutathione S-transferase mu (GST), nuclear factor erythroid 2-related factor 2 (Nrf2), heat shock protein-70 (Hsp70), tumor necrosis factor-alpha (TNF-α), apolipoprotein A-I (ApoA1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and fructose-bisphosphate aldolase B (ALDOB); while the gene expression of peroxiredoxin II (PrxII) was not significantly modified by graded Thr levels. These genes are involved in different functions including antioxidant, immune, and defense responses, energy metabolism and protein synthesis. Therefore, this study could provide a new molecular tool for studies in fish immunonutrition and shed light on the regulatory mechanisms that dietary Thr improved the antioxidant and immune capacities of fish. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Wet gas metering with the v-cone and neural nets

    Energy Technology Data Exchange (ETDEWEB)

    Toral, Haluk; Cai, Shiqian; Peters, Robert

    2005-07-01

    The paper presents analysis of extensive measurements taken at NEL, K-Lab and CEESI wet gas test loops. Differential and absolute pressure signals were sampled at high frequency across V-Cone meters. Turbulence characteristics of the flow captured in the sampled signals were characterized by pattern recognition techniques and related to the fractions and flow rates of individual phases. The sensitivity of over-reading to first and higher order features of the high frequency signals were investigated qualitatively. The sensitivities were quantified by means of the saliency test based on back propagating neural nets. A self contained wet gas meter based on neural net characterization of first and higher order features of the pressure, differential pressure and capacitance signals was proposed. Alternatively, a wet gas meter based on a neural net model of just pressure sensor inputs (based on currently available data) and liquid Froude number was shown to offer an accuracy of under 5% if the Froude number could be estimated with 25% accuracy. (author) (tk)

  13. 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.

  14. 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.

  15. Interferon Lambda: Modulating Immunity in Infectious Diseases.

    Science.gov (United States)

    Syedbasha, Mohammedyaseen; Egli, Adrian

    2017-01-01

    Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for Staphylococcus aureus and Mycobacterium tuberculosis . Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling via the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions via macrophage

  16. Learning Data Set Influence on Identification Accuracy of Gas Turbine Neural Network Model

    Science.gov (United States)

    Kuznetsov, A. V.; Makaryants, G. M.

    2018-01-01

    There are many gas turbine engine identification researches via dynamic neural network models. It should minimize errors between model and real object during identification process. Questions about training data set processing of neural networks are usually missed. This article presents a study about influence of data set type on gas turbine neural network model accuracy. The identification object is thermodynamic model of micro gas turbine engine. The thermodynamic model input signal is the fuel consumption and output signal is the engine rotor rotation frequency. Four types input signals was used for creating training and testing data sets of dynamic neural network models - step, fast, slow and mixed. Four dynamic neural networks were created based on these types of training data sets. Each neural network was tested via four types test data sets. In the result 16 transition processes from four neural networks and four test data sets from analogous solving results of thermodynamic model were compared. The errors comparison was made between all neural network errors in each test data set. In the comparison result it was shown error value ranges of each test data set. It is shown that error values ranges is small therefore the influence of data set types on identification accuracy is low.

  17. Event-driven processing for hardware-efficient neural spike sorting

    Science.gov (United States)

    Liu, Yan; Pereira, João L.; Constandinou, Timothy G.

    2018-02-01

    Objective. The prospect of real-time and on-node spike sorting provides a genuine opportunity to push the envelope of large-scale integrated neural recording systems. In such systems the hardware resources, power requirements and data bandwidth increase linearly with channel count. Event-based (or data-driven) processing can provide here a new efficient means for hardware implementation that is completely activity dependant. In this work, we investigate using continuous-time level-crossing sampling for efficient data representation and subsequent spike processing. Approach. (1) We first compare signals (synthetic neural datasets) encoded with this technique against conventional sampling. (2) We then show how such a representation can be directly exploited by extracting simple time domain features from the bitstream to perform neural spike sorting. (3) The proposed method is implemented in a low power FPGA platform to demonstrate its hardware viability. Main results. It is observed that considerably lower data rates are achievable when using 7 bits or less to represent the signals, whilst maintaining the signal fidelity. Results obtained using both MATLAB and reconfigurable logic hardware (FPGA) indicate that feature extraction and spike sorting accuracies can be achieved with comparable or better accuracy than reference methods whilst also requiring relatively low hardware resources. Significance. By effectively exploiting continuous-time data representation, neural signal processing can be achieved in a completely event-driven manner, reducing both the required resources (memory, complexity) and computations (operations). This will see future large-scale neural systems integrating on-node processing in real-time hardware.

  18. The challenges of neural mind-reading paradigms

    OpenAIRE

    Vilarroya, Oscar

    2013-01-01

    Neural mind-reading studies, based on multivariate pattern analysis (MVPA) methods, are providing exciting new studies. Some of the results obtained with these paradigms have raised high expectations, such as the possibility of creating brain reading devices. However, such hopes are based on the assumptions that: (a) the BOLD signal is a marker of neural activity; (b) the BOLD pattern identified by a MVPA is a neurally sound pattern; (c) the MVPA's feature space is a good mapping of the neura...

  19. The vagal innervation of the gut and immune homeostasis.

    Science.gov (United States)

    Matteoli, Gianluca; Boeckxstaens, Guy E

    2013-08-01

    The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. Recently, in animal models of sepsis, the vagus nerve (VN) has been proposed to play a crucial role in the regulation of the immune response, also referred to as the cholinergic anti-inflammatory pathway. The VN, through release of acetylcholine, dampens immune cell activation by interacting with α-7 nicotinic acetylcholine receptors. Recent evidence suggests that the vagal innervation of the gastrointestinal tract also plays a major role controlling intestinal immune activation. Indeed, VN electrical stimulation potently reduces intestinal inflammation restoring intestinal homeostasis, whereas vagotomy has the reverse effect. In this review, we will discuss the current understanding concerning the mechanisms and effects involved in the cholinergic anti-inflammatory pathway in the gastrointestinal tract. Deeper investigation on this counter-regulatory neuroimmune mechanism will provide new insights in the cross-talk between the nervous and immune system leading to the identification of new therapeutic targets to treat intestinal immune disease.

  20. 3D silicon neural probe with integrated optical fibers for optogenetic modulation.

    Science.gov (United States)

    Kim, Eric G R; Tu, Hongen; Luo, Hao; Liu, Bin; Bao, Shaowen; Zhang, Jinsheng; Xu, Yong

    2015-07-21

    Optogenetics is a powerful modality for neural modulation that can be useful for a wide array of biomedical studies. Penetrating microelectrode arrays provide a means of recording neural signals with high spatial resolution. It is highly desirable to integrate optics with neural probes to allow for functional study of neural tissue by optogenetics. In this paper, we report the development of a novel 3D neural probe coupled simply and robustly to optical fibers using a hollow parylene tube structure. The device shanks are hollow tubes with rigid silicon tips, allowing the insertion and encasement of optical fibers within the shanks. The position of the fiber tip can be precisely controlled relative to the electrodes on the shank by inherent design features. Preliminary in vivo rat studies indicate that these devices are capable of optogenetic modulation simultaneously with 3D neural signal recording.

  1. Transcriptional Profiling of Hypoxic Neural Stem Cells Identifies Calcineurin-NFATc4 Signaling as a Major Regulator of Neural Stem Cell Biology

    Science.gov (United States)

    Moreno, Marta; Fernández, Virginia; Monllau, Josep M.; Borrell, Víctor; Lerin, Carles; de la Iglesia, Núria

    2015-01-01

    Summary Neural stem cells (NSCs) reside in a hypoxic microenvironment within the brain. However, the crucial transcription factors (TFs) that regulate NSC biology under physiologic hypoxia are poorly understood. Here we have performed gene set enrichment analysis (GSEA) of microarray datasets from hypoxic versus normoxic NSCs with the aim of identifying pathways and TFs that are activated under oxygen concentrations mimicking normal brain tissue microenvironment. Integration of TF target (TFT) and pathway enrichment analysis identified the calcium-regulated TF NFATc4 as a major candidate to regulate hypoxic NSC functions. Nfatc4 expression was coordinately upregulated by top hypoxia-activated TFs, while NFATc4 target genes were enriched in hypoxic NSCs. Loss-of-function analyses further revealed that the calcineurin-NFATc4 signaling axis acts as a major regulator of NSC self-renewal and proliferation in vitro and in vivo by promoting the expression of TFs, including Id2, that contribute to the maintenance of the NSC state. PMID:26235896

  2. Orientation Encoding and Viewpoint Invariance in Face Recognition: Inferring Neural Properties from Large-Scale Signals.

    Science.gov (United States)

    Ramírez, Fernando M

    2018-05-01

    Viewpoint-invariant face recognition is thought to be subserved by a distributed network of occipitotemporal face-selective areas that, except for the human anterior temporal lobe, have been shown to also contain face-orientation information. This review begins by highlighting the importance of bilateral symmetry for viewpoint-invariant recognition and face-orientation perception. Then, monkey electrophysiological evidence is surveyed describing key tuning properties of face-selective neurons-including neurons bimodally tuned to mirror-symmetric face-views-followed by studies combining functional magnetic resonance imaging (fMRI) and multivariate pattern analyses to probe the representation of face-orientation and identity information in humans. Altogether, neuroimaging studies suggest that face-identity is gradually disentangled from face-orientation information along the ventral visual processing stream. The evidence seems to diverge, however, regarding the prevalent form of tuning of neural populations in human face-selective areas. In this context, caveats possibly leading to erroneous inferences regarding mirror-symmetric coding are exposed, including the need to distinguish angular from Euclidean distances when interpreting multivariate pattern analyses. On this basis, this review argues that evidence from the fusiform face area is best explained by a view-sensitive code reflecting head angular disparity, consistent with a role of this area in face-orientation perception. Finally, the importance is stressed of explicit models relating neural properties to large-scale signals.

  3. Wallerian degeneration: the innate-immune response to traumatic nerve injury

    Directory of Open Access Journals (Sweden)

    Rotshenker Shlomo

    2011-08-01

    Full Text Available Abstract Traumatic injury to peripheral nerves results in the loss of neural functions. Recovery by regeneration depends on the cellular and molecular events of Wallerian degeneration that injury induces distal to the lesion site, the domain through which severed axons regenerate back to their target tissues. Innate-immunity is central to Wallerian degeneration since innate-immune cells, functions and molecules that are produced by immune and non-immune cells are involved. The innate-immune response helps to turn the peripheral nerve tissue into an environment that supports regeneration by removing inhibitory myelin and by upregulating neurotrophic properties. The characteristics of an efficient innate-immune response are rapid onset and conclusion, and the orchestrated interplay between Schwann cells, fibroblasts, macrophages, endothelial cells, and molecules they produce. Wallerian degeneration serves as a prelude for successful repair when these requirements are met. In contrast, functional recovery is poor when injury fails to produce the efficient innate-immune response of Wallerian degeneration.

  4. Pathogen-secreted proteases activate a novel plant immune pathway.

    Science.gov (United States)

    Cheng, Zhenyu; Li, Jian-Feng; Niu, Yajie; Zhang, Xue-Cheng; Woody, Owen Z; Xiong, Yan; Djonović, Slavica; Millet, Yves; Bush, Jenifer; McConkey, Brendan J; Sheen, Jen; Ausubel, Frederick M

    2015-05-14

    Mitogen-activated protein kinase (MAPK) cascades play central roles in innate immune signalling networks in plants and animals. In plants, however, the molecular mechanisms of how signal perception is transduced to MAPK activation remain elusive. Here we report that pathogen-secreted proteases activate a previously unknown signalling pathway in Arabidopsis thaliana involving the Gα, Gβ, and Gγ subunits of heterotrimeric G-protein complexes, which function upstream of an MAPK cascade. In this pathway, receptor for activated C kinase 1 (RACK1) functions as a novel scaffold that binds to the Gβ subunit as well as to all three tiers of the MAPK cascade, thereby linking upstream G-protein signalling to downstream activation of an MAPK cascade. The protease-G-protein-RACK1-MAPK cascade modules identified in these studies are distinct from previously described plant immune signalling pathways such as that elicited by bacterial flagellin, in which G proteins function downstream of or in parallel to an MAPK cascade without the involvement of the RACK1 scaffolding protein. The discovery of the new protease-mediated immune signalling pathway described here was facilitated by the use of the broad host range, opportunistic bacterial pathogen Pseudomonas aeruginosa. The ability of P. aeruginosa to infect both plants and animals makes it an excellent model to identify novel immunoregulatory strategies that account for its niche adaptation to diverse host tissues and immune systems.

  5. Fault diagnosis system of electromagnetic valve using neural network filter

    International Nuclear Information System (INIS)

    Hayashi, Shoji; Odaka, Tomohiro; Kuroiwa, Jousuke; Ogura, Hisakazu

    2008-01-01

    This paper is concerned with the gas leakage fault detection of electromagnetic valve using a neural network filter. In modern plants, the ability to detect and identify gas leakage faults is becoming increasingly important. The main difficulty in detecting gas leakage faults by sound signals lies in the fact that the practical plants are usually very noisy. To solve this difficulty, a neural network filter is used to eliminate background noise and raise the signal noise ratio of the sound signal. The background noise is assumed as a dynamic system, and an accurate mathematical model of the dynamic system can be established using a neural network filter. The predicted error between predicted values and practical ones constitutes the output of the filter. If the predicted error is zero, then there is no leakage. If the predicted error is greater than a certain value, then there is a leakage fault. Through application to practical pneumatic systems, it is verified that the neural network filter was effective in gas leakage detection. (author)

  6. Signal analysis for failure detection

    International Nuclear Information System (INIS)

    Parpaglione, M.C.; Perez, L.V.; Rubio, D.A.; Czibener, D.; D'Attellis, C.E.; Brudny, P.I.; Ruzzante, J.E.

    1994-01-01

    Several methods for analysis of acoustic emission signals are presented. They are mainly oriented to detection of changes in noisy signals and characterization of higher amplitude discrete pulses or bursts. The aim was to relate changes and events with failure, crack or wear in materials, being the final goal to obtain automatic means of detecting such changes and/or events. Performance evaluation was made using both simulated and laboratory test signals. The methods being presented are the following: 1. Application of the Hopfield Neural Network (NN) model for classifying faults in pipes and detecting wear of a bearing. 2. Application of the Kohonnen and Back Propagation Neural Network model for the same problem. 3. Application of Kalman filtering to determine time occurrence of bursts. 4. Application of a bank of Kalman filters (KF) for failure detection in pipes. 5. Study of amplitude distribution of signals for detecting changes in their shape. 6. Application of the entropy distance to measure differences between signals. (author). 10 refs, 11 figs

  7. Roles of neural stem cells in the repair of peripheral nerve injury.

    Science.gov (United States)

    Wang, Chong; Lu, Chang-Feng; Peng, Jiang; Hu, Cheng-Dong; Wang, Yu

    2017-12-01

    Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways.

  8. Targeting the cytosolic innate immune receptors RIG-I and MDA5 effectively counteracts cancer cell heterogeneity in glioblastoma.

    Science.gov (United States)

    Glas, Martin; Coch, Christoph; Trageser, Daniel; Dassler, Juliane; Simon, Matthias; Koch, Philipp; Mertens, Jerome; Quandel, Tamara; Gorris, Raphaela; Reinartz, Roman; Wieland, Anja; Von Lehe, Marec; Pusch, Annette; Roy, Kristin; Schlee, Martin; Neumann, Harald; Fimmers, Rolf; Herrlinger, Ulrich; Brüstle, Oliver; Hartmann, Gunther; Besch, Robert; Scheffler, Björn

    2013-06-01

    Cellular heterogeneity, for example, the intratumoral coexistence of cancer cells with and without stem cell characteristics, represents a potential root of therapeutic resistance and a significant challenge for modern drug development in glioblastoma (GBM). We propose here that activation of the innate immune system by stimulation of innate immune receptors involved in antiviral and antitumor responses can similarly target different malignant populations of glioma cells. We used short-term expanded patient-specific primary human GBM cells to study the stimulation of the cytosolic nucleic acid receptors melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene I (RIG-I). Specifically, we analyzed cells from the tumor core versus "residual GBM cells" derived from the tumor resection margin as well as stem cell-enriched primary cultures versus specimens without stem cell properties. A portfolio of human, nontumor neural cells was used as a control for these studies. The expression of RIG-I and MDA5 could be induced in all of these cells. Receptor stimulation with their respective ligands, p(I:C) and 3pRNA, led to in vitro evidence for an effective activation of the innate immune system. Most intriguingly, all investigated cancer cell populations additionally responded with a pronounced induction of apoptotic signaling cascades revealing a second, direct mechanism of antitumor activity. By contrast, p(I:C) and 3pRNA induced only little toxicity in human nonmalignant neural cells. Granted that the challenge of effective central nervous system (CNS) delivery can be overcome, targeting of RIG-I and MDA5 could thus become a quintessential strategy to encounter heterogeneous cancers in the sophisticated environments of the brain. Copyright © 2013 AlphaMed Press.

  9. Phospholipase C-β in immune cells.

    Science.gov (United States)

    Kawakami, Toshiaki; Xiao, Wenbin

    2013-09-01

    Great progress has recently been made in structural and functional research of phospholipase C (PLC)-β. We now understand how PLC-β isoforms (β1-β4) are activated by GTP-bound Gαq downstream of G protein-coupled receptors. Numerous studies indicate that PLC-βs participate in the differentiation and activation of immune cells that control both the innate and adaptive immune systems. The PLC-β3 isoform also interplays with tyrosine kinase-based signaling pathways, to inhibit Stat5 activation by recruiting the protein-tyrosine phosphatase SHP-1, with which PLC-β3 and Stat5 form a multi-molecular signaling platform, named SPS complex. The SPS complex has important regulatory roles in tumorigenesis and immune cell activation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Evolutionary perspectives on innate immunity from the study of Caenorhabditis elegans.

    Science.gov (United States)

    Kim, Dennis H; Ausubel, Frederick M

    2005-02-01

    Genetic and functional genomic approaches have begun to define the molecular determinants of pathogen resistance in Caenorhabditis elegans. Conserved signal transduction components are required for pathogen resistance, including a Toll/IL-1 receptor domain adaptor protein that functions upstream of a conserved p38 MAP kinase pathway. We suggest that this pathway is an ancestral innate immune signaling pathway present in the common ancestor of nematodes, arthropods and vertebrates, which is likely to predate the involvement of canonical Toll signaling pathways in innate immunity. We anticipate that the study of pathogen resistance in C. elegans will continue to provide evolutionary and mechanistic insights into the signal transduction and physiology of innate immunity.

  11. Model-based Bayesian signal extraction algorithm for peripheral nerves

    Science.gov (United States)

    Eggers, Thomas E.; Dweiri, Yazan M.; McCallum, Grant A.; Durand, Dominique M.

    2017-10-01

    Objective. Multi-channel cuff electrodes have recently been investigated for extracting fascicular-level motor commands from mixed neural recordings. Such signals could provide volitional, intuitive control over a robotic prosthesis for amputee patients. Recent work has demonstrated success in extracting these signals in acute and chronic preparations using spatial filtering techniques. These extracted signals, however, had low signal-to-noise ratios and thus limited their utility to binary classification. In this work a new algorithm is proposed which combines previous source localization approaches to create a model based method which operates in real time. Approach. To validate this algorithm, a saline benchtop setup was created to allow the precise placement of artificial sources within a cuff and interference sources outside the cuff. The artificial source was taken from five seconds of chronic neural activity to replicate realistic recordings. The proposed algorithm, hybrid Bayesian signal extraction (HBSE), is then compared to previous algorithms, beamforming and a Bayesian spatial filtering method, on this test data. An example chronic neural recording is also analyzed with all three algorithms. Main results. The proposed algorithm improved the signal to noise and signal to interference ratio of extracted test signals two to three fold, as well as increased the correlation coefficient between the original and recovered signals by 10-20%. These improvements translated to the chronic recording example and increased the calculated bit rate between the recovered signals and the recorded motor activity. Significance. HBSE significantly outperforms previous algorithms in extracting realistic neural signals, even in the presence of external noise sources. These results demonstrate the feasibility of extracting dynamic motor signals from a multi-fascicled intact nerve trunk, which in turn could extract motor command signals from an amputee for the end goal of

  12. Application of Artificial Neural Networks in the Heart Electrical Axis Position Conclusion Modeling

    Science.gov (United States)

    Bakanovskaya, L. N.

    2016-08-01

    The article touches upon building of a heart electrical axis position conclusion model using an artificial neural network. The input signals of the neural network are the values of deflections Q, R and S; and the output signal is the value of the heart electrical axis position. Training of the network is carried out by the error propagation method. The test results allow concluding that the created neural network makes a conclusion with a high degree of accuracy.

  13. Neural network for recognizing signal-shape of nuclear detector output

    International Nuclear Information System (INIS)

    Mardiyanto M Panitra

    2006-01-01

    The use of artificial intelligent technique in the engineering field has been familiar especially in the field of pattern recognition. By using this technique, either simple routine works or complicated routine works can be done by the help of a digital camera and a personal computer. One of the complicated works that can not be solved easily is how to separate two kinds of nuclear radiation types which are mixed in the same field. The separation of the two kinds of radiation become is very important for the radiation dosimetry purposes. For doing this we have carried out a preliminary research in applying a neural network technique for recognizing C and T letters with right, left, up, and down positions. We arranged a three-layer neural network i.e. input layer (9 neurons with/without bias neuron), hidden layer (11 neurons), and output layer (1 neuron). From this preliminary study the use of a bias neuron gave faster learning process compared with the one without the bias neuron. The neural network could work successfully in determining the letter S and T without any mistake. (author)

  14. The commensal microbiota drives immune homeostasis

    Directory of Open Access Journals (Sweden)

    Marie-Claire eArrieta

    2012-03-01

    Full Text Available For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use to keep our immune system healthy, as opposed to trying to correct the immune imbalances caused by dysbiosis, may prove to be a more astute and efficient way of treating immune-mediated disease.

  15. Neurosecurity: security and privacy for neural devices.

    Science.gov (United States)

    Denning, Tamara; Matsuoka, Yoky; Kohno, Tadayoshi

    2009-07-01

    An increasing number of neural implantable devices will become available in the near future due to advances in neural engineering. This discipline holds the potential to improve many patients' lives dramatically by offering improved-and in some cases entirely new-forms of rehabilitation for conditions ranging from missing limbs to degenerative cognitive diseases. The use of standard engineering practices, medical trials, and neuroethical evaluations during the design process can create systems that are safe and that follow ethical guidelines; unfortunately, none of these disciplines currently ensure that neural devices are robust against adversarial entities trying to exploit these devices to alter, block, or eavesdrop on neural signals. The authors define "neurosecurity"-a version of computer science security principles and methods applied to neural engineering-and discuss why neurosecurity should be a critical consideration in the design of future neural devices.

  16. Optimization of a neural network model for signal-to-background prediction in gamma-ray spectrometry

    International Nuclear Information System (INIS)

    Dragovic, S.; Onjia, A. . E-mail address of corresponding author: sdragovic@inep.co.yu; Dragovic, S.)

    2005-01-01

    The artificial neural network (ANN) model was optimized for the prediction of signal-to-background (SBR) ratio as a function of the measurement time in gamma-ray spectrometry. The network parameters: learning rate (α), momentum (μ), number of epochs (E) and number of nodes in hidden layer (N) were optimized simultaneously employing variable-size simplex method. The most accurate model with the root mean square (RMS) error of 0.073 was obtained using ANN with online backpropagation randomized (OBPR) algorithm with α = 0.27, μ 0.36, E = 14800 and N = 9. Most of the predicted and experimental SBR values for the eight radionuclides ( 226 Ra, 214 Bi, 235 U, 40 K, 232 Th, 134 Cs, 137 Cs and 7 Be), studied in this work, reasonably agreed to within 15 %, which was satisfactory accuracy. (author)

  17. Energy-efficient neural information processing in individual neurons and neuronal networks.

    Science.gov (United States)

    Yu, Lianchun; Yu, Yuguo

    2017-11-01

    Brains are composed of networks of an enormous number of neurons interconnected with synapses. Neural information is carried by the electrical signals within neurons and the chemical signals among neurons. Generating these electrical and chemical signals is metabolically expensive. The fundamental issue raised here is whether brains have evolved efficient ways of developing an energy-efficient neural code from the molecular level to the circuit level. Here, we summarize the factors and biophysical mechanisms that could contribute to the energy-efficient neural code for processing input signals. The factors range from ion channel kinetics, body temperature, axonal propagation of action potentials, low-probability release of synaptic neurotransmitters, optimal input and noise, the size of neurons and neuronal clusters, excitation/inhibition balance, coding strategy, cortical wiring, and the organization of functional connectivity. Both experimental and computational evidence suggests that neural systems may use these factors to maximize the efficiency of energy consumption in processing neural signals. Studies indicate that efficient energy utilization may be universal in neuronal systems as an evolutionary consequence of the pressure of limited energy. As a result, neuronal connections may be wired in a highly economical manner to lower energy costs and space. Individual neurons within a network may encode independent stimulus components to allow a minimal number of neurons to represent whole stimulus characteristics efficiently. This basic principle may fundamentally change our view of how billions of neurons organize themselves into complex circuits to operate and generate the most powerful intelligent cognition in nature. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Agent-specific learning signals for self-other distinction during mentalising.

    Directory of Open Access Journals (Sweden)

    Sam Ereira

    2018-04-01

    Full Text Available Humans have a remarkable ability to simulate the minds of others. How the brain distinguishes between mental states attributed to self and mental states attributed to someone else is unknown. Here, we investigated how fundamental neural learning signals are selectively attributed to different agents. Specifically, we asked whether learning signals are encoded in agent-specific neural patterns or whether a self-other distinction depends on encoding agent identity separately from this learning signal. To examine this, we tasked subjects to learn continuously 2 models of the same environment, such that one was selectively attributed to self and the other was selectively attributed to another agent. Combining computational modelling with magnetoencephalography (MEG enabled us to track neural representations of prediction errors (PEs and beliefs attributed to self, and of simulated PEs and beliefs attributed to another agent. We found that the representational pattern of a PE reliably predicts the identity of the agent to whom the signal is attributed, consistent with a neural self-other distinction implemented via agent-specific learning signals. Strikingly, subjects exhibiting a weaker neural self-other distinction also had a reduced behavioural capacity for self-other distinction and displayed more marked subclinical psychopathological traits. The neural self-other distinction was also modulated by social context, evidenced in a significantly reduced decoding of agent identity in a nonsocial control task. Thus, we show that self-other distinction is realised through an encoding of agent identity intrinsic to fundamental learning signals. The observation that the fidelity of this encoding predicts psychopathological traits is of interest as a potential neurocomputational psychiatric biomarker.

  19. Probiotic Modulation of Innate Cell Pathogen Sensing and Signaling Events

    Directory of Open Access Journals (Sweden)

    Amy Llewellyn

    2017-10-01

    Full Text Available There is a growing body of evidence documenting probiotic bacteria to have a beneficial effect to the host through their ability to modulate the mucosal immune system. Many probiotic bacteria can be considered to act as either immune activators or immune suppressors, which have appreciable influence on homeostasis, inflammatory- and suppressive-immunopathology. What is becoming apparent is the ability of these probiotics to modulate innate immune responses via direct or indirect effects on the signaling pathways that drive these activatory or suppressive/tolerogenic mechanisms. This review will focus on the immunomodulatory role of probiotics on signaling pathways in innate immune cells: from positive to negative regulation associated with innate immune cells driving gut mucosal functionality. Research investigations have shown probiotics to modulate innate functionality in many ways including, receptor antagonism, receptor expression, binding to and expression of adaptor proteins, expression of negative regulatory signal molecules, induction of micro-RNAs, endotoxin tolerisation and finally, the secretion of immunomodulatory proteins, lipids and metabolites. The detailed understanding of the immunomodulatory signaling effects of probiotic strains will facilitate strain-specific selective manipulation of innate cell signal mechanisms in the modulation of mucosal adjuvanticity, immune deviation and tolerisation in both healthy subjects and patients with inflammatory and suppressive pathology.

  20. Probiotic Modulation of Innate Cell Pathogen Sensing and Signaling Events

    Science.gov (United States)

    Llewellyn, Amy; Foey, Andrew

    2017-01-01

    There is a growing body of evidence documenting probiotic bacteria to have a beneficial effect to the host through their ability to modulate the mucosal immune system. Many probiotic bacteria can be considered to act as either immune activators or immune suppressors, which have appreciable influence on homeostasis, inflammatory- and suppressive-immunopathology. What is becoming apparent is the ability of these probiotics to modulate innate immune responses via direct or indirect effects on the signaling pathways that drive these activatory or suppressive/tolerogenic mechanisms. This review will focus on the immunomodulatory role of probiotics on signaling pathways in innate immune cells: from positive to negative regulation associated with innate immune cells driving gut mucosal functionality. Research investigations have shown probiotics to modulate innate functionality in many ways including, receptor antagonism, receptor expression, binding to and expression of adaptor proteins, expression of negative regulatory signal molecules, induction of micro-RNAs, endotoxin tolerisation and finally, the secretion of immunomodulatory proteins, lipids and metabolites. The detailed understanding of the immunomodulatory signaling effects of probiotic strains will facilitate strain-specific selective manipulation of innate cell signal mechanisms in the modulation of mucosal adjuvanticity, immune deviation and tolerisation in both healthy subjects and patients with inflammatory and suppressive pathology. PMID:29065562

  1. Milk fermentation products of L. helveticus R389 activate calcineurin as a signal to promote gut mucosal immunity

    Directory of Open Access Journals (Sweden)

    Perdigón Gabriela

    2007-09-01

    Full Text Available Background Fermented milks containing probiotic bacteria are a way of delivering bioactive constituents to targets in the gastrointestinal tract. We reported previously that the fermentation of milk at constant pH 6 by L. helveticus R389 increased its content of peptide fractions, and the oral administration of the non-bacterial fraction (FMSpH6 to mice increased total secretory IgA in the intestinal lumen and enhanced the number of IgA and various cytokines producing cells as well as the secretion of IL-6 by small intestine epithelial cells. We also demonstrated that this FMSpH6 was effective for the prevention of Salmonella typhimurium infection in mice. In this work, we studied in mice the impact of the oral administration of the supernatant of milk fermented by L. helveticus R389 on the gut physiology by measuring parameters such as calcium channels and E-cadherin expression, the activation of the biological signal calcineurin and mast and goblet cells, as a way to determine some mechanisms involved in the immunomodulating effects of the milk fermentation products, observed in previous studies. We analyzed the impact of the supernatant of milk fermented by L. helveticus R389 at pH6-controlled on the expression of calcineurin and on the reinforcement of the ephitelial barrier, measuring parameters such as calcium channels and E-cadherin expression and in the reinforcement of the non-specific immunity determining mast cells and goblet cells associated to the gut. Results We observed an enhanced expression of TRPV6 channels in the duodenum, indicating an improved capacity for dietary Ca2+ uptake. We demonstrated an enhanced expression of calcineurin in the small intestine, able to upregulate immune parameters such as IL-2 and TNF production, with an increase in the number of these cytokines secreting cells. We determined an increase in the number of mucosal mast cells and goblet cells, which would mean an improved state of mucosal surveillance

  2. The AutoAssociative Neural Network in signal analysis: II. Application to on-line monitoring of a simulated BWR component

    International Nuclear Information System (INIS)

    Marseguerra, M.; Zoia, A.

    2005-01-01

    In this paper, Robust AutoAssociative Neural Networks (RAANN) are applied to a series of signals produced by the Halden simulator of the 1200MWe BWR Forsmark-3 plant in Sweden. The applications concern: - correction of drifts and gross errors in sensors, for diagnostic and control purposes, - cluster analysis, to individuate a failed component and the intensity of the failure, - forecasting system signals, for safety or economic purposes, - reconstruction of unmeasured signals (virtual sensors). In the attainment of the above results, the geometric interpretation of the mapping performed by the network, propounded in Part I of this work, has provided a reasoned choice of the most critical free parameter, i.e., the number f of nodes of the bottleneck layer, thus allowing a deep understanding of the network functioning and also avoiding the traditional and troubling procedure of selection by trial-and-error. The theoretical basis of this analysis, discussed in details in the companion paper, is founded on the idea of dimension and in particular of fractal dimension, which has been used as a numerical estimator of f

  3. Curating the innate immunity interactome.

    LENUS (Irish Health Repository)

    Lynn, David J

    2010-01-01

    The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks. A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks. InnateDB (http:\\/\\/www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity.

  4. 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.

  5. Two pore channel 2 differentially modulates neural differentiation of mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Zhe-Hao Zhang

    Full Text Available Nicotinic acid adenine dinucleotide phosphate (NAADP is an endogenous Ca(2+ mobilizing nucleotide presented in various species. NAADP mobilizes Ca(2+ from acidic organelles through two pore channel 2 (TPC2 in many cell types and it has been previously shown that NAADP can potently induce neuronal differentiation in PC12 cells. Here we examined the role of TPC2 signaling in the neural differentiation of mouse embryonic stem (ES cells. We found that the expression of TPC2 was markedly decreased during the initial ES cell entry into neural progenitors, and the levels of TPC2 gradually rebounded during the late stages of neurogenesis. Correspondingly, TPC2 knockdown accelerated mouse ES cell differentiation into neural progenitors but inhibited these neural progenitors from committing to neurons. Overexpression of TPC2, on the other hand, inhibited mouse ES cell from entering the early neural lineage. Interestingly, TPC2 knockdown had no effect on the differentiation of astrocytes and oligodendrocytes of mouse ES cells. Taken together, our data indicate that TPC2 signaling plays a temporal and differential role in modulating the neural lineage entry of mouse ES cells, in that TPC2 signaling inhibits ES cell entry to early neural progenitors, but is required for late neuronal differentiation.

  6. Noise immunity of optimal tracking demodulators

    Science.gov (United States)

    Uriadnikov, Iu. F.; Vasilev, N. A.

    1982-05-01

    The noise immunity of optimal discrete tracking demodulators, used in space communication systems, is analyzed in the case of an arbitrary relationship between the signal pulse repetition period and the interval of message correlation. Expressions are obtained which are then used to compare the noise immunities of discrete and continuous tracking demodulators, used for the transmission of messages with spectra approximated by Butterworth polynomials. It is shown that the noise immunity of the discrete demodulator significantly deteriorates

  7. Foreground removal from CMB temperature maps using an MLP neural network

    DEFF Research Database (Denmark)

    Nørgaard-Nielsen, Hans Ulrik; Jørgensen, H.E.

    2008-01-01

    the CMB temperature signal from the combined signal CMB and the foregrounds has been investigated. As a specific example, we have analysed simulated data, as expected from the ESA Planck CMB mission. A simple multilayer perceptron neural network with 2 hidden layers can provide temperature estimates over...... CMB signal it is essential to minimize the systematic errors in the CMB temperature determinations. Following the available knowledge of the spectral behavior of the Galactic foregrounds simple power law-like spectra have been assumed. The feasibility of using a simple neural network for extracting...

  8. Immune Privilege and Eye-Derived T-Regulatory Cells

    Directory of Open Access Journals (Sweden)

    Hiroshi Keino

    2018-01-01

    Full Text Available Certain cellular components of the eye, such as neural retina, are unable to regenerate and replicate after destructive inflammation. Ocular immune privilege provides the eye with immune protection against intraocular inflammation in order to minimize the risk to vision integrity. The eye and immune system use strategies to maintain the ocular immune privilege by regulating the innate and adaptive immune response, which includes immunological ignorance, peripheral tolerance to eye-derived antigens, and intraocular immunosuppressive microenvironment. In this review, we summarize current knowledge regarding the molecular mechanism responsible for the development and maintenance of ocular immune privilege via regulatory T cells (Tregs, which are generated by the anterior chamber-associated immune deviation (ACAID, and ocular resident cells including corneal endothelial (CE cells, ocular pigment epithelial (PE cells, and aqueous humor. Furthermore, we examined the therapeutic potential of Tregs generated by RPE cells that express transforming growth factor beta (TGF-β, cytotoxic T lymphocyte-associated antigen-2 alpha (CTLA-2α, and retinoic acid for autoimmune uveoretinitis and evaluated a new strategy using human RPE-induced Tregs for clinical application in inflammatory ocular disease. We believe that a better understanding of the ocular immune privilege associated with Tregs might offer a new approach with regard to therapeutic interventions for ocular autoimmunity.

  9. Immune Privilege and Eye-Derived T-Regulatory Cells.

    Science.gov (United States)

    Keino, Hiroshi; Horie, Shintaro; Sugita, Sunao

    2018-01-01

    Certain cellular components of the eye, such as neural retina, are unable to regenerate and replicate after destructive inflammation. Ocular immune privilege provides the eye with immune protection against intraocular inflammation in order to minimize the risk to vision integrity. The eye and immune system use strategies to maintain the ocular immune privilege by regulating the innate and adaptive immune response, which includes immunological ignorance, peripheral tolerance to eye-derived antigens, and intraocular immunosuppressive microenvironment. In this review, we summarize current knowledge regarding the molecular mechanism responsible for the development and maintenance of ocular immune privilege via regulatory T cells (Tregs), which are generated by the anterior chamber-associated immune deviation (ACAID), and ocular resident cells including corneal endothelial (CE) cells, ocular pigment epithelial (PE) cells, and aqueous humor. Furthermore, we examined the therapeutic potential of Tregs generated by RPE cells that express transforming growth factor beta (TGF- β ), cytotoxic T lymphocyte-associated antigen-2 alpha (CTLA-2 α ), and retinoic acid for autoimmune uveoretinitis and evaluated a new strategy using human RPE-induced Tregs for clinical application in inflammatory ocular disease. We believe that a better understanding of the ocular immune privilege associated with Tregs might offer a new approach with regard to therapeutic interventions for ocular autoimmunity.

  10. Robustness of a Neural Network Model for Power Peak Factor Estimation in Protection Systems

    International Nuclear Information System (INIS)

    Souza, Rose Mary G.P.; Moreira, Joao M.L.

    2006-01-01

    This work presents results of robustness verification of artificial neural network correlations that improve the real time prediction of the power peak factor for reactor protection systems. The input variables considered in the correlation are those available in the reactor protection systems, namely, the axial power differences obtained from measured ex-core detectors, and the position of control rods. The correlations, based on radial basis function (RBF) and multilayer perceptron (MLP) neural networks, estimate the power peak factor, without faulty signals, with average errors between 0.13%, 0.19% and 0.15%, and maximum relative error of 2.35%. The robustness verification was performed for three different neural network correlations. The results show that they are robust against signal degradation, producing results with faulty signals with a maximum error of 6.90%. The average error associated to faulty signals for the MLP network is about half of that of the RBF network, and the maximum error is about 1% smaller. These results demonstrate that MLP neural network correlation is more robust than the RBF neural network correlation. The results also show that the input variables present redundant information. The axial power difference signals compensate the faulty signal for the position of a given control rod, and improves the results by about 10%. The results show that the errors in the power peak factor estimation by these neural network correlations, even in faulty conditions, are smaller than the current PWR schemes which may have uncertainties as high as 8%. Considering the maximum relative error of 2.35%, these neural network correlations would allow decreasing the power peak factor safety margin by about 5%. Such a reduction could be used for operating the reactor with a higher power level or with more flexibility. The neural network correlation has to meet requirements of high integrity software that performs safety grade actions. It is shown that the

  11. Conducting polymer coated neural recording electrodes

    Science.gov (United States)

    Harris, Alexander R.; Morgan, Simeon J.; Chen, Jun; Kapsa, Robert M. I.; Wallace, Gordon G.; Paolini, Antonio G.

    2013-02-01

    Objective. Neural recording electrodes suffer from poor signal to noise ratio, charge density, biostability and biocompatibility. This paper investigates the ability of conducting polymer coated electrodes to record acute neural response in a systematic manner, allowing in depth comparison of electrochemical and electrophysiological response. Approach. Polypyrrole (Ppy) and poly-3,4-ethylenedioxythiophene (PEDOT) doped with sulphate (SO4) or para-toluene sulfonate (pTS) were used to coat iridium neural recording electrodes. Detailed electrochemical and electrophysiological investigations were undertaken to compare the effect of these materials on acute in vivo recording. Main results. A range of charge density and impedance responses were seen with each respectively doped conducting polymer. All coatings produced greater charge density than uncoated electrodes, while PEDOT-pTS, PEDOT-SO4 and Ppy-SO4 possessed lower impedance values at 1 kHz than uncoated electrodes. Charge density increased with PEDOT-pTS thickness and impedance at 1 kHz was reduced with deposition times up to 45 s. Stable electrochemical response after acute implantation inferred biostability of PEDOT-pTS coated electrodes while other electrode materials had variable impedance and/or charge density after implantation indicative of a protein fouling layer forming on the electrode surface. Recording of neural response to white noise bursts after implantation of conducting polymer-coated electrodes into a rat model inferior colliculus showed a general decrease in background noise and increase in signal to noise ratio and spike count with reduced impedance at 1 kHz, regardless of the specific electrode coating, compared to uncoated electrodes. A 45 s PEDOT-pTS deposition time yielded the highest signal to noise ratio and spike count. Significance. A method for comparing recording electrode materials has been demonstrated with doped conducting polymers. PEDOT-pTS showed remarkable low fouling during

  12. Disrupted PI3K p110δ Signaling Dysregulates Maternal Immune Cells and Increases Fetal Mortality In Mice

    Directory of Open Access Journals (Sweden)

    Jens Kieckbusch

    2015-12-01

    Full Text Available Maternal immune cells are an integral part of reproduction, but how they might cause pregnancy complications remains elusive. Macrophages and their dual function in inflammation and tissue repair are thought to play key yet undefined roles. Altered perinatal growth underpins adult morbidity, and natural killer (NK cells may sustain fetal growth by establishing the placental blood supply. Using a mouse model of genetic inactivation of PI3K p110δ, a key intracellular signaling molecule in leukocytes, we show that p110δ regulates macrophage dynamics and NK-cell-mediated arterial remodeling. The uterus of dams with inactive p110δ had decreased IFN-γ and MHC class IIlow macrophages but enhanced IL-6. Poor vascular remodeling and a pro-inflammatory uterine milieu resulted in fetal death or growth retardation. Our results provide one mechanism that explains how imbalanced adaptations of maternal innate immune cells to gestation affect offspring well-being with consequence perinatally and possibly into adulthood.

  13. Neural networks for the monitoring of rotating machinery

    International Nuclear Information System (INIS)

    Alguindigue, I.E.; Loskiewicz-Buczak

    1991-01-01

    Vibration monitoring of components in engineering systems and plants involves the collection of vibration data and detailed analysis to detect features which reflect the operational state of the machinery. The analysis leads to the identification of potential failures and their causes, and makes it possible to perform efficient preventive maintenance. This paper describes a methodology for the automation of some of the activities related to motion and vibration monitoring in these systems. The technique involves training a neural network to model the inter- relationship between signals from two related sensors mounted on an engineering system or component at a time when it is known to be operating properly. Then one signal (or its characteristics) is put into the neural network model to predict the second signal (or its characteristics). This predicted signal is continuously compared with the actual signal A deviation between the predicted and actual signal indicates a changing relationship, usually failure of the component or system. This deviation may be quantified and provides meaningful information about the degree of degradation and deterioration of the component

  14. Time to address the problems at the neural interface

    Science.gov (United States)

    Durand, Dominique M.; Ghovanloo, Maysam; Krames, Elliot

    2014-04-01

    Neural engineers have made significant, if not remarkable, progress in interfacing with the nervous system in the last ten years. In particular, neuromodulation of the brain has generated significant therapeutic benefits [1-5]. EEG electrodes can be used to communicate with patients with locked-in syndrome [6]. In the central nervous system (CNS), electrode arrays placed directly over or within the cortex can record neural signals related to the intent of the subject or patient [7, 8]. A similar technology has allowed paralyzed patients to control an otherwise normal skeletal system with brain signals [9, 10]. This technology has significant potential to restore function in these and other patients with neural disorders such as stroke [11]. Although there are several multichannel arrays described in the literature, the workhorse for these cortical interfaces has been the Utah array [12]. This 100-channel electrode array has been used in most studies on animals and humans since the 1990s and is commercially available. This array and other similar microelectrode arrays can record neural signals with high quality (high signal-to-noise ratio), but these signals fade and disappear after a few months and therefore the current technology is not reliable for extended periods of time. Therefore, despite these major advances in communicating with the brain, clinical translation cannot be implemented. The reasons for this failure are not known but clearly involve the interface between the electrode and the neural tissue. The Defense Advanced Research Project Agency (DARPA) as well as other federal funding agencies such as the National Science Foundation (NSF) and the National Institutes of Health have provided significant financial support to investigate this problem without much success. A recent funding program from DARPA was designed to establish the failure modes in order to generate a reliable neural interface technology and again was unsuccessful at producing a robust

  15. 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.

  16. Disruption of IL-21 signaling affects T cell-B cell interactions and abrogates protective humoral immunity to malaria.

    Directory of Open Access Journals (Sweden)

    Damián Pérez-Mazliah

    2015-03-01

    Full Text Available Interleukin-21 signaling is important for germinal center B-cell responses, isotype switching and generation of memory B cells. However, a role for IL-21 in antibody-mediated protection against pathogens has not been demonstrated. Here we show that IL-21 is produced by T follicular helper cells and co-expressed with IFN-γ during an erythrocytic-stage malaria infection of Plasmodium chabaudi in mice. Mice deficient either in IL-21 or the IL-21 receptor fail to resolve the chronic phase of P. chabaudi infection and P. yoelii infection resulting in sustained high parasitemias, and are not immune to re-infection. This is associated with abrogated P. chabaudi-specific IgG responses, including memory B cells. Mixed bone marrow chimeric mice, with T cells carrying a targeted disruption of the Il21 gene, or B cells with a targeted disruption of the Il21r gene, demonstrate that IL-21 from T cells signaling through the IL-21 receptor on B cells is necessary to control chronic P. chabaudi infection. Our data uncover a mechanism by which CD4+ T cells and B cells control parasitemia during chronic erythrocytic-stage malaria through a single gene, Il21, and demonstrate the importance of this cytokine in the control of pathogens by humoral immune responses. These data are highly pertinent for designing malaria vaccines requiring long-lasting protective B-cell responses.

  17. The Challenges of Neural Mind-reading Paradigms

    Directory of Open Access Journals (Sweden)

    Oscar eVilarroya

    2013-06-01

    Full Text Available Neural mind-reading studies, based on multivariate pattern analysis (MVPA methods, are providing exciting new studies. Some of the results obtained with these paradigms have raised high expectations, such as the possibility of creating brain reading devices. However, such hopes are based on the assumptions that: a the BOLD signal is a marker of neural activity; b the BOLD pattern identified by a MVPA is a neurally sound pattern; c the MVPA’s feature space is a good mapping of the neural representation of a stimulus, and d the pattern identified by a MVPA corresponds to a representation. I examine here the challenges that still have to be met before fully accepting such assumptions.

  18. The challenges of neural mind-reading paradigms.

    Science.gov (United States)

    Vilarroya, Oscar

    2013-01-01

    Neural mind-reading studies, based on multivariate pattern analysis (MVPA) methods, are providing exciting new studies. Some of the results obtained with these paradigms have raised high expectations, such as the possibility of creating brain reading devices. However, such hopes are based on the assumptions that: (a) the BOLD signal is a marker of neural activity; (b) the BOLD pattern identified by a MVPA is a neurally sound pattern; (c) the MVPA's feature space is a good mapping of the neural representation of a stimulus, and (d) the pattern identified by a MVPA corresponds to a representation. I examine here the challenges that still have to be met before fully accepting such assumptions.

  19. Protein signaling pathways in differentiation of neural stem cells

    Czech Academy of Sciences Publication Activity Database

    Skalníková, Helena; Vodička, Petr; Pelech, S.; Motlík, Jan; Gadher, S. J.; Kovářová, Hana

    2008-01-01

    Roč. 8, - (2008), s. 4547-4559 ISSN 1615-9853 R&D Projects: GA MŠk 1M0538 Institutional research plan: CEZ:AV0Z50450515 Keywords : antibody microarray * differentiation * neural stem cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.586, year: 2008

  20. How (and why) the immune system makes us sleep.

    Science.gov (United States)

    Imeri, Luca; Opp, Mark R

    2009-03-01

    Good sleep is necessary for physical and mental health. For example, sleep loss impairs immune function, and sleep is altered during infection. Immune signalling molecules are present in the healthy brain, where they interact with neurochemical systems to contribute to the regulation of normal sleep. Animal studies have shown that interactions between immune signalling molecules (such as the cytokine interleukin 1) and brain neurochemical systems (such as the serotonin system) are amplified during infection, indicating that these interactions might underlie the changes in sleep that occur during infection. Why should the immune system cause us to sleep differently when we are sick? We propose that the alterations in sleep architecture during infection are exquisitely tailored to support the generation of fever, which in turn imparts survival value.

  1. METHODS OF PROVIDING NOISE IMMUNITY IN AUTOMOBILE ANTI-THEFT SYSTEM CONTROL

    Directory of Open Access Journals (Sweden)

    Frolov, V.

    2013-06-01

    Full Text Available In modern ani-theft systems they use frequency and phase modulation. Since the width of the signal is limited, it is possible to intercept the signal and then switch off the alarm at the right time.To ensure the noise immunity and secrecy manufacturers use more sophisticated codes using the methods of cryptography. Significant increase in noise immunity in modern ani-theft systems is possible using broadband signals.

  2. The role of neuroimmune signaling in alcoholism.

    Science.gov (United States)

    Crews, Fulton T; Lawrimore, Colleen J; Walter, T Jordan; Coleman, Leon G

    2017-08-01

    Alcohol consumption and stress increase brain levels of known innate immune signaling molecules. Microglia, the innate immune cells of the brain, and neurons respond to alcohol, signaling through Toll-like receptors (TLRs), high-mobility group box 1 (HMGB1), miRNAs, pro-inflammatory cytokines and their associated receptors involved in signaling between microglia, other glia and neurons. Repeated cycles of alcohol and stress cause a progressive, persistent induction of HMGB1, miRNA and TLR receptors in brain that appear to underlie the progressive and persistent loss of behavioral control, increased impulsivity and anxiety, as well as craving, coupled with increasing ventral striatal responses that promote reward seeking behavior and increase risk of developing alcohol use disorders. Studies employing anti-oxidant, anti-inflammatory, anti-depressant, and innate immune antagonists further link innate immune gene expression to addiction-like behaviors. Innate immune molecules are novel targets for addiction and affective disorders therapies. This article is part of the Special Issue entitled "Alcoholism". Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Immune mediated liver failure.

    Science.gov (United States)

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

  4. Kin Rejection: Social Signals, Neural Response and Perceived Distress During Social Exclusion

    Science.gov (United States)

    Sreekrishnan, Anirudh; Herrera, Tania A.; Wu, Jia; Borelli, Jessica L.; White, Lars O.; Rutherford, Helena J. V.; Mayes, Linda C.; Crowley, Michael J.

    2014-01-01

    Across species, kin bond together to promote survival. We sought to understand the dyadic effect of exclusion by kin (as opposed to non-kin strangers) on brain activity of the mother and her child and their subjective distress. To this end, we probed mother-child relationships with a computerized ball-toss game Cyberball. When excluded by one another, rather than by a stranger, both mothers and children exhibited a significantly pronounced frontal P2. Moreover, upon kin-rejection versus stranger-rejection, both mothers and children showed incremented left frontal positive slow waves for rejection events. Children reported more distress upon exclusion than their own mothers. Similar to past work, relatively augmented negative frontal slow wave activity predicted greater self-reported ostracism distress. This effect, generalized to the P2, was limited to mother or child- rejection by kin, with comparable magnitude of effect across kin identity (mothers vs. children). For both mothers and children, the frontal P2 peak was significantly pronounced for kin-rejection versus stranger rejection. Taken together, our results document the rapid categorization of social signals as kin-relevant and the specificity of early and late neural markers for predicting felt ostracism. PMID:24909389

  5. Genetic Mechanisms of Immune Evasion in Colorectal Cancer.

    Science.gov (United States)

    Grasso, Catherine S; Giannakis, Marios; Wells, Daniel K; Hamada, Tsuyoshi; Mu, Xinmeng Jasmine; Quist, Michael; Nowak, Jonathan A; Nishihara, Reiko; Qian, Zhi Rong; Inamura, Kentaro; Morikawa, Teppei; Nosho, Katsuhiko; Abril-Rodriguez, Gabriel; Connolly, Charles; Escuin-Ordinas, Helena; Geybels, Milan S; Grady, William M; Hsu, Li; Hu-Lieskovan, Siwen; Huyghe, Jeroen R; Kim, Yeon Joo; Krystofinski, Paige; Leiserson, Mark D M; Montoya, Dennis J; Nadel, Brian B; Pellegrini, Matteo; Pritchard, Colin C; Puig-Saus, Cristina; Quist, Elleanor H; Raphael, Ben J; Salipante, Stephen J; Shin, Daniel Sanghoon; Shinbrot, Eve; Shirts, Brian; Shukla, Sachet; Stanford, Janet L; Sun, Wei; Tsoi, Jennifer; Upfill-Brown, Alexander; Wheeler, David A; Wu, Catherine J; Yu, Ming; Zaidi, Syed H; Zaretsky, Jesse M; Gabriel, Stacey B; Lander, Eric S; Garraway, Levi A; Hudson, Thomas J; Fuchs, Charles S; Ribas, Antoni; Ogino, Shuji; Peters, Ulrike

    2018-06-01

    To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 colorectal cancer primary tumor samples, including 179 classified as microsatellite instability-high (MSI-high). This set includes The Cancer Genome Atlas colorectal cancer cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of colorectal cancer, had a high rate of significantly mutated genes in important immune-modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy-number alterations and copy-neutral loss of heterozygosity. WNT/β-catenin signaling genes were significantly mutated in all colorectal cancer subtypes, and activated WNT/β-catenin signaling was correlated with the absence of T-cell infiltration. This large-scale genomic analysis of colorectal cancer demonstrates that MSI-high cases frequently undergo an immunoediting process that provides them with genetic events allowing immune escape despite high mutational load and frequent lymphocytic infiltration and, furthermore, that colorectal cancer tumors have genetic and methylation events associated with activated WNT signaling and T-cell exclusion. Significance: This multi-omic analysis of 1,211 colorectal cancer primary tumors reveals that it should be possible to better monitor resistance in the 15% of cases that respond to immune blockade therapy and also to use WNT signaling inhibitors to reverse immune exclusion in the 85% of cases that currently do not. Cancer Discov; 8(6); 730-49. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 663 . ©2018 American Association for Cancer Research.

  6. 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 R.

    2018-04-01

    Objective. 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 Cramér-Rao Bound on evoked calcium traces recorded

  7. Innate immunity in the pathogenesis of psoriasis.

    LENUS (Irish Health Repository)

    Sweeney, Cheryl M

    2011-12-01

    Psoriasis is a common, immune-mediated inflammatory skin disorder. T helper(h)1 and Th17 lymphocytes contribute to the pathogenesis of psoriasis through the release of inflammatory cytokines that promote further recruitment of immune cells, keratinocyte proliferation and sustained inflammation. The innate immune system is the first line of defence against infection and plays a crucial role in the initiation of the adaptive immune response. The presence of innate immune cells and their products in psoriatic skin plaques suggests a role for innate immunity in this disease. In addition, the innate immune system can direct the development of pathogenic Th cells in psoriasis. In this article, we will summarise the role of the innate immune system in psoriasis with particular emphasis on the role of cytokines, signalling pathways and cells of the innate immune system.

  8. Investigating Patterns for Self-Induced Emotion Recognition from EEG Signals

    Science.gov (United States)

    Zeng, Ying; Yang, Kai; Tong, Li; Yan, Bin

    2018-01-01

    Most current approaches to emotion recognition are based on neural signals elicited by affective materials such as images, sounds and videos. However, the application of neural patterns in the recognition of self-induced emotions remains uninvestigated. In this study we inferred the patterns and neural signatures of self-induced emotions from electroencephalogram (EEG) signals. The EEG signals of 30 participants were recorded while they watched 18 Chinese movie clips which were intended to elicit six discrete emotions, including joy, neutrality, sadness, disgust, anger and fear. After watching each movie clip the participants were asked to self-induce emotions by recalling a specific scene from each movie. We analyzed the important features, electrode distribution and average neural patterns of different self-induced emotions. Results demonstrated that features related to high-frequency rhythm of EEG signals from electrodes distributed in the bilateral temporal, prefrontal and occipital lobes have outstanding performance in the discrimination of emotions. Moreover, the six discrete categories of self-induced emotion exhibit specific neural patterns and brain topography distributions. We achieved an average accuracy of 87.36% in the discrimination of positive from negative self-induced emotions and 54.52% in the classification of emotions into six discrete categories. Our research will help promote the development of comprehensive endogenous emotion recognition methods. PMID:29534515

  9. Investigating Patterns for Self-Induced Emotion Recognition from EEG Signals.

    Science.gov (United States)

    Zhuang, Ning; Zeng, Ying; Yang, Kai; Zhang, Chi; Tong, Li; Yan, Bin

    2018-03-12

    Most current approaches to emotion recognition are based on neural signals elicited by affective materials such as images, sounds and videos. However, the application of neural patterns in the recognition of self-induced emotions remains uninvestigated. In this study we inferred the patterns and neural signatures of self-induced emotions from electroencephalogram (EEG) signals. The EEG signals of 30 participants were recorded while they watched 18 Chinese movie clips which were intended to elicit six discrete emotions, including joy, neutrality, sadness, disgust, anger and fear. After watching each movie clip the participants were asked to self-induce emotions by recalling a specific scene from each movie. We analyzed the important features, electrode distribution and average neural patterns of different self-induced emotions. Results demonstrated that features related to high-frequency rhythm of EEG signals from electrodes distributed in the bilateral temporal, prefrontal and occipital lobes have outstanding performance in the discrimination of emotions. Moreover, the six discrete categories of self-induced emotion exhibit specific neural patterns and brain topography distributions. We achieved an average accuracy of 87.36% in the discrimination of positive from negative self-induced emotions and 54.52% in the classification of emotions into six discrete categories. Our research will help promote the development of comprehensive endogenous emotion recognition methods.

  10. [Immune dysfunction and cognitive deficit in stress and physiological aging (Part I): Pathogenesis and risk factors].

    Science.gov (United States)

    Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

    2014-01-01

    The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets. The brain, immune and endocrine systems being the principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain cells secluded from the blood flow by a specialized blood-brain-barrier (BBB) can endogenously express pro- and anti-inflammatory cytokines without the intervention of the immune system. In normal brain the cytokine signaling rather contributes to exclusive brain function (e.g. long-term potentiation, synaptic plasticity, adult neurogenesis) than serves as immune communicator. The stress of different origin increases the serum cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Mass intrusion of biologically active peptides having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. In addition owing to BBB disruption dendritic cells and T cells also penetrate into the brain where they take up a perivascular position. The changes observed in stressed subject may accumulate during repeated episodes of stress forming a picture typical of the aging brain. Moreover long-term stress as well as physiological aging result in hormonal and immunological disturbances including hypothalamic-pituitary-adrenal axis depletion, regulatory T-cell accumulation and dehydroepiandrosterone decrease.

  11. Detecting impact signal in mechanical fault diagnosis under chaotic and Gaussian background noise

    Science.gov (United States)

    Hu, Jinfeng; Duan, Jie; Chen, Zhuo; Li, Huiyong; Xie, Julan; Chen, Hanwen

    2018-01-01

    In actual fault diagnosis, useful information is often submerged in heavy noise, and the feature information is difficult to extract. Traditional methods, such like stochastic resonance (SR), which using noise to enhance weak signals instead of suppressing noise, failed in chaotic background. Neural network, which use reference sequence to estimate and reconstruct the background noise, failed in white Gaussian noise. To solve these problems, a novel weak signal detection method aimed at the problem of detecting impact signal buried under heavy chaotic and Gaussian background noise is proposed. First, the proposed method obtains the virtual reference sequence by constructing the Hankel data matrix. Then an M-order optimal FIR filter is designed, which can minimize the output power of background noise and pass the weak periodic signal undistorted. Finally, detection and reconstruction of the weak periodic signal are achieved from the output SBNR (signal to background noise ratio). The simulation shows, compared with the stochastic resonance (SR) method, the proposed method can detect the weak periodic signal in chaotic noise background while stochastic resonance (SR) method cannot. Compared with the neural network method, (a) the proposed method does not need a reference sequence while neural network method needs one; (b) the proposed method can detect the weak periodic signal in white Gaussian noise background while the neural network method fails, in chaotic noise background, the proposed method can detect the weak periodic signal under a lower SBNR (about 8-17 dB lower) than the neural network method; (c) the proposed method can reconstruct the weak periodic signal precisely.

  12. The Influence of Maternal Prenatal and Early Childhood Nutrition and Maternal Prenatal Stress on Offspring Immune System Development and Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Andrea Horvath Marques

    2013-07-01

    Full Text Available The developing immune system and central nervous system in the fetus and child are extremely sensitive to both exogenous and endogenous signals. Early immune system programming, leading to changes that can persist over the life course, has been suggested, and other evidence suggests that immune dysregulation in the early developing brain may play a role in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. The timing of immune dysregulation with respect to gestational age and neurologic development of the fetus may shape the elicited response. This creates a possible sensitive window of programming or vulnerability. This review will explore the effects of prenatal maternal and infant nutritional status (from conception until early childhood as well as prenatal maternal stress and anxiety on early programming of immune function, and how this might influence neurodevelopment. We will describe fetal immune system development and maternal-fetal immune interactions to provide a better context for understanding the influence of nutrition and stress on the immune system. Finally, we will discuss the implications for prevention of neurodevelopmental disorders, with a focus on nutrition. Although certain micronutrient supplements have shown to both reduce the risk of neurodevelopmental disorders and enhance fetal immune development, we do not know whether their impact on immune development contributes to the preventive effect on neurodevelopmental disorders. Future studies are needed to elucidate this relationship, which may contribute to a better understanding of preventative mechanisms. Integrating studies of neurodevelopmental disorders and prenatal exposures with the simultaneous evaluation of neural and immune systems will shed light on mechanisms that underlie individual vulnerability or resilience to neurodevelopmental disorders and ultimately contribute to the development of primary preventions and early

  13. 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....

  14. Development of teeth in chick embryos after mouse neural crest transplantations

    OpenAIRE

    Mitsiadis, Thimios A.; Chéraud, Yvonnick; Sharpe, Paul; Fontaine-Pérus, Josiane

    2003-01-01

    Teeth were lost in birds 70–80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick ...

  15. Sex-specific consequences of an induced immune response on reproduction in a moth.

    Science.gov (United States)

    Barthel, Andrea; Staudacher, Heike; Schmaltz, Antje; Heckel, David G; Groot, Astrid T

    2015-12-16

    Immune response induction benefits insects in combatting infection by pathogens. However, organisms have a limited amount of resources available and face the dilemma of partitioning resources between immunity and other life-history traits. Since males and females differ in their life histories, sex-specific resource investment strategies to achieve an optimal immune response following an infection can be expected. We investigated immune response induction of females and males of Heliothis virescens in response to the entomopathogenic bacterium Serratia entomophila, and its effects on mating success and the female sexual signal. We found that females had higher expression levels of immune-related genes after bacterial challenge than males. However, males maintained a higher baseline expression of immune-related genes than females. The increased investment in immunity of female moths was negatively correlated with mating success and the female sexual signal. Male mating success was unaffected by bacterial challenge. Our results show that the sexes differed in their investment strategies: females invested in immune defense after a bacterial challenge, indicating facultative immune deployment, whereas males had higher baseline immunity than females, indicating immune maintenance. Interestingly, these differences in investment were reflected in the mate choice assays. As female moths are the sexual signallers, females need to invest resources in their attractiveness. However, female moths appeared to invest in immunity at the cost of reproductive effort.

  16. An Implantable Wireless Neural Interface System for Simultaneous Recording and Stimulation of Peripheral Nerve with a Single Cuff Electrode.

    Science.gov (United States)

    Shon, Ahnsei; Chu, Jun-Uk; Jung, Jiuk; Kim, Hyungmin; Youn, Inchan

    2017-12-21

    Recently, implantable devices have become widely used in neural prostheses because they eliminate endemic drawbacks of conventional percutaneous neural interface systems. However, there are still several issues to be considered: low-efficiency wireless power transmission; wireless data communication over restricted operating distance with high power consumption; and limited functionality, working either as a neural signal recorder or as a stimulator. To overcome these issues, we suggest a novel implantable wireless neural interface system for simultaneous neural signal recording and stimulation using a single cuff electrode. By using widely available commercial off-the-shelf (COTS) components, an easily reconfigurable implantable wireless neural interface system was implemented into one compact module. The implantable device includes a wireless power consortium (WPC)-compliant power transmission circuit, a medical implant communication service (MICS)-band-based radio link and a cuff-electrode path controller for simultaneous neural signal recording and stimulation. During in vivo experiments with rabbit models, the implantable device successfully recorded and stimulated the tibial and peroneal nerves while communicating with the external device. The proposed system can be modified for various implantable medical devices, especially such as closed-loop control based implantable neural prostheses requiring neural signal recording and stimulation at the same time.

  17. An Implantable Wireless Neural Interface System for Simultaneous Recording and Stimulation of Peripheral Nerve with a Single Cuff Electrode

    Directory of Open Access Journals (Sweden)

    Ahnsei Shon

    2017-12-01

    Full Text Available Recently, implantable devices have become widely used in neural prostheses because they eliminate endemic drawbacks of conventional percutaneous neural interface systems. However, there are still several issues to be considered: low-efficiency wireless power transmission; wireless data communication over restricted operating distance with high power consumption; and limited functionality, working either as a neural signal recorder or as a stimulator. To overcome these issues, we suggest a novel implantable wireless neural interface system for simultaneous neural signal recording and stimulation using a single cuff electrode. By using widely available commercial off-the-shelf (COTS components, an easily reconfigurable implantable wireless neural interface system was implemented into one compact module. The implantable device includes a wireless power consortium (WPC-compliant power transmission circuit, a medical implant communication service (MICS-band-based radio link and a cuff-electrode path controller for simultaneous neural signal recording and stimulation. During in vivo experiments with rabbit models, the implantable device successfully recorded and stimulated the tibial and peroneal nerves while communicating with the external device. The proposed system can be modified for various implantable medical devices, especially such as closed-loop control based implantable neural prostheses requiring neural signal recording and stimulation at the same time.

  18. Arthropod Innate Immune Systems and Vector-Borne Diseases.

    Science.gov (United States)

    Baxter, Richard H G; Contet, Alicia; Krueger, Kathryn

    2017-02-21

    Arthropods, especially ticks and mosquitoes, are the vectors for a number of parasitic and viral human diseases, including malaria, sleeping sickness, Dengue, and Zika, yet arthropods show tremendous individual variation in their capacity to transmit disease. A key factor in this capacity is the group of genetically encoded immune factors that counteract infection by the pathogen. Arthropod-specific pattern recognition receptors and protease cascades detect and respond to infection. Proteins such as antimicrobial peptides, thioester-containing proteins, and transglutaminases effect responses such as lysis, phagocytosis, melanization, and agglutination. Effector responses are initiated by damage signals such as reactive oxygen species signaling from epithelial cells and recognized by cell surface receptors on hemocytes. Antiviral immunity is primarily mediated by siRNA pathways but coupled with interferon-like signaling, antimicrobial peptides, and thioester-containing proteins. Molecular mechanisms of immunity are closely linked to related traits of longevity and fertility, and arthropods have the capacity for innate immunological memory. Advances in understanding vector immunity can be leveraged to develop novel control strategies for reducing the rate of transmission of both ancient and emerging threats to global health.

  19. The neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Berezin, V; Bock, E; Poulsen, F M

    2000-01-01

    During the past year, the understanding of the structure and function of neural cell adhesion has advanced considerably. The three-dimensional structures of several of the individual modules of the neural cell adhesion molecule (NCAM) have been determined, as well as the structure of the complex...... between two identical fragments of the NCAM. Also during the past year, a link between homophilic cell adhesion and several signal transduction pathways has been proposed, connecting the event of cell surface adhesion to cellular responses such as neurite outgrowth. Finally, the stimulation of neurite...

  20. Real-time immune-inspired optimum state-of-charge trajectory estimation using upcoming route information preview and neural networks for plug-in hybrid electric vehicles fuel economy

    Science.gov (United States)

    Mozaffari, Ahmad; Vajedi, Mahyar; Azad, Nasser L.

    2015-06-01

    The main proposition of the current investigation is to develop a computational intelligence-based framework which can be used for the real-time estimation of optimum battery state-of-charge (SOC) trajectory in plug-in hybrid electric vehicles (PHEVs). The estimated SOC trajectory can be then employed for an intelligent power management to significantly improve the fuel economy of the vehicle. The devised intelligent SOC trajectory builder takes advantage of the upcoming route information preview to achieve the lowest possible total cost of electricity and fossil fuel. To reduce the complexity of real-time optimization, the authors propose an immune system-based clustering approach which allows categorizing the route information into a predefined number of segments. The intelligent real-time optimizer is also inspired on the basis of interactions in biological immune systems, and is called artificial immune algorithm (AIA). The objective function of the optimizer is derived from a computationally efficient artificial neural network (ANN) which is trained by a database obtained from a high-fidelity model of the vehicle built in the Autonomie software. The simulation results demonstrate that the integration of immune inspired clustering tool, AIA and ANN, will result in a powerful framework which can generate a near global optimum SOC trajectory for the baseline vehicle, that is, the Toyota Prius PHEV. The outcomes of the current investigation prove that by taking advantage of intelligent approaches, it is possible to design a computationally efficient and powerful SOC trajectory builder for the intelligent power management of PHEVs.

  1. The function of the Mediator complex in plant immunity.

    Science.gov (United States)

    An, Chuanfu; Mou, Zhonglin

    2013-03-01

    Upon pathogen infection, plants undergo dramatic transcriptome reprogramming to shift from normal growth and development to immune response. During this rapid process, the multiprotein Mediator complex has been recognized as an important player to fine-tune gene-specific and pathway-specific transcriptional reprogramming by acting as an adaptor/coregulator between sequence-specific transcription factor and RNA polymerase II (RNAPII). Here, we review current understanding of the role of five functionally characterized Mediator subunits (MED8, MED15, MED16, MED21 and MED25) in plant immunity. All these Mediator subunits positively regulate resistance against leaf-infecting biotrophic bacteria or necrotrophic fungi. While MED21 appears to regulate defense against fungal pathogens via relaying signals from upstream regulators and chromatin modification to RNAPII, the other four Mediator subunits locate at different positions of the defense network to convey phytohormone signal(s). Fully understanding the role of Mediator in plant immunity needs to characterize more Mediator subunits in both Arabidopsis and other plant species. Identification of interacting proteins of Mediator subunits will further help to reveal their specific regulatory mechanisms in plant immunity.

  2. 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...

  3. Purinergic signaling during Porphyromonas gingivalis infection

    Directory of Open Access Journals (Sweden)

    Cássio Luiz Coutinho Almeida-da-Silva

    2016-08-01

    Full Text Available Despite recent advances unraveling mechanisms of host–pathogen interactions in innate immunity, the participation of purinergic signaling in infection-driven inflammation remains an emerging research field with many unanswered questions. As one of the most-studied oral pathogens, Porphyromonas gingivalis is considered as a keystone pathogen with a central role in development of periodontal disease. This pathogen needs to evade immune-mediated defense mechanisms and tolerate inflammation in order to survive in the host. In this review, we summarize evidence showing that purinergic signaling modulates P. gingivalis survival and cellular immune responses, and discuss the role played by inflammasome activation and cell death during P. gingivalis infection. Keywords: Purinergic receptors, Innate immunity, Porphyromonas gingivalis, P2X7 receptor, Oral microbes, Inflammasome

  4. Intestinal bacteria and the regulation of immune cell homeostasis.

    Science.gov (United States)

    Hill, David A; Artis, David

    2010-01-01

    The human intestine is colonized by an estimated 100 trillion bacteria. Some of these bacteria are essential for normal physiology, whereas others have been implicated in the pathogenesis of multiple inflammatory diseases including IBD and asthma. This review examines the influence of signals from intestinal bacteria on the homeostasis of the mammalian immune system in the context of health and disease. We review the bacterial composition of the mammalian intestine, known bacterial-derived immunoregulatory molecules, and the mammalian innate immune receptors that recognize them. We discuss the influence of bacterial-derived signals on immune cell function and the mechanisms by which these signals modulate the development and progression of inflammatory disease. We conclude with an examination of successes and future challenges in using bacterial communities or their products in the prevention or treatment of human disease.

  5. Artificial neural networks for plasma spectroscopy analysis

    International Nuclear Information System (INIS)

    Morgan, W.L.; Larsen, J.T.; Goldstein, W.H.

    1992-01-01

    Artificial neural networks have been applied to a variety of signal processing and image recognition problems. Of the several common neural models the feed-forward, back-propagation network is well suited for the analysis of scientific laboratory data, which can be viewed as a pattern recognition problem. The authors present a discussion of the basic neural network concepts and illustrate its potential for analysis of experiments by applying it to the spectra of laser produced plasmas in order to obtain estimates of electron temperatures and densities. Although these are high temperature and density plasmas, the neural network technique may be of interest in the analysis of the low temperature and density plasmas characteristic of experiments and devices in gaseous electronics

  6. Hardware implementation of stochastic spiking neural networks.

    Science.gov (United States)

    Rosselló, Josep L; Canals, Vincent; Morro, Antoni; Oliver, Antoni

    2012-08-01

    Spiking Neural Networks, the last generation of Artificial Neural Networks, are characterized by its bio-inspired nature and by a higher computational capacity with respect to other neural models. In real biological neurons, stochastic processes represent an important mechanism of neural behavior and are responsible of its special arithmetic capabilities. In this work we present a simple hardware implementation of spiking neurons that considers this probabilistic nature. The advantage of the proposed implementation is that it is fully digital and therefore can be massively implemented in Field Programmable Gate Arrays. The high computational capabilities of the proposed model are demonstrated by the study of both feed-forward and recurrent networks that are able to implement high-speed signal filtering and to solve complex systems of linear equations.

  7. 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.

  8. Apoptosis in neural crest cells by functional loss of APC tumor suppressor gene

    Science.gov (United States)

    Hasegawa, Sumitaka; Sato, Tomoyuki; Akazawa, Hiroshi; Okada, Hitoshi; Maeno, Akiteru; Ito, Masaki; Sugitani, Yoshinobu; Shibata, Hiroyuki; Miyazaki, Jun-ichi; Katsuki, Motoya; Yamauchi, Yasutaka; Yamamura, Ken-ichi; Katamine, Shigeru; Noda, Tetsuo

    2002-01-01

    Apc is a gene associated with familial adenomatous polyposis coli (FAP) and its inactivation is a critical step in colorectal tumor formation. The protein product, adenomatous polyposis coli (APC), acts to down-regulate intracellular levels of β-catenin, a key signal transducer in the Wnt signaling. Conditional targeting of Apc in the neural crest of mice caused massive apoptosis of cephalic and cardiac neural crest cells at about 11.5 days post coitum, resulting in craniofacial and cardiac anomalies at birth. Notably, the apoptotic cells localized in the regions where β-catenin had accumulated. In contrast to its role in colorectal epithelial cells, inactivation of APC leads to dysregulation of β-catenin/Wnt signaling with resultant apoptosis in certain tissues including neural crest cells. PMID:11756652

  9. Operational experiences with automated acoustic burst classification by neural networks

    International Nuclear Information System (INIS)

    Olma, B.; Ding, Y.; Enders, R.

    1996-01-01

    Monitoring of Loose Parts Monitoring System sensors for signal bursts associated with metallic impacts of loose parts has proved as an useful methodology for on-line assessing the mechanical integrity of components in the primary circuit of nuclear power plants. With the availability of neural networks new powerful possibilities for classification and diagnosis of burst signals can be realized for acoustic monitoring with the online system RAMSES. In order to look for relevant burst signals an automated classification is needed, that means acoustic signature analysis and assessment has to be performed automatically on-line. A back propagation neural network based on five pre-calculated signal parameter values has been set up for identification of different signal types. During a three-month monitoring program of medium-operated check valves burst signals have been measured and classified separately according to their cause. The successful results of the three measurement campaigns with an automated burst type classification are presented. (author)

  10. Embedding reward signals into perception and cognition

    Directory of Open Access Journals (Sweden)

    Luiz Pessoa

    2010-09-01

    Full Text Available Despite considerable interest in the neural basis of valuation, how valuation affects cognitive processing has received relatively less attention. Here, we review evidence from recent behavioral and neuroimaging studies supporting the notion that motivation can enhance perceptual and executive control processes to achieve more efficient goal-directed behavior. Specifically, in the context of cognitive tasks offering monetary gains, improved behavioral performance has been repeatedly observed in conjunction with elevated neural activations in task-relevant perceptual, cognitive, and reward-related regions. We address the neural basis of motivation-cognition interactions by suggesting various modes of communication between relevant neural networks: (1 global hub regions may integrate information from multiple inputs providing a communicative link between specialized networks, (2 point-to-point interactions allow for more specific cross-network communication, and (3 diffuse neuromodulatory systems can relay motivational signals to cortex and enhance signal processing. Together, these modes of communication allow information regarding motivational significance to reach relevant brain regions and shape behavior.

  11. Neural Mechanisms and Information Processing in Recognition Systems

    Directory of Open Access Journals (Sweden)

    Mamiko Ozaki

    2014-10-01

    Full Text Available Nestmate recognition is a hallmark of social insects. It is based on the match/mismatch of an identity signal carried by members of the society with that of the perceiving individual. While the behavioral response, amicable or aggressive, is very clear, the neural systems underlying recognition are not fully understood. Here we contrast two alternative hypotheses for the neural mechanisms that are responsible for the perception and information processing in recognition. We focus on recognition via chemical signals, as the common modality in social insects. The first, classical, hypothesis states that upon perception of recognition cues by the sensory system the information is passed as is to the antennal lobes and to higher brain centers where the information is deciphered and compared to a neural template. Match or mismatch information is then transferred to some behavior-generating centers where the appropriate response is elicited. An alternative hypothesis, that of “pre-filter mechanism”, posits that the decision as to whether to pass on the information to the central nervous system takes place in the peripheral sensory system. We suggest that, through sensory adaptation, only alien signals are passed on to the brain, specifically to an “aggressive-behavior-switching center”, where the response is generated if the signal is above a certain threshold.

  12. Ni-MH batteries state-of-charge prediction based on immune evolutionary network

    International Nuclear Information System (INIS)

    Cheng Bo; Zhou Yanlu; Zhang Jiexin; Wang Junping; Cao Binggang

    2009-01-01

    Based on clonal selection theory, an improved immune evolutionary strategy is presented. Compared with conventional evolutionary strategy algorithm (CESA) and immune monoclonal strategy algorithm (IMSA), experimental results show that the proposed algorithm is of high efficiency and can effectively prevent premature convergence. A three-layer feed-forward neural network is presented to predict state-of-charge (SOC) of Ni-MH batteries. Initially, partial least square regression (PLSR) is used to select input variables. Then, five variables, battery terminal voltage, voltage derivative, voltage second derivative, discharge current and battery temperature, are selected as the inputs of NN. In order to overcome the weakness of BP algorithm, the new algorithm is adopted to train weights. Finally, under the state of dynamic power cycle, the predicted SOC and the actual SOC are compared to verify the proposed neural network with acceptable accuracy (5%).

  13. The Tomato U-Box Type E3 Ligase PUB13 Acts With Group III Ubiquitin E2 Enzymes to Modulate FLS2-Mediated Immune Signaling

    Directory of Open Access Journals (Sweden)

    Bangjun Zhou

    2018-05-01

    Full Text Available In Arabidopsis and rice, the ubiquitin ligase PUB13-mediated protein degradation plays a significant role in plant pattern-triggered immunity (PTI and flowering time control. The Arabidopsis PUB13 has been shown to attenuate the pattern recognition receptor FLS2-mediated immune signaling by ubiquitinating FLS2 and consequently promoting its degradation by the 26S proteasome. Nevertheless, the cognate ubiquitin-conjugating enzymes (E2 with which PUB13 acts to modulate FLS2-mediated PTI are unknown. To address this question, we investigate here the tomato (Solanum lycopersicum homolog of PUB13, SlPUB13 by utilizing the recently characterized complete set of tomato E2s. Of the 13 groups of tomato E2s, only members in group III are found to interact and act with SlPUB13. Knocking-down of the group III E2 genes enhances callose deposition and induction of the RbohB gene in the immunity-associated, early oxidative burst after flg22 treatment. The group III E2s are also found to work with SlPUB13 to ubiquitinate FLS2 in vitro and are required for PUB13-mediated degradation of FLS2 in vivo upon flg22 treatment, suggesting an essential role for group III E2s in the modulation of FLS2-mediated immune signaling by PUB13. Additionally, another immunity-associated E3, NtCMPG1 is shown to also work specifically with members of group III E2 in the in vitro ubiquitination assay, which implies the group III E2 enzymes may cooperate with many E3 ligases to regulate different aspects of PTI. Taken together, these data corroborate the notion that group III E2 enzymes play an important role in PTI and build a foundation for further functional and mechanistic characterization of tomato PUB13.

  14. Stress proteins and the immune response.

    Science.gov (United States)

    Moseley, P

    2000-07-25

    , 243-282.]. This importance in immune regulation is best addressed using Matzinger's model of the immune response - The Danger Theory of Immunity [Matzinger, P., Fuchs, E.J., 1996. Beyond self and non-self: immunity is a conversation, not a war. J. NIH Res. 8, 35-39.]. Matzinger suggests that an immune system model based on the differentiation between "self and non-self" does not easily account for the changes that occur in the organism with growth and development. Why, for example does an organism not self-destruct when the immune system encounters the myriad of new peptides generated at puberty? Instead, she proposes a model of immune function based on the ability to detect and address dangers. This model states that the basic function of all cells of the organism is appropriately timed death "from natural causes". This type of cell death, or apoptosis, generates no stress signals. If, on the other hand, a cell is "murdered" by an infectious agent or dies an untimely death due to necrosis or ischemia, the cell undergoes a stress response with the liberation of stress protein-peptide complexes into the extracellular environment upon cell lysis. Not only do they serve as a "danger signal" to alert the immune system to the death of a cell under stress, but their role as protein carriers allows the immune effector cells to survey the peptides released by this stressed cell and to activate against new or unrecognized peptides carried by the stress protein. Matzinger bases the Danger Theory of Immunity on three "Laws of Lymphotics". These laws state that: (1) resting T lymphocytes require both antigen stimulation by an antigen-presenting cell (APC) and co-stimulation with a danger signal to become activated; (2) the co-stimulatory signal must be received through the APC; and (3) T cells receiving only antigen stimulation without the co-stimulatory signal undergo apoptosis. The Danger Theory gives a simple model for both tolerance and activation. (ABSTRACT TRUNCATED)

  15. Development of neural network for analysis of local power distributions in BWR fuel bundles

    International Nuclear Information System (INIS)

    Tanabe, Akira; Yamamoto, Toru; Shinfuku, Kimihiro; Nakamae, Takuji.

    1993-01-01

    A neural network model has been developed to learn the local power distributions in a BWR fuel bundle. A two layers neural network with total 128 elements is used for this model. The neural network learns 33 cases of local power peaking factors of fuel rods with given enrichment distribution as the teacher signals, which were calculated by a fuel bundle nuclear analysis code based on precise physical models. This neural network model studied well the teacher signals within 1 % error. It is also able to calculate the local power distributions within several % error for the different enrichment distributions from the teacher signals when the average enrichment is close to 2 %. This neural network is simple and the computing speed of this model is 300 times faster than that of the precise nuclear analysis code. This model was applied to survey the enrichment distribution to meet a target local power distribution in a fuel bundle, and the enrichment distribution with flat power shape are obtained within short computing time. (author)

  16. Neural network models of categorical perception.

    Science.gov (United States)

    Damper, R I; Harnad, S R

    2000-05-01

    Studies of the categorical perception (CP) of sensory continua have a long and rich history in psychophysics. In 1977, Macmillan, Kaplan, and Creelman introduced the use of signal detection theory to CP studies. Anderson and colleagues simultaneously proposed the first neural model for CP, yet this line of research has been less well explored. In this paper, we assess the ability of neural-network models of CP to predict the psychophysical performance of real observers with speech sounds and artificial/novel stimuli. We show that a variety of neural mechanisms are capable of generating the characteristics of CP. Hence, CP may not be a special model of perception but an emergent property of any sufficiently powerful general learning system.

  17. Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and motivation circuitries.

    Science.gov (United States)

    Fricchione, Gregory; Stefano, George B

    2005-05-01

    Evidence suggests that the placebo response is related to the tonic effects of constitutive nitric oxide in neural, vascular and immune tissues. Constitutive nitric oxide levels play a role in the modulation of dopamine outflow in the nigrostriatal movement and the mesolimbic and mesocortical reward and motivation circuitries. Endogenous morphine, which stimulates constitutive nitric oxide, may be an important signal molecule working at mu receptors on gamma aminobutyric acid B interneurons to disinhibit nigral and tegmental dopamine output. We surmise that placebo induced belief will activate the prefrontal cortex with downstream stimulatory effects on these dopamine systems as well as on periaqueductal grey opioid output neurons. Placebo responses in Parkinson's disease, depression and pain disorder may result. In addition, mesolimbic/mesocortical control of the stress response systems may provide a way for the placebo response to benefit other medical conditions.

  18. Nanotechnology, neuromodulation & the immune response: discourse, materiality & ethics.

    Science.gov (United States)

    Fins, Joseph J

    2015-04-01

    Drawing upon the American Pragmatic tradition in philosophy and the more recent work of philosopher Karen Barad, this paper examines how scientific problems are both obscured, and resolved by our use of language describing the natural world. Using the example of the immune response engendered by neural implants inserted in the brain, the author explains how this discourse has been altered by the advent of nanotechnology methods and devices which offer putative remedies that might temper the immune response in the central nervous system. This emergent nanotechnology has altered this problem space and catalyzed one scientific community to acknowledge a material reality that was always present, if not fully acknowledged.

  19. The innate immunity adaptor SARM translocates to the nucleus to stabilize lamins and prevent DNA fragmentation in response to pro-apoptotic signaling.

    Directory of Open Access Journals (Sweden)

    Chad R Sethman

    Full Text Available Sterile alpha and armadillo-motif containing protein (SARM, a highly conserved and structurally unique member of the MyD88 family of Toll-like receptor adaptors, plays an important role in innate immunity signaling and apoptosis. Its exact mechanism of intracellular action remains unclear. Apoptosis is an ancient and ubiquitous process of programmed cell death that results in disruption of the nuclear lamina and, ultimately, dismantling of the nucleus. In addition to supporting the nuclear membrane, lamins serve important roles in chromatin organization, epigenetic regulation, transcription, nuclear transport, and mitosis. Mutations and other damage that destabilize nuclear lamins (laminopathies underlie a number of intractable human diseases. Here, we report that SARM translocates to the nucleus of human embryonic kidney cells by using its amino-terminal Armadillo repeat region. Within the nucleus, SARM forms a previously unreported lattice akin to the nuclear lamina scaffold. Moreover, we show that SARM protects lamins from apoptotic degradation and reduces internucleosomal DNA fragmentation in response to signaling induced by the proinflammatory cytokine Tumor Necrosis Factor alpha. These findings indicate an important link between the innate immunity adaptor SARM and stabilization of nuclear lamins during inflammation-driven apoptosis in human cells.

  20. Hybrid digital signal processing and neural networks for automated diagnostics using NDE methods

    International Nuclear Information System (INIS)

    Upadhyaya, B.R.; Yan, W.

    1993-11-01

    The primary purpose of the current research was to develop an integrated approach by combining information compression methods and artificial neural networks for the monitoring of plant components using nondestructive examination data. Specifically, data from eddy current inspection of heat exchanger tubing were utilized to evaluate this technology. The focus of the research was to develop and test various data compression methods (for eddy current data) and the performance of different neural network paradigms for defect classification and defect parameter estimation. Feedforward, fully-connected neural networks, that use the back-propagation algorithm for network training, were implemented for defect classification and defect parameter estimation using a modular network architecture. A large eddy current tube inspection database was acquired from the Metals and Ceramics Division of ORNL. These data were used to study the performance of artificial neural networks for defect type classification and for estimating defect parameters. A PC-based data preprocessing and display program was also developed as part of an expert system for data management and decision making. The results of the analysis showed that for effective (low-error) defect classification and estimation of parameters, it is necessary to identify proper feature vectors using different data representation methods. The integration of data compression and artificial neural networks for information processing was established as an effective technique for automation of diagnostics using nondestructive examination methods